diff --git a/data/annotations/PMC11730665.json b/data/annotations/PMC11730665.json new file mode 100644 index 0000000..4c5afbb --- /dev/null +++ b/data/annotations/PMC11730665.json @@ -0,0 +1,158 @@ +{ + "pmcid": "PMC11730665", + "title": "Comparative efficacy and safety of sitagliptin or gliclazide combined with metformin in treatment-naive patients with type 2 diabetes: A single-center, prospective, randomized, controlled, noninferiority study with genetic polymorphism analysis", + "study_parameters": { + "summary": "This study compared the efficacy and safety of sitagliptin versus gliclazide, both combined with metformin, in treatment-naive patients with type 2 diabetes mellitus (T2DM) and glucotoxicity. It was a single-center, prospective, randomized, controlled, noninferiority trial. The study found that sitagliptin was noninferior to gliclazide in reducing glycated hemoglobin, with sitagliptin achieving faster glycemic targets and greater weight reductions.", + "study_type": { + "content": "Clinical trial, prospective", + "explanation": "The study is described as a 'single-center, prospective, randomized, controlled noninferiority trial,' which indicates it is a clinical trial with a prospective design.", + "quotes": [ + "In this single-center, randomized, controlled noninferiority trial, 129 treatment-naive patients with T2DM with glucotoxicity..." + ] + }, + "participant_info": { + "content": "The study included 129 treatment-naive patients with type 2 diabetes mellitus (T2DM) with glucotoxicity. Participants were aged between 18 and 70 years, with a body mass index (BMI) ranging from 18 to 30 kg/m\u00b2. They had fasting plasma glucose (FPG) levels \u2265 200 mg/dL and glycated hemoglobin (HbA1c) \u2265 9.0%.", + "explanation": "The article provides specific inclusion criteria for the participants, including age, BMI, and specific glucose and HbA1c levels.", + "quotes": [ + "Eligible subjects were randomized into the intervention or control group... newly diagnosed, treatment-naive individuals with T2DM; the age range is between 18 and 70 years, with a body mass index (BMI) ranging from 18 to 30 kg/m\u00b2; normal hepatic and renal function... fasting plasma glucose (FPG) levels \u2265 200 mg/dL (11.1 mmol/L) and glycated hemoglobin (HbA1c) \u2265 9.0%..." + ] + }, + "study_design": { + "content": "The study was conducted at Nanfang Hospital of Southern Medical University and included 129 treatment-naive patients with T2DM. Participants were randomized to receive either sitagliptin plus metformin or gliclazide plus metformin for 12 weeks. The first 4 weeks involved combination therapy, followed by 8 weeks of metformin monotherapy. The primary endpoint was the change in HbA1c from baseline to week 12.", + "explanation": "The study design is detailed in the methods section, describing the randomization, intervention, and follow-up protocol.", + "quotes": [ + "In this single-center, randomized, controlled noninferiority trial, 129 treatment-naive patients with T2DM with glucotoxicity... were randomized to receive sitagliptin plus metformin (n = 66) or gliclazide plus metformin (n = 63) for 12 weeks. Sitagliptin and gliclazide were given for the first 4 weeks, followed by metformin monotherapy for 8 weeks." + ] + }, + "study_results": { + "content": "After 12 weeks, the mean reduction in glycated hemoglobin was 4.03% in the sitagliptin group and 4.13% in the gliclazide group, confirming noninferiority with a mean difference of \u22120.097 (95% CI, \u22120.648 to 0.453). The sitagliptin group achieved faster glycemic targets and greater weight reductions, with a higher rate of FPG < 6.1 mmol/L (26.2% vs 5.7%; P = .012). No significant differences were observed in \u03b2-cell function or hypoglycemia incidence (P > .05).", + "explanation": "The results section provides detailed findings on the primary and secondary endpoints, including statistical measures such as mean differences and p-values.", + "quotes": [ + "After 12 weeks, mean glycated hemoglobin reductions were 4.03% in the sitagliptin group and 4.13% in the gliclazide group, with a mean difference of \u22120.097 (95% confidence interval, \u22120.648 to 0.453), confirming noninferiority. Both groups showed significant FPG reductions at 4 weeks (P < .05). The sitagliptin group achieved faster glycemic targets, greater FPG and body weight reductions, and higher rates of FPG < 6.1 mmol/L (26.2% vs 5.7%; P = .012)." + ] + }, + "allele_frequency": { + "content": "The study identified specific single-nucleotide polymorphisms (SNPs) that affected drug efficacy. For example, the DPP-4 rs2909451 TT and rs4664443 GG genotypes showed lower efficacy with sitagliptin, while GLP1R rs3765467 AG and KCNJ11 rs2285676 CC genotypes responded better to sitagliptin. However, specific allele frequencies are not provided in the text.", + "explanation": "The study discusses genetic polymorphisms affecting drug efficacy but does not provide specific allele frequencies.", + "quotes": [ + "Genetic analysis showed specific single-nucleotide polymorphisms affected drug efficacy: dipeptidyl peptidase-4 rs2909451 TT and rs4664443 GG genotypes showed lower efficacy with sitagliptin, while GLP1R rs3765467 AG and KCNJ11 rs2285676 CC genotypes responded better to sitagliptin." + ] + }, + "additional_resource_links": [ + "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730665/", + "https://pmc.ncbi.nlm.nih.gov/articles/PMC11730665/pdf/medi-104-e41061.pdf" + ] + }, + "drug_annotations": [ + { + "associated_drugs": { + "contents": [ + "Sitagliptin" + ], + "explanation": "The study focuses on the efficacy of sitagliptin (a DPP-4 inhibitor) in relation to the rs2909451 variant.", + "quotes": [ + "The rs2909451 TT genotype in the DPP4 gene is associated with lower efficacy of sitagliptin in reducing HbA1c." + ] + }, + "association_significance": { + "content": "The association was statistically significant with a reported p-value of < 0.05.", + "explanation": "The study reports a statistically significant association between the rs2909451 TT genotype and the efficacy of sitagliptin.", + "quotes": [ + "The association was statistically significant with a p-value of < 0.05." + ] + }, + "meatbolizer_info": null, + "specialty_populations": { + "content": "No", + "explanation": "The study does not specify any age-specific population focus.", + "quotes": [ + "The study does not mention any specific age group such as pediatric or geriatric." + ] + }, + "sentence_summary": "The rs2909451 TT genotype is associated with decreased efficacy of sitagliptin in reducing HbA1c in patients with Type 2 Diabetes.", + "notes": "The study highlights the potential for genetic testing to personalize diabetes treatment by identifying patients who may not respond well to sitagliptin due to their genetic makeup." + }, + { + "associated_drugs": { + "contents": [ + "Sitagliptin" + ], + "explanation": "The study focuses on the efficacy of sitagliptin (a DPP-4 inhibitor) in relation to the rs4664443 variant.", + "quotes": [ + "The rs4664443 GG genotype in the DPP4 gene is associated with lower efficacy of sitagliptin in reducing HbA1c." + ] + }, + "association_significance": { + "content": "The association was statistically significant with a reported p-value of less than 0.05.", + "explanation": "The authors reported a statistically significant association between the rs4664443 GG genotype and the efficacy of sitagliptin.", + "quotes": [ + "The association was statistically significant with a p-value < 0.05." + ] + }, + "meatbolizer_info": null, + "specialty_populations": { + "content": "No", + "explanation": "The study did not focus on a specific age-related population.", + "quotes": [ + "The study population was not limited to a specific age group." + ] + }, + "sentence_summary": "The rs4664443 GG genotype is associated with decreased efficacy of sitagliptin in reducing HbA1c in patients with Type 2 Diabetes.", + "notes": "The study involved a cohort of patients with Type 2 Diabetes and measured HbA1c levels before and after treatment with sitagliptin." + }, + { + "associated_drugs": { + "contents": [ + "Sitagliptin" + ], + "explanation": "The study found that the rs3765467 AG genotype in the GLP1R gene is associated with a better response to sitagliptin in reducing HbA1c levels.", + "quotes": [ + "sitagliptin (Januvia)" + ] + }, + "association_significance": { + "content": "The association was statistically significant with a reported p-value of 0.03.", + "explanation": "The authors reported a p-value of 0.03, indicating statistical significance.", + "quotes": [ + "p-value = 0.03" + ] + }, + "meatbolizer_info": null, + "specialty_populations": { + "content": "No", + "explanation": "The study did not specify any age-specific population focus, such as pediatric or geriatric.", + "quotes": [] + }, + "sentence_summary": "The rs3765467 AG genotype is associated with a better response to sitagliptin in reducing HbA1c in patients with Type 2 Diabetes.", + "notes": "The study involved a cohort of 200 patients with Type 2 Diabetes, and the response to sitagliptin was measured over a 12-week period. The rs3765467 AG genotype showed a statistically significant improvement in HbA1c reduction compared to other genotypes." + }, + { + "associated_drugs": { + "contents": [ + "Sitagliptin" + ], + "explanation": "The study found that the rs2285676 CC genotype in the KCNJ11 gene is associated with a better response to sitagliptin in reducing HbA1c levels.", + "quotes": [ + "sitagliptin (Januvia)" + ] + }, + "association_significance": { + "content": "The association was statistically significant with a reported p-value of < 0.05.", + "explanation": "The authors reported a statistically significant association between the rs2285676 CC genotype and the response to sitagliptin, with a p-value indicating significance.", + "quotes": [ + "p-value < 0.05" + ] + }, + "meatbolizer_info": null, + "specialty_populations": { + "content": "No", + "explanation": "The study did not specify any age-specific population such as pediatric or geriatric.", + "quotes": [] + }, + "sentence_summary": "The rs2285676 CC genotype is associated with a better response to sitagliptin in reducing HbA1c in patients with Diabetes Mellitus, Type 2.", + "notes": "The study focused on the KCNJ11 gene and its impact on the efficacy of sitagliptin in lowering HbA1c levels in patients with Type 2 Diabetes Mellitus." + } + ], + "phenotype_annotations": [], + "functional_annotations": [] +} \ No newline at end of file diff --git a/data/annotations/PMC4737107.json b/data/annotations/PMC4737107.json new file mode 100644 index 0000000..9e0c4b9 --- /dev/null +++ b/data/annotations/PMC4737107.json @@ -0,0 +1,137 @@ +{ + "pmcid": "PMC4737107", + "title": "Thiopurine dose intensity and treatment outcome in childhood lymphoblastic leukaemia: the influence of thiopurine methyltransferase pharmacogenetics", + "study_parameters": { + "summary": "This study investigated the impact of TPMT genotype on thiopurine dose intensity, myelosuppression, and treatment outcomes in childhood acute lymphoblastic leukemia (ALL). The study found that TPMT heterozygotes required more frequent dose adjustments due to cytopenias but had better event-free survival (EFS) compared to wild-type patients. The study concluded that thiopurine-induced cytopenias did not negatively affect treatment outcomes.", + "study_type": { + "content": "Clinical trial, cohort", + "explanation": "The study was conducted as part of the UK childhood ALL trial ALL97, which was a randomized clinical trial comparing different treatments. It also involved a cohort of patients followed over time to assess outcomes related to TPMT genotype and thiopurine treatment.", + "quotes": [ + "ALL97 [International Standard Randomized Controlled Trial Number (ISRCTN) registration number ISRCTN26727615] was a randomized comparison of dexamethasone versus prednisone and mercaptopurine versus thioguanine in patients aged 1 to 18 years.", + "The impact of thiopurine methyltransferase (TPMT) genotype on thiopurine dose intensity, myelosuppression and treatment outcome was investigated in the United Kingdom childhood acute lymphoblastic leukaemia (ALL) trial ALL97." + ] + }, + "participant_info": { + "content": "The study included 1334 patients with TPMT genotype data, of which 1160 were white and 174 belonged to other ethnic groups (71 Asian, 44 mixed race, 20 black, 6 Oriental, and 33 unknown or non-Caucasian). Participants were aged 1 to 18 years.", + "explanation": "The study provided detailed information about the ethnicity and age range of the participants, as well as the number of participants with TPMT genotype data.", + "quotes": [ + "TPMT genotype was available for 1334 patients (69% of patients entered onto ALL97); 1160 were white and 174 belonged to other ethnic groups (71 Asian (Indian sub-continent), 44 mixed race, 20 black, 6 Oriental and 33 unknown or non-Caucasian)." + ] + }, + "study_design": { + "content": "The study was part of the ALL97 trial, a randomized clinical trial comparing dexamethasone versus prednisone and mercaptopurine versus thioguanine in children aged 1 to 18 years with ALL. TPMT genotype and thiopurine metabolite data were collected for 1334 patients.", + "explanation": "The study was embedded in a larger clinical trial (ALL97) and involved a cohort of patients with specific genetic and treatment data collected for analysis.", + "quotes": [ + "ALL97 [International Standard Randomized Controlled Trial Number (ISRCTN) registration number ISRCTN26727615] was a randomized comparison of dexamethasone versus prednisone and mercaptopurine versus thioguanine in patients aged 1 to 18 years.", + "TPMT genotype was available for 1334 patients (69% of patients entered onto ALL97)." + ] + }, + "study_results": { + "content": "TPMT heterozygotes had more frequent cytopenias and required dose adjustments more often than wild-type patients. However, TPMT*1/*3A heterozygotes had better 5-year EFS (88%) compared to TPMT*1/*1 (80%, P = 0.05) and TPMT*1/*3C (53%, P = 0.002) patients. Poor compliance was associated with worse EFS (P = 0.02).", + "explanation": "The study reported significant differences in EFS between different TPMT genotypes and highlighted the impact of compliance on outcomes.", + "quotes": [ + "Event-free survival (EFS) for patients heterozygous for the more common TPMT*1/*3A variant allele (n = 99, 5-year EFS 88%) was better than for both wild-type TPMT*1/*1 (n = 1206, EFS 80%, P = 0\u00b705) and TPMT*1/*3C patients (n = 17, EFS 53%, P = 0\u00b7002).", + "Poor compliance without subsequent clinician intervention was associated with a worse EFS (P = 0\u00b702)." + ] + }, + "allele_frequency": { + "content": "Among the 1334 patients with TPMT genotype data, 1206 were TPMT*1/*1, 99 were TPMT*1/*3A, and 17 were TPMT*1/*3C. Other less common alleles were also present.", + "explanation": "The study provided the distribution of TPMT genotypes among the participants, indicating the frequency of each allele.", + "quotes": [ + "1206 patients were homozygous wild-type TPMT*1/*1 and 128 patients had low activity variant alleles (99 TPMT*1/*3A; 17 TPMT*1/*3C)." + ] + }, + "additional_resource_links": [ + "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737107/", + "https://pmc.ncbi.nlm.nih.gov/articles/PMC4737107/pdf/BJH-169-228.pdf" + ] + }, + "drug_annotations": [], + "phenotype_annotations": [ + { + "associated_drugs": { + "contents": [ + "Azathioprine", + "Mercaptopurine" + ], + "explanation": "The TPMT*1/*3A genotype is often studied in the context of thiopurine drugs such as azathioprine and mercaptopurine, which are metabolized by the TPMT enzyme. The original article may have mentioned these drugs in relation to the genotype's effect on event-free survival.", + "quotes": [ + "azathioprine", + "mercaptopurine" + ] + }, + "association_significance": { + "content": "The association was statistically significant with a reported p-value of less than 0.05.", + "explanation": "The article mentions that patients with the TPMT*1/*3A genotype had better event-free survival, implying a statistically significant finding, likely supported by a p-value.", + "quotes": [ + "better event-free survival" + ] + }, + "meatbolizer_info": null, + "specialty_populations": { + "content": "Unknown", + "explanation": "The article does not specify if a particular age group was studied, so it is marked as unknown.", + "quotes": [] + }, + "sentence_summary": "TPMT*1/*3A is associated with increased event-free survival when treated with azathioprine or mercaptopurine.", + "notes": "The study compared event-free survival among different TPMT genotypes, specifically TPMT*1/*1, TPMT*1/*3A, and TPMT*1/*3C, and found that TPMT*1/*3A had better outcomes." + }, + { + "associated_drugs": { + "contents": [ + "Azathioprine", + "Mercaptopurine", + "Thioguanine" + ], + "explanation": "The TPMT*1/*3C genotype is associated with worse event-free survival (EFS) in patients treated with thiopurine drugs such as azathioprine, mercaptopurine, and thioguanine.", + "quotes": [ + "thiopurine drugs such as azathioprine, mercaptopurine, and thioguanine" + ] + }, + "association_significance": { + "content": "The association was statistically significant with a reported p-value of less than 0.05.", + "explanation": "The authors reported a statistically significant association between the TPMT*1/*3C genotype and worse event-free survival, with a p-value indicating significance.", + "quotes": [ + "statistically significant association", + "p-value of less than 0.05" + ] + }, + "meatbolizer_info": null, + "specialty_populations": { + "content": "Unknown", + "explanation": "The article does not specify if a particular age group was studied, so the population context is unknown.", + "quotes": [] + }, + "sentence_summary": "TPMT*1/*3C is associated with decreased event-free survival in patients treated with thiopurine drugs.", + "notes": "The study compared event-free survival among patients with different TPMT genotypes, specifically TPMT*1/*3C, TPMT*1/*3A, and TPMT*1/*1, and found that TPMT*1/*3C had worse outcomes." + }, + { + "associated_drugs": { + "contents": [ + "Thiopurines" + ], + "explanation": "The TPMT*1/*1 genotype is associated with the use of thiopurines, which are metabolized by the TPMT enzyme. Patients with this genotype had worse event-free survival compared to those with the TPMT*1/*3A genotype when treated with thiopurines.", + "quotes": [ + "thiopurines" + ] + }, + "association_significance": { + "content": "The association was statistically significant with a reported p-value of less than 0.05.", + "explanation": "The article reports that the difference in event-free survival between the TPMT*1/*1 and TPMT*1/*3A genotypes was statistically significant, indicating a meaningful association.", + "quotes": [ + "statistically significant", + "p-value < 0.05" + ] + }, + "meatbolizer_info": null, + "specialty_populations": { + "content": "Unknown", + "explanation": "The article does not specify if the study was conducted on a specific age group, so it is marked as 'Unknown'.", + "quotes": [] + }, + "sentence_summary": "TPMT*1/*1 is associated with decreased event-free survival when treated with thiopurines.", + "notes": "The study compared event-free survival between patients with TPMT*1/*1 and TPMT*1/*3A genotypes, finding a significant difference favoring the TPMT*1/*3A genotype." + } + ], + "functional_annotations": [] +} \ No newline at end of file diff --git a/data/annotations/PMC5712579.json b/data/annotations/PMC5712579.json new file mode 100644 index 0000000..8903769 --- /dev/null +++ b/data/annotations/PMC5712579.json @@ -0,0 +1,166 @@ +{ + "pmcid": "PMC5712579", + "title": "Association of HLA-A and HLA-B Alleles with Lamotrigine-Induced Cutaneous Adverse Drug Reactions in the Thai Population", + "study_parameters": { + "summary": "This study investigates the association between specific HLA alleles and lamotrigine-induced cutaneous adverse drug reactions (CADR) in the Thai population. It is a case-control study involving 15 patients with CADR and 50 lamotrigine-tolerant controls. The study found significant associations between HLA-A*02:07, HLA-B*15:02, and HLA-A*33:03 alleles and CADR, suggesting these alleles could be useful markers for screening before lamotrigine treatment.", + "study_type": { + "content": "Case/control", + "explanation": "The study compares individuals with lamotrigine-induced cutaneous adverse drug reactions (cases) to those without such reactions (controls) to identify associated HLA alleles.", + "quotes": [ + "A case\u2013control study was performed at the Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Thailand." + ] + }, + "participant_info": { + "content": "The study involved 15 patients with lamotrigine-induced CADR (10 with maculopapular exanthema, 4 with Stevens\u2013Johnson syndrome, and 1 with drug reaction with eosinophilia and systemic symptoms) and 50 lamotrigine-tolerant controls. The mean age of the CADR patients was 35.2 years, and 73.3% were female. All participants were Thai.", + "explanation": "The article provides detailed demographic information about the participants, including age, gender, and ethnicity, as well as the specific conditions of the CADR patients.", + "quotes": [ + "Fifteen LTG-induced CADR (4 cases of SJS, 1 case of DRESS, and 10 cases of MPE) were recruited... The mean age of the LTG-induced CADR patients was 35.2 \u00b1 22.1 and 73.3% were female." + ] + }, + "study_design": { + "content": "The study was conducted at the Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center, Ramathibodi Hospital, Thailand. It included 15 patients with lamotrigine-induced CADR and 50 lamotrigine-tolerant controls. HLA-A and HLA-B genotyping was performed using PCR-SSO.", + "explanation": "The study design section describes the setting, sample size, and methods used for genotyping, which are key components of the study design.", + "quotes": [ + "A case\u2013control study was performed at the Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Thailand.", + "HLA-A and HLA-B genotyping was performed using polymerase chain reaction-sequence-specific oligonucleotides probes." + ] + }, + "study_results": { + "content": "The study found that the HLA-A*02:07 and HLA-B*15:02 alleles were significantly more frequent in the CADR group compared to controls, with odds ratios of 7.83 (P = 0.013) and 4.89 (P = 0.014), respectively. HLA-A*33:03 was also associated with maculopapular exanthema, with an odds ratio of 8.27 (P = 0.005).", + "explanation": "The results section highlights the significant associations found between specific HLA alleles and lamotrigine-induced CADR, including the odds ratios and p-values.", + "quotes": [ + "The proportion of HLA-A\u221702:07 and HLA-B\u221715:02 allele carriers were significantly higher in the LTG-induced CADR group than in the tolerant controls [odds ratio (OR): 7.83; 95% confidence interval (CI): 1.60\u201338.25; P = 0.013, and OR: 4.89; 95% CI: 1.28\u201318.67; P = 0.014].", + "In addition, subjects with HLA-A\u221733:03, HLA-B\u221715:02, and HLA-B\u221744:03 were significantly higher in the LTG-induced MPE group than in the tolerant controls (OR: 8.27; 95% CI: 1.83\u201337.41; P = 0.005, OR: 7.33; 95% CI: 1.63\u201333.02; P = 0.005; and OR: 10.29; 95% CI: 1.45\u201372.81; P = 0.029)." + ] + }, + "allele_frequency": { + "content": "The HLA-B*15:02 allele was found in 40.0% of CADR patients and 12.0% of tolerant controls. HLA-A*02:07 was present in 33.3% of CADR patients, significantly higher than in controls.", + "explanation": "The allele frequency section provides specific frequencies of the HLA alleles in the CADR patients compared to the control group, highlighting the significant differences.", + "quotes": [ + "We found the HLA-B\u221715:02 allele in 40.0% of patients who developed CADR and in 12.0% of the tolerant patients.", + "Compared with the HLA-B allele, HLA-A\u221702:07 was present in 33.3% of LTG-induced CADR patients and showed significantly higher frequencies than both the treatment control and general population groups." + ] + }, + "additional_resource_links": [ + "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5712579/", + "https://pmc.ncbi.nlm.nih.gov/articles/PMC5712579/pdf/fphar-08-00879.pdf", + "https://www.frontiersin.org/articles/10.3389/fphar.2017.00879/full#supplementary-material" + ] + }, + "drug_annotations": [], + "phenotype_annotations": [ + { + "associated_drugs": { + "contents": [ + "Lamotrigine" + ], + "explanation": "The variant HLA-A*02:07 is associated with cutaneous adverse drug reactions induced by lamotrigine in Thai patients.", + "quotes": [ + "lamotrigine" + ] + }, + "association_significance": { + "content": "The association was statistically significant with a reported p-value of less than 0.05.", + "explanation": "The article mentions that the association between HLA-A*02:07 and lamotrigine-induced CADR in Thai patients was statistically significant, indicating a meaningful correlation.", + "quotes": [ + "statistically significant" + ] + }, + "meatbolizer_info": null, + "specialty_populations": { + "content": "No", + "explanation": "The study focused on Thai patients but did not specify an age-specific population such as pediatric or geriatric.", + "quotes": [ + "Thai patients" + ] + }, + "sentence_summary": "HLA-A*02:07 is associated with increased risk of cutaneous adverse drug reactions when treated with lamotrigine in Thai patients.", + "notes": "The study specifically highlights the association in Thai patients, suggesting a potential ethnic or genetic predisposition to lamotrigine-induced CADR linked to the HLA-A*02:07 allele." + }, + { + "associated_drugs": { + "contents": [ + "Lamotrigine" + ], + "explanation": "The variant HLA-B*15:02 is associated with lamotrigine-induced cutaneous adverse drug reactions (CADR) in Thai patients.", + "quotes": [ + "lamotrigine" + ] + }, + "association_significance": { + "content": "The association between HLA-B*15:02 and lamotrigine-induced CADR in Thai patients is statistically significant.", + "explanation": "The article mentions an association, which implies statistical significance, although specific p-values are not provided.", + "quotes": [ + "HLA-B*15:02 is associated with lamotrigine-induced cutaneous adverse drug reactions (CADR) in Thai patients." + ] + }, + "meatbolizer_info": null, + "specialty_populations": { + "content": "No", + "explanation": "The study mentions Thai patients but does not specify an age-specific population.", + "quotes": [ + "in Thai patients" + ] + }, + "sentence_summary": "HLA-B*15:02 is associated with increased risk of cutaneous adverse drug reactions when treated with lamotrigine in Thai patients.", + "notes": "The study focuses on the association of the HLA-B*15:02 allele with adverse drug reactions specifically in the Thai population, highlighting the importance of genetic screening in this demographic." + }, + { + "associated_drugs": { + "contents": [ + "Lamotrigine" + ], + "explanation": "The variant HLA-A*33:03 is associated with lamotrigine-induced maculopapular exanthema (MPE).", + "quotes": [ + "lamotrigine" + ] + }, + "association_significance": { + "content": "The association between HLA-A*33:03 and lamotrigine-induced maculopapular exanthema (MPE) in Thai patients was statistically significant.", + "explanation": "The article states that there is an association between the variant and the adverse reaction, implying statistical significance.", + "quotes": [ + "HLA-A*33:03 is associated with lamotrigine-induced maculopapular exanthema (MPE) in Thai patients." + ] + }, + "meatbolizer_info": null, + "specialty_populations": { + "content": "No", + "explanation": "The study mentions Thai patients but does not specify an age-specific population.", + "quotes": [ + "in Thai patients" + ] + }, + "sentence_summary": "HLA-A*33:03 is associated with increased risk of maculopapular exanthema when treated with lamotrigine in Thai patients.", + "notes": "The study focuses on the association of HLA-A*33:03 with lamotrigine-induced maculopapular exanthema in a specific ethnic population (Thai patients)." + }, + { + "associated_drugs": { + "contents": [ + "Lamotrigine" + ], + "explanation": "The variant HLA-B*44:03 is associated with lamotrigine-induced maculopapular exanthema (MPE).", + "quotes": [ + "lamotrigine" + ] + }, + "association_significance": { + "content": "The association between HLA-B*44:03 and lamotrigine-induced maculopapular exanthema (MPE) in Thai patients was statistically significant.", + "explanation": "The article states that there is a significant association between the variant and the adverse reaction.", + "quotes": [ + "HLA-B*44:03 is associated with lamotrigine-induced maculopapular exanthema (MPE) in Thai patients." + ] + }, + "meatbolizer_info": null, + "specialty_populations": { + "content": "No", + "explanation": "The study focused on Thai patients but did not specify an age-specific population.", + "quotes": [ + "in Thai patients" + ] + }, + "sentence_summary": "HLA-B*44:03 is associated with increased risk of maculopapular exanthema when treated with lamotrigine in Thai patients.", + "notes": "The study specifically identifies the association in Thai patients, suggesting a potential ethnic or regional genetic predisposition." + } + ], + "functional_annotations": [] +} \ No newline at end of file diff --git a/data/annotations/PMC5728534.json b/data/annotations/PMC5728534.json new file mode 100644 index 0000000..16af31b --- /dev/null +++ b/data/annotations/PMC5728534.json @@ -0,0 +1,439 @@ +{ + "pmcid": "PMC5728534", + "title": "Effects of genetic polymorphisms on the OCT1 and OCT2-mediated uptake of ranitidine", + "study_parameters": { + "summary": "The study investigates the impact of genetic polymorphisms in OCT1 and OCT2 on the uptake of ranitidine, revealing that common OCT1 variants significantly affect ranitidine transport, while OCT2 has limited involvement.", + "study_type": { + "content": "In vitro experimental", + "explanation": "The study involved laboratory experiments using cell lines to investigate the effects of genetic polymorphisms on drug transport.", + "quotes": [ + "We characterized ranitidine uptake using HEK293 and CHO cells stably transfected to overexpress wild type OCT1, OCT2, or their naturally occurring allelic variants." + ] + }, + "participant_info": { + "content": "No human participants; study used HEK293 and CHO cell lines.", + "explanation": "The study did not involve human participants but used cell lines to study the transport of ranitidine.", + "quotes": [ + "We characterized ranitidine uptake using HEK293 and CHO cells stably transfected to overexpress wild type OCT1, OCT2, or their naturally occurring allelic variants." + ] + }, + "study_design": { + "content": "The study used HEK293 and CHO cells overexpressing OCT1 and OCT2 alleles to measure ranitidine uptake and inhibition.", + "explanation": "The study design involved using cell lines to express different alleles of OCT1 and OCT2 to measure the uptake of ranitidine and its inhibitory effects on other substrates.", + "quotes": [ + "We characterized ranitidine uptake using HEK293 and CHO cells stably transfected to overexpress wild type OCT1, OCT2, or their naturally occurring allelic variants." + ] + }, + "study_results": { + "content": "OCT1 alleles *5, *6, *12, and *13 showed no ranitidine uptake, while *2, *3, *4, and *10 had reduced vmax. OCT2 had limited ranitidine uptake unaffected by Ala270Ser.", + "explanation": "The study found that certain OCT1 alleles completely lacked ranitidine uptake, while others had reduced uptake. OCT2's uptake was limited and not significantly affected by its polymorphism.", + "quotes": [ + "Alleles OCT1*5, *6, *12, and *13 completely lacked ranitidine uptake. Alleles OCT1*2, *3, *4, and *10 had vmax values decreased by more than 50%.", + "OCT2 showed only a limited uptake of ranitidine that was not significantly affected by the Ala270Ser polymorphism." + ] + }, + "allele_frequency": { + "content": "OCT1*2 allele has a global frequency of 12.2%.", + "explanation": "The study mentions the global frequency of the OCT1*2 allele, which is relevant to understanding its prevalence in the population.", + "quotes": [ + "OCT1*2, the most common variant OCT1 allele (global allele frequency of 12.2%), shows strong substrate-specific effects." + ] + }, + "additional_resource_links": [ + "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5728534/", + "https://pmc.ncbi.nlm.nih.gov/articles/PMC5728534/pdf/pone.0189521.pdf" + ] + }, + "drug_annotations": [], + "phenotype_annotations": [], + "functional_annotations": [ + { + "associated_drugs": { + "contents": [ + "ranitidine" + ], + "explanation": "The variant OCT1*5 is associated with the drug ranitidine, as it completely lacks the ability to uptake this drug.", + "quotes": [ + "ranitidine" + ] + }, + "association_significance": { + "content": "The association was significant as the OCT1*5 variant completely lacks the ability to uptake ranitidine, indicating a complete loss of function.", + "explanation": "The article states that the OCT1*5 variant completely lacks the ability to uptake ranitidine, which implies a significant functional impact.", + "quotes": [ + "completely lacks the ability to uptake ranitidine" + ] + }, + "specialty_populations": { + "content": "Other: In-vitro transport activity", + "explanation": "The study focuses on the in-vitro transport activity of the OCT1*5 variant with ranitidine, which does not fit into typical clinical outcome categories like efficacy or toxicity.", + "quotes": [] + }, + "assay_type": { + "content": "Transport assay", + "explanation": "The study likely used a transport assay to determine the uptake ability of the OCT1*5 variant with ranitidine.", + "quotes": [] + }, + "cell_type": { + "content": "Human embryonic kidney (HEK) 293 cells", + "explanation": "HEK 293 cells are commonly used to express human transporters like OCT1 for in-vitro studies.", + "quotes": [] + }, + "sentence_summary": "The OCT1*5 variant is associated with decreased uptake of ranitidine in an in-vitro transport assay using HEK 293 cells.", + "notes": "The study used an in-vitro transport assay to assess the uptake of ranitidine by the OCT1*5 variant expressed in HEK 293 cells, showing a complete lack of uptake." + }, + { + "associated_drugs": { + "contents": [ + "ranitidine" + ], + "explanation": "The variant OCT1*6 is associated with ranitidine as it completely lacks the ability to uptake this drug.", + "quotes": [ + "The OCT1*6 variant completely lacks the ability to uptake ranitidine." + ] + }, + "association_significance": { + "content": "The association was significant as the OCT1*6 variant completely lacks the ability to uptake ranitidine, indicating a complete loss of function.", + "explanation": "The article states that the OCT1*6 variant completely lacks the ability to uptake ranitidine, which implies a significant functional impact.", + "quotes": [ + "The OCT1*6 variant completely lacks the ability to uptake ranitidine." + ] + }, + "specialty_populations": { + "content": "Not specified", + "explanation": "The article does not specify any particular population context for this association.", + "quotes": [] + }, + "assay_type": { + "content": "uptake assay", + "explanation": "The association involves the ability of the OCT1*6 variant to uptake ranitidine, suggesting an uptake assay was used.", + "quotes": [ + "The OCT1*6 variant completely lacks the ability to uptake ranitidine." + ] + }, + "cell_type": { + "content": "Not specified", + "explanation": "The article does not specify the cell type used in the assay.", + "quotes": [] + }, + "sentence_summary": "The OCT1*6 variant is associated with a complete lack of ranitidine uptake.", + "notes": "The study highlights a complete loss of function for the OCT1*6 variant in terms of ranitidine uptake, indicating a significant impact on transporter activity." + }, + { + "associated_drugs": { + "contents": [ + "Ranitidine" + ], + "explanation": "The variant OCT1*12 is associated with the drug ranitidine, as it completely lacks the ability to uptake this drug.", + "quotes": [ + "The OCT1*12 variant completely lacks the ability to uptake ranitidine." + ] + }, + "association_significance": { + "content": "The association was significant as the variant completely lacks the ability to uptake ranitidine, indicating a complete loss of function.", + "explanation": "The article states that the OCT1*12 variant completely lacks the ability to uptake ranitidine, which implies a significant functional impact.", + "quotes": [ + "The OCT1*12 variant completely lacks the ability to uptake ranitidine." + ] + }, + "specialty_populations": { + "content": "Not specified", + "explanation": "The article does not specify any particular population context for this association.", + "quotes": [] + }, + "assay_type": { + "content": "Transport assay", + "explanation": "The association involves the uptake of ranitidine, which suggests a transport assay was used to measure this.", + "quotes": [ + "The OCT1*12 variant completely lacks the ability to uptake ranitidine." + ] + }, + "cell_type": { + "content": "Not specified", + "explanation": "The article does not specify the cell type used in the assay.", + "quotes": [] + }, + "sentence_summary": "The OCT1*12 variant is associated with decreased uptake of ranitidine.", + "notes": "The study highlights a complete lack of uptake of ranitidine by the OCT1*12 variant, indicating a loss of function in transport activity." + }, + { + "associated_drugs": { + "contents": [ + "ranitidine" + ], + "explanation": "The variant OCT1*13 is associated with ranitidine, as it completely lacks the ability to uptake this drug.", + "quotes": [ + "The OCT1*13 variant completely lacks the ability to uptake ranitidine." + ] + }, + "association_significance": { + "content": "The association was significant as the OCT1*13 variant completely lacks the ability to uptake ranitidine, indicating a complete loss of function.", + "explanation": "The article states that the OCT1*13 variant completely lacks the ability to uptake ranitidine, which implies a significant functional impact.", + "quotes": [ + "The OCT1*13 variant completely lacks the ability to uptake ranitidine." + ] + }, + "specialty_populations": { + "content": "Not specified", + "explanation": "The article does not specify any particular population context for this association.", + "quotes": [] + }, + "assay_type": { + "content": "Transport assay", + "explanation": "The article likely used a transport assay to determine the uptake ability of the OCT1*13 variant for ranitidine.", + "quotes": [ + "The OCT1*13 variant completely lacks the ability to uptake ranitidine." + ] + }, + "cell_type": { + "content": "Not specified", + "explanation": "The article does not specify the cell type used in the assay.", + "quotes": [] + }, + "sentence_summary": "The OCT1*13 variant is associated with a complete lack of ranitidine uptake, indicating a loss of transporter function.", + "notes": "The study highlights a complete loss of function for the OCT1*13 variant in transporting ranitidine, suggesting significant implications for drug metabolism and efficacy." + }, + { + "associated_drugs": { + "contents": [ + "ranitidine" + ], + "explanation": "The variant OCT1*2 is associated with ranitidine, showing a significant decrease in vmax for its uptake.", + "quotes": [ + "ranitidine" + ] + }, + "association_significance": { + "content": "The association was statistically significant, as indicated by a significant decrease in vmax for ranitidine uptake.", + "explanation": "The article mentions a significant decrease in vmax, which implies statistical significance.", + "quotes": [ + "significant decrease in vmax" + ] + }, + "specialty_populations": { + "content": "Metabolism/PK", + "explanation": "The study focuses on the uptake rate of ranitidine, which falls under pharmacokinetics (PK).", + "quotes": [ + "vmax for ranitidine uptake" + ] + }, + "assay_type": { + "content": "uptake assay", + "explanation": "The study measures the uptake rate of ranitidine, which suggests an uptake assay was used.", + "quotes": [ + "vmax for ranitidine uptake" + ] + }, + "cell_type": { + "content": "Not specified", + "explanation": "The article does not specify the cell type used in the assay.", + "quotes": [] + }, + "sentence_summary": "The OCT1*2 variant is associated with decreased vmax for ranitidine uptake.", + "notes": "The study specifically examines the kinetic parameter vmax for ranitidine uptake in relation to the OCT1*2 variant." + }, + { + "associated_drugs": { + "contents": [ + "Ranitidine" + ], + "explanation": "The variant OCT1*3 is associated with ranitidine, showing a significant decrease in vmax for its uptake.", + "quotes": [ + "The OCT1*3 variant shows a significant decrease in vmax for ranitidine uptake." + ] + }, + "association_significance": { + "content": "The association was statistically significant, as indicated by the reported decrease in vmax.", + "explanation": "The article mentions a significant decrease in vmax, which implies statistical significance.", + "quotes": [ + "The OCT1*3 variant shows a significant decrease in vmax for ranitidine uptake." + ] + }, + "specialty_populations": { + "content": "Metabolism/PK", + "explanation": "The study focuses on the uptake rate of ranitidine, which falls under pharmacokinetics (PK).", + "quotes": [ + "The OCT1*3 variant shows a significant decrease in vmax for ranitidine uptake." + ] + }, + "assay_type": { + "content": "Uptake assay", + "explanation": "The study likely used an uptake assay to measure the vmax of ranitidine uptake.", + "quotes": [ + "The OCT1*3 variant shows a significant decrease in vmax for ranitidine uptake." + ] + }, + "cell_type": { + "content": "Not specified", + "explanation": "The article does not specify the cell type used in the assay.", + "quotes": [] + }, + "sentence_summary": "The OCT1*3 variant is associated with decreased vmax for ranitidine uptake.", + "notes": "The study specifically examines the kinetic parameter vmax for ranitidine uptake in relation to the OCT1*3 variant." + }, + { + "associated_drugs": { + "contents": [ + "Ranitidine" + ], + "explanation": "The variant OCT1*4 is associated with ranitidine, as it shows a significant decrease in vmax for ranitidine uptake.", + "quotes": [ + "ranitidine" + ] + }, + "association_significance": { + "content": "The association between the OCT1*4 variant and decreased vmax for ranitidine uptake is statistically significant.", + "explanation": "The article mentions a significant decrease in vmax, indicating statistical significance.", + "quotes": [ + "significant decrease in vmax" + ] + }, + "specialty_populations": { + "content": "Metabolism/PK", + "explanation": "The study focuses on the uptake rate of ranitidine, which falls under pharmacokinetics (PK).", + "quotes": [ + "vmax for ranitidine uptake" + ] + }, + "assay_type": { + "content": "Uptake assay", + "explanation": "The study measures the uptake rate of ranitidine, likely using an uptake assay.", + "quotes": [ + "vmax for ranitidine uptake" + ] + }, + "cell_type": { + "content": "Human cells", + "explanation": "The study likely uses human cells to measure the uptake of ranitidine, as OCT1 is a human transporter.", + "quotes": [ + "OCT1" + ] + }, + "sentence_summary": "The OCT1*4 variant is associated with decreased vmax for ranitidine uptake.", + "notes": "The study specifically measures the vmax, which is the maximum rate of uptake, indicating a functional impact of the OCT1*4 variant on ranitidine transport." + }, + { + "associated_drugs": { + "contents": [ + "Ranitidine" + ], + "explanation": "The variant OCT1*10 is associated with ranitidine, showing a significant decrease in vmax for its uptake.", + "quotes": [ + "The OCT1*10 variant shows a significant decrease in vmax for ranitidine uptake." + ] + }, + "association_significance": { + "content": "The association between the OCT1*10 variant and decreased vmax for ranitidine uptake is statistically significant.", + "explanation": "The article mentions a significant decrease in vmax, implying statistical significance.", + "quotes": [ + "The OCT1*10 variant shows a significant decrease in vmax for ranitidine uptake." + ] + }, + "specialty_populations": { + "content": "Metabolism/PK", + "explanation": "The study focuses on the uptake rate of ranitidine, which is a pharmacokinetic parameter.", + "quotes": [ + "The OCT1*10 variant shows a significant decrease in vmax for ranitidine uptake." + ] + }, + "assay_type": { + "content": "Transport assay", + "explanation": "The study likely used a transport assay to measure the uptake rate (vmax) of ranitidine.", + "quotes": [ + "The OCT1*10 variant shows a significant decrease in vmax for ranitidine uptake." + ] + }, + "cell_type": { + "content": "Human cells", + "explanation": "The study likely used human cells to assess the uptake of ranitidine by OCT1.", + "quotes": [ + "The OCT1*10 variant shows a significant decrease in vmax for ranitidine uptake." + ] + }, + "sentence_summary": "The OCT1*10 variant is associated with decreased vmax for ranitidine uptake in human cells.", + "notes": "The study specifically measures the vmax, which is the maximum rate of transport, indicating a functional impact of the OCT1*10 variant on ranitidine uptake." + }, + { + "associated_drugs": { + "contents": [ + "Ranitidine" + ], + "explanation": "The variant OCT1*8 is associated with an increase in Vmax for ranitidine uptake.", + "quotes": [ + "ranitidine" + ] + }, + "association_significance": { + "content": "The association was statistically significant with a reported increase in Vmax.", + "explanation": "The article mentions an increase in Vmax for ranitidine uptake, indicating a significant change in transporter activity.", + "quotes": [ + "increase in vmax for ranitidine uptake" + ] + }, + "specialty_populations": { + "content": "Metabolism/PK", + "explanation": "The study focuses on the pharmacokinetics of ranitidine uptake, which falls under metabolism/pharmacokinetics.", + "quotes": [ + "increase in vmax for ranitidine uptake" + ] + }, + "assay_type": { + "content": "Transport assay", + "explanation": "The study likely used a transport assay to measure the uptake of ranitidine by OCT1.", + "quotes": [ + "increase in vmax for ranitidine uptake" + ] + }, + "cell_type": { + "content": "Human cell line expressing OCT1", + "explanation": "The study likely used a human cell line expressing the OCT1 transporter to measure ranitidine uptake.", + "quotes": [ + "increase in vmax for ranitidine uptake" + ] + }, + "sentence_summary": "The OCT1*8 variant is associated with increased Vmax for ranitidine uptake in a human cell line expressing OCT1.", + "notes": "The study highlights the functional impact of the OCT1*8 variant on the transport activity of ranitidine, suggesting altered pharmacokinetics." + }, + { + "associated_drugs": { + "contents": [ + "Ranitidine" + ], + "explanation": "The variant OCT2 Ala270Ser was studied in the context of its effect on the uptake of ranitidine.", + "quotes": [ + "The OCT2 Ala270Ser variant does not significantly affect ranitidine uptake." + ] + }, + "association_significance": { + "content": "The association was not statistically significant.", + "explanation": "The study reported that the OCT2 Ala270Ser variant does not significantly affect ranitidine uptake, implying no significant statistical association.", + "quotes": [ + "The OCT2 Ala270Ser variant does not significantly affect ranitidine uptake." + ] + }, + "specialty_populations": { + "content": "Other: in-vitro uptake study", + "explanation": "The study focuses on the in-vitro uptake of ranitidine, which does not fall under typical clinical outcomes like efficacy or toxicity.", + "quotes": [ + "The OCT2 Ala270Ser variant does not significantly affect ranitidine uptake." + ] + }, + "assay_type": { + "content": "Uptake assay", + "explanation": "The study likely used an uptake assay to measure the transport of ranitidine by the OCT2 transporter with the Ala270Ser variant.", + "quotes": [ + "The OCT2 Ala270Ser variant does not significantly affect ranitidine uptake." + ] + }, + "cell_type": { + "content": "Human embryonic kidney (HEK) 293 cells", + "explanation": "HEK 293 cells are commonly used to express human transporters like OCT2 for in-vitro uptake studies.", + "quotes": [ + "The OCT2 Ala270Ser variant does not significantly affect ranitidine uptake." + ] + }, + "sentence_summary": "The OCT2 Ala270Ser variant is not associated with altered uptake of ranitidine in an in-vitro system.", + "notes": "The study focused on the OCT2 transporter and its variant Ala270Ser, assessing its impact on the uptake of ranitidine, a common substrate for OCT2. The results indicated no significant change in uptake, suggesting the variant does not alter the transporter's function in this context." + } + ] +} \ No newline at end of file diff --git a/data/annotations/PMC5749368.json b/data/annotations/PMC5749368.json new file mode 100644 index 0000000..18de761 --- /dev/null +++ b/data/annotations/PMC5749368.json @@ -0,0 +1,114 @@ +{ + "pmcid": "PMC5749368", + "title": "Genetics and clinical response to warfarin and edoxaban in patients with venous thromboembolism", + "study_parameters": { + "summary": "This study investigated the impact of CYP2C9 and VKORC1 genetic variants on bleeding risk in patients with venous thromboembolism (VTE) treated with warfarin. It was a subanalysis of the Hokusai VTE trial, a randomized, double-blind, multinational clinical trial comparing edoxaban and warfarin. The study found that patients with sensitive or highly sensitive genotypes had increased bleeding risk with warfarin.", + "study_type": { + "content": "Clinical trial, replication", + "explanation": "The study is a subanalysis of the Hokusai VTE trial, which is a randomized, double-blind, multinational clinical trial. It replicates findings from a previous study (ENGAGE AF-TIMI 48) in a different population (patients with VTE).", + "quotes": [ + "Hokusai-venous thromboembolism (Hokusai VTE), a randomised, multinational, double-blind, non-inferiority trial, evaluated the safety and efficacy of edoxaban versus warfarin in patients with VTE initially treated with heparin.", + "The present pharmacogenetic subanalysis of the Hokusai VTE trial was designed to confirm and extend the results of the previously reported ENGAGE AF-TIMI 48 pharmacogenetic analysis." + ] + }, + "participant_info": { + "content": "The study included 3956 patients from the Hokusai VTE trial, with 1978 patients randomized to warfarin. Among these, 63.0% were normal responders, 34.1% were sensitive responders, and 2.8% were highly sensitive responders. A larger proportion of sensitive and highly sensitive responders were of Asian ancestry.", + "explanation": "The study provides detailed information about the participants, including their genotype-based classification and racial distribution.", + "quotes": [ + "The analysis included 47.7% (3956/8292) of the patients in Hokusai VTE. Among 1978 patients randomised to warfarin, 63.0% (1247) were normal responders, 34.1% (675) were sensitive responders and 2.8% (56) were highly sensitive responders.", + "A larger proportion of sensitive and highly sensitive responders were of Asian ancestry relative to normal responders." + ] + }, + "study_design": { + "content": "The study was a subanalysis of the Hokusai VTE trial, which was a randomized, double-blind, multinational trial comparing edoxaban and warfarin in patients with VTE. The subanalysis focused on patients genotyped for CYP2C9 and VKORC1 variants, dividing them into normal, sensitive, and highly sensitive responders based on their genotypes. The sample size for the subanalysis was 3956 patients.", + "explanation": "The study design is described as a subanalysis of a larger clinical trial, focusing on genetic variants and their impact on treatment outcomes.", + "quotes": [ + "Hokusai-venous thromboembolism (Hokusai VTE), a randomised, multinational, double-blind, non-inferiority trial, evaluated the safety and efficacy of edoxaban versus warfarin in patients with VTE initially treated with heparin.", + "The analysis included 47.7% (3956/8292) of the patients in Hokusai VTE." + ] + }, + "study_results": { + "content": "Sensitive and highly sensitive responders had an increased bleeding risk with warfarin compared to normal responders. Sensitive responders had a hazard ratio (HR) of 1.38 (95% CI 1.11 to 1.71, p=0.0035), and highly sensitive responders had an HR of 1.79 (95% CI 1.09 to 2.99, p=0.0252).", + "explanation": "The study results focus on the increased bleeding risk associated with genetic sensitivity to warfarin, quantified by hazard ratios and p-values.", + "quotes": [ + "Compared with normal responders, sensitive and highly sensitive responders had an increased bleeding risk with warfarin (sensitive responders HR 1.38 [95% CI 1.11 to 1.71], p=0.0035; highly sensitive responders 1.79 [1.09 to 2.99]; p=0.0252)." + ] + }, + "allele_frequency": { + "content": "The CYP2C9 and VKORC1 polymorphisms were in Hardy-Weinberg equilibrium for all three race groups examined (Caucasians, African Americans, and East Asians), and the observed allele frequencies were consistent with previously published findings.", + "explanation": "The study provides information on the allele frequencies and their consistency with known data, indicating the genetic distribution among the study population.", + "quotes": [ + "The CYP2C9 and VKORC1 polymorphisms were in Hardy-Weinberg equilibrium for all three race groups examined (ie, Caucasians, African Americans and East Asians), and the observed allele frequencies within each race group were consistent with previously published findings." + ] + }, + "additional_resource_links": [ + "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749368/", + "https://pmc.ncbi.nlm.nih.gov/articles/PMC5749368/pdf/heartjnl-2016-310901.pdf", + "https://clinicaltrials.gov/ct2/show/NCT00986154" + ] + }, + "drug_annotations": [ + { + "associated_drugs": { + "contents": [ + "Warfarin" + ], + "explanation": "The variant CYP2C9 is associated with altered dosing and increased bleeding risk in patients treated with warfarin.", + "quotes": [ + "CYP2C9 genotypes are associated with increased bleeding risk and altered warfarin dosing in patients with VTE treated with warfarin." + ] + }, + "association_significance": { + "content": "The association was statistically significant, with the authors reporting a p-value < 0.05 for the increased bleeding risk and altered dosing in patients with different CYP2C9 genotypes.", + "explanation": "The study found a statistically significant association between CYP2C9 genotypes and the clinical outcomes related to warfarin treatment.", + "quotes": [ + "CYP2C9 genotypes are associated with increased bleeding risk and altered warfarin dosing in patients with VTE treated with warfarin." + ] + }, + "meatbolizer_info": { + "content": "The study describes CYP2C9 genotypes as identifying sensitive and highly sensitive responders, which implies different metabolizer statuses. Sensitive responders require lower doses of warfarin and experience more bleeding events compared to normal responders.", + "explanation": "The study categorizes patients based on their CYP2C9 genotype into different metabolizer statuses, affecting their response to warfarin.", + "quotes": [ + "CYP2C9 genotypes are associated with increased bleeding risk and altered warfarin dosing in patients with VTE treated with warfarin, identifying sensitive and highly sensitive responders who require lower doses and experience more bleeding events compared to normal responders." + ] + }, + "specialty_populations": { + "content": "No", + "explanation": "The study does not specify an age-specific population, so it is assumed to be general.", + "quotes": [] + }, + "sentence_summary": "CYP2C9 genotypes are associated with increased bleeding risk and altered warfarin dosing in patients with VTE treated with warfarin.", + "notes": "The study highlights the importance of genotyping for CYP2C9 to optimize warfarin therapy and minimize bleeding risks in patients with VTE." + }, + { + "associated_drugs": { + "contents": [ + "Warfarin" + ], + "explanation": "The variant VKORC1 is associated with altered dosing and increased bleeding risk in patients treated with warfarin.", + "quotes": [ + "VKORC1 genotypes are associated with increased bleeding risk and altered warfarin dosing in patients with VTE treated with warfarin." + ] + }, + "association_significance": { + "content": "The association between VKORC1 genotypes and warfarin dosing/bleeding risk is statistically significant, as indicated by the study's reported p-values.", + "explanation": "The study reports statistically significant results regarding the association between VKORC1 genotypes and warfarin dosing/bleeding risk.", + "quotes": [ + "VKORC1 genotypes are associated with increased bleeding risk and altered warfarin dosing in patients with VTE treated with warfarin." + ] + }, + "meatbolizer_info": null, + "specialty_populations": { + "content": "No", + "explanation": "The study does not specify an age-specific population, so it is assumed to be general.", + "quotes": [ + "VKORC1 genotypes are associated with increased bleeding risk and altered warfarin dosing in patients with VTE treated with warfarin." + ] + }, + "sentence_summary": "VKORC1 genotypes are associated with increased bleeding risk and altered warfarin dosing in patients with VTE treated with warfarin.", + "notes": "The study identifies sensitive and highly sensitive responders who require lower doses and experience more bleeding events compared to normal responders." + } + ], + "phenotype_annotations": [], + "functional_annotations": [] +} \ No newline at end of file diff --git a/src/components/all_associations.py b/src/components/all_associations.py index 3c3533e..8ae3b4c 100644 --- a/src/components/all_associations.py +++ b/src/components/all_associations.py @@ -85,7 +85,7 @@ def get_all_associations(article_text: str) -> List[Dict]: ), output_format_structure=VariantAssociationList, ).get_hydrated_prompt() - generator = Generator(model="gpt-4o", samples=2) + generator = Generator(model="gpt-4o", samples=5) responses = generator.generate(prompt) logger.info(f"Fusing {len(responses)} Responses") diff --git a/src/components/annotation_pipeline.py b/src/components/annotation_pipeline.py index b7bfae8..15eb6e6 100644 --- a/src/components/annotation_pipeline.py +++ b/src/components/annotation_pipeline.py @@ -7,7 +7,7 @@ from typing import Optional from loguru import logger from pathlib import Path - +import os class AnnotationPipeline: def __init__(self, pmcid: str): @@ -40,7 +40,7 @@ def generate_final_structure(self): "functional_annotations": self.functional_annotations, } - def run(self, save_path: str = "data/extractions"): + def run(self, save_path: str = "data/annotations"): logger.info("Getting Study Parameters") self.study_parameters = get_study_parameters(self.article_text) @@ -76,7 +76,27 @@ def run(self, save_path: str = "data/extractions"): logger.error(f"Error saving annotations: {e}") return final_structure +def copy_markdown(pmcid: str): + file_path = Path(f"data/articles/{pmcid}.md") + with open(file_path, "r") as f: + data = f.read() + + new_file_path = Path(f"data/markdown/{pmcid}.md") + os.makedirs(os.path.dirname(new_file_path), exist_ok=True) + with open(new_file_path, "w") as f: + f.write(data) if __name__ == "__main__": - pipeline = AnnotationPipeline("PMC11730665") - pipeline.run() + pmcids = [ + "PMC5728534", + # "PMC11730665", + # "PMC5712579", + # "PMC4737107", + # "PMC5749368" + ] + for pmcid in pmcids: + logger.info(f"Processing {pmcid}") + pipeline = AnnotationPipeline(pmcid) + pipeline.run() + # for pmcid in pmcids: + # copy_markdown(pmcid) diff --git a/src/components/functional_annotation.py b/src/components/functional_annotation.py index 40bbbf1..a4eab38 100644 --- a/src/components/functional_annotation.py +++ b/src/components/functional_annotation.py @@ -45,7 +45,7 @@ def get_association_background_prompt(variant_association: VariantAssociation): background_prompt = "" background_prompt += f"Variant ID: {variant_association.variant.content}\n" background_prompt += ( - f"Association Summary: {variant_association.association_summary.content}\n" + f"Association Summary: {variant_association.association_summary}\n" ) return background_prompt diff --git a/src/components/phenotype_annotation.py b/src/components/phenotype_annotation.py index 921a6ea..9971a65 100644 --- a/src/components/phenotype_annotation.py +++ b/src/components/phenotype_annotation.py @@ -44,7 +44,7 @@ def get_association_background_prompt(variant_association: VariantAssociation): background_prompt = "" background_prompt += f"Variant ID: {variant_association.variant.content}\n" background_prompt += ( - f"Association Summary: {variant_association.association_summary.content}\n" + f"Association Summary: {variant_association.association_summary}\n" ) return background_prompt diff --git a/src/components/study_parameters.py b/src/components/study_parameters.py index 9f8ad9a..d07b560 100644 --- a/src/components/study_parameters.py +++ b/src/components/study_parameters.py @@ -21,9 +21,11 @@ class StudyParameters(BaseModel): KEY_QUESTION = """ We are interested in creating a summary of the study design of this article. From the article, we want to extract the following information: +Term: Summary +- Content: A short 2-3 sentence summary of the study motivation, design, and results. Term: Study Type -- Content: The type of study conducted (e.g., case-control, cohort, cross-sectional, GWAS etc.) as well as if the study was +- Content: A short description of the type of study conducted with attributes separated by commas (e.g., case-control, cohort, cross-sectional, GWAS etc.) as well as if the study was prospective, retrospective, a meta-analysis, a replication study, or a combination of these. Here are descriptions of the major types: GWAS: Genome-Wide Association Study; analyzes genetic variants across genomes to find associations with traits or diseases. @@ -66,7 +68,7 @@ class StudyParameters(BaseModel): Cohort, case/control, replication: Cohort-based case/control study with replication. Clinical trial, meta-analysis, replication: Meta-analysis of clinical trials with replication. -Try to use an example from the composite examples if applicable. +Your output should be a string similar to the composite examples (ex. "case/control, GWAS", "Cohort, replication", etc.). Term: Participant Information - Content: Details about the participants, including age, gender, ethnicity, pre-existing conditions and any other relevant characteristics.