bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of immunomodulator and advanced therapies for primary sclerosing cholangitis-associated inflammatory bowel disease
Authors: Sayed Amr , Assis David N. , Silveira Marina G. , Deng Yanhong , Ciarleglio Maria , Gaidos Jill K.J. , Proctor Deborah D. , Al-Bawardy Badr 
Published: January 2023

Background
Inflammatory bowel disease (IBD) coexists in up to 80% of patients with primary sclerosing cholangitis (PSC). The aim of this study is to investigate the outcomes of immunomodulator (IMM)/advanced therapies for the treatment of PSC-IBD.

Methods
This was a single-center, retrospective study of patients with PSC from 1 January 2012 to 1 April 2021. Adult patients (age ≥ 18 years) with PSC-IBD were included. Primary outcomes were rates and predictors of IMM/advanced therapies to treat PSC-IBD. Secondary outcomes included rates of cholangitis, PSC-IBD clinical remission, and endoscopic healing.

Results
A total of 106 patients with PSC were reviewed and 72 (68%) with confirmed PSC-IBD were included in the study. The median age was 48 years (IQR, 33–59.5) and 69.4% were male. Overall, 28 patients (38.9%) required IMM/advanced therapies to treat PSC-IBD (22 biologic/small molecule therapy and six thiopurine monotherapy). Patients in the IMM/advanced therapies group were more likely to have small bowel involvement (32.1% vs. 4.6%; P = 0.002). In the IMM/advanced therapies group, clinical remission was achieved in 78.6% but endoscopic healing in only 50%. The rate of acute ascending cholangitis was 42.9% in the IMM/advanced therapies group compared with 31.8% in the non-IMM/advanced therapies group (P = 0.34).

Conclusion
In our cohort, up to a third of patients with PSC-IBD required IMM/advanced therapies with only 50% of these patients achieving endoscopic healing. The use of IMM/advanced therapies was not associated with a higher risk of cholangitis, but larger studies are needed to investigate the risk with different classes of advanced therapies.
Clinical characteristics and quality of life in patients with inflammatory bowel disease-associated anemia in Southeast China
Authors: Xue Mengli , Chen Jintong , Zheng Weiwei , Liu Yijuan , Lin Yijuan , Wang Chengdang 
Published: January 2023

Background/aims
Clinical characteristics of inflammatory bowel disease (IBD) with anemia have not been fully elucidated. This study aimed to investigate the frequency of, risk factors for, and management of anemia in IBD patients and to evaluate the quality of life (QOL) in IBD patients with anemia.

Methods
We included two patient cohorts. In cohort 1, clinical data from 697 IBD patients were retrospectively collected. In cohort 2, the Short Form-36 Health Survey (SF-36) and Fatigue Scale-14 (FS-14) questionnaires for IBD patients were completed to evaluate the QOL.

Results
Anemia was present in 35.6% of IBD patients [38.2% of Crohn’s disease (CD) patients vs. 29.3% of ulcerative colitis (UC) patients, P = 0.025]. Elevated platelet (PLT) count (CD: OR, 1.004; 95% CI, 1.001–1.007; P = 0.007; UC: OR, 1.010; 95% CI, 1.004–1.016; P = 0.001), elevated erythrocyte sedimentation rate (ESR) (CD: OR, 1.024; 95% CI, 1.012–1.036; P < 0.001; UC: OR, 1.025; 95% CI, 1.001–1.051; P = 0.044), and lower albumin levels (CD: OR, 0.801; 95% CI, 0.749–0.857; P < 0.001; UC: OR, 0.789; 95% CI, 0.720–0.864; P < 0.001) were associated with anemia. Among the IBD patients with anemia, only 25.8% received treatment for anemia. IBD patients with anemia had significantly lower SF-36 scores (P = 0.011) and higher FS-14 scores (P = 0.026) than those without anemia.

Conclusion
Anemia is common in IBD patients. Elevated PLT count and ESR are risk factors for anemia in IBD patients. Anemia may negatively impact IBD patients’ QOL, but few anemia patients receive treatment for anemia.
Ovarian Clear Cell Carcinoma and Markers of Epithelial-Mesenchymal Transition (EMT): Immunohistochemical Characterization of Tumor Budding
Authors: Lin Lawrence Hsu , Zamuco Ronaldo DeLeon , Shukla Pratibha S. 
Published: January 2023

Tumor budding, largely considered a manifestation of epithelial-mesenchymal transition (EMT) is an established prognostic marker for several cancers. In a recent study, tumor budding was associated with poor clinical outcomes in early-stage ovarian clear cell carcinoma. Here, we evaluated the immune expression of 3 proteins shown to be associated with EMT (E-cadherin, β-catenin, and glypican-3) in 72 primary tumors of ovarian clear cell carcinoma with median follow-up of 39.47 mo. E-cadherin and β-catenin expression was further evaluated in tumor buds in 29 (40%) cases. In the tumor mass, diffuse membranous expression of E-cadherin and β-catenin was seen in 83% (60/72) and 81% (58/72) cases, respectively. Nuclear accumulation of E-cadherin was seen in 7 (10%) cases, while none of the cases showed nuclear β-catenin expression. Glypican-3 expression was diffuse in 33.3% (24/72), patchy in 29.2% (21/72), and absent in 37.5% (27/72) cases. Evaluation of tumor buds showed aberrant patterns of expression (complete loss/cytoplasmic accumulation/diminished, discontinuous incomplete membranous staining) of E-cadherin in 29/29 (100%) and of β-catenin in 26/29 (90%) cases. E-cadherin, β-catenin, and glypican-3 expression in the main tumor mass had no association with stage, lymph node status, recurrent/progressive disease, status at last follow-up, survival and histopathologic features (P>0.05). Our finding of aberrant expression of both E-cadherin and β-catenin in tumor buds indicates involvement of Wnt signaling pathway/EMT in tumor budding and outlines its significance as a prognostic marker especially for early-stage ovarian clear cell carcinoma.
Anticholinergic Drug Burden and Risk of Incident MCI and Dementia
Authors: Gildengers Ariel , Stoehr Gary P. , Ran Xinhui , Jacobsen Erin , Teverovsky Esther , Chang Chung-Chou H. , Ganguli Mary 
Published: January 2023

Objective:
We investigated whether anticholinergic drug use was related to developing mild cognitive impairment (MCI) or dementia in older adults at the population level.

Methods:
We used an Anticholinergic Rating (ACR) scale, Clinical Dementia Rating, APOE genotype, and number of prescription medications. We examined time to incident MCI and incident dementia in a population-based cohort (n=1959). We assessed whether developing MCI or dementia was associated with (1) any anticholinergic drug use, (2) total ACR score, or (3) number of anticholinergic drugs taken.

Results:
Taking any anticholinergic drug was significantly associated with higher risk of developing MCI; however, higher ACR score or higher number of anticholinergic drugs, compared with lower, were not associated with greater risk of developing MCI. We found no significant relationship between anticholinergic use and developing dementia. The relationship between anticholinergic use and cognitive outcome was not affected by APOE genotype.

Conclusions:
Among cognitively normal older adults in a population-based sample, anticholinergic drug use is independently associated with subsequently developing MCI, but not dementia. Thus, anticholinergic drug use may influence risk of MCI that is nonprogressive to dementia and potentially be a modifiable risk factor for MCI.
Potential cost-effectiveness of individualized medicine in prodromal Alzheimer’s disease by demographic, clinical and cerebrospinal fluid proteomics factors
Authors: Handels Ron , Wesenhagen Kirsten , Tijms Betty , Teunissen Charlotte , Visser Pieter Jelle , Jönsson Linus 
Published: January 2023

ABSTRACTINTRODUCTIONThree distinct pathophysiological subtypes of Alzheimer’s disease (AD) have been identified based on CSF proteomics. We aim to estimate the potential incremental cost-effectiveness ratio of individualized hypothetical AD pharmacological treatment through stratification by these subtypes.METHODSIn a model-based health-economic evaluation usual care was compared to A) hypothetical treatment to in all subtypes and B) hypothetical treatment to those categorized as subtype 1 (high levels of BACE1) based on CSF proteomics; in a population of persons with MCI and positive amyloid and assuming hypothetical treatment efficacy in this subtype 1 only.RESULTSThe potential incremental cost-effectiveness ratio (ICER) was k€36 per quality-adjusted life year (QALY) for strategy A (no subtyping test, hypothetical treatment in all subtypes) as compared to usual care, and k€22 for strategy B (subtyping and hypothetical treatment for subtype 1 only) as compared to usual care. Compared to strategy A, strategy B was dominant, in terms of no difference in QALY and mean cost savings of k€6 per person.DISCUSSIONGiven the assumptions in this study, individualized hypothetical AD pharmacological treatment of specific subgroups of AD patients, here based on a proteomics biomarker profile, has the potential to gain health-economic benefits. Future research should focus on retrospective analysis of trial data to generate empirical evidence on treatment effect between CSF proteomics subgroups.
Longitudinal home self-collection of capillary blood usinghomeRNA correlates interferon and innate viral defense pathways with SARS-CoV-2 viral clearance
Authors: Lim Fang Yun , Kim Soo-Young , Kulkarni Karisma N. , Blazevic Rachel L. , Kimball Louise E. , Lea Hannah G. , Haack Amanda J. , Gower Maia. S. , Stevens-Ayers Terry , Starita Lea M. , Boeckh Michael , Schiffer Joshua T. , Hyrien Ollivier , Theberge Ashleigh B. , Waghmare Alpana 
Published: January 2023

ABSTRACTBlood transcriptional profiling is a powerful tool to evaluate immune responses to infection; however, blood collection via traditional phlebotomy remains a barrier to precise characterization of the immune response in dynamic infections (e.g., respiratory viruses). Here we present an at-home self-collection methodology,homeRNA, to study the host transcriptional response during acute SARS-CoV-2 infections. This method uniquely enables high frequency measurement of the host immune kinetics in non-hospitalized adults during the acute and most dynamic stage of their infection. COVID-19+ and healthy participants self-collected blood every other day for two weeks with daily nasal swabs and symptom surveys to track viral load kinetics and symptom burden, respectively. While healthy uninfected participants showed remarkably stable immune kinetics with no significant dynamic genes, COVID-19+ participants, on the contrary, depicted a robust response with over 418 dynamic genes associated with interferon and innate viral defense pathways. When stratified by vaccination status, we detected distinct response signatures between unvaccinated and breakthrough (vaccinated) infection subgroups; unvaccinated individuals portrayed a response repertoire characterized by higher innate antiviral responses, interferon signaling, and cytotoxic lymphocyte responses while breakthrough infections portrayed lower levels of interferon signaling and enhanced early cell-mediated response. Leveraging cross-platform longitudinal sampling (nasal swabs and blood), we observed thatIFI27, a key viral response gene, tracked closely with SARS-CoV-2 viral clearance in individual participants. Taken together, these results demonstrate that at-home sampling can capture key host antiviral responses and facilitate frequent longitudinal sampling to detect transient host immune kinetics during dynamic immune states.One Sentence SummarySelf-blood collection usinghomeRNA captures temporal dynamics in host transcriptional immune response during acute SARS-CoV-2 infection.
Associations of the 2018 World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) Cancer Prevention Recommendations with Stages of Colorectal Carcinogenesis
Authors: Kværner Ane Sørlie , Andersen Astrid Riseth , Henriksen Hege Berg , Knudsen Markus , Wetting Johansen Anne Marte , Hjartåker Anette , Bøhn Siv Kjølsrud , Paur Ingvild , Wiedswang Gro , Smeland Sigbjørn , Rounge Trine B. , Blomhoff Rune , Berstad Paula 
Published: January 2023

AbstractWhile adherence to cancer prevention recommendations is linked to lower risk of colorectal cancer (CRC), few have studied associations across the entire spectrum of colorectal carcinogenesis. Here, we studied the relationship of the standardized 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score for cancer prevention recommendations with colorectal carcinogenesis in a cross-sectional setting. Baseline data from two studies was combined to measure adherence to the seven-point 2018 WCRF/AICR Score in screening participants with a positive faecal immunochemical test and CRC patients in an intervention study. Dietary intake, body fatness and physical activity were assessed using self-administered questionnaires. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for screen-detected colorectal lesions and CRC. Of 1,914 participants, 548 were free from adenomas, 524 had non-advanced adenomas, 349 had advances lesions and 493 had CRC (63 screen-detected and 430 recruited from the intervention study). Adherence to the 2018 WCRF/AICR Score was inversely associated with advanced colorectal lesions; OR 0.82 (95% CI 0.71, 0.94,ptrend0.005) per score point, but not CRC. Adherence to the alcohol recommendation was the single factor most strongly inversely associated with CRC development, being significantly associated with advanced colorectal lesions and CRC. Adherence to the 2018 WCRF/AICR cancer prevention recommendations was associated with lower probability of screen-detected advanced colorectal lesions, but not CRC. Taking a holistic approach to cancer prevention is important to prevent the occurrence of precancerous colorectal lesions.What’s new?While several studies have documented an association between adherence to cancer prevention recommendations and risk colorectal cancer, data is sparse when it comes to the precancerous lesions. In this study, including participants representing the entire spectrum of colorectal carcinogenesis, strong inverse associations were observed between adherence to the 2018 World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) and the two main precursor lesion types (advanced adenoma and advanced serrated lesion), highlighting the importance of adopting a healthy lifestyle early on to prevent the development of colorectal cancer.Trial RegistrationClinicalTrials.govIdentifier:NCT01538550(Bowel Cancer Screening in Norway (BCSN) trial) andNCT01570010(CRC-NORDIET).
Exploring the Transmission Dynamics of the COVID-19 Outbreaks after Dec. 2022 in Shaanxi Province, China: Analysis of Baseline Data from A Large Scale Cohort
Authors: Zhang Tianxiao , Mi Baibing , Shen Mingwang , Nian Yunpeng , Cao Suixia , Liu Jingchun , Huang Hao , Wei Zhongxi , Liu Lixi , Wu Qian , Zhang Yi , Zhang Shaobai 
Published: January 2023

AbstractBackgroundsThe goal of this study is to explore the transmission dynamics for recent large-scale COVID-19 outbreaks in Shaanxi Province on the Chinese mainland. Furthermore, the potential effects of the Spring Festival travel rush on the ongoing COVID-19 pandemic were depicted.MethodsThis study uses baseline data from a large cohort to investigate the characteristics of the recent COVID-19 epidemic in Shaanxi province. A cluster sampling method was used to recruit the study participants during the COVID-19 pandemic in Shaanxi province since Dec. 1st, 2022. A total of 44 sampling cluster (11 village in rural areas and 33 residences in urban areas) were chosen for enrollment of study participants. A self-developed questionnaire was applied to data collection of socio-demographic and COVID-19 pandemic related information.ResultsA total of 14,744 study participants were enrolled in the baseline survey and 12,111 completed survey data were extracted for analysis. The cumulative infection attack rate (IAR) of COVID-19 among the study participants was 84.7%. The cumulative IAR in urban and rural areas were 85.6% and 83.7%, respectively. A peak of COVID-19 self-reported diagnosis could be observed from Dec. 15th, 2022 to Jan. 1st, 2023 in the provincial level. Beside this major peak of the recent epidemic (around Dec.20th, 2022), a small but steep rise could also be identified between Jan 13thto 14th, 2023. Individuals who escaped the first wave of COVID-19 outbreaks may face danger of infection from returnees during the 2023 Spring Festival.ConclusionAccording to the COVID-19 cumulative IAR data, the herd community was primarily achieved in Shaanxi province’s urban and rural areas. The epidemic in Shaanxi province has been exacerbated by mass population movement during the Spring Festival travel rush in both urban and rural areas. Further surveillance should be performed to monitor the spread of SARS-CoV-2 infections.
Multi-ancestry study of the genetics of problematic alcohol use in >1 million individuals
Authors: Zhou Hang , Kember Rachel L. , Deak Joseph D. , Xu Heng , Toikumo Sylvanus , Yuan Kai , Lind Penelope A. , Farajzadeh Leila , Wang Lu , Hatoum Alexander S. , Johnson Jessica , Lee Hyunjoon , Mallard Travis T. , Xu Jiayi , Johnston Keira J.A. , Johnson Emma C. , Galimberti Marco , Dao Cecilia , Levey Daniel F. , Overstreet Cassie , Byrne Enda M. , Gillespie Nathan A. , Gordon Scott , Hickie Ian B. , Whitfield John B. , Xu Ke , Zhao Hongyu , Huckins Laura M. , Davis Lea K. , Sanchez-Roige Sandra , Madden Pamela A. F. , Heath Andrew C. , Medland Sarah E. , Martin Nicholas G. , Ge Tian , Smoller Jordan W. , Hougaard David M. , Børglum Anders D. , Demontis Ditte , Krystal John H. , Gaziano J. Michael , Edenberg Howard J. , Agrawal Arpana ,   Million Veteran Program, Justice Amy C. , Stein Murray B. , Kranzler Henry R. , Gelernter Joel 
Published: January 2023

AbstractProblematic alcohol use (PAU) is a leading cause of death and disability worldwide. To improve our understanding of the genetics of PAU, we conducted a large cross-ancestry meta-analysis of PAU in 1,079,947 individuals. We observed a high degree of cross-ancestral similarity in the genetic architecture of PAU and identified 110 independent risk variants in within- and cross-ancestry analyses. Cross-ancestry fine-mapping improved the identification of likely causal variants. Prioritizing genes through gene expression and/or chromatin interaction in brain tissues identified multiple genes associated with PAU. We identified existing medications for potential pharmacological studies by drug repurposing analysis. Cross-ancestry polygenic risk scores (PRS) showed better performance in independent sample than single-ancestry PRS. Genetic correlations between PAU and other traits were observed in multiple ancestries, with other substance use traits having the highest correlations. The analysis of diverse ancestries contributed significantly to the findings, and fills an important gap in the literature.
Integrating NHANES and Toxicity Forecaster Data to Compare Pesticide Exposure and Bioactivity by Farmwork History and US Citizenship
Authors: Forté Chanese A. , Millar Jess A. , Colacino Justin 
Published: January 2023

AbstractIntroductionFarmworkers in the United States, especially migrant workers, face unique barriers to healthcare and have documented disparities in health outcomes. Exposure to pesticides, especially those persistent in the environment, may contribute to these health disparities.MethodsWe queried the National Health and Nutrition Examination Study (NHANES) from 1999-2014 for pesticide exposure biomarker concentrations among farmworkers and non-farmworkers by citizenship status. We combined this with toxicity assay data from the US Environmental Protection Agency’s (EPA’s) Toxicity Forecast Dashboard (ToxCast). We estimated adverse biological effects that occur across a range of human population-relevant pesticide doses.ResultsIn total, there were 1,137 people with any farmwork history and 20,205 non-farmworkers. Of the 14 commonly detectable pesticide biomarkers in NHANES, 2,4-dichlorophenol (OR= 4.32, p= 2.01×10−7) was significantly higher in farmworkers than non-farmworkers. Farmworkers were 1.37 times more likely to have a bioactive pesticide biomarker measurement in comparison to non-farmworkers (adjusted OR=1.37, 95% CI: 1.10, 1.71). Within farmworkers only, those without U.S. citizenships were 1.31 times more likely to have bioactive pesticide biomarker concentrations compared those with U.S. citizenship (adjusted OR 1.31, 95% CI: 0.75, 2.30). Additionally, non-citizen farmworkers were significantly more exposed to bioactive levels ofβ-hexachlorocyclohexane (BHC) (OR= 8.50, p= 1.23×10−9), p,p-DDE (OR= 2.98, p= 3.11×10−3), and p,p’-DDT (OR= 10.78, p= 8.70×10−4).DiscussionThese results highlight pesticide exposure disparities in farmworkers, particularly those without U.S. citizenship. Many of these exposures are occurring at doses which are bioactive in toxicological assays.
Progression and management of diabetes in Indian settings with universal access to health care: Protocol and plans for CHIPS cohort study
Authors: Kulkarni Anjali , Dilip TR , Shejul Yogesh K , Bhandarkar Prashant , Goswami Puja , Sharma Palak , Patil Priti , James KS 
Published: January 2023

AbstractThere is a demand for more comprehensive studies related to diabetes management in Indian settings covering; incidence, multimorbidity and complications in diabetes patients, clinical progression, medication, and treatment-seeking patterns. CHIPS study aims to bridge this research gap through a systematic analysis of the medical records maintained under an employees contributory health services scheme (CHSS). The CHSS based in an urban metropolitan area has 89,204 beneficiaries. The hospital information management system (HIMS) has records of lab reports, clinical summaries, prescriptions, and drugs and other medical consumables, supplied for every interaction with CHSS. Firstly, a cohort of 835 patients newly diagnosed as diabetic in the year 2011-2012 was identified from the HIMS. Their 10-year (2011-2021) medical history after getting diagnosed as a diabetic patient was elicited from the HIMS in a retrospective manner. For comparison needs another cohort of 1670 age-sex matched non-diabetic beneficiaries was created and similar 10-year medical history was created. A total of 144,511 lab records and 247,473 drug records from the HIMS for the period 2010-2012 were scrutinized to identify newly diabetic patients and their non-diabetic counterparts. The reconstructed 10-year medical history of these two groups will be used to investigate the burden of diabetes in the community, transitions from a non-diabetic and pre-diabetic to a diabetic, excess morbidity in diabetic patients, seasonal variation in glycaemic levels, association between glycaemic control and frequency of health care utilization, and COVID-19-induced temporal changes in glycaemic control.