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1. Maternal nutrition during mid-pregnancy and children’s body composition at seven years of age in the SELMA study

Author

Katherine Svensson, Chris Gennings, Lars Hagenäs, Alicja Wolk, Niclas Håkansson, Sverre Wikström, and Carl-Gustaf Bornehag

Subjects
Nutrition and Dietetics, Medicine (miscellaneous)
Abstract

Optimal nutrition during pregnancy is vital for both maternal and child health. Our objective was to explore if prenatal diet is associated with children’s height and body fat. Nutrient intake was assessed through a food-frequency questionnaire from 808 pregnant women and summarized to a nutrition index, “My Nutrition Index” (MNI). The association with children’s height and body fat (bioimpedance) was assessed with linear regression models. Secondary analysis was performed with BMI, trunk fat and skinfolds. Overall, higher MNI score was associated with greater height (β=0.47; (95% CI: 0.00, 0.94), among both sexes. Among boys, higher MNI was associated with 0.15 higher BMI z-scores, 0.12 body fat z-scores, 0.11 trunk fat z-scores, and larger triceps, and triceps + subscapular skinfolds (β=0.05 and β=0.06; on the log2 scale) (p-value

Published
2023

2. Dietary fibre in relation to lung function and respiratory symptoms from childhood to adulthood

Author

Emmanouela Sdona, Sandra Ekström, Jenny Hallberg, Niklas Andersson, Niclas Håkansson, Alicja Wolk, Inger Kull, Erik Melén, and Anna Bergström

Subjects
Pulmonary and Respiratory Medicine
Abstract

BackgroundEpidemiological studies suggest beneficial associations between dietary fibre intake, lung function and chronic respiratory symptoms in adults. Our aim was to investigate the association between dietary fibre intake in childhood and respiratory health up to adulthood.MethodsThe individual fibre intake of 1,956 participants from the Swedish population-based birth cohort BAMSE was estimated from 98 and 107 item food frequency questionnaires at ages 8 and 16 years, respectively. At 8, 16 and 24 years, lung function was measured by spirometry. Respiratory symptoms (cough, mucous production, breathing difficulties/wheeze) were assessed by questionnaires, and airway inflammation by FeNO (≥25 ppb) at 24 years. Longitudinal associations with lung function were analysed by mixed-effects linear regression; associations with respiratory symptoms and airway inflammation were analysed by logistic regression, adjusting for potential confounders.ResultsThere were no associations between fibre intake at 8 years, as total and from different sources, spirometry measurements and respiratory symptoms at 24 years. Higher fruit fibre intake tended to be inversely associated with airway inflammation at 24 years (OR 0.70, 95%CI 0.48-1.00), which became non-significant after exclusion of participants with food-related allergic symptoms (OR 0.74, 95% CI 0.49-1.10). No associations between fibre intake at 8 and 16 years as an updated lagged exposure and spirometry measurements up to 24 years were observed.ConclusionIn this longitudinal study, we observed no consistent association between dietary fibre intake in childhood and lung function or respiratory symptoms up to adulthood. Further research on dietary fibre in relation to respiratory health across the life-course is needed.

Published
2023

3. Retinal photoreceptor layer thickness has disease specificity and distinguishes predicted FTLD-Tau from biomarker-determined Alzheimer's disease

Author

Benjamin J. Kim, Murray Grossman, Tomas S. Aleman, Delu Song, Katheryn A. Q. Cousins, Corey T. McMillan, Adrienne Saludades, Yinxi Yu, Edward B. Lee, David Wolk, Vivianna M. Van Deerlin, Leslie M. Shaw, Gui-Shuang Ying, and David J. Irwin

Subjects
Aging, General Neuroscience, Neurology (clinical), Geriatrics and Gerontology, Developmental Biology
Published
2023

4. Alzheimer's Dementia After Exposure to Anesthesia and Surgery in the Elderly: A Matched Natural Experiment Using Appendicitis

Author

Joseph G. Reiter, Bijan A. Niknam, David A. Wolk, Siddharth Jain, Mark D. Neuman, Roderic G. Eckenhoff, Jeffrey H. Silber, Alexander S. Hill, Sean Hashemi, Dylan S. Small, Paul R. Rosenbaum, and Lee A. Fleisher

Subjects
Treated group, medicine.medical_specialty, business.industry, Hazard ratio, Small sample, Disease, medicine.disease, Appendicitis, Medicare, United States, Article, Surgery, Alzheimer Disease, Anesthesia, medicine, Humans, Alzheimer s dementia, Cognitive Dysfunction, Cognitive impairment, business, Aged
Abstract

OBJECTIVE: To determine if surgery and anesthesia in the elderly may promote Alzheimer’s Disease and Related Dementias (ADRD). BACKGROUND: There is a substantial conflicting literature concerning the hypothesis that surgery and anesthesia promotes ADRD. Much of the literature is confounded by indications for surgery or has small sample size. This study examines elderly patients with appendicitis, a common condition that strikes mostly at random after controlling for some known associations. METHODS: A matched natural experiment of patients undergoing appendectomy for appendicitis versus control patients without appendicitis using Medicare data from 2002 to 2017, examining 54,996 patients without previous diagnoses of ADRD, cognitive impairment, or neurological degeneration, who developed appendicitis between ages 68 through 77 years and underwent an appendectomy (the “Appendectomy” treated group), matching them 5:1 to 274,980 controls, examining the subsequent hazard for developing ADRD. RESULTS: The hazard ratio (HR) for developing ADRD or death was lower in the Appendectomy group than controls: HR = 0.96 (95% CI 0.94, 0.98), P < 0.0001, (28.2% in Appendectomy versus 29.1% in controls, at 7.5 years). The HR for death was 0.97 (0.95, 0.99), P = 0.002, (22.7% versus 23.1% at 7.5 years). The HR for developing ADRD alone was 0.89 (0.86, 0.92), P < 0.0001, (7.6% in Appendectomy versus 8.6% in controls, at 7.5 years). No subgroup analyses found significantly elevated rates of ADRD in the Appendectomy group. CONCLUSIONS: In this natural experiment involving 329,976 elderly patients, exposure to appendectomy surgery and anesthesia did not increase the subsequent rate of ADRD.

Published
2023

5. Neutrophilic granulocyte-derived B-cell activating factor supports B cells in skin lesions in hidradenitis suppurativa

Author

Robert Sabat, Deimantė Šimaitė, Johann Eli Gudjonsson, Theresa-Charlotte Brembach, Katrin Witte, Torben Krause, Georgios Kokolakis, Eckart Bartnik, Christos Nikolaou, Natascha Rill, Béma Coulibaly, Clément Levin, Matthias Herrmann, Gabriela Salinas, Thomas Leeuw, Hans-Dieter Volk, Kamran Ghoreschi, and Kerstin Wolk

Subjects
Immunology, Immunology and Allergy
Published
2023

10. Pathological combinations in neurodegenerative disease are heterogeneous and disease-associated

Author

John L Robinson, Sharon X Xie, Daniel R Baer, EunRan Suh, Vivianna M Van Deerlin, Nicholas J Loh, David J Irwin, Corey T McMillan, David A Wolk, Alice Chen-Plotkin, Daniel Weintraub, Theresa Schuck, Virginia M Y Lee, John Q Trojanowski, and Edward B Lee

Subjects
Neurology (clinical)
Abstract

Pathologies that are causative for neurodegenerative disease (ND) are also frequently present in unimpaired, older individuals. In this retrospective study of 1647 autopsied individuals, we report the incidence of 10 pathologies across ND and normal ageing in attempt to clarify which pathological combinations are disease-associated and which are ageing-related. Eight clinically defined groups were examined including unimpaired individuals and those with clinical Alzheimer’s disease, mixed dementia, amyotrophic lateral sclerosis, frontotemporal degeneration, multiple system atrophy, probable Lewy body disease or probable tauopathies. Up to seven pathologies were observed concurrently resulting in a heterogeneous mix of 161 pathological combinations. The presence of multiple additive pathologies associated with older age, increasing disease duration, APOE e4 allele and presence of dementia across the clinical groups. Fifteen to 67 combinations occurred in each group, with the unimpaired group defined by 35 combinations. Most combinations occurred at a

Published
2023

13. Differential Vulnerability of Hippocampal Subfields in Primary Age-Related Tauopathy and Chronic Traumatic Encephalopathy

Author

Kurt Farrell, Megan A Iida, Jonathan D Cherry, Alicia Casella, Thor D Stein, Kevin F Bieniek, Jamie M Walker, Timothy E Richardson, Charles L White, Victor E Alvarez, Bertrand R Huber, Dennis W Dickson, Ricardo Insausti, Kristen Dams-O'Connor, Jean-Paul Vonsattel, Andy F Teich, Marla Gearing, Jonathan Glass, Juan C Troncoso, Matthew P Frosch, Bradley T Hyman, Melissa E Murray, Johannes Attems, Margaret E Flanagan, Qinwen Mao, M-Marsel Mesulam, Sandra Weintraub, Randy L Woltjer, Thao Pham, Julia Kofler, Julie A Schneider, Lei Yu, Dushyant P Purohit, Vahram Haroutunian, Patrick R Hof, Sam Gandy, Mary Sano, Thomas G Beach, Wayne Poon, Claudia H Kawas, María M Corrada, Robert A Rissman, Jeff Metcalf, Sara Shuldberg, Bahar Salehi, Peter T Nelson, John Q Trojanowski, Edward B Lee, David A Wolk, Corey T McMillan, C Dirk Keene, Caitlin S Latimer, Thomas J Montine, Gabor G Kovacs, Mirjam I Lutz, Peter Fischer, Richard J Perrin, Nigel J Cairns, Ann C McKee, and John F Crary

Subjects
Cellular and Molecular Neuroscience, Neurology, Tauopathies, Humans, Neurofibrillary Tangles, tau Proteins, Neurology (clinical), General Medicine, Hippocampus, Pathology and Forensic Medicine, Chronic Traumatic Encephalopathy
Abstract

Chronic traumatic encephalopathy (CTE) is a tauopathy associated with repetitive mild head impacts characterized by perivascular hyperphosphorylated tau (p-tau) in neurofibrillary tangles (NFTs) and neurites in the depths of the neocortical sulci. In moderate to advanced CTE, NFTs accumulate in the hippocampus, potentially overlapping neuroanatomically with primary age-related tauopathy (PART), an age-related tauopathy characterized by Alzheimer disease-like tau pathology in the hippocampus devoid of amyloid plaques. We measured p-tau burden using positive-pixel counts on immunohistochemically stained and neuroanatomically segmented hippocampal tissue. Subjects with CTE had a higher total p-tau burden than PART subjects in all sectors (p = 0.005). Within groups, PART had significantly higher total p-tau burden in CA1/subiculum compared to CA3 (p = 0.02) and CA4 (p = 0.01) and total p-tau burden in CA2 trended higher than CA4 (p = 0.06). In CTE, total p-tau burden in CA1/subiculum was significantly higher than in the dentate gyrus; and CA2 also trended higher than dentate gyrus (p = 0.01, p = 0.06). When controlling for p-tau burden across the entire hippocampus, CA3 and CA4 had significantly higher p-tau burden in CTE than PART (p lt; 0.0001). These data demonstrate differences in hippocampal p-tau burden and regional distribution in CTE compared to PART that might be helpful in differential diagnosis and reveal insights into disease pathogenesis.

Published
2023

14. Testing for Alzheimer Disease Biomarkers and Disclosing Results Across the Disease Continuum

Author

Emily A. Largent, Joshua D. Grill, Kyra O'Brien, David Wolk, Kristin Harkins, and Jason Karlawish

Subjects
Neurology (clinical)
Abstract

Three pathologic processes are characteristic of Alzheimer disease (AD): β-amyloid, hyperphosphorylated tau, and neurodegeneration. Our understanding of AD is undergoing a transformation due to our ability to measure biomarkers of these processes across different stages of cognitive impairment. There is growing interest in using AD biomarker tests in care and research and, with this, a growing need for guidance on how to return these sensitive results to patients and participants. Here, we propose a 5-step approach informed by clinical and research experience designing and implementing AD biomarker disclosure processes, extant evidence describing how individuals react to AD biomarker information, ethics, law, and the literature on breaking bad news. The clinician should (1) determine the appropriateness of AD biomarker testing and return of results for the particular patient or research participant. If testing is appropriate, the next steps are to (2) provide pretest education and seek consent for testing from the individual and their support person, (3) administer testing, (4) return the results to the individual and their support person, and (5) follow-up to promote the recipient's well-being.

Published
2023

15. Primary care provider confidence in addressing opioid use disorder: A concept analysis

Author

Eleanor R. Turi, Amy McMenamin, Courtney Benjamin Wolk, and Lusine Poghosyan

Subjects
General Nursing
Abstract

Primary care providers (PCPs) are well-positioned to provide care for opioid use disorder (OUD), yet very few address OUD regularly. One contributing factor may be PCPs' lack of confidence in their ability to effectively treat OUD. Evidence demonstrates that clinician confidence in home care and hospital settings is associated with improved care delivery and patient outcomes. However, a conceptual definition of PCP confidence in addressing OUD has yet to be established. The aim of this concept analysis is to enhance conceptual understanding of PCP confidence in addressing OUD and inform future measurement strategies. Following Walker and Avant's method of concept analysis, PubMed, PsycINFO, and Google Scholar were searched in October 2021. Manuscripts were included if they referenced confidence in relation to PCPs who provide care to adult patients with OUD. Studies conducted outside the US and not published in English were excluded. The search resulted in 18 studies which were synthesized to conceptualize PCP confidence in addressing OUD. Defining attributes include self-efficacy, experience, and readiness to address OUD. These attributes may be influenced by organizational culture, training, support, and resources. Consequences of PCP confidence addressing OUD may include improved patient outcomes, improved delivery of and access to OUD care, and PCP attitude changes. This concept analysis-which grounds the concept of PCP confidence in addressing OUD in the theoretical and empirical literature-lays the framework for future measurement of the concept. This represents a critical first step towards developing strategies to enhance PCP confidence in addressing OUD.

Published
2023

16. Lifestyle factors for the prevention of inflammatory bowel disease

Author

Emily W, Lopes, Simon S M, Chan, Mingyang, Song, Jonas F, Ludvigsson, Niclas, Håkansson, Paul, Lochhead, Allan, Clark, Kristin E, Burke, Ashwin N, Ananthakrishnan, Amanda J, Cross, Domenico, Palli, Manuela M, Bergmann, James M, Richter, Andrew T, Chan, Ola, Olén, Alicja, Wolk, Hamed, Khalili, and Nick, Wareham

Subjects
crohn's disease, Gastroenterology, epidemiology, diet, ulcerative colitis
Abstract

ObjectiveTo estimate the proportion of cases of Crohn’s disease (CD) and ulcerative colitis (UC) that could be prevented by modifiable lifestyle factors.DesignIn a prospective cohort study of US adults from the Nurses’ Health Study (NHS; n=72 290), NHSII (n=93 909) and Health Professionals Follow-up Study (HPFS; n=41 871), we created modifiable risk scores (MRS; 0–6) for CD and UC based on established lifestyle risk factors, and healthy lifestyle scores (HLS; 0–9) derived from American healthy lifestyle recommendations. We calculated the population attributable risk by comparing the incidence of CD and UC between low-risk (CD-MRS≤1, UC-MRS≤2, HLS≥7) and high-risk groups. We externally validated our findings in three European cohorts: the Swedish Mammography Cohort (n=37 275), Cohort of Swedish Men (n=40 810) and European Prospective Investigation into Cancer and Nutrition (n=404 144).ResultsOver 5 117 021 person-years of follow-up (NHS, HPFS: 1986–2016; NHSII: 1991–2017), we documented 346 CD and 456 UC cases. Adherence to a low MRS could have prevented 42.9% (95% CI 12.2% to 66.1%) of CD and 44.4% (95% CI 9.0% to 69.8%) of UC cases. Similarly, adherence to a healthy lifestyle could have prevented 61.1% (95% CI 16.8% to 84.9%) of CD and 42.2% (95% CI 1.7% to 70.9%) of UC cases. In our validation cohorts, adherence to a low MRS and healthy lifestyle could have, respectively, prevented 43.9%–51.2% and 48.8%–60.4% of CD cases and 20.6%–27.8% and 46.8%–56.3% of UC cases.ConclusionsAcross six US and European cohorts, a substantial burden of inflammatory bowel diseases risk may be preventable through lifestyle modification.

Published
2022

18. The concept and content of the constitutional principle of justice

Author

Tetyana Vilchyk, Oksana Shcherbanyuk, and Kornelia Wolk

Abstract

This article aims to reveal the main models of implementation of the bar in the European Union and Central Asia. As some of European Union’s neighboring countries are about to embark on EU accession negotiations, they are looking to reform their justice systems to align them with EU standards. The article provides a comparative legal characteristic of the organization models of the advocate self-government bodies in the European Union and Central Asia countries from the point of view of compliance with international standards of Bar's independence. The authors have identified typical violations of the independence of lawyers' self-government bodies by the executive bodies of state power in Central Asian countries, shown the degree of their influence on protecting human rights and freedoms, and formulated recommendations aimed at overcoming existing violations’. Advocate self-government should be considered as a manifestation of the principle of independence of the Bar. Since the definition of "independence" is used in a narrow legal sense, it should be understood exclusively as a known measure of legal freedom, free discretion in actions within the boundaries outlined by law. With regard to the Bar, the term "independence" should be interpreted in the context of Recommendations Rec (2000) 21 to the Committee of Ministers to member states on the freedom of exercise of the profession of a lawyer as "freedom of the profession from any undue restrictions, influences, pressure, threats or interference, direct or indirect, from any side or for any reason. By "independence of the Bar" we mean such a legal status of the bodies of the advocates' community, established by law, which allows them to autonomously and independently from improper interference solve issues of their internal organization, as well as other tasks defined in the law, that is, to exercise self-government.

Published
2022

19. The impact of hidradenitis suppurativa on professional life

Author

Sylke Schneider-Burrus, Stefanie Kalus, Björn Fritz, Kerstin Wolk, Susana Gomis-Kleindienst, and Robert Sabat

Subjects
Dermatology
Abstract

Background Hidradenitis suppurativa (HS) is a chronic inflammatory disease that affects intertriginous skin. Objectives To determine the extent of work ability and productivity impairment as a result of HS in Germany. Methods A prospective, multicentre, epidemiological, noninterventional study of patients with HS was conducted. Medical history, medical examination performed by dermatologists and patient-reported outcomes [Work Ability Index (WAI) and Work Productivity and Activity Impairment (WPAI)] were collected. Results Of the 481 patients with HS included in the study, 99% were below the current statutory retirement age. In total, 53·3% of patients were working full time, 16·8% part time and 7·3% had retired. The unemployment rate was 12·6%, two times higher than in the general German population. Medical leave because of HS, within the last 6 months, was reported in 41·4% [95% confidence interval (CI) 36·9–46·0], with a duration of 39·3 days on average (95% CI 32·4–46·1). The mean HS-related WPAI absenteeism was 13.3% (95% CI 9·7–16·8), and the loss in productivity because of HS during working hours (WPAI presenteeism) was 25.2% (95% CI 21·8–28·6). Presenteeism was associated with HS disease severity. Overall work impairment because of HS was 33·4% (95% CI 29·3–37·6). The WAI score for patients was 32·2, ∼20% lower than for the average German employee. Only 62·8% of patients were relatively certain that they would be able to perform their work in the coming 2 years. Being more depressed and having more severe pain were associated with lower work ability and overall work impairment. The estimated annual loss of gross value added because of HS for Germany was ∼€12.6 billion (€3.3 billion related to a lower employment rate, €3.5 billion related to absenteeism and €5.8 billion related to presenteeism). Conclusions HS leads to a substantial decrease in work ability and productivity and considerable loss of gross value added. Impairment during working hours correlates with disease severity, underlining the socioeconomic importance of early and adequate treatment. Furthermore, decreased work ability and productivity is linked to depressed mood and severe pain, aspects that need more attention in patient care.

Published
2022

20. Clearing up misconceptions about project-based learning

Author

Steven Wolk

Subjects
Education
Abstract

After 30 years of practicing, researching, and teaching project-based learning (PBL), Steven Wolk offers insight into what he has learned. He discusses what PBL is and responds to common misunderstandings about how it works. He describes how PBL units are structured, the role of direct instruction in PBL, how students learn content and skills through PBL, and the importance of a culture of inquiry to a PBL classroom. And he shares inspirational ideas for how teachers and schools can take PBL even further, such as by designing problem-based PBL units.

Published
2022

21. TREM2 risk variants are associated with atypical Alzheimer’s disease

Author

Boram Kim, EunRan Suh, Aivi T. Nguyen, Stefan Prokop, Bailey Mikytuck, Olamide A. Olatunji, John L. Robinson, Murray Grossman, Jeffrey S. Phillips, David J. Irwin, Dawn Mechanic-Hamilton, David A. Wolk, John Q. Trojanowski, Corey T. McMillan, Vivianna M. Van Deerlin, and Edward B. Lee

Subjects
Cellular and Molecular Neuroscience, Membrane Glycoproteins, Alzheimer Disease, Humans, Neurodegenerative Diseases, Neurofibrillary Tangles, Microglia, Neurology (clinical), Receptors, Immunologic, Hippocampus, Pathology and Forensic Medicine
Abstract

Alzheimer's disease (AD) has multiple clinically and pathologically defined subtypes where the underlying causes of such heterogeneity are not well established. Rare TREM2 variants confer significantly increased risk for clinical AD in addition to other neurodegenerative disease clinical phenotypes. Whether TREM2 variants are associated with atypical clinical or pathologically defined subtypes of AD is not known. We studied here the clinical and pathological features associated with TREM2 risk variants in an autopsy-confirmed cohort. TREM2 variant cases were more frequently associated with non-amnestic clinical syndromes. Pathologically, TREM2 variant cases were associated with an atypical distribution of neurofibrillary tangle density with significantly lower hippocampal NFT burden relative to neocortical NFT accumulation. In addition, NFT density but not amyloid burden was associated with an increase of dystrophic microglia. TREM2 variant cases were not associated with an increased prevalence, extent, or severity of co-pathologies. These clinicopathological features suggest that TREM2 variants contribute to clinical and pathologic AD heterogeneity by altering the distribution of neurofibrillary degeneration and tau-dependent microglial dystrophy, resulting in hippocampal-sparing and non-amnestic AD phenotypes.

Published
2022

22. Deep learning generates synthetic cancer histology for explainability and education

Author

James M. Dolezal, Rachelle Wolk, Hanna M. Hieromnimon, Frederick M. Howard, Andrew Srisuwananukorn, Dmitry Karpeyev, Siddhi Ramesh, Sara Kochanny, Jung Woo Kwon, Meghana Agni, Richard C. Simon, Chandni Desai, Raghad Kherallah, Tung D. Nguyen, Jefree J. Schulte, Kimberly Cole, Galina Khramtsova, Marina Chiara Garassino, Aliya N. Husain, Huihua Li, Robert Grossman, Nicole A. Cipriani, and Alexander T. Pearson

Subjects
FOS: Computer and information sciences, Cancer Research, Oncology, Computer Vision and Pattern Recognition (cs.CV), FOS: Biological sciences, Image and Video Processing (eess.IV), FOS: Electrical engineering, electronic engineering, information engineering, Computer Science - Computer Vision and Pattern Recognition, Electrical Engineering and Systems Science - Image and Video Processing, Quantitative Biology - Quantitative Methods, Quantitative Methods (q-bio.QM)
Abstract

Artificial intelligence methods including deep neural networks (DNN) can provide rapid molecular classification of tumors from routine histology with accuracy that matches or exceeds human pathologists. Discerning how neural networks make their predictions remains a significant challenge, but explainability tools help provide insights into what models have learned when corresponding histologic features are poorly defined. Here, we present a method for improving explainability of DNN models using synthetic histology generated by a conditional generative adversarial network (cGAN). We show that cGANs generate high-quality synthetic histology images that can be leveraged for explaining DNN models trained to classify molecularly-subtyped tumors, exposing histologic features associated with molecular state. Fine-tuning synthetic histology through class and layer blending illustrates nuanced morphologic differences between tumor subtypes. Finally, we demonstrate the use of synthetic histology for augmenting pathologist-in-training education, showing that these intuitive visualizations can reinforce and improve understanding of histologic manifestations of tumor biology.

Published
2023

24. Adapting psychotherapy in collaborative care for treating opioid use disorder and co-occurring psychiatric conditions in primary care

Author

Rachel French, Julie Worley, Margaret Lowenstein, Hillary R. Bogner, Tara Calderbank, Dominick DePhilippis, Andrew Forrest, Mary Beth Connolly Gibbons, Rebecca Arden Harris, Saida Heywood, Kyle Kampman, David S. Mandell, James R. McKay, Schyler Tristen Newman, David W. Oslin, Steven Wadden, and Courtney Benjamin Wolk

Subjects
Psychiatry and Mental health, Applied Psychology
Published
2023

26. Data-driven neuropathological staging and subtyping of TDP-43 proteinopathies

Author

Alexandra L Young, Jacob W Vogel, John L Robinson, Corey T McMillan, Rik Ossenkoppele, David A Wolk, David J Irwin, Lauren Elman, Murray Grossman, Virginia M Y Lee, Edward B Lee, and Oskar Hansson

Subjects
Neurology (clinical)
Abstract

TAR DNA-binding protein-43 (TDP-43) accumulation is the primary pathology underlying several neurodegenerative diseases. Charting the progression and heterogeneity of TDP-43 accumulation is necessary to better characterize TDP-43 proteinopathies, but current TDP-43 staging systems are heuristic and assume each syndrome is homogeneous. Here, we use data-driven disease progression modelling to derive a fine-grained empirical staging system for the classification and differentiation of frontotemporal lobar degeneration due to TDP-43 (FTLD-TDP, n = 126), amyotrophic lateral sclerosis (ALS, n = 141) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) with and without Alzheimer’s disease (n = 304). The data-driven staging of ALS and FTLD-TDP complement and extend previously described human-defined staging schema for ALS and behavioural variant frontotemporal dementia. In LATE-NC individuals, progression along data-driven stages was positively associated with age, but negatively associated with age in individuals with FTLD-TDP. Using only regional TDP-43 severity, our data driven model distinguished individuals diagnosed with ALS, FTLD-TDP or LATE-NC with a cross-validated accuracy of 85.9%, with misclassifications associated with mixed pathological diagnosis, age and genetic mutations. Adding age and SuStaIn stage to this model increased accuracy to 92.3%. Our model differentiates LATE-NC from FTLD-TDP, though some overlap was observed between late-stage LATE-NC and early-stage FTLD-TDP. We further tested for the presence of subtypes with distinct regional TDP-43 progression patterns within each diagnostic group, identifying two distinct cortical-predominant and brainstem-predominant subtypes within FTLD-TDP and a further two subcortical-predominant and corticolimbic-predominant subtypes within ALS. The FTLD-TDP subtypes exhibited differing proportions of TDP-43 type, while there was a trend for age differing between ALS subtypes. Interestingly, a negative relationship between age and SuStaIn stage was seen in the brainstem/subcortical-predominant subtype of each proteinopathy. No subtypes were observed for the LATE-NC group, despite aggregating individuals with and without Alzheimer’s disease and a larger sample size for this group. Overall, we provide an empirical pathological TDP-43 staging system for ALS, FTLD-TDP and LATE-NC, which yielded accurate classification. We further demonstrate that there is substantial heterogeneity amongst ALS and FTLD-TDP progression patterns that warrants further investigation in larger cross-cohort studies.

Published
2023

28. Distinct Reproductive Risk Profiles for Intrinsic-Like Breast Cancer Subtypes: Pooled Analysis of Population-Based Studies

Author

Jung, Audrey Y, Ahearn, Thomas U, Behrens, Sabine, Middha, Pooja, Bolla, Manjeet K, Wang, Qin, Arndt, Volker, Aronson, Kristan J, Augustinsson, Annelie, Beane Freeman, Laura E, Becher, Heiko, Brenner, Hermann, Canzian, Federico, Carey, Lisa A, CTS Consortium, Czene, Kamila, Eliassen, A Heather, Eriksson, Mikael, Evans, D Gareth, Figueroa, Jonine D, Fritschi, Lin, Gabrielson, Marike, Giles, Graham G, Guénel, Pascal, Hadjisavvas, Andreas, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Hamann, Ute, Hoppe, Reiner, Hopper, John L, Howell, Anthony, Hunter, David J, Hüsing, Anika, Kaaks, Rudolf, Kosma, Veli-Matti, Koutros, Stella, Kraft, Peter, Lacey, James V, Le Marchand, Loic, Lissowska, Jolanta, Loizidou, Maria A, Mannermaa, Arto, Maurer, Tabea, Murphy, Rachel A, Olshan, Andrew F, Olsson, Håkan, Patel, Alpa V, Perou, Charles M, Rennert, Gad, Shibli, Rana, Shu, Xiao-Ou, Southey, Melissa C, Stone, Jennifer, Tamimi, Rulla M, Teras, Lauren R, Troester, Melissa A, Truong, Thérèse, Vachon, Celine M, Wang, Sophia S, Wolk, Alicja, Wu, Anna H, Yang, Xiaohong R, Zheng, Wei, Dunning, Alison M, Pharoah, Paul DP, Easton, Douglas F, Milne, Roger L, Chatterjee, Nilanjan, Schmidt, Marjanka K, García-Closas, Montserrat, Chang-Claude, Jenny, Jung, Audrey Y [0000-0003-0875-6673], Ahearn, Thomas U [0000-0003-0771-7752], Behrens, Sabine [0000-0002-9714-104X], Middha, Pooja [0000-0001-5503-8215], Wang, Qin [0000-0002-9139-0627], Arndt, Volker [0000-0001-9320-8684], Aronson, Kristan J [0000-0002-7865-7243], Becher, Heiko [0000-0002-8808-6667], Brenner, Hermann [0000-0002-6129-1572], Canzian, Federico [0000-0002-4261-4583], Czene, Kamila [0000-0002-3233-5695], Eliassen, A Heather [0000-0002-3961-6609], Figueroa, Jonine D [0000-0002-5100-623X], Fritschi, Lin [0000-0002-7692-3560], Gabrielson, Marike [0000-0002-3171-1556], Giles, Graham G [0000-0003-4946-9099], Guénel, Pascal [0000-0002-8359-518X], Hadjisavvas, Andreas [0000-0002-5636-0799], Håkansson, Niclas [0000-0001-7673-5554], Hall, Per [0000-0002-5640-9126], Hüsing, Anika [0000-0002-2685-9732], Koutros, Stella [0000-0001-5294-5485], Kraft, Peter [0000-0002-4472-8103], Le Marchand, Loic [0000-0001-5013-980X], Lissowska, Jolanta [0000-0003-2695-5799], Loizidou, Maria A [0000-0003-4503-7758], Mannermaa, Arto [0000-0001-8250-1930], Murphy, Rachel A [0000-0003-4383-5641], Olsson, Håkan [0000-0002-7721-4619], Patel, Alpa V [0000-0001-8834-9896], Perou, Charles M [0000-0001-9827-2247], Shu, Xiao-Ou [0000-0002-0711-8314], Southey, Melissa C [0000-0002-6313-9005], Stone, Jennifer [0000-0001-5077-0124], Tamimi, Rulla M [0000-0003-2306-8668], Vachon, Celine M [0000-0002-1962-9322], Wolk, Alicja [0000-0001-7387-6845], Dunning, Alison M [0000-0001-6651-7166], Pharoah, Paul DP [0000-0001-8494-732X], Easton, Douglas F [0000-0003-2444-3247], Milne, Roger L [0000-0001-5764-7268], Schmidt, Marjanka K [0000-0002-2228-429X], García-Closas, Montserrat [0000-0003-1033-2650], Chang-Claude, Jenny [0000-0001-8919-1971], and Apollo - University of Cambridge Repository

Subjects
Receptors, Estrogen, Receptor, ErbB-2, Risk Factors, Case-Control Studies, Biomarkers, Tumor, Humans, Female, Breast Neoplasms, Triple Negative Breast Neoplasms, Receptors, Progesterone
Abstract

BACKGROUND: Reproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER)-positive and ER-negative breast cancer. However, their associations with intrinsic-like subtypes are less clear. METHODS: Analyses included up to 23 353 cases and 71 072 controls pooled from 31 population-based case-control or cohort studies in the Breast Cancer Association Consortium across 16 countries on 4 continents. Polytomous logistic regression was used to estimate the association between reproductive factors and risk of breast cancer by intrinsic-like subtypes (luminal A-like, luminal B-like, luminal B-HER2-like, HER2-enriched-like, and triple-negative breast cancer) and by invasiveness. All statistical tests were 2-sided. RESULTS: Compared with nulliparous women, parous women had a lower risk of luminal A-like, luminal B-like, luminal B-HER2-like, and HER2-enriched-like disease. This association was apparent only after approximately 10 years since last birth and became stronger with increasing time (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.49 to 0.71; and OR = 0.36, 95% CI = 0.28 to 0.46 for multiparous women with luminal A-like tumors 20 to less than 25 years after last birth and 45 to less than 50 years after last birth, respectively). In contrast, parous women had a higher risk of triple-negative breast cancer right after their last birth (for multiparous women: OR = 3.12, 95% CI = 2.02 to 4.83) that was attenuated with time but persisted for decades (OR = 1.03, 95% CI = 0.79 to 1.34, for multiparous women 25 to less than 30 years after last birth). Older age at first birth (Pheterogeneity < .001 for triple-negative compared with luminal A-like breast cancer) and breastfeeding (Pheterogeneity < .001 for triple-negative compared with luminal A-like breast cancer) were associated with lower risk of triple-negative breast cancer but not with other disease subtypes. Younger age at menarche was associated with higher risk of all subtypes; older age at menopause was associated with higher risk of luminal A-like but not triple-negative breast cancer. Associations for in situ tumors were similar to luminal A-like. CONCLUSIONS: This large and comprehensive study demonstrates a distinct reproductive risk factor profile for triple-negative breast cancer compared with other subtypes, with implications for the understanding of disease etiology and risk prediction.

Published
2022

30. Associations between exploratory dietary patterns and incident type 2 diabetes: a federated meta-analysis of individual participant data from 25 cohort studies

Author

Jannasch, Franziska, Dietrich, Stefan, Bishop, Tom RP, Pearce, Matthew, Fanidi, Anouar, O'Donoghue, Gráinne, O'Gorman, Donal, Marques-Vidal, Pedro, Vollenweider, Peter, Bes-Rastrollo, Maira, Byberg, Liisa, Wolk, Alicja, Hashemian, Maryam, Malekzadeh, Reza, Poustchi, Hossein, Luft, Vivian C, De Matos, Sheila M Alvim, Kim, Jihye, Kim, Mi Kyung, Kim, Yeonjung, Stern, Dalia, Lajous, Martin, Magliano, Dianna J, Shaw, Jonathan E, Akbaraly, Tasnime, Kivimaki, Mika, Maskarinec, Gertraud, Le Marchand, Loïc, Martínez-González, Miguel Ángel, Soedamah-Muthu, Sabita S, EPIC-InterAct Consortium, Wareham, Nicholas J, Forouhi, Nita G, Schulze, Matthias B, Medical and Clinical Psychology, Jannasch, Franziska [0000-0003-3478-4758], Apollo - University of Cambridge Repository, EPIC-InterAct Consortium, University of Cambridge [UK] (CAM), Université de Lausanne = University of Lausanne (UNIL), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, G03/140, PI10/02293, PI10/02658, PI13/00615, PI14/01668, PI14/01764, PI14/01798, PI17/01795, PI20/00564, PNSD-2020/021, LSHM_CT_2006_037197, 82DZD00302, 122/2014, 27/2011, 45/2011, PNSD 2020/2021, FKZ: 01EA1806A, National Institutes of Health, NIH: R01AG056477, RF1AG062553, U01 CA164973, National Cancer Institute, NCI, American Institute for Cancer Research, AICR: 05B047, GlaxoSmithKline, GSK, Centre International de Recherche sur le Cancer, CIRC, Wellcome Trust, WT: 221854/Z/20/Z, Horizon 2020 Framework Programme, H2020: 824989, Seventh Framework Programme, FP7: 602068, Manchester Biomedical Research Centre, BRC: IS-BRC-1215-20014, Medical Research Council, MRC: MC_UU_00006/1and MC_UU_00006/3, Cancer Research UK, CRUK: C20/A5860, National Research Foundation, NRF, Department of Science and Technology, Ministry of Science and Technology, India, डीएसटी, Deutsche Forschungsgemeinschaft, DFG: 491394008, NFDI 13/1, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, SNF: 33CS30-139468, 33CS30-148401, 33CS30_177535/1, 33CSCO-122661, MRCMR/R024227/1, Bundesministerium für Bildung und Forschung, BMBF, Consejo Nacional de Ciencia y Tecnología, CONACYT: S0008-2009-1: 000000000115312, Kementerian Sains, Teknologi dan Inovasi, MOSTI, Nederlandse Zuivel Organisatie, NZO, Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq, Ministry of Science, ICT and Future Planning, MSIP: NRF-2017M3C9A6047623, Ministry of Health and Welfare, MOHW: 4845-301, 4851-302, Korea Centers for Disease Control and Prevention, KCDC, Seconda Università degli Studi di Napoli, SUN, Vetenskapsrådet, VR: 2017–00644, Universidad de Navarra, Tehran University of Medical Sciences and Health Services, TUMS: 81/15, Financiadora de Estudos e Projetos, FINEP: 01 06 0010.00, 01 06 0071.00, 01 06 0115.00, 01 06 0300.00, Ministério da Saúde, Mejeribrugets ForskningsFond, MFF, European Regional Development Fund, ERDF: RD 06/0045, Open Access funding enabled and organized by Projekt DEAL. The InterConnect project is funded by the European Union’s Seventh Framework Programme (grant number 602068). FJ and MBS acknowledge funding from the German Federal Ministry of Education and Research and the State of Brandenburg to the German Center for Diabetes Research (DZD) (82DZD00302). Furthermore, this work was supported by the NutriAct – Competence Cluster Nutrition Research Berlin-Potsdam funded by the German Federal Ministry of Education and Research (FKZ: 01EA1806A). This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 491394008. This work was done as part of the NFDI4Health Consortium ( www.nfdi4health.de ). We gratefully acknowledge the financial support of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – NFDI 13/1. NJW and NGF acknowledge funding from the Medical Research Council Epidemiology Unit (MC_UU_00006/1and MC_UU_00006/3) and NIHR Biomedical Research Centre Cambridge: Nutrition, Diet, and Lifestyle Research Theme (IS-BRC-1215-20014). NGF is an NIHR Senior Investigator (G111539). TB acknowledges funding from EUCAN-Connect under the European Union’s Horizon 2020 research and innovation programme (grant agreement number 824989). The InterAct project was funded by the EU FP6 programme (grant number LSHM_CT_2006_037197). MBR and MAMG acknowledge that the SUN Project has received funding from the Spanish Government-Instituto de Salud Carlos III, and the European Regional Development Fund (FEDER) (RD 06/0045, CIBER-OBN, Grants PI10/02658, PI10/02293, PI13/00615, PI14/01668, PI14/01798, PI14/01764, PI17/01795, PI20/00564 and G03/140), PNSD-2020/021, the Navarra Regional Government (27/2011, 45/2011, 122/2014), PNSD 2020/2021, and the University of Navarra. LB and AW acknowledge that the COSM and SMC are part of the Swedish Infrastructure for Medical Population-Based Life-Course and Environmental Research, SIMPLER. SIMPLER receives funding through the Swedish Research Council (grant no 2017–00644). RM acknowledges funding from the Tehran University of Medical Sciences (grant number: 81/15), Cancer Research UK (grant number: C20/A5860), the Intramural Research Program of the U.S. National Cancer Institute, NIH, and the International Agency for Research on Cancer. SMAM and VCL acknowledge that ELSA-Brasil was supported by the Brazilian Ministry of Health (Department of Science and Technology) and Ministry of Science, Technology and Innovation (Financiadora de Estudos e Projetos (FINEP), grant numbers 01 06 0010.00, 01 06 0212.00, 01 06 0300.00, 01 06 0278.00, 01 06 0115.00 and 01 06 0071.00) and the National Council for Scientific and Technological Development (CNPq). JK acknowledges funding from the Korea Centers for Disease Control and Prevention, Ministry for Health and Welfare, Republic of Korea (4845-301 and 4851-302), and the Collaborative Genome Program for Fostering New Post-Genome Industry of the National Research Foundation (NRF) funded by the Ministry of Science and ICT (NRF-2017M3C9A6047623). DS and ML acknowledge that this work of MTC was supported by the American Institute for Cancer Research (grant number 05B047) and the Consejo Nacional de Ciencia y Tecnología (CONACyT) (grant number S0008-2009-1: 000000000115312). LLM acknowledges funding from the US National Institutes of Health grant U01 CA164973, SSSM received the Wiebe Visser International Dairy Nutrition Prize and has received recent research funding (2019) for epidemiological studies on dairy products and cardiometabolic diseases from the Dutch Dairy Association and the Danish Dairy Research Foundation. PMV and PV acknowledge funding from GlaxoSmithKline, the Faculty of Biology and Medicine of Lausanne, and the Swiss National Science Foundation (grants 33CSCO-122661, 33CS30-139468, 33CS30-148401 and 33CS30_177535/1). MK and the Whitehall II study were supported by the UK Medical Research Council (MRCMR/R024227/1), the Wellcome Trust (221854/Z/20/Z) and the US National Institutes of Health (NIH, RF1AG062553, R01AG056477), during the conduct of the study. The funding sources did not participate in the design or conduct of the study, collection, management, analysis, or interpretation of the data, or preparation, review, or approval of the manuscript., We would like to thank the participants, principal investigators, and study teams of the individual cohorts included in this collaboration. The work presented herein was made possible using the OBiBa suite (http://www.obiba.org), a software suite developed by Maelstrom Research (www.maelstrom-research.org), and DataSHIELD (http://www.datashield.ac.uk), a software suite developed by the Data to Knowledge (D2K) Research Group. We thank EPIC-InterAct collaborators and Nicola Kerrison at the MRC Epidemiology Unit for assistance relating to the EPIC-InterAct dataset. We also thank the AusDiab Steering Committee for providing data from the AusDiab study. Moreover, we thank the NIH Biologic Specimen and Data Repository Information Coordinating Center and the ARIC, CARDIA, MESA, PRHHP and WHI OS study for providing data for this study., and HAL UVSQ, Équipe

Subjects
endocrine system diseases, Federated meta-analysis, Medicine (miscellaneous), BLOOD-PRESSURE, Endocrinology and Diabetes, PROFILE, Cohort Studies, Type 2 diabetes mellitus, Exploratory, Dietary patterns, DESIGN, Risk Factors, Humans, Prospective Studies, POPULATION, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, RISK, Diabetes Mellitus, Type 2/epidemiology, Diabetes Mellitus, Type 2/etiology, Diet, Incidence, Nutrition and Dietetics, OBJECTIVES, nutritional and metabolic diseases, CONSUMPTION, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Näringslära, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Diabetes Mellitus, Type 2, ATHEROSCLEROSIS, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Endokrinologi och diabetes, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, LIFE-STYLE, HEALTH, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

Funder: Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DIfE) (3440), PURPOSE: In several studies, exploratory dietary patterns (DP), derived by principal component analysis, were inversely or positively associated with incident type 2 diabetes (T2D). However, findings remained study-specific, inconsistent and rarely replicated. This study aimed to investigate the associations between DPs and T2D in multiple cohorts across the world. METHODS: This federated meta-analysis of individual participant data was based on 25 prospective cohort studies from 5 continents including a total of 390,664 participants with a follow-up for T2D (3.8-25.0 years). After data harmonization across cohorts we evaluated 15 previously identified T2D-related DPs for association with incident T2D estimating pooled incidence rate ratios (IRR) and confidence intervals (CI) by Piecewise Poisson regression and random-effects meta-analysis. RESULTS: 29,386 participants developed T2D during follow-up. Five DPs, characterized by higher intake of red meat, processed meat, French fries and refined grains, were associated with higher incidence of T2D. The strongest association was observed for a DP comprising these food groups besides others (IRRpooled per 1 SD = 1.104, 95% CI 1.059-1.151). Although heterogeneity was present (I2 = 85%), IRR exceeded 1 in 18 of the 20 meta-analyzed studies. Original DPs associated with lower T2D risk were not confirmed. Instead, a healthy DP (HDP1) was associated with higher T2D risk (IRRpooled per 1 SD = 1.057, 95% CI 1.027-1.088). CONCLUSION: Our findings from various cohorts revealed positive associations for several DPs, characterized by higher intake of red meat, processed meat, French fries and refined grains, adding to the evidence-base that links DPs to higher T2D risk. However, no inverse DP-T2D associations were confirmed.

Published
2022

31. Implementing evidence-based practices in nonspecialty mental health settings

Author

Courtney Benjamin Wolk, Kimberly T. Arnold, and Enola K. Proctor

Subjects
Mental Health Services, Psychiatry and Mental health, Mental Health, Evidence-Based Practice, Humans, Child, Applied Psychology, Implementation Science
Abstract

Mental health services are often implemented in settings in which mental health is not the primary mission. Schools, primary care clinics, criminal justice and child welfare institutions, and senior centers have been increasingly adding mental health care to their compendium of services owing to the high rates of mental health needs in these settings. Despite numerous challenges to implementing mental health practices in settings where mental health care has not traditionally been a part of the service model, the demand for mental health services in these settings is growing. Implementation science offers a lens through which to understand unique challenges and potential solutions to implementing mental health services in these settings, with the ultimate goal of ensuring the implementation of evidence-based services.In this conceptual article, we discuss common overarching barriers to implementing evidence-based mental health interventions in nonspecialty mental health settings, such as workforce challenges, competing priorities, and financial considerations. Then, using examples from schools and primary care, we elucidate unique contextual considerations and implementation challenges in these settings. Finally, we articulate a research agenda for advancing implementation of evidence-based practices in nonspecialty mental health including highlighting promising implementation strategies (e.g., task shifting, adaptation) and the most relevant implementation outcomes to assess in these contexts (e.g., appropriateness, feasibility).Given that nonspecialty mental health settings deliver a large proportion of mental health care to traditionally underserved populations, there are important public health implications to advancing research in this area and ensuring implemented services are evidence-based. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Published
2022

32. Selective decontamination of the digestive tract in colorectal surgery reduces anastomotic leakage and costs: a propensity score analysis

Author

Andreas Bogner, Maximilian Stracke, Ulrich Bork, Steffen Wolk, Mathieu Pecqueux, Sandra Kaden, Marius Distler, Christoph Kahlert, Jürgen Weitz, Thilo Welsch, and Johannes Fritzmann

Subjects
Gastrointestinal Tract, Elective Surgical Procedures, Humans, Surgical Wound Infection, Anastomotic Leak, Surgery, Middle Aged, Propensity Score, Colorectal Surgery, Decontamination, Aged, Anti-Bacterial Agents, Retrospective Studies
Abstract

Purpose Anastomotic leakage (AL) and surgical site infection (SSI) account for most postoperative complications in colorectal surgery. The aim of this retrospective trial was to investigate whether perioperative selective decontamination of the digestive tract (SDD) reduces these complications and to provide a cost-effectiveness model for elective colorectal surgery. Methods All patients operated between November 2016 and March 2020 were included in our analysis. Patients in the primary cohort (PC) received SDD and those in the historical control cohort (CC) did not receive SDD. In the case of rectal/sigmoid resection, SDD was also applied via a transanally placed Foley catheter (TAFC) for 48 h postoperatively. A propensity score-matched analysis was performed to identify risk factors for AL and SSI. Costs were calculated based on German diagnosis-related group (DRG) fees per case. Results A total of 308 patients (154 per cohort) with a median age of 62.6 years (IQR 52.5–70.8) were analyzed. AL was observed in ten patients (6.5%) in the PC and 23 patients (14.9%) in the CC (OR 0.380, 95% CI 0.174–0.833; P = 0.016). SSI occurred in 14 patients (9.1%) in the PC and 30 patients in the CC (19.5%), representing a significant reduction in our SSI rate (P = 0.009). The cost-effectiveness analysis showed that SDD is highly effective in saving costs with a number needed to treat of 12 for AL and 10 for SSI. Conclusion SDD significantly reduces the incidence of AL and SSI and saves costs for the general healthcare system.

Published
2022

36. Increased Risks for Suicide, Self-Harm, Substance Use, and Psychiatric Disorders in Adults With Inflammatory Bowel Disease: A Nationwide Study in the United States From 2007 to 2017

Author

Chung Sang Tse, Chien-Hsiang Weng, Michelle Kwon, Courtney Benjamin Wolk, Lily A Brown, Kanika Malani, Samir A Shah, and Sean D Fine

Subjects
Gastroenterology, Immunology and Allergy
Abstract

Lay Summary In an analysis of over 260 million emergency department visits across the United States from 2007 to 2017, inflammatory bowel disease conferred >10-fold risk for suicide deaths, self-harm, substance use, and psychiatric disorders, though the overall self-harm rates were low (

Published
2023

37. Integrating color deconvolution thresholding and weakly supervised learning for automated segmentation of neurofibrillary tangle and neuropil threads

Author

Hyung Seok Roh, David J. Irwin, Mónica Muñoz López, Maria Mercedes Iñiguez de Onzoño Martin, Ranjit Ittyerah, Sydney Lim, Madigan L. Bedard, John L. Robinson, Theresa Schuck, Emilio Artacho-Pérula, María del Mar Arroyo Jiménez, María Pilar Marcos Rabal, Francisco Javier Molina Romero, Sandra Cebada Sánchez, José Carlos Delgado González, Carlos de la Rosa-Prieto, Marta Córcoles Parada, Edward B. Lee, Daniel T. Ohm, Laura E. M. Wisse, David A. Wolk, James C. Gee, Ricardo Insausti, Paul A. Yushkevich, and Min Chen

Published
2023

38. Predictors of Adherence to Continuous Positive Airway Pressure in Older Adults With Apnea and Amnestic Mild Cognitive Impairment

Author

Kathy C Richards, Alicia J Lozano, Jennifer Morris, Stephen T Moelter, Wenyan Ji, Vani Vallabhaneni, Yanyan Wang, Luqi Chi, Eric M Davis, Cindy Cheng, Vanessa Aguilar, Sneha Khan, Mira Sankhavaram, Alexandra L Hanlon, David A Wolk, and Nalaka Gooneratne

Subjects
Aging, Geriatrics and Gerontology
Abstract

Background Almost 60% of adults with amnestic mild cognitive impairment (aMCI) have obstructive sleep apnea (OSA). Treatment with continuous positive airway pressure (CPAP) may delay cognitive decline, but CPAP adherence is often suboptimal. In this study, we report predictors of CPAP adherence in older adults with aMCI who have increased odds of progressing to dementia, particularly due to Alzheimer’s disease. Methods The data are from Memories 2, “Changing the Trajectory of Mild Cognitive Impairment with CPAP Treatment of Obstructive Sleep Apnea.” Participants had moderate to severe OSA, were CPAP naïve, and received a telehealth CPAP adherence intervention. Linear and logistic regression models examined predictors. Results The 174 participants (mean age 67.08 years, 80 female, 38 Black persons) had a mean apnea–hypopnea index of 34.78, and 73.6% were adherent, defined as an average of ≥4 hours of CPAP use per night. Only 18 (47.4%) Black persons were CPAP adherent. In linear models, White race, moderate OSA, and participation in the tailored CPAP adherence intervention were significantly associated with higher CPAP use at 3 months. In logistic models, White persons had 9.94 times the odds of adhering to CPAP compared to Black persons. Age, sex, ethnicity, education, body mass index, nighttime sleep duration, daytime sleepiness, and cognitive status were not significant predictors. Conclusions Older patients with aMCI have high CPAP adherence, suggesting that age and cognitive impairment should not be a barrier to prescribing CPAP. Research is needed to improve adherence in Black patients, perhaps through culturally tailored interventions.

Published
2023

39. Supplementary Tables 1-3 from A Genome-Wide Gene-Based Gene–Environment Interaction Study of Breast Cancer in More than 90,000 Women

Author

Sara Lindström, Jenny Chang-Claude, Peter Kraft, Li Hsu, Roger L. Milne, Douglas F. Easton, Håkan Olsson, Sophia Wang, James V. Lacey, Nick Orr, Anthony J. Swerdlow, Jack A. Taylor, Dale P. Sandler, Alicja Wolk, Kamila Czene, Per Hall, Anthony Howell, D. Gareth Evans, Rose Yang, Thomas Ahearn, Jonine Figueroa, Montserrat García-Closas, Heather Eliassen, Rulla Tamimi, Cheng Peng, Michael I. Love, Melissa A. Troester, Jirong Long, Wei Zheng, Mark S. Goldberg, Jacques Simard, Stacey Winham, Christopher Scott, Gertraud Maskarinec, Christopher A. Haiman, Graham G. Giles, Heiko Becher, Audrey Jung, Veli-Matti Kosma, Arto Mannermaa, Sabine Behrens, Wing-Yee Lo, Reiner Hoppe, Volker Arndt, Hermann Brenner, Rudolf Kaaks, Federico Canzian, James M. Hodge, Lauren R. Teras, Thérèse Truong, Pascal Guénel, Kristan Aronson, Rachel A. Murphy, Rana Shibli, Gad Rennert, Jennifer Stone, Laura E. Beane Freeman, Stella Koutros, Melissa C. Southey, John L. Hopper, Paul D.P. Pharoah, Kyriaki Michailidou, Qin Wang, Michael Lush, Alison M. Dunning, Joe Dennis, Manjeet K. Bolla, Yu-Ru Su, Pooja Middha Kapoor, Hongjie Chen, and Xiaoliang Wang

Abstract

Supplementary Table 1. Sample Size of each participated study, by case-control status and genotype platform. Supplementary Table 2. Association between fourteen environmental factors and the risk of breast cancer. Supplementary Table 3. Interactions between genes and fourteen environmental factors.

Published
2023

40. Data from A Genome-Wide Gene-Based Gene–Environment Interaction Study of Breast Cancer in More than 90,000 Women

Author

Sara Lindström, Jenny Chang-Claude, Peter Kraft, Li Hsu, Roger L. Milne, Douglas F. Easton, Håkan Olsson, Sophia Wang, James V. Lacey, Nick Orr, Anthony J. Swerdlow, Jack A. Taylor, Dale P. Sandler, Alicja Wolk, Kamila Czene, Per Hall, Anthony Howell, D. Gareth Evans, Rose Yang, Thomas Ahearn, Jonine Figueroa, Montserrat García-Closas, Heather Eliassen, Rulla Tamimi, Cheng Peng, Michael I. Love, Melissa A. Troester, Jirong Long, Wei Zheng, Mark S. Goldberg, Jacques Simard, Stacey Winham, Christopher Scott, Gertraud Maskarinec, Christopher A. Haiman, Graham G. Giles, Heiko Becher, Audrey Jung, Veli-Matti Kosma, Arto Mannermaa, Sabine Behrens, Wing-Yee Lo, Reiner Hoppe, Volker Arndt, Hermann Brenner, Rudolf Kaaks, Federico Canzian, James M. Hodge, Lauren R. Teras, Thérèse Truong, Pascal Guénel, Kristan Aronson, Rachel A. Murphy, Rana Shibli, Gad Rennert, Jennifer Stone, Laura E. Beane Freeman, Stella Koutros, Melissa C. Southey, John L. Hopper, Paul D.P. Pharoah, Kyriaki Michailidou, Qin Wang, Michael Lush, Alison M. Dunning, Joe Dennis, Manjeet K. Bolla, Yu-Ru Su, Pooja Middha Kapoor, Hongjie Chen, and Xiaoliang Wang

Abstract

Genome-wide association studies (GWAS) have identified more than 200 susceptibility loci for breast cancer, but these variants explain less than a fifth of the disease risk. Although gene–environment interactions have been proposed to account for some of the remaining heritability, few studies have empirically assessed this.We obtained genotype and risk factor data from 46,060 cases and 47,929 controls of European ancestry from population-based studies within the Breast Cancer Association Consortium (BCAC). We built gene expression prediction models for 4,864 genes with a significant (P < 0.01) heritable component using the transcriptome and genotype data from the Genotype-Tissue Expression (GTEx) project. We leveraged predicted gene expression information to investigate the interactions between gene-centric genetic variation and 14 established risk factors in association with breast cancer risk, using a mixed-effects score test.After adjusting for number of tests using Bonferroni correction, no interaction remained statistically significant. The strongest interaction observed was between the predicted expression of the C13orf45 gene and age at first full-term pregnancy (PGXE = 4.44 × 10−6).In this transcriptome-informed genome-wide gene–environment interaction study of breast cancer, we found no strong support for the role of gene expression in modifying the associations between established risk factors and breast cancer risk.Our study suggests a limited role of gene–environment interactions in breast cancer risk.

Published
2023

41. Supplementary Information from A Genome-Wide Gene-Based Gene–Environment Interaction Study of Breast Cancer in More than 90,000 Women

Author

Sara Lindström, Jenny Chang-Claude, Peter Kraft, Li Hsu, Roger L. Milne, Douglas F. Easton, Håkan Olsson, Sophia Wang, James V. Lacey, Nick Orr, Anthony J. Swerdlow, Jack A. Taylor, Dale P. Sandler, Alicja Wolk, Kamila Czene, Per Hall, Anthony Howell, D. Gareth Evans, Rose Yang, Thomas Ahearn, Jonine Figueroa, Montserrat García-Closas, Heather Eliassen, Rulla Tamimi, Cheng Peng, Michael I. Love, Melissa A. Troester, Jirong Long, Wei Zheng, Mark S. Goldberg, Jacques Simard, Stacey Winham, Christopher Scott, Gertraud Maskarinec, Christopher A. Haiman, Graham G. Giles, Heiko Becher, Audrey Jung, Veli-Matti Kosma, Arto Mannermaa, Sabine Behrens, Wing-Yee Lo, Reiner Hoppe, Volker Arndt, Hermann Brenner, Rudolf Kaaks, Federico Canzian, James M. Hodge, Lauren R. Teras, Thérèse Truong, Pascal Guénel, Kristan Aronson, Rachel A. Murphy, Rana Shibli, Gad Rennert, Jennifer Stone, Laura E. Beane Freeman, Stella Koutros, Melissa C. Southey, John L. Hopper, Paul D.P. Pharoah, Kyriaki Michailidou, Qin Wang, Michael Lush, Alison M. Dunning, Joe Dennis, Manjeet K. Bolla, Yu-Ru Su, Pooja Middha Kapoor, Hongjie Chen, and Xiaoliang Wang

Abstract

Funding and acknowledgements.

Published
2023

42. Supplementary Figure 1 from A Genome-Wide Gene-Based Gene–Environment Interaction Study of Breast Cancer in More than 90,000 Women

Author

Sara Lindström, Jenny Chang-Claude, Peter Kraft, Li Hsu, Roger L. Milne, Douglas F. Easton, Håkan Olsson, Sophia Wang, James V. Lacey, Nick Orr, Anthony J. Swerdlow, Jack A. Taylor, Dale P. Sandler, Alicja Wolk, Kamila Czene, Per Hall, Anthony Howell, D. Gareth Evans, Rose Yang, Thomas Ahearn, Jonine Figueroa, Montserrat García-Closas, Heather Eliassen, Rulla Tamimi, Cheng Peng, Michael I. Love, Melissa A. Troester, Jirong Long, Wei Zheng, Mark S. Goldberg, Jacques Simard, Stacey Winham, Christopher Scott, Gertraud Maskarinec, Christopher A. Haiman, Graham G. Giles, Heiko Becher, Audrey Jung, Veli-Matti Kosma, Arto Mannermaa, Sabine Behrens, Wing-Yee Lo, Reiner Hoppe, Volker Arndt, Hermann Brenner, Rudolf Kaaks, Federico Canzian, James M. Hodge, Lauren R. Teras, Thérèse Truong, Pascal Guénel, Kristan Aronson, Rachel A. Murphy, Rana Shibli, Gad Rennert, Jennifer Stone, Laura E. Beane Freeman, Stella Koutros, Melissa C. Southey, John L. Hopper, Paul D.P. Pharoah, Kyriaki Michailidou, Qin Wang, Michael Lush, Alison M. Dunning, Joe Dennis, Manjeet K. Bolla, Yu-Ru Su, Pooja Middha Kapoor, Hongjie Chen, and Xiaoliang Wang

Abstract

Quantile-Quantile plot (Q-Q plot) of the aMiSTi p-values for each set of the GxE interactions.

Published
2023

43. Supplementary Grant Support from Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

Author

Diether Lambrechts, Paul D.P. Pharoah, Rosalind Eeles, Georgia Chenevix-Trench, Douglas F. Easton, Simon A. Gayther, Per Hall, Fergus J. Couch, Stephen J. Chanock, Peter Kraft, Brian E. Henderson, David J. Hunter, Thomas A. Sellers, Amanda Spurdle, Christopher A. Haiman, Jacques Simard, Alison M. Dunning, Andrew Berchuck, Matthew L. Freedman, Fredrick Schumacher, Yu-Tang Gao, Xiao-Ou Shu, Wojciech Kluzniak, William J. Blot, Weiva Sieh, Wei Zheng, Walther Vogel, Volker Arndt, Vessela Kristensen, Veronica Wendy Setiawan, Veli-Matti Kosma, Vanio Mitev, Ute Hamann, Usha Menon, Todd L. Edwards, Tim J. Key, Tiina Wahlfors, Thomas Brüning, Thilo Dörk, Teuvo L.J. Tammela, Tanja Pejovic, Susanne Krüger Kjær, Susan M. Gapstur, Stig E. Bojesen, Stephen N. Thibodeau, Soo-Hwang Teo, Soo Chin Lee, Sonja Berndt, Sofia Maia, Shelley S. Tworoger, Shannon K. McDonnell, Sara H. Olson, Sara Benlloch, Ruth C. Travis, Roger L. Milne, Roberta Ness, Robert Winqvist, Robert N. Hoover, Robert J. MacInnis, Robert A. Stephenson, Rita K. Schmutzler, Reidun Kristin Kopperud, Ralf Butzow, Radka Kaneva, Qiyuan Li, Qiuyin Cai, Qin Wang, Peter Devilee, Peter A. Fasching, Per Broberg, Penelope M. Webb, Paula Paulo, Paul Brennan, Pascal Guénel, Paolo Peterlongo, Nora Pashayan, Nicolas Wentzensen, Nick Orr, Nhu D. Le, Nazneen Rahman, Natalia Bogdanova, Montserrat Garcia-Closas, Minouk J. Schoemaker, Ming-Feng Hou, Michelle A.T. Hildebrandt, Michael Lush, Michael Jones, Melissa C. Southey, Maureen Sanderson, Matthieu Moisse, Matthias W. Beckmann, Mary Anne Rossing, Markus Aly, Marjorie Riggan, Marjanka K. Schmidt, Marc T. Goodman, Manuel R. Teixeira, Manuel Luedeke, Manjeet K. Bolla, Malcolm C. Pike, Maartje J. Hooning, Lisa Cannon-Albright, Linda S. Cook, Liesel M. Fitzgerald, Leon F.A.G. Massuger, Lambertus A. Kiemeney, Kunle Odunsi, Kristiina Aittomäki, Kirsten B. Moysich, Kexin Chen, Kenneth Offitt, Kenneth Muir, Keitaro Matsuo, Kay-Tee Khaw, Kathleen Herkommer, Karen H. Lu, Kamila Czene, Jyotsna Batra, Julio Pow-Sang, Julie M. Cunningham, Julian Peto, Julia A. Knight, Judith A. Clements, Jonine Figueroa, Jong Y. Park, Jolanta Kupryjanczyk, John L. Hopper, Johanna Schleutker, Joellen M. Schildkraut, Joe Dennis, Jenny L. Donovan, Jenny Chang-Claude, Jennifer B. Permuth, Jennifer A. Doherty, Javier Benítez, Janet L. Stanford, Jan Lubiński, Jacek Gronwald, Ignace Vergote, Ian Campbell, Iain McNeish, Hui-Yi Lim, Honglin Song, Hoda Anton-Culver, Hiltrud Brauch, Hermann Brenner, Henrik Gronberg, Heli Nevanlinna, Helga B. Salvesen, Hatef Darabi, Harvey A. Risch, Hardev Pandha, Hans-Ulrich Ulmer, Hans Wildiers, Håkan Olsson, Graham G. Giles, Fredrik Wiklund, Freddie C. Hamdy, Francesmary Modugno, Florian Heitz, Fiona Bruinsma, Fengju Song, Estrid Høgdall, Elza Khusnutdinova, Ellen L. Goode, Elizabeth M. Poole, Elisa V. Bandera, Elinor J. Sawyer, Drakoulis Yannoukakos, Douglas A. Levine, Dominika Wokozorczyk, Digna R. Velez Edwards, Dieter Flesch-Janys, Diana Eccles, David E. Neal, Daniel W. Cramer, Daniel O. Stram, Daniel J. Schaid, Daniel C. Tessier, Daehee Kang, Craig C. Teerlink, Claus K. Høgdall, Christine B. Ambrosone, Christiane Maier, Christa Stegmaier, Chavdar Slavov, Cezary Cybulski, Celine Vachon, Celeste Leigh Pearce, Catriona McLean, Catherine Phelan, Carl Blomqvist, Børge G. Nordestgaard, Beth Y. Karlan, Barbara Burwinkel, Arif B. Ekici, Argyrios Ziogas, Anthony Swerdlow, Annika Lindblom, Anna H. Wu, Anna Gonzalez-Neira, Anja Rudolph, Angela Cox, Andrzej Kierzek, Ana Peixoto, Alvaro Monteiro, Alicja Wolk, Alice S. Whittemore, Aleksandra Gentry-Maharaj, Aida K. Dieffenbach, Agnieszka Michael, Agnieszka Dansonka-Mieszkowska, Adam S. Kibel, Deborah J. Thompson, Susan J. Ramus, Sara Lindstrom, Kate Lawrenson, ZSofia Kote-Jarai, Jonathan Tyrer, Kyriaki Michailidou, Ali Amin Al Olama, Jonathan Beesley, and Siddhartha P. Kar

Abstract

Supplementary Grant Support

Published
2023

44. Supplementary Methods, Figures S1 - S3 from Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

Author

Diether Lambrechts, Paul D.P. Pharoah, Rosalind Eeles, Georgia Chenevix-Trench, Douglas F. Easton, Simon A. Gayther, Per Hall, Fergus J. Couch, Stephen J. Chanock, Peter Kraft, Brian E. Henderson, David J. Hunter, Thomas A. Sellers, Amanda Spurdle, Christopher A. Haiman, Jacques Simard, Alison M. Dunning, Andrew Berchuck, Matthew L. Freedman, Fredrick Schumacher, Yu-Tang Gao, Xiao-Ou Shu, Wojciech Kluzniak, William J. Blot, Weiva Sieh, Wei Zheng, Walther Vogel, Volker Arndt, Vessela Kristensen, Veronica Wendy Setiawan, Veli-Matti Kosma, Vanio Mitev, Ute Hamann, Usha Menon, Todd L. Edwards, Tim J. Key, Tiina Wahlfors, Thomas Brüning, Thilo Dörk, Teuvo L.J. Tammela, Tanja Pejovic, Susanne Krüger Kjær, Susan M. Gapstur, Stig E. Bojesen, Stephen N. Thibodeau, Soo-Hwang Teo, Soo Chin Lee, Sonja Berndt, Sofia Maia, Shelley S. Tworoger, Shannon K. McDonnell, Sara H. Olson, Sara Benlloch, Ruth C. Travis, Roger L. Milne, Roberta Ness, Robert Winqvist, Robert N. Hoover, Robert J. MacInnis, Robert A. Stephenson, Rita K. Schmutzler, Reidun Kristin Kopperud, Ralf Butzow, Radka Kaneva, Qiyuan Li, Qiuyin Cai, Qin Wang, Peter Devilee, Peter A. Fasching, Per Broberg, Penelope M. Webb, Paula Paulo, Paul Brennan, Pascal Guénel, Paolo Peterlongo, Nora Pashayan, Nicolas Wentzensen, Nick Orr, Nhu D. Le, Nazneen Rahman, Natalia Bogdanova, Montserrat Garcia-Closas, Minouk J. Schoemaker, Ming-Feng Hou, Michelle A.T. Hildebrandt, Michael Lush, Michael Jones, Melissa C. Southey, Maureen Sanderson, Matthieu Moisse, Matthias W. Beckmann, Mary Anne Rossing, Markus Aly, Marjorie Riggan, Marjanka K. Schmidt, Marc T. Goodman, Manuel R. Teixeira, Manuel Luedeke, Manjeet K. Bolla, Malcolm C. Pike, Maartje J. Hooning, Lisa Cannon-Albright, Linda S. Cook, Liesel M. Fitzgerald, Leon F.A.G. Massuger, Lambertus A. Kiemeney, Kunle Odunsi, Kristiina Aittomäki, Kirsten B. Moysich, Kexin Chen, Kenneth Offitt, Kenneth Muir, Keitaro Matsuo, Kay-Tee Khaw, Kathleen Herkommer, Karen H. Lu, Kamila Czene, Jyotsna Batra, Julio Pow-Sang, Julie M. Cunningham, Julian Peto, Julia A. Knight, Judith A. Clements, Jonine Figueroa, Jong Y. Park, Jolanta Kupryjanczyk, John L. Hopper, Johanna Schleutker, Joellen M. Schildkraut, Joe Dennis, Jenny L. Donovan, Jenny Chang-Claude, Jennifer B. Permuth, Jennifer A. Doherty, Javier Benítez, Janet L. Stanford, Jan Lubiński, Jacek Gronwald, Ignace Vergote, Ian Campbell, Iain McNeish, Hui-Yi Lim, Honglin Song, Hoda Anton-Culver, Hiltrud Brauch, Hermann Brenner, Henrik Gronberg, Heli Nevanlinna, Helga B. Salvesen, Hatef Darabi, Harvey A. Risch, Hardev Pandha, Hans-Ulrich Ulmer, Hans Wildiers, Håkan Olsson, Graham G. Giles, Fredrik Wiklund, Freddie C. Hamdy, Francesmary Modugno, Florian Heitz, Fiona Bruinsma, Fengju Song, Estrid Høgdall, Elza Khusnutdinova, Ellen L. Goode, Elizabeth M. Poole, Elisa V. Bandera, Elinor J. Sawyer, Drakoulis Yannoukakos, Douglas A. Levine, Dominika Wokozorczyk, Digna R. Velez Edwards, Dieter Flesch-Janys, Diana Eccles, David E. Neal, Daniel W. Cramer, Daniel O. Stram, Daniel J. Schaid, Daniel C. Tessier, Daehee Kang, Craig C. Teerlink, Claus K. Høgdall, Christine B. Ambrosone, Christiane Maier, Christa Stegmaier, Chavdar Slavov, Cezary Cybulski, Celine Vachon, Celeste Leigh Pearce, Catriona McLean, Catherine Phelan, Carl Blomqvist, Børge G. Nordestgaard, Beth Y. Karlan, Barbara Burwinkel, Arif B. Ekici, Argyrios Ziogas, Anthony Swerdlow, Annika Lindblom, Anna H. Wu, Anna Gonzalez-Neira, Anja Rudolph, Angela Cox, Andrzej Kierzek, Ana Peixoto, Alvaro Monteiro, Alicja Wolk, Alice S. Whittemore, Aleksandra Gentry-Maharaj, Aida K. Dieffenbach, Agnieszka Michael, Agnieszka Dansonka-Mieszkowska, Adam S. Kibel, Deborah J. Thompson, Susan J. Ramus, Sara Lindstrom, Kate Lawrenson, ZSofia Kote-Jarai, Jonathan Tyrer, Kyriaki Michailidou, Ali Amin Al Olama, Jonathan Beesley, and Siddhartha P. Kar

Abstract

Supplementary Figure S1. LocusZoom regional association plots for the seven new cross-cancer loci that were > 1 Mb from known index SNPs. Supplementary Figure S2A-B. Box plots showing eQTL associations between (A) rs9375701 and L3MBTL3 in normal breast and prostate tissues and (B) rs8037137 and RCCD1 in normal breast and ovarian tissues. Supplementary Figure S3. Interactions between BCL2L11 and the 32 Biocarta "Death Pathway" genes. Interactions were identified using the GeneMania server. Circles contain gene names, lines represent interactions, and the color of the line indicates a specific type of interaction as listed in the legend.

Published
2023

45. Supplementary Tables S1 - S10 from Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

Author

Diether Lambrechts, Paul D.P. Pharoah, Rosalind Eeles, Georgia Chenevix-Trench, Douglas F. Easton, Simon A. Gayther, Per Hall, Fergus J. Couch, Stephen J. Chanock, Peter Kraft, Brian E. Henderson, David J. Hunter, Thomas A. Sellers, Amanda Spurdle, Christopher A. Haiman, Jacques Simard, Alison M. Dunning, Andrew Berchuck, Matthew L. Freedman, Fredrick Schumacher, Yu-Tang Gao, Xiao-Ou Shu, Wojciech Kluzniak, William J. Blot, Weiva Sieh, Wei Zheng, Walther Vogel, Volker Arndt, Vessela Kristensen, Veronica Wendy Setiawan, Veli-Matti Kosma, Vanio Mitev, Ute Hamann, Usha Menon, Todd L. Edwards, Tim J. Key, Tiina Wahlfors, Thomas Brüning, Thilo Dörk, Teuvo L.J. Tammela, Tanja Pejovic, Susanne Krüger Kjær, Susan M. Gapstur, Stig E. Bojesen, Stephen N. Thibodeau, Soo-Hwang Teo, Soo Chin Lee, Sonja Berndt, Sofia Maia, Shelley S. Tworoger, Shannon K. McDonnell, Sara H. Olson, Sara Benlloch, Ruth C. Travis, Roger L. Milne, Roberta Ness, Robert Winqvist, Robert N. Hoover, Robert J. MacInnis, Robert A. Stephenson, Rita K. Schmutzler, Reidun Kristin Kopperud, Ralf Butzow, Radka Kaneva, Qiyuan Li, Qiuyin Cai, Qin Wang, Peter Devilee, Peter A. Fasching, Per Broberg, Penelope M. Webb, Paula Paulo, Paul Brennan, Pascal Guénel, Paolo Peterlongo, Nora Pashayan, Nicolas Wentzensen, Nick Orr, Nhu D. Le, Nazneen Rahman, Natalia Bogdanova, Montserrat Garcia-Closas, Minouk J. Schoemaker, Ming-Feng Hou, Michelle A.T. Hildebrandt, Michael Lush, Michael Jones, Melissa C. Southey, Maureen Sanderson, Matthieu Moisse, Matthias W. Beckmann, Mary Anne Rossing, Markus Aly, Marjorie Riggan, Marjanka K. Schmidt, Marc T. Goodman, Manuel R. Teixeira, Manuel Luedeke, Manjeet K. Bolla, Malcolm C. Pike, Maartje J. Hooning, Lisa Cannon-Albright, Linda S. Cook, Liesel M. Fitzgerald, Leon F.A.G. Massuger, Lambertus A. Kiemeney, Kunle Odunsi, Kristiina Aittomäki, Kirsten B. Moysich, Kexin Chen, Kenneth Offitt, Kenneth Muir, Keitaro Matsuo, Kay-Tee Khaw, Kathleen Herkommer, Karen H. Lu, Kamila Czene, Jyotsna Batra, Julio Pow-Sang, Julie M. Cunningham, Julian Peto, Julia A. Knight, Judith A. Clements, Jonine Figueroa, Jong Y. Park, Jolanta Kupryjanczyk, John L. Hopper, Johanna Schleutker, Joellen M. Schildkraut, Joe Dennis, Jenny L. Donovan, Jenny Chang-Claude, Jennifer B. Permuth, Jennifer A. Doherty, Javier Benítez, Janet L. Stanford, Jan Lubiński, Jacek Gronwald, Ignace Vergote, Ian Campbell, Iain McNeish, Hui-Yi Lim, Honglin Song, Hoda Anton-Culver, Hiltrud Brauch, Hermann Brenner, Henrik Gronberg, Heli Nevanlinna, Helga B. Salvesen, Hatef Darabi, Harvey A. Risch, Hardev Pandha, Hans-Ulrich Ulmer, Hans Wildiers, Håkan Olsson, Graham G. Giles, Fredrik Wiklund, Freddie C. Hamdy, Francesmary Modugno, Florian Heitz, Fiona Bruinsma, Fengju Song, Estrid Høgdall, Elza Khusnutdinova, Ellen L. Goode, Elizabeth M. Poole, Elisa V. Bandera, Elinor J. Sawyer, Drakoulis Yannoukakos, Douglas A. Levine, Dominika Wokozorczyk, Digna R. Velez Edwards, Dieter Flesch-Janys, Diana Eccles, David E. Neal, Daniel W. Cramer, Daniel O. Stram, Daniel J. Schaid, Daniel C. Tessier, Daehee Kang, Craig C. Teerlink, Claus K. Høgdall, Christine B. Ambrosone, Christiane Maier, Christa Stegmaier, Chavdar Slavov, Cezary Cybulski, Celine Vachon, Celeste Leigh Pearce, Catriona McLean, Catherine Phelan, Carl Blomqvist, Børge G. Nordestgaard, Beth Y. Karlan, Barbara Burwinkel, Arif B. Ekici, Argyrios Ziogas, Anthony Swerdlow, Annika Lindblom, Anna H. Wu, Anna Gonzalez-Neira, Anja Rudolph, Angela Cox, Andrzej Kierzek, Ana Peixoto, Alvaro Monteiro, Alicja Wolk, Alice S. Whittemore, Aleksandra Gentry-Maharaj, Aida K. Dieffenbach, Agnieszka Michael, Agnieszka Dansonka-Mieszkowska, Adam S. Kibel, Deborah J. Thompson, Susan J. Ramus, Sara Lindstrom, Kate Lawrenson, ZSofia Kote-Jarai, Jonathan Tyrer, Kyriaki Michailidou, Ali Amin Al Olama, Jonathan Beesley, and Siddhartha P. Kar

Abstract

Supplementary Table S1. Known risk loci for each cancer. Supplementary Table S2. Regions where known index SNPs for at least two of the three cancers lie within 1 Mb of each other. Supplementary Table S3. Full results from the meta-analysis of breast, ovarian, and prostate cancer showing the 18 independent loci associated at P < 10-8 with the same direction of effect across all three cancers. Supplementary Table S4. Conditional analysis of the rs1469713 (breast-ovarian-prostate cancer) signal, conditioning on the rs4808801 (breast cancer-specific) signal that was < 1 Mb away using GCTA software. Supplementary Table S5. Most significantly-associated genotyped SNP at new loci where index SNPs were imputed. Supplementary Table S6. Expression QTL analysis results from the GTEx Portal for the new cross-cancer risk loci listed in main Table 2. Supplementary Table S7. SNPs with P < 10-8 at the new cross-cancer risk loci listed in main Table 2 that overlap predicted enhancers in at least two cell types. Supplementary Table S8. HaploReg and non-coding RNA annotation of variants with P < 10-8 at the new cross-cancer risk loci listed in main Table 2. Supplementary Table S9. Eight of the 32 genes involved in induction of apoptosis through DR3 and DR4/5 Death Receptors (MSigDB: Biocarta "Death Pathway") a that were < 1 Mb away from an independent P < 10-5 index SNP in the 3-cancer meta-analysis. Supplementary Table S10. INRICH pathway analysis results for pathways with empirical P < 0.05. Apoptosis-related pathways containing BCL2L11 are shaded.

Published
2023

46. Table S8 from A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk

Author

Jirong Long, Wei Zheng, Paul D.P. Pharoah, Thomas A. Sellers, Georgia Chenevix-Trench, Ellen L. Goode, Andrew Berchuck, Antonis C. Antoniou, Simon A. Gayther, Kristin K. Zorn, Drakoulis Yannoukakos, Anna H. Wu, Alicja Wolk, Emily White, Nicolas Wentzensen, Jeffrey N. Weitzel, Penelope M. Webb, Digna Velez Edwards, Ana Vega, Adriaan Vanderstichele, Elizabeth J. van Rensburg, Shelley S. Tworoger, Nadine Tung, Antonia Trichopoulou, Amanda E. Toland, Marc Tischkowitz, Mads Thomassen, Soo H. Teo, Manuel R. Teixeira, Anthony J. Swerdlow, Rebecca Sutphen, Amanda B. Spurdle, Melissa C. Southey, Honglin Song, Christian F. Singer, Jacques Simard, Weiva Sieh, Priyanka Sharma, Veronica W. Setiawan, Rita K. Schmutzler, Dale P. Sandler, Iwona K. Rzepecka, Mary Anne Rossing, Matti A. Rookus, Isabelle Romieu, Cristina Rodríguez-Antona, Gustavo C. Rodriguez, Harvey Risch, Gad Rennert, Susan J. Ramus, Miquel Angel Pujana, Catherine M. Phelan, Paolo Peterlongo, Tanja Pejovic, Petra H.M. Peeters, Michael T. Parsons, Sue K. Park, Ana Osorio, Håkan Olsson, Sara H. Olson, Olufunmilayo I. Olopade, Edith Olah, Kenneth Offit, Robert L. Nussbaum, Liene Nikitina-Zake, Finn C. Nielsen, Heli Nevanlinna, Susan L. Neuhausen, Marco Montagna, Francesmary Modugno, Melissa A. Merritt, Iain A. McNeish, Lesley McGuffog, Taymaa May, Amalia Mattiello, Douglas A. Levine, Fabienne Lesueur, Goska Leslie, Nhu D. Le, Ava Kwong, Susanne K. Kjaer, Lambertus A. Kiemeney, Linda E. Kelemen, Beth Y. Karlan, Paul James, Anna Jakubowska, Claudine Isaacs, Evgeny N. Imyanitov, David G. Huntsman, Peter J. Hulick, Antoinette Hollestelle, Claus K. Høgdall, Michelle A.T. Hildebrandt, Florian Heitz, Ute Hamann, Jacek Gronwald, Mark H. Greene, Marc T. Goodman, David E. Goldgar, Andrew K. Godwin, Graham G. Giles, Judy Garber, Patricia A. Ganz, Eitan Friedman, George Fountzilas, Renée T. Fortner, Peter A. Fasching, Diana M. Eccles, Douglas F. Easton, Thilo Dörk, Susan M. Domchek, Orland Diez, Joe Dennis, Anna deFazio, Mary B. Daly, Daniel W. Cramer, Fergus J. Couch, Kathleen B.M. Claes, Jenny Chang-Claude, Ian Campbell, Maria A. Caligo, Trinidad Caldes, Ralf Butzow, James Brenton, Line Bjorge, Javier Benitez, Daniel R. Barnes, Rosa B. Barkardottir, Elisa V. Bandera, Banu K. Arun, Hoda Anton-Culver, Irene L. Andrulis, Kirsten B. Moysich, Jamie K. Teer, Brett M. Reid, Jennifer B. Permuth, Yian A. Chen, Hae Kyung Im, Joellen M. Schildkraut, Bingshan Li, Xingyi Guo, Lang Wu, Alicia Beeghly-Fadiel, and Yingchang Lu

Abstract

Association results between minor alleles of 467 variants incorportated in cross tissue gene expression prediction model for the gene of CRHR1.

Published
2023

47. Supplementary Materials from Association of the Age at Menarche with Site-Specific Cancer Risks in Pooled Data from Nine Cohorts

Author

Robert N. Hoover, Regina G. Ziegler, Harold L. Van Dusen, Marc J. Gunter, Neil Murphy, David P. Check, Michael Spriggs, Kim Robien, Anna E. Prizment, Susanna C. Larsson, Alicja Wolk, Julie E. Buring, I-Min Lee, Alpa V. Patel, Mia M. Gaudet, Rachael Z. Stolzenberg-Solomon, Charles E. Matthews, Linda M. Liao, Neal D. Freedman, Hans-Olov Adami, Elisabete Weiderpass, Martha S. Linet, Amy Berrington de González, Cari M. Kitahara, Issam Makhoul, Celia Byrne, Steven C. Moore, and Barbara J. Fuhrman

Abstract

Tables 1-17, Figure S1, and acknowledgements.

Published
2023

48. Table S4 from A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk

Author

Jirong Long, Wei Zheng, Paul D.P. Pharoah, Thomas A. Sellers, Georgia Chenevix-Trench, Ellen L. Goode, Andrew Berchuck, Antonis C. Antoniou, Simon A. Gayther, Kristin K. Zorn, Drakoulis Yannoukakos, Anna H. Wu, Alicja Wolk, Emily White, Nicolas Wentzensen, Jeffrey N. Weitzel, Penelope M. Webb, Digna Velez Edwards, Ana Vega, Adriaan Vanderstichele, Elizabeth J. van Rensburg, Shelley S. Tworoger, Nadine Tung, Antonia Trichopoulou, Amanda E. Toland, Marc Tischkowitz, Mads Thomassen, Soo H. Teo, Manuel R. Teixeira, Anthony J. Swerdlow, Rebecca Sutphen, Amanda B. Spurdle, Melissa C. Southey, Honglin Song, Christian F. Singer, Jacques Simard, Weiva Sieh, Priyanka Sharma, Veronica W. Setiawan, Rita K. Schmutzler, Dale P. Sandler, Iwona K. Rzepecka, Mary Anne Rossing, Matti A. Rookus, Isabelle Romieu, Cristina Rodríguez-Antona, Gustavo C. Rodriguez, Harvey Risch, Gad Rennert, Susan J. Ramus, Miquel Angel Pujana, Catherine M. Phelan, Paolo Peterlongo, Tanja Pejovic, Petra H.M. Peeters, Michael T. Parsons, Sue K. Park, Ana Osorio, Håkan Olsson, Sara H. Olson, Olufunmilayo I. Olopade, Edith Olah, Kenneth Offit, Robert L. Nussbaum, Liene Nikitina-Zake, Finn C. Nielsen, Heli Nevanlinna, Susan L. Neuhausen, Marco Montagna, Francesmary Modugno, Melissa A. Merritt, Iain A. McNeish, Lesley McGuffog, Taymaa May, Amalia Mattiello, Douglas A. Levine, Fabienne Lesueur, Goska Leslie, Nhu D. Le, Ava Kwong, Susanne K. Kjaer, Lambertus A. Kiemeney, Linda E. Kelemen, Beth Y. Karlan, Paul James, Anna Jakubowska, Claudine Isaacs, Evgeny N. Imyanitov, David G. Huntsman, Peter J. Hulick, Antoinette Hollestelle, Claus K. Høgdall, Michelle A.T. Hildebrandt, Florian Heitz, Ute Hamann, Jacek Gronwald, Mark H. Greene, Marc T. Goodman, David E. Goldgar, Andrew K. Godwin, Graham G. Giles, Judy Garber, Patricia A. Ganz, Eitan Friedman, George Fountzilas, Renée T. Fortner, Peter A. Fasching, Diana M. Eccles, Douglas F. Easton, Thilo Dörk, Susan M. Domchek, Orland Diez, Joe Dennis, Anna deFazio, Mary B. Daly, Daniel W. Cramer, Fergus J. Couch, Kathleen B.M. Claes, Jenny Chang-Claude, Ian Campbell, Maria A. Caligo, Trinidad Caldes, Ralf Butzow, James Brenton, Line Bjorge, Javier Benitez, Daniel R. Barnes, Rosa B. Barkardottir, Elisa V. Bandera, Banu K. Arun, Hoda Anton-Culver, Irene L. Andrulis, Kirsten B. Moysich, Jamie K. Teer, Brett M. Reid, Jennifer B. Permuth, Yian A. Chen, Hae Kyung Im, Joellen M. Schildkraut, Bingshan Li, Xingyi Guo, Lang Wu, Alicia Beeghly-Fadiel, and Yingchang Lu

Abstract

Association results after the adjustment for nearby GWAS index SNPs for genes with predicted gene expression levels associated with ovarian cancer risk at P < 2.21E-6.

Published
2023

49. Supplementary Table 2 from The Risk of Ovarian Cancer Increases with an Increase in the Lifetime Number of Ovulatory Cycles: An Analysis from the Ovarian Cancer Cohort Consortium (OC3)

Author

Nicolas Wentzensen, Anne Zeleniuch-Jacquotte, Alicja Wolk, Lynne R. Wilkens, Kala Visvanathan, Piet A. van den Brandt, Antonia Trichopoulou, Ruth C. Travis, Anthony J. Swerdlow, Veronica W. Setiawan, Leo J. Schouten, Catherine Schairer, Dale P. Sandler, Thomas E. Rohan, Kim Robien, Elio Riboli, Jenny N. Poynter, Ulrike Peters, Alpa V. Patel, Kim Overvad, N. Charlotte Onland-Moret, Roger L. Milne, I-Min Lee, James V. Lacey, Marina Kvaskoff, Synnove F. Knutsen, Victoria A. Kirsh, Rudolf Kaaks, Michael E. Jones, Annika Idahl, Judith Hoffman Bolton, Holly R. Harris, Inger T. Gram, Graham G. Giles, Mia M. Gaudet, Gary E. Fraser, Laure Dossus, Julie E. Buring, Louise A. Brinton, Leslie Bernstein, Alan A. Arslan, Pilar Amiano, Emily White, Patricia Hartge, Edwin S. Iversen, Renée T. Fortner, Mary K. Townsend, Katie M. O'Brien, Shelley S. Tworoger, and Britton Trabert

Abstract

Associations between continuous total lifetime number of ovulatory cycles and ovarian cancer by tumor aggressiveness considering mutual adjustment for LOC component factors: duration of oral contraceptive use and pregnancies, Ovarian Cancer Cohort Consortium (OC3).

Published
2023

50. Supplementary Figure from Anthropometric Risk Factors for Cancers of the Biliary Tract in the Biliary Tract Cancers Pooling Project

Author

Jill Koshiol, Peter T. Campbell, Katherine A. McGlynn, Xuehong Zhang, Anne Zeleniuch-Jacquotte, Jian-Min Yuan, Alicja Wolk, Emily White, Stephanie J. Weinstein, Elisabete Weiderpass, Renwei Wang, Shoichiro Tsugane, Rachael Z. Stolzenberg-Solomon, Rashmi Sinha, Tracey G. Simon, Howard D. Sesso, Catherine Schairer, Norie Sawada, Dale P. Sandler, Kim Robien, Mark P. Purdue, Jenny N. Poynter, Ulrike Peters, Katie M. O’Brien, Marian L. Neuhouser, Kristine R. Monroe, Roger L. Milne, Emma E. McGee, Juhua Luo, Linda M. Liao, I-Min Lee, Susanna C. Larsson, Woon-Puay Koh, Synnove F. Knutsen, Cari M. Kitahara, Mazda Jenab, Patricia Hartge, Francine Grodstein, Eric J. Grant, Graham G. Giles, J. Michael Gaziano, Susan M. Gapstur, Yu-Tang Gao, Neal D. Freedman, Gary E. Fraser, Yu Chen, Andrew T. Chan, Julie E. Buring, Amy Berrington de González, Laura E. Beane Freeman, Gabriella Andreotti, Demetrius Albanes, Hans-Olov Adami, Jessica L. Petrick, Ruth M. Pfeiffer, Bin Zhu, Alison L. Van Dyke, and Sarah S. Jackson

Abstract

This file contains Supplementary Figure 1, parts A - D, and the figure description.

Published
2023

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