Digital Commons Network^™

Parent Needs, Recommendations, And Systemic Challenges Affecting Pediatric Hypertension Detection, Abbas H. Zaidi, Erica D. Sood, Sarah De Ferranti, Samuel Gidding, Varsha Zadokar, Jonathan M. Miller, Anne E Kazak

Department of Pediatrics Faculty Papers

Pediatric hypertension (HTN) affects 3%-5% of children in the United States, yet only 25% are diagnosed and 60% lack recommended follow-up care. Skepticism about elevated blood pressure (BP) readings and reluctance to use antihypertensive medications by parents and clinicians highlight the need for stakeholder-informed strategies to address these challenges. This study examined parents' perceived needs, their recommended strategies to improve HTN detection, and contextual health system challenges. Parents and clinicians from 10 pediatric primary care clinics participated in semi-structured qualitative interviews. Only parents of children with documented stage 2 BP readings and a HTN diagnosis, but with gaps in care …

Communicating Wastewater-Based Surveillance Data To Drive Action, Kata Farkas, Devrim Kaya, Rasha Maal-Bared, Ahmad I. Al-Mustapha, Sarmila Tandukar, Ishi Keenum, Teemu Gunnar, Aaron Bivins, Matthew J Wade, Kyle Bibby, Tarja M. Pitkänen, Ananda Tiwari

Michigan Tech Publications

As exemplified during the COVID-19 pandemic, wastewater-based surveillance (WBS) can deliver near real-time, population-level pathogen data to guide public health action. Its impact, however, hinges on timely, transparent, and context-specific communication to stakeholders, including health authorities, policymakers, scientists, clinicians, and the public. This review examines current WBS communication practices, identifies persistent challenges, and proposes strategies to enhance relevance. Key challenges include data complexity, lack of standardised communication frameworks, ethical and privacy concerns, and variable stakeholder capabilities. The strategic use of digital platforms, such as dashboards, reports, press releases, and social media, alongside traditional media, can broaden reach and aid interpretation. …

Reliability And Clinical Utility Of Heroin Craving Questionnaire Factors In Treatment-Enrolled Individuals With Opioid Use Disorder., April C. May, Breanna A. Mcnaughton-Long, Chrysantha B. Davis, Abigail J. Pleiman, Carmen Buchfink, Rayus Kuplicki, Hung-Wen Yeh, Martin P. Paulus, Jennifer L. Stewart

Manuscripts, Articles, Book Chapters and Other Papers

Psychometric properties of opioid craving assessments are underexamined, limiting their potential utility for treatment studies of opioid use disorder (OUD). To address this gap, the current study aimed to evaluate the predictive utility of the Heroin Craving Questionnaire (HCQ) for future substance use outcomes. Treatment-enrolled participants with OUD (n = 128) completed the Heroin Craving Questionnaire (HCQ) at baseline and were followed up to assess future return to use versus abstinence. Individuals who maintained abstinence at each of three follow-up visits also completed the HCQ again. Exploratory factor analysis (EFA) was performed on baseline HCQ items, and extracted factors were …

Synthetic Zfta Fusions Pinpoint Disordered Protein Domain Acquisition As A Mechanism Of Brain Tumorigenesis, A Arabzade, H K Shirnekhi, S Varadharajan, S M Ippagunta, A H Phillips, N Laboe, D W Baggett, Wahiduzzaman, M Jo, T Zheng, R Pathak, D Gee, D Bhimsaria, H Wu, X Gao, J Liu, E Emanus, A Bland, A Kardian, A Hancock, B Holcomb, T Wright, T Bugbee, H Sun, M Zhai, E Caesar, M Park, S Tripathi, A Shirinifard, K Lowe, A Khalighifar, R A Petersen, S King, D Stabley, A Pitre, G E Campbell, C-G Park, W T Freyaldenhoven, B Chandra, Y Xia, E Bonten, A Achari, S Kandikonda, A Carisey, S B Pounds, J Xu, D W Ellison, B Deneen, K C Bertrand, R W Kriwacki, S C Mack

Children’s Nutrition Research Center Staff Publications

Over 95% of ependymomas that arise in the cortex are driven by a gene fusion involving the zinc finger translocation-associated (ZFTA) protein. Here, using super-resolution and lattice light-sheet microscopy, we demonstrate that the most frequent fusion variant, ZFTA-RELA (ZR), forms dynamic nuclear condensates that are required for oncogene expression and tumorigenesis. Mutagenesis studies of ZR reveal a key intrinsically disordered region (IDR) in RELA that governs condensate formation. Condensate-modulating IDR mutations introduced into ZR impaired its genomic occupancy at oncogenic loci and inhibited the recruitment of transcriptional effector proteins, such as MED1, BRD4 and RNA polymerase II. Using nuclear magnetic …

Randomized Trial: Peppermint Oil (Menthol) Pharmacokinetics In Children And Effects On Gut Motility In Children With Functional Abdominal Pain: 540 Mg Vs. 900 Mg Dose Comparison, Robert J Shulman, Bruno P Chumpitazi, Daniel Gonzalez, Uttam Garg, Salma Musaad, Jiali Wen, Gregory L Kearns

Children’s Nutrition Research Center Staff Publications

Aims: There is a paucity of information on the pharmacokinetics (PK) and pharmacodynamics (PD) of menthol, the active ingredient in peppermint oil (PMO). We studied the PK of menthol (540 and 900 mg) in children and measured their effects on gut transit/contractility.

Methods: Children 7-12 years of age with functional abdominal pain underwent wireless motility capsule (WMC) testing. One week later, they were randomized to 540 mg or 900 mg of oral enteric-coated PMO. Blood was sampled over 24 h to determine menthol PK. The WMC test was repeated while they took their respective dose (180 mg thrice or 180 …

Drivers Of Frequent Emergency Department Use In Socioeconomically Disadvantaged Older Adults: A Qualitative Study, Anita Chary, Annika Bhananker, Michelle Suh, David Leavitt, Elise Brickhouse, Shreya Tamma, Jose Ramirez, Mariana Rios, Aanand D Naik, Margaret Samuels-Kalow, Naomi George

Faculty, Staff and Student Publications

Background: The emergency department (ED) is the safety net for and a common point of healthcare access for socioeconomically disadvantaged older adults. Little is known about socioeconomically disadvantaged older ED patients' perspectives on their health, healthcare access, and ED use. Such insights could guide tailored interventions to address unmet clinical and health-related social needs (HRSN).

Methods: We performed a qualitative study with older adults in a single public safety net hospital ED. We interviewed patients age 60+ who had ≥ 4 ED 4 visits in the past year. Semi-structured interviews explored perceived health needs and motivations underlying ED visits. We …

Maternal Sleep Disorders And Maternal And Birth Outcomes: A Retrospective Us Claims-Based Study, Anayeli Herrera Morales, Audrey C Choh, Cici X Bauer, Stefan A Czerwinski, Miryoung Lee

Faculty, Staff and Student Publications

Introduction: Sleep disturbances are commonly reported during pregnancy and have been associated with adverse maternal, fetal, and neonatal outcomes. However, self-reported sleep disturbances may not be accurately reflected in the prevalence of clinically diagnosed sleep disorders.

Methods: Using Optum's de-identified Clinformatics Data Mart Database, we conducted a cross-sectional study of 93,767 American women who were pregnant with singletons between January 1, 2015 and June 30, 2021, to (1) determine the prevalence of clinically diagnosed sleep disorders and breathing abnormalities; (2) examine their associations with maternal health outcomes; and (3) examine their associations with birth outcomes. Sleep disorders and breathing abnormalities …

Genome-Wide Association Study Provides Novel Insight Into The Genetic Architecture Of Severe Obesity, Mohanraj Krishnan, Mohammad Yaser Anwar, Anne E Justice, Geetha Chittoor, Hung-Hsin Chen, Rashedeh Roshani, Alyssa Scartozzi, Rachel R Dickerson, Roelof A J Smit, Michael H Preuss, Nathalie Chami, Benjamin S Hadad, Esteban J Parra, Miguel Cruz, Qin Hui, Peter W F Wilson, Yan V Sun, Xiaoyu Zhang, Gregorio V Linchangco, Sharon L R Kardia, Jessica D Faul, David R Weir, Lawrence F Bielak, Heather M Highland, Kristin L Young, Baiyu Qi, Yujie Wang, Myriam Fornage, Christopher Haiman, Iona Cheng, Ulrike Peters, Charles Kooperberg, Steven Buyske, Joseph B Mccormick, Susan P Fisher-Hoch, Frida Lona-Durazo, Jesus Peralta, Jamie Gomez-Zamudio, Stephen S Rich, Kendra R Ferrier, Ethan M Lange, Christopher R Gignoux, Eimear E Kenny, Genevieve L Wojcik, Kelly Cho, Michael J Gaziano, Luc Djousse, Shuwei Liu, Dhananjay Vaidya, Renée De Mutsert, Navya S Josyula, Christopher R Bauer, Wei Zhao, Ryan W Walker, Jennifer A Smith, Leslie A Lange, Mariah C Meyer, Ching-Ti Liu, Lisa R Yanek, Miryoung Lee, Laura M Raffield, Ruth J F Loos, Penny Gordon-Larsen, Jennifer E Below, Kari E North, Mariaelisa Graff

The Brown Foundation: Institute of Molecular Medicine

Severe obesity (SevO) is a primary driver of cardiovascular diseases (CVD), cardiometabolic diseases (CMD) and several cancers, with a disproportionate impact on marginalized populations. SevO is an understudied global health disease, limiting knowledge about its mechanisms and impacts. In genome-wide association study (GWAS) meta-analyses of the tail end of the BMI distribution (≥95th percentile BMI) and two SevO phenotypes [Obesity Class III BMI ≥ 40 kg/m2 and Obesity Class IV BMI ≥ 50 kg/m2] in 159,359 individuals across eleven ancestrally diverse population-based studies followed by replication in 480,897 individuals across six ancestrally diverse studies, we identified and replicated three novel …

Utilization Of Outpatient Mental Health Services During And 2 Years After The Covid-19 Pandemic, Michelle A Hayek, Hye-Chung Kum, Sulki Park, Robert Ohsfeldt, Mark A Lawley, Michelle J Bovin

The Brown Foundation: Institute of Molecular Medicine

Objective: Analyze the impact of COVID-19 on outpatient mental health (OP-MH) utilization patterns, particularly telehealth, across eight different MH conditions with a 2-year follow-up.

Methods: This population-based cohort study uses a 5% random sample of Medicare beneficiaries aged ≥18 and newly diagnosed with one of the eight MH disorders: psychotic, depressive, bipolar, anxiety, trauma-related, substance-use, other MH disorders, and two or more MH disorders. Monthly OP-MH utilization patterns were compared among patients in 2020-2021 newly diagnosed in 2019 to comparable prepandemic cohorts newly diagnosed in 2017. Multiple logistic regression models were conducted to examine differences in telehealth utilization across MH …

Preoperative Focused Echocardiography On Patients With Fractured Neck Of Femur. Echonof-Iii Trial: Study Protocol For A Multicenter Randomized Controlled Trial, Ximena Cid-Serra, Alistair Royse, Andrea Bowyer, David Canty, Daniel Sessler, Sandy Clarke-Errey, Andre Denault, Dina Logiudice, Guy Ludbrook, D-Yin Lin, Yang Yang, Kavi Haji, Lisa Zucherrelli, Andrew J Palmer, Benjamin Piper, Thar Nyan Lwin, Stefan Dieleman, David Eccleston, Alwin Chuan, Richard Cooper, Gregory Henderson, Colin Royse

Faculty, Staff and Student Publications

Background: Hip fractures are common in older people and are associated with high perioperative mortality. Prompt surgical intervention within the first 48 h of fraction reduces complications; however, surgical urgency often precludes a comprehensive preoperative cardiac evaluation. Preliminary data suggests that performing a focused cardiac ultrasound (FCU) before surgery may reduce postoperative complications. We therefore propose to test the primary hypothesis that FCU reduces a 30-day composite of mortality and serious complications.

Methods: We plan a definitive multicenter pragmatic randomized trial that will enroll 2000 adults with hip fractures. Participants will be randomized before surgery to either receive FCU as …

Polygenic Prediction Of Body Mass Index And Obesity Through The Life Course And Across Ancestries, Roelof A J Smit, Kaitlin H Wade, Qin Hui, Joshua D Arias, Xianyong Yin, Malene R Christiansen, Loic Yengo, Michael H Preuss, Mariam Nakabuye, Ghislain Rocheleau, Sarah E Graham, Victoria L Buchanan, Geetha Chittoor, Marielisa Graff, Marta Guindo-Martínez, Yingchang Lu, Eirini Marouli, Saori Sakaue, Cassandra N Spracklen, Sailaja Vedantam, Emma P Wilson, Shyh-Huei Chen, Teresa Ferreira, Yingjie Ji, Tugce Karaderi, Kreete Lüll, Moara Machado, Deborah E Malden, Carolina Medina-Gomez, Amy Moore, Sina Rüeger, Masato Akiyama, Matthew A Allison, Marcus Alvarez, Mette K Andersen, Vivek Appadurai, Liubov Arbeeva, Eric Bartell, Seema Bhaskar, Lawrence F Bielak, Joshua C Bis, Sailalitha Bollepalli, Jette Bork-Jensen, Jonathan P Bradfield, Yuki Bradford, Caroline Brandl, Peter S Braund, Jennifer A Brody, Ulrich Broeckel, Kristoffer S Burgdorf, Brian E Cade, Qiuyin Cai, Silvia Camarda, Archie Campbell, Marisa Cañadas-Garre, Jin-Fang Chai, Alessandra Chesi, Seung Hoan Choi, Paraskevi Christofidou, Christian Couture, Gabriel Cuellar-Partida, Rebecca Danning, Frauke Degenhardt, Graciela E Delgado, Alessandro Delitala, Ayşe Demirkan, Xuan Deng, Alexander Dietl, Maria Dimitriou, Latchezar Dimitrov, Rajkumar Dorajoo, Fabian Eichelmann, Anders U Eliasen, Jorgen E Engmann, Michael R Erdos, Zammy Fairhurst-Hunter, Aliki-Eleni Farmaki, Jessica D Faul, Juan-Carlos Fernandez-Lopez, Lukas Forer, Mirjam Frank, Sandra Freitag-Wolf, Lars G Fritsche, Christian Fuchsberger, Tessel E Galesloot, Yan Gao, Frank Geller, Olga Giannakopoulou, Franco Giulianini, Anette P Gjesing, Anuj Goel, Scott D Gordon, Mathias Gorski, Jakob Grove, Xiuqing Guo, Stefan Gustafsson, Jeffrey Haessler, Thomas F Hansen, Aki S Havulinna, Simon J Haworth, Nancy Heard-Costa, Daiane Hemerich, Heather M Highland, George Hindy, Yuk-Lam Ho, Edith Hofer, Elizabeth Holliday, Katrin Horn, Whitney E Hornsby, Jouke-Jan Hottenga, Hongyan Huang, Jie Huang, Alicia Huerta-Chagoya, Shaofeng Huo, Mi Yeong Hwang, Chii-Min Hwu, Hiroyuki Iha, Daisuke D Ikeda, Masato Isono, Anne U Jackson, Iris E Jansen, Yunxuan Jiang, Ingegerd Johansson, Anna Jonsson, Torben Jørgensen, Ioanna P Kalafati, Masahiro Kanai, Stavroula Kanoni, Line L Kårhus, Anuradhani Kasturiratne, Tomohiro Katsuya, Takahisa Kawaguchi, Rachel L Kember, Katherine A Kentistou, Daeeun Kim, Han-Na Kim, Young Jin Kim, Marcus E Kleber, Maria J Knol, Azra Kurbasic, Marie Lauzon, Phuong Le, Rodney Lea, Jong-Young Lee, Wen-Jane Lee, Hampton L Leonard, Hengtong Li, Shengchao A Li, Xiaohui Li, Xiaoyin Li, Jingjing Liang, Honghuang Lin, Kuang Lin, Jun Liu, Xueping Liu, Ken Sin Lo, Jirong Long, Laura Lores-Motta, Jian'an Luan, Valeriya Lyssenko, Leo-Pekka Lyytikäinen, Anubha Mahajan, Md Zubbair Malik, Vasiliki Mamakou, Massimo Mangino, Ani Manichaikul, Jonathan Marten, Manuel Mattheisen, Aaron F Mcdaid, Quanshun Mei, Heike Meiselbach, Tori L Melendez, Yuri Milaneschi, Jason E Miller, Iona Y Millwood, Pashupati P Mishra, Ruth E Mitchell, Line T Møllehave, Nina Mononen, Sören Mucha, Matthias Munz, Juha Mykkänen, Masahiro Nakatochi, Giuseppe Giovanni Nardone, Christopher P Nelson, Maria Nethander, Chu Won Nho, Aneta A Nielsen, Ilja M Nolte, Suraj S Nongmaithem, Raymond Noordam, Ioanna Ntalla, Teresa Nutile, Anita Pandit, Marc Pauper, Eva R B Petersen, Liselotte V Petersen, Francesco Piluso, Ozren Polašek, Alaitz Poveda, Saiju Pyarajan, Laura M Raffield, Hiromi Rakugi, Julia Ramirez, Asif Rasheed, Dennis Raven, Nigel W Rayner, Carlos Riveros, Rebecca Rohde, Daniela Ruggiero, Sanni E Ruotsalainen, Kathleen A Ryan, Maria Sabater-Lleal, Aurora Santin, Richa Saxena, Markus Scholz, Botong Shen, Jingchunzi Shi, Jae Hun Shin, Carlo Sidore, Julia Sidorenko, Xueling Sim, Roderick C Slieker, Albert V Smith, Jennifer A Smith, Laura J Smyth, Lorraine Southam, Valgerdur Steinthorsdottir, Liang Sun, Fumihiko Takeuchi, Kent D Taylor, Bamidele O Tayo, Catherine Tcheandjieu, Natalie Terzikhan, Paola Tesolin, Alexander Teumer, Elizabeth Theusch, Deborah J Thompson, Gudmar Thorleifsson, Paul R H J Timmers, Stella Trompet, Constance Turman, Simona Vaccargiu, Sander W Van Der Laan, Peter J Van Der Most, Jan B Van Klinken, Jessica Van Setten, Shefali S Verma, Niek Verweij, Yogasudha Veturi, Carol A Wang, Chaolong Wang, Jun-Sing Wang, Lihua Wang, Ya Xing Wang, Zhe Wang, Helen R Warren, Wen Bin Wei, Wanqing Wen, William A Wheeler, Ananda R Wickremasinghe, Matthias Wielscher, Bendik S Winsvold, Andrew Wong, Matthias Wuttke, Rui Xia, Ken Yamamoto, Jingyun Yang, Jie Yao, Hannah Young, Noha A Yousri, Lei Yu, Lingyao Zeng, Weihua Zhang, Xinyuan Zhang, Jing-Hua Zhao, Wei Zhao, Wei Zhou, Martina E Zimmermann, Magdalena Zoledziewska, Leen M 'T Hart, Linda S Adair, Hieab H H Adams, Carlos A Aguilar-Salinas, Fahd Al-Mulla, Donna K Arnett, Folkert W Asselbergs, Bjørn Olav Åsvold, John Attia, Bernhard Banas, Stefania Bandinelli, Lawrence J Beilin, David A Bennett, Tobias Bergler, Dwaipayan Bharadwaj, Ginevra Biino, Eric Boerwinkle, Carsten A Böger, Judith B Borja, Claude Bouchard, Donald W Bowden, Ivan Brandslund, Ben Brumpton, Julie E Buring, Mark J Caulfield, John C Chambers, Giriraj R Chandak, Stephen J Chanock, Nish Chaturvedi, Yii-Der Ida Chen, Zhengming Chen, Ching-Yu Cheng, Yoon Shin Cho, Kaare Christensen, Ingrid E Christophersen, Marina Ciullo, John W Cole, Francis S Collins, Maria Pina Concas, Richard S Cooper, Miguel Cruz, Francesco Cucca, Michael J Cutler, Scott M Damrauer, Thomas M Dantoft, Gert J De Borst, Eco J C De Geus, Lisette C P G M De Groot, Philip L De Jager, Dominique P V De Kleijn, H Janaka De Silva, George V Dedoussis, Anneke I Den Hollander, Shufa Du, Douglas F Easton, Kai-Uwe Eckardt, Petra J M Elders, A Heather Eliassen, Patrick T Ellinor, Sölve Elmståhl, Jeanette Erdmann, Michele K Evans, Diane Fatkin, Bjarke Feenstra, Mary F Feitosa, Luigi Ferrucci, Jose C Florez, Ian Ford, Myriam Fornage, Andre Franke, Paul W Franks, Barry I Freedman, Christian Gieger, Giorgia Girotto, Yvonne M Golightly, Clicerio Gonzalez-Villalpando, Penny Gordon-Larsen, Harald Grallert, Struan F A Grant, Niels Grarup, Lyn Griffiths, Vilmundur Gudnason, Christopher Haiman, Hakon Hakonarson, Torben Hansen, Catharina A Hartman, Andrew T Hattersley, Caroline Hayward, Iris M Heid, Chew-Kiat Heng, Christian Hengstenberg, Karl-Heinz Herzig, Alex W Hewitt, Haretsugu Hishigaki, David M Hougaard, Carel B Hoyng, Paul L Huang, Wei Huang, Wen-Yi Huang, Jennifer E Huffman, Steven C Hunt, Nina Hutri, Kristian Hveem, Elina Hyppönen, William G Iacono, Sahoko Ichihara, M Arfan Ikram, Carmen R Isasi, Marjo-Riitta Jarvelin, Zi-Bing Jin, Karl-Heinz Jöckel, Jost B Jonas, Peter K Joshi, Pekka Jousilahti, J Wouter Jukema, Mika Kähönen, Yoichiro Kamatani, Kui Dong Kang, Jaakko Kaprio, Sharon L R Kardia, Fredrik Karpe, Norihiro Kato, Maryam Kavousi, Frank Kee, Thorsten Kessler, Amit V Khera, Chiea Chuen Khor, Lambertus A L M Kiemeney, Bong-Jo Kim, Eung Kweon Kim, Hyung-Lae Kim, Paulus Kirchhof, Mika Kivimaki, Woon-Puay Koh, Heikki A Koistinen, Alexander Kokkinos, Jaspal S Kooner, Charles Kooperberg, Peter Kovacs, Adriaan Kraaijeveld, Peter Kraft, Ronald M Krauss, Meena Kumari, Zoltan Kutalik, Markku Laakso, Leslie A Lange, Claudia Langenberg, Lenore J Launer, Hyejin Lee, Nanette R Lee, Terho Lehtimäki, Rozenn N Lemaitre, Huaixing Li, Liming Li, Wolfgang Lieb, Xu Lin, Lars Lind, Allan Linneberg, Ching-Ti Liu, Jianjun Liu, Markus Loeffler, Barry London, Fan Lu, Steven A Lubitz, David A Mackey, Patrik K E Magnusson, Joann E Manson, Gregory M Marcus, Pedro Marques Vidal, Nicholas G Martin, Winfried März, Fumihiko Matsuda, Mark I Mccarthy, Robert W Mcgarrah, Matt Mcgue, Amy Jayne Mcknight, Sarah E Medland, Dan Mellström, Andres Metspalu, Braxton D Mitchell, Paul Mitchell, Dennis O Mook-Kanamori, Trevor A Mori, Andrew D Morris, Lorelei A Mucci, Patricia B Munroe, Mike A Nalls, Saman Nazarian, Amanda E Nelson, Matt J Neville, Christopher Newton-Cheh, Christopher S Nielsen, Harri Niinikoski, Kjell Nikus, Markus M Nöthen, Adesola Ogunniyi, Claes Ohlsson, Albertine J Oldehinkel, Lorena Orozco, Katja Pahkala, Päivi Pajukanta, Colin N A Palmer, Esteban J Parra, Cristian Pattaro, Oluf Pedersen, Craig E Pennell, Brenda W J H Penninx, Louis Perusse, Annette Peters, Patricia A Peyser, David J Porteous, Danielle Posthuma, Chris Power, Peter P Pramstaller, Michael A Province, Bruce M Psaty, Qibin Qi, Jia Qu, Daniel J Rader, Olli T Raitakari, Loukianos S Rallidis, Dabeeru C Rao, Susan Redline, Dermot F Reilly, Alexander P Reiner, Sang Youl Rhee, Paul M Ridker, Michiel Rienstra, Samuli Ripatti, Marylyn D Ritchie, Fernando Rivadeneira, Dan M Roden, Frits R Rosendaal, Jerome I Rotter, Igor Rudan, Femke Rutters, Seungho Ryu, Charumathi Sabanayagam, Babatunde Salako, Danish Saleheen, Veikko Salomaa, Nilesh J Samani, Dharambir K Sanghera, Naveed Sattar, Börge Schmidt, Helena Schmidt, Reinhold Schmidt, Matthias B Schulze, Heribert Schunkert, Laura J Scott, Rodney J Scott, Peter Sever, Wayne H H Sheu, M Benjamin Shoemaker, Xiao-Ou Shu, Eleanor M Simonsick, Mario Sims, Andrew B Singleton, Moritz F Sinner, J Gustav Smith, Harold Snieder, Tim D Spector, Beatrice Spedicati, Meir J Stampfer, Klaus J Stark, David P Strachan, Yasuharu Tabara, E Shyong Tai, Hua Tang, Jean-Claude Tardif, Thangavel A Thanaraj, Anke Tönjes, Tiinamaija Tuomi, Jaakko Tuomilehto, Maria-Teresa Tusié-Luna, Rob M Van Dam, Pim Van Der Harst, Nathalie Van Der Velde, Cornelia M Van Duijn, Natasja M Van Schoor, Veronique Vitart, Marie-Claude Vohl, Uwe Völker, Peter Vollenweider, Henry Völzke, Scott Vrieze, Niels H Wacher-Rodarte, Mark Walker, Gurpreet S Wander, Nicholas J Wareham, Richard M Watanabe, Hugh Watkins, David R Weir, Thomas M Werge, Elisabeth Widen, Gonneke Willemsen, Walter C Willett, James F Wilson, Peter W F Wilson, Tien Y Wong, Jeong-Taek Woo, Alan F Wright, Huichun Xu, Chittaranjan S Yajnik, Jian Yang, Mitsuhiro Yokota, Jian-Min Yuan, Eleftheria Zeggini, Babette S Zemel, Wei Zheng, Xiaofeng Zhu, M Carola Zillikens, Alan B Zonderman, John-Anker Zwart, Goncalo R Abecasis, Themistocles L Assimes, Adam Auton, Michael Boehnke, Daniel I Chasman, Tõnu Esko, Kari Stefansson, Guillaume Lettre, Cecilia M Lindgren, Maggie C Y Ng, Christopher J O'Donnell, Unnur Thorsteinsdottir, Peter M Visscher, Robin G Walters, Thomas W Winkler, Andrew R Wood, Panos Deloukas, Timothy M Frayling, Anne E Justice, Tuomas O Kilpeläinen, Adam E Locke, Karen L Mohlke, Kari E North, Yukinori Okada, Cristen J Willer, Kristin L Young, Segun Fatumo, Jeanne M Mccaffery, Nicholas J Timpson, Joel N Hirschhorn, Yan V Sun, Sonja I Berndt, Ruth J F Loos

Faculty, Staff and Student Publications

Polygenic scores (PGSs) for body mass index (BMI) may guide early prevention and targeted treatment of obesity. Using genetic data from up to 5.1 million people (4.6% African ancestry, 14.4% American ancestry, 8.4% East Asian ancestry, 71.1% European ancestry and 1.5% South Asian ancestry) from the GIANT consortium and 23andMe, Inc., we developed ancestry-specific and multi-ancestry PGSs. The multi-ancestry score explained 17.6% of BMI variation among UK Biobank participants of European ancestry. For other populations, this ranged from 16% in East Asian-Americans to 2.2% in rural Ugandans. In the ALSPAC study, children with higher PGSs showed accelerated BMI gain from …

Five-Year Change In Sleep Duration And Incident Alzheimer’S Disease And Related Dementias Among Lower-Income Older Adults, Hui Shi, Loren Lipworth, Qian Xiao, Xijing Han, Michael Mumma, Laura M Keohane, Danxia Yu, Corey J Bolton, Derek B Archer, Timothy J Hohman, Kelsie M Full

Faculty, Staff and Student Publications

Introduction: Little is known about change in sleep duration over time and Alzheimer's Disease and Related Dementias (ADRD) risk.

Methods: ADRD cases were identified among Southern Community Cohort Study participants enrolled in Medicare. Sleep duration was reported at enrollment and first study follow-up and categorized (short (< 7 hours), recommended (7-9) and long (> 9)), change was calculated between timepoints. Adjusted Cox proportional hazards regression was used to estimate hazard ratios (HRs, 95% CIs) for incident ADRD.

Results: We identified 2,093 ADRD cases among 17,945 participants. Compared to maintaining optimal sleep duration (7-9 hours) over 5 years, suboptimal changes were associated with 20-69% greater ADRD risk: adjusted …

Steroid Hormone Biosynthesis And Dietary Related Metabolites Associated With Excessive Daytime Sleepiness, Tariq Faquih, Kaitlin S Potts, Pavithra Nagarajan, Bing Yu, Robert Kaplan, Carmen R Isasi, Qibin Qi, Kent D Taylor, Peter Y Liu, Satu J Strausz, Hanna M Ollila, Tianyi Huang, Russell P Tracy, Craig Johnson, Stephen S Rich, Clary B Clish, Jerome I Rotter, Susan Redline, Tamar Sofer, Heming Wang

Faculty, Staff and Student Publications

Background: Excessive daytime sleepiness (EDS) is a complex sleep problem that affects approximately 33% of the United States population. Although EDS usually occurs in conjunction with insufficient sleep and other sleep and circadian disorders, recent studies have shown unique genetic markers and metabolic pathways underlying EDS. Here, we aimed to further elucidate the biological profile of EDS using large-scale single- and pathway-level metabolomics analyses.

Methods: Metabolomics data were available for 877 metabolites in 6071 individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). EDS was assessed using the Epworth Sleepiness Scale (ESS) questionnaire. We performed linear regression for each …

Reliability And Spatial Consistency Of Mr Diffusion Tensor Imaging Measures Along The Cerebral Perivascular Space, Enchao Qiu, Joga Chaganti, Phillip Phan, M. Alizadeh, Devon Middleton, Kiran Talekar, Prabath Mondel, Scott H. Faro, Feroze Mohamed, Hsiangkuo Yuan

Department of Radiology Faculty Papers

BACKGROUND AND PURPOSE: Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) has emerged as a promising noninvasive method for evaluating water motion that may reflect glymphatic system function. However, the reliability of DTI-ALPS measurements across different region-of-interest (ROI) selection methods remains underinvestigated. This study aimed to assess the interrater reliability among three neuroradiologists in native space and compare DTI-ALPS indices derived from ROIs placed in subjects' native space versus standardized Montreal Neurological Institute (MNI) space.

METHODS: DTI-ALPS indices from 16 healthy subjects were calculated from both left and right hemispheres using two ROI placement approaches: (1) native space ROIs …

Mechanisms Underlying Treatment-Resistant Depression: Exploring Sex-Based Biological Differences, Francisco E R Da Silva, Atakan Yucel, Antonio P M Menezes, Ana C Ruiz, Marcela C Carbajal Tamez, Tatiana Barichello, Giselli Scaini, Joao Quevedo

Faculty, Staff and Student Publications

Treatment-resistant depression (TRD) represents a severe and complex subtype of major depressive disorder (MDD), affecting approximately 30% of patients who fail to respond adequately to multiple standard antidepressant therapies. While the pathophysiology of TRD remains incompletely understood, emerging evidence suggests that sex-based biological differences might influence its onset, progression, and treatment response. Women are disproportionately affected by depression and are more likely to experience residual symptoms and treatment resistance, potentially due to hormonal fluctuations, immune system differences, and variations in brain circuitry and neuroplasticity. This narrative explores the current literature on the mechanisms underlying TRD, with a particular emphasis on …

Variational Temporal Deconfounder Network For Individualized Treatment Effect Estimation With Longitudinal Observational Data, Hao Dai, Yu Huang, Yuxi Liu, Xing He, Jingchuan Guo, Mattia Prosperi, Jiang Bian

Faculty, Staff and Student Publications

Objective: By leveraging real-world electronic health record (EHR) data, this study set out to estimate individualized treatment effects (ITE) in longitudinal observational settings to advance personalized medicine, addressing key challenges that are often observed in real-world clinical scenarios and pose statistical challenges, including hidden confounding and dynamic treatment regimens.

Methods: We propose the Variational Temporal Deconfounder Network (VTDNet), a novel framework designed to account for time-varying hidden confounding using a variational recurrent transformer-based autoencoder. Specifically, VTDNet comprises three critical components: a temporal Encoder-Decoder structure to capture hidden representation, a Treatment Block that captures interdependencies among multiple treatments, and a Potential …

Sex Differences In The Treatment With Pcsk9 Monoclonal Antibodies- Real World Experience From A Dedicated Preventive Cardiology Clinic, Lital Hodeda, Alon Eisen, Aviad Rotholz, Ran Kornowski, Chen Gurevitz

Faculty, Staff and Student Publications

Purpose: Proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9 mAb) lower low-density lipoprotein cholesterol (LDL-C) levels and reduce atherosclerotic cardiovascular disease (ASCVD). Data regarding sex differences in PCSK9 mAb treatment remain lacking. This study examines sex differences in patients' characteristics, indications, efficacy, and safety of PCSK9 mAb treatment.

Methods: Retrospective study based on data from the Preventive Cardiology and Lipids Clinic in Rabin Medical Center on patients prescribed with PCSK9 mAb. Collected data included medical background, medications, indications and laboratory data, analyzed by sex.

Results: 246 patients were included (mean age 67y, ASCVD 78.8 %, mean baseline LDL-C 128.2 mg/dL). …

Mucinous Cystic Neoplasms Of The Pancreas And Liver Share A Similar Dna Methylation Profile With Mucinous Ovarian Tumors, Zoe Leoni, Teodor G Calina, Tobias Janik, Elena Grafenhorst, Eliane T Taube, Christopher Cm Neumann, Baoqing Chen, Elena I Braicu, Jalid Sehouli, Thomas Malinka, Wenzel Schöning, Johann Pratschke, George A Calin, David S Klimstra, Jamal K Benhamida, Irene Esposito, Markus Möbs, David Horst, Simon Schallenberg, David Capper, Mihnea P Dragomir

Faculty, Staff and Student Publications

The origin of mucinous cystic neoplasms (MCNs) remains a major challenge in hepato-pancreato-biliary pathology. These cystic tumors are defined by their mucinous epithelium and ovarian-like stroma, with an estimated 10% risk of progression to invasive carcinoma. The origin of the ovarian-like stroma remains a subject of debate. In this study, we conducted immunohistochemical profiling, targeted DNA sequencing, and genome-wide DNA methylation analysis on a cohort of 15 pancreatic MCNs (MCN-P) and six hepatic MCNs (MCN-L). Using immunohistochemistry and targeted DNA sequencing, we unequivocally established the diagnosis of MCN. Unsupervised DNA methylation profile analysis of reference classes of pancreatic neoplasms (11 …

The Antifungal Mechanism Of Entv-Derived Peptides Is Associated With A Reduction In Extracellular Vesicle Release, Giuseppe Buda De Cesare, Melissa R Cruz, Shane A Cristy, Luis A Vega, Robert Zarnowski, Antonino Zito, Shantanu Guha, David R Andes, Danielle A Garsin, Michael C Lorenz

Faculty, Staff and Student Publications

Candida albicans, an opportunistic fungal pathogen, causes systemic and superficial infections, especially in immunocompromised patients. Treatment of fungal infections is complicated by limited antifungal options and the development of drug resistance. Previous work from our group demonstrated the efficacy of the anti-virulence peptide EntV and shorter variants against C. albicans infection in various animal models, including mouse models of oropharyngeal candidiasis and disseminated infection and a rat venous catheter model. However, the mechanism of action, which abrogates fungal virulence without fungicidal or fungistatic activity, has remained unknown. We used a combination of cell biological, biochemical, genomic, and genetic approaches to …

Integrating Environmental Risk Factors Into Pediatric Cancer Care: Laying The Groundwork For Improved Outcomes And Primary Prevention., Nicole Wood, Omar Shakeel, Juan A. Ortega-Garcia, Mark D. Miller

Manuscripts, Articles, Book Chapters and Other Papers

Childhood cancer incidence has steadily risen both in the United States and worldwide, yet its environmental contributors remain underrecognized in clinical care. Children and cancer survivors are particularly susceptible to environmental exposures due to their unique physiology and the long-term health vulnerabilities that follow cancer treatment. Although exposures to substances such as pesticides, air pollution, and household chemicals are linked to increased cancer risk, limited clinical frameworks and clinician training leave oncologists underprepared to address growing environmental health concerns from families. A holistic pediatric oncology environmental health program in Murcia, Spain offers a scalable vision for embedding the environment into …

Trop2 Expression In Salivary Gland Adenoidcystic Carcinoma (Acc) According To Histologic Subtype: Therapeutic Implications, Juliana Mota Siqueira, Yoshitsugu Mitani, Mario L Marques-Piubelli, Camilla Oliveira Hoff, Flavia Bonini, Luana Guimaraes De Sousa, Mutsumi Mitani, Giovanna Lopes Carvalho, Fabio Daumas Nunes, Leandro Luongo Matos, Shiaw-Yih Lin, Michael T Spiotto, Ehab Y Hanna, Daniel J Mcgrail, Adel K El-Naggar, Renata Ferrarotto

Faculty, Staff and Student Publications

Background: Adenoid cystic carcinoma (ACC) is a common salivary gland carcinoma with high recurrence and distant metastasis rates. Currently, there is no standard systemic treatment available. TROP2 is a transmembrane glycoprotein involved in the oncogenesis of several tumors that can be therapeutically targeted by a TROP2-antibody-drug conjugate (ADC). We aimed to characterize TROP2 expression in ACC and assess TROP2 as a potential therapeutic target.

Methods: TROP2 immunohistochemistry was performed in a tissue microarray including 165 ACC of salivary gland. The tumors were grouped according to the histological pattern as non-solid, solid + non-solid, or solid. TROP2 protein expression in ACC …

Which Score For What? Operationalizing Standardized Cognitive Test Performance For The Assessment Of Change, Cristan Farmer, Audrey Thurm, Tanvi Das, E Martina Bebin, Jonathan A Bernstein, Elizabeth Berry-Kravis, Joseph D Buxbaum, Charis Eng, Thomas Frazier, Antonio Y Hardan, Alexander Kolevzon, Darcy A Krueger, Julian A Martinez-Agosto, Hope Northrup, Craig M Powell, Latha Valluripalli Soorya, Joyce Y Wu, Mustafa Sahin, Developmental Synaptopathies Consortium

Faculty, Staff and Student Publications

Developmental domains, such as cognitive, language, and motor, are key concepts of interest in longitudinal studies of intellectual and developmental disabilities (IDD). Normative scores (e.g., IQ) are often used to operationalize performance on standardized tests of these concepts, but it is the interval-distributed person-ability scores that are intended for the assessment of within-individual change. Here we illustrate the use and interpretation of several Stanford Binet, 5th Edition score types (IQ, extended IQ, Z-normalized raw score, developmental quotient, raw sum score, age equivalent, and ability score) using data from two longitudinal studies of rare genetic conditions associated with IDD. We found …

Auricular Point Acupressure For Older Adults With Chronic Low Back Pain: A Randomized Controlled Trial, Jennifer Kawi, Chao Hsing Yeh, Nada Lukkahatai, Hulin Wu, Natalia E Morone, Ronald Glick, Elizabeth A Schlenk, Claudia Campbell, Johannes Thrul, Xinran Huang, Hongyu Wang, Hejingzi Monica Jia, Paul Christo, Constance Johnson

Faculty, Staff and Student Publications

Objective: Efficacious modalities are limited in chronic low back pain (cLBP). We determined the efficacy of auricular point acupressure (APA) in older adults with cLBP.

Design: 3-arm randomized controlled trial.

Setting: Baltimore, Maryland.

Participants: Participants, ≥60 years with cLBP, were randomized (1:1:1) to APA with ear points targeted to cLBP (T-APA, n = 92), points nontargeted to cLBP (NT-APA, n = 91), or waitlist education control (n = 89), and followed up to 6 months (6M). Participants in the APA groups received 4 weekly APA sessions; the education control group received 4 weekly educational sessions.

Intervention: APA.

Main outcomes and …

The Late Positive Potential Predicts Contingency Management Outcomes For Cocaine Use Disorder, Heather E Webber, Douglas J Calvillo, Francesco Versace, Constanza De Dios, Robert Suchting, Charles E Green, Scott D Lane, Joy M Schmitz

Faculty, Staff and Student Publications

Contingency management (CM) relies on motivation and reward processing and is among the most effective treatments available for cocaine use disorder (CUD), yet success rates do not meet desired clinical efficacy. To improve treatment-individual fit, we investigated the late positive potential (LPP), a measure of incentive salience to cues, as a predictor of treatment response. Treatment-seeking adults with CUD (N = 58) completed an EEG task where they viewed pleasant, unpleasant, cocaine, and neutral images. Participants received CM and counseling for four weeks. Urine was collected thrice weekly. We defined incentive salience to cues by A) cluster analyses on LPP …

Leveraging Existing Cohort Studies Of Mexican Women To Better Understand Hispanic Health And Cancer Risk, Dalia Stern, Liliana Gomez-Flores-Ramos, Britton Trabert, V Wendy Setiawan, Loïc Le Marchand, Henry Gomez, Paul A Scheet, Humberto Parada, Amber Pirzada, Martin Lajous, Leslie V Farland

Faculty, Staff and Student Publications

Background: Hispanics have been historically underrepresented in epidemiologic cancer research. Existing cohort studies focused on recruiting Hispanic participants have been relatively small, making studying cancer outcomes challenging. Therefore, we aimed to compare the distribution of cancer risk factors among Hispanic women of Mexican heritage (HWMH) participating in existing cohorts to explore the possibility of future data pooling efforts.

Methods: We used baseline data of HWMH from three US-based studies, the Mexican American Cohort (MAC; n = 19,797; 2001-2017), the Multiethnic Cohort (MEC; n = 18,007; 1993-1996), and the Hispanic Community Health Study/Study of Latinos (HCHS/SOL; n = 4,022; 2008-2011), and …

Variants In Cald1, Esrp1, And Rbfox1 Are Associated With Orofacial Cleft Risk, Jenna C Carlson, Xinyi Zhang, Zeynep Erdogan-Yildirim, Terri H Beaty, Azeez Butali, Carmen J Buxó, Lord J J Gowans, Jacqueline T Hecht, Ross E Long, Lina Moreno, Jeffrey C Murray, Ieda M Orioli, Carmencita Padilla, George L Wehby, Eleanor Feingold, Elizabeth J Leslie-Clarkson, Seth M Weinberg, Mary L Marazita, John R Shaffer

Faculty, Staff and Student Publications

Nonsyndromic orofacial clefts (OFCs) are common, heritable birth defects caused by both genetic and environmental risk factors. Despite the identification of many genetic loci harboring OFC-risk variants, there are many unknown genetic determinants of OFC. Furthermore, while the process of embryonic facial development is well characterized, the molecular mechanisms that underly it are not. This represents a major hurdle in understanding how disruptions in these biological processes result in OFC. Thus, we sought to identify novel OFC-risk loci through a genome-wide multi-ancestry study of five nested OFC phenotypes (isolated cleft lip [CLO], isolated cleft palate [CPO], cleft lip and palate …

Mature And Migratory Dendritic Cells Promote Immune Infiltration And Response To Anti-Pd-1 Checkpoint Blockade In Metastatic Melanoma, Jiekun Yang, Cassia Wang, Doris Fu, Li-Lun Ho, Kyriakitsa Galani, Lee Chen, Jose Gonzalez, Jolene Fu, Amy Y Huang, Dennie T Frederick, Liang He, Mukta Asnani, Rahul Tacke, Emily J Robitschek, Sandeep K Yadav, Wentao Deng, Kelly P Burke, Tatyana Sharova, Ryan J Sullivan, Sarah Weiss, Kunal Rai, David Liu, Genevieve M Boland, Manolis Kellis

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, yet most patients fail to achieve durable responses. To better understand the tumor microenvironment (TME), we analyze single-cell RNA-seq (~189 K cells) from 36 metastatic melanoma samples, defining 14 cell types, 55 subtypes, and 15 transcriptional hallmarks of malignant cells. Correlations between cell subtype proportions reveal six distinct clusters, with a mature dendritic cell subtype enriched in immunoregulatory molecules (mregDC) linked to naive T and B cells. Importantly, mregDC abundance predicts progression-free survival (PFS) with ICIs and other therapies, especially when combined with the TCF7 + /- CD8 T cell ratio. Analysis …

Generation Of Human Induced Pluripotent Stem Cell Line From A Familial Alzheimer’S Disease Patient Carrying Missense Mutations In Psen1 And Mapt Genes, Ashaq H Najar, Sofia E Sepulveda, Camila Gherardelli, Fatemeh Elahian, Amber Fontenot-Roberts, Aleksandar Bajic, David H Hunter, Claudio Soto, Paul E Schulz, Abhisek Mukherjee

Faculty, Staff and Student Publications

Alzheimer's disease (AD), pathologically characterized by misfolding and accumulation of amyloid beta (Aβ) and hyperphosphorylated tau, is the leading cause of neurodegenerative dementia, accounting for 60-80 % of cases. The familial form of AD is caused by mutations in amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) genes. Here, we report the generation of an iPSC line from a 39-year-old AD patient carrying a missense mutation in PSEN1 (F177S), leading to very early onset of AD. The patient also carries a rare variant Q49E in the microtubule-associated protein tau gene (MAPT) with an as yet unknown clinical significance.

Secretogranin 2 Binds Lilrb4 Resulting In Immunosuppression, Xing Yang, Ryan Huang, Meng Fang, Yubo He, Jingjing Xie, Xiaoye Liu, Chengcheng Zhang, Qi Lou, Mi Deng, Wei Xiong, Cheryl Lewis, Zade Sadek, Ankit Gupta, Lianqi Chen, Xuewu Zhang, Lei Guo, Lin Xu, Ningyan Zhang, Zhiqiang An, Cheng Cheng Zhang

Faculty, Staff and Student Publications

Immunosuppressive myeloid cells are important in a variety of physiological and pathological contexts, including tumor development, but how hormones might regulate their activity is unclear. Secretogranins, a family of secretory proteins in endocrine and neuronal cells, are proposed to function as prohormones or hormones, but their specific receptors are unknown. Here we show that secretogranin 2 (SCG2), a granin family member, functionally interacts with leukocyte immunoglobulin-like receptor B4 (LILRB4) on monocytic cells. Tumor-derived SCG2 promotes tumor growth in myeloid-specific LILRB4 transgenic mice in a T cell-dependent manner, whereas SCG2 deficiency in host mice impairs tumor progression and reduces infiltration of …

The Brescia International Multidisciplinary Consensus Guidelines On The Optimal Pathology Assessment And Multidisciplinary Pathways Of Non-Pancreatic Neoplasms In And Around The Ampulla Of Vater (Peripan), Mohammad Abu Hilal, Bas A Uijterwijk, Daniël H L Lemmers, Boris V Janssen, Marc G Besselink, Denise Bianchi, Arantza Fariña, Noriyoshi Fukushima, Anthony J Gill, Seung-Mo Hong, Alyssa Krasinskas, Claudio Luchini, Laura Melocchi, Giulio Rossi, Aldo Scarpa, Olca Basturk, Deyali Chatterjee, Angela Chou, Irene Esposito, Roger Feakins, Bas Groot Koerkamp, Ralph H Hruban, Stefano La Rosa, Chanjuan Shi, Aatur Singhi, Joanne Verheij, Huamin Wang, Sergio Alfieri, Fabio Ausania, Adnan Alseidi, Marco J Bruno, Ugo Boggi, Claudio Bnà, Christos Dervenis, Massimo Falconi, Michele Ghidini, Jakob W Kist, Giovanni Marchegiani, Michele Milella, Roberto Salvia, Ajith Siriwardena, Hanneke Wilmink, Alberto Zaniboni, Shaimaa Al-Janabi, Maia Blomhoff Holm, Eva Roos, Naoki Sano, In Hye Song, Zeynep Tarcan, Gianpaolo Balzano, Isabella Frigerio, Alfredo Guglielmi, Giuseppe Malleo, Horacio Asbun, Volkan Adsay, Caroline Verbeke

Faculty, Staff and Student Publications

IMPORTANCE: The lack of multidisciplinary workflow guidelines and clear definitions and classifications for neoplasms in and around the ampulla of Vater results in inconsistencies affecting patient care and research.

OBJECTIVE: The PERIPAN international multidisciplinary consensus group aimed to standardize the multidisciplinary diagnostic workflow and achieve consensus on definitions and classifications in order to ensure proper classification and optimal diagnostic assessment and consequently to improve patient care and future research.

DESIGN: An international team of 43 experts (pathologists, surgeons, radiologists, gastroenterologists, oncologists) from 12 countries identified knowledge gaps, reviewed 37061 articles, and proposed recommendations using the Scottish Intercollegiate Guidelines Network methodology …