Endocrinology, Diabetes, and Metabolism Commons^™

A Conserved Oxalyl-Coenzyme A Decarboxylase In Oxalate Catabolism, Ninghui Cheng, Vincent Paris, Xiaolan Rao, Xiaoqiang Wang, Paul A Nakata

Children’s Nutrition Research Center Staff Publications

The ability to biosynthesize oxalic acid can provide beneficial functions to plants; however, uncontrolled or prolonged exposure to this strong organic acid results in multiple physiological problems. Such problems include a disruption of membrane integrity, mitochondrial function, metal chelation, and free radical formation. Recent work suggests that a CoA-dependent pathway of oxalate catabolism plays a critical role in regulating tissue oxalate concentrations in plants. Although this CoA-dependent pathway of oxalate catabolism is important, large gaps in our knowledge of the enzymes catalyzing each step remain. Evidence that an oxalyl-CoA decarboxylase (OXC) catalyzes the second step in this pathway, accelerating the …

Influence Of Waist Circumference Measurement Site On Visceral Fat And Metabolic Risk In Youth, Sojung Lee, Yejin Kim, Minsub Han

Faculty, Staff and Student Publications

Although the rate of childhood obesity seems to have plateaued in recent years, the prevalence of obesity among children and adolescents remains high. Childhood obesity is a major public health concern as overweight and obese youth suffer from many co-morbid conditions once considered exclusive to adults. It is now well demonstrated that abdominal obesity as measured by waist circumference (WC) is an independent risk factor for cardiovascular disease and metabolic dysfunction in youth. Despite the strong associations between WC and cardiometabolic risk factors, there is no consensus regarding the optimal WC measurement sites to assess abdominal obesity and obesity-related health …

Measurement Of Force And Intramuscular Pressure Changes Related To Thrust Spinal Manipulation In An In Vivo Animal Model, William R Reed, Carla R Lima, Michael A K Liebschner, Christopher P Hurt, Peng Li, Maruti R Gudavalli

Faculty, Staff and Students Publications

Simple Summary

Spinal manipulation is recommended by clinical guidelines to treat low back pain. However, our understanding of how spinal manipulation alleviates pain and knowledge of the role that viscoelastic tissue properties play in the dampening of applied spinal manipulation forces in vivo is limited. Superficial and deep intramuscular pressures and applied forces were measured using miniature pressure catheters and a force transducer during low back spinal manipulation using a clinically available spinal manipulation device (Activator V) or a feedback motor in a deeply anesthetized animal model. Viscoelastic properties of muscle and other soft tissues greatly diminished applied spinal manipulative …

Lifestyle Tools For Men’S Health And Disease Prevention: Well-Being Through Nutrition, Physical Activity, Stress Management, And Connection, Leigh A. Frame

Clinical Research and Leadership Faculty Publications

Mental health is an often-overlooked aspect of overall health and wellness (well-being). Mental illness is increasingly common with 1 in 5 American adults experiencing it annually, and 1 in 20 suffering from a serious mental illness each year [1]. Treatment rates for mental illness are lower in men (37.4%) compared to women (51.2%) [1]. Globally, treatment rates are similar with an estimated cost to the global economy of $1 trillion annually, yet less than 2% of government health expenditure is for mental health worldwide [2]. Despite this, only nine studies have been published specifically targeting men’s mental health through lifestyle …

Pleiomorphism Plurihormonal Pit-1-Positive Macroadenoma With Central Hyperthyroidism: A Rare Case Report And Literature Review, Guiliang Peng, Chuanhong Guo, Yangfan Lv, Dandan Li, Ling Zhou, Rufei Shen, Yong Chen, Xin Zheng, Zheng Sun, Hongting Zheng, Min Long

Faculty, Staff and Students Publications

BACKGROUND: Thyrotropin-secreting pituitary neuroendocrine tumors (PitNETs) are rare pituitary adenomas that are occasionally accompanied by hypersecretion of other anterior pituitary hormones, such as growth hormone (GH) and prolactin (PRL). The clinical, biochemical, and pathological characteristics may represent diverse circumstances.

CASE PRESENTATION: In this report, a 33-year-old female diagnosed with a TSH PitNET co-secreting GH presented no obvious clinical symptoms. The main characteristics were elevated thyroid-stimulating hormone (TSH), free tri-iodothyronine (FT3), and free thyroxine (FT4) levels accompanied by slightly elevated GH and insulin-like growth factor-1 (IGF-1) levels. Magnetic resonance imaging (MRI) detected a pituitary macroadenoma (18 × 16 × 16 mm) …

Does Receiving A Sars-Cov-2 Antibody Test Result Change Covid-19 Protective Behaviors? Testing Risk Compensation In Undergraduate Students With A Randomized Controlled Trial, Christina Ludema, Molly S Rosenberg, Jonathan T Macy, Sina Kianersi, Maya Luetke, Chen Chen, Lilian Golzarri-Arroyo, Erin Ables, Kevin Maki, David B Allison

Children’s Nutrition Research Center Staff Publications

Background: Risk compensation, or matching behavior to a perceived level of acceptable risk, can blunt the effectiveness of public health interventions. One area of possible risk compensation during the SARS-CoV-2 pandemic is antibody testing. While antibody tests are imperfect measures of immunity, results may influence risk perception and individual preventive actions. We conducted a randomized control trial to assess whether receiving antibody test results changed SARS-CoV-2 protective behaviors.

Purpose: Assess whether objective information about antibody status, particularly for those who are antibody negative and likely still susceptible to SARS-CoV-2 infection, increases protective behaviors. Secondarily, assess whether a positive antibody test …

Progressive Acceleration Of Insulin Exposure Over 7 Days Of Infusion Set Wear, Jasmin R. Kastner, Timothy S. Bailey, Poul Strange, Leon Shi, Keith A. Oberg, Paul J. Strasma, Jeffrey I. Joseph, Douglas B. Muchmore

Department of Anesthesiology Faculty Papers

Insulin exposure varies over 3 days of insulin infusion set (IIS) wear making day-to-day insulin dosing challenging for people with diabetes (PWD). Here we report insulin pharmacodynamic (PD) and pharmacokinetic (PK) data extending these observations to 7 days of IIS wear. PWD (A1C ≤8.5%, C-peptide tmax (P < 0.001), Cmax (P < 0.05), and mean residence time (P < 0.0001). Area under the insulin concentration curve (AUC0–300) declined by ∼24% from days 0 to 7 (P < 0.05). These results confirm/extend previous observations showing progressive acceleration of insulin exposure over IIS wear time. This may have implications for PWD and designers of closed-loop algorithms, although larger studies are necessary to confirm this. The study was registered in clinicaltrials.gov (NCT04398030).

Improving Glycemic Control During The Covid-19 Pandemic: A Quality Improvement Project, Megan Henderson

Doctors of Nursing Practice (DNP) Final Projects, 2020-current

Diabetes is a costly, chronic health condition. The COVID-19 pandemic has significantly impacted the delivery of health care and exacerbated chronic health conditions, such as diabetes. Diabetes is one of the most significant comorbid conditions associated with poor COVID-19 outcomes (Cariou et al., 2020). Control of blood glucose levels during the COVID-19 pandemic has proved challenging to maintain. The purpose of this quality improvement project is to identify gaps in diabetic self-care and then implement a diabetic toolkit to improve self-efficacy of diabetes self-management. According to the American Diabetes Association (2022), self-management of diabetes, education, and support from providers is …

3d Imaging Analysis On An Organoid-Based Platform Guides Personalized Treatment In Pancreatic Ductal Adenocarcinoma, Ya'an Kang, Jenying Deng, Jianhua Ling, Xinqun Li, Yi-Ju Chiang, Eugene J Koay, Huamin Wang, Jared K Burks, Paul J Chiao, Mark W Hurd, Manoop S Bhutani, Jeffrey H Lee, Brian R Weston, Anirban Maitra, Naruhiko Ikoma, Ching-Wei D Tzeng, Jeffrey E Lee, Ronald A Depinho, Robert A Wolff, Shubham Pant, Florencia Mcallister, Matthew Hg Katz, Jason B Fleming, Michael P Kim

Faculty, Staff and Student Publications

BACKGROUNDPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with unpredictable responses to chemotherapy. Approaches to assay patient tumors before treatment and identify effective treatment regimens based on tumor sensitivities are lacking. We developed an organoid-based platform (OBP) to visually quantify patient-derived organoid (PDO) responses to drug treatments and associated tumor-stroma modulation for personalized PDAC therapy.METHODSWe retrospectively quantified apoptotic responses and tumor-stroma cell proportions in PDOs via 3D immunofluorescence imaging through annexin A5, α-smooth muscle actin (α-SMA), and cytokeratin 19 (CK-19) levels. Simultaneously, an ex vivo organoid drug sensitivity assay (ODSA) was used to measure responses to standard-of-care …

Evaluation Of Recombinant Live-Attenuated Respiratory Syncytial Virus (Rsv) Vaccines Rsv/Δns2/Δ1313/I1314l And Rsv/276 In Rsv-Seronegative Children, Coleen K Cunningham, Ruth A Karron, Petronella Muresan, Matthew S Kelly, Elizabeth J Mcfarland, Charlotte Perlowski, Jennifer Libous, Jennifer Oliva, Patrick Jean-Philippe, Jack Moye, Elizabeth Schappell, Emily Barr, Vivian Rexroad, Benjamin Johnston, Ellen G Chadwick, Mikhaela Cielo, Mary Paul, Jaime G Deville, Mariam Aziz, Lijuan Yang, Cindy Luongo, Peter L Collins, Ursula J Buchholz, International Maternal Pediatric Adolescent Aids Clinical Trials (Impaact) 2018 Study Team

Children’s Nutrition Research Center Staff Publications

Background: This United States-based study compared 2 candidate vaccines: RSV/ΔNS2/Δ1313/I1314L, attenuated by NS2 gene-deletion and temperature-sensitivity mutation in the polymerase gene; and RSV/276, attenuated by M2-2 deletion.

Methods: RSV-seronegative children aged 6-24 months received RSV/ΔNS2/Δ1313/I1314L (106 plaque-forming units [PFU]), RSV/276 (105 PFU), or placebo intranasally. Participants were monitored for vaccine shedding, reactogenicity, and RSV serum antibodies, and followed over the subsequent RSV season.

Results: Enrollment occurred September 2017 to October 2019. During 28 days postinoculation, upper respiratory illness and/or fever occurred in 64% of RSV/ΔNS2/Δ1313/I1314L, 84% of RSV/276, and 58% of placebo recipients. Symptoms were generally mild. Cough was more …

Exploring Alternative Treatment Options For A Patient With Heavy Menstrual Bleeding And Mistrust Of The Healthcare System, Rachel A. O'Dell

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Tinelli A, Gustapane S, D’Oria O, Licchelli M, Panese G. Nutraceuticals in fibroid management after ulipristal acetate administration: An observational study on patients’ compliance. International Journal of Gynecology and Obstetrics; 2022;156(1):133-138. https://doi.org/10.1002/ijgo.13692

for a patient with chronic, symptomatic anemia with menorrhagia and uterine fibroid.

The Importance Of Stigma Theory For Clinical Decisions Related To Diabetic Foot Amputations, Rachael Garcia, Callie Bartkowiak, Alison Nesbitt Do

Clinical Research in Practice: The Journal of Team Hippocrates

The authors examine the unconsidered impact of social stigma theory on the shared clinical decision-making process for a patient with foot osteomyelitis and MRSA bacteremia facing the prospect of an amputation.

Glucocentric Drugs In Cardiovascular Disease Protection And Heart Failure, Khawaja M. Talha, Gregg C. Fonarow, Salim S. Virani, Javed Butler

Office of the Provost

Evidence for cardiovascular outcomes with older-generation antihyperglycemic drugs in the management of type 2 diabetes is based on aggregated data from prior randomized controlled trials and observational studies that were not focused on prespecified cardiovascular end points. Newer antihyperglycemic medications have undergone a rigorous evaluation of cardiovascular outcomes through randomized controlled trials since the US Food and Drug Administration imposed a mandatory requirement for all glucose-lowering drugs in 2008. The three classes of drugs that have been most extensively studied are dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter-2 (SGLT2) inhibitors, the latter two reporting significant …

The Integrative Conjugative Element Icespym92 Contributes To Pathogenicity Of Emergent Antimicrobial-Resistant Emm92 Group A Streptococcus, Ji-Sun Lee, Michael W Lero, Jose Mercado-Matos, Sha Zhu, Minjeong Jo, Claire E Tocheny, Jennifer S Morgan, Leslie M Shaw

Faculty, Staff and Student Publications

Despite the strong association of the insulin/insulin-like growth factor (IGF) signaling (IIS) pathway with tumor initiation, recurrence, and metastasis, the mechanism by which this pathway regulates cancer progression is not well understood. Here, we report that IIS supports breast cancer stem cell (CSC) self-renewal in an IRS2-phosphatidylinositol 3-kinase (PI3K)-dependent manner that involves the activation and stabilization of MYC. IRS2-PI3K signaling enhances MYC expression through the inhibition of GSK3β activity and suppression of MYC phosphorylation on threonine 58, thus reducing proteasome-mediated degradation of MYC and sustaining active pS62-MYC function. A stable T58A-Myc mutant rescues CSC function in Irs2−/− cells, supporting …

Heavy Metals As Risk Factors For Human Diseases - A Bayesian Network Approach, M Perrelli, R Wu, D J Liu, R G Lucchini, L Del Bosque-Plata, Michael Vergare, M P Akhter, J Ott, Claudia Gragnoli

Division of Endocrinology, Diabetes and Metabolic Diseases Faculty Papers

Modern industrial agricultural processes expose human beings to multifactorial environmental pollution including heightened levels of heavy metals. The effects of acute heavy metal exposures at toxic levels are usually known; they are tested for and treated promptly. The effects of low/moderate-level chronic heavy metal exposures are less known as they may be subclinical, and pathogenic effects may only manifest clinically over time under the disguise of a diagnosable disease or miscellaneous symptoms attributed to aging. Consequently, the health impact of low-moderate heavy metal exposure is unlikely to be identified. Furthermore, established heavy metal safety levels often fail to recognize the …

Rising Costs Of Insulin And Effects Of Self-Management In Type 1 Diabetes, Justine Yadao

Nursing | Senior Theses

Background

Type 1 diabetes, also known as juvenile diabetes or insulin-dependent diabetes is a chronic condition where the pancreas may not be able to produce little to no insulin. This type of diabetes can be attributed to some factors such as age, family history, environmental factors or types of viruses. It is seen more often in children or adolescence but can develop in adults, averaging approximately 5-10% of the population.

Insulin is a type of hormone produced in the pancreas naturally or can be manufactured in the laboratory. People with Type 1 Diabetes need insulin from an exogenous source to …

Dietary And Complementary Feeding Practices Of Us Infants, 6 To 12 Months: A Narrative Review Of The Federal Nutrition Monitoring Data, Regan L Bailey, Jaime S Stang, Teresa A Davis, Timothy S Naimi, Barbara O Schneeman, Kathryn G Dewey, Sharon M Donovan, Rachel Novotny, Ronald E Kleinman, Elsie M Taveras, Lydia Bazzano, Linda G Snetselaar, Janet De Jesus, Kellie O Casavale, Eve E Stoody, Joseph D Goldman, Alanna J Moshfegh, Donna G Rhodes, Kirsten A Herrick, Kristin Koegel, Cria G Perrine, Tusarebecca Pannucci

Children’s Nutrition Research Center Staff Publications

Complementary foods and beverages (CFBs) are key components of an infant’s diet in the second 6 months of life. This article summarizes nutrition and feeding practices examined by the 2020 Dietary Guidelines Advisory Committees during the CFB life stage. Breastfeeding initiation is high (84%), but exclusive breastfeeding at 6 months (26%) is below the Healthy People 2030 goal (42%). Most infants (51%) are introduced to CFBs sometime before 6 months. The primary mode of feeding (ie, human milk fed [HMF]; infant formula or mixed formula and human milk fed [FMF]) at the initiation of CFBs is associated with the timing …

Randomization, Design And Analysis For Interdependency In Aging Research: No Person Or Mouse Is An Island, Daniella E Chusyd, Steven N Austad, Stephanie L Dickinson, Keisuke Ejima, Gary L Gadbury, Lilian Golzarri-Arroyo, Richard J Holden, Yasaman Jamshidi-Naeini, Doug Landsittel, Tapan Mehta, J Michael Oakes, Arthur H Owora, Greg Pavela, Javier Rojo, Michael W Sandel, Daniel L Smith, Colby J Vorland, Pengcheng Xun, Roger Zoh, David B Allison

Children’s Nutrition Research Center Staff Publications

Investigators traditionally use randomized designs and corresponding analysis procedures to make causal inferences about the effects of interventions, assuming independence between an individual's outcome and treatment assignment and the outcomes of other individuals in the study. Often, such independence may not hold. We provide examples of interdependency in model organism studies and human trials and group effects in aging research and then discuss methodologic issues and solutions. We group methodologic issues as they pertain to (1) single-stage individually randomized trials; (2) cluster-randomized controlled trials; (3) pseudo-cluster-randomized trials; (4) individually randomized group treatment; and (5) two-stage randomized designs. Although we present …

Incidence Of An Insulin-Requiring Hyperglycemic Syndrome In Sars-Cov-2-Infected Young Individuals: Is It Type 1 Diabetes?, Massimo Pietropaolo, Peter Hotez, Nick Giannoukakis

Center for Medical Ethics and Health Policy Staff Publications

Pancreatic ACE2 receptor expression, together with increased prevalence of insulin-requiring hyperglycemia in patients with coronavirus disease 2019 (COVID-19), suggested that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pancreatic infection might trigger a β-cell-selective inflammation precipitating autoimmune type 1 diabetes (T1D). We examined T1D incidence in patients with COVID-19 inside a large, global population using a "big data" approach. The incidence in 0-30-year-old patients with confirmed COVID-19 over an ∼15-month period from the beginning of the COVID-19 pandemic was compared with an age-matched population without COVID-19 inside the TriNetX COVID-19 Research Network (>80 million deidentified patient electronic medical records globally). …

Impact Of Diabetes Status And Related Factors On Covid-19-Associated Hospitalization: A Nationwide Retrospective Cohort Study Of 116,370 Adults With Sars-Cov-2 Infection., Erin M. Tallon, Osagie Ebekozien, Janine Sanchez, Vincent S. Staggs, Diana Ferro, Ryan Mcdonough, Carla Demeterco-Berggren, Sarit Polsky, Patricia Gomez, Neha Patel, Priya Prahalad, Ori Odugbesan, Priyanka Mathias, Joyce M. Lee, Chelsey Smith, Chi-Ren Shyu, Mark A. Clements

Manuscripts, Articles, Book Chapters and Other Papers

Aims: We examined diabetes status (no diabetes; type 1 diabetes [T1D]; type 2 diabetes [T2D]) and other demographic and clinical factors as correlates of coronavirus disease 2019 (COVID-19)-related hospitalization. Further, we evaluated predictors of COVID-19-related hospitalization in T1D and T2D.

Methods: We analyzed electronic health record data from the de-identified COVID-19 database (December 2019 through mid-September 2020; 87 US health systems). Logistic mixed models were used to examine predictors of hospitalization at index encounters associated with confirmed SARS-CoV-2 infection.

Results: In 116,370 adults ( >=18 years old) with COVID-19 (93,098 no diabetes; 802 T1D; 22,470 T2D), factors that independently increased …

International Pooled Patient-Level Meta-Analysis Of Ketamine Infusion For Depression: In Search Of Clinical Moderators, Rebecca B Price, Nicholas Kissel, Andrew Baumeister, Rebecca Rohac, Mary L Woody, Elizabeth D Ballard, Carlos A Zarate, William Deakin, Chadi G Abdallah, Adriana Feder, Dennis S Charney, Michael F Grunebaum, J John Mann, Sanjay J Mathew, Bronagh Gallagher, Declan M Mcloughlin, James W Murrough, Suresh Muthukumaraswamy, Rebecca Mcmillan, Rachael Sumner, George Papakostas, Maurizio Fava, Rebecca Hock, Jennifer L Phillips, Pierre Blier, Paulo Shiroma, Peter Šóš, Tung-Ping Su, Mu-Hong Chen, Mikael Tiger, Johan Lundberg, Samuel T Wilkinson, Meredith L Wallace

Children’s Nutrition Research Center Staff Publications

Depression is disabling and highly prevalent. Intravenous (IV) ketamine displays rapid-onset antidepressant properties, but little is known regarding which patients are most likely to benefit, limiting personalized prescriptions. We identified randomized controlled trials of IV ketamine that recruited individuals with a relevant psychiatric diagnosis (e.g., unipolar or bipolar depression; post-traumatic stress disorder), included one or more control arms, did not provide any other study-administered treatment in conjunction with ketamine (although clinically prescribed concurrent treatments were allowable), and assessed outcome using either the Montgomery-Åsberg Depression Rating Scale or the Hamilton Rating Scale for Depression (HRSD-17). Individual patient-level data for at least …

Analysis Of Genome-Wide Knockout Mouse Database Identifies Candidate Ciliopathy Genes, Kendall Higgins, Bret A Moore, Zorana Berberovic, Hibret A Adissu, Mohammad Eskandarian, Ann M Flenniken, Andy Shao, Denise M Imai, Dave Clary, Louise Lanoue, Susan Newbigging, Lauryl M J Nutter, David J Adams, Fatima Bosch, Robert E Braun, Steve D M Brown, Mary E Dickinson, Michael Dobbie, Paul Flicek, Xiang Gao, Sanjeev Galande, Anne Grobler, Jason D Heaney, Yann Herault, Martin Hrabe De Angelis, Hsian-Jean Genie Chin, Fabio Mammano, Chuan Qin, Toshihiko Shiroishi, Radislav Sedlacek, J-K Seong, Ying Xu, Impc Consortium, K C Kent Lloyd, Colin Mckerlie, Ala Moshiri

Faculty, Staff and Students Publications

We searched a database of single-gene knockout (KO) mice produced by the International Mouse Phenotyping Consortium (IMPC) to identify candidate ciliopathy genes. We first screened for phenotypes in mouse lines with both ocular and renal or reproductive trait abnormalities. The STRING protein interaction tool was used to identify interactions between known cilia gene products and those encoded by the genes in individual knockout mouse strains in order to generate a list of "candidate ciliopathy genes." From this list, 32 genes encoded proteins predicted to interact with known ciliopathy proteins. Of these, 25 had no previously described roles in ciliary pathobiology. …

Dawn-To-Dusk Dry Fasting Induces Anti-Atherosclerotic, Anti-Inflammatory, And Anti-Tumorigenic Proteome In Peripheral Blood Mononuclear Cells In Subjects With Metabolic Syndrome, Ayse L Mindikoglu, Jihwan Park, Antone R Opekun, Mustafa M Abdulsada, Zoe R Wilhelm, Prasun K Jalal, Sridevi Devaraj, Sung Yun Jung

Faculty, Staff and Students Publications

BACKGROUND: Metabolic syndrome characterized by abdominal obesity, high blood pressure, elevated fasting glucose and triglyceride levels and low high-density lipoprotein cholesterol level is associated with pro-inflammatory state, increased risk for atherosclerosis, and multiple cancers. Our previous results on subjects with metabolic syndrome showed that 4-week dawn-to-dusk (sunset) dry fasting resulted in significant changes in the serum proteome and improvement in several metabolic risk factors. Peripheral blood mononuclear cells (PBMC) proteomics is a powerful tool that can provide mechanistic insights into how dawn-to-dusk dry fasting affects protein expression in metabolic pathways at cellular level. In this study, we determined whether dawn-to-dusk …

Human Islet Amyloid Polypeptide (Hiapp) Protofibril-Specific Antibodies For Detection And Treatment Of Type 2 Diabetes, Angelina S Bortoletto, W Vallen Graham, Gabriella Trout, Alessandra Bonito-Oliva, Manija A Kazmi, Jing Gong, Emily Weyburne, Brandy L Houser, Thomas P Sakmar, Ronald J Parchem

Faculty, Staff and Students Publications

Type 2 diabetes mellitus (T2D) is a major public health concern and is characterized by sustained hyperglycemia due to insulin resistance and destruction of insulin-producing β cells. One pathological hallmark of T2D is the toxic accumulation of human islet amyloid polypeptide (hIAPP) aggregates. Monomeric hIAPP is a hormone normally co-secreted with insulin. However, increased levels of hIAPP in prediabetic and diabetic patients can lead to the formation of hIAPP protofibrils, which are toxic to β cells. Current therapies fail to address hIAPP aggregation and current screening modalities do not detect it. Using a stabilizing capping protein, monoclonal antibodies (mAbs) can …

Mechanisms Of Cancer Metastasis, Maria Castaneda, Petra Den Hollander, Nick A Kuburich, Jeffrey M Rosen, Sendurai A Mani

Faculty, Staff and Students Publications

Metastatic cancer is almost always terminal, and more than 90% of cancer deaths result from metastatic disease. Combating cancer metastasis and post-therapeutic recurrence successfully requires understanding each step of metastatic progression. This review describes the current state of knowledge of the etiology and mechanism of cancer progression from primary tumor growth to the formation of new tumors in other parts of the body. Open questions, avenues for future research, and therapeutic approaches with the potential to prevent or inhibit metastasis through personalization to each patient's mutation and/or immune profile are also highlighted.

Digital Biomarkers Of Gait And Balance In Diabetic Foot, Measurable By Wearable Inertial Measurement Units: A Mini Review, Gu Eon Kang, Angeloh Stout, Ke'vaughn Waldon, Seungmin Kang, Amanda L Killeen, Peter A Crisologo, Michael Siah, Daniel Jupiter, Bijan Najafi, Ashkan Vaziri, Lawrence A Lavery

Center on Aging Staff Publications

People with diabetic foot frequently exhibit gait and balance dysfunction. Recent advances in wearable inertial measurement units (IMUs) enable to assess some of the gait and balance dysfunction associated with diabetic foot (i.e., digital biomarkers of gait and balance). However, there is no review to inform digital biomarkers of gait and balance dysfunction related to diabetic foot, measurable by wearable IMUs (e.g., what gait and balance parameters can wearable IMUs collect? Are the measurements repeatable?). Accordingly, we conducted a web-based, mini review using PubMed. Our search was limited to human subjects and English-written papers published in peer-reviewed journals. We identified …

Variation In Human Water Turnover Associated With Environmental And Lifestyle Factors, Yosuke Yamada, Xueying Zhang, Mary E T Henderson, Hiroyuki Sagayama, Herman Pontzer, Daiki Watanabe, Tsukasa Yoshida, Misaka Kimura, Philip N Ainslie, Lene F Andersen, Liam J Anderson, Lenore Arab, Issad Baddou, Kweku Bedu-Addo, Ellen E Blaak, Stephane Blanc, Alberto G Bonomi, Carlijn V C Bouten, Pascal Bovet, Maciej S Buchowski, Nancy F Butte, Stefan G Camps, Graeme L Close, Jamie A Cooper, Richard Cooper, Sai Krupa Das, Lara R Dugas, Simon Eaton, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Annelies H Goris, Michael Gurven, Lewis G Halsey, Catherine Hambly, Asmaa El Hamdouchi, Marije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek M Joosen, Peter Katzmarzyk, Kitty P Kempen, William E Kraus, Wantanee Kriengsinyos, Robert F Kushner, Estelle V Lambert, William R Leonard, Nader Lessan, Corby K Martin, Anine C Medin, Erwin P Meijer, James C Morehen, James P Morton, Marian L Neuhouser, Theresa A Nicklas, Robert M Ojiambo, Kirsi H Pietiläinen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Roberto A Rabinovich, Susan B Racette, David A Raichlen, Eric Ravussin, Leanne M Redman, John J Reilly, Rebecca M Reynolds, Susan B Roberts, Albertine J Schuit, Luis B Sardinha, Analiza M Silva, Anders M Sjödin, Eric Stice, Samuel S Urlacher, Giulio Valenti, Ludo M Van Etten, Edgar A Van Mil, Jonathan C K Wells, George Wilson, Brian M Wood, Jack A Yanovski, Alexia J Murphy-Alford, Cornelia U Loechl, Amy H Luke, Jennifer Rood, Klaas R Westerterp, William W Wong, Motohiko Miyachi, Dale A Schoeller, John R Speakman

Children’s Nutrition Research Center Staff Publications

Water is essential for survival, but one in three individuals worldwide (2.2 billion people) lack access to safe drinking water. Water intake requirements largely reflect water turnover (WT), the water used by the body each day. We investigated the determinants of human WT in 5,604 people from the ages of 8 days to 96 years from 26 countries using isotope tracking (2H) methods. Age, body size, and composition were significantly associated with WT as were physical activity, athletic status, pregnancy, socioeconomic status, and environmental characteristics (latitude, altitude, air temperature, and humidity). People in countries with low human development index (HDI) …

From Model Organisms To Humans, The Opportunity For More Rigor In Methodologic And Statistical Analysis, Design, And Interpretation Of Aging And Senescence Research, Daniella E Chusyd, Steven N Austad, Andrew W Brown, Xiwei Chen, Stephanie L Dickinson, Keisuke Ejima, David Fluharty, Lilian Golzarri-Arroyo, Richard Holden, Yasaman Jamshidi-Naeini, Doug Landsittel, Stella Lartey, Edward Mannix, Colby J Vorland, David B Allison

Children’s Nutrition Research Center Staff Publications

This review identifies frequent design and analysis errors in aging and senescence research and discusses best practices in study design, statistical methods, analyses, and interpretation. Recommendations are offered for how to avoid these problems. The following issues are addressed: (a) errors in randomization, (b) errors related to testing within-group instead of between-group differences, (c) failing to account for clustering, (d) failing to consider interference effects, (e) standardizing metrics of effect size, (f) maximum life-span testing, (g) testing for effects beyond the mean, (h) tests for power and sample size, (i) compression of morbidity versus survival curve squaring, and (j) other …

Cardiovascular/Stroke Risk Stratification In Diabetic Foot Infection Patients Using Deep Learning-Based Artificial Intelligence: An Investigative Study., Narendra N Khanna, Mahesh A Maindarkar, Vijay Viswanathan, Anudeep Puvvula, Sudip Paul, Mrinalini Bhagawati, Puneet Ahluwalia, Zoltan Ruzsa, Aditya Sharma, Raghu Kolluri, Padukone R Krishnan, Inder M Singh, John R Laird, Mostafa Fatemi, Azra Alizad, Surinder K Dhanjil, Luca Saba, Antonella Balestrieri, Gavino Faa, Kosmas I Paraskevas, Durga Prasanna Misra, Vikas Agarwal, Aman Sharma, Jagjit S Teji, Mustafa Al-Maini, Andrew Nicolaides, Vijay Rathore, Subbaram Naidu, Kiera Liblik, Amer M Johri, Monika Turk, David W Sobel, Martin Miner, Klaudija Viskovic, George Tsoulfas, Athanasios D Protogerou, Sophie Mavrogeni, George D Kitas, Mostafa M Fouda, Mannudeep K Kalra, Jasjit S Suri

Heart and Vascular Articles

A diabetic foot infection (DFI) is among the most serious, incurable, and costly to treat conditions. The presence of a DFI renders machine learning (ML) systems extremely nonlinear, posing difficulties in CVD/stroke risk stratification. In addition, there is a limited number of well-explained ML paradigms due to comorbidity, sample size limits, and weak scientific and clinical validation methodologies. Deep neural networks (DNN) are potent machines for learning that generalize nonlinear situations. The objective of this article is to propose a novel investigation of deep learning (DL) solutions for predicting CVD/stroke risk in DFI patients. The Preferred Reporting Items for Systematic …

Spatial Definition Of The Human Progesterone Receptor-B Transcriptional Complex, Xinzhe Yu, Ping Yi, Anil K Panigrahi, Lance Edward V Lumahan, John P Lydon, David M Lonard, Steven J Lutdke, Zhao Wang, Bert W O'Malley

Faculty, Staff and Students Publications

We report the quaternary structure of core transcriptional complex for the full-length human progesterone receptor-B (PR-B) homodimer with primary coactivator steroid receptor coactivator-2 (SRC-2) and the secondary coactivator p300/CREB-binding protein (CBP). The PR-B homodimer engages one SRC-2 mainly through its activation function 1 (AF1) in N-terminus. SRC-2 is positioned between PR-B and p300 leaving space for direct interaction between PR-B and p300 through PR-B's C-terminal AF2 and its unique AF3. Direct AF3/p300 interaction provides long-desired structural insights into the known functional differences between PR-B and the PR-A isoform lacking AF3. We reveal the contributions of each AF and demonstrate their …