Miracle-dz/UniFAR-FTUs huggingface dataset:
The medical management of menopause: A four country comparison of urban care

Objective—To compare the medical management of menopause across urban areas in four countries which differ by level of income and degree of medicalization. Methods—Surveys of health providers who advise women on the menopausal transition were carried out in Beirut, Lebanon (n=100), Madrid, Spain (n=60), Worcester, Massachusetts, U.S. (n=59), and Rabat, Morocco (n=50) from 2002 to 2004. Physician characteristics, hormone therapy (HT) prescribing practices, and concerns about the management of menopause were compared across countries using chi-square and logistic regression analyses. Results—After controlling for physician specialty and sex, physicians in Madrid (OR 3.228) and Massachusetts (OR 7.641) were more likely to write >5 prescriptions for HT per month compared with physicians in Beirut. Physicians in Massachusetts (OR 3.961) were most likely to recommended HT for 10 years or more. Physicians in Madrid were significantly less likely to talk with patients about menopause for ≥ 15 minutes (OR 0.160), and were less likely to say that the benefit of HT was “very high” for symptom alleviation (OR 0.253) or osteoporosis prevention (OR 0.146). Physicians in Beirut were most likely to obtain a mammogram and an endometrial biopsy prior to treating symptoms. Physicians in Massachusetts (OR 0.298) and Rabat (OR 0.399) were significantly less apt to describe their concern about breast cancer as “serious. ” Conclusions—Prescription patterns and perceived benefits of HT appear to reflect local medical culture rather than simply physician characteristics. The impact of the WHI study was seen in prescribing patterns and concerns about HT. Physicians in all 4 countries were generally well informed. Corresponding author: Lynnette Leidy Sievert, Department of Anthropology, Machmer Hall, 240 Hicks Way, UMass Amherst, Amherst, MA 01003-9278, (413) 545-1379 fax (413) 545-9494, leidy@anthro.umass. edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author Manuscript Maturitas. Author manuscript; available in PMC 2009 January 20. Published in final edited form as: Maturitas. 2008 January 20; 59(1): 7–21. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript
Cardiovascular Risk in Patients with Psoriasis

Psoriasis is a chronic inflammatory skin disease, which affects 2-3% of the U.S. population. The immune response in psoriasis includes enhanced activation of T cells and myeloid cells, platelet activation, and upregulation of interferons, tumor necrosis factor-α, and interleukin (IL)s IL-23, IL-17, and IL-6, which are linked to vascular inflammation and atherosclerosis development. Patients with psoriasis are up to 50% more likely to develop cardiovascular disease (CV) disease, and this CV risk increases with skin severity. Major society guidelines now advocate incorporating a psoriasis diagnosis into CV risk prediction and prevention strategies. While registry data suggest treatment targeting psoriasis skin disease reduces vascular inflammation, coronary plaque burden, and may reduce CV risk, randomized placebo-controlled trials are inconclusive to date. Further studies are required to define traditional CV risk factor goals, the optimal role of lipid-lowering and antiplatelet therapy, and targeted psoriasis therapies on CV risk. Condensed Abstract: Psoriasis is a chronic inflammatory skin disease linked to enhanced cardiovascular (CV) risk. The inflammatory milieu in psoriasis includes T-cells, myeloid cells, and cytokines such as interferons, TNF-α, and the interleukin (IL)s IL-23, IL-17, and IL-6, which are linked to atherosclerosis development. Guidelines now suggest incorporating a psoriasis diagnosis into CV risk prediction and prevention strategies. While observational data suggests treatment of psoriasis can reduce CV risk, randomized controlled trials assessing treatments to reduce CV risk Address for correspondence: Michael S. Garshick, Cardio-Rheumatology Program, Center for the Prevention of Cardiovascular Disease, New York University Langone Health, 435 East 30th Street, 7th Floor, New York City, NY 10016, T 646-501-8361, F 212-263-7908, Michael.garshick@nyumc.org, Twitter: @garshick. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access Author manuscript J Am Coll Cardiol. Author manuscript; available in PMC 2022 April 06. Published in final edited form as: J Am Coll Cardiol. 2021 April 06; 77(13): 1670–1680. doi:10.1016/j.jacc. 2021.02. 009. A uhor M anscript
Computational analysis of the binding mode of 8-oxo-guanine to formamidopyrimidine-DNA glycosylase

8-oxo-guanine (8OG) is the most prevalent form of oxidative DNA damage. In bacteria, 8OG is excised by formamidopyrimidine glycosylase (Fpg) as the initial step in base excision repair. To efficiently excise this lesion, Fpg must discriminate between 8OG and an excess of guanine in duplex DNA. In this study, we explore the structural basis underlying this high degree of selectivity. Two structures have been reported in which Fpg is bound to DNA, differing with respect to the position of the lesion in the active site, one structure showing 8OG bound in the syn conformation, the other in anti. Remarkably, the results of our all-atom simulations are consistent with both structures. The syn conformation observed in the crystallographic structure of Fpg obtained from B. stearothermophilus is stabilized through interaction with E77, a non-conserved residue. Replacement of E77 by Ser, creating the Fpg sequence found in E. coli and other bacteria, results in preferred binding of 8OG in the anti conformation. Our calculations provide novel insights into the roles of active site residues in binding and recognition of 8OG by Fpg. DNA is a major target of oxidative damage which, in turn, has been linked to human diseases associated with aging, including cancer (1, 2). 8-oxoguanine (8OG) (3) is one of the most common forms of oxidative DNA damage(4); failure to repair this lesion prior to DNA replication leads to G:C to A:T transversion mutations in bacterial and mammalian cells(5). In E. coli, Fpg (MutM), MutY and MutT work in concert to counter the potentially deleterious effects of 8OG (6, 7). Fpg is an 8-oxoguanine-DNA glycosylase/AP lyase which excises 8OG from oxidatively damaged DNA. This multi-step process is initiated by nucleophilic attack on C1′ by the N-terminal proline of Fpg, forming a Schiff base intermediate. Proton abstraction leads to βelimination of the 3′ phosphate, followed by hydrolysis of the Schiff base and δ-elimination, generating a single base gap (8, 9). To whom correspondence should be addressed: carlos.simmerling@stonybrook.edu, (631-632-1336 (phone), 631-632-1555 (fax)). Supporting information available: Figures S1–S4, Table S1. This material is available free of charge via the Internet at http:// pubs.acs. org HHS Public Access Author manuscript Biochemistry. Author manuscript; available in PMC 2021 July 22. Published in final edited form as: Biochemistry. 2006 September 12; 45(36): 10886–10894. doi:10.1021/bi060380m. A uhor M anscript
Patient Specific Organ and Effective Dose Estimates in Adult Oncology Computed Tomography

Purpose—Patient specific organ and effective dose provides essential information for CT protocol optimization. However, such information is not readily available in the scan records. This study is to develop a method to obtain accurate examinationand patient-specific organ and effective dose estimates employing available scan data and patient body size information for a large cohort of patients.
Modeling Combination Hepatitis C Virus Treatment and Prevention Strategies in a Network of People Who Inject Drugs in the United States

Received 2 September 2019; editorial decision 4 February 2020; accepted 13 February 2020; published online February 15, 2020. Correspondence: A. Zelenev, AIDS Program, Section of Infectious Diseases, Department of Internal Medicine, Yale School of Medicine, 135 College St, New Haven, CT 06510-2283 (alexei. zelenev@yale.edu). Clinical Infectious Diseases 2021;72(5):755–63 © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. DOI: 10.1093/cid/ciaa142 Modeling Combination Hepatitis C Virus Treatment and Prevention Strategies in a Network of People Who Inject Drugs in the United States
HLA class II polymorphisms modulate gut microbiota and EAE phenotype

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system in which the interaction between genetic and environmental factors plays an important role in disease pathogenesis. Although environmental factors account for 70% of disease risk, the exact environmental factors associated with MS are unknown. Recently, gut microbiota has emerged as a potential missing environmental factor linked with the pathobiology of MS. Yet, how genetic factors, such as HLA class-II gene(s), interact with gut microbiota and influence MS is unclear. In the present study, we investigated whether HLA class-II genes that regulate EAE and MS susceptibility also influence gut microbiota. Previously, we have shown that HLA-DR3 transgenic mice lacking endogenous mouse class II genes (AE-KO) were susceptible to myelin proteolipid protein (PLP91-110)-induced experimental autoimmune encephalomyelitis (EAE), an animal model of MS, while AE-KO.HLA-DQ8 transgenic mice were resistant. Surprisingly, HLA-DR3.DQ8 double transgenic mice showed higher disease incidence and severity compared to HLA-DR3 mice. Gut microbiota analysis showed that HLA-DR3, HLA-DQ8, and HLA-DR3.DQ8 double transgenic mice microbiota are compositionally different from AE-KO mice. Within HLA-class-II transgenic mice, the microbiota of HLA-DQ8 mice were more similar to HLA-DR3.DQ8 than HLA-DR3. As the presence of DQ8 on an HLA-DR3 background increases disease severity, our data suggests that HLA-DQ8-specific microbiota may contribute to disease severity in HLADR3.DQ8 mice. Altogether, our study provides evidence that the HLA-DR and -DQ genes linked to specific gut microbiota contribute to EAE susceptibility or resistance in a transgenic animal model of MS. Corresponding Author Ashutosh K. Mangalam, Ph.D., Department of Pathology, University of Iowa Carver College of Medicine, 25 S. Grand Avenue, 1080A ML, Iowa City, IA 52242, Phone: 1-319-335-8558, Fax: 1-319-384-0848 ashutoshmangalam@uiowa.edu. |Authors contributed equally Disclosure of potential conflicts of interest: AKM is an inventor of the use of Prevotella histicola for treatment of autoimmune disease and the patent is owned by Mayo Clinic Rochester, USA. The technology has been licensed by Mayo Clinic to Evelo Biosciences. AKM received royalties from Mayo Clinic (paid by Evelo Biosciences). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. HHS Public Access Author manuscript Immunohorizons. Author manuscript; available in PMC 2022 January 05. Published in final edited form as: Immunohorizons. ; 5(8): 627–646. doi:10.4049/immunohorizons.2100024. A uhor M anscript
SIGNIFICANCE OF DIM ERS TO THE SIZE OF NEWLY SYNTHESIZED DNA IN UV-IRRADIATED CHINESE HAMSTER OVARY CELLS

DNA synthesized after UV irradiation is smaller than that in unirradiated cells even when pulse-labeling times are increased to compensate for the overall reduction in the rate ofDNA replication. By isolating newly replicated DNA, incubating it with dimer-specific endonuclease from Micrococcus luteus, and analyzing it on alkaline sucrose gradients, we have been able to demonstrate that this DNA is synthesized in segments corresponding in size to the interdimer distance on the parental strand. In addition, the same DNA analyzed on neutral gradients shows no reduction in molecular weight as a result of UV irradiation and/or endonuclease digestion. Our data are thus inconsistent with the presence of "gaps" in newly synthesized DNA opposite the dimers on the parental strand. We suggest that if such gaps are produced as a result of delayed synthesis around dimers, they are filled before the growing point reaches the next dimer.
PHOTODISSOCIATION OF CO AND 02 FROM a AND 1 HEMOGLOBIN CHAINS STUDIED BY USING PICOSECOND ABSORPTION SPECTROSCOPY

The picosecond photodissociation of the CO and 02 forms of a and 13 chains of hemoglobin were studied by following rr* Soret absorption changes using a Nd3+ phosphate-glass laser, 531-nm pump pulse, 8 ps full width half maximum, and a pump-probe double-beam absorption apparatus. Three intermediates were observed within the first 50 ps after photon absorption. The most notable differences between the two monomers are the extent and rate of geminate recombination with the two ligands. We attribute this result to differences between the tertiary protein structure of the a and ,B forms of Hb, both distal and proximal.
Noonan Syndrome

Type 1 neurofibromatosis (NFl), Watson syndrome (WS), and Noonan syndrome (NS) show some overlap in clinical manifestations. In addition, WS has been shown to be linked to markers flanking the NF1 locus and a deletion at the NF1 locus demonstrated in a WS patient. This suggests either that WS and NF1 are allelic or that phenotypes arise from mutations in very closely linked genes. Here we provide evidence for the former by demonstrating a mutation in the NF1 gene in a family with features of both WS and NS. The mutation is an almost perfect in-frame tandem duplication of 42 bases in exon 28 of the NFl gene. Unlike the mutations previously described in classical NF1, which show a preponderance of null alleles, the mutation in this family would be expected to result in a mutant neurofibromin product.
CRITICAL REVIEW Nutritional Aspects of Gastrointestinal Wound Healing

Significance: Although the wound healing cascade is similar in many tissues, in the gastrointestinal tract mucosal healing is critical for processes such as inflammatory bowel disease and ulcers and healing of the mucosa, submucosa, and serosal layers is needed for surgical anastomoses and for enterocutaneous fistula. Failure of wound healing can result in complications including infection, prolonged hospitalization, critical illness, organ failure, readmission, new or worsening enterocutaneous fistula, and even death. Recent Advances: Recent advances are relevant for the role of specific micronutrients, such as vitamin D, trace elements, and the interplay between molecules with proand antioxidant properties. Our understanding of the role of other small molecules, genes, proteins, and macronutrients is also rapidly changing. Recent work has elucidated relationships between oxidative stress, nutritional supplementation, and glucose metabolism. Thresholds have also been established to define adequate preoperative nutritional status. Critical Issues: Further work is needed to establish standards and definitions for measuring the extent of wound healing, particularly for inflammatory bowel disease and ulcers. In addition, a mounting body of evidence has determined the need for adequate preoperative nutritional supplementation for elective surgical procedures. Future Directions: A large portion of current work is restricted to model systems in rodents. Therefore, additional clinical and translational research is needed in this area to promote gastrointestinal wound healing in humans, particularly those suffering from critical illness, patients with enterocutaneous fistula, inflammatory bowel disease, and ulcers, and those undergoing surgical procedures.
Differential item functioning in the CAMDEX depression scale across middle age and late-life

A long-standing and critical problem in the study of aging and depression is the comparability of measurement across age groups. While psychological measures of depression typically show increased incidence of symptoms with increasing age, rates of depression diagnosis do not show the same age trend. This analysis presents tests of differential item functioning on the depression section of the CAMDEX interview schedule, using factor analysis-derived affective and somatic subscales (McGue & Christensen, 1997). Results for the affective subscale show significant differences in item functioning in the majority of the affective items as a function of age (Items “Happy Life”, “Lonely”, “Nervous” “Worthless” and “Future”: = [30.193, 255.971] across items, all p<.0001). Analyses for the somatic subscale show differential item functioning is limited to a single item relating to coping ( = 180.754, p<.0001). These results indicate that differences in depression symptoms across age groups are not entirely consistent with a unidimensional depression trait, and that the measurement structure of depression varies over the lifespan.
Integrin αIIbβ3 in a Membrane Environment Remains the Same Height after Mn2+ Activation when Observed by Cryo-electron Tomography

Integrins perform the critical function of signalling cell attachment to the extracellular matrix or to other cells. This signalling is done through a structural change propagated bidirectionally across the plasma membrane. Integrin activation has been extensively studied with ectodomain constructs, but the structural change within intact, membrane-bound molecules remains a subject of live debate. Using cryoelectron tomography, we examined the simplest predication of the different integrin activation models, i.e. the change in height of the molecules. Analysis using techniques that compensate for the missing wedge during alignment and averaging and that search for patterns in the structure of the aligned molecular subvolumes extracted from the tomogram reveals that the vast majority of molecules show no dramatic height change upon Mn2+ induced activation of membrane bound integrins when compared with an inactive integrin control group. Thus, the result is inconsistent with the switchblade activation model.
The papillomavirus E 7 proteins

E7 is an accessory protein that is not encoded by all papillomaviruses. The E7 amino terminus contains two regions of similarity to conserved regions 1 and 2 of the adenovirus E1A protein, which are also conserved in the simian vacuolating virus 40 large tumor antigen. The E7 carboxyl terminus consists of a zinc-binding motif, which is related to similar motifs in E6 proteins. E7 proteins play a central role in the human papillomavirus life cycle, reprogramming the cellular environment to be conducive to viral replication. E7 proteins encoded by the cancer-associated alpha human papillomaviruses have potent transforming activities, which together with E6, are necessary but not sufficient to render their host squamous epithelial cell tumorigenic. This article strives to provide a comprehensive summary of the published research studies on human papillomavirus E7 proteins.
Mad3p, a pseudosubstrate inhibitor of APC in the spindle assembly checkpoint

Inappropriate attachment/tension between chromosomal kinetochores and the kinetochore microtubules activates the spindle assembly checkpoint, which delays anaphase by blocking the ubiquitin-mediated degradation of securin/Pds1p by APC. The checkpoint proteins Mad2 and Mad3/BubR1 bind to Cdc20, although how they inhibit APC is unclear. We investigated the roles of two evolutionarily conserved KEN boxes and a D box within Mad3/BubR1. Although such motifs usually mediate APC-substrate recognition and ubiquitination, they have no apparent role in Mad3p turnover in Saccharomyces cerevisiae. Instead, these motifs are important for Mad3p function in the checkpoint and for binding to Cdc20p. We show that the Mad3p D box and KEN boxes function together to mediate Cdc20p–Mad3p interaction and that Mad3p and an anaphase-promoting complex (APC) substrate, Hsl1p, compete for Cdc20p binding in a D-boxand KEN-box-dependent manner. In vivo, we observed an increased binding of Cdc20p to Mad3p and decreased binding to Hsl1p upon checkpoint activation. Furthermore, we demonstrate that Mad2p stimulates the association between Mad3p and Cdc20p and that this stimulated binding requires KEN box 1 within Mad3p. These findings implicate Mad3p as a pseudosubstrate inhibitor of APC, competing with APC substrates for Cdc20p binding. We present a model aimed at unifying previous analyses of checkpoint function by focusing on the Mad3–Cdc20 interaction.
An Input–Process–Output Model of Pilot Core Competencies

The aim of this study was to investigate the relationship between the flight-related core competencies for professional airline pilots and to structuralize them as components in a team performance framework. To achieve this, the core competency scores from a total of 2,560 OPC (Operator Proficiency Check) missions were analyzed. A principal component analysis (PCA) of pilots’ performance scores across the different competencies was conducted. Four principal components were extracted and a path analysis model was constructed on the basis of these factors. The path analysis utilizing the core competencies extracted adopted an input–process–output’ (IPO) model of team performance related directly to the activities on the flight deck. The results of the PCA and the path analysis strongly supported the proposed IPO model.
Lipidomic and proteomic analysis of C. elegans lipid droplets and identification of ACS-4 as a lipid droplet-associated protein

Lipid droplets are cytoplasmic organelles that store neutral lipids for membrane synthesis and energy reserves. In this study, we characterized the lipid and protein composition of purified C. elegans lipid droplets. These lipid droplets are composed mainly of triacylglycerols, surrounded by a phospholipid monolayer composed primarily of phosphatidylcholine and phosphatidylethanolamine. The fatty acid composition of the triacylglycerols is rich in fatty acid species obtained from the dietary E. coli, including cyclopropane fatty acids and cis-vaccenic acid. Unlike other organisms, C. elegans lipid droplets contain very little cholesterol or cholesterol esters. Comparison of the lipid droplet proteomes of wild type and high-fat daf-2 mutant strains shows a very similar proteome in both strains, except that the most abundant protein in the C. elegans lipid droplet proteome, MDT-28, is relatively less abundant in lipid droplets isolated from daf-2 mutants. Functional analysis of lipid droplet proteins identified in our proteomic studies indicated an enrichment of proteins required for growth and fat homeostasis in C. elegans. Finally, we confirmed the localization of one of the newly identified lipid droplet proteins, ACS-4. We found that ACS-4 localizes to the surface of lipid droplets in the C. elegans intestine and skin. This study bolsters C. elegans as a model to study the dynamics and functions of lipid droplets in a multicellular organism.