bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Mixed-Methods Systematic Review on Syndemics in Rheumatology
Authors: Ramírez-Flores María F. , Cadena-Trejo Cinthya , Motte-García Emilio , Juárez-Cruz Isaac D. , Fernandez-García Maria V. , Gastelum-Strozzi Alfonso , Alpizar-Rodriguez Deshire , Hernandez-Garduño Adolfo , Peláez-Ballestas Ingris 
Published: November 2022

Abstract
A syndemic framework assesses the multidimensionality of the interrelationships of diseases and their circumstances. This approach has given important insights into other nonrheumatic diseases.

Objective
We aimed to assess the use of framework and corresponding methodology to document syndemics and its impact in rheumatic and musculoskeletal diseases (RMDs).

Methods
Using a mixed-methods systematic review, studies using the syndemic framework approach for RMDs were identified and published from January 2003 to January 2021. The Joanna Briggs Institute, Cochrane Collaboration, and PRISMA guidelines were followed to search, retrieve, revise, and analyze.

Results
A total of 658 potential articles were identified, but only 10 were initially eligible. After a full-text review, 4 were included. Following a full-text review, 2 quantitative, 1 qualitative, and 1 mixed-methods study were included. In the first, network analysis found that RMDs were associated with comorbidities, unhealthy habits, low educational level, living in rural areas, socioeconomic conditions, and health inequality in indigenous communities. In the second, SSEM and cluster analysis demonstrated an association between low back pain and factors, such as comorbidities and indigenous status, among others, in urban/rural communities. The qualitative study examined 3 fishing family generations and reported less syndemic vulnerability. The mixed-methods study focused on osteoarthritis with multimorbidities in African American population, where lack of education added to worsening outcomes.

Conclusions
Even though the insights syndemic studies have given to other areas, its use in rheumatology is scarce. The complexity of the clinical and social determinants related to RMDs makes it necessary to conduct further studies from a syndemic perspective.
Antithrombin, protein C and protein S: Genome and transcriptome wide association studies identify 7 novel loci regulating plasma levels
Authors: Ji Yuekai , Temprano-Sagrera Gerard , Holle Lori A , Bebo Allison , Brody Jennifer , Le Ngoc-Quynh , Brown Michael R , Martinez-Perez Angel , Sitlani Colleen M , Suchon Pierre , Kleber Marcus E , Emmert David B , Ozel Ayse Bilge , A Dobson Dre’Von , Tang Weihong , Llobet Dolors , Tracy Russell P , Deleuze Jean-François , Delgado Graciela E , Gögele Martin , Wiggins Kerri L , Souto Juan Carlos , Pankow James S , Taylor Kent D , Trégouët David-Alexandre , Moissl Angela P , Fuchsberger Christian , Rosendaal Frits R , Morrison Alanna C , Soria Jose Manuel , Cushman Mary , Morange Pierre-Emmanuel , März Winfried , Hicks Andrew A , Desch Karl C , Johnson Andrew D , de Vries Paul S ,   CHARGE Consortium Hemostasis Working Group,   INVENT Consortium, Wolberg Alisa S , Smith Nicholas L , Sabater-Lleal Maria 
Published: November 2022

ABSTRACTObjectiveAntithrombin, protein C (PC) and protein S (PS) are circulating natural-anticoagulant proteins that regulate hemostasis and of which partial deficiencies are causes of venous thromboembolism. Previous genetic association studies involving antithrombin, PC, and PS were limited by modest sample sizes or by being restricted to candidate genes. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, we meta-analyzed across ancestries the results from 10 genome-wide association studies (GWAS) of plasma levels of antithrombin, PC, PS free and PS total.Approach and ResultsStudy participants were of European and African ancestries and genotype data were imputed to TOPMed, a dense multi-ancestry reference panel. Each of 10 studies conducted a GWAS for each phenotype and summary results were meta-analyzed, stratified by ancestry. We also conducted transcriptome-wide association analyses and multi-phenotype analysis to discover additional associations. Novel GWAS findings were validated byin vitrofunctional experiments. Mendelian randomization was performed to assess the causal relationship between these proteins and cardiovascular outcomes.GWAS meta-analyses identified 4 newly associated loci: 3 with antithrombin levels (GCKR, BAZ1B, andHP-TXNL4B) and 1 with PS levels (ORM1-ORM2). TWAS identified 3 newly associated genes: 1 with antithrombin level (FCGRT), 1 with PC (GOLM2), and 1 with PS (MYL7). In addition, we replicated 7 independent loci reported in previous studies. Functional experiments provided evidence for the involvement ofGCKR, SNX17, andHPgenes in antithrombin regulation.ConclusionThe use of larger sample sizes, diverse populations, and a denser imputation reference panel allowed the detection of 7 novel genomic loci associated with plasma antithrombin, PC, and PS levels.
Multimodal profiling of term human decidua reveals tissue-specific immune adaptations with maternal obesity
Authors: Sureshchandra Suhas , Doratt Brianna M. , Mendoza Norma , Rincon Monica , Marshall Nicole E. , Messaoudi Ilhem 
Published: November 2022

ABSTRACTThe leukocyte diversity of early maternal-fetal interface has been recently described, however, characterization of decidua at term is still pending. We, therefore, profiled the CD45+ compartment within human term decidua collected via cesarean section. Relative to the first trimester, our analyses revealed a shift from NK cells and macrophages to T-cells and enhanced activation of all immune cells. T-cells in the decidua were phenotypically distinct from their blood counterparts and demonstrated significant clonotype sharing. Using pseudo-temporal analyses of macrophages, we characterize previously undescribed diversity of bonafide tissue resident decidual macrophages. The frequency of this population correlated with high pregravid maternal body mass index but responded poorly to bacteria ligands. Collectively, these findings provide evidence of skewing of decidual myeloid cells towards immunoregulation representing a possible mechanism to safeguard the fetus. This immune cell atlas of term decidua is an asset for future studies investigating pathological conditions that compromise reproductive success.One sentence summaryHuman immune cell atlas of term decidua and observed alterations with pre-gravid obesity.
Multilevel human secondary lymphoid immune system compartmentalization revealed by complementary multiplexing and mass spectrometry imaging approaches
Authors: Oyler Benjamin L. , Valencia-Dávila Jeferson A. , Moysi Eirini , Molyvdas Adam , Ioannidou Kalliopi , March Kylie , Ambrozak David , de Leval Laurence , Fabozzi Giulia , Woods Amina S. , Koup Richard A. , Petrovas Constantinos 
Published: November 2022

AbstractSecondary human lymphoid tissue immune reactions take place in a highly coordinated environment with compartmentalization representing a fundamental feature of this organization.In situprofiling methodologies are indispensable for the understanding of this compartmentalization. Here, we propose a complementary experimental approach aiming to reveal different aspects of this process. The analysis of human tonsils, using a combination of single cell phenotypic analysis based on flow cytometry and multiplex imaging and mass spectrometry-based methodologies, revealed a compartmentalized organization at cellular and molecular level. More specifically, the skewed distribution of highly specialized immune cell subsets and relevant soluble mediators was accompanied by a compartmentalized localization of several lipids across different anatomical areas of the tonsillar tissue. The performance of such combinatorial experimental approaches could lead to the identification of novelin situinteractions and molecular targets for thein vivomanipulation of lymphoid organ, particularly the germinal center, immune reactions.
Comparing the effects of host species richness on different metrics of disease
Authors: Cortez Michael H. 
Published: November 2022

ABSTRACTChanges in host species richness can alter infection risk and disease levels in communities. I review theoretical predictions for direct and environmental transmission pathogens about the effects of host additions (or removals) on three common disease metrics: the pathogen community reproduction number (ℛ0) and the proportion (i.e., infection prevalence) and density of infected individuals in a focal host. To help explain why predictions differ between studies and between metrics, I analyze an SIR-type model of an environmentally transmitted pathogen and multiple host species that compete for resources. I use local sensitivity analysis to explore and compare how variation in an added host’s ability to transmit a pathogen, its density, and the pathogen transmission mechanism affect each disease metric. I find that if an added host species is a weak interspecific competitor, then each metric typically increases or decreases, respectively, when the added host has a high or low ability to transmit the pathogen. However, if the added host species is a strong interspecific competitor, then the response of each metric can be strengthened, weakened, or reversed depending on how the competitive effects of the added host propagate through the community and alter the densities of all host species in the community. The three metrics often respond in the same direction, but the metrics can respond in different directions for three reasons: (1) strong density-mediated feedbacks driven by high disease-induced mortality; (2) host additions or removals cause large changes in focal host density via competition or disease-induced mortality; and (3) the metrics use different quantities to define a host’s ability to transmit disease: the quantities for infection prevalence and infected density depend on the instantaneous production rates of infectious propagules whereas the quantities for ℛ0depend on lifetime production of infectious propagules. This study provides a framework that unifies prior theoretical studies and identifies rules governing the context-dependent relationships between host species richness and the three metrics of disease.
Dynamic growth re-orientation orchestrates flatness in the Arabidopsis leaf
Authors: Harline Kate , Fruleux Antoine , Lane Brendan , Mosca Gabriella , Strauss Soeren , Tavakolian Nik , Satterlee James W. , Li Chun-Biu , Singh Abhyudai , Smith Richard S. , Boudaoud Arezki , Roeder Adrienne H.K. 
Published: November 2022

AbstractThe growth and division of cells in plant leaves is highly dynamic in time and space, all while the cells cannot move relative to their neighbors. Given these constraints, models predict that long range regulatory systems must exist to maintain flat forms. Juxtaposed microRNA (miR-NA) networks could serve as one of these regulatory systems. One of these miRNAs, miR319 is thought to be expressed from the base of leaves and to promote growth by degrading class II TCP transcription factor mRNAs. A miR319 overexpression mutant,jagged and wavy(jaw-D) exhibits rippling and undulating leaves, consistent with biomechanical predictions that without genetic spatial coordination, tissues will deform. It has been theorized thatjaw-Drippling results from overgrowth at the margins, however this does not fully address how miR319 expression from the base of wild-type (WT) leaves allows them to flatten. Here, we track the growth, cell division and cell maturation in live WT andjaw-Dleaves to ask how miR319 expression in WT promotes flattening. This data revealed the importance of spatially distinct growth, division and differentiation patterns in WT leaves, which are missing injaw-D.We propose that WT leaf cells respond to differentiation cues to dynamically re-orient growth in specific tissue locations and regulate flattening.
Racial/ethnic differences in pre-pregnancy conditions and adverse maternal outcomes in the nuMoM2b cohort: a population-based cohort study
Authors: Meredith Meghan E. , Steimle Lauren N. , Stanhope Kaitlyn K. , Platner Marissa H. , Boulet Sheree L. 
Published: November 2022

AbstractObjectiveTo: (1) determine how pre-existing conditions contribute to racial disparities in adverse maternal outcomes; and (2) incorporate these conditions into models to improve risk prediction for racial minority subgroups.DesignSecondary data analysis of a population-based cohort study.SettingAcademic healthcare institutions in the United States.PopulationA cohort of 8,729 women included in the “Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b)”.MethodsPoisson regression to estimate adjusted risk ratios, and mediation analysis to evaluate the contribution of multimorbidity to racial/ethnic disparities. Area under the receiver operating characteristic curve (AUC) to evaluate model performance.Main Outcome MeasuresIncidence of severe preeclampsia, postpartum readmission, and blood transfusion.ResultsIn the nuMoM2b cohort (n=8729), accounting for pre-existing conditions attenuated the association between non-Hispanic Black race/ethnicity and risk of severe preeclampsia. Cardiovascular and kidney conditions were associated with risk for severe preeclampsia among all women (aRR, 1.77; CI, 1.61-1.96, and aRR, 1.27; CI, 1.03-1.56 respectively). The mediation analysis results were not statistically significant; however, cardiovascular conditions explained 36.6% of the association between severe preeclampsia and non-Hispanic Black race/ethnicity (p=0.07). The addition of pre-pregnancy conditions increased model performance for the prediction of blood transfusion and severe preeclampsia.ConclusionsPre-existing conditions may explain some of the association between severe preeclampsia and non-Hispanic Black race/ethnicity. Specific pre-pregnancy conditions were associated with adverse maternal outcomes and the incorporation of comorbidities improved the performance of most risk prediction models.FundingResearch reported in this publication was supported in part by Imagine, Innovate and Impact (I3) from the Emory School of Medicine, Georgia Tech, and through the Georgia CTSA NIH award (UL1-TR002378) and by the National Science Foundation under grant number DGE-2039655 (Meredith); any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation.
Racial disparities in nephrectomy and mortality among patients with renal cell carcinoma: Findings from SEER
Authors: Ikuemonisan Joshua , Aremu Taiwo Opeyemi , Oyejinmi Isaac , Ajala Christopher , Anikpezie Nnabuchi , Akinso Oyindamola , Mtengwa Mutsa , David Adeyemo , Olokede Olugbenga , Adejoro Oluwakayode 
Published: November 2022

AbstractPurposeTo assess racial differences in the receipt of nephrectomy in patients diagnosed RCC in the US.Materials and Methods2005 to 2015 data from the SEER database was analyzed and 70059 patients with RCC were identified. We compared demographic and tumor characteristics between Blacks and Whites. We applied logistic regression to assess the influence of race on the odds of the receipt of nephrectomy. We also applied Cox proportional hazards model to assess the impact of race on cancer-specific mortality (CSM) and all-cause mortality (ACM) in patients diagnosed with RCC in the US.ResultsOverall, there was a relative increase in the use of nephrectomy from 2007 (p<0.0001). However, Blacks had 18% lower odds of receiving nephrectomy compared to Whites (p < 0.0001). The odds of the receipt of nephrectomy also reduced with age at diagnosis. In addition, patients with T3 stage had the greatest odds of receiving nephrectomy when compared to T1 (p < 0.0001). There was no difference in the risk of cancer-specific mortality between Blacks and Whites, Blacks had 27% greater odds of all-cause mortality than Whites (p < 0.0001). Patients who did not receive nephrectomy had a 42% and 35% higher risk of CSM and ACM respectively, when compared to patients who received nephrectomy.ConclusionsBlacks diagnosed with RCC in the US have a greater ACM risk and are less likely than Whites to receive nephrectomy. Systemic changes are needed to eliminate racial disparity in the treatment and outcomes of RCC in the US.
A Fast Solution for Automated Single-Molecule Force Spectroscopy Data Collection and Processing
Authors: Xu Shuai , Kang Yafeng , Liu Zhiqiang , Shi Hang 
Published: November 2022

AbstractForce spectroscopy is a sophisticated technology for studying the physical chemistry of polymers at the single-molecule level. Its implication in biomolecules, e.g., proteins, DNA or RNA, yielded tremendous information on their structures, folding, and functions. In a routine procedure, an experimenter pulls the molecule of interest to generate the force-extension (FE) curve using technologies that include atomic force microscopy (AFM), magnetic force spectroscopy (MFS), optical tweezer and acoustic force spectroscopy (AFS), then extract parameters characteristic to the polymer. The latter step requires fitting the FE curve with mathematical models. Although several models have been widely applied for over 20 years, the fitting of the experimental data was not as straightforward. This step can be time-consuming, prone to mistakes, and sometimes cause debate. To lower the technical barriers for users and to reduce the time consumption and errors involved in force spectroscopy data processing, we optimized the fitting procedure for three classical worm-like chain (WLC) models into an automated software package named Single Molecule Force Spectroscopy Toolkit (SMFST). Our MATLAB-based software with a graphical user interface demonstrated robust fitting for three models in a wide range of forces and provided convenient tools for batch data processing to meet future requirements of high-throughput data collection.
Using evolutionary constraint to define novel candidate driver genes in medulloblastoma
Authors: Roy Ananya , Sakthikumar Sharadha , Kozyrev Sergey V. , Nordin Jessika , Pensch Raphaela , Pettersson Mats ,   Zoonomia Consortium, Karlsson Elinor , Lindblad-Toh Kerstin , Forsberg-Nilsson Karin 
Published: November 2022

AbstractCurrent knowledge of cancer genomics is biased against non-coding mutations. Here, we use whole genome sequencing data from pediatric brain tumors, combined with evolutionary constraint inferred from 240 mammals to identify genes enriched in non-coding constraint mutations (NCCMs). We compare medulloblastoma (MB, malignant) to pilocytic astrocytoma (PA, benign) and find drastically different NCCM frequencies between the two. In PA, a high NCCM frequency only affects theBRAFlocus, while in MB, >500 genes have high levels of NCCMs. Intriguingly, many genes are associated with different age of onset, such asHOXB1in young patients andNUAK1in adult patients. Our analysis points to different molecular pathways in different patient groups. These novel candidate driver genes may assist patient stratification in MB and may be useful for treatment options.One-Sentence SummaryNon-coding constraint mutations implicate novel candidate genes to stratify medulloblastoma by age and subgroups.
Room-temperature crystallography reveals altered binding of small-molecule fragments to PTP1B
Authors: Mehlman Tamar (Skaist) , Biel Justin T. , Azeem Syeda Maryam , Nelson Elliot R. , Hossain Sakib , Dunnett Louise E. , Paterson Neil G. , Douangamath Alice , Talon Romain , Axford Danny , Orins Helen , von Delft Frank , Keedy Daniel A. 
Published: November 2022

AbstractMuch of our current understanding of how small-molecule ligands interact with proteins stems from X-ray crystal structures determined at cryogenic (cryo) temperature. For proteins alone, room-temperature (RT) crystallography can reveal previously hidden, biologically relevant alternate conformations. However, less is understood about how RT crystallography may impact the conformational landscapes of protein-ligand complexes. Previously we showed that small-molecule fragments cluster in putative allosteric sites using a cryo crystallographic screen of the therapeutic target PTP1B (Keedy*, Hill*, 2018). Here we have performed two RT crystallographic screens of PTP1B using many of the same fragments, representing the largest RT crystallographic screens of a diverse library of ligands to date, and enabling a direct interrogation of the effect of data collection temperature on protein-ligand interactions. We show that at RT, fewer ligands bind, and often more weakly -- but with a variety of temperature-dependent differences, including unique binding poses, changes in solvation, new binding sites, and distinct protein allosteric conformational responses. Overall, this work suggests that the vast body of existing cryogenic-temperature protein-ligand structures may provide an incomplete picture, and highlights the potential of RT crystallography to help complete this picture by revealing distinct conformational modes of protein-ligand systems. Our results may inspire future use of RT crystallography to interrogate the roles of protein-ligand conformational ensembles in biological function.
The biophysical nature and not only the size of protein aggregates determines the strength of the immune response against dengue ED3
Authors: Kibria Md. Golam , Shiwaku Yukari , Brindha Subbaian , Kuroda Yutaka 
Published: November 2022

AbstractHere we used domain 3 of dengue virus serotype 3 envelope protein (D3ED3), a natively folded globular low-immunogenicity protein, to ask whether the biophysical nature of amorphous aggregates can affect immunogenicity. We prepared amorphous oligomers in five distinct ways. One oligomer type was produced using our SCP tag (Solubility Controlling Peptide) made of 5 Isoleucines (C5I). The others were prepared by miss-shuffling the SS bonds (Ms), heating (Ht), stirring (St), and freeze-thaw (FT). Dynamic light scattering showed that all five formulations contained oligomers of approximately identical sizes with hydrodynamic radii (Rh) between 30 and 55 nm. Circular dichroism (cd) indicated that the secondary structure content of oligomers formed by stirring and freeze-thaw was essentially identical to that of the native monomeric D3ED3. The secondary structure content of the Ms showed moderate changes, whereas the C5I and heat-induced (Ht) oligomers exhibited a significant change. Immunization in JcL:ICR mice showed that both C5I and Ms significantly increased the anti-D3ED3 IgG titer. Ht, St, and FT were barely immunogenic, similar to the monomeric D3ED3. Cell surface CD marker analysis by flow cytometry confirmed that immunization with Ms generated a strong central and effector T-cell memory. This result adds a new dimension to earlier studies where the strength of the immune response was associated solely with the presence and sizes of the oligomers. It also suggests that controlled oligomerization can provide a new, adjuvant-free method for increasing a protein’s immunogenicity, yielding a potentially powerful platform for protein-based vaccines.SignificanceProtein aggregation is suspected to increase the immunogenicity of proteins. Here we show that the strength of the immune response depends not merely on the size of the oligomers/aggregates but also on their biophysical properties. Dengue virus 3 envelop protein domain 3 (D3ED3) was oligomerized/aggregated in five different ways. All five formulations contained oligomers with hydrodynamic radii between 30 and 55 nm. Two formulations, where D3 ED3 was natively folded, were not or poorly immunogenic. On the other hand, two others, where D3ED 3 was in a molten globule-like state, were strongly immunogenic. This result adds a new dimension to earlier studies where the strength of the immune response was associated solely with the presence and sizes of the oligomers.