bluuebunny/crossref_metadata_2025_split huggingface dataset:
The actual, long-term cost of intentional injury care among a cohort of Maryland Medicaid recipients
Authors: Dezman Zachary D.W. , Thurman Paul , Stockwell Ian 
Published: October 2021

BACKGROUND
Intentional injury (both self-harm and interpersonal) is a major cause of morbidity and mortality, yet there are little data on the per-person cost of caring for these patients. Extant data focus on hospital charges related to the initial admission but does not include actual dollars spent or follow-up outpatient care. The Affordable Care Act has made Medicaid the primary payor of intentional injury care (39%) in the United States and the ideal source of cost data for these patients. We sought to determine the total and per-person long-term cost (initial event and following 24 months) of intentional injury among Maryland Medicaid recipients.

METHODS
Retrospective cohort study of Maryland Medicaid claims was performed. Recipients who submitted claims after receiving an intentional injury, as defined by the International Classification of Diseases, Tenth Revision, between October 2015 and October 2017, were included in this study. Subjects were followed for 24 months (last participant enrolled October 2017 and followed to October 2019). Our primary outcome was the dollars paid by Medicaid. We examined subgroups of patients who harmed themselves and those who received repeated intentional injury.

RESULTS
Maryland Medicaid paid $11,757,083 for the care of 12,172 recipients of intentional injuries between 2015 and 2019. The per-person, 2-year health care cost of an intentional injury was a median of $183 (SD, $5,284). These costs were highly skewed: min, $2.56; Q
1 = 117.60, median, $182.80; Q
3 = $480.82; and max, $332,394.20. The top 5% (≥95% percentile) required $3,000 (SD, $6,973) during the initial event and $8,403 (SD, $22,024) per served month thereafter, or 55% of the overall costs in this study.

CONCLUSION
The long-term, per-person cost of intentional injury can be high. Private insurers were not included and may experience different costs in other states.

LEVEL OF EVIDENCE
Economic and Value Based Evaluations; level III.
COVID-19 in Solid Organ Transplantation: Results of the National COVID Cohort Collaborative
Authors: Vinson Amanda J. , Agarwal Gaurav , Dai Ran , Anzalone Alfred J. , Lee Stephen B. , French Evan , Olex Amy , Madhira Vithal , Mannon Roslyn B. 
Published: October 2021

Background.
Coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and mortality in solid organ transplant (SOT) recipients. The National COVID Cohort Collaborative was developed to facilitate analysis of patient-level data for those tested for COVID-19 across the United States.

Methods.
In this study, we identified a cohort of SOT recipients testing positive or negative for COVID-19 (COVID+ and COVID−, respectively) between January 1, 2020, and November 20, 2020. Univariable and multivariable logistic regression were used to determine predictors of a positive result among those tested. Outcomes following COVID-19 diagnosis were also explored.

Results.
Of 18 121 SOT patients tested, 1925 were positive (10.6%). COVID+ SOT patients were more likely to have a kidney transplant and be non-White race. Comorbidities were common in all SOT patients but significantly more common in those who were COVID+. Of COVID+ SOT, 42.9% required hospital admission. COVID+ status was the strongest predictor of acute kidney injury (AKI), rejection, and graft failure in the 90 d after testing. A total of 40.9% of COVID+ SOT experienced a major adverse renal or cardiac event, 16.3% experienced a major adverse cardiac event, 35.3% experienced AKI, and 1.5% experienced graft loss.

Conclusions.
In the largest US cohort of COVID+ SOT recipients to date, we identified patient factors associated with the diagnosis of COVID-19 and outcomes following infection, including a high incidence of major adverse renal or cardiac event and AKI.
SARS-CoV-2 PLpro whole human proteome cleavage prediction and enrichment/depletion analysis
Authors: Prescott Lucas 
Published: October 2021

AbstractA novel coronavirus (SARS-CoV-2) has caused a pandemic that has killed millions of people, worldwide vaccination and herd immunity are still far away, and few therapeutics are approved by regulatory agencies for widespread use. The coronavirus 3-chymotrypsin-like protease (3CLpro) is a commonly investigated target in COVID-19, however less work has been directed toward the equally important papain-like protease (PLpro). PLpro is less characterized due to its fewer and more diverse cleavages in coronavirus proteomes and the assumption that it mainly modulates host pathways with its deubiquitinating activity. Here, I extend my previous work on 3CLpro human cleavage prediction and enrichment/depletion analysis to PLpro.[1] Using three sets of neural networks trained on different taxonomic ranks of dataset with a maximum of 463 different putative PLpro cleavages, Matthews correlation coefficients of 0.900, 0.948, and 0.966 were achieved for Coronaviridae, Betacoronavirus, and Sarbecovirus, respectively. I predict that more than 1,000 human proteins may be cleaved by PLpro depending on diversity of the training dataset and that many of these proteins are distinct from those previously predicted to be cleaved by 3CLpro. PLpro cleavages are similarly nonrandomly distributed and result in many annotations shared with 3CLpro cleavages including ubiquitination, poly(A) tail and 5’ cap RNA binding proteins, helicases, and endogenous viral proteins. Combining PLpro with 3CLpro cleavage predictions, additional novel enrichment analysis was performed on known substrates of cleaved E3 ubiquitin ligases with results indicating that many pathways including viral RNA sensing are affected indirectly by E3 ligase cleavage independent of traditional PLpro deubiquitinating activity. As with 3CLpro, PLpro whole proteome cleavage prediction revealed many novel potential therapeutic targets against coronaviruses, although experimental verification is similarly required.
Evaluation of flow cytometry for cell count and detection of bacteria in biological fluids
Authors: Dossou N. , Gaubert I. , Moriceau C. , Cornet E. , Le Hello S. , Malandain D. 
Published: October 2021

AbstractThe analysis of biological fluids is crucial for the diagnosis and monitoring of diseases causing effusions and helps in the diagnosis of infectious diseases. The gold standard method for cell count in biological fluids is the manual method using counting chambers. The microbiological routine procedures consist of Direct Gram staining and culture on solid or liquid media. We evaluate the analytical performance of SYSMEX UF4000 (Sysmex, Kobe, Japan) and Sysmex XN10 (Sysmex, Kobe, Japan) in comparison with cytological and microbiological routine procedures. A total of 526 biological fluid samples were included in this study (42 ascitic, 31 pleural, 31 peritoneal, 125 cerebrospinal, 281 synovial, and 16 peritoneal dialysis fluids). All samples were analysed by flow cytometry and subsequently processed following cytological and/or microbiological routine procedures. With regards to cell counts, UF4000 (Sysmex, Kobe, Japan) showed a performance which was at least equivalent to those of the reference methods and superior to those of XN10 (Sysmex, Kobe, Japan). Moreover, the bacterial count obtained with UF4000 (Sysmex, Kobe, Japan) was significantly higher among culture or Direct Gram stain positive samples. We established 3 optimal cut-off points to predict Direct Gram stain positive samples for peritoneal (465.0 bacteria/μL), synovial (1200.0 bacteria/μL), and cerebrospinal fluids (17.2 bacteria/μL) with maximum sensitivity and negative predictive values. Cell count and detection of bacteria by flow cytometry could be used upstream cytological and microbiological routine procedures to improve and accelerate the diagnosis of infection of biological fluid samples.
Revealing the function of HMGB1 N-terminal acetylation by a protein semi-synthesis approach
Authors: Wei Tongyao , Liu Jiamei , Tan Yi , Li Can , Wei Ruohan , Wang Jinzheng , Wu Hongxiang , Li Qingrong , Liu Heng , Tang Yubo , Li Xuechen 
Published: October 2021

AbstractHMGB1 (high-mobility group box 1) protein is a nonhistone chromatin-associated protein that has been widely reported to be a representative damage-associated molecular pattern (DAMP) and to play a pivotal role in proinflammatory process once it is in an extracellular location. Accumulating evidence has shown HMGB1 undergoes extensive PTMs that remarkably regulated its conformation, localization, and intermolecular interaction. However, the PTMrelated study has been dramatically hindered by the difficulty to access to homogenous proteins with site-specific PTMs of interest. Here, we introduce a protein semi-synthesis strategy via salicylaldehyde ester-mediated chemical ligations (Ser/Thr ligation and Cys/Pen ligation, STL/CPL). This methodology has enabled us to generate N-terminal acetylated HMGB1 proteins in high purity. Further studies revealed that the acetylation on N-terminus regulates its interaction with heparin and modulates its stability, representing a regulatory switch to control the HMGB1’s activity.
A Probabilistic Approach for Registration of Multi-Modal Spatial Transcriptomics Data
Authors: Qiang Yu , He Shixu , Ding Renpeng , Ma Kailong , Hou Yong , Zhou Yan , Rohr Karl 
Published: October 2021

ABSTRACTObserving the spatial characteristics of gene expression by image-based spatial transcriptomics technology allows studying gene activity across different cells and intracellular structures. We present a probabilistic approach for the registration and analysis of transcriptome images and immunostaining images. The method is based on particle filters and jointly exploits intensity information and image features. We applied our approach to synthetic data as well as real transcriptome images and immunostaining microscopy images of the mouse brain. It turns out that our approach accurately registers the multi-modal images and yields better results than a state-of-the-art method.
Machine learning-based tissue of origin classification for cancer of unknown primary diagnostics using genome-wide mutation features
Authors: Nguyen Luan , van Hoeck Arne , Cuppen Edwin 
Published: October 2021

AbstractTumor tissue of origin (TOO) is an important factor for guiding treatment decisions. However, TOO cannot be determined for ~3% of metastatic cancer patients and are categorized as cancers of unknown primary (CUP). As whole genome sequencing (WGS) of tumors is now transitioning from the research domain to diagnostic practice in order to address the increasing demand for biomarker detection, its use for detection of TOO in routine diagnostics also starts becoming within reach. While proof of concept for the use of genome-wide features has been demonstrated before, more complex WGS mutation features, including structural variant (SV) driver and passenger events, have never been integrated into TOO-classifiers even though they bear highly characteristic links with tumor TOO. Using a uniformly processed dataset containing 6820 whole-genome sequenced primary and metastatic tumors, we have developed Cancer of Unknown Primary Location Resolver (CUPLR), a random forest based TOO classifier that employs 502 features based on simple and complex somatic driver and passenger mutations. Our model is able to distinguish 33 cancer (sub)types with an overall accuracy of 91% and 89% based on cross-validation (n=6139) and hold out set (n=681) predictions respectively. We found that SV derived features increase the accuracy and utility of TOO classification for specific cancer types. To ensure that predictions are human-interpretable and suited for use in routine diagnostics, CUPLR reports the top contributing features and their values compared to cohort averages. The comprehensive output of CUPLR is complementary to existing histopathological procedures and may thus improve diagnostics for patients with CUP.
Systematic identification of intron retention associated variants from massive publicly available transcriptome sequencing data
Authors: Shiraishi Yuichi , Okada Ai , Chiba Kenichi , Omori Ikuko , Mateos Raúl Nicolás , Iida Naoko , Yamauchi Hirofumi , Kosaki Kenjiro , Yoshimi Akihide 
Published: October 2021

AbstractMany disease-associated genomic variants disrupt gene function through abnormal splicing. With the advancement of genomic medicine, identifying disease-associated splicing associated variants has become more important than ever. Most bioinformatics approaches to detect splicing associated variants require both genome and transcriptomic data. However, there are not many datasets where both of them are available. In this study, we developed a methodology to detect genomic variants that cause splicing changes (more specifically, intron retention), using transcriptome sequencing data alone. After demonstrating its high sensitivity and precision, we have applied it to 230,988 transcriptome sequencing data from the publicly available repository and identified 27,937 intron retention associated variants (IRAVs). In addition, by exploring positional relationships with variants registered in existing disease databases, we extracted 3,077 putative disease-associated IRAVs, which range from cancer drivers to variants linked with autosomal recessive disorders. The new in-silico screening framework proposed here provides a foundation for a platform that can automatically acquire medical knowledge making the most of massively accumulated publicly available sequencing data. Collections of IRAVs identified in this study are available through IRAVDB (https://iravdb.io/).
Antiviral CD19+CD27+ Memory B Cells Are Associated with Protection from Recurrent Asymptomatic Ocular Herpes Infection
Authors: Dhanushkodi Nisha R. , Prakash Swayam , Srivastava Ruchi , Coulon Pierre-Gregoire A. , Arellano Danielle , Kapadia Rayomand V. , Fahim Raian , Suzer Berfin , Jamal Leila , BenMohamed Lbachir 
Published: October 2021

ABSTRACTReactivation of herpes simplex virus 1 (HSV-1) from latently infected neurons of the trigeminal ganglia (TG) leads to blinding recurrent herpetic disease in symptomatic (SYMP) individuals. Although the role of T cells in herpes immunity seen in asymptomatic (ASYMP) individuals is heavily explored, the role of B cells is less investigated. In the present study, we evaluated whether B cells are associated with protective immunity against recurrent ocular herpes. The frequencies of circulating HSV-specific memory B cells and of memory follicular helper T cells (CD4+ Tfh cells), that help B cells produce antibodies, were compared between HSV-1 infected SYMP and ASYMP individuals. The levels of IgG/IgA and neutralizing antibodies were compared in SYMP and ASYMP individuals. We found that: (i) the ASYMP individuals had increased frequencies of HSV-specific CD19+CD27+ memory B cells; and (ii) high frequencies of HSV-specific switched IgG+CD19+CD27+ memory B cells detected in ASYMP individuals were directly proportional to high frequencies of CD45R0+CXCR5+CD4+ memory Tfh cells. However, no differences were detected in the level of HSV-specific IgG/IgA antibodies in SYMP and ASYMP individuals. Using the UV-B-induced HSV-1 reactivation mouse model, we found increased frequencies of HSV-specific antibody-secreting plasma HSV-1 gD+CD138+ B cells within the TG and circulation of ASYMP mice compared to SYMP mice. In contrast, no significant differences in the frequencies of B cells were found in the cornea, spleen, and bone-marrow. Our findings suggest that circulating antibody-producing HSV-specific memory B cells recruited locally to the TG may contribute to protection from symptomatic recurrent ocular herpes.IMPORTANCEReactivation of herpes simplex virus 1 (HSV-1) from latently infected neurons of the trigeminal ganglia (TG) leads to blinding recurrent herpetic disease in symptomatic (SYMP) individuals. Although the role of T cells in herpes immunity against blinding recurrent herpetic disease is heavily explored, the role of B cells is less investigated. In the present study, we found that in both asymptomatic (ASYMP) individuals and ASYMP mice there was increased frequencies of HSV-specific memory B cells that were directly proportional to high frequencies of memory Tfh cells. Moreover, following UV-B induce reactivation, we found increased frequencies of HSV-specific antibody-secreting plasma B cells within the TG and circulation of ASYMP mice, compared to SYMP mice. Our findings suggest that circulating antibody-producing HSV-specific memory B cells recruited locally to the TG may contribute to protection from recurrent ocular herpes.
Regulation of Sox8 through lncRNA Mrhl mediated chromatin looping in mouse spermatogonia
Authors: Kayyar Bhavana , Ravikkumar Anjhana C. , Bhaduri Utsa , Rao M.R.S 
Published: October 2021

AbstractSox8 is a developmentally important transcription factor that plays an important role in sex maintenance and fertility of adult mice. In the B-type spermatogonial cells, Sox8 is regulated by the lncRNA Mrhl in a p68-dependant manner under the control of the Wnt signalling pathway. The downregulation of Mrhl leads to the meiotic commitment of the spermatogonial cells in a Sox8-dependant manner. While the molecular players involved in the regulation of transcription at the Sox8 promoter have been worked out, our current study points to the involvement of the architectural proteins CTCF and cohesin in mediating a chromatin loop that brings the Sox8 promoter in contact with a silencer element present within the gene body in the presence of lncRNA Mrhl concomitant with transcriptional repression. Further, lncRNA Mrhl interacts with the Sox8 locus through the formation of a DNA:DNA:RNA triplex which is necessary for the recruitment of PRC2 to the locus. The downregulation of lncRNA Mrhl results in the promoter-silencer loop giving way to a promoter-enhancer loop. This active transcription associated chromatin loop is mediated by YY1 and brings the promoter in contact with the enhancer present downstream of the gene.
Red cell folate status among a subset of Canadian children with Down Syndrome post-fortification
Authors: Jory Joan 
Published: October 2021

ABSTRACTBackgroundTrisomy 21 or Down Syndrome (DS) is associated with altered methylation pathways. Children with DS may therefore represent a population subgroup with vulnerability to increased exposures to folic acid, which is involved in one-carbon metabolism. Folic acid (FA) fortification of flour and maternal FA supplementation are intended to reduce neural tube defects related to folate deficiency. The interventions have been widely successful in Canada. Emerging evidence suggests that higher FA exposures may also have potential negative consequences, including implications for DNA methylation. This retrospective chart review provides insight on the RBC folate status of a subset of Canadian children and infants with DS, post-fortification.MethodChildren with DS in 2 Canadian provinces were assessed in the community. Access to RBC folate testing was variable, limiting sample size to 39 (n=27 for children ≤ 6 years; n=12 for children 6-18 years). All children with DS and an RBC folate result were included. Use of FA-containing supplements and formula was documented.ResultsAmong children 6-18 years, 100% had RBC folates > 1000 nmol/L, 50% were > 2000 nmol/L and 25% had levels above the reporting limit. Among the younger children (< 6 years), 52 % had RBC folates >2000 nmol and 2 children exceeded 3000 nmol/L. Among exclusively breast-fed infants (<12 months), 100% had RBC folates > 1000 nmol/L and 50% had levels > 2000 nmol/L, suggestive of in-utero or maternal exposures. RBC folate status among this subset of Canadian children with DS is higher than documented for the larger Canadian population, and higher than among US children with DS.ConclusionsYoung Canadian children with DS demonstrated high post-fortification RBC folate status. RBC folate status was higher than reported for the larger Canadian population, and higher than for US children with Down Syndrome. Consumption of folic acid-containing formula and/or supplements was relatively low among these Canadian children with DS, suggesting maternal FA supplements and/or FA-fortified foods may be important etiological factors. A larger, prospective study is needed to validate these results, and to explore potential health implications among this vulnerable population.
Variation in influenza vaccine assessment, receipt, and refusal by the concentration of Medicare Advantage enrollees in U.S. nursing homes
Authors: Moyo Patience , Bosco Elliott , Bardenheier Barbara H. , Rivera-Hernandez Maricruz , van Aalst Robertus , Chit Ayman , Gravenstein Stefan , Zullo Andrew R. 
Published: October 2021

ABSTRACTBackgroundMore older adults enrolled in Medicare Advantage (MA) are entering nursing homes (NHs), and MA concentration could affect vaccination rates through shifts in resident characteristics and/or payer related influences on preventive services use. We investigated whether rates of influenza vaccination and refusal differ across NHs with varying concentrations of MA-enrolled residents.MethodsWe analyzed 2014-2015 Medicare enrollment data and Minimum Data Set clinical assessments linked to NH-level characteristics, star ratings, and county-level MA penetration rates. The independent variable was the percentage of residents enrolled in MA at admission and categorized into three groups. We examined three NH-level outcomes: percentage of residents assessed and appropriately provided the influenza vaccine, receiving influenza vaccine, and refusing influenza vaccine.ResultsThere were 936,513 long-stay residents in 12,384 NHs. Categories for the prevalence of MA enrollment in NHs were low (0% to 3.3%; n=4131 NHs), moderate (3.4% to 18.6%; n=4127 NHs) and high (>18.6%; n=4126 NHs). Adjusting for covariates, influenza vaccination rates among long-stay residents were higher in NHs with moderate (1.7%,P<0.0001), or high (3.1%,P<0.0001) MA versus the lowest prevalence of MA. Influenza vaccine refusal was lower in NHs with moderate (−3.1%,P<0.0001), or high (−4.6%P<0.0001) MA compared with NHs with the lowest prevalence of MA. Among 753,616 short-stay residents in 12,205 NHs, there was no association between MA concentration and influenza vaccination receipt but vaccine refusal was greater in NHs with higher MA prevalence (high or moderate vs. low MA: 5.2%,P<0.0001).ConclusionThe relationship between MA concentration and influenza vaccination measures varied among post-acute and long-term NH residents. As MA takes a larger role in the Medicare program, and more MA beneficiaries enter NHs, there is need to consider how managed care can be leveraged to improve the delivery of preventive services such as influenza vaccinations in NH settings.