bluuebunny/crossref_metadata_2025_split huggingface dataset:
SpaceX: gene co-expression network estimation for spatial transcriptomics
Authors: Acharyya Satwik , Zhou Xiang , Baladandayuthapani Veerabhadran 
Published: September 2022

Abstract

Motivation
The analysis of spatially resolved transcriptome enables the understanding of the spatial interactions between the cellular environment and transcriptional regulation. In particular, the characterization of the gene–gene co-expression at distinct spatial locations or cell types in the tissue enables delineation of spatial co-regulatory patterns as opposed to standard differential single gene analyses. To enhance the ability and potential of spatial transcriptomics technologies to drive biological discovery, we develop a statistical framework to detect gene co-expression patterns in a spatially structured tissue consisting of different clusters in the form of cell classes or tissue domains.

Results
We develop SpaceX (spatially dependent gene co-expression network), a Bayesian methodology to identify both shared and cluster-specific co-expression network across genes. SpaceX uses an over-dispersed spatial Poisson model coupled with a high-dimensional factor model which is based on a dimension reduction technique for computational efficiency. We show via simulations, accuracy gains in co-expression network estimation and structure by accounting for (increasing) spatial correlation and appropriate noise distributions. In-depth analysis of two spatial transcriptomics datasets in mouse hypothalamus and human breast cancer using SpaceX, detected multiple hub genes which are related to cognitive abilities for the hypothalamus data and multiple cancer genes (e.g. collagen family) from the tumor region for the breast cancer data.

Availability and implementation
The SpaceX R-package is available at github.com/bayesrx/SpaceX.

Supplementary information
Supplementary data are available at Bioinformatics online.
Top-Down Crawl: a method for the ultra-rapid and motif-free alignment of sequences with associated binding metrics
Authors: Cooper Brendon H , Chiu Tsu-Pei , Rohs Remo 
Published: September 2022

Abstract

Summary
Several high-throughput protein–DNA binding methods currently available produce highly reproducible measurements of binding affinity at the level of the k-mer. However, understanding where a k-mer is positioned along a binding site sequence depends on alignment. Here, we present Top-Down Crawl (TDC), an ultra-rapid tool designed for the alignment of k-mer level data in a rank-dependent and position weight matrix (PWM)-independent manner. As the framework only depends on the rank of the input, the method can accept input from many types of experiments (protein binding microarray, SELEX-seq, SMiLE-seq, etc.) without the need for specialized parameterization. Measuring the performance of the alignment using multiple linear regression with 5-fold cross-validation, we find TDC to perform as well as or better than computationally expensive PWM-based methods.

Availability and implementation
TDC can be run online at https://topdowncrawl.usc.edu or locally as a python package available through pip at https://pypi.org/project/TopDownCrawl.

Supplementary information
Supplementary data are available at Bioinformatics online.
SNCA inhibits epithelial–mesenchymal transition and correlates to favorable prognosis of breast cancer
Authors: Zhou Lin-xi , Zheng Hong , Tian Yuan , Luo Ke-fei , Ma Shu-juan , Wu Zi-wei , Tang Peng , Jiang Jun , Wang Ming-hao 
Published: September 2022

AbstractAlpha-synuclein (SNCA) is a pathological hallmark of Parkinson’s disease, known to be involved in cancer occurrence and development; however, its specific effects in breast cancer remain unknown. Data from 150 patients with breast cancer were retrieved from tissue microarray and analyzed for SNCA protein level using immunohistochemistry. Functional enrichment analysis was performed to investigate the potential role of SNCA in breast cancer. SNCA-mediated inhibition of epithelial-mesenchymal transition (EMT) was confirmed with western blotting. The effects of SNCA on invasion and migration were evaluated using transwell and wound-healing experiments. Furthermore, the potential influence of SNCA expression level on drug sensitivity and tumor infiltration by immune cells was analyzed using the public databases. SNCA is lowly expressed in breast cancer tissues. Besides, in vitro and in vivo experiments, SNCA overexpression blocked EMT and metastasis, and the knockdown of SNCA resulted in the opposite effect. A mouse model of metastasis verified the restriction of metastatic ability in vivo. Further analysis revealed that SNCA enhances sensitivity to commonly used anti-breast tumor drugs and immune cell infiltration. SNCA blocks EMT and metastasis in breast cancer and its expression levels could be useful in predicting the chemosensitivity and evaluating the immune microenvironment in breast cancer.
Living Alone During Old Age and the Risk of Dementia: Assessing the Cumulative Risk of Living Alone
Authors: Shaw Benjamin A , Yang Tse-Chuan , Kim Seulki 
Published: September 2022

AbstractObjectivesThis study examines the association between living alone during old age and dementia. Whereas most previous studies on this topic utilize measures of living alone status that were obtained at a single point in time, we compare this typical approach to one that measures long-term exposure to living alone among older adults and assesses whether dementia is more likely to occur within individuals with more accumulated time living alone.MethodsData come from the Health and Retirement Study, with a follow-up period of 2000–2018. A total of 18,171 older adults were followed during this period, resulting in 78,490 person-waves analyzed in a series of multi-level logistic models. Contemporaneous living alone was recorded when a respondent’s household size was equal to 1 in a given wave. Cumulative living alone was calculated by adding the number of living alone statuses up to a given wave.ResultsContemporaneous living alone was either not associated (male-only subsample), or inversely associated (female-only subsample) with dementia. By contrast, a one-unit (i.e., one wave) increase in cumulative living alone was associated with about a 10% increase in the odds of dementia for both men (odds ratio [OR] = 1.111) and women (OR = 1.088), net of several covariates, including marital status, age, social activities, and social support.DiscussionLiving alone during late life is an important risk factor for dementia, but the cognitive effects of solitary living probably do not take hold immediately for most older adults and potentially demonstrate a dose–response relationship.
The Impact of Living in Housing With Care and Support on Loneliness and Social Isolation: Findings From a Resident-Based Survey
Authors: Beach Brian , Willis Paul , Powell Jillian , Vickery Alex , Smith Randall , Cameron Ailsa 
Published: September 2022

Abstract

Background and Objectives
Housing with care is often lauded as a way to combat loneliness and social isolation in later life. This study examined whether housing with care created better outcomes for residents in terms of loneliness and social isolation than they might expect if they were living in the community.

Research Design and Methods
A survey was distributed to residents of housing with care as part of the Diversity in Care Environments project. It was designed to enable comparison with the English Longitudinal Study of Ageing. Propensity score matching was applied to identify the effect of housing with care residence on loneliness and social isolation.

Results
People living in housing with care had lower levels of loneliness than would be expected if they lived in the general community, with an average treatment effect on the treated (ATT) of −0.407 (95% CI = −0.601, −0.214). In contrast, social isolation was found to be slightly higher for residents than would be expected if they were in the community (ATT = 0.134 [95% CI = 0.022, 0.247]). Higher social isolation appears driven by less frequent contact with friends and reduced organizational membership rather than any difference in contact with family and children.

Discussion and Implications
Our research has shown a positive impact on subjective social experiences from housing with care residence, despite a slight increase in objective social isolation. The findings underscore the importance of looking at loneliness and social isolation as distinct concepts as well as the effectiveness of housing with care at improving later-life outcomes.
Establishment and management of a workplace health promotion network in rural areas: a case study
Authors: Hente Luisa , Hodeck Alexander , Schlesinger Torsten 
Published: September 2022

Summary
Health is an increasingly important issue in the workplace, but the dissemination of health-promoting interventions in companies, especially in small and medium-sized enterprises (SMEs), remains limited. Inter-organizational networks seem to be a promising approach to promote and implement workplace health management (WHM) in SMEs. This study analyses the establishment and coordination of the network ‘ERZgesund—Healthy Companies in the Ore Mountains’ for WHM in SMEs in a rural area of Germany. The case study, which builds on a mixed method approach (expert interviews, participant observations and document analysis), finds that ERZgesund evolved from a top-down approach (politically initiated, regionally anchored and financed from promotional funds). The network’s hierarchy is disproportionately vertical, and the project group has limited decision-taking power and limited opportunities to act, which has reduced their overall engagement in the network. We conclude that although long and stable relationships are important for successful networks, change—especially at the leadership level—can lead to increased engagement of network participants if the hierarchy within the network is horizontally aligned. The findings of this explorative case study contribute to the planning process, the development and implementation of network structures, and successful WHM interventions.
Activation of nucleotide-binding oligomerization domain 2 by muramyl dipeptide negatively regulates Toll-like receptor 9-mediated colonic inflammation through the induction of deubiquitinating enzyme A expression
Authors: Masuta Yasuhiro , Minaga Kosuke , Kurimoto Masayuki , Sekai Ikue , Hara Akane , Omaru Naoya , Okai Natsuki , Otsuka Yasuo , Takada Ryutaro , Yoshikawa Tomoe , Masaki Sho , Kamata Ken , Honjo Hajime , Arai Yasuyuki , Yamashita Kouhei , Kudo Masatoshi , Watanabe Tomohiro 
Published: September 2022

Abstract
Mutations in nucleotide-binding oligomerization domain 2 (NOD2) are associated with Crohn’s disease (CD). Although NOD2 activation contributes to the maintenance of intestinal homeostasis through the negative regulation of pro-inflammatory cytokine responses mediated by Toll-like receptors (TLRs), the effects of NOD2 activation on interferon (IFN)-α responses induced by TLR9 have been poorly defined. To explore the cross-talk between NOD2 and TLR9, human monocytes or dendritic cells (DCs) were stimulated with NOD2 and/or TLR9 ligands to measure IFN-α production. The severity of dextran sodium sulfate (DSS)-induced colitis was compared in mice treated with NOD2 and/or TLR9 ligands. Expression of IFN-α and IFN-stimulated genes (ISGs) was examined in the colonic mucosa of patients with inflammatory bowel disease (IBD). NOD2 activation reduced TLR9-induced IFN-α production by monocytes and DCs in a deubiquitinating enzyme A (DUBA)-dependent manner. Activation of DUBA induced by the co-stimulation of TLR9 and NOD2 inhibited Lys63-linked polyubiquitination of TRAF3 and suppressed TLR9-mediated IFN-α production. NOD2 activation in hematopoietic cells protected mice from TLR9-induced exacerbation of DSS-induced colitis by down-regulating IFN-α responses and up-regulating DUBA expression. Colonic mucosa of patients with active and remitted IBD phases was characterized by the enhanced and reduced expression of ISGs, respectively. Expression levels of IFN-α and IL-6 positively correlated in the active colonic mucosa of patients with ulcerative colitis and CD, whereas DUBA expression inversely correlated with that of IFN-α in patients with CD. Collectively, these data suggest that DUBA-dependent negative effect of NOD2 on TLR9-mediated IFN-α responses contributes to the maintenance of intestinal homeostasis.
Paeoniflorin combined with norfloxacin ameliorates drug-resistant Streptococcus suis infection
Authors: Li Jinpeng , Fan Qingying , Zuo Jing , Xue Bingqian , Zhang Xiaoling , Wei Ying , Sun Liyun , Grenier Daniel , Yi Li , Hou Xiaogai , Wang Yang 
Published: September 2022

Abstract

Background
The increased resistance of bacterial pathogens to fluoroquinolones (FQs), such as norfloxacin and ciprofloxacin, supports the need to develop new antibacterial drugs and combination therapies using conventional antibiotics. The LuxS/AI-2 quorum sensing (QS) system can regulate the complex group behaviour of Streptococcus suis and impact its susceptibility to FQs.

Objectives
We investigated the combination of paeoniflorin and norfloxacin as a novel and effective strategy against FQ-resistant S. suis.

Methods
FIC, AI-2 activity assay, real-time RT–PCR and biofilm inhibition assays were performed to investigate the in vitro effect of paeoniflorin combined with norfloxacin. Mouse protection and mouse anti-infection assays were performed to investigate the in vivo effect of paeoniflorin combined with norfloxacin.

Results
FIC results showed that paeoniflorin and norfloxacin exert a synergistic bactericidal effect. Evidence was brought that paeoniflorin reduces the S. suis AI-2 activity and significantly down-regulates the transcription of the FQ efflux pump gene. In addition, paeoniflorin can inhibit biofilm formation, thereby promoting the ability of norfloxacin to kill S. suis. Finally, we showed in a mouse model that paeoniflorin in association with norfloxacin is effective to treat S. suis infections.

Conclusions
This study highlighted the inhibitory potential of paeoniflorin on the LuxS/AI-2 QS system of S. suis, and provided evidence that it can inhibit the FQ efflux pump and prevent biofilm formation to cooperate with norfloxacin in the treatment of resistant S. suis-related infections.
Take on transplant: human-centered design of a patient education tool to facilitate informed discussions about lung transplant among people with cystic fibrosis
Authors: Hartzler Andrea L , Bartlett Lauren E , Hobler Mara R , Reid Nick , Pryor Joseph B , Kapnadak Siddhartha G , Berry Donna L , Lober William B , Goss Christopher H , Ramos Kathleen J ,   for the Take on Transplant Study Group, Dunitz Jordan , Saavedra Milene , Pilewski Joseph M , Brown Cynthia D , Jia Shijing , Sears Edmund H , Neuringer Isabel , Polenakovik Hari M , Tsai Cynthia 
Published: September 2022

Abstract

Objective
Lung transplant (LTx) saves lives in cystic fibrosis (CF). However, many potential candidates express uncertainty about LTx and die before receiving this treatment. CF guidelines recommend LTx education and clinical discussions well before the need for LTx arises, but limited patient resources exist.

Materials and Methods
We engaged people with CF and CF physicians in human-centered design of “Take On Transplant” (TOT), a web-based education tool to prepare patients for LTx discussions. Across 3 phases, needs assessment, design groups, and iterative user testing of TOT, we refined TOT from wireframe prototypes, to an interactive website, to a fully functional intervention ready for clinical trials.

Results
Fifty-five people with CF and 105 physicians identified information needs to prepare for LTx discussions. Design groups (n = 14 participants) then established core requirements: didactic education (“Resource Library”), patient narratives (“CF Stories”), frequently asked questions (“FAQ”), and self-assessment to tailor content (“My CF Stage”). Iterative usability testing (n = 39) optimized the design of CF Stories and prototype layout. We then developed the TOT website and demonstrated feasibility and preliminary efficacy of use through 2-week field testing (n = 9).

Discussion
Our human-centered design process provided guidance for educational tools to serve the evolving needs of potential LTx candidates. Our findings support the process of patient deliberation as a foundation for shared decision-making in CF, and inform educational tools that could potentially translate beyond LTx.

Conclusion
TOT fills a critical gap in preparing people with CF for shared decision-making about LTx and may serve as a model for educational tools for other preference-sensitive decisions.
Using event logs to observe interactions with electronic health records: an updated scoping review shows increasing use of vendor-derived measures
Authors: Rule Adam , Melnick Edward R , Apathy Nate C 
Published: September 2022

Abstract

Objective
The aim of this article is to compare the aims, measures, methods, limitations, and scope of studies that employ vendor-derived and investigator-derived measures of electronic health record (EHR) use, and to assess measure consistency across studies.

Materials and Methods
We searched PubMed for articles published between July 2019 and December 2021 that employed measures of EHR use derived from EHR event logs. We coded the aims, measures, methods, limitations, and scope of each article and compared articles employing vendor-derived and investigator-derived measures.

Results
One hundred and two articles met inclusion criteria; 40 employed vendor-derived measures, 61 employed investigator-derived measures, and 1 employed both. Studies employing vendor-derived measures were more likely than those employing investigator-derived measures to observe EHR use only in ambulatory settings (83% vs 48%, P = .002) and only by physicians or advanced practice providers (100% vs 54% of studies, P &lt; .001). Studies employing vendor-derived measures were also more likely to measure durations of EHR use (P &lt; .001 for 6 different activities), but definitions of measures such as time outside scheduled hours varied widely. Eight articles reported measure validation. The reported limitations of vendor-derived measures included measure transparency and availability for certain clinical settings and roles.

Discussion
Vendor-derived measures are increasingly used to study EHR use, but only by certain clinical roles. Although poorly validated and variously defined, both vendor- and investigator-derived measures of EHR time are widely reported.

Conclusion
The number of studies using event logs to observe EHR use continues to grow, but with inconsistent measure definitions and significant differences between studies that employ vendor-derived and investigator-derived measures.
Separation of Nonivamide and Capsaicin by Ultrahigh-Performance Liquid Chromatography for Routine Analysis of Capsaicinoids in Capsicum Products
Authors: Yang Jinchuan , Pointer Ben , Rainville Paul 
Published: September 2022

AbstractBackgroundBaseline separation of nonivamide (NON) and capsaicin (CAP) has not been achieved by using the existing liquid chromatography (LC) methods for the capsaicinoid analysis. This could lead to large errors in the determination of capsaicinoids for capsicum products.ObjectiveThe development of an ultrahigh-performance liquid chromatography (UHPLC) method that simultaneously separates NON and CAP as well as other capsaicinoids for the routine analysis of capsaicinoids in capsicum products.MethodCapsaicinoids were separated on a Waters CORTECSTM T3 Column (2.1 mm i.d. × 150 mm, 1.6 μm particle size) that was maintained at 45°C on a UHPLC system with a 3-step gradient elution using a binary mobile phase system consisting of water and acetonitrile. Florescence detection was set at 280 nm excitation wavelength and 325 nm emission wavelength.ResultsThe UHPLC method was able to simultaneously separate NON and CAP, with a minimum resolution of 1.5, as well as other seven capsaicinoids with a total run time of 27 min. Method selectivity, robustness, accuracy, and precision were evaluated, and excellent performance was achieved.ConclusionsThe UHPLC method for NON and CAP and other seven capsaicinoids has been successfully developed and found suitable for the routine analysis of capsaicinoids.HighlightsFor the first time, NON and CAP are well separated (Rs &gt;1.5) in a 27 min LC separation. This UHPLC method offers a suitable solution for the determination of nine capsaicinoids in QC labs.
Burn Injury and Augmented Renal Clearance: A Case for Optimized Piperacillin-Tazobactam Dosing
Authors: Torian Sterling C , Wiktor Arek J , Roper Sara E , Laramie Kate E , Miller Matthew A , Mueller Scott W 
Published: September 2022

Abstract
Patients with burn injuries are at high risk for infection as well as altered antimicrobial pharmacokinetics. Patients suffering from a burn injury, generally encompassing a total body surface area (TBSA) ≥ 20%, have been cited as at risk for augmented renal clearance (ARC). Our case report describes an obese patient with 3.2% TBSA partial thickness burns who suffered from burn wound cellulitis with Pseudomonas aeruginosa. Measured CLcr documented the presence of ARC, and 22.5 grams daily continuous infusion of piperacillin-tazobactam was initiated. Therapeutic monitoring of piperacillin at steady state was 78 mcg/mL, achieving the prespecified goal piperacillin concentration of 100% 4-times the minimum inhibitory concentration assuming MIC for susceptible P. aeruginosa at 16/4 mcg/mL per Clinical Laboratory Standards Institute. Available literature suggests younger critically ill patients with lower organ failure scores, and for a burn injury, a higher percentage of TBSA, are most likely to exhibit ARC which does not entirely align with the characteristics of our patient. In addition, piperacillin-tazobactam has been associated with altered pharmacokinetics in ARC, burn, and obese populations, demonstrating failure to meet target attainment with standard doses. We suggest a continuous infusion of piperacillin-tazobactam be used when ARC is identified. This case report describes the unique findings of ARC in a non-critically ill burn patient and rationalizes the need for further prospective research to classify incidence, risk factors, and appropriate antimicrobial regimens for burn patients with ARC.
Data-based dynamic compartment model: Modeling ofE. colifed-batch fermentation in a 600 m3 bubble column
Authors: Bisgaard Jonas , Zahn James A , Tajsoleiman Tannaz , Rasmussen Tue , Huusom Jakob K , Gernaey Krist V 
Published: September 2022

AbstractMathematical modeling is a powerful and inexpensive approach to provide a quantitative basis for improvements that minimize the negative effects of bioreactor heterogeneity. For a model to accurately represent a heterogeneous system, a flow model that describes how mass is channeled between different zones of the bioreactor volume is necessary. In this study, a previously developed compartment model approach based on data from flow-following sensor devices was further developed to account for dynamic changes in volume and flow rates and thus enabling simulation of the widely used fed-batch process. The application of the dynamic compartment model was demonstrated in a study of an industrial fermentation process in a 600 m3 bubble column bioreactor. The flow model was used to evaluate the mixing performance by means of tracer simulations and was coupled with reaction kinetics to simulate concentration gradients in the process. The simulations showed that despite the presence of long mixing times and significant substrate gradients early in the process, improving the heterogeneity did not lead to overall improvements in the process. Improvements could, however, be achieved by modifying the dextrose feeding profile.