bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cumulative Effects of Comorbid Burden and Overactive Bladder Symptoms on Fall Risk Among Older Women Seeking Treatment for Urogynecologic Conditions
Authors: Fisher Steve R. , Halder Gabriela E. , Lee Mi Jung , Allen Lindsay , Kilic Gokhan S. 
Published: August 2023

Importance
Overactive bladder (OAB) syndrome and urinary incontinence, age, and comorbid burden are strong risk factors for falls in women. Less is known about their cumulative effects on fall risk in a urogynecologic population.

Objective
The purpose of this study was to investigate the effects of coexisting OAB, older age, and comorbidities on risk of falling among treatment seeking women with pelvic floor disorders.

Study Design
We conducted a retrospective medical records review of 348 consecutive women presenting to a urogynecology clinic over 6 months. Fall risk was determined by the Centers for Disease Control and Prevention’s, Stopping Elderly Accidents, Deaths, and Injuries screening tool. Clinical and sociodemographic measures were abstracted from the electronic medical record. Odds of screening positive for high fall risk based on different patient profiles were calculated. We then used a classification and regression tree analysis to determine the relative importance of the different variables on fall risk within the homogeneous subgroups.

Results
Of the 348 women (mean age, 58.7 ± 15.8 years) who completed the fall risk screen, 124 (36%) screened positive for increased fall risk. Overactive bladder symptoms increased the likelihood of a positive fall risk screen across all combinations of age and comorbid burden. The patient profile of ≥3 OAB symptoms, ≥4 comorbid conditions, and age 65 years or older increased the odds of screening positive for high fall risk more than 6-fold (odds ratio, 6.4; 95% confidence interval, 3.1–12.9). In the following order of importance, the combination of high comorbid burden, OAB, and older age identified approximately 3 in 4 patients (73.3%) at high risk of falling.

Conclusion
The presence of 3 easily identifiable patient characteristics is strongly associated with a risk of falls in women seeking care for pelvic floor disorders.
ORCHID: A Comprehensive Oral Cancer Histology Image Database for Histopathological Analytics and Diagnostics
Authors: Chaudhary Nisha , Rai Arpita , Rao Aakash Madhav , Faizan Md Imam , Augustine Jeyaseelan , Chaurasia Akhilanand , Mishra Deepika , Chandra Akhilesh , Chauhan Varnit , Kutum Rintu , Ahmad Tanveer 
Published: August 2023

AbstractOral cancer is a global health challenge with a difficult histopathological diagnosis. The accurate histopathological interpretation of oral cancer tissue samples remains difficult. However, early diagnosis is very challenging due to a lack of experienced pathologists and inter-observer variability in diagnosis. The application of artificial intelligence (deep learning algorithms) for oral cancer histology images is very promising for rapid diagnosis. However, it requires a quality annotated dataset to build AI models. We present ORCHID (ORalCancerHistologyImageDatabase), a specialized database generated to advance research in AI-based histology image analytics of oral cancer and precancer. The ORCHID database is an extensive multicenter collection of 300,000 image patches, encapsulating various oral cancer and precancer categories, such as oral submucous fibrosis (OSMF) and oral squamous cell carcinoma (OSCC). Additionally, it also contains grade-level sub-classifications for OSCC, such as well-differentiated (WD), moderately-differentiated (MD), and poorly-differentiated (PD). Furthermore, the database seeks to bolster the creation and validation of innovative artificial intelligence-based rapid diagnostics for OSMF and OSCC, along with subtypes.
Endotoxin, unidentified material, and low amounts of defined toxicants are confounding factors when using the air pollution Standard Reference Material (SRM) 2786 in biological experiments
Authors: Miller Charles 
Published: August 2023

AbstractThe National Institute of Standards and Technology (NIST) provides the reference sample SRM 2786 for use in analytical studies of particulate air pollution. The sample originated from an atypical source and possibly contains materials that are unrelated to air pollution. Investigators conducting studies with SRM 2786 should note the relatively low amounts of toxic components listed in the certificate of analysis as well as a large amount of uncharacterized material. Additionally, there is no unsized reference material that can be used as a control for the particulate nature of SRM 2786. The presence of a low amount of endotoxin in SRM 2786 is reported here. Endotoxin and other uncharacterized material in SRM 2786 may influence results and conclusions for biological studies using this reference material.
Unified cross-modality integration and analysis of T-cell receptors and T-cell transcriptomes
Authors: Gao Yicheng , Dong Kejing , Gao Yuli , Jin Xuan , Liu Qi 
Published: August 2023

AbstractSingle-cell RNA sequencing and T-cell receptor sequencing (scRNA-seq and TCR-seq, respectively) technologies have emerged as powerful tools for investigating T-cell heterogeneity. However, the integrated analysis of gene expression profiles and TCR sequences remains a computational challenge. Herein, we present UniTCR, a unified framework designed for the cross-modality integration and analysis of TCRs and T-cell transcriptomes for a series of challenging tasks in computational immunology. By utilizing a dual-modality contrastive learning module and a single-modality preservation module to effectively embed each modality into a common latent space, UniTCR demonstrates versatility across various tasks, including single-modality analysis, modality gap analysis, epitope-TCR binding prediction and TCR profile cross-modality generation. Extensive evaluations conducted on multiple scRNA-seq/TCR-seq paired datasets showed the superior performance of UniTCR. Collectively, UniTCR is presented as a unified and extendable framework to tackle diverse T-cell-related downstream applications for exploring T-cell heterogeneity and enhancing the understanding of the diversity and complexity of the immune system.
LIANA+: an all-in-one cell-cell communication framework
Authors: Dimitrov Daniel , Schäfer Philipp Sven Lars , Farr Elias , Rodriguez Mier Pablo , Lobentanzer Sebastian , Dugourd Aurelien , Tanevski Jovan , Ramirez Flores Ricardo Omar , Saez-Rodriguez Julio 
Published: August 2023

AbstractThe growing availability of single-cell and spatially-resolved transcriptomics has led to the rapidly growing popularity of methods to infer cell-cell communication. Many approaches have emerged, each capturing only a partial view of the complex landscape of cell-cell communication.Here, we present LIANA+, a scalable framework to decode coordinated inter- and intracellular signalling events from single- and multi-condition datasets in both single-cell and spatially-resolved data. Beyond integrating and extending established methodologies and a rich knowledge base, LIANA+ enables novel analyses using diverse molecular mediators, including those measured in multi-omics data. Accessible as an open-source Python package athttps://github.com/saezlab/liana-py, LIANA+ provides a comprehensive set of synergistic components to study cell-cell communication.Abstract Figure
Cross-tissue comparison of telomere length and quality metrics of DNA among individuals aged 8 to 70 years
Authors: Wolf Sarah E. , Hastings Waylon J. , Ye Qiaofeng , Etzel Laura , Apsley Abner T. , Chiaro Christopher , Heim Christine C. , Heller Thomas , Noll Jennie G. , Schreier Hannah M.C. , Shenk Chad E. , Shalev Idan 
Published: August 2023

AbstractTelomere length (TL) is an important biomarker of cellular aging, yet its links with health outcomes may be complicated by use of different tissues. We evaluated within- and between-individual variability in TL and quality metrics of DNA across five tissues using a cross-sectional dataset ranging from 8 to 70 years (N=197). DNA was extracted from all tissue cells using the Gentra Puregene DNA Extraction Kit. Absolute TL (aTL) in kilobase pairs was measured in buccal epithelial cells, saliva, dried blood spots (DBS), buffy coat, and peripheral blood mononuclear cells (PBMCs) using qPCR. aTL significantly shortened with age for all tissues except saliva and buffy coat, although buffy coat was available for a restricted age range (8 to 15 years). aTL did not significantly differ across blood-based tissues (DBS, buffy coat, PBMC), which had significantly longer aTL than buccal cells and saliva. Additionally, aTL was significantly correlated for the majority of tissue pairs, with partial Spearman’s correlations controlling for age and sex ranging from ⍴ = 0.18 to 0.51. We also measured quality metrics of DNA including integrity, purity, and quantity of extracted DNA from all tissues and explored whether controlling for DNA metrics improved predictions of aTL. We found significant tissue variation: DNA from blood-based tissues had high DNA integrity, more acceptable A260/280 and A260/230 values, and greater extracted DNA concentrations compared to buccal cells and saliva. Longer aTL was associated with lower DNA integrity, higher extracted DNA concentrations, and higher A260/230, particularly for saliva. Model comparisons suggested that incorporation of quality DNA metrics improves models of TL, although relevant metrics vary by tissue. These findings highlight the merits of using blood-based tissues and suggest that incorporation of quality DNA metrics as control variables in population-based studies can improve TL predictions, especially for more variable tissues like buccal and saliva.
Interspecific continuity of normative systems (the end of the paradigm of human exceptionalism)
Authors: Gandarillas Chicote L. , De La Cuesta Aguado P.M. 
Published: August 2023

AbstractAfter fifteen years observing a troop of western lowland gorillas (Gorilla gorilla) outside their natural habitat under human care we believe we can demonstrate that gorillas govern their behavior and social interactions by norms functionally equivalent to legal norms that pursue group stability and social peace maintenance and can be “translated” into concepts created for legal science. Consequently, we conclude that also in the legal sciences and, especially, in the juridicial-criminal science, the paradigm of human exceptionality must be overcome to open the doors to reflect on the possibility of establishing the paradigm of continuity between human and non-human normative systems.
Paneth cells disruption and intestinal dysbiosis contribute to the development of Hirschsprung-associated enterocolitis in a benzalkonium chloride-induced Hirschsprung’s disease rat model
Authors: Budianto Iskandar Rahardjo , Kusmardi Kusmardi , Maulana Andi Muhammad , Arumugam Somasundaram , Afrin Rejina , Soetikno Vivian 
Published: August 2023

AbstractBackgroundHirschsprung-associated enterocolitis (HAEC) is a life-threatening complication of Hirschsprung’s disease (HSCR). This study investigated the role of Paneth cells (PCs) and gut microbiota in HAEC development.MethodsMale Sprague-Dawley rats with HSCR were established by exposure of 0.1% (n = 30) benzalkonium chloride (BAC) to rectosigmoid serosa and sacrificed at 1-, 3-, 5-, 8-, and 12-weeks postintervention. The sham group was included and sacrificed on Week 12. Hematoxylin-Eosin staining was conducted to count the number of ganglionic cells and analyze the degree of enterocolitis. Intestinal barrier function was assessed for the ratio of anti-peripherin, occludin and acetylcholinesterase (AChE)/butyrylcholinesterase (BChE). PCs antimicrobial peptide (AMP) was evaluated by cryptdins, secretory Phospholipase A2, and lysozyme levels by qRT-PCR, respectively. 16S rRNA high throughput sequencing on faecal samples was used to analyze the changes in intestinal microbiota diversity in each group.ResultsCompared with sham groups, 0.1% BAC group rats had fewer ganglion cells after 1-week postintervention. Occludin and peripherin were decreased, and AChE/BChE ratio was increased, respectively. Sigmoid colon tissues from BAC-treated rats showed increased α-defensins positive PCs on Week 5 postintervention. Conversely, PCs-produced AMP tended to decrease from Week 5 to Week 12. Rats in the sham group demonstrated increasedLactobacillusand decreasedBacteroides, while rats in the 0.1% BAC exhibited reciprocal changes. Enterocolitis occurred from Week 1 postintervention onwards.ConclusionDisruption of PCs in the Week 5 postintervention and dysbiosis exacerbate the occurrence of HAEC. This research sheds new light on the cellular mechanisms of HAEC development.
Connection between drug-mediated neurotransmission and salivary microbiome
Authors: Hisamatsu Daisuke , Ogata Yusuke , Takeshige-Amano Haruka , Suda Wataru , Hatano Taku , Asaoka Daisuke , Mabuchi Yo , Naraoka Yuna , Sato Nobuhiro , Asada Takashi , Hattori Nobutaka , Hattori Masahira , Akazawa Chihiro 
Published: August 2023

SummarySalivary microbiome alterations associated with cognitive function have been reported in patients with neurodegenerative diseases1–3. Gut microorganisms can modulate therapeutic efficacy via drug metabolism4–7. Additionally, several drugs against diabetes and inflammatory bowel disease can lead to microbial dysbiosis8–10. However, the effect of central nervous system (CNS) drug use on the microbiome remains unknown. Here, we show that the usage of anti-dementia drugs, including donepezil and memantine, more largely affects the salivary microbiome composition than the gut microbiome composition. We observed salivary microbiome diversity reduction in patients with neurodegenerative diseases who receivedN-methyl-D-aspartate receptor inhibitor drugs. Furthermore, the use of acetylcholine-modulating drugs contributed to the salivary microbiome composition, suggesting that the salivary microbiome responds to changes in CNS drug-induced cerebral acetylcholine and glutamate levels. Multivariate analysis adjusted with or without the use of anti-dementia drugs demonstrated that the difference in the salivary microbiome correlated with cognitive function. We show the unique salivary microbiome structure of CNS drug users, suggesting the possibility of monitoring pharmacokinetics using the salivary microbiome. Our results also provide evidence of the presence of the microbiome–oral–brain axis and will accelerate the elucidation of the interplay between the salivary microbiome and neurodegeneration.
The Lifespan Trajectories of Brain Activities Related to Cognitive Control
Authors: Li Zhenghan , Petersen Isaac T. , Wang Lingxiao , Radua Joaquim , Yang Guo-chun , Liu Xun 
Published: August 2023

AbstractCognitive control plays a pivotal role in guiding human goal-directed behavior. While existing studies have documented an inverted U-shaped trajectory of cognitive control both behaviorally and anatomically, little is known about the corresponding changes in functional brain activation with age. To bridge this gap, we conducted a comprehensive meta-analysis of 129 neuroimaging studies using conflict tasks, encompassing 3,388 participants aged from 5 to 85 years old. We have three major findings: 1) The inverted U-shaped trajectory is the predominant pattern; 2) Cognitive control-related brain regions exhibit heterogeneous lifespan trajectories: the frontoparietal control network follows inverted U-shaped trajectories, peaking between 24 and 40 years, while the dorsal attention network demonstrates no clear trajectories; 3) Both the youth and the elderly show weaker brain activities and greater left laterality than young to middle-aged adults. These results reveal the lifespan trajectories of cognitive control, highlighting heterogeneous fluctuations in brain networks with age.Classification:Biological Sciences/Psychological and Cognitive Sciences
Injectable butyrate-prodrug micelles induce long-acting immune modulation and suppress autoimmune arthritis in mice
Authors: Cao Shijie , Budina Erica , Wang Ruyi , Sabados Matthew , Solanki Ani , Nguyen Mindy , Hultgren Kevin , Dhar Arjun , Hubbell Jeffrey A. 
Published: August 2023

AbstractDysbiosis is linked to autoimmune diseases such as rheumatoid arthritis (RA), where microbial metabolites, such as short chain fatty acids (SCFAs), mediate the so-called gut-joint axis. The therapeutic potential of SCFAs is limited due to the frequent and high oral dosage requirements. RA is characterized by aberrant activation of peripheral T cells and myeloid cells. We aim to deliver butyrate, an SCFA, directly to the lymphatics using a polymeric micelle as a butyrate prodrug, creating a depot for inducing long-lasting immunomodulatory effects. Notably, negatively charged micelles (Neg-ButM) demonstrate superior efficacy in targeting the lymphatics post-subcutaneous administration, and were retained in the draining lymph nodes, spleen, and liver for over a month. In a mouse RA model, we found that Neg-ButM substantially mitigated arthritis symptoms and promoted tolerogenic phenotypes in T cells and myeloid cells, both locally and systemically. These findings suggest potential applications of this approach in treating inflammatory autoimmune diseases.
Robust Adaptive Deep Brain Stimulation Control of Non-Stationary Cortex-Basal Ganglia-Thalamus Network Models in Parkinson’s Disease
Authors: Fang Hao , Berman Stephen A. , Wang Yueming , Yang Yuxiao 
Published: August 2023

AbstractClosed-loop deep brain stimulation (DBS) is a promising therapy for Parkinson’s disease (PD) that works by adjusting DBS patterns in real time from the guidance of feedback neural activity. Current closed-loop DBS mainly uses threshold-crossing on-off controllers or linear time-invariant (LTI) controllers to regulate the basal ganglia (BG) beta band oscillation power. However, the critical cortex-BG-thalamus network dynamics underlying PD are nonlinear, non-stationary, and noisy, hindering the accurate and robust control of PD neural dynamics using current closed-loop DBS methods. Here, we develop a new robust adaptive closed-loop DBS method for regulating cortex-BG-thalamus network dynamics in PD. We first build an adaptive state-space model to quantify the dynamic, nonlinear, and non-stationary neural activity. We then construct an adaptive estimator to track the nonlinearity and non-stationarity in real time. We next design a robust controller to automatically determine the DBS frequency based on the estimated PD neural state while reducing the system’s sensitivity to high-frequency noise. We adopt and tune a biophysical cortex-BG-thalamus network model as a testbed to simulate various nonlinear and non-stationary neural dynamics for evaluating DBS methods. We find that under different nonlinear and non-stationary neural dynamics, our robust adaptive DBS method achieved accurate regulation of the BG beta band oscillation power with small control error, bias, and deviation. Moreover, the accurate regulation generalizes across different therapeutic targets and consistently outperforms state-of-the-art on-off and LTI DBS methods. These results have implications for future designs of clinically-viable closed-loop DBS systems to treat PD and other neurological and neuropsychiatric disorders.
Canonical Wnt transcriptional complexes are essential for induction of nephrogenesis but not maintenance or proliferation of nephron progenitors
Authors: Bugacov Helena , Der Balint , Kim Sunghyun , Lindström Nils O. , McMahon Andrew P. 
Published: August 2023

AbstractWnt regulated transcriptional programs are associated with both the maintenance of mammalian nephron progenitor cells (NPC) and their induction, initiating the process of nephrogenesis. How opposing transcriptional roles are regulated remain unclear. Using anin vitromodel replicatingin vivoevents, we examined the requirement for canonical Wnt transcriptional complexes in NPC regulation. In canonical transcription, Lef/Tcf DNA binding proteins associate the transcriptional co-activator β-catenin. Wnt signaling is readily substituted by CHIR99021, a small molecule antagonist of glycogen synthase kinase-3β (GSK3β). GSK3β inhibition blocks Gskβ-dependent turnover of β-catenin, enabling formation of Lef/Tcf/β-catenin transcriptional complexes, and enhancer-mediated transcriptional activation. Removal of β-catenin activity from NPCs under cell expansion conditions (low CHIR) demonstrated a non-transcriptional role for β-catenin in the CHIR-dependent proliferation of NPCs. In contrast, CHIR-mediated induction of nephrogenesis, on switching from low to high CHIR, was dependent on Lef/Tcf and β-catenin transcriptional activity. These studies point to a non-transcriptional mechanism for β-catenin in regulation of NPCs, and potentially other stem progenitor cell types. Further, analysis of the β-catenin-directed transcriptional response provides new insight into induction of nephrogenesis.Summary StatementThe study provides a mechanistic understanding of Wnt/ β-catenin activity in self-renewal and differentiation of mammalian nephron progenitors.
A patient-derived blood-brain barrier model for screening copper bis(thiosemicarbazone) complexes as potential therapeutics in Alzheimer’s disease
Authors: Wasielewska Joanna M. , Szostak Kathryn , McInnes Lachlan E. , Quek Hazel , Chaves Juliana C. S. , Liddell Jeffrey R. , Koistinaho Jari , Oikari Lotta E. , Donnelly Paul S. , White Anthony R. 
Published: August 2023

AbstractAlzheimer’s disease (AD) is the most prevalent cause of dementia characterised by progressive cognitive decline. Addressing neuroinflammation represents a promising therapeutic avenue to treat AD, however, the development of effective anti-neuroinflammatory compounds is often hindered by their limited blood-brain barrier (BBB) permeability. Consequently, there is an urgent need for accurate, preclinical AD patient-specific BBB models to facilitate the early identification of immunomodulatory drugs capable of efficiently crossing human AD BBB.This study presents a unique approach to BBB drug permeability screening as it utilises the familial AD patient-derived induced brain endothelial-like cells (iBEC)-based model, which exhibits increased disease relevance and serves as an improved BBB drug permeability assessment tool when compared to traditionally employedin vitromodels. To demonstrate its utility as a small molecule drug candidate screening platform, we investigated the effects of CuII(atsm) and a library of novel metal bis(thiosemicarbazone) complexes – a class of compounds exhibiting anti-neuroinflammatory therapeutic potential in neurodegenerative disorders. By evaluating the toxicity, cellular accumulation and permeability of those compounds in the AD patient-derived iBEC, we have identified CuII(dtsm) as an emerging drug candidate with enhanced transport across the AD BBB. Furthermore, we have developed a multiplex approach where AD patient-derived iBEC were combined with immune modulators TNFα and IFNγ to establish anin vitromodel representing the characteristic neuroinflammatory phenotype at the patient’s BBB. Here we observed that treatment with CuII(dtsm) not only reduced the expression of proinflammatory cytokine genes but also reversed the detrimental effects of TNFα and IFNψ on the integrity and function of the AD iBEC monolayer. This suggests a novel pathway through which copper bis(thiosemicarbazone) complexes may exert neurotherapeutic effects in AD by mitigating BBB neuroinflammation and related BBB integrity impairment.Together, the presented model provides an effective and easily scalablein vitroBBB platform for screening AD drug candidates. Its improved translational potential makes it a valuable tool for advancing the development of metal-based compounds aimed at modulating neuroinflammation in AD.Graphical abstract