bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing retinal thickness and vascular structures in an Alzheimer's disease mouse model APP NL‐F/NL‐F
Authors: Sanchez‐Puebla Lidia , López‐Cuenca Inés , Jiménez María González , Salobrar‐Garcia Elena , Matamoros José A. , Lozano María Pilar Rojas , Fernández‐Albarral José A. , Elvira‐Hurtado Lorena , Ramirez Ana Isabel , Salazar Juan Jose , Nieto‐Vaquero Carmen , Desviat María Isabel Cuartero , Moro María Ángeles , Saito Takashi , Saido Takaomi C. , Ramirez Jose Manuel , de Hoz Rosa 
Published: January 2025

Aims/Purpose: In Alzheimer's disease (AD), there are histopathological aspects that cannot be studied in patients, demanding the use of murine models of the disease. The APPNL‐F/NL‐F model reproduces the pathophysiology quite faithfully. The aim of the present study was to analyze the retinal vascular structures and retinal thickness in an AD model at different ages and compares these findings to age‐matched wild type (WT) controls.Methods: A diachronic study was conducted using spectral‐domain OCT angiography (SD‐OCTA) and AngioTool software to assess retinal vascular structures, alongside OCT for measuring inner and outer retina thickness. We include two study groups: the APPNL‐F/NL‐F AD model and WT controls at 6, 9, 12, 15, 17, and 20 months old. The analysis focused on the three vascular plexus and retinal thickness, using the Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. We considered statistically significant a p‐value < 0.05.Results: Compared to WT, the APPNL‐F/NL‐F group exhibited both vascular and structural changes starting as early as 6 months, with these changes persisting and evolving at 15, 17, and 20 months. Significant vascular alterations, particularly in the superficial vascular complex (SVC), were noted. There was a marked decrease in vessel area and total vessel length in the SVC, as well as in the intermediate and deep capillary plexus. Additionally, the inner retina predominantly showed a thickness decrease, while the outer retina demonstrated an increased thickness at most time points compared to the control group.Conclusions: The study identifies early retinal vascular and structural changes in the APPNL‐F/NL‐F model that precede cognitive changes observed at later stages. These findings suggest that the retinal changes in this model more closely resemble those in human AD compared to other transgenic models, highlighting the potential of retinal assessments in early AD diagnosis.
Post‐secondary education in young patients with inflammatory bowel disease: A population‐based cohort study
Authors: Rasmussen Julie , Nørgård Bente Mertz , Gaardskær Nielsen Rasmus , Qvist Niels , Bøggild Henrik , Fonager Kirsten 
Published: January 2025

AbstractAimInflammatory bowel disease (IBD) diagnosed in adolescence may have adverse effects on educational attainment. The study aims to examine post‐secondary educational attainment in patients with IBD and how it is affected by disease severity and comorbid mental health disorders.MethodsThis cohort study used nationwide Danish registries. In a cohort of patients with IBD and matched references, the time to attainment of post‐secondary education was examined using Cox regression. In the analysis for disease severity and mental health disorders, the relative risk of attainment of post‐secondary education was evaluated using binomial regression.ResultsWe identified 1136 patients with IBD and 8791 references. Overall, patients with Crohn's disease (CD) or ulcerative colitis (UC) attained a post‐secondary education as often as references (CD: hazard ratio (HR) 1.10 (95% confidence interval (CI) 0.99–1.22); UC: HR 0.97 (95% CI 0.88–1.06)). Patients with both severe IBD and mental health disorders had a significantly lower chance of attaining a post‐secondary education compared to patients with severe IBD without mental health disorders.ConclusionsPatients with IBD attained a post‐secondary education at the same rate as references. Having both severe IBD and mental health disorder negatively affected post‐secondary educational attainment.
Pharmacological profiling of small molecule modulators of the TMEM16A channel and their implications for the control of artery and capillary function
Authors: Al‐Hosni Rumaitha , Agostinelli Emilio , Ilkan Zeki , Scofano Lara , Kaye Rachel , Dinsdale Ria L. , Acheson Kathryn , MacDonald Andrew , Rivers Dean , Biosa Alice , Gunthorpe Martin J. , Platt Frances , Tammaro Paolo 
Published: January 2025

AbstractBackground and purposeTMEM16A chloride channels constitute a depolarising mechanism in arterial smooth muscle cells (SMCs) and contractile cerebral pericytes. TMEM16A pharmacology is incompletely defined. We elucidated the mode of action and selectivity of a recently identified positive allosteric modulator of TMEM16A (PAM_16A) and of a range of TMEM16A inhibitors. We also explore the consequences of selective modulation of TMEM16A activity on arterial and capillary function.Experimental approachPatch‐clamp electrophysiology, isometric tension recordings, live imaging of cerebral cortical capillaries and assessment of cell death were employed to explore the effect of selective pharmacological control of TMEM16A on vascular function.Key ResultsIn low intracellular free Ca2+ concentrations ([Ca2+]i), nanomolar concentrations of PAM_16A activated heterologous TMEM16A channels, while being almost ineffective on the closely related TMEM16B channel. In either the absence of Ca2+ or in saturating [Ca2+]i, PAM_16A had no effect on TMEM16A currents at physiological potentials. PAM_16A selectively activated TMEM16A currents in SMCs and enhanced aortic contraction caused by phenylephrine or angiotensin‐II and capillary (pericyte) constriction evoked by endothelin‐1 or oxygen–glucose deprivation (OGD) to simulate cerebral ischaemia. Conversely, selective TMEM16A inhibition with Ani9 facilitated aortic, mesenteric and pericyte relaxation, and protected against OGD‐mediated pericyte cell death. Unlike PAM_16A and Ani9, a range of other available modulators were found to interfere with endogenous cationic currents in SMCs.Conclusions and implicationsArterial tone and capillary diameter can be controlled with TMEM16A modulators, highlighting TMEM16A as a target for disorders with a vascular component, including hypertension, stroke, Alzheimer's disease and vascular dementia.
Clinical value of the Japanese version of patient‐reported multiple sclerosis neuropsychological screening questionnaire
Authors: Muryoi Atsuya , Nei Michiko , Fujimori Juichi , Nakashima Ichiro 
Published: January 2025

AbstractBackgroundNeuropsychological abnormalities are common in patients with multiple sclerosis (MS); however, unlike motor and sensory deficits, their measurement in a clinical setting can be difficult.MethodsWe evaluated 80 patients with MS using the newly created Japanese version of a patient‐report form of the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) and compared the results with those of processing speed tests (PST), namely, CogEval, and health‐related quality of life (QOL). QOL was evaluated using the Medical Outcomes Study Short Form‐36 Health Survey (SF‐36).ResultsThe partial correlation coefficient, after excluding the effect of disease duration, showed that the total MSNQ score was significantly correlated with PST (r = −0.2798, P = .0125), mental component summary (MCS) (r = −0.2913, P = .0092), and social role component summary (RCS) (r = −0.2591, P = .0211) in SF‐36. Multiple linear regression analyses showed that physical component summary was significantly associated with age (P = .0158), EDSS (P = .0005), and CogEval raw score (P = .0029), whereas MCS was significantly associated with MSNQ (P = .0007). When patients with MS were divided into two groups using a median total MSNQ score threshold of 17, those with high MSNQ scores showed significantly higher EDSS scores (P = .0101), lower PST scores (P = .0426), and lower MCS scores in SF‐36 (P = .0083).ConclusionThe Japanese version of the patient‐reported MSNQ can be useful in identifying patients with decreased mental QOL, which might be more difficult than to capture physical QOL.
An interdisciplinary approach to improving conservation outcomes for parasites
Authors: Brown Timothy M. , Dunn Alison M. , Quinnell Rupert J. , Clarke Ellen , Cunningham Andrew A. , Goodman Simon J. 
Published: January 2025

AbstractParasites represent a significant proportion of Earth's biodiversity and play important roles in the ecology and biology of ecosystems and hosts, making them an important target for conservation. Despite increasing calls to prioritize protection for parasites in the academic literature, they remain undervalued and underrepresented in global biodiversity conservation efforts, not least due to the perception that the interests of parasite and host conservation are opposing and the common misconception that parasites are a threat, rather than a benefit, to conservation. We considered whether taking an interdisciplinary approach to parasite conservation research will generate novel insights and solutions concerning why and how parasite conservation should be practiced for the benefit of parasites, their hosts, ecosystems, and people. We argue that 2 of the main barriers to more widespread parasite conservation are the knowledge gap concerning the role of sociocultural factors affecting the willingness to enact parasite conservation and the lack of a consistent and cohesive philosophical basis for parasite conservation. Possible sociocultural barriers to parasite conservation include misconceptions of the risks posed by parasites, taxonomic bias, differences in conservation values, economic constraints, and technical challenges. The use of social science can generate insights into levels of awareness and support for parasite conservation and improve understanding of how human values and attitudes mediate conservation practices concerning parasites. Such knowledge will have a critical role in addressing sociocultural barriers and improving support for parasite conservation. Issues with the current philosophical basis for parasite conservation include contradictory accounts of which parasites merit conservation, insufficient explanation of how different conservation values apply to parasite biodiversity, and the existence of a false antagonism between host and parasite conservation. Greater engagement with philosophical work on environmental ethics and biological unitization will strengthen existing arguments for parasite conservation and will support conservation decision‐making processes.
Dapagliflozin modulates hepatic lipid metabolism through the proprotein convertase subtilisin/kexin type 9/low density lipoprotein receptor pathway
Authors: Lu Fengyuan , Li En , Gao Yifeng , Zhang Yan , Kong Lijuan , Yang Xiaoyu 
Published: January 2025

AbstractBackgroundProprotein convertase subtilisin/kexin type 9 (PCSK9) is mainly secreted by the liver, and plays a crucial role in lipid metabolism disorder. Sodium‐glucose cotransporter 2 inhibitors (SGLT2i) can regulate lipid metabolism through various pathways, including reducing visceral fat accumulation, modulating serum lipoprotein levels and alleviating hepatic steatosis. However, the specific regulatory mechanisms remain unclear.MethodsWe built a model of glucose and lipid metabolism disorder in vivo and in vitro, and explored the regulatory mechanism of dapagliflozin in regulating liver lipid metabolism.ResultsWe found that the SGLT2i dapagliflozin significantly reduced serum levels of PCSK9, total cholesterol (TC), low density lipoprotein cholesterol (LDL‐C) in high‐fat diet (HFD)‐fed mice, while also improving hepatic steatosis. In vitro studies confirmed that dapagliflozin increased LDL receptor (LDLR) expression in HepG2 cells, enhancing their ability to uptake LDL‐C.ConclusionsFurther mechanistic studies revealed that the hepatocyte nuclear factor‐1‐alpha (HNF1α)/PCSK9/LDLR signalling pathway may be involved in dapagliflozin's regulation of lipid metabolism homeostasis.
Development and Preliminary Validation of a Novel Instrument to Assess Re‐Injury Associated Anxiety Following Traumatic Orofacial and Dental Injury in Young Boxers
Authors: Ravi Mugilan , Tewari Nitesh , Mathur Vijay Prakash , Haldar Partha , Bhargava Rachna , Deep Raman , Rahul Morankar , Bansal Kalpana , Goel Shubhi , Raghuthaman Sruthila 
Published: January 2025

ABSTRACTBackground/AimAn injury sustained during sports activity can lead to the development of reinjury anxiety and hamper performance. Although tools exist to assess re‐injury anxiety, a domain of interest in the field of sports medicine, research in the psychological impact of an orofacial injury is rudimentary. The present study envisaged to develop an instrument to assess the presence of reinjury anxiety following orofacial and dental injury in boxers aged between 10 and 16 years.MethodsIn Phase 1, items were generated following literature search and focus‐group discussions (FGD). In Phase 2, a group discussion was conducted with three experienced boxing coaches to assess face validity, followed by two rounds of scrutiny by expert groups to assess the content validity through the content‐validity‐index (CVI), respectively. In Phase 3, the modified tool was pre‐tested on an independent sample of young boxers. Finally, in Phase 4, to determine dimensionality, the modified tool was administered to 183 young boxers and their responses were subject to an exploratory factor analysis through Principal component analysis, followed by Promax rotation to determine the factor loading. Internal consistency reliability was measured through calculation of Cronbach's‐alpha.ResultsFrom the 29‐items devised initially, the tool was sequentially modified. Analysis of the responses by the second expert group, an average Scale‐level‐CVI of 0.9 and Universal agreement of 0.526 was obtained, which resulted in the inclusion of 20 items for the final phase of the study. From the factor analysis, the items were found to fit to a five‐factor structure, which explained 56.4% of the variance in the constructs. Internal consistency of the tool was measured to be 0.74.ConclusionA 10‐item oral re‐injury anxiety scale for young boxers (ORAS‐YB) tool was developed. It was found to have high face and content validity, and acceptable reliability. Further research with a larger sample is required to confirm the factor structure and determine test–retest reliability of the developed tool.
Living in Biological Darkness II: Impact of Winter Habitual Daytime Light on Night‐Time Sleep
Authors: Nowozin Claudia , Wahnschaffe Amely , de Zeeuw Jan , Papakonstantinou Alexandra , Hädel Sven , Rodenbeck Andrea , Bes Frederik , Kunz Dieter 
Published: January 2025

ABSTRACTTiming and architecture of sleep are co‐driven by circadian rhythms modulated by their major Zeitgeber light and darkness. In a natural environment, one is exposed to 3.000 lx (cloudy winter sky) to 100.000 lx (bright sunny sky). The aim of the study was to assess (1) habitual daytime light exposure in urban winter and (2) impact of daytime urban light on objective night‐time sleep. Eleven healthy participants (mean age ± SD: 25.4 ± 2.8 years; 6 male) wore eyeglass frames continuously recording daytime illuminance levels vertically to the eye by mounted sensors (range: 1–40.000 lx) during four consecutive days in winter 2008 in Berlin, Germany. In‐lab polysomnography was performed over two nights in nine participants. Median light exposure over 4 days was the following: full day 7:00–19:00 h: 23 lx (12–37 lx); morning 7:00–11:00 h: 81 lx (19–201 lx); midday 11:00–15:00 h: 68 lx (19–164 lx); afternoon 15:00–19:00 h: 22 lx (6–58 lx), resulting in only 36 min > 500 lx per day. Timing of daytime light intensity was significantly associated with subsequent sleep: lower midday illuminance with shorter REM latency (Rho = 0.817; p = 0.049) and earlier REM polarity (less prevalence of REM at end‐of‐sleep; Rho = 0.817; p = 0.049). Humans, living in an urban environment, appear to be exposed to extremely low light levels, which we named as ‘Living in Biological Darkness’. Most fascinating, physiology seems to adapt and responds to variation in light intensity on such low levels. Interestingly, the observed changes in sleep architecture with low light levels are reminiscent of those suspected to constitute biological markers of depression some 40–50 years ago.
Causal Relationship Between Intestinal Microbiota, Inflammatory Cytokines, Peripheral Immune Cells, Plasma Metabolome and Parkinson's Disease: A Mediation Mendelian Randomization Study
Authors: Wang Chengcheng , Tang Yuhang , Yang Tao , Wang Yuhao , Niu Zihui , Zhang Kang , Lin Ning , Li Qun 
Published: January 2025

ABSTRACTParkinson's disease (PD) is a neurodegenerative disease involving multiple factors. We explored the connection between intestinal microbiome levels and PD by examining inflammatory cytokines, peripheral immune cell counts and plasma metabolomics as potential factors. By obtaining the Genome‐Wide Association Study (GWAS) data needed for this study from GWAS Catalog, including summary data for 473 intestinal microbiota traits (N = 5959), 91 inflammatory cytokine traits (N = 14,824), 118 peripheral immune cell count traits (N = 3757), 1400 plasma metabolite traits (N = 8299) and PD traits (N = 482,730). We used two‐step Mendelian randomization (MR) mediated analysis to investigate possible pathways from intestinal microbiota to PD mediated by inflammatory cytokines, peripheral immune cells and plasma metabolites. MR has revealed the causal effects of 19 intestinal microbiota, 1 inflammatory cytokine and 12 plasma metabolites on PD, whereas there is no significant causal relationship between immune cell count characteristics and the occurrence of PD. Mediation analysis showed that the associations between the genus Demequina and PD were mediated by tryptophan with mediated proportions of 17.51% (p = 0.0393). Our study demonstrates that genus Demequina may promote the occurrence of PD by reducing the levels of tryptophan.
Hemispheric Asymmetry of Intracortical Myelin Orientation in the Mouse Auditory Cortex
Authors: Ruthig Philip , Müller Gesine Fiona , Fink Marion , Scherf Nico , Morawski Markus , Schönwiesner Marc 
Published: January 2025

ABSTRACTCommunication sound processing in mouse AC is lateralized. Both left and right AC are highly specialised and differ in auditory stimulus representation, functional connectivity and field topography. Previous studies have highlighted intracortical functional circuits that explain hemispheric stimulus preference. However, the underlying microstructure remains poorly understood. In this study, we examine structural lateralization of AC on the basis of immunohistochemically stained and tissue‐cleared adult mouse brains (n = 11). We found hemispheric asymmetries of intracortical myelination, most prominently in layer 2/3, which featured more intercolumnar connections in the right AC. Furthermore, we found a larger structural asymmetry in the right AC. We also investigated sex differences. In male mice, myelination direction in the right AC is tilted to the anterior side. This pattern is inverted in female mice. However, the spatial distribution of neuronal cell bodies in the left and right AC along the laminar axis of the cortex was remarkably symmetric in all samples. These results suggest that basic developmentally defined structures such as cortical columns remain untouched by lateral specialisation, but more plastic myelinated axons show diverse hemispheric asymmetries. These asymmetries may contribute to specialisation on lateralized tasks such as vocal communication processing or specialisation on spectral or temporal complexity of stimuli.
Relationship Between Structural and Functional Network Connectivity Changes for Patients With Traumatic Brain Injury and Chronic Health Symptoms
Authors: Kang Xiaojian , Grossner Emily , Yoon Byung C. , Adamson Maheen M. 
Published: January 2025

ABSTRACTCombination of structural and functional brain connectivity methods provides a more complete and effective avenue into the investigation of cortical network responses to traumatic brain injury (TBI) and subtle alterations in brain connectivity associated with TBI. Structural connectivity (SC) can be measured using diffusion tensor imaging to evaluate white matter integrity, whereas functional connectivity (FC) can be studied by examining functional correlations within or between functional networks. In this study, the alterations of SC and FC were assessed for TBI patients, with and without chronic symptoms (TBIcs/TBIncs), compared with a healthy control group (CG). The correlation between global SC and FC was significantly increased for both TBI groups compared with CG. SC was significantly lower in the TBIcs group compared with CG, and FC changes were seen in the TBIncs group compared with CG. When comparing TBI groups, FC differences were observed in the TBIcs group compared with the TBIncs group. These observations show that the presence of chronic symptoms is associated with a distinct pattern of SC and FC changes including the atrophy of the SC and a mixture of functional hypoconnectivity and hyperconnectivity, as well as loss of segregation of functional networks.
The impact of radiofrequency thermocoagulation on brain connectivity in drug‐resistant epilepsy: Insights from stereo‐electroencephalography and cortico‐cortical evoked potentials
Authors: Gula Justyna , Slegers Rutger J. , Van Hoof Raf H. M. , Krishnan Balu , Mischi Massimo , van Kranen‐Mastenbroek Vivianne H. J. M. , Van Straaten Ilse E. C. W. , Hilkman Danny , Wagner Louis , Colon Albert , Schijns Olaf E. M. G. , Hunyadi Borbála , Jansen Jacobus F. A. , Tousseyn Simon ,   The ACE Epilepsy Surgery group
Published: January 2025

AbstractObjectiveTo investigate whether local lesions created by stereo‐electroencephalography (SEEG)–guided radiofrequency thermocoagulation (RFTC) affect distant brain connectivity and excitability in patients with focal, drug‐resistant epilepsy (DRE).MethodsTen patients with focal DRE underwent SEEG implantation and subsequently 1 Hz bipolar repetitive electrical stimulation (RES) for 30 s before and after RFTC. Root mean square (RMS) of cortico‐cortical evoked potentials (CCEPs) was calculated for 15 ms to 300 ms post‐stimulation with baseline correction. Contact pairs were categorized as both coagulated, hybrid, or both non‐coagulated. The data were divided into nine categories based on the stimulating and recording contact pair combinations. RMS of CCEPs was compared before and after (<12 h) RFTC using a two‐sample t test (Hochberg corrected, p < 0.05) for each patient. Boost score, indicating power increase during seizures before RFTC relative to baseline, was analyzed in 4 s windows with 1 s overlap during seizure duration.ResultsRFTC altered connectivity across all categories. Of interest, decreases and increases in RMS were observed in connections between non‐coagulated contacts distant from coagulation site (range: 1.09–85 mm, median = 17.7 mm, interquartile range [IQR] 10.1–32.3). Contact pairs involved in significantly altered non‐coagulated connections showed a higher boost score correlation in the theta, beta, and gamma bands, as well as a stronger maximum correlation with coagulated sites in the delta band than contacts for which connectivity did not change after RFTC.SignificanceThis study highlights how local lesions alter distant brain connectivity, providing insights for future research on epilepsy network changes and seizure outcomes following RFTC.