bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Prevascularization on Immunological Environment and Early Engraftment in Subcutaneous Islet Transplantation
Authors: Inoguchi Kenta , Anazawa Takayuki , Fujimoto Nanae , Tada Seiichiro , Yamane Kei , Emoto Norio , Izuwa Aya , Su Hang , Fujimoto Hiroyuki , Murakami Takaaki , Nagai Kazuyuki , Hatano Etsuro 
Published: January 2024

Background.
The utilization of islet-like cells derived from pluripotent stem cells may resolve the scarcity of islet transplantation donors. The subcutaneous space is a promising transplantation site because of its capacity for graft observation and removal, thereby ensuring safety. To guarantee subcutaneous islet transplantation, physicians should ensure ample blood supply. Numerous methodologies, including prevascularization, have been investigated to augment blood flow, but the optimal approach remains undetermined.

Methods.
From C57BL/6 mice, 500 syngeneic islets were transplanted into the prevascularized subcutaneous site of recipient mice by implanting agarose rods with basic fibroblast growth factor at 1 and 2 wk. Before transplantation, the blood glucose levels, cell infiltration, and cytokine levels at the transplant site were evaluated. Furthermore, we examined the impact of the extracellular matrix capsule on graft function and the inflammatory response.

Results.
Compared with the 1-wk group, the 2-wk group exhibited improved glycemic control, indicating that longer prevascularization enhanced transplant success. Flow cytometry analysis detected immune cells, such as neutrophils and macrophages, in the extracellular matrix capsules, whereas cytometric bead array analysis indicated the release of inflammatory and proinflammatory cytokines. Treatment with antitumor necrosis factor and anti-interleukin-6R antibodies in the 1-wk group improved graft survival, similar to the 2-wk group.

Conclusions.
In early prevascularization before subcutaneous transplantation, neutrophil and macrophage accumulation prevented early engraftment owing to inflammatory cytokine production.
Vestibular syncope
Authors: Choi Jeong-Yoon , Lee Eek-Sung , Kim Ji-Soo 
Published: January 2024

Purpose of review
This review considers recent observations on vestibular syncope in terms of clinical features, laboratory findings, and potential mechanisms.

Recent findings
Vestibular syncope, potentially associated with severe fall-related injuries, may develop multiple times in about one-third of patients. Meniere's disease and benign paroxysmal positional vertigo are the most common causes of vestibular syncope, but the underlying disorders remain elusive in 62% of cases with vestibular syncope. The postictal orthostatic blood pressure test exhibits a lower diagnostic yield. Vestibular function tests, such as cervical vestibular-evoked myogenic potentials and video head impulse tests, can reveal one or more abnormal findings, suggesting compensated or ongoing minor vestibular dysfunctions. The pathomechanism of syncope is assumed to be the erroneous interaction between the vestibulo-sympathetic reflex and the baroreflex that have different operating mechanisms and action latencies. The central vestibular system, which estimates gravity orientation and inertia motion may also play an important role in abnormal vestibulo-sympathetic reflex.

Summary
Vestibular disorders elicit erroneous cardiovascular responses by providing false vestibular information. The results include vertigo-induced hypertension or hypotension, which can ultimately lead to syncope in susceptible patients.
Association Between Magnetoencephalography-Localized Epileptogenic Zone, Surgical Resection Volume, and Postsurgical Seizure Outcome
Authors: Poghosyan Vahe , Algethami Hanin , Alshahrani Ashwaq , Asiri Safiyyah , Aldosari Mubarak M. 
Published: January 2024

Purpose:
Surgical resection of magnetoencephalography (MEG) dipole clusters, reconstructed from interictal epileptiform discharges, is associated with favorable seizure outcomes. However, the relation of MEG cluster resection to the surgical resection volume is not known nor is it clear whether this association is direct and causal, or it may be mediated by the resection volume or other predictive factors. This study aims to clarify these open questions and assess the diagnostic accuracy of MEG in our center.

Methods:
We performed a retrospective cohort study of 68 patients with drug-resistant epilepsy who underwent MEG followed by resective epilepsy surgery and had at least 12 months of postsurgical follow-up.

Results:
Good seizure outcomes were associated with monofocal localization (χ2 = 6.94, P = 0.001; diagnostic odds ratio = 10.2) and complete resection of MEG clusters (χ2 = 22.1, P < 0.001; diagnostic odds ratio = 42.5). Resection volumes in patients with and without removal of MEG clusters were not significantly different (t = 0.18, P = 0.86; removed: M = 20,118 mm3, SD = 10,257; not removed: M = 19,566 mm3, SD = 10,703). Logistic regression showed that removal of MEG clusters predicts seizure-free outcome independent of the resection volume and other prognostic factors (P < 0.001).

Conclusions:
Complete resection of MEG clusters leads to favorable seizure outcomes without affecting the volume of surgical resection and independent of other prognostic factors. MEG can localize the epileptogenic zone with high accuracy. MEG interictal epileptiform discharges mapping should be used whenever feasible to improve postsurgical seizure outcomes.
National Trends and Clinical Outcomes after Scooter Injury in the US: 2016 to 2020
Authors: Cho Nam Yong , Kim Shineui , Tran Zachary , Hadaya Joseph , Ali Konmal , Kronen Elsa , Burruss Sigrid , Benharash Peyman 
Published: January 2024

BACKGROUND:
In recent years, the adoption of electric scooters has been accompanied by a surge of scooter-related injuries in the US, raising concerns for their severity and associated healthcare costs. This study aimed to assess temporal trends and outcomes of scooter-related hospital admissions compared with bicycle-related hospitalizations.

STUDY DESIGN:
This was a retrospective cohort study using the 2016 to 2020 National Inpatient Sample for patients younger than 65 years who were hospitalized after bicycle- and scooter-related injuries. The Trauma Mortality Prediction Model was used to quantify injury severity. The primary outcomes of interest were temporal trends of micromobility injuries. In-hospital mortality, rates of long bone fracture, traumatic brain injury, paralysis, length of stay, hospitalization costs, and nonhome discharge were secondarily assessed.

RESULTS:
Among 92,815 patients included in the study, 6,125 (6.6%) had scooter-related injuries. Compared with patients with bicycle-related injuries, patients with scooter-related injuries were more commonly younger than 18 years (26.7% vs 16.4%, p < 0.001) and frequently underwent major operations (55.8% vs 48.1%, p < 0.001). After risk adjustment, scooter-related injuries were associated with greater risks of long bone fracture (adjusted odds ratio 1.40, 95% CI 1.15 to 1.70) and paralysis (adjusted odds ratio 2.06, 95% CI 1.16 to 3.69) compared with bicycle-related injuries. Additionally, patients with bicycle- or scooter-related injuries had comparable index hospitalization durations of stay and costs.

CONCLUSIONS:
The prevalence and severity of scooter-related injuries have significantly increased in the US, thereby attributing to a substantial cost burden on the healthcare system. Multidisciplinary efforts to inform safety policies and enact targeted interventions are warranted to reduce scooter-related injuries.
Adherence Rate to Alliance for Clinical Trials in Oncology Z0011 Trial Based on Breast Cancer Subtype
Authors: Maramara Taylor , Hsieh Mei-Chin , Janjua Mahin , Li Tingting , Wu Xiao-Cheng , Williams Mallory , Shoup Margo , Chu Quyen D 
Published: January 2024

BACKGROUND:
The American College of Surgeons Oncology Group Z0011 (ACOSOG Z0011 or Z11) trial demonstrated no survival advantage with completion axillary lymph node dissection (ALND) for patients with T1-2 breast cancer, 1 to 2 positive SLNs who received adjuvant chemoradiation therapy. More than 70% of the cohort had estrogen receptor (ER)+ tumors. There is paucity of data on the adherence rate to Z11, as well as a dearth of data on the applicability of Z11 for the different subtypes. We conducted a large hospital-based study to evaluate the adherence rate to Z11 based on subtypes.

STUDY DESIGN:
The National Cancer Database was queried to evaluate 33,859 patients diagnosed with T1-2, N1, and M0 breast cancer treated with lumpectomy with negative margins, and adjuvant chemoradiation therapy between 2012 and 2018. Patients were classified into 3 groups: (1) ER+/HER2−, (2) ER−/HER2−, and (3) HER2+ regardless of ER status. The revised Scope of the Regional Lymph Node Surgery 2012 was used to classify patients into those who underwent an SLN or ALND. Differences in use of ALND by subtypes were compared. The Kaplan–Meier method and log-rank test were used to compare overall survival (OS). A p value of <0.05 was considered statistically significant.

RESULTS:
For ER+/human epidermal growth factor receptor 2 (HER2)−, ER−/HER2−, and HER2+ tumors, the rate of ALND was 43.6%, 50.2%, and 47.8%, respectively. The 5-year OS for SLN and ALND for the entire cohort was 94.0% and 93.1% (p = 0.0004); for ER+/HER2−, it was 95.4% and 94.7% (p = 0.04); for ER−/HER2−, it was 84.1% and 84.3% (p = 0.41); for HER2+, it was 94.2% and 93.2% (p = 0.20). Multivariable cox proportional hazard regression analysis demonstrated no significant survival differences between SLN and ALND (p = 0.776).

CONCLUSIONS:
Z11 is applicable for women with early N1 disease, regardless of subtypes. ALND did not confer a survival advantage over SLN. Despite this, up to 50% of patients who fit Z11 criteria continue to undergo ALND.
Structural Changes in Depressed Patients Directly After Treatment With Electroconvulsive Therapy and 3 Months Later
Authors: Jaarsveld Stevie , Mulders Peter , Tendolkar Indira , van Eijndhoven Philip 
Published: January 2024

Objectives
It is assumed that neuroplasticity plays a central role in the effect of electroconvulsive therapy (ECT) on patients with major depressive disorder. We carried out an explorative study to map out the extent in which gray matter volume changes could be found directly after ECT treatment and after follow-up.

Methods
Initially, 12 patients with treatment-resistant depression were recruited from the Radboud Medical Center. Magnetic resonance imaging scans were conducted at the following 3 time points: before ECT (n = 12), after ECT (n = 10), and at 3-month follow-up (n = 8). Subcortical volume, hippocampal subfield volume, and cortical thickness were analyzed using FreeSurfer.

Results
The extensive, generalized changes in gray matter volume are largely transient after treatment with ECT, with the noted exceptions being a sustained increase in volume of the right amygdala and a part of the left cornu ammonis. Post hoc testing revealed no significant correlation with clinical response.

Discussion
Our results suggest that the neuroplastic effects of ECT may not be mediators of clinical response and could be transient epiphenomena.
MoCoLo: a testing framework for motif co-localization
Authors: Xu Qi , del Mundo Imee M.A. , Zewail-Foote Maha , Luke Brian T. , Vasquez Karen M. , Kowalski Jeanne 
Published: January 2024

AbstractSequence-level data offers insights into biological processes through the interaction of two or more genomic features from the same or different molecular data types. Within motifs, this interaction is often explored via the co-occurrence of feature genomic tracks using fixed-segments or analytical tests that respectively require window size determination and risk of false positives from over-simplified models. Moreover, methods for robustly examining the co-localization of genomic features, and thereby understanding their spatial interaction, have been elusive. We present a new analytical method for examining feature interaction by introducing the notion of reciprocal co-occurrence, define statistics to estimate it, and hypotheses to test for it. Our approach leverages conditional motif co-occurrence events between features to infer their co-localization. Using reverse conditional probabilities and introducing a novel simulation approach that retains motif properties (e.g., length, guanine-content), our method further accounts for potential confounders in testing. As a proof-of-concept, MoCoLo confirmed the co-occurrence of histone markers in a breast cancer cell line. As a novel analysis, MoCoLo identified significant co-localization of oxidative DNA damage within non-B DNA forming regions that significantly differed between non-B DNA structures. Altogether, these findings demonstrate the potential utility of MoCoLo for testing spatial interactions between genomic features via their co-localization.
Interferon Regulatory Factor 6 Determines Intestinal Epithelial Cell Development and Immunity
Authors: Wright Austin P. , Harris Sydney , Madden Shelby , Reyes Bryan Ramirez , Mulamula Ethan , Gibson Alexis , Rauch Isabella , Constant David A. , Nice Timothy J. 
Published: January 2024

AbstractIntestinal epithelial cell (IEC) responses to interferon (IFN) favor antiviral defense with minimal cytotoxicity, but IEC-specific factors that regulate these responses remain poorly understood. Interferon regulatory factors (IRFs) are a family of nine related transcription factors, and IRF6 is preferentially expressed by epithelial cells, but its roles in IEC immunity are unknown. In this study, CRISPR screens found thatIrf6deficiency enhanced IFN-stimulated antiviral responses in transformed mouse IECs but not macrophages. Furthermore, KO ofIrf6in IEC organoids resulted in profound changes to homeostasis and immunity gene expression.Irf6KO organoids grew more slowly, and single-cell RNA sequencing indicated reduced expression of genes in epithelial differentiation and immunity pathways. IFN-stimulated gene expression was also significantly different inIrf6KO organoids, with increased expression of stress and apoptosis-associated genes. Functionally, the transcriptional changes inIrf6KO organoids were associated with increased cytotoxicity upon IFN treatment or inflammasome activation. These data indicate a previously unappreciated role for IRF6 in IEC biology, including regulation of epithelial development and moderation of innate immune responses to minimize cytotoxicity and maintain barrier function.
Pathogen and host adapt pH responses during enteric infection
Authors: Woodward Sarah E. , Neufeld Laurel M.P. , Peña-Díaz Jorge , Feng Wenny , Serapio-Palacios Antonio , Tarrant Isabel , Finlay B. Brett 
Published: January 2024

AbstractEnteric pathogens navigate distinct regional micro-environments within the intestine which cue important adaptive behaviours. We investigated the response ofCitrobacter rodentium, a model of human pathogenicEscherichia coliinfection, to regional gastrointestinal pH. We found that small intestinal pH (4.4-4.8) triggered virulence gene expression and altered cell morphology, supporting initial intestinal attachment, while higher pH, representative ofC. rodentium’s replicative niches further along the intestine, supported pathogen growth. Gastric pH, a key barrier to intestinal colonization, caused significant accumulation of intra-bacterial reactive oxygen species, inhibiting growth ofC. rodentiumand related human pathogens. Within-host adaptation increased gastric acid survival, which may be due to a robust acid tolerance response induced at colonic pH. However, we also found that host gastric pH decreases post-infection, corresponding to increased serum gastrin levels and altered host expression of acid secretion-related genes. Similar responses followingSalmonellainfection may indicate a protective host response to limit further pathogen ingestion. Together, we highlight adaptive pH responses as an important component of host-pathogen co-evolution.
An ecological investigation of the effect of background noise on speech processing in a Virtual Classroom
Authors: Levy Orel , Korisky Adi , Zvilichovsky Yair , Zion Golumbic Elana 
Published: January 2024

AbstractMany real-life situations can be extremely noisy. Psychoacoustic studies have shown that background noise can have a detrimental effect on the ability to process and understand speech. However, most studies use stimuli and task designs that are highly artificial, limiting their generalization to more realistic contexts. Moreover, to date, we do not fully understand the neurophysiological consequences of trying to pay attention to speech in a noisy place.To address this lab to real-life gap and increase the ecological validity of speech in noise research, here we introduce a novel audiovisual Virtual Reality (VR) experimental platform. Combined with neurophysiological measurements of neural activity (EEG), eye-gaze and skin conductance (GSR) we studied the effects of background noise in a realistic context where the ability to process and understand continuous speech is especially important: A VR Classroom.Participants (n=32) sat in a VR Classroom and were told to pay attention to mini-lecture segments by a virtual teacher. Trials were either Quiet or contained background construction noise, emitted from outside the classroom window, which was either Continuous (drilling) or Intermittent (air hammers).Result show that background noise had a detrimental effect on learning outcomes, which was also accompanied by reduced neural tracking of the teacher’s speech. Comparison of the two noise types showed that the intermittent construction noise was more disruptive than continuous noise, as index by both behavioral and neural measures, and it also elicited higher skin-conductance levels, reflecting heightened arousal. Interesting, eye-gaze dynamics were not affected by the presence of noise.This study advances our understanding of the neurophysiological effects of background noise and extends it to more ecologically relevant contexts. It also emphasizes the role that temporal dynamics play for processing speech in noise, highlighting the need to consider the features of realistic noises, as we expand speech in noise research to increasingly realistic circumstances.
Cardiac stress leads to regulation of Filamin C dimerisation via an ancient phosphorylation-modulated interaction with HSPB7
Authors: Wang Zihao , Cao Guodong , Collier Miranda P. , Qiu Xingyu , Broadway-Stringer Sophie , Šaman Dominik , Ng Jediael Z.Y. , Sen Navoneel , Azad Amar J. , Hooper Charlotte , Zimmermann Johannes , McDonough Michael , Brem Jürgen , Rabe Patrick , Song Haigang , Reid Alderson T. , Schofield Christopher J. , Bolla Jani R. , Djinovic-Carugo Kristina , Fürst Dieter O. , Warscheid Bettina , Degiacomi Matteo T. , Allison Timothy M. , Hochberg Georg K.A. , Robinson Carol V. , Gehmlich Katja , Benesch Justin L.P. 
Published: January 2024

AbstractThe biomechanical properties and responses of tissues underpin a variety of physiological functions and pathologies. In striated muscle, the actin-binding protein filamin C (FLNC) is a key protein whose variants causative for a wide range of cardiomyopathies and musculoskeletal pathologies. Seemingly a multi-functional protein that interacts with a variety of partners, how FLNC is regulated at the molecular level is not well understood. Here we have investigated its interaction with HSPB7, a cardiac-specific molecular chaperone whose absence is embryonically lethal. We found that FLNC and HSPB7 interact in cardiac tissue under biomechanical stress, forming a strong hetero-dimer whose structure we have solved by means of X-ray crystallography. Our quantitative analyses show that the hetero-dimer out-competes the FLNC homo-dimer interface, potentially acting to abrogate the ability of the protein to cross-link the actin cytoskeleton, and to enhance its diffusive mobility. We show that phosphorylation of FLNC at threonine 2677, located at the dimer interface and associated with cardiac stress, acts to favour the homo-dimer. Conversely, phosphorylation at tyrosine 2683, also at the dimer interface, has the opposite effect and shifts the equilibrium towards the hetero-dimer. Evolutionary analysis and ancestral sequence reconstruction reveals this interaction and its mechanisms of regulation to date around the time primitive hearts evolved in chordates. Our work rationalises on the molecular level how FLNC might switch between stabilising functions in the cell, and reveals how HSPB7 acts as a specific molecular chaperone that regulates FLNC.
Genetically encoded Boolean logic operators to sense and integrate phenylpropanoid metabolite levels in plants
Authors: Ferreira Savio S. , Antunes Mauricio S. 
Published: January 2024

SummarySynthetic biology has the potential to revolutionize biotechnology, public health and agriculture. Recent studies have shown the enormous potential of plants as chassis for synthetic biology applications. However, tools to precisely manipulate metabolic pathways for bioproduction in plants are still needed.We have adapted bacterial allosteric transcription factors (aTFs) to control gene expression in plants in a ligand-specific manner. The aTFs used here function as transcription repressors of semi-synthetic promoters, and aTF activity is regulated by specific plant metabolites, especially phenylpropanoid-related molecules. Using these aTFs, we also designed synthetic genetic circuits capable of computing Boolean logic operations.Three aTFs, CouR, FapR and TtgR, were able to achieve ∼95% repression of their respective target promoters. For TtgR, a 6-fold de-repression could be triggered by inducing its ligand (naringenin) accumulation, showing its use as biosensor. Moreover, we designed synthetic genetic circuits that use AND, NAND, IMPLY and NIMPLY Boolean logic operations and integrate metabolite levels as input to the circuit.We showed that biosensors can be implemented in plants to detect phenylpropanoid-related metabolites and activate a genetic circuit that follows a pre-defined logic, demonstrating their potential as tools for exerting control over plant metabolic pathways and facilitating the bioproduction of natural products.
Using FINDeM for rapid, CRISPR-based detection of the emerging salamandrid fungal pathogen,Batrachochytrium salamandrivorans
Authors: Hoenig Brandon D. , Böning Philipp , Plewnia Amadeus , Richards-Zawacki Corinne L. 
Published: January 2024

AbstractThe fungal pathogenBatrachochytrium salamandrivorans(Bsal) is one of two species (the other,B. dendrobatidis/Bd) that cause amphibian chytridiomycosis, an emerging infectious disease that has been indicated in the declines of hundreds of amphibian species worldwide. WhileBdhas been near-globally distributed for well over a century,Bsalis a more recently emerged pathogen, having been identified just over a decade ago with current impacts localized to salamandrids in parts of Europe. However, because there is concern thatBsalwill cause widespread declines if introduced to naïve regions – such as the Americas where the greatest diversity of salamandrids exist – it is imperative that widespread testing and monitoring strategies be implemented to mitigate the spread ofBsal. As standard diagnostic approaches tend to be expensive, time-consuming, or require specialized instrumentation and training, we have developed a simplified, rapid, CRISPR-based approach forBsal-DNA identification and provide suggestions for its future application.