bluuebunny/crossref_metadata_2025_split huggingface dataset:
Barriers and Facilitators of Vestibular Rehabilitation: Patients and Physiotherapists’ Perspectives
Authors: Kalderon Liran , Kaplan Azriel , Wolfovitz Amit , Levy-Tzedek Shelly , Gimmon Yoav 
Published: March 2024

Background and Purpose:
Poor adherence to vestibular rehabilitation protocols is a known barrier to optimal care. Vestibular clinicians’ comprehensive understanding of the barriers and facilitators to vestibular home exercise programs (VHEP) is a key element to achieving optimal care in the context of vestibular rehabilitation. The aims of this study are as follows: (1) to identify primary barriers and facilitators to VHEP from the perspective of patients with vestibular dysfunction and vestibular physical therapists (PTs); and (2) to provide strategies for clinicians to improve adherence and outcomes of VHEP.

Methods:
A qualitative research with single-session focus groups conducted separately for: (1) patients with vestibular disorders and (2) vestibular PTs. Six focus groups were conducted, 3 for each population, with a total of 39 participants. An online survey was conducted to evaluate the estimates of adherence rates, followed by a structured discussion over barriers and facilitators to VHEP as perceived by patients and PTs. Thematic data analyses were performed using a mixed deductive-inductive approach.

Results:
Eighteen patients with vestibular disorders and 21 experienced vestibular PTs participated in this study. Six barrier categories and 5 facilitator categories were identified. Barriers included motivation aspects, provocation of symptoms, time management, associated impairments, missing guidance and feedback, and psychosocial factors. Facilitators included motivation aspects, time management, patient education and exercise instructions, exercise setting, and associated symptom management.

Discussion and Conclusions:
Clinicians who prescribe home exercise to patients with vestibular disorders can use this information about common barriers and facilitators for patient education and to provide optimal care and improve rehabilitation outcomes.

Video Abstract available
for more insights from the authors (see the video, Supplemental Digital Content, available at: http://links.lww.com/JNPT/A467).
A Systematically Optimized Miniaturized Mesoscope (SOMM) for large-scale calcium imaging in freely moving mice
Authors: Zhang Yuanlong , Yuan Lekang , Wu Jiamin , Nöbauer Tobias , Zhang Rujin , Xiao Guihua , Wang Mingrui , Xie Hao , Dai Qionghai , Vaziri Alipasha 
Published: March 2024

Understanding how neuronal dynamics gives rise to ethologically relevant behavior requires recording of neuronal population activity via technologies that are compatible with unconstrained animal behavior. However, realizations of cellular resolution head-mounted microscopes for mice have been based on conventional microscope designs that feature various forms of ad-hoc miniaturization and weight reduction measures necessary for compatibility with the weight-limits for free animal behavior. As a result, they have typically remained limited to a small field of view (FOV) or low resolution, a shallow depth range and often remain susceptible to motion-induced artifacts.Here, we present a systematically optimized miniaturized mesoscope (SOMM), a widefield, head-mounted fluorescent mesoscope based on a principled optimization approach that allows for mesoscale, cellular resolution imaging of neuroactivity while offering robustness against motion-induced artifacts. This is achieved by co-optimization of a compact diffractive optical element and the associated computational algorithm under form-factor and weight constraints while maximizing the obtainable FOV, depth of field (DOF), and resolution. SOMM enables recordings of neuronal population activity at up to 16 Hz within a FOV of 3.6 × 3.6 mm2in the cortex of freely moving mice while featuring 4-µm resolution, a DOF of 300 µm at a weight of less than 2.5 g. We show SOMM’s performance of recording large-scale neuronal population activity during social interactions, during conditioning-type experiments and by investigating neurovascular coupling using dual-color imaging.
Fifty Years After: The N1 Effect Travels Down to the Brainstem
Authors: Strauss Daniel J. , Corona-Strauss Farah I. , Mai Adrian , Hillyard Steven A. 
Published: February 2024

AbstractFifty years ago, it was reported that selective attention affects the N1 wave in auditory event–related potentials. We revisited the original study design but integrated the state of the art knowledge on short auditory stimuli and neural signal processing. In particular, one series of tone bursts has been replaced by chirp stimuli which are optimized to evoke consistent brainstem potentials at low and medium stimulation levels. Auditory selective attention affected the chirp– evoked response in subcortical structures, even at level of the inferior colliculi. A single–trial time–frequency analysis of the full–range (0–250ms) event–related potentials showed that selective attention increases the spectrotemporal consistency across trials in the corticofugal auditory pathway, at least from the N1 wave down to the auditory brainstem response.
A single-cell atlas of the murine pancreatic ductal tree identifies novel cell populations with potential implications in pancreas regeneration and exocrine pathogenesis
Authors: Fernández Ángel , Casamitjana Joan , Holguín-Horcajo Adrián , Coolens Katarina , Mularoni Loris , Pasquali Lorenzo , Bailey-Lundberg Jennifer M. , Rooman Ilse , Wang Yue J. , Rovira Meritxell 
Published: March 2024

ABSTRACTBackground and aimsPancreatic ducts form an intricate network of tubules that secrete bicarbonate and drive acinar secretions into the duodenum. This network is formed by centroacinar cells, terminal, intercalated, intracalated ducts, and the main pancreatic duct. Ductal heterogeneity at the single-cell level has been poorly characterized; therefore, our understanding of the role of ductal cells in pancreas regeneration and exocrine pathogenesis has been hampered by the limited knowledge and unexplained diversity within the ductal network.MethodsWe used scRNA-seq to comprehensively characterize mouse ductal heterogeneity at single-cell resolution of the entire ductal epithelium from centroacinar cells to the main duct. Moreover, we used organoid cultures, injury models and pancreatic tumor samples to interrogate the role of novel ductal populations in pancreas regeneration and exocrine pathogenesis.ResultsWe have identified the coexistence of 15 ductal populations within the healthy pancreas and characterized their organoid formation capacity and endocrine differentiation potential. Cluster isolation and subsequent culturing let us identify ductal cell populations with high organoid formation capacity and endocrine and exocrine differentiation potentialin vitro, including Wnt-responsive-population, ciliated-population and FLRT3+cells. Moreover, we have characterized the location of these novel ductal populations in healthy pancreas, chronic pancreatitis, and tumor samples, highlighting a putative role of WNT-responsive, IFN-responsive and EMT-populations in pancreatic exocrine pathogenesis as their expression increases in chronic pancreatitis and PanIN lesions.ConclusionsIn light of our discovery of previously unidentified ductal populations, we unmask the potential roles of specific ductal populations in pancreas regeneration and exocrine pathogenesis.
scConfluence : single-cell diagonal integration with regularized Inverse Optimal Transport on weakly connected features
Authors: Samaran Jules , Peyré Gabriel , Cantini Laura 
Published: March 2024

AbstractThe abundance of unpaired multimodal single-cell data has motivated a growing body of research into the development of diagonal integration methods. However, the state-of-the-art suffers from the loss of biological information due to feature conversion and struggles with modality-specific populations. To overcome these crucial limitations, we here introduced scConfluence, a novel method for single-cell diagonal integration. scConfluence combines uncoupled autoencoders on the complete set of features with regularized Inverse Optimal Transport on weakly connected features. We extensively benchmark scConfluence in several single-cell integration scenarios proving that it outperforms the state-of-the-art. We then demonstrate the biological relevance of scConfluence in three applications. We predict spatial patterns forScgn, SynprandOlahin scRNA-smFISH integration. We improve the classification of B cells and Monocytes in highly heterogeneous scRNA-scATAC-CyTOF integration. Finally, we reveal the joint contribution ofFezf2and apical dendrite morphology in Intra Telencephalic neurons, based on morphological images and scRNA.
Gut microbes of the cecum versus the colon drive more severe lethality and multi-organ damage
Authors: Xu Kejia , Tan Juan , Lin Dongyang , Chu Yimin , Zhou Luting , Zhang Junjie , Lu Yinzhong 
Published: March 2024

AbstractAn intestinal perforation or puncture leads to a high risk of sepsis-associated morbidity. A perforation initiates the transfer of the intestinal contents (ICs) to the peritoneal cavity, leading to abdominal infections and varying with different prognoses. However, the mechanisms associated with different perforations in the cecum and colon remain unknown. We sought to examine how different gut flora contribute to prognoses in different intestinal perforation sites. We compared the microbiome of the ICs in the cecum and colon in a fecal-induced peritonitis mouse model. The results showed that cecum ICs developed more severe sepsis than colon ICs, including a shorter median survival time, increased biochemical indicators, more pathological changes in multiple organs and overwhelmed systematic inflammation. Moreover, our results demonstrated that cecum ICs hold more bacterial burden in unit weight than colon ICs, and the microbial communities differed between the ICs from the cecum and colon. A more detailed comparison of the two microbiome groups showed that the abundance of potentially pathogenic bacteria increased in the cecum ICs. Our data suggest that the sepsis severity developed by perforation was associated with bacterial burden and increased abundance of potentially pathogenic bacteria in the cecum. Our findings first compared the differences in the lethality associated with the ICs of the cecum and colon, which pointed out that the site of perforation could help providers predict the severity of sepsis.
Retrograde tracing of breast cancer-associated sensory neurons
Authors: Kallogjerovic Svetllana , Velázquez-Quesada Inés , Hadap Rutva , Gligorijevic Bojana 
Published: March 2024

ABSTRACTBreast cancer is one of the leading causes of mortality among women. The tumor microenvironment, consisting of host cells and extracellular matrix, has been increasingly studied for its interplay with cancer cells, and the resulting effect on tumor progression. While the breast is one of the most innervated organs in the body, the role of neurons, and specifically sensory neurons, has been understudied, mostly for technical reasons. One of the reasons is the anatomy of sensory neurons: sensory neuron somas are located in the spine, and their axons can extend longer than a meter across the body to provide innervation in the breast. Next, neurons are challenging to culture, and there are no cell lines adequately representing the diversity of sensory neurons. Finally, sensory neurons are responsible for transporting several different types of signals to the brain, and there are many different subtypes of sensory neurons. The subtypes of sensory neurons which innervate and interact with breast tumors are unknown. To establish the tools for labeling and subtyping neurons that interact with breast cancer cells, we utilized two retrograde tracer’s standards in neuroscience, wheat-germ agglutinin (WGA) and cholera toxin subunit B (CTB).In vitro, we employed primary sensory neurons isolated from mouse dorsal root ganglia, cultured in a custom-built microfluidic device DACIT, that mimics the anatomical compartmentalization of the sensory neuron’s soma and axons.In vivo, we utilized both syngeneic and transgenic mouse models of mammary carcinoma. We show that CTB and WGA trace different but overlapping sensory neuronal subpopulations: while WGA is more efficient in labeling CGRP+ neurons, CTB is superior in labeling the NF200+ neurons. Surprisingly, both tracers are also taken up by a significant population of breast cancer cells, bothin vitroandin vivo. In summary, we have established methodologies for retrograde tracing of sensory neurons interacting with breast cancer cells. Our tools will be useful for future studies of breast tumor innervation, and development of therapies targeting breast cancer-associated neuron subpopulations of sensory neurons.
Xylazine does not enhance fentanyl reinforcement in rats: a behavioral economic analysis
Authors: St. Onge Celsey M. , Canfield Jeremy R. , Ortiz Allison , Sprague Jon E. , Banks Matthew L. 
Published: March 2024

AbstractThe adulteration of illicit fentanyl with the alpha-2 agonist xylazine has been designated an emerging public health threat. The clinical rationale for combining fentanyl with xylazine is currently unclear, and the inability to study fentanyl/xylazine interactions in humans warrants the need for preclinical research. We studied fentanyl and xylazine pharmacodynamic and pharmacokinetic interactions in male and female rats using drug self-administration behavioral economic methods. Fentanyl, but not xylazine, functioned as a reinforcer under both fixed-ratio and progressive-ratio drug self-administration procedures. Xylazine combined with fentanyl at three fixed dose-proportion mixtures did not significantly alter fentanyl reinforcement as measured using behavioral economic analyses. Xylazine produced a proportion-dependent decrease in the behavioral economic Q0endpoint compared to fentanyl alone. However, xylazine did not significantly alter fentanyl self-administration at FR1. Fentanyl and xylazine co-administration did not result in changes to pharmacokinetic endpoints. The present results demonstrate that xylazine does not enhance the addictive effects of fentanyl or alter fentanyl plasma concentrations. The premise for why illicitly manufacture fentanyl has been adulterated with xylazine remains to be determined.
The nutrient-sensing Rag-GTPase complex in B cells controls humoral immunity via TFEB/TFE3-dependent mitochondrial fitness
Authors: Zhu Xingxing , Wu Yue , Li Yanfeng , Zhou Xian , Watzlawik Jens O. , Chen Yin Maggie , Raybuck Ariel L. , Billadeau Daniel , Shapiro Virginia , Springer Wolfdieter , Sun Jie , Boothby Mark R. , Zeng Hu 
Published: March 2024

AbstractDuring the humoral immune response, B cells undergo rapid metabolic reprogramming with a high demand for nutrients, which are vital to sustain the formation of the germinal centers (GCs). Rag-GTPases sense amino acid availability to modulate the mechanistic target of rapamycin complex 1 (mTORC1) pathway and suppress transcription factor EB (TFEB) and transcription factor enhancer 3 (TFE3), members of the microphthalmia (MiT/TFE) family of HLH-leucine zipper transcription factors. However, how Rag-GTPases coordinate amino acid sensing, mTORC1 activation, and TFEB/TFE3 activity in humoral immunity remains undefined. Here, we show that B cell-intrinsic Rag-GTPases are critical for the development and activation of B cells. RagA/RagB deficient B cells fail to form GCs, produce antibodies, and generate plasmablasts in both T-dependent (TD) and T-independent (TI) humoral immune responses. Deletion of RagA/RagB in GC B cells leads to abnormal dark zone (DZ) to light zone (LZ) ratio and reduced affinity maturation. Mechanistically, the Rag-GTPase complex constrains TFEB/TFE3 activity to prevent mitophagy dysregulation and maintain mitochondrial fitness in B cells, which are independent of canonical mTORC1 activation. TFEB/TFE3 deletion restores B cell development, GC formation in Peyer’s patches and TI humoral immunity, but not TD humoral immunity in the absence of Rag-GTPases. Collectively, our data establish Rag-GTPase-TFEB/TFE3 pathway as an mTORC1 independent mechanism to coordinating nutrient sensing and mitochondrial metabolism in B cells.One sentence summaryRag-GTPases restrain TFEB/TFE3 to prevent abnormal mitophagy, maintain mitochondrial fitness, and support B cell development, Peyer’s patch germinal center formation, and T-independent humoral immunity.
Biogenesis of circular RNAsin vitroandin vivofrom theDrosophila Nk2.1/scarecrowgene
Authors: Son Suhyeon , Jeong Hyunjin , Lee Gyunghee , Park Jae H. , Yoo Siuk 
Published: March 2024

Abstractscarecrow(scro) encodes a fly homolog of mammalianNkx2.1that is vital for early fly development as well as for optic lobe development. Interestingly,scrowas reported to produce a circular RNA (circRNA). In this study, we identified 12 differentscrocircRNAs, which are either mono- or multi-exonic forms. The most abundant forms are circE2 carrying the second exon only and bi-exonic circE3-E4. Levels of circE2 show an age-dependent increase in adult heads, supporting a general trend of high accumulation of circRNAs in aged fly brains. Aligning sequences of introns flanking exons uncovered two pairs of intronic complementary sequences (ICSs); one pair residing in introns 1 and 2 and the other in introns 2 and 4. The first pair was demonstrated to be essential for the circE2 production in cell-based assays; furthermore, deletion of the region including potential ICS components in the intron-2 reducedin vivoproduction of circE2 and circE3-E4 by 80%, indicating them to be essential for the biogenesis of these isoforms. Besides the ICS, the intron regions immediately abutting exons seemed to be responsible for a basal level of circRNA formation. Moreover, the replacement ofscro-ICS with those derived fromlaccase2was comparably effective inscro-circRNA production, buttressing the importance of the hairpin-loop structure formed by ICS for the biogenesis of circRNA. Lastly, overexpressedscroaffected outcomes of both linear and circular RNAs from the endogenousscrolocus, suggesting that Scro plays a direct or indirect role in regulating expression levels of either or both forms.
An injury-induced tissue niche shaped by mesenchymal plasticity coordinates the regenerative and disease response in the lung
Authors: Jones Dakota L. , Morley Michael P. , Li Xinyuan , Ying Yun , Cardenas-Diaz Fabian L. , Li Shanru , Zhou Su , Schaefer Sarah E. , Chembazhi Ullas V. , Nottingham Ana , Lin Susan , Cantu Edward , Diamond Joshua M. , Basil Maria C. , Vaughan Andrew E. , Morrisey Edward E. 
Published: March 2024

AbstractSevere lung injury causes basal stem cells to migrate and outcompete alveolar stem cells resulting in dysplastic repair and a loss of gas exchange function. This “stem cell collision” is part of a multistep process that is now revealed to generate aninjury-inducedtissue niche (iTCH) containing Keratin 5+ epithelial cells and plastic Pdgfra+ mesenchymal cells. Temporal and spatial single cell analysis reveals that iTCHs are governed by mesenchymal proliferation and Notch signaling, which suppresses Wnt and Fgf signaling in iTCHs. Conversely, loss of Notch in iTCHs rewires alveolar signaling patterns to promote euplastic regeneration and gas exchange. The signaling patterns of iTCHs can differentially phenotype fibrotic from degenerative human lung diseases, through apposing flows of FGF and WNT signaling. These data reveal the emergence of an injury and disease associated iTCH in the lung and the ability of using iTCH specific signaling patterns to discriminate human lung disease phenotypes.
Genome assembly variation and its implications for gene discovery in nematode species
Authors: Mariene Grace M. , Wasmuth James D. 
Published: March 2024

AbstractGenome assemblers are a critical component of genome science, but the choice of assembly software and protocols can be daunting. Here, we investigate genome assembly variation and its implications for gene discovery across three nematode species—Caenorhabditis bovis,Haemonchus contortus, andHeligmosomoides bakeri—highlighting the critical interplay between assembly choice and downstream genomic analysis. Selecting popular genome assemblers, we generated multiple assemblies for each species, analyzing their structure, completeness, and effect on gene family analysis. Our findings demonstrate that assembly variations can significantly affect gene family composition, with notable differences in critical gene families likecyp,gst,ugt, andnhr. Despite broadly similar performance using various assembly metrics, comparisons of assemblies with a single species revealed underlying structural rearrangements and inconsistencies in gene content. This emphasizes the imperative for continuous refinement of genomic resources. Our findings advocate for a cautious and informed approach to genome assembly and annotation to ensure reliable and insightful genomic interpretations.
A Micro-scale Humanized Ventilator-on-a-Chip to Examine the Injurious Effects of Mechanical Ventilation
Authors: Gabela-Zuniga Basia , Shukla Vasudha C. , Bobba Christopher , Higuita-Castro Natalia , Powell Heather M. , Englert Joshua A. , Ghadiali Samir N. 
Published: March 2024

AbstractPatients with compromised respiratory function frequently require mechanical ventilation to survive. Unfortunately, non-uniform ventilation of injured lungs generates complex mechanical forces that lead to ventilator induced lung injury (VILI). Although investigators have developed lung-on-a-chip systems to simulate normal respiration, modeling the complex mechanics of VILI as well as the subsequent recovery phase is a challenge. Here we present a novel humanized in vitro ventilator-on-a-chip (VOC) model of the lung microenvironment that simulates the different types of injurious forces generated in the lung during mechanical ventilation. We used transepithelial/endothelial electrical resistance (TEER) measurements to investigate how individual and simultaneous application of the different mechanical forces alters real-time changes in barrier integrity during and after injury. We find that compressive stress (i.e. barotrauma) does not significantly alter barrier integrity while over-distention (20% cyclic radial strain, volutrauma) results in decreased barrier integrity that quickly recovers upon removal of mechanical stress. Conversely, surface tension forces generated during airway reopening (atelectrauma), result in a rapid loss of barrier integrity with a delayed recovery relative to volutrauma. Simultaneous application of cyclic stretching (volutrauma) and airway reopening (atelectrauma), indicate that the surface tension forces associated with reopening fluid-occluded lung regions is the primary driver of barrier disruption. Thus, our novel VOC system can monitor the effects of different types of injurious forces on barrier disruption and recovery in real-time and can be used to identify the biomechanical mechanisms of VILI.