bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential therapeutic benefit of spinal cord stimulation in restless legs syndrome: scoping review and mechanistic considerations
Authors: Pagani-Estévez Gabriel L , Holland Marshall T , Tippmann-Peikert Maja , Benarroch Eduardo E , Silber Michael H , Carvalho Diego Z 
Published: October 2023

Abstract

Background
Restless legs syndrome (RLS) is a prevalent sensorimotor disorder that can dramatically impair sleep quality, daytime function, and quality of life. Although many patients benefit from standard pharmacological therapy, some patients suffer from insufficient treatment response or medication intolerance. Novel treatment approaches are therefore necessary.

Objective
Given the overlap between RLS and pain syndromes in both pathophysiological mechanisms and certain treatment options, we aimed to perform a scoping review of the available evidence on spinal cord stimulation (SCS) for RLS and discuss potential mechanistic implications.

Methods
We identified a total of 16 cases of patients with RLS who underwent SCS, all from case reports or case series.

Discussion
The published evidence is insufficient to assess SCS efficacy in patients with RLS, but SCS remains a promising investigational therapy in RLS on the basis of its potential mitigatory effects in the central hyperexcitability of the sensorimotor cortex through neuromodulation of spinal, subcortical, and cortical areas. A call for further research in this field is presented, with suggestions for future directions and trial designs.
High-frequency spinal cord stimulation (10 kHz) alters sensory function and nerve fiber density in painful diabetic neuropathy: a pilot prospective open-label study
Authors: Chen Jeffrey , Frizzi Katie , Zardouz Shawn , Province-Azalde Rose , Furnish Tim , Wallace Mark , Castellanos Joel , Tayarani Alireza , Halter Kenneth , Lam Katie , Banducci Sarah , Chieu Alex , Calcutt Nigel 
Published: October 2023

Abstract

Objective
Spinal cord stimulation at 10 kHz has provided effective pain relief and improved function in painful diabetic peripheral neuropathy. This study aims to confirm the clinical outcomes for 10-kHz spinal cord stimulation treatment of painful diabetic peripheral neuropathy and explore its impact on objective quantitative measures of nerve pathology and function.

Methods
This single–academic center, prospective, open-label, observational study examined the pain relief success of 10-kHz spinal cord stimulation in patients &gt;18 years of age with diabetic peripheral neuropathy. Patients underwent skin biopsies to measure intra-epidermal nerve fiber densities and corneal confocal microscopy measurements before implantation and at the 3-, 6-, and 12-month follow-up visits. Numerical rating scale for pain, visual analog scale, neuropathy pain scale, Short Form-36, and Neuropen (pin prick and monofilament) assessments were also conducted.

Results
Eight patients met the criteria and were enrolled in the study. A successful trial was achieved in 7 subjects, and 6 completed the study. Significant pain relief (P &lt; .001) was achieved at all follow-up visits. Neurological assessments showed reduced numbers of “absent” responses and increased “normal” responses from baseline to 12 months. Both proximal and distal intra-epidermal nerve fiber densities were higher at 12 months than at baseline (P &lt; .01). Confocal microscopy measurements showed a steady increase in nerve density from baseline (188.8% increase at 12 months; P = .029).

Conclusions
We observed pain relief and improvements in sensory function after stimulation that were accompanied by increases in lower-limb intra-epidermal nerve fiber density and corneal nerve density. Further evaluation with a blinded and controlled study is needed to confirm the preliminary findings in this study.
The multiple faces of police identity in Wales: A case study in public order policing
Authors: Harrison Michael 
Published: October 2023

AbstractThis article explores how policing identities shape and inform understanding and practice within public order (PO) policing. Of particular focus is how police use and apply their national identity as a means of explaining their PO policing approach. The study was based in South Wales, UK and findings are drawn from a qualitative multi-methodological approach with the regional police force. I identified that officers drew upon a stereotypical version of Welsh identity to explain their approach to PO policing that was largely characterised as friendly and interactive. Officers claimed that it was their reflexive instinct to engage in this way because this was simply a manifestation of their Welsh identity and character. While this was an important characteristic and source of pride for officers, I argue that this identity appeared to mask, or in some cases enable, PO policing that had a more traditional focus of law and order.
Melatonin protects mice from 5-FU hepatotoxicity and improves 5-FU antitumor effects by an apoptotic pathway dependent on cell cycle arrest in A549 human lung cancer cells
Authors: Elbanan Mona E , Amer Maggie E , El-Missiry Mohamed A , Othman Azza I , Shabana Sameh M 
Published: October 2023

Abstract

Objectives
This study determined if melatonin (MLT) can be used with 5-fluorouracil (5-FU), an anticancer drug as adjuvants to reduce A549 lung cancer cell proliferation and sensitise those cells to 5-FU at lower doses while protecting mice from hepatotoxicity.

Methods
In vitro, MTT assays assessed cell proliferation, and Annexin-V flow cytometry measured A549 cell apoptosis. RT-qPCR measured apoptotic markers tumour suppressor gene P53, KI-67, Bax, Bcl-2, and caspase3; and immunoblotting evaluated cell cycle parameters P21, CDK2, and cyclin E. ELISA biochemical analysis examined liver function, reactive oxygen species (ROS) and antioxidant assays, and inflammatory markers, in vivo. Masson’s trichome, haematoxylin, and eosin stains examined histopathological changes and fibrosis under a microscope.

Key findings
MLT combined with 5-FU elevated chemo-sensitization by decreasing A549 cell proliferation, lowering the IC50, increasing P21, P53, and Bax, decreasing Bcl-2, Ki-67, CDK2, and cyclin E, and inducing apoptosis and cell cycle arrest at G0/G1. After 5-FU [intraperitoneal (IP)]/MLT (oral) co-administration in vivo, all parameters improved and reversed. Liver enzymes (aspartate aminotransferase and alanine transaminase), bilirubin, albumin, total protein, albumin/globulin ratio, ROS, 4-HNE, H2O2, and pro-inflammatory cytokines; IL-6, IL-1β, and TNFα declined while antioxidant enzymes like SOD, CAT, GSH, and GPx, and IL-10 (anti-inflammatory) increased in combined MLT/5-FU treated groups compared with untreated and 5-FU alone treated groups. Histopathology confirmed these results.

Conclusions
MLT protected A549 cells from 5-FU-induced hepatotoxicity and enhanced 5-FU’s antitumor effect in vitro. These results support MLT/5-FU’s benefits, suggesting a more effective lung cancer treatment with fewer hepatotoxicity side effects. That could provide a novel therapeutic strategy for lung cancer.
The Validation of a Simultaneous Ocular and Cervical VEMP Recording Protocol to Unilateral AC Stimuli
Authors: Verrecchia Luca , Jansson Karl-Johan Fredén , Reinfeldt Sabine , Håkansson Bo 
Published: October 2023

Introduction
A simultaneous recording of cervical and ocular vestibular evoked myogenic potential (sVEMP) to unilateral air-conducted (AC) stimulation reduces the test time and halves the sound load.

Materials and Methods
The sVEMP has been compared with the conventional sequential unilateral AC cervical and ocular VEMP in a consecutive cohort of 120 subjects attending the vestibular laboratory. The stimulus was a 500-Hz 6-ms tone burst, at 130 dB peSPL for sequential recordings but at 125 dB for the added sVEMP, for cumulative sound load containment. Amplitudes, latencies, and amplitude asymmetry ratios (ARs) were the parameters included in analysis.

Results
Relevant results were as follows: 1) significantly lower amplitudes in sVEMP versus VEMP (ocular recordings, median = 2.90 [IQR = 0–4.98] vs. 4.15 [1.73–8.98] μV, p < 0.001; cervical, 0.84 [0.30–1.69] vs. 1.36 [0.60–2.30], p < 0.001; electromyography scaled values); 2) 10% lower response rate at cervical recordings and 11% at ocular recordings in sVEMP, particularly in older subjects; 3) significant correlations between cervical amplitudes (r
s = 0.88, p < 0.001), ocular amplitudes (r
s = 0.71, p < 0.001), peak latencies (r
s = 0.36–0.67, p < 0.001), and ARs (ocular, r
s = 0.56; cervical, r
s = 68, p < 0.001); and 4) good agreement in pathological AR detection (cervical recordings, Cohen’s κ = 0.649, p < 0.001; ocular, κ = 0.589, p < 0.001).

Discussion
AC sVEMP showed good correlation/agreement with sequential AC VEMP. Test time containment and halved sound load are clinical adds in sVEMP, opening to its use as laboratory standard. However, AC sVEMP presented reduced amplitudes and response rates, secondary to the reduced AC stimulation used in this study to allow checking of the null responses and the pathological ARs at AC sVEMP with conventional AC VEMP.
Causal Role of the Frontal Eye Field in Attention-induced Ocular Dominance Plasticity
Authors: Song Fangxing , Dong Xue , Zhao Jiaxu , Wang Jue , Sang Xiaohui , He Xin , Bao Min 
Published: October 2023

AbstractPrevious research has found that prolonged eye-based attention can bias ocular dominance. If one eye long-termly views a regular movie meanwhile the opposite eye views a backward movie of the same episode, perceptual ocular dominance will shift towards the eye previously viewing the backward movie. Yet it remains unclear whether the role of eye-based attention in this phenomenon is causal or not. To address this issue, the present study relied on both the functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) techniques. We found robust activation of the frontal eye field (FEF) and intraparietal sulcus (IPS) when participants were watching the dichoptic movie while focusing their attention on the regular movie. Interestingly, we found a robust effect of attention-induced ocular dominance shift when the cortical function of vertex or IPS was transiently inhibited by continuous theta burst stimulation (cTBS), yet the effect was significantly attenuated to a negligible extent when cTBS was delivered to FEF. A control experiment verified that the attenuation of ocular dominance shift after inhibitory stimulation of FEF was not due to any impact of the cTBS on the binocular rivalry measurement of ocular dominance. These findings suggest that the fronto-parietal attentional network is involved in controlling eye-based attention in the “dichoptic-backward-movie” adaptation paradigm, and in this network, FEF plays a crucial causal role in generating the attention-induced ocular dominance shift.
TreePPL: A Universal Probabilistic Programming Language for Phylogenetics
Authors: Senderov Viktor , Kudlicka Jan , Lundén Daniel , Palmkvist Viktor , Braga Mariana P. , Granqvist Emma , Çaylak Gizem , Virgoulay Thimothée , Broman David , Ronquist Fredrik 
Published: October 2023

ABSTRACTWe present TreePPL, a universal probabilistic programming language (PPL) designed for probabilistic modeling and inference in phylogenetics. In TreePPL, the model is expressed as a computer program, which can generate simulations from the model conditioned on some input data. Specialized inference machinery then uses this program to estimate the posterior probability distribution. The aim is to allow the user to focus on describing the model, and provide the inference machinery for free. The TreePPL modeling language is meant to be familiar to users of R or Python, and utilizes a functional programming style that facilitates the application of generic inference algorithms. The model program can be conveniently compiled and run from a Python or R environment, which can be used for pre-processing, feeding the model with the observed data, controlling and running the inference, and receiving and post-processing the output data. The inference machinery is generated by a compiler framework developed specifically for supporting domain-specific modeling and inference, the Miking CorePPL framework. It currently supports a range of inference strategies—including sequential Monte Carlo, Markov chain Monte Carlo, and combinations thereof—and is based on several recent innovations that are important for efficient PPL inference on phylogenetic models. It also allows advanced users to implement novel inference strategies for models described using TreePPL or other domain-specific modeling languages. We briefly describe the TreePPL modeling language and the Python environment, and give some examples of modeling and inference with TreePPL. The examples illustrate how TreePPL can be used to address a range of common problem types considered in statistical phylogenetics, from diversification and tree inference to complex trait evolution. A few major challenges remain to be addressed before the phylogenetic model space is adequately covered by efficient automatic inference techniques, but several of them are being addressed in ongoing work on TreePPL. We end the paper by discussing how probabilistic programming can facilitate further use of machine learning in addressing important challenges in statistical phylogenetics.
Cognitive Reserve Against Alzheimer’s Pathology Is Linked to Brain Activity During Memory Formation
Authors: Vockert Niklas , Machts Judith , Kleineidam Luca , Nemali Aditya , Schütze Hartmut , Yakupov Renat , Peters Oliver , Gref Daria , Schneider Luisa Sophie , Preis Lukas , Priller Josef , Spruth Eike Jakob , Altenstein Slawek , Schneider Anja , Fliessbach Klaus , Wiltfang Jens , Rostamzadeh Ayda , Glanz Wenzel , Incesoy Enise I. , Teipel Stefan , Kilimann Ingo , Goerss Doreen , Laske Christoph , Munk Matthias H. , Spottke Annika , Roy Nina , Heneka Michael T. , Brosseron Frederic , Wagner Michael , Wolfsgruber Steffen , Dobisch Laura , Dechent Peter , Hetzer Stefan , Scheffler Klaus , Zeidman Peter , Stern Yaakov , H.Schott Björn , Jessen Frank , Düzel Emrah , Maass Anne , Ziegler Gabriel ,   the DELCODE study group
Published: October 2023

AbstractThe cognitive reserve (CR) hypothesis posits that individuals can differ in how their brain function is disrupted by pathology associated with aging and neurodegeneration. Here, we tested this hypothesis in the Alzheimer’s disease continuum using longitudinal data from 490 participants of the DELCODE multicentric observational study. Brain function was measured using task fMRI of visual memory encoding. Using a multivariate moderation analysis we identified a CR-related activity pattern underlying successful memory encoding that moderated the detrimental effect of AD pathological load on cognitive performance. CR was mainly represented by a more pronounced expression of the task-active network encompassing the default mode network (DMN), anterior cingulate cortex (ACC) and inferior temporal regions including the fusiform gyrus. We devised personalized fMRI-based CR scores that moderated the impact of AD pathology on cognitive performance and were positively associated with years of education. Furthermore, higher CR scores were associated with slower cognitive decline over time. Our findings suggest maintenance of core cognitive circuits including the DMN and ACC as the primary mechanism of CR. Individual brain activity levels of these areas during memory encoding have prognostic value for future cognitive decline.
CytoPipeline & CytoPipelineGUI: A Bioconductor R package suite for building and visualizing automated pre-processing pipelines for flow cytometry data
Authors: Hauchamps Philippe , Bayat Babak , Delandre Simon , Hamrouni Mehdi , Toussaint Marie , Temmerman Stéphane , Lin Dan , Gatto Laurent 
Published: October 2023

AbstractBackgroundWith the increase of the dimensionality in flow cytometry data over the past years, there is a growing need to replace or complement traditional manual analysis (i.e. iterative 2D gating) with automated data analysis pipelines. A crucial part of these pipelines consists of pre-processing and applying quality control filtering to the raw data, in order to use high quality events in the downstream analyses. This part can in turn be split into a number of elementary steps : signal compensation or unmixing, scale transformation, debris, doublets and dead cells removal, batch effect correction, etc. However, assembling and assessing the pre-processing part can be challenging for a number of reasons. First, each of the involved elementary steps can be implemented using various methods and R packages. Second, the order of the steps can have an impact on the downstream analysis results. Finally, each method typically comes with its specific, non standardized diagnostic and visualizations, making objective comparison difficult for the end user.ResultsHere, we presentCytoPipelineandCytoPipelineGUI, twoRpackages to build, compare and assess pre-processing pipelines for flow cytometry data. To exemplify these new tools, we present the steps involved in designing a pre-processing pipeline on a real life dataset and demonstrate different visual assessment use cases. We also set up a benchmarking comparing two pre-processing pipelines differing by their quality control methods, and show how the package visualization utilities can provide crucial user insight into the obtained benchmark metrics.ConclusionCytoPipelineandCytoPipelineGUIare two BioconductorRpackages that help building, visualizing and assessing pre-processing pipelines for flow cytometry data. They increase productivity during pipeline development and testing, and complement benchmarking tools, by providing user intuitive insight into benchmarking results.
Biological aging of two innate behaviors ofDrosophila melanogaster: escape climbing versus courtship learning and memory
Authors: Thiem Jessica , Viskadourou Maria , Gaitanidis Alexandros , Stravopodis Dimitrios J , Strauß Roland , Duch Carsten , Consoulas Christos 
Published: October 2023

ABSTRACTMotor and cognitive aging can severely affect life quality of elderly people and burden health care systems. In search for diagnostic behavioral biomarkers, it has been suggested that walking speed can predict forms of cognitive decline, but in humans, it remains challenging to separate the effects of biological aging and lifestyle. We examined a possible association of motor and cognitive decline in Drosophila, a genetic model organism of healthy aging. Long term courtship memory is present in young flies but absent already during mid life (4-8 weeks). By contrast, courtship learning index and short term memory (STM) are surprisingly robust and remain stable through mid (4-8 weeks) and healthy late life (>8 weeks), until courtship performance collapses suddenly at ∼4.5 days prior to death. By contrast, climbing speed declines gradually during late life (>8 weeks). The collapse of courtship performance and short term memory close to the end of life are not related to the gradual late life decline in climbing speed. Thus, during healthy aging in Drosophila, climbing and courtship motor behaviors decline differentially, unlikely share a common cause, and motor and cognitive performance decline are not closely associated to each other.
Programmable delivery of fluoxetine via wearable bioelectronics for wound healing in vivo
Authors: Li Houpu , Yang Hsin-ya , Asefifeyzabadi Narges , Baniya Prabhat , Lopez Andrea Medina , Gallegos Anthony , Zhu Kan , Hsieh Hao-Chieh , Nguyen Tiffany , Hernandez Cristian , Zlobina Ksenia , Recendez Cynthia , Tebyani Maryam , Carrión Héctor , Selberg John , Luo Le , Alhamo Moyasar A. , Soulika Athena M. , Levin Michael , Norouzi Narges , Gomez Marcella , Zhao Min , Teodorescu Mircea , Isseroff Roslyn Rivkah , Rolandi Marco 
Published: October 2023

AbstractThe ability to deliver drugs with precise dosages at specific time points can significantly improve disease treatment while reducing side effects. Drug encapsulation for gradual delivery has opened up the doors for superior treatment regimen. To expand on this ability, programming bioelectronic devices to deliver small molecules enables ad-hoc personalized therapeutic profiles that are more complex than simple gradual release. Here, we introduce a wearable bioelectronic bandage with an integrated electrophoretic ion pump that affords on-demand drug delivery with precise dose control. Delivery of fluoxetine to wounds in mice resulted in a 27.2% decrease in the macrophage ratio (M1/M2) and a 39.9% increase in re-epithelialization, indicating a shorter inflammatory phase and faster overall healing. Programmable drug delivery using wearable bioelectronics in wounds introduces a broadly applicable strategy for the long-term delivery of a prescribed treatment regimen with minimal external intervention.
Highly biased agonism for GPCR ligands via nanobody tethering
Authors: Sachdev Shivani , Creemer Brendan A. , Gardella Thomas J. , Cheloha Ross W. 
Published: October 2023

AbstractLigand-induced activation of G protein-coupled receptors (GPCRs) can initiate signaling through multiple distinct pathways with differing biological and physiological outcomes. There is intense interest in understanding how variation in GPCR ligand structure can be used to promote pathway selective signaling (“biased agonism”) with the goal of promoting desirable responses and avoiding deleterious side effects. Here we present a new approach in which a conventional peptide ligand for the type 1 parathyroid hormone receptor (PTHR1) is converted from an agonist which induces signaling through all relevant pathways to a compound that is highly selective for a single pathway. This is achieved not through variation in the core structure of the agonist, but rather by linking it to a nanobody tethering agent that binds with high affinity to a separate site on the receptor not involved in signal transduction. The resulting conjugate represents the most biased agonist of PTHR1 reported to date. This approach holds promise for facile generation of pathway selective ligands for other GPCRs.
Identification of a novel SNP in the miR172 binding site ofQhomoeologAP2L-D5is associated with spike compactness and agronomic traits in wheat (Triticum aestivumL.)
Authors: Zeng Victoria , Uauy Cristobal , Chen Yi 
Published: October 2023

AbstractSpike architecture is a key determinant of wheat yield, a crop which supports much of the human diet but whose yield gains are stagnating. Spike architecture mutants offer opportunities to identify genetic factors contributing to inflorescence development. Here, we investigate the locus underlying the compact spike phenotype of mutant line ANK-15 by conducting mRNA-sequencing and genetic mapping using ANK-15 and its non-compact spike near-isogenic line Novosibirskaya 67 (N67). Previous literature has placed the compact spike locus of ANK-15 to chromosome 2B. However, based on the single nucleotide polymorphisms (SNPs) identified using mRNA-seq data, we were unable to detect polymorphisms between N67 and ANK-15 in the putative chromosome 2B region. We performed differential expression analysis of developing rachis and found thatAP2L-D5, theDhomoeolog of the domesticationQgene, is upregulated in ANK-15 in comparison to N67. ANK-15 carries a SNP in the microRNA172 binding site ofAP2L-D5, which is predicted to lead to higher expression ofAP2L-D5due to decreased miRNA172-mediated degradation. Furthermore, we performed genetic mapping using an ANK-15 × N67 F2population and found a single quantitative trait locus on chromosome 5D coinciding with the position ofAP2L-D5. This result suggests thatAP2L-D5is likely the underlying causal gene for the compact spike phenotype in ANK-15. We performed a field trial to investigate the effect of theAP2L-D5allele on agronomic traits and found that theAP2L-D5allele from ANK-15 is associated with a significant reduction in height, increased thousand grain weight (TGW), and increased grain width.