bluuebunny/crossref_metadata_2025_split huggingface dataset:
Objective and subjective evaluation of walking ability with and without the use of a passive brace for hip flexor muscles in individuals with multiple sclerosis
Authors: Prada Valeria , Grange Erica , Sgarito Caterina , Pedrazzoli Elisabetta , Konrad Giovanna , Di Giovanni Rachele , Brichetto Giampaolo , Solaro Claudio 
Published: November 2023

Background:
Multiple sclerosis (MS) affects the cognitive and motor domains. Muscle weakness often leads to abnormal gait. Several solutions are rising, including the use of passive exoskeletons.

Objective:
The purpose of this study is to evaluate the effect of a first-ever use of a passive exoskeleton on walking ability in people with MS.

Methods:
We recruited 50 persons with MS. All subjects were assessed using the 2-min walking test, the timed 25-foot walk test, and a two-stage rate of perceived exertion (RPE) without the exoskeleton (T0) and with the exoskeleton (T1).

Results:
The data showed a significant decrease in walking endurance while the exoskeleton is worn (2-min walking test: T0: 65.19 ± 23.37 m; T1: 59.40 ± 22.99; p < 0.0001) and a not significant difference in walking speed on a shortened distance (T0: 15.71 ± 10.30 s; T1: 15.73 ± 11.86 s; p = 0.25). No significant differences were also found for the effort perception scale (RPE: T0: 13.24 ± 3.01; T1: 13.60 ± 2.9; p = 0.3). Seventy-two percent of subjects reported a positive or neutral global perceived effect.

Conclusions:
The exoskeleton does not add any fatiguing or negative effects. Although the walking performance decreases, the overall perception of the subjects is positive. Further studies are needed to evaluate the effect of the exoskeleton on gait quality.
Radio-Guided Occult Lesion Localization With 99mTc for the Localization of Nonpalpable Melanoma and Soft Tissue Sarcoma Lesions: A Feasibility Study
Authors: Reijers Sophie J.M. , Mook Fleur J. , Groen Harald C. , Schrage Yvonne , Stokkel Marcel P.M. , Donswijk Maarten L. , van Houdt Winan J. 
Published: November 2023

Purpose of the ReportLocalization techniques are needed to facilitate resection of nonpalpable lesions. In this study, the feasibility of radio-guided occult lesion localization (ROLL) with99mTc is investigated for the localization of nonpalpable, small, suspicious, or proven melanoma or soft tissue sarcoma lesions at various locations throughout the body.Patients and MethodsPatients with nonpalpable, suspicious, or proven melanoma or soft tissue sarcoma lesions were selected for this study. Within 24 hours before surgery, a median dose of 33.92 MBq99mTc-labeled human albumin particles (99mTc-NA or99mTc-MAA) was injected in the lesion under ultrasound guidance. A hand-held gamma probe was used to detect the radioactive signal and guidance during surgery.ResultsIn this study, 20 patients with a total of 25 lesions were included and analyzed. The median size of the lesions was 1.8 cm (interquartile range [IQR], 1.8–4.0 cm), of which 44% were intramuscular located and 36% were subcutaneous, and 20% consisted of suspicious lymph nodes, mostly in the lower extremity. At median 4 hours (IQR, 3–6 hours) postinjection,99mTc ROLL showed a 100% intraoperative identification rate with proper signal identification with the gamma probe in all patients. With a median surgery time of 76 minutes (IQR, 45–157 minutes), all targeted lesions could be resected without99mTc-related complications, resulting in 88% microscopically margin-negative resection. No reoperations were needed for the same lesion.ConclusionsThe99mTc ROLL procedure is feasible for the localization and excision of small, nonpalpable melanoma and soft tissue sarcoma lesions at various locations in the body.
Correlation between COVID-19 vaccination and inflammatory musculoskeletal disorders
Authors: Park Young Hwan , Kim Min Ho , Choi Myeong Geun , Chun Eun Mi 
Published: November 2023

AbstractImportanceEarlier research on COVID-19 vaccines identified a range of adverse reactions related to proinflammatory actions that can lead to an excessive immune response and sustained inflammation. However, no study has been conducted on the association between inflammatory musculoskeletal disorders and COVID-19 vaccines.ObjectiveTo investigate the incidence rates of inflammatory musculoskeletal disorders following COVID-19 vaccination and to compare them with those of unvaccinated individuals.Design, Setting, and ParticipantsThis retrospective nationwide cohort study used data from the Korean National Health Insurance Service (NHIS) database, involving 2,218,715 individuals. Data were collected from January 1, 2021, to 12 weeks after the second dose of vaccine for vaccinated individuals and 12 weeks after September 30, 2021, for unvaccinated individuals.ExposuresStatus was categorized as unvaccinated and vaccinated with mRNA vaccine, viral vector vaccine, and mixing and matching.Main Outcomes and MeasuresThe primary outcome was the occurrence of inflammatory musculoskeletal disorders that were selected as plantar fasciitis (ICD code, M72.2), rotator cuff syndrome (M75.1), adhesive capsulitis (M75.0), herniated intervertebral disc (HIVD) (M50.2/M51.2), spondylosis (M47.9), bursitis (M71.9), Achilles tendinitis (M76.6), and de-Quervain tenosynovitis (M65.4). Multivariate logistic regression analysis was used to determine the risk factors of musculoskeletal disorders after adjusting for potential confounders.ResultsAmong the 2,218,715 individuals, 1,882,640 (84.9%) received two doses of the COVID-19 vaccine, and 336,075 (15.1%) did not. At 12 weeks after vaccination, the incidences of plantar fasciitis (0.14-0.17%), rotator cuff syndrome (0.29-0.42%), adhesive capsulitis (0.29-0.47%), HIVD (0.18-0.23%), spondylosis (0.14-0.23%), bursitis (0.02-0.03%), Achilles tendinitis (0.0-0.05%), and de-Quervain tenosynovitis (0.04-0.05%) were higher in all three vaccinated groups (mRNA, cDNA, and mixing and matching vaccines) when compared to the unvaccinated group. All COVID-19 vaccines were identified as significant risk factors for each inflammatory musculoskeletal disorder (odds ratio, 1.404-3.730), except for mixing and matching vaccines for de-Quervain tenosynovitis.Conclusions and RelevanceThis cohort study found that individuals who received any COVID-19 vaccine were more likely to be diagnosed with inflammatory musculoskeletal disorders than those who did not. This information will be useful in clarifying the adverse reactions to COVID-19 vaccines and informing people about their potential for inflammatory musculoskeletal disorders after vaccination.
ChatGPT for assessing risk of bias of randomized trials using the RoB 2.0 tool: A methods study
Authors: Pitre Tyler , Jassal Tanvir , Talukdar Jhalok Ronjan , Shahab Mahnoor , Ling Michael , Zeraatkar Dena 
Published: November 2023

AbstractBackgroundInternationally accepted standards for systematic reviews necessitate assessment of the risk of bias of primary studies. Assessing risk of bias, however, can be time- and resource-intensive. AI-based solutions may increase efficiency and reduce burden.ObjectiveTo evaluate the reliability of ChatGPT for performing risk of bias assessments of randomized trials using the revised risk of bias tool for randomized trials (RoB 2.0).MethodsWe sampled recently published Cochrane systematic reviews of medical interventions (up to October 2023) that included randomized controlled trials and assessed risk of bias using the Cochrane-endorsed revised risk of bias tool for randomized trials (RoB 2.0). From each eligible review, we collected data on the risk of bias assessments for the first three reported outcomes. Using ChatGPT-4, we assessed the risk of bias for the same outcomes using three different prompts: a minimal prompt including limited instructions, a maximal prompt with extensive instructions, and an optimized prompt that was designed to yield the best risk of bias judgements. The agreement between ChatGPT’s assessments and those of Cochrane systematic reviewers was quantified using weighted kappa statistics.ResultsWe included 34 systematic reviews with 157 unique trials. We found the agreement between ChatGPT and systematic review authors for assessment of overall risk of bias to be 0.16 (95% CI: 0.01 to 0.3) for the maximal ChatGPT prompt, 0.17 (95% CI: 0.02 to 0.32) for the optimized prompt, and 0.11 (95% CI: -0.04 to 0.27) for the minimal prompt. For the optimized prompt, agreement ranged between 0.11 (95% CI: -0.11 to 0.33) to 0.29 (95% CI: 0.14 to 0.44) across risk of bias domains, with the lowest agreement for the deviations from the intended intervention domain and the highest agreement for the missing outcome data domain.ConclusionOur results suggest that ChatGPT and systematic reviewers only have “slight” to “fair” agreement in risk of bias judgements for randomized trials. ChatGPT is currently unable to reliably assess risk of bias of randomized trials. We advise against using ChatGPT to perform risk of bias assessments. There may be opportunities to use ChatGPT to streamline other aspects of systematic reviews, such as screening of search records or collection of data.
A mean-field model of gamma-frequency oscillations in networks of excitatory and inhibitory neurons
Authors: Tahvili Farzin , Destexhe Alain 
Published: November 2023

AbstractGamma oscillations are widely seen in the cerebral cortex in different states of the wake-sleep cycle and are thought to play a role in sensory processing and cognition. Here, we study the emergence of gamma oscillations at two levels, in networks of spiking neurons, and a mean-field model. At the network level, we consider two different mechanisms to generate gamma oscillations and show that they are best seen if one takes into account the synaptic delay between neurons. At the mean-field level, we show that, by introducing delays, the mean-field can also produce gamma oscillations. The mean-field matches the mean activity of excitatory and inhibitory populations of the spiking network, as well as their oscillation frequencies, for both mechanisms. This mean-field model of gamma oscillations should be a useful tool to investigate large-scale interactions through gamma oscillations in the brain.
Polymer-mediated oligonucleotide delivery enables construction of barcoded 3D cultures for spatial single-cell analysis
Authors: King Jessica J. , Mowla Alireza , Kretzmann Jessica A. , Norret Marck , Kadolsky Ulrich D. , Iqbal Munir , Saxena Alka , Mamsa Somayra S.A. , Amos Sebastian E. , Choi Yu Suk , Kennedy Brendan F. , Iyer K. Swaminathan , Smith Nicole M. , Evans Cameron W. 
Published: November 2023

AbstractSpatial transcriptomics has been widely used to capture gene expression profiles, realised as a two-dimensional (2D) projection of RNA captured from tissue sections. Wree-dimensional (3D) cultures such as spheroids and organoids are highly promising alternatives to oversimplified and homogeneous 2D cell culture models, but existing spatial transcriptomic platforms do not currently have sufficient resolution for robust analysis of 3D cultures. We present a transfection-based method for fluorescent DNA barcoding of cell populations, and the subsequent construction of spheroidal cellular architectures using barcoded cells in a layer-by-layer approach. For the first time, changes in gene expression throughout this 3D culture architecture are interrogated using multiplex single-cell RNA sequencing in which DNA barcodes are used to encode the spatial positioning of cells. We show that transfection with fluorophore-conjugated barcode oligonucleotides enables both imaging and sequencing at single-cell resolution, providing spatial maps of gene expression and drug response. Additionally, we show that fluorophore-conjugated DNA barcodes support correlative imaging studies such as mechano-microscopy to capture information about spatially-varying mechanical heterogeneity in 3D cultures. We ability to create customised, encoded cellular assemblies is a general approach that can resolve spatial differences in gene expression in 3D cell culture models.
Decreases in purchases of energy, sodium, sugar, and saturated fat three years after implementation of the Chilean Food Labelling and Marketing Law
Authors: Taillie Lindsey Smith , Bercholz Maxime , Popkin Barry , Rebolledo Natalia , Reyes Marcela , Corvalán M. Camila 
Published: November 2023

AbstractBackgroundIn 2016, Chile implemented a multi-phase set of policies that mandated warning labels, restricted food marketing to children, and banned school sales of unhealthy foods and beverages. Chile’s law, particularly the warning label component, set the precedent for a rapid global proliferation of similar policies. While our initial evaluation showed policy-linked decreases in purchases of products carrying the warning label, a longer-term evaluation is needed, particularly as later phases of Chile’s law included stricter nutrient thresholds and introduced a daytime ban on advertising of labeled foods for all audiences. The objective is to evaluate changes in purchases of energy, sugar, sodium, and saturated fat purchased after Phase 2 implementation of the Chilean policies.Methods and FindingsThis before- and after-study used longitudinal data on monthly food and beverage purchases from 2,844 Chilean households (138,391 household-months) from July 1, 2013 until June 30, 2019. Nutrition facts panel data from food and beverage packages were linked at the product level and reviewed by nutritionists. Products were considered to carry the warning label if they contained added sugar, sodium, or saturated fat, and exceeded the final phase nutrient or calorie thresholds (thus would carry the warning label). Using correlated random-effects models and an interrupted time series design, we estimated the nutrient content of food and beverage purchases associated with Phase 1 and Phase 2 compared to a counterfactual scenario based on pre-policy trends. Compared to the counterfactual, we observed significant decreases in purchases of foods and beverages carrying the warning label during Phase 2, including a relative 36.8% reduction in sugar (−30.3 calories, 95% CI −34.5, −26.3), a 23.0% relative reduction in energy (−51.6 calories, 95% CI −60.7, −42.6), a 21.9% relative reduction in sodium (−85.8 mg, 95% CI −105.0, −66.7) and a 15.7% relative reduction in saturated fat (−6.4 calories, 95% CI −8.4, −4.3). Decreases were partially offset by increases in non-labeled purchases, but the net effect shows a significant decrease in total nutrients of concern purchased during Phase 2. Reductions in sugar and energy were driven by beverage purchases, whereas reductions in sodium and saturated fat were driven by foods. The pattern of declines in purchases was similar for households of lower vs. higher socioeconomic status. A key limitation of this study is that the data include only a portion of what Chilean households purchase that, while including important categories impacted by the law, do not cover an entire diet.ConclusionsThe Chilean policies on food labeling, marketing, and school food sales led to declines in nutrients of concern during a more complete phase of implementation, particularly from foods and drinks carrying the warning label.
Within-host virus spreading and tolerance to infection are key factors of theArabidopsis thalianaage-dependent susceptibility to viral infections
Authors: Melero Izan , Gómez-Cadenas Aurelio , González Rubén , Elena Santiago F. 
Published: November 2023

SummaryArabidopsis thalianais more susceptible to certain viruses during its later developmental stages. The reasons for this age-dependent susceptibility are not fully understood. Here we explored the possible causes by studying theA. thalianainfection response to turnip mosaic virus at three developmental stages: vegetative, bolting and flowering. We found that infected plants at later stages downregulate cell wall fortification genes and that this downregulation facilitates the viral spread and systemic infection. Despite being more susceptible to infection, infected flowering plants are more fertile (i.e., produce more viable seeds) than vegetative and bolting infected plants; that is, they have greater fitness than plants infected at these earlier developmental stages. Treatment of postbolting plants with salicylic acid increases resistance to infections at the cost of significantly reducing fertility. Together, these observations suggest a negative trade-off between viral susceptibility and plant fertility. Our findings point towards a development-dependent tolerance to infection.
Single-molecule systems for detection and monitoring of plasma circulating nucleosomes and oncoproteins in Diffuse Midline Glioma
Authors: Erez Nir , Furth Noa , Fedyuk Vadim , Wadden Jack , Aittaleb Rayan , Schwark Kallen , Niculcea Michael , Miclea Madeline , Mody Rajen , Franson Andrea , Eze Augistine , Nourmohammadi Niku , Nazarian Javad , Venneti Sriram , Koschmann Carl , Shema Efrat 
Published: November 2023

SummaryThe analysis of cell-free tumor DNA (ctDNA) and proteins in the blood of cancer patients potentiates a new generation of non-invasive diagnostics and treatment monitoring approaches. However, confident detection of these tumor-originating markers is challenging, especially in the context of brain tumors, in which extremely low amounts of these analytes circulate in the patient’s plasma. Here, we applied a sensitive single-molecule technology to profile multiple histone modifications on millions of individual nucleosomes from the plasma of Diffuse Midline Glioma (DMG) patients. The system reveals epigenetic patterns that are unique to DMG, significantly differentiating this group of patients from healthy subjects or individuals diagnosed with other cancer types. We further develop a method to directly capture and quantify the tumor-originating oncoproteins, H3-K27M and mutant p53, from the plasma of children diagnosed with DMG. This single-molecule system allows for accurate molecular classification of patients, utilizing less than 1ml of liquid-biopsy material. Furthermore, we show that our simple and rapid detection strategy correlates with MRI measurements and droplet-digital PCR (ddPCR) measurements of ctDNA, highlighting the utility of this approach for non-invasive treatment monitoring of DMG patients. This work underscores the clinical potential of single-molecule-based, multi-parametric assays for DMG diagnosis and treatment monitoring.
Density dependent survival drives variation in density dependent population growth of an insect pest
Authors: Buddh Shyamsunder , Krishna Sandeep , Agashe Deepa 
Published: November 2023

ABSTRACTSeveral ecological processes – from population dynamics to species co-existence – are driven by density dependence (DD) in population growth rate. Thus, to predict and manage ecological outcomes, we need a deep understanding of which factors and demographic traits drive variation in DD. In the insect pestTribolium castaneum, we found large variation in DD across habitats but not across source populations. We modeled DD in population growth as the product of DD in fecundity and survival, experimentally estimating each parameter. Across habitats, survival parameters varied more than fecundity, including in simulations with varying parameter values. Thus, DD in survival drives variation in density-dependent population growth, and should evolve rapidly under strong density-dependent selection. Our general framework combining detailed experiments and simulations with a simple model can be used for other species to better understand the causes and consequences of density dependent population growth.
Defining minimal selective concentrations of amoxicillin, doxycycline and enrofloxacin in broiler-derived cecal fermentations by phenotype, microbiome and resistome
Authors: Swinkels Aram F. , Fischer Egil A.J. , Korving Lisa , Kusters Nina E. , Wagenaar Jaap A. , Zomer Aldert L. 
Published: November 2023

AbstractAntimicrobial resistance (AMR) is an emerging worldwide problem. Exposure to antimicrobials selects for resistant bacteria which are a health threat for humans and animals. The concentration at which selection for resistant bacteria occurs is often lower than the minimum inhibitory concentration (MIC) and also differs between environments. Defining this minimal selective concentration (MSC) under natural conditions is essential to understand the selective window for resistant bacteria which are exposed to residual antimicrobials in humans, animals and the environment.In this study we estimated the MSCs of three antimicrobial compounds, amoxicillin, doxycycline and enrofloxacin in a complex microbial community by conducting fermentation assays with cecal material derived from broilers. We examined the phenotypic resistance ofEscherichia coli, resistome and microbiome after 6 and 30 hours of fermenting in the presence of antimicrobials of interest. The concentrations are 10 to 100 times lower than the epidemiological cut-off values inE. colifor the respective antimicrobials as determined by EUCAST (https://mic.eucast.org/). In contrast to the amoxicillin and doxycycline exposure we could not determine any molecular resistance mechanism in the resistome analysis for the enrofloxacin exposure, likely because they are the result of point mutations.Our findings show at which concentrations there still is selection for AMR bacteria. This knowledge can be used to manage the risk of the emergence of AMR bacteria.ImportanceAntimicrobial resistance is an emerging threat to the health of humans and animals; it might affect economic prosperity in the future. The rise of antimicrobial resistant bacteria is a consequence of the use of antimicrobial compounds in humans and animals which selects for resistant bacteria. It is critical to understand the relation between the concentrations of antimicrobial compounds and their selection for antimicrobial resistant bacteria. In our study we are providing the minimal selective concentrations for amoxicillin, doxycycline and enrofloxacin by using cecal fermentations assays.
The role of IL-6 in dopamine dysregulation underlying anhedonia phenotype in rats
Authors: Varela Roger B , Macpherson Heather , Houghton Tristan , Daygon Dara , Tye Susannah J 
Published: November 2023

ABSTRACTAimsTo investigate the role of peripheral metabolic change and chronic low-grade inflammation on striatal dopamine dynamics and anhedonia-like behaviour induced by hypothalamic–pituitary–adrenal (HPA) axis disruption.MethodsWistar rats were trained in a progressive-ratio/concurrent effort-related choice paradigm to assess effort-related decision making. After reaching a stable baseline, animals received daily injections of adrenocorticotrophic hormone (ACTH) or saline for 24 days. On the 23rdand 24thday, animals received a bupropion challenge (10mg/kg and 20mg/kg respectively) 30 minutes prior to the behavioural testing session. On the 25thday, animals received a single injection of bupropion (20mg/kg) 30 minutes prior to euthanasia. Peripheral and central inflammatory markers were assessed through ELISA and In-Cell Western assay; glucose transport activity was assessed in peripheral blood mononuclear cells though a commercial assay kit; brain levels of dopaminergic and inflammatory markers were assessed in the nucleus accumbens (NAc) and prefrontal cortex (PFC) through immunohistochemistry; and serum central carbon metabolism metabolites were assessed through a metabolomics approach.ResultsACTH induced an anhedonia-like phenotype, decreased tyrosine hydroxylase (TH) levels in the NAc, increased peripheral IL-6 levels, and decreased glucose transport activity and glucose metabolites when compared to control group. Bupropion treatment was not able to reverse the anhedonic phenotype. Glucose uptake was positively correlated to behaviour; TH levels were correlated to microglia volume; metabolites were correlated to TH levels; and IL6 was correlated to TH levels and metabolites.ConclusionChronic ACTH treatment can induce treatment-resistant anhedonia in rats, and the interaction between peripheral immunometabolic state and central dopamine synthesis is a potential mechanism underlying this phenotype.