bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating mediators of the effect of varenicline preloading on smoking abstinence in a randomized controlled trial
Authors: Johnstone Samantha , Cooper Robert K. , Wray Jennifer M. , Tonkin Sarah S. , Knapp Kyler S. , Colder Craig R. , Maguin Eugene , Mahoney Martin C. , Tiffany Stephen T. , Brandon Thomas H. , Ashare Rebecca L. , Tyndale Rachel F. , Hawk Larry W. 
Published: February 2025

AbstractBackground and aimsMechanisms of varenicline preloading in promoting smoking abstinence have not been evaluated. Based on an extinction of reinforcement framework, we tested the hypothesis that pre‐quit reductions in smoking rate mediate the effect of extended preloading on abstinence. We also tested alternative indicators of change in smoking reinforcement, as well as smoking aversion, nausea and abstinence self‐efficacy as candidate mediators.Design, participants and interventionRandomized, double‐blind, placebo‐controlled trial (NCT03262662) comparing extended (4‐week varenicline) to standard (3 weeks of placebo, 1‐week varenicline) preloading, preceding 11 weeks of open‐label varenicline, in 320 adults (56% female). The primary outcome was self‐reported continuous smoking abstinence during the last 4 weeks of treatment, with cotinine bio‐verification at end of treatment (EOT).SettingUniversity at Buffalo, State University of New York, USA (part of the trial was conducted at participants' homes due to the COVID‐19 pandemic).MeasurementsCandidate mediators, including smoking rate and subjective effects of smoking (reward, satisfaction, aversion), self‐reported craving, withdrawal, nausea and abstinence self‐efficacy, were assessed daily during the pre‐quit period with ecological momentary assessment. At two laboratory visits participants completed a choice task to assess smoking reinforcement.FindingsThere was a statistically significant indirect effect of extended preloading on greater EOT abstinence rates through pre‐quit declines in smoking rate [a*b = 0.284, 95% confidence interval (0.072,0.616)] and percent reduction in smoking across the pre‐quit period [a*b = 0.225, (0.080,0.437)]. There were also statistically significant indirect effects through reductions in pre‐quit craving [a*b = 0.150, (0.01,0.420)] and increases in pre‐quit self‐efficacy [a*b = 0.157, (0.038,0.375)]. Sex‐specific analyses suggested these mediated effects were consistently limited to females. No other candidate mediators yielded statistically significant indirect effects.ConclusionsExtended varenicline preloading mediated smoking abstinence through reduced pre‐quit smoking and craving among female smokers seeking to quit; increased pre‐quit abstinence self‐efficacy was also a significant mediator.
Integrating QTL and expression QTL of PigGTEx to improve the accuracy of genomic prediction for small population in Yorkshire pigs
Authors: Shi Haoran , Geng He , Yang Bin , Yin Zongjun , Liu Yang 
Published: February 2025

AbstractThe size of the reference population and sufficient phenotypic records are crucial for the accuracy of genomic selection. However, for small‐to‐medium‐sized pig farms or breeds with limited population sizes, conducting genomic breeding programs presents significant challenges. In this study, 2295 Yorkshire pigs were selected from three distinct regions, including 1500 from an American line, 500 from a Canadian line, and 295 from a Danish line. All populations were genotyped using the GeneSeek 50K GGP Porcine HD chip. To enhance genomic selection accuracy, we proposed strategies that combined multiple populations and leveraged multi‐omics prior information. Cis‐QTL from the PigGTEx database and QTL identified through genome‐wide association studies were incorporated into the genomic feature best linear unbiased prediction (GFBLUP) model to predict the ADG100 and the BF100 traits. Results demonstrated that combining multiple populations effectively improved prediction accuracy for small population, accuracy for ADG100 increased by an average of 0.29 and accuracy for BF100 by 0.05. The GFBLUP model, which integrates biological priors, showed some improvements in prediction accuracy for the BF100 trait. Specifically, for the small population, accuracy increased by 0.09 in Scheme 1, where each population size was predicted independently. In Scheme 3, where the large population was used as a reference group to predict the small population, accuracy increased by 0.03. However, the GFBLUP model did not provide additional benefits in predicting the ADG100 trait. These findings offer effective strategies for genetic improvement in developing regions and highlight the potential of multi‐omics integration to enhance prediction models.
Human T‐cell leukemia virus type 1‐associated myelopathy/tropical spastic paraparesis and multiple sclerosis: Viral strategies and their implications
Authors: Nakashima Makoto , Yamano Yoshihisa 
Published: February 2025

AbstractHuman T‐cell leukemia virus type 1 (HTLV‐1)‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic inflammatory disease of the central nervous system (CNS), particularly affecting the spinal cord, and is caused by HTLV‐1 infection. The biased geographic distribution of HTLV‐1‐infected individuals facilitated the early identification of a causal relationship between HTLV‐1 infection and related diseases soon after the discovery of the virus. In contrast, such a relationship would have been challenging to establish without this geographic clustering. Similarly, Epstein–Barr virus (EBV), which infects ~95% of the global population, has recently been implicated in the pathogenesis of multiple sclerosis (MS), another chronic inflammatory CNS disease. Advances in seroepidemiology, immunology, genomics, and biomarker research in large MS cohorts have shed light on EBV's critical role in disease development. These insights provide a framework for understanding the molecular mechanisms underlying both MS and HAM/TSP, which remain incompletely elucidated. In this review, we compare HTLV‐1 with EBV, focusing on their shared strategies for establishing long‐term latency in the host and their roles in CNS inflammation. By analyzing the relationship between HAM/TSP and MS through virological and molecular biological perspectives, we propose that both conditions may represent chronic inflammatory diseases of the CNS triggered by viral infections. This hypothesis offers a novel perspective on the pathogenesis of these diseases. Finally, we discuss current challenges and future directions in the treatment and prevention of HAM/TSP and MS.
Effects of transcranial direct current stimulation on multiple sclerosis and neuromyelitis optica spectrum disorder: A double‐blind, randomized, crossover trial
Authors: Shibuya Ryoko , Ishikuro Koji , Hattori Noriaki , Takasawa Shuhei , Hirosawa Hiroaki , Yamamoto Mamoru , Konishi Hirofumi , Nakane Shunya , Noguchi Kyo , Nakatsuji Yuji 
Published: February 2025

AbstractObjectivesThere are no effective therapies for nonmotor symptoms of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), including cognitive impairment, fatigue, depression, and pain. Transcranial direct current stimulation (tDCS), a neuromodulatory technique, enhances rehabilitation effects, and has been applied to multiple neurological diseases. We attempted to clarify the effectiveness of tDCS on the nonmotor symptoms of MS/NMOSD.MethodsA double‐blind, randomized cros‐over trial was conducted with five MS/NMOSD patients randomly assigned to active (real) or sham tDCS groups. Patients received 10 sessions of tDCS combined with rehabilitation, with assessments at baseline and poststimulation, A second session under the alternate condition followed. The anodal electrode was placed over M1 (C3 in the 10–20 system), and the cathode over Fp2, delivering 1.0 mA for 900 s. Functional magnetic resonance imaging was conducted before and after stimulation to assess functional connectivity (FC) using region of interest (ROI)‐to‐ROI analysis across six ROIs.ResultsNo adverse events related to tDCS were observed. A significant improvement was observed in working memory and information‐processing ability, as assessed by using the Paced Auditory Serial Addition 2‐s version after active stimulation compared to sham stimulation. In the anterior cingulate cortex‐precuneus FC, significant changes were observed following active stimulation.ConclusionAnodal tDCS over M1 may be a useful means of improving cognitive function in patients with MS/NMOSD and altered FCs beyond M1.
Berberine Alleviates Kainic Acid‐Induced Acute Epileptic Seizures in Mice via Reshaping Gut Microbiota‐Associated Lipid Metabolism
Authors: Dai Wen‐Ting , Zhu Yong , Jiang Zui‐Ming , Xiang Yi , Mao Xiao‐Yuan , Liu Zhao‐Qian 
Published: February 2025

ABSTRACTBackgroundBerberine (BBR) has been reported to mitigate epileptic seizures. However, the potential mechanism of its anti‐seizure effect remains uncharacterized.AimsThis study aimed to investigate the protective effect of BBR on acute epileptic seizures induced by kainic acid (KA) in mice and further explore its mechanism of action in the aspect of analysis of gut microbiota.Materials and MethodsThe protective effect of BBR against acute epileptic seizures was assessed via Racine score and Nissl training. Alterations of gut microbiota and metabolites in seizure mice after BBR treatment were analyzed through 16S sequencing and lipidomics, respectively.ResultsOur results showed that the BBR remarkably alleviated acute epileptic seizures and hippocampal neuron damage in KA‐induced mice. The analysis of gut microbiota indicated that BBR reduced the acute epileptic seizures in KA‐induced mice by increasing the abundance of Bacteroidetes and Alloprevotella, regulating short‐chain fatty acids (SCFAs). Results of lipidomics also identified 21 candidate metabolites in the colon and hippocampus possibly involved in the protective effect of BBR against acute seizures.ConclusionThese findings suggest that BBR exerts neuroprotection against KA‐induced epileptic seizures through remodeling gut microbiota‐associated lipid metabolism in the colon and hippocampus. BBR may serve as a valuable candidate drug for curing patients with epilepsy.
Cui prodest? A firm‐level analysis of hiring credits
Authors: Santoni Edoardo , Patriarca Fabrizio , Scarlato Margherita 
Published: February 2025

ABSTRACTIn the aftermath of the Great Recession, hiring credits have become popular worldwide. The empirical literature shows positive but moderate effects of such interventions on employment. However, an in‐depth analysis of the characteristics of the beneficiary firms and their wage‐setting policies is still lacking. By using a linked employer–employee dataset, this paper presents a firm‐level analysis of a three‐year employer‐borne payroll tax cut for permanent hirings introduced in Italy in 2015. After estimating firm and worker fixed effects through the standard AKM model, we show that the take‐up of hiring credits is significantly higher for firms that pay lower wages, are less productive, employ workers with lower mean abilities, and have a lower retention rate. This result is robust to several specifications and stratifications of the sample, and provides a further and different perspective from which to question the use of active labour market policies based on employer‐borne payroll tax cuts.
Impacts of Recreational Hunting on an Introduced Population of Fallow Deer (Dama dama) in Tasmania, Australia
Authors: Comte Sebastien , Bengsen Andrew J. , Botterill‐James Thomas , Brausch Chris , Bryant Sally L. , Dickson Catherine R. , Hamer Rowena , Hamilton David G. , Seaman James , Taylor Pip , Forsyth David M. 
Published: February 2025

ABSTRACTNon‐native deer populations are increasing in many parts of the world. Recreational hunting has commonly been advocated as a method for reducing deer population densities on private land, but there have been few robust evaluations of its effectiveness. We quantified the impacts of recreational hunting on a population of non‐native fallow deer (Dama dama) on a private conservation reserve in Tasmania, Australia. We used a grid of 64 motion‐sensitive cameras to estimate seasonal deer population density for three consecutive years. Recreational hunters recorded their hunting effort (date and duration of hunts), deer seen, and deer killed, and used a GPS to record where they hunted. Throughout the three‐year period, deer density remained between 3.95 and 4.96 deer per km2, well above the mean 2.7 deer per km2 estimated for Tasmania. The 28 hunters killed a total of 128 deer (33 males, 87 females and 8 unknown) during 306 hunts. The annual harvest comprised 21%–26% of the total deer population (28%–38% of the female population). During the four‐week ‘buck’ season (March), hunters exhibited more selective hunting behaviour characterised by frequent hunts that targeted mostly antlered males with low catch per unit effort (0.03 deer killed per hour). In contrast, the 8‐month antlerless season (March–November) was characterised by a more opportunistic hunting behaviour with fewer hunts and a higher catch per unit effort (0.11 deer killed per hour). Our results show that the current regime of recreational hunting is not reducing the population. If landowners decide to rely on recreational hunting to reduce deer densities on their properties, more deer, especially females, need to be harvested annually. Changes to regulations that increase the number of deer harvested should be considered in parallel with greater incentives for recreational hunters to harvest more females. Other deer control methods, such as helicopter‐based shooting and professional ground‐based shooting, are likely to provide faster and greater reductions in the densities of non‐native deer populations than recreational hunting while non‐lethal management should be considered for local asset protection.
More and Less Fear in Serotonin Transporter Knockout Mice
Authors: Lima João , Panayi Marios C. , Sharp Trevor , McHugh Stephen B. , Bannerman David M. 
Published: February 2025

ABSTRACTRecent theories suggest that reduced serotonin transporter (5‐HTT) function, which increases serotonin (5‐HT) levels at the synapse, enhances neural plasticity and affects sensitivity to environmental cues. This may promote learning about emotionally relevant events. However, the boundaries that define such emotional learning remain to be established. This was investigated using 5‐HTT knockout (5‐HTTKO) mice which provide a model of long‐term elevated 5‐HT transmission and are associated with increased anxiety. Compared to wild‐type controls, 5‐HTTKO mice were faster to discriminate between an auditory cue that predicted footshock (CS+) and a cue predicting no footshock (CS−). Notably, this enhanced discrimination performance was driven not by faster learning that the CS+ predicted footshock, but rather by faster learning that the CS− cue signals the absence of footshock and thus provides temporary relief from fear/anxiety. Similarly, 5‐HTTKO mice were also faster to reduce their fear of the CS+ cue during subsequent extinction. These findings are consistent with facilitated inhibitory learning that predicts the absence of potential threats in 5‐HTTKO mice. However, 5‐HTTKO mice also exhibited increased generalisation of fear learning about ambiguous aversive cues in a novel context, different from the training context. Thus, 5‐HTTKO mice can exhibit both more and less fear compared to wild‐type controls. Taken together, our results support the idea that loss of 5‐HTT function, and corresponding increases in synaptic 5‐HT availability, may facilitate learning by priming of aversive memories. This both facilitates inhibitory learning for fear memories but also enhances generalisation of fear.
How to Make a Rock in 150 Days: Observations of Biofilms Promoting Rapid Beachrock Formation
Authors: Hibner Brianna M. , Cantine Marjorie D. , Trower Elizabeth J. , Dodd Jacqueline E. , Gomes Maya L. 
Published: February 2025

ABSTRACTBeachrock is a type of carbonate‐cemented rock that forms via rapid cementation in the intertidal zone. Beachrock is a valuable geological tool as an indicator of paleoshorelines and may protect shorelines from erosion. Previous studies present a range of hypotheses about the processes enabling rapid beachrock formation, which span purely physicochemical mechanisms to a significant role for microbially mediated carbonate precipitation. We designed a set of in situ field experiments to explore the rates and mechanisms of beachrock formation on Little Ambergris Cay (Turks and Caicos Islands). Our field site has evidence for rapid beachrock cementation, including the incorporation of 20th century anthropogenic detritus into beachrock. We deployed pouches of sterilized ooid sand in the upper intertidal zone and assessed the extent of cementation and biofilm development after durations of 4 days, 2.5 months, and 5 months. We observed incipient meniscus cements after only 4 days of incubation in the field, suggesting that physicochemical processes are important in driving initial cementation. After 2.5 months, we observed substantial biofilm colonization on our experimental substrates, with interwoven networks of Halomicronema filaments binding clusters of ooids to the nylon pouches. After 5 months, we observed incipient beachrock formation in the form of coherent aggregates of ooids up to 1 cm in diameter, bound together by both networks of microbial filaments and incipient cements. We interpret that the cyanobacteria‐dominated beachrock biofilm community on Little Ambergris Cay plays an important role in beachrock formation through the physical stabilization of sediment as cementation proceeds. Together, this combination of physicochemical and microbial mechanisms enables fresh rock to form in as little as 150 days.
Joint and Myofascial Manual Therapy Techniques in Haemophilic Ankle Arthropathy: A Randomized Pilot Study
Authors: Truque‐Díaz Carlos , Meroño‐Gallut Javier , Cuesta‐Barriuso Rubén , Pérez‐Llanes Raúl 
Published: February 2025

ABSTRACTBackgroundHaemophilic ankle arthropathy is characterized by chronic pain, loss of strength and proprioception, decreased range of motion (ROM) and impaired functionality.ObjectiveTo evaluate the safety and efficacy of a manual therapy protocol based on joint and myofascial techniques in patients with haemophilic ankle arthropathy.MethodsA randomized, single‐blind pilot study. Twenty‐four patients with haemophilia were randomized to the experimental (manual therapy) and control (no intervention) groups. The intervention lasted for 3 weeks, with one 50‐min weekly session. Techniques used: active‐passive joint mobilization, articulatory technique, joint decompression and high‐speed and short‐stroke manipulation, and sustained myofascial induction techniques. The study variables were safety of the intervention (number of hemarthroses), joint pain intensity (visual analogue scale), pressure pain threshold (pressure algometer), range of ankle motion (Leg Motion) and joint condition (Haemophilia Joint Health Score).ResultsNone of the patients developed ankle hemarthrosis during the intervention. After the intervention there were intergroup differences in the variables pain intensity (MD = −0.45; p < 0.001), ROM (MD = 0.19; p = 0.003), joint condition (MD = 0.04; p = 0.03) and pressure pain threshold in the internal malleolus (MD = 1.36; p = 0.01). For the interaction time*group after the follow‐up period, there were statistically significant differences in pain intensity (F = 6.94; p = 0.01) and dorsal flexion (F = 3.36; p = 0.04) of the ankle.ConclusionsManual therapy based on joint and myofascial techniques is safe in haemophilia patients. A protocol implementing joint and myofascial techniques having the dosage and safety parameters established in this study can improve the intensity of pain and dorsal flexion of the ankle in these patients.Trial RegistrationClinicalTrials.gov identifier: NCT05549843
Editor's Highlights—March 2025
Authors: Kemény Lajos 
Published: February 2025

ABSTRACTManaging chronic inflammatory skin diseases such as hidradenitis suppurativa (HS) and psoriasis extends beyond clinical measures; it should also consider patient‐reported outcomes, treatment burden, and overall satisfaction. Successful therapy in both conditions is influenced by factors such as residual disease activity, the psychological profiles of patients, and the availability of new treatment options. The coexistence of psoriasis and atopic dermatitis can pose significant diagnostic and therapeutic challenges. In such rare cases, Janus kinase inhibitors may be considered a treatment option instead of biologics.
Update on chronic pain management
Authors: Glare Paul , Mahendran Melani , Weiss Andrew D. 
Published: February 2025

AbstractPain is a common presenting symptom to consultant physicians, both in the hospital and in the clinic or rooms. Biologically, pain serves as warning of tissue damage. But this is no longer the case when pain is present for months or years, especially when it has been fully investigated. There can be a substantial discrepancy between the magnitude of pain, disability and distress reported by a patient with chronic pain and the extent of tissue damage identified. From the 1990s until the mid‐2010s, opioids were promoted as a safe and effective panacea for chronic non‐cancer pain. This led to overprescribing with unfortunate consequences of misuse, abuse and overdose deaths. The response to the so‐called ‘opioid epidemic’ has led to a renewed focus on how chronic pain should be managed. The aim of this article is to update fellows and trainees on the assessment and management of chronic pain in adult medical patients. In particular, we address the role of pharmacotherapy post‐opioid epidemic (primarily antidepressants and anticonvulsants in neuropathic pain), the place of interventional procedures and the nature and effectiveness of pain self‐management training in people with chronic pain, many of whom have had pain for a year or more and failed other treatments.
The Response of Patients' Immune System After Facial Mesotherapy
Authors: Bobowska‐Guglas Olga , Chalcarz Michał , Oskar Grabarek Beniamin , Sirek Tomasz , Żurawski Jakub 
Published: February 2025

ABSTRACTBackgroundFacial mesotherapy is a minimally invasive cosmetic procedure involving the injection of active substances into the dermis and subcutaneous tissue. Although generally considered safe, complications such as granulomatous inflammation can arise due to improper techniques or unregulated products. This case report highlights the immune response to facial mesotherapy and its clinical management.Materials and MethodsA 50‐year‐old woman presented with erythematous, hard, and painless facial nodules three weeks after undergoing mesotherapy in a non‐medical setting. A detailed clinical examination, laboratory tests, histopathological analysis, and immunohistochemical evaluation were performed. Tissue expression of CD3, CD20, and CD68 markers was quantified using morphometric analysis. Statistical analysis was conducted to compare the expression of immune markers.ResultsHistopathological examination revealed granulomatous inflammation dominated by macrophages. Immunohistochemical analysis showed significantly higher macrophage activity (CD68, mean reaction area: 5,982.76 µm2) compared to T lymphocytes (CD3, 1,775.12 µm2) and B lymphocytes (CD20, 187.55 µm2) (p < 0.001). Initial treatment included antibiotics, corticosteroids, and topical therapies. Subsequent interventions involved intralesional triamcinolone, oral glucocorticoids, and platelet‐rich plasma therapy. Significant clinical improvement was observed within three months, with satisfactory cosmetic outcomes achieved after one year.ConclusionGranulomatous inflammation is a potential complication of facial mesotherapy, particularly when performed in non‐medical settings. Effective management requires timely diagnosis, a combination of systemic and topical treatments, and long‐term follow‐up. This case underscores the need for standardized mesotherapy protocols and medical oversight to minimize risks.