bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcranial direct current stimulation to the left dorsolateral prefrontal cortex enhances early dexterity skills with the left non-dominant hand: a randomized controlled trial
Authors: Watanabe Akihiro , Sawamura Daisuke , Nakazono Hisato , Tokikuni Yukina , Miura Hiroshi , Sugawara Kazuhiro , Fuyama Kanako , Tohyama Harukazu , Yoshida Susumu , Sakai Shinya 
Published: February 2023

Abstract
Background
The left dorsolateral prefrontal cortex (DLPFC) is involved in early-phase manual dexterity skill acquisition when cognitive control processes, such as integration and complexity demands, are required. However, the effectiveness of left DLPFC transcranial direct current stimulation (tDCS) on early-phase motor learning and whether its effectiveness depends on the cognitive demand of the target task are unclear. This study aimed to investigate whether tDCS over the left DLPFC improves non-dominant hand dexterity performance and determine if its efficacy depends on the cognitive demand of the target task.

Methods
In this randomized, double-blind, sham-controlled trial, 70 healthy, right-handed, young adult participants were recruited. They were randomly allocated to the active tDCS (2 mA for 20 min) or sham groups and repeatedly performed the Purdue Pegboard Test (PPT) left-handed peg task and left-handed assembly task three times: pre-tDCS, during tDCS, and post tDCS.

Results
The final sample comprised 66 healthy young adults (mean age, 22.73 ± 1.57 years). There were significant interactions between group and time in both PPT tasks, indicating significantly higher performance of those in the active tDCS group than those in the sham group post tDCS (p < 0.001). Moreover, a greater benefit was observed in the left-handed assembly task performance than in the peg task performance (p < 0.001). No significant correlation between baseline performance and benefits from tDCS was observed in either task.

Conclusions
These results demonstrated that prefrontal tDCS significantly improved early-phase manual dexterity skill acquisition, and its benefits were greater for the task with high cognitive demands. These findings contribute to a deeper understanding of the underlying neurophysiological mechanisms of the left DLPFC in the modulation of early-phase dexterity skill acquisition.
Trial registration: This study was registered in the University Hospital Medical Information Network Clinical Trial Registry in Japan (UMIN000046868), Registered February 8, 2022 https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000053467
Matrine alleviates depressive-like behaviors via modulating microbiota–gut–brain axis in CUMS-induced mice
Authors: Zhang Ming , Li Aoqiang , Yang Qifang , Li Jingyi , Zheng Lihua , Wang Guannan , Sun Ying , Huang Yanxin , Zhang Muqing , Song Zhenbo , Liu Lei 
Published: February 2023

Abstract
Background
The realization of the “microbiota–gut–brain” axis plays a critical role in neuropsychiatric disorders, particularly depression, is advancing rapidly. Matrine is a natural bioactive compound, which has been found to possess potential antidepressant effect. However, the underlying mechanisms of regulation of the “microbiota–gut–brain” axis in the treatment of depression by oral matrine remain elusive.

Methods
Its antidepressant effects were initially evaluated by behavioral tests and relative levels of monoamine neurotransmitters, and matrine has been observed to attenuate the depression-like behavior and increase neurotransmitter content in CUMS-induced mice. Subsequently, studies from the “gut” to “brain” were conducted, including detection of the composition of gut microbiota by 16S rRNA sequencing; the metabolomics detection of gut metabolites and the analysis of differential metabolic pathways; the assessment of relative levels of diamine oxidase, lipopolysaccharide, pro-inflammatory cytokines, and brain-derived neurotrophic factor (BDNF) by ELISA kits or immunofluorescence.

Results
Matrine could regulate the disturbance of gut microbiota and metabolites, restore intestinal permeability, and reduce intestinal inflammation, thereby reducing the levels of pro-inflammatory cytokines in peripheral blood circulation and brain regions, and ultimately increase the levels of BDNF in brain.

Conclusion
Matrine may ameliorate CUMS-induced depression in mice by modulating the “microbiota–gut–brain” axis.
Identification of MET fusions as novel therapeutic targets sensitive to MET inhibitors in lung cancer
Authors: Sun Dantong , Wu Weizheng , Wang Li , Qu Jialin , Han Qiman , Wang Huiyun , Song Shanai , Liu Ning , Wang Yongjie , Hou Helei 
Published: February 2023

Abstract
Introduction
Alterations in the MET gene, including amplifications and exon 14 skipping mutations, have been identified as actionable oncogenic alterations. However, MET fusions are rarely detected in lung cancer, and their sensitivity to therapeutics has not been systematically analyzed.

Methods
The data from 30876 lung cancer patients from the LAVA database and 7966 patients from cBioPortal database were screened. Basic demographic and clinical information for the patients harboring MET fusions were collected. A lung squamous cell cancer patient harboring a novel EML4-MET fusion was treated with crizotinib. Additionally, a literature review was performed to summarize the cases of patients harboring MET fusions and their treatment information.

Results
MET fusions were found in only 0.2% to 0.3% of lung cancer patients and appeared in almost all exons of the MET gene. Intragenic MET fusions were found in 52.6% (41/78) of the included patients. Crizotinib was effective for MET fusions, including a novel identified EML4-MET fusion, even after the failure of multiple lines of treatment. This result suggested that acquired MET fusions become more regionally selective, as they usually occurred in exons encoding the extracellular region. Interestingly, the MET-fused genes in primary MET fusions or acquired MET fusions were very different, which indicated the different functions and influences of the disease.

Conclusion
MET fusions are rare, and half of the fusion types were intragenic fusions. Lung cancer patients harboring primary or acquired MET fusions could benefit from crizotinib. In addition, EML4-MET was first reported in this study as a novel MET fusion type.
Concerted phenotypic flexibility of avian erythrocyte size and number in response to dietary anthocyanin supplementation
Authors: Dzialo Maciej , Bryła Amadeusz , DeMoranville Kristen J. , Carbeck Katherine M. , Fatica Olivia , Trost Lisa , Pierce Barbara , Sadowska Edyta T. , McWilliams Scott R. , Bauchinger Ulf 
Published: February 2023

Abstract
Background
Endurance flight impose substantial oxidative costs on the avian oxygen delivery system. In particular, the accumulation of irreversible damage in red blood cells can reduce the capacity of blood to transport oxygen and limit aerobic performance. Many songbirds consume large amounts of anthocyanin-rich fruit, which is hypothesized to reduce oxidative costs, enhance post-flight regeneration, and enable greater aerobic capacity. While their antioxidant benefits appear most straightforward, the effects of anthocyanins on blood composition remain so far unknown. We fed thirty hand-raised European starlings (Sturnus vulgaris) two semisynthetic diets (with or without anthocyanin supplement) and manipulated the extent of flight activity in a wind tunnel (daily flying or non-flying for over two weeks) to test for their interactive effects on functionally important haematological variables.

Results
Supplemented birds had on average 15% more and 4% smaller red blood cells compared to non-supplemented individuals and these diet effects were independent of flight manipulation. Haemoglobin content was 7% higher in non-supplemented flying birds compared to non-flying birds, while similar haemoglobin content was observed among supplemented birds that were flown or not. Neither diet nor flight activity influenced haematocrit.

Conclusion
The concerted adjustments suggest that supplementation generally improved antioxidant protection in blood, which could prevent the excess removal of cells from the bloodstream and may have several implications on the oxygen delivery system, including improved gas exchange and blood flow. The flexible haematological response to dietary anthocyanins may also suggest that free-ranging species preferentially consume anthocyanin-rich fruits for their natural blood doping, oxygen delivery-enhancement effects.
Translating knowledge into action for child obesity treatment in partnership with Parks and Recreation: study protocol for a hybrid type II trial
Authors: Neshteruk Cody D. , Skinner Asheley C. , Counts Julie , D’Agostino Emily M. , Frerichs Leah , Howard Janna , Story Mary , Armstrong Sarah C. 
Published: February 2023

Abstract
Background
Safe and effective treatment exists for childhood obesity, but treatment recommendations have largely not been translated into practice, particularly among racial and ethnic minorities and low-wealth populations. A key gap is meeting the recommended treatment of ≥26 h of lifestyle modification over 6–12 months. Fit Together is an effective treatment model that meets these recommendations by integrating healthcare and community resources. Pediatric providers screen children for obesity, deliver counseling, and treat co-morbidities, while Parks and Recreation partners provide recreation space for a community nutrition and physical activity program.

Methods
This study will use a hybrid type II implementation-effectiveness design to evaluate the effectiveness of an online implementation platform (the Playbook) for delivering Fit Together. Clinical and community partners in two North Carolina communities will implement Fit Together, using the Playbook, an implementation package designed to facilitate new partnerships, guide training activities, and provide curricular materials needed to implement Fit Together. An interrupted time series design anchored in the Process Redesign Framework will be used to evaluate implementation and effectiveness outcomes in intervention sites. Implementation measures include semi-structured interviews with partners, before and after the implementation of Fit Together, and quantitative measures assessing several constructs within the Process Redesign Framework. The participants will be children 6–11 years old with obesity and their families (n=400). Effectiveness outcomes include a change in child body mass index and physical activity from baseline to 6 and 12 months, as compared with children receiving usual care. Findings will be used to inform the design of a dissemination strategy guided by the PCORI Dissemination Framework.

Discussion
This project addresses the knowledge-to-action gap by developing evidence-based implementation tools that allow clinicians and communities to deliver effective pediatric obesity treatment recommendations. Future dissemination of these tools will allow more children who have obesity and their families to have access to effective, evidence-based care in diverse communities.

Trial registration
ClinicalTrials.gov identifier: NCT05455190. Registered on 13 July 2022
Cutaneous protothecosis in a dog successfully treated with oral itraconazole in pulse dosing
Authors: Gmyterco Vanessa Cunningham , Jagielski Tomasz , Baldasso Gustavo , Bacher Louise Helene , Ribeiro Márcio Garcia , de Farias Marconi Rodrigues 
Published: February 2023

Abstract
Background
Protothecosis is a rare infectious disease caused by unicellular, achlorophyllous, microalgae of the genus Prototheca, ubiquitously distributed in nature. The algae are emerging pathogens, whose incidence is increasing in both human and animal populations and serious systemic infections related to this pathogen have been increasingly described in humans in recent years. After mastitis in dairy cows, canine protothecosis is the second most prevalent form of the protothecal disease in animals. Here, we report the first case of chronic cutaneous protothecosis due to P. wickerhamii in a dog in Brazil, successfully treated with a long-term therapy with itraconazole in pulse.

Case presentation
Upon clinical examination, exudative nasolabial plaque, ulcered, and painful lesions in central and digital pads and lymphadenitis were observed in a 2-year-old mixed-breed dog, with a 4-month history of cutaneous lesions and contact with sewage water. Histopathological examination revealed intense inflammatory reaction, with numerous spherical to oval, encapsulated structures stained with Periodic Acid Schiff, compatible with Prototheca morphology. Tissue culture on Sabouraud agar revealed yeast-like, greyish-white colonies after 48 h of incubation. The isolate was subjected to mass spectrometry profiling and PCR-sequencing of the mitochondrial cytochrome b (CYTB) gene marker, leading to identification of the pathogen as P. wickerhamii. The dog was initially treated with oral itraconazole at a dosage of 10 mg/kg once daily. After six months, the lesions resolved completely, yet recurred shortly after cessation of therapy. The dog was then treated with terbinafine at a dose of 30 mg/kg, once daily for 3 months, with no success. The resolution of clinical signs, with no recurrence over a 36-months follow-up period, was achieved after 3 months of treatment with itraconazole (20 mg/kg) in pulse intermittently on two consecutive days a week.

Conclusions
This report highlights the refractoriness of skin infections by Prototheca wickerhamii with therapies proposed in the literature and suggests a new treatment option with oral itraconazole in pulse dosing for long-term disease control successfully performed in a dog with skin lesions.
Fluid balance control in critically ill patients: results from POINCARE-2 stepped wedge cluster-randomized trial
Authors: Bollaert Pierre-Edouard , Monnier Alexandra , Schneider Francis , Argaud Laurent , Badie Julio , Charpentier Claire , Meziani Ferhat , Bemer Michel , Quenot Jean-Pierre , Buzzi Marie , Outin Hervé , Bruel Cédric , Ziegler Laurent , Gibot Sébastien , Virion Jean-Marc , Alleyrat Camille , Louis Guillaume , Agrinier Nelly 
Published: February 2023

Abstract
Background
In critically ill patients, positive fluid balance is associated with excessive mortality. The POINCARE-2 trial aimed to assess the effectiveness of a fluid balance control strategy on mortality in critically ill patients.

Methods
POINCARE-2 was a stepped wedge cluster open-label randomized controlled trial. We recruited critically ill patients in twelve volunteering intensive care units from nine French hospitals. Eligible patients were ≥ 18 years old, under mechanical ventilation, admitted to one of the 12 recruiting units for > 48 and ≤ 72 h, and had an expected length of stay after inclusion > 24 h. Recruitment started on May 2016 and ended on May 2019. Of 10,272 patients screened, 1361 met the inclusion criteria and 1353 completed follow-up. The POINCARE-2 strategy consisted of a daily weight-driven restriction of fluid intake, diuretics administration, and ultrafiltration in case of renal replacement therapy between Day 2 and Day 14 after admission. The primary outcome was 60-day all-cause mortality. We considered intention-to-treat analyses in cluster-randomized analyses (CRA) and in randomized before-and-after analyses (RBAA).

Results
A total of 433 (643) patients in the strategy group and 472 (718) in the control group were included in the CRA (RBAA). In the CRA, mean (SD) age was 63.7 (14.1) versus 65.7 (14.3) years, and mean (SD) weight at admission was 78.5 (20.0) versus 79.4 (23.5) kg. A total of 129 (160) patients died in the strategy (control) group. Sixty-day mortality did not differ between groups [30.5%, 95% confidence interval (CI) 26.2–34.8 vs. 33.9%, 95% CI 29.6–38.2, p = 0.26]. Among safety outcomes, only hypernatremia was more frequent in the strategy group (5.3% vs. 2.3%, p = 0.01). The RBAA led to similar results.

Conclusion
The POINCARE-2 conservative strategy did not reduce mortality in critically ill patients. However, due to open-label and stepped wedge design, intention-to-treat analyses might not reflect actual exposure to this strategy, and further analyses might be required before completely discarding it.
Trial registration POINCARE-2 trial was registered at ClinicalTrials.gov (NCT02765009). Registered 29 April 2016.
DIMPLE: deep insertion, deletion, and missense mutation libraries for exploring protein variation in evolution, disease, and biology
Authors: Macdonald Christian B. , Nedrud David , Grimes Patrick Rockefeller , Trinidad Donovan , Fraser James S. , Coyote-Maestas Willow 
Published: February 2023

AbstractInsertions and deletions (indels) enable evolution and cause disease. Due to technical challenges, indels are left out of most mutational scans, limiting our understanding of them in disease, biology, and evolution. We develop a low cost and bias method, DIMPLE, for systematically generating deletions, insertions, and missense mutations in genes, which we test on a range of targets, including Kir2.1. We use DIMPLE to study how indels impact potassium channel structure, disease, and evolution. We find deletions are most disruptive overall, beta sheets are most sensitive to indels, and flexible loops are sensitive to deletions yet tolerate insertions.
Efficacy and auditory biomarker analysis of fronto-temporal transcranial direct current stimulation (tDCS) in targeting cognitive impairment associated with recent-onset schizophrenia: study protocol for a multicenter randomized double-blind sham-controlled trial
Authors: Dondé Clément , Bastin Julien , Pouchon Arnaud , Costes Nicolas , Fakra Eric , Galvão Filipe , Gay Aurélia , Haesebaert Frédéric , Lamalle Laurent , Mérida Inès , Rigon Maxence , Schneider Fabien , Troprès Irène , Brunelin Jérôme , Polosan Mircea 
Published: February 2023

Abstract
Background
In parallel to the traditional symptomatology, deficits in cognition (memory, attention, reasoning, social functioning) contribute significantly to disability and suffering in individuals with schizophrenia. Cognitive deficits have been closely linked to alterations in early auditory processes (EAP) that occur in auditory cortical areas. Preliminary evidence indicates that cognitive deficits in schizophrenia can be improved with a reliable and safe non-invasive brain stimulation technique called tDCS (transcranial direct current stimulation). However, a significant proportion of patients derive no cognitive benefits after tDCS treatment. Furthermore, the neurobiological mechanisms of cognitive changes after tDCS have been poorly explored in trials and are thus still unclear.

Method
The study is designed as a randomized, double-blind, 2-arm parallel-group, sham-controlled, multicenter trial. Sixty participants with recent-onset schizophrenia and cognitive impairment will be randomly allocated to receive either active (n=30) or sham (n=30) tDCS (20-min, 2-mA, 10 sessions during 5 consecutive weekdays). The anode will be placed over the left dorsolateral prefrontal cortex and the cathode over the left auditory cortex. Cognition, tolerance, symptoms, general outcome and EAP (measured with EEG and multimodal MRI) will be assessed prior to tDCS (baseline), after the 10 sessions, and at 1- and 3-month follow-up. The primary outcome will be the number of responders, defined as participants demonstrating a cognitive improvement ≥Z=0.5 from baseline on the MATRICS Consensus Cognitive Battery total score at 1-month follow-up. Additionally, we will measure how differences in EAP modulate individual cognitive benefits from active tDCS and whether there are changes in EAP measures in responders after active tDCS.

Discussion
Besides proposing a new fronto-temporal tDCS protocol by targeting the auditory cortical areas, we aim to conduct a randomized controlled trial (RCT) with follow-up assessments up to 3 months. In addition, this study will allow identifying and assessing the value of a wide range of neurobiological EAP measures for predicting and explaining cognitive deficit improvement after tDCS. The results of this trial will constitute a step toward the use of tDCS as a therapeutic tool for the treatment of cognitive impairment in recent-onset schizophrenia.

Trial registration
ClinicalTrials.gov NCT05440955. Prospectively registered on July 1st, 2022.
Monoclonal antibody infusion reaction with bamlanivimab and etesevimab in a 5-year-old male with coronavirus disease 2019: a case report
Authors: Pillai Rajapillai L. I. , Dziel Caroline , Vogel Stephanie , Szczerba Frank , Chang Weijen W. , Camelo Ingrid Y. , Paez Armando 
Published: February 2023

Abstract
Background
Bamlanivimab and etesevimab had been granted emergency use authorization in children under 12 years who are at risk of progression from mild/moderate coronavirus disease 2019 to severe disease and hospitalization.

Case report
We report on a 5-year-old white male with preexisting conditions, predisposing him to severe disease, who developed hypoxia and flushing 3 minutes into his infusion, thus meeting the criteria for anaphylaxis.

Conclusions
We believe this patient developed either an immunoglobulin E-mediated anaphylactic or a non-immunoglobulin E-mediated anaphylactoid reaction to bamlanivimab and etesevimab, which is an important possibility to consider on administration.
Interventions to improve the detection of depression in primary healthcare: systematic review
Authors: Habtamu Kassahun , Birhane Rahel , Demissie Mekdes , Fekadu Abebaw 
Published: February 2023

Abstract
Background
Several studies have been conducted on the effect of interventions on the detection of depression in primary healthcare (PHC). Systematic reviews have also been done on the effectiveness of separate interventions. However, systematic reviews are not done on the comparative effectiveness of several interventions. This study, therefore, aimed at synthesizing the global evidence on the effectiveness of interventions to improve the detection of depression in PHC.

Methods
We searched PubMed, Embase, PsycINFO, Web of Science, Cochrane Database of Systematic Reviews, Global Index Medicus, African Index Medicus, and African Journals Online, from the inception of the databases to until the 4th week of April 2020. We also searched references of the included articles. We included randomized trials, cluster randomized trials, or quasi-experimental studies, which evaluated the effectiveness of an intervention to improve detection of depression in the PHC setting. Two of the review authors independently extracted data from the included studies. The methodological quality of the included studies was assessed using the Assessment Tool for Quantitative Studies developed by the Effective Public Health Practice Project. The protocol for the review was registered on PROSPERO (CRD42020166291).

Results
Of 23,305 records identified, we included 58 articles in the review. Diverse types of interventions were evaluated to improve clinician diagnosis of depression in the PHC setting. Interventions related to implementation of guidelines, screening with feedback, educational interventions which incorporated active learning and clinical practice, and disclosure of screening results were found to be mostly effective. Interventions which combined education, screening, and feedback were particularly more effective. Most of the included studies were weak or moderate in their methodological quality.

Conclusions
Our review indicates that implementation of a single type of intervention does not improve the detection of depression in PHC. Combining aspects of each type of intervention which are more effective may be useful. Education and training interventions which include more simulation and role playing are found to be effective over time. Most of the studies conducted in the area are from high-income countries and are weak in their methodological quality. There is need to conduct more number of studies in low-income settings.