bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of β-cell death by ADP-ribosylhydrolase ARH3 via lipid signaling in insulitis
Authors: Sarkar Soumyadeep , Deiter Cailin , Kyle Jennifer E. , Guney Michelle A. , Sarbaugh Dylan , Yin Ruichuan , Li Xiangtang , Cui Yi , Ramos-Rodriguez Mireia , Nicora Carrie D. , Syed Farooq , Juan-Mateu Jonas , Muralidharan Charanya , Pasquali Lorenzo , Evans-Molina Carmella , Eizirik Decio L. , Webb-Robertson Bobbie-Jo M. , Burnum-Johnson Kristin , Orr Galya , Laskin Julia , Metz Thomas O. , Mirmira Raghavendra G. , Sussel Lori , Ansong Charles , Nakayasu Ernesto S. 
Published: February 2024

Abstract
Background
Lipids are regulators of insulitis and β-cell death in type 1 diabetes development, but the underlying mechanisms are poorly understood. Here, we investigated how the islet lipid composition and downstream signaling regulate β-cell death.

Methods
We performed lipidomics using three models of insulitis: human islets and EndoC-βH1 β cells treated with the pro-inflammatory cytokines interlukine-1β and interferon-γ, and islets from pre-diabetic non-obese mice. We also performed mass spectrometry and fluorescence imaging to determine the localization of lipids and enzyme in islets. RNAi, apoptotic assay, and qPCR were performed to determine the role of a specific factor in lipid-mediated cytokine signaling.

Results
Across all three models, lipidomic analyses showed a consistent increase of lysophosphatidylcholine species and phosphatidylcholines with polyunsaturated fatty acids and a reduction of triacylglycerol species. Imaging assays showed that phosphatidylcholines with polyunsaturated fatty acids and their hydrolyzing enzyme phospholipase PLA2G6 are enriched in islets. In downstream signaling, omega-3 fatty acids reduce cytokine-induced β-cell death by improving the expression of ADP-ribosylhydrolase ARH3. The mechanism involves omega-3 fatty acid-mediated reduction of the histone methylation polycomb complex PRC2 component Suz12, upregulating the expression of Arh3, which in turn decreases cell apoptosis.

Conclusions
Our data provide insights into the change of lipidomics landscape in β cells during insulitis and identify a protective mechanism by omega-3 fatty acids.
Dimethyl fumarate improves cognitive impairment and neuroinflammation in mice with Alzheimer’s disease
Authors: Wang Ting , Sobue Akira , Watanabe Seiji , Komine Okiru , Saido Takaomi C. , Saito Takashi , Yamanaka Koji 
Published: February 2024

Abstract
Background
Neuroinflammation substantially contributes to the pathology of Alzheimer’s disease (AD), the most common form of dementia. Studies have reported that nuclear factor erythroid 2-related factor 2 (Nrf2) attenuates neuroinflammation in the mouse models of neurodegenerative diseases, however, the detailed mechanism remains unclear.

Methods
The effects of dimethyl fumarate (DMF), a clinically used drug to activate the Nrf2 pathway, on neuroinflammation were analyzed in primary astrocytes and AppNL−G−F (App-KI) mice. The cognitive function and behavior of DMF-administrated App-KI mice were evaluated. For the gene expression analysis, microglia and astrocytes were directly isolated from the mouse cerebral cortex by magnetic-activated cell sorting, followed by quantitative PCR.

Results
DMF treatment activated some Nrf2 target genes and inhibited the expression of proinflammatory markers in primary astrocytes. Moreover, chronic oral administration of DMF attenuated neuroinflammation, particularly in astrocytes, and reversed cognitive dysfunction presumably by activating the Nrf2-dependent pathway in App-KI mice. Furthermore, DMF administration inhibited the expression of STAT3/C3 and C3 receptor in astrocytes and microglia isolated from App-KI mice, respectively, suggesting that the astrocyte–microglia crosstalk is involved in neuroinflammation in mice with AD.

Conclusion
The activation of astrocytic Nrf2 signaling confers neuroprotection in mice with AD by controlling neuroinflammation, particularly by regulating astrocytic C3-STAT3 signaling. Furthermore, our study has implications for the repositioning of DMF as a drug for AD treatment.
A systematic review on the birth prevalence of metachromatic leukodystrophy
Authors: Chang Shun-Chiao , Bergamasco Aurore , Bonnin Mélanie , Bisonó Teigna Arredondo , Moride Yola 
Published: February 2024

Abstract
Background
Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease caused by deficiency in arylsulfatase A (ASA) activity arising primarily from ASA gene (ARSA) variants. Late-infantile, juvenile and adult clinical subtypes are defined by symptom onset at ≤ 2.5, > 2.5 to < 16 and ≥ 16 years, respectively. Epidemiological data were sought to address knowledge gaps and to inform decisions regarding the clinical development of an investigational drug.

Methods
To synthesize all available estimates of MLD incidence and birth prevalence worldwide and in selected countries, Ovid MEDLINE and Embase were searched systematically (March 11, 2022) using a population, intervention, comparator, outcome, time and setting framework, complemented by pragmatic searching to reduce publication bias. Where possible, results were stratified by clinical subtype. Data were extracted from non-interventional studies (clinical trials, non-clinical studies and case reports were excluded; reviews were used for snowballing only).

Results
Of the 31 studies included, 14 reported birth prevalence (13 countries in Asia–Pacific, Europe, the Middle East, North America and South America), one reported prevalence and none reported incidence. Birth prevalence per 100,000 live births ranged from 0.16 (Japan) to 1.85 (Portugal). In the three European studies with estimates stratified by clinical subtypes, birth prevalence was highest for late-infantile cases (0.31–1.12 per 100,000 live births). The distribution of clinical subtypes reported in cases diagnosed over various time periods in 17 studies varied substantially, but late-infantile and juvenile MLD accounted for at least two-thirds of cases in most studies.

Conclusions
This review provides a foundation for further analysis of the regional epidemiology of MLD. Data gaps indicate the need for better global coverage, increased use of epidemiological measures (e.g. prevalence estimates) and more stratification of outcomes by clinical and genetic disease subtype.
To allow or avoid pain during shoulder rehabilitation exercises for patients with chronic rotator cuff tendinopathy-Study protocol for a randomized controlled trial (the PASE trial)
Authors: Kjær Birgitte Hougs , Cools Ann M. , Johannsen Finn E. , Trøstrup Jeanette , Bieler Theresa , Siersma Volkert , Magnusson Peter S. 
Published: February 2024

AbstractBackgroundRotator cuff (RC) tendinopathy is the most reported shoulder disorder in the general population with highest prevalence in overhead athletes and adult working-age population. A growing body of evidence support exercise therapy as an effective intervention, but to date there are no prospective randomized controlled trials addressing pain as an intervention variable.MethodsA single-site, prospective, pragmatic, assessor-blinded randomized controlled superiority trial. Eighty-four patients aged 18–55 years with chronic (symptom duration over 3 months) RC tendinopathy are randomized 1:1 to receive shoulder exercise during which pain is either allowed or avoided. The intervention period lasts 26 weeks. During that period, participants in both groups are offered 8 individual on-site sessions with an assigned sports physiotherapist. Participants perform home exercises and are provided with a pain and exercise logbook and asked to report completed home-based exercise sessions and reasons for not completing sessions (pain or other reasons). Patients are also asked to report load and the number of sets and repetitions per sets for each exercise session. The logbooks are collected continuously throughout the intervention period. The primary and secondary outcomes are obtained at baseline, 6 weeks, 26 weeks, and 1 year after baseline. The primary outcome is patient-reported pain and disability using the Shoulder PAin and Disability Index (SPADI). Secondary outcomes are patient-reported pain and disability using Disability Arm Shoulder and Hand short-form (Quick DASH), and shoulder pain using Numeric Pain Rating Scale. Objective outcomes are shoulder range of motion, isometric shoulder muscle strength, pain sensitivity, working ability, and structural changes in the supraspinatus tendon and muscle using ultrasound.DiscussionThe results of this study will contribute knowledge about the treatment strategies for patients with RC tendinopathy and help physiotherapists in clinical decision-making. This is the first randomized controlled trial comparing the effects of allowing pain versus avoiding pain during shoulder exercises in patients with chronic RC tendinopathy. If tolerating pain during and after exercise proves to be effective, it will potentially expand our understanding of “exercising into pain” for this patient group, as there is currently no consensus.Trial registrationClinicalTrials.gov NCT05124769. Registered on August 11, 2021.
Investigating the added effects of guidance in digital psychological self-care for alcohol problems (ALVA)—protocol for a randomized factorial optimization trial
Authors: Sundström Christopher , Ivanova Ekaterina , Lindner Philip , Johansson Magnus , Kraepelien Martin 
Published: February 2024

Abstract
Background
The continual development and implementation of effective digital interventions is one important strategy that may serve to bridge the well-known treatment gap related to problematic alcohol use. Research suggests that clinician guidance, provided in different ways during the digital intervention (i.e., written weekly messages, phone calls etc.), can boost intervention engagement and effects. Digital psychological self-care (DPSC) is a new delivery format wherein an unguided digital intervention is provided within the framework of a structured care process that includes initial clinical assessment and follow-up interviews. In a recent feasibility study, a DPSC intervention for problematic alcohol use, ALVA, provided without any extra guidance, was found safe and credible and to have promising within-group effects on alcohol consumption. The aim of the current study is to gather information on the effects and efficiency of different forms of guidance added to ALVA, in order to optimize the intervention.

Methods
This protocol describes a randomized factorial trial where the effects of two different ways of providing guidance (mid-treatment interview, weekly written messages, respectively) in DPSC for problematic alcohol use are investigated. Optimization criteria will be applied to the results regarding how effective the intervention is at reducing alcohol consumption measured by the number of standard drinks per week together with the clinician time spent on guidance.

Discussion
This study will investigate the added benefit of different forms of guidance to DPSC for problematic alcohol use. These added effects will be compared to the added cost of guidance, according to pre-defined optimization criteria.

Trial registration
Clinicaltrials.gov: NCT05649982. Registered on 06 December 2022. Prospectively registered.
Low CO2 concentration, a key environmental factor for developing plateau adapted rapeseed
Authors: Liu Sha , Tang Lin , Fu Jingyan , Zhao Caixia , Zhang Ying , Yin Meng , Wang Maolin , Wang Rui , Zhao Yun 
Published: February 2024

Abstract
Background
Photosynthesis is a fundamental process that underlies the formation of crop yield, wherein light serves as the driving force and carbon dioxide (CO2) as the raw material. These two factors have a direct influence on the progress and efficiency of photosynthesis in crops. Rapeseed is one of the four major oilseed crops worldwide. Plateau rapeseed has now become a research hotspot. However, the lack of high-yielding rapeseed germplasm resources on the plateau and the highly efficient strategy for screening them severely affect the development of rapeseed industry in plateau.

Results
In the rapeseed experimental fields located on the plateau (Lhasa, Tibet), we measured abundant sunlight, characterized by an average daily photosynthetically active radiation (PAR) of 1413 μmol m−2 s−1. In addition, the atmospheric CO2 concentrations range from 300 to 400 ppm, which is only two-thirds of that in the plain (Chengdu, Sichuan). We found that under different measurement conditions of light intensity and CO2 concentration, different rapeseed genotypes showed significant differences in leaf photosynthetic efficiency during the seedling stage. Moreover, the rapeseed materials with high photosynthetic efficiency under low CO2 concentrations rather than high light intensity, exhibited significant advantages in biomass, yield, and oil content when cultivated on the plateau, indicating that the CO2 is the key environmental factor which limited rapeseed production in plateau. Based on photosynthetic efficiency screening under low CO2 concentrations, six rapeseed varieties SC3, SC10, SC25, SC27, SC29 and SC37, shown significantly higher yields in plateau environment compared to local control variety were obtained. In addition, the adaptability of rapeseed to plateau was found to be related to the activities of key Calvin cycle enzymes and the accumulation of photosynthetic products.

Conclusions
This study established a screening strategy for plateau high-yielding rapeseed materials, obtained six varieties which were suitable for plateau cultivation, explored the mechanism of rapeseed response to the plateau environment, and thus provides a feasible strategy for plateau-adapted rapeseed breeding.
Evaluation of point-of-care ultrasound training among healthcare providers: a pilot study
Authors: Al-Absi Dima Tareq , Simsekler Mecit Can Emre , Omar Mohammed Atif , Soliman-Aboumarie Hatem , Abou Khater Noha , Mehmood Tahir , Anwar Siddiq , Kashiwagi Deanne Tomie 
Published: February 2024

Abstract
Background
The use of Point-of-Care Ultrasound (POCUS) has become prevalent across a variety of clinical settings. Many healthcare professionals have started getting hands-on training. To evaluate the effectiveness of such training programs, this study aimed to assess a 4 day POCUS training course on healthcare providers’ skills and knowledge acquisition. A secondary objective of this study is to gain valuable insights into the degree of perception, attitude, interest levels and perceived barriers of medical providers performing POCUS.

Methods
This is a prospective cohort study performed on healthcare providers in an integrated healthcare facility in Abu Dhabi undergoing the POCUS training course in February 2022. Course participants took a pre-course survey to evaluate their baseline knowledge, skills, confidence, perception, and interest in POCUS. The same survey was repeated immediately post-course. In total, seven healthcare professionals responded to the survey with a response rate of 53.8%. All data and information gathered were used to understand the effectiveness of POCUS training and gain insights into the degree of perception, interest and preparedness of POCUS among healthcare professionals in practice.

Results
Our results demonstrated that the brief POCUS course was effective in improving POCUS skills, knowledge and confidence amongst in-practice healthcare providers from varying medical specialties. The median skill score increased from 25% pre-course to 50% post-course. There is a notable increase in all skills scores after the POCUS training course with the greatest change in scores seen for adjusting ‘gain and depth of image (54.84%), assessing VeXUS score (52.38%) and evaluating lung congestion (50%). The study also provided valuable insights into the perception, attitude, interest and potential barriers of POCUS implementation. Although significant barriers to POCUS are present including the lack of POCUS curriculum, what is challenging is lack of expertise and skills to perform POCUS. Therefore, medical providers must acquire prespecified skills to fully utilize POCUS effectively.

Conclusion
The study confirmed the effectiveness of short POCUS training in improving the skills, knowledge and confidence of medical providers in practice. Healthcare professionals can master POCUS skills and techniques and gain confidence through brief training courses.
The usefulness of point-of-care ultrasound in dehydrated patients in a pediatric emergency department
Authors: Bellini Tommaso , Chianucci Benedetta , D’Alessandro Matteo , Ricci Margherita , Calevo Maria Grazia , Misley Silvia , Piccotti Emanuela , Moscatelli Andrea 
Published: February 2024

Abstract
Backgrounds
Dehydration is among the most common causes of Pediatric Emergency Department admission; however, no clinical signs, symptoms, or biomarkers have demonstrated sufficient sensitivity, specificity, or reliability to predict dehydration.

Methods
We conducted a prospective, monocentric, observational study at Giannina Gaslini Hospital, a tertiary care pediatric hospital. Our study aimed to compare inferior vena cava ultrasound measurement with volume depletion biomarkers to understand if point-of-care ultrasound could help grade, evaluate, and better manage dehydration in children presenting to the pediatric emergency department. We enrolled patients under the age of 14 who required blood tests in the suspect of dehydration; for each patient, we collected values of venous pH, natremia, bicarbonatemia, uric acid, chloremia, and blood urea nitrogen. For each patient, we performed two ultrasound scans to calculate the Inferior Vena Cava/Aorta area ratio and to assess the IVC collapsibility index; moreover, we described the presence of the “kiss sign” (100% IVC walls collapsing during the inspiratory phase).

Results
Patients with the “kiss sign” (25/65 patients, 38.5% of the total) showed worse blood tests, in particular, uric acid levels (p = 0.0003), bicarbonatemia (p = 0.001) and natriemia (p = 0.0003). Moreover, patients with the “kiss sign” showed a high frequency of ≥ 2 pathological blood tests (p = 0.0002). We found no statistical significant difference when comparing the IVC/Ao ratio and IVC-CI with the considered blood tests.

Conclusions
The “kiss sign” seems to be related to worse hydration state, whereas IVC/Ao and IVC-CI are not. In an emergency setting, where physicians must take diagnostic-therapeutic decisions quickly, the presence of the “kiss sign” in patients suspected to be dehydrated can be a helpful tool in their management.
Thoracic ultrasound use in hospitalized and ambulatory adult patients: a quantitative picture
Authors: Xirouchaki N. , Bolaki M. , Psarologakis C. , Pediaditis E. , Proklou A. , Papadakis E. , Kondili E. , Georgopoulos D. 
Published: February 2024

Abstract
Introduction and objectives
Thoracic ultrasound (TUS) has been established as a powerful diagnostic and monitoring tool in the Intensive Care Unit (ICU). However, studies outside the critical care setting are scarce. The aim of this study was to investigate the value of TUS for hospitalized or ambulatory community patients.

Materials and methods
This was a retrospective study conducted from 2016 to 2020 in the TUS clinic at Heraklion University Hospital. TUS examination was performed using a standard ultrasound machine (EUB HITACHI 8500), and a high-frequency microconvex probe (5–8 MHz). Patients had been referred by their primary physician to address a range of different questions. The various respiratory system entities were characterised according to internationally established criteria.

Results
762 TUS studies were performed on 526 patients due to underlying malignancy (n = 376), unexplained symptoms/signs (n = 53), pregnancy related issues (n = 42), evaluation of abnormal findings in X-ray (n = 165), recent surgery/trauma (n = 23), recent onset respiratory failure (n = 12), acute respiratory infection (n = 66) and underlying non-malignant disease (n = 25). Pleural effusion was the commonest pathologic entity (n = 610), followed by consolidation (n = 269), diaphragmatic dysfunction/paradox (n = 174) and interstitial syndrome (n = 53). Discrepancies between chest X-ray and ultrasonographic findings were demonstrated in 96 cases. The TUS findings guided invasive therapeutic management in 448 cases and non-invasive management in 43 cases, while follow-up monitoring was decided in 271 cases.

Conclusions
This study showed that TUS can identify the most common respiratory pathologic entities encountered in hospitalized and community ambulatory patients, and is especially useful in guiding the decision making process in a diverse group of patients.
Timing and clinical risk factors for early acquisition of gut pathogen colonization with multidrug resistant organisms in the intensive care unit
Authors: Shamalov Loren , Heath Madison , Lynch Elissa , Green Daniel A. , Gomez-Simmonds Angela , Freedberg Daniel E. 
Published: February 2024

Abstract
Background
Microbiome restitution therapies are being developed to prevent gut pathogen colonization among patients in the intensive care unit (ICU) and in other select populations. If preventive therapies are to be effective, they must be administered prior to pathogen acquisition. The timing and risk factors for early acquisition of gut pathogen colonization (within 72 h) are currently unknown and could be helpful to guide ICU trial design.

Methods
This was a prospective cohort study. Patients in the ICU had deep rectal swabs performed within 4 h of ICU admission and exactly 72 h later. Early gut pathogen colonization was classified as the new presence (based on culture of rectal swabs) of one or more of the following organisms of interest: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant (VRE), and Gram-negative bacteria that showed multidrug resistance (MDR) or third generation Cephalosporin resistance (Ceph-R). Clinical risk factors for early acquisition of gut pathogen colonization were captured using the Acute Physiology and Chronic Health Evaluation IV (APACHE IV) scoring system.

Findings
Among 131 patients who were swabbed at ICU admission and 72 h later, the rates of gut pathogen colonization at ICU admission were 11.4%, 10.6%, 38.6%, and 8.3% for MRSA, VRE, MDR and Ceph-R Gram-negatives respectively. Among the patients who were negative for a given pathogen at ICU admission, the rates of early acquisition of gut pathogen colonization were 7.8% for MRSA (95% CI 3.6 to 14.2%), 7.7% for VRE (95% CI 3.6 to 14.1%), 11.3% for MDR Gram-negatives (95% CI 4.4 to 18.8%), and 4.2% for Ceph-R Gram-negatives (95% CI 1.4 to 9.5%). There were no clinical risk factors which independently predicted early acquisition of gut pathogen colonization.

Interpretation
Early gut pathogen colonization was common in the ICU, but our single-center study could not identify any clinical risk factors which were significantly associated with acquisition of gut pathogens.