bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of SGLT-2 inhibitors on adipose tissue distribution in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials
Authors: Wang Xianghong , Wu Niujian , Sun Chuanchuan , Jin Donghua , Lu Hongyun 
Published: May 2023

Abstract
Objective
Sodium-glucose cotransporter-2 (SGLT-2) inhibitors therapies were reported to affect adipose tissue distribution. However, the available evidence about the effect of SGLT-2 inhibitor on adipose tissue is contradictory. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of SGLT-2 inhibitors on adipose tissue distribution in patients with type 2 diabetes mellitus (T2DM).

Methods
RCTs on SGLT-2 inhibitors on adipose distribution affect in patients with T2DM published in full-text journal databases such as PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched. The fixed or random effect model was used for meta-analysis, the I2 test was used to evaluate the heterogeneity between studies, and the sensitivity analysis and subgroup analysis were used to explore the source of heterogeneity. Funnel chart and Begg’s test were used to estimate publication bias.

Results
Overall, 18 RCTs involving 1063 subjects were evaluated. Compared with placebo or other hypoglycemic drugs, SGLT-2 inhibitors significantly reduced visceral adipose tissue (standard mean deviation [SMD] = − 1.42, 95% confidence interval [CI] [− 2.02, − 0.82], I2 = 94%, p < 0.0001), subcutaneous adipose tissue (SMD = − 1.21, 95% CI [− 1.99, − 0.42], I2 = 93%, p = 0.003), ectopic liver adipose tissue (SMD = − 0.70, 95% CI [− 1.20, − 0.20], I2 = 73%, p = 0.006). In addition, body weight (mean deviation [MD] = − 2.60, 95% CI [− 3.30, − 1.89], I2 = 95%, p < 0.0001), waist circumference (MD = − 3.65, 95% CI [− 4.10, − 3.21], I2 = 0%, p < 0.0001), and body mass index (BMI) (MD = − 0.81, 95% CI [− 0.91, − 0.71], I2 = 23%, p < 0.0001) were significantly decreased. However, epicardial fat tissue showed an insignificant reduction (SMD = 0.03, 95% CI [− 0.52, 0.58], I2 = 69%, p = 0.71). Subgroup analysis revealed that appropriate treatment duration (16 – 40 weeks) or young patients with nonalcoholic fatty liver disease (NAFLD) and obesity were the decisive factors for SGLT-2 inhibitors to effectively reduce visceral and subcutaneous adipose tissues.

Conclusions
Our meta-analysis provides evidence that in patients with T2DM, SGLT-2 inhibitors significantly reduce visceral adipose tissue, subcutaneous adipose tissue, and ectopic liver fat, especially in young T2DM patients with NAFLD and high BMI. Appropriate dosing time (16–40 weeks) may have a more significant and stable beneficial effect on VAT and SAT reduction.
Genome-wide CRISPR/Cas9 library screening identified ATM signaling network genes as critical drivers for resistance to ATR inhibition in soft-tissue sarcomas: synthetic lethality and therapeutic implications
Authors: Spalato-Ceruso M , Laroche-Clary A , Perret R , Valverde Y , Chaire V , Derieppe Marie-Alix , Velasco V , Bourdon A , Italiano A 
Published: May 2023

AbstractSoft-tissue sarcoma (STS) are a heterogeneous group of rare tumors with different biological behavior that are fatal in more than 40% of cases, due to their metastatic evolution and inadequate treatment options. ATR inhibition already showed an activity, even if modest, in broad pre-clinical models of STS. By using genome-wide CRISPR/Cas9 library screening, we identified ATM signaling network genes as critical drivers for resistance to the specific ATR inhibitor AZD6738. The role of such genes in resistance to AZD6738 was confirmed by using CRISPR/Cas9 knockout models. More strikingly, the ATM inhibitor AZD0156 works synergistically with AZD6738 in vitro and abolishes STS growth in vivo in our models of most frequent histotypes (such as dedifferentiated liposarcoma, leiomyosarcoma, and undifferentiated pleomorphic sarcoma among others). Moreover, the combination of AZD6738 and AZD0156 induced significantly higher levels of DNA damage than either drug used as single agent alone. In summary, our results demonstrate that targeting ATM is an effective approach to overcome resistance to ATR inhibition in different STS subtypes, including the most frequent histologies.
Single-cell technologies in multiple myeloma: new insights into disease pathogenesis and translational implications
Authors: Chen Mengping , Jiang Jinxing , Hou Jian 
Published: May 2023

AbstractMultiple myeloma (MM) is a hematological malignancy characterized by clonal proliferation of plasma cells. Although therapeutic advances have been made to improve clinical outcomes and to prolong patients’ survival in the past two decades, MM remains largely incurable. Single-cell sequencing (SCS) is a powerful method to dissect the cellular and molecular landscape at single-cell resolution, instead of providing averaged results. The application of single-cell technologies promises to address outstanding questions in myeloma biology and has revolutionized our understanding of the inter- and intra-tumor heterogeneity, tumor microenvironment, and mechanisms of therapeutic resistance in MM. In this review, we summarize the recently developed SCS methodologies and latest MM research progress achieved by single-cell profiling, including information regarding the cancer and immune cell landscapes, tumor heterogeneities, underlying mechanisms and biomarkers associated with therapeutic response and resistance. We also discuss future directions of applying transformative SCS approaches with contribution to clinical translation.
Astrocytic pathology in Alpers’ syndrome
Authors: Smith Laura A , Chen Chun , Lax Nichola Z , Taylor Robert W , Erskine Daniel , McFarland Robert 
Published: May 2023

AbstractRefractory epilepsy is the main neurological manifestation of Alpers’ syndrome, a severe childhood-onset mitochondrial disease caused by bi-allelic pathogenic variants in the mitochondrial DNA (mtDNA) polymerase gamma gene (POLG). The pathophysiological mechanisms underpinning neuronal hyperexcitabilty leading to seizures in Alpers’ syndrome remain unknown. However, pathological changes to reactive astrocytes are hypothesised to exacerbate neural dysfunction and seizure-associated cortical activity in POLG-related disease. Therefore, we sought to phenotypically characterise astrocytic pathology in Alpers’ syndrome. We performed a detailed quantitative investigation of reactive astrocytes in post-mortem neocortical tissues from thirteen patients with Alpers’ syndrome, eight neurologically normal controls and five sudden unexpected death in epilepsy (SUDEP) patients, to control for generalised epilepsy-associated astrocytic pathology. Immunohistochemistry to identify glial fibrillary acidic protein (GFAP)-reactive astrocytes revealed striking reactive astrogliosis localised to the primary visual cortex of Alpers’ syndrome tissues, characterised by abnormal-appearing hypertrophic astrocytes. Phenotypic characterisation of individual GFAP-reactive astrocytes demonstrated decreased abundance of mitochondrial oxidative phosphorylation (OXPHOS) proteins and altered expression of key astrocytic proteins including Kir4.1 (subunit of the inwardly rectifying K+ ion channel), AQP4 (astrocytic water channel) and glutamine synthetase (enzyme that metabolises glutamate). These phenotypic astrocytic changes were typically different from the pathology observed in SUDEP tissues, suggesting alternative mechanisms of astrocytic dysfunction between these epilepsies. Crucially, our findings provide further evidence of occipital lobe involvement in Alpers’ syndrome and support the involvement of reactive astrocytes in the pathogenesis of POLG-related disease.
Sustainable development goals in nephrology nursing to support social development for Japan’s changing population: recommendations for a new paradigm
Authors: Mimura Nadami , Takuwa Yoshiko , Tamura Yui , Kawamura Harumi , Nishimura Misato , Yamaguchi Noriko 
Published: May 2023

Abstract
Background
In accordance with the United Nations' 2030 Agenda for Sustainable Development and Japan's Diet Members Caucus on Global Health, we prepared a report and recommendations for nephrology nursing care in the context of population aging in Japan. Goals and strategies to support social activities are discussed.

Summary
As the population continues to age in Japan, nephrology nursing must evolve to support society amid changes. We should aim for two goals: (1) the construction of a new social system to support people with kidney disease, and (2) the development of clinical nursing by securing nurses who are involved in nephrology nursing.

Conclusions
Creating a new paradigm for nephrology nursing care in communities, creating knowledge, and advancing nursing practices for patients with renal failure care within community settings and at home, developing nurses with high expertise in nephrology nursing practice, and recognizing that nurses involved in the care of renal insufficiency will elevate the value of nephrology nursing. Promoting the role of nurses in the specialty of renal care will, in turn, heighten their ability to continue to provide support to society and contribute to its development.
Economic and environmental analysis of a grid-connected hybrid power system for a University Campus
Authors: Akindeji Kayode Timothy , Ewim Daniel Raphael Ejike 
Published: May 2023

Abstract
Background
The generation of clean and affordable energy by 2030 is a challenging task, necessitating the integration of renewable energy sources to reduce greenhouse gas emissions associated with coal, crude oil, and natural gas. This study examines the optimization and performance analysis of a hybrid microgrid for a university campus as a potential solution to achieve this goal. The primary objective is to decrease the cost of energy and reduce CO2 emissions on the campus using a hybrid approach.

Results
The Howard college campus of the University of KwaZulu Natal (UKZN) was used as a case study, with meteorological data obtained from NASA and real hourly electrical load data for 2019 from the university smart meters. HOMER, an optimization software, was employed to model and simulate the case study. The results demonstrated significant savings of R15.7 million (approximately $ 820 000) in annual utility bills, a 51% reduction in CO2 emissions, a return on investment of 20%, and a payback period of 4 years.

Conclusion
The study's findings suggest that universities can become self-sustaining during load shedding periods, as recently experienced in South Africa. The implementation of a hybrid microgrid system on a university campus offers considerable economic and environmental benefits, providing a potential blueprint for other large institutions seeking to achieve similar sustainability goals.
Robust conductive skin hydrogel e-skin constructed by top–down strategy for motion-monitoring
Authors: Liu Jiachang , Fan Xin , Astruc Didier , Gu Haibin 
Published: May 2023

AbstractThe construction of biomass-based conductive hydrogel e-skins with high mechanical properties is the research hotspot and difficulty in the field of biomass materials. Traditional collagen-based conductive hydrogels, constructed by the typical “bottom–up” strategy, normally have the incompatible problem between high mechanical property and high collagen content, and the extraction of collagen is often necessary. To solve these problems, inspired by the high mechanical properties and high collagen content of animal skins, this work proposed a “top–down” construction strategy, in which the extraction of collagen was unnecessary and the skin collagen skeleton (SCS) with the 3D network structure woven by natural collagen fibers in goatskin was preserved and used as the basic framework of hydrogel. Following a four-step route, namely, pretreatment → soaking in AgNPs (silver nanoparticles) solution → soaking in the mixed solution containing HEA (2-hydroxyethyl methacrylate) and AlCl3 → polymerization, this work successfully achieved the fabrication of a new skin-based conductive hydrogel e-skin with high mechanical properties (tensile strength of 2.97 MPa, toughness of 6.23 MJ·m−3 and breaking elongation of 428%) by using goatskin as raw material. The developed skin hydrogel (called PH@Ag) possessed a unique structure with the collagen fibers encapsulated by PHEA, and exhibited satisfactory adhesion, considerable antibacterial property, cytocompatibility, conductivity (3.06 S·m−1) and sensing sensitivity (the maximum gauge factor of 5.51). The PH@Ag e-skin could serve as strain sensors to accurately monitor and recognize all kinds of human motions such as swallowing, frowning, walking, and so on, and thus is anticipated to have considerable application prospect in many fields including flexible wearable electronic devices, health and motion monitoring.
Graphical abstract
Development and validation of a stability-indicating RP-HPLC method for estimation of Lefamulin in pure and pharmaceutical drug products
Authors: Usman Muhammad , Abbas Tauqeer 
Published: May 2023

Abstract
Background
Commonly occurring serious lung parenchymal infection is community-acquired bacterial pneumonia (CABP). Lefamulin acetate drug products are useful for the treatment of community-acquired bacterial pneumonia (CABP). The main objective of the study was the development and validation of a quick reverse-phase high performance liquid chromatographic analytical testing method for Lefamulin in pure and pharmaceutical dosage forms. The C18 column was the stationary phase for reverse-phase high performance liquid chromatographic separation, and the mobile phase consisted of 0.05 M phosphate buffer with a pH adjustment of 2.5 mixed with an equal volume of acetonitrile. A flow rate of 1.0 mL/min, a column temperature of 30 °C, an injection volume of 10 µL, and a detection wavelength of 210 nm were used as optimum conditions.

Results
The developed method reported that Lefamulin peak’s retention time was 3.1 min, the average theoretical plate count 5000, and the average peak asymmetry 1.12. In both pure and pharmaceutical dosage forms, the method was found to be accurate, precise, specific, linear calibration curve, and robust. Quantitative assay results from laboratory-made formulations showed similarity to existing commercial products of Lefamulin. Lefamulin is stable in acidic and photolytic environmental circumstances, while it degraded in oxidative, basic, and thermal humidity environment, according to the results of stress studies.

Conclusions
The developed analytical method is fast, economic and stability indicating. It is useful for routine pharmaceutical analysis where the Lefamulin is synthesized in pure form, pharmaceutical tablet formulation, and parenteral dosage form, for their quality and safety.
Functional ability in knee osteoarthritis: role of neuropathic pain and central sensitization
Authors: Elsehrawy Gehad Gamal , Ibrahim Maha Emad , Elshaarawy Nashwa Kamel , Hefny Mohamed Ahmed , A.moneim Nermeen Hassan 
Published: May 2023

Abstract
Background
Pain in osteoarthritis (OA) has been attributed traditionally to local tissue injury causing ‘nociceptive pain’. However, recent studies suggest that neuropathic and central sensitization mechanisms may contribute to the pain experience. However, the relationship between these pain mechanisms and physical function has not been thoroughly addressed. This study aimed to assess the association of central sensitization and neuropathic pain with physical function in knee OA.

Results
Participants with a positive central sensitization inventory score (CSI) (≥ 40) had a decreased total Knee injury and Osteoarthritis Outcome Score (KOOS) and its subscales (p < 0.001), a longer timed up and go test time (p = 0.002) and a higher PainDETECT questionnaire (PD-Q) and visual analogue scale (p < 0.001, p = 0.026 respectively). The severity of Kellgren-Lawrence grading (KL) (p < 0.001), depressive and anxiety symptoms (p < 0.001) increased with neuropathic pain severity. In addition, participants with a high PD-Q score (≥ 19) had a longer timed up and go test time (p < 0.001) and a decreased total KOOS score (p < 0.001). Moreover, we found that CSI score, KOOS score, and KL grading were significantly predicted the PD-Q score (p = 0.046, p < 0.001, p = 0.007, respectively). Regarding the physical function predictors, multivariate linear regression analysis revealed that pressure pain threshold at right elbow and right knee (p = 0.005, p < 0.001) in addition to PD-Q (P < 0.001) were significantly associated with KOOS score, while CSI and Hospital Anxiety Depression Scale were not.

Conclusion
Knee OA patients with significant central sensitization and neuropathic pain reported increased pain, more functional impairment, more anxiety and depressive symptoms than OA patients without central sensitization and neuropathic pain. Additionally, neuropathic pain and presence of central sensitization were significant predictors for functional ability.
Optimization of plastic waste integration in cement bricks
Authors: El-Metwally Yara , Dewidar Khaled , Ismail Mostafa , El-Mahallawi Iman 
Published: May 2023

AbstractImplementing plastic waste in construction materials is a sustainable disposal method to overcome plastic pollution. The current study aims to optimize the integration of plastic waste in cement bricks regarding their thermomechanical properties in order to develop an eco-friendly building material. Polyethylene terephthalate (PET) and high-density polyethylene (HDPE) partially substituted cement with different ratios (0, 2.5, 5, 7.5, 10, 20%). The type that achieved better thermomechanical performance further replaced the other brick components; sand and coarse aggregates to determine the optimum replacement scenario and best design mix. Laboratory experiments have been carried out to measure the compressive strength, indirect tensile strength, bulk density, and thermal conductivity of the new composites. The measured results revealed better performance for the samples with HDPE than PET. A boost in the compressive strength and indirect tensile strength was noticed for the samples obtaining a limited amount (up to 7.5%) of HDPE. However, a reduction in the tested mechanical properties occurs with higher substitution levels. With respect to thermal conductivity and bulk density, they decreased with the increase of plastic waste. The best mechanical behavior and the highest thermal resistance were obtained by partial replacement of coarse aggregates with 7.5% and 20% HDPE respectively. The results represent a good contribution to energy conservation, waste management and sustainability.
New technologies in anesthesia and intensive care: take your ticket for the future
Authors: Bignami Elena , Lanza Roberto , Cussigh Giacomo , Bellini Valentina 
Published: May 2023

AbstractThe modern world runs all around hi-tech, which surrounds us in our everyday life. The medical field is no less; the introduction of the novel disruptive technologies are transforming every healthcare system. Anesthesia, intensive care, and pain medicine are fields in which the application of new technologies is proving to have great potential. However, it is crucial that this digital medical transformation always takes place under the coordination of natural (human) intelligence.
Risks and benefits of animal-assisted interventions for critically ill patients admitted to intensive care units
Authors: Fiore Marco , Cortegiani Andrea , Friolo Giansaverio , Frigieri Covani Francesca , Cardia Luigi , Ferraro Fausto , Alampi Daniela 
Published: May 2023

Abstract
Background
Pets offer significant health benefits, from decreased cardiovascular risks to anxiety and post-traumatic stress improvements. Animal-assisted interventions (AAI) are not frequently practiced in the intensive care unit (ICU) for fear of health risk for critical patients because there is a hypothetical risk of zoonoses.

Objectives
This systematic review aimed to collect and summarize available evidence about AAI in the ICU. The Review questions were “Do AAI improve the clinical outcome of Critically Ill Patients admitted to ICUs?” and “Are the zoonotic infections the cause of negative prognosis?”.

Methods
The following databases were searched on 5 January 2023: Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, and PubMed. All controlled studies (randomized controlled, quasi-experimental, and observational studies) were included. The systematic review protocol has been registered on the International Prospective Register of Systematic Review (CRD42022344539).

Results
A total of 1302 papers were retrieved, 1262 after the duplicate remotion. Of these, only 34 were assessed for eligibility and only 6 were included in the qualitative synthesis. In all the studies included the dog was the animal used for the AAI with a total of 118 cases and 128 controls. Studies have high variability, and no one has used increased survival or zoonotic risk as outcomes.

Conclusions
The evidence on the effectiveness of AAIs in ICU settings is scarce and no data are available on their safety. AAIs use in the ICU must be considered experimental and follow the related regulation until further data will be available. Given the potential positive impact on patient-centered outcomes, a research effort for high-quality studies seems to be justified.
Point of care assay for blood aripiprazole concentrations: development, validation and utility
Authors: Atkins Matthew , Taylor David , Catalan Ana , Desouza Neville , Chesney Edward , Reilly Thomas J. , Baburina Irina , Hilaire Mary Rose , Dratcu Luiz , Harland Robert , Salamone Salvatore J. , McGuire Philip 
Published: May 2023

BackgroundThe antipsychotic aripiprazole is often used in the treatment of first-episode psychosis. Measuring aripiprazole blood levels provides an objective measure of treatment adherence, but this currently involves taking a venous blood sample and sending to a laboratory for analysis.AimsTo detail the development, validation and utility of a new point of care (POC) test for finger-stick capillary blood concentrations of aripiprazole.MethodAnalytical performance (sensitivity, precision, recovery and linearity) of the assay were established using spiked whole blood and control samples of varying aripiprazole concentration. Assay validation was performed over a 14-month period starting in July 2021. Eligible patients were asked to provide a finger-stick capillary sample in addition to their usual venous blood sample. Capillary blood samples were tested by the MyCare™ Insite POC analyser, which provided measurement of aripiprazole concentration in 6 min, and the venous blood sample was tested by the standard laboratory method.ResultsA total of 101 patients agreed to measurements by the two methods. Venous blood aripiprazole concentrations as assessed by the laboratory method ranged from 17 to 909 ng/mL, and from 1 to 791 ng/mL using POC testing. The correlation coefficient between the two methods (r) was 0.96 and there was minimal bias (slope 0.91, intercept 4 ng/ml).ConclusionsThe MyCare Insite POC analyser is sufficiently accurate and reliable for clinical use. The availability of this technology will improve the assessment of adherence to aripiprazole and the optimising of aripiprazole dosing.
In Defense of Facelessness
Authors: Tidwell Christy 
Published: May 2023

Abstract
Christy Tidwell reflects on the shift from teaching in person to teaching online asynchronous classes during COVID-19. This shift involved a combination of labor-based grading and using Discord as a central space for the class, both of which aimed to center and engage students and relationships with students rather than further automate the class. Tidwell concludes by commenting on ways that these tools and techniques remain useful even when returning to the in-person classroom.