bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shared patterns of glial transcriptional dysregulation link Huntington’s disease and schizophrenia
Authors: Huynh Nguyen P T , Osipovitch Mikhail , Foti Rossana , Bates Janna , Mansky Benjamin , Cano Jose C , Benraiss Abdellatif , Zhao Chuntao , Lu Q Richard , Goldman Steven A 
Published: July 2024

Abstract
Huntington’s disease and juvenile-onset schizophrenia have long been regarded as distinct disorders. However, both manifest cell-intrinsic abnormalities in glial differentiation, with resultant astrocytic dysfunction and hypomyelination. To assess whether a common mechanism might underlie the similar glial pathology of these otherwise disparate conditions, we used comparative correlation network approaches to analyse RNA-sequencing data from human glial progenitor cells (hGPCs) produced from disease-derived pluripotent stem cells.
We identified gene sets preserved between Huntington’s disease and schizophrenia hGPCs yet distinct from normal controls that included 174 highly connected genes in the shared disease-associated network, focusing on genes involved in synaptic signalling. These synaptic genes were largely suppressed in both schizophrenia and Huntington’s disease hGPCs, and gene regulatory network analysis identified a core set of upstream regulators of this network, of which OLIG2 and TCF7L2 were prominent. Among their downstream targets, ADGRL3, a modulator of glutamatergic synapses, was notably suppressed in both schizophrenia and Huntington’s disease hGPCs. Chromatin immunoprecipitation sequencing confirmed that OLIG2 and TCF7L2 each bound to the regulatory region of ADGRL3, whose expression was then rescued by lentiviral overexpression of these transcription factors.
These data suggest that the disease-associated suppression of OLIG2 and TCF7L2-dependent transcription of glutamate signalling regulators may impair glial receptivity to neuronal glutamate. The consequent loss of activity-dependent mobilization of hGPCs may yield deficient oligodendrocyte production, and hence the hypomyelination noted in these disorders, as well as the disrupted astrocytic differentiation and attendant synaptic dysfunction associated with each. Together, these data highlight the importance of convergent glial molecular pathology in both the pathogenesis and phenotypic similarities of two otherwise unrelated disorders, Huntington’s disease and schizophrenia.
Scenario of solar energy and policies in India
Authors: Kumar M Sathish , Kumari Prity , Lad Y A , Maria Sherin 
Published: July 2024

Abstract
Solar power is energy from the Sun that is converted into thermal or electrical energy. China, the USA, and India have the world’s richest solar energy sources. India receives solar radiation with an average intensity of 200 MW/km2 and 250–300 sunny days a year. The solar radiation in India varies from 4 to 7 kWh/m2/day, with 2300–3200 sunshine hours yearly, depending on the region. Badhla Solar Park, Jodhpur, India, is the world’s largest solar plant, with 2.25 GW of installed capacity. Solar energy is the best alternative electricity source used explicitly in the agricultural sector. In the farming sector, the consumption of solar energy has been increasing. The major issues were the installation costs, low availability of technicians, and poor quality of panels. The focus on skill development equips the workforce to drive innovation, efficiency, and sustained growth in the renewable-energy field. With the support of international collaboration and a skilled workforce, India’s progress in solar energy development is a boon for the industry.
Genetic testing in early-onset atrial fibrillation
Authors: Kany Shinwan , Jurgens Sean J , Rämö Joel T , Christophersen Ingrid E , Rienstra Michiel , Chung Mina K , Olesen Morten S , Ackerman Michael J , McNally Elizabeth M , Semsarian Christopher , Schnabel Renate B , Wilde Arthur A M , Benjamin Emelia J , Rehm Heidi L , Kirchhof Paulus , Bezzina Connie R , Roden Dan M , Shoemaker M Benjamin , Ellinor Patrick T 
Published: July 2024

Abstract
Atrial fibrillation (AF) is a globally prevalent cardiac arrhythmia with significant genetic underpinnings, as highlighted by recent large-scale genetic studies. A prominent clinical and genetic overlap exists between AF, heritable ventricular cardiomyopathies, and arrhythmia syndromes, underlining the potential of AF as an early indicator of severe ventricular disease in younger individuals. Indeed, several recent studies have demonstrated meaningful yields of rare pathogenic variants among early-onset AF patients (∼4%–11%), most notably for cardiomyopathy genes in which rare variants are considered clinically actionable. Genetic testing thus presents a promising opportunity to identify monogenetic defects linked to AF and inherited cardiac conditions, such as cardiomyopathy, and may contribute to prognosis and management in early-onset AF patients. A first step towards recognizing this monogenic contribution was taken with the Class IIb recommendation for genetic testing in AF patients aged 45 years or younger by the 2023 American College of Cardiology/American Heart Association guidelines for AF. By identifying pathogenic genetic variants known to underlie inherited cardiomyopathies and arrhythmia syndromes, a personalized care pathway can be developed, encompassing more tailored screening, cascade testing, and potentially genotype-informed prognosis and preventive measures. However, this can only be ensured by frameworks that are developed and supported by all stakeholders. Ambiguity in test results such as variants of uncertain significance remain a major challenge and as many as ∼60% of people with early-onset AF might carry such variants. Patient education (including pretest counselling), training of genetic teams, selection of high-confidence genes, and careful reporting are strategies to mitigate this. Further challenges to implementation include financial barriers, insurability issues, workforce limitations, and the need for standardized definitions in a fast-moving field. Moreover, the prevailing genetic evidence largely rests on European descent populations, underscoring the need for diverse research cohorts and international collaboration. Embracing these challenges and the potential of genetic testing may improve AF care. However, further research—mechanistic, translational, and clinical—is urgently needed.
Low CD4 counts predict excessive weight gains during first-line treatment for HIV
Authors: Hill Andrew , Tovar Sanchez Tamara , Delaporte Eric , Sokhela Simiso , Simmons Bryony , Kouanfack Charles , Mccann Kaitlyn , Levi Jacob , Fairhead Cassandra , Venter Francois 
Published: July 2024

Abstract

Background
Weight gain is common after antiretroviral initiation, especially among females, those of black race and lower baseline CD4, although this may potentially be due to lower baseline weight. Use of tenofovir disoproxil fumarate or efavirenz can suppress weight gain.

Methods
Data were pooled from the ADVANCE (n = 1053), NAMSAL (n = 613) and WHRI001 (n = 536) trials investigating first-line regimen. Week 96 weight and body mass index (BMI) was stratified by baseline CD4. Multivariable models of weight change and incident obesity (BMI ≥30 kg/m2) were adjusted for baseline CD4, age, sex, tenofovir disoproxil fumarate, efavirenz, baseline BMI and trial.

Results
Participants across all treatment arms experienced weight gain from baseline to week 96, with baseline CD4 count, baseline HIV RNA, tenofovir alafenamide and dolutegravir use, and female sex significant predictors. Mean unadjusted weight change was highest with CD4 &lt; 100 (+8.6 kg; SD = 8.2) and lowest with CD4 ≥ 350 (+3.0 kg; SD = 6.5). This weight gain in CD4 &lt; 100 was highest for participants on tenofovir alafenamide-inclusive treatment, such that absolute weight at week 96 was highest in the CD4 &lt; 100 group. Although not statistically significant, obesity rate (BMI ≥ 30 kg/m2) in those taking TAF/FTC + DTG with CD4 &lt; 100 overtook that seen in CD4 ≥ 350, despite lower baseline obesity prevalence. The unadjusted findings were corroborated in multivariable longitudinal models.

Conclusions
Participants with low CD4 may demonstrate significant ‘overshoot’ weight gain, in addition to ‘return to health’, with a trend towards increased risk of obesity when initiated on TAF/FTC + DTG. Use of tenofovir disoproxil fumarate and efavirenz were associated with smaller weight gains. Effective weight management strategies are needed, especially for individuals with low baseline CD4.
(360) WHICH OF PDE5 INHIBITORS IS MOST EFFECTIVE IN THE TREATMENT OF ERECTILE DYSFUNCTION IN PATIENTS WITH SPINAL CORD INJURY? A NETWORK META-ANALYSIS
Authors: Tienforti Dr Daniele , Castellini Chiara , Barbonetti Prof Arcangelo 
Published: July 2024

Abstract

Objectives
PDE5 inhibitors (PDE5i) represent the first-line drugs in the treatment of spinal cord injury (SCI)-related erectile dysfunction (ED). Available molecules have differences that should guide personalization of treatment. We compared the efficacy of PDE5 inhibitors to define which is more effective in treating SCI-related ED.

Methods
A systematic search was performed. A traditional pairwise meta-analyses were conducted including only studies in which PDE5i were directly compared with placebo, then a network meta-analysis (NMA) was conducted. Based on the assumption of transitivity, if two treatments, A and B, have never been compared with each other but both have been compared with a third treatment (e.g., a placebo), the NMA can provide information on the A vs. B comparison by means of the statistical method of “indirect comparison”. With this approach, multiple treatments are compared within a single statistical model generating an efficacy hierarchy to drive clinical practice.

Results
The search identified 10 trials. The most common comparison was between sildenafil and placebo. All three molecules were compared at least once with each other and with placebo. The results of the NMA confirmed a significant improvement in erectile function with each of the three molecules. At the comparative analysis, tadalafil, which was 5 times more effective than placebo, was associated with the highest surface under the cumulative ranking curve (SUCRA) value (0.81), thus proving to be the best PDE5i in the treatment of SCI-related ED, followed by vardenafil (0.68) and sildenafil (0.49) (Figure 1).

Conclusions
In men with SCI who are candidates for PDE5i treatment for ED, the clinician's choice should fall on tadalafil, leaving vardenafil and sildenafil as second-line choices. Further head-to-head comparison studies will be needed to confirm these results and to identify most useful clinical and neurological features for selecting patients who are candidates for prescription of the different molecules.

Conflicts of Interest
The authors have no conflicts of interest to declare.
Revisiting the dead time effects of Insight-HXMT/ME on timing analysis
Authors: Tuo Youli , Li Xiaobo , Tan Ying , Wu Baiyang , Jiang Weichun , Song Liming , Qu Jinlu , Gogate Sudeep , Zhang Shuang-Nan , Santangelo Andrea 
Published: July 2024

ABSTRACT
Dead time is a common instrumental effect of X-ray detectors, which would alter the behaviour of timing properties of astronomical signals, such as distorting the shape of power density spectra (PDS), affecting the root-mean-square of potential quasi-periodic oscillation signals, etc. We revisit the effects of the dead time of Medium Energy X-ray telescope (ME) onboard Insight-HXMT based on the simulation of electronic read-out mechanism that causes the dead time and the real data. We investigate dead time effects on the pulse profile as well as the quasi–periodic oscillation (QPO) signals. The dead time coefficient suggests a linear correlation with the observed count rate in each phase bin of the pulse profile according to the simulation of periodic signal as well as the real data observed on Swift J0243.6+6124. The Fourier-amplitude-difference (FAD) method could well recover the intrinsic shape of the observed PDS in the case that the PDS is from two identical detectors. We apply this technique on ME, by splitting the nine FPGA modules into two groups. The results indicate that the FAD technique suits the case when two groups of detectors are not largely different; and the recovered PDS of Sco X-1 observed by ME slightly enhances the significance of the previously known QPO signal, meanwhile the root-mean-square of QPO is significantly improved. We provide the FAD correction tool implemented in HXMTDAS for users in the future to better analyse QPO signals.
Epidural Blood Patch for the Treatment of Spontaneous Intracranial Hypotension: A Case Series
Authors: Gomez Maria , Sharma Manas , Chan Tommy Lik Hang , Bellingham Geoff , Chui Jason 
Published: July 2024

Background:
Epidural blood patch (EBP) is frequently used for the treatment of spontaneous intracranial hypotension (SIH) and anesthesiologists are often involved in performing such procedures. However, the optimal technique and approach of EBP remains uncertain.

Methods:
This case series included adult patients with SIH who underwent EBPs at London Health Science Centre, Ontario, Canada between 2010 and 2022. Demographics, clinical presentations, investigations, and EBP treatment details were collected and analyzed. Univariate analysis was used to investigate the association of the variables with the likelihood of EBP 1-month efficacy and the efficacy duration of EBP.

Results:
The study included 36 patients with SIH who received at least 1 EBP. EBPs provided immediate relief in almost all patients, albeit with diminishing effects over time. The 1-month efficacy improved with increasing number of EBP attempts (P=0.032, Fisher exact test), though no particular EBP technique or volume of injectate was associated with better efficacy (P=0.38, Fisher exact test). Though permanent resolution of symptoms was observed in only 24 of 82 EBPs (29%), 24 of 36 patients (67%) had permanent symptom resolution following repeated EBPs.

Conclusions:
EBP is a promising treatment and symptomatic relief option in patients suffering from the debilitating symptoms of SIH. Tailored EBP techniques, including use of targeted higher volume EBP and a multi-level catheter guided technique for refractory cases, showed efficacy in our institutional setting. Despite its limitations, this study contributes valuable insights and experiences into the use of EBP for treatment of SIH.
Development and Validation of a Machine Learning COVID-19 Veteran (COVet) Deterioration Risk Score
Authors: Govindan Sushant , Spicer Alexandra , Bearce Matthew , Schaefer Richard S. , Uhl Andrea , Alterovitz Gil , Kim Michael J. , Carey Kyle A. , Shah Nirav S. , Winslow Christopher , Gilbert Emily , Stey Anne , Weiss Alan M. , Amin Devendra , Karway George , Martin Jennie , Edelson Dana P. , Churpek Matthew M. 
Published: July 2024

BACKGROUND AND OBJECTIVE:
To develop the COVid Veteran (COVet) score for clinical deterioration in Veterans hospitalized with COVID-19 and further validate this model in both Veteran and non-Veteran samples. No such score has been derived and validated while incorporating a Veteran sample.

DERIVATION COHORT:
Adults (age ≥ 18 yr) hospitalized outside the ICU with a diagnosis of COVID-19 for model development to the Veterans Health Administration (VHA) (n = 80 hospitals).

VALIDATION COHORT:
External validation occurred in a VHA cohort of 34 hospitals, as well as six non-Veteran health systems for further external validation (n = 21 hospitals) between 2020 and 2023.

PREDICTION MODEL:
eXtreme Gradient Boosting machine learning methods were used, and performance was assessed using the area under the receiver operating characteristic curve and compared with the National Early Warning Score (NEWS). The primary outcome was transfer to the ICU or death within 24 hours of each new variable observation. Model predictor variables included demographics, vital signs, structured flowsheet data, and laboratory values.

RESULTS:
A total of 96,908 admissions occurred during the study period, of which 59,897 were in the Veteran sample and 37,011 were in the non-Veteran sample. During external validation in the Veteran sample, the model demonstrated excellent discrimination, with an area under the receiver operating characteristic curve of 0.88. This was significantly higher than NEWS (0.79; p < 0.01). In the non-Veteran sample, the model also demonstrated excellent discrimination (0.86 vs. 0.79 for NEWS; p < 0.01). The top three variables of importance were eosinophil percentage, mean oxygen saturation in the prior 24-hour period, and worst mental status in the prior 24-hour period.

CONCLUSIONS:
We used machine learning methods to develop and validate a highly accurate early warning score in both Veterans and non-Veterans hospitalized with COVID-19. The model could lead to earlier identification and therapy, which may improve outcomes.
Severe acute respiratory syndrome coronavirus 2-specific T-cell responses are induced in people living with human immunodeficiency virus after booster vaccination
Authors: Wang Xiuwen , Li Yongzheng , Jin Junyan , Chai Xiaoran , Ma Zhenglai , Duan Junyi , Zhang Guanghui , Huang Tao , Zhang Xin , Zhang Tong , Wu Hao , Cao Yunlong , Su Bin 
Published: July 2024

ABSTRACT

Background:
T-cell-mediated immunity is crucial for the effective clearance of viral infection, but the T-cell-mediated immune responses that are induced by booster doses of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in people living with human immunodeficiency virus (PLWH) remain unclear.

Methods:
Forty-five PLWH who had received antiretroviral therapy (ART) for more than two years and 29 healthy controls (HCs) at Beijing Youan Hospital were enrolled to assess the dynamic changes in T-cell responses between the day before the third vaccine dose (week 0) and 4 or 12 weeks (week 4 or week 12) after receiving the third dose of inactivated SARS-CoV-2 vaccine. Flow cytometry, enzyme-linked immunospot (ELISpot), and multiplex cytokines profiling were used to assess T-cell responses at the three timepoints in this study.

Results:
The results of the ELISpot and activation-induced marker (AIM) assays showed that SARS-CoV-2-specific T-cell responses were increased in both PLWH and HCs after the third dose of the inactivated SARS-CoV-2 vaccine, and a similar magnitude of immune response was induced against the Omicron (B.1.1.529) variant compared to the wild-type strain. In detail, spike-specific T-cell responses (measured by the ELISpot assay for interferon γ [IFN-γ] release) in both PLWH and HCs significantly increased in week 4, and the spike-specific T-cell responses in HCs were significantly stronger than those in PLWH 4 weeks after the third vaccination. In the AIM assay, spike-specific CD4+ T-cell responses peaked in both PLWH and HCs in week 12. Additionally, significantly higher spike-specific CD8+ T-cell responses were induced in PLWH than in HCs in week 12. In PLWH, the release of the cytokines interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-α), and IL-22 by peripheral blood mononuclear cells (PBMCs) that were stimulated with spike peptides increased in week 12. In addition, the levels of IL-4 and IL-5 were higher in PLWH than in HCs in week 12. Interestingly, the magnitude of SARS-CoV-2-specific T-cell responses in PLWH was negatively associated with the extent of CD8+ T-cell activation and exhaustion. In addition, positive correlations were observed between the magnitude of spike-specific T-cell responses (determined by measuring IFN-γ release by ELISpot) and the amounts of IL-4, IL-5, IL-2 and IL-17F.

Conclusions:
Our findings suggested that SARS-CoV-2-specific T-cell responses could be enhanced by the booster dose of inactivated COVID-19 vaccines and further illustrate the importance of additional vaccination for PLWH.
Necrotizing Fasciitis of the Hand: Management with Literature Review
Authors: Delavari Sarina , Megas Ioannis-Fivos , Billner Moritz , Reichert Bert , Breidung David 
Published: July 2024

Summary:
This report presents a case of necrotizing fasciitis following a seemingly minor injury sustained from handling a spiny plant. Despite initial primary care by a physician, the patient presented with severe septic shock and necrotizing fasciitis of the hand, necessitating emergency surgical intervention. The use of scoring systems aided in the prompt recognition of the condition. Subsequent surgery was required due to infection progression, leading to significant soft tissue defects and functional impairment. The patient underwent multiple reconstructive procedures, including placement of dermis-replacement material and, ultimately, free flap reconstruction, to restore the hand function. This case report highlights the importance of rapid identification of potential cases of necrotizing fasciitis in cases of hand infections, demonstrates that scoring systems can assist in smaller affected body sites such as the hand, and illustrates the difficulties of defect reconstruction following necrotizing fasciitis.
PGD2/DP1 axis promotes liver regeneration by secreting Wnt2 in KCs in mice
Authors: Li Juanjuan , Zheng Yinghong , Duan Zhenzhen , Zeng Qingye , Qu Jin , Zhang Jincheng , Liu Jiao , Shang Wenlong , Tao Xixi , Yu Tingting , Li Xinzhi , Wang Lifu , Yang Liming , Kong Deping , Yu Ying 
Published: July 2024

Background and Aims:
The liver possesses a remarkable regenerative capacity in response to injuries or viral infections. Various growth factors and cytokines are involved in regulating liver regeneration. Prostaglandin D2, a pro-resolution lipid mediator, is the most abundant hepatic prostanoid. However, the role of prostaglandin D2 in the injury-induced liver regeneration remains unclear.

Approach and Results:
Two-thirds partial hepatectomy (70% PH), massive hepatectomy (85% resection), and carbon tetrachloride-induced chronic injury were performed in mice to study the mechanisms of live regeneration. Hepatic prostaglandin D2 production was elevated in mice after PH. Global deletion of D prostanoid receptor (DP) 1, but not DP2, slowed PH-induced liver regeneration in mice, as evidenced by lower liver weight to body weight ratio, less Ki67+ hepatocyte proliferation, and G2/M phase hepatocytes. In addition, DP1 deficiency, specifically in resident KCs, and not in endothelial cells or HSCs, retarded liver regeneration in mice after PH. Conversely, the overexpression of exogenous DP1 in KCs accelerated liver regeneration in mice. Mechanistically, DP1 activation promoted Wnt2 transcription in a PKA/CREB-dependent manner in resident KCs and mediated hepatocyte proliferation through Frizzled8/β-catenin signaling. Adeno-associated virus vector serotype 8–mediated Frizzled8 knockdown in hepatocytes attenuated accelerated liver regeneration in KC-DP1 transgenic mice after PH. Treatment with the DP1 receptor agonist BW245C promotes PH-induced liver regeneration in mice.

Conclusions:
DP1 activation mediates crosstalk between KCs and hepatocytes through Wnt2 and facilitates liver regeneration. Hence, DP1 may serve as a novel therapeutic target in acute and chronic liver diseases.