Search

Abstract Background Studies have found that the ratio of total cholesterol to high‐density lipoprotein cholesterol (TC/HDL‐C) was associated with the development of chronic kidney disease (CKD). However, the relationship in different genders was rarely discussed. The aim of this study was to explore this relationship and assess its predictive power for both males and females. Methods Based on a prospective cohort platform in northwest China, 32,351 participants without CKD were collected in the baseline and followed up for approximately 5 years. Cox proportional hazard model and restricted cubic spline regression analysis were performed to investigate the association between TC, HDL‐C, TC/HDL‐C and CKD in adult female and male. The clinical application value of the indicators in predicting CKD was evaluated by the receiver operator characteristic curve. Results During a mean follow‐up of 2.2 years, 484 males and 164 females developed CKD. After adjusted for relevant confounders, for every one standard deviation increase in TC, HDL‐C and TC/HDL‐C, the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for CKD were 1.17 (1.05–1.31), 0.84 (0.71–0.99), and 1.15 (1.06–1.25) for males, 0.94 (0.78–1.13), 0.58 (0.35–0.95), and 1.19 (1.01–1.40) for females, respectively. The results also showed that TC, HDL‐C, and TC/HDL‐C were associated with CKD in a linear dose–response relationship. The TC/HDL‐C had the largest area under the curve (AUC) compared to TC and HDL‐C, and the AUC among the females was larger than that among males. Conclusions The TC/HDL‐C was significantly associated with CKD in adult males and females and has better clinical value in predicting CKD than TC and HDL‐C, especially in females.

Abstract The stability of hybrid organic–inorganic halide perovskite semiconductors remains a significant obstacle to their application in photovoltaics. To this end, the use of low‐dimensional (LD) perovskites, which incorporate hydrophobic organic moieties, provides an effective strategy to improve their stability, yet often at the expense of their performance. To address this limitation, supramolecular engineering of noncovalent interactions between organic and inorganic components has shown potential by relying on hydrogen bonding and conventional van der Waals interactions. Here, the capacity to access novel LD perovskite structures that uniquely assemble through unorthodox S‐mediated interactions is explored by incorporating benzothiadiazole‐based moieties. The formation of S‐mediated LD structures is demonstrated, including one‐dimensional (1D) and layered two‐dimensional (2D) perovskite phases assembled via chalcogen bonding and S–π interactions. This involved a combination of techniques, such as single crystal and thin film X‐ray diffraction, as well as solid‐state NMR spectroscopy, complemented by molecular dynamics simulations, density functional theory calculations, and optoelectronic characterization, revealing superior conductivities of S‐mediated LD perovskites. The resulting materials are applied in n‐i‐p and p‐i‐n perovskite solar cells, demonstrating enhancements in performance and operational stability that reveal a versatile supramolecular strategy in photovoltaics.

Abstract Organic‐hybrid particle‐based materials are increasingly important in (opto)electronics, sensing, and catalysis due to their printability and stretchability as well as their potential for unique synergistic functional effects. However, these functional properties are often limited due to poor electronic coupling between the organic shell and the nanoparticle. N‐heterocyclic carbenes (NHCs) belong to the most promising anchors to achieve electronic delocalization across the interface, as they form robust and highly conductive bonds with metals and offer a plethora of functionalization possibilities. Despite the outstanding potential of the conductive NHC‐metal bond, synthetic challenges have so far limited its application to the improvement of colloidal stabilities, disregarding the potential of the conductive anchor. Here, NHC anchors are used to modify redox‐active gold nanoparticles (AuNPs) with conjugated triphenylamines (TPA). The resulting AuNPs exhibit excellent thermal and redox stability benefiting from the robust NHC‐gold bond. As electrochromic materials, the hybrid materials show pronounced color changes from red to dark green, a highly stable cycling stability (1000 cycles), and a fast response speed (5.6 s/2.1 s). Furthermore, TPA‐NHC@AuNP exhibits an ionization potential of 5.3 eV and a distinct out‐of‐plane conductivity, making them a promising candidate for application as hole transport layers in optoelectronic devices.

Abstract Background Hemifacial macrosomia (HFM, OMIM 164210) is a complex and highly heterogeneous disease. FORKHEAD BOX I3 (FOXI3) is a susceptibility gene for HFM, and mice with loss of function of Foxi3 did exhibit a phenotype similar to craniofacial dysmorphism. However, the specific pathogenesis of HFM caused by FOXI3 deficiency remains unclear till now. Method In this study, we first constructed a Foxi3 deficiency (Foxi3−/−) mouse model to verify the craniofacial phenotype of Foxi3−/− mice, and then used RNAseq data for gene differential expression analysis to screen candidate pathogenic genes, and conducted gene expression verification analysis using quantitative real‐time PCR. Results By observing the phenotype of Foxi3−/− mice, we found that craniofacial dysmorphism was present. The results of comprehensive bioinformatics analysis suggested that the craniofacial dysmorphism caused by Foxi3 deficiency may be involved in the PI3K‐Akt signaling pathway. Quantitative real‐time PCR results showed that the expression of PI3K‐Akt signaling pathway‐related gene Akt2 was significantly increased in Foxi3−/− mice. Conclusion The craniofacial dysmorphism caused by the deficiency of Foxi3 may be related to the expression of Akt2 and PI3K‐Akt signaling pathway. This study laid a foundation for understanding the function of FOXI3 and the pathogenesis and treatment of related craniofacial dysmorphism caused by FOXI3 dysfunction.

Abstract Background Montelukast is a highly selective and specific cysteinyl leukotriene receptor antagonist used in the treatment of asthma. Whether montelukast as adjuvant therapy can significantly and safely treat adults with cough variant asthma (CVA) remains inconclusive. Aims This meta‐analysis systematically evaluated the efficacy and safety of montelukast as an adjuvant treatment for adults with CVA. Materials and methods Randomized controlled trials (RCTs) on montelukast combined with inhaled corticosteroids (ICS) and long‐acting β2 agonists (LABAs) to treat CVA in adults, from inception to March 6, 2023, were retrieved from the CNKI, Wanfang, VIP, CBM, PubMed, Embase, Cochrane Library, and Web of Science databases and Clinical Trials website. Review Manager (version 5.4) and Stata (version 15.0) were used to conduct the meta‐analysis. Results A total of 15 RCTs were ultimately included in the meta‐analysis. It was established that montelukast as adjuvant therapy raised the total effective rate (RR = 1.20, 95% confidence interval [CI] [1.13, 1.27], P < 0.01) and improved the FEV1% (SMD = 0.91, 95% CI [0.40, 1.41], P < 0.01), PEF% (SMD = 0.63, 95% CI [0.38, 0.88], P < 0.01), FEV1 (SMD = 1.15, 95% CI [0.53, 1.77], P < 0.01), PEF (SMD = 0.64, 95% CI [0.42, 0.86], P < 0.01), and FEV1/FVC% (SMD = 0.76, 95% CI [0.51, 1.01], P < 0.01) and reduced the recurrence rate (RR = 0.28, 95% CI [0.15, 0.53], P < 0.01). The incidence of adverse reactions was higher in the montelukast auxiliary group compared to the control group but with no statistical difference (RR = 1.32, 95% CI [0.89, 1.96], P = 0.17). Conclusion Existing evidence indicated that the use of montelukast as an adjuvant therapy had therapeutic efficacy superior to ICS + LABA alone for the treatment of adult patients with CVA. However, further research is needed, especially a combination of high‐quality long‐term prospective studies and carefully designed RCTs.

Abstract Background Pediatric interventional oncology (PIO) is a growing field intended to provide additional or alternative treatment options for pediatric patients with benign or malignant tumors. Large series of patients treated uniformly and subjected to rigorous endpoints for efficacy are not available. Methods We designed a collaborative initiative to capture data from pediatric patients with benign and malignant tumors who underwent a therapeutic interventional radiology procedure. Modified Response Evaluation Criteria in Solid Tumors (mRECIST) was utilized as a measure of radiologic response and data were collected regarding improvement in pain and functional endpoints. Cumulative incidence of progressive disease was calculated using both the treated site and the patient as the analytic unit. Findings Forty patients, 16 with malignant tumors and 24 with benign tumors, underwent a total of 88 procedures. Cryo‐ and radiofrequency ablation were the most frequently utilized techniques for both cohorts of patients. A complete or partial response, or prolonged disease stability, were achieved in approximately 40% of patients with malignant tumors and 60% of patients with benign tumors. No patients had progressive disease as their best response. Resolution of pain and improved mobility with return‐to‐baseline activity were demonstrated across patients from both cohorts. Only minor complications were experienced. Interpretation Interventional radiology‐guided interventions can serve as an alternative or complementary approach to the treatment of benign and malignant tumors in pediatric patients. Prospective, multi‐institutional trials are required to adequately study utility, treatment endpoints, and durability of response.

Conclusion: We intend to educate providers on the appropriate time to intervene to reduce mortality and subsequent hospitalizations for those with advanced liver disease.

Abstract Background The understanding of the heterogeneous cellular microenvironment of colonic polyps in paediatric patients with solitary juvenile polyps (SJPs), polyposis syndrome (PJS) and Peutz–Jeghers syndrome (PJS) remains limited. Methods We conducted single‐cell RNA sequencing and multiplexed immunohistochemistry (mIHC) analyses on both normal colonic tissue and different types of colonic polyps obtained from paediatric patients. Results We identified both shared and disease‐specific cell subsets and expression patterns that played important roles in shaping the unique cellular microenvironments observed in each polyp subtype. As such, increased myeloid, endothelial and epithelial cells were the most prominent features of SJP, JPS and PJS polyps, respectively. Noticeably, memory B cells were increased, and a cluster of epithelial–mesenchymal transition (EMT)‐like colonocytes existed across all polyp subtypes. Abundant neutrophil infiltration was observed in SJP polyps, while CX3CR1hi CD8+ T cells and regulatory T cells (Tregs) were predominant in SJP and JPS polyps, while GZMAhi natural killer T cells were predominant in PJS polyps. Compared with normal colonic tissues, myeloid cells exhibited specific induction of genes involved in chemotaxis and interferon‐related pathways in SJP polyps, whereas fibroblasts in JPS polyps had upregulation of myofiber‐associated genes and epithelial cells in PJS polyps exhibited induction of a series of nutrient absorption‐related genes. In addition, the TNF‐α response was uniformly upregulated in most cell subsets across all polyp subtypes, while endothelial cells and fibroblasts separately showed upregulated cell adhesion and EMT signalling in SJP and JPS polyps. Cell–cell interaction network analysis showed markedly enhanced intercellular communication, such as TNF, VEGF, CXCL and collagen signalling networks, among most cell subsets in polyps, especially SJP and JPS polyps. Conclusion These findings strengthen our understanding of the heterogeneous cellular microenvironment of polyp subtypes and identify potential therapeutic approaches to reduce the recurrence of polyps in children.

Introduction Importance:Tenecteplase (TNK) use is more prevalent as the thrombolytic drug of choice for acute ischemic stroke (AIS), given its ease of use with results from randomized trials showing non‐ inferiority and comparable safety to Alteplase (tPA). However, there is conflicting data in terms of intracranial hemorrhage risk. Objective: We are reporting the rate of symptomatic intracranial hemorrhage(sICH) in TNK and tPA treated stroke populations across two large hospital systems. Methods Design: Retrospective cohort observational study. Data was collected from April 1, 2022 through March 29, 2023. Setting: Data was collected from 15 stroke centers: 10 primary and 5 comprehensive stroke centers in Texas. Participants: Inclusion criteria: 18 years or older, suspected to have an AIS were eligible to receive thrombolytic therapy, and received either IV TNK or tPA at the standard dose. A total of 431 patients were included. 216 patients received alteplase and 215 patients received tenecteplase. Exposure: Data was collected 90 days before and 90 days after the stroke center changed from tPA to TNK. Main Outcomes: The primary endpoint was to compare the incidence of sICH according to SITS‐MOST/ECASS‐3 criteria in the tPA and TNK groups. Secondary endpoints included the radiographic pattern of hemorrhagic conversion according to the Heidelberg bleeding classification (HBc). Results A total of 431 patients; half of them had been administered Alteplase (n=216) and the other half had Tenecteplase (n=215). Approximately half of them were females 110 (51%) for alteplase and 117 (54%) for Tenecteplase. Almost 2/3 of the study population never smoked; 66% for alteplase 64% for Tenecteplase. Majority of the patient population got thrombolytic therapy within 3 hours 174 (81%) for alteplase versus 176 (82%) for Tenecteplase. 34 patients (15%) in the alteplase group as compared to 26 patients (12%) in the Tenecteplase group had endovascular thrombectomy attempted. 7 patients in the tPA group (3.2%) and 14 patients (6.5%) in the TNK group had sICH. An increase in the NIHSS on arrival (p=0.048) was a statistically significant predictor of sICH. A two sample proportion test on TNK produced a statistically significant increase in Heidelberg Bleed class 3 (HBc3) (p=0.040) over tPA. Conclusion We observed increased cases of bleeding associated with TNK administration with statistically significant increase in the HBc3 when compared to patients who received tPA. Suggested mechanisms of bleeding are hemorrhagic conversion in clinically silent infarcts, and contusions underlying the lesions. These findings suggest a potential need to reevaluate the criteria for administering TNK to patients. Larger studies are required to confirm this data.

Key Clinical Message Treatment of recurrent myelodysplastic syndrome (MDS) after hematopoietic cell transplantation (HCT) remains challenging. We present a 4‐year‐old girl experiencing early MDS relapse post‐HCT treated with a multimodal strategy encompassing a second HCT and innovative targeted therapies. We underscore the potential of a comprehensive treatment approach in managing recurrent pediatric MDS.

Abstract Background Dysferlinopathy has a high prevalence in relatively isolated ethnic groups where consanguineous marriages are characteristic and/or the founder effect exists. However, the frequency of endemic mutations in most isolates has not been investigated. Methods The prevalence of the pathological DYSF gene variant (NM_003494.4); c.200_201delinsAT, p. Val67Asp (rs121908957) was investigated in an isolated Avar population in the Republic of Dagestan. Genetic screenings were conducted in a remote mountainous region characterized by a high level of consanguinity among its inhabitants. In total, 746 individuals were included in the screenings. Results This pathological DYSF gene variant causes two primary phenotypes of dysferlinopathy: limb‐girdle muscular dystrophy (LGMD) type R2 and Miyoshi muscular dystrophy type 1. Results indicated a high prevalence of the allele at 14% (95% confidence interval [CI]: 12–17; 138 out of 1518 alleles), while the allele in the homozygous state was detected in 29 cases—3.8% (CI: 2.6–5.4). The population load for dysferlinopathy was 832.3 ± 153.9 per 100,000 with an average prevalence of limb‐girdle muscular dystrophies ranging from 0.38 ± 0.38 to 5.93 ± 1.44 per 100,000. Conclusion A significant burden of the allele was due to inbreeding, as evidenced by a deficiency of heterozygotes and the Wright fixation index equal to 0.14 (CI 0.06–0.23).

Abstract This paper examines business performance and crisis‐mitigation strategies among micro, small, and medium‐sized enterprises (MSMEs) in Indonesia during the COVID‐19 pandemic. We utilise a new primary dataset based on administrative records, survey data, and follow‐up interviews with merchants using the digital application GoFood, an on‐demand cooked food delivery service. Three empirical findings emerge: first, the overall employment size of women‐owned businesses shrank more than men‐owned businesses after the onset of the pandemic; second, women were more likely than men to cut personal expenditures and use government assistance as crisis‐mitigation strategies; and third, competition increased sharply as new merchants entered the platform, with the service areas of both incumbents and entrants shrinking over time. These results have implications for policies on womenʼs entrepreneurship, the uptake of business development services, and financing programs for MSMEs.

Abstract The IMPROVE study (NCT02408315) compared the efficacy and safety of vaginal and buccal administration of misoprostol for full‐term, uncomplicated labor induction. This report compares the pharmacokinetics of misoprostol between vaginal and buccal routes. Women greater than or equal to 14 years of age undergoing induction of labor greater than or equal to 37 weeks gestation without significant complications were randomized to vaginal or buccal misoprostol 25 μg followed by 50 μg doses every 4 h. Misoprostol acid concentrations were determined using liquid chromatography‐tandem mass spectrometry for the first 8 h in a subgroup of participants. A population pharmacokinetic model was developed using NONMEM. Plasma concentrations (n = 469) from 47 women were fit to a one‐compartment nonlinear clearance model. The absorption rate constant (ka) was dependent on both route and dose of administration: buccal 25 μg 0.724 (95% confidence interval, 0.54–0.92) h−1; 50 μg 0.531 (0.37–0.63) h−1; vaginal 25 μg 0.507 (0. 2–1. 4) h−1; and 50 μg 0.246 (0.103–0.453) h−1. Relative bioavailability for vaginal compared to buccal route was 2.4 (1.63–4.77). There was no effect of body mass index or age on apparent clearance 705 (431–1099) L/h or apparent volume of distribution 632 (343–1008) L. The area under the concentration–time curve to 4 h following the first 25 μg dose of misoprostol was 16.5 (15.4–17.5) pg h/ml for buccal and 34.3 (32.5–36.1) pg h/ml for vaginal administration. The rate of buccal absorption was two times faster than that of vaginal, whereas bioavailability of vaginal administration was 2.4 times higher than that of buccal. Decreased time to delivery observed with vaginal dosing may be due to higher exposure to misoprostol acid compared to buccal.

Abstract Introduction Following approval in 2009 of vagus nerve stimulation (VNS Therapy) for drug‐resistant epilepsy (DRE) in the Russian Federation, this is the first multicenter study across Russia to evaluate the safety and efficacy of adjunctive VNS Therapy. Methods The retrospective, observational registry included 58 pediatric patients with DRE (5–17 years old at implantation) who had ≥2 years of VNS. To ensure a robust evaluation process, changes in seizure frequency were evaluated for all seizure types as well as “most disabling” seizures (defined as seizures accompanied by falls, physical trauma, and/or incontinence in the absence of preventative measures). Results With 2 years of VNS Therapy, 37 of 49 patients (76%) experiencing the most disabling epileptic seizures had a >50% decrease in frequency of such seizures, and 16 (33%) reported no longer experiencing the “most disabling” seizure type. In addition, based on the McHugh Outcome scale, VNS Therapy had a positive outcome on both frequency and severity of all epileptic seizure types, with a >50% decrease in frequency of all epileptic seizure types noted in 37 of 58 patients (64%), and 31% of patients had a Class I outcome, including 11 patients (19%) who achieved seizure freedom. VNS Therapy also had a positive effect on the frequency of status epilepticus: 13 patients (22%) had status epilepticus prior to implantation with a mean rate of 9.4 ± 17.7 events per year (range, 0–52), and after VNS Therapy, only one patient continued to experience status epilepticus (at 1 event per 4–6 months). VNS Therapy had an acceptable safety profile and no adverse events leading to VNS discontinuation were reported. Conclusions The results demonstrate that VNS Therapy is being safely and effectively applied to pediatric patients in the Russian healthcare system.

Availability of haploidentical donors has broadened utilization of allogeneic hematopoietic cell transplantation (allo-HCT). Peripheral blood stem cells (PBSC) are being used with increased frequency in haploidentical allo-HCT. We evaluated extent of HLA disparity (2–3/8 versus 4/8 HLA antigen mismatches) on post-allograft outcomes when using T-cell replete PBSC from haploidentical donors for acute myeloid leukemia in first complete remission. Primary objectives entailed assessing cumulative incidence of grade 2–4 acute graft-versus-host disease (GVHD) and chronic GVHD (any grade). A total of 645 patients received a haploidentical allo-HCT from a donor with either 2–3 of 8 HLA antigen mismatches (n = 180) or with 4 of 8 HLA antigen mismatches (n = 465). Presence of 2–3 of 8 versus 4 of 8 HLA mismatches did not affect the incidence of acute GVHD (grade 2–4) and chronic GVHD (any grade). Overall survival (OS), leukemia-free survival (LFS) relapse incidence (RI), nonrelapse mortality and the composite endpoint of GVHD-free relapse-free survival were also similar among the groups. Pertaining to HLA-B leader matching effect, our analysis did not discern any difference in aforementioned post-allograft outcomes for this variable. However, in univariate analysis, absence of an antigen mismatch in HLA-DPB1 showed a trend for better OS. Notwithstanding inherent limitations associated with registry data, our results did not show an advantage of selecting a haploidentical donor with 2–3 of 8 HLA antigen mismatches over one with 4 of 8 HLA antigen mismatches when using PBSC as the cell source. Adverse cytogenetics remains a major adverse determinant of inferior OS and LFS and a higher RI. Using reduced-intensity conditioning yielded worse OS and LFS.

Abstract Driven by their many unique features, perovskite solar cells (PSCs) have become one of the most promising candidates in the photovoltaic field. Two‐step preparation of perovskite film is advantageous for its higher stability and reproducibility compared to the one‐step method, which is more suitable for practical application. However, the incomplete conversion of the dense lead iodide (PbI2) layer during the sequential spin‐coating of formamidinium/methylammonium (FA+/MA+) organic amine salts severely affect the performance of PSCs. Herein, sodium bicarbonate (NaHCO3) is used to induce the formation of porous PbI2, which facilitates the penetration of the FA+/MA+ ions and the formation of a perovskite film with high crystallinity and large grain microstructure. Meanwhile, the introduction of Na+ not only improves the energetic alignment of the PSC, but also increases the conductivity via p‐doping. As a result, the optimized NaHCO3‐modified PSC achieves a champion power conversion efficiency of 24.0% with suppressed hysteresis. Moreover, the significant reduction in defect density and ion migration as well as a mild alkaline environment enhance the stability of device. The unencapsulated NaHCO3‐modified PSCs maintain over 90% of their original efficiency upon storage in ambient air (30%–40% relative humidity) for 2160 h. We have demonstrated an ingenious strategy for controlling the quality of perovskite and improving the performance of device by low‐temperature foaming of simple inorganic molecules of NaHCO3.

Abstract Named entity recognition (NER) is an important task in the field of natural language processing, but it is more challenging in Chinese because of the lack of natural delimiters. The traditional character‐based Chinese NER model directly uses long short‐term memory (LSTM), gated recurrent units, and other sequence models to extract sentence‐level information from character sequences, resulting in the lack of word‐level information in the model. Therefore, a Chinese NER model called ChineseBERT‐CNNs‐BiLSTM‐CRF was proposed, which uses the ChineseBERT pretrained model as the embedding layer so that the vector representation of each Chinese character contained pinyin, glyph, and conventional character information. In addition, a CNN‐based neural network structure called CNNs was presented to extract word‐level information from character sequences and alleviate the problem of entity boundary recognition. BiLSTM was used to extract global features (i.e., sentence‐level information) and predict the corresponding labels of character sequences. Further, conditional random field (CRF) was employed to impose certain rules on the prediction of BiLSTM to enhance the recognition effect of the model. The experimental results revealed that the F1 values of the model on MSRA, people's Daily, and Weibo datasets reached 95.76, 96.61, and 70.00%, respectively, highlighting the effectiveness of the model.

Abstract Metal halide perovskites are an emerging class of crystalline semiconductors of great interest for application in optoelectronics. Their properties are dictated not only by their composition, but also by their crystalline structure and microstructure. While significant efforts are dedicated to the development of strategies for microstructural control, significantly less is known about the processes that govern the formation of their crystalline structure in thin films, in particular in the context of crystalline orientation. This work investigates the formation of highly oriented triple cation perovskite films fabricated by utilizing a range of alcohols as an antisolvent. Examining the film formation by in situ grazing‐incidence wide‐angle X‐ray scattering reveals the presence of a short‐lived highly oriented crystalline intermediate, which is identified as FAI‐PbI2‐xDMSO. The intermediate phase templates the crystallization of the perovskite layer, resulting in highly oriented perovskite layers. The formation of this dimethylsulfoxide (DMSO) containing intermediate is triggered by the selective removal of N,N‐dimethylformamide (DMF) when alcohols are used as an antisolvent, consequently leading to differing degrees of orientation depending on the antisolvent properties. Finally, this work demonstrates that photovoltaic devices fabricated from the highly oriented films, are superior to those with a random polycrystalline structure in terms of both performance and stability.

Abstract Background Patients with acute alcohol‐associated hepatitis (AH) have immune dysfunction. Mitochondrial function is critical for immune cell responses and regulates senescence. Clinical translational studies using complementary bioinformatics‐experimental validation of mitochondrial responses were performed in peripheral blood mononuclear cells (PBMC) from patients with AH, healthy controls (HC), and heavy drinkers without evidence of liver disease (HD). Methods Feature extraction for differentially expressed genes (DEG) in mitochondrial components and telomere regulatory pathways from single‐cell RNAseq (scRNAseq) and integrated ‘pseudobulk’ transcriptomics from PBMC from AH and HC (n = 4 each) were performed. After optimising isolation and processing protocols for functional studies in PBMC, mitochondrial oxidative responses to substrates, uncoupler, and inhibitors were quantified in independent discovery (AH n = 12; HD n = 6; HC n = 12) and validation cohorts (AH n = 10; HC n = 7). Intermediary metabolites (gas‐chromatography/mass‐spectrometry) and telomere length (real‐time PCR) were quantified in subsets of subjects (PBMC/plasma AH n = 69/59; HD n = 8/8; HC n = 14/27 for metabolites; HC n = 13; HD n = 8; AH n = 72 for telomere length). Results Mitochondrial, intermediary metabolite, and senescence‐regulatory genes were differentially expressed in PBMC from AH and HC in a cell type–specific manner at baseline and with lipopolysaccharide (LPS). Fresh PBMC isolated using the cell preparation tube generated optimum mitochondrial responses. Intact cell and maximal respiration were lower (p ≤ .05) in AH than HC/HD in the discovery and validation cohorts. In permeabilised PBMC, maximum respiration, complex I and II function were lower in AH than HC. Most tricarboxylic acid (TCA) cycle intermediates in plasma were higher while those in PBMC were lower in patients with AH than those from HC. Lower telomere length, a measure of cellular senescence, was associated with higher mortality in AH. Conclusion Patients with AH have lower mitochondrial oxidative function, higher plasma TCA cycle intermediates, with telomere shortening in nonsurvivors.

Abstract Introduction People who inject drugs (PWID) in Ukraine have high prevalences of HIV and hepatitis C virus (HCV). Non‐governmental organizations (NGOs) provide PWID with needles/syringes, condoms, HIV/HCV testing and linkage to opioid agonist treatment (OAT) and antiretroviral therapy (ART). We estimated their impact and cost‐effectiveness among PWID. Methods A dynamic HIV and HCV transmission model among PWID was calibrated using data from four national PWID surveys (2011–2017). The model assumed 37–49% coverage of NGOs among community PWID, with NGO contact reducing injecting risk and increasing condom use and recruitment onto OAT and ART. We estimated the historic (1997–2021) and future (2022–2030, compared to no NGO activities from 2022) impact of NGOs in terms of the proportion of HIV/HCV infections averted and changes in HIV/HCV incidence. We estimated the future impact of scaling‐up NGOs to 80% coverage with/without scale‐up in OAT (5–20%) and ART (64–81%). We estimated the cost per disability‐adjusted life‐year (DALY) averted of current NGO provision over 2022–2041 compared to NGO activities stopping over 2022–2026, but restarting after that till 2041. We assumed average unit costs of US$80–90 per person‐year of NGO contact for PWID. Results With existing coverage levels of NGOs, the model projects that NGOs have averted 20.0% (95% credibility interval: 13.3–26.1) and 9.6% (5.1–14.1) of new HIV and HCV infections among PWID over 1997–2021, respectively, and will avert 31.8% (19.6–39.9) and 13.7% (7.5–18.1) of HIV and HCV infections over 2022–2030. With NGO scale‐up, HIV and HCV incidence will decrease by 54.2% (43.3–63.8) and 30.2% (20.5–36.2) over 2022–2030, or 86.7% (82.9–89.3) and 39.8% (31.4–44.8) if OAT and ART are also scaled‐up. Without NGOs, HIV and HCV incidence will increase by 51.6% (23.6–76.3) and 13.4% (4.8–21.9) over 2022–2030. Current NGO provision over 2022–2026 will avert 102,736 (77,611–137,512) DALYs when tracked until 2041 (discounted 3% annually), and cost US$912 (702–1222) per DALY averted; cost‐effective at a willingness‐to‐pay threshold of US$1548/DALY averted (0.5xGDP). Conclusions NGO activities have a crucial preventative impact among PWID in Ukraine which should be scaled‐up to help achieve HIV and HCV elimination. Disruptions could have a substantial detrimental impact.

Abstract Background Chronic obstructive pulmonary disease (COPD) patients exhibit skeletal muscle atrophy, denervation, and reduced mitochondrial oxidative capacity. Whilst chronic tobacco smoke exposure is implicated in COPD muscle impairment, the mechanisms involved are ambiguous. The aryl hydrocarbon receptor (AHR) is a ligand‐activated transcription factor that activates detoxifying pathways with numerous exogenous ligands, including tobacco smoke. Whereas transient AHR activation is adaptive, chronic activation can be toxic. On this basis, we tested the hypothesis that chronic smoke‐induced AHR activation causes adverse muscle impact. Methods We used clinical patient muscle samples, and in vitro (C2C12 myotubes) and in vivo models (mouse), to perform gene expression, mitochondrial function, muscle and neuromuscular junction morphology, and genetic manipulations (adeno‐associated virus‐mediated gene transfer). Results Sixteen weeks of tobacco smoke exposure in mice caused muscle atrophy, neuromuscular junction degeneration, and reduced oxidative capacity. Similarly, smoke exposure reprogrammed the muscle transcriptome, with down‐regulation of mitochondrial and neuromuscular junction genes. In mouse and human patient specimens, smoke exposure increased muscle AHR signalling. Mechanistically, experiments in cultured myotubes demonstrated that smoke condensate activated the AHR, caused mitochondrial impairments, and induced an AHR‐dependent myotube atrophy. Finally, to isolate the role of AHR activity, expression of a constitutively active AHR mutant without smoke exposure caused atrophy and mitochondrial impairments in cultured myotubes, and muscle atrophy and neuromuscular junction degeneration in mice. Conclusions These results establish that chronic AHR activity, as occurs in smokers, phenocopies the atrophy, mitochondrial impairment, and neuromuscular junction degeneration caused by chronic tobacco smoke exposure.

Abstract Noninvasive assessment of pulmonary hemodynamics is often performed by echocardiographic estimation of the pulmonary artery systolic pressure (ePASP), despite limitations in the advanced lung disease population. Other noninvasive hemodynamic variables, such as echocardiographic pulmonary vascular resistance (ePVR), have not been studied in this population. We performed a retrospective analysis of 147 advanced lung disease patients who received both echocardiography and right heart catheterization for lung transplant evaluation. The ePVR was estimated by four previously described equations. Noninvasive and invasive hemodynamic parameters were compared in terms of correlation, agreement, and accuracy. The ePVR models strongly correlated with invasively determined PVR and had good accuracy with biases of

Abstract The design and characterization of spatiotemporal nano‐/micro‐structural arrangement that enable real‐time and wide‐spectrum molecular analysis is reported and demonestrated in new horizons of biomedical applications, such as wearable‐spectrometry, ultra‐fast and onsite biopsy‐decision‐making for intraoperative surgical oncology, chiral‐drug identification, etc. The spatiotemporal sesning arrangement is achieved by scalable, binder‐free, functionalized hybrid spin‐sensitive (

Abstract Interventions in Africa designed to stop biodiversity decline have often failed because they were based on a top‐down approach to management and focused on enforcing restrictive rules and imposing bans. They were equally misaligned with the values and needs of local actors. This paper presents an African perspective on the discourse regarding the bushmeat crisis and shows that bushmeat in Africa goes beyond being a source of livelihood, having a multifaceted use that must be considered when designing interventions. We show that current conservation initiatives often do not address the right issues, by neglecting nonmonetary dimensions of bushmeat use, inadequately planning interventions, failing to align wildlife laws with realities on the ground, and carrying out ineffective law enforcement characterized by poor governance and corruption. We recommend a revision of current legal frameworks to enhance local ownership, tenure rights, and the sustainable economic empowerment of local communities to reduce hunting. We also call for development of regionally led innovative programs that invest in nature‐based solutions and payments for environmental services. Finally, we identify where more research is needed to understand why wildlife use in Africa is overlooked in national development policies and not considered in national accounting.

Abstract Background Hepatits C virus (HCV) rates have lowered due to direct‐acting antiviral treatment. Nonalcoholic steatohepatitis (NASH)/nonalcoholic fatty liver disease (NAFLD) is rising with no available therapy. We employed text‐mining to analyze trends in HCV and NAFLD research from the past two decades. Materials and Methods We queried PubMed for all HCV and NASH/NAFLD entries published between 2000 and 2020. We compared the total number of publications on both etiologies. We performed subanalyses for different terms of interest and for geographic origin. Results Overall, 75,934 HCV‐related entries and 24,987 NASH/NAFLD‐related entries were published during the study period. Up to 2015, there was a linear upward slope in the number of annual HCV publications (154.9 publications/year, p

Abstract Background Charcot‐Leyden crystals (CLCs) are recognized to be classic hallmarks of eosinophilic inflammation. Both protein and mRNA levels of CLC in nasal secretions and nasal brushing samples have been associated with nasal polyp recurrence. However, whether the crystalline CLC structures in nasal tissue could serve as an effective biomarker to predict polyp recurrence remains unclear. Methods A total of 110 patients with chronic rhinosinusitis with nasal polyps (CRSwNP) completing the postoperative follow‐up over a period of 24 months were recruited. Hematoxylin and eosin staining was employed for CLCs identification. The predictive factors for polyp recurrence were determined by binary logistic regression analysis. Results Thirty three (30.00%) patients developed recurrence during a 24‐month postoperative follow‐up, in which 84.85% (28/33) patients had crystalline CLC structures. Logistic regression analysis showed that crystalline CLC structure in nasal tissues is predictive of polyp recurrence. Youden index demonstrated crystalline CLC structure higher than 1 per high power field can predict postoperative polyp recurrence with 84.80% sensitivity and 98.70% specificity. Conclusions The crystalline CLC structures in nasal tissues may serve as an easy‐counting and promising biomarker to predict CRSwNP recurrence.

Abstract A comprehensive study of the optical properties of CsPbBr3 perovskite multiple quantum wells (MQW) with organic barrier layers is presented. Quantum confinement is observed by a blue‐shift in absorption and emission spectra with decreasing well width and agrees well with simulations of the confinement energies. A large increase of emission intensity with thinner layers is observed, with a photoluminescence quantum yield up to 32 times higher than that of bulk layers. Amplified spontaneous emission (ASE) measurements show very low thresholds down to 7.3 µJ cm−2 for a perovskite thickness of 8.7 nm, significantly lower than previously observed for CsPbBr3 thin‐films. With their increased photoluminescence efficiency and low ASE thresholds, MQW structures with CsPbBr3 are excellent candidates for high‐efficiency perovskite‐based LEDs and lasers.