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In the ever-evolving world of materials science, modifying natural polymers has garnered significant attention across diverse industries, driven by their inherent availability and cost-effectiveness. Among these, chitosan, a pseudo-natural cationic polymer, has emerged as a versatile player, finding applications in medical, pharmaceutical, filtration, and textile sectors, owing to its exceptional biodegradability, non-allergenicity, antimicrobial properties, and eco-friendly nature. However, the limitations of chitosan, such as low surface area, poor solubility at neutral to alkaline pH, and inadequate thermal-mechanical properties, have prompted researchers to explore innovative modification strategies, including graft copolymerization, quaternization, and cross-linking. This review delves into the remarkable potential of a specific chitosan derivative, N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan salts (N-HTCS), a quaternized form of chitosan. This review uniquely examines the properties and multifaceted applications of N-HTCS, spanning biomedical, textile, food packaging, and environmental domains. The outstanding features of N-HTCS, including antioxidant, anticancer, and antimicrobial bioactivity, as well as biocompatibility, biodegradability, hemostatic, piezoelectric, superparamagnetic, water solubility, and permeation-enhancing effects, offer novel solutions to the limitations of unmodified chitosan. Notably, while previous reviews have addressed the significance of chitosan, this work presents a groundbreaking focus on the N-HTCS derivative, providing a fresh perspective and paving the way for the design and engineering of cutting-edge N-HTCS-based devices and applications. The comprehensive coverage of this review aims to inspire researchers and industry professionals to explore the untapped potential of this remarkable chitosan derivative, unlocking new frontiers in material science and technology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Neuropsychiatric symptoms are common in people with Alzheimer's disease (AD) across all severity stages. Their heterogeneous presentation and variable temporal association with cognitive decline suggest shared and distinct biological mechanisms. We hypothesized that specific patterns of gene expression associate with distinct NIMH Research Domain Criteria (RDoC) domains in AD., Methods: Post-mortem bulk RNAseq on the insula and anterior cingulate cortex from 60 brain donors representing the spectrum of canonical AD neuropathology combined with natural language processing approaches based on the RDoC Clinical Domains., Results: Distinct sets of >100 genes (p FDR <0.05) were specifically associated with at least one clinical domain (Cognitive, Social, Negative, Positive, Arousal). In addition, dysregulation of immune response pathways was shared across domains and brain regions., Discussion: Our findings provide evidence for distinct transcriptional profiles associated with RDoC domains suggesting that each dimension is characterized by specific sets of genes providing insight into the underlying mechanisms.

Background: Low temperature seriously limited the development of grass and crops in plateau. Thus, it is urgent to develop an effective strategy for improving the plant cold tolerance and elucidate the underlying mechanisms., Results: We found that MT alleviated the effects of cold stress on suppressing ENG growth, then improved cold tolerance of ENG. Integration of transcriptome and metabolome profiles showed that both cold exposure (TW) and MT reprogrammed the transcription pattern of galactose and flavonoids biosynthesis, leading to changes in compositions of soluble sugar and flavonoids in ENG. Additionally, TW inhibited the photosynthesis, and destroyed the antioxidant system of ENG, leading to accumulation of oxidant radicals represented by MDA. By contrast, MT promoted activities of antioxidant enzymes and flavonoid accumulation in ENG under cold condition, then reduced the MDA content and maintained normal expression of photosynthesis-related genes in ENG even under TW. Importantly, MT mainly enhanced cold tolerance of ENG via activating zeatin synthesis to regulate flavonoid biosynthesis in vivo. Typically, WRKY11 was identified to regulate MT-associated zeatin synthesis in ENG via directly binding on zeatin3 promoter., Conclusions: MT could enhance ENG tolerance to cold stress via strengthening antioxidant system and especially zeatin synthesis to promote accumulation of flavonoids in ENG. Thus, our research gain insight into the global mechanisms of MT in promoting cold tolerance of ENG, then provided guidance for protecting plant from cold stress in plateau., (© 2024. The Author(s).)

Prior research has demonstrated genome-wide transcriptional changes related to fear and anxiety across species, often focusing on individual brain regions or cell types. However, the extent of gene expression differences across brain regions and how these changes interact at the level of transcriptional connectivity remains unclear. To address this, we performed spatial transcriptomics RNAseq analyses in an auditory threat conditioning paradigm in mice. We generated a spatial transcriptomic atlas of a coronal mouse brain section covering cortical and subcortical regions, corresponding to histologically defined regions. Our finding revealed widespread transcriptional responses across all brain regions examined, particularly in the medial and lateral habenula, and the choroid plexus. Network analyses highlighted altered transcriptional connectivity between cortical and subcortical regions, emphasizing the role of steroidogenic factor 1. These results provide new insights into the transcriptional networks involved in auditory threat conditioning, enhancing our understanding of molecular and neural mechanisms underlying fear and anxiety disorders.

Background: Major Depressive Disorder (MDD) is a heterogenous and etiologically complex disease often presenting with divergent appetitive phenotypes including Hyperphagic MDD (characterized by an increased appetite) and Hypophagic MDD (characterized by a decrease in appetite) which are closely related to comorbidities, including cardiometabolic disorders. Hyperphagia is associated with atypical depression, decreased stress-hormone signaling, a pro-inflammatory status, hypersomnia, and poorer clinical outcomes. Yet, our understanding of associated biological correlates of Hyperphagic and Hypophagic MDD remain fragmented., Methods: We performed an exploratory study on peripheral blood RNA profiling using bulk RNAseq in unmedicated individuals with Hyperphagic and Hypophagic MDD (n = 7 and n = 13, respectively)., Results: At baseline, we discovered an increased expression of TADA2B in hyperphagic MDD with the significant enrichment of 72 gene ontology pathways mainly related to inflammation. In addition, we used the Maastricht Acute Stress Task to uncover stress-related transcriptomic profiles in Hyper- and Hypophagic MDD and discovered the upregulation of CCDC196 and the downregulation of SPATA33 in hyperphagic MDD. Gene ontology enrichment analysis after stress exposure showed pathways related to ribosomal activity., Limitations: The present findings are tempered primarily by the limited sample size, which requires independent replication of this exploratory study. However, stringent methods controlling for false positive findings mitigate the risk associated with sample size limitations., Discussion: Limitations notwithstanding, findings suggest that hyper- and hypophagic MDD is associated with divergent RNA expression profiles in peripheral blood that are amplified by exposure to a controlled stress test. Our findings in a well-controlled study provide evidence for peripheral markers of a relevant endophenotype of MDD., Competing Interests: Declaration of competing interest The authors do not declare any relevant conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Sympathetic nerves play a pivotal role in promoting tumor growth through crosstalk with tumor and stromal cells. Chemotherapy exacerbates the infiltration of sympathetic nerves into tumors, thereby providing a rationale for inhibiting sympathetic innervation to enhance chemotherapy. Here, we discovered that doxorubicin increases the density and activity of sympathetic nerves in breast cancer mainly by upregulating the expression of nerve growth factors (NGFs) in cancer cells. To address this, we developed a combination therapy by co-encapsulating small interfering RNA (siRNA) and doxorubicin within breast cancer-targeted poly (lactic-co-glycolic acid) (PLGA) nanoparticles, aiming to suppress NGF expression post-chemotherapy. Incorporating NGF blockade into the nanoplatform for chemotherapy effectively mitigated the chemotherapy-induced proliferation of sympathetic nerves. This not only bolstered the tumoricidal activity of chemotherapy, but also amplified its stimulatory impact on the antitumor immune response by increasing the infiltration of immunostimulatory cells into tumors while concurrently reducing the frequency of immunosuppressive cells. Consequently, the combined nanodrug approach, when coupled with anti-PD-L1 treatment, exhibited a remarkable suppression of primary and deeply metastatic tumors with minimal systematic toxicity. Importantly, the nanoplatform relieved chemotherapy-induced peripheral neuropathic pain (CIPNP) by diminishing the expression of pain mediator NGFs. In summary, this research underscores the significant potential of NGF knockdown in enhancing immunochemotherapy outcomes and presents a nanoplatform for the highly efficient and low-toxicity treatment of breast cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Austocystin D is a natural compound that induces cytochrome P450 (CYP) monooxygenase-dependent DNA damage and growth inhibition in certain cancer cell lines. Cancer cells exhibiting higher sensitivity to austocystin D often display elevated CYP2J2 expression. However, the essentiality and the role of CYP2J2 for the cytotoxicity of this compound remain unclear. In this study, we demonstrate that CYP2J2 depletion alleviates austocystin D sensitivity and DNA damage induction, while CYP2J2 overexpression enhances them. Moreover, the investigation into genes involved in austocystin D cytotoxicity identified POR and PGRMC1, positive regulators for CYP activity, and KAT7, a histone acetyltransferase. Through genetic manipulation and analysis of multiomics data, we elucidated a role for KAT7 in CYP2J2 transcriptional regulation. These findings strongly suggest that CYP2J2 is crucial for austocystin D metabolism and its subsequent cytotoxic effects. The potential use of austocystin D as a therapeutic prodrug is underscored, particularly in cancers where elevated CYP2J2 expression serves as a biomarker., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

In identifying biomarkers for anticancer drugs, the lack of objectivity in selecting candidate factors makes interpretation difficult. We performed preclinical analysis and a translational validation study to identify candidate biomarkers for regorafenib efficacy in metastatic colorectal cancer (mCRC). Using in silico COMPARE analysis with a human cancer cell line panel, JFCR39, we selected candidate biomarkers whose expression correlates with regorafenib sensitivity. We validated predictive values in mCRC patients receiving regorafenib (discovery, n = 53) and FTD/TPI (control, n = 16). Blood samples were obtained at baseline (BL), before the second cycle (2nd), and at progressive disease (PD), and biomarker levels were measured using ELISA. Our analysis showed that high matrix metalloproteinase (MMP)-14 expression was associated with a high sensitivity to regorafenib. In the discovery cohort, high MMP-14 levels at BL and PD were correlated with tumor shrinkage and longer progression-free survival (PFS). A subsequent analysis of other related factors further indicated that the patients with decreased MMP-9 levels at the 2nd had higher disease control rates, tumor shrinkage, longer PFS, and overall survival than those with increased changes. These findings were not observed in the control cohort. Our study suggests MMP-14 and MMP-9 may serve as prognostic markers for regorafenib and provide insights into novel combination therapies with anti-MMP-9 agents or FTD/TPI.

In artificial synaptic devices aimed at mimicking neuromorphic computing systems, electrical or optical pulses, or both, are generally used as stimuli. In this work, we introduce chiral materials for tailoring the characteristics of photonic synaptic devices to achieve handedness-dependent neuromorphic computing and in-memory logic gates. In devices based on a pair of chiral perovskites, the use of circularly polarized light (CPL) as the optical stimuli mimicked a series of electrical and opto-synaptic functionalities in order to emulate the multifunctional complex behavior of the human brain. Upon illumination in this two-terminal device, anisotropy in current has been observed due to the out-of-plane carrier transport, originating from spin-selective carrier transport. More importantly, the logic gate achieved in devices based on optoelectronic memristors turned out to be chirality-dependent; while an R -device functioned as an AND gate, the device based on the same perovskite of the opposite chirality ( S -device) acted as a NOR gate toward in-memory logic operations. These findings in chiral perovskite-based artificial synapses can identify further strategies for future neuromorphic computing, vision simulation, and artificial intelligence.

Interference in cell cycle progression has been noted as one of the important properties of anticancer drugs. In this study, we developed the cell cycle prediction model using high-content imaging data of recipient cells after drug exposure and DNA-staining with a low-toxic DNA dye, SiR-DNA. For this purpose, we exploited HeLa and MCF7 cells introduced with a fluorescent ubiquitination-based cell cycle indicator (Fucci). Fucci-expressing cancer cells were subjected to high-content imaging analysis using OperettaCLS after 36-h exposure to anticancer drugs; the nuclei were segmented, and the morphological and intensity properties of each nucleus characterized by SiR-DNA staining were calculated using imaging analysis software, Harmony. For the use of training, we classified cells into each phase of the cell cycle using the Fucci system. Training data (n = 7500) and validation data (n = 2500) were randomly sampled and the binary classification prediction models for G1, early S, and S/G2/M phases of the cell cycle were developed using four supervised machine learning algorithms. We selected random forest as the model with the best performance through 10-fold cross-validation; the accuracy rate was approximately 75%-87%. Regarding feature importance, variables expected to be biologically related to the cell cycle, for example, signal intensity and nuclear size, were highly ranked, suggesting the validity of the model. These results showed that the cell cycle can be predicted in cancer cells by simply exploiting the current prediction model using fluorescent images of DNA-staining dye, and the model could be applied for the use of future ex vivo drug sensitivity diagnosis., (© 2024 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Introduction: Medical deserts are a growing phenomenon across many European countries. They are usually defined as (i) rural areas, (ii) underserved areas or (iii) by applying a measure of distance/time to a facility or a combination of the three characteristics. The objective was to define medical deserts in Spain as well as map their driving factors and approaches to mitigate them., Methods: A mixed methods approach was applied following the project "A Roadmap out of medical deserts into supportive health workforce initiatives and policies" work plan. It included the following elements: (i) a scoping literature review; (ii) a questionnaire survey; (iii) national stakeholders' workshop; (iv) a descriptive case study on medical deserts in Spain., Results: Medical deserts in Spain exist in the form of mostly rural areas with limited access to health care. The main challenge in their identification and monitoring is local data availability. Diversity of both factors contributing to medical deserts and solutions applied to eliminate or mitigate them can be identified in Spain. They can be related to demand for or supply of health care services. More national data, analyses and/or initiatives seem to be focused on the health care supply dimension., Conclusions: Addressing medical deserts in Spain requires a comprehensive and multidimensional approach. Effective policies are needed to address both the medical staff education and planning system, working conditions, as well as more intersectoral approach to the population health management., (© 2024 The Authors. The International Journal of Health Planning and Management published by John Wiley & Sons Ltd.)

A position identification system for wandering elderly people uses BLE to transmit ID information. The objective of this study is to make the BLE module batteryless using a piezoelectric element. The piezoelectric element is mounted on the sole of a shoe, and when pressure is applied to the piezoelectric element by walking, a voltage is generated between both electrodes of the piezoelectric element. This voltage is used to store the necessary power as a battery to operate the BLE module. In this paper, we provide a step-by-step design approach using piezoelectric elements attached to a shoe to power an actual BLE module. We derive an equivalent circuit for the piezoelectric element under walking conditions and, through circuit simulation and actual measurements, clarify the amount of time required to charge the voltage to drive the BLE, demonstrating the possibility of a batteryless BLE module for use in locating a wanderer while they are walking.

Background: Various immune checkpoint inhibitors, such as programmed cell death protein-1 (PD-1) and its ligand (PD-L1), have been approved for use, but they have side effects on the endocrine glands., Methods: Adverse event reports related to PD-1/PD-L1 inhibitors from the FDA Adverse Event Reporting System (FAERS) from the first quarter of 2019 to the first quarter of 2023 were extracted, and the reported Odds ratio methods (ROR method) and comprehensive standard methods (MHRA methods) were used for data mining and analysis., Results: A total of 5,322 reports (accounts for 6.68% of the total reports)of AEs in endocrine system were collected, including 1852 of pabolizumab (34.80%), 2,326 of navuliumab (43.71%), 54 of cimipriliumab (1.01%), 800 of atilizumab (15.03%), 222 of duvariumab (4.17%) and 68 of averumab (1.28%). Endocrine system-related AEs were mainly present in men (excluding those treated with pembrolizumab) aged ≥65 years. The ratio of AEs components in the endocrine system for the six drugs was approximately 3-8%. The main endocrine glands involved in AEs were the thyroid (pembrolizumab), pituitary and adrenal (nivolumab), adrenal (cemiplimab, atezolizumab, and avelumab), and thyroid (durvalumab). Most patients experienced AEs between 30 and 365 (mean, 117) days,the median time was 61d. AEs resulted in prolonged hospitalization in >40% and death in >10% of cases after administration of pembrolizumab, nivolumab, or durvalumab., Conclusion: Men aged ≥65 years should be concerned about endocrine-related AEs. There was a lengthy interval between the use of PD-1/PD-L1 inhibitors and endocrine system-related AEs, but the outcome was serious. Special attention should be given to endocrine system-related AEs when using pembrolizumab, nivolumab, or durvalumab., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Shi, He, Dan, Yang, Wang, Chen and Chen.)

Background: Phosphoinositide 3-kinases (PI3Ks) are critical regulators of diverse cellular functions and have emerged as promising targets in cancer therapy. Despite significant progress, existing PI3K inhibitors encounter various challenges such as suboptimal bioavailability, potential off-target effects, restricted therapeutic indices, and cancer-acquired resistance. Hence, novel inhibitors that overcome some of these challenges are needed. Here, we describe the characterization of KTC1101, a novel pan-PI3K inhibitor that simultaneously targets tumor cell proliferation and the tumor microenvironment. Our studies demonstrate that KTC1101 significantly increases the anti-PD-1 efficacy in multiple pre-clinical mouse models., Methods: KTC1101 was synthesized and characterized employing chemical synthesis, molecular modeling, Nuclear Magnetic Resonance (NMR), and mass spectrometry. Its target specificity was confirmed through the kinase assay, JFCR39 COMPARE analysis, and RNA-Seq analysis. Metabolic stability was verified via liver microsome and plasma assays, pharmacokinetics determined by LC-MS/MS, and safety profile established through acute toxicity assays to determine the LD50. The antiproliferative effects of KTC1101 were evaluated in a panel of cancer cell lines and further validated in diverse BALB/c nude mouse xenograft, NSG mouse xenograft and syngeneic mouse models. The KTC1101 treatment effect on the immune response was assessed through comprehensive RNA-Seq, flow cytometry, and immunohistochemistry, with molecular pathways investigated via Western blot, ELISA, and qRT-PCR., Results: KTC1101 demonstrated strong inhibition of cancer cell growth in vitro and significantly impeded tumor progression in vivo. It effectively modulated the Tumor Microenvironment (TME), characterized by increased infiltration of CD8 + T cells and innate immune cells. An intermittent dosing regimen of KTC1101 enhanced these effects. Notably, KTC1101 synergized with anti-PD-1 therapy, significantly boosting antitumor immunity and extending survival in preclinical models., Conclusion: KTC1101's dual mechanism of action-directly inhibiting tumor cell growth and dynamically enhancing the immune response- represents a significant advancement in cancer treatment strategies. These findings support incorporating KTC1101 into future oncologic regimens to improve the efficacy of immunotherapy combinations., (© 2024. The Author(s).)

Objective: We aimed to evaluate the sputum culture conversion time of DR-TB patients and its related factors., Methods: PubMed, The Cochrane Library, Embase, CINAHL, Web of Science, CNKI, Wan Fang, CBM and VIP databases were electronically searched to collect studies on sputum culture conversion time in patients with DR-TB. Meta-analysis was performed by using the R 4.3.0 version and Stata 16 software., Results: A total of 45 studies involving 17373 patients were included. Meta-analysis results showed that the pooled median time to sputum culture conversion was 68.57 days (IQR 61.01,76.12). The median time of sputum culture conversion in patients with drug-resistant tuberculosis was different in different WHO regions, countries with different levels of development and different treatment schemes. And female (aHR = 0.59,95%CI: s0.46,0.76), alcohol history (aHR = 0.70,95%CI:0.50,0.98), smoking history (aHR = 0.58,95%CI:0.38,0.88), history of SLD use (aHR = 0.64,95%CI:0.47,0.87), BMI < 18.5 kg/m 2 (aHR = 0.69,95%CI:0.60,0.80), lung cavity (aHR = 0.70,95%CI:0.52,0.94), sputum smear grading at baseline (Positive) (aHR = 0.56,95%CI:0.36,0.87), (grade 1 + ) (aHR = 0.87,95%CI:0.77,0.99), (grade 2 + ) (aHR = 0.81,95%CI:0.69,0.95), (grade 3 + ) (aHR = 0.71,95%CI:0.61,0.84) were the related factor of sputum culture conversion time in patients with DR-TB., Conclusion: Patients with DR-TB in Europe or countries with high level of economic development have earlier sputum culture conversion, and the application of bedaquiline can make patients have shorter sputum culture conversion time. Female, alcohol history, smoking history, history of SLD use, BMI < 18.5 kg/m 2 , lung cavity, sputum smear grading at baseline (Positive, grade 1 + , grade 2 + , grade 3 + ) may be risk factors for longer sputum culture conversion time. This systematic review has been registered in PROSPERO, the registration number is CRD42023438746., (© 2024. The Author(s).)

Background: Despite the demonstrated benefits of insulin therapy, many general practitioners (GPs) are hesitant to administer it due to challenges such as a lack of knowledge, time constraints, and patient reluctance. The barriers that prevent a GP from initiating insulin therapy may vary in comparison to those encountered by a diabetic patient; this aspect of clinical research in the South Shanghai metropolitan area has received limited attention so far., Objective: This is a 6-months of interventional analytic cohort study. The prime aim is to investigate the barriers general practitioners (GPs) face when initiating insulin therapy for patients with type 2 diabetes (T2D)., Materials and Methods: As part of a training program, all 189 registered GPs in Nanhui Health Service Center in Shanghai were given a structured online-multi-choice questionnaire before and after a six-month interval, during which the GPs received sessions of training on insulin therapy either on theoretic classes or clinical practices., Results: Before and after training, via the methods of multiple-response analyses, the results showed that social, GP's, and patient barriers to initiating insulin therapy were comparable. However, through the crosstabs chi-square test, we found significant changes in the basal insulin initiation following the prescription of the senior endocrinologists, the titration of insulin, and the need for training (p<0.05). The Spearman analyses discovered significant changes associated with the cause of initial insulin refusal and the factors influencing insulin administration. Finally, the binary logistic regression analysis revealed that distinct causes such as social factors, insurance, GP experience, insulin dosage calculation, follow-up, and patients' feelings are related to insulin treatment application before and after training., Conclusion: According to this study, training increased general practitioners' confidence in initiating insulin administration, especially basal insulin. General practitioners require additional education on insulin therapy, with a potential need for increased face-to-face training for insulin initiation., Competing Interests: The authors declare that there are no competing interests related to this study., (© 2024 Wen et al.)

HIV incidence in eastern and southern Africa has historically been concentrated among girls and women aged 15-24 years. As new cases decline with HIV interventions, population-level infection dynamics may shift by age and gender. Here, we integrated population-based surveillance of 38,749 participants in the Rakai Community Cohort Study and longitudinal deep-sequence viral phylogenetics to assess how HIV incidence and population groups driving transmission have changed from 2003 to 2018 in Uganda. We observed 1,117 individuals in the incidence cohort and 1,978 individuals in the transmission cohort. HIV viral suppression increased more rapidly in women than men, however incidence declined more slowly in women than men. We found that age-specific transmission flows shifted: whereas HIV transmission to girls and women (aged 15-24 years) from older men declined by about one-third, transmission to women (aged 25-34 years) from men that were 0-6 years older increased by half in 2003 to 2018. Based on changes in transmission flows, we estimated that closing the gender gap in viral suppression could have reduced HIV incidence in women by half in 2018. This study suggests that HIV programmes to increase HIV suppression in men are critical to reduce incidence in women, close gender gaps in infection burden and improve men's health in Africa., (© 2023. The Author(s).)

Purpose: To describe a novel surgical technique to unfold congenital falciform folds., Method: A retrospective, interventional case series was performed where a novel technique was applied to treat five cases of congenital falciform folds. Twenty-five-gauge vitrectomy was performed along with the removal of all vitreous adhesions. The internal limiting membrane was peeled from the macula and around the macular fold area. A Tano diamond-dusted membrane scraper was used to stretch the folded retina mechanically. Then, subretinal balanced salt solution was injected using a 38-gauge subretinal needle to create multiple blebs around the folded retina. Finally, 20% sulfur hexafluoride gas was used for tamponade. Follow-up was conducted for a minimum of 6 months., Results: Vision improved from preoperative mean best-corrected visual acuity logMAR 1.44 (20/550) ± 0.32 to postoperative mean best-corrected visual acuity logMAR 0.75 (20/112) ± 0.17 ( P value = 0.0208) after intervention. There was a reduction in the macular fold. Postoperatively, a macular hole with retinal detachment developed in one of five (20%) eyes., Conclusion: The novel technique of vitrectomy with combined internal limiting membrane peeling and subretinal balanced salt solution injection is visually rewarding in treating congenital falciform folds.

The current study investigated the potentially harmful consequences of pure glyphosate or Roundup® on CYP family members and lipid metabolism in newly hatched chicks. On the sixth day, 225 fertilized eggs were randomly divided into three treatments: (1) the control group injected with deionized water, (2) the glyphosate group injected with 10 mg pure glyphosate/Kg egg mass and (3) the Roundup group injected 10 mg the active ingredient glyphosate in Roundup®/Kg egg. The results of the study revealed a reduction in hatchability in chicks treated with Roundup ® . Moreover, change of Lipid concentration in serum and the liver-treated groups. Additionally, increased liver function enzymes and increased oxidative stress in the glyphosate and Roundup ® groups. Furthermore, liver tissues showed histological changes and several lipid deposits in glyphosate-treated groups. Hepatic CYP1A2 and CYP1A4 expressions were significantly increased ( p  < .05) after glyphosate exposure, and suppression of CYP1C1 mRNA expression was significant ( p  < .05) after Roundup ® exposure. The pro-inflammatory cytokines genes IFN-γ and IL-1β expression were significantly increased ( p  < .05) after Roundup ® exposure. In addition, there were significant differences in the levels of expression genes which are related to lipid synthesis or catabolism in the liver. In conclusion, in ovo glyphosate exposure caused disruption of biotransformation, pro-inflammatory and lipid metabolism in chicks.

Rationale: Prostate tuberculosis (PTB) has no specific symptoms, or insidious presentation in male reproductive system tuberculosis, and is difficult to detect in the early stage. When PTB develops to the late stage, it leads to disease progression and irreversible organ and tissue damage. At present, the imaging manifestations of prostate tuberculosis vary and are not well known to imaging physicians and urologists., Diagnoses and Interventions: This case was a PTB patient, whose main manifestation was elevated serum prostate-specific antigen and the diagnosis was confirmed by ultrasound-guided prostate biopsy. We analyzed the imaging performance of various imaging techniques, and summarized and explored the imaging characteristics reported in the previous literature, with the aim of improving the early detection rate and providing evidence-based practice for early regular antituberculosis treatment in PTB., Outcomes: The multiparametric transrectal ultrasound performance of PTB is characteristic, and can be used for the differential diagnosis of prostate cancer causing elevated prostate-specific antigen levels in aged men., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Resting comfort may influence sleep-related lying postures in cattle. This study aimed to investigate the effects of bed cleanliness on tucked (TSP) and extended (ESP) head positions in sleep-related lying postures., Methods: The study was conducted over two experimental periods. In each period, four Japanese Black fattening cattle were assigned to the cleaning treatment (CL), in which bedding material was replaced once during each experimental period. Four cattle were assigned to the control treatment (CON) with no bed cleaning. Daily duration, bout frequency, and bout length of sleep-related lying postures were measured, and bed moisture, ammonia concentration in the air, plasma cortisol, and serotonin concentration were also measured within one week before and after cleaning treatment in each period., Results: The bed moisture and ammonia concentrations decreased in CL after bed cleaning. Following bed cleaning, the duration and bout frequency of TSP in CL decreased compared to that observed in CON, whereas ESP in CL increased after bed cleaning. Total duration of sleep-related lying postures and cortisol and serotonin levels did not differ between CL and CON., Conclusion: These results suggest that cattle in sleep-related lying postures shifted from tucked head positions to extended head positions in response to improved bed cleanliness.

Naturally occurring protein kinase C (PKC) activators such as phorbol esters, teleocidins, and aplysiatoxins, have the potential to become anti-cancer agents, since they are anti-proliferative against specific cancer cell lines in vitro. However, their potent tumor-promoting and proinflammatory activities have hampered their clinical uses. Recently, we developed 10-methyl-aplog-1 (1), a simplified analog of tumor-promoting debromoaplysiatoxin (DAT), which retained anti-proliferative activity comparable to DAT, but induced neither tumorigenesis nor inflammation on mouse skin. Our previous study suggested that PKCα and δ were involved in the cell line-selective anti-proliferative activity of 1, but the downstream signaling of PKC isozymes remained unknown. In this study, we confirmed that 1 inhibited the growth of three aplog-sensitive cancer cell lines (NCI-H460, HCC-2998, and HBC-4) without severe side effects in mice xenograft models. In addition, in vitro analysis using A549, one of the aplog-sensitive cell lines in vitro, revealed that PKCα induced PP2A-mediated attenuation of the Akt/S6 signaling axis. Since S6 inhibition in A549 was reported to result in G1 arrest, this pathway could be involved in the PKCα-dependent anti-proliferative activity of 1., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims/hypothesis: Type 2 diabetes in people in the healthy weight BMI category (<25 kg/m 2 ), herein defined as 'normal-weight type 2 diabetes', is associated with sarcopenia (low muscle mass). Given this unique body composition, the optimal exercise regimen for this population is unknown., Methods: We conducted a parallel-group RCT in individuals with type 2 diabetes (age 18-80 years, HbA 1c 47.5-118.56 mmol/mol [6.5-13.0%]) and BMI <25 kg/m 2 ). Participants were recruited in outpatient clinics or through advertisements and randomly assigned to a 9 month exercise programme of strength training alone (ST), aerobic training alone (AER) or both interventions combined (COMB). We used stratified block randomisation with a randomly selected block size. Researchers and caregivers were blinded to participants' treatment group; however, participants themselves were not. Exercise interventions were conducted at community-based fitness centres. The primary outcome was absolute change in HbA 1c level within and across the three groups at 3, 6 and 9 months. Secondary outcomes included changes in body composition at 9 months. Per adherence to recommended exercise protocol (PP) analysis included participants who completed at least 50% of the sessions., Results: Among 186 individuals (ST, n=63; AER, n=58; COMB, n=65) analysed, the median (IQR) age was 59 (53-66) years, 60% were men and 83% were Asian. The mean (SD) HbA 1c level at baseline was 59.6 (13.1) mmol/mol (7.6% [1.2%]). In intention-to-treat analysis, the ST group showed a significant decrease in HbA 1c levels (mean [95% CI] -0.44 percentage points [-0.78, -0.12], p=0.002), while no significant change was observed in either the COMB group (-0.35 percentage points, p=0.13) or the AER group (-0.24 percentage points, p=0.10). The ST group had a greater improvement in HbA 1c levels than the AER group (p=0.01). Appendicular lean mass relative to fat mass increased only in the ST group (p=0.0008), which was an independent predictor of HbA 1c change (beta coefficient -7.16, p=0.01). Similar results were observed in PP analysis. Only one adverse event, in the COMB group, was considered to be possibly associated with the exercise intervention., Conclusions/interpretation: In normal-weight type 2 diabetes, strength training was superior to aerobic training alone, while no significant difference was observed between strength training and combination training for HbA 1c reduction. Increased lean mass relative to decreased fat mass was an independent predictor of reduction in HbA 1c level., Trial Registration: ClinicalTrials.gov NCT02448498., Funding: This study was funded by the National Institutes of Health (NIH; R01DK081371)., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ferroelectric perovskites, where ferroelectricity is embedded in the structure, are being considered for different device applications. In this study, we introduce Cs 2 PbI 2 Cl 2 , an all-inorganic 2D Ruddlesden-Popper (RP) halide perovskite, as a ferroelectric material suitable for pyro-phototronic applications. Thin-films of the all-inorganic perovskite are successfully cast, and they demonstrate ferroelectric properties. Unlike hybrid materials, the ferroelectricity in Cs 2 PbI 2 Cl 2 does not rely on the organic moiety possessing an electric dipole moment. Instead, the 2D-layer-forming octahedra are twisted and tilted due to a distortion in the bond lengths, leading to the emergence of spontaneous electric polarization. Based on the properties, we fabricate p - i - n heterojunctions by integrating the perovskite with carrier-transport layers. To determine the band-energies of the materials, scanning tunneling spectroscopy and Kelvin probe force microscopy are employed. The band-edges evidence a type-II band-alignment at both interfaces, enabling the material to exhibit both photovoltaic and pyroelectric behaviors when subjected to pulsed illumination. The devices based on the all-inorganic RP perovskite developed in this study exhibit pyro-phototronic effects and serve as self-powered photodetectors without any need for an external bias.

Intrinsic or acquired chemoresistance represents a major obstacle in cancer treatment. Multiple mechanisms can contribute to cancer cells' resistance to chemotherapy. Among them, an aberrantly strengthened DNA repair mechanism is responsible for a large proportion of drug resistance to alkylating agents and radiation therapy. In cancer cells, damping overactivated DNA repair system can overcome survival advantages conferred by chromosomal translocations or mutations and lead to cytostatic effects or cytotoxic. Therefore, selectively targeting DNA repair system in cancer cells holds promise for overcoming chemoresistance. In this study, we revealed that the endonuclease Flap Endonuclease 1 (FEN1), essential for DNA replication and repair, directly interacts with phosphatidylinositol 3-phosphate [PI(3)P], and FEN1-R378 is the primary PI(3)P-binding site. PI(3)P-binding deficient FEN1 mutant (FEN1-R378A) cells exhibited abnormal chromosomal structures and were hypersensitized to DNA damage. The PI(3)P-mediated FEN1 functionality was essential for repairing DNA damages caused by multiple mechanisms. Furthermore, VPS34, the major PI(3)P synthesizing enzyme, was negatively associated with patients' survival in various cancer types, and VPS34 inhibitors significantly sensitized chemoresistant cancer cells to genotoxic agents. These findings open up an avenue for counteracting chemoresistance by targeting VPS34-PI(3)P-mediated DNA repair pathway, and call for assessing the efficacy of this strategy in patients suffering from chemoresistance-mediated cancer recurrence in clinical trials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Transdiagnostic dimensional phenotypes are essential to investigate the relationship between continuous symptom dimensions and pathological changes. This is a fundamental challenge to post-mortem work, as assessments of phenotypic concepts need to rely on existing records., Methods: We adapted well-validated methodologies to compute National Institute of Mental Health Research Domain Criteria (RDoC) scores using natural language processing (NLP) from electronic health records (EHRs) obtained from post-mortem brain donors and tested whether cognitive domain scores were associated with Alzheimer's disease neuropathological measures., Results: Our results confirm an association of EHR-derived cognitive scores with neuropathological findings. Notably, higher neuropathological load, particularly neuritic plaques, was associated with higher cognitive burden scores in the frontal (ß = 0.38, P  = 0.0004), parietal (ß = 0.35, P = 0.0008), temporal (ß = 0.37, P = 0.0004) and occipital (ß = 0.37, P = 0.0003) lobes., Discussion: This proof-of-concept study supports the validity of NLP-based methodologies to obtain quantitative measures of RDoC clinical domains from post-mortem EHR. The associations may accelerate post-mortem brain research beyond classical case-control designs., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Dihydroorotate dehydrogenase (DHODH) is a central enzyme of the de novo pyrimidine biosynthesis pathway and is a promising drug target for the treatment of cancer and autoimmune diseases. This study presents the identification of a potent DHODH inhibitor by proteomic profiling. Cell-based screening revealed that NPD723, which is reduced to H-006 in cells, strongly induces myeloid differentiation and inhibits cell growth in HL-60 cells. H-006 also suppressed the growth of various cancer cells. Proteomic profiling of NPD723-treated cells in ChemProteoBase showed that NPD723 was clustered with DHODH inhibitors. H-006 potently inhibited human DHODH activity in vitro , whereas NPD723 was approximately 400 times less active than H-006. H-006-induced cell death was rescued by the addition of the DHODH product orotic acid. Moreover, metabolome analysis revealed that H-006 treatment promotes marked accumulation of the DHODH substrate dihydroorotic acid. These results suggest that NPD723 is reduced in cells to its active metabolite H-006, which then targets DHODH and suppresses cancer cell growth. Thus, H-006-related drugs represent a potentially powerful treatment for cancer and other diseases., Competing Interests: The authors declare that they have no conflicts of interest to report regarding the present study., (© 2023 Kawatani et al.)

Objectives: To investigate the clinical features and treatment strategies of multisystemic inflammatory syndrome in children (MIS-C) after severe acute respiratory syndrome coronavirus 2 infection., Methods: A retrospective analysis was performed on the medical data of four children with MIS-C who were admitted to the Department of Cardiology, Xuzhou Children's Hospital, Xuzhou Medical Universityfrom January to February 2023., Results: All four children had multiple organ involvements and elevated inflammatory markers, with a poor response to standard therapy for Kawasaki disease after admission. Two children were treated with intravenous immunoglobulin therapy pulse therapy twice, and all four children were treated with glucocorticoids. The children had a good prognosis after the treatment., Conclusions: MIS-C often appears within 4-6 weeks or a longer time after severe acute respiratory syndrome coronavirus 2 infection, and anti-inflammatory therapy in addition to the standard treatment regimen for Kawasaki disease can help to achieve a favorable treatment outcome.

Study Objectives: Asian Americans report higher rates of insufficient sleep than non-Hispanic Whites (NHWs). It is unclear how sleep outcomes differ among disaggregated Asian subgroups., Methods: The National Health Interview Survey (2006-2018) was used to analyze self-reported sleep duration and quality measures for Asian American subgroups (Chinese [n = 11,056], Asian Indian [n = 11,249], Filipino [n = 13,211], and other Asians [n = 21,767]). Outcomes included hours of sleep per day, the number of days reporting trouble falling asleep, staying asleep, waking up rested, and taking sleep medication in the past week. Subsetted multivariate logistic regression was used to assess factors impacting sleep outcomes by ethnicity., Results: 29.2% of NHWs, 26.4% of Chinese, 24.5% of Asian Indians, and 38.4% of Filipinos reported insufficient sleep duration. Filipinos were less likely to report sufficient sleep duration (odds ratio 0.55, [confidence interval 95% 0.50-0.59]) and more likely to report trouble falling asleep (1.16 [1.01-1.33]) than NHWs. Chinese and Asian Indians had less trouble staying asleep (0.67 [0.58-0.77], 0.51 [0.44-0.59]) and falling asleep (0.77 [0.66-0.89], 0.72, [0.62-0.82]) than NHWs, and Asian Indians were more likely to wake feeling well rested (1.66 [1.48-1.87]). All Asian subgroups were less likely to report using sleep medications than NHWs. Foreign-born status had a negative association with sufficient sleep duration in Filipinos but a positive association in Asian Indians and Chinese., Conclusions: Filipinos report the highest burden of poor sleep outcomes, and Asian Indians report significantly better sleep outcomes. These findings highlight the importance of disaggregating Asian ethnic subgroups to address their health needs., Citation: Wang RZ, Jamal A, Wang Z, et al. Toward precision sleep medicine: variations in sleep outcomes among disaggregated Asian Americans in the National Health Interview Survey (2006-2018). J Clin Sleep Med . 2023;19(7):1259-1270., (© 2023 American Academy of Sleep Medicine.)

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), large-scale social contact surveys are now longitudinally measuring the fundamental changes in human interactions in the face of the pandemic and non-pharmaceutical interventions. Here, we present a model-based Bayesian approach that can reconstruct contact patterns at 1-year resolution even when the age of the contacts is reported coarsely by 5 or 10-year age bands. This innovation is rooted in population-level consistency constraints in how contacts between groups must add up, which prompts us to call the approach presented here the Bayesian rate consistency model. The model can also quantify time trends and adjust for reporting fatigue emerging in longitudinal surveys through the use of computationally efficient Hilbert Space Gaussian process priors. We illustrate estimation accuracy on simulated data as well as social contact data from Europe and Africa for which the exact age of contacts is reported, and then apply the model to social contact data with coarse information on the age of contacts that were collected in Germany during the COVID-19 pandemic from April to June 2020 across five longitudinal survey waves. We estimate the fine age structure in social contacts during the early stages of the pandemic and demonstrate that social contact intensities rebounded in an age-structured, non-homogeneous manner. The Bayesian rate consistency model provides a model-based, non-parametric, computationally tractable approach for estimating the fine structure and longitudinal trends in social contacts and is applicable to contemporary survey data with coarsely reported age of contacts as long as the exact age of survey participants is reported., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Dan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To evaluate the safety and clinical effect of tubular esophagogastric anastomosis in laparoscopic radical proximal gastrectomy., Methods: A retrospective analysis was conducted involving 191 patients who underwent laparoscopic radical proximal gastrectomy in the Department of Gastrointestinal Surgery, Qilu Hospital of Shandong University from January 2017 to October 2020. Patients were divided into tubular esophagogastric anastomosis group (TG group) and traditional esophagogastric anastomosis group (EG group) according to the digestive tract reconstruction. Their intraoperative conditions, perioperative recovery and postoperative follow-up were compared. Patients were also divided into indocyanine green group and non-indocyanine green group according to whether or not indocyanine green tracer technology was used during the operation. Their intraoperative condition and perioperative recovery were compared and analyzed after propensity score matching., Results: The operation was successfully completed in all patients. Compared with the EG group, the TG group had less volume of gastric tube drainage, shorter gastric tube drainage time and proton pump inhibitors application time, and lower reuse rate of proton pump inhibitors. However, the TG group had a higher anastomotic stenosis at three months after surgery, as measured using anastomotic width and dysphagia score. Nevertheless, the incidence of reflux esophagitis and postoperative quality of life score in the TG group were lower compared with the EG group at 1st and 2nd year after surgery. In the indocyanine green analysis, the indocyanine green group had significantly shorter total operation time and lymph node dissection time and less intraoperative blood loss compared with the non-indocyanine green group. However, compared with the non-indocyanine green group, more postoperative lymph nodes were obtained in the indocyanine green group., Conclusion: Laparoscopic radical proximal gastrectomy is safe and effective treatment option for upper gastric cancer. Tubular esophagogastric anastomosis has more advantages in restoring postoperative gastrointestinal function and reducing reflux, but it has a higher incidence of postoperative anastomotic stenosis compared with traditional esophagogastrostomy. The application of indocyanine green tracer technique in laparoscopic radical proximal gastrectomy has positive significance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Meng, Ya-di, Wei-bo, Ru-dong, Ze-wei, Ou Yang, Ze-peng, Chuan-qi, Yi-ze, Dan-ping and Wen-bin.)

Objective: To assess the reporting quality of systematic review (SR) abstracts published in leading general dental journals according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Abstracts (PRISMA-A) guidelines, and to identify factors associated with overall reporting quality., Methods: We identified SR abstracts published in 10 leading general dental journals and assessed their reporting quality. For each abstract, an overall reporting score (ORS, range: 0-13) was calculated. Risk ratio (RR) was calculated to compare the reporting quality of abstracts in Pre-PRISMA (2011-2012) and Post-PRISMA (2017-2018) periods. Univariable and multivariable linear regression analyses were performed to identify factors associated with reporting quality., Results: A total of 104 eligible abstracts were included. The mean ORS was 5.59 (SD = 1.48) and 6.97 (1.74) respectively in the Pre- and Post-PRISMA abstracts, with statistically significant difference (mean difference = 1.38; 95% CI: 0.70, 2.05). Reporting of the exact P-value (B = 1.22; 95% CI: 0.45, 1.99) was a significant predictor of higher reporting quality., Conclusion: The reporting quality of SR abstracts published in leading general dental journals improved after the release of PRISMA-A guidelines, but is still suboptimal. Relevant stakeholders need to work together to enhance the reporting quality of SR abstracts in dentistry., (Copyright © 2022 Elsevier Inc. All rights reserved.)

DNA double-strand breaks (DSBs) seriously damage DNA and promote genomic instability that can lead to cell death. They are the source of conditions such as carcinogenesis and aging, but also have important applications in cancer therapy. Therefore, rapid detection and quantification of DSBs in cells are necessary for identifying carcinogenic and anticancer factors. In this study, we detected DSBs using a flow cytometry-based high-throughput method to analyze γH2AX intensity. We screened a chemical library containing 9600 compounds and detected multiple DNA-damaging compounds, although we could not identify mechanisms of action through this procedure. Thus, we also profiled a representative compound with the highest DSB potential, DNA-damaging agent-1 (DDA-1), using a bioinformatics-based method we termed "molecular profiling." Prediction and verification analysis revealed DDA-1 as a potential inhibitor of topoisomerase IIα, different from known inhibitors such as etoposide and doxorubicin. Additional investigation of DDA-1 analogs and xenograft models suggested that DDA-1 is a potential anticancer drug. In conclusion, our findings established that combining high-throughput DSB detection and molecular profiling to undertake phenotypic analysis is a viable method for efficient identification of novel DNA-damaging compounds for clinical applications., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Translocation-related sarcomas (TRSs) harbor an oncogenic fusion gene generated by chromosome translocation and account for approximately one-third of all sarcomas; however, effective targeted therapies have yet to be established. We previously reported that a pan-phosphatidylinositol 3-kinase (PI3K) inhibitor, ZSTK474, was effective for the treatment of sarcomas in a phase I clinical trial. We also demonstrated the efficacy of ZSTK474 in a preclinical model, particularly in cell lines from synovial sarcoma (SS), Ewing's sarcoma (ES) and alveolar rhabdomyosarcoma (ARMS), all of which harbor chromosomal translocations. ZSTK474 selectively induced apoptosis in all these sarcoma cell lines, although the precise mechanism underlying the induction of apoptosis remained unclear. In the present study, we aimed to determine the antitumor effect of PI3K inhibitors, particularly with regards to the induction of apoptosis, against various TRS subtypes using cell lines and patient-derived cells (PDCs). All of the cell lines derived from SS (six), ES (two) and ARMS (one) underwent apoptosis accompanied by the cleavage of poly-(ADP-ribose) polymerase (PARP) and the loss of mitochondrial membrane potential. We also observed apoptotic progression in PDCs from SS, ES and clear cell sarcoma (CCS). Transcriptional analyses revealed that PI3K inhibitors triggered the induction of PUMA and BIM and the knockdown of these genes by RNA interference efficiently suppressed apoptosis, suggesting their functional involvement in the progression of apoptosis. In contrast, TRS-derived cell lines/PDCs from alveolar soft part sarcoma (ASPS), CIC-DUX4 sarcoma and dermatofibrosarcoma protuberans failed to undergo apoptosis nor induce PUMA and BIM expression, as well as cell lines derived from non-TRSs and carcinomas. Thus, we conclude that PI3K inhibitors induce apoptosis in selective TRSs such as ES and SS via the induction of PUMA and BIM and the subsequent loss of mitochondrial membrane potential. This represents proof of concept for PI3K-targeted therapy, particularly such TRS patients., (© 2023. The Author(s).)

Background: Medical deserts are considered a problematic issue for many Western countries which try to employ multitude of policies and initiatives to achieve a better distribution of their health workforce (HWF). The aim of this study was to systematically map research and provide an overview of definitions, characteristics, contributing factors and approaches to mitigate medical deserts within the European Union (EU)-funded project "ROUTE-HWF" (a Roadmap OUT of mEdical deserts into supportive Health WorkForce initiatives and policies)., Methods: We performed a scoping review to identify knowledge clusters/research gaps in the field of medical deserts focusing on HWF issues. Six databases were searched till June 2021. Studies reporting primary research from Western countries on definitions, characteristics, contributing factors, and approaches were included. Two independent reviewers assessed studies for eligibility, extracted data and clustered studies according to the four defined outcomes., Results: Two-hundred and forty studies were included (n=116, 48% Australia/New Zealand; n=105, 44% North America; n=20, 8% Europe). All used observational designs except for five quasi-experimental studies. Studies provided definitions (n=171, 71%), characteristics (n=95, 40%), contributing factors (n=112, 47%), and approaches to mitigate medical deserts (n=87, 36%). Most medical deserts were defined by the density of the population in an area. Contributing factors to HWF issues in medical deserts consisted in work-related (n=55, 23%) and lifestyle-related factors (n=33, 14%) of the HWF as well as sociodemographic characteristics (n=79, 33%). Approaches to mitigate them focused on training adapted to the scope of rural practice (n=67, 28%), HWF distribution (n=3, 1%), support/infrastructure (n=8, 3%) and innovative models of care (n=7, 3%)., Conclusion: Our study provides the first scoping review that presents and categorizes definitions, characteristics, contributing factors, and approaches to mitigate HWF issues in medical deserts. We identified gaps such as the scarcity of longitudinal studies to investigate the impact of factors contributing to medical deserts, and interventional studies to evaluate the effectiveness of approaches to mitigate HWF issues., (© 2023 The Author(s); Published by Kerman University of Medical Sciences This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

This study investigates the effect of sacubitril/valsartan (Sac/Val) in patients diagnosed with nonvalvular atrial fibrillation (AF) without systolic heart failure (SHF).Nonvalvular AF patients without SHF admitted to the People's Hospital of Bortala Mongol Autonomous Prefecture from December 2020 to December 2021 were enrolled and randomly divided into Sac/Val treatment group (group T) and valsartan treatment group (group C, control). For subgroup analysis, patients were divided into subgroups with and without diastolic heart failure (DHF). After 1-month adaptive phase and subsequent 3-month treatment period, patients were followed up in the cardiology clinic. Plasma levels of biochemical markers and echocardiographic parameters before and after treatment were evaluated, and DHF scores were computed to assess diastolic function.Of 61 enrolled patients, 46 patients completed follow-up. Sac/Val treatment did not increase the percentage of sinus rhythm. Although N-terminal pro-B-type natriuretic peptide (NT-proBNP) expression tended to be reduced in both groups after 3 months of treatment, the differences compared with respective baseline levels and between groups were not significant. According to subgroup analysis, although NT-proBNP expression in the subgroup with DHF was lower at follow-up compared to baseline, the difference was not statistically significant. Similarly, no marked differences in echocardiographic parameters or tissue Doppler parameters related to DHF were detected between the groups (P > 0.05). Additionally, a subgroup analysis found no significant variations in the echocardiographic measures (P > 0.05).Sac/Val is not superior to valsartan for the short-term treatment of patients suffering with AF without SHF in improving NT-proBNP level and cardiac function.

Introduction: Medical deserts are increasingly considered problematic and many countries employ a multitude of actions and initiatives to achieve a better distribution of the health workforce (HWF). This study systematically maps research and provides an overview of the definitions/characteristics of medical deserts. It also identifies contributing factors and approaches to mitigate medical deserts., Methods: Embase, MEDLINE, CINAHL, Web of Science Core Collection, Google Scholar and The Cochrane Library were searched from inception to May 2021. Studies reporting primary research on definitions, characteristics, contributing factors and approaches to mitigate medical deserts were included. Two independent reviewers assessed studies for eligibility, extracted data and clustered studies., Results: Two-hundred and forty studies were included (49% Australia/New Zealand, 43% North America, 8% Europe). All used observational designs except for five quasi-experimental studies. Studies provided definitions (n=160), characteristics (n=71), contributing/associated factors (n=113), and approaches to mitigate medical deserts (n=94). Most medical deserts were defined by the density of the population in an area. Contributing/associated factors consisted in sociodemographic/characteristics of HWF (n=70), work-related factors (n=43) and lifestyle conditions (n=34). Approaches focused on training adapted to the scope of rural practice (n=79), HWF distribution (n=3), support and infrastructure (n=6) and innovative models of care (n=7)., Discussion: Our study provides the first scoping review on definitions, characteristics, contributing/associated factors and approaches to mitigate medical deserts. We identified gaps such as the scarcity of longitudinal studies to investigate factors contributing to medical deserts, and interventional studies to evaluate the effectiveness of approaches to mitigate medical deserts.

Background: Considering the numerous nutritional and estrogenic compounds of palm pollen and their effect on sexual function, this study was performed to investigate the effect of palm pollen extract on sexual disorders in postmenopausal women., Methods: In this three-blind clinical trial, 110 postmenopausal women from December 2019 to December 2020 from Rafsanjan comprehensive health service centers were randomly assigned to two groups, using a lottery method. The intervention group received 300 mg capsule of palm pollen extract, and the control group received placebo for 4 weeks. Sexual disorders were assessed with a 6-item female sexual function index before, at the end of the intervention, and 4 weeks after the end of the intervention. Independent t-test, Chi-square and repeated measures ANOVA were used to analyze the data through SPSS software version 21. The statistically significant level was considered P value less than 0.05., Results: The mean scores of sexual disorders before the intervention in the intervention and control groups were 15.36±5.01 and 14.13±4.67 (P=0.68); at the end of the intervention, they were 15.18±4.50 and 14.22±3.91 (P=0.43) and 4 weeks after the end of the intervention we obtained 15.7±4.77 and 14.44±3.78, respectively (P=0.90)., Conclusions: According to the results, daily consumption of 300 mg of date pollen extract had no effect on improving sexual disorders in postmenopausal women. Further studies in this field are suggested. Trial Registration Number: IRCT20160308026971N1., Competing Interests: None declared., (Copyright: © International Journal of Community Based Nursing and Midwifery.)

Background & Aims: Noninvasive modalities for assessing active endoscopic and histologic inflammation in Crohn's disease and ulcerative colitis patients are critically needed. Fecal wash host shed-cell transcriptomics has been shown to be a robust classifier of endoscopic and histologic inflammation in inflammatory bowel disease patients with distal colitis. Whether such fecal washes can inform on inflammatory processes occurring in more proximal intestinal segments is currently unknown., Methods: Fifty-nine inflammatory bowel disease patients and 50 controls were prospectively enrolled. Biopsy specimens and fecal washes from the distal colon, proximal colon, and terminal ileum were compared. Host transcriptomics were performed on the biopsy specimens and fecal washes obtained during colonoscopy at predefined locations throughout the colon and terminal ileum and results were associated with concurrent clinical, endoscopic, and histologic parameters., Results: We found that host transcriptomics of distal fecal washes robustly classify histologic inflammation in ileal and proximal colonic Crohn's disease, even without distal colonic involvement (area under the receiver operating characteristic curve, 0.94 ± 0.09). We further found that fecal washes consist of modules of co-expressed genes of immune, stromal, and epithelial origin that are indicative of endoscopic disease severity. Fecal wash host transcriptomics also captures expression of gene modules previously associated with a lack of response to biological therapies., Conclusions: Our study establishes the accuracy of distal colonic fecal washes for identifying and scoring inflammatory processes throughout the entire ileal-colonic axis., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Vaccination rates may be improved through culturally tailored messages, but little is known about them among disaggregated Asian American subgroups. We assessed the vaccination rates for key vaccines among these subgroups., Methods: Using the National Health Interview Survey, we analyzed recent vaccination rates (2015-2018, n =188,250) and trends (2006-2018) among Asians (Chinese [ n =3,165], Asian Indian [ n =3,525], Filipino [ n =3,656], other Asian [ n =5,819]) and non-Hispanic White adults ( n =172,085) for 6 vaccines (the human papillomavirus, hepatitis B, pneumococcal, influenza, tetanus-diphtheria [tetanus], and shingles vaccines). We controlled demographic, socioeconomic, and health-related variables in multivariable logistic regression and predicted marginal modeling analyses. We also computed vaccination rates among Asian American subgroups on the 2015-2018 National Health Interview Survey data stratified by foreign-born and U.S.-born status. We used Joinpoint regression to analyze trends in vaccination rates. All analyses were conducted in 2021 and 2022., Results: Among Asians, shingles (29.2%; 95% CI=26.6, 32.0), tetanus (53.7%; 95% CI=51.8, 55.6), and pneumococcal (53.8%; 95% CI=50.1, 57.4) vaccination rates were lower than among non-Hispanic Whites. Influenza (47.9%; 95% CI=46.2, 49.6) and hepatitis B (40.5%; 95% CI=39.0, 42.7) vaccination rates were similar or higher than among non-Hispanic Whites (48.4%; 95% CI=47.9, 48.9 and 30.7%; 95% CI=30.1, 31.3, respectively). Among Asians, we found substantial variations in vaccination rates and trends. For example, Asian Indian women had lower human papillomavirus vaccination rates (12.9%; 95% CI=9.1, 18.0) than all other Asian subgroups (Chinese: 37.9%; 95% CI=31.1, 45.2; Filipinos: 38.7%; 95% CI=29.9, 48.3; other Asians: 30.4%; 95% CI=24.8, 36.7) and non-Hispanic Whites (36.1%; 95% CI=34.8, 37.5). Being male, having lower educational attainment and income, having no health insurance or covered by public health insurance only, and lower frequency of doctor visits were generally associated with lower vaccine uptakes. Foreign-born Asian aggregate had lower vaccination rates than U.S.-born Asian aggregate for all vaccines except for influenza. We also found subgroup-level differences in vaccination rates between foreign-born and U.S.-born Asians. We found that (1) foreign-born Chinese, Asian Indians, and other Asians had lower human papillomavirus and hepatitis B vaccination rates; (2) foreign-born Chinese and Filipinos had lower pneumococcal vaccination rates; (3) foreign-born Chinese and Asian Indians had lower influenza vaccination rates; and (4) all foreign-born Asian subgroups had lower tetanus vaccination rates., Conclusions: Vaccination rates and trends differed among Asian American subgroups. Culturally tailored messaging and interventions may improve vaccine uptakes., (© 2022 The Author(s).)

We report the formation of CuIn (1- x ) Ga x S 2 (CIGS) thin films through a solution approach, namely, successive ionic layer adsorption and reaction (SILAR) technique. The obtained films possessed a high degree of crystallinity indicating the efficacy of the deposition process in forming CIGS films. A series of alloys have evidenced band gap bowing, that is, the optical band gap does not follow a linear relationship with the composition; the band gap of an intermediate compound is higher than that is interpolated from a linear relationship or Vegard's law. The composition-dependent band gap followed a quadratic relationship evidencing reverse band gap bowing, manifesting an upward convex behavior. With scanning tunneling spectroscopy (STS) and thereby the density of states of the disordered semiconductors, we have observed a bowing behavior in the transport gap as well and identified the roles of the conduction and valence bands in yielding the bowing phenomenon. The results are explained in terms of the anionic and cationic orbitals involved in forming the two bands. The STS studies have been analyzed further to derive the Urbach energy of the disordered semiconductors. When STS studies are combined with Kelvin probe force microscopy, which in effect provides the Fermi energy of the alloyed semiconductors, we could derive the band edges and the Fermi energy of the whole series in an absolute energy scale during the manifestation of the bowing phenomenon.

Background: To evaluate the comparative efficacy and safety of baricitinib with different dosages in patients with rheumatoid arthritis (RA)., Methods: PubMed, Embase, and the Cochrane Library were retrieved by computer to gather randomized controlled trials (RCTs) of baricitinib for RA from their beginning to September 2021. After 2 researchers independently screened the literature and extracted the data, the risk of bias of included RCTs was assessed, and Bayesian network meta-analysis was performed by GeMTC0.14.3 and Stata15.1 software., Results: Ten publications reporting 9 RCTs were included, with 4129 patients randomized to receive 1 of the 7 interventions. Seven interventions were baricitinib 1 mg + conventional disease-modifying antirheumatic drugs (cDMARD), baricitinib 2 mg + cDMARD, baricitinib 4 mg + cDMARD, baricitinib 8 mg + cDMARD, baricitinib 4 mg, placebo + cDMARD, and cDMARD. In the efficacy outcomes at 12 weeks, nearly all doses of baricitinib with or without cDMARD were superior to placebo plus cDMARD and baricitinib 8 mg combined with cDMARD might have the best curative effect in most outcomes. In the efficacy outcomes at 24 weeks, all doses of baricitinib with or without cDMARD were superior to placebo plus cDMARD and baricitinib 4 mg monotherapy might have the best curative effect in most outcomes. The intervention with the highest incidence of adverse events (AEs) might be baricitinib 8 mg combined with cDMARD, and the intervention with the highest incidence of infections might be baricitinib 4 mg combined with cDMARD., Conclusions: Baricitinib 8 mg combined with cDMARDs was suitable for short-term control of RA symptoms, and baricitinib 4 mg was more effective for treating RA over a longer period of time. But attention should be paid for the risk of baricitinib at 4 to 8 mg in clinical application due to the high incidence of AEs and infections., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

The primary factor impacting the tight sandstone reservoirs and fluid flow capacity represents the pore-throat structure. On the basis of petrophysical characteristics test, scanning electron microscopy (SEM), and casting thin-section examination of tight sandstone reservoir specimens from the Permian Lucaogou Formation in Jimsar Sag, Junggar Basin., the full-size pore-throat parameters and distribution characteristics were determined by constant-rate mercury injection (CRMI) analysis. Using fractal theory and multifractal theory, the pore architectures of sandstone pores are analyzed. Mercury intrusion capillary pressure (MICP) is used to compute the dimensions of fractals using various fractal models and multifractal characteristics. Analysis is done on the relationships between tight sandstone pore architectures and fractal and multifractal characteristics. According to the research, a network of tightly packed sandstone pores may be assessed using the dimensions of fractals computed from a 3D capillary model. When displacement pressure is increased, the dimensions of fractals rise; when permeability, pore-throat diameter, and variable coefficient are increased, it falls. Tight sandstone pores exhibit multifractal features, according to the multifractal analysis, and multifractal parameters may depict the size, concentration, and asymmetry of the pore size distribution (PSD). Sandstone's PSD is comparable when its multifractal parameters (Δα, Δ f , α 0 , α 1 , α 2 ) are identical. Pore diameters of tight sandstone are positively connected with information dimensions D 1 and correlation dimensions D 2 . Additionally, the 3D capillary model's dimensions of fractals and D 1 have a greater impact on PSD than correlation dimensions D 2 . Additionally, the 3D capillary model's dimensions of fractals and D 1 exhibit a substantial negative association. These findings play a significant guiding role in the quantitative characterization of unconventional reservoir pore structures. The multifractal technique is effective to define the heterogeneity of the sandstone pore system and to differentiate between distinct PSD in heterogeneity., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

The structural and magnetic properties of hole doped double perovskite La 1.5 Ca 0.5 CoFeO 6 have been investigated by measuring x-ray photoemission spectroscopy, neutron powder diffraction and magnetization. A ferrimagnetic transition is observed at T C ∼ 167 K. The presence of anti-site disorder (ASD) in La 1.5 Ca 0.5 CoFeO 6 has also been demonstrated. Double re-entrant cluster glass transitions ( T 1 ∼ 11 K and T S ∼ 35 K) were observed which has been attributed to the ASD effect. The presence of both large spontaneous exchange bias H SEB ∼ 2.106 kOe and giant conventional exchange bias H CEB ∼ 1.56 T at 5 K has also been observed which can be attributed to the coexistence of long range magnetic ordering and glassy state. The experimental observations were explained with the results obtained by the density functional theory calculation. The presence of double glassy states, large exchange-bias effect and different magnetic phases make this system a potential candidate for spintronic applications., (© 2022 IOP Publishing Ltd.)