Evaluating the effectiveness and feasibility of a digital health intervention to community-based rehabilitation in older adults: A cluster randomized controlled trial study protocol.

Objective: The escalating global aging population underscores the need to effectively manage geriatric diseases, constituting a significant public health concern. Community-based rehabilitation has emerged as a crucial and accessible paradigm for the rehabilitation of older adults. In China, however, the practical implementation of community-based rehabilitation faces formidable challenges, including a dearth of specialized rehabilitation therapists, substantial disparities between demand and supply, and suboptimal satisfaction rates. We aimed to develop a community-based rehabilitation management platform for older adults centered around digital health technology, with the plan to conduct a cluster randomized controlled trial to gather more evidence to explore the best practices and service models of community-based rehabilitation based on digital health technology. Methods: This cluster randomized controlled trial will be conducted in Zunyi City, China. We will recruit 286 adults aged ≥60 years and randomly allocate 20 subdistricts in a 1:1 ratio into either the intervention group, which will use the Rehabilitation Journey application, or the control group, which will be given a Rehabilitation Information Booklet for Older Adults. Both groups will undergo a 12-month rehabilitation management program, encompassing six months of guidance and an additional six months of follow-up through online and offline methods. The evaluation indicators will be assessed at enrollment and at 3rd, 6th, and 12th month. Discussion: This study endeavors to furnish novel insights to develop a tailored community-based rehabilitation management program for older adults, delivering customized, intelligent, and precise rehabilitation services.

Identification of a novel MYO1D variant associated with laterality defects, congenital heart diseases, and sperm defects in humans.

The establishment of left-right asymmetry is a fundamental process in animal development. Interference with this process leads to a range of disorders collectively known as laterality defects, which manifest as abnormal arrangements of visceral organs. Among patients with laterality defects, congenital heart diseases (CHD) are prevalent. Through multiple model organisms, extant research has established that myosin-Id (MYO1D) deficiency causes laterality defects. This study investigated over a hundred cases and identified a novel biallelic variant of MYO1D (NM_015194: c.1531G>A; p.D511N) in a consanguineous family with complex CHD and laterality defects. Further examination of the proband revealed asthenoteratozoospermia and shortened sperm. Afterward, the effects of the D511N variant and another known MYO1D variant (NM_015194: c.2293C>T; p.P765S) were assessed. The assessment showed that both enhance the interaction with ß-actin and SPAG6. Overall, this study revealed the genetic heterogeneity of this rare disease and found that MYO1D variants are correlated with laterality defects and CHD in humans. Furthermore, this research established a connection between sperm defects and MYO1D variants. It offers guidance for exploring infertility and reproductive health concerns. The findings provide a critical basis for advancing personalized medicine and genetic counseling.

Functional and Structural Abnormalities in the Pain Network of Generalized Anxiety Disorder Patients with Pain Symptoms.

Pain symptoms significantly impact the well-being and work capacity of individuals with generalized anxiety disorder (GAD), and hinder treatment and recovery. Despite existing literature focusing on the neural substrate of pain and anxiety separately, further exploration is needed to understand the possible neuroimaging mechanisms of the pain symptoms in GAD patients. We recruited 73 GAD patients and 75 matched healthy controls (HC) for clinical assessments, as well as resting-state functional and structural magnetic resonance imaging scans. We defined a pain-related network through a published meta-analysis, including the insula, thalamus, periaqueductal gray, prefrontal cortex, anterior cingulate cortex, amygdala, and hippocampus. Subsequently, we conducted the regional homogeneity (ReHo) and the gray matter volume (GMV) within the pain-related network. Correlation analysis was then employed to explore associations between abnormal regions and self-reported outcomes, assessed using the Patient Health Questionnaire-15 (PHQ-15) and pain scores. We observed significantly increased ReHo in the bilateral insula but decreased GMV in the bilateral thalamus of GAD compared to HC. Further correlation analysis revealed a positive correlation between ReHo of the left anterior insula and pain scores in GAD patients, while a respective negative correlation between GMV of the bilateral thalamus and PHQ-15 scores. In summary, GAD patients exhibit structural and functional abnormalities in pain-related networks. The enhanced ReHo in the left anterior insula is correlated with pain symptoms, which might be a crucial brain region of pain symptoms in GAD.

Heterogeneous Brain Abnormalities in Schizophrenia Converge on a Common Network Associated With Symptom Remission.

BACKGROUND AND HYPOTHESIS: There is a huge heterogeneity of magnetic resonance imaging findings in schizophrenia studies. Here, we hypothesized that brain regions identified by structural and functional imaging studies of schizophrenia could be reconciled in a common network. STUDY DESIGN: We systematically reviewed the case-control studies that estimated the brain morphology or resting-state local function for schizophrenia patients in the literature. Using the healthy human connectome (n = 652) and a validated technique "coordinate network mapping" to identify a common brain network affected in schizophrenia. Then, the specificity of this schizophrenia network was examined by independent data collected from 13 meta-analyses. The clinical relevance of this schizophrenia network was tested on independent data of medication, neuromodulation, and brain lesions. STUDY RESULTS: We identified 83 morphological and 60 functional studies comprising 7389 patients with schizophrenia and 7408 control subjects. The "coordinate network mapping" showed that the atrophy and dysfunction coordinates were functionally connected to a common network although they were spatially distant from each other. Taking all 143 studies together, we identified the schizophrenia network with hub regions in the bilateral anterior cingulate cortex, insula, temporal lobe, and subcortical structures. Based on independent data from 13 meta-analyses, we showed that these hub regions were specifically connected with regions of cortical thickness changes in schizophrenia. More importantly, this schizophrenia network was remarkably aligned with regions involving psychotic symptom remission. CONCLUSIONS: Neuroimaging abnormalities in cross-sectional schizophrenia studies converged into a common brain network that provided testable targets for developing precise therapies.

Mitochondrial disturbance related to increased caspase-1 of CD4+T cells in HIV-1 infection.

BACKGROUND: In HIV-1 infection, more than 95% of CD4+T cells die of caspase-1 mediated pyroptosis. What governs the increased susceptibility of CD4+T cells to pyroptosis is poorly understood. METHODS: Blood samples were obtained from 31 untreated HIV-infected patients (UNT), 29 antiretroviral therapy treated HIV-infected patients (ART), and 21 healthy control donors (HD). Plasma levels of IL-18 and IL-1ß, caspase-1 expression, mitochondrial mass (MM) and mitochondrial fusion/fisson genes of CD4+T subsets were measured. RESULTS: A significantly higher IL-18 level in plasma and MM level of CD4+T cells were found in HIV-infected patients (UNT and ART) compared to HD, and the MMhigh phenotype was manifested, related to increased caspase-1 expression. Moreover, the increased MM was more pronounced in the early differentiated and inactivated CD4+T cells. However, higher MM was not intrinsically linked to T cell differentiation disorder or excessive activation of the CD4+T cells. Mechanistically, the increased MM was significantly correlated with an elevated level of expression of the mitochondrial fusion gene mitofusin1. CONCLUSION: An increase in MM was associated with heightened sensitivity of CD4+T cells to pyroptosis, even in early differentiated and inactivated CD4+T cells, in patients with HIV-1 infection, regardless of whether patients were on antiretroviral therapy or not. These new revelations have uncovered a previously unappreciated challenge to immune reconstitution with antiretroviral therapy.

Effect of hospital-community online management on medication management of elderly patients with peritoneal dialysis during COVID-19.

INTRODUCTION: The study aimed to explore feasibility and effect of hospital-community online management on the medication management of elderly peritoneal dialysis (PD) patients with end-stage renal disease (ESRD) during COVID-19. METHODS: A total of 160 patients receiving PD were randomly divided into the control (n = 80, outpatient follow-up management mode) and observation (n = 80, hospital-community online management mode) groups. The self-efficacy (General Self-Efficacy Scale [GSES]), medication adherence (8-item Morisky medication adherence scale [MMAS-8]), quality of life (kidney disease quality of life short form [KDQOL-SF]), and degree of depression (beck depression inventory [BDI]) before and after the intervention were compared. RESULTS: After the intervention, the scores of GSES (4.20 ± 0.46 vs. 3.09 ± 0.33), MMAS-8 (5.82 ± 0.92 vs. 5.13 ± 1.25), and KDQOL-SF were significantly higher, whereas the BDI score (9.50 ± 2.86 vs. 12.08 ± 2.95) was significantly lower in the observation group than in the control group (p < 0.05). CONCLUSION: Hospital-community online management presents good effects in the medication management of PD patients with ESRD.

Lipid reprogramming induced by the NNMT-ABCA1 axis enhanced membrane fluidity to promote endometrial cancer progression.

Elucidating the mechanism for the high metastasis capacity of Endometrial cancer (EC) is crucial to improve treatment outcomes of EC. We have recently reported that nicotinamide N-methyltransferase (NNMT) is overexpressed in EC, especially in EC, and predicts poor survival of chemotherapy patients. Here, we aimed to determine the function and mechanism of NNMT on metastasis of EC. Additionally, analysis of public datasets indicated that NNMT is involved in cholesterol metabolism. In vitro, NNMT overexpression promoted migration and invasion of EC by reducing cholesterol levels in the cytoplasm and cell membrane. Mechanistically, NNMT activated ABCA1 expression, leading to cholesterol efflux and membrane fluidity enhancement, thereby promoting EC's epithelial-mesenchymal transition (EMT). In vivo, the metastasis capacity of EC was weakened by targeting NNMT. Our findings suggest a new molecular mechanism involving NNMT in metastasis, poor survival of EC mediated by PP2A and affecting cholesterol metabolism.

Thyroid dysfunction induced by immune checkpoint inhibitors and tumor progression during neoadjuvant therapy of non­small cell lung cancer: A case report and literature review.

Immune checkpoint inhibitors (ICIs) have a demonstrable treatment response in patients with resectable non-small cell lung cancer (NSCLC). However, immune-related adverse events and tumor progression in patients administered ICIs are of great concern. The present case study is of a 59-year-old male with NSCLC (squamous, stage IIIA) who received neoadjuvant immunotherapy combined with chemotherapy before surgery. The patient first developed hyperthyroidism and then hypothyroidism, indicating that ICI-related thyroid dysfunction had occurred. Furthermore, the patient suffered from tumor progression and could not undergo resection. The present case called attention to the prevention and management of irAEs, and the precaution that should be taken with regard to tumor progression. The case also suggested that the development of ICI-related thyroid dysfunction may not predict an improved response to ICI therapies, which needs further evidence to illustrate.

Abnormal hemispheric specialization and inter-hemispheric functional cooperation in generalized anxiety disorder.

Abnormal hemispheric specialization and inter-hemispheric interactions may contribute to the pathogenesis of general anxiety disorder (GAD). The current study investigated these abnormalities in GAD patients based on the two analytic approaches and examined whether such abnormalities are correlated with anxiety symptom severity. Seventy-three patients with GAD and 60 matched healthy controls were recruited. All participants completed anxiety symptoms assessment and resting-state functional magnetic resonance imaging (rs-fMRI). The autonomy index (AI) and Connectivity between Functionally Homotopic voxels (CFH) were applied to measure and compared between groups. Compared to controls, patients showed stronger AI in the right middle temporal gyrus (MTG). Seed-based analysis revealed stronger functional connectivity (FC) of the right MTG with both right precuneus and right dorsolateral prefrontal cortex (dlPFC) in patients. Patients also exhibited greater CFH in right anterior cingulate cortex (ACC) but decreased CFH in bilateral postcentral gyrus (PCG) and superior occipital gyrus (SOG). Further there were significant correlations between these regional CFH and anxiety symptoms severity. GAD patients demonstrate right hemispheric specialization and aberrant inter-hemispheric functional cooperation, and abnormal inter-hemispheric coordination is associated with anxiety symptom severity. These findings provide a clue to understanding the neuropathological mechanisms of GAD.

IMC-MDA: Prediction of miRNA-disease association based on induction matrix completion.

To comprehend the etiology and pathogenesis of many illnesses, it is essential to identify disease-associated microRNAs (miRNAs). However, there are a number of challenges with current computational approaches, such as the lack of "negative samples", that is, confirmed irrelevant miRNA-disease pairs, and the poor performance in terms of predicting miRNAs related with "isolated diseases", i.e. illnesses with no known associated miRNAs, which presents the need for novel computational methods. In this study, for the purpose of predicting the connection between disease and miRNA, an inductive matrix completion model was designed, referred to as IMC-MDA. In the model of IMC-MDA, for each miRNA-disease pair, the predicted marks are calculated by combining the known miRNA-disease connection with the integrated disease similarities and miRNA similarities. Based on LOOCV, IMC-MDA had an AUC of 0.8034, which shows better performance than previous methods. Furthermore, experiments have validated the prediction of disease-related miRNAs for three major human diseases: colon cancer, kidney cancer, and lung cancer.

Risk of Urinary Tract Infection in Patients with Type 2 Diabetes Mellitus Treated with Dapagliflozin: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND OBJECTIVE: To investigate whether dapagliflozin (as a selective inhibitor of sodium-glucose cotransporter 2), increases the risk of urinary tract infection (UTI) in the treatment of type 2 diabetes mellitus (T2DM) remains an ongoing issue. We performed a systematic review and meta-analysis of randomized clinical trials (RCTs) to estimate the short-term and long-term risks of UTI in patients with T2DM who received dapagliflozin at different doses. METHODS: The PubMed, EMBASE, and the Cochrane Library and ClinicalTrials.gov website were searched up to December 31, 2022. Only RCTs involving adult T2DM patients with a trial duration of at least 12 weeks were included. The data were summarized using random- or fixed-effects models based on overall heterogeneity. A subgroup analysis was also performed. The review protocol was previously registered in the PROSPERO database (CRD42022299899). RESULTS: In total, 42 RCTs involving 35,938 patients were assessed for eligibility. The results showed that dapagliflozin imposed a higher risk of UTI compared to placebo and other active treatments, with a heterogeneity of 11% (odds ratio [OR] 1.17, 95% CI 1.04-1.31, p = 0.006). In the subgroup analysis, dapagliflozin 10 mg/day with a treatment period of > 24 weeks was associated with a significantly higher UTI risk than placebo or other active treatments (OR 1.27, 95% CI 1.13-1.43, p < 0.0001). The ORs for dapagliflozin as monotherapy and combination therapy in the control group were 1.05 (95% CI 0.88-1.25, p = 0.571) and 1.27 (95% CI 1.09-1.48, p = 0.008), respectively. CONCLUSIONS: High-dose, long-term treatment, and add-on therapy of dapagliflozin call for careful consideration of the risk of UTI in T2DM patients.

Apathy in melancholic depression and abnormal neural activity within the reward-related circuit.

Major depressive disorder is a heterogeneous syndrome, of which the most common subtype is melancholic depression (MEL). Previous studies have indicated that anhedonia is frequently a cardinal feature in MEL. As a common syndrome of motivational deficit, anhedonia is closely associated with dysfunction in reward-related networks. However, little is currently known about apathy, another syndrome of motivational deficits, and the underlying neural mechanisms in MEL and non-melancholic depression (NMEL). Herein, the Apathy Evaluation Scale (AES) was used to compare apathy between MEL and NMEL. On the basis of resting-state functional magnetic resonance imaging, functional connectivity strength (FCS) and seed-based functional connectivity (FC) were calculated within reward-related networks and compared among 43 patients with MEL, 30 patients with NMEL, and 35 healthy controls. Patients with MEL had higher AES scores than those with NMEL (t = -2.20, P = 0.03). Relative to NMEL, MEL was associated with greater FCS (t = 4.27, P < 0.001) in the left ventral striatum (VS), and greater FC of the VS with the ventral medial prefrontal cortex (t = 5.03, P < 0.001) and dorsolateral prefrontal cortex (t = 3.18, P = 0.005). Taken together the results indicate that reward-related networks may play diverse pathophysiological roles in MEL and NMEL, thus providing potential directions for future interventions in the treatment of various depression subtypes.

Flexible aqueous supercapacitors with excellent cycling performance and high-energy density based on mesocrystalline NiCo-LDHs.

Flexible aqueous supercapacitors are promising candidates as safe power sources for wearable electronic devices (WEDs). However, the absence of advanced electrode materials with high structural stability has become the most critical factor hindering the development, which is closely related to the poor interface combination between the active substances and flexible collectors. Herein, a unique rigid layered double hydroxide (LDH) nanorod array with the mesocrystalline feature is created using the NiO-Ni layer as the inducer by the electrodeposition strategy. Differing from the traditional NiCo-LDH nanosheets directly grown on a carbon cloth, an elaborately designed NiO-Ni buffer can simultaneously and effectively improve the bidirectional combination with active substances and collectors, also the mesocrystalline LDH showed enhanced intrinsic stability through the reinforcing effect of grain boundaries. Benefiting from these, the assembled supercapacitor exhibited pre-eminent cycle stability (increased from 64% of the initial capacity after 10 000 cycles to no significant attenuation after 50 000 cycles) and ultrahigh energy density. When it was used as a flexible device, a remarkable energy density of 70.4 W h kg-1 could be harvested and processed with high flexibility in the bending state and good temperature adaptability. This study provides an excellent design strategy for the development of next-generation flexible supercapacitors with the goal of better comprehensive performances.

Abnormal resting-state function within language network and its improvement among post-stroke aphasia.

Several studies with resting-state magnetic resonance imaging (rs-fMRI) have examined functional impairments and plasticity within language network in patients with post-stroke aphasia (PSA). However, there is still ubiquitous inconsistency across these studies, partly due to restricted to very small sample size and the absence of validation with follow-up data. In the current study, we aimed at providing relatively strong evidence to support functional impairments and its reorganization in PSA. Here, the amplitude of low frequency fluctuations (ALFF) and functional connectivity were used to assess functional alterations of PSA with moderate sample size at baseline (thirty-five PSA patients and thirty-five healthy controls). Functional abnormalities at baseline were observed whether improved among sixteen follow-up patients. Compared with controls, PSA at baseline presented decreased ALFF in the left inferior frontal gyrus (IFG) and decreased functional connectivity of the left IFG with the bilateral supplementary motor area (SMA) and right superior temporal gyrus (STG). The decreased ALFF in IFG, decreased IFG-SMA and IFG-STG connectivity were enhanced among follow-up patients and was synchronized with language-performance improvement. Our results revealed reduced intrinsic neural activity and inter-connections within language network in PSA, which would be normalized synchronously as the improvement of language performance.

Molten Salt-Assisted Construction of Hollow Carbon Spheres with Outer-Order and Inner-Disorder Heterostructure for Ultra-Stable Potassium Ion Storage.

The central goal of high-performance potassium ion storage is to control the function of the anode material via rational structural design. Herein, N- and S-doped hollow carbon spheres with outer-short-range-order and inner-disorder structures are constructed to achieve highly efficient and ultra-stable potassium ion storage using a low-temperature molten salt system. The ultrathin carbon walls and uniform mesoporous as well as unique heterostructure synergistically realize significant potassium storage performance via facilitating rapid diffusion of potassium ions and alleviating substantial volume expansion. Furthermore, as the anode of a potassium ion battery, the as-prepared MSTC electrode demonstrates a state-of-the-art cycling capability of 221.3 mAh g-1 at 1 A g-1 after 20,000 cycles. The assembled potassium ion hybrid capacitor device demonstrates a high energy of 157 Wh kg-1 at 956 W kg-1 and excellent reversibility at a current density of 5.0 A g-1 after 20,000 cycles with 82.7% capacity retention. Accordingly, our work provides new ideas for designing advanced carbon anode materials and understanding the charge storage mechanism in potassium ion battery, as well as constructing high energy-power density potassium-ion hybrid capacitors (PIHCs).

Achieving Ultrahigh Energy-Density Aqueous Supercapacitors via a Novel Acidic Radical Adsorption Capacity-Activation Mechanism in Ni(SeO3 )/Metal Sulfide Heterostructure.

Transitional metal chalcogenide (TMC) is considered as one promising high-capacity electrode material for asymmetric supercapacitors. More evidence indicates that TMCs have the same charge storage mechanism as hydroxides, but the reason why TMC electrode materials always provide higher capacity is rare to insight. In this work, a Nix Coy Mnz S/Ni(SeO3 ) (NCMS/NSeO) heterostructure is prepared on Ni-plated carbon cloth, validating that both NCMS and NSeO can be transformed into hydroxides in electrochemical process as accompanying with the formation of SeO3 2- and SOx 2- in confined spaces of NCMS/NSeO/Ni sandwich structure. Based on density functional theory calculation and experimental results, a novel space-confined acidic radical adsorption capacity-activation mechanism is proposed for the first time, which can nicely explain the capacity enhancement of NCMS/NSeO electrode materials. Thanks to the unique capacity enhancement mechanism and stable NCMS/NSeO/Ni sandwich structure, the optimized electrodes exhibit a high capacity of 536 mAh g-1 at 1 A g-1 and the impressive rate capability of 140.5 mAh g-1 at the amazing current density of 200 A g-1 . The assembled asymmetric supercapacitor achieves an ultrahigh energy density of 141 Wh Kg-1 and an impressive high-rate capability and cyclability combination with 124% capacitance retention after 10 000 cycles at a large current density of 50 A g-1 .

A latent class analysis of community-based rehabilitation needs among Chinese older adults: a mixed study protocol.

Background: Geriatric diseases (e.g., chronic diseases and geriatric syndromes) may result in impaired physical performance and a decline in the quality of life. The results of previous studies reported the positive effects of comprehensive community-based rehabilitation (CBR) services on physical and social functioning and psychosocial wellbeing. However, to provide adequate and personalised rehabilitation services, it is essential to understand the needs of the older adults population. There have been no studies on the need for CBR in older adults populations that consider their heterogeneity. Therefore, high-quality studies are required to recognise the heterogeneity and latent classes of CBR needs in older adults population groups. This study aims to identify the heterogeneity of the rehabilitation needs of older adults in the community and explore whether older adults with similar characteristics have similar needs through a cross-sectional survey and latent class analysis (LCA) to provide support for personalised rehabilitation services. Methods: The study is structured into four phases. The first phase will focus on constructing a comprehensive questionnaire to assess rehabilitation needs. In the second phase, a pilot study will be conducted to evaluate the reliability and validity of the completed questionnaire. This step ensures the robustness of the instrument for data collection. The third phase will involve cross-sectional surveys using the finalised questionnaires to collect the necessary data from the targeted population. The fourth phase will focus on conducting LCA to determine the CBR needs of the older adult population. Discussion: The results of this study will provide novel and critical information for a better understanding of the rehabilitation needs, potential categories, and influencing factors of older adults in the community. The study will be conducted in Guizhou Province in western China, where economic and social development is relatively low, and the results will inform and benefit other regions and developing countries facing similar challenges. However, because of the complete social security and rehabilitation service systems in developed areas, our research results may not fully reflect the situation in these areas. Future studies may need to be conducted in places with different levels of social development. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=191398, ChiCTR2300071478.

Corrigendum to "Lenvatinib plus sintilimab versus lenvatinib monotherapy as first-line treatment for advanced HBV-related hepatocellular carcinoma: A retrospective, real-world study" [Heliyon 8 (6) (2022) e09538].

[This corrects the article DOI: 10.1016/j.heliyon.2022.e09538.].