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Abstract Background Enteral nutrition for stroke patients in China presents major shortcomings. This aspect of care involves multiple components, and poor implementation of any one of them may affect the patients’ enteral nutrition. Most current studies only confirm the effectiveness of the application of single interventions and lack any scientific evaluation of the overall ensemble of enteral nutrition interventions in stroke patients. This study focuses on evaluating the overall effectiveness of a care bundles for the management of enteral nutrition in stroke patients by targeting multiple simultaneous interventions. Methods This study is to be conducted over 10 periods in the stroke patient wards of eight hospitals across China. As the trial progresses, each hospital begins by receiving the control group care and then shifts to the intervention group care. The point at which each hospital shifts care is randomised. During this time, the control group implements its usual care, while the intervention group implements an evidence-based care bundles for enteral nutrition management in stroke patients. The primary indicator in this study is feeding intolerance; indicators for the evaluation of nutritional status, gastrointestinal complications, and disease prognosis are also included. Discussion We anticipate that the care bundles developed by pooling this evidence will be manifestly more beneficial than harmful and will be worthy of replication. Hence, we chose a stepped wedge cluster randomised trial to validate the application of these interventions. This study will provide experience and reference on how to promote the clinical translation of evidence-based evidence and standardise enteral nutrition care management in stroke patients. Trial registration ChiCTR2300067930. Registered on January 31, 2023.

Abstract Background Accurate reporting of outcomes is crucial for interpreting the results of randomized controlled trials (RCTs). However, selectively reporting outcomes in publications to achieve researchers’ anticipated results still occurs frequently. This study aims to investigate the prevalence of selective reporting of outcomes in RCTs on treating acute ischemic stroke (AIS), identify factors contributing to this issue, and assess its potential impact on the degree and direction of intervention effect. Methods A search was conducted in MEDLINE, Embase, and the Cochrane Library to collect interventional RCTs on AIS published from 2020 to 2022. Full texts of RCTs were reviewed, and only those reporting International Clinical Trials Registry Platform primary registry numbers were included. Registration information of the RCTs was extracted from the registry platforms and compared with the publications’ details to assess the selective reporting of outcomes. Bayesian multilevel logistic regression was used to analyze the reasons behind selective reporting. Results Among the total of 159 AIS RCTs identified, 82 (51.6%) were ultimately included, as they reported registration numbers, which encompassed 819 outcomes. Among them, 72 RCTs (87.8%) and 497 outcomes (60.7%) exhibited selective reporting. Omission-type selective reporting (downgrading, omitting, or ambiguously reporting) accounted for 36.4%, while addition-type selective reporting (upgrading, adding, or altering the measurement scope of outcomes) comprised 63.6%. Omission-type selective reporting correlated with negative results (OR: 7.39; 95% CI: 4.08—13.44), whereas addition-type selective reporting correlated with positive results (OR: 2.07; 95% CI: 1.34—3.26) and publication in journals that are not in the top quartile of the Journal Citation Reports (OR: 2.48; 95% CI: 1.15—5.38). Conclusions Registered interventional AIS RCTs still face significant issues regarding selective reporting of outcomes. Therefore, it is necessary to further evaluate the influence of selective reporting bias on the positive results obtained from individual AIS RCTs and the systematic reviews based on these RCTs.

Based on X ray diffraction and Fourier transform infrared spectroscopy, the microcrystalline structure characteristics and evolution patterns of a total of 6 coal samples from the eastern Junggar, southern Junggar, Tuha, and Kubai coalfields in Xinjiang were investigated. The peak shape of 002 and 100 peaks in low-rank coal is gentle, the peak 002 becomes sharper and the “symmetry” becomes better with the increase of coal rank, and the peak height of the peak 100 gradually increases but the peak width gradually shrinks. The height of the peak 100 gradually increases but the width gradually narrows; with the increase of coal sample metamorphism, the stacking height, elongation and quantity of aromatic laminates increase gradually, the spacing of aromatic laminates decreases on the whole, and the condensation degree of aromatic structures in coal increases gradually; the peak shape of aromatic compounds and oxygen-containing functional groups is sharp, and the peak shape of aliphatic hydrocarbons and hydroxyl functional groups is gentle, which gradually widens and slows down with the rise of coal rank; with the increase of coal rank, the aromaticity, fat chain length, branched chain degree and maturity gradually decrease, while the polycondensation degree and hydrocarbon (oil) generation ability gradually increase. The evolution process of coal is characterized by the shedding of oxygen-containing functional groups, the enrichment of aliphatic hydrocarbons, and the condensation of some aromatics.

Abstract Background Meta-epidemiological research plays a vital role in providing empirical evidence needed to develop methodological manuals and tools, but the reporting quality has not been comprehensively assessed, and the influence of reporting guidelines remains unclear. The current study aims to evaluate the reporting quality of meta-epidemiological studies, assess the impact of reporting guidelines, and identify factors influencing reporting quality. Methods We searched PubMed and Embase for meta-epidemiological studies. The reporting quality of these studies was assessed for adherence to established reporting guidelines. Two researchers independently screened the studies and assessed the quality of the included studies. Time-series segmented linear regression was used to evaluate changes in reporting quality over time, while beta-regression analysis was performed to identify factors significantly associated with reporting quality. Results We initially identified 1720 articles, of which 125 meta-epidemiological studies met the inclusion criteria. Of these, 65 (52%) had low reporting quality, 60 (48%) had moderate quality, and none achieved high quality. Of the 24 items derived from established reporting guidelines, 4 had poor adherence, 13 had moderate adherence, and 7 had high adherences. High journal impact factor (≥ 10) (OR = 1.42, 95% CI: 1.13, 1.80; P = 0.003) and protocol registration (OR = 1.70, 95% CI: 1.30, 2.22; P

Abstract Background Given the critical importance of medication adherence in HIV/AIDS treatment, this study aims to compare medication adherence measured by self-report (SR) and indirect measurement among antiretroviral therapy (ART) patients, exploring the differences of adherence results measured by different tools. Methods We systematically searched PubMed, Embase, and the Cochrane Library to identify all relevant literature published up to November 22, 2023, without language restrictions, reporting adherence to ART measured by both SR and indirect measurement methods, while also analyzing individual and group adherence separately. Discrepancies between SR and indirect measurement results were assessed using the Mann–Whitney U test or Wilcoxon signed-rank test, with correlations evaluated using the Pearson correlation coefficient. Following one-to-one comparisons, meta-epidemiological one-step analysis was conducted, and network meta-analysis techniques were applied to compare results obtained through specific adherence assessment tools reported in the identified articles. Results The analysis encompassed 65 original studies involving 13,667 HIV/AIDS patients, leading to 112 one-to-one comparisons between SR and indirect measurement tools. Statistically significant differences were observed between SR and indirect measurement tools regarding both individual and group adherence (P

IntroductionThe COVID-19 pandemic has placed nurses at the forefront of healthcare, exposing them to various mental health challenges such as depression, anxiety, and post-traumatic stress disorder (PTSD). However the long-term effects and risk factors of the COVID-19 pandemic on nurses’ mental health are unknown. The objective of our study is to investigate the enduring impact of the COVID-19 pandemic on the psychological distress and PTSD of nurses, while also identifying the factors that influence these outcomesMethodsTo investigate this question, we conducted a self-reported questionnaire survey of 8785 registered nurses recruited using snowball sampling methodology from 22 provinces in China, at five time points (T0-T4). At all times, we took measures of general health, while at the last four times we also measured PTSD. And we used logistic regression analysis to explore their impacts.ResultsThe incidence of whole levels psychological distress among nurses was 27.7% at T0, peaking at 57.6% at T4. For severe psychological distress, it began at 5.5% at T0 and rose to 9.5% at T4. PTSD rates among nurses were recorded at 7.8% in T1, reaching a maximum of 14.7% in T4. They all got progressively worse in the volatility. In all times, coping strategies are independent factors for various levels of psychological distress and PTSD, while social support is a key factor for severe psychological distress and PTSD.ConclusionsOur findings indicated a gradual deterioration in the mental health of nurses following the COVID-19 outbreak. In all instances, coping strategies exhibit an independent correlation with all grades of psychological distress and post-traumatic stress disorder (PTSD), whereas social support emerges as an independent protective factor mitigating the risk of severe psychological distress and PTSD.

This research focuses on the challenge of defining the ellipsoidal boundaries of the reachable set (RS) for neutral-type dynamical systems with time delays. A novel analytical approach is proposed, leveraging the development of new Lyapunov functions and matrix inequality techniques. These methods provide powerful tools for determining the ellipsoidal boundaries of the system's RS. A comparative analysis, supported by numerical examples, demonstrates that the approach outlined in this study can accurately identify smaller yet effective RS boundaries compared to existing literature. This precise boundary determination offers significant theoretical support for state estimation and control design in dynamical systems, thereby enhancing their effectiveness and reliability in real-world applications.

Abstract Background HIV-tuberculosis (HIV-TB) co-infection is a significant public health concern worldwide. TB delay, consisting of patient delay, diagnostic delay, treatment delay, increases the risk of adverse anti-TB treatment (ATT) outcomes. Except for individual level variables, differences in regional levels have been shown to impact the ATT outcomes. However, few studies appropriately considered possible individual and regional level confounding variables. In this study, we aimed to assess the association of TB delay on treatment outcomes in HIV-TB co-infected patients in Liangshan Yi Autonomous Prefecture (Liangshan Prefecture) of China, using a causal inference framework while taking into account individual and regional level factors. Methods We conducted a study to analyze data from 2068 patients with HIV-TB co-infection in Liangshan Prefecture from 2019 to 2022. To address potential confounding bias, we used a causal directed acyclic graph (DAG) to select appropriate confounding variables. Further, we controlled for these confounders through multilevel propensity score and inverse probability weighting (IPW). Results The successful rate of ATT for patients with HIV-TB co-infection in Liangshan Prefecture was 91.2%. Total delay (OR = 1.411, 95% CI: 1.015, 1.962), diagnostic delay (OR = 1.778, 95% CI: 1.261, 2.508), treatment delay (OR = 1.749, 95% CI: 1.146, 2.668) and health system delay (OR = 1.480 95% CI: (1.035, 2.118) were identified as risk factors for successful ATT outcome. Sensitivity analysis demonstrated the robustness of these findings. Conclusions HIV-TB co-infection prevention and control policy in Liangshan Prefecture should prioritize early treatment for diagnosed HIV-TB co-infected patients. It is urgent to improve the health system in Liangshan Prefecture to reduce delays in diagnosis and treatment.

PurposeFibroblast activation protein (FAP) is highly expressed in the mesenchyme of most malignant epithelial tumors, while its expression is low in normal tissues. FAP inhibitors (FAPIs) bind specifically to FAP and are used for tumor-targeted diagnosis and therapy. The aim of this study was to radiosynthesize a novel molecular probe 131I-FAPI and evaluate its in-vitro targeting and biological characteristics.MethodsThe structurally modified FAPI was labelled with 131I through the chloramine-T method. The radiolabeling rate was then detected by thin-layer chromatography (TLC). The stability of 131I-FAPI was determined at PBS (room temperature) and serum (37°C). Its hydrophilicity was calculated by measuring its lipid-water partition coefficient. Pancreatic cancer PANC-1 cell line and glioma U87 cell line were cultured in vitro. Cell uptake assay was used to show the binding ability of 131I-FAPI. The CCK-8 assay was used to calculate the inhibitory effects of 131I-FAPI at different time points (4h, 8h, 12h, 24h, 48h) after comparing with the 131I and FAPI. The before-and-after-24h scratch areas of the two cells were determined in order to verify the effect of 131I-FAPI on the migration ability of the cells.ResultsThe radiolabeling rate was (84.9 ± 1.02) %. The radiochemical purity of 131I-FAPI remained over 80% in both 25°C PBS and 37°C serum. The value of the lipid-water partition coefficient was -0.869 ± 0.025, indicating the hydrophilic of the probe. The cellular uptake assay showed that U87 cells had a specific binding capacity for 131I-FAPI. In cell inhibition assays, the inhibitory effect of 131I-FAPI on U87 cells increased with time. The results of cell scratch assay showed that 131I-FAPI had the strongest inhibitory effect on the migratory ability of U87 cells compared with 131I and FAPI (P

Abstract Purpose The temporal evolution of ventricular trabecular complexity and its correlation with major adverse cardiovascular events (MACE) remain indeterminate in patients presenting with acute ST elevation myocardial infarction (STEMI). Methods This retrospective analysis enrolled patients undergoing primary percutaneous coronary intervention (pPCI) for acute STEMI, possessing cardiac magnetic resonance (CMR) data in the acute (within 7 days), subacute (1 month after pPCI), and chronic phases (6 months after pPCI) from January 2015 to January 2020 at the three participating sites. Fractal dimensions (FD) were measured for the global, infarct, and remote regions of left ventricular trabeculae during each phase. The potential association of FD with MACE was analyzed using multivariate Cox regression. Results Among the 200 analyzed patients (182 men; median age, 61 years; age range, 50–66 years), 37 (18.5%) encountered MACE during a median follow-up of 31.2 months. FD exhibited a gradual decrement (global FD at acute, subacute, and chronic phases: 1.253 ± 0.049, 1.239 ± 0.046, 1.230 ± 0.045, p

Abstract Background The relaxation of the “zero-COVID” policy on Dec. 7, 2022, in China posed a major public health threat recently. Complete blood count test was discovered to have complicated relationships with COVID-19 after the infection, while very few studies could track long-term monitoring of the health status and identify the characterization of hematological parameters prior to COVID-19. Methods Based on a 13-year longitudinal prospective health checkup cohort of ~ 480,000 participants in West China Hospital, the largest medical center in western China, we documented 998 participants with a laboratory-confirmed diagnosis of COVID-19 during the 1 month after the policy. We performed a time-to-event analysis to explore the associations of severe COVID-19 patients diagnosed, with 34 different hematological parameters at the baseline level prior to COVID-19, including the whole and the subtypes of white and red blood cells. Results A total of 998 participants with a positive SARS-CoV-2 test were documented in the cohort, 42 of which were severe cases. For white blood cell-related parameters, a higher level of basophil percentage (HR = 6.164, 95% CI = 2.066–18.393, P = 0.001) and monocyte percentage (HR = 1.283, 95% CI = 1.046–1.573, P = 0.017) were found associated with the severe COVID-19. For lymphocyte-related parameters, a lower level of lymphocyte count (HR = 0.571, 95% CI = 0.341–0.955, P = 0.033), and a higher CD4/CD8 ratio (HR = 2.473, 95% CI = 1.009–6.059, P = 0.048) were found related to the risk of severe COVID-19. We also observed that abnormality of red cell distribution width (RDW), mean corpuscular hemoglobin concentration (MCHC), and hemoglobin might also be involved in the development of severe COVID-19. The different trajectory patterns of RDW-SD and white blood cell count, including lymphocyte and neutrophil, prior to the infection were also discovered to have significant associations with the risk of severe COVID-19 (all P

Ubiquitination is a highly conserved and dynamic post-translational modification in which protein substrates are modified by ubiquitin to influence their activity, localization, or stability. Deubiquitination enzymes (DUBs) counter ubiquitin signaling by removing ubiquitin from the substrates. Ubiquitin-specific proteases (UBPs), the largest subfamily of DUBs, are conserved in plants, serving diverse functions across various cellular processes, although members within the same group often exhibit functional redundancy. Here, we briefly review recent advances in understanding the biological roles of UBPs, particularly the molecular mechanism by which UBPs regulate plant development and growth, morphogenesis, and stress response, which sheds light on the mechanistic roles of deubiquitination in plants.

Abstract The Golden2-like (GLK) transcription factors are plant-specific transcription factors (TFs) that perform extensive and significant roles in regulating chloroplast development. Here, genome-wide identification, classification, conserved motifs, cis-elements, chromosomal locations, evolution and expression patterns of the PtGLK genes in the woody model plant Populus trichocarpa were analyzed in detail. In total, 55 putative PtGLKs (PtGLK1-PtGLK55) were identified and divided into 11 distinct subfamilies according to the gene structure, motif composition and phylogenetic analysis. Synteny analysis showed that 22 orthologous pairs and highly conservation between regions of GLK genes across P. trichocarpa and Arabidopsis were identified. Furthermore, analysis of the duplication events and divergence times provided insight into the evolutionary patterns of GLK genes. The previously published transcriptome data indicated that PtGLK genes exhibited distinct expression patterns in various tissues and different stages. Additionally, several PtGLKs were significantly upregulated under the responses of cold stress, osmotic stress, and methyl jasmonate (MeJA) and gibberellic acid (GA) treatments, implying that they might take part in abiotic stress and phytohormone responses. Overall, our results provide comprehensive information on the PtGLK gene family and elucidate the potential functional characterization of PtGLK genes in P. trichocarpa.

The project of China initiative Accelerator Driven Subcritical (CiADS) system has been started to construct in southeast China's Guangdong province since 2019, which is expected to be checked and accepted in the year 2025. In order to make the students in University of Chinese Academy of Sciences (UCAS) better understand the main characteristic and the operation condition in the subcritical nuclear facility, the training platform for CiADS has been developed based on the Cave Automatic Virtual Environment (CAVE) in the Institute of Modern Physics Chinese Academy of Sciences (IMPCAS). The CAVE platform is a kind of non-head mounted virtual reality display system, which can provide the immersive experience and the alternative training platform to substitute the dangerous operation experiments with strong radioactivity. In this paper, the CAVE platform for the training scenarios in CiADS system has been presented with real-time simulation feature, where the required devices to generate the auditory and visual senses with the interactive mode have been detailed. Moreover, the three dimensional modeling database has been created for the different operation conditions, which can bring more freedom for the teachers to generate the appropriate training courses for the students. All the user-friendly features will offer a deep realistic impression to the students for the purpose of getting the required knowledge and experience without the large costs in the traditional experimental nuclear reactor.

Abstract. Background:. This study aimed to develop a comprehensive instrument for evaluating and ranking clinical practice guidelines, named Scientific, Transparent and Applicable Rankings tool (STAR), and test its reliability, validity, and usability. Methods:. This study set up a multidisciplinary working group including guideline methodologists, statisticians, journal editors, clinicians, and other experts. Scoping review, Delphi methods, and hierarchical analysis were used to develop the STAR tool. We evaluated the instrument's intrinsic and interrater reliability, content and criterion validity, and usability. Results:. STAR contained 39 items grouped into 11 domains. The mean intrinsic reliability of the domains, indicated by Cronbach's α coefficient, was 0.588 (95% confidence interval [CI]: 0.414, 0.762). Interrater reliability as assessed with Cohen's kappa coefficient was 0.774 (95% CI: 0.740, 0.807) for methodological evaluators and 0.618 (95% CI: 0.587, 0.648) for clinical evaluators. The overall content validity index was 0.905. Pearson's r correlation for criterion validity was 0.885 (95% CI: 0.804, 0.932). The mean usability score of the items was 4.6 and the median time spent to evaluate each guideline was 20 min. Conclusion:. The instrument performed well in terms of reliability, validity, and efficiency, and can be used for comprehensively evaluating and ranking guidelines.

Inspired by state-of-the-art material science, computer techniques, artificial intelligence, and automatic control, new-generation transportation infrastructures are becoming digitalized and intelligent. Many major developed countries around the globe are actively promoting the application of innovative intelligence-based technologies in transportation infrastructures in accordance with local conditions. This review begins with a brief discussion on the basic definition, scientific foundation, and development process for the intellectualization of transportation infrastructures. Then, following the whole life-cycle chain of design, construction, operational maintenance, and elimination, the current research status and major challenges presented by intellectualization technologies are systematically investigated. Subsequently, recent achievements in intellectual technologies are comprehensively presented by selecting the Beijing–Zhangjiakou High-Speed Railway—the world’s first railway built based on the concept of intelligent construction—as an example. Finally, a discussion on the future development of the intellectualization of transportation infrastructures is provided from the three dimensions of standard systems, theoretical methods, and talent training.

ABSTRACTThe MCL1 inhibitors are undergoing clinical testing for multiple leukemia. However, because that MCL1 inhibition has on-target hematopoietic, hepatic and cardiac toxicities, there is substantial interest in finding agents can sensitize leukemia cells to the MCL1 inhibitors. Here we describe that the AKT inhibitors MK-2206 and Gsk690693 sensitize multiple leukemia cells to the MCL1 inhibitor S63845. Further experiments demonstrate that MK-2206 and Gsk690693 sensitize S63845 through the mitochondrial apoptosis pathway. Moreover, MK-2206 downregulates the anti-apoptotic protein BCLXL and induces the BH3-only pro-apoptotic protein BAD dephosphorylation and mitochondrial translocation. Knockdown of BAD significantly inhibits MK-2206-induced sensitization to S63845. Thus, our results suggest that MK-2206 sensitizes multiple leukemia cells to S63845-induced apoptosis, with the mechanisms involving BAD dephosphorylation and BCLXL downregulation.

Abstract Background The Chinese government stipulates all food for special medical purposes (FSMP) designed for specific diseases to be tested in clinical trials before approving it for registration. The process of developing core outcome sets (COSs), the minimum sets of outcomes supposed to be measured and reported, provides an economical and practical option for stakeholders to communicate and cooperate in conducting clinical trials as well as in reporting FSMP outcomes. This study uses type 2 diabetes mellitus (T2DM) as an example to develop COS for clinical trials of FSMP. Methods The COS for FSMP-T2DM will be divided into 3 phases and developed following COS-STAP and COS-STAD: (1) Generate a list of relevant outcomes identified from a systematic review, in which information sources will mainly include published studies, regulatory documentation, and qualitative interviews of stakeholders. The identified outcomes will be categorized using a conceptual framework and formatted into the first round of the Delphi survey questionnaire items. (2) At least 2 rounds of Delphi surveys will be performed among stakeholders to create the COS for FSMP-T2DM. Patients, clinical dietitians, physicians, COS researchers, journal editors, FSMP manufacturers, and regulatory representatives will be invited to score each outcome from aspects of importance. (3) Hold a face-to-face or online consensus meeting to refine the content of the COS for FSMP-T2DM. Key stakeholders will be invited to attend the meeting to discuss and agree on the final COS. Discussion We have prepared an alternative solution of the Likert scale selection, Delphi survey rounds, scoring group, and consensus definitions in case of an unexpected situation. Trial registration COMET (1547). Registered on March 23, 2020.

Abstract Fibroblast activation protein (FAP) is higher expressed on cancer-associated fibroblasts (CAFs) in most malignant epithelial neoplasms, which is lower expressed in normal tissues. As a promising small molecular probe, FAP inhibitor (FAPI) shows the specific binding to FAP. This study aimed to explore a novel molecular probe [99mTc]Tc-HYNIC-FAPI targeting CAFs. The in vitro characteristics of the probe were also evaluated. The FAPI targeting FAP was designed, synthesized and conjugated with the chelator 6-hydrazinylnicotinic acid (HYNIC) for radiolabeling with 99mTc. The radiolabeling yield, radiochemical purity and stability were evaluated by Instant thin-layer chromatography (ITLC) and High performance liquid chromatography (HPLC). Lipophilicity was performed by the distribution coefficient test. The binding and migration ability of the probe was assessed using the FAP transfected tumor cell line. The radiolabeling yield of [99mTc]Tc-HYNIC-FAPI was (97.29 ± 0.46) %. The radiochemical purity was more than 90% and kept stable until 6 h. The radioligand was shown as lower lipophilicity, of which logD7.4 value was − 2.38 $$\pm$$ ± 0.13. In vitro experiments, the results indicated that the probe showed binding properties, and inhibited the migration of tumor cells. The novel [99mTc]Tc-HYNIC-FAPI probe was successfully radiosynthesized and exhibited good radiochemical purity, stability and in vitro binding ability to tumor cells. The [99mTc]Tc-HYNIC-FAPI will be a promising SPECT/CT imaging probe.

The core power control is an important issue for the study of dynamic characteristics in China initiative accelerator driven subcritical system (CiADS), which has direct impact on the control strategy and safety analysis process. The CiADS is an experimental facility that is only controlled by the proton beam intensity without considering the control rods in the current engineering design stage. In order to get the optimized operation scheme with the stable and reliable features, the variation of beam intensity using the continuous and periodic control approaches has been adopted, and the change of collimator and the adjusting of duty ratio have been proposed in the power control process. Considering the neutronics and the thermal-hydraulics characteristics in CiADS, the physical model for the core power control has been established by means of the point reactor kinetics method and the lumped parameter method. Moreover, the multi-inputs single-output (MISO) logical structure for the power control process has been constructed using proportional integral derivative (PID) controller, and the meta-heuristic algorithm has been employed to obtain the global optimized parameters for the stable running mode without producing large perturbations. Finally, the verification and validation of the control method have been tested based on the reference scenarios in considering the disturbances of spallation neutron source and inlet temperature respectively, where all the numerical results reveal that the optimization method has satisfactory performance in the CiADS core power control scenarios.

Abstract Objectives To explore the causes of sudden unexpected death (SUD) and to search for high-risk people, whole exome sequencing (WES) was performed in families with SUDs. Methods Whole exome sequencing of 25 people from 14 SUD families were screened based on cardiac disease-associated gene variants, and their echocardiograms and electrocardiograms (ECG) were also examined. The protein function of mutated genes was predicted by SIFT, PolyPhen2 and Mutation Assessor. Results In the group of 25 people from 14 SUD families, 49 single nucleotide variants (SNVs) of cardiac disease-associated genes were found and verified by Sanger sequencing. 29 SNVs of 14 cardiac disorder-related genes were predicted as pathogens by software. Among them, 7 SNVs carried by two or more members were found in 5 families, including SCN5A (c.3577C > T), IRX4 (c.230A > G), LDB3 (c.2104 T > G), MYH6 (c.3G > A), MYH6 (c.3928 T > C), TTN (c.80987C > T) and TTN (c.8069C > T). 25 ECGs were collected. In summary, 4 people had J-point elevation, 2 people had long QT syndrome (LQTS), 4 people had prolonged QT interval, 3 people had T-wave changes, 3 people had sinus tachycardia, 4 people had sinus bradycardia, 4 people had left side of QRS electrical axis, and 3 people had P wave broadening. Echocardiographic results showed that 1 person had atrial septal defect, 1 person had tricuspid regurgitation, and 2 people had left ventricular diastolic dysfunction. Conclusions Of the 14 heart disease-associated genes in 14 SUDs families, there are 7 possible pathological SNVS may be associated with SUDs. Our results indicate that people with ECG abnormalities, such as prolonged QT interval, ST segment changes, T-wave change and carrying the above 7 SNVs, should be the focus of prevention of sudden death.

Transparency Ecosystem for Research and Journals in Medicine (TERM) working group summarized the essential recommendations that should be considered to review and publish a high-quality guideline. These recommendations from editors and reviewers included 10 components of essential requirements: systematic review of existing relevant guidelines, guideline registration, guideline protocol, stakeholders, conflicts of interest, clinical questions, systematic reviews, recommendation consensus, guideline reporting and external review. TERM working group abbreviates them as PAGE (essential requirements for Publishing clinical prActice GuidelinEs), and recommends guideline authors, editors, and peer reviewers to use them for high-quality guidelines.

With the rapid development of our country, the construction and development of power system has shown the continuous growth of load, and the proportion of new generation energy has also expanded. The impact of these problems on our life cannot be underestimated. Therefore, the development of new energy has become a necessary way to realize the transformation of energy production to green and renewable energy, which is an important direction and necessary decision-making Energy and economy can achieve sustainable development goals all over the world. In order to improve the peak shaving capacity of the power system, this paper proposes to introduce the load side into high energy consuming enterprises to participate in the regulation, and carry out joint optimal dispatching with conventional thermal power units. The optimization goal is to minimize the sum of all day waste air volume of the next day, and the simulation software is used to optimize it. Compared with the regulation of a single thermal power unit, the effect is better, it plays a positive role in reducing wind abandonment, improves the utilization rate of wind power, and has high economic and environmental benefits.

Chemotherapy-related cognitive impairment (CRCI) or “chemo brain” is a devastating neurotoxic sequela of cancer-related treatments, especially for the elderly individuals. Here we show that PTPRO, a tyrosine phosphatase, is highly enriched in the hippocampus, and its level is tightly associated with neurocognitive function but declined significantly during aging. To understand the protective role of PTPRO in CRCI, a mouse model was generated by treating Ptpro–/– female mice with doxorubicin (DOX) because Ptpro–/– female mice are more vulnerable to DOX, showing cognitive impairments and neurodegeneration. By analyzing PTPRO substrates that are neurocognition-associated tyrosine kinases, we found that SRC and EPHA4 are highly phosphorylated/activated in the hippocampi of Ptpro–/– female mice, with increased sensitivity to DOX-induced CRCI. On the other hand, restoration of PTPRO in the hippocampal CA3 region significantly ameliorate CRCI in Ptpro–/– female mice. In addition, we found that the plant alkaloid berberine (BBR) is capable of ameliorating CRCI in aged female mice by upregulating hippocampal PTPRO. Mechanistically, BBR upregulates PTPRO by downregulating miR-25-3p, which directly targeted PTPRO. These findings collectively demonstrate the protective role of hippocampal PTPRO against CRCI.

Purpose: Fibroblast activation protein (FAP) is highly expressed in the mesenchyme of most malignant epithelial tumors, while its expression is low in normal tissues. FAP inhibitors (FAPIs) bind specifically to FAP and are used for tumor-targeted diagnosis and therapy. The aim of this study was to radiosynthesize a novel molecular probe 131I-FAPI and evaluate its in-vitro targeting and biological characteristics. Methods: The structurally modified FAPI was labelled with 131I through the chloramine-T method. The radiolabeling rate was then detected by thin-layer chromatography (TLC). The stability of 131I-FAPI was determined at PBS (room temperature) and serum (37°C). Its hydrophilicity was calculated by measuring its lipid-water partition coefficient. Pancreatic cancer PANC-1 cell line and glioma U87 cell line were cultured in vitro. Cell uptake assay was used to show the binding ability of 131I-FAPI. The CCK-8 assay was used to calculate the inhibitory effects of 131I-FAPI at different time points (4h, 8h, 12h, 24h, 48h) after comparing with the 131I and FAPI. The before-and-after-24h scratch areas of the two cells were determined in order to verify the effect of 131I-FAPI on the migration ability of the cells. Results: The radiolabeling rate was (84.9 ± 1.02) %. The radiochemical purity of 131I-FAPI remained over 80% in both 25°C PBS and 37°C serum. The value of the lipid-water partition coefficient was -0.869 ± 0.025, indicating the hydrophilic of the probe. The cellular uptake assay showed that U87 cells had a specific binding capacity for 131I-FAPI. In cell inhibition assays, the inhibitory effect of 131I-FAPI on U87 cells increased with time. The results of cell scratch assay showed that 131IFAPI had the strongest inhibitory effect on the migratory ability of U87 cells compared with 131I and FAPI (P<0.001). Conclusion: 131I-FAPI was synthesized with good in-vitro stability and hydrophilic properties. It can be specifically bound by U87 cells. The proliferation and migration of U87 cells can be effectively inhibited. 131I-FAPI is promising to become a therapeutic probe. [ABSTRACT FROM AUTHOR]

Deepfake can be used to combine human voices,faces and body movements into fake content,switch gender and change age,etc.There are some problems of gender-forged face images based on generative adversarial image translation networks such as the irrelevant image domain changes easily and insufficient face details in generated images.To solve these problems,an gene-ration model of gender-forged face image based on improved CycleGAN is proposed.Firstly,the generator is optimized by using the attention mechanism and adaptive residual blocks to extract richer facial features.Then,with the aim to improve the ability of the discriminator,the loss function is modified by the idea of relative loss.Finally,a model training strategy based on age constraints is proposed to reduce the impact of age changes on the generated images.Performing experiments on the CelebA and IMDB-WIKI datasets,the experimental results show that,compared with the original CycleGAN method and the UGATIT method,theproposed method can generate more real gender-forged face images.The average content accuracy of fake male images and fake female images is 82.65% and 78.83%,and the average FID score is 32.14 and 34.50,respectively.

Acquiring welding domain relationships and forming a knowledge graph can positively impact complex engineering problem solving and intelligent manufacturing applications. However, relationships are lacking in the welding domain. The relationship extraction and processing solution are designed to handle data with different characteristics in welding fabrication. The BiLSTM+Attention and CR-CNN models are employed to extract relations in unstructured documents. The neighborhood rough set-based association rule model is proposed for project-specific documents to accomplish relationship acquisition, in which invalid attributes are removed via neighborhood rough sets and attribute values are related via association rules. In addition, the knowledge graph is built based on extracted relationships, and unique empirical relationships are handled by introducing relational nodes and databases. The results show that BiLSTM+Attention gets a good score with Macro-average metrics (0.788 for Precision, 0.846 for Recall, and 0.816 for F1-score). The relational rules obtained via the proposed model are consistent with the production experience. The constructed knowledge graph effectively handles empirical relationships while positively impacting knowledge retrieval, intelligent question and answer, and decision-making for complex engineering problems.

Objectives In this study, we aimed to investigate the characteristics of robot-assisted surgery studies registered on ClinicalTrials.gov and identify factors associated with early trial discontinuation and timely results reporting.Design We searched ClinicalTrials.gov to identify interventional studies on robot-assisted surgery on 24 May 2021. All structured information of the potential studies was downloaded and reviewed. A descriptive analysis was performed. Logistic and Cox regression analyses were respectively performed to determine the significance of the association of study characteristics with results reporting and early discontinuation.Results A total of 529 interventional studies on robot-assisted surgery were included, with 45 studies reporting results and 54 studies being stopped early. Of the 289 due studies, only 45 (16%) had submitted their results, and only 6 (2%) had submitted their results within the 1-year deadline. Funding source was associated with results reporting: academic funded were 63% less likely than industry to report results (OR=0.37, 95% CI: 0.16 to 0.83, p=0.02). Studies related to device feasibility were associated with greater risk of early discontinuation compared to treatment-related studies (HR=2.30, 95% CI: 1.08 to 4.89, p=0.03). Surprisingly, National Institutes of Health-funded studies were at greater hazard of discontinuation compared to industry-funded studies (HR=3.30, 95% CI: 1.09 to 10.00, p=0.04).Conclusions There was poor compliance with results reporting requirements for robot-assisted surgical studies. It is important that investigators remain informed about the regulatory requirements, and should be helped to develop a sense of responsibility for reporting results. Also, they need to ensure the careful design of the study protocol and adequate resources to reduce the risk of early discontinuation.

IntroductionPrevalence of functional limitations (FLs) and disabled activities of daily living (ADL) cause heavy burdens to the health of the older people. Stratified by gender, this study aimed to explore the effects of FL and ADL on the mortality of the older people in China, and the mechanism was then discussed.MethodsWe used survey data of a prospective 10-year cohort (2008–2018), from the China Longitudinal Healthy Longevity Survey (CLHLS). The primary outcome was all-cause mortality, and Independent variables included FL, basic ADL (BADL), and instrumental ADL (IADL). Covariates involved socio-demographic characteristics, health-related behaviors, and health status of the participants in the CLHLS project.ResultsThere were 967 (19.20%) male and 2,235 (32.36%) female older people performed functional limitations, and their survival time was 60.98 (SE = 0.66) and 55.19 (SE = 0.55) months, respectively. Old adults with FL had significantly poorer survival than the ones without (Log-rank test, P < 0.001). Weibull regression suggested that FL (P < 0.001), abnormal BADL (P < 0.001) and IADL (P < 0.001) were negatively associated with the survival of the older people. Further analysis showed that BADL and IADL performed significantly mediating roles in the relation of FL and survival time in old adults; additionally, for female older people, BADL also exhibited a significant moderating role in the effect of FL on survival.ConclusionsPrevalence of FL was serious among the older people in China, especially for the women. Disabilities of BADL and IADL and FL were negatively associated with the survival time of the older people in China. Regarding the effect of FL on survival, BADL and IADL performed significantly mediating roles, and the moderating role of BADL existed only for the female. These suggested evidence to implement strategies to maintain health in the older people.

Abstract The complex relationships among social support, experienced stigma, psychological distress, and quality of life (QOL) among tuberculosis (TB) patients are insufficiently understood. The purpose of this study was to explore the interrelationships among social support, experienced stigma, psychological distress, and QOL and to examine whether experienced stigma and psychological distress play a mediating role. A cross-sectional survey was conducted between November 2020 and March 2021 in Dalian, Liaoning Province, Northeast China. Data were obtained from 473 TB patients using a structured questionnaire. Structural equation modelling was used to examine the hypothetical model. The research model provided a good fit to the measured data. All research hypotheses were supported: (1) social support, experienced stigma and psychological distress were associated with QOL; (2) experienced stigma fully mediated the effect of social support on psychological distress; (3) psychological distress fully mediated the effect of experienced stigma on QOL; and (4) experienced stigma and psychological distress were sequential mediators between social support and QOL. This study elucidated the pathways linking social support, experienced stigma, and psychological distress to QOL and provides an empirical basis for improving the QOL of TB patients.

Abstract High doses of radiation can cause serious side effects and efficient radiosensitizers are urgently needed. To overcome this problem, we developed a biomimetic nanozyme system (CF) by coating pyrite (FeS2) into tumor-derived exosomes for enhanced low-dose radiotherapy (RT). CF system give FeS2 with immune escape and homologous targeting abilities. After administration, CF with both glutathione oxidase (GSH-OXD) and peroxidase (POD) activities can significantly lower the content of GSH in tumor tissues and catalyze intracellular hydrogen peroxide (H2O2) to produce a large amount of ·OH for intracellular redox homeostasis disruption and mitochondria destruction, thus reducing RT resistance. Experiments in vivo and in vitro showed that combining CF with RT (2 Gy) can provide a substantial suppression of tumor proliferation. This is the first attempt to use exosomes bionic FeS2 nanozyme for realizing low-dose RT, which broaden the prospects of nanozymes. Graphical Abstract

Abstract Background Surgery remains the major treatment for early breast cancer (BC), but surgery itself is also a trauma which might induce alterations in lipid metabolism. The aim of this study was to investigate the changes in lipid profiles and to explore factors associated with lipid changes pre- and postoperation. Methods We retrospectively analyzed the pre- and postoperative serum lipid profiles of 1934 BC patients. Results The levels of triglycerides (TG) (p 24 (34.92%) had a higher incidence of dyslipidemia than patients with BMI ≤ 24 (24.84%; p = 0.001). Moreover, the magnitudes of the TG increase (p

Rib fracture is the most common injury in chest trauma. Most of patients with rib fractures were treated conservatively, but up to 50% of patients, especially those with combined injury such as flail chest, presented chronic pain or chest wall deformities, and more than 30% had long-term disabilities, unable to retain a full-time job. In the past two decades, surgery for rib fractures has achieving good outcomes. However, in clinic, there are still some problems including inconsistency in surgical indications and quality control in medical services. Before the year of 2018, there were 3 guidelines on the management of regional traumatic rib fractures were published at home and abroad, focusing on the guidance of the overall treatment decisions and plans; another clinical guideline about the surgical treatment of rib fractures lacks recent related progress in surgical treatment of rib fractures. The Chinese Society of Traumatology, Chinese Medical Association, and the Chinese College of Trauma Surgeons, Chinese Medical Doctor Association organized experts from cardiothoracic surgery, trauma surgery, acute care surgery, orthopedics and other disciplines to participate together, following the principle of evidence-based medicine and in line with the scientific nature and practicality, formulated the Chinese consensus for surgical treatment of traumatic rib fractures (STTRF 2021). This expert consensus put forward some clear, applicable, and graded recommendations from seven aspects: preoperative imaging evaluation, surgical indications, timing of surgery, surgical methods, rib fracture sites for surgical fixation, internal fixation method and material selection, treatment of combined injuries in rib fractures, in order to provide guidance and reference for surgical treatment of traumatic rib fractures.

In recent years, ultra-fine-grained Fe–C alloy have received widespread attention because of their high levels of strength, hardness, and wear resistance. However, these alloy have strict requirements on control of the process parameters during production to meet product specifications. This study was aimed at designing a prediction model for their mechanical properties, which could ultimately promote the industrial development of ultra-fine-grained Fe–C alloy. The effect of process parameters on the mechanical properties of ultra-fine-grained Fe–C alloy was analyzed by electron backscatter diffraction (EBSD) and scanning electron microscope (SEM). By fusing experimental combinations of alloy composition, rolling process, annealing process, and resultant mechanical properties into a dataset for training and verification, a machine-learning-based prediction model of mechanical properties of ultra-fine-grained Fe–C alloy was constructed and tested. When choosing the machine learning algorithm, the best network model was obtained for this application by optimizing a conventional backpropagation (BP) network structure: a three-layer network structure, with a learning rate of 0.5, 18 hidden layer neurons, and activation functions of the hidden and output layers, namely Tansig and Purelin (MATLAB functions), respectively. Finally, the sample data was divided into training set and verification set, and the prediction accuracy, efficiency and generalization ability of BP neural network (BPNN), genetic neural network (GA-BP) and support vector machine (SVM) were compared and analyzed. The superiority of BPNN in the prediction of mechanical properties of ultrafine grained Fe–C alloy was determined, and the mean absolute percentage error (MAPE) of the BPNN for tensile strength, yield strength and uniform elongation are 3.02%, 4.47% and 6.47% respectively, and the number of training steps is 412, which are less than the other two models. The result lays a foundation for the production of high stability and high performance steel products.

Abstract This paper proposes an effective fault management scheme for medium‐voltage direct current (MVDC) networks, which includes a virtual‐impedance‐based fault current limiter (VI‐FCL) on the DC side and a positive‐negative‐sequence (PNS) control scheme on the AC side. Depending on the fault current value, different protection strategies are adopted, which include either isolating the fault by opening circuit breakers or riding through the fault with the proposed VI‐FCL. It is known that unbalanced grid voltage can be found in conventional AC distribution feeders due to unbalanced loading conditions among three phases. The unbalanced grid voltage could induce double line‐frequency (2ω) ripples on both DC voltage and current, which could thereby trigger protection malfunction in the DC sub‐sections. Therefore, the PNS control scheme is used to eliminate the 2ω ripples of both DC voltages and currents caused by unbalanced AC voltages. Furthermore, a detailed 2ω mathematical model of the MVDC network under unbalanced AC voltage condition is derived to investigate how the 2ω ripple propagates across the network. A voltage source converter based multi‐terminal MVDC network is built to test DC faults with different fault currents, unbalanced AC voltages, and different control schemes. The test results verify both the proposed fault management scheme and the 2ω ripple propagation analysis.

Musculoskeletal soft tissue injuries are very common and usually occur during both sporting and everyday activities. The intervention of adjuvant therapies to promote tissue regeneration is of great importance to improving people’s quality of life and extending their productive lives. Though many studies have focused on the positive results and effectiveness of the LIPUS on soft tissue, the molecular mechanisms standing behind LIPUS effects are much less explored and reported, especially the intracellular signaling pathways. We incorporated all research on LIPUS in soft tissue diseases since 2005 and summarized studies that uncovered the intracellular molecular mechanism. This review will also provide the latest evidence-based research progress in this field and suggest research directions for future experiments.

IntroductionAcupuncture and acupressure are widely used for treating cancer pain and depression and recognized as safe and effective by the international medical community. In this study, we systematically evaluated the efficacy, safety, and clinical significance of acupuncture and acupressure in treating cancer-related depression.MethodsWe searched MEDLINE, PubMed, Science Direct, Google Scholar, Web of Science and Embase and Chinese-language databases for randomized clinical trials (RCTs). To assess efficacy, rating scales administered by clinicians or experts were preferred, including the Hamilton Depression Rating Scale (HAMD), Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS), and Quality of Life Questionnaire-Core 30 (QLQ-C30) and the total effective rate after treatment. In all, Sixteen RCTs involving 1019 cancer patients were included in the Meta-analysis.ResultsEleven (69%) of these studies reported the post-treatment total effective rate. Three hundred fifty-three patients received antidepressants; the total effective rate was 72.5%. Three hundred sixty-one patients underwent acupuncture and acupressure; the total effective rate was 90%. Meta-analysis results showed I2 = 0%, no heterogeneity, (Z = 5.84, p < 0.00001); and combined OR = 3.55, (95% CI = 2.32 to 5.43).DiscussionThis study found that acupuncture and acupressure are as effective as medication in the treatment of cancer-related depression, provide a reliable basis for the clinical use of acupuncture to treat cancer-related depression, help promote nonpharmacological treatment for cancer-related complications. These approaches thus help reduce drug resistance and adverse reactions and improve patients’ quality of life.

Continuum robots have good adaptability in unstructured and complex environments. However, affected by their inherent nature of flexibility and slender structure, there are challenges in high-precision motion and load. Thus, stiffness adjustment for continuum robots has consistently attracted the attention of researchers. In this paper, a stiffness adjustment mechanism (SAM) is proposed and built in a growth-controllable continuum robot (GCCR) to improve the motion accuracy in variable scale motion. The self-stiffness adjustment is realized by antagonism through cable force transmission during the length change of the continuum robot. With a simple structure, the mechanism has a scarce impact on the weight and mass distribution of the robot and required no independent actuators for stiffness adjustment. Following this, a static model considering gravity and end load is established. The presented theoretical static model is applicable to predict the shape deformations of robots under different loads. The experimental validations showed that the maximum error ratio is within 5.65%. The stiffness of the robot can be enhanced by nearly 79.6%.

Voice information processing technology is developing rapidly under the impetus of deep learning.The combination of speech synthesis and voice conversion technology can achieve real-time high-fidelity voice output of designated objects and content,and has broad application prospects in man-machine interaction,pan-entertainment and other fields.This paper aims to provide an overview of speech synthesis and voice conversion technology based on deep learning.First,this paper briefly reviews the development of speech synthesis and voice conversion technology.Next,it enumerates the common public datasets in these fields so that it is convenient for researchers to carry out related explorations.Then,it discusses the TTS models,including the classic and cutting-edge models and algorithms in terms of style,rhythm,speed,and compares their effects and development potentials respectively.Then,it reviews voice conversion by summarizing the voice conversion methods and optimization methods.Finally,it summarizes the applications and challenges of speech synthesis and voice conversion,and looks forward to their future development direction in model compression,few-shot learning and forgery detection,based on the problems faced by them in terms of model,application and regulation.

Abstract Background The deubiquitinase (DUB) family constitutes a group of proteases that regulate the stability or reverse the ubiquitination of many proteins in the cell. These enzymes participate in cell-cycle regulation, cell division and differentiation, diverse physiological activities such as DNA damage repair, growth and development, and response to stress. However, limited information is available on this family of genes in woody plants. Results In the present study, 88 DUB family genes were identified in the woody model plant Populus trichocarpa, comprising 44 PtrUBP, 3 PtrUCH, 23 PtrOTU, 4 PtrMJD, and 14 PtrJAMM genes with similar domains. According to phylogenetic analysis, the PtrUBP genes were classified into 16 groups, the PtrUCH genes into two, the PtrOTU genes into eight, the PtrMJD genes into two, and the PtrJAMM genes into seven. Members of same subfamily had similar gene structure and motif distribution characteristics. Synteny analysis of the DUB family genes from P. thrchocarpa and four other plant species provided insight into the evolutionary traits of DUB genes. Expression profiles derived from previously published transcriptome data revealed distinct expression patterns of DUB genes in various tissues. On the basis of the results of analysis of promoter cis-regulatory elements, we selected 16 representative PtrUBP genes to treatment with abscisic acid, methyl jasmonate, or salicylic acid applied as a foliar spray. The majority of PtrUBP genes were upregulated in response to the phytohormone treatments, which implied that the genes play potential roles in abiotic stress response in Populus. Conclusions The results of this study broaden our understanding of the DUB family in plants. Analysis of the gene structure, conserved elements, and expression patterns of the DUB family provides a solid foundation for exploration of their specific functions in Populus and to elucidate the potential role of PtrUBP gene in abiotic stress response.

BackgroundEmpirical research on the relationship between family functioning and delinquency has been sparse, although many studies have focused on the influence of family functioning on adolescent development. The current research aimed to fill this gap by exploring the influences of family functioning on adolescent delinquency and the mechanisms connecting the processes.MethodsWe derived the baseline data from a prospective observational school-based cohort Chengdu Positive Child Development (CPCD) project. Students responded to a questionnaire containing validated measures of family functioning, positive behavior recognition, and delinquent behavior. We utilized structural equation modeling and maximum likelihood estimation to test the relationships.ResultsAcross 8811 Chinese adolescents, the incidence of delinquency behaviors among Chinese adolescents was relatively low. Family functioning and positive behavior recognition negatively predict delinquency (p < 0.001). Further, positive behavior recognition partially mediated the influence of family functioning on delinquency [p < 0.001, std. error = 0.01, 95% CI = (0.04, 0.07)]. Adolescents with better family functioning had little delinquency behavior, with positive behavior recognition and delinquency behavior negatively reinforcing each other.ConclusionsThis study demonstrated that family functioning was a protective factor against adolescent delinquency and revealed that positive behavior recognition was a critical mediating mechanism linking family functioning to delinquency.