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Irritable bowel syndrome (IBS) was found in 11% of the general population worldwide. The current pharmacologic management of IBS was unsatisfactory, and it was accompanied by a number of adverse events. Melatonin was found to play an important role in gastrointestinal smooth muscle motility. Dysregulation of endogenous melatonin secretion has been found in IBS patients. Exogenous melatonin supplement has become one alternative treatment for IBS, but the evidence is inconclusive. The current meta-analysis sought to determine the efficacy of exogenous melatonin supplement in improving IBS severity in IBS patients.We included randomized controlled trials (RCTs) that investigated the efficacy of exogenous melatonin supplement in ameliorating IBS severity in IBS patients. This meta-analysis was conducted using a random effects model. The primary target outcomes were changes in IBS severity associated with melatonin or placebo.This meta-analysis of 4 RCTs and 115 participants revealed that exogenous melatonin supplement was associated with significantly better improvement in overall IBS severity than placebo (k = 4, Hedges' g = 0.746, 95% confidence intervals = 0.401-1.091, p 0.001). The subgroup without concurrent medication had the same result (p 0.001). In addition, exogenous melatonin supplement was also associated with significantly better improvement in IBS pain severity (p 0.001) and quality of life (p = 0.007) than placebo, but not in abdominal distension (p = 0.111) or sleep quality (p = 0.142). Finally, melatonin was associated with similar safety profiles with placebo.This meta-analysis provides evidence for the use of exogenous melatonin in IBS patients to ameliorate overall IBS severity, IBS pain severity, and quality of life.PROSPERO CRD42021269451.

The Industrial Internet of Things (IIoT) has evolved industrial operations to be more efficient and reliable. The fastener forming process (FFP) used to rely on the judgments of in-process inspectors and experienced operators. Since no critical information was transmitted between machines, the machining status during production was unable to reveal. Now, with sensors installed in the machines of FFP, manufacturing data can be collected, analyzed, and responded to the machines. This IIoT-embedded FFP can not only carry out real-time data, pre-processing, and feature engineering but also enable optimally selecting classification algorithms for preventive maintenance. Consequently, the FFP establishes machine-health indicators for the production site and the heading process recognizes the abnormal situations between punches. The operator-delayed response leads to a great amount of loss that can be avoided. Besides, with the integration of enterprise resource planning (ERP) and manufacturing execution system (MES), this IIoT-embedded FFP converts receiving customer orders into work orders and coordinates operations and sales within enterprises. This system integration catches the status of various production indicators and further advances accurate materials preparation and inventory costs control. Overall, this IIoT-embedded FFP system becomes no necessity for increasing inventory and reserving backlog funds to cope with the impact of a vast number of scrap products. Finally, other types of machining processes or systems can adopt this systematic approach in the future.

This meta-analysis aimed at exploring the impact of opioid-free anesthesia (OFA) on pain score and opioid consumption in patients undergoing bariatric surgery (BS). Literature search identified eight eligible trials. Forest plot revealed a significantly lower pain score (mean difference (MD) = - 0.96, p = 0.0002; 318 patients), but not morphine consumption (MD = - 5.85 mg, p = 0.1; 318 patients) at postoperative 24 h in patients with OFA than in those without. Pooled analysis also showed a lower pain score (p = 0.002), morphine consumption (p = 0.0003) in the postanesthetic care unit, and risk of postoperative nausea/vomiting (p = 0.0003) in the OFA group compared to the controls. In conclusion, this meta-analysis demonstrated that opioid-free anesthesia improved pain outcomes immediately and at 24 h after surgery without a beneficial impact on opioid consumption at postoperative 24 h. KEY POINTS: • Roles of opioid-free anesthesia (OFA) in bariatric surgery (BS) were investigated. • Outcomes included postoperative pain score, opioid use, and nausea/vomiting risk. • OFA was associated with lower 24-h pain score but not opioid consumption. • Lower pain score and opioid consumption were noted in the postanesthetic care unit. • OFA correlated with a lower risk of postoperative nausea/vomiting.

BackgroundThis meta-analysis aimed at investigating the pooled evidence regarding the effects of intravenous vitamin C (IVVC) on mortality rate in critically ill patients.MethodsDatabases including Medline, Embase, and Cochrane Library were searched from inception to October, 2022 to identify RCTs. The primary outcome was the risk of overall mortality. Subgroup analyses were performed based on IVVC dosage (i.e., cut-off value: 100 mg/kg/day or 10000 mg/day). Trial sequential analysis (TSA) was used to examine the robustness of evidence.ResultsA total of 12 trials including 1,712 patients were analyzed. Although meta-analysis demonstrated a lower risk of mortality in patients with IVVC treatment compared to those without [risk ratio (RR): 0.76, 95% CI: 0.6 to 0.97, p = 0.02, I2 = 36%, 1,711 patients), TSA suggested the need for more studies for verification. Moreover, subgroup analyses revealed a reduced mortality risk associated with a low IVVC dosage (RR = 0.72, p = 0.03, 546 patients), while no beneficial effect was noted with high IVVC dosage (RR = 0.74, p = 0.13, I2 = 60%, 1,165 patients). The durations of vasopressor [mean difference (MD): −37.75 h, 404 patients) and mechanical ventilation (MD: −47.29 h, 388 patients) use were shorter in the IVVC group than those in the controls, while there was no significant difference in other prognostic outcomes (e.g., length of stay in intensive care unit/hospital) between the two groups.ConclusionAlthough intravenous vitamin C as a monotherapy reduced pooled mortality, durations of vasopressor use and mechanical ventilation, further research is required to support our findings and to identify the optimal dosage of vitamin C in the critical care setting.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022371090.

Developing growth techniques for the manufacture of wide band gap III-nitrides semiconductors is important for the further improvement of optoelectronic applications. A plasma-assisted halide phase vapor epitaxy (PA-HVPE) approach is demonstrated for the manufacture of undoped and In-doped GaN layers at ~600 °C. A dielectric barrier discharge (DBD) plasma source is utilized for the low-temperature activation of ammonia. The use of the plasma source at a growth temperature of ~600 °C increases the growth rate from ~1.2 to ~4–5 µm/h. Furthermore, the possibility for the growth of InGaN at ~600 °C has been studied. Precursors of GaCl and InCl/InCl3 are formed in situ in the reactor by flowing HCl gas over a melt of metallic Ga and In, respectively. The In concentration was low, in the order of a few percent, as the incorporation of In is reduced by plasma due to the activation of chlorine-containing species that etch the relatively poorly bonded In atoms. Nevertheless, the approach of using plasma for ammonia activation is a very promising approach to growing epitaxial III-nitrides at low temperatures.

This study primarily aimed at investigating the efficacy of analgesia nociception index (ANI) for guiding intraoperative opioid administration in patients receiving surgery under general anesthesia.The Medline, Embase, Google scholar, and the Cochrane Library databases were searched from inception to April 2022 for randomized controlled trials. The primary outcome was intraoperative opioid administration, while the secondary outcomes included postoperative opioid consumption, pain score, emergency time, risk of nausea/vomiting (PONV), and postanesthesia care unit (PACU) stay.Six studies including 399 participants (published from 2015 to 2022) focused on non-cardiac surgery, including spine surgery (two trials), breast surgery (two trials), gynecologic surgery (one trial), and laparoscopic cholecystectomy (one trial) were included. Meta-analysis revealed no difference in intraoperative opioid administration with the use of ANI-guided analgesia compared to the control group that used conventional clinical measurements (e.g., heart rate) to guide opioid use [standardized mean difference (SMD)=-0.17, 95% CI: -0.56 to 0.22, p=0.39, I2=72%, six trials, 399 participants]. Gender-based subgroup analysis showed effectiveness of ANI for reducing opioid administration in female patients (SMD=-0.53, p=0.02). There were no differences in postoperative recovery characteristics including pain score [Mean difference (MD): -0.03, p=0.79], opioid consumption (SMD: -0.34, p=0.08), emergence time (MD=1.12, p=0.47), length of stay in the PACU (MD: -0.56, p=0.83), and risk of PONV [risk ratio(RR): 0.75, p=0.46] between the two groups.Analgesia nociception index-guided analgesia was unable to reduce intraoperative opioid administration compared to monitoring using conventional clinical parameters. Further studies are required to support our findings.

Background Dementia [i.e., Alzheimer disease (AD)], the most common neurodegenerative disease, causes profound negative impacts on executive function and quality of life. Available pharmacological treatments often fail to achieve satisfactory outcomes. Noninvasive brain stimulation (NIBS) techniques, which focally modify cortical function and enhance synaptic long-term potentiation, are potentially beneficial for the cognition in patients with AD. The aim of the current network meta-analysis (NMA) was to evaluate the efficacy and safety of different NIBS interventions in patients with AD through NMA. Methods Only randomized controlled trials (RCTs) examining NIBS interventions in patients with AD had been included. All NMA procedures were performed under the frequentist model. The primary and secondary outcomes were changes in cognitive function and quality of life, respectively. Results Nineteen RCTs (639 participants) were included. The mean treatment and follow-up durations were 5.7 and 10.5 weeks, respectively. The combination of cathodal tDCS of the left dorsolateral prefrontal cortex and anodal tDCS over the right supraorbital region (c-tDCS-F3 + a-tDCS-Fp2) was associated with a significant beneficial effect on cognition compared with sham controls (standardized mean difference=2.43, 95% confidence interval=0.61–4.26, n=12 and 11). It was also associated with the greatest beneficial effect on cognition among all the investigated NIBS approaches. All the methods were well tolerated with regard to the safety profile, as reflected in the rates of adverse events or local discomfort, as well as acceptability, as indicated by dropout rate. Conclusions The present findings provide evidence of the benefits of NIBS, especially tDCS, for beneficial effect on cognition in patients with AD. However, because of few studies included, this effect was not replicated yet in the other studies. Therefore, future larger-scale and longer follow-up duration RCTs should be warranted. Trial registration PROSPERO CRD42020209516. The current study had been approved by the Institutional Review Board of the Tri-Service General Hospital, National Defense Medical Center (TSGHIRB No. B-109-29).

Study objectiveTo assess the association between prognostic nutritional index (PNI) and risk of postoperative delirium (POD) in adult patients.MethodsMEDLINE, Google scholar, EMBASE, and Cochrane library databases were searched from inception till April 2022. The primary outcome was the association between PNI and the risk of POD, while the secondary outcomes were correlations of other prognostic factors with POD risk. The correlation between PNI and the incidence of POD was assessed with three approaches: Difference in preoperative PNI between POD and non-POD groups (Model 1) as well as the association of PNI as a continuous parameter (Model 2) or as a binary variable (i.e., low vs. high using a PNI cut-off value of 50) (Model 3) with POD risk.ResultsAnalysis of nine observational studies published from 2010 to 2021 recruiting 3,743 patients showed a POD incidence of 6.4–35%. Our meta-analysis demonstrated a lower PNI among patients in the POD group (MD: −3.78, 95% CI: −4.85 to −2.71, p < 0.0001, I2 = 54.2%) compared to the non-POD group (Model 1). Pooled results revealed a negative association between PNI and POD risk for both Model 2 (OR: 0.91, 95% CI: 0.86–0.97, p = 0.002, I2 = 71%) and Model 3 (OR: 1.68, 95% CI: 1.26–2.23, p < 0.0001, I2 = 0%). Besides, while our results supported an age-dependent increase in POD risk, other factors including body-mass index, surgical time, health status, hypertension, diabetes mellitus, and male gender were non-significant predictors of POD.ConclusionOur results demonstrated a negative association between PNI and POD, which warrant further large-scale studies for validation.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022323809.

The combination of mirror therapy (MT) and neuromuscular electrical stimulation (NMES) has been devised as an intervention method in stroke rehabilitation; however, few studies have investigated its efficacy in lower extremity motor function recovery. In this systematic review and meta-analysis, we examined the effectiveness of combined MT and NMES therapy in improving poststroke walking speed, gait ability, and balance. Randomized controlled trials (RCTs) were selected from PubMed, Cochrane Library, EMBASE, and Scopus databases. In total, six RCTs which involving 181 participants were included. Our findings indicate that MT combined with NMES elicits greater improvement relative to control group in walking speed (SMD = 0.67, 95% confidence interval [CI]: 0.26–1.07, P = 0.001), Berg Balance Scale (SMD = 5.47; 95% CI: 1.22–9.72; P = 0.01), cadence (SMD = 10.35, 95% CI: 1.15–19.55, P = 0.03), step length (SMD = 6.03, 95% CI: 2.52–9.54, P = 0.0008), and stride length (SMD = 13.10, 95% CI: 3.20–22.99, P = 0.009) but not in modified Ashworth scale (SMD = − 0.35, 95% CI: −0.75 to 0.06, P = 0.09). Our findings suggest that MT combined with NMES may be a suitable supplemental intervention to conventional therapy in stroke survivors.

Comprehensive detailed characterization of new mouse models can be challenging due to the individual focus involved in developing these models. Often models are engineered to test a specific hypothesis in a limited number of tissues, stages, and/or other contexts. Whether or not the model produces the desired phenotypes, phenotyping beyond the desired context can be extremely work intensive and these studies are often not undertaken. However, the general information resulting from broader phenotyping can be invaluable to the wider scientific community. The International Mouse Phenotyping Consortium (IMPC) and its subsidiaries, like the Knockout Mouse Project (KOMP), has made great strides in streamlining this process. In particular, the use of microCT has been an invaluable resource in examining internal organ systems throughout fetal/developmental stages. Here, we provide several novel vignettes demonstrating the utility of microCT in uncovering cardiac phenotypes both based on human disease correlations and those that are unpredicted.

N6-methyladenosine (m6A), one of the most prevalent mRNA modifications in eukaryotes, plays a critical role in modulating both biological and pathological processes. However, it is unknown whether mutant p53 neomorphic oncogenic functions exploit dysregulation of m6A epitranscriptomic networks. Here, we investigate Li-Fraumeni syndrome (LFS)-associated neoplastic transformation driven by mutant p53 in iPSC-derived astrocytes, the cell-of-origin of gliomas. We find that mutant p53 but not wild-type (WT) p53 physically interacts with SVIL to recruit the H3K4me3 methyltransferase MLL1 to activate the expression of m6A reader YTHDF2, culminating in an oncogenic phenotype. Aberrant YTHDF2 upregulation markedly hampers expression of multiple m6A-marked tumor-suppressing transcripts, including CDKN2B and SPOCK2, and induces oncogenic reprogramming. Mutant p53 neoplastic behaviors are significantly impaired by genetic depletion of YTHDF2 or by pharmacological inhibition using MLL1 complex inhibitors. Our study reveals how mutant p53 hijacks epigenetic and epitranscriptomic machinery to initiate gliomagenesis and suggests potential treatment strategies for LFS gliomas.

Embryogenesis of cetaceans (whales, dolphins, porpoises) is well known in Stenella attenuata, the pan-tropical spotted dolphin, based on a remarkably complete and well-studied series prenatal ontogenetic stages. Our study expands understanding of cetacean embryology by adding two additional cetacean taxa: the beluga whale (Delphinapterus leucas, Odontoceti), and the bowhead whale (Balaena mysticetus, Mysticeti). We identify key features that characterize these taxa at specific stages and highlight heterochrony between the odontocetes and mysticetes. A presomitic Delphinapterus embryo is also described. This study therefore applies the Carnegie staging system to two more cetacean taxa and forms a framework for future research on cetacean developmental genetics and modeling of fetal growth. This article is protected by copyright. All rights reserved.

The development of growth processes for the synthesis of high-quality epitaxial layers is one of the requirements for utilizing the ultrawide band gap semiconductor Ga2O3 for high-voltage, high-power electronics. A halide vapor phase epitaxy (HVPE) process used to grow β-Ga2O3 layer was optimized by modifying the gas inlet, resulting in improved growth uniformity. A conventional tube acting as an inlet for the Ga precursor GaCl gas was replaced with a shower head with four outlets at 45 degrees to the horizontal axis of the reactor. The modification was performed based on numerical calculations of the three-dimensional distribution of gases inside the growth chamber with different designs of the GaCl precursor inlet. It was shown that variation in the Ga/O ratio over the substrate holder was ~10% for a shower head compared with ~40% for a tube. In addition, growth with a tube leads to the film thickness varying by a factor of ~4 depending on the position on the holder, whereas when using a shower head, the thickness of the grown Ga2O3 layers became much more uniform with a total spread of just ~30% over the entire substrate holder.

To investigate the association between labor epidural analgesia exposure and the risk of autism spectrum disorder in offspring, this meta-analysis reviewed relevant literature from Medline, Cochrane Library, Google Scholar, and EMBASE databases from inception to May 2022 to evaluate the overall adjusted risk of autism spectrum disorder in offspring (primary outcome) and adjusted risks of autism spectrum disorder focusing on sibling-matched data, children who were delivered vaginally, and duration of labor epidural analgesia exposure (secondary outcomes). Pooled results of seven eligible observational studies involving 4,021,406 children revealed slightly higher risks of autism spectrum disorder in children with labor epidural analgesia exposure than those without (hazard ratio = 1.11, 95% confidence interval: 1.06–1.16, I2 = 67%, seven studies, level of evidence: very low). Consistent findings were found in subgroup analysis focusing on sibling data (hazard ratio: 1.10, 95% confidence interval: 1.02–1.18, I2 = 0%, five studies) and children delivered vaginally (hazard ratio: 1.11, 95% confidence interval: 1.06–1.17, I2 = 64%, seven studies). The tendency of an increased risk of autism spectrum disorder in children exposed to labor epidural analgesia 8 h (two studies). Although our results demonstrated a slightly increased risk of autism spectrum disorder in offspring with previous labor epidural analgesia exposure, the small effect size and lack of cumulative dose–response effect precluded tangible evidence supporting the association. Lay abstract A previous meta-analysis has demonstrated a superior analgesic efficacy of epidural analgesia (e.g. labor epidural analgesia) in comparison with non-epidural approaches. The widely accepted safety of labor epidural analgesia also endorses its current popularity in obstetric practice. However, the results of a recent large-scale longitudinal study that demonstrated a significant increase in risk of autism spectrum disorder in offspring from mothers with labor epidural analgesia exposure have raised some concerns over the safety of its use. The current meta-analysis aimed at examining the strength of evidence regarding this issue based on updated clinical data. Through systematically reviewing seven eligible observational studies involving 4,021,406 children from electronic databases, our results showed a slight but statistically significant increase in risk of autism spectrum disorder in children with exposure to labor epidural analgesia compared with those without. The finding was consistent in subgroup analysis focusing on siblings and children delivered vaginally. Nevertheless, despite the tendency of an increased risk of autism spectrum disorder in children exposed to labor epidural analgesia 8 h (data from two studies). In conclusion, the level of evidence linking labor epidural analgesia to autism spectrum disorder development in offspring was very low based on the latest data because of the small effect size and the finding of a lack of cumulative dose–response effect in the current analysis. Further studies are warranted to provide an insight into this issue.

This meta-analysis aimed at investigating the effectiveness of laryngeal mask airway (LMA) against postoperative pharyngolaryngeal complications after thyroidectomy. MEDLINE, Cochrane Library, google scholar, and EMBASE databases were searched from inception through February, 2021, for randomized controlled trials (RCTs) comparing the incidence of pharyngolaryngeal complications following the use of LMA or endotracheal tube (ETT). Pooled results from seven RCTs involving 600 patients showed an association of LMA with a reduced risk of postoperative sore throat (POST) at 24 h [risk ratio (RR) 0.75, p = 0.006, four trials], but not at 1 h and 48 h after thyroidectomy. POST severity and hoarseness risk were lower in the LMA group than the ETT group at 1 h, 24 h, and 48 h (all p p = 0.008, three trials]. Moreover, the risk of emergence cough was lower in patients using LMA than those receiving ETT (RR = 0.14, p = 0.002, two trials). The two groups did not differ in the severity of dysphagia at postoperative 1 h, 24 h, and 48 h. This meta-analysis showed that LMA may be associated with fewer pharyngolaryngeal complications compared to ETT without airway impacts. The limited number of included studies warrants further research to support our findings.

Specific feedback is considered an important strategy in communication skills training (CST). However, the effects of specific feedback on CST have not been comprehensively investigated. Therefore, this study aimed to investigate the effects of specific feedback based on an in-depth assessment tool for CST (CST-SF) on occupational therapy interns’ communication skills (CS). A one-group pre-test and post-test study design was conducted. Thirty-six interns received the CST-SF and completed three interviews with different patients. After the interviews, clinical instructors provided interns brief feedback based on the Gap-Kalamazoo Communication Skills Assessment Form (GKCSAF) and experts gave specific feedback based on the Communication Skills Measure for Therapists. The first and last interviews were assessed by clinical instructors, interns, and patients using the GKCSAF, and were then rated by experts based on the transcripts. The differences in first and last interview GKCSAF scores were analysed using the Wilcoxon signed-rank test. The results indicated that the interns significantly improved in terms of total scores and the scores of four CS domains in the GKCSAF: “builds a relationship,” “gathers information,” “shares information,” and “provides closure” (p r = 0.29 to 0.37). The clinical instructors and interns both reported significant improvements in the scores of two CS domains: “gathers information” and “provides closure,” but the patients reported no significant change in the interns’ CS. The CST-SF could impact the CS of occupational therapy interns, especially in the four aforementioned CS domains.

Tissue clearing for whole organ cell profiling has revolutionized biology and imaging for exploration of organs in three-dimensional space without compromising tissue architecture. But complicated, laborious procedures, or expensive equipment, as well as the use of hazardous, organic solvents prevent the widespread adoption of these methods. Here, we report a simple and rapid tissue clearing method, EZ Clear, that can clear whole adult mouse organs in 48 hr in just three simple steps. Samples stay at room temperature and remain hydrated throughout the clearing process, preserving endogenous and synthetic fluorescence, without altering sample size. After wholemount clearing and imaging, samples processed with EZ Clear can be subjected to downstream applications, such as tissue embedding and cryosectioning followed by standard histology or immunofluorescent staining without loss of fluorescence signal from endogenous or synthetic reporters. Furthermore, we demonstrate that wholemount adult mouse brains processed with EZ Clear can be successfully immunolabeled for fluorescent imaging while still retaining signal from endogenous fluorescent reporters. Overall, the simplicity, speed, and flexibility of EZ Clear make it easy to adapt and implement in diverse imaging modalities in biomedical research.

Background and aims- Nicotine is a highly addictive substance in tobacco products that dysregulates several neurotransmitters in the brain and impairs executive function. Non-invasive brain stimulation (NIBS) methods such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are promising treatments for nicotine dependence. We investigated the efficacy and acceptability of NIBS in managing smoking cessation through a systematic review and network meta-analysis (NMA). Methods- We conducted a systematic review to identify randomized controlled trials (RCTs) that investigated the efficacy of NIBS for smoking cessation. All pairwise meta-analyses and NMA procedures were conducted using random-effects and frequentist models. The co-primary outcomes were (1) the change in number of cigarettes smoked per day (change in frequency of smoking) in patients with nicotine dependence after NIBS and (2) acceptability (the dropout rate). The effect sizes for co-primary outcomes of change in frequency of smoking and acceptability were assessed according to standardized mean difference (SMD) and odds ratio, respectively. Results- Twelve RCTs with 710 participants (mean age: 44.2 years, 31.2% female) were included. Compared with the sham control, 10-Hz rTMS over the left dorsolateral prefrontal cortex (DLPFC) was associated with the largest changes in smoking frequency [SMD = −1.22, 95% confidence interval (95% CI) = −1.77 to −0.66]. The 2-mA bifrontal tDCS (SMD = −0.97, 95% CI = −1.32 to −0.62) and 10-Hz deep rTMS over the bilateral DLPFC with cue provocation (SMD = −0.77, 95% CI = −1.20 to −0.34) were associated with a significantly larger decrease in smoking frequency versus the sham. None of the investigated NIBSs was associated with dropout rates significantly different from those of the sham control groups. Conclusion- Prefrontal non-invasive brain stimulation interventions appear to reduce the number of cigarettes smoked with good acceptability.

Background/purpose In 2017, Long-Fa Temple, an illegal religious asylum in Taiwan, was forced to shut down. Hundreds of chronic mentally ill patients were incarcerated there but provided with no modern psychiatric treatment. This study investigated the effectiveness of providing psychiatric intervention for patients subsequently transferred from Long-Fa Temple to a medical center. Methods In total, 88 patients (mean age: 57.2 years, 52.3% male) who had been incarcerated at Long-Fa Temple were transferred to a southern medical center. The patients underwent comprehensive biological, psychological, and social treatment for 18 months. The patients were evaluated once a month in terms of their psychotic symptoms, self-care, nutrition status, cognitive function, occupational function, and family function. Results Regarding the patients' length of stay, 18.2% were incarcerated in Long-Fa Temple for less than 10 years, 21.6% for 10–20 years, and 60.2% for more than 20 years. In terms of psychiatric diagnosis, 98.9% of the patients had been diagnosed with a schizophrenia spectrum disorder. During the 18-month treatment period, negative symptoms decreased significantly, while the patients’ self-care ability, nutrition status, cognition, occupational function, and family function all significantly improved over time. Patients who had been incarcerated for less than 10 years demonstrated better improvements in psychotic symptoms, self-care, nutrition status, and cognitive function. Conclusion Contemporary psychiatric intervention is beneficial for chronically untreated mentally ill patients, and the patients who had a shorter duration of illness had a better reserve of recovery. These findings can serve as an important reference for psychiatric intervention in developing countries.

Phosphorothioate-modified antisense oligonucleotide (PS-ASO) drugs are commonly used to modulate gene expression through RNase H1-mediated cleavage of target RNAs. Upon internalization through endocytic pathways into cells, PS-ASOs must be released from membraned endosomal organelles to act on target RNAs, a limiting step of PS-ASO activity. Here we report that Hsc70 protein mediates productive release of PS-ASOs from endosomes. Hsc70 protein was enriched in endosome fractions shortly after PS-ASO incubation with cells. Reduction of Hsc70 significantly decreased the activities of PS-ASOs in reducing target RNAs. PS-ASO uptake and transport from early endosomes to late endosomes (LEs) were not affected upon Hsc70 reduction; however, endosomal release of PS-ASOs was impaired. Reduction of Hsc70 led to more scattered mannose-6-phosphate receptor (M6PR) localization at LEs in the cytoplasm, in contrast to the perinuclear localization at trans-Golgi network (TGN) in control cells, suggesting that retrograde transport of M6PR from LEs to TGN was affected. Consistently, reduction of Hsc70 increased colocalization of M6PR and PS-ASOs at LEs, and also delayed M6PR antibody transport from LE to TGN. Together, these results suggest that Hsc70 protein is involved in M6PR vesicle escape from LEs and may thus enhance PS-ASO release from LEs.

Objective To compare differences in efficacy during maintenance treatment for bipolar disorder (BD) according to lithium serum levels. A multicenter retrospective cohort study and a dose‐response meta‐analysis were conducted. Methods The cohort study was conducted in Taiwan from 2001 to 2019 to identify patients with euthymic BD according to different serum levels (

Comprehensive detailed characterization of new mouse models can be challenging due to the individual focus involved in developing these models. Often models are engineered to test a specific hypothesis in a limited number of tissues, stages, and/or other contexts. Whether or not the model produces the desired phenotypes, phenotyping beyond the desired context can be extremely work intensive and these studies are often not undertaken. However, the general information resulting from broader phenotyping can be invaluable to the wider scientific community. The International Mouse Phenotyping Consortium (IMPC) and its subsidiaries, like the Knockout Mouse Project (KOMP), has made great strides in streamlining this process. In particular, the use of microCT has been an invaluable resource in examining internal organ systems throughout fetal/developmental stages. Here, we provide several novel vignettes demonstrating the utility of microCT in uncovering cardiac phenotypes both based on human disease correlations and those that are unpredicted.

Coenzyme Q10 (CoQ10) is a popular nutritional supplement, an antioxidant and an essential component of the mitochondrial electron transport chain. Several clinical studies have suggested that fatigue can be reduced by antioxidant supplementation. However, the data on this topic has been sparse to date. Hence, we conducted this meta-analysis with the aim of investigating the effectiveness of fatigue reduction via CoQ10 supplementation. More specifically, we searched electronic databases for randomized controlled trials (RCTs) published from the database inception to January 2022. A random effects model was implemented to conduct the meta-analysis among 13 RCTs (with a total of 1,126 participants). As compared with the placebo groups evaluated in each RCT, the CoQ10 group showed a statistically significant reduction in fatigue scores (Hedges’ g = −0.398, 95% confidence interval = −0.641 to −0.155, p = 0.001). The directions of the treatment effects were consistent between the healthy and diseased participants. Compared with the placebo group, the effect of reducing fatigue was statistically significant in the subgroup using the CoQ10-only formulation but not in the subgroup using CoQ10 compounds. The results of our meta-regression demonstrate that increases in the daily dose (coefficient = −0.0017 per mg, p < 0.001) and treatment duration (coefficient = −0.0042 per day, p = 0.007) of CoQ10 supplementation were correlated with greater fatigue reduction. There was only one adverse (gastrointestinal) event in the 602 participants who underwent the CoQ10 intervention. Based on the results of this meta-analysis, we conclude that CoQ10 is an effective and safe supplement for reducing fatigue symptoms.Systematic Review Registration:https://inplasy.com/inplasy-2022-1-0113/, identifier INPLASY202210113

In recent decades, the prevalence of amphetamine and methamphetamine use disorders has at least doubled in some regions/countries, with accompanying high risks of drug overdose-associated mortality. Noninvasive brain stimulation (NIBS) methods may be effective treatments. However, the comparative efficacy of the NIBS protocol for amphetamine/methamphetamine use disorder (AUD/MUD) remains unknown to date. The aim of this network meta-analysis (NMA) was to compare the efficacy and acceptability of various NIBS methods/protocols for AUD/MUD management.A frequentist model-based NMA was conducted. We included randomized controlled trials (RCTs) that investigated the efficacy of NIBS and guideline-recommended pharmacologic treatments to reduce craving severity in patients with either AUD or MUD.Twenty-two RCTs including 1888 participants met the eligibility criteria. Compared with the sham/placebo group (study = 19, subjects = 891), a combination of intermittent theta burst stimulation over the left dorsolateral prefrontal cortex (DLPFC) and continuous TBS over the left ventromedial prefrontal cortex (study = 1, subjects = 19) was associated with the largest decreases in craving severity [standardized mean difference (SMD) = -1.50; 95% confidence intervals (95%CIs) = -2.70 to -0.31]. High-frequency repetitive transcranial magnetic stimulation over the left DLPFC was associated with the largest improvements in depression and quality of sleep (study = 3, subjects = 86) (SMD = -2.48; 95%CIs = -3.25 to -1.71 and SMD = -2.43; 95%CIs = -3.38 to -1.48, respectively). The drop-out rate of most investigated treatments did not significantly differ between groups.The combined TBS protocol over the prefrontal cortex was associated with the greatest improvement in craving severity. Since few studies were available for inclusion, additional large-scale randomized controlled trials are warranted.

Objective Month of birth (MOB) is associated with specified mental disorders (MDs). However, whether these relationships extend to all MDs remains unclear. We investigate the association using a population‐based cohort study and a meta‐analysis. Methods First, we examined patients with 34 DSM‐5‐classified MDs in the Taiwan national database. We estimated the relative risk ratios (RR) of each illness in each MOB relative to that in the general population and assessed the periodicity, with six further sensitivity analyses. Second, we searched PubMed, Embase, and Cochrane for related articles through 31 December 2020. We used a random‐effects model, pooled RRs with 95% confidence intervals of each MOB from the identified studies, and transformed them from MOB to relative age in a year or season. Results The cohort included 1,951,777 patients. Except for posttraumatic stress disorder, dissociative disorders, feeding/eating disorders, gender dysphoria, and paraphilic disorders, the other MDs had significant MOB periodicity. The meta‐analysis included 51 studies investigating 10 MDs. The youngest age at the start of school owing to MOB was associated with the highest RRs of intellectual disability (1.13), autism (1.05), attention‐deficit/hyperactivity disorder (1.13). Winter births had significant risks of schizophrenia (1.04), bipolar I disorder (1.02), and major depressive disorder (1.01), and autumn births had a significant risk of alcohol use disorder (1.02). No significant associations between season of birth and Alzheimer's disease, or eating disorders were found. Conclusions MOB is related to the risks of certain MDs. This finding provides a reference for future research on the etiology of MDs.

Background: Oropharyngeal/esophageal candidiasis are the most common opportunistic infections observed in patients with human immunodeficiency virus (HIV). While the commonly recommended treatment ...

To ensure safety, most public spaces now deploy monitoring systems. However, in most scenarios, the tracking operations of these monitoring systems are performed manually. These operations should be automated. This paper proposes using a conditional random field (CRF) to formulate the automatic execution problem as a cost minimization problem. The appearance of pedestrians and the time taken by them to cross the view of a camera are used to solve the automatic execution problem. Crowd psychology is used to define constraints and construct a CRF graph. A Siamese convolutional neural network is employed to recognize pedestrian appearance. The time spent by pedestrians crossing the view of a camera is modeled using a normal distribution. The results of two models are considered as the costs of nodes and edges. The proposed algorithm is applied under constraints to determine matches at the minimum cost. The accuracy of the proposed method is compared with that of other methods by using common datasets and benchmarks. Superior results are obtained when both appearance and spatiotemporal information are employed for solving the automatic execution problem than when using appearance alone.

Background/objectives Obesity has recently been recognized as a neurocognitive disorder involving circuits associated with the reward system and the dorsolateral prefrontal cortex (DLPFC). Noninvasive brain stimulation (NIBS) has been proposed as a strategy for the management of obesity. However, the results have been inconclusive. The aim of the current network meta-analysis (NMA) was to evaluate the efficacy and acceptability of different NIBS modalities for weight reduction in participants with obesity. Methods Randomized controlled trials (RCTs) examining NIBS interventions in patients with obesity were analyzed using the frequentist model of NMA. The coprimary outcome was change in body mass index (BMI) and acceptability, which was calculated using the dropout rate. Results Overall, the current NMA, consisting of eight RCTs, revealed that the high-frequency repetitive transcranial magnetic stimulation (TMS) over the left DLPFC was ranked to be associated with the second-largest decrease in BMI and the largest decrease in total energy intake and craving severity, whereas the high-frequency deep TMS over bilateral DLPFC and the insula was ranked to be associated with the largest decrease in BMI. Conclusion This pilot study provided a "signal" for the design of more methodologically robust and larger RCTs based on the findings of the potentially beneficial effect on weight reduction in participants with obesity by different NIBS interventions.

Several diagnostic criteria have been developed to effectively diagnose systemic lupus erythematosus (SLE). Three criteria are most common, namely the American College of Rheumatology (ACR)-1997, the Systemic Lupus International Collaborating Clinics (SLICC)-2012, and the European League Against Rheumatism (EULAR/ACR)-2019. Whether they also apply to juvenile SLE is unclear.To examine the diagnostic accuracy of ACR-1997, SLICC-2012, and EULAR/ACR-2019 for juvenile SLE.A comprehensive search of PubMed, Cochrane, and Embase was conducted up to 26 March 2022.We included all study designs in which patients had any index tests for ACR-1997, SLICC-2012, or EULAR/ACR-2019; both full-text papers and conference abstracts published in English were used. Exclusion criteria were as follows: (1) case reports; (2) adult subjects; or (3) did not report sufficient information to acquire true positive, false positive, true negative, and false negative values of diagnostic criteria.Two authors independently screened studies, extracted relevant data, and assessed the risk of bias.First, a meta-analysis of the diagnostic accuracy of EULAR/ACR-2019 and a hierarchical summary receiver operating characteristic (HSROC) model was performed to estimate sensitivity and specificity with 95% confidence intervals (CIs). We then carried out a network meta-analysis to compare the performances of these three diagnostic criteria.In total, 17 relevant studies that included 2339 juvenile SLE patients were eligible to analyze pooled accuracy. In the meta-analysis, 10 studies (1613 cases) reported the diagnostic performance of EULAR/ACR-2019, showing a pooled sensitivity of 0.92 (95% CI, 0.89-0.95), pooled specificity of 0.89 (0.77-0.95), and area under HSROC of 0.96 (0.94-0.97). In the network meta-analysis, the SLICC-2012 (0.94, 0.92-0.96) had the highest sensitivity, followed by EULAR/ACR-2019 (0.93, 0.90-0.95), and ACR-1997 (0.78, 0.72-0.82); the ACR-1997 (0.96, 0.92-0.98) demonstrated the highest specificity. EULAR/ACR-2019 (0.92, 0.87-0.96) and SLICC-2012 (0.92, 0.86-0.96) had the similar specificity.We found that the applicability of the new EULAR/ACR-2019 criteria in juvenile SLE is not yet the best diagnostic tool.PROSPERO CRD42022321514.

Acute mania is a psychiatric emergency requiring rapid management. However, randomised controlled trials (RCTs) have shown considerable individual differences in treatment effects on manic symptoms with antimanic drugs.We searched the MEDLINE, CENTRAL, EMBASE, PsycINFO, and ClinicalTrials.gov to identify RCTs without language restrictions from inception to April 19, 2022. We included double-blind RCTs of oral antimanic monotherapy versus placebo in adult patients. The primary outcome was variability in improvement of manic symptoms (assessed using the coefficient of variation ratio [CVR]). The secondary outcomes were overall improvement of manic symptoms and acceptability (i.e., discontinuation for any reason). The pooled effects of outcomes were calculated by random-effects meta-analyses using restricted maximum likelihood methods. The quality of the included studies was assessed using the Cochrane Risk of Bias (ROB) Assessment Tool. This study was registered with OSF (DOI:10.17605/OSF.IO/G4JNY).We included 39 RCTs (N=12150; mean age=39·9 years, interquartile range [IQR]=38·7-41·1; mean proportion of female=48·6%, IQR=42·3%-52·3%) and investigated 14 antimanic drugs. We found that eight antimanic drugs compared to placebo were associated with lower CVRs (95% confidence interval [CI]; IWe demonstrated that eight antimanic drugs were associated with lower variability and better efficacy than placebo, suggesting that these antimanic drugs were associated with more homogenous and predictable improvements of manic symptoms in patients with acute mania.The study was supported by from the Ministry of Science and Technology (MOST-110-2314-B-016-035, MOST-111-2314-B-016-054), Medical Affairs Bureau (MND-MAB-D-111102), and Tri-service General Hospital (TSGH-E-111229).

To integrate all evidence derived from randomized controlled trials (RCTs) of both pharmacological and nonpharmacological augmentation interventions for clozapine-resistant schizophrenia (CRS).Six major electronic databases were systematically searched for RCTs published until July 10, 2021. The primary outcome was change in overall symptoms, and the secondary outcomes were positive and negative symptoms and acceptability. We performed random-effects network meta-analysis. Normalized entropy was calculated to examine the uncertainty of treatment ranking.We identified 35 RCTs (1472 patients with 23 active augmentation treatments) with a mean daily clozapine dose of 440.80 (91.27) mg for 1168.22 (710.28) days. Network meta-analysis of overall symptoms (reported as standardized mean difference; 95 % confidence interval) with consistent results indicated that mirtazapine (-4.41; -5.61, -3.21), electroconvulsive therapy (ECT) (-4.32; -5.43, -3.21), and memantine (-2.02; -3.14, -0.91) were ranked as the best three treatments. For positive symptoms, ECT (-5.18; -5.86, -4.49) was ranked the best with less uncertainty. For negative symptoms, memantine (-3.38; -4.50, -2.26), duloxetine (-3.27; -4.25, -2.29), and mirtazapine (-1.73; -2.71, -0.74) were ranked the best three treatments with less uncertainty. All antipsychotics, N-methyl d-aspartate receptor agonists, and antiepileptics were not associated with more efficacy than placebo. Compared to placebo, only amisulpride had statistically significant lower discontinuation rate (risk ratio: 0.21; 95 % CI: 0.05, 0.93).Add-on mirtazapine, ECT, and memantine were the most efficacious augmentation options for CRS. Data on other important outcomes such as cognitive functioning or quality of life were rarely reported, making further large-scale, well-designed RCTs necessary. (PROSPERO number, CRD42021262197.).

STUDY OBJECTIVES: The aim of this study is to evaluate the relationship between the month of birth (MOB) and the risk of narcolepsy. METHODS: We conducted a systematic review of the electronic databases PubMed, Embase, and Cochrane CENTRAL from their inception to September 30, 2021. We also added data on narcolepsy from the National Health Insurance Research Database in Taiwan. Then we extracted the relative risk (RR) ratios of narcolepsy in each month of birth to those of the general population and transformed them from MOB to season. A random-effects model was used to calculate pooled RR ratios from the meta-analysis and 95% confidence interval (CI). RESULTS: The meta-analysis analyzed 7 studies and included 3,776 patients from 8 areas (Canada, China, France, Germany, Hong Kong, Netherlands, Taiwan, and United States). The RR ratio was highest in March (1.11; 95% CI, 0.99–1.26) and August (1.11; 95% CI, 0.98–1.26) and lowest in April (0.90; 95% CI, 0.78–1.03). However, none of the MOBs reached statistical significance. Moreover, the narcolepsy risk patterns on the 3 continents (Asia, Europe, and North America) were different. In North America, the highest and lowest significant risks were found in March (1.47; 95% CI, 1.20–1.79) and September (0.75; 95% CI, 0.56–0.99). In Asia, the lowest notable risk was in April (0.80; 95% CI, 0.66–0.97). In Europe, the risk of narcolepsy was not significantly related to any MOB. In terms of seasons, only spring MOBs in North America had a significantly higher risk (1.21; 95% CI, 1.06–1.38). CONCLUSIONS: The findings indicated that the risk of narcolepsy and MOB differed across the 3 continents. This study indicates the important role of environmental factors in narcolepsy. SYSTEMATIC REVIEW REGISTRATION: Registry: PROSPERO; Identifier: CRD42020186660. CITATION: Hsu C-W, Tseng P-T, Tu Y-K, et al. Month of birth and the risk of narcolepsy: a systematic review and meta-analysis. J Clin Sleep Med. 2022;18(4):1113–1120.

The rapid growth of multimedia data and the improvement of deep learning technology has allowed high-accuracy models to be trained for various fields. Video tools such as video classification, temporal action detection, and video summary are now available for the understanding of videos. In daily life, many social events start with a small conflict event. If conflicts and the subsequent dangers can be learned about from a video, we can prevent social incidents from occurring early on. This research presents a video and audio reasoning network that infers possible conflict events through video and audio features. To make the respective model more generalizable to other tasks, we have also added a predictive network to predict the risk of conflict events. We use multitasking to render the characteristics of movies and voices more generalizable to other similar tasks. We also propose several methods to integrate video features and audio features, improving the reasoning performance of the model. There’s a model we proposed is called the video and audio reasoning Network (VARN) which is more accurate than other models. Compared with RandomNet, it achieves a 2.9 times greater accuracy.

Background Depression is a common morbidity after traumatic brain injury. This network meta-analysis investigated the efficacy and tolerability of pharmacologic and nonpharmacologic interventions for depression after traumatic brain injury. Methods We extracted randomized controlled trials examining pharmacologic or nonpharmacologic interventions with placebo- or active-controlled designs from PubMed, the Cochrane Library and ScienceDirect, from inception to October 30, 2018. We based study selection and extraction of a predefined list of variables on the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, and conducted meta-analysis procedures using random effects modelling. Primary outcomes were changes in depressive symptom severity after pharmacologic or nonpharmacologic treatment; the secondary outcome was tolerability, reflected in overall patient dropout rates. Results Our analysis of 27 randomized controlled trials (10 pharmacologic, total n = 483, mean age = 37.9 yr; 17 nonpharmacologic, total n = 1083, mean age = 38.0 yr) showed that methylphenidate had significantly superior efficacy compared to placebo or control (standardized mean difference -0.91, 95% confidence interval [CI] -1.49 to -0.33). Sertraline was associated with significantly lower tolerability (i.e., a higher dropout rate) compared to placebo or control (odds ratio 2.65, 95% CI 1.27 to 5.54). No nonpharmacologic treatment was more effective than the others, and we found no significant differences in tolerability (i.e., dropout rates) among the nonpharmacologic treatments. Limitations Heterogeneity in participant characteristics (e.g., comorbidities), study designs (e.g., trial duration) and psychopathology assessment tools, as well as small trial numbers for some treatment arms, could have been confounders. Conclusion The present network meta-analysis suggests that methylphenidate might be the best pharmacologic intervention for depressive symptoms related to traumatic brain injury. None of the nonpharmacologic interventions was associated with better improvement in depressive symptoms than the others or than control conditions. None of the pharmacologic or nonpharmacologic treatments had inferior tolerability compared to placebo or controls except for sertraline, which had significantly lower tolerability than placebo.

Widespread electric vehicle (EV) adoption is crucial for achieving California's climate goals. The inclusion of marginalized populations in this process is important and will require that they have access to charging infrastructure. Public EV charging stations may help reduce the EV adoption barriers affecting these populations. This study combines public charging station location data with American Community Survey data at the census block group level in California, finding that public charger access is lower in block groups with below-median household incomes and in those with a Black and Hispanic majority populations. These public charger access disparities are more pronounced in areas with a higher proportion of multi-unit housing, where they are critical for EV operation due to a lower likelihood of residential charger access. Controlling for distance to the nearest highway or freeway, multi-unit housing unit rate, and median household income, we find that Black and Hispanic majority block groups are the only race and ethnicity group that is significantly less likely to have access to any public charger in their block groups compared to the rest of the state. The odds of having public charger access for the group is 0.7-times that of the no majority reference group. The access gap is even larger for the publicly-funded charging stations where Black and Hispanic majority block groups are approximately half as likely as the no-majority reference group to have access. Hence directing a larger portion of the funding to underserved communities and further government involvement in filling the public charger access gap can be crucial in achieving widespread and equitable EV adoption.

The initial stages of metal organic chemical vapor deposition (MOCVD) of AlN on epitaxial graphene at temperatures in excess of 1200 degrees C have been rationalized. The use of epitaxial graphene, in conjunction with high deposition temperatures, can deliver on the realization of nanometer thin AlN whose material quality is characterized by the appearance of luminescent centers with narrow spectral emission at room temperature. It has been elaborated, based on our previous comprehensive ab initio molecular dynamics simulations, that the impact of graphene on AlN growth consists in the way it promotes dissociation of the trimethylaluminum, (CH3)(3)Al, precursor with subsequent formation of Al adatoms during the initial stages of the deposition process. The high deposition temperatures ensure adequate surface diffusion of the Al adatoms which is an essential factor in material quality enhancement. The role of graphene in intervening with the dissociation of another precursor, trimethylgallium, (CH3)(3)Ga, has accordingly been speculated by presenting a case of propagation of ultrathin GaN of semiconductor quality. A lower deposition temperature of 1100 degrees C in this case has better preserved the structural integrity of epitaxial graphene. Breakage and decomposition of the graphene layers has been deduced in the case of AlN deposition at temperatures in excess of 1200 degrees C. Funding Agencies|FLAG-ERA 2015 JTC project GRIFONE through the Swedish Research Council [VR2015-06816]; National Research Development and Innovation Office, Hungary [NN 118914]; Swedish Research CouncilSwedish Research Council [SNIC 2020/5-146, SNIC 2020/14-17, VR2018-05973]; Olle Engkvist Foundation; [VR2017-04071]; [AF15-557]; [AF18-266]; [VR2016-05362]

California faces crisis conditions on its forested landscapes. A century of aggressive logging and fire suppression in combination with conditions exacerbated by climate change have created an ongoing ecological, economic, and public health emergency. Between commercial harvests on California’s working forestlands and the increasing number of acres the state treats each year for fire risk reduction and carbon sequestration, California forests generate millions of tons of woody residues annually—residues that are typically left or burned in the field. State policymakers have turned to biomass electricity generation as a key market for woody biomass in the hope that it can support sustainable forest management activities while also providing low-carbon renewable electricity. However, open questions surrounding the climate and air pollution performance of electricity generation from woody biomass have made it difficult to determine how best to manage the risks and opportunities posed by forest residues. The California Biomass Residue Emissions Characterization (C-BREC) model offers a spatially-explicit life cycle assessment framework to rigorously and transparently establish the climate and air pollution impacts of biopower from forest residues in California under current conditions. The C-BREC model characterizes the variable emissions from different biomass supply chains as well as the counterfactual emissions from prescribed burn, wildfire, and decay avoided by residue mobilization. We find that the life cycle ‘carbon footprint’ of biopower from woody residues generated by recent forest treatments in California ranges widely—from comparable with solar photovoltaic on the low end to comparable with natural gas on the high end. This variation stems largely from the heterogeneity in the fire and decay conditions these residues would encounter if left in the field, with utilization of residue that would otherwise have been burned in place offering the best climate and air quality performance. California’s energy and forest management policies should account for this variation to ensure desired climate benefits are achieved.