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Patients with major depressive disorder (MDD) often exhibit an inadequate treatment response or failure to achieve remission following treatment with antidepressant drugs. Treatment-resistant depression (TRD) is proposed to identify this clinical scenario. Compared to those without TRD, patients with TRD have significantly lower health-related quality of life in mental and physical dimensions, more functional impairment and productivity loss, and higher healthcare costs. TRD imposes a massive burden on the individual, family, and society. However, a lack of consensus on the TRD definition limits the comparison and interpretation of TRD treatment efficacy across trials. Furthermore, because of the various TRD definitions, there is scarce treatment guideline specifically for TRD, in contrast to the rich treatment guidelines for MDD. In this chapter, common issues related to TRD, such as proper definitions of an adequate antidepressant trial and TRD, were carefully reviewed. Prevalence of and clinical outcomes related to TRD were summarized. We also summarized the staging models ever proposed for the diagnosis of TRD. Furthermore, we highlighted variations in the definition regarding the lack of or an inadequate response in treatment guidelines for depression. Up-to-date treatment options for TRD, including pharmacological strategies, psychotherapeutic interventions, neurostimulation techniques, glutamatergic compounds, and even experimental agents were reviewed., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Because of a relative dearth of longitudinal studies, the directionality of the relationship between mood and inflammation among patients with bipolar disorder (BD) is still unclear. We aimed to investigate the longitudinal associations of pro-inflammatory markers with mood symptom severity in BD., Methods: Hundred and thirty-two adult patients with BD were enrolled. At the baseline and 1-year follow-up visit, all participants received mood assessment with Montgomery Åsberg depression rating scale (MADRS) and Young mania rating scale, and underwent blood draws to quantify metabolic profile and serum levels of the pro-inflammatory markers, including soluble interleukin-6 receptor, soluble tumor necrosis factor-α receptor type 1 (sTNF-αR1), monocyte chemoattractant protein-1, and C-reactive protein. A four-factor model of MADRS, consisting of sadness, negative thoughts, detachment, and neurovegetative symptoms, were applied., Results: At baseline, 65 patients with BD were in depressed state, and 67 patients with BD were in euthymic state. Among patients in depressed state, baseline MADRS total score positively correlated with sTNF-αR1 level at follow-up. While baseline sTNF-αR1 level positively predicted sadness symptom in euthymic patients with BD who later developed depression (n = 22), sadness in patients with bipolar depression predicted later increase in serum sTNF-αR1 level even after remission (n = 17). Moreover, lithium had a stronger effect of lowering peripheral sTNF-αR1 level as compared with other mood stabilizers., Conclusion: Our results indicate the bidirectional inflammation-depression relationship in BD., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In forensic physical evidence identification, the accurate identification of the individual origin and their body fluid composition of the biological samples obtained from the crime scene play a critical role in determining the nature of a crime. In recent years, RNA profiling has become one of the fastest developing methods for body fluids identification. Due to the characteristics of tissue or body fluid specific expression, various types of RNA markers have been proven to be promising candidate markers for body fluids identification in previous studies. This review summarizes the research progress of RNA markers in body fluids identification, including the RNA markers that have been effectively verified in current research and their advantages and disadvantages. Meanwhile, this review prospects the application of RNA markers in forensic medicine.

Objectives: To investigate the genetic polymorphism of InDel loci in SifalnDel 45plex system in the Han population in Jiangsu Province and the Mongolian population in Inner Mongolia, and to evaluate the effectiveness of the system in forensic medicine., Methods: SifaInDel 45plex system was used for genotyping in blood samples of 398 unrelated individuals from the above two populations, and allele frequencies and population genetic parameters of the two populations were calculated respectively. Eight intercontinental populations in the gnomAD database were used as reference populations. The genetic distances between the two studied populations and eight reference populations were calculated based on the allele frequencies of 27 autosomal-InDels (A-InDels). The phylogenetic trees and multidimensional scaling (MDS) analysis diagrams were constructed accordingly., Results: Among two studied populations, the 27 A-InDels and 16 X-InDels showed no linkage disequilibrium between each other and the allele frequency distributions were in Hardy-Weinberg equilibrium. The CDP of the 27 A-InDels in two studied populations were all higher than 0.999 999 999 9, and the CPE trio were all less than 0.999 9. The CDP of the 16 X-InDels in Han in Jiangsu and Mongolian in Inner Mongolia female and male samples were 0.999 997 962, 0.999 998 389, and 0.999 818 940, 0.999 856 063, respectively. The CMEC trio were all less than 0.999 9. The results of population genetics showed that the Jiangsu Han nationality, Inner Mongolia Mongolian nationality and East Asian population clustered into one branch, showing closer genetic relationship. The other 7 intercontinental populations clustered into another group. And the above 3 populations displayed distant genetic relationships with the other 7 intercontinental populations., Conclusions: The InDels in the SifaInDel 45plex system have good genetic polymorphism in the two studied populations, which can be used for forensic individual identification or as an effective complement for paternity identification, and to distinguish different intercontinental populations.

In recent years, due to the rapid development of Internet of things (IoTs), various physical things (objects) in IoTs are smart enough to make their own decisions without the involvement of humans. The smart devices embedded in a drone can sense, collect, and transmit real-time data back to the controller from a designated environment via wireless communication technologies. The mobility, flexibility, reliability and energy efficiency of drones makes them more widely used in IoT environments such as commercial, military, entertainment applications, traffic surveillance and aerial photography. In a generalized IoD architecture, we have communications among the drones in a flying zone, among the drones and the control server, and also among the drones and authorized user. IoD still has many critical issues that need to be addressed, such as data access being carried out through a public channel and battery operated drones. To address these concerns in IoD communications, in this paper, an efficient authentication and secure communication scheme with privacy preservation is proposed and it only uses secure one-way hash function and bitwise XOR operations when control server, drone and user mutually authenticate each other. After the successful authentication, both IoD-based participants can agree on a common session key to secure the subsequent communication messages. The widely accepted ProVerif and BAN logic analysis have been used to assure that the proposed scheme is provably secure against existing well-known security attacks and ensures privacy. Finally, a comparative analysis is presented to demonstrate the proposed scheme preserves efficiency when compared to existing competitive schemes.

Background: A significant proportion of patients with major depressive disorder (MDD) failed to respond to antidepressant medications. Repetitive transcranial magnetic stimulation (rTMS) is an effective option for treating such treatment-resistant patients with MDD (TRD). Reliable clinical predictors for antidepressant responses to rTMS remain elusive., Methods: In total, 212 patients with MDD who failed to respond to at least one adequate antidepressant trial and had a detailed evaluation before rTMS were recruited for chart review. Demographic data, clinical characteristics, psychiatric comorbidities, symptom ratings [e.g., objective and subjective depression, life stress, depression refractoriness by Maudsley Staging Method (MSM)], and antidepressant treatment responses were analyzed., Results: MSM-subitem1 (duration of current depressive episode; Beta = 0.209, p = 0.004), MSM-subitem5 (a history of ECT treatment; Beta = -0.210, p = 0.004), and psychiatric admissions (Beta = 0.241, p = 0.001) predicted antidepressant response of rTMS treatment. ECT was underutilized (only 3.3%). Psychiatric admissions [Exp(B) = 1.382, p = 0.021], a comorbidity of OCD [0.047, 0.005], and life stress level [0.984, 0.029] predicted the history of ECT treatment., Conclusion: Several clinical variables (e.g., number of psychiatric admissions, OCD as a comorbidity, and life stress level) were reliable clinical factors associated with antidepressant responses of rTMS treatment and may be utilized in combination with MSM subitems to evaluate levels of TRD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past co-authorship with one of the author S-JT., (Copyright © 2022 Li, Su, Cheng, Chen, Bai and Tsai.)

Aim: 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., Methods: 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., Results: 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., Conclusion: 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., (© 2022 The Authors. Psychiatry and Clinical Neurosciences © 2022 Japanese Society of Psychiatry and Neurology.)

Autistic spectrum disorder (ASD) is a common developmental disorder in children. The latest non-intrusive brain stimulation (NIBS) technology-transcranial pulse stimulation (TPS)-has been proven effective in older adults with mild neurocognitive disorders and adults with major depressive disorder. Nonetheless, there is so far no robust randomized controlled trial (RCT) conducted on adolescents with ASD nationwide. This study proposes a two-armed (verum TPS group vs. sham TPS group), double-blinded, randomized, sham-controlled trial. Both groups will be measured at four timepoints, namely, baseline (T1), 2 weeks immediately after post-TPS intervention (T2), and at the 1-month (T3) and 3-month (T4) follow-ups. Thirty-four subjects, aged between 12 and 17, diagnosed with ASD will be recruited in this study. All subjects will be computerized randomised into the verum TPS group or the sham TPS group on a 1:1 ratio. All subjects will undertake functional MRI (fMRI) before and after the 2-weeks TPS interventions, which will be completed in 2 weeks' time. This will be the first RCT evaluating the efficacy of TPS adolescents with ASD in Hong Kong. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT05408793.

The developmental transcriptomes of Sarcomyxa edulis were assessed to explore the molecular mechanisms underlying lignocellulose degradation. Six stages were analyzed, spanning the entire developmental process: growth of mycelium until occupying half the bag (B1), mycelium under low-temperature stimulation after occupying the entire bag (B2), appearance of mycelium in primordia (B3), primordia (B4), mycelium at the harvest stage (B5), and mature fruiting body (B6). Samples from all six developmental stages were used for transcriptome sequencing, with three biological replicates for all experiments. A co-expression network of weighted genes associated with extracellular enzyme physiological traits was constructed using weighted gene co-expression network analysis (WGCNA). We obtained 19 gene co-expression modules significantly associated with lignocellulose degradation. In addition, 12 key genes and 8 kinds of TF families involved in lignocellulose degradation pathways were discovered from the four modules that exhibited the highest correlation with the target traits. These results provide new insights that advance our understanding of the molecular genetic mechanisms of lignocellulose degradation in S. edulis to facilitate its utilization by the edible mushroom industry., (© 2022. The Author(s).)

Background: Hepatic steatosis is a common radiologic finding. Some imaging inklings are the absence of a mass effect, and there is currently no report of hepatic steatosis with mass effect., Case Summary: A 23-year-old female was admitted due to a liver mass for half a month. No obvious abnormalities were found in physical and laboratory examinations. Ultrasound, computed tomography, and magnetic resonance imaging showed a huge mass between the liver and stomach with a significant mass effect, and the caudate lobe and left lobe of the liver were involved. The signal on T2- and T1- weighted fat-saturated images of the mass was significantly reduced, and the enhanced scan showed inhomogeneous enhancement. Surgical and pathological findings indicated the diagnosis of hepatic steatosis. The operation and re-review of the patient's images showed that the lesion was supplied by the branch of the hepatic artery. The signal on T1-weighted out-of-phase images of the lesion was lower than on in-phase images, and there was no black rim cancellation artifact around the hepatic steatosis area on T1-weighted out-of-phase images. The dynamic enhancement pattern of the lesion was similar to that of the adjacent normal liver parenchyma. The above characteristics suggested that the lesion was hepatic steatosis. However, in this case, the lesion showed exogenous growth and was mass-like, with an obvious mass effect, which has not been reported previously., Conclusion: Hepatic steatosis could grow exogenously and has an obvious mass effect. It needs to be distinguished from fat-rich tumors. The T1-weighted in- and out-of-phase images and dynamic enhanced scanning are valuable for differential diagnosis of this lesion., Competing Interests: Conflict-of-interest statement: All authors declare that they have no conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Carbonyl ylides have proven to be powerful synthons for the efficient construction of various valuable O-heterocycles, and the formation of carbonyl ylides by the reaction of metal carbenes with carbonyls has attracted increasing attention over the past decades. However, a catalyst-controlled highly enantioselective reaction of carbonyl ylides from metal carbenes is extremely challenging. Herein, we report a novel copper-catalyzed asymmetric formal [2+1] and [4+1] annulations of diynes with ketones via carbonyl ylides. Importantly, this protocol not only represents the first example of successful asymmetric epoxidation via carbonyl ylides, but also constitutes the first reaction of vinyl cations with carbonyl compounds. This method leads to the divergent, practical and atom-economical synthesis of a range of chiral oxiranes and dihydrofurans in moderate to excellent yields with generally excellent enantioselectivities and diastereoselectivities via remote-stereocontrol strategy., (© 2022 Wiley-VCH GmbH.)

Source-camera identification tools assist image forensics investigators to associate an image with a camera. The Photo Response Non-Uniformity (PRNU) noise pattern caused by sensor imperfections has been proven to be an effective way to identify the source camera. However, the PRNU is susceptible to camera settings, scene details, image processing operations (e.g., simple low-pass filtering or JPEG compression), and counter-forensic attacks. A forensic investigator unaware of malicious counter-forensic attacks or incidental image manipulation is at risk of being misled. The spatial synchronization requirement during the matching of two PRNUs also represents a major limitation of the PRNU. To address the PRNU's fragility issue, in recent years, deep learning-based data-driven approaches have been developed to identify source-camera models. However, the source information learned by existing deep learning models is not able to distinguish individual cameras of the same model. In light of the vulnerabilities of the PRNU fingerprint and data-driven techniques, in this paper, we bring to light the existence of a new robust data-driven device-specific fingerprint in digital images that is capable of identifying individual cameras of the same model in practical forensic scenarios. We discover that the new device fingerprint is location-independent, stochastic, and globally available, which resolves the spatial synchronization issue. Unlike the PRNU, which resides in the high-frequency band, the new device fingerprint is extracted from the low- and mid-frequency bands, which resolves the fragility issue that the PRNU is unable to contend with. Our experiments on various datasets also demonstrate that the new fingerprint is highly resilient to image manipulations such as rotation, gamma correction, and aggressive JPEG compression.

Background: This posthoc analysis compared the antidepressant and antisuicidal effects of low-dose ketamine infusion with those of repetitive transcranial magnetic stimulation (rTMS) on treatment-resistant depression (TRD)., Methods: In the ketamine infusion trial, 48 patients with TRD were randomized to receive a single infusion of 0.5 mg/kg ketamine or normal saline. In the rTMS trial, 105 patients were randomly assigned to intermittent theta-burst stimulation (iTBS), 10-Hz rTMS, or sham stimulation. The 17-item Hamilton Rating Scale for Depression (HDRS) was administered., Results: The antidepressant effect was prominent at Day 7 postinfusion in the ketamine group but steadily accumulated with the treatment duration from Day 7 to 14 in the iTBS and 10-Hz rTMS groups, regardless of the level of treatment resistance (all p < .01). Low-dose ketamine infusion and iTBS exerted superior effects on suicidal symptoms (HDRS item 3) than the other three groups (p < .001). The antidepressant effect of iTBS/10-Hz rTMS may persist for up to 3 months; however, the antidepressant effect of a single low-dose ketamine infusion did not persist over a month., Discussion: Both low-dose ketamine infusion and rTMS/TBS must be included in TRD treatment but may be applied in different clinical situations., Competing Interests: Declaration of Competing Interest None of the authors in this study had any conflict of interest to declare., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aim: Bipolar disorder and major depressive disorder (MDD) have been demonstrated to be associated with proinflammatory states and cognitive function deficits. We aimed to investigate the differences of cognitive function and proinflammatory cytokines between patients with bipolar I disorder (BDI), bipolar II disorder (BDII), and MDD., Methods: Thirty-seven patients with BDI, 33 with BDII, 25 with MDD, and 54 age-, sex-matched controls were enrolled. All patients had a clinical global impression-severity scale ≤2. Serum levels of proinflammatory markers, including soluble interleukin-6 receptor, C-reactive protein, and soluble tumor necrosis factor receptor 1 (sTNF-αR1) were measured. Performance in the Word List Memory Task (WLMT), Wisconsin Card Sorting Task (WCST), 2-back task, Go/No-Go task, and divided attention task was assessed., Results: Patients with BDI had higher levels of sTNF-αR1 than patients with MDD and controls (P < 0.001). Patients with BDI performed worse on WLMT, WCST, 2-back task, divided attention&#95;visual and divided attention&#95;auditory tasks than the other three groups (all P < 0.05). Furthermore, sTNF-αR1 levels were negatively correlated with cognitive function measured using the WLMT and divided attention&#95;auditory (all P < 0.05)., Conclusions: Patients with BDI had higher levels of sTNF-αR1 and cognitive function impairments than the remaining groups. Future studies are needed to explore the pathophysiology of sTNF-αR1 in the contribution of cognitive alterations., (© 2022 The Authors. Psychiatry and Clinical Neurosciences © 2022 Japanese Society of Psychiatry and Neurology.)

Objectives: To study the genetic polymorphism and population genetic parameters of 16 X-STR loci in Xinjiang Uygur population., Methods: The Golden e ye ® DNA identification system 17X was used to amplify 16 X-STR loci in 502 unrelated individuals (251 females and 251 males). The amplified products were detected by 3130 xl genetic analyzer. Allele frequencies and population genetic parameters were analyzed statistically. The genetic distances between Uygur and other 8 populations were calculated. Multidimensional scaling and phylogenetic tree were constructed based on genetic distance., Results: In the 16 X-STR loci, a total of 67 alleles were detected in 502 Xinjiang Uygur unrelated individuals. The allele frequencies ranged from 0.001 3 to 0.572 4. PIC ranged from 0.568 8 to 0.855 3. The cumulative discrimination power in females and males were 0.999 999 999 999 999 and 0.999 999 999 743 071, respectively. The cumulative mean paternity exclusion chance in trios and in duos were 0.999 999 997 791 859 and 0.999 998 989 000 730, respectively. The genetic distance between Uygur population and Kazakh population was closer, and the genetic distance between Uygur and Han population was farther., Conclusions: The 16 X-STR loci are highly polymorphic and suitable for identification in Uygur population, which can provide a powerful supplement for the study of individual identification, paternity identification and population genetics.

Background: Major depressive disorder (MDD), particularly treatment-resistant ones, is associated with abnormal fronto-limbic glucose metabolism. 10-Hz repetitive transcranial magnetic stimulation (rTMS) over left prefrontal cortex (PFC) is believed to normalize the abnormal metabolism to treat depression. However, the exact molecular mechanisms underlying the mood circuit of depressed brains and whether brain stimulation techniques regulate the underlying molecules remain elusive., Methods: Whole-brain glucose metabolism and cortical excitatory and inhibitory markers including P30, N45, P60, N100, and LICI (long-interval cortical inhibition) of TMS-evoked potentials from left DLPFC were measured in 40 subjects with MDD patients. The neurophysiological markers were repeated immediately after 1st session of left PFC rTMS, intermittent theta-burst stimulation (iTBS), and sham (randomly assigned)., Results: Brain glucose metabolism in the limbic structures significantly correlated with left PFC P30 (mainly GABA-A and glutamate receptor mediated) and with LICI (mainly GABA-B receptor mediated inhibition) (FWE-corrected p < 0.001). Correlations between other neurophysiological markers (left PFC N45, P60, and N100) and posterior cingulate cortex, a key region in the default mode network, were also noted. One session of rTMS significantly decreased left PFC P60 (mainly glutamate receptor mediated), while a significant group effect was found for LICI (iTBS < sham)., Conclusion: The first study showed that the underlying molecular mechanisms of fronto-limbic circuit of MDD brains involved glutamatergic excitation and GABAergic inhibition at specific time points. In addition, one session of rTMS mainly modulated glutamatergic neurotransmission at left PFC, while the mechanisms of iTBS might involve GABA-B receptor mediated inhibition., Clinical Trials Registry Number: UMIN000044951., (Copyright © 2022. Published by Elsevier B.V.)

The title compound, C 10 H 10 N 4 2+ ·NO 3 - ·ClO 4 - , was obtained unexpectedly by the reaction of Co(ClO 4 ) 2 ·6H 2 O and cytidine-5'-monophosphate with 4,4'-azo-pyridine in an aqueous solution of nitric acid. The mol-ecular structure comprises two planar 4,4'-diazenediyldipyridinium dications lying on inversion centres and perchlorate and nitrate anions in general positions. In the crystal, N-H⋯O hydrogen bonds between dications and anions lead to the formation of [232] chains., (© Qiu et al. 2022.)

Importance: Negative symptoms have a detrimental impact on functional outcomes and quality of life in people with schizophrenia, and few therapeutic options are considered effective for this symptomatic dimension. Studies have suggested that noninvasive brain stimulation (NIBS) interventions may be effective in treating negative symptoms. However, the comparative efficacy of different NIBS protocols for relieving negative symptoms remains unclear., Objective: To compare the efficacy and acceptability of different NIBS interventions for treating negative symptoms., Data Sources: The ClinicalKey, Cochrane CENTRAL, Embase, ProQuest, PubMed, ScienceDirect, ClinicalTrials.gov, and Web of Science electronic databases were systematically searched from inception through December 7, 2021., Study Selection: A frequentist model network meta-analysis was conducted to assess the pooled findings of trials that evaluated the efficacy of repetitive transcranial magnetic stimulation (rTMS), theta-burst stimulation, transcranial random noise stimulation, transcutaneous vagus nerve stimulation, and transcranial direct current stimulation on negative symptoms in schizophrenia. Randomized clinical trials (RCTs) examining NIBS interventions for participants with schizophrenia were included., Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed. Data were independently extracted by multiple observers. The pair-wise meta-analytic procedures were conducted using a random-effects model., Main Outcomes and Measures: The coprimary outcomes were changes in the severity of negative symptoms and acceptability (ie, dropout rates owing to any reason). Secondary outcomes were changes in positive and depressive symptoms., Results: Forty-eight RCTs involving 2211 participants (mean [range] age, 38.7 [24.0-57.0] years; mean [range] proportion of female patients, 30.6% [0%-70.0%]) were included. Compared with sham control interventions, excitatory NIBS strategies (standardized mean difference [SMD]: high-definition transcranial random noise stimulation, -2.19 [95% CI, -3.36 to -1.02]; intermittent theta-burst stimulation, -1.32 [95% CI, -1.88 to -0.76]; anodal transcranial direct current stimulation, -1.28 [95% CI, -2.55 to -0.02]; high-frequency rTMS, -0.43 [95% CI, -0.68 to -0.18]; extreme high-frequency rTMS, -0.45 [95% CI, -0.79 to -0.12]) over the left dorsolateral prefrontal cortex with or without other inhibitory stimulation protocols in the contralateral regions of the brain were associated with significantly larger reductions in negative symptoms. Acceptability did not significantly differ between the groups., Conclusions and Relevance: In this network meta-analysis, excitatory NIBS protocols over the left dorsolateral prefrontal cortex were associated with significantly large improvements in the severity of negative symptoms. Because relatively few studies were available for inclusion, additional well-designed, large-scale RCTs are warranted.

Accumulating evidence suggests the critical role of cortical thinning in the pathophysiology of major depressive disorder. However, the association of cortical thickness and cognitive impairment with treatment-resistant depression (TRD) has rarely been investigated. In total, 48 adult patients with TRD and 48 healthy controls were recruited and administered a series of neurocognitive and neuroimaging examinations, including 1-back and 2-back working memory tasks and brain magnetic resonance imaging (MRI). Whole-brain cortical thickness analysis was performed to investigate the differences in the cortical thickness between patients with TRD and controls. The patients had reduced cortical thickness in the frontal cortex, particularly at the left frontal pole, left inferior frontal cortex, and left anterior cingulate cortex, and left middle temporal cortex compared with the healthy controls. Moreover, in the 2-back working memory task, the cortical thickness in the left frontal pole and left anterior cingulate cortex was positively associated with mean error in the patients, but not in the controls. Reduced cortical thickness in the frontal pole and anterior cingulate cortex is associated with TRD and related cognitive impairment. Our study indicated the crucial effects of the frontal and temporal cortical thickness on the pathophysiology of TRD and cognitive impairment in patients with TRD., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2021 Society for the Study of Addiction.)

Objectives: To estimate the system efficiency of uncle-nephew relationship identification by increasing STR markers and adding reference samples based on the test results of simulated data and real samples, so as to provide references for selecting the appropriate number of STRs and reference samples for uncle-nephew relationship identification., Methods: Five common models of uncle-nephew relationship identification were constructed by adding different reference samples. In each model, the likelihood ratio (LR) for 10 000 pairs of uncle-nephew relationships and 10 000 pairs of unrelated individuals were simulated by detecting 19, 39 or 55 STRs, and the system efficiency at different thresholds was simulated. The samples of the Han population in Zhejiang were collected, and 55 autosomal STRs were obtained by using SiFaSTR TM 23plex kit, Golden e ye ® DNA ID 22NC kit and AGCU 21+1 PCR amplification kit. When 19, 39 and 55 STRs were detected, the LR of each model and system efficiency under different thresholds were calculated and compared with the simulation results., Results: Under the same detection system, the calculated results of simulated data and corresponding true samples were basically consistent. In the same model, there was a positive correlation between the system efficiency of uncle-nephew relationship identification and the number of STRs detected. Moreover, the system efficiency of introducing relatives was higher than identifying only two individuals. The order of preference for the introduction of relatives was the full sibling (or mother) of the uncle and the full sibling (or mother) of the nephew., Conclusions: The system efficiency of uncle-nephew relationship identification could be improved by increasing the number of STRs and introducing known relatives, which would provide the basis for selecting the most appropriate detection system and reference individuals in actual cases.

The direct impact of chronic hepatitis B and hepatitis C on neurocognition remains elusive due to the frequent comorbidities, and the domains of the neurocognitive functions affected have rarely been investigated comprehensively. We cross-sectionally assessed the neurocognitive functions of the individuals with chronic hepatitis B, chronic hepatitis C, treated chronic hepatitis C with a sustained virologic response, and their healthy control counterparts. Laboratory examinations were used to investigate the impact of inflammation on neurocognition, exclude the medical conditions that could interfere with neurocognition assessment, and assess liver function and fibrotic severity of the liver of the participants. This study found the detrimental impact of chronic hepatitis B on language and executive functions. In contrast, individuals with chronic hepatitis C showed deficits in executive functions, psychomotor speed, memory, and attention. Successful elimination of hepatitis C resulted in improved liver function, but not neuropsychological test performance. Moreover, erythrocyte sedimentation rate level was found to mediate the deficits in the attention of individuals with chronic hepatitis C. These results demonstrate the neurocognitive deficits and the difference in the profiles of neurocognitive deficits in individuals with chronic hepatitis B and chronic hepatitis C. Our study also provided results suggesting the mediation by systemic inflammation on the attention deficit in individuals with chronic hepatitis C., (© 2022. The Author(s).)

Background: Subcortical volumetric abnormalities in schizophrenia, bipolar disorder and major depressive disorder (MDD) have been consistently found on a single-diagnosis basis in previous studies. However, whether such volumetric abnormalities are specific to a particular disorder or shared by other disorders remains unclear., Methods: We analyzed the structural MRIs of 160 patients with schizophrenia, 160 patients with bipolar disorder, 160 patients with MDD and 160 healthy controls. We calculated the volumes of the thalamus, hippocampus, amygdala, accumbens, putamen, caudate, pallidum and lateral ventricles using FreeSurfer 7.0 and compared them among the groups using general linear models., Results: We found a significant group effect on the volumes of the thalamus, hippocampus, accumbens and pallidum. Further post hoc analysis revealed that thalamic volumes in patients with schizophrenia, bipolar disorder and MDD were significantly reduced compared to those in healthy controls, but did not differ from one another. Patients with schizophrenia and bipolar disorder also shared a significant reduction in hippocampal volumes. Among the 3 clinical groups, patients with schizophrenia showed significantly lower hippocampal volumes and higher pallidal volumes than patients with bipolar disorder and MDD., Limitations: Differences in psychotropic use and duration of illness among the patient groups may limit the interpretation of our findings., Conclusion: Our findings indicate that decreased thalamic volume is a common feature of schizophrenia, bipolar disorder and MDD. Smaller hippocampal and larger pallidal volumes differentiate schizophrenia from bipolar disorder and MDD and may provide clues to the biological basis for the Kraepelinian distinction between these illnesses., Competing Interests: Competing interests: None declared., (© 2022 CMA Impact Inc. or its licensors.)

Background: Electronic media use (EMU) becomes one of the most common activities in adolescents. The present study investigated the deleterious influence of excessive EMU and EMU before bedtime on social, emotional, and behavioral difficulties (SEBD) in adolescents. The role of sleep and circadian problems in mediating the association of EMU with SEBD was examined., Methods: A cross-sectional survey study was conducted with 3,455 adolescents (55.7% female, mean age = 14.8 ± 1.57 years, 36.6% monthly family income < HK$15,000) between December 2011 and March 2012 in Hong Kong. The associations of EMU with sleep and circadian problems and SEBD were analyzed using multiple binary logistic regression and path analysis. Sleep problems were measured by the Insomnia Severity Index and the reduced Horne and Östberg Morningness and Eveningness Questionnaire. Circadian problems were calculated based on established formulas. SEBD was measured using the Strengths and Difficulties Questionnaire. Participants' mental health status was assessed by the General Health Questionnaire., Results: A longer duration of EMU, excessive EMU (daily duration ≥ 2 h), and bedtime EMU (an hour before bedtime) were associated with the risk of sleep and circadian problems, poor mental health, and SEBD ( p < 0.05). Insomnia, eveningness, social jetlag, and sleep deprivation were found to mediate the associations of EMU (including bedtime EMU of computers, electronic game consoles, phones, and televisions, together with excessive EMU of computers for leisure purposes and phones) with mental health and SEBD., Conclusions: The findings suggest the need for setting up guidelines and advocacy for education for appropriate EMU and intervention for the associated sleep and circadian problems to ameliorate EMU-related mental and behavioral health problems in adolescents., Competing Interests: Y-KW received a consultation fee for delivering a lecture from Eisai Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Chan, Li, Chen, Chan, Liu, Li, Li, Zhang and Wing.)

Objective: Suicidal behavior and different mood states of bipolar I disorder (BD) have been shown to be associated with dysregulated proinflammatory cytokines. Only a few studies have examined the association between inflammation and SB in BD, and the association between proinflammatory cytokines, SB, and cognitive deficits in patients with BD remains unclear., Methods: 77 patients with BD and 61 age-/sex-matched healthy controls were recruited. Patients were divided into two groups: with suicidal ideation (SI; n = 21) and no SI (n = 56). SI was defined by a score of ≥1 in item 10 of Montgomery Åsberg Depression Rating Scale. Levels of proinflammatory cytokines, including soluble interleukin-6 receptor (sIL-6R), soluble tumor necrosis factor-α receptor type 1 (sTNF-αR1), and C-reactive protein (CRP), were measured, and cognitive function was assessed using 2-back task and Go/No-Go task., Results: Patients with SI had higher levels of sTNF-αR1 than those without SI and the controls (p = .004). BD patients with or without a history of suicide attempt had higher levels of CRP than the controls. SI was associated with serum levels of sTNF-αR1 and IL-6sR, even after additionally controlling for working memory and inhibitory control (p < .05)., Conclusion: This study indicates that serum levels of sTNF-αR1 have distinct differences between BD patients with or without SI, and our findings strengthen the hypothesis of a link between suicidal behavior and neuro-inflammation pathophysiology in BD., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Family coaggregation of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD) and schizophrenia have been presented in previous studies. The shared genetic and environmental factors among psychiatric disorders remain elusive., Methods: This nationwide population-based study examined familial coaggregation of major psychiatric disorders in first-degree relatives (FDRs) of individuals with ASD. Taiwan's National Health Insurance Research Database was used to identify 26 667 individuals with ASD and 67 998 FDRs of individuals with ASD. The cohort was matched in 1:4 ratio to 271 992 controls. The relative risks (RRs) and 95% confidence intervals (CI) of ADHD, ASD, BD, MDD and schizophrenia were assessed among FDRs of individuals with ASD and ASD with intellectual disability (ASD-ID)., Results: FDRs of individuals with ASD have higher RRs of major psychiatric disorders compared with controls: ASD 17.46 (CI 15.50-19.67), ADHD 3.94 (CI 3.72-4.17), schizophrenia 3.05 (CI 2.74-3.40), BD 2.22 (CI 1.98-2.48) and MDD 1.88 (CI 1.76-2.00). Higher RRs of schizophrenia (4.47, CI 3.95-5.06) and ASD (18.54, CI 16.18-21.23) were observed in FDRs of individuals with both ASD-ID, compared with ASD only., Conclusions: The risk for major psychiatric disorders was consistently elevated across all types of FDRs of individuals with ASD. FDRs of individuals with ASD-ID are at further higher risk for ASD and schizophrenia. Our results provide leads for future investigation of shared etiologic pathways of ASD, ID and major psychiatric disorders and highlight the importance of mental health care delivered to at-risk families for early diagnoses and interventions.

Chemical investigation of Paxillus involutus (Batsch) Fr. led to the isolation of a pair of new enantiomers ( E )-5-(4-methoxy-2-oxo-2H-pyran-6-yl)pent-4-en-1-yl 2-hydroxypropanoate ( 1a / 1b ) along with 14 known compounds ( 2 - 15 ) for the first time from this mushroom. The structures of new compounds were elucidated based on extensive spectroscopic data analysis of MS, 1D and 2D NMR, and their absolute configurations were confirmed by comparison of the experimental and calculated ECD data. Compounds 1a and 1b exhibited radical scavenging activities with IC 50 values ranging from 10.39 ± 2.26 to 20.43 ± 3.74 μg/mL. Compounds 1a and 1b also showed moderate anti-tyrosinase activity with IC 50 value of 25.66 ± 2.84 and 26.82 ± 3.19 μg/mL.

Sarcomyxa edulis is a widely harvested mushroom of Northeastern Asia. Its development can be divided into six stages: growth of mycelium until occupying half the bag (B1), mycelium under low-temperature stimulation after occupying the entire bag (B2), appearance of mycelium in primordia (B3), primordia (B4), mycelium at the harvest stage (B5), and mature fruiting body (B6). Differentially expressed gene (DEG) analysis and weighted gene coexpression network analysis (WGCNA) are important bioinformatic methods for screening key genes. To explore the growth and development mechanisms of the mushroom S. edulis and clarify its genetic background, DEG and WGCNA analyses were combined to screen key genes at different developmental stages. From A1 to A6, respectively, 459, 97, 885, 169, 277, and 712 key genes were identified. Then the Gene Ontology (GO) terms and KEGG pathways of key genes were analyzed, and GO and KEGG analyses were performed on all genes across different periods using GSEA. In summary, the genes in A1 were mainly involved in amino sugar and nucleotide sugar metabolism, structural molecule activity, and oxidative phosphorylation. At the A2 stage, genes were mainly involved in peptidase activity, peroxidase activity, oxidoreductase activity, antioxidant activity, biosynthesis of secondary metabolites, and glycolysis and gluconeogenesis. A3 genes were involved in gene expression, RNA metabolism, spliceosome, RNA transport, and ribosome biogenesis. A4 genes were mainly involved in the biosynthesis of secondary metabolites, proteasome complex, cellular protein complex assembly, actin filament-based processes, oxidative phosphorylation, and carbon metabolism. The A5 stage genes were involved in the carbohydrate metabolic process, polysaccharide metabolic process, and the biosynthesis of secondary metabolites, leucine, isoleucine, and ABC transporters. Finally, A6 genes were mainly involved in the cell cycle, meiosis of yeast, MAPK signaling pathway, cellular response to DNA damage stimulus, DNA metabolic process, DNA replication, and DNA repair. The combination of multiple analyses provides us with an in-depth understanding of the network that regulates mushroom development., (Copyright © 2022. Published by Elsevier B.V.)

Increasing evidence suggests that patients with bipolar disorder are more likely to develop malignant cancer than in the general population. However, the overall cancer risk in the unaffected siblings of such patients remains unknown. From the National Health Insurance Research Database of Taiwan, 25 356 patients with bipolar disorder, 25 356 age-matched unaffected siblings of patients with bipolar disorder and 101 422 age-matched controls without severe mental disorders between 1996 and 2010 were enrolled in our study. Patients who developed cancer between the time of enrollment and the end of 2011 were identified. Cancers were divided into three subgroups based on the related layer of embryonic development: ectodermal, mesodermal and endodermal cancers. Patients with bipolar disorder (odds ratio [OR] = 1.22, 95% confidence interval [CI]: [1.06, 1.40]) and unaffected siblings of such patients (OR = 1.17, 95% CI [1.02, 1.34]) had greater risk of developing malignant cancer than did controls. Furthermore, only those aged <50 years, for both patients with bipolar disorder (OR = 1.90, 95% CI [1.38, 2.61]) and unaffected siblings (OR = 1.65, 95% CI [1.19, 2.28]), were more likely to develop the ectodermal cancer, especially breast cancer, than the control group. The associations of bipolar disorder and susceptibility to bipolar disorder with increased cancer risk in the younger population may imply a genetic overlap in neurodevelopment and malignancy pathogenesis. Our findings may encourage clinicians to monitor cancer risk factors and warning signs closely in patients with bipolar disorder and unaffected siblings of such patients., (© 2021 UICC.)

In recent years, asymmetric catalysis of ynamides has attracted much attention, but these reactions mostly constructed central chirality, except for a few examples on the synthesis of axially chiral compounds which exclusively relied on noble-metal catalysis. Herein, a facile access to axially chiral N-heterocycles enabled by chiral Brønsted acid-catalyzed 5-endo-dig cyclization of ynamides is disclosed, which represents the first metal-free protocol for the construction of axially chiral compounds from ynamides. This method allows the practical and atom-economical synthesis of valuable N-arylindoles in excellent yields with generally excellent enantioselectivities. Moreover, organocatalysts and ligands based on such axially chiral N-arylindole skeletons are demonstrated to be applicable to asymmetric catalysis., (© 2022 Wiley-VCH GmbH.)

Background: Frontal asymmetry plays a major role in depression. However, patients with treatment-resistant depression (TRD) have widespread hypofrontality. We investigated whether patients with TRD have a characteristic frontal activation pattern in functional near-infrared spectroscopy (fNIRS) findings and how the frontal cortex responds to different levels of cognitive tasks., Methods: We enrolled 27 right-handed patients with TRD, 27 patients without TRD and 27 healthy controls. We used multichannel fNIRS to evaluate activation of the bilateral dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC) and left motor area in response to 3 tasks: finger tapping, a low cognitive-load motor task; verbal fluency, a moderate cognitive-load task; and a dual task involving simultaneous finger tapping and verbal fluency, a high cognitive-load task., Results: We found significant between-group differences in left DLPFC activation for all 3 tasks. The healthy controls had cortical activation in the left motor area during finger tapping and the bilateral frontal cortex during the dual task. However, patients without TRD had right VLPFC activation during finger tapping and left DLPFC activation during the dual task. Patients with TRD had bilateral DLPFC activation during finger tapping but exhibited increased bilateral VLPFC and left motor area activation during verbal fluency and increased left motor area activation during the dual task. In healthy controls and patients without TRD, we found that the right VLPFC was positively correlated with depression severity., Limitations: Our cohort included only patients with late-onset depression., Conclusion: We found different patterns of abnormal frontal activation between patients with and without TRD. In patients without TRD, the right prefrontal cortex (PFC) was recruited during simple motor tasks. However, in patients with TRD, the bilateral PFC was recruited during simple tasks and motor cortical resources were used compensatorily during PFC-demanding complex cognitive tasks., Competing Interests: Competing interests: None declared., (© 2022 CMA Impact Inc. or its licensors.)

Introduction: This study aimed to investigate the effects of a home-based occupational therapy telerehabilitation (TR) via smartphone in enhancing functional and motor performance and fall efficacy for outpatients receiving day hospital rehabilitation after hip fracture surgery in Hong Kong., Methods: This was a feasibility randomised controlled trial with two groups - an experimental group and a comparison group - and a sample of 31 older adults attending a geriatric day hospital who had undergone hip fracture surgery within 12 weeks of diagnosis. Patients were assessed at baseline, immediately after a three-week intervention and at three-week post-intervention follow-up for motor performance, activities of daily living (ADL) functioning and fall efficacy. The experimental group received a home programme using the Caspar Health e-system and a mobile app for smartphones, while the comparison group received paper-and-pencil instructions for the home programme on a weekly basis for three weeks., Results: Compared to the comparison group, significant improvements in fall efficacy and instrumental ADL performance at post intervention and follow-up were found in the experimental group. However, in the comparison group, inadequate social support was a factor contributing to better muscle strength testing in both the affected and non-affected legs. There were no significant differences between the two groups in regard to the other variables., Discussion: This study supports the potential use of TR via smartphone as an alternative home programme for use in occupational therapy practice with older adults after hip fracture surgery.

In recent years, more and more forensic genetics laboratories have begun to apply massively parallel sequencing (MPS) technology, that is, next-generation sequencing (NGS) technology, to detect common forensic genetic markers, including short tandem repeat (STR), single nucleotide polymorphism (SNP), the control region or whole genome of mitochondrial DNA (mtDNA), as well as messenger RNA (mRNA), etc., for forensic practice, such as individual identification, kinship analysis, ancestry inference and body fluid identification. As the most widely used genetic marker in forensic genetics, STR is currently mainly detected by capillary electrophoresis (CE) platform. Compared with CE platform, MPS technology has the advantages of simultaneous detection of a large number of genetic markers, massively parallel detection of samples, the polymorphism of sequence detected by NGS makes STR have the advantages of higher resolution and system efficiency. However, MPS technology is expensive, there is no uniform standard so far, and there are problems such as how to integrate MPS-STR data with the existing CE-STR database. This review summarizes the current status of the application of MPS technology in the detection of STR genetic markers in forensic genetics, puts forward the main problems that need to be solved urgently, and prospects the application prospect of this technology in forensic genetics.

Objectives: To construct a Felis catus STR loci multiplex amplification system and to evaluate its application value by testing the technical performance., Methods: The published Felis catus STR loci data were reviewed and analyzed to select the STR loci and sex identification loci that could be used for Felis catus individual identification and genetic identification. The fluorescent labeling primers were designed to construct the multiplex amplification system. The system was validated for sensitivity, accuracy, balance, stability, species specificity, tissue identity and mixture analysis, and investigated the genetic polymorphisms in 145 unrelated Felis catus samples., Results: Sixteen Felis catus autosomal STR loci and one sex determining region of Y (SRY) were successfully selected, and constructed a multiplex amplification system containing the above loci. The complete profile of all alleles could still be obtained when the amount of DNA template was as low as 0.25 ng. There was no specific amplification peak in other common animal samples. Population genetic surveys showed that total discrimination power (TDP) of the 16 STR loci was 1-3.57×10 -20 , the cumulative probability of exclusion (CPE) was 1-6.35×10 -5 and the cumulative probability of matching was 3.61×10 -20 ., Conclusions: The Felis catus STR multiplex amplification system constructed in this study is highly sensitive, species-specific, and accurate in typing results, which can provide an effective solution for Felis catus species identification, individual identification and kinship identification in the field of forensic science.

Nine collections of gymnopoid fungi were studied based on morpho-molecular characteristics. The macromorphology was made according to the photograph of fresh basidiomata and field notes, while the micromorphology was examined via an optical microscope. Simultaneously, the phylogenetic analyses were performed by maximum likelihood and Bayesian inference methods based on a combined dataset of nrITS1-nr5.8S-nrITS2-nrLSU sequences. Integrated analysis of these results was therefore, G. efibulatus belonging to sect. Androsacei , G. iodes and G. sinopolyphyllus belonging to sect. Impudicae and G. strigosipes belonging to sect. Levipedes are proposed as new to science. The detailed descriptions, colour photos of basidiomata and line-drawings of microscopic structures are provided. The comparisons with closely related species and a key to known species of Gymnopus s. str. reported with morpho-molecular evidence in China is also given.

The rapid growth in the number of vehicles has led to traffic congestion, pollution, and delays in logistic transportation in metropolitan areas. IoT has been an emerging innovation, moving the universe towards automated processes and intelligent management systems. This is a critical contribution to automation and smart civilizations. Effective and reliable congestion management and traffic control help save many precious resources. An IoT-based ITM system set of sensors is embedded in automatic vehicles and intelligent devices to recognize, obtain, and transmit data. Machine learning (ML) is another technique to improve the transport system. The existing transport-management solutions encounter several challenges resulting in traffic congestion, delay, and a high fatality rate. This research work presents the design and implementation of an Adaptive Traffic-management system (ATM) based on ML and IoT. The design of the proposed system is based on three essential entities: vehicle, infrastructure, and events. The design utilizes various scenarios to cover all the possible issues of the transport system. The proposed ATM system also utilizes the machine-learning-based DBSCAN clustering method to detect any accidental anomaly. The proposed ATM model constantly updates traffic signal schedules depending on traffic volume and estimated movements from nearby crossings. It significantly lowers traveling time by gradually moving automobiles across green signals and decreases traffic congestion by generating a better transition. The experiment outcomes reveal that the proposed ATM system significantly outperformed the conventional traffic-management strategy and will be a frontrunner for transportation planning in smart-city-based transport systems. The proposed ATM solution minimizes vehicle waiting times and congestion, reduces road accidents, and improves the overall journey experience.

Background: Metformin is the most widely used drug for treating type 2 diabetes mellitus (DM), which frequently co-occurs with depressive disorders. Thus, patients with depression are likely to receive metformin. Metformin activates AMP-activated kinase (AMPK), which inhibits mechanistic target of rapamycin complex 1 (mTORC1) signaling. mTORC1 activation is essential for the antidepressant effects of ketamine and scopolamine. Thus, we hypothesized that metformin may attenuate ketamine- or scopolamine-induced antidepressant efficacies by blocking their mTORC1 activation., Methods: We assessed the acute and sustained antidepressant-like actions of ketamine and scopolamine in male Sprague-Dawley rats subjected to the forced swim test with or without metformin pretreatment. The expressions of AMPK, mTORC1, and brain-derived neurotrophic factor (BDNF) in their prefrontal cortex were assessed., Results: Metformin (50 mg/kg) attenuated the sustained, but not acute, antidepressant-like effects of ketamine (10 mg/kg) and scopolamine (25 μg/kg). Although metformin reduced mTORC1 downstream activated P70S6K, it did not significantly alter mTORser2448 activation and even increased BDNF expression. Notably, ketamine, scopolamine, and metformin all exerted significant antidepressant-like actions, as evidenced by increased AMPK phosphorylation and BDNF expression., Conclusions: Metformin-induced attenuation of sustained antidepressant-like effects are not directly dependent on AMPK-deactivated mTORC1. Our results indicate the complexity of interactions between AMPK, BDNF, and mTORC1. Further research, including mechanistic studies, is warranted to comprehensively evaluate the application of metformin in patients receiving mTORC1-based antidepressants., (© 2021. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.)

Prefrontal cortex (PFC) is the cognitive center that integrates and regulates global brain activity. However, the whole-brain organization of PFC axon projections remains poorly understood. Using single-neuron reconstruction of 6,357 mouse PFC projection neurons, we identified 64 projectome-defined subtypes. Each of four previously known major cortico-cortical subnetworks was targeted by a distinct group of PFC subtypes defined by their first-order axon collaterals. Further analysis unraveled topographic rules of soma distribution within PFC, first-order collateral branch point-dependent target selection and terminal arbor distribution-dependent target subdivision. Furthermore, we obtained a high-precision hierarchical map within PFC and three distinct functionally related PFC modules, each enriched with internal recurrent connectivity. Finally, we showed that each transcriptome subtype corresponds to multiple projectome subtypes found in different PFC subregions. Thus, whole-brain single-neuron projectome analysis reveals organization principles of axon projections within and outside PFC and provides the essential basis for elucidating neuronal connectivity underlying diverse PFC functions., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: The acute onset of insomnia following surgical operations has long been neglected, and long-term outcomes are not clear. Our aims were (1) to evaluate the risk of postoperative insomnia, (2) to identify which surgeries are related, and (3) to follow patients with postoperative insomnia for the development of major mental and physical disorders., Methods: We conducted a case-crossover study comprising 9898 participants with new-onset insomnia from the Taiwan National Health Insurance Research Database between 1997 and 2011. We determined the odds of having surgery in the case period (30 days) before the onset of insomnia by logistic regression analysis. Types of surgery that postoperative insomniacs had undergone were compared with age-/gender-/timing-matched controls. Longitudinal follow-up of postoperative and non-postoperative insomniacs was performed., Results: The odds ratio of surgical exposure vs. nonexposure within 30 days was 12.05 (p < 0.001) before new-onset insomnia. Surgery of musculoskeletal and nervous systems predisposed to insomnia. The duration of hypnotic drug use (0.83 years) was shorter and with a nearly 2-fold faster remission rate in postoperative than in non-postoperative insomniacs (1.45 years). Approximately 25% of each insomnia group developed persistent sleep disturbance., Conclusion: Surgery is associated with subsequent insomnia, which has a shorter duration and a faster remission than non-postoperative insomnia. Our data provide a reference for postoperative care, and warrant future studies., Competing Interests: Conflicts of interest: Dr. Tung-Ping Su, an editorial board member at Journal of the Chinese Medical Association, had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2022, the Chinese Medical Association.)

Repetitive transcranial magnetic stimulation (rTMS) is an alternative treatment for depression, but the neural correlates of the treatment are currently inconclusive, which might be a limit of conventional analytical methods. The present study aimed to investigate the neurophysiological evidence and potential biomarkers for rTMS and intermittent theta burst stimulation (iTBS) treatment. A total of 61 treatment-resistant depression patients were randomly assigned to receive prolonged iTBS (piTBS; N = 19), 10 Hz rTMS (N = 20), or sham stimulation (N = 22). Each participant went through a treatment phase with resting state electroencephalography (EEG) recordings before and after the treatment phase. The aftereffects of stimulation showed that theta-alpha amplitude modulation frequency (f am ) was associated with piTBS&#95;Responder, which involves repetitive bursts delivered in the theta frequency range, whereas alpha carrier frequency (f c ) was related to 10 Hz rTMS, which uses alpha rhythmic stimulation. In addition, theta-alpha amplitude modulation frequency was positively correlated with piTBS antidepressant efficacy, whereas the alpha frequency was not associated with the 10 Hz rTMS clinical outcome. The present study showed that TMS stimulation effects might be lasting, with changes of brain oscillations associated with the delivered frequency. Additionally, theta-alpha amplitude modulation frequency may be as a function of the degree of recovery in TRD with piTBS treatment and also a potential EEG-based predictor of antidepressant efficacy of piTBS in the early treatment stage, that is, first 2 weeks., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Since numerous RNAs and RBPs prevalently localize to active chromatin regions, many RNA-binding proteins (RBPs) may be potential transcriptional regulators. RBPs are generally thought to regulate transcription via noncoding RNAs. Here, we describe a distinct, dual mechanism of transcriptional regulation by the previously uncharacterized tRNA-modifying enzyme, hTrmt13. On one hand, hTrmt13 acts in the cytoplasm to catalyze 2'-O-methylation of tRNAs, thus regulating translation in a manner depending on its tRNA-modification activity. On the other hand, nucleus-localized hTrmt13 directly binds DNA as a transcriptional co-activator of key epithelial-mesenchymal transition factors, thereby promoting cell migration independent of tRNA-modification activity. These dual functions of hTrmt13 are mutually exclusive, as it can bind either DNA or tRNA through its CHHC zinc finger domain. Finally, we find that hTrmt13 expression is tightly associated with poor prognosis and survival in diverse cancer patients. Our discovery of the noncatalytic roles of an RNA-modifying enzyme provides a new perspective for understanding epitranscriptomic regulation., (© 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)

Background: To study the safety and patients' tolerance of transcranial magnetic stimulation (TMS), we conducted a systematic review and meta-analysis of the major depressive disorder population., Methods: Our study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the literature published before April 30th, 2021 and performed a random-effects meta-analyses which included drop-out due to adverse events, serious adverse events and other non-serious adverse events as primary and secondary outcomes., Results: A total of 53 randomized sham-controlled trials with 3,273 participants were included. There was no increased risk of drop-out due to an adverse event (active TMS intervention group=3.3%, sham TMS intervention group=2.3%, odds ratio = 1.30, 95% CI= 0.78-2.16, P = 0.31) or a serious adverse event (active TMS intervention group=0.9%, sham TMS intervention group=1.5%, odds ratio = 0.67, 95% CI= 0.29-1.55, P = 0.35). Our findings suggest that TMS intervention may significantly increase the risk of non-serious adverse events including: headaches (active TMS intervention group=22.6%, sham TMS intervention group=16.2%, odds ratio = 1.48, 95% CI= 1.15-1.91, P = 0.002), discomfort (active TMS intervention group=10.9%, sham TMS intervention group=5.0%, odds ratio 1.98, 95% CI= 1.22-3.21, P = 0.006) and pain (active TMS intervention group=23.8%, sham TMS intervention group=5.2%, odds ratio= 8.09, 95% CI= 4.71-13.90, P < 0.001) at the stimulation site, but these non-serious events were mostly mild and transient after TMS treatment., Conclusions: These findings provide evidence for the safety and patients' tolerance of transcranial magnetic stimulation technique as an alternative monotherapy or as an add-on treatment for major depressive disorder., (Copyright © 2022. Published by Elsevier B.V.)

Introduction: Pretreatment neurocognitive function may predict the treatment response to low-dose ketamine infusion in patients with treatment-resistant depression (TRD). However, the association between working memory function at baseline and the antidepressant efficacy of ketamine infusion remains unclear., Methods: A total of 71 patients with TRD were randomized to one of three treatment groups: 0.5 mg/kg ketamine, 0.2 mg/kg ketamine, or normal saline. Depressive symptoms were measured using the 17-item Hamilton Depression Rating Scale (HDRS) at baseline and after treatment. Cognitive function was evaluated using working memory and go-no-go tasks at baseline., Results: A generalized linear model with adjustments for demographic characteristics, treatment groups, and total HDRS scores at baseline revealed only a significant effect of working memory function (correct responses and omissions) on the changes in depressive symptoms measured by HDRS at baseline (F=12.862, p<0.05). Correlation analysis further showed a negative relationship (r=0.519, p=0.027) between pretreatment working memory function and changes in HDRS scores in the 0.5 mg/kg ketamine group., Discussion: An inverse relationship between pretreatment working memory function and treatment response to ketamine infusion may confirm that low-dose ketamine infusion is beneficial and should be reserved for patients with TRD., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Whether a single low-dose ketamine infusion may have rapid antidepressant and antisuicidal effects in patients with treatment-resistant double depression remains unclear., Methods: This study enrolled 35 patients with treatment-resistant double depression, 12 of whom received 0.5 mg/kg ketamine, 11 received 0.2 mg/kg ketamine, and 12 received normal saline as a placebo. The patients were assessed using the 17-item Hamilton Rating Scale for Depression (HDRS) prior to the initiation of infusions, at 40 and 240 min post-infusion, and sequentially on Days 2-7 and on Day 14 after ketamine or placebo infusions., Results: A single 0.5 mg/kg ketamine infusion had rapid antidepressant (p = 0.031, measured by the HDRS) and antisuicidal (p = 0.033, measured by the HDRS item 3 scores) effects in patients with treatment-resistant double depression. However, 0.2 mg/kg ketamine was insufficient to exert rapid antidepressant and antisuicidal effects in this patient population with severe and chronic illness., Discussion: In this patient population, the commonly used dose of 0.5 mg/kg was sufficient. Additional studies are required to investigate whether repeated infusions of low-dose ketamine may also maintain antidepressant and antisuicidal effects in patients with treatment-resistant double depression., (© 2021 John Wiley & Sons Ltd.)

Objective: To evaluate the long-term safety and efficacy of intranasal esketamine in patients with treatment-resistant depression from the Asian subgroup of the SUSTAIN-2 study., Methods: SUSTAIN-2 was a phase 3, open-label, single-arm, multicenter study comprising a 4-week screening, 4-week induction, 48-week optimization/maintenance, and 4-week follow-up (upon esketamine discontinuation) phase. Patients with treatment-resistant depression received esketamine plus an oral antidepressant during the treatment period., Results: The incidence of ≥ 1 serious treatment-emergent adverse event (TEAE) among the 78 subjects from the Asian subgroup (Taiwan: 33, Korea: 26, Malaysia: 19) was 11.5% (n = 9); with no fatal TEAE. 13 Asian patients (16.7%) discontinued esketamine due to TEAEs. The most common TEAEs were dizziness (37.2%), nausea (29.5%), dissociation (28.2%), and headache (21.8%). Most TEAEs were mild to moderate in severity, transient and resolved on the same day. Upon discontinuation of esketamine, no trend in withdrawal symptoms was observed to associate long-term use of esketamine with withdrawal syndrome. There were no reports of drug seeking, abuse, or overdose. Improvements in symptoms, functioning and quality of life, occurred during in the induction phase and were generally maintained through the optimization/maintenance phases of the study., Conclusion: The safety and efficacy of esketamine in the Asian subgroup was generally consistent with the total SUSTAIN-2 population. There was no new safety signal and no indication of a high potential for abuse with the long-term (up to one year) use of esketamine in the Asian subgroup. Most of the benefits of esketamine occurred early during the induction phase.

Cognitive dysfunction is associated with functional impairment of patients with Major Depressive Disorder (MDD). The goals were to explore the associated factors of cognitive impairment in MDD and to develop and validate a brief and culture-relevant questionnaire, the Taiwan Cognition Questionnaire (TCQ), among patients with MDD. This was a cross-sectional, multi-center observational study of MDD patients in Taiwan. Participants of Group 1 from 10 centers contributed to the validation of the TCQ by their response and sociodemographics. The participants of Group 2 from one center received an objective cognitive assessment for clarification of the relationship between the TCQ score and its associated factors. In Group 1, 493 participants were recruited. As for Group 2, an extra 100 participants were recruited. The global Cronbach's alpha for the TCQ was 0.908. According to the coordinates of the ROC curve, 9/10 was the ideal cut-off point. With the criteria, the sensitivity/specificity of the TCQ was 0.610/0.689. The TCQ score was positively associated with a history of being admitted to acute psychiatric care and the severity of depression and negatively associated with objective cognitive measures. The TCQ provides a reliable, valid, and convenient measure of subjective cognitive dysfunction in patients with MDD.

To analyze and summarize the contrast-enhanced ultrasound (CEUS) characteristics in patients with IgG4 related autoimmune pancreatitis (IgG4-AIP). A total of 54 patients (aged 26 to 76 years old) with IgG4-AIP were collected and retrospectively analyzed. The results demonstrated that there is a variety of enhanced performance on CEUS in patients with IgG4-AIP in the early stage, for some them, especially for those with mass-type pancreatitis, their sonographic appearance and the CEUS characteristics are similar when compared with the patients with pancreatic carcinoma, with varying degrees of low enhancement in the arterial phase, venous phase and delayed stage. Therefore, it is not advisable to make a differential diagnosis based on CEUS alone, and comprehensive evaluation is warranted.