MnO2@CeOx-GAMP radiosensitizer with oxygen vacancies depended mimicking enzyme-like activities for radiosensitization-mediated STING pathway activation.

Activation of the stimulator of interferon genes (STING) pathway by radiotherapy (RT) has a significant effect on eliciting antitumor immune responses. The generation of hydroxyl radical (·OH) storm and the sensitization of STING-relative catalytic reactions could improve radiosensitization-mediated STING activation. Herein, multi-functional radiosensitizer with oxygen vacancies depended mimicking enzyme-like activities was fabricated to produce more dsDNA which benefits intracellular 2', 3'-cyclic GMP-AMP (cGAMP) generation, together with introducing exogenous cGAMP to activate immune response. MnO2@CeOx nanozymes present enhanced superoxide dismutase (SOD)-like and peroxidase (POD)-like activities due to induced oxygen vacancies accelerate the redox cycles from Ce4+ to Ce3+ via intermetallic charge transfer. CeOx shells not only serve as radiosensitizer, but also provide the conjugation site for AMP/GMP to form MnO2@CeOx-GAMP (MCG). Upon X-ray irradiation, MCG with SOD-like activity facilitates the conversion of superoxide anions generated by Ce-sensitization into H2O2 within tumor microenvironment (TME). The downstream POD-like activity catalyzes the elevated H2O2 into a profusion of ·OH for producing more damage DNA fragments. TME-responsive decomposed MCG could supply exogenous cGAMP, meanwhile the releasing Mn2+ improve the sensitivity of cyclic GMP-AMP synthase to dsDNA for producing more cGAMP, resulting in the promotion of STING pathway activation.

Generative Large Language Models in Electronic Health Records for Patient Care Since 2023: A Systematic Review.

BACKGROUND: Generative Large language models (LLMs) represent a significant advancement in natural language processing, achieving state-of-the-art performance across various tasks. However, their application in clinical settings using real electronic health records (EHRs) is still rare and presents numerous challenges. OBJECTIVE: This study aims to systematically review the use of generative LLMs, and the effectiveness of relevant techniques in patient care-related topics involving EHRs, summarize the challenges faced, and suggest future directions. METHODS: A Boolean search for peer-reviewed articles was conducted on May 19th, 2024 using PubMed and Web of Science to include research articles published since 2023, which was one month after the release of ChatGPT. The search results were deduplicated. Multiple reviewers, including biomedical informaticians, computer scientists, and a physician, screened the publications for eligibility and conducted data extraction. Only studies utilizing generative LLMs to analyze real EHR data were included. We summarized the use of prompt engineering, fine-tuning, multimodal EHR data, and evaluation matrices. Additionally, we identified current challenges in applying LLMs in clinical settings as reported by the included studies and proposed future directions. RESULTS: The initial search identified 6,328 unique studies, with 76 studies included after eligibility screening. Of these, 67 studies (88.2%) employed zero-shot prompting, five of them reported 100% accuracy on five specific clinical tasks. Nine studies used advanced prompting strategies; four tested these strategies experimentally, finding that prompt engineering improved performance, with one study noting a non-linear relationship between the number of examples in a prompt and performance improvement. Eight studies explored fine-tuning generative LLMs, all reported performance improvements on specific tasks, but three of them noted potential performance degradation after fine-tuning on certain tasks. Only two studies utilized multimodal data, which improved LLM-based decision-making and enabled accurate rare disease diagnosis and prognosis. The studies employed 55 different evaluation metrics for 22 purposes, such as correctness, completeness, and conciseness. Two studies investigated LLM bias, with one detecting no bias and the other finding that male patients received more appropriate clinical decision-making suggestions. Six studies identified hallucinations, such as fabricating patient names in structured thyroid ultrasound reports. Additional challenges included but were not limited to the impersonal tone of LLM consultations, which made patients uncomfortable, and the difficulty patients had in understanding LLM responses. CONCLUSION: Our review indicates that few studies have employed advanced computational techniques to enhance LLM performance. The diverse evaluation metrics used highlight the need for standardization. LLMs currently cannot replace physicians due to challenges such as bias, hallucinations, and impersonal responses.

Advances in ferroptosis in head and neck cancer (Review).

Ferroptosis is an iron-dependent form of cell death that was discovered in 2012. It encompasses the coordinated orchestration of three fundamental biological pathways: Iron homeostasis, glutathione regulation and lipid metabolism. Head and neck cancer (HNC) is a heterogeneous group of cancers occurring on the mucosal surfaces of the upper respiratory and digestive tracts. Head and neck squamous cell carcinoma is the most common type of HNC, accounting for >90% of HNC cases, and has high morbidity and mortality rates. Despite improvements in diagnosis and treatment, the 5-year survival rate hovers at a dismal 50-60%, with recurrence afflicting nearly 30% of patients, highlighting the inadequacies of currently available treatments. Of note, research exploring the nexus between ferroptosis and HNC remains scarce; however, the present review endeavors to synthesize current knowledge surrounding ferroptosis. The present review elaborated on the normal physiological role of ferroptosis and discussed its potential involvement in HNC pathogenesis. Therapeutic strategies and prognostic paradigms for HNC that target ferroptosis were also reviewed. This review aims to provide direction to catalyze future investigations into ferroptosis in HNC.

DNA Methylation and Subgenome Dominance Reveal the Role of Lipid Metabolism in Jinhu Grouper Heterosis.

Heterosis of growth traits in economic fish has benefited the production of aquaculture for many years, yet its genetic and molecular basis has remained obscure. Nowadays, a new germplasm of hybrid Jinhu grouper (Epinephelus fuscoguttatus ♀ × E. tukula ♂), abbreviated as EFT, exhibiting paternal-biased growth heterosis, has provided an excellent model for investigating the potential regulatory mechanisms of heterosis. We integrated transcriptome and methylome to unravel the changes of gene expression, epigenetic modification, and subgenome dominance in EFT compared with maternal E. fuscoguttatus. Integration analyses showed that the heterotic hybrids showed lower genomic DNA methylation levels than the purebred parent, and the up-regulated genes were mostly DNA hypomethylation. Furthermore, allele-specific expression (ASE) detected paternal subgenome dominance-regulated paternal-biased heterosis, and paternal bias differentially expressed genes (DEGs) were wholly up-regulated in the muscle. Multi-omics results highlighted the role of lipid metabolism, particularly "Fatty acid synthesis", "EPA biosynthesis", and "Signaling lipids", in EFT heterosis formation. Coherently, our studies have proved that the eicosapentaenoic acid (EPA) of EFT was greater than that of maternal E. fuscoguttatus (8.46% vs. 7.46%). Finally, we constructed a potential regulatory network for control of the heterosis formation in EFT. Among them, fasn, pparg, dgat1, igf1, pomca, fgf8a, and fgfr4 were identified as key genes. Our results provide new and valuable clues for understanding paternal-biased growth heterosis in EFT, taking a significant step towards the molecular basis of heterosis.

NK cell-based immunotherapy in hepatocellular carcinoma: An attractive therapeutic option for the next decade.

Hepatocellular carcinoma (HCC), a major subtype of liver cancer, poses significant therapeutic challenges due to its late diagnosis and rapid progression. The evolving landscape of immunotherapy offers a beacon of hope, with natural killer (NK) cells emerging as pivotal players in combating HCC. NK cells are unique cytotoxic lymphocytes that are essential in the fight against infections and malignancies. Phenotypic and functional NK cell abnormalities have been shown in HCC patients, indicating their significance as a component of the innate immune system against cancer. This review elucidates the critical role of NK cells in combating HCC, focusing on their interaction with the tumor microenvironment, the development of NK cell-based therapies, and the innovative strategies to enhance their efficacy in the immunosuppressive milieu of HCC. The review delves into the various therapeutic strategies, including autologous and allogeneic NK cell therapies, genetic engineering to improve NK cell resilience and targeting, and the integration of NK cells with other immunotherapeutic approaches like checkpoint inhibitors and oncolytic virotherapy. By highlighting recent advancements and the ongoing challenges in the field, this review sets the stage for future research directions that could unlock the full potential of NK cell-based immunotherapy for HCC, offering a beacon of hope for patients battling this formidable cancer.

The Anti-Diabetic Effect of Non-Starch Polysaccharides Extracted from Wheat Beer on Diet/STZ-Induced Diabetic Mice.

Diabetes mellitus (DM), a major cause of mortality, is characterized by insulin resistance and ß-cell dysfunction. The increasing prevalence of DM is linked to lifestyle changes and there is a need for alternative approaches to conventional oral hypoglycemic agents. Polysaccharides, particularly non-starch polysaccharides (NSPs), have been identified as promising hypoglycemic agents. Cereals, especially wheat, are key sources of dietary polysaccharides, with NSPs derived from wheat beer attracting significant interest. This study aimed to investigate the hypoglycemic and hypolipidemic effects of NSPs extracted from wheat beer in STZ-induced diabetic C57BL/6J male mice. The results showed that NSPs extract positively influenced blood glucose regulation, lipid profiles, and liver and kidney functions, by attenuating liver AST and kidney CRE levels in a dose-dependent manner. The NSPs demonstrated anti-oxidative and anti-inflammatory properties, potentially providing significant benefits in managing diabetes and its complications. Moreover, the study revealed the histoprotective effects of NSPs on the liver and pancreas, reducing lipid deposition, necrosis, and inflammation. These findings highlight the multifaceted advantages of NSPs and suggest their potential as effective agents in diabetes management. This study supports the need for further research into the therapeutic potential of NSPs and their application in developing innovative treatments for diabetes and its associated complications.

A hemin/rGO/MWCNT nanocomposite-based dual signal electrochemical aptasensor for sensitive detection of NSE.

Neuron-specific enolase (NSE), a tumor marker of small cell lung cancer (SCLC), has high application value in the early diagnosis of SCLC. In this study, a dual signal electrochemical aptasensor for NSE was constructed based on hemin/reduced graphene oxide/multi-walled carbon nanotube (H-rGO-MWCNT) nanocomposites. Hemin played a dual role, functioning not only as an in situ electrochemical probe but also exhibiting excellent peroxidase-like properties, effectively catalyzing the electroreduction of H2O2. Reduced graphene oxide and multi-walled carbon nanotubes exhibited excellent conductivity. Through their binding with hemin, the nanocomposites achieved a larger specific surface area, providing numerous active sites for capturing the NSE aptamer. In the presence of NSE, the specific adsorption between the antigen and the aptamer formed a stable antigen-aptamer structure, which inhibited the performance of hemin, resulting in the weakening of the electrochemical signals of hemin and H2O2. Leveraging these characteristics, the sensitive and cost-effective dual-signal electrochemical aptasensor has been fabricated for the detection of NSE. One signal corresponded to differential pulse voltammetry (DPV) of hemin, while the other signal was derived from chronoamperometry, capturing the catalytic reduction of H2O2. The linear ranges for NSE were 1 pg mL-1 to 1 µg mL-1 and 100 pg mL-1 to 100 ng mL-1 with the limit of detection (LOD) of 0.21 pg mL-1 and 11.22 pg mL-1 by DPV and chronoamperometry, respectively. In addition, this aptasensor exhibited good reproducibility, stability and specificity. The recovery of NSE in human blood serum samples was from 89% to 131%. It provided a promising strategy for the detection of NSE in clinical diagnostics.

In-Depth Characterization for Methionine Oxidization in Complementary Domain Region by Hydrophobic Interaction Chromatography.

The oxidation of the complementarity-determining region (CDR) in monoclonal antibodies (mAbs) is a critical quality attribute that can affect the clinical efficacy and safety of recombinant mAb therapeutics. In this study, a robust hydrophobic interaction chromatography (HIC) method was developed to quantify and characterize CDR oxidation variants in mAb-A by using a Proteomix Butyl-NP5 column. The HIC analysis revealed oxidation variants that eluted earlier than the main species with weaker hydrophobicity. It was found that Met105 in the CDR was more susceptible to oxidation. Additionally, it was noted that the oxidation of Met105 on a single heavy chain resulted in elution at a distinct position compared to the oxidation on two heavy chains. This observation led to the fractionation and enrichment of the oxidized variants for further evaluation of their biofunction. The study also demonstrated that the oxidation of Met105 did not impact the antigen-binding capacity but significantly reduced the PD-1/PD-L1 blockade activity of mAb-A. The HIC method, which was employed to quantify CDR oxidation, underwent validation and was subsequently utilized for stability studies as well as for assessing the similarity between mAb-A and its reference product.

Association Between Sarcopenia, Clinical Outcomes, and Survival in Patients with Extensive-Stage Small Cell Lung Cancer Treated with First-Line Immunochemotherapy: A Prospective Cohort Study.

OBJECTIVE: To investigate the association between sarcopenia, short-term efficacy, and long-term survival in patients with extensive small-cell lung cancer (SCLC) treated with standard first-line immunochemotherapy. METHODS: A total of 63 patients initially diagnosed with extensive-stage small cell lung cancer were enrolled in the prospective study from December 1, 2020 to December 31, 2022. The clinical characteristics, body composition, blood test results, and image data were obtained before treatment. Patients were divided into sarcopenia and non-sarcopenia groups according to the diagnostic criteria of the Asian Sarcopenia Working Group 2019. The primary outcome was overall survival (OS) and comprehensive survival analyses were performed. Secondary outcomes included short-term efficacy and adverse events associated with first-line immunochemotherapy. RESULTS: The median age of the 63 patients enrolled in our study was 63.0 years (40-80 years). The incidence of sarcopenia was 19.0% (12/63) in patients with extensive SCLC. Compared with non-sarcopenia patients, extensive-stage SCLC patients with sarcopenia were significantly older (69.0 vs. 62.0, P = 0.017), and had lower body mass index (BMI) (20.29 vs. 24.27, P < 0.001), hand grip strength (HGS) (20.42 vs. 30.75, P < 0.001), and albumin (35.9 vs. 41.40, P < 0.001). The objective response rate after two cycles of standard first-line immunochemotherapy in the sarcopenia group was lower than in the non-sarcopenia group (30.0 vs. 78.9%, P = 0.012). There was no significant difference in chemotherapy-related hematological toxicity between the two groups. During a median follow-up of 15 months (3-33 months), patients with extensive SCLC had a median OS of 24 months, with 1-year survival of 75% and 2-year survival of 52%, respectively. Compared to non-sarcopenia patients, the median OS in the sarcopenia group was significantly shorter (9 vs. 24 months, P = 0.0014). Multivariate Cox analysis showed that sarcopenia was an independent risk factor for OS in patients with extensive SCLC (HR = 4.993, 95%CI = 1.106-22.538, P = 0.037). CONCLUSIONS: Patients with Extensive SCLC and sarcopenia had worse clinical outcomes and shorter OS. Sarcopenia is a prognostic factor affecting first-line treatment efficacy and long-term survival of patients with SCLC in the era of immunotherapy.

Metformin attenuates white matter injury in neonatal mice through activating NRF2/HO-1/NF-κB pathway.

White matter injury (WMI) is a major form of brain injury that occurs in preterm infants and develops into lifelong disabilities, including cerebral palsy, impaired cognitive function, and psychiatric disorders. Metformin (MET) has been reported to have neuroprotective effects. However, whether MET is responsible for neuroprotection against WMI remains unclear. In this study, we established a WMI model in neonatal mice to explore the neuroprotective effects of MET and attempted to elucidate its potential mechanisms. Our results showed that MET increased the expression of myelin basic protein (MBP), oligodendrocyte transcription factor 2 (Olig2), and CC1, improved the thickness and density of the myelin sheath, and reduced oxidative stress and microglial infiltration after chronic hypoxia induction. Moreover, MET improved memory, learning, and motor abilities as well as relieved anxiety-like behaviors in mice with WMI. These protective effects of MET may involve the upregulation of the nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase-1(HO-1)/NF-κB pathway related protein expressions. In addition, the NRF2 inhibitor ML385 could significantly reverse the effects of MET. In conclusion, this study suggested that MET attenuated chronic hypoxia-induced WMI through activating the NRF2/HO-1/NF-κB pathway, indicating that MET might be a promising therapeutic option for WMI.

Individual suicide risk factors with resting-state brain functional connectivity patterns in bipolar disorder patients based on latent Dirichlet allocation model.

BACKGROUND: The widespread problem of suicide and its severe burden in bipolar disorder (BD) necessitate the development of objective risk markers, aiming to enhance individual suicide risk prediction in BD. METHODS: This study recruited 123 BD patients (61 patients with prior suicide attempted history (PSAs), 62 without (NSAs)) and 68 healthy controls (HEs). The Latent Dirichlet Allocation (LDA) model was used to decompose the resting state functional connectivity (RSFC) into multiple hyper/hypo-RSFC patterns. Thereafter, according to the quantitative results of individual heterogeneity over latent factor dimensions, the correlations were analyzed to test prediction ability. RESULTS: Model constructed without introducing suicide-related labels yielded three latent factors with dissociable hyper/hypo-RSFC patterns. In the subsequent analysis, significant differences in the factor distributions of PSAs and NSAs showed biases on the default-mode network (DMN) hyper-RSFC factor (factor 3) and the salience network (SN) and central executive network (CEN) hyper-RSFC factor (factor 1), indicating predictive value. Correlation analysis of the individuals' expressions with their Nurses' Global Assessment of Suicide Risk (NGASR) revealed factor 3 positively correlated (r = 0.4180, p < 0.0001) and factor 1 negatively correlated (r = - 0.2492, p = 0.0055) with suicide risk. Therefore, it could be speculated that patterns more associated with suicide reflected hyper-connectivity in DMN and hypo-connectivity in SN, CEN. CONCLUSIONS: This study provided individual suicide-associated risk factors that could reflect the abnormal RSFC patterns, and explored the suicide related brain mechanisms, which is expected to provide supports for clinical decision-making and timely screening and intervention for individuals at high risks of suicide.

Genome-Wide Analyses of MADS-Box Genes Reveal Their Involvement in Seed Development and Oil Accumulation of Tea-Oil Tree (Camellia oleifera).

The seeds of Camellia oleifera produce high amount of oil, which can be broadly used in the fields of food, industry, and medicine. However, the molecular regulation mechanisms of seed development and oil accumulation in C. oleifera are unclear. In this study, evolutionary and expression analyses of the MADS-box gene family were performed across the C. oleifera genome for the first time. A total of 86 MADS-box genes (ColMADS) were identified, including 60 M-type and 26 MIKC members. More gene duplication events occurred in M-type subfamily (6) than that in MIKC subfamily (2), and SEP-like genes were lost from the MIKCC clade. Furthermore, 8, 15, and 17 differentially expressed ColMADS genes (DEGs) were detected between three developmental stages of seed (S1/S2, S2/S3, and S1/S3), respectively. Among these DEGs, the STK-like ColMADS12 and TT16-like ColMADS17 were highly expressed during the seed formation (S1 and S2), agreeing with their predicted functions to positively regulate the seed organogenesis and oil accumulation. While ColMADS57 and ColMADS07 showed increasing expression level with the seed maturation (S2 and S3), conforming to their potential roles in promoting the seed ripening. In all, these results revealed a critical role of MADS-box genes in the C. oleifera seed development and oil accumulation, which will contribute to the future molecular breeding of C. oleifera.

Insecticidal activities of three recombinant venom proteins of the predatory stink bug, Arma custos.

BACKGROUND: Widespread resistance of insect pests to insecticides and transgenic crops in the field is a significant challenge for sustainable agriculture, and calls for the development of novel alternative strategies to control insect pests. One potential resource for the discovery of novel insecticidal molecules is natural toxins, particularly those derived from the venoms of insect predators. RESULTS: In this study, we identified three insecticidal proteinaceous toxins from the venom glands (VGs) of the predatory stink bug, Arma custos (Hemiptera: Asopinae). Transcriptomic analysis of A. custos VGs revealed 151 potentially secreted VG-rich venom proteins. Three VG-rich venom proteins (designated AcVP1 ~ 3) were produced by overexpression in Escherichia coli. Injection of the recombinant proteins into tobacco cutworm (Spodoptera litura) larvae showed that all of the three recombinant proteins caused paralysis, liquefaction and death. Injection of recombinant proteins into rice brown planthopper (Nilaparvata lugens) nymphs showed higher insecticidal activities, among which a trypsin (AcVP2) caused 100% mortality postinjection at 1.27 pmol mg-1 body weight. CONCLUSION: A natural toolkit for the discovery of insecticidal toxins from predatory insects has been revealed by the present study. © 2024 Society of Chemical Industry.

Coordinated analysis of groundwater spatiotemporal chemical characteristics, water quality, and potential human health risks with sustainable development in semi-arid regions.

The emergence of large-scale time-series data and advancements in computational power have opened new avenues for analyzing the spatiotemporal evolution of groundwater chemistry, water quality, and human health risks. This paper utilizes hydrogeochemical methods to elucidate the controlling factors of water chemical components based on the test results of 124 groundwater samples collected from 31 monitoring wells in Fuxin City, Liaoning Province, China, from 2018 to 2021. By integrating the Random Forest and Enhanced Water Quality Index methods for water quality assessment and employing the Human Health Risk Assessment (HHRA) model to analyze human health risks, our findings indicate that the groundwater is mildly alkaline, with SO4·Cl-Ca·Mg and HCO3-Ca·Mg as the dominant hydrochemical types, primarily derived from the dissolution of carbonate and silicate minerals such as dolomite, limestone, and andesite, and cation exchange reactions. The EI_RF water quality evaluation model reveals that the overall water quality in the study area is poor, with Class I and II water quality zones mainly located in the northeastern and central parts of the study area, showing a gradual transition from Class I and II in the northeast to Classes IV and V in the southwest, significantly influenced by NO3-, TH, TDS, and SO42-. The HHRA model results indicate that the potential non-carcinogenic risk of groundwater nitrates has a severe impact on infants, with the spatial distribution being low in the northeast and high in the southwest. Due to industrial activities, agricultural practices, and population growth, certain areas in developing countries such as China and India exhibit nitrate concentrations significantly higher than those in most international regions, highlighting global environmental and public health challenges. This underscores the importance of enhancing groundwater monitoring and implementing measures to mitigate pollution. These research outcomes hold significant implications for the government in formulating rational protection and management measures to ensure the sustainable utilization of groundwater resources.

Effect of positive airway pressure on obese patients undergoing surgery: a systematic review and meta-analysis.

This systematic review and meta-analysis (SRMA) evaluates the efficacy and safety of Positive Airway Pressure (PAP) therapy in perioperative care for obese surgical patients. We reviewed 24 studies, encompassing data up to March 23, 2023, analyzing the impacts of Continuous Positive Airway Pressure (CPAP) and Bilevel Positive Airway Pressure (BIPAP) on postoperative adverse outcomes, oxygenation, and pulmonary function. Our findings underscore the significant potential of PAP therapy in managing obese patients during the perioperative period, particularly those at substantial risk for postoperative respiratory complications. PAP therapy not only enhances oxygenation levels and lung function but also substantially reduces the incidence of atelectasis and shortens hospital stays, thereby affirming its vital role in improving perioperative outcomes for this patient population.

Engineering a universal and fully automatic analyzer for multichannel and on-site biochemical detection in body fluids.

OBJECTIVE: Rising concerns over wellness and aging have heightened the demand for convenient and efficient on-site health monitoring and disease screening. Current research, focused on specific biomarker detection, often neglects the complexities of sample matrix interference and the absence of a comprehensive, automated platform. To address these issues, we have developed a universal, fully automated analyzer for multifaceted, on-site biochemical analysis of body fluids. METHODS: This analyzer integrates automated sample pretreatment, automatic dilution, detection, and self-cleaning functionalities seamlessly. It is designed to detect a wide range of analytes, from small molecules to macromolecules, including ions and proteins, utilizing spectrophotometric sensing. After optimization, the analyzer achieves performance comparable to traditional Enzyme-Linked Immunosorbent Assay (ELISA), while significantly expanding its detection range through automated dilution. RESULTS: Demonstrations of small molecule detection include the simultaneous assessment of citric acid (CA) and oxalic acid (OA) in urine, achieving recovery rates between 96.65%-106.42% and 93.13%-112.50%, respectively. For protein detection, the analyzer successfully identified Cyfra21-1 in saliva with a recovery rate of 104.93%-111.31%. The pre-treatment process requires only 8.8 minutes, showing enhanced recovery rates for CA and OA at 97.8% and 97.6% respectively, which are superior and more rapid than manual methods. CONCLUSION: The exemplary pretreatment and detection performance of the analyzer underlines its effectiveness in multifaceted, on-site biomarker detection, establishing it as a promising and versatile tool for disease screening and health monitoring. SIGNIFICANCE: This analyzer offers a powerful technological solution for on-site fluid testing, advancing community health care by facilitating more reliable and rapid diagnostics.

Whole-genome sequence and annotation of Diaporthe australafricana strain CBS 118571.

We report the whole-genome sequence of Diaporthe australafricana Crous & J.M. van Niekerkusing using Oxford Nanopore long-read sequencing and Illumina short-read sequencing. The hybrid genome consists of 11 contigs with a total length of 53.509 Mb, and a GC content of 52.40%.

Neuromodulation treatments for post-traumatic stress disorder: A systematic review and network meta-analysis covering efficacy, acceptability, and follow-up effects.

Neuromodulation treatments are novel interventions for post-traumatic stress disorder (PTSD), but their comparative effects at treatment endpoint and follow-up and the influence of moderators remain unclear. We included randomized controlled trials (RCTs) that explored neuromodulation, both as monotherapy and in combination, for treating patients with PTSD. 21 RCTs with 981 PTSD patients were included. The neuromodulation treatment was classified into nine protocols, including subtypes of transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), cervical vagal nerve stimulation (VNS), and trigeminal nerve stimulation (TNS). This Bayesian network meta-analysis demonstrated that (1) dual-tDCS (SMD = -1.30), high-frequency repetitive TMS (HF-rTMS) (SMD = -0.97), intermittent theta burst stimulation (iTBS) (SMD = -0.93), and low-frequency repetitive TMS (LF-rTMS) (SMD = -0.76) were associated with significant reductions in PTSD symptoms at the treatment endpoint, but these effects were not significant at follow-up; (2) no difference was found between any active treatment with sham controls; (3) regarding co-morbid additions, synchronized TMS (sTMS) was significantly associated with reductions of depression symptoms at treatment endpoint (SMD = -1.80) and dual-tDCS was associated with reductions in anxiety symptoms at follow-up (SMD = -1.70). Findings suggested dual-tDCS, HF-rTMS, iTBS, and LF-rTMS were effective for reducing PTSD symptoms, while their sustained efficacy was limited.