bluuebunny/crossref_metadata_2025_split huggingface dataset:
Robotic-assisted thoracic surgery following neoadjuvant chemoimmunotherapy in patients with stage III non-small cell lung cancer: A real-world prospective cohort study
Authors: Gao Yang , Jiang Juan , Xiao Desheng , Zhou Yanwu , Chen Yufan , Yang Huaping , Wang Lijing , Zeng Jun , He Baimei , He Ruoxi , Li Min , Liu Zhaoqian 
Published: August 2022

ObjectiveStage III non-small cell lung cancer (NSCLC) is a heterogeneous group of diseases. For this subset of patients, clinical management is still under debate and prognosis remains poor so far. In the present study, we aimed to evaluate the feasibility and safety of robotic-assisted thoracic surgery after neoadjuvant chemoimmunotherapy in stage III NSCLC.MethodsA real-world prospective cohort study was performed in a single-center setting from April 2021 to May 2022. Patients who were diagnosed with resectable or potentially resectable stage IIIA–B NSCLC and received neoadjuvant chemoimmunotherapy followed by robotic-assisted thoracic surgery were enrolled. Pathological response to neoadjuvant chemoimmunotherapy, treatment-related adverse events, and surgical outcomes of these patients were evaluated.ResultsA total of 44 patients who underwent robotic-assisted thoracic surgery after three doses of neoadjuvant chemoimmunotherapy were included in this study. Of these, 36 of 44 (81.8%) patients had a major pathological response, and 26 (59.1%) had a pathological complete response based on pathological examination of surgical specimen. Eight patients (18.2%) suffered grade 3 treatment-related adverse events, including neutropenia (n = 4), increased aminotransferases (n = 3), anemia (n = 1), and cutaneous capillary endothelial proliferation (n = 1). Robotic-assisted thoracic surgery was performed subsequently, and R0 resection was achieved in all patients. Only two (4.5%) patients required conversion to thoracotomy. Surgical complications occurred in five (11.4%) patients, including air leak (n = 3), chylothorax (n = 2), and surgical site infection (n = 1). There was no re-surgery or postoperative mortality within 90 days.ConclusionRobotic-assisted thoracic surgery following neoadjuvant chemoimmunotherapy showed good feasibility and safety in stage III NSCLC. It was not associated with unexpected perioperative morbidity or mortality and may be a promising therapeutic option in stage III NSCLC. These results need further confirmation by more large-scale clinical trials.
Cell-free fetal DNA as a non-invasive method using pyrosequencing in detecting beta-globin gene mutation: A pilot study from area with limited facilities in Indonesia
Authors: Maskoen Ani Melani , Rahayu Nurul Setia , Laksono Bremmy , Fibriani Azzania , Soewondo Willyanti , Mose Johanes C. , Sahiratmadja Edhyana , Panigoro Ramdan 
Published: August 2022

BackgroundThalassemia is a monogenic, autosomal recessive, inherited disorder of the red blood cells caused by mutations or deletions in the globin gene. Approximately 6–10% of the Indonesian population carries the β-globin gene mutation; however, premarital screening is rarely conducted, and antenatal screening is optional. We explored the use of cell-free fetal DNA (cffDNA) as a potential non-invasive method of detecting the fetal β-globin gene mutation prenatally in pregnant women.Materials and methodsPregnant mothers (n = 10), who were known carriers of thalassemia and who had a history of having borne a baby with thalassemia major, and their carrier husbands (n = 4) were recruited after providing consent. EDTA blood was drawn, and maternal DNA, including cffDNA, and paternal DNA were isolated. Maternal contamination tests were conducted using the variable number tandem repeat test for ApoB and D1S80 loci. Allele quantification was performed by pyrosequencing. Known mutations from the bio-archived DNA of patients with thalassemia major (n = 16) were run alongside as a control.ResultsIn total, 7 out of 10 cffDNA successfully passed the maternal contamination test. The results of the allele quantification showed that six fetuses were predictive carriers of IVS1nt5 and one was predictive normal, in line with the allele quantification for the bio-archived DNA from patients with thalassemia major. The minimum threshold percentage for mutant A allele at cd26 was 32%, mutant T allele at IVS1nt1 was 23%, and mutant C allele at IVS1nt5 was 39%.ConclusionTaking cffDNA from the mother’s blood proved useful as a non-invasive means of detecting the β-globin gene mutation using pyrosequencing allele quantification. This non-invasive method is of great interest for prenatal diagnosis in settings with limited facilities, as it minimizes the risk of abortion. Further study of other mutations of the β-globin gene is needed.
Molecular mechanism of the spider toxin κ-LhTx-I acting on the bacterial voltage-gated sodium channel NaChBac
Authors: Xiao Zhen , Li Yaqi , Zhao Piao , Wu Xiangyue , Luo Guoqing , Peng Shuijiao , Liu Hongrong , Tang Cheng , Liu Zhonghua 
Published: August 2022

The bacterial sodium channel NaChBac is the prokaryotic prototype for the eukaryotic NaV and CaV channels, which could be used as a relatively simple model to study their structure–function relationships. However, few modulators of NaChBac have been reported thus far, and the pharmacology of NaChBac remains to be investigated. In the present study, we show that the spider toxin κ-LhTx-1, an antagonist of the KV4 family potassium channels, potently inhibits NaChBac with an IC50 of 491.0 ± 61.7 nM. Kinetics analysis revealed that κ-LhTx-1 inhibits NaChBac by impeding the voltage-sensor activation. Site-directed mutagenesis confirmed that phenylalanine-103 (F103) in the S3–S4 extracellular loop of NaChBac was critical for interacting with κ-LhTx-1. Molecular docking predicts the binding interface between κ-LhTx-1 and NaChBac and highlights a dominant hydrophobic interaction between W27 in κ-LhTx-1 and F103 in NaChBac that stabilizes the interface. In contrast, κ-LhTx-1 showed weak activity on the mammalian NaV channels, with 10 µM toxin slightly inhibiting the peak currents of NaV1.2–1.9 subtypes. Taken together, our study shows that κ-LhTx-1 inhibits the bacterial sodium channel, NaChBac, using a voltage-sensor trapping mechanism similar to mammalian NaV site 4 toxins. κ-LhTx-1 could be used as a ligand to study the toxin–channel interactions in the native membrane environments, given that the NaChBac structure was successfully resolved in a nanodisc.
Safety and efficacy of intravenous hydromorphone patient-controlled analgesia versus intramuscular pethidine in acute pancreatitis: An open-label, randomized controlled trial
Authors: Chen Zhiyao , Jiang Kun , Liu Fei , Zhu Ping , Cai Fei , He Yanqiu , Jin Tao , Lin Ziqi , Li Qian , Hu Cheng , Tan Qingyuan , Yang Xiaonan , Guo Jia , Huang Wei , Deng Lihui , Xia Qing 
Published: August 2022

Background: Hydromorphone patient-controlled analgesia (PCA) provides satisfactory postoperative pain therapy, but its effect has not been assessed in acute pancreatitis (AP).Aim: To assess the safety and efficacy of intravenous hydromorphone PCA for pain relief in AP.Methods: This open-label trial included AP patients admitted within 72 h of symptom onset, aged 18–70 years old, and with Visual Analog Scale (VAS) for pain intensity ≥5. They were randomized to receive intravenous hydromorphone PCA (0.05 mg/h with 0.2 mg on-demand) or intramuscular pethidine (50 mg as required) for three consecutive days. Intramuscular dezocine (5 mg on demand) was the rescue analgesia. The primary outcome was the change of VAS score recorded every 4 h for 3 days. Interim analysis was conducted by an Independent Data and Safety Monitoring Committee (IDSMC).Results: From 26 July 2019 to 15 January 2020, 77 patients were eligible for the intention-to-treat analysis in the interim analysis (39 in the hydromorphone group and 38 in the pethidine group). Baseline parameters were comparable between groups. No difference in VAS between the two groups was found. Hydromorphone PCA was associated with higher moderately severe to severe cases (82.1% vs. 55.3%, p = 0.011), acute peripancreatic fluid collections (53.9% vs. 28.9%, p = 0.027), more cumulative opioid consumption (median 46.7 vs. 5 mg, p &lt; 0.001), higher analgesia costs (median 85.5 vs. 0.5 $, p &lt; 0.001) and hospitalization costs (median 3,778 vs. 2,273 $, p = 0.007), and more adverse events (20.5% vs. 2.6%, p = 0.087). The per-protocol analysis did not change the results. Although a sample size of 122 patients was planned, the IDSMC halted further recruitment as disease worsening or worse clinical outcomes between the groups in the interim analysis.Conclusion: Hydromorphone PCA was not superior to pethidine in relieving pain in AP patients and might have worse clinical outcomes. Therefore, its use is not recommended.Clinical Trial Registration: Chictr.org.cn. ChiCTR1900025971
Music and neuro-cognitive deficits in depression
Authors: Raghavendra Prathima A. , Hegde Shantala , Philip Mariamma , Kesavan Muralidharan 
Published: August 2022

BackgroundCognitive deficits are one of the core features of major depressive disorder (MDD) that play crucial role in functional recovery. Studies have explored cognitive deficits in MDD, however, given inconsistent results, especially in mild-moderate MDD. Recently, studies have explored music as cognitive ability in various clinical conditions. In MDD, large focus has been on evaluating emotion deficits and just a handful on music cognition. With growing evidence on use of music based intervention to target cognitive deficits, it is imperative to explore nature of music cognitive ability in MDD.AimTo examine musical and neuro-cognitive deficits in patients with mild-moderate MDD.MethodsPatients diagnosed with mild or moderate MDD (n = 19) and matched healthy controls (HC) (n = 18) were evaluated on selected tests from NIMHANS Neuropsychological test battery and Montreal battery for evaluation of amusia (MBEA).ResultsMDD group performed significantly lower than HC on working memory (p = 0.007), verbal learning (p = 0.02) and retention (p = 0.03). Three indices were computed for a comprehensive evaluation. Groups did not differ significantly in any of the indices- focused attention, executive function, learning and memory as well as on music cognition. Focused attention and memory index predicted music cognition in HC and the combined group (MDD + HC) (p &lt; 0.01). Attention alone contributed to 62.1% of variance in music cognition. Similarly, music cognition significantly predicted focused attention (p &lt; 0.01).ConclusionIndividuals with mild-moderate MDD show significant deficits in working memory, verbal learning and memory, however, not in music cognition. There exists a significant relationship between music cognition and attention, which could be implicated in use of music interventions to ameliorate cognitive deficits. Limitations of study include small sample size and heterogeneity. Future studies on larger cohort examining musical emotion perception and neurocognition is imperative to have deeper understanding of this debilitating condition.
Empowering teachers to screen, guide, and refer schoolchildren with behavioral and mental health problems. A pilot study to promote mental health in Iran
Authors: Afshari Ramin , Kaveh Mohammad Hossein , Lankarani Kamran Bagheri , Doolub Damien , Jaafari Nematollah , Ostovarfar Jeyran 
Published: August 2022

BackgroundSchools are ideal for promoting the mental health of school-age children, but the teachers' current knowledge is insufficient to play an influential role in mental health services at schools. Fortunately, however, teachers have a high sense of responsibility, interest, and talent to receive knowledge and the ability to participate in this field. This study aimed to examine whether a protocol focused on the role of teachers could identify, guide, and care for school-age children with behavioral and mental health problems.MethodThe current research was a “before and after” pilot quasi-experimental study conducted in three elementary, secondary, and high schools. The main intervention consisted of a 5-h workshop based on a ready-to-use booklet for teachers conducted separately in each school. A total of 58 teachers and 872 school-age children were included using a judgmental sampling technique.ResultsThe pre-and post-workshop mean scores of teachers' knowledge about common mental disorders in school-age children were 6.21 ± 4.58 and 12.50 ± 7.27, respectively. According to the Strengths and Difficulties Questionnaire (SDQ), the teachers made 127 referrals, of whom 102 school-age children had problems. Consultants diagnosed 114 school children who reflected 90% of all teachers' recommendations needing psychological care and counseling. Finally, only 50 diagnosed school-age children were followed up and attended therapy sessions at counseling centers. The sensitivity and specificity of this brief intervention in detecting school-age children with psychological problems were respectively 80.3 and 98.0%.ConclusionsThis study's results support teacher empowerment training's effectiveness in identifying and guiding school-age children needing mental health care. Psychological counseling programs in schools in various quantitative and qualitative dimensions, including responding to school-age children's needs and psychological problems, should be adequately evaluated, and appropriate measures should be taken to promote mental health services. Collaboration between health systems and the education department will increase the effectiveness of mental health programs' promotion and drug abuse prevention. These pilot data lead the way to designing scientifically sound follow-up studies that will concretely ascertain the benefit of this program.
Moderators of pre-post changes in school-based mental health promotion: Psychological stress symptom decrease for adolescents with mental health problems, knowledge increase for all
Authors: Lehner Laya , Gillé Vera , Baldofski Sabrina , Bauer Stephanie , Becker Katja , Diestelkamp Silke , Kaess Michael , Krämer Jennifer , Lustig Sophia , Moessner Markus , Rummel-Kluge Christine , Thomasius Rainer , Eschenbeck Heike ,   the ProHEAD Consortium
Published: August 2022

BackgroundSchool-based mental health promotion aims to strengthen mental health and reduce stress. Results on the effectiveness of such programs are heterogeneous. This study realized a school-based mental health promotion program (StresSOS) for all students and aimed to identify moderators (mental health status, gender, grade level) of pre- to post-changes in stress symptoms and knowledge.MethodsParticipants were N = 510 adolescents (from 29 classes; 46.7% female) aged 12–18 years (M = 13.88, SD = 1.00; grade levels 7–10). They were without mental health problems (65.9%), at risk for mental health problems (21.6%), or with mental health problems (12.5%) and participated in a 90 min per week face-to-face training with 8 sessions in class at school. Demographic variables, mental health status, stress symptoms, and knowledge about stress and mental health were collected at baseline. Program acceptance, stress symptoms, and knowledge were collected post-intervention. Multilevel mixed effects models were conducted with the fixed effects time (within factor), mental health status, gender, and grade level (between factors). Random effects for students within classes were included.ResultsIn the pre-post comparison, mental health status moderated the changes on psychological stress symptoms (p &lt; 0.05). In adolescents with mental health problems the largest reduction in stress symptoms was observed between pre- and post-assessment. Gender and grade level were less relevant. For all adolescents knowledge gains were revealed (p &lt; 0.001). Program acceptance was moderated by mental health status and grade level (p &lt; 0.01). Mentally healthy adolescents and within the group of adolescents at-risk or with mental health problems, especially younger students (7th/8th grade), rated program acceptance higher.ConclusionPsychological stress symptoms decreased among adolescents with mental health problems and not among adolescents at risk for or without mental health problems. Mental health-related knowledge increased for all adolescents. The results add to knowledge on school-based mental health intervention research and practice. Its implications for different prevention strategies (universal, selective or a combination of both) are discussed.
An assessor-blinded, randomized comparative trial of transcutaneous auricular vagus nerve stimulation (taVNS) combined with cranial electroacupuncture vs. citalopram for depression with chronic pain
Authors: Li Shaoyuan , Zhang Zixuan , Jiao Yue , Jin Guixing , Wu Yue , Xu Fengquan , Zhao Yufeng , Jia Hongxiao , Qin Zongshi , Zhang Zhangjin , Rong Peijing 
Published: August 2022

BackgroundDepression accompanying chronic pain (CP) is one of the most common comorbid psychiatric disorders. This study aimed to investigate the effectiveness of transcutaneous auricular vagus nerve stimulation (taVNS) combined with electroacupuncture at Baihui (GV20) and Yintang (GV29) acupoints compared with citalopram.MethodsSixty patients with depression and pain comorbidity were enrolled in a prospective 8-week, single-blind, randomized controlled trial. Participants were randomly assigned to receive either taVNS combined with electroacupuncture treatment (taVNS: 8 weeks, 3 sessions per week; electroacupuncture: 8 weeks, twice per day, no drugs) or citalopram treatment (8 weeks, 40 mg/day). The primary outcome was Montgomery–Åsberg Depression Rating Scale (MADRS). The secondary endpoints were evaluated using the McGill Pain Questionnaire (SF-MPQ), self-reported 36-Item Short Form Survey (SF-36), Pittsburgh Sleep Quality Index (PSQI), Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Scale (HAMA).ResultsBoth the taVNS combined with electroacupuncture and citalopram groups had significant reductions in depressive and pain symptoms, as indicated by the decrease in MARDS and SF-MPQ scores. Regarding the analgesic effect, the pain intensity score of the SF-MPQ showed a larger reduction with citalopram than with taVNS combined with electroacupuncture at 6 weeks (P = 0.036). The reduction in the BP score of the SF-36 was higher at week 4 (P = 0.000), with no significant difference observed at week 8 (P = 0.1110). This result indicated that the pain intensity can be improved rapidly with citalopram compared with taVNS combined with electroacupuncture. Similarly, the comparison of PSQI scores at 4, 6, and 8 weeks indicates that there was no significant difference between groups, except in the use of sleeping medications. At week 6, higher medication use was found in the citalopram group than in the taVNS combined with electroacupuncture group (P = 0.049).ConclusionIn summary, compared with citalopram, taVNS combined with electroacupuncture produces similar positive effects on depressive and pain symptoms in patients with depression and chronic pain, which last for at least 8 weeks.
Identification of molecular signatures associated with sleep disorder and Alzheimer’s disease
Authors: Liang Lucong , Yan Jing , Huang Xiaohua , Zou Chun , Chen Liechun , Li Rongjie , Xie Jieqiong , Pan Mika , Zou Donghua , Liu Ying 
Published: August 2022

BackgroundAlzheimer’s disease (AD) and sleep disorders are both neurodegenerative conditions characterized by impaired or absent sleep. However, potential common pathogenetic mechanisms of these diseases are not well characterized.MethodsDifferentially expressed genes (DEGs) were identified using publicly available human gene expression profiles GSE5281 for AD and GSE40562 for sleep disorder. DEGs common to the two datasets were used for enrichment analysis, and we performed multi-scale embedded gene co-expression network analysis (MEGENA) for common DEGs. Fast gene set enrichment analysis (fGSEA) was used to obtain common pathways, while gene set variation analysis (GSVA) was applied to quantify those pathways. Subsequently, we extracted the common genes between module genes identified by MEGENA and genes of the common pathways, and we constructed protein-protein interaction (PPI) networks. The top 10 genes with the highest degree of connectivity were classified as hub genes. Common genes were used to perform Metascape enrichment analysis for functional enrichment. Furthermore, we quantified infiltrating immune cells in patients with AD or sleep disorder and in controls.ResultsDEGs common to the two disorders were involved in the citrate cycle and the HIF-1 signaling pathway, and several common DEGs were related to signaling pathways regulating the pluripotency of stem cells, as well as 10 other pathways. Using MEGENA, we identified 29 modules and 1,498 module genes in GSE5281, and 55 modules and 1,791 module genes in GSE40562. Hub genes involved in AD and sleep disorder were ATP5A1, ATP5B, COX5A, GAPDH, NDUFA9, NDUFS3, NDUFV2, SOD1, UQCRC1, and UQCRC2. Plasmacytoid dendritic cells and T helper 17 cells had the most extensive infiltration in both AD and sleep disorder.ConclusionAD pathology and pathways of neurodegeneration participate in processes contributing in AD and sleep disorder. Hub genes may be worth exploring as potential candidates for targeted therapy of AD and sleep disorder.
Recruiting and exploring vulnerabilities among young people at risk, or in the early stages of serious mental illness (borderline personality disorder and first episode psychosis)
Authors: Gajwani Ruchika , Wilson Naomi , Nelson Rebecca , Gumley Andrew , Smith Michael , Minnis Helen 
Published: August 2022

IntroductionMany gaps exist in our understanding of the developmental pathways to severe mental illness (SMI), including borderline personality disorder (BPD) and psychosis. However, those who have experienced adverse childhood experiences (ACEs) are at an increased risk and there is evidence to suggest that one of the earliest markers is emotional dysregulation. An area which has received relatively less research attention is the role neurodevelopmental disorders (NDDs) play. The aim of this feasibility study was therefore to explore the clinical profiles of young people early in the course of SMI, including their profiles of ACEs, emotional regulation difficulties, borderline personality traits and NDDs.MethodsA cross-sectional study of young people (aged 15–25) at risk of SMI, currently being seen within NHS mental health services, was conducted. This included those with early symptoms of psychosis and/or BPD as assessed by diagnostic interview. Eligible participants self-completed a battery of sociodemographic, clinical, and psychological measures in the company of a researcher. This included assessments of: symptoms of NDDs; borderline pathology traits; ACEs; and difficulties in emotional regulation. Statistical analyses included Mann–Whitney U tests and multiple regression.ResultsOf the 118 potentially eligible participants who were referred, 48 were ultimately included in the study. Young people early in the course of SMI reported a high prevalence of ACEs and deficits in emotional regulation. In total, 79% met criteria for attention deficit hyperactivity disorder (ADHD) and/or autism spectrum disorder (ASD). Emotional dysregulation was found to significantly mediate the association between both ACEs and the frequency of NDDs and borderline personality traits, however given the small sample size these results are preliminary in nature.ConclusionYoung people early in the course of SMI are at an increased risk of experiencing multiple childhood adversities and our results indicate a high prevalence of NDDs amongst them. Emotional dysregulation emerged as a potentially significant early marker of future clinical severity. We suggest that the clinical implications of our findings include routine screening for NDDs and ACEs and an increased recognition of the significance of emotional dysregulation. However, larger scale longitudinal studies are needed to investigate these preliminary findings further.