bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expanding the applications of immune checkpoint inhibitors in advanced lung cancer beyond disease progression
Authors: Chen Chao , Xiong Xi , Cheng Ying , Gen Haiyun , Zhu Wenqiang , Zhang Fei , Zhu Chuandong , Han Siqi , Liu Xiufeng 
Published: September 2023

BackgroundImmunotherapy, particularly the utilization of immune checkpoint inhibitors (ICIs), assumes a pivotal role in the comprehensive management of advanced lung cancer. There has been substantial deliberation regarding the appropriateness of extending ICIs treatment beyond the point of disease progression. This study delves into the potential benefits of sustained utilization of ICIs subsequent to disease progression in patients.MethodsA retrospective analysis was conducted on a cohort of 248 patients diagnosed with advanced lung cancer who received treatment with ICIs. The study population comprised 99 patients in the treatment beyond progression (TBP) group and 42 patients in the non-treatment beyond progression (NTBP) group. Parameters including progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR) were assessed. The Cox proportional hazard regression model was employed to analyze prognostic factors related to immunotherapy.ResultsPatients undergoing primary treatment with PD-1/PD-L1 inhibitors exhibited a median progression-free survival (mPFS) of 5.3 months. In the context of disease progression, a comparison between the TBP and NTBP groups was performed with respect to mPFS. The results demonstrated that the TBP group manifested an mPFS of 8.6 months, contrasting with the NTBP group’s mPFS of 4.0 months (p=0.028). The mean overall survival (mOS) in the TBP group exhibited a statistically significant increase in comparison to the NTBP group (14.1 months vs. 6.0 months, p=0.028). Evaluation of the objective response rate (ORR) between the TBP and NTBP groups revealed a substantial distinction. The TBP group displayed an ORR of 12.1%, while the NTBP group exhibited a lower ORR of 2.4%. The statistical analysis yielded a p-value of 0.068, signifying a notable trend towards significance. The disease control rate (DCR) was also assessed and exhibited a noteworthy variance between the two groups, with a higher DCR of 92.9% in contrast to 71.4% in the control group (p = 0.001).ConclusionSubsequent to ICIs treatment, a subset of patients may derive continued benefits from anticancer therapy, notwithstanding the progression of their advanced lung cancer.
Sevoflurane sedation in COVID-19 acute respiratory distress syndrome: an observational study with a propensity score matching model
Authors: Consales Guglielmo , Cappellini Iacopo , Freschi Benedetta , Campiglia Laura , Parise Maddalena , Zamidei Lucia 
Published: September 2023

IntroductionThe management of severe COVID-19-induced acute respiratory distress syndrome (C-ARDS) often involves deep sedation. This study evaluated the efficacy of sevoflurane, a volatile anesthetic, as an alternative to traditional intravenous sedation in this patient population.MethodsThis single-center, retrospective cohort study enrolled 112 patients with C-ARDS requiring invasive mechanical ventilation. A propensity score matching model was utilized to pair 56 patients receiving sevoflurane sedation with 56 patients receiving intravenous sedation. The primary outcome was mortality, with secondary outcomes being changes in oxygenation (PaO2/FiO2 ratio), pulmonary compliance, and levels of D-Dimer, CRP, and creatinine.ResultsThe use of sevoflurane was associated with a statistically significant reduction in mortality (OR 0.40, 95% CI 0.18–0.87, beta = −0.9, p = 0.02). In terms of secondary outcomes, an increase in the PaO2/FiO2 ratio and pulmonary static compliance was observed, although the results were not statistically significant. No significant differences were noted in the levels of D-Dimer, CRP, and creatinine between the two groups.ConclusionOur findings suggest an association between the use of sevoflurane and improved outcomes in C-ARDS patients requiring invasive mechanical ventilation. However, due to the single-center, retrospective design of the study, caution should be taken in interpreting these results, and further research is needed to corroborate these findings. The study offers promising insights into potential alternative sedation strategies in the management of severe C-ARDS.
Research and development of the sOLVe Tube™ dual lumen endobronchial tube: from concept to construct
Authors: Nwajuaku Patricia , Barjaktarevic Igor , Hoftman Nir 
Published: September 2023

IntroductionDual lumen endobronchial tubes (DLTs) are frequently used for lung isolation and one lung ventilation in thoracic surgery and other specialized clinical scenarios. Modern DLTs are large and rigid, and account for half of all tracheobronchial injuries. Their 70 year old design has numerous flaws which limit their safety and clinical utility. Our research team set out to design a new and improved DLT to mitigate these shortcomings, and then test the proposed device to ensure proper function.MethodsUsing published airway anatomy data and computed tomography imaging from 195 thoracic surgery patients, we designed a new DLT with a single size/configuration that would fit into adult surgery patients. This single “Universal design” was intended to replace both left and right sided 35Fr-41Fr DLTs (8 total products), while remaining small in diameter (35Fr). Other design goals included: 1) making intubation easier and safer, 2) allowing full sized therapeutic bronchoscopes to fit into this tube, 3) making the DLT more resistant to dislodgement. After design process completion the proposed dimensions were tested against 195 patients' left and right mainstem bronchi for radiographic fit. Once production prototypes were manufactured, they were tested in large adult Yorkshire pigs and fresh human cadavers for anatomic fit and performance.ResultsThe proposed design passed the radiographic fit test in all 195 patients for both left and right mainstem endobronchial placement. Intubation was successful and deemed atraumatic in all pigs and cadavers, and the device appropriately fit in both the right and left mainstem bronchi. Lung isolation was successfully achieved and the device proved resistant to axial force dislodgement.ConclusionWe propose a new design for a novel DLT meant to replace 8 currently supplied adult configurations with a single, one size/configuration fits all product that allows for large bore bronchoscopy and resists axial force dislodgement.
Soil microbiota plays a key regulatory role in the outbreak of tobacco root rot
Authors: Li Pengfei , Gu Songsong , Zhu Yanmei , Xu Tianyang , Yang Yishuai , Wang Zhengqiang , Deng Xiangdong , Wang Bin , Li Wei , Mei Wenqiang , Hu Qiulong 
Published: September 2023

IntroductionRoot rot caused by the fungal pathogenFusariumsp. poses significant challenges to tobacco cultivation in China, leading to major economic setbacks. The interplay between this pathogen and the wider soil microbial community remains poorly understood.MethodsHigh-throughput sequencing technology was utilized to evaluate soil prokaryotic, fungal, and protistan communities. We compared microbial communities in infected soils to those in healthy soils from the same field. Additionally, the influence of pH on the microbial communities was assessed.ResultsInfected soils displayed elevated levels of soil nutrients but diminished observed richness across prokaryotic, fungal, and protistan groups. The pathogenic fungiFusarium solani fsp.eumartii’sabundance was notably increased in infected soils. Infection withF. solanisignificantly altered the soil’s microbial community structure and interactions, manifested as a decrease in network scale and the number of keystone species. An evaluation of prokaryotes’ role inF. solani’sinvasion revealed an increased number of connecting nodes in infected soils. Additionally, relationships between predatory protists and fungi were augmented, whereas predation onF. solanideclined.DiscussionThe study underscores the significance of comprehending the interactions among soil microorganisms and brings to light the susceptibility of soil microbial communities to pathogen invasion. It offers insights into the multifaceted relationships and potential vulnerabilities within the soil ecosystem in the context ofFusariumsp. invasion.
Novel variants in the CLCN4 gene associated with syndromic X-linked intellectual disability
Authors: Li Sinan , Zhang Wenxin , Liang Piao , Zhu Min , Zheng Bixia , Zhou Wei , Wang Chunli , Zhao Xiaoke 
Published: September 2023

ObjectiveThe dysfunction of the CLCN4 gene can lead to X-linked intellectual disability and Raynaud–Claes syndrome (MRXSRC), characterized by severe cognitive impairment and mental disorders. This study aimed to investigate the genetic defects and clinical features of Chinese children with CLCN4 variants and explore the effect of mutant ClC-4 on the protein expression level and subcellular localization through in vitro experiments.MethodsA total of 401 children with intellectual disabilities were screened for genetic variability using whole-exome sequencing (WES). Clinical data, including age, sex, perinatal conditions, and environmental exposure, were collected. Cognitive, verbal, motor, and social behavioral abilities were evaluated. Candidate variants were verified using Sanger sequencing, and their pathogenicity and conservation were analyzed using in silico prediction tools. Protein expression and localization of mutant ClC-4 were measured using Western blotting (WB) and immunofluorescence microscopy. The impact of a splice site variant was assessed with a minigene assay.ResultsExome analysis identified five rare CLCN4 variants in six unrelated patients with intellectual disabilities, including two recurrent heterozygous de novo missense variants (p.D89N and p.A555V) in three female patients, and two hemizygous missense variants (p.N141S and p.R694Q) and a splicing variant (c.1390-12T &gt; G) that are maternally inherited in three male patients. The p.N141S variant and the splicing variant c.1390-12(T &gt; G were novel, while p.R694Q was identified in two asymptomatic heterozygous female patients. The six children with CLCN4 variants exhibited a neurodevelopmental spectrum disease characterized by intellectual disability (ID), delayed speech, autism spectrum disorders (ASD), microcephaly, hypertonia, and abnormal imaging findings. The minigene splicing result indicated that the c.1390-12T &gt; G did not affect the splicing of CLCN4 mRNA. In vitro experiments showed that the mutant protein level and localization of mutant protein are similar to the wild type.ConclusionThe study identified six probands with CLCN4 gene variants associated with X-linked ID. It expanded the gene and phenotype spectrum of CLCN4 variants. The bioinformatic analysis supported the pathogenicity of CLCN4 variants. However, these CLCN4 gene variants did not affect the ClC-4 expression levels and protein location, consistent with previous studies. Further investigations are necessary to investigate the pathogenetic mechanism.
Posterior spinal decompression in adults with spinal cord injury without traumatic compromise of the spinal canal: what is the data?
Authors: Solou Mary , Politis Anastasios A. , Ydreos Ιoannis , Papadopoulos Evangelos K. , Banos Stamatios , Savvanis Georgios , Gavra Maria M. , Boviatsis Efstathios J. , Stavrinou Lampis C. 
Published: September 2023

BackgroundSpinal cord injury (SCI) can be caused by a variety of factors and its severity can range from a mild concussion to a complete severing of the spinal cord. Τreatment depends on the type and severity of injury, the patient’s age and overall health. Reduction of dislocated or fractured vertebrae via closed manipulation or surgical procedures, fixation and removal of bony fragments and debris that compromise the spinal canal are indicated for decompression of the spinal cord and stabilization of the spine. However, when there is no obvious traumatic obstruction of spinal canal, the question arises as to whether laminectomy is needed to be performed to improve neurological outcome.MethodsA literature review covering all indexed studies published between 2013 and 2023 was performed using keywords to identify the patient group of interest (spinal cord injury, SCI, spinal cord trauma, cervical, thoracic, lumbar, thoracolumbar),central cord syndrome (CCS) and the interventions (laminectomy, laminoplasty, decompression, duroplasty).ResultsThis review includes6 observational studies investigating the outcome of posterior spinal decompression in patients suffering from spinal cord injury without traumatic spinal cord stenosis. Most patients already had degenerative stenosis. From a total of 202, 151 patients (74.7%) improved neurologically by at least one grade at ASIA scale, after being treated with either laminectomy, laminoplasty, duroplasty or a combination of these techniques.ConclusionEarly decompression in SCI patients remains a reasonable practice option and can be performed safely, but no specific evidence supports the use of laminectomy alone. There is emerging evidence that intended durotomy followed by extended meningoplasty may improve the neurological outcome in patients suffering from SCI when meta-traumatic edema is apparent. However, the lack of high-quality evidence and results support the need for further research.
Associations between psychotropic drugs and rsEEG connectivity and network characteristics: a cross-sectional study in hospital-admitted psychiatric patients
Authors: Zandstra Melissa G. , Meijs Hannah , Somers Metten , Stam Cornelis J. , de Wilde Bieke , van Hecke Jan , Niemegeers Peter , Luykx Jurjen J. , van Dellen Edwin 
Published: September 2023

IntroductionResting-state EEG (rsEEG) characteristics, such as functional connectivity and network topology, are studied as potential biomarkers in psychiatric research. However, the presence of psychopharmacological treatment in study participants poses a potential confounding factor in biomarker research. To address this concern, our study aims to explore the impact of both single and multi-class psychotropic treatments on aforementioned rsEEG characteristics in a psychiatric population.MethodsRsEEG was analyzed in a real-world cross-sectional sample of 900 hospital-admitted psychiatric patients. Patients were clustered into eight psychopharmacological groups: unmedicated, single-class treatment with antipsychotics (AP), antidepressants (AD) or benzodiazepines (BDZ), and multi-class combinations of these treatments. To assess the associations between psychotropic treatments and the macroscale rsEEG characteristics mentioned above, we employed a general linear model with post-hoc tests. Additionally, Spearman’s rank correlation analyses were performed to explore potential dosage effects.ResultsCompared to unmedicated patients, single-class use of AD was associated with lower functional connectivity in the delta band, while AP was associated with lower functional connectivity in both the delta and alpha bands. Single-class use of BDZ was associated with widespread rsEEG differences, including lower functional connectivity across frequency bands and a different network topology within the beta band relative to unmedicated patients. All of the multi-class groups showed associations with functional connectivity or topology measures, but effects were most pronounced for concomitant use of all three classes of psychotropics. Differences were not only observed in comparison with unmedicated patients, but were also evident in comparisons between single-class, multi-class, and single/multi-class groups. Importantly, multi-class associations with rsEEG characteristics were found even in the absence of single-class associations, suggesting potential cumulative or interaction effects of different classes of psychotropics. Dosage correlations were only found for antipsychotics.ConclusionOur exploratory, cross-sectional study suggests small but significant associations between single and multi-class use of antidepressants, antipsychotics and benzodiazepines and macroscale rsEEG functional connectivity and network topology characteristics. These findings highlight the importance of considering the effects of specific psychotropics, as well as their interactions, when investigating rsEEG biomarkers in a medicated psychiatric population.
“What” and “when” predictions modulate auditory processing in a mutually congruent manner
Authors: Cappotto Drew , Luo Dan , Lai Hiu Wai , Peng Fei , Melloni Lucia , Schnupp Jan Wilbert Hendrik , Auksztulewicz Ryszard 
Published: September 2023

IntroductionExtracting regularities from ongoing stimulus streams to form predictions is crucial for adaptive behavior. Such regularities exist in terms of the content of the stimuli and their timing, both of which are known to interactively modulate sensory processing. In real-world stimulus streams such as music, regularities can occur at multiple levels, both in terms of contents (e.g., predictions relating to individual notes vs. their more complex groups) and timing (e.g., pertaining to timing between intervals vs. the overall beat of a musical phrase). However, it is unknown whether the brain integrates predictions in a manner that is mutually congruent (e.g., if “beat” timing predictions selectively interact with “what” predictions falling on pulses which define the beat), and whether integrating predictions in different timing conditions relies on dissociable neural correlates.MethodsTo address these questions, our study manipulated “what” and “when” predictions at different levels – (local) interval-defining and (global) beat-defining – within the same stimulus stream, while neural activity was recorded using electroencephalogram (EEG) in participants (N = 20) performing a repetition detection task.ResultsOur results reveal that temporal predictions based on beat or interval timing modulated mismatch responses to violations of “what” predictions happening at the predicted time points, and that these modulations were shared between types of temporal predictions in terms of the spatiotemporal distribution of EEG signals. Effective connectivity analysis using dynamic causal modeling showed that the integration of “what” and “when” predictions selectively increased connectivity at relatively late cortical processing stages, between the superior temporal gyrus and the fronto-parietal network.DiscussionTaken together, these results suggest that the brain integrates different predictions with a high degree of mutual congruence, but in a shared and distributed cortical network. This finding contrasts with recent studies indicating separable mechanisms for beat-based and memory-based predictive processing.
A preliminary study for the clinical effect of one combinational physiotherapy and its potential influence on gut microbial composition in children with Tourette syndrome
Authors: Bao Chun , Wei Meng , Pan Hongguo , Wen Ming , Liu Ziming , Xu Yue , Jiang Huihui 
Published: September 2023

IntroductionTourette syndrome (TS) is a chronic neuropsychiatric disorder with unknown causes and inadequate therapies. Inspired by the important roles of gut microbiota in some mental illnesses, the interactions between gut microbiota and TS via the gut-brain axis have gained more and more attention. This study aimed to characterize the gut microbial profiles in children with TS, and explore the clinical effects of one combinational physiotherapy and its potential influence on gut microbial composition.MethodsThe gut microbial profiles were depicted based on the sequence data of 32 patients and 29 matched health children by 16S rDNA amplicon pyrosequencing. Thirty of thirty-two patients underwent uninterrupted two 10-day courses of combinational physiotherapy, which included a 60-minute cranial electrotherapy stimulation (CES) training followed by a 30-minute biofeedback training per session, 2 sessions a day.ResultsOur results indicated that the gut microbial composition in children with TS was different from that in healthy controls. Multiple GBM neurotransmitter modules obtained through Picrust2 functional predictive analysis were significantly increased in patients, including Histamine degradation, Dopamine degradation, and DOPAC synthesis. Moreover, this combinational physiotherapy could significantly diminish tic activity, whose positive effects were first reported in children with TS. Lastly, different gut microbial compositions and predictive metabolic pathways were also observed between patients before and after this treatment, with lower abundances of the genera (e.g., Dorea) and significant decreases of GBM neurotransmitter modules (e.g. dopamine degradation) in patients after this treatment, indicating that improved clinical symptoms might be accompanied by an improvement of intestinal microenvironment.DiscussionChildren with TS showed a cognizable gut microbial profile, and certain enriched bacteria with pro-inflammatory potential might induce neuroinflammatory responses. This combinational physiotherapy could significantly diminish tic activity, and the gut microbial compositions in patients after this treatment were different from those without any treatment, indicating the existence of bidirectional communication of the gut-brain axis in TS. But studies on the gut microbial characteristics in TS patients, the influences of gut microbiota on tic severity, the efficacy and safety of this treatment, and the bidirectional regulatory mechanism between brain signals and gut microbiota in TS still need to be explored.
A pharmacist-led opioid de-escalation program after completion of chemoradiotherapy in locally advanced head and neck cancer
Authors: Horinouchi Ai , Enokida Tomohiro , Suzuki Shinya , Kamata Hayato , Kaneko Asumi , Matsuyama Chihiro , Fujisawa Takao , Ueda Yuri , Ito Kazue , Okano Susumu , Kawasaki Toshikatsu , Tahara Makoto 
Published: September 2023

BackgroundPersistent opioid use frequently leads to substantial negative impacts on quality of life, and as the outlook for numerous cancer types continues to improve, these complications become increasingly crucial. It is essential to acknowledge that extended or excessive opioid use may result in adverse effects in patients who completed radiation therapy (RT).MethodsIn this time-series analysis, we compared the outcomes of patients who participated in the pharmacist-led opioid de-escalation (PLODE) program after completing concurrent radiotherapy (CRT) between June 2018 and February 2019 against patients who completed CRT between June 2017 and March 2018 and did not participate in the program.ResultsAmong 61 patients, 16 (26%) used opioids after completing CRT and participated in the PLODE program. Before starting the program, 93 patients completed CRT between June 2017 and March 2018 and 32 (34%) used opioids at CRT completion. These patients were deemed the control group. In the PLODE group, outpatient pharmacist intervention was performed, with 29 total interventions related to opioid use, of which 16 (55%) recommended tapering or discontinuing opioids according to the definition of this program. Patients who participated in the PLODE program discontinued opioids significantly earlier than those in the control group (median time to opioid discontinuation 11 days vs. 24.5 days, p &lt; 0.001). None of the patients in the PLODE group resumed opioid use following discontinuation or escalated opioid dosing due to worsening pain.ConclusionThis study showed the utility of pharmacist-initiated interventions for opioid use in patients with head and neck cancer who had completed CRT.