bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soluble Immune Checkpoint-Related Proteins in Blood Are Associated With Invasion and Progression in Non-Small Cell Lung Cancer
Authors: Wang Qinchuan , He Yue , Li Wanlu , Xu Xiaohang , Hu Qingfeng , Bian Zilong , Xu Andi , Tu Huakang , Wu Ming , Wu Xifeng 
Published: July 2022

BackgroundImmune checkpoint inhibition therapy has been achieved significant success in the treatment of non-small cell lung cancer (NSCLC). However, the role of soluble immune checkpoint- related proteins in NSCLC remains obscure.MethodsWe evaluated the circulating levels of 14 immune checkpoint-related proteins panel (BTLA, LAG-3, GITR, IDO, PD-L2, PD-L1, PD-1, HVEM, Tim-3, CD28, CD27, CD80, CD137 and CTLA-4) and their associations with the risk of invasive disease and the risk of NSCLC in 43 pre-invasive (AIS), 81 invasive NSCLC (IAC) patients and matched 35 healthy donors using a multiplex Luminex assay. Gene expression in tumors from TCGA were analyzed to elucidate potential mechanisms. The multivariate logistic regression model was applied in the study. ROC(receiver operator characteristic) curve and calibration curve were used in the performance evaluation.ResultsWe found that sCD27, sCD80, CD137 and sPDL2 levels were significantly increased in IAC cases compared to AIS cases (P= 1.05E-06, 4.44E-05, 2.30E-05 and 1.16E-06, respectively), whereas sPDL1 and sPDL2 levels were significantly increased in NSCLC cases compared to healthy controls (P=3.25E-05 and 1.49E-05, respectively). Unconditional univariate logistic regression analysis indicated that increased sCD27, sCD80, sCD137, and sPDL2 were significantly correlated with the risk of invasive diseases. The model with clinical variables, sCD27 and sPDL2 demonstrated the best performance (AUC=0.845) in predicting the risk of IAC. CD27 and PDCD1LG2 (PDL2) showed significant association with cancer invasion signature in TCGA dataset.ConclusionOur study provides evidence that soluble immune checkpoint-related proteins may associate with the risk of IAC, and we further established an optimized multivariate predictive model, which highlights their potential application in the treatment of NSCLC patients. Future studies may apply these biomarkers to test their predictive value of survival and treatment outcome during immunotherapy in NSCLC patients.
Systematic Review of Safety and Efficacy of IL-1-Targeted Biologics in Treating Immune-Mediated Disorders
Authors: Arnold Dennis D. , Yalamanoglu Ayla , Boyman Onur 
Published: July 2022

BackgroundThe cytokine interleukin (IL)-1 plays a pivotal role in immune-mediated disorders, particularly in autoinflammatory diseases. Targeting this cytokine proved to be efficacious in treating numerous IL-1-mediated pathologies. Currently, three IL-1 blockers are approved, namely anakinra, canakinumab and rilonacept, and two additional ones are expected to receive approval, namely gevokizumab and bermekimab. However, there is no systematic review on the safety and efficacy of these biologics in treating immune-mediated diseases.ObjectiveTo evaluate safety and efficacy of anakinra, canakinumab, rilonacept, gevokizumab, and bermekimab for the treatment of immune-mediated disorders compared to placebo, standard-of-care treatment or other biologics.MethodsThe PRISMA checklist guided the reporting of the data. We searched the PubMed database between 1 January 1984 and 31 December 2020 focusing on immune-mediated disorders. Our PubMed literature search identified 7363 articles. After screening titles and abstracts for the inclusion and exclusion criteria and assessing full texts, 75 articles were included in a narrative synthesis.ResultsAnakinra was both efficacious and safe in treating cryopyrin-associated periodic syndromes (CAPS), familial Mediterranean fever (FMF), gout, macrophage activation syndrome, recurrent pericarditis, rheumatoid arthritis (RA), and systemic juvenile idiopathic arthritis (sJIA). Conversely, anakinra failed to show efficacy in graft-versus-host disease, Sjögren’s syndrome, and type 1 diabetes mellitus (T1DM). Canakinumab showed efficacy in treating CAPS, FMF, gout, hyper-IgD syndrome, RA, Schnitzler’s syndrome, sJIA, and TNF receptor-associated periodic syndrome. However, use of canakinumab in the treatment of adult-onset Still’s disease and T1DM revealed negative results. Rilonacept was efficacious and safe for the treatment of CAPS, FMF, recurrent pericarditis, and sJIA. Contrarily, Rilonacept did not reach superiority compared to placebo in the treatment of T1DM. Gevokizumab showed mixed results in treating Behçet’s disease-associated uveitis and no benefit when assessed in T1DM. Bermekimab achieved promising results in the treatment of hidradenitis suppurativa.ConclusionsThis systematic review of IL-1-targeting biologics summarizes the current state of research, safety, and clinical efficacy of anakinra, bermekimab, canakinumab, gevokizumab, and rilonacept in treating immune-mediated disorders.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021228547.
Downregulation of TCF1 in HIV Infection Impairs T-cell Proliferative Capacity by Disrupting Mitochondrial Function
Authors: Cai Hong-Jiao , Shi Jue , Yin Lin-Bo , Zheng Jie-Fu , Fu Ya-Jing , Jiang Yong-Jun , Shang Hong , Zhang Zi-Ning 
Published: July 2022

BackgroundDespite the benefits of antiretroviral therapy (ART) for people with HIV, T-cell dysfunction cannot be fully restored. Metabolic dysregulation is associated with dysfunction of HIV-1-specific T-cells. Exploration of the factors regulating metabolic fitness can help reverse T-cell dysfunction and provide new insights into the underlying mechanism.MethodsIn this study, HIV-infected individuals and HIV-negative control individuals (NCs) were enrolled. T-cell factor (TCF)1 expression in cells was determined by quantitative reverse-transcriptase polymerase chain reaction and flow cytometry. Relevant microarray data from the GEO database were analyzed to explore the underlying mechanism. The effects of TCF1 on T-cell function and metabolic function were assessed in vitro.ResultsTCF7 mRNA expression in peripheral blood mononuclear cells was downregulated in rapid progressors compared with long-term non-progressors individuals and NCs. TCF1 expression on CD4+ and CD8+ T-cells was downregulated in treatment-naïve HIV-infected individuals compared with NCs. Interleukin (IL)2 production and proliferative capacity were impaired in TCF1 knockdown T-cells. Moreover, glycolytic capacity and mitochondrial respiratory function were decreased in TCF1 knockdown T-cells, and depolarized mitochondria were increased in TCF1 knockdown T-cells.ConclusionDownregulation of TCF1 in HIV infection impairs T-cell proliferative capacity by disrupting mitochondrial function. These findings highlight the metabolic regulation as a pivotal mechanism of TCF1 in the regulation of T-cell dysfunction.
Practice Effect of Repeated Cognitive Tests Among Older Adults: Associations With Brain Amyloid Pathology and Other Influencing Factors
Authors: Zheng Bang , Udeh-Momoh Chinedu , Watermeyer Tamlyn , de Jager Loots Celeste A. , Ford Jamie K. , Robb Catherine E. , Giannakopoulou Parthenia , Ahmadi-Abhari Sara , Baker Susan , Novak Gerald P. , Price Geraint , Middleton Lefkos T. 
Published: July 2022

BackgroundPractice effects (PE), after repeated cognitive measurements, may mask cognitive decline and represent a challenge in clinical and research settings. However, an attenuated practice effect may indicate the presence of brain pathologies. This study aimed to evaluate practice effects on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scale, and their associations with brain amyloid status and other factors in a cohort of cognitively unimpaired older adults enrolled in the CHARIOT-PRO SubStudy.Materials and Methods502 cognitively unimpaired participants aged 60-85 years were assessed with RBANS in both screening and baseline clinic visits using alternate versions (median time gap of 3.5 months). We tested PE based on differences between test and retest scores in total scale and domain-specific indices. Multiple linear regressions were used to examine factors influencing PE, after adjusting for age, sex, education level, APOE-ε4 carriage and initial RBANS score. The latter and PE were also evaluated as predictors for amyloid positivity status based on defined thresholds, using logistic regression.ResultsParticipants’ total scale, immediate memory and delayed memory indices were significantly higher in the second test than in the initial test (Cohen’s dz = 0.48, 0.70 and 0.35, P &lt; 0.001). On the immediate memory index, the PE was significantly lower in the amyloid positive group than the amyloid negative group (P = 0.022). Older participants (≥70 years), women, non-APOE-ε4 carriers, and those with worse initial RBANS test performance had larger PE. No associations were found between brain MRI parameters and PE. In addition, attenuated practice effects in immediate or delayed memory index were independent predictors for amyloid positivity (P &lt; 0.05).ConclusionSignificant practice effects on RBANS total scale and memory indices were identified in cognitively unimpaired older adults. The association with amyloid status suggests that practice effects are not simply a source of measurement error but may be informative with regard to underlying neuropathology.
Robot-Assisted Bimanual Training Improves Hand Function in Patients With Subacute Stroke: A Randomized Controlled Pilot Study
Authors: Ma Di , Li Xin , Xu Quan , Yang Fei , Feng Yutong , Wang Wenxu , Huang Jian-Jia , Pei Yu-Cheng , Pan Yu 
Published: July 2022

Study DesignA randomized controlled pilot study.BackgroundBimanual therapy (BMT) is an effective neurorehabilitation therapy for the upper limb, but its application to the distal upper limb is limited due to methodological difficulties. Therefore, we applied an exoskeleton hand to perform robot-assisted task-oriented bimanual training (RBMT) in patients with stroke.ObjectiveTo characterize the effectiveness of RBMT in patients with hemiplegic stroke with upper limb motor impairment.InterventionsA total of 19 patients with subacute stroke (1–6 months from onset) were randomized and allocated to RBMT and conventional therapy (CT) groups. The RBMT and CT groups received 90 min of training/day (RBMT: 60 min RBMT + 30 min CT; CT: 60 min CT for hand functional training + 30 min regular CT), 5 days/week, for 4 weeks (20 sessions during the experimental period).AssessmentsClinical assessments, including the Fugl–Meyer assessment of the upper extremity (FMA-UE), action research arm test (ARAT), and wolf motor arm function test (WMFT), were conducted before and after the intervention.ResultsWithin-group analysis showed a significant improvement in the FMA-UE and WMFT in both the CT and RBMT groups. A significant improvement in the Fugl–Meyer assessment (FMA) of the wrist and hand for the distal part in the RBMT group occurred earlier than that in the CT group. A significant improvement in WMFT time was found in both groups, but the WMFT functional ability assessment was only found in the RBMT group. No significant improvements in ARAT assessment were observed in either the CT or RBMT groups. Compared with CT, significant improvements were found in terms of the proportion of minimally clinically important differences after RBMT in FMA-UE (χ2 = 4.34, p = 0.037). No adverse events were reported by any of the participants across all sessions.ConclusionsThis study is the first to apply RBMT to the distal part of the upper limb. Both RBMT and CT are effective in improving the upper limb function in patients with subacute stroke. RBMT shows superior potential efficacy in facilitating recovery of the distal part of upper extremity (UE) motor function in the early stage. Future randomized control studies with a large sample size and follow-up assessments are needed to validate the present conclusions.
Derkash's Classification and Vas Visual Analog Scale to Access the Long-Term Outcome of Neurothoracic Outlet Syndrome: A Meta-Analysis and Systematic Review
Authors: Lingyun Wei , Ke Sha , Jinmin Zhao , Yu Qiao , Jun Qin 
Published: July 2022

ObjectiveMany publications report outcomes of surgical treatment for neurothoracic outlet syndrome (NTOS); however, high-quality meta-analyses regarding objective evaluation system accessing the long-term outcome of NTOS are lacking. This meta-analysis summarizes and compares the outcomes of Derkosh's classification and vas visual analog scale of the supraclavicular neuroplastic of brachial plexus (SNBP) and trams auxiliary first rib resection (TFRR).MethodsThe Cochrane Library, PubMed, EMBASE, Allied and Complementary Medicine (AMED) were searched for papers published between January 1980 and February 2021, using the keywords “thoracic outlet syndrome,” “treatment, surgical.” Articles were eligible for inclusion if the following criteria were met studies describing outcomes of surgery for NTOS, published in English, human studies, and available in full text. The exclusion criteria were case reports (n &lt; 10), reviews, abstracts, and studies lacking a control group or without evaluation for two types of surgery.ResultsWe included 10 studies with 1,255 cases, out of which 622 were in the SNBP group; and 633 were in the TFRR group. After surgery (≥12 months), Derkash's classification was improved in 425 cases with SNBP and 364 cases with TFRR. OR = 1.34 (95% CI: 0.94, 1.92), P = 0.03; vas visual analog scale was improved in 282 cases in the SNBP group and 214 cases in the TFRR group. OR = 1.08 (95% CI: 0.63, 1.85), P = 0.78.ConclusionThis meta-analysis shows that both SNBP and TFRR are effective for NTOS, but that SNBP is better than TFRR in improving Derkash's classification in the long term. Although patients treated with SNBP are more satisfactory, there is no significant difference in vas visual analog scale from TFRR.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42021254203, PROSPERO CRD42021254203.
Can CT Radiomics Detect Acquired T790M Mutation and Predict Prognosis in Advanced Lung Adenocarcinoma With Progression After First- or Second-Generation EGFR TKIs?
Authors: Yang Xiaohuang , Fang Chao , Li Congrui , Gong Min , Yi Xiaochun , Lin Huashan , Li Kunyan , Yu Xiaoping 
Published: July 2022

ObjectiveTo explore the potential of CT radiomics in detecting acquired T790M mutation and predicting prognosis in patients with advanced lung adenocarcinoma with progression after first- or second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy.Materials and MethodsContrast-enhanced thoracic CT was collected from 250 lung adenocarcinoma patients (with acquired T790M mutation, n = 146, without mutation, n = 104) after progression on first- or second-generation TKIs. Radiomic features were extracted from each volume of interest. The maximum relevance minimum redundancy and the least absolute shrinkage and selection operator (LASSO) regression method were used to select the optimized features in detecting acquired T790M mutation. Univariate Cox regression and LASSO Cox regression were used to establish the radiomics model to predict the progression-free survival of osimertinib treatment. Finally, nomograms (which) combined clinical factors with radscore to predict the acquired T790M mutation and prognosis were built separately. In addition, the two nomograms were validated by the concordance index (C-index), decision curve analysis (DCA), and calibration curve analysis where appropriate.ResultsClinical factors including the progression-free survival of first-line EGFR TKIs, EGFR mutation, and N stage and 12 radiomic features were useful in predicting the acquired T790M mutation. The area under the receiver operating characteristic curves (AUC) of clinical, radiomics, and nomogram models were 0.70, 0.74, and 0.78 in the training set and 0.71, 0.71, and 0.76 in the validation set, respectively. The DCA and calibration curve analysis demonstrated a good performance of the nomogram model. Clinical factors including age and first-generation EGFR TKIs and 12 radiomic features were useful in patients’ outcome prediction. The C-index of the combined nomogram was 0.686 in the training set and 0.630 in the validation set, respectively. Calibration curves demonstrated a relatively poor performance of the nomogram model.ConclusionNomogram combined clinical factors with radiomic features might be helpful to detect whether patients developed acquired T790M mutation or not after progression on first- or second-generation EGFR TKIs. Nomogram prognostic model combined clinical factors with radiomic features might have a limited value in predicting the survival of patients harboring acquired T790M mutation treated with osimertinib.
Differences in Cardiopulmonary Fitness Between Boy and Girls With Repaired Tetralogy of Fallot
Authors: Chang Yung-Liang , Kuan Tzu-Hsuan , Chen Chia-Hsin , Tsai Yi-Ju , Chen Guan-Bo , Lin Ko-Long , Tuan Sheng-Hui 
Published: July 2022

ObjectiveMany studies have demonstrated that patients with repaired tetralogy of Fallot (rTOF) have generally poorer cardiopulmonary fitness (CPF). However, little is known about how the disease results in different CPF in each sex. Therefore, this study aimed to investigate whether sex (and gender) differences affect CPF in children and adolescents with rTOF.MethodsThis retrospective study recruited adolescents and children (aged 10–18) with rTOF following an acute stage of tetralogy of Fallot (TOF) who received cardiopulmonary exercise testing (CPET) in the past 10 years. CPF was determined by symptom-limited CPET with a treadmill under ramped Bruce protocol. Boys and girls were categorized into groups based on body mass index (BMI) and fat mass index (FMI). The BMI was grouped by Taiwanese obesity cutoff points. The FMI was categorized by the body fat percentage. Excess adiposity was defined as (1) “overweight” and “obese” by BMI and (2) greater than the sex- and age-specific 75th percentile of whole subjects by FMI.ResultsA total of 185 participants (104 boys and 81 girls) with rTOF were recruited for the final analysis. Within the BMI category, 76 boys and 63 girls were in the normal group, whereas 28 boys and 18 girls were in the excessive adiposity group. Within the FMI category, 77 boys and 60 girls were in the normal group, whereas 27 boys and 21 girls were in the excessive adiposity group. The analysis of the body composition of rTOF subjects showed that there was no statistically significant difference between the subgroups of the two sexes, but both showed a smaller body size than normal Taiwanese children. When comparing the CPF within different BMI and FMI groups, the children in the excessive adiposity group had significantly lower values in metabolic equivalents (MET) at anaerobic threshold, peak MET, and measured peak oxygen consumption (VO2) to predicted peak VO2, regardless of sex. Moreover, boys (60.90%) presented poorer CPF than girls (74.22%, p &lt; 0.001).ConclusionIn Taiwan, patients with rTOF had poorer CPF than healthy peers. This study found that girls with rTOF had better CPF than boys with rTOF. The effect of gender stereotypes on sports participation and self-efficacy might be one of the contributing factors; however, further investigations are warranted to determine the causal effect.
Gastric Point-of-Care Ultrasound in Acutely and Critically Ill Children (POCUS-ped): A Scoping Review
Authors: Valla Frederic V. , Tume Lyvonne N. , Jotterand Chaparro Corinne , Arnold Philip , Alrayashi Walid , Morice Claire , Nabialek Tomasz , Rouchaud Aymeric , Cercueil Eloise , Bouvet Lionel 
Published: July 2022

IntroductionPoint-of-care ultrasound (POCUS) use is increasing in pediatric clinical settings. However, gastric POCUS is rarely used, despite its potential value in optimizing the diagnosis and management in several clinical scenarios (i.e., assessing gastric emptying and gastric volume/content, gastric foreign bodies, confirming nasogastric tube placement, and hypertrophic pyloric stenosis). This review aimed to assess how gastric POCUS may be used in acute and critically ill children.Materials and MethodsAn international expert group was established, composed of pediatricians, pediatric intensivists, anesthesiologists, radiologists, nurses, and a methodologist. A scoping review was conducted with an aim to describe the use of gastric POCUS in pediatrics in acute and critical care settings. A literature search was conducted in three databases, to identify studies published between 1998 and 2022. Abstracts and relevant full texts were screened for eligibility, and data were extracted, according to the JBI methodology (Johanna Briggs Institute).ResultsA total of 70 studies were included. Most studies (n = 47; 67%) were conducted to assess gastric emptying and gastric volume/contents. The studies assessed gastric volume, the impact of different feed types (breast milk, fortifiers, and thickeners) and feed administration modes on gastric emptying, and gastric volume/content prior to sedation or anesthesia or during surgery. Other studies described the use of gastric POCUS in foreign body ingestion (n = 6), nasogastric tube placement (n = 5), hypertrophic pyloric stenosis (n = 8), and gastric insufflation during mechanical ventilatory support (n = 4). POCUS was performed by neonatologists, anesthesiologists, emergency department physicians, and surgeons. Their learning curve was rapid, and the accuracy was high when compared to that of the ultrasound performed by radiologists (RADUS) or other gold standards (e.g., endoscopy, radiography, and MRI). No study conducted in critically ill children was found apart from that in neonatal intensive care in preterms.DiscussionGastric POCUS appears useful and reliable in a variety of pediatric clinical settings. It may help optimize induction in emergency sedation/anesthesia, diagnose foreign bodies and hypertrophic pyloric stenosis, and assist in confirming nasogastric tube placement, avoiding delays in obtaining confirmatory examinations (RADUS, x-rays, etc.) and reducing radiation exposure. It may be useful in pediatric intensive care but requires further investigation.