bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atypical cortical thickness and folding of language regions in Chinese nonsyndromic cleft lip and palate children after speech rehabilitation
Authors: Wang Shi , Fang Lei , Miao Guofu , Li Zhichao , Rao Bo , Cheng Hua 
Published: September 2022

ObjectiveEven after palatoplasty and speech rehabilitation, patients with cleft lip and palate (CLP) remain to produce pronunciation errors. We hypothesized that nonsyndromic CLP (NSCLP) after speech rehabilitation had structural abnormalities in language-related brain regions. This study investigates structural patterns in NSCLP children after speech rehabilitation using surface-based morphometry (SBM) analysis.MethodsForty-two children with NSCLP and 42 age- and gender-matched healthy controls were scanned for 3D T1-weighted images on a 3T MRI scanner. After reconstructing each brain surface, we computed SBM parameters and assessed between-group differences using two-sample t-tests and permutation tests (5,000 times). Then, we assessed the relationship between the SBM parameters and the Chinese language clear degree scale (CLCDS) using Pearson's correlation analysis.ResultThe speech-rehabilitated children with NSCLP showed lower cortical thickness and higher gyrification index mainly involving left language-related brain regions (permutation tests, p &lt; 0.05). Furthermore, the lower cortical thickness of the left parahippocampal gyrus was positively correlated with CLCDS scores (r = 0.370, p = 0.017) in patients with NSCLP.ConclusionThe SBM analysis showed that the structural abnormalities of speech-rehabilitated children with NSCLP mainly involved language-related brain regions, especially the dominant cerebral hemisphere. The structural abnormalities of the cortical thickness and folding in the language-related brain regions might be the neural mechanisms of speech errors in NSCLP children after speech rehabilitation. The cortical thickness of the parahippocampal gyrus may be a biomarker to evaluate pronunciation function.
Exploration of acupuncture therapy in the treatment of mild cognitive impairment based on the brain-gut axis theory
Authors: Jin Yuanyuan , Hu Fen , Zhu Jianfang 
Published: September 2022

BackgroundMild cognitive impairment (MCI) is an intermediary state between normal aging and dementia. Early intervention for MCI may be a key opportunity in managing dementia. Recent studies have demonstrated the alterations in the gut microbial communities associated with MCI. This study aims to evaluate if acupuncture can improve cognitive function in subjects with MCI and explore the possible mechanism of acupuncture by better defining the interactions of gut microbiota.MethodsA randomized assessor-blind controlled study is proposed. A total of 62 subjects will be recruited and randomly allocated into two groups in a 1:1 ratio: the treatment and control groups. Participants in the treatment group will receive active acupuncture and exercise/cognitive training (conventional treatment). The control group will receive sham acupuncture and exercise/cognitive training. Each participant will receive active or sham acupuncture for 12 weeks. The primary outcome will be the Montreal Cognitive Assessment (MoCA) score and intestinal flora. Secondary outcomes will include mini-mental state examination (MMSE) and activity of daily living (ADL) scores. Various scales will be collected at baseline, during the treatment (weeks 4 and 8), week 12, and months 4 and 6 after the intervention. Feces will be collected before and after the treatment based on 16S rRNA gene sequencing technology for each participant to characterize the intestinal flora. Adverse events will be recorded by monthly follow-up.ResultsThe trial is expected to show that cognitive function can be improved by acupuncture and produce reliable clinical outcomes in MCI patients. It will also provide preliminary data on the possible mechanism based on the changes in the intestinal flora. Collected data will be used to support future large-scale fundamental studies.ConclusionAcupuncture is an effective method to improve cognitive function for MCI. This study will provide data on the relationship between gut microbiota and the effectiveness of acupuncture in patients with MCI from a new angle.Clinical trial registration[www.ClinicalTrials.gov], identifier [MR-33-22-002376].
Unified framework for brain connectivity-based biomarkers in neurodegenerative disorders
Authors: Kim Sung-Woo , Song Yeong-Hun , Kim Hee Jin , Noh Young , Seo Sang Won , Na Duk L. , Seong Joon-Kyung 
Published: September 2022

BackgroundBrain connectivity is useful for deciphering complex brain dynamics controlling interregional communication. Identifying specific brain phenomena based on brain connectivity and quantifying their levels can help explain or diagnose neurodegenerative disorders.ObjectiveThis study aimed to establish a unified framework to identify brain connectivity-based biomarkers associated with disease progression and summarize them into a single numerical value, with consideration for connectivity-specific structural attributes.MethodsThis study established a framework that unifies the processes of identifying a brain connectivity-based biomarker and mapping its abnormality level into a single numerical value, called a biomarker abnormality summarized from the identified connectivity (BASIC) score. A connectivity-based biomarker was extracted in the form of a connected component associated with disease progression. BASIC scores were constructed to maximize Kendall's rank correlation with the disease, considering the spatial autocorrelation between adjacent edges. Using functional connectivity networks, we validated the BASIC scores in various scenarios.ResultsOur proposed framework was successfully applied to construct connectivity-based biomarker scores associated with disease progression, characterized by two, three, and five stages of Alzheimer's disease, and reflected the continuity of brain alterations as the diseases advanced. The BASIC scores were not only sensitive to disease progression, but also specific to the trajectory of a particular disease. Moreover, this framework can be utilized when disease stages are measured on continuous scales, resulting in a notable prediction performance when applied to the prediction of the disease.ConclusionOur unified framework provides a method to identify brain connectivity-based biomarkers and continuity-reflecting BASIC scores that are sensitive and specific to disease progression.
Real-world efficacy and safety of mobocertinib in EGFR exon 20 insertion-mutated lung cancer
Authors: Kian Waleed , Christopoulos Petros , Remilah Areen A. , Levison Esther , Dudnik Elizabeth , Shalata Walid , Krayim Bilal , Marei Ranin , Yakobson Alexander , Faehling Martin , Kahala Dolev , Sara Granot Inbal , Levitas Dina , Peled Nir , Roisman Laila C. 
Published: September 2022

BackgroundNon-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertions (EGFRex20ins) is relatively resistant to the existing EGFR tyrosine kinase inhibitors (TKIs). Mobocertinib is a novel TKI that selectively targets EGFRex20ins and has demonstrated therapeutic efficacy in pretreated patients with tumors harboring these mutations.MethodsThis is a retrospective, non-interventional, multicenter real-world study aimed at assessing the efficacy and safety of mobocertinib in patients with EGFRexon20ins who received 160 mg QD monotherapy as part of expanded access. Data collection was based on patients’ records. PET-CT or CT scans were used to measure systemic response, while brain MRIs were used to examine intracranial response as part of the follow-up.Results16 patients were included in this report. Mobocertinib was administered to 31.3% (5) of patients as first-line, 50% (8) as second-line, and 18.7% (3) as a later-line therapy. The median age was 65 years (range, 38-83), 75% (12/16) were female, and 50% (8/16) had brain metastases at baseline before mobocertinib treatment. The objective response rate (ORR) to mobocertinib was 25% (4/16) (1/5 for first line and 3/11 for other lines), disease control rate (DCR) was 75% (12/16) with a follow-up period of 11 months. The median duration of treatment (mDoT) was 5.6 months across all patients, and 8.6 months in responders. Based on the presence or absence of brain metastasis, the mDoT was 14.8 and 5.4 months (p=0.01), respectively. Mobocertinib Grade ≥3 treatment-related adverse events (TRAEs) included diarrhea (19%), nausea (6%) and renal failure (6%). Dose reduction was reported in 25% of cases to 80 mg.ConclusionMobocertinib in compassionate use exhibited an ORR of 25%, which is very similar to that of the phase 2 EXCLAIM study and clearly better than historical data of monochemotherapy or conventional EGFR inhibitors. The greatest benefit was noted in patients without brain metastases, who showed durable effects with mDoT 14.8 months, while intracranial activity was limited. These findings may assist therapeutic considerations, inasmuch as results from the EXCLAIM cohort-3 dedicated to brain lesions are not available yet.
Evaluation of colorectal cancer liver metastases based on liquid biopsy combined with folate receptor– Positive circulating tumor cells and HSP90
Authors: Huang Maosen , Cheng Linyao , Mo SiSi , Ru Haiming , Mo Xianwei , Yan Linhai 
Published: September 2022

ObjectiveLiver metastasis of colorectal cancer (LMCRC) is a major cause of cancer-related deaths worldwide. We can reduce the mortality rate by discerning the risk of liver metastases in patients with colorectal cancer at an early stage. Hence, we combined the use of folate receptor (FR)–labeled circulating tumor cells (FR+CTCs) and the metastasis-related marker, heat shock protein 90 (HSP90), to screen patients with colorectal cancer and explore the prognostic factors of patients with high expression of FR+CTC and HSP90.Patients and methodsA retrospective study of 356 patients with measurable colorectal cancer was performed. Negative enrichment and FR-targeted fluorescence quantitative PCR was utilized to detect FR+CTC. An ELISA kit was used to detect HSP90 expression. A timely follow-up study of patients with colorectal cancer was made.ResultsColorectal patients with liver metastases showed high expression of FR+CTCs and HSP90. The diagnostic ability of the combined receiver operating characteristic curve of FR+CTC and HSP90 (area under the curve [AUC]=0.79, sensitivity 70.55%, specificity 92.66%) was significantly greater than that of a single index. The results of timely follow-up of patients showed that the high expression of FR+CTC significantly shortened the median disease-free survival (mDFS) of 36.5 months (95% confidence interval [CI]: 14.13–58.87, Logrank p &lt; 0.0001) compared with the low expression cohort. The mDFS of the HSP90 high-expression cohort was significantly higher than that of the low-expression cohort (Logrank p = 0.0002), mDFS=58.47 months (95% CI: 37.12–79.81, Logrank p &lt; 0.0001). We performed univariate and multivariate analyses to show that FR+CTC and HSP90 were risk factors for the progression of metastatic colorectal cancer (MCRC) disease. We then constructed a high- and low-risk score model of risk factors to evaluate MCRC. The diagnostic sensitivity of the risk model for MCRC was significantly improved (AUC=0.89, sensitivity 85.29%, specificity 81.33%), and the mDFS of patients in a high-risk group increased to 33.28 months (95% CI: 27.24–39.31, Logrank p &lt; 0.0001). The establishment of the model improves the early screening of patients with MCRC.ConclusionPatients with colorectal cancer and high expression of FR+CTC and HSP90 are at risk of liver metastasis and this suggests a poor prognosis. Combining the two markers can improve the early screening and diagnosis of LMCRC patients. In addition, combining a multivariate risk model can further assist patients in appropriate stratification and the design of tailored treatment regimens. However, further validation these markers is needed before their routine clinical application.
Chinese herbal injections versus intrapleural cisplatin for lung cancer patients with malignant pleural effusion: A Bayesian network meta-analysis of randomized controlled trials
Authors: Xu Yi-Fang , Chen Yun-Ru , Bu Fan-Long , Huang Yu-Bei , Sun Yu-Xin , Li Cheng-Yin , Sellick Jodi , Liu Jian-Ping , Qin Dan-Mei , Liu Zhao-Lan 
Published: September 2022

BackgroundMalignant pleural effusion (MPE) is a common complication in patients with advanced lung cancer that can severely compromise the quality of life and limit life expectancy. Randomized controlled trials (RCTs) have shown that Chinese herbal injections (CHIs) may be beneficial in improving quality of life. This network meta-analysis (NMA) aims to explore several CHIs used for lung cancer patients with MPE.MethodsSeven databases were systematically searched for eligible RCTs from inception to November 2021. The primary outcome was the clinical effective rate. Secondary outcomes were the improvement rate of Karnofsky performance status (KPS) score and incidence of adverse events (AEs). The Cochrane risk of bias 2 tool was used to assess the quality of included studies. Data analysis was performed using STATA 16.0 and R software 4.1.0. Both pairwise meta-analysis and Bayesian NMA were conducted. Competing interventions were ranked using the surface under the cumulative ranking (SUCRA) probabilities. Evidence grading was evaluated using the Confidence in Network Meta-Analysis online software (https://cinema.ispm.unibe.ch/).ResultsA total of 44 studies involving 2,573 patients were included. The combined Huachansu injection (HCS) with intrapleural cisplatin (cis-diamminedichloro-platinum, DDP) had the highest probability of improving the clinical effective rate (SUCRA, 84.33%). The Kangai injection (KA) combined with DDP had the most improvement rate of KPS score (SUCRA, 80.82%), while the Fufangkushen injection (FFKS) alone was more likely to reduce AEs including gastrointestinal reactions (SUCRA, 89.92%), leukopenia (SUCRA, 91.85%), and chest pain (SUCRA, 98.17%). FFKS combined with DDP ranked the best in reducing the incidence of fever (SUCRA, 75.45%).ConclusionsOur NMA showed that CHIs alone or combined with DDP could improve clinical effectiveness and quality of life and reduce AEs, compared to DDP alone. HSC and KA, combined with DDP, may be the most effective considering clinical effective rate and improvement of KPS score, respectively. FFKS, either used alone or in combination therapy with DDP, may be the best in reducing AEs. However, high-quality RCTs with larger sample sizes are needed to further support the evidence.Systematic review registrationPROSPERO https://www.crd.york.ac.uk/prospero/, identifier CRD42021285275.
Electrochemotherapy for the treatment of cutaneous squamous cell carcinoma: The INSPECT experience (2008-2020)
Authors: Bertino Giulia , Groselj Ales , Campana Luca G. , Kunte Christian , Schepler Hadrian , Gehl Julie , Muir Tobian , Clover James A. P. , Quaglino Pietro , Kis Erika , Mascherini Matteo , Bisase Brian , Pecorari Giancarlo , Bechara Falk , Matteucci Paolo , Odili Joy , Russano Francesco , Orlando Antonio , Pritchard-Jones Rowan , Moir Graeme , Mowatt David , Silvestri Barbara , Seccia Veronica , Saxinger Werner , de Terlizzi Francesca , Sersa Gregor 
Published: September 2022

IntroductionCutaneous squamous cell carcinoma (cSCC) is a frequent skin cancer with a high risk of recurrence characterized by tumor infiltration and, in advanced cases, a poor prognosis. ECT (electrochemotherapy) is an alternative treatment option for locally advanced or recurrent cSCC that is unsuitable for surgical resection. In this study, we aimed to evaluate the data in the InspECT (International Network for Sharing Practice on ECT) registry of the referral centers and to clarify the indications for the use of ECT as a treatment modality for cSCC.Materials and methodsPatients with primary, recurrent or locally advanced cSCC from 18 European centers were included. They underwent at least one ECT session with bleomycin between February 2008 and November 2020, which was performed following the European Standard Operating Procedures.ResultsThe analysis included 162 patients (mean age of 80 years; median, 1 lesion/patient). Side effects were mainly local and mild (hyperpigmentation, 11%; ulceration, 11%; suppuration, 4%). The response to treatment per patient was 62% complete and 21% partial. In the multivariate model, intravenous drug administration and small tumor size showed a significant association with a positive outcome (objective response). One-year local progression-free survival was significantly better (p&lt;0.001) in patients with primary tumors (80% (95% C.I. 70%-90%) than in patients with locally advanced disease (49% (95% C.I. 30%-68%).ConclusionIn the present study, ECT showed antitumor activity and a favorable safety profile in patients with complex cSCC for whom there was no widely accepted standard of care. Better results were obtained in primary and small tumors (&lt;3 cm) using intravenous bleomycin administration.
Diagnostic performance of elastosonography in the differential diagnosis of benign and malignant salivary gland tumors: A meta-analysis
Authors: Wu Jiangfeng , Zhou Zhijuan , Wang Xiaoyun , Jin Yun , Wang Zhengping , Jin Guilong 
Published: September 2022

PurposeThe clinical practice of elastosonography for the detection of salivary gland tumors is still a controversial issue. The objective of this meta-analysis was to evaluate the effect of elastosonography for the diagnosis of salivary gland tumors and to compare the diagnostic value of elastosonography and conventional ultrasound in the diagnosis of salivary gland tumors.MethodsA comprehensive literature search through PubMed, EMBASE, and Cochrane Library was carried out from inception to November 2021. Two researchers independently extracted the data from the enrolled papers using a standard data extraction form. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were calculated to evaluate the diagnostic performance of elastosonography. The Quality Assessment of Diagnostic Accuracy Studies—2 (QUADAS-2) tool was utilized to evaluate the quality of each included study. Meta-DiSc version 1.4, Review Manager 5.3, and StataSE 15 were used.ResultsSixteen studies with a total of 1105 patients with 1146 lesions were included in this meta-analysis. The pooled sensitivity, specificity, PLR, NLR, and DOR of elastosonography for the differentiation between benign and malignant salivary gland tumors were 0.73 (95%CI, 0.66–0.78), 0.64 (95%CI, 0.61–0.67), 2.83 (95%CI, 1.97–4.07), 0.45 (95%CI, 0.32–0.62), and 9.86 (95%CI, 4.49–21.62), respectively, with an AUC of 0.82. Four studies provided data regarding the conventional ultrasound for the differentiation between benign and malignant salivary gland tumors. The pooled sensitivity, specificity, and DOR were 0.62 (95%CI, 0.50–0.73), 0.93 (95%CI, 0.90–0.96), and 25.07 (95%CI, 4.28–146.65), respectively. The meta-regression and subgroup analyses found that assessment methods were associated with significant heterogeneity, and quantitative or semiquantitative elastosonography performed better than the qualitative one.ConclusionsElastosonography showed a limited value for diagnosing malignant salivary gland tumors; it could be considered as a supplementary diagnostic technology to conventional ultrasound, and quantitative or semiquantitative elastosonography was superior to the qualitative one.
Development and validation of a screening model for lung cancer using machine learning: A large-scale, multi-center study of biomarkers in breath
Authors: Li Jing , Zhang Yuwei , Chen Qing , Pan Zhenhua , Chen Jun , Sun Meixiu , Wang Junfeng , Li Yingxin , Ye Qing 
Published: September 2022

ObjectivesLung cancer (LC) is the largest single cause of death from cancer worldwide, and the lack of effective screening methods for early detection currently results in unsatisfactory curative treatments. We herein aimed to use breath analysis, a noninvasive and very simple method, to identify and validate biomarkers in breath for the screening of lung cancer.Materials and methodsWe enrolled a total of 2308 participants from two centers for online breath analyses using proton transfer reaction time-of-flight mass spectrometry (PTR-TOF-MS). The derivation cohort included 1007 patients with primary LC and 1036 healthy controls, and the external validation cohort included 158 LC patients and 107 healthy controls. We used eXtreme Gradient Boosting (XGBoost) to create a panel of predictive features and derived a prediction model to identify LC. The optimal number of features was determined by the greatest area under the receiver‐operating characteristic (ROC) curve (AUC).ResultsSix features were defined as a breath-biomarkers panel for the detection of LC. In the training dataset, the model had an AUC of 0.963 (95% CI, 0.941–0.982), and a sensitivity of 87.1% and specificity of 93.5% at a positivity threshold of 0.5. Our model was tested on the independent validation dataset and achieved an AUC of 0.771 (0.718–0.823), and sensitivity of 67.7% and specificity of 73.0%.ConclusionOur results suggested that breath analysis may serve as a valid method in screening lung cancer in a borderline population prior to hospital visits. Although our breath-biomarker panel is noninvasive, quick, and simple to use, it will require further calibration and validation in a prospective study within a primary care setting.