bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of prognostic biomarkers in the CMTM family genes of human ovarian cancer through bioinformatics analysis and experimental verification
Authors: Zhang Mengjun , Wang Jialin , Yue Haodi , Zhang Lindong 
Published: August 2022

Background: Ovarian cancer (OV) is one of the most common gynecological malignancies worldwide, and its immunotherapy has considerable prospects. Multiple members of the CMTM family were aberrantly expressed in human cancers and controlled key malignant biological processes and immune regulation in cancer development. However, little is known about the function of this gene family in ovarian cancer, especially in terms of immunity.Methods: GEPIA, Oncomine, HPA, Kaplan–Meier plotter, cBioPortal, GeneMANIA, and TIMER were used to analyze the differential gene expression, prognostic value, genetic alterations, and alterations in the immune microenvironment of the CMTM family in patients with ovarian cancer. Importantly, RT-qPCR was used to verify the gene expression of the CMTM family.Results: CMTM1/3/4/6/7/8 showed abnormally high expression at the mRNA and protein levels in OV tissues based on the GEPIA and HPA databases. RT-qPCR showed that CMTM1/6/8 was highly expressed in ovarian cancer cell lines. IHC verified that CMTM8 is highly expressed in ovarian cancer tissues and is closely related to Ki-67. Survival analysis showed that high expression of CMTM1/2/3/5/8 can lead to a significant reduction in overall survival and progression-free survival. There were many types of genetic alterations in the CMTM family. Also, CMTM1/2/3/6 had a certain correlation with the changes in the immune microenvironment such as immune cell infiltration and immune checkpoint expression, which may be the potential mechanism of the CMTM family in ovarian cancer. IHC verified that CMTM6 is highly expressed in ovarian cancer tissues and is closely related to PD-L1.Conclusion: This study confirmed that the CMTM family has abnormal expression in ovarian cancer and CMTM8 can be used as a biomarker for prognostic evaluation. Also, the CMTM family may be used as a potential target for immunotherapy based on the suppression of immune checkpoints.
Genomic study of nonsyndromic hearing loss in unaffected individuals: Frequency of pathogenic and likely pathogenic variants in a Brazilian cohort of 2,097 genomes
Authors: Quaio Caio Robledo D’ Angioli Costa , Coelho Antonio Victor Campos , Moura Livia Maria Silva , Guedes Rafael Lucas Muniz , Chen Kelin , Ceroni Jose Ricardo Magliocco , Minillo Renata Moldenhauer , Caraciolo Marcel Pinheiro , Reis Rodrigo de Souza , Azevedo Bruna Mascaro Cordeiro de , Nobrega Maria Soares , Teixeira Anne Caroline Barbosa , Martinelli Lima Matheus , Mota Thamara Rayssa da , Matta Marina Cadena da , Colichio Gabriela Borges Cherulli , Roncalho Aline Lulho , Ferreira Ana Flavia Martinho , Campilongo Gabriela Pereira , Perrone Eduardo , Virmond Luiza do Amaral , Moreno Carolina Araujo , Prota Joana Rosa Marques , França Marina de , Cervato Murilo Castro , Almeida Tatiana Ferreira de , Oliveira Filho Joao Bosco de 
Published: August 2022

Hearing loss (HL) is a common sensory deficit in humans and represents an important clinical and social burden. We studied whole-genome sequencing data of a cohort of 2,097 individuals from the Brazilian Rare Genomes Project who were unaffected by hearing loss to investigate pathogenic and likely pathogenic variants associated with nonsyndromic hearing loss (NSHL). We found relevant frequencies of individuals harboring these alterations: 222 heterozygotes (10.59%) for sequence variants, 54 heterozygotes (2.58%) for copy-number variants (CNV), and four homozygotes (0.19%) for sequence variants. The top five most frequent genes and their corresponding combined allelic frequencies (AF) were GJB2 (AF = 1.57%), STRC (AF = 1%), OTOA (AF = 0.69%), TMPRSS3 (AF = 0.41%), and OTOF (AF = 0.29%). The most frequent sequence variant was GJB2:c.35del (AF = 0.72%), followed by OTOA:p. (Glu787Ter) (AF = 0.61%), while the most recurrent CNV was a microdeletion of 57.9 kb involving the STRC gene (AF = 0.91%). An important fraction of these individuals (n = 104; 4.96%) presented variants associated with autosomal dominant forms of NSHL, which may imply the development of some hearing impairment in the future. Using data from the heterozygous individuals for recessive forms and the Hardy–Weinberg equation, we estimated the population frequency of affected individuals with autosomal recessive NSHL to be 1:2,222. Considering that the overall prevalence of HL in adults ranges from 4–15% worldwide, our data indicate that an important fraction of this condition may be associated with a monogenic origin and dominant inheritance.
Prognostic and immune-related value of complement C1Q (C1QA, C1QB, and C1QC) in skin cutaneous melanoma
Authors: Yang Huanglong , Che Dehui , Gu Yuxiang , Cao Dongsheng 
Published: August 2022

Background: Skin cutaneous melanoma (SKCM) is a common malignancy that is associated with increased morbidity and mortality. Complement C1Q is composed of C1QA, C1QB, and C1QC and is involved in the occurrence and development of many malignant tumours. However, the effect of C1QA, C1QB, and C1QC expression on tumour immunity and prognosis of cutaneous melanoma remains unclear.Methods: First, we analysed C1QA, C1QB, and C1QC expression levels and prognostic values using Gene Expression Profiling Interactive Analysis (GEPIA) and Tumour Immune Estimation Resource (TIMER) analysis, and further validation was performed using RT-qPCR, The Human Protein Atlas, The Cancer Genome Atlas (TCGA) dataset, and Gene Expression Omnibus dataset. We then performed univariate/multivariate Cox proportional hazard model, clinicopathological correlation, and receiver operating characteristic curve analysis using TCGA dataset and established a nomogram model. Differentially expressed genes associated with C1QA, C1QB, and C1QC in SKCM were identified and analysed using LinkedOmics, TIMER, the Search Tool for the Retrieval of Interacting Genes database, and Metascape and Cytoscape software platforms. We used TIMER, GEPIA, and single-sample gene set enrichment analysis (ssGSEA) to analyse the relationship between the three genes and the level of immune cell infiltration, biomarkers, and checkpoint expression in SKCM. Finally, GSEA was utilized to study the functional pathways of C1QA, C1QB, and C1QC enrichment in SKCM.Results: The overexpression of C1QA, C1QB, and C1QC provided significant value in the diagnosis of SKCM and has been associated with better overall survival (OS). Multivariate Cox regression analysis indicated that C1QA, C1QB, and C1QC are independent prognostic biomarkers for patients with SKCM. Immune cell infiltration, biomarkers, and checkpoints were positively correlated with the expression of C1QA, C1QB, and C1QC. Furthermore, the results of functional and pathway enrichment analysis showed that immune-related and apoptotic pathways were significantly enriched in the high-expression group of C1QA, C1QB, and C1QC.Conclusion: We found that C1QA, C1QB, and C1QC can be used as biomarkers for the diagnosis and prognosis of SKCM patients. The upregulated expression levels of these three complement components benefit patients from OS and may increase the effect of immunotherapy. This result may be due to the dual effects of anti-tumour immunity and apoptosis.
Rich and underreported: First integrated assessment of the diversity of mesopelagic fishes in the Southwestern Tropical Atlantic
Authors: Eduardo Leandro Nolé , Bertrand Arnaud , Lucena-Frédou Flávia , Villarins Bárbara Teixeira , Martins Júlia Rodrigues , Afonso Gabriel Vinícius Felix , Pietsch Theodore Wells , Frédou Thierry , Di Dario Fabio , Mincarone Michael Maia 
Published: August 2022

Mesopelagic fishes play critical ecological roles by sequestering carbon, recycling nutrients, and acting as a key trophic link between primary consumers and higher trophic levels. They are also an important food source for harvestable economically valuable fish stocks and a key link between shallow and deep-sea ecosystems. Despite their relevance, mesopelagic ecosystems are increasingly threatened by direct and indirect human activities while representing some of the largest and least understood environments on Earth. The composition, diversity, and other aspects of the most basic biological features of numerous mesopelagic groups of fishes are still poorly known. Here, we provide the first integrative study of the biodiversity of mesopelagic fishes of the southwestern Tropical Atlantic (SWTA), based on two expeditions in northeastern Brazil in 2015 and 2017. A full list of mesopelagic fishes of the region is provided, including rare species and new records for the Brazilian Exclusive Economic Zone and the indication of potentially new species in groups such as the Stomiiformes and Beryciformes. Key aspects of the diversity of mesopelagic fishes of the region were also assessed, considering different depth strata and diel periods. At least 200 species, 130 genera, 56 families, and 22 orders of the Teleostei and one shark (Isistius brasiliensis, Dalatiidae, Squaliformes) were recorded, including potentially eight new species (4%) and 50 (25%) new records for Brazilian waters. Five families accounted for 52% of the diversity, 88% of specimens collected, and 66% of the total biomass: Stomiidae (38 spp., 8% of specimens, 21% of biomass), Myctophidae (34 spp., 36%, 24%), Melamphaidae (11 spp., 2%, 7%), Sternoptychidae (9 spp., 26%, 10%), and Gonostomatidae (7 spp., 16%, 4%). During the day, richness and diversity were higher at lower mesopelagic depths (500–1000 m), with contributions of typically bathypelagic species likely associated with seamounts and oceanic islands. At night, richness and diversity increased at epipelagic depths, indicating the diel ascension of several species (e.g., myctophids and sternoptychids) that can endure temperature ranges of up to 25°C. Information on the geographic distribution of several rare species worldwide is also provided.
Opioid-free total intravenous anesthesia for thyroid and parathyroid surgery: Protocol for a randomized, double-blind, controlled trial
Authors: Wang Dan , Long Yu-qin , Sun Yan , Zhu Ya-juan , Feng Xiao-mei , Liu Hong , Ji Fu-hai , Peng Ke 
Published: August 2022

BackgroundOpioid-free anesthesia (OFA) may improve postoperative outcomes by reducing opioid-related adverse effects. This study aims to evaluate the effects of OFA on postoperative nausea and vomiting (PONV), postoperative pain, and 30-day outcomes after thyroid and parathyroid surgery.MethodsThis two-center, randomized, double-blind, controlled trial will include 400 adult patients scheduled for thyroid and parathyroid surgery. Patients will be randomly assigned, 1:1 and stratified by sex and site, to an OFA group (esketamine, lidocaine, and dexmedetomidine) or a control group (opioid-based anesthesia with sufentanil). All patients will receive propofol-based total intravenous anesthesia and PONV prophylaxis with dexamethasone and ondansetron. The primary outcome is the incidence of PONV (defined as experiencing any event of nausea, retching, or vomiting) during the first 48 h postoperatively. The secondary outcomes include the severity of PONV, antiemetic rescue therapy, pain scores at rest and while coughing, need for rescue analgesia, perioperative adverse effects related to anesthetics or analgesics (hypotension, bradycardia, hypertension, tachycardia, desaturation, dizziness, headache, hallucination, and nightmare), time to extubation, length of post-anesthesia care unit stay, length of postoperative hospital stay, patient satisfaction, and a composite of 30-day major adverse events (myocardial infarction, cardiac arrest, cerebrovascular accident, coma, acute renal failure, pulmonary embolism, sepsis, septic shock, deep neck space infection, reintubation, reoperation, blood transfusion, failure to wean off ventilator, and death). Analyses will be performed in the modified intention-to-treat population.DiscussionWe hypothesize that our OFA regimen reduces PONV after thyroid and parathyroid surgery. We will also investigate whether OFA leads to improvements in postoperative pain and major adverse events. Our results will offer evidence for optimizing anesthesia regimens in patients who undergo thyroid and parathyroid surgical procedures.Clinical trial registrationhttp://www.chictr.org.cn, identifier: ChiCTR2200059656.
Is ectopic Cushing’s syndrome underdiagnosed in patients with small cell lung cancer?
Authors: Piasecka Marta , Larsson Martin , Papakokkinou Eleni , Olsson Lena , Ragnarsson Oskar 
Published: August 2022

IntroductionEctopic Cushing’s syndrome (ECS) is an uncommon disorder. Recently, however, a larger proportion of patients with endogenous Cushing’s syndrome (CS) had ECS than has previously been reported.ObjectiveThe aim of this study was to determine whether ECS is an underdiagnosed disorder in patients with small-cell lung cancer (SCLC).Materials and methodsMedical records from consecutive patients diagnosed with SCLC at our hospital between 2013 and 2019 were reviewed (N = 213; mean age 69.5 ± 9 years; range, 36–89 years). The probability of having ECS was evaluated by review of biochemical and clinical features, including presence of recent onset diabetes mellitus, therapy resistant hypertension and/or spontaneous hypokalaemia.ResultsOf 213 identified patients with SCLC, one (0.5%) patient had confirmed ECS, two (1%) patients had probable ECS, and twenty-three (11%) patients had possibly ECS. Patients with SCLC and possibly or probable ECS exhibited a significantly shorter survival than patients only with SCLC (8 vs. 14 months, respectively).ConclusionsOur findings indicate that ECS is underdiagnosed in patients with SCLC. Given the serious consequences of untreated ECS, the low detection rate highlights the need to improve endocrine work-up of patients with SCLC who present with biochemical and clinical features associated with ECS. Prospective studies are needed to establish a reliable assessment of the incidence of ECS and to optimise early detection strategies.
Comparison of clinical safety and efficacy of dexmedetomidine, remifentanil, and propofol in patients who cannot tolerate non-invasive mechanical ventilation: A prospective, randomized, cohort study
Authors: Altınkaya Çavuş Mine , Gökbulut Bektaş Serife , Turan Sema 
Published: August 2022

Background and objectivesNon-invasive ventilation (NIV) is used in intensive care units (ICUs) to treat of respiratory failure. Sedation and analgesia are effective and safe for improving compliance in patients intolerant to NIV. Our study aimed to evaluate the effects of dexmedetomidine, remifentanil, and propofol on the clinical outcomes in NIV intolerant patients.MethodsThis prospective randomized cohort study was conducted in a tertiary ICU, between December 2018 and December 2019. We divided a total of 120 patients into five groups (DEXL, DEXH, REML, REMH, PRO). IBM SPSS Statistics 20 (IBM Corporation, Armonk, New York, USA) was used to conduct the statistical analyses.ResultsThe DEXL, DEXH, REML, and REMH groups consisted of 23 patients each while the PRO group consisted of 28 patients. Seventy-five patients (62.5%) became tolerant of NIV after starting the drugs. The NIV time, IMV time, ICU LOS, hospital LOS, intubation rate, side effects, and mortality were significantly different among the five groups (P = 0.05). In the groups that were given dexmedetomidine (DEXL, and DEXH), NIV failure, mortality, ICU LOS, and hospital LOS were lower than in the other groups.ConclusionIn this prospective study, we compared the results of three drugs (propofol, dexmedetomidine, and remifentanil) in patients with NIV intolerance. The use of sedation increased NIV success in patients with NIV intolerance. NIV failure, mortality, ICU LOS, IMV time, and hospital LOS were found to be lower with dexmedetomidine.
Alzheimer’s Disease Polygenic Risk Score Is Not Associated With Cognitive Decline Among Older Adults With Type 2 Diabetes
Authors: Manzali Sigalit B. , Yu Eric , Ravona-Springer Ramit , Livny Abigail , Golan Sapir , Ouyang Yuxia , Lesman-Segev Orit , Liu Lang , Ganmore Ithamar , Alkelai Anna , Gan-Or Ziv , Lin Hung-Mo , Heymann Anthony , Schnaider Beeri Michal , Greenbaum Lior 
Published: August 2022

ObjectivesMultiple risk loci for late-onset Alzheimer’s disease (LOAD) have been identified. Type 2 diabetes (T2D) is a risk factor for cognitive decline, dementia and Alzheimer’s disease (AD). We investigated the association of polygenic risk score (PRS) for LOAD with overall cognitive functioning and longitudinal decline, among older adults with T2D.MethodsThe study included 1046 Jewish participants from the Israel Diabetes and Cognitive Decline (IDCD) study, aged ≥ 65 years, diagnosed with T2D, and cognitively normal at baseline. The PRS included variants from 26 LOAD associated loci (at genome-wide significance level), and was calculated with and without APOE. Outcome measures, assessed in 18 months intervals, were global cognition and the specific domains of episodic memory, attention/working memory, executive functions, and language/semantic categorization. Random coefficient models were used for analysis, adjusting for demographic variables, T2D-related characteristics, and cardiovascular factors. Additionally, in a subsample of 202 individuals, we analyzed the association of PRS with the volumes of total gray matter, frontal lobe, hippocampus, amygdala, and white matter hyperintensities. Last, the association of PRS with amyloid beta (Aβ) burden was examined in 44 participants who underwent an 18F-flutemetamol PET scan.ResultsThe PRS was not significantly associated with overall functioning or decline in global cognition or any of the specific cognitive domains. Similarly, following correction for multiple testing, there was no association with Aβ burden and other brain imaging phenotypes.ConclusionOur results suggest that the cumulative effect of LOAD susceptibility loci is not associated with a greater rate of cognitive decline in older adults with T2D, and other pathways may underlie this link.
Exploring brain changes of impulse control disorders in Parkinson's disease: An ALE study
Authors: Gu Lihua , Shu Hao , Wang Yanjuan , Xu Hui 
Published: August 2022

BackgroundPrevious neuroimaging studies reported inconsistent results for comparison between Parkinson's disease (PD) with impulse control disorder (PD-ICD) and without ICD (PD-no ICD).MethodsA search was performed in databases (PubMed and Web of Science) to identify studies published before May 2022. An anatomic likelihood estimation (ALE) method study was made for neuroimaging studies in PD-ICD.ResultsThe study included 20 studies (including 341 PD-ICD and 437 PD-no ICD). PD-ICD patients showed significant cortical thinning in the right inferior frontal gyrus (IFG), the right middle frontal gyrus (MFG), the left superior frontal gyrus (SFG), the right precentral gyrus (PCG) and the left cingulate gyrus (CG), compared to PD-no ICD patients. The ALE study showed reduced resting-state brain activation in the right IFG, the right PCG, the left insula and the right transverse temporal gyrus (TTG) in PD-ICD, compared to PD-no ICD patients. In addition, PD-ICD showed increased resting-state brain activation in the right caudate, the bilateral insula and the left orbital gyrus (OG), compared to PD-no ICD patients. The study indicated reduced task-related brain activation in the right caudate, the right MFG, the right lentiform nucleus (LN) and the right precuneus (PCUN) in PD-ICD, compared to PD-no ICD patients. The study showed increased task-related brain activation in the left inferior parietal lobule (IPL), the right medial frontal gyrus, the right caudate and the right PCG in PD-ICD, compared to PD-no ICD patients.ConclusionsThe present ALE analysis has confirmed that brain changes in frontal, temporal and basal ganglia regions are among the most frequently reported regions in PD-ICD. Deficits in these regions could play a role in diagnosis of PD-ICD.
Structural magnetic resonance imaging findings and histopathological correlations in motor neuron diseases—A systematic review and meta-analysis
Authors: Zejlon Charlotte , Nakhostin Dominik , Winklhofer Sebastian , Pangalu Athina , Kulcsar Zsolt , Lewandowski Sebastian , Finnsson Johannes , Piehl Fredrik , Ingre Caroline , Granberg Tobias , Ineichen Benjamin Victor 
Published: August 2022

ObjectivesThe lack of systematic evidence on neuroimaging findings in motor neuron diseases (MND) hampers the diagnostic utility of magnetic resonance imaging (MRI). Thus, we aimed at performing a systematic review and meta-analysis of MRI features in MND including their histopathological correlation.MethodsIn a comprehensive literature search, out of 5941 unique publications, 223 records assessing brain and spinal cord MRI findings in MND were eligible for a qualitative synthesis. 21 records were included in a random effect model meta-analysis.ResultsOur meta-analysis shows that both T2-hyperintensities along the corticospinal tracts (CST) and motor cortex T2*-hypointensitites, also called “motor band sign”, are more prevalent in ALS patients compared to controls [OR 2.21 (95%-CI: 1.40–3.49) and 10.85 (95%-CI: 3.74–31.44), respectively]. These two imaging findings correlate to focal axonal degeneration/myelin pallor or glial iron deposition on histopathology, respectively. Additionally, certain clinical MND phenotypes such as amyotrophic lateral sclerosis (ALS) seem to present with distinct CNS atrophy patterns.ConclusionsAlthough CST T2-hyperintensities and the “motor band sign” are non-specific imaging features, they can be leveraged for diagnostic workup of suspected MND cases, together with certain brain atrophy patterns. Collectively, this study provides high-grade evidence for the usefulness of MRI in the diagnostic workup of suspected MND cases.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020182682.
Cost-Effectiveness of Pembrolizumab for the treatment of Non–Small-Cell lung cancer: A systematic review
Authors: Zhang Chuan , Zhang Jiaxu , Tan Jing , Tian Panwen , Li Weimin 
Published: August 2022

IntroductionPembrolizumab, an immune checkpoint inhibitor for treating non-small cell lung cancer (NSCLC), can impose a high financial burden. Several studies have explored the cost-effectiveness of this expensive agent. We conducted a systematic review and pooled analysis to evaluate the quality of the existing pharmacoeconomic studies on pembrolizumab strategies for NSCLC treatment as well as to conclude the cost-effectiveness of such strategies.MethodsEnglish and Chinese databases were searched to collect health economic studies on pembrolizumab therapies (monotherapy or a combination with chemotherapy) compared with chemotherapy for the treatment of NSCLC patients. The reporting quality, modeling methods, and results of incremental cost-effectiveness analysis of the included literature were descriptively analyzed.ResultsA total of 24 studies, 3 in Chinese and 21 in English, were selected. All reports satisfy a median of 31 out of 40 reporting quality assessment items based on a quality checklist for pharmacoeconomic evaluations. 12 studies used the Markov model and 11 used the partitioned survival model. A common problem identified in the modeling methods was the insufficient justification of the choices of model structure and data inputs. Pembrolizumab was found to be cost-effective in the United States and Switzerland, but not in China, France, the UK, or Singapore.ConclusionThe current cost-effectiveness studies on pembrolizumab for the treatment of NSCLC are of moderate quality, and the relevant decision-analytic modeling methods have much scope for improvement. The cost-effectiveness of pembrolizumab strategies for NSCLC varies across countries, warranting the need to pay more attention to the methodologies of pharmacoeconomic research in order to produce correct outcomes in terms of cost-effectiveness for different countries.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021250480