bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of osteoporosis in patients with nephrolithiasis and vice versa: a cumulative analysis
Authors: Jia Shunjie , Liao Jian , Wang Yucheng , Zheng Wenbiao , Jin Jinghua , Xu Weifang , Zheng Qi 
Published: July 2023

PurposeNephrolithiasis is thought to be a risk factor for osteoporosis, but data assessing if osteoporosis predisposes to the risk of nephrolithiasis are lacking. The present study aims to investigate whether patients with nephrolithiasis have a prominently higher prevalence of osteoporosis than the controls and vice versa via a cumulative analysis.MethodsFour databases were used to detect the eligible studies. We calculated the relative risk (RR) with a 95% confidence interval (CI) to assess the combined effect. The methodologies for conducting this study followed the PRISMA guidelines and were registered in the PROSPERO (ID: CRD42023395875),ResultsNine case-control or cohort studies with a total of 454,464 participants were finally included. Combined results indicated that there was a significantly higher prevalence of osteoporosis in patients with nephrolithiasis as compared to the general population without nephrolithiasis (overall RR from six studies= 1.204, 95%CI: 1.133 to 1.28, P&lt; 0.001; heterogeneity: I2 = 34.8%, P= 0.162). Conversely, osteoporosis was significantly correlated to an increased risk of nephrolithiasis as compared to the controls without osteoporosis (overall RR from four studies= 1.505, 95%CI: 1.309 to 1.731, P&lt; 0.001; I2 = 89.8%, P&lt; 0.001). Sensitivity analysis on the two categories validated the above findings. No significant publication bias was identified in this study.ConclusionsThe present study highlighted a significantly high prevalence of osteoporosis in patients with nephrolithiasis and vice versa. This reciprocal association reminded the clinicians to conduct a regular follow-up assessment when managing patients with nephrolithiasis or osteoporosis, especially for the elderly.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#searchadvanced, identifier CRD42023395875.
Low cross reactivity between wild type and deamidated AAV can lead to false negative results in immune monitoring T-cell assays
Authors: Bing So Jin , Warrington Stephanee , Mazor Ronit 
Published: July 2023

During gene therapy trials, immune responses against adeno-associated virus (AAV) vectors are monitored by antibody assays that detect the humoral and T-cell mediated cellular responses to AAV vectors. T cell assays commonly utilize the collection of patients’ peripheral blood mononuclear cells (PBMCs) and stimulation with AAV-derived overlapping peptides. We recently described that spontaneous deamidation coincides with T cell epitopes in AAV capsids and that spontaneous deamidation may enhance or decrease immunogenicity in some individuals. This raised the concern for false negative results of antibody detection and PBMC immune monitoring assays because these assays use wild-type (WT) AAV or WT peptides for T cell re-stimulation and these peptides may not re-activate T cells that were stimulated with deamidated AAV capsid. To investigate this concern, we modeled the scenario by expanding T cells with deamidated peptides and evaluated the cross-reactivity of expanded T cells to WT peptides. In the majority of samples, cells that were expanded with deamidated peptides and restimulated with WT peptide had significantly lowered IL-2 and IFN-γ production. Spiking the four deamidated peptides to the WT peptide pool used for re-stimulation, restored the signal and corrected the performance of the assay. We also evaluated the impact of deamidation on anti AAV binding antibodies and did not observe a major impact on seroprevalence detection of AAV9. These data indicate that a high level of deamidation in AAV therapy may result in underestimation or even failure to detect immune responses against WT peptides during cellular immune monitoring.
Post-mortem findings in Spanish patients with COVID-19; a special focus on superinfections
Authors: Ruiz-Cáceres Inmaculada , Hermida Romero Teresa , Guerra Merino Isabel , Portu Zapirain Joseba , Pérez-Mies Belén , Sánchez-Conde Matilde , Riaño Marina Alonso , Rubio Rafael , Fortés Alen Jose , Vidal González Ánxela , Salas Antón Clara , Múñez Elena , Sánchez Sánchez Rafael , Corona-Mata Diana , Aldecoa Ansorregui Iban , Miró José M. , Beloqui Pérez de Obanos Raquel , Ibero Carlos , Gómez-Román Javier , Fariñas M. Carmen , Tabuyo Bello Teresa , de Alava Enrique , Cisneros José Miguel , Matías-Guiu Xavier , Rivero Antonio ,   on behalf of the NECROCOVID Study Group
Published: July 2023

IntroductionWhole-body autopsies may be crucial to understand coronavirus disease 2019 (COVID-19) pathophysiology. We aimed to analyze pathological findings in a large series of full-body autopsies, with a special focus on superinfections.MethodsThis was a prospective multicenter study that included 70 COVID-19 autopsies performed between April 2020 and February 2021. Epidemiological, clinical and pathological information was collected using a standardized case report form.ResultsMedian (IQR) age was 70 (range 63.75–74.25) years and 76% of cases were males. Most patients (90%,) had at least one comorbidity prior to COVID-19 diagnosis, with vascular risk factors being the most frequent. Infectious complications were developed by 65.71% of the patients during their follow-up. Mechanical ventilation was required in most patients (75.71%) and was mainly invasive. In multivariate analyses, length of hospital stay and invasive mechanical ventilation were significantly associated with infections (p = 0.036 and p = 0.013, respectively). Necropsy findings revealed diffuse alveolar damage in the lungs, left ventricular hypertrophy in the heart, liver steatosis and pre-infection arteriosclerosis in the heart and kidneys.ConclusionOur study confirms the main necropsy histopathological findings attributed to COVID-19 in a large patient series, while underlining the importance of both comorbid conditions and superinfections in the pathology.
Clinical features and treatment outcomes of Vibrio vulnificus infection in the coastal city of Ningbo, China
Authors: Wang Jieyi , Weng Xingbei , Weng Yuesong , Xu Quanjun , Lu Yao , Mo Yijun 
Published: July 2023

BackgroundVibrio vulnificus is a gram-negative, opportunistic pathogen common to warm waters worldwide. Human V. vulnificus infection is rare and typically affects those residing in coastal areas during the summer months, but it causes rapid deterioration and is fatal.MethodsThe medical records of six patients with sepsis caused by V. vulnificus infection who were treated at the First Affiliated Hospital of Ningbo University from 2020 to 2022 were retrospectively reviewed. The patient demographics, clinical symptoms, laboratory test results, treatments, and outcomes are summarized.ResultsVibrio vulnificus infection was confirmed by blood or pus culture, 16S ribosomal DNA sequencing, and metagenomic next-generation sequencing. All six patients were male with pre-existing liver diseases and two reported consuming seafood before the onset of symptoms. Of the six patients, four succumbed to the disease, two recovered, and one underwent leg amputation.ConclusionVibrio vulnificus infection progresses rapidly and is highly fatal, thus prompt and aggressive treatment is necessary. Vibrio vulnificus infection should be considered in older (&gt;40 years) patients with a history of liver disease and recent consumption of seafood or exposure to seawater, especially those residing in coastal areas during the summer months.
Prediction of rehabilitation induced motor recovery after stroke using a multi-dimensional and multi-modal approach
Authors: Salvalaggio Silvia , Turolla Andrea , Andò Martina , Barresi Rita , Burgio Francesca , Busan Pierpaolo , Cortese Anna Maria , D’Imperio Daniela , Danesin Laura , Ferrazzi Giulio , Maistrello Lorenza , Mascotto Eleonora , Parrotta Ilaria , Pezzetta Rachele , Rigon Elena , Vedovato Anna , Zago Sara , Zorzi Marco , Arcara Giorgio , Mantini Dante , Filippini Nicola 
Published: July 2023

BackgroundStroke is a debilitating disease affecting millions of people worldwide. Despite the survival rate has significantly increased over the years, many stroke survivors are left with severe impairments impacting their quality of life. Rehabilitation programs have proved to be successful in improving the recovery process. However, a reliable model of sensorimotor recovery and a clear identification of predictive markers of rehabilitation-induced recovery are still needed. This article introduces the cross-modality protocols designed to investigate the rehabilitation treatment’s effect in a group of stroke survivors.Methods/designA total of 75 stroke patients, admitted at the IRCCS San Camillo rehabilitation Hospital in Venice (Italy), will be included in this study. Here, we describe the rehabilitation programs, clinical, neuropsychological, and physiological/imaging [including electroencephalography (EEG), transcranial magnetic stimulation (TMS), and magnetic resonance imaging (MRI) techniques] protocols set up for this study. Blood collection for the characterization of predictive biological biomarkers will also be taken. Measures derived from data acquired will be used as candidate predictors of motor recovery.Discussion/summaryThe integration of cutting-edge physiological and imaging techniques, with clinical and cognitive assessment, dose of rehabilitation and biological variables will provide a unique opportunity to define a predictive model of recovery in stroke patients. Taken together, the data acquired in this project will help to define a model of rehabilitation induced sensorimotor recovery, with the final aim of developing personalized treatments promoting the greatest chance of recovery of the compromised functions.
Cardiocerebrovascular risk in sensorineural hearing loss: results from the National Health and Nutrition Examination Survey 2015 to 2018
Authors: Zheng Jianrong , Cheng Yajing , Zhan Ying , Liu Cong , Lu Bihua , Hu Jun 
Published: July 2023

ObjectiveThis study aims to determine whether the risks of cardiocerebrovascular disease are relevant to sensorineural hearing loss (SNHL) based on a national database.MethodsA total of 1,321 participants aged from 18 to 69 with complete data including medical history and audiometry from the NHANES database (2015–2018) were analyzed. All included participants had available hearing data and the average thresholds of the hearing data were measured and calculated as low-frequency pure-tone average (LFPTA; 500, 1,000, and 2,000 Hz) and high-frequency pure-tone average (HFPTA; 3,000, 4,000, 6,000, and 8,000 kHz). SNHL was defined as an average pure tone of more than or equal to 20 dB in at least one better ear. Multivariable models to assess the association between cardiocerebrovascular risks and SNHL were used in this study.ResultsThe prevalence of stroke was 1.6% in individuals with SNHL and 0.4% in individuals without SNHL (p = 0.023). A higher cardiovascular risk score was observed in SNHL patients compared to participants without SNHL (1.58 vs. 0.90, p &lt; 0.001). Stroke was associated with a 3.67-fold increase in the risk of SNHL (95% CI: 1.12–12.00, p = 0.032) in univariable logistic regression, and the association (OR = 4.22, 95%CI = 1.28–13.93, p = 0.020) remained significant after adjusting for several covariates. Multivariable logistic regression models indicated a positive correlation between cardiovascular risk and SNHL (OR = 1.66, 95% CI = 1.40–1.96, p &lt; 0.001), but no significant relationship was shown with all covariates adjusted. However, significant associations were found between SNHL and both age and sex in both univariable and multivariable logistic regression models.ConclusionOur findings suggested that a higher cardiocerebrovascular risk burden was associated with an increased risk of SNHL, and the relationship may be influenced by age and sex. Future longitudinal studies are needed to investigate the mechanistic and pathologic vascular hypothesis of SNHL.
Electrocardiogram monitoring as a predictor of neurological and survival outcomes in patients with out-of-hospital cardiac arrest: a single-center retrospective observational study
Authors: Takahashi Masaki , Ogura Kentaro , Goto Tadahiro , Hayakawa Mineji 
Published: July 2023

IntroductionThis study hypothesized that monitoring electrocardiogram (ECG) waveforms in patients with out-of-hospital cardiac arrest (OHCA) could have predictive value for survival or neurological outcomes. We aimed to establish a new prognostication model based on the single variable of monitoring ECG waveforms in patients with OHCA using machine learning (ML) techniques.MethodsThis observational retrospective study included successfully resuscitated patients with OHCA aged ≥ 18 years admitted to an intensive care unit in Japan between April 2010 and April 2020. Waveforms from ECG monitoring for 1 h after admission were obtained from medical records and examined. Based on the open-access PTB-XL dataset, a large publicly available 12-lead ECG waveform dataset, we built an ML-supported premodel that transformed the II-lead waveforms of the monitoring ECG into diagnostic labels. The ECG diagnostic labels of the patients in this study were analyzed for prognosis using another model supported by ML. The endpoints were favorable neurological outcomes (cerebral performance category 1 or 2) and survival to hospital discharge.ResultsIn total, 590 patients with OHCA were included in this study and randomly divided into 3 groups (training set, n = 283; validation set, n = 70; and test set, n = 237). In the test set, our ML model predicted neurological and survival outcomes, with the highest areas under the receiver operating characteristic curves of 0.688 (95% CI: 0.682–0.694) and 0.684 (95% CI: 0.680–0.689), respectively.ConclusionOur ML predictive model showed that monitoring ECG waveforms soon after resuscitation could predict neurological and survival outcomes in patients with OHCA.
A diagnostic model of nerve root compression localization in lower lumbar disc herniation based on random forest algorithm and surface electromyography
Authors: Wang Hujun , Wang Yingpeng , Li Yingqi , Wang Congxiao , Qie Shuyan 
Published: July 2023

ObjectiveThis study aimed to investigate the muscle activation of patients with lumbar disc herniation (LDH) during walking by surface electromyography (SEMG) and establish a diagnostic model based on SEMG parameters using random forest (RF) algorithm for localization diagnosis of compressed nerve root in LDH patients.MethodsFifty-eight patients with LDH and thirty healthy subjects were recruited. The SEMG of tibialis anterior (TA) and lateral gastrocnemius (LG) were collected bilaterally during walking. The peak root mean square (RMS-peak), RMS-peak time, mean power frequency (MPF), and median frequency (MF) were analyzed. A diagnostic model based on SEMG parameters using RF algorithm was established to locate compressed nerve root, and repeated reservation experiments were conducted for verification. The study evaluated the diagnostic efficiency of the model using accuracy, precision, recall rate, F1-score, Kappa value, and area under the receiver operating characteristic (ROC) curve.ResultsThe results showed that delayed activation of TA and decreased activation of LG were observed in the L5 group, while decreased activation of LG and earlier activation of LG were observed in the S1 group. The RF model based on eight SEMG parameters showed an average accuracy of 84%, with an area under the ROC curve of 0.93. The RMS peak time of TA was identified as the most important SEMG parameter.ConclusionThese findings suggest that the RF model can assist in the localization diagnosis of compressed nerve roots in LDH patients, and the SEMG parameters can provide further references for optimizing the diagnosis model in the future.
The effect of the alpha-specific PI3K inhibitor alpelisib combined with anti-HER2 therapy in HER2+/PIK3CA mutant breast cancer
Authors: Cataldo Maria Letizia , De Placido Pietro , Esposito Daniela , Formisano Luigi , Arpino Grazia , Giuliano Mario , Bianco Roberto , De Angelis Carmine , Veneziani Bianca Maria 
Published: July 2023

BackgroundHER2 is amplified or overexpressed in around 20% of breast cancers (BC). HER2-targeted therapies have significantly improved the prognosis of patients with HER2+ BC, however, de novo and acquired resistance to anti-HER2 treatment is common. Activating mutations in the PIK3CA gene are reported in ∼30% of HER2+ BC and are associated with resistance to anti-HER2 therapies and a poor prognosis. Here, we investigated the in vitro and in vivo antitumor efficacy of the alpha-specific PI3K inhibitor alpelisib alone or in combination with anti-HER2 therapy using a panel of HER2+ BC cell lines. We also generated models of acquired resistance to alpelisib to investigate the mechanisms underlying resistance to alpha-specific PI3K inhibition.Materials and methodsPIK3CA mutant (HCC1954, KPL4 and JMT1) and wild-type (BT474 and SKBR3) HER2+ BC cell lines were used. The HCC1954 and KPL4 cells were chronically exposed to increasing concentrations of alpelisib or to alpelisib + trastuzumab in order to generate derivatives with acquired resistance to alpelisib (AR) and to alpelisib + trastuzumab (ATR). The transcriptomic profiles of HCC1954, KPL4 and their AR and ATR derivatives were determined by RNA sequencing. Cell growth was assessed by MTT assay. Changes in the protein levels of key PI3K pathway components were assessed by Western blotting. Gene expression, cellular and patients’ data from the Cancer Dependency Map (DepMap) and KMPlot datasets were interrogated.ResultsHER2+ BC cell lines harboring activating mutations in PIK3CA were less sensitive to single or dual anti-HER2 blockade compared to PIK3CA wild-type cells. Alpelisib treatment resulted in dose-dependent inhibition of the growth of cells with or without PIK3CA mutations and enhanced the antitumor efficacy of anti-HER2 therapies in vitro. In addition, alpelisib greatly delayed tumor growth of HCC1954 xenografts in vivo. Functional annotation of the significantly differentially expressed genes suggested the common activation of biological processes associated with oxidation reduction, cell proliferation, immune response and RNA synthesis in alpelisib-resistant models compared with native cells. Eight commonly upregulated genes (log2 fold-change &gt;1, False Discovery Rate [FDR] &lt;0.05) in models with acquired resistance to alpelisib or alpelisib + trastuzumab were identified. Among these, AKR1C1 was associated with alpelisib-resistance in vitro and with a poor prognosis in patients with HER2+ BC.ConclusionsOur findings support the use of an alpha-selective PI3K inhibitor to overcome the therapeutic limitations associated with single or dual HER2 blockade in PIK3CA-mutant HER2+ breast cancer. Future studies are warranted to confirm the potential role of candidate genes/pathways in resistance to alpelisib.
GHRL as a prognostic biomarker correlated with immune infiltrates and progression of precancerous lesions in gastric cancer
Authors: Wang Jinyun , Liu Dingwei , Xie Yong 
Published: July 2023

ObjectiveGhrelin is a protein that regulate appetite and energy balance in the human body, which is encoded by the ghrelin prepropeptide gene (GHRL). GHRL is linked with carcinogenesis and immune regulation. However, the correlation of GHRL to prognosis and tumor-infiltrating lymphocytes in gastric cancer (GC) remains unclear.MethodsIn this study, we assessed the transcriptional expression, prognosis, and different clinicopathological features about GHRL and the correlation between GHRL and tumor infiltration immune cells in GC patients based on the data published in the following databases: TIMER, GEPIA, GEO, STRING, UALCAN, TISIDB, and Kaplan–Meier Plotter. Furthermore, R software analysis for GC Correa’ cascade was also provided. Finally, GHRL expression in GC tissues was assayed using quantitative real-time polymerase chain reaction and immunohistochemistry.ResultsWe found that GHRL expression in GC samples was lower than in normal samples and verified by quantitative PCR (qPCR) and immunohistochemistry. However, sample type, cancer stage, and worse survival were correlated to high GHRL expression. We also found that the expression of GHRL in dysplasia was significantly lower than that in CNAG and in GC. High GHRL expression was connected with immunomodulators, chemokines, and infiltrating levels of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells in GC.ConclusionsGHRL is a prognostic biomarker for GC patients, and it is correlated with progression of precancerous lesions in GC. It might lead to poor prognosis by regulating tumor immune microenvironment. Studies are important to explore therapeutic targeting GHRL in the future.
Copine 7 promotes colorectal cancer proliferation through PKM2 interaction and MAPK signaling pathway
Authors: Yu Tianwen , Huang Changhao , Lai Chen , He Qing , Yuan Weijie , Chen Zihua 
Published: July 2023

IntroductionColorectal cancer (CRC) is currently the third most common cancer in the world, and its prevalence and mortality rate continue to increase.MethodsBased on an analysis of The Cancer Genome Atlas database, Tumor Immune Estimation Resource and Gene Expression Profiling Interactive Analysis, we explored the expression of CPNE7 in tumors. Immunohistochemistry and quantitative polymerase chain reaction analysis the expression of CPNE7 in colorectal cancer. Our study explored how CPNE7 promotes CRC cell proliferation and migration in vitro and in vivo. Transcriptome sequencing and Co-IP assay explored the underlying mechinaism of CPNE7 founction.ResultsWe found the CPNE7 was overexpressed in CRC by database and IHC. CPNE7 promoted CRC cells proliferstion and migration in vitro and in vivo. Comparing and analyzing transcriptome sequencing between exogenous up-/downregulated CPNE7 CRC cells and the controls, we found that CPNE7 activates mitogen-activated protein kinase (MAPK) signaling pathway stimulating cancer cell proliferation. Coimmunoprecipitation experiments revealed an interaction between CPNE7 and pyruvate kinase muscle protein (PKM2). We also found the activity of MAPK signaling is regulated by exogenous CPNE7 expression.DiscussionThese results imply that CPNE7 may promote the progression of CRC by interacting with PKM2 and initiating the MAPK signaling pathway.