bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-Invasive Multimodal Neuromonitoring in Non-Critically Ill Hospitalized Adult Patients With COVID-19: A Systematic Review and Meta-Analysis
Authors: Battaglini Denise , Premraj Lavienraj , Huth Samuel , Fanning Jonathon , Whitman Glenn , Arora Rakesh C. , Bellapart Judith , Bastos Porto Diego , Taccone Fabio Silvio , Suen Jacky Y. , Li Bassi Gianluigi , Fraser John F. , Badenes Rafael , Cho Sung-Min , Robba Chiara ,   the COVID-19 Critical Care Consortium
Published: April 2022

IntroductionNeurological complications are frequent in patients with coronavirus disease-2019 (COVID-19). The use of non-invasive neuromonitoring in subjects without primary brain injury but with potential neurological derangement is gaining attention outside the intensive care unit (ICU). This systematic review and meta-analysis investigates the use of non-invasive multimodal neuromonitoring of the brain in non-critically ill patients with COVID-19 outside the ICU and quantifies the prevalence of abnormal neuromonitoring findings in this population.MethodsA structured literature search was performed in MEDLINE/PubMed, Scopus, Cochrane, and EMBASE to investigate the use of non-invasive neuromonitoring tools, including transcranial doppler (TCD); optic nerve sheath diameter (ONSD); near-infrared spectroscopy (NIRS); pupillometry; and electroencephalography (EEG) inpatients with COVID-19 outside the ICU. The proportion of non-ICU patients with CVOID-19 and a particular neurological feature at neuromonitoring at the study time was defined as prevalence.ResultsA total of 6,593 records were identified through literature searching. Twenty-one studies were finally selected, comprising 368 non-ICU patients, of whom 97 were considered for the prevalence of meta-analysis. The pooled prevalence of electroencephalographic seizures, periodic and rhythmic patterns, slow background abnormalities, and abnormal background on EEG was.17 (95% CI 0.04–0.29), 0.42 (95% CI 0.01–0.82), 0.92 (95% CI 0.83–1.01), and.95 (95% CI 0.088–1.09), respectively. No studies investigating NIRS and ONSD outside the ICU were found. The pooled prevalence for abnormal neuromonitoring findings detected using the TCD and pupillometry were incomputable due to insufficient data.ConclusionsNeuromonitoring tools are non-invasive, less expensive, safe, and bedside available tools with a great potential for both diagnosis and monitoring of patients with COVID-19 at risk of brain derangements. However, extensive literature searching reveals that they are rarely used outside critical care settings.Systematic Review Registration:www.crd.york.ac.uk/prospero/display_record.php?RecordID=265617, identifier: CRD42021265617.
Simplified Post-stroke Functioning Assessment Based on ICF via Dichotomous Mokken Scale Analysis and Rasch Modeling
Authors: Feng Chun , Jiang Zhong-Li , Sun Ming-Xue , Lin Feng 
Published: April 2022

PurposeThis study aims to accomplish two tasks for International Classification of Functioning, Disability and Health (ICF) application among persons with stroke: (1) to make an ICF tool for measuring personal abilities with simplified assessment operations; (2) to quantitatively evaluate ICF categories for being functioning rather than being disabled.MethodsA total of 130 inpatients with stroke via convenience sampling were evaluated by the extended comprehensive ICF core set for stroke, modified Rankin scale, and modified Barthel index (MBI). This study investigated the responses to 118 stroke-related ICF items (59 items in b and d domains individually) using Mokken scale analysis followed with Rasch modeling.ResultsA Mokken scale with 47 items was extracted from the binary data (1 as no-impairment or mild-impairment and 0 as moderate to complete impairment). A Rasch model with 45 items was derived from the Mokken scale. The conversion chart was available involving the original ordinal scores to Rasch-transformed scores from 0 to 100 (interval scale). Total scores exhibited a high correlation with the personal abilities estimated by the Rasch model. The personal ability also demonstrated a significantly strong correlation with the score of the MBI. Thus, the 45 ICF items were suggested to rate potential functional ability as a single measurement.ConclusionBased on simple “functioning or disabled” judgment tasks, ICF assessment can be simplified to a questionnaire with answering “yes-or-no” questions for each category. Functioning level for each person and difficulty of being functioning for each category can be estimated by the Rasch model of this questionnaire.
Influential Factors, Treatment and Prognosis of Autoimmune Encephalitis Patients With Poor Response to Short-Term First-Line Treatment
Authors: Liu Fei , Zhang Bingbing , Huang Teng , Wang Baojie , Wang Chunjuan , Hao Maolin , Guo Shougang 
Published: April 2022

ObjectiveThis study was performed to assess the potential factors for poor short-term first-line treatment response, the appropriate further treatment options, and the prognosis in patients with autoimmune encephalitis (AE).MethodsThis retrospective study consisted of 135 patients with AE. According to their short-term first-line treatment response, patients were divided into the response group and the non-response group. The demographics, clinical characteristics, main accessory examinations, immunotherapy, and outcomes of patients were compared between the two groups. Univariate and multivariate logistic regression models were used to analyze whether non-responders have poor long-term outcomes. Further treatment and prognosis of non-responders were also analyzed.ResultsOf the 128 patients who were treated with first-line immunotherapy, 59 (46.1%) were non-responders. Patients in the non-response group had more symptoms and exhibited a higher proportion of mental behavior disorder, central hypoventilation, and autonomic nervous dysfunction. The modified Rankin scale (mRS) scores and neutrophil-to-lymphocyte ratio (NLR) levels were significantly higher and albumin, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A (apoA) levels were significantly lower in the non-response group (p &lt; 0.05, all). Multivariate logistic regression analysis showed that the number of clinical symptoms, mental behavior disorder, central hypoventilation, maximum mRS score, and albumin level was independently associated with non-response to short-term first-line treatment. Non-responders had poor long-term outcomes compared with the responders at all times of followed-up (p &lt; 0.05, all). In multivariable analysis, initial first-line treatment response was independently associated with the long-term prognosis, both at 12-month [odds ratio (OR), 4.74, 95% CI, 1.44–15.59, and p=0.010] and 24-month follow-ups (OR, 8.81, 95% CI, 1.65–47.16; and p = 0.011). Among the non-responders, a higher improvement of mRS scores was observed in those who received second-line treatment than those who had no further treatment or repetition of first-line immunotherapy in the follow-up. However, the rate of a good outcome and median mRS scores were not significantly different among the three groups.ConclusionDisease severity, clinical features, anti-N-methyl-D-aspartate receptor subtypes, antibody titers, NLR, albumin, HDL-C, and apoA levels were all associated with non-response to short-term first-line treatment. The short-term first-line treatment response is a valuable predictor of long-term outcomes in patients with AE. Second-line immunotherapy may be a more aggressive treatment option for patients who failed short-term first-line immunotherapy.
Use of Benzodiazepines and Z-Drugs in Multiple Sclerosis
Authors: Marrie Ruth Ann , Fisk John D. , Walld Randy , Bolton James M. , Sareen Jitender , Patten Scott B. , Singer Alexander , Lix Lisa M. , Hitchon Carol A. , El-Gabalawy Renée , Katz Alan , Marriott James J. , Bernstein Charles N. ,   the CIHR Team in Defining the Burden Managing the Effects of Psychiatric Comorbidity in Chronic Immunoinflammatory Disease
Published: April 2022

ObjectiveUse of benzodiazepines and Z-drugs (non-benzodiazepine sedative hypnotics) is controversial due to adverse health outcomes in the general population. However, little is known about their use in people with multiple sclerosis (MS). We estimated the incidence and prevalence of benzodiazepine and Z-drug use (jointly BZD) in the MS population as compared to an age-, sex- and geographically-matched population without MS, and examined the association of mood/anxiety disorders with the use of BZD over a twenty-year period.MethodsUsing administrative data from Manitoba, Canada, we identified 2,985 persons with incident MS and 14,891 persons without MS matched 5:1 on sex, birth year and region. We applied validated case definitions to identify persons with any mood/anxiety disorder. Dispensations of BZD were identified. To assess the association between MS, mood/anxiety disorders and BZD use we constructed generalized linear models adjusting for age, sex, index year, socioeconomic status, urban/rural residence, physical comorbidities, and health care use. We also examined patterns of BZD use.ResultsIn 2016, the crude incidence of benzodiazepine use in the MS cohort was 2.10% (95%CI: 1.43–2.98%), 1.49-fold higher than in the non-MS cohort (1.41%; 95%CI: 1.18–1.67%). The crude incidence of Z-drug use in the MS cohort was 1.77% (95%CI: 1.20–2.51%), 1.78-fold higher than in the non-MS cohort (0.99%; 95%CI: 0.81–1.21%). After adjusting for covariates, among individuals without an active mood/anxiety disorder, the MS cohort had a 39% increased incidence rate of benzodiazepine use and a 72% increased incidence rate of Z-drug use as compared to the non-MS cohort. Among individuals with an active mood/anxiety disorder, the incidence of BZD use did not differ between the MS and non-MS cohorts. A higher proportion of people with MS used BZD for ≥6 months than people without MS.ConclusionUse of BZD is more common in people with MS than in general population controls, and use of these agents is in persons with MS is often chronic.
Cyclotrons Operated for Nuclear Medicine and Radiopharmacy in the German Speaking D-A-CH Countries: An Update on Current Status and Trends
Authors: Zippel Claus , Ermert Johannes , Patt Marianne , Gildehaus Franz Josef , Ross Tobias L. , Reischl Gerald , Kuwert Torsten , Solbach Christoph , Neumaier Bernd , Kiss Oliver , Mitterhauser Markus , Wadsak Wolfgang , Schibli Roger , Kopka Klaus 
Published: April 2022

BackgroundCyclotrons form a central infrastructure and are a resource of medical radionuclides for the development of new radiotracers as well as the production and supply of clinically established radiopharmaceuticals for patient care in nuclear medicine.AimTo provide an updated overview of the number and characteristics of cyclotrons that are currently in use within radiopharmaceutical sciences and for the development of radiopharmaceuticals to be used for patient care in Nuclear Medicine in Germany (D), Austria (A) and Switzerland (CH).MethodsPublicly available information on the cyclotron infrastructure was (i) consolidated and updated, (ii) supplemented by selective desktop research and, last but not least, (iii) validated by members of the committee of the academic “Working Group Radiochemistry and Radiopharmacy” (AGRR), consisting of radiochemists and radiopharmacists of the D-A-CH countries and belonging to the German Society of Nuclear Medicine (DGN), as well as the Radiopharmaceuticals Committee of the DGN.ResultsIn total, 42 cyclotrons were identified that are currently being operated for medical radionuclide production for imaging and therapy in Nuclear Medicine clinics, 32 of them in Germany, 4 in Austria and 6 in Switzerland. Two thirds of the cyclotrons reported (67%) are operated by universities, university hospitals or research institutions close to a university hospital, less by/in cooperation with industrial partners (29%) or a non-academic clinic/ PET-center (5%). Most of the cyclotrons (88%) are running with up to 18 MeV proton beams, which is sufficient for the production of the currently most common cyclotron-based radionuclides for PET imaging.DiscussionThe data presented provide an academically-updated overview of the medical cyclotrons operated for the production of radiopharmaceuticals and their use in Nuclear Medicine in the D-A-CH countries. In this context, we discuss current developments and trends with a view to the cyclotron infrastructure in these countries, with a specific focus on organizational aspects.
Gene Mutations Associated With Clinical Characteristics in the Tumors of Patients With Breast Cancer
Authors: Hao Chunfang , Wang Chen , Lu Ning , Zhao Weipeng , Li Shufen , Zhang Li , Meng Wenjing , Wang Shuling , Tong Zhongsheng , Zeng Yanwu , Lu Leilei 
Published: April 2022

BackgroundClinical characteristics including estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) are important biomarkers in the treatment of breast cancer, but how genomic mutations affect their status is rarely studied. This study aimed at finding genomic mutations associated with these clinical characteristics.MethodsThere were 160 patients with breast cancer enrolled in this study. Samples from those patients were used for next-generation sequencing, targeting a panel of 624 pan-cancer genes. Short nucleotide mutations, copy number variations, and gene fusions were identified for each sample. Fisher’s exact test compared each pair of genes. A similarity score was constructed with the resulting P-values. Genes were clustered with the similarity scores. The identified gene clusters were compared to the status of clinical characteristics including ER, PR, HER2, and a family history of cancer (FH) in terms of the mutations in patients.ResultsGene-by-gene analysis found that CCND1 mutations were positively correlated with ER status while ERBB2 and CDK12 mutations were positively correlated with HER2 status. Mutation-based clustering identified four gene clusters. Gene cluster 1 (ADGRA2, ZNF703, FGFR1, KAT6A, and POLB) was significantly associated with PR status; gene cluster 2 (COL1A1, AXIN2, ZNF217, GNAS, and BRIP1) and gene cluster 3 (FGF3, FGF4, FGF19, and CCND1) were significantly associated with ER status; gene cluster 2 was also negatively associated with a family history of cancer; and gene cluster 4 was significantly negatively associated with age. Patients were classified into four corresponding groups. Patient groups 1, 2, 3, and 4 had 24.1%, 36.5%, 38.7%, and 41.3% of patients with an FDA-recognized biomarker predictive of response to an FDA-approved drug, respectively.ConclusionThis study identified genomic mutations positively associated with ER and PR status. These findings not only revealed candidate genes in ER and PR status maintenance but also provided potential treatment targets for patients with endocrine therapy resistance.
Improved Survival Prediction by Combining Radiological Imaging and S-100B Levels Into a Multivariate Model in Metastatic Melanoma Patients Treated With Immune Checkpoint Inhibition
Authors: Burgermeister Simon , Gabryś Hubert S. , Basler Lucas , Hogan Sabrina A. , Pavic Matea , Bogowicz Marta , Martínez Gómez Julia M. , Vuong Diem , Tanadini-Lang Stephanie , Foerster Robert , Huellner Martin W. , Dummer Reinhard , Levesque Mitchell P. , Guckenberger Matthias 
Published: April 2022

PurposeWe explored imaging and blood bio-markers for survival prediction in a cohort of patients with metastatic melanoma treated with immune checkpoint inhibition.Materials and Methods94 consecutive metastatic melanoma patients treated with immune checkpoint inhibition were included into this study. PET/CT imaging was available at baseline (Tp0), 3 months (Tp1) and 6 months (Tp2) after start of immunotherapy. Radiological response at Tp2 was evaluated using iRECIST. Total tumor burden (TB) at each time-point was measured and relative change of TB compared to baseline was calculated. LDH, CRP and S-100B were also analyzed. Cox proportional hazards model and logistic regression were used for survival analysis.ResultsiRECIST at Tp2 was significantly associated with overall survival (OS) with C-index=0.68. TB at baseline was not associated with OS, whereas TB at Tp1 and Tp2 provided similar predictive power with C-index of 0.67 and 0.71, respectively. Appearance of new metastatic lesions during follow-up was an independent prognostic factor (C-index=0.73). Elevated LDH and S-100B ratios at Tp2 were significantly associated with worse OS: C-index=0.73 for LDH and 0.73 for S-100B. Correlation of LDH with TB was weak (r=0.34). A multivariate model including TB change, S-100B, and appearance of new lesions showed the best predictive performance with C-index=0.83.ConclusionOur analysis shows only a weak correlation between LDH and TB. Additionally, baseline TB was not a prognostic factor in our cohort. A multivariate model combining early blood and imaging biomarkers achieved the best predictive power with regard to survival, outperforming iRECIST.
Epstein–Barr Virus, But Not Human Papillomavirus, Is Associated With Preinvasive and Invasive Ocular Surface Squamous Neoplasias in Zambian Patients
Authors: Julius Peter , Siyumbwa Stepfanie N. , Moonga Phyllis , Maate Fred , Kaile Trevor , Haynatski Gleb , Minhas Veenu , Snow Jazmine , Peterson Kerstin , Gihozo Patience , Streeter Sam , Kaur Salan , Evans Annika , Gonzalez Daniela , Samwel Kandali , Kang Guobin , West John T. , Wood Charles , Angeletti Peter C. 
Published: April 2022

BackgroundThe etiopathogenesis of ocular surface squamous neoplasia (OSSN) is not fully understood. We assessed the frequency of oncogenic viruses in OSSN by immunohistochemistry (IHC) and polymerase chain reaction (PCR) for human papillomavirus (HPV), Epstein–Barr virus (EBV), Merkel cell polyomavirus (MCPyV), Kaposi sarcoma virus, and adenovirus. Cases from Zambia were prospectively enrolled using a cross-sectional study design between November 2017 and March 2020.MethodsDemographic and clinical data [age, sex, HIV status, antiretroviral therapy (ART) history, CD4 count, plasma viral load] and tumor biopsies were collected from 243 consenting patients. Tumor samples were bisected, and half was used for DNA isolation, while the other half was formalin fixed and paraffin embedded (FFPE) for histopathology analysis. The expressions of latent EBV nuclear antigen 1 (EBNA1), CDKN2A/p16INK4A (p16), and MCPyV large T-antigen (LT) were tested by IHC. Multiplex PCR was used to detect 16 HPV genotypes and four other DNA tumor viruses [Kaposi’s sarcoma-associated herpesvirus (KSHV), EBV, MCPyV, and adenovirus]. Relationships between HIV status, viral DNA and protein expression, and tumor grades were determined by statistical analysis.ResultsOSSN tumors from patients were 29.6% preinvasive and 70.4% invasive. Patients presented with unilateral tumors that were 70.4% late stage (T3/T4). OSSN patients were HIV positive (72.8%). IHC on 243 FFPE biopsies resulted in the detection of EBNA1 (EBV), p16 high-risk HPV (HR-HPV), and MCPyV LT expression in 89.0%, 4.9%, and 0.0%, respectively. EBNA1 was expressed in all grades of preinvasive [cornea–conjunctiva intraepithelial neoplasia (CIN)1, 100%; CIN2, 85.7%; CIN3, 95.8%; and carcinoma in situ (CIS), 83.8%] and in invasive (89.2%) OSSN. PCR on 178 samples detected EBV, HR-HPV, and MCPyV in 80.3%, 9.0%, and 13.5% of tumors, respectively. EBV was detected in all grades of preinvasive and invasive OSSN. EBV detection was associated with high HIV viral loads (p = 0.022). HR-HPV was detected in 0.0% CIN1, 0.0% CIN2, 5.6% CIN3, 13.0% CIS, and 7.0% invasive OSSN.ConclusionsOur findings of EBV DNA and EBNA1 protein in all the grades of preinvasive and especially invasive OSSN are consistent with a potential causal role for EBV in OSSN. A role of HPV in OSSN was not clearly established in this study.
Prognostic Implication of Energy Metabolism-Related Gene Signatures in Lung Adenocarcinoma
Authors: Mu Teng , Li Haoran , Li Xiangnan 
Published: April 2022

BackgroundLung adenocarcinoma (LUAD) is the major non-small-cell lung cancer pathological subtype with poor prognosis worldwide. Herein, we aimed to build an energy metabolism-associated prognostic gene signature to predict patient survival.MethodsThe gene expression profiles of patients with LUAD were downloaded from the TCGA and GEO databases, and energy metabolism (EM)-related genes were downloaded from the GeneCards database. Univariate Cox and LASSO analyses were performed to identify the prognostic EM-associated gene signatures. Kaplan–Meier and receiver operating characteristic (ROC) curves were plotted to validate the predictive effect of the prognostic signatures. A CIBERSORT analysis was used to evaluate the correlation between the risk model and immune cells. A nomogram was used to predict the survival probability of LUAD based on a risk model.ResultsWe constructed a prognostic signature comprising 13 EM-related genes (AGER, AHSG, ALDH2, CIDEC, CYP17A1, FBP1, GNB3, GZMB, IGFBP1, SORD, SOX2, TRH and TYMS). The Kaplan–Meier curves validated the good predictive ability of the prognostic signature in TCGA AND two GEO datasets (p&lt;0.0001, p=0.00021, and p=0.0034, respectively). The area under the curve (AUC) of the ROC curves also validated the predictive accuracy of the risk model. We built a nomogram to predict the survival probability of LUAD, and the calibration curves showed good predictive ability. Finally, a functional analysis also unveiled the different immune statuses between the two different risk groups.ConclusionOur study constructed and verified a novel EM-related prognostic gene signature that could improve the individualized prediction of survival probability in LUAD.
Hemato-Oncological Diseases as Risk Factor for Recurrence or Metastasis of Pleomorphic Dermal Sarcoma
Authors: Helbig Doris 
Published: April 2022

BackgroundAtypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are increasingly common sarcomas of the skin with a genetic UV signature. Immunosuppression is a known risk factor for developing other UV-induced skin cancers such as cutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC), and Merkel cell carcinoma with increased mortality. In case reports or small case series of AFX/PDS patients, immunosuppression has been hypothesized as a risk factor for the development of distant metastases. The aim of the present study was to analyze immunosuppression as a risk factor for AFX/PDS in a large patient cohort.MethodsA cohort of 164 patients with AFX/PDS (47 AFX and 117 PDS) was collected between 2003 and 2021 and analyzed for clinicopathological data with a special focus on immunosuppression.ResultsOf all patients, 29.9% had any kind of immunosuppression; 6.4% of the AFX and 12.0% of the PDS patients had underlying hemato-oncological diseases. Patients with immunosuppression due to an underlying hemato-oncological disease had a significantly increased risk of progressing to (p = 0.010) and developing distant organ metastases (p = 0.000).ConclusionsImmunosuppression seems to be a risk factor for developing AFX/PDS with worse clinical outcomes. Therefore, immunosuppression, especially underlying hemato-oncological diseases, should be considered in the treatment and follow-up care of patients with AFX/PDS.