bluuebunny/crossref_metadata_2025_split huggingface dataset:
Race, Ethnic, and Sex Differences in Prevalence of and Trends in Hallucinogen Consumption Among Lifetime Users in the United States Between 2015 and 2019
Authors: Davis Alan K. , Arterberry Brooke J. , Xin Yitong , Agin-Liebes Gabrielle , Schwarting Corrine , Williams Monnica T. 
Published: March 2022

BackgroundThe current study is one of the first to examine race, ethnic, and sex differences in the prevalence of and trends in hallucinogen use among lifetime users in the United States.MethodsData came from the 2015–2019 National Survey on Drug Use and Health and included respondent's reporting ever-using hallucinogens (n = 41,060; female = 40.4%). Descriptive and multinomial logistic regression analyses were conducted in Stata.ResultsHighest prevalence of past year hallucinogen use was among Asian females (35.06%), which was two-or-more times larger than prevalence of past year use among White males/females and Native American males. More than half of White males/females, Multiracial males, and Hispanic males reported had ever-used psilocybin or LSD, whereas less than one-quarter of Black males/females reported lifetime psilocybin use, and less than a third of Black females reported lifetime LSD use. Native American males had the lowest prevalence of lifetime MDMA use (17.62–33.30%) but had the highest lifetime prevalence of peyote use (40.37–53.24%). Pacific Islander males had the highest prevalence of lifetime mescaline use (28.27%), and lifetime DMT use was highest among Pacific Islander males/females (15.68–38.58%). Black, Asian, and Multiracial people had greater odds of past-year (ORs = 1.20–2.02; ps &lt; 0.05) and past-month (ORs = 1.39–2.06; ps &lt; 0.05) hallucinogen use compared to White people. Females had lower odds of past-year (OR = 0.79; ps &lt; 0.05), past-month (OR = 0.78; ps &lt; 0.05) hallucinogen use compared to males, except for lifetime use of MDMA (OR = 1.29; ps &lt; 0.05).ConclusionsThese findings should inform public health initiatives regarding potential benefits and risks of hallucinogen use among racial/ethnic groups and women.
ACE2 Serum Levels as Predictor of Infectability and Outcome in COVID-19
Authors: Maza María del Carmen , Úbeda María , Delgado Pilar , Horndler Lydia , Llamas Miguel A. , van Santen Hisse M. , Alarcón Balbino , Abia David , García-Bermejo Laura , Serrano-Villar Sergio , Bastolla Ugo , Fresno Manuel 
Published: March 2022

BackgroundCOVID‐19 can generate a broad spectrum of severity and symptoms. Many studies analysed the determinants of severity but not among some types of symptoms. More importantly, very few studies analysed patients highly exposed to the virus that nonetheless remain uninfected.MethodsWe analysed serum levels of ACE2, Angiotensin II and anti-Spike antibodies in 2 different cohorts at high risk of viral exposure, highly exposed but uninfected subjects, either high risk health care workers or persons cohabiting with infected close relatives and seropositive patients with symptoms. We tested the ability of the sera of these subjects to neutralize lentivirus pseudotyped with the Spike-protein.ResultsWe found that the serum levels of ACE2 are significantly higher in highly exposed but uninfected subjects. Moreover, sera from this seronegative persons can neutralize SARS-CoV-2 infection in cellular assays more strongly that sera from non-exposed negative controls eventhough they do not have anti-CoV-2 IgG antibodies suggesting that high levels of ACE2 in serum may somewhat protect against an active infection without generating a conventional antibody response. Finally, we show that among patients with symptoms, ACE2 levels were significantly higher in infected patients who developed cutaneous as compared with respiratory symptoms and ACE2 was also higher in those with milder symptoms.ConclusionsThese findings suggest that soluble ACE2 could be used as a potential biomarker to predict SARS-CoV-2 infection risk and to discriminate COVID-19 disease subtypes.
Effective Diagnosis of Prostate Cancer Based on mRNAs From Urinary Exosomes
Authors: Gan Jiahua , Zeng Xing , Wang Xiong , Wu Ya , Lei Ping , Wang Zhihua , Yang Chunguang , Hu Zhiquan 
Published: March 2022

BackgroundNovel non-invasive biomarkers are urgently required to improve the diagnostic sensitivity and specificity of prostate cancer (PCa). Therefore, the diagnostic value of following candidate genes (ERG, PCA3, ARV7, PSMA, CK19, and EpCAM) were estimated by testing mRNAs from urinary exosomes of patients with primary PCa.MethodsExosomes were obtained using size-exclusion chromatography (SEC), out of which RNAs were extracted, then analyzed by quantitative reverse transcription-polymerase chain reaction according to manufacturer’s protocol.ResultsThe expression of urinary exosomal ERG, PCA3, PSMA, CK19, and EpCAM were significantly increased in patients with PCa compared with healthy males. In addition, the levels of urinary exosomal ERG, ARV7, and PSMA were intimately correlated with the Gleason score in PCa patients (P &lt; 0.05). The receiver operating characteristic curves (ROCs) showed that urinary exosomal ERG, PCA3, PSMA, CK19, and EpCAM were able to distinguish patients with PCa from healthy individuals with the area under the curve (AUC) of 0.782, 0.783, 0.772, 0.731, and 0.739, respectively. Urinary exosomal PCA3 and PSMA distinguished PCa patients from healthy individuals with an AUC of 0.870. Combination of urinary exosomal PCA3, PSMA with serum PSA and PI-RADS achieved higher AUC compared with PSA alone (0.914 and 0.846, respectively). Kaplan-Meier curves demonstrated that PCA3, ARV7, and EpCAM were associated in androgen-deprivation therapy (ADT) failure time which is defined as from the initiation of ADT in hormone-sensitive stage to the development of castration-resistant prostate cancer.ConclusionThese findings suggested that mRNAs from urinary exosomes have the potential in serving as novel and non-invasive indicators for PCa diagnosis and prediction.
Patient-Reported Symptoms and Sequelae 12 Months After COVID-19 in Hospitalized Adults: A Multicenter Long-Term Follow-Up Study
Authors: Comelli Agnese , Viero Giulia , Bettini Greta , Nobili Alessandro , Tettamanti Mauro , Galbussera Alessia Antonella , Muscatello Antonio , Mantero Marco , Canetta Ciro , Martinelli Boneschi Filippo , Arighi Andrea , Brambilla Paolo , Vecchi Maurizio , Lampertico Pietro , Bonfanti Paolo , Contoli Marco , Blasi Francesco , Gori Andrea , Bandera Alessandra 
Published: March 2022

ObjectiveOur knowledge on the long-term consequences of COVID-19 is still scarce despite the clinical relevance of persisting syndrome. The aim of this study was to analyze patient-reported outcomes, including assessment by specific questionnaires of health impairment and symptoms.MethodsThis is a prospective, observational and multicenter cohort study coordinated by Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico di Milano and Istituto di Ricerche Farmacologiche Mario Negri IRCCS including eight hospitals located in North and Central Italy. A telephone interview to assess rehospitalization, access to health care resources, general health status subjective evaluation, and symptoms was performed at 12 months after the discharge in patients admitted to hospital because of COVID-19 from February 2020 to the end of May 2020.ResultsAmong the 776 patients discharged alive, 44 (5.7%) died, 456 subjects (58.8%) completed the questionnaire and 276 (35.6%) were not reachable or refused to join the telephone interview. The mean age of the study population was 59.4 years (SD 14.1), 69.8% of individuals needed oxygen support during hospitalization and 10.4% were admitted to ICU. Overall, 91.7% of participants reported at least one symptom/sequela at 12 months. Exertional dyspnea (71.7%), fatigue (54.6%), and gastrointestinal symptoms (32.8%) were the most reported ones. Health issues after discharge including hospitalization or access to emergency room were described by 19.4% of subjects. Female and presence of comorbidities were independent predictors of whealth impairment and presence of ≥2 symptoms/sequelae after 12 months from hospitalization for COVID-19.ConclusionsPatient-reported symptoms and sequelae, principally dyspnea and fatigue, are found in most individuals even 12 months from COVID-19 hospitalization. Long-term follow-up based on patient-centered outcome can contribute to plan tailored interventions.
Significance of D-Dimer in Acute Ischemic Stroke Patients With Large Vessel Occlusion Accompanied by Active Cancer
Authors: Pan Kwang Hyun , Kim Jaeyoun , Chung Jong-Won , Kim Keon Ha , Bang Oh Young , Jeon Pyoung , Kim Gyeong-Moon , Seo Woo-Keun 
Published: March 2022

BackgroundThis study aimed to investigate clinical outcome predictors of acute stroke patients with large vessel occlusion and active cancer and validate the significance of D-dimer levels for endovascular thrombectomy decisions.MethodsWe analyzed a prospectively collected hospital-based stroke registry to determine clinical EVT outcomes of acute stroke patients within 24 h with following criteria: age ≥18 years, NIHSS ≥6, and internal carotid artery or middle cerebral artery lesion. All patients were classified into EVT and non-EVT groups. Patients were divided into two groups by initial D-dimer level. We explored variables potentially associated with successful recanalization as well as 3-month functional outcomes and mortality rates.ResultsAmong 68 patients, 36 were treated with EVT, with successful recanalization in 55.6%. The low D-dimer group showed a higher rate of successful recanalization and favorable outcome than the high D-dimer group. The mortality rate was higher in the high D-dimer group. No EVT and high D-dimer level were independent predictors of mortality, whereas lesion volume and low D-dimer level were independently associated with favorable outcomes.ConclusionsD-dimer level is a prognostic factor in acute LVO stroke patients with active cancer, and its high value for EVT decisions provisionally supports its testing in this patient population.
Expansion of Clinical and Genetic Spectrum of DDX3X Neurodevelopmental Disorder in 23 Chinese Patients
Authors: Dai Yuwei , Yang Zhuanyi , Guo Jialing , Li Haoyu , Gong Jiaoe , Xie Yuanyuan , Xiao Bo , Wang Hua , Long Lili 
Published: March 2022

AimDe novo DDX3X variants account for 1–3% of unexplained intellectual disability cases in females and very rarely in males. Yet, the clinical and genetic features of DDX3X neurodevelopmental disorder in the Chinese cohort have not been characterized.MethodA total of 23 Chinese patients (i.e., 22 female and 1 male) with 22 de novo DDX3X deleterious variants were detected among 2,317 probands with unexplained intellectual disability (ID) undertaking whole exome sequencing (WES). The age, sex, genetic data, feeding situation, growth, developmental conditions, and auxiliary examinations of the cohort were collected. The Chinese version of the Gesell Development Diagnosis Scale (GDDS-C) was used to evaluate neurodevelopment of DDX3X patients. The Social Communication Questionnaire (SCQ)-Lifetime version was applied as a primary screener to assess risk for autism spectrum disorder (ASD).ResultA total of 17 DDX3X variants were novel and 22 were de novo. Missense variants overall were only slightly more common than loss-of-function variants and were mainly located in two functional subdomains. The average age of this cohort was 2.67 (±1.42) years old. The overlapping phenotypic spectrum between this cohort and previously described reports includes intellectual disability (23/23, 100%) with varying degrees of severity, muscle tone abnormalities (17/23, 73.9%), feeding difficulties (13/23, 56.5%), ophthalmologic problems (11/23, 47.8%), and seizures (6/23, 26.1%). A total of 15 individuals had notable brain anatomical disruption (15/23, 65.2%), including lateral ventricle enlargement, corpus callosum abnormalities, and delayed myelination. Furthermore, 9 patients showed abnormal electroencephalogram results (9/23, 39.1%). Hypothyroidism was first noted as a novel clinical feature (6/23, 26.1%). The five primary neurodevelopmental domains of GDDS-C in 21 patients were impaired severely, and 13 individuals were above the “at-risk” threshold for ASD.InterpretationAlthough a certain degree of phenotypic overlap with previously reported cohorts, our study described the phenotypic and variation spectrum of 23 additional individuals carrying DDX3X variants in the Chinese population, adding hypothyroidism as a novel finding. We confirmed the importance of DDX3X as a pathogenic gene in unexplained intellectual disability, supporting the necessity of the application of WES in patients with unexplained intellectual disability.
Urine- and Blood-Based Molecular Profiling of Human Prostate Cancer
Authors: Chen Gang , Jia Guojin , Chao Fan , Xie Feng , Zhang Yue , Hou Chuansheng , Huang Yong , Tang Haoran , Yu Jianjun , Zhang Jihong , Jia Shidong , Xu Guoxiong 
Published: March 2022

ObjectiveProstate cancer (PCa) is one of the most common malignant tumors, accounting for 20% of total tumors ranked first in males. PCa is usually asymptomatic at the early stage and the specificity of the current biomarkers for the detection of PCa is low. The present study evaluates circulating tumor DNA (ctDNA) in blood or urine, which can be used as biomarkers of PCa and the combination of these markers may increase the sensitivity and specificity of the detection of PCa.MethodsTissue, blood, and urine samples were collected from patients with PCa. All prostate tissue specimens underwent pathological examination. A hybrid-capture-based next-generation sequencing assay was used for plasma and urinary ctDNA profiling. Sequencing data were analyzed by an in-house pipeline for mutation calling. Mutational profiles of PCa and BPH were compared in both plasma and urine samples. Associations of detected mutations and clinical characteristics were statistically analyzed.ResultsA significant association of mutation allele frequencies (MAFs) in the blood samples with patients with metastatic PCa rather than patients with primary PCa, and MAFs are changed after treatment in patients with PCa. Further, the number of mutations in urine is not associated with clinical characteristics of PCa patients, but the frequencies of mutation alleles in the urine are associated with patient age. Comparison of cfDNA aberration profiles between urine and blood reveals more alterations in urine than in blood, including TP53, AR, ATM, MYC, and SPOP mutations.ConclusionThis work provides the potential clinical application of urine, in addition to blood, as a powerful and convenient non-invasive approach in personalized medicine for patients with PCa.
Multimorbidity Is Associated With Pain Over 6 Years Among Community-Dwelling Mexican Americans Aged 80 and Older
Authors: Milani Sadaf Arefi , Raji Mukaila A. , Kuo Yong-Fang , Lopez David S. , Markides Kyriakos S. , Al Snih Soham 
Published: March 2022

IntroductionMultimorbidity, the co-occurrence of two or more chronic conditions, is common among older adults and is associated with decreased quality of life, greater disability, and increased mortality. Yet, the association of multimorbidity with pain, another significant contributor to decreased quality of life, has not been widely studied. This is especially understudied among very old (aged ≥ 80) Mexican Americans, a fast-growing segment of the United States (US) population.ObjectiveTo assess the association of multimorbidity with pain in very old Mexican Americans, over six years of follow-up.MethodsWe used data from Waves 7 (2010/2011) to 9 (2015/2016) of the Hispanic Established Populations for the Epidemiologic Study of the Elderly, a longitudinal study of older Mexican Americans residing in the Southwestern US. Multimorbidity was defined as reporting two or more chronic health conditions. Pain was defined as (1) pain on weight-bearing, (2) pain in back, hips, knees, ankles/feet, legs, entire body, or two or more locations, and (3) pain that limits daily activities. We use generalized estimation equations to estimate the odds ratio of pain as a function of multimorbidity over 6 years.ResultsAt baseline (n = 841), 77.3% of participants had multimorbidity. Those with multimorbidity had greater odds [2.27, 95% confidence interval (CI): 1.74, 2.95] of reporting pain on weight-bearing over time, compared to those without multimorbidity. Also, those with multimorbidity had 2.12 times the odds of reporting pain that limited their daily activities (95% CI: 1.61, 2.78) compared to those without multimorbidity. Lastly, those with multimorbidity had higher odds of reporting pain in their back, knee, ankles/feet, legs, hips, entire body, or two or more locations, compared to those without multimorbidity.ConclusionsThose with multimorbidity consistently had higher odds of all types of pain, highlighting the need for early management of pain among those with multiple chronic conditions and complex health needs. This is especially important among very old Mexican Americans, who have a high burden of chronic health conditions.
Real-World Metastatic Renal Cell Carcinoma Treatment Patterns and Clinical Outcomes in The Netherlands
Authors: van Laar S.A. , Gombert-Handoko K.B. , Groenwold R.H.H. , van der Hulle T. , Visser L.E. , Houtsma D. , Guchelaar H.J. , Zwaveling J. 
Published: March 2022

The number of treatment options for patients with metastatic renal cell carcinoma (mRCC) has significantly grown in the last 15 years. Although randomized controlled trials are fundamental in investigating mRCC treatment efficacy, their external validity can be limited. Therefore, the efficacy of the different treatment options should also be evaluated in clinical practice. We performed a chart review of electronic health records using text mining software to study the current treatment patterns and outcomes. mRCC patients from two large hospitals in the Netherlands, starting treatment between January 2015 and May 2020, were included. Data were collected from electronic health records using a validated text mining tool. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan–Meier method. Most frequent first-line treatments were pazopanib (n = 70), sunitinib (n = 34), and nivolumab with ipilimumab (n = 28). The overall median PFS values for first-line treatment were 15.7 months (95% confidence interval [95%CI], 8.8–20.7), 16.3 months (95%CI, 9.3–not estimable [NE]) for pazopanib, and 6.9 months (95% CI, 4.4–NE) for sunitinib. The overall median OS values were 33.4 months (95%CI, 28.1–50.9 months), 39.3 months (95%CI, 29.5–NE) for pazopanib, and 28.1 months (95%CI, 7.0–NE) for sunitinib. For nivolumab with ipilimumab, median PFS and median OS were not reached. Of the patients who finished first- and second-line treatments, 64 and 62% received follow-up treatments, respectively. With most patients starting on pazopanib and sunitinib, these real-world treatment outcomes were most likely better than in pivotal trials, which may be due to extensive follow-up treatments.
Olmesartan Attenuates Single-Lung Ventilation Induced Lung Injury via Regulating Pulmonary Microbiota
Authors: Lu Di , Wang Zhizhi , Chen Zhiming , Fan Jiayang , Zhai Jianxue , Fang Duopei , Cai He , Liu Xiguang , Wu Hua , Cai Kaican 
Published: March 2022

Single-lung ventilation (SLV) associated acute lung injury is similar to ischemia reperfusion (IR) injury which is usually occurred during lung surgery. Olmesartan (Olm), a novel angiotensin receptor blocker (ARB), has been reported to ameliorate organ IR injury. Several recent studies have shown that lung microbiota may be involved in pulmonary diseases, but the effect of pulmonary microbiota in SLV-induced lung injury has not been reported. This study aims to determine the mechanism of how Olm attenuates SLV induced lung injury. Our data showed that 7 days Olm treatment before modeling markedly alleviated SLV-induced lung injury by suppressing inflammation and reactive oxygen species. Bronchoalveolar lavage fluid samples from the injured side were collected for 16S rRNA gene-based sequencing analysis and 53 different bacteria at the genus and species levels were identified. Furthermore, the injured lung samples were collected for metabolomics analysis using liquid chromatography-mass spectrometry analyses to explore differential metabolites. The Kyoto Encyclopedia of Genes and Genomes (KEGG) was applied to analyze the correlation between differential metabolites and lung microbiota. A total of 38 pathways were identified according to differential metabolites and 275 relevant pathways were enriched via analyzing the microbial community, 24 pathways were both identified by analyzing either metabolites or microbiota, including pyrimidine metabolism, purine metabolism, aminoacyl-tRNA biosynthesis and ATP-binding cassette transporter. Besides classical blockage of the renin-angiotensin II system, Olm could also alleviate SLV-induced lung injury by rewiring the interaction between pulmonary microbiota and metabolites.
Sirtuin 2 Alleviates Chronic Neuropathic Pain by Suppressing Ferroptosis in Rats
Authors: Zhang Xiaojiao , Song Tao , Zhao Mengnan , Tao Xueshu , Zhang Bohan , Sun Cong , Wang Pinying , Wang Kunpeng , Zhao Lin 
Published: March 2022

Neuropathic pain (NP) is chronic and associated with poor effects of general analgesia. It affects patients’ health and quality of life. The apoptotic process of lipid peroxidation caused by iron overload is called ferroptosis, which may be associated with nervous system disease. A recent study has found that sirtuin 2 (SIRT2) achieves a neuroprotective effect by suppressing ferroptosis. Herein, we aimed to examine whether SIRT2 regulated spared nerve injury (SNI)-induced NP by suppressing ferroptosis in rats. A rat model of NP was induced in adult male Sprague-Dawley rats weighing 200–250 g. Mechanical allodynia was observed from the first day after SNI and continued for 14 days. Compared with age-matched control rats, the expression of SIRT2 and ferroportin 1 (FPN1) decreased in the L4-6 spinal cord of the SNI-induced NP rats. In addition, we observed that the levels of both iron and anti-acyl-coenzyme A synthetase long-chain family member 4 (ACSL4) were significantly increased in the spinal cord after SNI, while the expression of glutathione peroxidase 4 (GPX4) was decreased. Furthermore, an intrathecal injection of SIRT2 overexpressed recombinant adenovirus, which upregulated the expression of SIRT2, attenuated mechanical allodynia, enhanced the level of FPN1, inhibited intracellular iron accumulation, and reduced oxidant stress levels, thereby reversing the changes to ACSL4 and GPX4 expression in the SNI rats. This evidence suggests that SIRT2-targeted therapeutics may help relieve the symptoms of chronic NP.