bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cannabis use and associated factors among 15–16-year-old adolescents in Estonia 2003–2019: Results from cross-sectional ESPAD surveys
Authors: Tamson Merili , Vorobjov Sigrid , Sokurova Diana , Pärna Kersti 
Published: April 2021

Aims: (1) To describe the time trends of monthly cannabis use and (2) to analyse the association between the trends of monthly cannabis use and trends of different explanatory factors among adolescents in Estonia in 2003–2019. Methods: Nationally representative data from five waves of the cross-sectional European School Survey Project on Alcohol and Other Drugs (ESPAD) among 15–16-year-old adolescents ( n = 11,348) in Estonia were analysed. Tests for trends were used to assess significant changes in monthly cannabis use and explanatory variables over time. Logistic regression analysis was used to analyse the association between monthly cannabis use and perceived easiness of getting cannabis, perceived health risk of cannabis use, parental factors, risk behaviours, and leisure time activities. The model included interaction terms between the study year and each explanatory variable. Gender-adjusted odds ratios ( OR) with 95% confidence intervals (CI) were calculated. Results: Monthly cannabis use increased from 5.3% in 2003 to 7.7% in 2015 and thereafter decreased to 6.6% in 2019 among adolescents in Estonia ( P = 0.007). The association between monthly cannabis use and alcohol use was significant over the study period and the interaction of alcohol use with study year indicated significantly increased effect of alcohol use over time ( P = 0.038). The association between monthly cannabis use and perceived easiness of obtaining cannabis, perceived low health risk from cannabis use and smoking was significant, but remained unchanged over the study period. The relationship between monthly cannabis use and low parental control was significant in two last study years but did not show any changes over time. Conclusions: The findings of this study demonstrate the need for the implementation of multi-component substance use prevention programmes among adolescents in Estonia that also pay attention to the factors associated with the cannabis use.
A Beam Projection-Based Modified Gamma Analysis Scheme for Clinically Interpretable Pre-Treatment Dose Verification
Authors: Wang Yiling , Yin Gang , Wang Jie , Zhao Yue , Liu Min , Lang Jinyi 
Published: April 2021

Purpose: To investigate a novel gamma analysis system for dose verification results in terms of clinical significance. Methods and Materials: The modified scheme redefined the computational domain of the conventional gamma analysis with the projections of beams and the regions of interest (ROI). We retrospectively studied 6 patients with the conventional and the modified gamma analysis schemes while compared their performances. The cold spots ratio of the planning target volume (PTV) and the hot spots ratio of the organs at risk (OAR) were also computed by the modified scheme to assess the clinical significance. Results: The result of the gamma passing rate in the modified method was conformable to that in the conventional method with a cut-off threshold of 5%. The cold spots ratio of PTV and hot spots ratio of OAR were able to be evaluated by the modified scheme. For an introduced 7.1% dose error, the discrimination ratio in gamma passing rate of the conventional method was lower than 2%, while it was improved to 5% by the modified method. Conclusions: The modified gamma analysis scheme had a comparable quality as the conventional scheme in terms of dose inspection. Besides, it could improve the clinical significance of the QA result and provide the assessment for ROI-specific discrepancy. The modified scheme could also be conveniently integrated into the conventional dose verification process, benefiting the less developed regions where high-end 3D dose verification devices are not affordable.
An epidemiological investigation of the 2019 suspected pertussis outbreak in northwestern Nigeria
Authors: Semeeh Omoleke , Getachew Biniam , Taofik Yusuf , Surajudeen Lukman , Hassan Assad , Nagudale Bello 
Published: April 2021

Introduction: In 2019, we investigated the profile of the cases and controls and the determinants of pertussis transmission in Kebbi State, Northwestern Nigeria, to inform better immunization and surveillance strategies. Methods: Community-based unmatched case–control study and review of the 2019 pertussis routine surveillance data in the affected settlements in the state were conducted. A total of 52 suspected cases of pertussis and 107 control from two local government areas in Kebbi State were recruited. Data were analyzed using descriptive and inferential statistics. Results: The highest attack rate was observed among between 1- and 4-year age group followed by children less than 1-year old, and the least attack rate was among those above 15 years. The overall attack rate and the case fatality rate were 2.10% and 0.10%, respectively. A higher attack rate was observed among women, whereas the case fatality rate was more among males. From the community survey, we observed that the cases were less likely to have pertussis vaccination history (adjusted odds ratio = 0.28, 95% confidence interval = 0.11–0.74) compared with the controls. Knowing pertussis prevention methods were found protective for pertussis transmission (adjusted odds ratio = 0.14, 95% confidence interval = 0.04–0.45). Conclusion: This study showed the vulnerability of children under 5 years, especially under 1 year, to vaccine-preventable diseases in rural populations, where “real” immunization coverage is sub-optimal, and the dominant socio-demographic factors are supportive of disease transmission. We found immunization and knowledge of the preventive measures to be protective against pertussis outbreaks. Therefore, routine immunization services must be intensified to improve coverage and prevent future pertussis outbreak(s).
Analysis of Risk Factors in COVID-19 Adult Mortality in Russia
Authors: Kirillov Youri , Timofeev Sergei , Avdalyan Ashot , Nikolenko Vladimir N. , Gridin Leonid , Sinelnikov Mikhail Y. 
Published: April 2021

Background and Objective Epidemiological data obtained during the ongoing SARS-CoV-2 pandemic suggests that COVID-19 mortality has specific age and gender associations. However, limited epidemiological studies explored specific populational risk factors, including comorbidities, and patient clinical characteristics. The main aim of our retrospective cohort study was to analyze associations between age, gender, and comorbidities in deceased COVID-19 patients. Materials and Methods A retrospective cohort analysis was performed to assess significant risk factors in adult patients deceased from COVID-19 infection by evaluating Electronic Medical Records and post-mortem analysis in COVID-19 patients deceased between April 2020 to October 2020. All patients underwent post-mortem evaluation along with medical history analysis, including data on disease duration, hospitalization, and clinical peculiarities. Results Medical records of 1487 COVID-19 patients revealed that the prevalence of males was higher (by 23%) than females; the median age for males was 71 years of age whereas for females it was 78. The most prevalent comorbid pathologies were: hypertension, obesity, diabetes, and cancer. Males are at significantly increased risk of lethal outcome, even in younger age groups, with comorbid conditions. Conclusion The study concluded that comorbidities, such as hypertension, obesity, diabetes, cancer are the most important risk factors for comorbid mortality in COVID-19 patients. In addition to lung damage, multiple organ dysfunctions may be a crucial reason for COVID-19 induced death. Special precautions, such as early hospitalization, increased monitoring, and preventative tactics should be taken for at-risk patients.
The 50 Most Cited Articles in Meniscal Injury Research
Authors: Damodar Dhanur , Plotsker Ethan , Greif Dylan , Rizzo Michael G. , Baraga Michael G. , Kaplan Lee D. 
Published: April 2021

Background: Meniscal injuries are among the most common orthopaedic injuries, with a significant volume of published literature. Purpose: To perform a comprehensive bibliometric analysis that appropriately evaluates the 50 most cited articles in meniscal research. Study Design: Cross-sectional study. Methods: We performed a keyword search of the ISI Web of Knowledge database and then pared the results down to the 50 most cited articles using specific inclusion and exclusion criteria. Data extracted included title, first author, citation count, year of publication, topic, journal, article type, country of origin, and level of evidence. Correlation coefficients were calculated between publication date and citation density and between publication date and raw citation count. Results: The 50 most cited articles were published from 1975 to 2013. The mean number of citations was 258.24 (range, 163-926; median, 225). The majority of articles were published in The American Journal of Sports Medicine (19%), the Journal of Bone and Joint Surgery (12%), and Arthritis & Rheumatology (14%). Most articles focused on either the anatomy and biomechanics of meniscal injury or on prevention and physical rehabilitation (12 papers each). Conclusion: The most popular fields of meniscal research involved anatomy/biomechanics and prevention/rehabilitation, and both are areas that will likely increase the probability of an article’s being highly cited in the future. This study provided a quality selection of the most cited articles on meniscal injury and may provide a foundation for both beginner and senior clinician readers for further discussion and research.
Variation in medical management and neurosurgical treatment of patients with supratentorial spontaneous intracerebral haemorrhage
Authors: Sondag Lotte , Jacobs Floor AE , Schreuder Floris HBM , Boogaarts Jeroen D , Peter Vandertop W , Dammers Ruben , Klijn Catharina JM 
Published: April 2021

Introduction The role of surgery in spontaneous intracerebral haemorrhage (sICH) remains controversial. This leads to variation in the percentage of patients who are treated with surgery between countries. Patients and methods We sent an online survey to all neurosurgeons (n = 140) and to a sample of neurologists (n = 378) in Dutch hospitals, with questions on management in supratentorial sICH in general, and on treatment in six patients, to explore current variation in medical and neurosurgical management. We assessed patient and haemorrhage characteristics influencing treatment decisions. Results Twenty-nine (21%) neurosurgeons and 92 (24%) neurologists responded. Prior to surgery, neurosurgeons would more frequently administer platelet-transfusion in patients on clopidogrel (64% versus 13%; p = 0.000) or acetylsalicylic acid (61% versus 11%; p = 0.000) than neurologists. In the cases, neurosurgeons and neurologists were similar in their choice for surgery as initial treatment (24% and 31%; p = 0.12), however variation existed amongst physicians in specific cases. Neurosurgeons preferred craniotomy with haematoma evacuation (74%) above minimally-invasive techniques (5%). Age, Glasgow Coma Scale score and ICH location were important factors influencing decisions on treatment for neurosurgeons and neurologists. 69% of neurosurgeons and 80% of neurologists would randomise patients in a trial evaluating the effect of minimally-invasive surgery on functional outcome. Discussion Our results reflect the lack of evidence about the right treatment strategy in patients with sICH. Conclusion New high quality evidence is needed to guide treatment decisions for patients with ICH. The willingness to randomise patients into a clinical trial on minimally-invasive surgery, contributes to the feasibility of such studies in the future.
Allele-specific expression of GATA2 due to epigenetic dysregulation in CEBPA double-mutant AML
Authors: Mulet-Lazaro Roger , van Herk Stanley , Erpelinck Claudia , Bindels Eric , Sanders Mathijs A. , Vermeulen Carlo , Renkens Ivo , Valk Peter , Melnick Ari M. , de Ridder Jeroen , Rehli Michael , Gebhard Claudia , Delwel Ruud , Wouters Bas J. 
Published: April 2021

Abstract
Transcriptional deregulation is a central event in the development of acute myeloid leukemia (AML). To identify potential disturbances in gene regulation, we conducted an unbiased screen of allele-specific expression (ASE) in 209 AML cases. The gene encoding GATA binding protein 2 (GATA2) displayed ASE more often than any other myeloid- or cancer-related gene. GATA2 ASE was strongly associated with CEBPA double mutations (DMs), with 95% of cases presenting GATA2 ASE. In CEBPA DM AML with GATA2 mutations, the mutated allele was preferentially expressed. We found that GATA2 ASE was a somatic event lost in complete remission, supporting the notion that it plays a role in CEBPA DM AML. Acquisition of GATA2 ASE involved silencing of 1 allele via promoter methylation and concurrent overactivation of the other allele, thereby preserving expression levels. Notably, promoter methylation was also lost in remission along with GATA2 ASE. In summary, we propose that GATA2 ASE is acquired by epigenetic mechanisms and is a prerequisite for the development of AML with CEBPA DMs. This finding constitutes a novel example of an epigenetic hit cooperating with a genetic hit in the pathogenesis of AML.
Acquired platelet GPVI receptor dysfunction in critically ill patients with sepsis
Authors: Weiss Lukas J. , Manukjan Georgi , Pflug Annerose , Winter Nadine , Weigel Mathis , Nagler Nils , Kredel Markus , Lâm Thiên-Trí , Nieswandt Bernhard , Weismann Dirk , Schulze Harald 
Published: April 2021

Abstract
Glycoprotein VI (GPVI), the platelet immunoreceptor tyrosine activating motif (ITAM) receptor for collagen, plays a striking role on vascular integrity in animal models of inflammation and sepsis. Understanding ITAM-receptor signaling defects in humans suffering from sepsis may improve our understanding of the pathophysiology, especially during disease onset. In a pilot study, platelets from 15 patients with sepsis were assessed consecutively at day of admission, day 5 to 7, and the day of intensive care unit (ICU) discharge and subjected to comprehensive analyses by flow cytometry, aggregometry, and immunoblotting. Platelet function was markedly reduced in all patients. The defect was most prominent after GPVI stimulation with collagen-related peptide. In 14 of 15 patients, GPVI dysfunction was already present at time of ICU admission, considerably before the critical drop in platelet counts. Sepsis platelets failed to transduce the GPVI-mediated signal to trigger tyrosine phosphorylation of Syk kinase or LAT. GPVI deficiency was partially inducible in platelets of healthy donors through coincubation in whole blood, but not in plasma from patients with sepsis. Platelet aggregation upon GPVI stimulation increased only in those patients whose condition ameliorated. As blunted GPVI signaling occurred early at sepsis onset, this defect could be exploited as an indicator for early sepsis diagnosis, which needs to be confirmed in prospective studies.
The spleen as a sanctuary site for residual leukemic cells following ABT-199 monotherapy in ETP-ALL
Authors: Di Grande Alessandra , Peirs Sofie , Donovan Paul D. , Van Trimpont Maaike , Morscio Julie , Lintermans Beatrice , Reunes Lindy , Vandamme Niels , Goossens Steven , Nguyen Hien Anh , Lavie Arnon , Lock Richard B. , Prehn Jochen H. M. , Van Vlierberghe Pieter , Ní Chonghaile Triona 
Published: April 2021

AbstractB-cell lymphoma 2 (BCL-2) has recently emerged as a therapeutic target for early T-cell progenitor acute lymphoblastic leukemia (ETP-ALL), a high-risk subtype of human T-cell ALL. The major clinical challenge with targeted therapeutics, such as the BCL-2 inhibitor ABT-199, is the development of acquired resistance. We assessed the in vivo response of luciferase-positive LOUCY cells to ABT-199 monotherapy and observed specific residual disease in the splenic microenvironment. Of note, these results were confirmed by using a primary ETP-ALL patient-derived xenograft. Splenomegaly has previously been associated with poor prognosis in diverse types of leukemia. However, the exact mechanism by which the splenic microenvironment alters responses to specific targeted therapies remains largely unexplored. We show that residual LOUCY cells isolated from the spleen microenvironment displayed reduced BCL-2 dependence, which was accompanied by decreased BCL-2 expression levels. Notably, this phenotype of reduced BCL-2 dependence could be recapitulated by using human splenic fibroblast coculture experiments and was confirmed in an in vitro chronic ABT-199 resistance model of LOUCY. Finally, single-cell RNA-sequencing was used to show that ABT-199 triggers transcriptional changes in T-cell differentiation genes in leukemic cells obtained from the spleen microenvironment. Of note, increased expression of CD1a and sCD3 was also observed in ABT199-resistant LOUCY clones, further reinforcing the idea that a more differentiated leukemic population might display decreased sensitivity toward BCL-2 inhibition. Overall, our data reveal the spleen as a site of residual disease for ABT-199 treatment in ETP-ALL and provide evidence for plasticity in T-cell differentiation as a mechanism of therapy resistance.
Electroencephalographic dynamics of etomidate‐induced loss of consciousness
Authors: Zhang Lei , Fan Shunqin , Zhang Jiawei , Fang Kun , Wang Lei , Cao Yuanyuan , Chen Lijian , Liu Xuesheng , Gu Erwei 
Published: April 2021

AbstractBackgroundHighly structured electroencephalography (EEG) oscillations can occur in adults during etomidate-induced general anesthesia, but the link between these two phenomena is poorly understood. Therefore, in the present study, we investigated the electroencephalogram dynamics of etomidate-induced loss of consciousness (LOC) in order to understand the neurological mechanism of etomidate-induced LOC.MethodsThis study is a prospective observational study. Etomidate-induced anesthesia was performed on eligible patients undergoing elective surgery. We analyzed EEG data from 20 patients who received etomidate for the induction of general anesthesia. We used power spectra and coherence methods to process and analyze the EEG data. Our study was based on 4-channel EEG recordings.ResultsCompared with the baseline (awake period), etomidate induced an increase in power in delta, theta, alpha and beta waves during LOC. Compared with the awake period, the delta-wave (1–4 Hz), alpha-wave(8–13 Hz), and theta-wave(4–8 Hz) coherence increased significantly during LOC, while the slow-wave (< 1 Hz) coherence decreased. However, the delta wave (1.0–4.0 Hz) during etomidate-induced LOC was more coherent than during the awake period (1.86–3.17 Hz, two-group test for coherence,p < 0.001).ConclusionsThe neural circuit mechanism of etomidate-induced LOC is closely related to the induction of oscillation in delta, theta, alpha and beta waves and the enhancement of delta-wave coherence.Trial registrationChiCTR1800017110
Co-infection of HIV in patients with Buruli ulcer disease in Central Ghana
Authors: Amoako Yaw Ampem , Loglo Aloysius Dzigbordi , Frimpong Michael , Agbavor Bernadette , Abass Mohammed Kabiru , Amofa George , Ofori Elizabeth , Ampadu Edwin , Asiedu Kingsley , Stienstra Ymkje , Wansbrough-Jones Mark , van der Werf Tjip , Phillips Richard Odame 
Published: April 2021

Abstract
Background
Previous studies have reported that presence and severity of Buruli ulcer (BU) may reflect the underlying immunosuppression in HIV infected individuals by causing increased incidence of multiple, larger and ulcerated lesions. We report cases of BU-HIV coinfection and the accompanying programmatic challenges encountered in central Ghana.

Methods
Patients with PCR confirmed BU in central Ghana who were HIV positive were identified and their BU01 forms were retrieved and reviewed in further detail. A combined 16S rRNA reverse transcriptase / IS2404 qPCR assay was used to assess the Mycobacterium ulcerans load. The characteristics of coinfected patients (BU+HIV+) were compared with a group of matched controls.

Results
The prevalence of HIV in this BU cohort was 2.4% (compared to national HIV prevalence of 1.7%). Eight of 9 BU+HIV+ patients had a single lesion and ulcers were the most common lesion type. The lesions presented were predominantly category II (5/9) followed by category I lesions. The median (IQR) time to healing was 14 (8–28) weeks in the BU+HIV+ compared to 28 (12–33) weeks in the control BU+HIV− group (p = 0.360). Only one BU+HIV+ developed a paradoxical reaction at week 16 but the lesion healed completely at week 20. The median bacterial load (16SrRNA) of BU+HIV+ patients was 750 copies /ml (95% CI 0–398,000) versus 500 copies/ml (95% CI 0–126,855,500) in BU+HIV− group. Similarly, the median count using the IS2404 assay was 500 copies/ml (95% CI 0–500) for BU+HIV+ patients versus 500 copies/ml (95% CI 500–31,000) for BU+HIV− patients. BU+HIV− patients mounted a significantly higher interferon-γ response compared to the BU+HIV+ co-infected patients with respective median (range) responses of [1687(81.11–4399) pg/ml] versus [137.5(4.436–1406) pg/ml, p = 0.03]. There were challenges with the integration of HIV and BU care in this cohort.

Conclusion
The prevalence of HIV in the BU+ infected population was not significantly increased when compared to the prevalence of HIV in the general population. There was no clear relationship between BU lesion severity and HIV viral load or CD4 counts. Efforts should be made to encourage the integration of care of patients with BU-HIV coinfection.
Molecular characterization of multidrug-resistant tuberculosis against levofloxacin, moxifloxacin, bedaquiline, linezolid, clofazimine, and delamanid in southwest of China
Authors: Zheng Huiwen , He Wencong , Jiao Weiwei , Xia Hui , Sun Lin , Wang Shengfen , Xiao Jing , Ou Xichao , Zhao Yanlin , Shen Adong 
Published: April 2021

Abstract
Objectives
To explore the drug susceptibility of levofloxacin (LFX), moxifloxacin (MFX), bedaquiline (BDQ), linezolid (LZD), clofazimine (CFZ) and delamanid (DLM) against multidrug resistant tuberculosis (MDR-TB) isolates from drug resistance survey of southwest China, and to illustrate the genetic characteristics of MDR-TB isolates with acquired drug resistance.

Methods
A total of 339 strains were collected from smear-positive TB patients in the drug resistance survey of southwest China between January 2014 and December 2016. The MICs for the above mentioned drugs were determined for MDR-TB by conventional drug susceptibility testing. Genes related to drug resistance were amplified with their corresponding pairs of primers.

Results
MDR was observed in 88 (26.0%; 88/339) isolates. LFX had the highest resistance rate (50.0%; 44/88), followed by MFX (38.6%; 34/88). The resistance rate to LZD, CFZ, and DLM was 4.5% (4/88), 3.4% (3/88), and 4.5% (4/88), respectively, and the lowest resistance rate was observed in BDQ (2.3%; 2/88). Of the 45 isolates resistant to LFX and MFX, the most prevalent resistance mutation was found in gyrA with the substitution of codon 94 (34/45, 75.6%). Two strains with CFZ - BDQ cross resistance had a mutation in the Rv0678 gene. Of the four LZD resistant isolates, two carried mutations in rplC gene. For the four isolates resistant to DLM, one isolate had mutations in codon 318 of fbiC gene, and two isolates were with mutations in codon 81 of ddn gene.

Conclusion
This study provided evidence of the usefulness of new anti-TB drugs in the treatment of MDR-TB in China.