bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-Wide Association Studies for the Detection of Genetic Variants Associated With Daptomycin and Ceftaroline Resistance in Staphylococcus aureus
Authors: Weber Robert E. , Fuchs Stephan , Layer Franziska , Sommer Anna , Bender Jennifer K. , Thürmer Andrea , Werner Guido , Strommenger Birgit 
Published: February 2021

BackgroundAs next generation sequencing (NGS) technologies have experienced a rapid development over the last decade, the investigation of the bacterial genetic architecture reveals a high potential to dissect causal loci of antibiotic resistance phenotypes. Although genome-wide association studies (GWAS) have been successfully applied for investigating the basis of resistance traits, complex resistance phenotypes have been omitted so far. For S. aureus this especially refers to antibiotics of last resort like daptomycin and ceftaroline. Therefore, we aimed to perform GWAS for the identification of genetic variants associated with DAP and CPT resistance in clinical S. aureus isolates.Materials/methodsTo conduct microbial GWAS, we selected cases and controls according to their clonal background, date of isolation, and geographical origin. Association testing was performed with PLINK and SEER analysis. By using in silico analysis, we also searched for rare genetic variants in candidate loci that have previously been described to be involved in the development of corresponding resistance phenotypes.ResultsGWAS revealed MprF P314L and L826F to be significantly associated with DAP resistance. These mutations were found to be homogenously distributed among clonal lineages suggesting convergent evolution. Additionally, rare and yet undescribed single nucleotide polymorphisms could be identified within mprF and putative candidate genes. Finally, we could show that each DAP resistant isolate exhibited at least one amino acid substitution within the open reading frame of mprF. Due to the presence of strong population stratification, no genetic variants could be associated with CPT resistance. However, the investigation of the staphylococcal cassette chromosome mec (SCCmec) revealed various mecA SNPs to be putatively linked with CPT resistance. Additionally, some CPT resistant isolates revealed no mecA mutations, supporting the hypothesis that further and still unknown resistance determinants are crucial for the development of CPT resistance in S. aureus.ConclusionWe hereby confirmed the potential of GWAS to identify genetic variants that are associated with antibiotic resistance traits in S. aureus. However, precautions need to be taken to prevent the detection of spurious associations. In addition, the implementation of different approaches is still essential to detect multiple forms of variations and mutations that occur with a low frequency.
Upper Motor Neuron Signs in the Cervical Region of Patients With Flail Arm Syndrome
Authors: Xu Yingsheng , Chen Junyi , Zhang Shuo , Fan Dongsheng 
Published: February 2021

Objective: We investigated upper motor neuron (UMN) signs in the cervical region in a Chinese clinic-based cohort of patients with flail arm syndrome (FAS) by clinical examination and neurophysiological tests such as triple stimulation technique (TST) and pectoralis tendon reflex testing.Methods: A total of 130 consecutive FAS patients from Peking University Third Hospital underwent physical examination and neurophysiological tests at baseline and 3 months, 6 months, 9 months, and 12 months later. Pyramidal signs, pectoralis tendon reflex and TST results were evaluated to estimate the function of cervical spinal UMNs.Results: At the first visit, weakness of the bilateral proximal upper limbs was found in 99 patients, while weakness of a single proximal upper limb was found in 31 patients. There were 49 patients with tendon hyperreflexia, 42 patients with tendon hyporeflexia and 39 patients with tendon areflexia. All except 4 of the patients had brisk pectoralis tendon reflex. The UMN score of the cervical region was 1.7 ± 0.4, and the lower motor neuron score of that region was 3.5 ± 0.3. The TSTtest/TSTcontrol amplitude ratio was 65.7 ± 7.5%. The latency of quantitative detection of the pectoralis tendon reflex was 7.7 ± 1.2 ms. In the follow-up study, the UMN score and the TSTtest/TSTcontrol amplitude ratio decreased, while the lower motor neuron score increased, and the latency of quantitative detection of the pectoralis tendon reflex remained steady.Conclusion: Although the signs of cervical spinal UMN dysfunction in patients with FAS were often concealed by muscle atrophy in the progression of the disease, TST and pectoralis tendon reflex could reveal it.
Endovascular Therapy for Basilar Arterial Trunk Aneurysms
Authors: Wang Yiheng , Xu Kan , Song Jia , Yu Jinlu 
Published: February 2021

Background: Although aneurysms rarely occur in the basilar artery (BA) trunk, the majority of those that do are dissection aneurysms. Currently, the mainstream therapy for BA trunk aneurysms is endovascular therapy (EVT), which mainly includes single coiling or conventional low-metal-coverage stent-assisted EVT, but the efficacy remains to be evaluated.Methods: A retrospective study was performed for the patients who were admitted to our institution for BA trunk aneurysms and underwent EVT. A total of 28 patients were collected in this study.Results: The patients were aged 23–71 years (53.7 ± 11.5 years on average); nine were female (32.1%, 9/28), and 19 were male (67.9%, 19/28). The patients were given single coiling or conventional low-metal-coverage stent-assisted EVT. Among the 28 patients, 10 (35.7%, 10/28) developed complications, 90% (9/10) of which were ischemic and 10% (1/10) were hemorrhagic. Among the 28 patients, 5 (17.9%, 5/28) died. The surviving 23 patients (82.1%, 23/28) recovered well.Conclusions: This study found that for BA trunk aneurysms, single coiling or conventional low-metal-coverage stent-assisted EVT still had some risks. The risks are mainly from brainstem ischemia. Therefore, the perforators of the BA trunk must be carefully evaluated and prevented from receiving damage from the EVT procedure. This study also shows that 82.1% of patients recovered well. Therefore, EVT can result in an acceptable prognosis.
Six Weeks of Aerobic Exercise in Untrained Men With Overweight/Obesity Improved Training Adaptations, Performance and Body Composition Independent of Oat/Potato or Milk Based Protein-Carbohydrate Drink Supplementation
Authors: Pettersson Stefan , Edin Fredrik , Hjelte Carl , Scheinost David , Wagner Sandro , Ekblom Björn , Jessen Niels , Madsen Klavs , Andersson-Hall Ulrika 
Published: February 2021

Background: Protein availability around aerobic exercise might benefit aerobic capacity and body composition in normal weight adults. However, it is unknown if individuals with overweight/obesity elicit similar adaptations or improve other cardiometabolic/health-related markers in response to different types of protein. Thus, our aim was to study the effect of supplementation of two different protein drinks in conjunction with exercise on aerobic capacity, body composition and blood health markers in untrained subjects with overweight or obesity.Methods: The present study measured training adaptation and health parameters over a 6 week period in untrained men with overweight/obesity (n = 28; BMI 30.4 ± 2.2 kg/m2) ingesting either plant- (Oat/Potato; n = 8) or animal-based (Milk; n = 10) protein-carbohydrate drinks (10 g of protein/serving), or a control carbohydrate drink (n = 10) acutely before and after each training session (average three sessions/week @ 70% HRmax). Pre-post intervention V˙O2peak, muscle biopsies and blood samples were collected, body composition measured (DXA) and two different exercise tests performed. Body weight was controlled with participants remaining weight stable throughout the intervention.Results: For the groups combined, the training intervention significantly increased V˙O2peak (8%; P &lt; 0.001), performance in a time-to-exhaustion trial (~ 100%; P &lt; 0.001), mitochondrial protein content and enzyme activity (~20–200%). Lean body mass increased (1%; P &lt; 0.01) and fat mass decreased (3%; P &lt; 0.01). No significant effects on fasting blood glucose, insulin, lipids or markers of immune function were observed. There were no significant interactions between drink conditions for training adaptation or blood measurements. For body composition, the Oat/Potato and carbohydrate group decreased leg fat mass significantly more than the Milk group (interaction P &lt; 0.05).Conclusions: Aerobic capacity and body composition were improved and a number of mitochondrial, glycolytic and oxidative skeletal muscle proteins and enzyme activities were upregulated by a 6 week training intervention. However, none of the parameters for endurance training adaptation were influenced by protein supplementation before and after each training session.
A Phase II, Single-Arm Study of Apatinib and Oral Etoposide in Heavily Pre-Treated Metastatic Breast Cancer
Authors: Hu Nanlin , Zhu Anjie , Si Yiran , Yue Jian , Wang Xue , Wang Jiayu , Ma Fei , Xu Binghe , Yuan Peng 
Published: February 2021

IntroductionWe performed this clinical trial to evaluate the efficacy and safety of apatinib and oral etoposide in patients with HER2-negative locally advanced or metastatic breast cancer (MBC).MethodsPatients with HER2-negative MBC previously treated with anthracycline and taxanes and failed ≥1 prior chemotherapy regimens were recruited. The starting dose of apatinib was 500 and 425 mg in patients with ECOG scores of 0–1 and 2, respectively. The etoposide capsules were given at 50 mg/m2 on days 1 to 10 for 21 days. The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety.ResultsThirty-one eligible patients were enrolled. The median follow-up time was 11 months. The median PFS for all patients was 6.9 months [95% confidence interval (CI) 6.0–7.9], and 6.9 months (95% CI 5.3–8.6) and 6.6 months (95% CI 1.4–11.7) for patients with apatinib 425 and 500mg once daily, respectively. The ORR was 35.5% (11/31). The DCR was 87.1% (27/31). The median OS was 20.4 months (95% CI 11.4–29.3). The median PFS of patients who had hypertension and proteinuria was longer than that for those without hypertension and proteinuria. The most common grade 3/4 treatment-related AEs were hypertension (12/31, 38.7%), fatigue (3/31, 9.7%), thrombocytopenia (3/31, 9.7%).ConclusionApatinib combined with etoposide capsules is effective and tolerable in heavily pretreated, metastatic HER2-negative breast cancer patients. A lower apatinib dose provide equivalent efficacy and reduced toxicity.Clinical Trial Registrationhttps://clinicaltrials.gov/, identifier NCT03535961.
Survival Status of Esophageal Cancer Patients and its Determinants in Ethiopia: A Facility Based Retrospective Cohort Study
Authors: Hassen Hamid Yimam , Teka Mohammed Ahmed , Addisse Adamu 
Published: February 2021

BackgroundGlobally, the incidence and mortality due to esophageal cancer are increasing, particularly in low- and middle-income countries. Cancer of the esophagus is the eighth in incidence and seventh in cancer mortality in Ethiopia. A few studies have shown an increasing burden, however, little is known about the survival pattern and its determinants among esophageal cancer patients in Ethiopia. Therefore, we assessed the survival pattern and its determinants among esophageal cancer patients.MethodsWe conducted a retrospective cohort study among 349 esophageal cancer patients who were diagnosed at or referred to Tikur Anbessa Specialized Hospital, Ethiopia from January 2010 to May 2017. Using an abstraction form, nurses who were working at the oncology department extracted the data from patient charts. To estimate and compare the probability of survival among covariate categories, we performed a Kaplan–Meier survival analysis with the log-rank test. To identify the prognostic determinants of survival, we performed a multivariable Cox proportional regression analysis.ResultsThe median follow-up time was 32 months with interquartile range of 15 to 42. Overall, the median survival time after diagnosis with esophageal cancer was 4 months with one-, two- and three-year survival of 14.4, 6.3, and 2.4% respectively. In the multivariable Cox proportional hazards model, receiving chemotherapy [Adjusted Hazard Ratio (AHR)=0.36, 95%CI: 0.27–0.49], radiotherapy [AHR=0.38, 95%CI: 0.23–0.63] and surgery [AHR=0.70, 95%CI: 0.54–0.89] were statistically significant.ConclusionsIn Ethiopia, esophageal cancer patients have a very low one-, two- and three-year survival. Despite a very low overall survival, patients who received either chemotherapy, radiotherapy or surgery showed a better survival compared with those who did not receive any treatment. Hence, it is essential to improve the survival of patients with esophageal cancer through early detection and timely initiation of the available treatment options.
Stillbirths, Neonatal Morbidity, and Mortality in Health-Facility Deliveries in Urban Gambia
Authors: Camara Bully , Oluwalana Claire , Miyahara Reiko , Lush Alyson , Kampmann Beate , Manneh Kebba , Okomo Uduak , D'Alessandro Umberto , Roca Anna 
Published: February 2021

Background: The Gambia Demographic and Health Survey 2013 data showed that up to 63% of deliveries in the country occur in health facilities. Despite such a high rate, there are few facility-based studies on delivery outcomes in the country. This analysis ancillary to a randomized control trial describes occurrence of poor pregnancy outcomes in a cohort of women and their infants delivering in a government health facility in urban Gambia.Methods: Using clinical information obtained during the trial, we calculated rates of poor pregnancy outcomes including stillbirths, hospitalization and neonatal deaths. Logistic regression was used to calculate odds ratio (OR) and 95% confidence interval (CI) in the risk factors analysis.Results: Between April 2013 and 2014, 829 mothers delivered 843 babies, including 13 stillbirths [15.4 (7.1–23.8)] per 1,000 births. Among 830 live born infants, 7.6% (n = 63) required hospitalization during the 8-week follow-up period. Most of these hospitalizations (74.6%) occurred during the early neonatal period (&lt;7 days of life). Severe clinical infections (i.e., sepsis, meningitis and pneumonia) (n = 27) were the most common diagnoses, followed by birth asphyxia (n = 13), major congenital malformations (n = 10), jaundice (n = 6) and low birth weight (n = 5). There were sixteen neonatal deaths, most of which also occurred during the early neonatal period. Overall, neonatal mortality rate (NMR) and perinatal mortality rate (PMR) were 19.3 (CI: 9.9–28.7) per 1,000 live births and 26.1 (CI: 15.3–36.9) per 1,000 total births, respectively. Severe clinical infections and birth asphyxia accounted for 37 and 31% of neonatal deaths, respectively. The risk of hospitalization was higher among neonates with severe congenital malformations, low birth weight, twin deliveries, and those born by cesarean section. Risk of mortality was higher among neonates with severe congenital malformations and twin deliveries.Conclusion: Neonatal hospitalization and deaths in our cohort were high. Although vertical interventions may reduce specific causes of morbidity and mortality, data indicate the need for a holistic approach to significantly improve the rates of poor pregnancy outcomes. Critically, a focus on decreasing the high rate of stillbirths is warranted.Clinical Trial Registration:ClinicalTrials.gov Identifier: NCT01800942.
Vanillic Acid Reduces Pain-Related Behavior in Knee Osteoarthritis Rats Through the Inhibition of NLRP3 Inflammasome-Related Synovitis
Authors: Ma Zhenyuan , Huang Zhengquan , Zhang Li , Li Xiaochen , Xu Bo , Xiao Yancheng , Shi Xiaoqing , Zhang Haosheng , Liao Taiyang , Wang Peimin 
Published: February 2021

Objectives: Synovitis plays an important role in knee osteoarthritis (KOA) pain. The activation of the NOD-like receptor protein 3 (NLRP3) inflammasome in fibroblast-like synoviocytes (FLSs) promotes KOA development. In this study, we aimed to investigate whether vanillic acid (VA), a monomer derived from Chinese herbal medicines, could target NLRP3 inflammasome-related synovitis to reduce pain.Methods: Rats in the KOA and KOA + VA groups were injected with monosodium iodoacetate (MIA) in the knee to induce KOA. From day 14, the KOA + VA group was given VA at 30 mg/kg every day via gastric intubation. FLSs were collected from the synovial tissues. We examined both the protein and gene expression of caspase-1, apoptosis-associated speck-like protein with a caspase recruitment domain (ASC), NLRP3, components of the NLRP3 inflammasome, and interleukin-1β (IL-1β) and IL-18 in vivo and in vitro.Results: The upregulation of caspase-1, ASC, and NLRP3 in the KOA model were reduced by VA. VA also lowered the level of IL-1β and IL-18 in the KOA model. In addition, VA relieved pain-related behavior of KOA model rats and downregulated the pain mediators CGRP, NGF, and TrkA in FLSs. Interestingly, we also observed reduced synovial fibrosis in the animal experiments.Conclusion: Our research showed that VA reduces synovitis and pain-related behaviors in a rat model of KOA, which provides the basis for further investigations into the potential therapeutic impact of VA in KOA.
Sleep and Safety Improve Physicians’ Psychological Functioning at Work During Covid-19 Epidemic
Authors: Zupancic Nina , Bucik Valentin , Ihan Alojz , Dolenc-Groselj Leja 
Published: February 2021

PurposeThe COVID-19 pandemic caused a massive healthcare crisis. To investigate what makes healthcare system resilient and physicians better at coping during a crisis situation, our study investigated the role risk exposure, such as working at COVID-19 entry points, sleep, and perceived work safety played in reducing negative psychological functioning at work, as well as their effects on adverse and potentially fatal incidences of compromised safety and medical errors.MethodsOur study included a representative sample of 1,189 physicians, from all 12 Slovenian regions and all medical occupations, as registered by the Medical Chamber of Slovenia. For the purposes of this study, a Questionnaire of Sleep and Psychological Functioning at Work was developed in the form of an online retrospective self-report. Additionally, our study included items assessing physicians perceived work safety and frequency of negative outcomes (compromised safety and medical errors) during the first month of the Covid-19 epidemic.ResultsPhysicians working at COVID-19 entry points were more likely to experience night awakening, slept less than 5 h per night, experience nightmares, and had lower levels of psychological functioning in comparison to other physicians. Both hypothesized models showed adequate fit. A higher score on the sleep scale (sleep quantity, sleep quality, and shorter sleep latency) has been shown to predict lower levels of negative psychological functioning at work and, indirectly, reduced incidences of compromised safety and medical errors. Contrary to our expectations, no significant direct effect of sleep on compromised safety and medical errors was found. When perceived work safety was added into the model, the model showed improved fit, with perceived work safety predicting better sleep, less negative psychological functioning at work, and less compromised safety.ConclusionSleep and safety both play an important role in reducing negative psychological functioning at work and, by doing so, decreasing the negative and potentially fatal incidents during the pandemic, such as compromised safety and medical errors. Further, research is needed to see how medical guidelines can be updated to ensure physicians sleep and that their safety is protected.
Depressive and Anxiety Symptoms Among People Under Quarantine During the COVID-19 Epidemic in China: A Cross-Sectional Study
Authors: Yan Tong , Zhizhong Wang , Jianzhong Zheng , Yubo Ying , Jie Liu , Junjun Zhang , Guangtian Liu 
Published: February 2021

Background: During the coronavirus disease 2019 (COVID-19) pandemic, quarantine as an effective public health measure has been widely used in China and elsewhere to slow down the spread, while high-risk psychological response populations remain under-reported.Objective: The aim of the study is to investigate the depressive and anxiety symptoms among the high-risk individuals quarantined during the COVID-19 pandemic in China.Methods: An online survey was conducted from February 29 to April 10, 2020, among individuals quarantined for at least 2 weeks due to the high-risk exposure. Chinese versions of the nine-item Patient Health Questionnaire (PHQ-9) with a seven-item Generalized Anxiety Disorder (GAD-7) were applied to assess depressive and anxiety symptoms, respectively. Compliance with quarantine and knowledge of COVID-19 was also assessed. An unconditional logistic regression model was performed to identify the correlators.Results: Of the 1,260 participants completing the full survey, 14.0% (95% CI: 12.2–16.1%), 7.1% (95% CI: 5.9–8.7%), and 6.3% (95% CI: 5.1–7.8%) had at least moderate symptoms of depression, anxiety, and a combination of depression and anxiety (CDA), respectively; 14.8% (95% CI: 13.0–16.9%) had at least one condition. Multivariate analysis showed that participants with an undergraduate or above degree were more likely to report depressive (OR = 2.98, 95% CI: 1.56–5.72) and anxiety symptoms (OR = 2.95, 95% CI: 1.14–7.63) than those with middle school education. Those who were unemployed (OR = 0.37, 95% CI: 0.21–0.65 for depression; OR = 0.31, 95% CI: 0.14–0.73 for anxiety), students (OR = 0.14, 95% CI: 0.04–0.48 for depression; OR = 0.11, 95% CI: 0.01–0.85 for anxiety), and more knowledgeable of COVID-19 (OR = 0.84, 95% CI: 0.73–0.96 for depression, OR = 0.82, 95% CI: 0.68–0.98 for anxiety) were less likely to report depressive and anxiety symptoms. Higher quarantine compliance correlated with lower risks of depressive (OR = 0.94, 95% CI: 0.91–0.96) and anxiety symptoms (OR = 0.95, 95% CI: 0.91–0.98).Conclusion: Individuals under quarantine during the COVID-19 pandemic suffered prevalent depressive and anxiety symptoms. Consequently, comprehensive interventional measures, including knowledge dissemination, timely virus tests, and strengthened communication, may minimize quarantine's adverse effects.