bluuebunny/crossref_metadata_2025 huggingface dataset:
Transmission patterns of rifampicin resistant Mycobacterium tuberculosis complex strains in Cameroon: a genomic epidemiological study
Authors: Merker Matthias , Egbe Nkongho F. , Ngangue Yannick R. , Vuchas Comfort , Kohl Thomas A. , Dreyer Viola , Kuaban Christopher , Noeske Jürgen , Niemann Stefan , Sander Melissa S.
Published: August 2021

Background

Determining factors affecting the transmission of rifampicin (RR) and multidrug-resistant (MDR) Mycobacterium tuberculosis complex strains under standardized tuberculosis (TB) treatment is key to control TB and prevent the evolution of drug resistance.

Methods

We combined bacterial whole genome sequencing (WGS) and epidemiological investigations for 37% (n = 195) of all RR/MDR-TB patients in Cameroon (2012–2015) to identify factors associated with recent transmission.

Results

Patients infected with a strain resistant to high-dose isoniazid, and ethambutol had 7.4 (95% CI 2.6–21.4), and 2.4 (95% CI 1.2–4.8) times increased odds of being in a WGS-cluster, a surrogate for recent transmission. Furthermore, age between 30 and 50 was positively correlated with recent transmission (adjusted OR 3.8, 95% CI 1.3–11.4). We found high drug-resistance proportions against three drugs used in the short standardized MDR-TB regimen in Cameroon, i.e. high-dose isoniazid (77.4%), ethambutol (56.9%), and pyrazinamide (43.1%). Virtually all strains were susceptible to fluoroquinolones, kanamycin, and clofazimine, and treatment outcomes were mostly favourable (87.5%).

Conclusion

Pre-existing resistance to high-dose isoniazid, and ethambutol is associated with recent transmission of RR/MDR strains in our study. A possible contributing factor for this observation is the absence of universal drug susceptibility testing in Cameroon, likely resulting in prolonged exposure of new RR/MDR-TB patients to sub-optimal or failing first-line drug regimens.
Anti-tuberculosis drug-induced acute liver failure requiring transplantation in the second trimester of pregnancy: a case report
Authors: Zhu Zhoufeng , Zhang Min , Li Yang
Published: August 2021

Background

Treatment of tuberculosis (TB) during pregnancy can reduce maternal and foetal complications. However, it may also induce fatal liver injury.

Case presentation

We present a case of a 26-year-old pregnant woman who underwent orthotopic liver transplantation for anti-TB drug-induced fulminant hepatic failure (FHF). Her tuberculous pleurisy was treated with rifampin, isoniazid and pyrazinamide. An artificial liver support system (ALSS) was unable to reverse the liver injury while serving as a bridge to liver transplantation. She had a successful liver transplantation operation at 17 3/7 weeks of gestation. The foetal ultrasound scan showed mild foetal bilateral ventriculomegaly at 21 5/7 weeks of gestation, and labour was induced via double-balloon catheter as soon as the allograft function was stable. Despite immunosuppression, the TB was well controlled with linezolid, levofloxacin and pyridoxine at the 8 months follow-up.

Conclusions

Anti-TB drug-induced liver failure during pregnancy is rare. We present a case of successful treatment of FHF in which an artificial liver support system combined with liver transplantation. The FHF was caused by anti-TB drugs with difficulties due to pregnancy status and post-transplant anti-TB treatment. Mild foetal ventriculomegaly was found in our case. Further research is still needed to identify the risks of TB treatment and liver transplantation in pregnant women. A multidisciplinary team coordinated properly to optimize patient outcomes.
Impact of very preterm birth and post-discharge growth on cardiometabolic outcomes at school age: a retrospective cohort study
Authors: Yun Jungha , Jung Young Hwa , Shin Seung Han , Song In Gyu , Lee Young Ah , Shin Choong Ho , Kim Ee-Kyung , Kim Han-Suk
Published: August 2021

Background

Adverse metabolic outcomes later in life have been reported among children or young adults who were born as preterm infants. This study was conducted to examine the impact of very preterm/very low birth weight (VP/VLBW) birth and subsequent growth after hospital discharge on cardiometabolic outcomes such as insulin resistance, fasting glucose, and systolic and diastolic blood pressure (BP) among children at 6–8 years of age.

Methods

This retrospective cohort study included children aged 6–8 years and compared those who were born at < 32 weeks of gestation or weighing < 1,500 g at birth (n = 60) with those born at term (n = 110). Body size, fat mass, BP, glucose, insulin, leptin, adiponectin, and lipid profiles were measured. Weight-for-age z-score changes between discharge and early school-age period were also calculated, and factors associated with BP, fasting glucose, and insulin resistance were analyzed.

Results

Children who were born VP/VLBW had significantly lower fat masses, higher systolic BP and diastolic BP, and significantly higher values of fasting glucose, insulin, and homeostatic model assessment of insulin resistance (HOMA-IR), compared to children born at term. VP/VLBW was correlated with HOMA-IR and BPs after adjusting for various factors, including fat mass index and weight-for-age z-score changes. Weight-for-age z-score changes were associated with HOMA-IR, but not with BPs.

Conclusions

Although children aged 6–8 years who were born VP/VLBW showed significantly lower weight and fat mass, they had significantly higher BPs, fasting glucose, HOMA-IR, and leptin levels. The associations of VP/VLBW with cardiometabolic factors were independent of fat mass and weight gain velocity.
The COVID-19 Pandemic Mental Health Questionnaire (CoPaQ): psychometric evaluation and compliance with countermeasures in psychiatric inpatients and non-clinical individuals
Authors: Rek Stephanie V. , Bühner Markus , Reinhard Matthias A. , Freeman Daniel , Keeser Daniel , Adorjan Kristina , Falkai Peter , Padberg Frank
Published: August 2021

Background

The COVID-19 pandemic has greatly impacted people’s lives across a broad spectrum of psychosocial domains. We report the development and psychometric evaluation of the self-report COVID-19 Pandemic Mental Health Questionnaire (CoPaQ), which assesses COVID-19 contamination anxiety, countermeasure necessity and compliance, mental health impact, stressor impact, social media usage, interpersonal conflicts, paranoid ideations, institutional & political trust, conspiracy beliefs, and social cohesion. Further, we illustrate the questionnaire’s utility in an applied example investigating if higher SARS-Cov-2 infection rates in psychiatric patients could be explained by reduced compliance with preventive countermeasures.

Methods

A group of 511 non-clinical individuals completed an initial pool of 111 CoPaQ items (Open Science Framework:https://osf.io/3evn9/) and additional scales measuring psychological distress, well-being, and paranoia to assess construct validity and lifetime mental health diagnosis for criterion validity. Factor structure was determined by exploratory factor analyses and validated by conducting confirmatory factor analysis in the accompanying longitudinal sample (n = 318) and an independent psychiatric inpatient sample primarily admitted for major depressive-, substance abuse-, personality-, and anxiety disorders (n = 113). Internal consistency was assessed by Cronbach’s Alpha and McDonald’s Omega. For the applied research example, Welch t-tests and correlational analyses were conducted.

Results

Twelve out of 16 extracted subscales were retained in the final questionnaire version, which provided preliminary evidence for adequate psychometric properties in terms of factor structure, internal consistency, and construct and criterion validity. Our applied research example showed that patients exhibited greater support for COVID-19 countermeasures than non-clinical individuals. However, this requires replication in future studies.

Conclusions

We demonstrate that the CoPaQ is a comprehensive and valid measure of the psychosocial impact of the pandemic and could allow to a degree to disentangle the complex psychosocial phenomena of the pandemic as exemplified by our applied analyses.
Significance and agreement between obesity anthropometric measurements and indices in adults: a population-based study from the United Arab Emirates
Authors: Mahmoud Ibrahim , Sulaiman Nabil
Published: August 2021

Background

The rates of overweight and obese adults in the United Arab Emirates (UAE) have increased dramatically in recent decades. Several anthropometric measurements are used to assess body weight status. Some anthropometric measurements might not be convenient to use in certain communities and settings. The objective of this study was to assess the agreement of four anthropometric measurements and indices of weight status and to investigate their associations with cardiometabolic risks.

Methods

The study design was a cross-section population-based study. Adults living in the Northern Emirates were surveyed. Fasting blood samples, blood pressure readings and anthropometric measurements were also collected.

Results

A total of 3531 subjects were included in this study. The prevalence of obesity/overweight was 66.4% based on body mass index (BMI), 61.7% based on waist circumference (WC), 64.6% based on waist–hip ratio (WHR) and 71% based on neck circumference (NC). There were moderate agreements between BMI and WC and between WC and WHR, with kappa (k) ranging from 0.41 to 0.60. NC showed poor agreement with BMI, WC and WHR, with k ranging from 0 to 0.2. Overweight and obesity based on BMI, WC and WHR were significantly associated with cardiometabolic risks.

Conclusion

Overall, there was a moderate to a poor agreement between BMI, WC, WHR and NC. Particularly, NC showed poor agreement with BMI, WC and WHR. BMI and WC showed better performance for identifying cardiometabolic risks than WHR and NC.
Prevalence and incidence of work-related musculoskeletal disorders in secondary industries of 21st century Europe: a systematic review and meta-analysis
Authors: Govaerts Renée , Tassignon Bruno , Ghillebert Jo , Serrien Ben , De Bock Sander , Ampe Toon , El Makrini Ilias , Vanderborght Bram , Meeusen Romain , De Pauw Kevin
Published: August 2021

Objective

Over the course of the twenty-first century, work-related musculoskeletal disorders are still persisting among blue collar workers. At present, no epidemiological overview exists. Therefore, a systematic review and meta-analysis was performed on the epidemiology of work-related musculoskeletal disorders (WMSD) within Europe’s secondary industries.

Methods

Five databases were screened, yielding 34 studies for the qualitative analysis and 17 for the quantitative analysis. Twelve subgroups of WMSDs were obtained for the meta-analysis by means of predefined inclusion criteria: back (overall), upper back, lower back, neck, shoulder, neck/shoulder, elbow, wrist/hand, leg (overall), hip, knee, and ankle/feet.

Results

The most prevalent WMSDs were located at the back (overall), shoulder/neck, neck, shoulder, lower back and wrist WMSDs with mean 12-month prevalence values of 60, 54, 51, 50, 47, and 42%, respectively. The food industry was in the majority of subgroups the most prominent researched sector and was frequently associated with high prevalence values of WMSDs. Incidence ratios of upper limb WMSDs ranged between 0.04 and 0.26. Incidence ratios could not be calculated for other anatomical regions due to the lack of sufficient articles.

Conclusion

WMSDs are still highly present among blue collar workers. Relatively high prevalence values and low incidence ratios indicate a limited onset of WMSDs with however long-term complaints.
Technique and results after immediate orthotopic replantation of extracorporeally irradiated tumor bone autografts with and without fibular augmentation in extremity tumors
Authors: Klein Alexander , Bakhshai Yasmin , Roeder Falk , Birkenmaier Christof , Baur-Melnyk Andrea , Dürr Hans Roland
Published: August 2021

Background

Reconstruction of the skeletal defects resulting from the resection of bone tumors remains a considerable challenge and one of the possibilities is the orthotopic replantation of the irradiated bone autograft. One technical option with this technique is the addition of a vital autologous fibular graft, with or without microvascular anastomosis. The aim of our study was to evaluate the clinical results of the treatment of our patient cohort with a specific view to the role of fibular augmentation.

Methods

Twenty-one patients with 22 reconstructions were included. In all cases, the bone tumor was resected with wide margins and in 21 of them irradiated with 300 Gy. In the first case, thermal sterilization in an autoclave was used. The autograft was orthotopically replanted and stabilized with plates and screws. Fifteen patients underwent an additional fibular augmentation, 8 of which received microvascular anastomoses or, alternatively, a locally pedicled fibular interposition.

Results

the most common diagnosis was a Ewing sarcoma (8 cases) and the most common location was the femur (12 cases). The mean follow-up time was 70 months (16–154 months). For our statistical analysis, the one case with autoclave sterilization and 3 patients with tumors in small bones were excluded. During follow-up of 18 cases, 55.6% of patients underwent an average of 1.56 revision surgeries. Complete bony integration of the irradiated autografts was achieved in 88.9% of cases after 13.6 months on average. In those cases with successful reintegration, the autograft was shorter (n.s.). Microvascular anastomosis in vascularized fibular strut grafts did not significantly influence the rate of pseudarthrosis.

Conclusions

the replantation of extracorporeally irradiated bone autografts is an established method for the reconstruction of bone defects after tumor resection. Our rate of complications is comparable to those of other studies and with other methods of bone reconstruction (e.g. prosthesis). In our opinion, this method is especially well suited for younger patients with extraarticular bone tumors that allow for joint preservation. However, these patients should be ready to accept longer treatment periods.
Problems with the outcome measures in randomized controlled trials of traditional Chinese medicine in treating chronic heart failure caused by coronary heart disease: a systematic review
Authors: Hu Jiayuan , Qiu Ruijin , Li Chengyu , Li Min , Dai Qianqian , Chen Shiqi , Zhao Chen , Shang Hongcai
Published: August 2021

Background

Traditional Chinese medicine (TCM) has gained widespread application in treating chronic heart failure (CHF) secondary to coronary heart disease (CHD). However, the sound clinical evidence is still lacking. Corresponding clinical trials vary considerably in the outcome measures assessing the efficacy of TCM, some that showed the improvement of clinical symptoms are not universally acknowledged. Rational outcome measures are the key to evaluate efficacy and safety of each treatment and significant elements of a convincing clinical trial. We aimed to summarize and analyze outcome measures in randomized controlled trials (RCTs) of TCM in treating CHF caused by CHD, subsequently identify the present problems and try to put forward solutions.

Methods

We systematically searched databases including Embase, PubMed, Cochrane Library, CBM, CNKI, VIP and Wanfang from inception to October 8, 2018, to identify eligible RCTs using TCM interventions for treating CHF patients caused by CHD. Cochrane Database of Systematic Reviews (CDSR) was searched to include Cochrane systematic reviews (CSRs) of CHF. Two authors independently assessed the risk of bias of the included RCTs according to the Cochrane Handbook. Outcome measures of each trial were extracted and analyzed those compared with the CSRs. We also evaluated the reporting quality of the outcome measures.

Results

A total of 31 RCTs were included and the methodology quality of the studies was generally low. Outcome measures in these RCTs were mortality, rehospitalization, efficacy of cardiac function, left ventricular ejection fraction (LVEF), 6 min’ walk distance (6MWD) and Brain natriuretic peptide (BNP), of which mortality and rehospitalization are clinical end points while the others are surrogate outcomes. The reporting rate of mortality and rehospitalization was 12.90% (4/31), the other included studies reported surrogate outcomes. As safety measure, 54.84% of the studies reported adverse drug reactions. Two trials were evaluated as high in reporting quality of outcomes and that of the other 29 studies was poor due to lack of necessary information for reporting.

Conclusions

The present RCTs of TCM in treating CHF secondary to CHD did not concentrate on the clinical end points of heart failure, which were generally small in size and short in duration. Moreover, these trials lacked adequate safety evaluation, had low quality in reporting outcomes and certain risk of bias in methodology. For objective assessment of the efficacy and safety of TCM in treating CHF secondary to CHD, future research should be rigorous designed, set end points as primary outcome measures and pay more attention to safety evaluation throughout the trial.
Adaptations in anesthesiology residency programs amid the COVID-19 pandemic: virtual approaches to applicant recruitment
Authors: Lee Donaldson C. , Kofskey Alexander M. , Singh Nikhi P. , King Timothy W. , Piennette Paul D.
Published: August 2021

Background

The COVID-19 pandemic significantly impacted residency recruitment in 2020, posing unique challenges for programs and applicants alike. Anesthesiology programs have adopted alternate methods of recruitment, including virtual open houses and social media, due to limiting personal contact rules implemented by AAMC. This study was undertaken to determine the frequency of virtual events hosted and social media accounts created by programs.

Methods

Anesthesiology residency programs and departments were examined for social media presence on Twitter, Instagram, and Facebook. Programs’ websites and social media posts were reviewed for virtual open house opportunities. Available sub-internships were collected from the Visiting Student Application Service database. Data was collected after 2020–2021 pre-interview recruitment in October 2020.

Results

Of 153 total anesthesiology residency programs, 96 (63%) had some form of social media presence. The platforms of choice for programs with social media accounts included Twitter (71, or 46%), Instagram (67, or 44%), and Facebook (47, or 31%). Forty of seventy-six residency-affiliated accounts were created after March 1, 2020; Instagram accounts (26 of 40) represented most of these. Most Anesthesiology programs (59%) offered virtual open houses for prospective applicants. Twitter (25%), Instagram (22%), and Facebook (8%) were used by programs to advertise these events.

Conclusions

Social media presence of anesthesiology residency programs has grown steadily over the past decade, with exponential growth experienced in 2020. This data suggests that anesthesiology residency programs are employing new, mostly virtual, methods to reach prospective applicants during an unprecedented application cycle amidst the COVID-19 pandemic.
The effect of learning style and general self-efficacy on satisfaction of e-Learning in dental students
Authors: Baherimoghadam Tahereh , Hamedani Shahram , mehrabi Manoosh , Naseri Navid , Marzban Nooshin
Published: August 2021

Introduction

The COVID-19 pandemic has had a significant impact on education. e-Learning has been becoming most popular. Satisfaction of the student is one of important goal of e-Learning, therefore factors affecting this satisfaction should be considered extensively. This study aims to evaluate the effect of learning style and General Self-Efficacy (GSE) on satisfaction of e-Learning in dental student.

Method

Electronic questionnaires were sent to 85 fifth and sixth-year students who had passed the face-to-face orthodontics course in the previous semester and were studying online orthodontics at the time of this study. Three questionnaires were used including Soloman and Felder learning styles index, General self-efficacy questionnaire and Satisfaction questionnaire for online education.

Results

The results of the reliability test showed that Cronbach’s alpha index for the self-efficacy and satisfaction questionnaire was 0.836 and 0.96, respectively. The correlation between satisfaction and the dimensions of learning style showed that the active dimension of processing information had a significant relationship with the level of satisfaction. In the understanding dimension, a relatively strong correlation was observed in the Global dimension. Moderate significant relationship between the total score of self-efficacy and the level of satisfaction has been found.

Conclusion

The results of the present study highlight the necessity of more studies regarding defining effective on student satisfaction during e-Learning. GSES and active learning style in the processing dimension and global learning style in the understanding dimension affect students' satisfaction.
Exploring the experiences of nurses’ moral distress in long-term care of older adults: a phenomenological study
Authors: Nikbakht Nasrabadi Alireza , Wibisono Ahmad Hasyim , Allen Kelly-Ann , Yaghoobzadeh Ameneh , Bit-Lian Yee
Published: August 2021

Background

Moral distress is a poorly defined and frequently misunderstood phenomenon, and little is known about its triggering factors during ICU end-of-life decisions for nurses in Iran. This study aimed to explore the experiences of nurses’ moral distress in the long-term care of older adults via a phenomenological study.

Methods

A qualitative, phenomenological study was conducted with 9 participants using in-depth semi-structured interviews. The purpose was to gain insight into the lived experiences and perceptions of moral distress among ICU nurses in hospitals affiliated with Tehran University of Medical Sciences during their long-term care of older adults.

Results

Five major themes are identified from the interviews: advocating, defense mechanisms, burden of care, relationships, and organizational issues. In addition, several subthemes emerged including respectful end of life care, symptom management, coping, spirituality, futile care, emotional work, powerlessness, relationships between patients and families, relationships with healthcare teams, relationships with institutions, inadequate staffing, inadequate training, preparedness, education/mentoring, workload, and support.

Conclusions

This qualitative study contributes to the limited knowledge and understanding of the challenges nurses face in the ICU. It also offers possible implications for implementing supportive interventions.
Asymmetric expansions of FT and TFL1 lineages characterize differential evolution of the EuPEBP family in the major angiosperm lineages
Authors: Bennett Tom , Dixon Laura E.
Published: August 2021

Background

In flowering plants, precise timing of the floral transition is crucial to maximize chances of reproductive success, and as such, this process has been intensively studied. FLOWERING LOCUS T (FT) and TERMINAL FLOWER1 (TFL1) have been identified as closely related eukaryotic phosphatidylethanolamine-binding proteins (‘EuPEBPs’) that integrate multiple environmental stimuli, and act antagonistically to determine the optimal timing of the floral transition. Extensive research has demonstrated that FT acts similar to hormonal signals, being transported in the phloem from its primary site of expression in leaves to its primary site of action in the shoot meristem; TFL1 also appears to act as a mobile signal. Recent work implicates FT, TFL1, and the other members of the EuPEBP family, in the control of other important processes, suggesting that the EuPEBP family may be key general regulators of developmental transitions in flowering plants. In eudicots, there are a small number of EuPEBP proteins, but in monocots, and particularly grasses, there has been a large, but uncharacterized expansion of EuPEBP copy number, with unknown consequences for the EuPEBP function.

Results

To systematically characterize the evolution of EuPEBP proteins in flowering plants, and in land plants more generally, we performed a high-resolution phylogenetic analysis of 701 PEBP sequences from 208 species. We refine previous models of EuPEBP evolution in early land plants, demonstrating the algal origin of the family, and pin-pointing the origin of the FT/TFL1 clade at the base of monilophytes. We demonstrate how a core set of genes (MFT1, MFT2, FT, and TCB) at the base of flowering plants has undergone differential evolution in the major angiosperm lineages. This includes the radical expansion of the FT family in monocots into 5 core lineages, further re-duplicated in the grass family to 12 conserved clades.

Conclusions

We show that many grass FT proteins are strongly divergent from other FTs and are likely neo-functional regulators of development. Our analysis shows that monocots and eudicots have strongly divergent patterns of EuPEBP evolution.
Multiple malignant tumors in a patient with familial chordoma, a case report
Authors: Sumransub Nuttavut , Murugan Paari , Marette Shelly , Clohisy Denis R. , Skubitz Keith M.
Published: August 2021

Background

Chordoma is a rare bone tumor that is typically resistant to chemotherapy and is associated with genetic abnormalities of the T-box transcription factor T (TBXT) gene, which encodes the transcription factor brachyury. Brachyury is felt to be a major contributor to the development of chordomas.

Case presentation

We describe a 67-year-old woman who developed an undifferentiated pleomorphic sarcoma in her thigh. Despite treatment with standard chemotherapy regimens, she had a rapidly progressive course of disease with pulmonary metastases and passed away 8 months from diagnosis with pulmonary complications. Her medical history was remarkable in that she had a spheno-occipital chordoma at age 39 and later developed multiple other tumors throughout her life including Hodgkin lymphoma and squamous cell carcinoma and basal cell carcinoma of the skin. She had a family history of chordoma and her family underwent extensive genetic study in the past and were found to have a duplication of the TBXT gene.

Conclusions

Brachyury has been found to associate with tumor progression, treatment resistance, and metastasis in various epithelial cancers, and it might play roles in tumorigenesis and aggressiveness in this patient with multiple rare tumors and germ line duplication of the TBXT gene. Targeting this molecule may be useful for some malignancies.
The oncogenic role of HIF-1α/miR-182-5p/ZFP36L1 signaling pathway in nasopharyngeal carcinoma
Authors: Wang Gang , Zhou Fangzheng , Ou Tong , Sun Haiyan , Shan Zhirui , Lu Yingshen , Chen Gui , Yuan Simin , Zhang Xiaowen , Wu Song
Published: August 2021

Background

Accumulating evidence indicates that dysregulation of miR-182-5p can serve as diagnostic and prognostic biomarkers for some cancers, whereas the role of miR-182-5p has not been explored in nasopharyngeal carcinoma (NPC). Our study aims to elucidate the biological function of miR-182-5p in NPC and the potential molecular mechanism involved.

Methods

Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine miR-182-5p expression in NPC primary tissues and cell lines. Immunohistochemistry (IHC) for ZFP36L1 was conducted in NPC samples. Western blot was used to evaluate protein expression in cell lines. A series of functional assays were carried out to evaluate the roles of miR-182-5p and ZFP36L1 in tumor development and progression of NPC. Bioinformatics tools and luciferase reporter assays were utilized to identify the potential mechanisms of action. Moreover, rescue experiments were applied to explore whether ZFP36L1 mediated the effects of miR-182-5p in NPC.

Results

Up-regulation of miR-182-5p was significantly associated with tumor development and poor prognosis in patients with NPC. Functional study demonstrated that miR-182-5p overexpression enhanced, whereas suppression of miR-182-5p impeded NPC cell proliferation, migration, tumorigenesis and metastasis. Mechanistically, miR-182-5p interacted with ZFP36L1 at two sites in its 3′ un-translated region (UTR) and repressed ZFP36L1 expression in NPC. Consistently, an inverse correlation was observed between the expression levels of miR-182-5p and ZFP36L1 using clinical NPC tissues, and down-regulation of ZFP36L1 in NPC predicts poor survival. Furthermore, overexpression of miR-182-5p in NPC was partly attributable to the transcriptional activation effect induced by hypoxia-inducible factor 1α (HIF-1α).

Conclusions

Our data suggests that miR-182-5p facilitates cell proliferation and migration in NPC through its ability to down-regulate ZFP36L1 expression, and that the HIF-1α/miR-182-5p/ZFP36L1 axis may serve as a novel therapeutic target in the management of NPC.
Effect of a single dose of oral azithromycin on malaria parasitaemia in children: a randomized controlled trial
Authors: Coulibaly Boubacar , Sié Ali , Dah Clarisse , Bountogo Mamadou , Ouattara Mamadou , Compaoré Adama , Nikiema Moustapha , Tiansi Jérôme Nankoné , Sibiri Nestor Dembélé , Brogdon Jessica M. , Lebas Elodie , Doan Thuy , Porco Travis C. , Lietman Thomas M. , Oldenburg Catherine E.
Published: August 2021

Background

Azithromycin has recently been shown to reduce all-cause childhood mortality in sub-Saharan Africa. One potential mechanism of this effect is via the anti-malarial effect of azithromycin, which may help treat or prevent malaria infection. This study evaluated short- and longer-term effects of azithromycin on malaria outcomes in children.

Methods

Children aged 8 days to 59 months were randomized in a 1:1 fashion to a single oral dose of azithromycin (20 mg/kg) or matching placebo. Children were evaluated for malaria via thin and thick smear and rapid diagnostic test (for those with tympanic temperature ≥ 37.5 °C) at baseline and 14 days and 6 months after treatment. Malaria outcomes in children receiving azithromycin versus placebo were compared at each follow-up timepoint separately.

Results

Of 450 children enrolled, 230 were randomized to azithromycin and 220 to placebo. Children were a median of 26 months and 51% were female, and 17% were positive for malaria parasitaemia at baseline. There was no evidence of a difference in malaria parasitaemia at 14 days or 6 months after treatment. In the azithromycin arm, 20% of children were positive for parasitaemia at 14 days compared to 17% in the placebo arm (P = 0.43) and 7.6% vs. 5.6% in the azithromycin compared to placebo arms at 6 months (P = 0.47).

Conclusions

Azithromycin did not affect malaria outcomes in this study, possibly due to the individually randomized nature of the trial.

Trial registration This study is registered at clinicaltrials.gov (NCT03676751; registered 19 September 2018).
Hypoxia-inducible transcription factor-1α inhibition by topotecan protects against lipopolysaccharide-induced inflammation and apoptosis of cardiomyocytes
Authors: Zhang Ying , Xu Yi , Zhou Ke , Kao Guoying , Yan Meng , Xiao Jun
Published: August 2021

Background

Myocarditis, an inflammatory disease of the myocardium, is a serious hazard to human life due to the expansion of inflammatory lesions in the myocardium. The aim of this study was to investigate the role of hypoxia-inducible transcription factor (HIF)-1α and its inhibitor topotecan in the pathogenesis of myocarditis.

Methods

H9c2 cardiomyoblasts was stimulated with lipopolysaccharide (LPS) to simulate myocarditis model in vitro. The levels of myocardial damage markers were determined using commercially available kits. Western blotting was used to evaluate HIF-1α expression after LPS challenge. Then, after HIF-1α silencing, the contents of inflammatory factors were determined with enzyme-linked immunosorbent assay (ELISA). Cell viability was tested by means of a cell counting kit-8 (CCK-8) assay. Cell apoptosis was assessed by flow cytometry, and the expression of apoptotic proteins was examined using western blot analysis. Subsequently, HIF-1α was overexpressed and topotecan was employed to treat H9c2 cells under LPS exposure condition. The biological functions were detected again.

Results

LPS significantly elevated the levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) and cardiac troponin-I (cTn-I) in supernatant of H9c2 cell lysates. Additionally, LPS led to the notably upregulated expression of HIF-1α. HIF-1α-knockdown markedly decreased the concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8 compared with the LPS-induced group. Moreover, the cell viability was conspicuously enhanced and cell apoptotic ratio was remarkably reduced, accompanied by downregulated expression of Bax, Bim, caspase 3 and caspase 9 after HIF-1α silencing. Consistently, HIF-1α gain-of-function significantly promoted the production of inflammatory cytokines and cell apoptosis, which was partially counteracted by topotecan administration.

Conclusion

To conclude, these findings demonstrated that HIF-1α inhibition by topotecan ameliorates LPS-induced myocarditis in vitro, providing a new approach in the treatment of myocarditis.
Blau syndrome: a case report from Palestine
Authors: Iriqat Salam , Safieh Mohammed Abu , Fatouleh Manuel , Alkaiyat Abdulsalam
Published: August 2021

Background

This case study documents the first familial case of Blau syndrome (BS) in Palestine characterized with mutation in CARD15/NOD2.

Case presentation

Eighteen years old female was initially misdiagnosed with Juvenile idiopathic arthritis (JIA). The patient had been on steroids and methotrexate treatment for the last 16 years, but did not respond well to treatment. Initial examination at Saint John of Jerusalem Eye Hospital Group clinic showed bilateral intermediate uveitis with camptodactyly. The patient’s sister (aged 19 years) had bilateral intermediate uveitis and camptodactyly. Both eyes of their father had signs of old posterior uveitis. Father’s left eye showed 360 degrees posterior synechia, mature cataract with old Keratic precipitates (KPs). He also had camptodactyly. The patient was referred to pediatric rheumatologist to rule out sarcoidosis.

Lung CT scan showed bronchiectasis, genetic consultation followed. Complete eye examination, full history, refraction, and Optical coherence tomography (oct) were done. Systemic and topical steroid therapy could not control the ocular inflammation. The family then was referred to a geneticist. Genetic analyses showed that the proband and all three family members had an R334q mutation in the CARD15/Nod2 gene.

Conclusions

BS should be considered in the differential diagnosis of childhood uveitis, especially in low and middle income countries where it is misdiagnosed in many cases, which delay appropriate diagnosis and thus control. Genetic analysis of the CARD15/Nod2 gene is helpful in the diagnosis. Steroids alone are not enough to control the disease, other immunosuppressants and biologics are needed.
Hippocampal glucose uptake as a surrogate of metabolic change of microglia in Alzheimer’s disease
Authors: Choi Hongyoon , Choi Yoori , Lee Eun Ji , Kim Hyun , Lee Youngsun , Kwon Seokjun , Hwang Do Won , Lee Dong Soo ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: August 2021

Background

Dynamically altered microglia play an important role in the progression of Alzheimer’s disease (AD). Here, we found a close association of the metabolic reconfiguration of microglia with increased hippocampal glucose uptake on [18F]fluorodeoxyglucose (FDG) PET.

Methods

We used an AD animal model, 5xFAD, to analyze hippocampal glucose metabolism using both animal FDG PET and ex vivo FDG uptake test. Cells of the hippocampus were isolated to perform single-cell RNA-sequencing (scRNA-seq). The molecular features of cells associated with glucose metabolism were analyzed at a single-cell level. In order to apply our findings to human brain imaging study, brain FDG PET data obtained from the Alzheimer’s Disease Neuroimaging Initiative were analyzed. FDG uptake in the hippocampus was compared according to the diagnosis, AD, mild cognitive impairment, and controls. The correlation analysis between hippocampal FDG uptake and soluble TREM2 in cerebrospinal fluid was performed.

Results

In the animal study, 8- and 12-month-old 5xFAD mice showed higher FDG uptake in the hippocampus than wild-type mice. Cellular FDG uptake tests showed that FDG activity in hippocampal microglia was increased in the AD model, while FDG activity in non-microglial cells of the hippocampus was not different between the AD model and wild-type. scRNA-seq data showed that changes in glucose metabolism signatures including glucose transporters, glycolysis and oxidative phosphorylation, mainly occurred in microglia. A subset of microglia with higher glucose transporters with defective glycolysis and oxidative phosphorylation was increased according to disease progression. In the human imaging study, we found a positive association between soluble TREM2 and hippocampal FDG uptake. FDG uptake in the hippocampus at the baseline scan predicted mild cognitive impairment conversion to AD.

Conclusions

We identified the reconfiguration of microglial glucose metabolism in the hippocampus of AD, which could be evaluated by FDG PET as a feasible surrogate imaging biomarker for microglia-mediated inflammation.
Electrocardiographic abnormalities in medically screened German military aircrew
Authors: Guettler Norbert , Sammito Stefan
Published: August 2021

Background

A resting electrocardiogram (ECG) is a well-tolerated, non-invasive, and inexpensive test for overt electrical signs of cardiac pathology and is widely used in the screening of aircrew and other high-hazard occupations. Given the low number of pathological results leading to disqualification or restriction however, there is an ongoing debate as to how often screening ECGs should be performed in different age groups.

Methods

We restrospectively analyzed 8275 resting 12-lead ECGs registered between 2007 and 2020 in the German Air Force Centre of Aerospace Medicine. Findings were categorized according to consensus recommendations published by the NATO Working Group on Occupational Cardiology in Military Aircrew, based on ECG screening criteria published for athletes which were used at the time of registration. Age, sex, height, weight, and body mass index of the probands were also captured. Additionally, 4839 pilot and non-pilot aircrew members were analyzed longitudinally over a maximum period of 13.4 years.

Results

Out of all the ECGs only 18 revealed findings requiring further investigation, and only one individual was temporarily disqualified because of a ventricular pre-excitation (delta wave) as a sign of an antegrade conducting accessory pathway. The longitudinal analysis of 25,829 ECGs revealed 28 abnormalities requiring further investigation, and only two ECG findings (in probands aged 48.8 and 59.1 years) led to temporary, or permanent disqualification. In a third case, the ECG showed signs of a myocardial infarction, which was already known from the proband’s history.

Conclusions

Initial ECG screening for asymptomatic aircrew revealed extremely low numbers of individuals requiring further investigation in our cohort. This would appear to justify an initial screening ECG and follow-up ECGs at certain intervals starting at a certain age, but routine ECG screening of applicants in professions with a higher risk tolerance or frequent, e.g. annual, follow-up ECGs in younger aircrew is not supported by our data because of the minimal yield of ECG findings requiring further investigation.
Case report: Rare myeloid sarcoma development following renal transplantation with KRAS and DNMT3A gene mutations
Authors: Wu Danyang , Lu Xiaoxuan , Yan Xiaojing , Gao Ran
Published: August 2021

Background

A high incidence of malignant tumors, such as post-transplant lymphoproliferative disorders (PTLD), Kaposi sarcoma, and renal cancer is common in solid organ and bone marrow transplant recipients. However, myeloid sarcoma (MS) after renal transplantation has rarely been reported and the diagnosis is challenging due to its low incidence.

Case presentation

Here, we report a rare case of a 49-year-old man who developed myeloid sarcoma (MS) in the transplanted kidney two years after renal transplantation. Next-generation sequencing (NGS) showed mutations of KRAS and DNMT3A genes in the MS, and no gene mutations in the bone marrow. He presented a normal karyotype of 46, XY. Following treatment with 6 cycles of systemic chemotherapy, the patient was in satisfactory condition with stable serum creatinine (sCr) levels at the 1-year follow-up. In addition, we performed a detailed review with emphasis on the clinical manifestations, and the diagnostic and therapeutic processes of another 7 patients who developed MS following renal transplantation.

Conclusions

Our report illustrates the clinical utility of comprehensive genomic profiling in benefiting the diagnosis of MS, the selection of therapeutic strategy and the determination of whether MS is donor-derived.
Combined effect of dose gradient and rotational error on prescribed dose coverage for single isocenter multiple brain metastases in frameless stereotactic radiotherapy
Authors: Yoon Jai-Woong , Park Soah , Cheong Kwang-Ho , Kang Sei-Kwon , Han Tae Jin
Published: August 2021

Background

To evaluate the combined effect of rotational error and dose gradient on target dose coverage in frameless stereotactic radiotherapy.

Methods

Three spherical targets of different diameters (1, 1.5, and 2 cm) were drawn and placed equidistantly on the same axial brain computed tomography (CT) images. To test the different isocenter-target distances, 2.5- and 5-cm configurations were prepared. Volumetric modulated arc therapy plans were created for different dose gradients from the target, in which the dose gradients were modified using the maximum dose inside the target. To simulate the rotational error, CT images and targets were rotated in two ways by 0.5°, 1°, and 2°, in which one rotation was in the axial plane and the other was in three dimensions. The initial optimized plan parameters were copied to the rotated CT sets, and the doses were recalculated. The coverage degradation after rotation was analyzed according to the target dislocation and 12-Gy volume.

Results

A shallower dose gradient reduced the loss of target coverage under target dislocation, and the effect was clearer for small targets. For example, the coverage of the 1-cm target under 1-mm dislocation increased from 93 to 95% by increasing the Paddick gradient index from 5.0 to 7.9. At the same time, the widely accepted necrosis indicator, the 12-Gy volume, increased from 1.2 to 3.5 cm3, which remained in the tolerable range. From the differential dose volume histogram (DVH) analysis, the shallower dose gradient ensured that the dose-deficient under-covered target volume received a higher dose similar to that in the prescription.

Conclusions

For frameless stereotactic brain radiotherapy, the gradient, alongside the margin addition, can be adjusted as an ancillary parameter for small targets to increase target coverage or at least limit coverage reduction in conditions with probable positioning error.
WISC-IV performance of children with Chronic Tic Disorder, Obsessive–Compulsive Disorder and Attention-Deficit/Hyperactivity Disorder: results from a German clinical study
Authors: Wanderer Sina , Roessner Veit , Strobel Anja , Martini Julia
Published: August 2021

Background

Chronic Tic Disorder (CTD), Obsessive–Compulsive Disorder (OCD) and Attention-Deficit/Hyperactivity Disorder (ADHD) are complex neuropsychiatric disorders that frequently co-occur. The aim of this study was to examine WISC-IV performance of a clinical cohort of children with CTD, OCD and/or ADHD.

Methods

N = 185 children aged 6 to 17 years from Germany with CTD, OCD and/or ADHD were examined with the WISC-IV that comprises four index scores (VCI: Verbal Comprehension Index, PRI: Perceptual Reasoning Index, WMI: Working Memory Index, PSI: Processing Speed Index) and a Full Scale Intelligence Quotient (FSIQ). WISC-IV profiles of children with CTD-only, OCD-only, ADHD-only, CTD+ADHD, CTD+OCD and CTD+OCD+ADHD were compared with the WISC-IV norm (N = 1650, M = 100 and SD = 15) and among each other.

Results

Unpaired t-tests revealed that children with ADHD-only showed significant lower PSI scores, whereas children with CTD-only and OCD-only had significant higher VCI scores as compared to the German WISC-IV norm. One-way ANOVA revealed that children with ADHD-only showed significant lower WMI scores as compared to children with CTD+OCD.

Conclusions

We were able to confirm previous evidence on WISC-IV profiles in ADHD in a German clinical sample and contribute new findings on cognitive performance in children with (non-)comorbid CTD and OCD that have to be seen in light of the study’s limitations.
Adolescents amid the COVID-19 pandemic: a prospective study of psychological functioning
Authors: Daniunaite Ieva , Truskauskaite-Kuneviciene Inga , Thoresen Siri , Zelviene Paulina , Kazlauskas Evaldas
Published: August 2021

Background

The spread of coronavirus disease (COVID-19) and the accompanying countermeasures can significantly impact the wellbeing of adolescents. There is a lack of longitudinal studies that can shed light on potential social, emotional, and behavioral development in adolescents. We aimed to identify potential changes in adolescent psychosocial functioning from pre-pandemic to peri-pandemic assessment, and secondly, to identify specific patterns of change.

Methods

This longitudinal study was based on a Lithuanian community sample of 331 adolescents aged 12–16 at T1 (M  =  13.87, SD  =  1.59). T1 data collected before the pandemic (March–June, 2019) was compared with T2 data collected during the COVID-19 outbreak (October 2020). Psychosocial functioning was assessed by The Strengths and Difficulties Questionnaire (SDQ). Multivariate latent change modeling and latent class change approaches were used to identify patterns of change.

Results

We found a small but significant increase in hyperactivity/inattention, emotional symptoms, but also prosocial behavior from before to during the pandemic, even adjusting for resilience, lifetime abuse experience, and socio-demographic situation. Three change profiles were identified in the latent change analysis: (1) a majority (70.7%) experienced a significant increase in psychosocial problems; (2) a smaller sub-group (19.6%) with increased peer problems only; (3) a small group (9.7%) showing no negative change and an increase in prosocial behavior.

Conclusions

The study found a significant negative impact of the COVID-19 pandemic on mental health in the majority of adolescents, as well as indications of positive social development in a small group. These findings highlight the importance of identifying and supporting adolescents in the time of the pandemic more effectively. Accumulating knowledge about human responses to the coronavirus, particularly in young people, is pivotal to societal preparedness for future pandemics.
A new case of 17p13.3p13.1 microduplication resulted from unbalanced translocation: clinical and molecular cytogenetic characterization
Authors: Markova Zhanna G. , Minzhenkova Marina E. , Bessonova Lyudmila A. , Shilova Nadezda V.
Published: August 2021

Copy number gain 17 p13.3p13.1 was detected by chromosomal microarray (CMA) in a girl with developmental/speech delay and facial dysmorphism. FISH studies made it possible to establish that the identified genomic imbalance is the unbalanced t(9;17) translocation of maternal origin. Clinical features of the patient are also discussed. The advisability of using the combination of CMA and FISH analysis is shown. Copy number gains detected by clinical CMA should be confirmed using FISH analysis in order to determine the physical location of the duplicated segment. Parental follow-up studies is an important step to determine the origin of genomic imbalance. This approach not only allows a most comprehensive characterization of an identified chromosomal/genomic imbalance but also provision of an adequate medical and genetic counseling for a family taking into account a balanced chromosomal rearrangement.