bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased biological relevance of transcriptome analyses in human skeletal muscle using a model-specific pipeline
Authors: Khan Yusuf , Hammarström Daniel , Rønnestad Bent R. , Ellefsen Stian , Ahmad Rafi
Published: November 2020

Background

Human skeletal muscle responds to weight-bearing exercise with significant inter-individual differences. Investigation of transcriptome responses could improve our understanding of this variation. However, this requires bioinformatic pipelines to be established and evaluated in study-specific contexts. Skeletal muscle subjected to mechanical stress, such as through resistance training (RT), accumulates RNA due to increased ribosomal biogenesis. When a fixed amount of total-RNA is used for RNA-seq library preparations, mRNA counts are thus assessed in different amounts of tissue, potentially invalidating subsequent conclusions. The purpose of this study was to establish a bioinformatic pipeline specific for analysis of RNA-seq data from skeletal muscles, to explore the effects of different normalization strategies and to identify genes responding to RT in a volume-dependent manner (moderate vs. low volume). To this end, we analyzed RNA-seq data derived from a twelve-week RT intervention, wherein 25 participants performed both low- and moderate-volume leg RT, allocated to the two legs in a randomized manner. Bilateral muscle biopsies were sampled fromm. vastus lateralisbefore and after the intervention, as well as before and after the fifth training session (Week 2).

Result

Bioinformatic tools were selected based on read quality, observed gene counts, methodological variation between paired observations, and correlations between mRNA abundance and protein expression of myosin heavy chain family proteins. Different normalization strategies were compared to account for global changes in RNA to tissue ratio. After accounting for the amounts of muscle tissue used in library preparation, global mRNA expression increased by 43–53%. At Week 2, this was accompanied by dose-dependent increases for 21 genes in rested-state muscle, most of which were related to the extracellular matrix. In contrast, at Week 12, no readily explainable dose-dependencies were observed. Instead, traditional normalization and non-normalized models resulted in counterintuitive reverse dose-dependency for many genes. Overall, training led to robust transcriptome changes, with the number of differentially expressed genes ranging from 603 to 5110, varying with time point and normalization strategy.

Conclusion

Optimized selection of bioinformatic tools increases the biological relevance of transcriptome analyses from resistance-trained skeletal muscle. Moreover, normalization procedures need to account for global changes in rRNA and mRNA abundance.
A general index for linear and nonlinear correlations for high dimensional genomic data
Authors: Yao Zhihao , Zhang Jing , Zou Xiufen
Published: November 2020

Background

With the advance of high throughput sequencing, high-dimensional data are generated. Detecting dependence/correlation between these datasets is becoming one of most important issues in multi-dimensional data integration and co-expression network construction. RNA-sequencing data is widely used to construct gene regulatory networks. Such networks could be more accurate when methylation data, copy number aberration data and other types of data are introduced. Consequently, a general index for detecting relationships between high-dimensional data is indispensable.

Results

We proposed a Kernel-Based RV-coefficient, named KBRV, for testing both linear and nonlinear correlation between two matrices by introducing kernel functions into RV2 (the modified RV-coefficient). Permutation test and other validation methods were used on simulated data to test the significance and rationality of KBRV. In order to demonstrate the advantages of KBRV in constructing gene regulatory networks, we applied this index on real datasets (ovarian cancer datasets and exon-level RNA-Seq data in human myeloid differentiation) to illustrate its superiority over vector correlation.

Conclusions

We concluded that KBRV is an efficient index for detecting both linear and nonlinear relationships in high dimensional data. The correlation method for high dimensional data has possible applications in the construction of gene regulatory network.
QTL mapping of winter dormancy and associated traits in two switchgrass pseudo-F1 populations: lowland x lowland and lowland x upland
Authors: M. Razar Rasyidah , Missaoui Ali
Published: November 2020

Background

Switchgrass (Panicum virgatum) undergoes winter dormancy by sensing photoperiod and temperature changes. It transitions to winter dormancy in early fall following at the end of reproduction and exits dormancy in the spring. The duration of the growing season affects the accumulation of biomass and yield. In this study, we conducted QTL mapping of winter dormancy measured by fall regrowth height (FRH) and normalized difference vegetation index (NDVI), spring emergence (SE), and flowering date (FD) in two bi-parental pseudo-F1 populations derived from crosses between the lowland AP13 with the lowland B6 (AB) with 285 progenies, and the lowland B6 with the upland VS16 (BV) with 227 progenies.

Results

We identified 18 QTLs for FRH, 18 QTLs for NDVI, 21 QTLs for SE, and 30 QTLs for FD. The percent variance explained by these QTLs ranged between 4.21–23.27% for FRH, 4.47–24.06% for NDVI, 4.35–32.77% for SE, and 4.61–29.74% for FD. A higher number of QTL was discovered in the BV population, suggesting more variants in the lowland x upland population contributing to the expression of seasonal dormancy underlying traits. We identified 9 regions of colocalized QTL with possible pleiotropic gene action. The positive correlation between FRH or NDVI with dry biomass weight suggests that winter dormancy duration could affect switchgrass biomass yield. The medium to high heritability levels of FRH (0.55–0.64 H2) and NDVI (0.30–0.61 H2) implies the possibility of using the traits for indirect selection for biomass yield.

Conclusion

Markers found within the significant QTL interval can serve as genomic resources for breeding non-dormant and semi-dormant switchgrass cultivars for the southern regions, where growers can benefit from the longer production season.
Preoperative intravenous rehydration for patients with pheochromocytomas and paragangliomas: is it necessary? A propensity score matching analysis
Authors: Kong Hao , Yang Jiao-Nan , Tian Jie , Li Nan , Zhang Yu-Xiu , Ye Peng-Cheng , Li Xue-Ying , Zhang Zheng
Published: November 2020

Background

Preoperative intravenous rehydration for patients with pheochromocytomas and paragangliomas (PPGLs) is widely used in many medical centers, but its usefulness has not been well evaluated. The objective of this study was to compare the perioperative hemodynamics and early outcome between patients who received preoperative intravenous rehydration and those without for resection of PPGLs.

Methods

In this retrospective propensity score-matched cohort study, the data of patients who underwent surgery for PPGLs were collected. Patients were divided into two groups depending on whether they received or did not receive intravenous rehydration preoperatively. The primary endpoint was intraoperative hypotension, described as the cumulative time of mean arterial pressure < 65 mmHg averaged by surgery duration.

Results

Among 231 enrolled patients, 113 patients received intravenous rehydration of ≥2000 ml daily for ≥2 days before surgery and 118 patients who did not have any intravenous rehydration before surgery. After propensity score matching, 85 patients remained in each group. The median cumulative time of mean arterial pressure < 65 mmHg averaged by surgery duration was not significantly different between rehydrated patients and non-rehydrated patients (median 3.0% [interquartile range 0.2–12.2] versus 3.8% [0.0–14.2], median difference 0.0, 95%CI − 1.2 to 0.8, p = 0.909). The total dose of catecholamines given intraoperatively, volume of intraoperative fluids, intraoperative tachycardia and hypertension, percentage of patients who suffered from postoperative hypotension, postoperative diuretics use, and postoperative early outcome between the two groups were not significantly different either.

Conclusions

For patients with PPGLs, preoperative intravenous rehydration failed to optimize perioperative hemodynamics or improve early outcome.
Retraction Note: Psychometric properties of a short version of the Job Anxiety Scale
Authors: Schmalbach Bjarne , Kalkbrenner Andreas , Bassler Markus , Hinz Andreas , Petrowski Katja
Published: November 2020

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12874-020-01166-w.
Using Trial Sequential Analysis for estimating the sample sizes of further trials: example using smoking cessation intervention
Authors: Claire Ravinder , Gluud Christian , Berlin Ivan , Coleman Tim , Leonardi-Bee Jo
Published: November 2020

Background

Assessing benefits and harms of health interventions is resource-intensive and often requires feasibility and pilot trials followed by adequately powered randomised clinical trials. Data from feasibility and pilot trials are used to inform the design and sample size of the adequately powered randomised clinical trials. When a randomised clinical trial is conducted, results from feasibility and pilot trials may be disregarded in terms of benefits and harms.

Methods

We describe using feasibility and pilot trial data in the Trial Sequential Analysis software to estimate the required sample size for one or more trials investigating a behavioural smoking cessation intervention. We show how data from a new, planned trial can be combined with data from the earlier trials using trial sequential analysis methods to assess the intervention’s effects.

Results

We provide a worked example to illustrate how we successfully used the Trial Sequential Analysis software to arrive at a sensible sample size for a new randomised clinical trial and use it in the argumentation for research funds for the trial.

Conclusions

Trial Sequential Analysis can utilise data from feasibility and pilot trials as well as other trials, to estimate a sample size for one or more, similarly designed, future randomised clinical trials. As this method uses available data, estimated sample sizes may be smaller than they would have been using conventional sample size estimation methods.
Patient involvement to inform the design of a clinical trial in postbariatric hypoglycaemia
Authors: Hepprich Matthias , Donath Marc Y. , Hemkens Lars G.
Published: November 2020

Background

Bariatric surgery may lead to symptomatic postprandial hypoglycaemia as a major side effect without established therapy so far. We aimed to develop an evidence-based study design of a clinical trial that tests treatment options and can provide useful patient-relevant evidence.

Methods

We searched systematically for guidance of core outcome sets to determine the most relevant types of outcomes and duration of such a trial. Our search comprised literature databases, a database of core outcome sets and self-help organizations. We then developed a simple online questionnaire based on interviews with German-speaking patients with postprandial hypoglycaemia after bariatric surgery. We recruited participants by reaching out to all German speaking endocrinologists in Switzerland and large Swiss bariatric centres. We asked for preferences regarding outcome types and acceptable duration of being included in a corresponding clinical trial.

Results

The literature search did not identify evidence-based guidance for informing our study design. Experience of clinical and research routine as well as patient interviews helped in identifying potential outcomes and the design of an online questionnaire. Therein, a total of 29 persons started the questionnaire and 22 answered questions related to the primary outcome. Of these, 17 (77.3%) deemed quality of life more relevant as primary outcome than the rate of hypoglycaemic episodes. A trial length of four weeks or longer was regarded as acceptable for 19 of 21 respondents to this question (91.4%) and of six months or longer for 12 respondents (56%).

Conclusions

In situations with no other guidance, a simple questionnaire may help to inform trial design decisions. This study identifies a patient preference for “quality of life” as a primary outcome and supports the evidence-based conception of a patient-centred clinical trial in postbariatric hypoglycaemia.
Tele-ECG consulting and outcomes on primary care patients in a low-to-middle income population: the first experience from Makassar telemedicine program, Indonesia
Authors: Mappangara Idar , Qanitha Andriany , Uiterwaal Cuno S. P. M. , Henriques Jose P. S. , de Mol Bastianus A. J. M.
Published: November 2020

Background

Telemedicine has been a popular tool to overcome the lack of access to healthcare facilities, primarily in underprivileged populations. We aimed to describe and assess the implementation of a tele-electrocardiography (ECG) program in primary care settings in Indonesia, and subsequently examine the short- and mid-term outcomes of patients who have received tele-ECG consultations.

Methods

ECG recordings from thirty primary care centers were transmitted to Makassar Cardiac Center, Indonesia from January to July 2017. We cross-sectionally measured the performance of this tele-ECG program, and prospectively sent a detailed questionnaire to general practitioners (GPs) at the primary care centers. We performed follow-up at 30 days and at the end of the study period to assess the patient outcomes.

Results

Of 505 recordings, all (100%) ECGs were qualified for analysis, and about half showed normal findings. The mean age of participants was 53.3 ± 13.6 years, and 40.2% were male. Most (373, 73.9%) of these primary care patients exhibited manifested CVD symptom with at least one risk factor. Male patients had more ischemic ECGs compared to women (p < 0.01), while older age (> 55 years) was associated with ischemic or arrhythmic ECGs (p < 0.05). Factors significantly associated with a normal ECG were younger age, female gender, lower blood pressure and heart rate, and no history of previous cardiovascular disease (CVD) or medication. More patients with an abnormal ECG had a history of hypertension, known diabetes, and were current smokers (p < 0.05). Of all tele-consultations, GPs reported 95% of satisfaction rate, and 296 (58.6%) used tele-ECG for an expert opinion. Over the total follow-up (14 ± 6.6 months), seven (1.4%) patients died and 96 (19.0%) were hospitalized for CVD. Of 88 patients for whom hospital admission was advised, 72 (81.8%) were immediately referred within 48 h following the tele-ECG consultation.

Conclusions

Tele-ECG can be implemented in Indonesian primary care settings with limited resources and may assist GPs in immediate triage, resulting in a higher rate of early hospitalization for indicated patients.
Long term follow-up of a simplified and less burdened pancreatic duct ligation model of exocrine pancreatic insufficiency in Goettingen Minipigs
Authors: Luu Andreas Minh , Brock Alexander , Ritz Sabrina , Junghänel Sandra , Aldag Ingo , Edskes Stella , Hartmann Marcus , Hessler Michael , Praktiknjo Michael , Arnemann Philip , Ertmer Christian , Uhl Waldemar , Schnekenburger Juergen , Herzog Torsten
Published: November 2020

Background

Pancreatic duct ligation in a minipig model leads to exocrine pancreatic insufficiency (EPI). This allows the study of digestive processes and pancreatic enzyme replacement therapies. However, detailed descriptions of the surgical procedure, perioperative management, a determination of exocrine pancreatic insufficiency are scarce in the literature. Data of the long-term health status of minipigs upon EPI induction are still not available. Therefore, the present study describes in detail an experimental approach to the induction of exocrine pancreatic insufficiency via pancreatic duct ligation in minipigs and the long term follow up of the animal’s health state.

Methods

14 Goettingen minipigs underwent pancreatic duct ligation via midline laparotomy for the induction of exocrine pancreatic insufficiency. Fecal fat content, fat absorption, chymotrypsin levels, body weight and blood vitamin and glucose levels were determined.

Results

Exocrine pancreatic insufficiency was successfully induced in 12 Goettingen minipigs. Two minipigs failed to develop exocrine insufficiency most likely due to undetected accessory pancreatic ducts. All animals tolerated the procedure very well and gained weight within 8 weeks after surgery without requiring pancreatic enzyme replacement therapy. The follow up for approx. 180 weeks showed a stable body weight and health state of the animals with normal blood glucose levels (Table 1). From approx. 130 weeks post pancreatic duct ligation, all animals were supplemented with pancreatic enzymes and vitamins resulting in blood concentrations almost within the reference range.

Conclusions

Pancreatic duct ligation in minipigs is an excellent method of inducing exocrine pancreatic insufficiency. It is important to identify and ligate accessory pancreatic ducts since persistence of accessory ducts will lead to maintenance of exocrine pancreatic function. The EPI model caused no persistent side effects in the animals and has the potential to be used in long-term EPI studies with up to 100 weeks post-OP without supplementation with enzymes and vitamins.
Progression to invasive cancer after snare polypectomy of intracholecystic papillary neoplasms during gallbladder stone removal by percutaneous transhepatic choledochoscopy: a case report
Authors: Oh Chi Hyuk , Dong Seok Ho
Published: November 2020

Background

Intracholecystic papillary neoplasms (ICPNs) of the gallbladder are rare, preinvasive lesions characterized by an intracholecystic papillary growth that may be associated with invasive adenocarcinoma. The natural history of ICPN is unknown. Here, we report a case of ICPN, highlighting its natural course.

Case presentation

A 79-year-old woman presented to the emergency department with perforated cholecystitis. After percutaneous transhepatic gallbladder drainage, due to the presence of surgical risk factors, we opted to perform gallstone removal through percutaneous transhepatic cholangioscopy instead of cholecystectomy. ICPN, which was accidentally detected after the removal of the gallbladder stones, was also endoscopically removed. After 4 years, the patient came back to the hospital with a large gallbladder mass. After cholecystectomy, pathological examination revealed ICPN with invasive adenocarcinoma.

Conclusion

The current case showed endoscopic findings of ICPN and its natural progression, particularly its clinicopathological features and outcomes.
Does working memory protect against auditory distraction in older adults?
Authors: Mahajan Yatin , Kim Jeesun , Davis Chris
Published: November 2020

Background

Past research indicates that when younger adults are engaged in a visual working memory task, they are less distracted by novel auditory stimuli than when engaged in a visual task that does not require working memory. The current study aimed to determine whether working memory affords the same protection to older adults.

Method

We examined behavioral and EEG responses in 16 younger and 16 older adults to distractor sounds when the listeners performed two visual tasks; one that required working memory (W1) and the other that did not (W0). Auditory distractors were presented in an oddball paradigm, participants were exposed to either standard tones (600 Hz: 80%) or various novel environmental sounds (20%).

Results

It was found that: 1) when presented with novel vs standard sounds, older adults had faster correct response times in the W1 visual task than in the W0 task, indicating that they were less distracted by the novel sound; there was no difference in error rates. Younger adults did not show a task effect for correct response times but made slightly more errors when a novel sound was presented in the W1 task compared to the W0 task. 2) In older adults (but not the younger adults), the amplitude of N1 was smaller in the W1 condition compared to the W0 condition. 3) The working memory manipulation had no effect on MMN amplitude in older adults. 4) For the W1 compared to W0 task, the amplitude of P3a was attenuated for the older adults but not for the younger adults.

Conclusions

These results suggest that during the working memory manipulation older adults were able to engage working memory to reduce the processing of task-irrelevant sounds.
Incident tuberculosis disease in patients receiving biologic therapies in the Western Cape, South Africa from 2007 to 2018
Authors: du Toit Tessa , Esterhuizen Tonya M. , Tiffin Nicki , Abulfathi Ahmed A. , Reuter Helmuth , Decloedt Eric H.
Published: November 2020

Background

South Africa has one of the highest tuberculosis incidence rates. Biologic disease-modifying anti-rheumatic drugs are associated with an increased risk of tuberculosis. The objective of this study was to describe the tuberculosis disease incidence rate among public sector patients receiving biologic therapies in the Western Cape Province.

Methods

A retrospective, descriptive analysis was undertaken using routine health data collated by the Provincial Health Data Centre from January 2007 (first use of biologic therapy in the Western Cape) to September 2018.

Results

We identified 609 patients treated with tumour necrosis factor-alpha (TNF-α) or non-TNF-α biologic therapies. Thirty-seven (37) patients developed tuberculosis after biologic therapy exposure, of whom the majority (78%) had an immune mediated inflammatory disease and the remainder (22%) a haematologic malignancy. The incidence rate of tuberculosis per 100,000 person-years was 2227 overall [95% confidence interval (CI): 1591, 3037]. Patients treated with TNF-α inhibitors and non-TNF-α inhibitors had estimated incidence rates of 2819 [95% CI: 1669, 4480] and 1825 [95% CI: 1131, 2797], respectively (p = 0.10).

Conclusion

Patients exposed to both TNF-α and non-TNF-α biologic therapies may have a higher incidence of tuberculosis disease compared to the background risk of 681 cases per 100,000 per year in the Western Cape.
Aetiology of acute febrile illness among children attending a tertiary hospital in southern Ethiopia
Authors: Shimelis Techalew , Tadesse Birkneh Tilahun , W/Gebriel Fitsum , Crump John A. , Schierhout Gill , Dittrich Sabine , Kaldor John M , Vaz Nery Susana
Published: November 2020

Background

The diagnosis of non-malarial aetiologies, which now represent the majority of febrile illnesses, has remained problematic in settings with limited laboratory capacity. We aimed to describe common aetiologies of acute febrile illness among children in a setting where malaria transmission has declined.

Methods

A prospective cross-sectional study was conducted among children aged at least 2 months and under 13 years presenting with fever (temperature of ≥37.5 °C or a history of fever in the past 48 h) to Hawassa Comprehensive Specialized Hospital, southern Ethiopia, from May 2018 through February 2019. Clinical and demographic data were gathered for consecutive participants, and malaria microscopy, HIV testing, and blood and urine cultures were performed regardless of clinical presentation. Additionally, stool analyses (culture and rotavirus/adenovirus RDT) and throat swab for group A Streptococcus (GAS) and urine Streptococcus pneumoniae were performed by RDTs for children with specific conditions. The antimicrobial susceptibility of bacterial isolates was determined using disc diffusion method.

Results

During the study period 433 children were recruited, median age 20 months (range, 2 months – 12 years) and 178 (41.1%) female. Malaria was diagnosed in 14 (3.2%) of 431 children, and 3 (0.7%) had HIV infection. Bacteraemia or fungaemia was detected in 27 (6.4%) of 421 blood cultures, with Staphylococcus aureus isolated in 16 (3.8%). Urinary tract infections (UTIs) were detected in 74 (18.4%) of 402, with Escherichia coli isolated in 37 (9.2%). Among 56 children whose stool specimens were tested, 14 (25%) were positive for rotavirus, 1 (1.8%) for Salmonella Paratyphi A, and 1 (1.8%) for Shigella dysenteriae. Among those with respiratory symptoms, a throat swab test for GAS and urine test for S. pneumoniae were positive in 28 (15.8%) of 177 and 31 (17.0%) of 182, respectively. No test was positive for a pathogen in 266 (61.4%) of 433 participants. Bacterial isolates were frequently resistant to ampicillin, trimethoprim-sulfamethoxazole, tetracycline, and amoxicillin and clavulanic acid.

Conclusion

Our results showed low proportions of malaria and bacteraemia among febrile children. In contrast, the frequent detection of UTI emphasize the need to support enhanced diagnostic capacity to ensure appropriate antimicrobial intervention.
Prevalence and determinants of TB infection in a rural population in northeastern Myanmar
Authors: Lwin Theint Theint , Apidechkul Tawatchai , Saising Jongkon , Upala Panupong , Tamornpark Ratipark , Chomchoei Chalitar , Yeemard Fartima , Suttana Wipob , Sunsern Rachanee
Published: November 2020

Background

Tuberculosis (TB) is a major human threat, as evidenced by the large numbers of cases and deaths, particularly in developing countries with poor economic and educational statuses. Myanmar has one of the highest TB burdens in the world, but no TB information is available for people living in the rural northeastern regions of Myanmar. The present study estimated the prevalence of TB and identified factors associated with TB infection in people living in rural communities in Shan State.

Methods

A cross-sectional study was performed to gather information from participants. People aged 18–59 years who lived in the three areas with the highest numbers of TB cases in Shan State in northeastern Myanmar were included in the study population. A simple random method was used to select the sample from the villages. A validated questionnaire was used for data collection in face-to-face interviews after obtaining signed informed consent from the selected participants. The Mantoux tuberculin skin test (TST) was administered to detect TB infection, and a result that was 10 mm or greater after 48 h was considered positive. Chi-squared tests and logistic regression were used to identify the associations between the variables at a significance level of α = 0.05.

Results

A total of 303 participants were recruited for the study; 64.7% were females, and the mean age was 37 years (SD = 12.5). Most participants were Burmese (25.4%), and 14.95% were Shan. Sixty-three participants (20.8%) had a positive TST. Four variables were associated with TB infection in the multivariate model. Males had a greater chance of TB infection than females (AOR = 2.51; 95% CI = 1.32–4.76). Participants who were ever married had a greater chance of TB infection than participants who were single (AOR = 3.93; 95% CI = 1.18–13.00). Participants who used wood and charcoal as their main sources of energy for cooking had a greater chance of TB infection than participants who used electricity (AOR = 4.23; 95% CI = 1.25–9.64). Participants who had a low level of TB prevention and care knowledge had a greater chance of TB infection than participants with a high level of TB prevention and care knowledge (AOR = 4.49; 95% CI = 1.88–10.72).

Conclusions

Public health programs that focus on improving knowledge of TB prevention and care and avoiding the use of wood and charcoal as the primary sources of energy for cooking, particularly in males and ever-married individuals, are urgently needed.
Seroprevalence of toxoplasmosis among reproductive-aged women in Myanmar and evaluation of luciferase immunoprecipitation system assay
Authors: Aye Khin Myo , Nagayasu Eiji , Nyunt Myat Htut , Zaw Ni Ni , Thant Kyaw Zin , Kyaw Myat Phone , Maruyama Haruhiko
Published: November 2020

Backgrounds

Primary infection with Toxoplasma gondii during pregnancy can pose serious health problems for the fetus. However, the epidemiological status of toxoplasmosis among reproductive-aged population in Myanmar is largely unknown. Although luciferase immunoprecipitation system (LIPS) assays for serodiagnosis of toxoplasmosis was developed mostly using mouse infection model, had not been tested by using field-derived human samples.

Methods

A total of 251 serum samples were collected from reproductive-aged women, residing in Shwegyin township, Bago region, Myanmar and analyzed with a commercial ELISA kit, as well as in-house LIPS assays.

Results

The overall seroprevalence for Toxoplasma gondii infection by the commercial ELISA was 11.5%. No clear risk factor was identified except for being in the younger age group (15–30 years old). Overall, LIPS assays showed low sensitivity when the commercial ELSA was used as a reference test.

Conclusion

We identified the epidemiological situation of toxoplasmosis in some rural communities in Myanmar. The data obtained here will serve as a primary information for the effort to reduce toxoplasmosis in this region. Although looked promising in the previous experiments with mouse infection model, we found that the reported LIPS procedures need further improvements to increase the sensitivities.
Net ultrafiltration prescription survey in Europe
Authors: Lumlertgul Nuttha , Murugan Raghavan , Seylanova Nina , McCready Patricia , Ostermann Marlies
Published: November 2020

Background

Fluid overload is common in patients in the intensive care unit (ICU) and ultrafiltration (UF) is frequently required. There is lack of guidance on optimal UF practice. We aimed to explore patterns of UF practice, barriers to achieving UF targets, and concerns related to UF practice among practitioners working in Europe.

Methods

This was a sub-study of an international open survey with focus on adult intensivists and nephrologists, advanced practice providers, and ICU and dialysis nurses working in Europe.

Results

Four hundred eighty-five practitioners (75% intensivists) from 31 countries completed the survey. The most common criteria for UF initiation was persistent oliguria/anuria (45.6%), followed by pulmonary edema (16.7%). Continuous renal replacement therapy was the preferred initial modality (90.0%). The median initial and maximal rate of net ultrafiltration (UFNET) prescription in hemodynamically stable patients were 149 mL/hr. (IQR 100–200) and 300 mL/hr. (IQR 201–352), respectively, compared to a median UFNET rate of 98 mL/hr. (IQR 51–108) in hemodynamically unstable patients and varied significantly between countries.

Two-thirds of nurses and 15.5% of physicians reported assessing fluid balance hourly. When hemodynamic instability occurred, 70.1% of practitioners reported decreasing the rate of fluid removal, followed by starting or increasing the dose of a vasopressor (51.3%). Most respondents (90.7%) believed in early fluid removal and expressed willingness to participate in a study comparing protocol-based fluid removal versus usual care.

Conclusions

There was a significant variation in UF practice and perception among practitioners in Europe. Future research should focus on identifying the best strategies of prescribing and managing ultrafiltration in critically ill patients.
The association of maternal-fetal attachment with smoking and smoking cessation during pregnancy in The FinnBrain Birth Cohort Study
Authors: Jussila Heidi , Pelto Juho , Korja Riikka , Ekholm Eeva , Pajulo Marjukka , Karlsson Linnea , Karlsson Hasse
Published: November 2020

Background

Smoking in pregnancy constitutes a preventable risk factor for fetal/child development and maternal-fetal attachment (MFA) seems to contain a momentum that can break the chain of adverse outcomes by promoting maternal prenatal health practices. This study aimed to explore the association of MFA with smoking at any time during pregnancy and smoking cessation in early pregnancy, and the modifying role of MFA on the expected effects of education and prenatal psychological distress (PPD) on prenatal smoking behavior.

Methods

The pregnant women (n = 3766) participated in the The FinnBrain Birth Cohort Study in Finland between December 2011 and April 2015. The binary outcomes, smoking at any time during pregnancy and smoking cessation in early pregnancy, were obtained from self-reports at gestational weeks (gwks) 14 and 34 and The Finnish Medical Birth Register. MFA was assessed with the Maternal-Fetal Attachment Scale (MFAS) at gwks 24 and 34. Logistic regression analyses were used to determine the association between MFA and maternal prenatal smoking behavior.

Findings

The prevalence of smoking was 16.5%, and 58.1% of the smokers quit smoking during pregnancy. The independent associations of total MFA scores with prenatal smoking behavior were not established (aOR = 1.00-1.02, multiplicity adjustedp > 0.05). A higher score in the altruistic subscale of MFA,Giving of self, associated with a higher probability of smoking cessation (24 gwks: aOR = 1.13, 95% CI [1.04, 1.24],p = 0.007, multiplicity adjustedp = 0.062; 34 gwks: aOR = 1.17, 95% CI [1.07, 1.29],p < 0.001, multiplicity adjustedp = 0.008). The modifying effect of MFA on the observed associations between PPD and smoking in pregnancy and between maternal education and smoking in pregnancy / smoking cessation in early pregnancy was not demonstrated.

Conclusions

The altruistic dimension of maternal-fetal attachment associates with an increased probability of smoking cessation during pregnancy and therefore strengthening altruistic maternal-fetal attachment may constitute a promising novel approach for interventions aiming at promoting smoking cessation during pregnancy.
Blood pressure trajectories during pregnancy and associations with adverse birth outcomes among HIV-infected and HIV-uninfected women in South Africa: a group-based trajectory modelling approach
Authors:   for the PIMS Study Group, Malaba Thokozile R. , Cois Annibale , Madlala Hlengiwe P. , Matjila Mushi , Myer Landon , Newell Marie-Louise
Published: November 2020

Background

High blood pressure (BP) late in pregnancy is associated with preterm delivery (PTD); BP has also been associated with HIV and antiretroviral therapy (ART), but whether the relationship between BP assessed longitudinally over pregnancy and PTD and low birthweight (LBW) is modified by HIV/ART is unclear. We hypothesise the presence of distinctive BP trajectories and their association with adverse birth outcomes may be mediated by HIV/ART status.

Methods

We recruited pregnant women at a large primary care facility in Cape Town. BP was measured throughout pregnancy using automated monitors. Group-based trajectory modelling in women with ≥3 BP measurements identified distinct joint systolic and diastolic BP trajectory groups. Multinomial regression assessed BP trajectory group associations with HIV/ART status, and Poisson regression with robust error variance was used to assess risk of PTD and LBW.

Results

Of the 1583 women in this analysis, 37% were HIV-infected. Seven joint trajectory group combinations were identified, which were categorised as normal (50%), low normal (25%), high normal (20%), and abnormal (5%). A higher proportion of women in the low normal group were HIV-infected than HIV-uninfected (28% vs. 23%), however differences were not statistically significant (RR 1.27, 95% CI 0.98–1.63, reference category: normal). In multivariable analyses, low normal trajectory (aRR0.59, 0.41–0.85) was associated with decreased risk of PTD, while high normal (aRR1.48, 1.12–1.95) and abnormal trajectories (aRR3.18, 2.32–4.37) were associated with increased risk of PTD, and abnormal with increased risk of LBW (RR2.81, 1.90–4.15).

Conclusions

While HIV/ART did not appear to mediate the BP trajectories and adverse birth outcomes association, they did provide more detailed insights into the relationship between BP, PTD and LBW for HIV-infected and uninfected women.
Eltrombopag inhibits the proliferation of Ewing sarcoma cells via iron chelation and impaired DNA replication
Authors: Waters Torin , Goss Kelli L. , Koppenhafer Stacia L. , Terry William W. , Gordon David J.
Published: November 2020

Background

The treatment of Ewing sarcoma, an aggressive bone and soft tissue sarcoma, is associated with suboptimal outcomes and significant side-effects. Consequently, there is an urgent need to identify novel therapies that will improve outcomes for children and adults with Ewing sarcoma tumors while also decreasing treatment-related toxicities.

Methods

We analyzed data from the PRISM drug repurposing screen, which tested the activity of 4518 drugs across 578 cancer cell lines, to identify drugs that selectively inhibit the growth of Ewing sarcoma cell lines. We then tested the effects of a top hit from the screen on cell proliferation, cell cycle progression, and activation of the DNA damage pathway using Ewing sarcoma cell lines. We also used a CRISPR/Cas9 gene knockout approach to investigate the role of Schlafen 11 (SLFN11), a restriction factor for DNA replication stress that is overexpressed in Ewing sarcoma tumors, in mediating the sensitivity of Ewing sarcoma cells to the drug.

Results

We found that eltrombopag, an FDA-approved thrombopoietin-receptor agonist (TPO-RA) that is currently being evaluated as a treatment for chemotherapy-induced thrombocytopenia, inhibits the growth of Ewing sarcoma cell lines in vitro in proliferation and colony formation assays. However, from a mechanistic standpoint, the thrombopoietin receptor is not expressed in Ewing sarcoma cells and we show that eltrombopag impairs DNA replication and causes DNA damage in Ewing sarcoma cells by chelating iron, a known “off-target” effect of the drug. We also found that the sensitivity of Ewing sarcoma cells to eltrombopag is mediated, in part, by SLFN11, which regulates the cellular response to DNA replication stress.

Conclusions

Ewing sarcoma cell lines are sensitive to eltrombopag and this drug could improve outcomes for patients with Ewing sarcoma tumors by both targeting the tumor, via chelation of iron and inhibition of DNA replication, and reducing chemotherapy-induced thrombocytopenia, via stimulation of the thrombopoietin receptor.
Spatio-temporal mapping of breast and prostate cancers in South Iran from 2014 to 2017
Authors: Montazeri Mahdieh , Hoseini Benyamin , Firouraghi Neda , Kiani Fatemeh , Raouf-Mobini Hosein , Biabangard Adele , Dadashi Ali , Zolfaghari Vahideh , Ahmadian Leila , Eslami Saeid , Bergquist Robert , Bagheri Nasser , Kiani Behzad
Published: November 2020

Background

The most common gender-specific malignancies are cancers of the breast and the prostate. In developing countries, cancer screening of all at risk is impractical because of healthcare resource limitations. Thus, determining high-risk areas might be an important first screening step. This study explores incidence patterns of potential high-risk clusters of breast and prostate cancers in southern Iran.

Methods

This cross-sectional study was conducted in the province of Kerman, South Iran. Patient data were aggregated at the county and district levels calculating the incidence rate per 100,000 people both for cancers of the breast and the prostate. We used the natural-break classification with five classes to produce descriptive maps. A spatial clustering analysis (Anselin Local Moran’sI) was used to identify potential clusters and outliers in the pattern of these cancers from 2014 to 2017.

Results

There were 1350 breast cancer patients (including, 42 male cases) and 478 prostate cancer patients in the province of Kerman, Iran during the study period. After 45 years of age, the number of men with diagnosed prostate cancer increased similarly to that of breast cancer for women after 25 years of age. The age-standardised incidence rate of breast cancer for women showed an increase from 29.93 to 32.27 cases per 100,000 people and that of prostate cancer from 13.93 to 15.47 cases per 100,000 during 2014–2017. Cluster analysis at the county level identified high-high clusters of breast cancer in the north-western part of the province for all years studied, but the analysis at the district level showed high-high clusters for only two of the years. With regard to prostate cancer, cluster analysis at the county and district levels identified high-high clusters in this area of the province for two of the study years.

Conclusions

North-western Kerman had a significantly higher incidence rate of both breast and prostate cancer than the average, which should help in designing tailored screening and surveillance systems. Furthermore, this study generates new hypotheses regarding the potential relationship between increased incidence of cancers in certain geographical areas and environmental risk factors.
Value of oesophagoscopy and bronchoscopy in diagnosis of synchronous malignancies in patients with head and neck squamous cell carcinomas
Authors: Ho Shi Yeung , Tsang Raymond King Yin
Published: November 2020

Background

Routine screening of patients with head and neck squamous cell carcinomas (HNSCCs) for synchronous malignancies using oesophagoscopy and bronchoscopy had been controversial. The aim of this study is therefore to find out the rate of synchronous malignancies in patients with primary HNSCCs, the risk factors for its occurrence and the effectiveness of oesophagoscopy and bronchoscopy from a 10-year experience in a single centre.

Methods

A retrospective review of medical records was conducted from July 2008 to June 2018 in a tertiary referral centre in Hong Kong. All patients with newly diagnosed HNSCCs were screened with oesophagoscopy and bronchoscopy at the time of diagnosis and therefore all patients were included in the study. The incidence of synchronous malignancies along the aerodigestive tract and the yield of oesophagoscopy and bronchoscopy were studied.

Results

Of the 702 patients included in the study, the overall rate of synchronous malignancies was 8.3% (58/702), with the rate of synchronous oesophageal and lung malignancies being 5.8% (41/702) and 0.85% (6/702) respectively. Fourteen out of the 41 oesophageal malignancies were only detectable with oesophagoscopy. Only one of the synchronous lung malignancies was detectable by bronchoscopy. Risk factors for synchronous malignancies include male gender, smokers, drinkers and primary hypopharyngeal cancer.

Conclusions

Oesophagoscopy is essential for detecting synchronous oesophageal malignancies in patients with HNSCCs especially in male patients, smokers and drinkers, and it is most valuable in primary hypopharyngeal cancer patients among all primary subsites. Bronchoscopy had a low yield for synchronous lung malignancies and can be potentially replaced by imaging techniques.
Contemporary epidemiology of rising atrial septal defect trends across USA 1991–2016: a combined ecological geospatiotemporal and causal inferential study
Authors: Reece Albert Stuart , Hulse Gary Kenneth
Published: November 2020

Background

Cardiovascular anomalies are the largest group of congenital anomalies and the major cause of death in young children, with various data linking rising atrial septal defect incidence (ASDI) with prenatal cannabis exposure. Objectives / Hypotheses. Is cannabis associated with ASDI in USA? Is this relationship causal?

Methods

Geospatiotemporal cohort study, 1991–2016. Census populations of adults, babies, congenital anomalies, income and ethnicity. Drug exposure data on cigarettes, alcohol abuse, past month cannabis use, analgesia abuse and cocaine taken from National Survey of Drug Use and Health (78.9% response rate). Cannabinoid concentrations from Drug Enforcement Agency. Inverse probability weighted (ipw) regressions. Analysis conducted in R.

Results

ASDI rose nationally three-fold from 27.4 to 82.8 / 10,000 births 1991–2014 during a period when tobacco and alcohol abuse were falling but cannabis was rising. States including Nevada, Kentucky, Mississippi and Tennessee had steeply rising epidemics (Time: Status β-estimate = 10.72 (95%C.I. 8.39–13.05), P < 2.0 × 10 − 16). ASDI was positively related to exposure to cannabis and most cannabinoids.

Drug exposure data was near-complete from 2006 thus restricting spatial modelling from 2006 to 2014, N = 282. In geospatial regression models cannabis: alcohol abuse term was significant (β-estimate = 19.44 (9.11, 29.77), P = 2.2 × 10 − 4); no ethnic or income factors survived model reduction. Cannabis legalization was associated with a higher ASDI (Time: Status β-estimate = 0.03 (0.01, 0.05), P = 1.1 × 10 -3). Weighted panel regression interactive terms including cannabis significant (from β-estimate = 1418, (1080.6, 1755.4), P = 7.3 × 10 -15). Robust generalized linear models utilizing inverse probability weighting interactive terms including cannabis appear (from β-estimate = 78.88, (64.38, 93.38), P = 1.1 × 10 -8). Marginal structural models with machine-aided SuperLearning association of ASDI with high v. low cannabis exposure R.R. = 1.32 (1.28, 1.36). Model e-values mostly > 1.5.

Conclusions

ASDI is associated with cannabis use, frequency, intensity and legalization in a spatiotemporally significant manner, robust to socioeconomicodemographic adjustment and fulfilled causal criteria, consistent with multiple biological mechanisms and similar reports from Hawaii, Colorado, Canada and Australia. Not only are these results of concern in themselves, but they further imply that our list of the congenital teratology of cannabis is as yet incomplete, and highlight in particular cardiovascular toxicology of prenatal cannabinoid and drug exposure.
Anaemia prevalence and determinants in under 5 years children: findings of a cross-sectional population-based study in Sudan
Authors: Elmardi Khalid Abdelmutalab , Adam Ishag , Malik Elfatih Mohamed , Ibrahim Abdalla Ahmed , Elhassan Asma Hashim , Kafy Hmooda Toto , Nawai Lubna Mohammed , Abdin Mujahid Sheikhedin , Kremers Stef
Published: November 2020

Background

Early childhood is an age at risk of anaemia and its deleterious consequences. In Sudan, there is limited evidence on the prevalence and determinant of anaemia in under-five children. This study was conducted in Sudan to assess the prevalence of anaemia in children and to identify its determinants.

Methods

We conducted a household survey involving children aged 6 months to 5 years in November 2016. A representative population was sampled across rural, urban and camps settlements across 18 states in Sudan. We used a pre-designed questionnaire data collection. Haemoglobin (Hb) level and malaria infection were checked. In this cross-sectional study, we dichotomized the outcome variable and performed logistic regression analyses.

Results

A total of 3094 children under 5 years enrolled in the study, 1566 (50.6%) of them were female and 690 (22.3%) of them were under 2 years old. Anaemia prevalence in the whole cohort (6 months - < 5 years) was 49.4% and the mean haemoglobin concentration was 108.1 (standard deviation (SD): 15.4) g/L. The prevalence in younger (6 months - < 2 years) children (61.9%) was higher than in older (2 - < 5 years) children (45.6%) (p < 0.001). Severe anaemia (Hb < 70 g/L) prevalence in the whole population was 1.6%. Age (Odds ratio (OR) 2.25, 95% confidence interval (95%CI) 1.75–2.90, p < 0.001), type of place of residence (OR 0.37, 95%CI 0.18–0.74, p = 0.005), maternal anaemia (OR 1.74, 95%CI 1.39–2.17, p < 0.001), and malaria infection (OR 2.82, 95%CI 1.56–5.11, p < 0.001) were the identified predictors of anaemia in the whole cohort. In younger children, only the economic class was an anaemia predictor, with a lower anaemia risk among the rich wealth class (OR 2.70, 95%CI 1.29–5.62, p = 0.008). However, in older children, three anaemia predictors were identified. These are maternal anaemia (OR 1.79, 95%CI 1.40–2.28, < 0.001), malaria infection (OR 2.77, 95%CI 1.48–5.21, p = 0.002), and type of residency (where camps’ residents were less likely affected with anaemia than rural children (OR 0.38, 95%CI 0.17–0.87, p = 0.022)).

Conclusions

About half of the under-5 children in Sudan are anaemic, with worse prevalence in younger children. Efforts targeted at improving socio-economic status, decreasing maternal anaemia and childhood malaria infection may mitigate this alarming trend.