bluuebunny/crossref_metadata_2025 huggingface dataset:
What should we consider in the case of combined Down- and 47,XY,+i(X)(q10) Klinefelter syndromes? The unique case of a male newborn and review of the literature
Authors: Pinti Eva , Lengyel Anna , Fekete Gyorgy , Haltrich Iren
Published: January 2020

Background

Double aneuploidies - especially in combination with structural aberrations - are extremely rare among liveborns. The most frequent association is that of Down (DS) and Klinefelter syndromes (KS). We present the case of a male newborn with a unique 47,XY,+ 21[80%]/48,XY,+i(X)(q10),+ 21[20%] karyotype, hypothesize about his future phenotype, discuss the aspects of management and review the literature.

Case presentation

The additional association of isochromosome Xq (i(X)(q10)) could be the result of a threefold non-disjunction event. 47,XY,+i(X)(q10) KS is not common and its symptoms differ from the classical KS phenotype. In combined DS and i(X)(q10) KS, the anticipatory phenotype is not simply the sum of the individual syndromic characteristics. This genotype is associated with higher risk for several diseases and certain conditions with more pronounced appearance: emotional and behavioral disorders; poorer mental and physical quality of life; lower muscle mass/tone/strength; connective tissue weakness; muscle hypotonia and feeding difficulties; osteopenia/−porosis with earlier beginning and faster progression; different types of congenital heart diseases; more common occurrence of hypertension; increased susceptibility to infections and female predominant autoimmune diseases; higher risk for hematological malignancies and testicular tumors.

Conclusions

In multiple aneuploidies, the alterations have the potential to weaken or enhance each other, or they may not have modifying effects at all. Prenatal ultrasound signs are not obligatory symptoms of numerous chromosomal anomalies (specifically those involving supernumerary sex chromosomes), therefore combined prenatal screening has pertinence in uncomplicated pregnancies as well.
Context of Violence in Adolescence Cohort (CoVAC) study: protocol for a mixed methods longitudinal study in Uganda
Authors: Devries Karen , Parkes Jenny , Knight Louise , Allen Elizabeth , Namy Sophie , Datzberger Simone , Nalukenge Winifred , Atuhaire Lydia , Kyegombe Nambusi , Walakira Eddy , Seeley Janet , Weiss Helen A. , Naker Dipak
Published: January 2020

Background

Violence exposure in adolescence is associated with a range of poor health and social outcomes, including both the perpetration and experience of violence in later intimate relationships. However, there is little longitudinal evidence on how both individual and contextual characteristics encourage or interrupt these associations. We designed the Contexts of Violence in Adolescence Cohort study (CoVAC) to provide evidence on these pathways for Ugandan adolescents, with the aim of providing information to improve the design of violence prevention interventions for adolescents and young adults.

Methods

CoVAC is a mixed-methods prospective cohort study with three parallel strands. Between 2014 and 2022, the study comprises three waves of quantitative survey data collection; qualitative data from five time points; and a series of workshops to facilitate direct use of emerging findings by intervention developers at Uganda-based NGO Raising Voices in their ongoing work to prevent violence. 3431 adolescents participated in a survey in 2014 when the majority were aged 11–14 years, and agreed to be re-contacted for a Wave 2 survey in 2018 (aged about 15–18 years); and again in 2021 (aged 18–21 years). 36 young people from Wave 1 survey sample will be invited to participate in longitudinal qualitative data collection. Adolescents aged 18 years and over will provide informed consent; for those under age 18 years, adolescents will be invited to assent, except in cases where caregivers, following notification, have opted not to consent to their adolescent’s participation. Quantitative and qualitative data will be analysed iteratively, and triangulation will be used to confirm, clarify and deepen our interpretation of findings. We will hold regular structured meetings so that emerging findings can be integrated into intervention development.

Discussion

This will be the first longitudinal study on the aetiology of violence over adolescence in sub-Saharan Africa which will enable examination of pathways using mixed methods at multiple time points. Quantitative mediation analysis, and annual qualitative fieldwork will provide detailed insights into how adolescents’ violence-related experiences, perspectives and practices relate to their social contexts and how these change over time. Results will feed directly into intervention development to reduce violence and harmful sequelae.

Trial registration

This study is a long-term follow up of participants in the Good Schools Study (NCT01678846, clinicaltrials.gov). This protocol is for cohort follow-up only; we have a separate protocol paper describing an evaluation of the long-term effects of the Good School Toolkit (In preparation).
Implementation of Basic Life Support training in schools: a randomised controlled trial evaluating self-regulated learning as alternative training concept
Authors: Süss-Havemann Christoph , Kosan Janina , Seibold Thomas , Dibbern Nils Martin , Daubmann Anne , Kubitz Jens Christian , Beck Stefanie
Published: January 2020

Background

The Kids save lives statement recommends annual Basic Life Support (BLS) training for school children but the implementation is challenging. Trainings should be easy to realise and every BLS training should be as effective as possible to prepare learners for lifesaving actions. Preparedness implies skills and positive beliefs in the own capability (high self-efficacy).

Methods

This randomized controlled cluster study investigates, if self-regulated learning promotes self-efficacy and long-term retention of practical BLS skills. Students in the age of 12 years participated in a practical training in BLS and a scenario testing of skills. In the control group the practical training was instructor-led. In the intervention group the students self-regulated their learning processes and feedback was provided by the peer-group. The primary outcome self-efficacy for helping in cardiac arrest after the training and 9 months later was analysed using a multilevel mixed model. Means and pass-rates for BLS skills were secondary outcomes.

Results

Contrary to the assumptions, this study could not measure a higher self-efficacy for helping in cardiac arrest of the students participating in the intervention (n = 307 students) compared to the control group (n = 293 students) after training and at the follow-up (mean difference: 0.11 points, 95% CI: − 0.26 to 0.04, P = 0.135). The odds to pass all items of the BLS exam was not significantly different between the groups (OR 1.11, 95% CI: 0.81 to 1.52, p = 0.533). Self-regulated learning was associated with a higher performance of male students in the BLS exam (mean score: 7.35) compared to females of the intervention (female: 7.05) and compared to males of the control (7.06).

Conclusion

This study could not resolve the question, if self-regulated learning in peer-groups improves self-efficacy for helping in cardiac arrest. Self-regulated learning is an effective alternative to instructor-led training in BLS skills training and may be feasible to realise for lay-persons. For male students self-regulated learning seems to be beneficial to support long-term retention of skills.

Trial registration

ISRCTN17334920, retrospectively registered 07.03.2019.
MiR93-5p inhibits chondrocyte apoptosis in osteoarthritis by targeting lncRNA CASC2
Authors: Sun Yun , Kang Simiao , Pei Shuyan , Sang Changmin , Huang Yijun
Published: January 2020

Background

It has been reported that miR-93-5p and long non-coding RNA (lncRNA) Cancer Susceptibility 2 (CASC2) play opposite roles in regulating chondrocyte apoptosis, indicating the possible interaction between them. This study aimed to investigate the interaction between miR-93-5p and lncRNA CASC2 in chondrocyte apoptosis, which plays critical roles in osteoarthritis (OA).

Methods

The interaction between CASC2 and miR-93-5p was analyzed by dual luciferase assay and overexpression experiments. Levels of CASC2 and miR-93-5p in plasma sample from OA patients and healthy controls were measured by RT-qPCR. The roles of CASC2 and miR-93-5p in regulating the apoptosis of chondrocyte induced by LPS were analyzed by cell apoptosis assay.

Results

Through bioinformatics analysis we observed the potential interaction between CASC2 and miR-93-5p, which was confirmed by dual luciferase assay. In OA patients, miR-93-5p was downregulated, while CASC2 was upregulated, and they were inversely correlated. LPS treatment led to downregulated miR-93-5p and upregulated CASC2. Overexpression of miR-93-5p led to the downregulated CASC2 in chondrocytes. Under LPS treatment, CASC2 overexpression promoted the apoptosis of chondrocyte. MiR-93-5p overexpression played an opposite role and attenuated the effects of CASC2 overexpression.

Conclusion

MiR-93-5p was downregulated in OA may inhibit LPS-induced chondrocyte apoptosis by targeting lncRNA CASC2.
Primary hyperparathyroidism presenting as a brown tumor in the mandible: a case report
Authors: Xu Bojin , Yu Jie , Lu Yingli , Han Bing
Published: January 2020

Background

Primary hyperparathyroidism is characterized by hypercalcemia and elevated or inappropriately normal serum levels of parathyroid hormone. Brown tumor of bone is a rare non-neoplastic lesion resulted from abnormal bone metabolism in hyperparathyroidism. However, nowadays, skeletal disease caused by primary hyperparathyroidism is uncommon. We report a case of brown tumor in the mandible as the initial exhibition of primary hyperparathyroidism associated with an atypical parathyroid adenoma.

Case presentation

The patient was a 49-year-old female, she had a pain mass on the right mandible a year ago and was treated with root canal therapy and marginal resection. After seven months, the mass recurred and enlarged. Enhanced CT scan, laboratory examination, Ultrasonography, 99mTc-MIBI SPECT-CT scintiscan and pathological examination were used to confirm the diagnosis of brown tumor. The patient’s symptom improved after parathyroidectomy.

Conclusions

99mTc-MIBI SPECT/CT scintigraphy is a highly sensitive examination of the localization diagnosis of hyperparathyroidism. Brown tumors should be considered in the differential diagnosis of osteolytic lesions to avoid unnecessary and harmful interventions.
Walkability and its association with prevalent and incident diabetes among adults in different regions of Germany: results of pooled data from five German cohorts
Authors: Kartschmit Nadja , Sutcliffe Robynne , Sheldon Mark Patrick , Moebus Susanne , Greiser Karin Halina , Hartwig Saskia , Thürkow Detlef , Stentzel Ulrike , van den Berg Neeltje , Wolf Kathrin , Maier Werner , Peters Annette , Ahmed Salman , Köhnke Corinna , Mikolajczyk Rafael , Wienke Andreas , Kluttig Alexander , Rudge Gavin
Published: January 2020

Background

Highly walkable neighbourhoods may increase transport-related and leisure-time physical activity and thus decrease the risk for obesity and obesity-related diseases, such as type 2 diabetes (T2D).

Methods

We investigated the association between walkability and prevalent/incident T2D in a pooled sample from five German cohorts. Three walkability measures were assigned to participant’s addresses: number of transit stations, points of interest, and impedance (restrictions to walking due to absence of intersections and physical barriers) within 640 m. We estimated associations between walkability and prevalent/incident T2D with modified Poisson regressions and adjusted for education, sex, age at baseline, and cohort.

Results

Of the baseline 16,008 participants, 1256 participants had prevalent T2D. Participants free from T2D at baseline were followed over a mean of 9.2 years (SD: 3.5, minimum: 1.6, maximum: 14.8 years). Of these, 1032 participants developed T2D. The three walkability measures were not associated with T2D. The estimates pointed toward a zero effect or were within 7% relative risk increase per 1 standard deviation with 95% confidence intervals including 1.

Conclusion

In the studied German settings, walkability differences might not explain differences in T2D.
Clinical characterization of patients with primary aldosteronism plus subclinical Cushing’s syndrome
Authors: Yasuda Shigemitsu , Hikima Yusuke , Kabeya Yusuke , Iida Shinichiro , Oikawa Yoichi , Isshiki Masashi , Inoue Ikuo , Shimada Akira , Noda Mitsuhiko
Published: January 2020

Background

Primary aldosteronism (PA) plus subclinical Cushing’s syndrome (SCS), PASCS, has occasionally been reported. We aimed to clinically characterize patients with PASCS who are poorly profiled.

Methods

A population-based, retrospective, single-center, observational study was conducted in 71 patients (age, 58.2 ± 11.2 years; 24 males and 47 females) who developed PA (n = 45), SCS (n = 12), or PASCS (n = 14). The main outcome measures were the proportion of patients with diabetes mellitus (DM), serum potassium concentration, and maximum tumor diameter (MTD) on the computed tomography (CT) scans.

Results

The proportion of DM patients was significantly greater in the PASCS group than in the PA group (50.0% vs. 13.9%,p <  0.05), without a significant difference between the PASCS and SCS groups. Serum potassium concentration was significantly lower in the PASCS group than in the SCS group (3.2 ± 0.8 mEq/L vs. 4.0 ± 0.5 mEq/L;p <  0.01), without a significant difference between the PASCS and PA groups. Among the 3 study groups of patients who had a unilateral adrenal tumor, MTD was significantly greater in the PASCS group than in the PA group (2.7 ± 0.1 cm vs. 1.4 ± 0.1 cm;p <  0.001), without a significant difference between the PASCS and SCS groups.

Conclusions

Any reference criteria were not obtained that surely distinguish patients with PASCS from those with PA or SCS. However, clinicians should suspect the presence of concurrent SCS in patients with PA when detecting a relatively large adrenal tumor on the CT scans.
A qualitative analysis of junior doctors’ journeys to preparedness in acute care
Authors: Burridge Samuel , Shanmugalingam Thurkaa , Nawrozzadeh Fatima , Leedham-Green Kathleen , Sharif Amar
Published: January 2020

Background

New doctors are expected to assess and manage acutely deteriorating patients from their first days in the hospital. However, current evidence suggests that medical graduates are not prepared for this. We aimed to explore junior doctors’ first experiences with unwell patients and how they developed preparedness over time.

Methods

We conducted seven semi-structured interviews with doctors in their first postgraduate year. The interview transcripts underwent inductive thematic analysis using consensual qualitative research approaches. Themes identified were categorised into early experiences of unpreparedness, first experiences of genuine preparedness, and making sense of how they became prepared. Reflection on how participants progressed between the two was facilitated through a sorting and ranking exercise.

Results

Most participants initially felt unprepared when responding to acutely unwell patients. They described feeling overwhelmed, apprehensive and challenged. Two main challenges involved knowing when to escalate, and feeling expected to perform beyond their level of competency. A lack of acute care exposure at medical school was a common thread. All participants felt prepared to respond to unwell patients three to six months after starting work. Hands-on experience, reflection, simulation and multidisciplinary team-working were consistently ranked as the most useful learning experiences.

Conclusion

Starting work as a doctor is a challenging time and preparedness to manage an acutely deteriorating patient is a common area of concern. As preparedness in acute care ranks poorly compared to other outcomes, we see this as an important area for improvement. Our findings suggest that undergraduates may lack sufficient opportunities for scaffolded decision making in acute care, and that increasing the intensity of clinical shadowing may improve preparedness and should inform future educational interventions.
An evaluation of the Zambia influenza sentinel surveillance system, 2011–2017
Authors: Simusika Paul , Tempia Stefano , Chentulo Edward , Polansky Lauren , Mazaba Mazyanga Lucy , Ndumba Idah , Mbewe Quinn K. , Monze Mwaka
Published: January 2020

Background

Over the past decade, influenza surveillance has been established in several African countries including Zambia. However, information on the on data quality and reliability of established influenza surveillance systems in Africa are limited. Such information would enable countries to assess the performance of their surveillance systems, identify shortfalls for improvement and provide evidence of data reliability for policy making and public health interventions.

Methods

We used the Centers for Disease Control and Prevention guidelines to evaluate the performance of the influenza surveillance system (ISS) in Zambia during 2011–2017 using 9 attributes: (i) data quality and completeness, (ii) timeliness, (iii) representativeness, (iv) flexibility, (v) simplicity, (vi) acceptability, (vii) stability, (viii) utility, and (ix) sustainability. Each attribute was evaluated using pre-defined indicators. For each indicator we obtained the proportion (expressed as percentage) of the outcome of interest over the total. A scale from 1 to 3 was used to provide a score for each attribute as follows: < 60% (as obtained in the calculation above) scored 1 (weak performance); 60–79% scored 2 (moderate performance); ≥80% scored 3 (good performance). An overall score for each attribute and the ISS was obtained by averaging the scores of all evaluated attributes.

Results

The overall mean score for the ISS in Zambia was 2.6. Key strengths of the system were the quality of data generated (score: 2.9), its flexibility (score: 3.0) especially to monitor viral pathogens other than influenza viruses, its simplicity (score: 2.8), acceptability (score: 3.0) and stability (score: 2.6) over the review period and its relatively low cost ($310,000 per annum). Identified weaknesses related mainly to geographic representativeness (score: 2.0), timeliness (score: 2.5), especially in shipment of samples from remote sites, and sustainability (score: 1.0) in the absence of external funds.

Conclusions

The system performed moderately well in our evaluation. Key improvements would include improvements in the timeliness of samples shipments and geographical coverage. However, these improvements would result in increased cost and logistical complexity. The ISSS in Zambia is largely reliant on external funds and the acceptability of maintaining the surveillance system through national funds would require evaluation.
Reductions in sugar sales from soft drinks in the UK from 2015 to 2018
Authors: Bandy L. K. , Scarborough P. , Harrington R. A. , Rayner M. , Jebb S. A.
Published: January 2020

Background

The consumption of free sugars in the UK is more than double the guideline intake for adults and close to triple for children, with soft drinks representing a significant proportion. The aim of this study was to assess how individual soft drink companies and consumers have responded to calls to reduce sugar consumption, including the soft drink industry levy (SDIL), between 2015 and 2018.

Methods

This was an annual cross-sectional study using nutrient composition data of 7377 products collected online, paired with volume sales data for 195 brands offered by 57 companies. The main outcome measures were sales volume, sugar content and volume of sugars sold by company and category, expressed in total and per capita per day terms.

Results

Between 2015 and 2018, the volume of sugars sold per capita per day from soft drinks declined by 30%, equivalent to a reduction of 4.6 g per capita per day. The sales-weighted mean sugar content of soft drinks fell from 4.4 g/100 ml in 2015 to 2.9 g/100 ml in 2018. The total volume sales of soft drinks that are subject to the SDIL (i.e. contain more than 5 g/100 ml of sugar) fell by 50%, while volume sales of low- and zero-sugar (< 5 g/100 ml) drinks rose by 40%.

Conclusion

Action by the soft drinks industry to reduce sugar in products and change their product portfolios, coupled with changes in consumer purchasing, has led to a significant reduction in the total volume and per capita sales of sugars sold in soft drinks in the UK. The rate of change accelerated between 2017 and 2018, which also implies that the implementation of the SDIL acted as an extra incentive for companies to reformulate above and beyond what was already being done as part of voluntary commitments to reformulation, or changes in sales driven by consumer preferences.
Involvement of collagen XVII in pluripotency gene expression and metabolic reprogramming of lung cancer stem cells
Authors: Hsu Han-Shui , Liu Chen-Chi , Lin Jiun-Han , Hsu Tien-Wei , Hsu Jyuan-Wei , Li Anna Fen-Yau , Hung Shih-Chieh
Published: January 2020

Background

Recent advancements in cancer biology field suggest that glucose metabolism is a potential target for cancer treatment. However, little if anything is known about the metabolic profile of cancer stem cells (CSCs) and the related underlying mechanisms.

Methods

The metabolic phenotype in lung CSC was first investigated. The role of collagen XVII, a putative stem cell or CSC candidate marker, in regulating metabolic reprogramming in lung CSC was subsequently studied. Through screening the genes involved in glycolysis, we identified the downstream targets of collagen XVII that were involved in metabolic reprogramming of lung CSCs. Collagen XVII and its downstream targets were then used to predict the prognosis of lung cancer patients.

Results

We showed that an aberrant upregulation of glycolysis and oxidative phosphorylation in lung CSCs is associated with the maintenance of CSC-like features, since blocking glycolysis and oxidative phosphorylation reduces sphere formation, chemoresistance, and tumorigenicity. We also showed that the Oct4-hexokinase 2 (HK2) pathway activated by collagen XVII-laminin-332 through FAK-PI3K/AKT-GSB3β/β-catenin activation induced the upregulation of glycolysis and maintenance of CSC-like features. Finally, we showed that collagen XVII, Oct4, and HK2 could be valuable markers to predict the prognosis of lung cancer patients.

Conculsions

These data suggest the Oct4-HK2 pathway regulated by collagen XVII plays an important role in metabolic reprogramming and maintenance of CSC-like features in lung CSCs, which may aid in the development of new strategies in cancer treatment.
Development and initial validation of the bronchiectasis exacerbation and symptom tool (BEST)
Authors: Artaraz Amaia , Crichton Megan L. , Finch Simon , Abo-Leyah Hani , Goeminne Pieter , Aliberti Stefano , Fardon Thomas , Chalmers James D.
Published: January 2020

Background

Recurrent bronchiectasis exacerbations are related to deterioration of lung function, progression of the disease, impairment of quality of life, and to an increased mortality. Improved detection of exacerbations has been accomplished in chronic obstructive pulmonary disease through the use of patient completed diaries. These tools may enhance exacerbation reporting and identification. The aim of this study was to develop a novel symptom diary for bronchiectasis symptom burden and detection of exacerbations, named the BEST diary.

Methods

Prospective observational study of patients with bronchiectasis conducted at Ninewells Hospital, Dundee. We included patients with confirmed bronchiectasis by computed tomography, who were symptomatic and had at least 1 documented exacerbation of bronchiectasis in the previous 12 months to participate. Symptoms were recorded daily in a diary incorporating cough, sputum volume, sputum colour, dyspnoea, fatigue and systemic disturbance scored from 0 to 26.

Results

Twenty-one patients were included in the study. We identified 29 reported (treated exacerbations) and 23 unreported (untreated) exacerbations over 6-month follow-up. The BEST diary score showed a good correlation with the established and validated questionnaires and measures of health status (COPD Assessment Test, r = 0.61, p = 0.0037, Leicester Cough Questionnaire, r = − 0.52,p = 0.0015, St Georges Respiratory Questionnaire, r = 0.61,p < 0.0001 and 6 min walk test, r = − 0.46,p = 0.037). The mean BEST score at baseline was 7.1 points (SD 2.2). The peak symptom score during exacerbation was a mean of 16.4 (3.1), and the change from baseline to exacerbation was a mean of 9.1 points (SD 2.5). Mean duration of exacerbations based on time for a return to baseline symptoms was 15.3 days (SD 5.7). A minimum clinically important difference of 4 points is proposed.

Conclusions

The BEST symptom diary has shown concurrent validity with current health questionnaires and is responsive at onset and recovery from exacerbation. The BEST diary may be useful to detect and characterise exacerbations in bronchiectasis clinical trials.
Extracorporeal membrane oxygenation as a bridge to lung transplantation: analysis of Korean organ transplantation registry (KOTRY) data
Authors:   the Korean Organ Transplantation Registry Study Group, Ko Ryoung-Eun , Lee Jin Gu , Kim Song Yee , Kim Young Tae , Choi Sun Mi , Kim Do Hyung , Cho Woo Hyun , Park Seung-Il , Jo Kyung-Wook , Kim Hong Kwan , Paik Hyo Chae , Jeon Kyeongman
Published: January 2020

Background

The use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation has greatly increased. However, data regarding the clinical outcomes of this approach are lacking. The objective of this multicenter prospective observational cohort study was to evaluate lung transplantation outcomes in Korean Organ Transplantation Registry (KOTRY) patients for whom ECMO was used as a bridge to transplantation.

Methods

Between March 2015 and December 2017, a total of 112 patients received lung transplantation and were registered in the KOTRY, which is a prospective, multicenter cohort registry. The entire cohort was divided into two groups: the control group (n = 85, 75.9%) and bridge-ECMO group (n = 27, 24.1%).

Results

There were no significant differences in pre-transplant and intraoperative characteristics except for poorer oxygenation, more ventilator use, and longer operation time in the bridge-ECMO group. The prevalence of primary graft dysfunction at 0, 24, 48, and 72 h after transplantation did not differ between the two groups. Although postoperative hospital stays were longer in the bridge-ECMO group than in the control group, hospital mortality did not differ between the two groups (25.9% vs. 13.3%, P = 0.212). The majority of patients (70.4% of the bridge-ECMO group and 77.6% of the control group) were discharged directly to their homes. Finally, the use of ECMO as a bridge to lung transplantation did not significantly affect overall survival and graft function.

Conclusions

Short- and long-term post-transplant outcomes of bridge-ECMO patients were comparable to recipients who did not receive ECMO.
Effects of ccpA gene deficiency in Lactobacillus delbrueckii subsp. bulgaricus under aerobic conditions as assessed by proteomic analysis
Authors: Zhang Guofang , Liu Libo , Li Chun
Published: January 2020

Background

Aerobic growth provides benefits in biomass yield and stress tolerance of Lactobacillus delbrueckii subsp. bulgaricus (L. bulgaricus). Catabolite control protein A (CcpA) is a master regulator involved in the aerobic and anaerobic growth, metabolic production and stress response in L. bulgaricus, but its potential molecular mechanisms remains unclear. The aim of this study is to elucidate the role of CcpA in L. bulgaricus in aerobic growth at the proteomic perspective.

Results

The differential proteomic analysis was performed on the L. bulgaricus ATCC11842 and its ccpA inactivated mutant strain using iTRAQ technology. A total of 132 differentially expressed proteins were obtained, among which 58 were up-regulated and 74 were down-regulated. These proteins were mainly involved in the cellular stress response, carbohydrate and energy metabolism, amino acid transport and protein synthesis, genetic information processing. Moreover, inactivation of ccpA negatively affected the expression of key enzymes involved in glycolysis pathway, while it enhanced the expression of proteins related to the pyruvate pathway, supporting the conclusion that CcpA mediated the shift from homolactic fermentation to mixed acid fermentation in L. bulgaricus.

Conclusions

Overall, these results showed that the role of CcpA in L. bulgaricus as a pleiotropic regulator in aerobic metabolism and stress response. This proteomic analysis also provide new insights into the CcpA-mediated regulatory network of L. bulgaricus and potential strategies to improve the production of starter and probiotic cultures based on the metabolic engineering of global regulators.
Homogeneous production and characterization of recombinant N-GlcNAc-protein in Pichia pastoris
Authors: Wang Shengjun , Rong Yongheng , Wang Yaoguang , Kong Decai , Wang Peng George , Chen Min , Kong Yun
Published: January 2020

Background

Therapeutic glycoproteins have occupied an extremely important position in the market of biopharmaceuticals. N-Glycosylation of protein drugs facilitates them to maintain optimal conformations and affect their structural stabilities, serum half-lives and biological efficiencies. Thus homogeneous N-glycoproteins with defined N-glycans are essential in their application in clinic therapeutics. However, there still remain several obstacles to acquire homogeneous N-glycans, such as the high production costs induced by the universal utilization of mammalian cell expression systems, the non-humanized N-glycan structures and the N-glycosylation microheterogeneities between batches.

Results

In this study, we constructed a Pichia pastoris (Komagataella phaffii) expression system producing truncated N-GlcNAc-modified recombinant proteins through introducing an ENGase isoform (Endo-T) which possesses powerful hydrolytic activities towards high-mannose type N-glycans. The results showed that the location of Endo-T in different subcellular fractions, such as Endoplasmic reticulum (ER), Golgi or cell membrane, affected their hydrolytic efficiencies. When the Endo-T was expressed in Golgi, the secreted IgG1-Fc region was efficiently produced with almost completely truncated N-glycans and the N-GlcNAc modification on the glycosite Asn297 was confirmed via Mass Spectrometry.

Conclusion

This strategy develops a simple glycoengineered yeast expression system to produce N-GlcNAc modified proteins, which could be further extended to different N-glycan structures. This system would provide a prospective platform for mass production of increasing novel glycoprotein drugs.
Microsatellite instability: a review of what the oncologist should know
Authors: Li Kai , Luo Haiqing , Huang Lianfang , Luo Hui , Zhu Xiao
Published: January 2020

The patients with high microsatellite instability (MSI-H)/mismatch repair deficient (dMMR) tumors recently have been reported that can benefit from immunotherapy, and MSI can be used as a genetic instability of a tumor detection index. However, many studies have shown that there are many heterogeneous phenomena in patients with MSI tumors in terms of immunotherapy, prognosis and chemotherapy sensitivity. Here we mainly review the research results of MSI detection methods, the mechanisms of MSI occurrence and its relationship with related tumors, aiming to make a brief analysis of the current research status of MSI and provide comparable reference and guidance value for further research in this field.
Willingness-to-pay for long-lasting insecticide-treated bed nets: a discrete choice experiment with real payment in Ghana
Authors: Alfonso Y. Natalia , Lynch Matthew , Mensah Elorm , Piccinini Danielle , Bishai David
Published: January 2020

Background

Expanding access to long-lasting insecticidal nets (LLINs) is difficult if one is limited to government and donor financial resources. Private commercial markets could play a larger role in the continuous distribution of LLINs by offering differentiated LLINs to middle-class Ghanaians. This population segment has disposable income and may be willing to pay for LLINs that meet their preferences. Measuring the willingness-to-pay (WTP) for LLINs with specialty features that appeal to middle-class Ghanaians could help malaria control programmes understand what is the potential for private markets to work alongside fully subsidized LLIN distribution channels to assist in spreading this commodity.

Methods

This study conducted a discrete choice experiment (DCE) including a real payment choice among a representative sample of 628 middle-income households living in Ashanti, Greater Accra, and Western regions in Ghana. The DCE presented 18 paired combinations of LLIN features and various prices. Respondents indicated which LLIN of each pair they preferred and whether they would purchase it. To validate stated willingness-to-pay, each participant was given a cash payment of $14.30 (GHS 65) that they could either keep or immediately spend on one of the LLIN products.

Results

The households’ average probability of purchasing a LLIN with specialty features was 43.8% (S.D. 0.07) and WTP was $7.48 (GHS34.0). The preferred LLIN features were conical or rectangular one-point-hang shape, queen size, and zipper entry. The average WTP for a LLIN with all the preferred features was $18.48 (GHS 84). In a scenario with the private LLIN market, the public sector outlay could be reduced by 39% and private LLIN sales would generate $8.1 million ($311 per every 100 households) in revenue in the study area that would support jobs for Ghanaian retailers, distributors, and importers of LLINs.

Conclusion

Results support a scenario in which commercial markets for LLINs could play a significant role in improving access to LLINs for middle-income Ghanaians. Manufacturers interested could offer LLIN designs with features that are most highly valued among middle-income households in Ghana and maintain a retail price that could yield sufficient economic returns.
Analysis of anti-Plasmodium IgG profiles among Fulani nomadic pastoralists in northern Senegal to assess malaria exposure
Authors: Seck Mame Cheikh , Thwing Julie , Badiane Aida Sadikh , Rogier Eric , Fall Fatou Ba , Ndiaye Pape Ibrahima , Diongue Khadim , Mbow Moustapha , Ndiaye Mouhamadou , Diallo Mamadou Alpha , Gomis Jules François , Mbaye Aminata , Ndiaye Tolla , Gaye Aminata , Sy Mohamad , Déme Awa Bineta , Ndiaye Yaye Die , Ndiaye Daouda
Published: January 2020

Background

Northern Senegal is a zone of very low malaria transmission, with an annual incidence of < 5/1000 inhabitants. This area, where the Senegal National Malaria Control Programme has initiated elimination activities, hosts Fulani, nomadic, pastoralists that spend the dry season in the south where malaria incidence is higher (150–450/1000 inhabitants) and return to the north with the first rains. Previous research demonstrated parasite prevalence of < 1% in this Fulani population upon return from the south, similar to that documented in the north in cross-sectional surveys.

Methods

A modified snowball sampling survey of nomadic pastoralists was conducted in five districts in northern Senegal during September and October 2014. Demographic information and dried blood spots were collected. Multiplex bead-based assays were used to assess antibody responses to merozoite surface protein (MSP-119) antigen of the four primary Plasmodium species, as well as circumsporozoite protein (CSP) and liver stage antigen (LSA-1) of Plasmodium falciparum.

Results

In the five study districts, 1472 individuals were enrolled, with a median age of 22 years (range 1 to 80 years). Thirty-two percent of subjects were under 14 years and 57% were male. The overall seroprevalence of P. falciparum MSP-119, CSP and LSA-1 antibodies were 45, 12 and 5%, respectively. Plasmodium falciparum MSP-119 antibody responses increased significantly with age in all study areas, and were significantly higher among males. The highest seroprevalence to P. falciparum antigens was observed in the Kanel district (63%) and the lowest observed in Podor (28%). Low seroprevalence was observed for non-falciparum species in all the study sites: 0.4, 0.7 and 1.8%, respectively, for Plasmodium ovale, Plasmodium vivax and Plasmodium malariae MSP-1. Antibody responses to P. vivax were observed in all study sites except Kanel.

Conclusion

Prevalence of P. falciparum MSP-119 antibodies and increases by study participant age provided data for low levels of exposure among this transient nomadic population. In addition, antibody responses to P. falciparum short half-life markers (CSP and LSA-1) and non-falciparum species were low. Further investigations are needed to understand the exposure of the Fulani population to P. vivax.
Evaluation of sex differences in dietary behaviours and their relationship with cardiovascular risk factors: a cross-sectional study of nationally representative surveys in seven low- and middle-income countries
Authors: McKenzie Briar L. , Santos Joseph Alvin , Geldsetzer Pascal , Davies Justine , Manne-Goehler Jennifer , Gurung Mongal Singh , Sturua Lela , Gathecha Gladwell , Aryal Krishna K. , Tsabedze Lindiwe , Andall-Brereton Glennis , Bärnighausen Till , Atun Rifat , Vollmer Sebastian , Woodward Mark , Jaacks Lindsay M. , Webster Jacqui
Published: January 2020

Background

Cardiovascular diseases (CVD) are the leading causes of death for men and women in low-and-middle income countries (LMIC). The nutrition transition to diets high in salt, fat and sugar and low in fruit and vegetables, in parallel with increasing prevalence of diet-related CVD risk factors in LMICs, identifies the need for urgent action to reverse this trend. To aid identification of the most effective interventions it is crucial to understand whether there are sex differences in dietary behaviours related to CVD risk.

Methods

From a dataset of 46 nationally representative surveys, we included data from seven countries that had recorded the same dietary behaviour measurements in adults; Bhutan, Eswatini, Georgia, Guyana, Kenya, Nepal and St Vincent and the Grenadines (2013–2017). Three dietary behaviours were investigated: positive salt use behaviour (SUB), meeting fruit and vegetable (F&V) recommendations and use of vegetable oil rather than animal fats in cooking. Generalized linear models were used to investigate the association between dietary behaviours and waist circumference (WC) and undiagnosed and diagnosed hypertension and diabetes. Interaction terms between sex and dietary behaviour were added to test for sex differences.

Results

Twenty-four thousand three hundred thirty-two participants were included. More females than males reported positive SUB (31.3 vs. 27.2%p-value < 0.001), yet less met F&V recommendations (13.2 vs. 14.8%,p-value< 0.05). The prevalence of reporting all three dietary behaviours in a positive manner was 2.7%, varying by country, but not sex. Poor SUB was associated with a higher prevalence of undiagnosed hypertension for females (13.1% vs. 9.9%,p-value = 0.04), and a higher prevalence of undiagnosed diabetes for males (2.4% vs. 1.5%,p-value = 0.02). Meeting F&V recommendations was associated with a higher prevalence of high WC (24.4% vs 22.6%,p-value = 0.01), but was not associated with undiagnosed or diagnosed hypertension or diabetes.

Conclusion

Interventions to increase F&V intake and positive SUBs in the included countries are urgently needed. Dietary behaviours were not notably different between sexes. However, our findings were limited by the small proportion of the population reporting positive dietary behaviours, and further research is required to understand whether associations with CVD risk factors and interactions by sex would change as the prevalence of positive behaviours increases.
Gated recurrent unit-based heart sound analysis for heart failure screening
Authors: Gao Shan , Zheng Yineng , Guo Xingming
Published: January 2020

Background

Heart failure (HF) is a type of cardiovascular disease caused by abnormal cardiac structure and function. Early screening of HF has important implication for treatment in a timely manner. Heart sound (HS) conveys relevant information related to HF; this study is therefore based on the analysis of HS signals. The objective is to develop an efficient tool to identify subjects of normal, HF with preserved ejection fraction and HF with reduced ejection fraction automatically.

Methods

We proposed a novel HF screening framework based on gated recurrent unit (GRU) model in this study. The logistic regression-based hidden semi-Markov model was adopted to segment HS frames. Normalized frames were taken as the input of the proposed model which can automatically learn the deep features and complete the HF screening without de-nosing and hand-crafted feature extraction.

Results

To evaluate the performance of proposed model, three methods are used for comparison. The results show that the GRU model gives a satisfactory performance with average accuracy of 98.82%, which is better than other comparison models.

Conclusion

The proposed GRU model can learn features from HS directly, which means it can be independent of expert knowledge. In addition, the good performance demonstrates the effectiveness of HS analysis for HF early screening.
Associations of Perfluoroalkyl substances with blood lipids and Apolipoproteins in lipoprotein subspecies: the POUNDS-lost study
Authors: Liu Gang , Zhang Bo , Hu Yang , Rood Jennifer , Liang Liming , Qi Lu , Bray George A. , DeJonge Lilian , Coull Brent , Grandjean Philippe , Furtado Jeremy D. , Sun Qi
Published: January 2020

Background

The associations of perfluoroalkyl substance (PFAS) exposure with blood lipids and lipoproteins are inconsistent, and existing studies did not account for metabolic heterogeneity of lipoprotein subspecies. This study aimed to examine the associations between plasma PFAS concentrations and lipoprotein and apolipoprotein subspecies.

Methods

The study included 326 men and women from the 2-year Prevention of Obesity Using Novel Dietary Strategies (POUNDS) Lost randomized trial. Five PFASs, including perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA), were measured in plasma at baseline. For lipoprotein and apolipoprotein subspecies, total plasma was fractionated first by apolipoprotein (apo) C-III content and then by density. Each subfraction was then measured for apoB, apoC-III, and apoE concentrations, as well as triglyceride and cholesterol contents, both at baseline and at 2 years.

Results

For lipids and apolipoproteins in total plasma at baseline, elevated plasma PFAS concentrations were significantly associated with higher apoB and apoC-III concentrations, but not with total cholesterol or triglycerides. After multivariate adjustment of lifestyle factors, lipid-lowering medication use, and dietary intervention groups, PFAS concentrations were primarily associated with lipids or apolipoprotein concentrations in intermediate-to-low density lipoprotein (IDL + LDL) and high-density lipoprotein (HDL) that contain apoC-III. Comparing the highest and lowest tertiles of PFOA, the least-square means (SE) (mg/dl) were 4.16 (0.4) vs 3.47 (0.4) for apoB (P trend = 0.04), 2.03 (0.2) vs 1.66 (0.2) for apoC-III (P trend = 0.04), and 8.4 (0.8) vs 6.8 (0.8) for triglycerides (P trend = 0.03) in IDL + LDL fraction that contains apoC-III. For HDL that contains apoC-III, comparing the highest and lowest tertiles of PFOA, the least-square means (SE) (mg/dl) of apoC-III were 11.9 (0.7) vs 10.4 (0.7) (P trend = 0.01). In addition, elevated PFNA and PFDA concentrations were also significantly associated with higher concentrations of apoE in HDL that contains apoC-III (P trend< 0.01). Similar patterns of associations were demonstrated between baseline PFAS concentrations and lipoprotein subspecies measured at 2 years. Baseline PFAS levels were not associated with changes in lipoprotein subspecies during the intervention.

Conclusions

Our results suggest that plasma PFAS concentrations are primarily associated with blood lipids and apolipoproteins in subspecies of IDL, LDL, and HDL that contain apoC-III, which are associated with elevated cardiovascular risk in epidemiological studies. Future studies of PFAS-associated cardiovascular risk should focus on lipid subfractions.
Prognostic value of point-of-care ultrasound during cardiac arrest: a systematic review
Authors: Kedan Ilan , Ciozda William , Palatinus Joseph A. , Palatinus Helen N. , Kimchi Asher
Published: January 2020

Background

Despite significant improvements in cardiopulmonary resuscitation, sudden cardiac arrest is one of the leading causes of mortality in the United States. Ultrasound is a widely available tool that can be used to evaluate the presence of cardiac wall motion during cardiac arrest. Several clinical studies have evaluated the use of ultrasound to visualize cardiac motion as a predictor of mortality in cardiac arrest patients. However, there are limited data summarizing the prognostic value of point of care ultrasound evaluation during resuscitation. We performed a systematic literature review of the existing evidence examining the clinical utility of point-of-care ultrasound evaluation of cardiac wall motion as a predictor of cardiac resuscitation outcomes.

Methods/results

We performed a systematic PubMed search of clinical studies up to July 23, 2019 evaluating point-of-care sonographic cardiac motion as a predictor of mortality following cardiac resuscitation. We included studies written in English that reviewed short-term outcomes and included adult populations. Fifteen clinical studies met inclusion criteria for assessing cardiac wall motion with point-of-care ultrasound and outcomes following cardiac resuscitation. Fourteen of the fifteen studies showed a statistically significant correlation between the presence of cardiac motion on ultrasound and short-term survival. This was most evident in patients with ventricular fibrillation or ventricular tachycardia as a presenting rhythm. Absence of cardiac motion non-survival. The data were pooled and the overall pooled odds ratio for return of spontaneous circulation in the presence of cardiac motion during CPR was 12.4 +/1 2.7 (p <  0.001).

Conclusion

Evaluation of cardiac motion on transthoracic echocardiogram is a valuable tool in the prediction of short-term cardiac resuscitation outcomes. Given the safety and availability of ultrasound in the emergency department, it is reasonable to apply point-of-care ultrasound to cardiopulmonary resuscitation as long as its use does not interrupt resuscitation.