bluuebunny/crossref_metadata_2025 huggingface dataset:
Millefy: visualizing cell-to-cell heterogeneity in read coverage of single-cell RNA sequencing datasets
Authors: Ozaki Haruka , Hayashi Tetsutaro , Umeda Mana , Nikaido Itoshi
Published: March 2020

Background

Read coverage of RNA sequencing data reflects gene expression and RNA processing events. Single-cell RNA sequencing (scRNA-seq) methods, particularly “full-length” ones, provide read coverage of many individual cells and have the potential to reveal cellular heterogeneity in RNA transcription and processing. However, visualization tools suited to highlighting cell-to-cell heterogeneity in read coverage are still lacking.

Results

Here, we have developed Millefy, a tool for visualizing read coverage of scRNA-seq data in genomic contexts. Millefy is designed to show read coverage of all individual cells at once in genomic contexts and to highlight cell-to-cell heterogeneity in read coverage. By visualizing read coverage of all cells as a heat map and dynamically reordering cells based on diffusion maps, Millefy facilitates discovery of “local” region-specific, cell-to-cell heterogeneity in read coverage. We applied Millefy to scRNA-seq data sets of mouse embryonic stem cells and triple-negative breast cancers and showed variability of transcribed regions including antisense RNAs, 3 ′ UTR lengths, and enhancer RNA transcription.

Conclusions

Millefy simplifies the examination of cellular heterogeneity in RNA transcription and processing events using scRNA-seq data. Millefy is available as an R package (https://github.com/yuifu/millefy) and as a Docker image for use with Jupyter Notebook (https://hub.docker.com/r/yuifu/datascience-notebook-millefy).
New genome assemblies reveal patterns of domestication and adaptation across Brettanomyces (Dekkera) species
Authors: Roach Michael J. , Borneman Anthony R.
Published: March 2020

Background

Yeasts of the genusBrettanomycesare of significant interest, both for their capacity to spoil, as well as their potential to positively contribute to different industrial fermentations. However, considerable variance exists in the depth of research and knowledgebase of the five currently known species ofBrettanomyces. For instance,Brettanomyces bruxellensishas been heavily studied and many resources are available for this species, whereasBrettanomyces nanusis rarely studied and lacks a publicly available genome assembly altogether. The purpose of this study is to fill this knowledge gap and explore the genomic adaptations that have shaped the evolution of this genus.

Results

Strains for each of the five widely accepted species ofBrettanomyces(Brettanomyces anomalus,B. bruxellensis,Brettanomyces custersianus,Brettanomyces naardenensis, andB. nanus) were sequenced using a combination of long- and short-read sequencing technologies. Highly contiguous assemblies were produced for each species. Structural differences between the species’ genomes were observed with gene expansions in fermentation-relevant genes (particularly inB. bruxellensisandB. nanus) identified. Numerous horizontal gene transfer (HGT) events in allBrettanomycesspecies’, including an HGT event that is probably responsible for allowingB. bruxellensisandB. anomalusto utilize sucrose were also observed.

Conclusions

Genomic adaptations and some evidence of domestication that have taken place inBrettanomycesare outlined. These new genome assemblies form a valuable resource for future research inBrettanomyces.
The optimal dose of succinylcholine for rapid sequence induction: a systematic review and meta-analysis of randomized trials
Authors: Putzu Alessandro , Tramèr Martin R. , Giffa Maxim , Czarnetzki Christoph
Published: March 2020

Background

The evidence base for the widely accepted standard regimen of succinylcholine for rapid sequence induction (1.0 mg kg− 1) remains unclear.

Methods

We performed a systematic review and meta-analysis of randomized trials comparing any succinylcholine regimen with the standard regimen (1.0 mg kg− 1) and reporting on intubating conditions and/or apnoea times. Results were expressed as absolute risk differences (ARD) for dichotomous data and mean differences (MD) for continuous data.

Results

We retrieved six trials with relevant data of 864 patients (ASA 1 or 2, aged 18–65 years, body mass index < 30 kg m− 2). Four regimens (0.3, 0.4, 0.5, 0.6 mg kg− 1) were compared with 1.0 mg kg− 1 in at least three trials each, and three (0.8, 1.5, 2 mg kg− 1) in one each. With 0.3 to 0.5 mg kg− 1, the likelihood of excellent intubating conditions was significantly decreased (ARD − 22% to − 67%). With 0.3 and 0.4 mg kg− 1, but not with 0.5, 0.6, 0.8, 1.5 and 2.0 mg kg− 1, the likelihood of unacceptable intubating conditions was significantly increased (ARD + 22% and + 32%, respectively). With 2.0 mg kg− 1, but not with 0.8 or 1.5 mg kg− 1, the likelihood of excellent intubating conditions was significantly increased (ARD + 23%). Apnoea times were significantly shorter with regimens ≤0.8 mg kg− 1 (MD − 1.0 to − 3.4 min) but were not reported with 1.5 or 2.0 mg kg− 1.

Conclusions

With succinylcholine regimens ≤0.5 mg kg− 1, excellent intubating conditions are less likely and apnoea times are shorter, compared with 1 mg kg− 1. With 0.3 and 0.4 mg kg− 1, unacceptable intubating conditions are more common. Succinylcholine 1.5 mg kg− 1 does not produce more often excellent conditions compared with 1 mg kg− 1, while 2.0 mg kg− 1 does, but the database with these regimens is weak and apnoea times remain unknown. Limited information size and strong statistical heterogeneity decrease the certainty of the evidence.
Intractable mechanical hemolytic anemia complicating mitral valve surgery: a case series study
Authors: Wang Jin , Zhang Hanlin , Fan Hongyang , Chen Kang , Zhang Yuelun , Song Kaicheng , Ao Hushan , Yu Chunhua
Published: March 2020

Background

Intractable, mechanical hemolytic anemia (IMHA) is a rare catastrophic complication following mitral valve surgery. We analyzed patient characteristics and IMHA management by reoperations after mitral valve surgery.

Methods

We collected medical records from mitral valve patients requiring reoperation due to IMHA. Inclusion criteria: hemoglobin < 100 g/L; positive hemolysis tests and echocardiography results; and exclusion of other hemolysis causes.

Results

Data from 25 IMHA cases included 10 (40%) early onset (1.3 (0.3,3.0) months) and 15 (60%) late onset (120 (24,204) months) cases. Early IMHA etiologies included surgical defects (6, 60%), uncontrolled infection (3, 30%) and Bechet’s disease (1, 10%). Late IMHA etiologies included degeneration (13, 87%), new infection (1, 7%) and trauma (1, 7%). There were more mechanical valves (15, 88%) than bio-valves (2, 12%); the main valvular dysfunction was paravalvular leak (16, 64%). IMHA manifestations included jaundice (18, 72%), dark urine (21, 84%), heart failure (16, 64%), acute kidney injury (11, 44%), hepatomegaly (15, 60%), splenomegaly (15, 60%) and pancreatitis (1, 4%). Laboratory results showed decreased hemoglobin (70 ± 14 g/L) and increased bilirubin (72 ± 57 μmol/L), lactate dehydrogenase (2607 ± 2142 IU/L) and creatinine (136 ± 101 μmol/L) levels. Creatinine level negatively correlated with hemoglobin level (B = -3.33, S.E. B = 1.31, Exp(B) = 368.15, P = 0.018). Preoperative medications included iron supplements (20, 80%), erythropoietin (16, 64%) and beta-blocker (22, 88%). Two patients died of cardiac causes before reoperation. The other 23 underwent reoperation with long surgical times (aortic cross clamp 124 ± 50 min, cardiopulmonary bypass 182 ± 69 min) and blood transfusions (red blood cells 6 (6, 8) units, plasma 600 (400,800) ml, platelet 1(0,2) units). Postoperative complications included cardiac dysfunction (5, 22%), arrhythmia (10, 43%), sepsis (6, 26%), pulmonary infection (5, 22%), gastrointestinal bleeding (3, 13%), cerebral hemorrhage (2, 9%), chronic renal dysfunction (1, 4%) and surgical hemorrhage (1, 4%). Five (33%) patients died after reoperation from cardiac dysfunction (3, 60%), septic shock (1, 20%) and self-discharge (1, 20%).

Conclusions

IMHA induces severe multi-organ dysfunction, contributing to high mortality. Perioperative management should focus on etiological treatment, organ protection, and blood management.
Norm values and psychometric properties for the German health regulatory focus scale – results of a representative survey
Authors: Schmalbach Bjarne , Zenger Markus , Brähler Elmar , Petrowski Katja
Published: March 2020

Background

The health regulatory focus is an application of Higgins’ regulatory focus theory to a health-specific context. It explains individual differences in health motivation, strategies, and behavior. Previous research found the Health Regulatory Focus Scale (HRFS) to be a reliable and valid measure for the construct. However, an evaluation of the HRFS in a representative sample has not been performed as of yet. Neither are there any normative values available.

Methods

We collected a representative sample from the German general population to perform a confirmatory factor analysis, an analysis of measurement invariance, and to calculate norm values.

Results

A two-factor model evinced good model fit with a good reliability for the two subscales. We found evidence for strict invariance across gender groups and partial strict invariance across age groups. In addition, we are presenting normative values for the general population.

Conclusions

The findings of the present study are in line with previous research in confirming the HRFS as a valid and reliable tool suitable for the assessment of the health regulatory focus. The reported normative values allow for comparisons of individuals with their respective sociodemographic group.
Comprehensive proteomics investigation of P. vivax-infected human plasma and parasite isolates
Authors: Venkatesh Apoorva , Aggarwal Shalini , Kumar Swati , Rajyaguru Srushti , Kumar Vipin , Bankar Sheetal , Shastri Jayanthi , Patankar Swati , Srivastava Sanjeeva
Published: March 2020

Background

In recent times,Plasmodium vivax (P. vivax)has become a serious threat to public health due to its ability to cause severe infection with fatal outcomes. Its unique biology makes it resilient to control measures that are otherwise effective againstP. falciparum. A deeper understanding ofP. vivaxbiology and pathogenesis is, therefore, essential for developing the right control strategies. Proteomics ofP. falciparumhas been helpful in studying disease biology and elucidating molecular mechanisms involved in the development of disease. However, unlikeP. falciparum, proteomics data forP. vivaxinfection is minimal due to the absence of a continuous culture system. The dependence on clinical samples and animal models has drastically limitedP. vivaxresearch, creating critical knowledge gaps in our understanding of the disease. This study describes an in-depth proteomics analysis ofP. vivax-infected human plasma and parasite isolates, to understand parasite biology, pathogenesis, and to identify new diagnostic targets forP. vivaxmalaria.

Methods

A mass-spectrometry- (MS) based proteomics approach (Q Exactive) was applied to analyze human plasma and parasite isolates from vivax malaria patients visiting a primary health centre in India. Additionally, a targeted proteomics assay was standardized for validating unique peptides of most recurring parasite proteins.

Results

Thirty-eightP. vivaxproteins were detected in human plasma with high confidence. Several glycolytic enzymes were found along with hypothetical, cytoskeletal, ribosomal, and nuclear proteins. Additionally, 103 highly abundantP. vivaxproteins were detected in parasite isolates. This represents the highest number of parasite proteins to be reported from clinical samples so far. Interestingly, five of these; threePlasmodiumexported proteins (PVX_003545, PVX_003555 and PVX_121935), a hypothetical protein (PVX_083555) and Pvstp1 (subtelomeric transmembrane protein 1, PVX_094303) were found in both plasma and parasite isolates.

Conclusions

A parasite proteomics investigation is essential to understand disease pathobiology and design novel interventions. Control strategies againstP. vivaxalso depend on early diagnosis. This work provides deeper insights into the biology ofP. vivaxby identifying proteins expressed by the parasite during its complex life-cycle within the human host. The study also reports antigens that may be explored as diagnostic candidates.
Identification of a rare SEPT9 variant in a family with autosomal dominant Charcot-Marie-Tooth disease
Authors: Grosse Gerrit M. , Bauer Christine , Kopp Bruno , Schrader Christoph , Osmanovic Alma
Published: March 2020

Background

Charcot-Marie-Tooth disease (CMT) is one of the most commonly inherited neurological disorders. A growing number of genes, involved in glial and neuronal functions, have been associated with different subtypes of CMT leading to improved diagnostics and understanding of pathophysiological mechanisms. However, some patients and families remain genetically unsolved.

Methods

We report on a German family including four affected members over three generations with a CMT phenotype accompanied by cognitive deficits, predominantly with regard to visual abilities and episodic memory.

Results

A comprehensive clinical characterization followed by a sequential diagnostic approach disclosed a heterozygous rare SEPT9 missense variant c.1406 T > C, p.(Val469Ala), that segregates with disease. SEPT9 has been linked to various intracellular functions, such as cytokinesis and membrane trafficking. Interestingly, SEPT9-mutations are known to cause hereditary neuralgic amyotrophy (HNA), a recurrent focal peripheral neuropathy.

Conclusion

We, for the first time, present a SEPT9 variant associated to a CMT phenotype and suggest SEPT9 as new sufficient candidate gene in CMT.
Effect of a tailored leaflet to promote diabetic retinopathy screening among young adults with type 2 diabetes: a randomised controlled trial
Authors: Lake Amelia J. , Hateley-Browne Jessica L. , Rees Gwyneth , Speight Jane
Published: March 2020

Background

Young adults with type 2 diabetes (aged 18–39 years) are at risk of early onset and rapid progression of diabetic retinopathy, the leading cause of blindness and vision loss in working age adults. Early detection via retinal screening can prevent most vision loss, yet screening rates are consistently lower among this priority population than the general diabetes population. We aimed to test the effect of a tailored, evidence-based brief health behaviour change intervention (leaflet) on self-reported screening uptake, and previously identified social cognitive determinants of retinal screening.

Methods

A pragmatic, two-arm randomised controlled trial was conducted from September 2014 to April 2015. Participants were stratified by prior screening uptake (Yes/No) and randomly allocated to intervention (leaflet) or ‘usual care’ control (no leaflet). Primary outcome was self-reported screening uptake four weeks post-intervention for ‘No’ participants who had not previously screened for diabetic retinopathy. Secondary outcome variables were changes in knowledge, attitudes, normative beliefs, intention and behavioural skills for all participants, irrespective of prior screening behaviour. To assess intervention effects on secondary outcome variables, we conducted independent samples t-tests (two-tailed) on pre-post change scores.

Results

129 young adults (26% no prior retinal screen) completed baseline; 101 completed post-intervention. Power to determine effect on the primary outcome was curtailed by low recruitment of individuals with no prior retinal screen and loss to follow-up. Attrition was associated significantly with country of birth, language spoken at home, and marital status. Significant intervention effect was observed for one secondary outcome variable: knowledge of diabetic retinopathy (p = .03) with moderate effect (partial eta squaredη2 = .05); no adverse effects were reported. Control group participants received the leaflet at study completion.

Conclusions

This study confirms that a well-designed eye health and retinal screening promotion leaflet can increase knowledge of diabetic retinopathy, an important screening predictor. The study highlights the challenges of conducting ‘real-world’ health behaviour change research with this priority population, providing insights for clinicians and researchers. Strategies to recruit, engage and retain hard-to-reach populations are discussed including nonconventional alternatives to randomised controlled trial designs. Trial registration: ACTRN12614001110673, UTN No.: U1111–1161-9803. Registered 20 October 2014 - retrospectively registeredhttps://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367127.
Perspectives of adolescents with severe obesity on social Media in Preparation for weight-loss surgery: a qualitative study
Authors: Parks Elizabeth Prout , Finnerty Darra D. , Panganiban Jennifer , Frasso Rosemary , Bishop-Gilyard Chanelle , Tewksbury Colleen M. , Williams Noel N. , Dumon Kristoffel R. , Cordero Gaby , Hill Douglas L. , Sarwer David B.
Published: March 2020

Background

Currently the most effective treatment for severe obesity in adolescents is weight-loss surgery coupled with lifestyle behavior change. In preparation for weight-loss surgery, adolescents are required to make changes to eating and activity habits (lifestyle changes) to promote long term success. Social media support groups, which are popular among adolescents, have the potential to augment preoperative lifestyle changes. The purpose of this study was to qualitatively assess the perceived role of social media as a support tool for weight-loss, and to identify motivators and constraints to lifestyle changes and social media use in adolescents preparing for weight-loss surgery.

Methods

Thematic analysis of social media comments from 13 (3 male, 10 female) adolescents aged 16 ± 1.3 years with a body mass index (BMI) 45 ± 7.3 kg/m2 enrolled in a weight-management program preparing for bariatric surgery and who participated in a 12-week pilot social media intervention was performed. Participants commented on moderator posts and videos of nutrition, physical activity, and motivation that were shared three to four times per week. Social media comments were coded using NVivo 11.0 to identify recurrent themes and subthemes.

Results

1) Social media provided accountability, emotional support, and shared behavioral strategies. 2) Motivators for lifestyle changes included family support, personal goals, and non-scale victories. 3) Challenges included negative peers, challenges with planning and tracking, and time constraints.

Conclusion

Adolescents considering bariatric surgery identified social media as a tool for social support and reinforcement of strategies for successful behavior change. Important motivators and challenges to lifestyle changes were identified.
Burden of prehypertension among adults in Kenya: a retrospective analysis of findings from the Healthy Heart Africa (HHA) Programme
Authors: Mecha Jared O. , Kubo Elizabeth N. , Odhiambo Collins O. , Kinoti Freda G. , Njau Kennedy , Yonga Gerald , Ogola Elijah N.
Published: March 2020

Background

Hypertension is the leading risk factor for mortality globally. African countries, including Kenya, have a high and rising prevalence of hypertension. Prehypertension is associated with an increased risk of progression to overt hypertension and a higher risk of cardiovascular disease and mortality. Despite this, little is documented on the prevalence and distribution of prehypertension in sub-Saharan Africa. This study sought to estimate the overall burden of prehypertension in Kenyan adults enrolled in a large hypertension control programme, Healthy Heart Africa. The distribution and determinants of prehypertension in the sample were explored as secondary objectives.

Methods

This was a post hoc analysis of cross-sectional data obtained from population-level blood pressure (BP) screening of adults aged ≥18 years in the community and ambulatory care facilities in 17/47 sub-national administrative units in Kenya. All participants with a complete record for systolic and diastolic BP were included. Descriptive analyses were performed for sociodemographic characteristics. Pearson’s chi-square test was used to assess differences in categorical variables. Multivariate logistic regression analysis was performed to identify factors independently associated with prehypertension.

Results

Of 5,985,185 participant records that were included in the analysis, 34% were men (mean age: 45 [SD 2.9] years). The majority (63%) lived in rural Kenya. The prevalence of prehypertension was 54.5% and that of hypertension was 20.8%. Characteristics that were independently associated with prehypertension (adjusted odds ratio [95% CI]) included male sex (1.23 [±0.0023], p <  0.001 for all age groups > 25 years) and rural residence (1.60 [±0.023], p <  0.001).

Conclusions

Approximately one in every two Kenyan adults has prehypertension. This calls for urgent development and roll-out of a national BP screening and control programme. It also provides a strong basis for the formulation of multisectoral national policies that will ensure implementation of evidence-based, low-cost public health interventions geared towards primary prevention of hypertension, especially in population groups that are traditionally considered at low risk, such as young adults and rural residents.
Progression of planovalgus deformity in patients with cerebral palsy
Authors: Min Jae Jung , Kwon Soon-Sun , Sung Ki Hyuk , Lee Kyoung Min , Chung Chin Youb , Park Moon Seok
Published: March 2020

Background

Analyzing radiographic changes of pes planovalgus(PV) deformity of cerebral palsy(CP) patients according to age and influencing factors.

Methods

CP patients with PV deformity younger than 18 years old who had undergone more than a year of follow-up with at least two standing foot radiographs were included. Anteroposterior and lateral talo-first metatarsal(talo-1stMT), talo-second metatarsal(talo-2ndMT), and hallux valgus(HV) angles were measured on the radiographs. The rate of progression was adjusted by multiple factors using the linear mixed model, with the Gross Motor Function Classification System(GMFCS) level as the fixed effect and age and each subject as random effects.

Results

Overall, 194 patients were enrolled in this study, and 1272 standing foot radiographs were evaluated. The AP talo-2ndMT angle progressed by 0.59° (p < 0.0001) and 0.64° (p = 0.0007) in GMFCS level II and III patients, respectively; however, there was no significant change in GMFCS level I patients (p = 0.3269). HV was significantly affected by age in all three GMFCS groups; it increased by 0.48° (p < 0.0001), 0.66° (p < 0.0001), and 1.19° (p < 0.0001) for levels I, II, and III, respectively. The lateral talo-1stMT angle showed improvements in GMFCS level I and II patients (0.43°, p < 0.0001, and 0.61°, p < 0.0001, respectively). In GMFCS level III patients, there was no significant improvement in the lateral talo-1stMT angle (p = 0.0535).

Conclusions

The GMFCS level was the single most important factor influencing the progression of radiographic indices in PV deformity in CP. The AP talo-1stMT and talo-2ndMT angles progressed in patients with GMFCS levels II and III. Physicians should take this result into consideration when planning the timing of the surgery.

Level of evidence

Prognostic Level IV.
The collaborative learning development exercise (CLeD-EX): an educational instrument to promote key collaborative learning behaviours in medical students
Authors: Pervaz Iqbal Maha , Velan Gary M. , O’Sullivan Anthony J. , Balasooriya Chinthaka
Published: March 2020

Background

Modern clinical practice increasingly relies on collaborative and team-based approaches to care. Regulatory bodies in medical education emphasise the need to develop collaboration and teamwork competencies and highlight the need to do so from an early stage of medical training. In undergraduate medical education, the focus is usually on collaborative learning, associated with feedback and reflection on this learning This article describes a novel educational instrument, the Collaborative Learning Development Exercise (CLeD-EX), which aims to foster the development of key collaborative learning competencies in medical students. In this article we report on the effectiveness, feasibility and educational impact of the CLeD-EX.

Methods

In this study, the “educational design research” framework was used to develop, implement and evaluate the CLeD-EX. This involved adopting a systematic approach towards designing a creative and innovative instrument which would help solve a real-world challenge in developing collaborative learning skills. The systematic approach involved a qualitative exploration of key collaborative learning behaviours which are influential in effective collaborative learning contexts. The identified competencies were employed in the design of the CLeD-EX. The design of the CLeD-EX included features to facilitate structured feedback by tutors to students, complemented by self-evaluation and reflection. The CLeD-EX was field-tested with volunteer junior medical students, using a controlled pre-test post-test design. Analysis of the completed CLeD-EX forms, self-perception surveys (i.e. pre-test and post-test surveys) and analyses of reflective reports were used to explore the educational impact of CLeD-EX, as well as its utility and practicality.

Results

After using the CLeD-EX, students showed a significant improvement in critical thinking and group process as measured by a previously validated instrument. Both students and tutors recognised CLeD-EX as an effective instrument, especially as a structured basis for giving and receiving feedback and for completing the feedback loop. CLeD-EX was also found to be feasible, practical and focused, while promoting learning and effective interactions in small group learning.

Conclusion

The findings of this study support the introduction of an effective and feasible educational instrument such as the CLeD-EX, to facilitate the development of students’ skills in collaborative learning.
Design and clinical validation of a software program for automated measurement of mammographic breast density
Authors: Araújo Adriano L. C. , Soares Heliana B. , Carvalho Daniel F. , Mendonça Roberto M. , Oliveira Antonio G.
Published: March 2020

Background

Mammographic breast density is an important predictor of breast cancer, but its measurement has limitations related to subjectivity of visual evaluation or to difficult access for automatic volumetric measurement methods. Herein, we describe the design and clinical validation of Aguida, a software program for automated quantification of breast density from flat mammography images.

Materials and methods

The software program was developed in MatLab. After image segmentation separating the background from the breast image, the operator positions a cursor defining a region of interest on the pectoralis major muscle from the mediolateral oblique view. Then, in the craniocaudal view, the threshold for separation of the dense tissue is based on the optical density of the pectoral muscle, and the proportion of dense tissue is calculated by the program. Mammograms obtained from 2 different occasions in 291 women were used for clinical evaluation.

Results

The intraclass correlation coefficient (ICC) between breast density measurements by the software and by a radiologist was 0.96, with a bias of only 0.67 percentage points and a 95% limit of agreement of 13.5 percentage points; the ICC was 0.94 in the interobserver reliability assessment by two radiologists with different experience; and the ICC was 0.98 in the intraobserver reliability assessment. The distribution among the density classes was close to the values obtained with the volumetric software.

Conclusions

Measurement of breast density with the Aguida program from flat mammography images showed high agreement with the visual determination by radiologists, and high inter- and intra-observer reliability.
Spatio-temporal variations of licensed doctor distribution in China: measuring and mapping disparities
Authors: Zhu Bin , Hsieh Chih-Wei , Mao Ying
Published: March 2020

Background

The licensed doctor misdistribution is one of the major challenges faced by China. However, this subject remains underexplored as spatial distribution characteristics (such as spatial clustering patterns) have not been fully mapped out by existing studies. To fill the void, this study aims to explore the spatio-temporal dynamics and spatial clustering patterns of different subtypes of licensed doctors (i.e., clinicians, traditional Chinese medicine doctors, dentists, public health doctors, general practitioners) in China.

Methods

Data on the licensed doctor quantity and population during 2012–2016 was obtained from the National Health (and Family Planning) Yearbook. Functional boxplots were used to visualize and compare the temporal trends of densities of different subtypes of licensed doctors. This study adopted two complementary spatial statistics (space-time scan statistics and Moran’s I statistics) to explore the spatio-temporal dynamics and spatial clustering patterns of licensed doctor distribution in China. The former was used to explore the spatial variations in the temporal trends of licensed doctor density during 2012–2016, and the latter was adopted to explore the spatial changing patterns of licensed doctor distribution during the research period.

Results

The results show that the densities of almost all subtypes of licensed doctors displayed upward trends during 2012–2016, though some provincial units were left behind. Besides, spatial distribution characteristics varied across different subtypes of licensed doctors, with the low-low cluster area of general practitioners being the largest.

Conclusions

The misdistribution of licensed doctors is a global problem and China is no exception. In order to achieve a balanced distribution of licensed doctors, the government is suggested to introduce a series of measures, such as deliberative policy design and effective human resource management initiatives to educate, recruit, and retain licensed doctors and prevent a brain drain of licensed doctors from disadvantaged units.
The effectiveness of frequent antibiotic use in reducing the risk of infection-related hospital admissions: results from two large population-based cohorts
Authors: van Staa Tjeerd Pieter , Palin Victoria , Li Yan , Welfare William , Felton Timothy W. , Dark Paul , Ashcroft Darren M.
Published: March 2020

Background

Previous research reported that individuals prescribed antibiotics frequently develop antimicrobial resistance. The objective of this study was to evaluate whether frequent antibiotic use is associated with reduced hospital admissions for infection-related complications.

Methods

Population-based cohort study analysing electronic health records from primary care linked to hospital admission records. The study population included patients prescribed a systemic antibiotic, recent record of selected infections and no history of chronic obstructive pulmonary disease. Propensity-matched cohorts were identified based on quintiles of prior antibiotic use in 3 years before.

Results

A total of 1.8 million patients were included. Repeated antibiotic use was frequent. The highest rates of hospital admissions for infection-related complications were observed shortly after antibiotic start in all prior exposure quintiles. For patients with limited prior antibiotic use, rates then dropped quickly and substantially. In contrast, reductions over time were substantially less in patients with frequent prior antibiotic use, with rates remaining elevated over the following 6 months. In patients without comorbidity comparing the highest to lowest prior exposure quintiles in the Clinical Practice Research Databank, the IRRs were 1.18 [95% CI 0.90–1.55] in the first 3 days after prescription, 1.44 [95% CI 1.14–1.81] in the days 4–30 after and 3.22 [95% CI 2.29–4.53] in the 3–6 months after.

Conclusions

Repeated courses of antibiotics, although common practice, may have limited benefit and indicator of adverse outcomes. A potential mechanism is that antibiotics may cause dysbiosis (perturbations of intestinal microbiota), contributing to colonization with resistant bacteria. Antibiotics should be used judiciously and only periodically unless indicated. Antimicrobial stewardship should include activities focusing on the substantive number of patients who repeatedly but intermittently get antibiotics.
Applied mathematical modelling to inform national malaria policies, strategies and operations in Tanzania
Authors: Runge Manuela , Molteni Fabrizio , Mandike Renata , Snow Robert W. , Lengeler Christian , Mohamed Ally , Pothin Emilie
Published: March 2020

Background

More than ever, it is crucial to make the best use of existing country data, and analytical tools for developing malaria control strategies as the heterogeneity in malaria risk within countries is increasing, and the available malaria control tools are expanding while large funding gaps exist. Global and local policymakers, as well as funders, increasingly recognize the value of mathematical modelling as a strategic tool to support decision making. This case study article describes the long-term use of modelling in close collaboration with the National Malaria Control Programme (NMCP) in Tanzania, the challenges encountered and lessons learned.

Case description

In Tanzania, a recent rebound in prevalence led to the revision of the national malaria strategic plan with interventions targeted to the malaria risk at the sub-regional level. As part of the revision, a mathematical malaria modelling framework for setting specific predictions was developed and used between 2016 and 2019 to (1) reproduce setting specific historical malaria trends, and (2) to simulate in silico the impact of future interventions. Throughout the project, multiple stakeholder workshops were attended and the use of mathematical modelling interactively discussed.

Evaluation

In Tanzania, the model application created an interdisciplinary and multisectoral dialogue platform between modellers, NMCP and partners and contributed to the revision of the national malaria strategic plan by simulating strategies suggested by the NMCP. The uptake of the modelling outputs and sustained interest by the NMCP were critically associated with following factors: (1) effective sensitization to the NMCP, (2) regular and intense communication, (3) invitation for the modellers to participate in the strategic plan process, and (4) model application tailored to the local context.

Conclusion

Empirical data analysis and its use for strategic thinking remain the cornerstone for evidence-based decision-making. Mathematical impact modelling can support the process both by unifying all stakeholders in one strategic process and by adding new key evidence required for optimized decision-making. However, without a long-standing partnership, it will be much more challenging to sensibilize programmes to the usefulness and sustained use of modelling and local resources within the programme or collaborating research institutions need to be mobilized.
Bayesian spatiotemporal modeling with sliding windows to correct reporting delays for real-time dengue surveillance in Thailand
Authors: Rotejanaprasert Chawarat , Ekapirat Nattwut , Areechokchai Darin , Maude Richard J.
Published: March 2020

Background

The ability to produce timely and accurate estimation of dengue cases can significantly impact disease control programs. A key challenge for dengue control in Thailand is the systematic delay in reporting at different levels in the surveillance system. Efficient and reliable surveillance and notification systems are vital to monitor health outcome trends and early detection of disease outbreaks which vary in space and time.

Methods

Predicting the trend in dengue cases in real-time is a challenging task in Thailand due to a combination of factors including reporting delays. We present decision support using a spatiotemporal nowcasting model which accounts for reporting delays in a Bayesian framework with sliding windows. A case study is presented to demonstrate the proposed nowcasting method using weekly dengue surveillance data in Bangkok at district level in 2010.

Results

The overall real-time estimation accuracy was 70.69% with 59.05% and 79.59% accuracy during low and high seasons averaged across all weeks and districts. The results suggest the model was able to give a reasonable estimate of the true numbers of cases in the presence of delayed reports in the surveillance system. With sliding windows, models could also produce similar accuracy to estimation with the whole data.

Conclusions

A persistent challenge for the statistical and epidemiological communities is to transform data into evidence-based knowledge that facilitates policy making about health improvements and disease control at the individual and population levels. Improving real-time estimation of infectious disease incidence is an important technical development. The effort in this work provides a template for nowcasting in practice to inform decision making for dengue control.
PARP inhibitors in pancreatic cancer: molecular mechanisms and clinical applications
Authors: Zhu Heng , Wei Miaoyan , Xu Jin , Hua Jie , Liang Chen , Meng Qingcai , Zhang Yiyin , Liu Jiang , Zhang Bo , Yu Xianjun , Shi Si
Published: March 2020

Pancreatic cancer is a highly lethal disease with a poor prognosis, and existing therapies offer only limited effectiveness. Mutation gene sequencing has shown several gene associations that may account for its carcinogenesis, revealing a promising research direction. Poly (ADP-ribose) polymerase (PARP) inhibitors target tumor cells with a homologous recombination repair (HRR) deficiency based on the concept of synthetic lethality. The most prominent target gene is BRCA, in which mutations were first identified in breast cancer and ovarian cancer. PARP inhibitors can trap the PARP-1 protein at a single-stranded break/DNA lesion and disrupt its catalytic cycle, ultimately leading to replication fork progression and consequent double-strand breaks. For tumor cells with BRCA mutations, HRR loss would result in cell death. Pancreatic cancer has also been reported to have a strong relationship with BRCA gene mutations, which indicates that pancreatic cancer patients may benefit from PARP inhibitors. Several clinical trials are being conducted and have begun to yield results. For example, the POLO (Pancreatic Cancer Olaparib Ongoing) trial has demonstrated that the median progression-free survival was observably longer in the olaparib group than in the placebo group. However, PARP inhibitor resistance has partially precluded their use in clinical applications, and the major mechanism underlying this resistance is the restoration of HRR. Therefore, determining how to use PARP inhibitors in more clinical applications and how to avoid adverse effects, as well as prognosis and treatment response biomarkers, require additional research. This review elaborates on future prospects for the application of PARP inhibitors in pancreatic cancer.
Assessing whether ad hoc clinician-generated patient questionnaires provide psychometrically valid information
Authors: Lee Minji K. , Basford Jeffrey R. , Heinemann Allen W. , Cheville Andrea
Published: March 2020

Background

The provision of psychometrically valid patient reported outcomes (PROs) improves patient outcomes and reflects their quality of life. Consequently, ad hoc clinician-generated questionnaires of the past are being replaced by more rigorous instruments. This change, while beneficial, risks the loss/orphaning of decades-long information on difficult to capture/chronically ill populations. The goal of this study was to assess to the quality of data retrieved from these legacy questionnaires.

Methods

Participants included 8563 patients who generated a total of 12,626 hospital admissions over the 2004–2014 study period. Items used to screen for issues related to function, mood, symptoms, and social support among patients with chronic disease were identified in our medical center’s patient information questionnaire. Cluster and exploratory factor analyses (EFA) followed by multidimensional item response theory (MIRT) analyses were used to select items that defined factors. Scores were derived with summation and MIRT approaches; inter-factor relationships and relationships of factor scores to assigned diagnostic codes were assessed. Rasch analyses assessed the constructs’ measurement properties.

Results

Literature review and clinician interviews yielded four hypothesized constructs: psychological distress/wellbeing, symptom burden, social support, and physical function. Rasch analyses showed that, while all had good measurement properties, only one, function, separated individuals well. In exploratory factor analyses (EFA), 11 factors representing depression, respiratory symptoms, musculoskeletal pain, family support, mobility, activities of daily living, alcohol consumption, weight loss, fatigue, neurological disorders, and fear at home were identified. Based on the agreement between EFA and cluster analyses as well as Cronbach’s alpha, six domains were retained for analyses. Correlations were strong between activities of daily living and mobility (.84), and moderate between pain and mobility (.37) and psychological distress (.59) Known-group validity was supported from the relationships between factor scores and the relevant diagnostic code assignments (.12 to .20).

Conclusions and discussion

Items from ad hoc clinician-generated patient information questionnaires can be aggregated into valid factors that assess supportive care domains among chronically ill patients. However, the binary response options offered by many screening items limit their information content and consequently, as highlighted by Rasch analyses, their ability to meaningfully discriminate trait levels in these populations.
An engineering probiotic producing defensin-5 ameliorating dextran sodium sulfate-induced mice colitis via Inhibiting NF-kB pathway
Authors: Zeng Lishan , Tan Jiasheng , Xue Meng , Liu Le , Wang Mingming , Liang Liping , Deng Jun , Chen Wei , Chen Ye
Published: March 2020

Background

Human defensin-5 (HD-5) is a key antimicrobial peptide which plays an important role in host immune defense, while the short half-life greatly limits its clinical application. The purpose of this study was to investigate the effects of an engineering probiotic producing HD-5 on intestinal barrier and explore its underlying mechanism

Methods

We constructed the pN8148-SHD-5 vector, and transfected this plasmid into Lactococcus lactis (L. lactis) to create the recombinant NZ9000SHD-5 strain, which continuously produces mature HD-5. NZ9000SHD-5 was administrated appropriately in a dextran sodium sulfate (DSS)-induced colitis model. Alterations in the wounded intestine were analyzed by hematoxylin–eosin staining. The changes of intestinal permeability were detected by FITC-dextran permeability test, the tight junction (TJ) proteins ZO-1 and occludin and cytokines were analyzed by western blotting or enzyme linked immunosorbent assay. In Caco-2 cell monolayers, the permeability were analyzed by transepithelial electrical resistance, and the TJ proteins were detected by western blotting and immunofluorescence. In addition, NF-κB signaling pathway was investigated to further analyze the molecular mechanism of NZ9000SHD-5 treatment on inducing intestinal protection in vitro.

Results

We found oral administration with NZ9000SHD-5 significantly reduced colonic glandular structure destruction and inflammatory cell infiltration, downregulated expression of several inflammation-related molecules and preserved epithelial barrier integrity. The same protective effects were observed in in vitro experiments, and pretreatment of macrophages with NZ9000SHD-5 culture supernatants prior to LPS application significantly reduced the expression of phosphorylated nuclear transcription factor-kappa B (NF-κB) p65 and its inhibitor IκBα.

Conclusions

These results indicate the NZ9000SHD-5 can alleviate DSS-induced mucosal damage by suppressing NF-κB signaling pathway, and NZ9000SHD-5 may be a novel therapeutic means for ulcerative colitis.
Experiences of pregnancy in adolescence of internally displaced women in Bogotá: an ethnographic approach
Authors: Cadena-Camargo Yazmin , Krumeich Anja , Duque-Páramo Maria Claudia , Horstman Klasien
Published: March 2020

Background

Pregnancy in adolescence is higher among internally displaced women in Colombia than non-displaced women. It is defined as a problem with significant negative outcomes by both biomedical and epidemiological approaches. However, little is known about pregnancy during adolescence from the perspective of women who experienced this in the specific context of armed conflict and displacement.

Aim

This article focuses on how internally displaced women understand their experiences of pregnancy in adolescence in the context of armed conflict through an ethnographic approach in a receptor community of internally displaced women in Bogotá, Colombia.

Methods

Based on 10 years of experience in the community, we conducted 1 year of fieldwork, using an ethnographic approach. We collected life stories of 20 internally displaced women through in-depth interviews and ran 8 workshops with them and other women from the community. We used thematic analysis to analyse the responses of internally-displaced women and understand how they made meaning around their experiences of adolescent pregnancy in the context of displacement.

Results

The main themes that emerged from participants’ experiences include rural violence, early family life (characterized by violence and mistreatment at home), meanings of pregnancy at an early age (including being challenged and feelings of love), and reactions to their pregnancies during adolescence (such as stigmatization) from their families and partners.

Conclusion

Our analysis of the in-depth interviews and the workshops suggests that adolescent pregnancy among women who are internally displaced has complex dynamics, characterized by the violent context of the rural areas, but primarily by the violence experienced during their childhood. The experience of pregnancy during adolescence brings feelings of ownership and also challenges, together with the forced displacement. This understanding will provide insights for policy makers and healthcare providers on how to work with this specific population who have experienced pregnancy in adolescence.