bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of hospital language on the rate of in-hospital harm. A retrospective cohort study of home care recipients in Ontario, Canada
Authors: Reaume Michael , Batista Ricardo , Talarico Robert , Rhodes Emily , Guerin Eva , Carson Sarah , Prud’homme Denis , Tanuseputro Peter 
Published: April 2020

Abstract
Background
Patients who live in minority language situations are generally more likely to experience poor health outcomes, including harmful events. The delivery of healthcare services in a language-concordant environment has been shown to mitigate the risk of poor health outcomes related to chronic disease management in primary care. However, data assessing the impact of language-concordance on the risk of in-hospital harm are lacking. We conducted a population-based study to determine whether admission to a language-discordant hospital is a risk factor for in-hospital harm.

Methods
We used linked administrative health records to establish a retrospective cohort of home care recipients (from 2007 to 2015) who were admitted to a hospital in Eastern or North-Eastern Ontario, Canada. Patient language (obtained from home care assessments) was coded as English (Anglophone group), French (Francophone group), or other (Allophone group); hospital language (English or bilingual) was obtained using language designation status according to the French Language Services Act. We identified in-hospital harmful events using the Hospital Harm Indicator developed by the Canadian Institute for Health Information.

Results
The proportion of hospitalizations with at least 1 harmful event was greater for Allophones (7.63%) than for Anglophones (6.29%, p <  0.001) and Francophones (6.15%, p <  0.001). Overall, Allophones admitted to hospitals required by law to provide services in both French and English (bilingual hospitals) had the highest rate of harm (9.16%), while Francophones admitted to these same hospitals had the lowest rate of harm (5.93%). In the unadjusted analysis, Francophones were less likely to experience harm in bilingual hospitals than in hospitals that were not required by law to provide services in French (English-speaking hospitals) (RR = 0.88, p = 0.048); the opposite was true for Anglophones and Allophones, who were more likely to experience harm in bilingual hospitals (RR = 1.17, p <  0.001 and RR = 1.41, p <  0.001, respectively). The risk of harm was not significant in the adjusted analysis.

Conclusions
Home care recipients residing in Eastern and North-Eastern Ontario were more likely to experience harm in language-discordant hospitals, but the risk of harm did not persist after adjusting for confounding variables.
Resource implications of the latent tuberculosis cascade of care: a time and motion study in five countries
Authors: Alsdurf H. , Oxlade O. , Adjobimey M. , Ahmad Khan F. , Bastos M. , Bedingfield N. , Benedetti A. , Boafo D. , Buu T. N. , Chiang L. , Cook V. , Fisher D. , Fox G. J. , Fregonese F. , Hadisoemarto P. , Johnston J. C. , Kassa F. , Long R. , Moayedi Nia S. , Nguyen T. A. , Obeng J. , Paulsen C. , Romanowski K. , Ruslami R. , Schwartzman K. , Sohn H. , Strumpf E. , Trajman A. , Valiquette C. , Yaha L. , Menzies D. 
Published: April 2020

Abstract
Background
The End TB Strategy calls for global scale-up of preventive treatment for latent tuberculosis infection (LTBI), but little information is available about the associated human resource requirements. Our study aimed to quantify the healthcare worker (HCW) time needed to perform the tasks associated with each step along the LTBI cascade of care for household contacts of TB patients.

Methods
We conducted a time and motion (TAM) study between January 2018 and March 2019, in which consenting HCWs were observed throughout a typical workday. The precise time spent was recorded in pre-specified categories of work activities for each step along the cascade. A linear mixed model was fit to estimate the time at each step.

Results
A total of 173 HCWs in Benin, Canada, Ghana, Indonesia, and Vietnam participated. The greatest amount of time was spent for the medical evaluation (median: 11 min; IQR: 6–16), while the least time was spent on reading a tuberculin skin test (TST) (median: 4 min; IQR: 2–9). The greatest variability was seen in the time spent for each medical evaluation, while TST placement and reading showed the least variability. The total time required to complete all steps along the LTBI cascade, from identification of household contacts (HHC) through to treatment initiation ranged from 1.8 h per index TB patient in Vietnam to 5.2 h in Ghana.

Conclusions
Our findings suggest that the time requirements are very modest to perform each step in the latent TB cascade of care, but to achieve full identification and management of all household contacts will require additional human resources in many settings.
Effect of centralization on geographic accessibility of maternity hospitals in Finland
Authors: Huotari Tiina , Rusanen Jarmo , Keistinen Timo , Lähderanta Tero , Ruha Leena , Sillanpää Mikko J. , Antikainen Harri 
Published: April 2020

AbstractBackgroundIn the past two decades, the number of maternity hospitals in Finland has been reduced from 42 to 22. Notwithstanding the benefits of centralization for larger units in terms of increased safety, the closures will inevitably impair geographical accessibility of services.MethodsThis study aimed to employ a set of location-allocation methods to assess the potential impact on accessibility, should the number of maternity hospitals be reduced from 22 to 16. Accurate population grid data combined with road network and hospital facilities data is analyzed with three different location-allocation methods: straight, sequential and capacitatedp-median.ResultsDepending on the method used to assess the impact of further reduction in the number of maternity hospitals, 0.6 to 2.7% of mothers would have more than a two-hour travel time to the nearest maternity hospital, while the corresponding figure is 0.5 in the current situation. The analyses highlight the areas where the number of births is low, but a maternity hospital is still important in terms of accessibility, and the areas where even one unit would be enough to take care of a considerable volume of births.ConclusionsEven if the reduction in the number of hospitals might not drastically harm accessibility at the level of the entire population, considerable changes in accessibility can occur for clients living close to a maternity hospital facing closure. As different location-allocation analyses can result in different configurations of hospitals, decision-makers should be aware of their differences to ensure adequate accessibility for clients, especially in remote, sparsely populated areas.
Stress testing journals: a quasi-experimental study of rejection rates of a previously published paper
Authors: Cobey Kelly D. , Rice Danielle B. , Lalu Manoj M. , Abramowitz Daniel , Ahmadzai Nadera , Cunningham Heather , Ayala Ana Patricia , Raffoul Hana , Khan Faizan , Shamseer Larissa , Moher David 
Published: April 2020

Abstract
Background
When a journal receives a duplicate publication, the ability to identify the submitted work as previously published, and reject it, is an assay to publication ethics best practices. The aim of this study was to evaluate how three different types of journals, namely open access (OA) journals, subscription-based journals, and presumed predatory journals, responded to receiving a previously published manuscript for review.

Methods
We performed a quasi-experimental study in which we submitted a previously published article to a random sample of 602 biomedical journals, roughly 200 journals from each journal type sampled: OA journals, subscription-based journals, and presumed predatory journals. Three hundred and three journals received a Word version in manuscript format, while 299 journals received the formatted publisher’s PDF version of the published article. We then recorded responses to the submission received after approximately 1 month. Responses were reviewed, extracted, and coded in duplicate. Our primary outcome was the rate of rejection of the two types of submitted articles (PDF vs Word) within our three journal types.

Results
We received correspondence back from 308 (51.1%) journals within our study timeline (32 days); (N = 46 predatory journals, N = 127 OA journals, N = 135 subscription-based journals). Of the journals that responded, 153 received the Word version of the paper, while 155 received the PDF version. Four journals (1.3%) accepted our paper, 291 (94.5%) journals rejected the paper, and 13 (4.2%) requested a revision. A chi-square test looking at journal type, and submission type, was significant (χ2 (4) = 23.50, p < 0.001). All four responses to accept our article came from presumed predatory journals, 3 of which received the Word format and 1 that received the PDF format. Less than half of journals that rejected our submissions did so because they identified ethical issues such as plagiarism with the manuscript (133 (45.7%)).

Conclusion
Few journals accepted our submitted paper. However, our findings suggest that all three types of journals may not have adequate safeguards in place to recognize and act on plagiarism or duplicate submissions.
Synthesis of the character impact compound raspberry ketone and additional flavoring phenylbutanoids of biotechnological interest with Corynebacterium glutamicum
Authors: Milke Lars , Mutz Mario , Marienhagen Jan 
Published: April 2020

Abstract
Background
The phenylbutanoid 4-(4-hydroxyphenyl)butan-2-one, commonly known as raspberry ketone, is responsible for the typical scent and flavor of ripe raspberries. Chemical production of nature-identical raspberry ketone is well established as this compound is frequently used to flavor food, beverages and perfumes. However, high demand for natural raspberry ketone, but low natural abundance in raspberries, render raspberry ketone one of the most expensive natural flavoring components.

Results
In this study, Corynebacterium glutamicum was engineered for the microbial synthesis of the character impact compound raspberry ketone from supplemented p-coumaric acid. In this context, the NADPH-dependent curcumin/dihydrocurcumin reductase CurA from Escherichia coli was employed to catalyze the final step of raspberry ketone synthesis as it provides a hitherto unknown benzalacetone reductase activity. In combination with a 4-coumarate: CoA ligase from parsley (Petroselinum crispum) and a monofunctional benzalacetone synthase from Chinese rhubarb (Rheum palmatum), CurA constitutes the synthetic pathway for raspberry ketone synthesis in C. glutamicum. The resulting strain accumulated up to 99.8 mg/L (0.61 mM) raspberry ketone. In addition, supplementation of other phenylpropanoids allowed for the synthesis of two other naturally-occurring and flavoring phenylbutanoids, zingerone (70 mg/L, 0.36 mM) and benzylacetone (10.5 mg/L, 0.07 mM).

Conclusion
The aromatic product portfolio of C. glutamicum was extended towards the synthesis of the flavoring phenylbutanoids raspberry ketone, zingerone and benzylacetone. Key to success was the identification of CurA from E. coli having a benzalacetone reductase activity. We believe, that the constructed C. glutamicum strain represents a versatile platform for the production of natural flavoring phenylbutanoids at larger scale.
Lattice complex assembled by noncompetitive anti-EGFR antibodies regulates actin cytoskeletal reorganization
Authors: Huang Dianshuai , Lu Tianqi , Du Xingyu , Xi Xi , Zhang Xin , Zhang Xitian , Zhang Haoran , Sun Fei 
Published: April 2020

Abstract
Background
Recent evidence of clinical trials highlights that the combination of two noncompetitive anti-EGFR antibodies can benefit patients with several cancers. Previous studies propose that a lattice complex assembled by antibodies and EGFR down-regulates surface EGFR by rapid internalization of the complex. However, there remains a paucity of evidence and understanding on the existence of a lattice complex on cell surface and its cellular processes of internalization.

Methods
Herein, we used three dimensions structured illumination microscopy to directly observe the actual morphology of the lattice complex formed on Hela cell membrane after noncompetitive anti-EGFR antibody combinations, and we explored the internalized mechanism of noncompetitive antibody combinations by constructing a PIP2 consumption system.

Result
We observed the lattice complex (length > 1 μm) on the surface of living cell after preincubation with Cetuximab and H11, but combination of Cetuximab and single domain antibody 7D12 fails to assemble the lattice, these results demonstrates the importance of symmetrical structure of conventional antibody for lattice formation. Interestingly, the lattice complex assembles along with cytoskeletal fibers, and its internalization recruits a large amount of PIP2 and triggers the rearrangement of F-actin.

Conclusions
The above data suggests that large-size lattice complex affects membrane fluidity and dynamic reorganization of cytoskeletal, which may be responsible for its rapid internalization. These new insight will aid in current rational combination design of anti-EGFR antibodies.
Enhanced inflammasome activation and reduced sphingosine-1 phosphate S1P signalling in a respiratory mucoobstructive disease model
Authors: Tran Hai B. , Macowan Matthew G. , Abdo Adrian , Donnelley Martin , Parsons David , Hodge Sandra 
Published: April 2020

Abstract
Background
Inflammasomes and sphingosine-1-phosphate (S1P) signalling are increasingly subject to intensive research in human diseases. We hypothesize that in respiratory muco-obstructive diseases, mucus obstruction enhances NLRP3 inflammasome activation and dysregulated S1P signalling.

Methods
Lung tissues from mice overexpressing the beta-unit of the epithelial sodium channel (βENaC) and their littermate controls were examined by histology, immunofluorescence and confocal microscopy, followed by ImageJ quantitative analysis.

Results
Lower airways in βENaC mice showed patchy patterns of mucus obstruction and neutrophil-dominant infiltrations. In contrast to a ubiquitous distribution of TNFα specks, significantly (p < 0.05) increased specks of bronchiolar NLRP3, IL-1β, and IgG in the βENaC mouse lungs were localized to the vicinity of mucus obstruction sites. Bright Spinster homologue 2 (SPNS2) at the epithelial apex and positive correlation with sphingosine kinase 1 (SPHK1) (R2 = 0.640; p < 0.001) supported the normal bronchial epithelium as an active generator of extracellular S1P. SPNS2 in βENaC mice was sharply reduced (38%, p < 0.05) and lost apical localization at sites of mucus obstruction. A significant (34%; p < 0.01) decrease in epithelial SPHK2 was also noted at mucus obstruction sites.

Conclusion
These results support that mucus obstruction may enhance NLRP3 inflammasome activation and dysregulated S1P signaling.
How many and which physicians? A comparative study of the evolution of the supply of physicians and specialist training in Brazil and Spain
Authors: Scheffer Mário César , Pastor-Valero Maria , Cassenote Alex Jones Flores , Compañ Rosique Antonio F. 
Published: April 2020

AbstractBackgroundIn the face of the medical workforce shortage, several countries have promoted the opening of medical schools and the expansion of undergraduate and specialization education in medicine. Few studies have compared the characteristics and effects of expanding the supply of general practitioners and specialist physicians between countries. Brazil and Spain, two countries with distinct historical processes and socioeconomic scenarios, yet both with universal public health systems and common aspects in training and medical work, have registered a significant increase in the number of physicians and can be used to understand the challenges of strategic planning for the medical workforce.MethodsThis study provides a descriptive approach using longitudinal data from official databases in Brazil and Spain from 1998 to 2017. Among the comparable indicators, the absolute numbers of physicians, the population size, and the physician’s ratio by inhabitants were used. The number of medical schools and undergraduate places in public and private institutions, the supply of residency training posts, and the number of medical specialists and medical residents per 100 000 inhabitants were also used to compare both countries. Seventeen medical specialties with the highest number of specialists and comparability between the two countries were selected for further comparison.ResultsDue to the opening of medical schools, the density of physicians per 1 000 inhabitants grew by 28% in Spain and 51% in Brazil between 1998 and 2017. In that period, Spain and Brazil increased the supply of annual undergraduate places by 60% and 137%, respectively. There is a predominance of private institutions providing available undergraduate places, and the supply of medical residency posts is smaller than the contingent of medical graduates/general practitioners each year.ConclusionBoth countries have similar specialist densities in cardiology, dermatology, and neurosurgery specialties. However, family medicine and community in Spain has 91.27 specialists per 100 000 inhabitants, while in Brazil, the density is only 2.64. The comparative study indicated the complexity of the countries’ decisions on increasing the medical supply of general practitioners and specialist physicians. Research and planning policies on the medical workforce must be aligned with the actual health needs of populations and health systems.
Association between local immune cell infiltration, mismatch repair status and systemic inflammatory response in colorectal cancer
Authors: Gunnarsson Ulf , Strigård Karin , Edin Sofia , Gkekas Ioannis , Mustonen Harri , Kaprio Tuomas , Böckelman Camilla , Hagström Jaana , Palmqvist Richard , Haglund Caj 
Published: April 2020

Abstract
Background
Systemic inflammatory response in colorectal cancer (CRC) has been established as a prognostic factor for impaired cancer-specific survival, predominantly in patients with right-sided tumors. On the other hand, defective mismatch repair (dMMR) tumors, primarily located in the right colon, are known to have favorable survival and dense local immune infiltration. The aim of this study was to see if there is any form of relationship between these seemingly diverse entities.

Methods
Complete clinical and long-term survival data were retrieved for 316 CRC patients operated at Helsinki University Hospital between the years 1998 and 2003. Tissue microarrays were prepared from surgical specimens and further processed and analyzed for local immune cell infiltration using multispectral imaging with a Vectra quantitative pathology imaging system and Inform software. Multiplex immunohistochemistry was applied using antibodies against CD66b, CD8, CD20, FoxP3, CD68 and pan-Cytokeratin. After exclusions, data on immune infiltration were available for 275 patients. Mismatch repair status was determined by immunohistochemistry.

Results
CRP was seen to be an independent predictor of cancer-specific survival but not overall survival in uni- and multivariable (HR 1.01 (1.00–1.02); p = 0.028) analyses of non-irradiated patients. There was no significant difference in CRP according to mismatch repair status, but all cases (n = 10) with CRP ≥ 75 mg/l had proficient mismatch repair (pMMR). There was a significant negative correlation between intratumor stromal infiltration by T-regulatory FOXP3+ cells and CRP (p = 0.006). There was significantly lower intratumor stromal infiltration by FOXP3+ cells (p = 0.043) in the right colon compared to the rectum, but no significant difference in CRP (p = 0.44). CRP was not a predictor of overall survival (HR 0.99, 95% CI 0.98–1.01) nor cancer-specific survival in irradiated patients (HR 0.94, 95% CI 0.94–1.02).

Conclusions
There was a significant negative relationship between SIR, defined as an elevated CRP, and intratumor stromal infiltration by T-regulatory FOXP3+ cells. This and the fact that all cases with a CRP > 75 mg/l had pMMR suggests that SIR and dMMR are independent entities in CRC. Indeed, the general lack of difference in CRP between cases with dMMR and pMMR may be evidence of overlap in cases with a less pronounced SIR.
Study protocol: a cluster randomized trial to evaluate the effectiveness and implementation of onsite GeneXpert testing at community health centers in Uganda (XPEL-TB)
Authors: Reza Tania F. , Nalugwa Talemwa , Farr Katherine , Nantale Mariam , Oyuku Denis , Nakaweesa Annet , Musinguzi Johnson , Vangala Moksha , Shete Priya B. , Tucker Austin , Ferguson Olivia , Fielding Katherine , Sohn Hojoon , Dowdy David , Moore David A. J. , Davis J. Lucian , Ackerman Sara L. , Handley Margaret A. , Katamba Achilles , Cattamanchi Adithya 
Published: April 2020

Abstract
Background
Delays in diagnosis and treatment of tuberculosis (TB) remain common in high-burden countries. To improve case detection, substantial investments have been made to scale-up Xpert MTB/RIF (Xpert), a cartridge-based nucleic acid amplification test that can detect TB within 2 hours, as a replacement for sputum smear microscopy. However, the optimal strategy for implementation of Xpert testing remains unclear.

Methods
The Xpert Performance Evaluation for Linkage to Tuberculosis Care (XPEL-TB) trial uses an ultra-pragmatic, hybrid type II effectiveness-implementation design to assess the effectiveness and implementation of a streamlined strategy for delivery of Xpert testing in real-world settings. Twenty health centers with TB microscopy units were selected to participate in the trial, with ten health centers randomized to the intervention strategy (onsite molecular testing using GeneXpert Edge, process redesign to facilitate same-day TB diagnosis and treatment, and performance feedback) or routine care (onsite sputum smear microscopy plus referral of sputum samples to Xpert testing sites). The primary outcome is the number of patients with microbiologically confirmed TB who were initiated on treatment within 14 days of presentation to the health center, which reflects successful completion of the TB diagnostic evaluation process. Secondary outcomes include health outcomes (6-month vital status), as well as measures of the reach, adoption, and implementation of the intervention strategy.

Discussion
The design elements and implementation approach for the XPEL-TB trial were intentionally selected to minimize disruptions to routine care procedures, with the goal of limiting their influence on key primary and secondary outcomes. Trial findings may result in increased support and funding for rapid, onsite molecular testing as the standard-of-care for all patients being evaluated for TB.

Trial registration
US National Institutes of Health’s ClinicalTrials.gov, NCT03044158. Registered 06 February 2017.
Pan African Clinical Trials Registry, PACTR201610001763265. Registered 03 September 2016.