bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ability of dietary factors to affect homocysteine levels in mice: a review
Authors: Brütting Christine , Hildebrand Pia , Brandsch Corinna , Stangl Gabriele I. 
Published: June 2021

AbstractHomocysteine is associated with several diseases, and a series of dietary factors are known to modulate homocysteine levels. As mice are often used as model organisms to study the effects of dietary hyperhomocysteinemia, we collected data about concentrations of vitamin B12, vitamin B6, folate, methionine, cystine, and choline in mouse diets and the associated plasma/serum homocysteine levels. In addition, we more closely examined the composition of the control diet, the impact of the mouse strain, sex and age, and the duration of the dietary intervention on homocysteine levels. In total, 113 out of 1103 reviewed articles met the inclusion criteria. In the experimental and control diets, homocysteine levels varied from 0.1 to 280 µmol/l. We found negative correlations between dietary vitamin B12 (rho = − 0.125; p < 0.05), vitamin B6 (rho = − 0.191; p < 0.01) and folate (rho = − 0.395; p < 0.001) and circulating levels of homocysteine. In contrast, a positive correlation was observed between dietary methionine and homocysteine (methionine: rho = 0.146; p < 0.05). No significant correlations were found for cystine or choline and homocysteine levels. In addition, there was no correlation between the duration of the experimental diets and homocysteine levels. More importantly, the data showed that homocysteine levels varied widely in mice fed control diets as well. When comparing control diets with similar nutrient concentrations (AIN-based), there were significant differences in homocysteine levels caused by the strain (ANOVA, p < 0.05) and age of the mice at baseline (r = 0.47; p < 0.05). When comparing homocysteine levels and sex, female mice tended to have higher homocysteine levels than male mice (9.3 ± 5.9 µmol/l vs. 5.8 ± 4.5 µmol/l; p = 0.069). To conclude, diets low in vitamin B12, vitamin B6, or folate and rich in methionine are similarly effective in increasing homocysteine levels. AIN recommendations for control diets are adequate with respect to the amounts of homocysteine-modulating dietary parameters. In addition, the mouse strain and the age of mice can affect the homocysteine level.
Impact of mining projects on water and sanitation infrastructures and associated child health outcomes: a multi-country analysis of Demographic and Health Surveys (DHS) in sub-Saharan Africa
Authors: Dietler Dominik , Farnham Andrea , Loss Georg , Fink Günther , Winkler Mirko S. 
Published: June 2021

Abstract
Background
Access to improved water and sanitation infrastructures are key determinants of health. The sub-Saharan African region in particular is lagging behind the ambitious goal of the 2030 Agenda for Sustainable Development to ensure universal access to improved and reliable water and sanitation for all (Sustainable Development Goal (SDG) 6). Large mining projects can promote economic growth and hence investments in water and sanitation infrastructures, but at the same time lead to rapid population growth and environmental degradation. In turn, these changes can pose risks and opportunities for child health (SDG 3). In this study we aim to quantify the impacts of mining projects on access to water and sanitation infrastructure as well as diarrhea and malnutrition among children using data from 131 Demographic and Health Surveys from sub-Saharan Africa.

Results
From a sample of around 1.2 million households, data within the proximity of 52 mine-panels were selected for longitudinal analyses, resulting in 41,896 households and 32,112 children. Improvements in access to modern water and sanitation infrastructures after mine opening were much larger in households near mining sites than in comparison areas located further away (adjusted relative risk ratio (aRRR) water: 18.60, 95 % confidence interval (CI): 13.08–26.46 and aRRR sanitation: 2.56, 95 % CI: 1.32–4.99). However, these associations were weaker among poorer households. In areas close to the mining sites, stunting and underweight prevalence decreased more strongly upon mine opening (adjusted odds ratio (aOR) stunting: 0.62, 95 % CI: 0.43–0.90; aOR underweight: 0.55, 95 % CI: 0.36–0.84). No differential changes were seen for wasting and diarrhea. Large impact heterogeneity was observed both within and across countries.

Conclusions
Our results suggest that the opening of mines is associated with improvements in access to modern water and sanitation infrastructures (SDG 6) as well as in some health outcomes (SDG 3). However, the large impact heterogeneity suggests that the assessment and management of mining-related impacts on communities should have an increased equity-focus, in order to “leave no one behind” in the work towards the 2030 Agenda for Sustainable Development. Overall, the findings of this study underscore that the resource extraction sector has the potential to make positive and substantial contributions towards achieving the SDGs.
A systematic review of moral reasons on orphan drug reimbursement
Authors: Zimmermann Bettina M. , Eichinger Johanna , Baumgartner Matthias R. 
Published: June 2021

AbstractBackgroundThe number of market approvals of orphan medicinal products (OMPs) has been increasing steadily in the last 3 decades. While OMPs can offer a unique chance for patients suffering from rare diseases, they are usually very expensive. The growing number of approved OMPs increases their budget impact despite their low prevalence, making it pressing to find solutions to ethical challenges on how to fairly allocate scarce healthcare resources under this context. One potential solution could be to grant OMPs special status when considering them for reimbursement, meaning that they are subject to different, and less stringent criteria than other drugs. This study aims to provide a systematic analysis of moral reasons for and against such a special status for the reimbursement of OMPs in publicly funded healthcare systems from a multidisciplinary perspective.ResultsWith a systematic review of reasons, we identified 39 reasons represented in 243 articles (scientific and grey literature) for and against special status for the reimbursement of OMPs, then categorized them into nine topics. Taking a multidisciplinary perspective, we found that most articles came from health policy (n = 103) and health economics (n = 49). More articles took the position for a special status of OMPs (n = 97) than those against it (n = 31) and there was a larger number of reasons identified in favour (29 reasons) than against (10 reasons) this special status.ConclusionResults suggest that OMP reimbursement issues should be assessed and analysed from a multidisciplinary perspective. Despite the higher occurrence of reasons and articles in favour of a special status, there is no clear-cut solution for this ethical challenge. The binary perspective of whether or not OMPs should be granted special status oversimplifies the issue: both OMPs and rare diseases are too heterogeneous in their characteristics for such a binary perspective. Thus, the scientific debate should focus less on the question of disease prevalence but rather on how the important variability of different OMPs concerning e.g. target population, cost-effectiveness, level of evidence or mechanism of action could be meaningfully addressed and implemented in Health Technology Assessments.
Oral ulcers in children- a clinical narrative overview
Authors: Légeret Corinne , Furlano Raoul 
Published: June 2021

AbstractThe prevalence of oral ulcers in children is reported to be 9%, however diagnosis of oral lesions can be challenging, being an unspecific symptom of several diseases. Differential diagnosis can range from classic infectious disease of childhood (e.g. herpangina, hand-foot-and-mouth-disease) over nutritional deficiencies, gastrointestinal disorders, inflammations (e.g. pemphigus vulgaris, lichen planus, mucous membrane pemphigoid) to side effects of medications (Stevens-Johnson Syndrome) or chronic dieseases (e.g. sarcoidosis, systemic Lupus erythematodes, familial Mediterrenean fever). Therefore, children with oral ulcers are treated by many different specialists such as dentists, family doctors, paediatricians, rheumatologists, haematologists, gastroenterologists and otorhinolaryngologists.A systematic literature search and a narrative literature review about the potential 48 diseases connected to oral ulcers were performed. According to the duration of symptoms and size of the lesions, a tabular overview was created to support the clinician in making a correct diagnosis, additionally different treatment options are presented.
Monocyte distribution width (MDW) performance as an early sepsis indicator in the emergency department: comparison with CRP and procalcitonin in a multicenter international European prospective study
Authors: Hausfater Pierre , Robert Boter Neus , Morales Indiano Cristian , Cancella de Abreu Marta , Marin Adria Mendoza , Pernet Julie , Quesada Dolores , Castro Iris , Careaga Diana , Arock Michel , Tejidor Liliana , Velly Laetitia 
Published: June 2021

Abstract
Background
Early sepsis diagnosis has emerged as one of the main challenges in the emergency room. Measurement of sepsis biomarkers is largely used in current practice to improve the diagnosis accuracy. Monocyte distribution width (MDW) is a recent new sepsis biomarker, available as part of the complete blood count with differential. The objective was to evaluate the performance of MDW for the detection of sepsis in the emergency department (ED) and to compare to procalcitonin (PCT) and C-reactive protein (CRP).

Methods
Subjects whose initial evaluation included a complete blood count were enrolled consecutively in 2 EDs in France and Spain and categorized per Sepsis-2 and Sepsis-3 criteria. The performance of MDW for sepsis detection was compared to that of procalcitonin (PCT) and C-reactive protein (CRP).

Results
A total of 1,517 patients were analyzed: 837 men and 680 women, mean age 61 ± 19 years, 260 (17.1%) categorized as Sepsis-2 and 144 patients (9.5%) as Sepsis-3. The AUCs [95% confidence interval] for the diagnosis of Sepsis-2 were 0.81 [0.78–0.84] and 0.86 [0.84–0.88] for MDW and MDW combined with WBC, respectively. For Sepsis-3, MDW performance was 0.82 [0.79–0.85]. The performance of MDW combined with WBC for Sepsis-2 in a subgroup of patients with low sepsis pretest probability was 0.90 [0.84–0.95]. The AUC for sepsis detection using MDW combined with WBC was similar to CRP alone (0.85 [0.83–0.87]) and exceeded that of PCT. Combining the biomarkers did not improve the AUC. Compared to normal MDW, abnormal MDW increased the odds of Sepsis-2 by factor of 5.5 [4.2–7.1, 95% CI] and Sepsis-3 by 7.6 [5.1–11.3, 95% CI].

Conclusions
MDW in combination with WBC has the diagnostic accuracy to detect sepsis, particularly when assessed in patients with lower pretest sepsis probability. We suggest the use of MDW as a systematic screening test, used together with qSOFA score to improve the accuracy of sepsis diagnosis in the emergency department.
Trial Registration ClinicalTrials.gov (NCT03588325).
Evaluation of thiamine as adjunctive therapy in COVID-19 critically ill patients: a two-center propensity score matched study
Authors: Al Sulaiman Khalid , Aljuhani Ohoud , Al Dossari Maram , Alshahrani Asma , Alharbi Aisha , Algarni Rahmah , Al Jeraisy Majed , Al Harbi Shmeylan , Al Katheri Abdulmalik , Al Eidan Fahad , Al Bekairy Abdulkareem M. , Al Qahtani Nouf , Al Muqrin Mashael , Vishwakarma Ramesh , Al Ghamdi Ghassan 
Published: June 2021

Abstract
Background
Thiamine is a precursor of the essential coenzyme thiamine pyrophosphate required for glucose metabolism; it improves the immune system function and has shown to reduce the risk of several diseases. The role of thiamine in critically ill septic patient has been addressed in multiple studies; however, it’s role in COVID-19 patients is still unclear. The aim of this study was to evaluate the use of thiamine as an adjunctive therapy on mortality in COVID-19 critically ill patients.

Methods
This is a two-center, non-interventional, retrospective cohort study for critically ill patients admitted to intensive care units (ICUs) with a confirmed diagnosis of COVID19. All patients aged 18 years or older admitted to ICUs between March 1, 2020, and December 31, 2020, with positive PCR COVID-19 were eligible for inclusion. We investigated thiamine use as an adjunctive therapy on the clinical outcomes in critically ill COVID-19 patients after propensity score matching.

Results
A total of 738 critically ill patients with COVID-19 who had been admitted to ICUs were included in the study. Among 166 patients matched using the propensity score method, 83 had received thiamine as adjunctive therapy. There was significant association between thiamine use with in-hospital mortality (OR = 0.39; 95% CI 0.19–0.78; P value = 0.008) as well as the 30-day mortality (OR = 0.37; 95% CI 0.18–0.78; P value = 0.009). Moreover, patients who received thiamine as an adjunctive therapy were less likely to have thrombosis during ICU stay [OR (95% CI) 0.19 (0.04–0.88), P value = 0.03].

Conclusion
Thiamine use as adjunctive therapy may have potential survival benefits in critically ill patients with COVID-19. Additionally, it was associated with a lower incidence of thrombosis. Further interventional studies are required to confirm these findings.
Increased time from physiological derangement to critical care admission associates with mortality
Authors: Whebell Stephen F. , Prower Emma J. , Zhang Joe , Pontin Megan , Grant David , Jones Andrew T. , Glover Guy W. 
Published: June 2021

Abstract
Background
Rapid response systems aim to achieve a timely response to the deteriorating patient; however, the existing literature varies on whether timing of escalation directly affects patient outcomes. Prior studies have been limited to using ‘decision to admit’ to critical care, or arrival in the emergency department as ‘time zero’, rather than the onset of physiological deterioration. The aim of this study is to establish if duration of abnormal physiology prior to critical care admission [‘Score to Door’ (STD) time] impacts on patient outcomes.

Methods
A retrospective cross-sectional analysis of data from pooled electronic medical records from a multi-site academic hospital was performed. All unplanned adult admissions to critical care from the ward with persistent physiological derangement [defined as sustained high National Early Warning Score (NEWS) > / = 7 that did not decrease below 5] were eligible for inclusion. The primary outcome was critical care mortality. Secondary outcomes were length of critical care admission and hospital mortality. The impact of STD time was adjusted for patient factors (demographics, sickness severity, frailty, and co-morbidity) and logistic factors (timing of high NEWS, and out of hours status) utilising logistic and linear regression models.

Results
Six hundred and thirty-two patients were included over the 4-year study period, 16.3% died in critical care. STD time demonstrated a small but significant association with critical care mortality [adjusted odds ratio of 1.02 (95% CI 1.0–1.04, p = 0.01)]. It was also associated with hospital mortality (adjusted OR 1.02, 95% CI 1.0–1.04, p = 0.026), and critical care length of stay. Each hour from onset of physiological derangement increased critical care length of stay by 1.2%. STD time was influenced by the initial NEWS, but not by logistic factors such as out-of-hours status, or pre-existing patient factors such as co-morbidity or frailty.

Conclusion
In a strictly defined population of high NEWS patients, the time from onset of sustained physiological derangement to critical care admission was associated with increased critical care and hospital mortality. If corroborated in further studies, this cohort definition could be utilised alongside the ‘Score to Door’ concept as a clinical indicator within rapid response systems.
Altered hypothalamic DNA methylation and stress-induced hyperactivity following early life stress
Authors: Fitzgerald Eamon , Sinton Matthew C. , Wernig-Zorc Sara , Morton Nicholas M. , Holmes Megan C. , Boardman James P. , Drake Amanda J. 
Published: June 2021

AbstractExposure to early life stress (ELS) during childhood or prenatally increases the risk of future psychiatric disorders. The effect of stress exposure during the neonatal period is less well understood. In preterm infants, exposure to invasive procedures is associated with altered brain development and future stress responses suggesting that the neonatal period could be a key time for the programming of mental health. Previous studies suggest that ELS affects the hypothalamic epigenome, making it a good candidate to mediate these effects. In this study, we used a mouse model of early life stress (modified maternal separation; MMS). We hypothesised MMS would affect the hypothalamic transcriptome and DNA methylome, and impact on adult behaviour. MMS involved repeated stimulation of pups for 1.5 h/day, whilst separated from their mother, from postnatal day (P) 4–6. 3’mRNA sequencing and DNA methylation immunoprecipitation (meDIP) sequencing were performed on hypothalamic tissue at P6. Behaviour was assessed with the elevated plus, open field mazes and in-cage monitoring at 3–4 months of age. MMS was only associated with subtle changes in gene expression, but there were widespread alterations in DNA methylation. Notably, differentially methylated regions were enriched for synapse-associated loci. MMS resulted in hyperactivity in the elevated plus and open field mazes, but in-cage monitoring revealed that this was not representative of habitual hyperactivity. ELS has marked effects on DNA methylation in the hypothalamus in early life and results in stress-specific hyperactivity in young adulthood. These results have implications for the understanding of ELS-mediated effects on brain development.
Healthcare workers’ behaviors on infection prevention and control and their determinants during the COVID-19 pandemic: a cross-sectional study based on the theoretical domains framework in Wuhan, China
Authors: Yang Qiuxia , Wang Xuemei , Zhou Qian , Tan Li , Zhang Xinping , Lai Xiaoquan 
Published: June 2021

Abstract
Background
Infection prevention and control (IPC) measures are crucial to combat the COVID-19 pandemic. This study aimed to explore the levels and determinants of HCWs’ IPC behaviors based on the theoretical domains framework (TDF), which has been shown to be effective in guiding behavior change.

Methods
A cross-sectional survey was conducted in Wuhan, China in January 2020. Self-reported hand hygiene and droplet isolation behaviors (including the use of masks, gloves, goggles and gowns) were set as dependent variables. TDF domains and HCWs’ characteristics were independent variables. Negative binomial regression analyses were performed to explore their relationships.

Results
HCWs reported good IPC behaviors, while the compliance with goggle and gown use was relatively low (below 85%). Environmental context and resources domain was significantly related to hand hygiene (β = 0.018, p = 0.026), overall droplet isolation behaviors (β = 0.056, p = 0.001), goggle (β = 0.098, p = 0.001) and gown use (β = 0.101. p < 0.001). Knowledge domain was significantly related to goggle (β = 0.081, p = 0.005) and gown use (β = 0.053, p = 0.013). Emotion domain was a predictor of overall droplet isolation behaviors (β = 0.043, p = 0.016), goggle (β = 0.074, p = 0.026) and gown use (β = 0.106, p < 0.001). Social influences domain was a predictor of overall droplet isolation behaviors (β = 0.031, p = 0.029) and gown use (β = 0.039, p = 0.035). HCWs in high-risk departments had better behaviors of gown use (β = 0.158, p = 0.032). HCWs who had encountered confirmed or suspected patients reported worse behaviors of goggle (β = − 0.127, p = 0.050) and gown use (β = − 0.153, p = 0.003).

Conclusions
Adequate personal protective materials and human resources, education and training, as well as supervision and role model setting are necessary to improve IPC behaviors regarding the COVID-19 pandemic.
Assessing the impact of corporate entrepreneurship in the financial performance of subsidiaries of Colombian business groups: under environmental dynamism moderation
Authors: Rodríguez-Peña Antonio 
Published: June 2021

AbstractCorporate entrepreneurship creates opportunities in employment, technological advances, value creation, and cultural transformation for entrepreneurial ecosystems, entrepreneurs, governments, economies, and society around the globe. The purpose of this study is to assess the impact of corporate entrepreneurship on the financial performance of subsidiaries in Colombian business groups under the moderating effect of the environmental dynamism, because the relationship between corporate entrepreneurship and financial performance in emerging economies must differ from developed economies. Using a cross-sectional structural equation modeling analysis, this study assessed the impact of entrepreneurial orientation and corporate venturing on the firm financial performance of 87 subsidiaries of Colombian business groups at different levels of environmental dynamism. This study also confirms that the relationship between corporate entrepreneurship and performance is context-dependent and that entrepreneurial orientation has a strong and positive causal relationship with corporate venturing. Additionally, subsidiaries of Colombian business groups increase their financial performance when also does the entrepreneurial orientation, and decrease financial performance when so does corporate venturing. Furthermore, the results show that environmental dynamism does not have a moderating effect on the relationship between corporate entrepreneurship of subsidiaries in Colombian business groups and their performance. This paper would contribute to important areas in Latin America business, where such studies are scarce.
Crime and COVID-19: effect of changes in routine activities in Mexico City
Authors: Estévez-Soto Patricio R. 
Published: June 2021

Abstract
Background
This study aimed to determine whether crime patterns in Mexico City changed due to the COVID-19 pandemic, and to test whether any changes observed were associated with the disruption of routine activities, as measured by changes in public transport passenger numbers.

Method
The first objective was assessed by comparing the observed incidence of crime after the COVID-19 pandemic was detected in the country with that expected based on ARIMA forecasts based on the pre-pandemic trends. The second objective was assessed by examining the association between crime incidence and the number of passengers on public transport using regressions with ARIMA errors.

Results
Results indicated that most crime categories decreased significantly after the pandemic was detected in the country or after a national lockdown was instituted. Furthermore, the study found that some of the declines observed were associated with the reductions seen in public transport passenger numbers. However, the findings suggested that the changes in mobility explain part of the declines observed, with important variations per crime type.

Conclusion
The findings contribute to the global evaluation of the effects of COVID-19 on crime and propose a robust method to explicitly test whether the changes observed are associated with changes in routine activities.