bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in infant mortality and stillbirth rates in Scotland by socio-economic position, 2000–2018: a longitudinal ecological study
Authors: Harpur Alice , Minton Jon , Ramsay Julie , McCartney Gerry , Fenton Lynda , Campbell Harry , Wood Rachael 
Published: May 2021

Abstract
Background
As Scotland strives to become a country where children flourish in their early years, it is faced with the challenge of socio-economic health inequalities, which are at risk of widening amidst austerity policies. The aim of this study was to explore trends in infant mortality rates (IMR) and stillbirth rates by socio-economic position (SEP) in Scotland, between 2000 and 2018, inclusive.

Methods
Data for live births, infant deaths, and stillbirths between 2000 and 2018 were obtained from National Records of Scotland. Annual IMR and stillbirth rates were calculated and visualised for all of Scotland and when stratified by SEP. Negative binomial regression models were used to estimate the association between SEP and infant mortality and stillbirth events, and to assess for break points in trends over time. The slope (SII) and relative (RII) index of inequality compared absolute and relative socio-economic inequalities in IMR and stillbirth rates before and after 2010.

Results
IMR fell from 5.7 to 3.2 deaths per 1000 live births between 2000 and 2018, with no change in trend identified. Stillbirth rates were relatively static between 2000 and 2008 but experienced accelerated reduction from 2009 onwards. When stratified by SEP, inequalities in IMR and stillbirth rates persisted throughout the study and were greatest amongst the sub-group of post-neonates. Although comparison of the SII and RII in IMR and stillbirths before and after 2010 suggested that inequalities remained stable, descriptive trends in mortality rates displayed a 3-year rise in the most deprived quintiles from 2016 onwards.

Conclusion
Whilst Scotland has experienced downward trends in IMR and stillbirth rates between 2000 and 2018, the persistence of socio-economic inequalities and suggestion that mortality rates amongst the most deprived groups may be worsening warrants further action to improve maternal health and strengthen support for families with young children.
Frequency and reasons for delayed treatment initiation after HIV diagnosis: cross-sectional study in Lahore, Pakistan
Authors: Ali Hassan , Zakar Rubeena , Junaid Khunsa , Khan Amjad , Fischer Florian 
Published: May 2021

Abstract
Background
Well-timed initiation of HIV therapy enhances life expectancy, decreases mortality and morbidity, and inhibits the transmission of HIV and complications related to it. The purpose of the present survey is to investigate the frequency and reasons for delayed initiation of anti-retroviral therapy (ART) and to determine its relationship with various socio-demographic variables and HIV-related characteristics.

Methods
The analysis is based on a cross-sectional study involving 355 people living with HIV (diagnosed by PCR) who were more than 18 years of age and not receiving HIV therapy before enrolment at the HIV clinics of two selected tertiary-care teaching hospitals in Lahore, Pakistan. In this study, delayed initiation of ART was defined as not attending the HIV management centre or a clinic for ART within 3 months of a confirmed diagnosis. The participants were selected using a systematic probability sampling technique. Bivariate logistic regression was performed using a backward stepwise technique to establish the variables related to delayed onset of HIV therapy. Factors significant at p ≤ 0.20 were considered for multivariate analysis, which was used to describe the association between independent factors and delayed initiation of treatment.

Results
Delayed onset of ART was observed in 28.5% of individuals. Factors such as no schooling (AOR = 5.92; 95% CI: 1.38–25.41; p = 0.017) and occasional household income (AOR = 3.88; 95% CI: 1.01–14.89; p = 0.048) were significantly associated with late onset of ART. Our research findings also indicated that the main reasons for late beginning of HIV therapy were: feeling healthy (45.5%), did not have time to go to the HIV treatment centre (42.6%), did not want to discuss HIV test result (37.6%), and fear of stigma and discrimination within their community (35.6%).

Conclusions
Late commencement of HIV therapy in Pakistan is common, and an improved connection is needed between identification of HIV and beginning of therapy. HIV management centres should counsel and monitor patients from the time of a positive HIV test result until they initiate therapy.
A posterolateral sheared fracture of the tibial plateau: a case presentation
Authors: Feng Jinyi , Gu Yang , You Wuji , Rui Gang 
Published: May 2021

Abstract
Background
Among tibial plateau fractures, one specialized type is the posterolateral column fracture. There are few published studies on posterolateral tibial plateau fractures with a sheared fragment that was wedged into the intercondylar fossa without the anterior cruciate ligament (ACL) rupture. According to our research, this case presentation is the first to describe in detail the treatment and long-term follow-up for this uncommon subtype of posterolateral tibial plateau fracture.

Case presentation
A 46-year-old female injured her right knee when she was riding a motorbike and was diagnosed with a posterolateral sheared tibial plateau fracture with a wedge-shaped fragment inserted into the femoral intercondylar fossa. The fracture was repaired with open reduction internal fixation surgery. The patient’s recovery was followed for four years. The degree of healing as indicated by clinical and radiological examinations was substantial. The patient exhibited an excellent range of motion for the repaired knee (0-145°) and little discomfort. The Lysholm score was 96, the hospital for special surgery score was 98, the Rasmussen clinical assessment was 28, and the Rasmussen radiological assessment was 18.

Conclusion
This study revealed that a posterolateral sheared tibial plateau, as seen in this case, can be reset and fixed sufficiently to achieve excellent long-term postoperative recovery.
Readmission after rectal resection in the ERAS-era: is a loop ileostomy the Achilles heel?
Authors: Van Butsele Johanna , Bislenghi Gabriele , D’Hoore André , Wolthuis Albert M. 
Published: May 2021

Abstract
Background
Rectal resection surgery is often followed by a loop ileostomy creation. Despite improvements in surgical technique and development of enhanced recovery after surgery (ERAS) protocols, the readmission-rate after rectal resection is still estimated to be around 30%. The purpose of this study was to identify risk factors for readmission after rectal resection surgery. This study also investigated whether elderly patients (≥ 65 years old) dispose of a distinct patient profile and associated risk factors for readmission.

Methods
This is a retrospective study of prospectively collected data from patients who consecutively underwent rectal resection for cancer within an ERAS protocol between 2011 and 2016. The primary study endpoint was 90-day readmission. Patients with and without readmission within 90 days were compared. Additional subgroup analysis was performed in patients ≥ 65 years old.

Results
A total of 344 patients were included, and 25% (n = 85) were readmitted. Main reasons for readmission were acute renal insufficiency (24%), small bowel obstruction (20%), anastomotic leakage (15%) and high output stoma (11%). In multivariate logistic regression, elevated initial creatinine level (cut-off values: 0.67–1.17 mg/dl) (OR 1.95, p = 0.041) and neoadjuvant radiotherapy (OR 2.63, p = 0.031) were significantly associated with readmission. For ileostomy related problems, elevated initial creatinine level (OR 2.76, p = 0.021) was identified to be significant.

Conclusion
Recovery after rectal resection within an ERAS protocol is hampered by the presence of a loop ileostomy. ERAS protocols should include stoma education and high output stoma prevention.
hnRNPA2B1 regulates the alternative splicing of BIRC5 to promote gastric cancer progression
Authors: Peng Wei-zhao , Zhao Jin , Liu Xin , Li Chao-feng , Si Shuang , Ma Ren 
Published: May 2021

Abstract
Background
Systematic profiling studies have implicated regulators of pre-mRNA splicing as important disease determinants in gastric cancer (GC), but the underlying mechanisms have remained elusive. Here we focused on hnRNPA2B1 splicing factor-dependent mechanisms governing GC development.

Methods
The expression of hnRNPA2B1 was analyzed among the Cancer Genome Atlas (TCGA) datasets of GC and validated at mRNA level. The function of hnRNPA2B1 in GC cells was analyzed and its downstream gene was identified using RNA immunoprecipitation. Further, effect of hnRNPA2B1 on BIRC5 alternative splicing was investigated.

Results
We show that overexpression of hnRNPA2B1 in GC is correlated with poor survival, and hnRNPA2B1 is required for maintaining GC malignant phenotype by promoting cell proliferation, inhibiting cell apoptosis and increasing cell metastasis. Mechanistically, hnRNPA2B1 co-expressed with several core spliceosome components and controls alternative splicing of anti-apoptotic factor BIRC5. BIRC5 isoform 202 (BIRC5-202) played the oncogenic function in GC cells, and overexpression of the BIRC5-202 transcript partly rescued the decrease in cisplatin resistance induced by downregulation of hnRNPA2B1.

Conclusions
We demonstrate that hnRNPA2B1 regulates BIRC5 splicing and might act as a therapeutic target of chemo-resistant GC cells.
Comparison of outcome between blood culture positive and negative infective endocarditis patients undergoing cardiac surgery
Authors: Meidrops Kristians , Zuravlova Arina , Osipovs Janis Davis , Kalejs Martins , Groma Valerija , Petrosina Eva , Reinis Aigars , Strike Eva , Dumpis Uga , Erglis Andrejs , Stradins Peteris 
Published: May 2021

Abstract
Background
Up to 30% or even more of all infective endocarditis (IE) cases are recognized as blood culture negative, meaning that the causative agent is left unidentified. The prompt diagnosis together with the identification of causative microorganism and targeted antibiotic treatment can significantly impact the prognosis of the disease and further patient’s health status. In some studies, blood culture negative endocarditis has been shown to be associated with delayed diagnosis, worse outcome and course of the disease, and a greater number of intra and postoperative complications.

Methods
We retrospectively analysed the medical records of all patients who underwent cardiac surgery for endocarditis between years 2016 and 2019. The aim of this study was to analyse short and long-term mortality and differences of laboratory, clinical and echocardiography parameters in patients with blood culture positive endocarditis (BCPE) and blood culture negative endocarditis (BCNE) and its possible impact on the clinical outcome.

Results
In our study population were 114 (55.1%) blood culture positive and 93 (44.9%) blood culture negative cases of infectious endocarditis. The most common pathogens in the blood culture positive IE group were S.aureus in 36 cases (31.6%), Streptococcus spp. in 27 (23.7%), E.faecalis in 24 (21.1%), and other microorganisms in 27 (23.7%). Embolic events were seen in 60 patients (28.9%). In univariate analyses, detection of microorganism, elevated levels of procalcitonin were found to be significantly associated with intrahospital death, however it did not reach statistical significance in multivariate analyses. Among microorganisms, S.aureus was significantly associated with intrahospital death in both univariate and multivariate analyses.

Conclusions
There are no statistically significant differences between groups of BCPE and BCNE in terms of intrahospital mortality, hospital and ICU stay or 3-year mortality.
There were higher levels of procalcitonin in BCPE group, however procalcitonin failed to show independent association with mortality in multivariate analysis.
The most common microorganism in the BCPE group was S.aureus. It was associated with independently higher intrahospital mortality when compared to other causative microorganisms.
FFAR4: A New Player in Cardiometabolic Disease?
Authors: Stuttgen Gage M , Sahoo Daisy 
Published: May 2021

Abstract
Free fatty acids (FFAs) are implicated in the pathogenesis of metabolic diseases that includes obesity, type 2 diabetes mellitus, and cardiovascular disease (CVD). FFAs serve as ligands for free fatty acid receptors (FFARs) that belong to the family of rhodopsin-like G protein–coupled receptors (GPCRs) and are expressed throughout the body to maintain energy homeostasis under changing nutritional conditions. Free fatty acid receptor 4 (FFAR4), also known as G protein–coupled receptor 120, is a long-chain fatty acid receptor highly expressed in adipocytes, endothelial cells, and macrophages. Activation of FFAR4 helps maintain metabolic homeostasis by regulating adipogenesis, insulin sensitivity, and inflammation. Furthermore, dysfunction of FFAR4 is associated with insulin resistance, obesity, and eccentric remodeling in both humans and mice, making FFAR4 an attractive therapeutic target for treating or preventing metabolic diseases. While much of the previous literature on FFAR4 has focused on its role in obesity and diabetes, recent studies have demonstrated that FFAR4 may also play an important role in the development of atherosclerosis and CVD. Most notably, FFAR4 activation reduces monocyte–endothelial cell interaction, enhances cholesterol efflux from macrophages, reduces lesion size in atherogenic mouse models, and stimulates oxylipin production in myocytes that functions in a feed-forward cardioprotective mechanism. This review will focus on the role of FFAR4 in metabolic diseases and highlights an underappreciated role of FFAR4 in the development of atherosclerosis and CVD.
Lipid metabolism in focus: how the build-up and breakdown of lipids affects stem cells
Authors: Madsen Sofia , Ramosaj Mergim , Knobloch Marlen 
Published: May 2021

ABSTRACTCellular metabolism has recently emerged as a key regulator of stem cell behavior. Various studies have suggested that metabolic regulatory mechanisms are conserved in different stem cell niches, suggesting a common level of stem cell regulation across tissues. Although the balance between glycolysis and oxidative phosphorylation has been shown to be distinct in stem cells and their differentiated progeny, much less is known about lipid metabolism in stem cell regulation. In this Review, we focus on how stem cells are affected by two major lipid metabolic pathways: the build-up of lipids, called de novo lipogenesis, and the breakdown of lipids, called fatty acid beta-oxidation. We cover the recent literature on hematopoietic stem cells, intestinal stem cells, neural stem/progenitor cells and cancer stem cells, where these two lipid pathways have been studied in more depth.
Predictors of macular pigment and contrast threshold in Spanish healthy normolipemic subjects (45–65 years) with habitual food intake
Authors: Olmedilla-Alonso Begoña , Rodríguez-Rodríguez Elena , Beltrán-de-Miguel Beatriz , Estévez-Santiago Rocío , Sánchez-Prieto Milagros 
Published: May 2021

Introduction
The dietary carotenoids lutein (L) and zeaxanthin (Z) are transported in the bloodstream by lipoproteins, sequestered by adipose tissue, and eventually captured in the retina where they constitute macular pigment. There are no L&Z dietary intake recommendations nor desired blood/tissue concentrations for the Spanish general population. Our aim was to assess the correlation of L&Z habitual dietary intake (excluding food supplements), resulting serum concentrations and lipid profile with macular pigment optical density (MPOD) as well as the contrast sensitivity (CT), as visual outcome in normolipemic subjects (n = 101) aged 45–65.

Methods
MPOD was measured by heterochromatic flicker photometry, serum L&Z by HPLC, the dietary intake by a 3-day food records and CT using the CGT-1000-Contrast-Glaretester at six stimulus sizes, with and without glare.

Results
Lutein and zeaxanthin concentrations (median) in serum: 0.361 and 0.078 μmol/L, in dietary intake: 1.1 mg L+Z/day. MPOD: 0.34du. L+Z intake correlates with their serum concentrations (rho = 0.333, p = 0.001), which in turn correlates with MPOD (rho = 0.229, p = 0.000) and with fruit and vegetable consumption (rho = 0.202, p = 0.001), but not with lutein+zeaxanthin dietary intake. MPOD correlated with CT, with and without glare (rho ranges: -0.135, 0.160 and -0.121, –0.205, respectively). MPOD predictors: serum L+Z, L+Z/HDL-cholesterol (β-coeficient: -0.91±0.2, 95%CI: -1.3,-0.5) and HDL-cholesterol (R2 = 15.9%). CT predictors: MPOD, mainly at medium and smaller visual angles (corresponding to spatial frequencies for which sensitivity declines with age) and gender (β-coefficients ranges: -0.95,-0.39 and -0.13,-0.39, respectively).

Conclusion
A higher MPOD is associated with a lower ratio of L+Z/HDL-cholesterol and with a lower CT (higher contrast sensitivity). The HDL-cholesterol would also act indirectly on the CT improving the visual function.
Neutrophil-to-lymphocyte ratio associated with an increased risk of mortality in patients with critical limb ischemia
Authors: Su Min-I. , Liu Cheng-Wei 
Published: May 2021

Purpose
Association of the neutrophil-to-lymphocyte ratio (NLR) with mortality has not been comprehensively explored in critical limb ischemia (CLI) patients. We investigated the association between the NLR and clinical outcomes in CLI.

Materials and methods
We retrospectively enrolled consecutive CLI patients between 1/1/2013 and 12/31/2018. Receiver operating characteristic curve analysis determined NLR cutoffs for 1-year in-hospital, all-cause and cardiac-related mortality; major adverse cardiovascular events (MACEs); and major adverse limb events (MALEs).

Results
Among 195 patients (age, 74.0 years, SD: 11.5; 51.8% male; body mass index, 23.4 kg/m2, SD: 4.2), 14.4% exhibited acute limb ischemia. After 1 year, patients with NLR>8 had higher in-hospital mortality (21.1% vs. 3.6%, P<0.001), all-cause mortality (54.4% vs. 13.8%, P<0.001), cardiac-related mortality (28.1% vs. 6.5%, P<0.001), MACE (29.8% vs. 13.0%, P = 0.008), and MALE (28.1% vs. 13.0%, P = 0.021) rates than those with NLR<8. In multivariate logistic regression, NLR≥8 was significantly associated with all-cause (P<0.001) and cardiac-related (adjusted HR: 5.286, 95% CI: 2.075–13.47, P<0.001) mortality, and NLR≥6 was significantly associated with MALEs (adjusted HR: 2.804, 95% CI: 1.292–6.088, P = 0.009). Each increase in the NLR was associated with increases in all-cause (adjusted HR: 1.028, 95% CI: 1.008–1.049, P = 0.007) and cardiac-related (adjusted HR:1.027, 95% CI: 0.998–1.057, P = 0.073) mortality but not in-hospital mortality or MACEs.

Conclusion
CLI patients with high NLRs had significantly higher risks of 1-year all-cause and cardiac-related mortality and MALEs. The NLR can be used for prognostic prediction in these patients.
Time in blood glucose range 70 to 180 mg/dL and survival rate in critically ill patients: A retrospective cohort study
Authors: Naraba Hiromu , Goto Tadahiro , Shirakawa Toru , Sonoo Tomohiro , Kanda Naoki , Nakano Hidehiko , Takahashi Yuji , Hashimoto Hideki , Nakamura Kensuke 
Published: May 2021

BackgroundWhile time in targeted blood glucose range (TIR) 70–140 mg/dL is a known factor associated with mortality in critically ill patients, it remains unclear whether TIR is associated with 28-day mortality under the glycemic control with a less tight target glucose range of 70–180 mg/dL. We aimed to examine whether TIR 70–180 mg/dL was associated with 28-day mortality.MethodsThis is a retrospective cohort study using data from a tertiary care center in Japan collected from January 2016 through October 2019. We included adult patients (aged ≥20 years) admitted to the ICU. We excluded patients 1) with diabetic ketoacidosis patients, 2) discharged within 48 hours, 3) with repeated ICU admissions. We calculated TIR 70–180 mg/dL using the measured blood glucose values (≥3 times per day). The primary outcome was 28-day mortality. We examined the association between TIR and 28-day mortality using a logistic regression and Cox proportional hazard models with a stratification by glycosylated hemoglobin (HbA1c) level of 6.5%. Additionally, we repeated the analyses using the TIR category to assess the optimal TIR. For the sensitivity analysis, we repeated the primary analysis using TIR during the first three days from ICU admission.ResultsOf 1,230 patients, the median age was 72 years, 65% were male, and 250 patients (20%) had HbA1c ≥6.5% on admission. In patients with HbA1c <6.5%, TIR <80% was associated with an increased risk of 28-day mortality, with an adjusted odds ratio (OR) of 1.88 (95%CI: 1.36–2.61). Likewise, when using 10% incremental TIR as a categorical variable, lower TIR was associated with a worse 28-day mortality compared with TIR ≥90% (e.g., adjusted OR of TIR <60%, 3.62 [95%CI 2.36–5.53]). Similar associations were found in the analyses using Cox proportional hazards model and using TIR during the first three days. By contrast, in patients with HbA1c ≥6.5%, there was no consistent association of TIR with 28-day mortality.ConclusionsWe found that lower TIR 70–180 mg/dL was associated with a higher 28-day mortality in critically ill patients with HbA1c <6.5%, whereas there was no consistent association in patients with HbA1c ≥6.5%.
Global antibiotic dosing strategies in hospitalised children: Characterising variation and implications for harmonisation of international guidelines
Authors: Clements Michelle N. , Russell Neal , Bielicki Julia A. , Ellis Sally , Gastine Silke , Hsia Yingfen , Standing Joseph F. , Walker A. Sarah , Sharland Mike 
Published: May 2021

BackgroundPaediatric global antibiotic guidelines are inconsistent, most likely due to the limited pharmacokinetic and efficacy data in this population. We investigated factors underlying variation in antibiotic dosing using data from five global point prevalence surveys.Methods & findingsData from 3,367 doses of the 16 most frequent intravenous antibiotics administered to children 1 month–12 years across 23 countries were analysed. For each antibiotic, we identified standard doses given as either weight-based doses (in mg/kg/day) or fixed daily doses (in mg/day), and investigated the pattern of dosing using each strategy. Factors underlying observed variation in weight-based doses were investigated using linear mixed effects models. Weight-based dosing (in mg/kg/day) clustered around a small number of peaks, and all antibiotics had 1–3 standard weight-based doses used in 5%-48% of doses. Dosing strategy was more often weight-based than fixed daily dosing for all antibiotics apart from teicoplanin, which had approximately equal proportions of dosing attributable to each strategy. No strong consistent patterns emerged to explain the historical variation in actual weight-based doses used apart from higher dosing seen in central nervous system infections, and lower in skin and soft tissue infections compared to lower respiratory tract infections. Higher dosing was noted in the Americas compared to the European region.ConclusionsAntibiotic dosing in children clusters around a small number of doses, although variation remains. There is a clear opportunity for the clinical, scientific and public health communities to consolidate behind a consistent set of global antibiotic dosing guidelines to harmonise current practice and prioritise future research.