bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impaired Hepcidin Metabolism Promotes Hemolysis Induced Hepatobiliary Injury in Sickle Cell Disease
Authors: Vats Ravi , Novelli Enrico M , Sundd Prithu , Gladwin Mark T , Pradhan Tirthadipa 
Published: November 2020

Sickle cell disease (SCD) is an autosomal-recessive-genetic disorder that affects millions of people worldwide. Although hepatic crisis affects 10-40% of hospitalized SCD patients and can progress to fatal liver failure, the current treatment is primarily supportive and the molecular pathophysiology remains largely unknown. We found that transgenic, humanized SCD mice developed liver injury with age, manifested by increased inflammation, necrosis and hepatic iron accumulation. The presence of iron particles in SCD liver was confirmed by transmission electron micrograph (TEM) analysis and prussian blue staining which revealed increased iron accumulation in the central and midzonal region of the SCD liver tissue. An increase in aggregates of iron pigment reminiscent of hemosiderin-laden macrophages was also observed in SCD liver tissue. Interestingly, the SCD mice also showed significant enrichment of both hepatic (p=0.02) and serum iron (p=0.04) compared to control AS mice. We determined the expression level of genes commonly involved in iron homeostasis by RT-PCR. Interestingly, a significantly lower expression level of hepcidin transcripts was observed in the hepatocytes of SCD mice compared to control mice (AS) (p=0.01).
In order to define the pathways controllinghepcidintranscription in SCD, we performed an RNA-seq analysis in the liver of SCD mice. Remarkably, our data showed significant misexpression of BMP signaling pathways. Further analysis revealed a significant misexpression in BMP2 and 6 levels in the liver of SCD mice by western blot. Reduced levels of hepcidin were also confirmed in serum samples from SCD patients compared to controls. Work is currently underway to understand how BMP2/6 might hypothetically regulate hepcidin expression in the liver. In summary, our results reveal a significant defect in iron homeostasis in the liver of SCD mice, suggesting that impaired iron homeostasis may contribute to hepatobiliary injury in SCD independent of blood transfusions. Our study also highlights the importance of hepcidin as potential therapeutic target in regulation of hepatic injury in SCD.

Disclosures
No relevant conflicts of interest to declare.
CD4+ T-cell reconstitution predicts survival outcomes after acute graft-versus-host-disease: a dual-center validation
Authors: de Koning Coco , Prockop Susan , van Roessel Ichelle , Kernan Nancy , Klein Elizabeth , Langenhorst Jurgen , Szanto Celina , Belderbos Mirjam , Bierings Marc , Boulad Farid , Bresters Dorine , Cancio Maria , Curran Kevin , Kollen Wouter , O’Reilly Richard , Scaradavou Andromachi , Spitzer Barbara , Versluijs Birgitta , Huitema Alwin , Lindemans Caroline , Nierkens Stefan , Boelens Jaap Jan 
Published: November 2020

Abstract
Acute graft-versus-host-Disease (aGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). We previously showed that early CD4+ T-cell immune reconstitution (IR; CD4+ IR) predicts survival after HCT. Here, we studied the relation between CD4+ IR and survival in patients developing aGVHD. Pediatric patients undergoing first allogeneic HCT at University Medical Center Utrecht (UMC)/Princess Máxima Center (PMC) or Memorial Sloan Kettering Cancer Center (MSK) were included. Primary outcomes were nonrelapse mortality (NRM) and overall survival (OS), stratified for aGVHD and CD4+ IR, defined as ≥50 CD4+ T cells per μL within 100 days after HCT or before aGVHD onset. Multivariate and time-to-event Cox proportional hazards models were applied, and 591 patients (UMC/PMC, n = 276; MSK, n = 315) were included. NRM in patients with grade 3 to 4 aGVHD with or without CD4+ IR within 100 days after HCT was 30% vs 80% (P = .02) at UMC/PMC and 5% vs 67% (P = .02) at MSK. This was associated with lower OS without CD4+ IR (UMC/PMC, 61% vs 20%; P = .04; MSK, 75% vs 33%; P = .12). Inadequate CD4+ IR before aGVHD onset was associated with significantly higher NRM (74% vs 12%; P &lt; .001) and inferior OS (24% vs 78%; P &lt; .001). In this retrospective analysis, we demonstrate that early CD4+ IR, a simple and robust marker predictive of outcomes after HCT, is associated with survival after moderate to severe aGVHD. This association must be confirmed prospectively but suggests strategies to improve T-cell recovery after HCT may influence survival in patients developing aGVHD.
Effects of the anesthesiologist’s experience on postoperative hoarseness after double-lumen endotracheal tube intubation: a single-center propensity score-matched analysis
Authors: Kamimura Yuji , Nakanishi Toshiyuki , Sato Aiji Boku , Osaga Satoshi , Kako Eisuke , Sobue Kazuya 
Published: November 2020

Abstract

Background
Postoperative hoarseness after general anesthesia is associated with patient discomfort and dissatisfaction. A recent large retrospective study showed that single-lumen endotracheal tube intubation by a trainee did not alter the incidence of postoperative pharyngeal symptoms compared with intubation by a senior anesthesiologist. However, there is limited information about the relationship between the anesthesiologist’s experience and hoarseness after double-lumen endotracheal tube intubation. We tested the hypothesis that double-lumen endotracheal tube intubation performed by a trainee increases the incidence of postoperative hoarseness compared to intubation by a senior anesthesiologist.

Methods
This retrospective observational study included patients who underwent lung resection between April 2015 and March 2018 at a university hospital. Double-lumen endotracheal tube intubation was carried out with a Macintosh laryngoscope. We divided the patients into 2 groups - one group comprised of patients who were intubated by a trainee anesthesiologist with < 2 years of experience, and the other group comprised of those who underwent intubation by a senior anesthesiologist with ≥2 years of experience. The primary outcome was the incidence of postoperative hoarseness 24 h after surgery and we collected data on postoperative hoarseness using a checklist of postanesthetic adverse events. One-to-one propensity score matching was conducted and P values < 0.05 were considered statistically significant.

Results
There was a total of 256 eligible patients, of which 153 underwent intubation by trainee anesthesiologists, and the remaining 103 patients were intubated by a senior anesthesiologist. The one-to-one propensity score matching resulted in 96 pairs of patients for the groups. The incidence of postoperative hoarseness 24 h after surgery was significantly higher in patients who were intubated by a trainee anesthesiologist than in patients who were intubated by a senior anesthesiologist (9.4% vs. 2.1%, respectively; P = 0.03).

Conclusions
Double-lumen endotracheal tube intubation by trainee anesthesiologists with < 2 years of experience increased the incidence of postoperative hoarseness 24 h after surgery compared to intubation by senior anesthesiologists with ≥2 years of experience.
Changes in treatment strategy over time for arteriovenous malformation in a Japanese high-volume center
Authors: Komatsu Katsuya , Takagi Yasushi , Ishii Akira , Kikuchi Takayuki , Yamao Yukihiro , Yoshida Kazumichi , Miyamoto Susumu 
Published: November 2020

Abstract

Background
Despite rapid developments in devices used to treat arteriovenous malformation (AVM), a randomised trial of Unruptured Brain Arteriovenous malformations published in 2014 recommended conservative treatment for nonhemorrhagic AVM. The purpose of the current retrospective study was to confirm how AVM treatment in Japan has changed and to assess the safety of treatment for hemorrhagic and nonhemorrhagic AVMs.

Methods
We enrolled 242 consecutive patients with AVM; each patient’s treatment was selected and performed at our hospital. The type of onset, Spetzler–Martin (S–M) grade, age, sex, selected treatment, mortality, and morbidity were compared between the first and second periods of our study.

Results
In patients with grade I–III AVM, the selected treatment changed between the first and second periods; however, in grade IV and V patients, the selected treatment did not change. Overall, interventions by microsurgery alone decreased (p < 0.001), the proportion of total treatments including microsurgery decreased (p = 0.005), interventions using stereotactic radiosurgery (SRS) alone increased (p = 0.009), and interventions including SRS increased (p = 0.002). Morbidity associated with intervention was 0.92% in the first period and 0% in the second period, and mortality was 0.92% in the first period and 1.67% in the second.

Conclusions
With the development of new devices, the selected treatment was changed in patients with S–M grade I–III AVM, but was not changed in patients with grade IV and V. The complication rate was low and did not change throughout the periods. These findings suggest that the safety of treatment depends on a full understanding of device development and the selection of proper treatment, not on hemorrhagic onset. Further treatment innovations are expected to change the treatment for grade IV and V AVMs.
The South African National HIV Pregnancy Cohort: evaluating continuity of care among women living with HIV
Authors: Clouse Kate , Malope-Kgokong Babatyi , Bor Jacob , Nattey Cornelius , Mudau Maanda , Maskew Mhairi 
Published: November 2020

Abstract

Background
South Africa is home to more people living with HIV than any other country, including nearly one in three pregnant women attending antenatal care. Access to antiretroviral therapy (ART) has increased substantially since the start of the national ART program in 2004, with > 95% ART coverage during pregnancy and delivery, and vertical transmission of HIV greatly reduced. However, women who initiate ART during pregnancy are at heightened risk of dropping out of care, particularly after delivery, leading to the potential for viral transmission, morbidity and mortality. It is difficult to evaluate the success of policies of expanded access to ART care, and assess continuity of care, due to the lack of a national longitudinal HIV care database. Also, patient movement between unlinked facilities. For the first time on a national level, we propose to utilize routinely-collected laboratory data to develop and validate a cohort of pregnant women living with HIV in South Africa in a way that is uniquely robust to facility transfer.

Methods
Using laboratory test data matched to facility type, we will identify entry to antenatal care to build the cohort, then describe key treatment milestones, including 1) engagement in antenatal care, 2) initiation of ART, 3) HIV viremia, and 4) continuity of HIV care in the postpartum period. Second, we will measure the effect of system-wide factors impacting continuity of care among pregnant women. We will assess policies of expanded treatment access on continuity of care using regression-discontinuity analyses. We then will assess mobility and its effect on continuity of care during and after pregnancy. Third, we will identify individual-level risk factors for loss from HIV care in order to develop targeted interventions to improve engagement in HIV care.

Discussion
This work will create the world’s largest national cohort of pregnant women living with HIV. This novel cohort will be a powerful tool available to policymakers, clinicians and researchers for improving our understanding of engagement in care among pregnant women in South Africa and assessing the performance of the South African national ART program in caring for pregnant women living with HIV.

Trial registration
N/A (not a clinical trial).
Antimicrobial activities and mechanism of action of Cymbopogon khasianus (Munro ex Hackel) Bor essential oil
Authors: Singh Gurpreet , Katoch Meenu 
Published: November 2020

Abstract

Background
Due to concerns regarding the safety of the chemical control measures, the trend is shifting globally towards the use of natural compounds as antimicrobial agent especially, plant essential oils.

Results
This study presented the antibacterial potential of Cymbopogon khasianus essential oil (CKEO) against human pathogens: Pseudomonas aeruginosa, Salmonella typhimurium, Escherichia coli, Klebsiella pneumoniae, Bacillus subtilis, Staphylococcus aureus and Candida albicans with MIC ranging from 20 to 100 μg/mL. CKEO, in comparison to its major constituent, geraniol, showed better MICs against tested pathogens. In combination studies, the effective concentrations of CKEO and streptomycin were reduced from 20 to 5 μg/mL and 11 to 0.7 ng/mL against E. coli. This suggests their synergistic action. However, CKEO showed partial synergy with ciprofloxacin. To understand the efficacy of CKEO, time-kill kinetics was performed. CKEO took the half time to show the bactericidal effect in comparison to streptomycin at their 2x MICs (double the MIC), while their combination took only 30 min for this. Fluorescence and surface electron microscopic and protein estimation studies suggested the multi-target action of CKEO-streptomycin combination against E. coli. Further, CKEO alone/in combination exhibited less than 10% haemolytic activity at its MIC.

Conclusion
These results indicate that CKEO is a potentially safe alternative for the treatment of various pathogenic bacterial strains. It could be used for a variety of applications including human health, food storage, aquaculture, etc.
Systematic review and meta-analysis of risk factor for postoperative delirium following spinal surgery
Authors: Zhang Hao Jie , Ma Xue Hai , Ye Jin Biao , Liu Cong Zhi , Zhou Zhi Yang 
Published: November 2020

Abstract

Background
Postoperative delirium is a common psychiatric disorder among patients who undergo spinal surgery. The purpose of current meta-analysis was to assess the potential risk factors related to delirium in spinal surgery.

Methods
We searched the following databases: PubMed, EMBASE, the Cochrane Library, and Web of Science, from inception to July 2020. Two reviewers independently assessed the quality of the included studies using the previously described Newcastle-Ottawa Scale (NOS). We included spinal surgery patients who suffered with delirium or not. Stata 12.0 was used for meta-analysis.

Results
Thirteen trial studies that met our inclusion criteria were incorporated into the meta-analysis. Postoperative delirium was associated with an increase of the duration of hospital stay (P = 0.044) and increased perioperative readmission rate (P = 0.013) and economic costs (P = 0.002). This meta-analysis demonstrates that there were twenty-two risk factors: general characteristic: old age, female patients, history of surgery, diabetes mellitus, hypertension; preoperative data: low hematocrit, low hemoglobin, low albumin, low sodium, depression; operative data: operating time, total blood loss; postoperative data: low sodium, low hemoglobin, low hematocrit, low albumin, fever, low potassium, blood sugar, and visual analog scale (VAS).

Conclusions
Delirium not only prolongs the length of hospital stay, but also increases readmission rate and the economic costs. Several risk factors including old age, female patients, history of surgery, diabetes mellitus, low hematocrit, low hemoglobin, low albumin, low sodium, depression; operative data: operating time, total blood loss, low sodium, low hemoglobin, low hematocrit, low albumin, fever, low potassium, blood sugar, and VAS were significant predictors for postoperative delirium after spinal surgery.
Health-related articles on Syria before and after the start of armed conflict: a scoping review for The Lancet-American University of Beirut Commission on Syria
Authors: Abdul-Khalek Rima A. , Kayyal Walaa , Akkawi Abdul Rahman , Almalla Mohamad , Arif Khurram , Bou-Karroum Lama , El-Harakeh Amena , Elzalabany Manal K. , Fadlallah Racha , Ghaddar Fatima , Kashlan Danna , Kassas Sara , Khater Tania , Mobayed Nisreen , Rahme Dalal , Saifi Omran , Jabbour Samer , El-Jardali Fadi , Akl Elie A. , Jawad Mohammed 
Published: November 2020

Abstract

Introduction
Armed conflict may influence the size and scope of research in Arab countries. We aimed to assess the impact of the 2011 Syrian conflict on health articles about Syria published in indexed journals.

Methods
We conducted a scoping review on Syrian health-related articles using seven electronic databases. We included clinical, biomedical, public health, or health system topics published between 1991 and 2017. We excluded animal studies and studies conducted on Syrian refugees. We used descriptive and social network analyses to assess the differences in rates, types, topics of articles, and authorship before and after 2011, the start of the Syrian conflict.

Results
Of 1138 articles, 826 (72.6%) were published after 2011. Articles published after 2011 were less likely to be primary research; had a greater proportion reporting on mental health (4.6% vs. 10.0%), accidents and injuries (2.3% vs. 18.8%), and conflict and health (1.7% vs. 7.8%) (all p < 0.05); and a lower proportion reporting on child and maternal health (8.1 to 3.6%, p = 0.019). The proportion of research articles reporting no funding increased from 1.1 to 14.6% (p < 0.01). While international collaborations increased over time, the number of articles with no authors affiliated to Syrian institutions overtook those with at least one author affiliation to a Syrian institution for the first time in 2015.

Conclusion
To our knowledge, this is the first study to examine the impact of armed conflict on health scholarship in Syria. The Syrian conflict was associated with a change in the rates, types, and topics of the health-related articles, and authors’ affiliations. Our findings have implications for the prioritization of research funding, development of inclusive research collaborations, and promoting the ethics of conducting research in complex humanitarian settings.
Comprehensive genetic testing combined with citizen science reveals a recently characterized ancient MC1R mutation associated with partial recessive red phenotypes in dog
Authors: Anderson Heidi , Honkanen Leena , Ruotanen Päivi , Mathlin Julia , Donner Jonas 
Published: November 2020

AbstractBackgroundThe Melanocortin 1 Receptor (MC1R) plays a central role in regulation of coat color determination in various species and is commonly referred to as the “E (extension) Locus”. Allelic variation of theMC1Rgene is associated with coat color phenotypesEM(melanistic mask),EG(grizzle/domino) ande1–3(recessive red) in dogs. In addition, a previous study of archeological dog specimens over 10,000 years of age identified a variant p.R301C in theMC1Rgene that may have influenced coat color of early dogs.ResultsCommercial genotyping of 11,750 dog samples showed the R301C variant of theMC1Rgene was present in 35 breeds or breed varieties, at an allele frequency of 1.5% in the tested population. We detected no linkage disequilibrium between R301C and other tested alleles of the E locus. Based on current convention we propose that R301C should be considered a novel allele of the E locus, which we have termedeAfor “e ancient red”. Phenotype analysis of owner-provided dog pictures reveals that theeAallele has an impact on coat color and is recessive to wild typeEand dominant to theealleles. In dominant black (KB/*) dogs it can prevent the phenotypic expression of the K locus, and the expressed coat color is solely determined by the A locus. In the absence of dominant black,eA/eAandeA/egenotypes result in the coat color patterns referred to in their respective breed communities as domino in Alaskan Malamute and other Spitz breeds, grizzle in Chihuahua, and pied in Beagle.ConclusionsThis study demonstrates a large genotype screening effort to identify the frequency and distribution of theMC1RR301C variant, one of the earliest mutations captured by canine domestication, and citizen science empowered characterization of its impact on coat color.
Augmented wealth in Switzerland: the influence of pension wealth on wealth inequality
Authors: Kuhn Ursina 
Published: November 2020

AbstractEntitlements for social security and occupational pensions present a major wealth component and play a central role for financial security. However, most individual-level data lacks information on pension wealth. By linking various data sources, this contribution estimates the present value of future pension entitlements in Switzerland for statutory pensions, occupational pensions and third pillar accounts and analyses the distribution of augmented wealth, which combines pension wealth and net worth. The CH-SILC survey from 2015 is used to estimate real assets, financial assets and pension wealth of retired individuals. The pension entitlements of non-retired individuals are simulated on the basis of their earning history from administrative records following the accrual method and assuming a real discount rate of 2%. When pension wealth is added to net worth, average wealth doubles, and the Gini-coefficient declines by 26%. The equalising effect is particularly strong for social security pensions. The wealth distribution differs strongly between the three pillars of the pension system; there are also strong differences between gender and age groups. In Switzerland, wealth accumulation continues after retirement age.
Adverse drug reactions associated with treatment in patients with chronic rheumatic diseases in childhood: a retrospective real life review of a single center cohort
Authors: Said Manar Amanouil , Silva Liana Soido Teixeira e , de Oliveira Rocha Aline Maria , Alves Gustavo Guimarães Barreto , Piotto Daniela Gerent Petry , Len Claudio Arnaldo , Terreri Maria Teresa 
Published: November 2020

Abstract

Background
Adverse drug reactions (ADRs) are the sixth leading causes of death worldwide; monitoring them is fundamental, especially in patients with disorders like chronic rheumatic diseases (CRDs). The study aimed to describe the ADRs investigating their severity and associated factors and resulting interventions in pediatric patients with CRDs.

Methods
A retrospective, descriptive and analytical study was conducted on a cohort of children and adolescents with juvenile idiopathic arthritis (JIA), juvenile systemic lupus erythematosus (JSLE) and juvenile dermatomyositis (JDM). The study evaluated medical records of the patients to determine the causality and the management of ADRs. In order to investigate the risk factors that would increase the risk of ADRs, a logistic regression model was carried out on a group of patients treated with the main used drug.

Results
We observed 949 ADRs in 547 patients studied. Methotrexate (MTX) was the most frequently used medication and also the cause of the most ADRs, which occurred in 63.3% of patients, followed by glucocorticoids (GCs). Comparing synthetic disease-modifying anti-rheumatic drugs (sDMARDs) vs biologic disease-modifying anti-rheumatic drugs (bDMARDs), the ADRs attributed to the former were by far higher than the latter. In general, the severity of ADRs was moderate and manageable. Drug withdrawal occurred in almost a quarter of the cases. In terms of risk factors, most patients who experienced ADRs due to MTX, were 16 years old or younger and received MTX in doses equal or higher than 0.6 mg/kg/week. Patients with JIA and JDM had a lower risk of ADRs than patients with JSLE. In the multiple regression model, the use of GCs for over 6 months led to an increase of 0.5% in the number of ADRs.

Conclusions
Although the ADRs highly likely affect a wide range of children and adolescents with CRDs they were considered moderate and manageable cases mostly. However, triggers of ADRs need further investigations.