bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical outcome of patients with COVID-19 Pneumonia treated with corticosteroids and colchicine in Colombia
Authors: Pinzón Miguel Alejandro , Cardona Arango Doris , Betancur Juan Felipe , Ortiz Santiago , Holguín Héctor , Arias Arias Carolina , Muñoz Palacio Bernardo J. , Amarillo Michael , Llano Juan Felipe , Montoya Pablo 
Published: September 2021

Abstract
Background
To date, there is no specific antiviral therapy for severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) that causes Coronavirus disease 2019 (Covid-19). Since there is no specific therapy against SARS-CoV2, current efforts aim to prevent contagion through public health measures and develop a protective vaccine. While waiting for the latter, it is necessary to evaluate the drugs that at least, in initial studies, suggested some degree of utility in the management of Covid-19 or its complications. The main objective of the study was to describe the clinical manifestations and outcomes of patients with severe Covid-19 Pneumonia treated with corticosteroids and colchicine.

Materials and methods
A cross sectional study of 301 adult patients with Covid-19 Pneumonia confirmed by Real-Time Polymerase Chain Reaction for SARS-CoV2 (RT-PCR SARS-CoV2), Berlin protocol, who required hospitalization in three hospitals in Antioquia, Colombia. Patients were treated according to the institutional protocol (from March 20, 2020 to June 30, 2020) with corticosteroid if the patient required supplemental oxygen. From July 1, 2020, the management protocol changed with the addition of colchicine to all patients admitted to the institutions. The treatment was supervised and monitored by the same specialist in Infectology of the institutions. We describe the clinical manifestations and outcomes of the patients who received these treatments. The information of the patients was analyzed according to the outcome of interest (alive/dead) with univariate, bivariate, and multivariate measures to adjust the variables that presented statistical association.

Results
All patients had pneumonia documented by chest computed tomography with ground glass images and presented an alveolar pressure/inspired oxygen fraction (PaFi) less than 300. Three hundred one patients were included, 240 (79.7%) received corticosteroids, within these 145 (48.2%) received colchicine also, and the remaining 61 (20.3%) patients did not receive corticosterioids or colchicine. Mortality in the group that received colchicine was lower compared to the group that did not receive it (9.6 vs 14.6%, p-value = 0.179).

Conclusions
Treatment with corticosteroids and colchicine for managing patients with severe Covid-19 Pneumonia was associated with low mortality at the hospital level. Randomized, placebo-controlled studies are required to evaluate the effect of corticosteroids and colchicine on complications or death from Covid-19.
Contextualization of cost-effectiveness evidence from literature for 382 health interventions for the Ethiopian essential health services package revision
Authors: Hailu Alemayehu , Eregata Getachew Teshome , Yigezu Amanuel , Bertram Melanie Y. , Johansson Kjell Arne , Norheim Ole F. 
Published: September 2021

Abstract
Background
Cost-effectiveness of interventions was a criterion decided to guide priority setting in the latest revision of Ethiopia’s essential health services package (EHSP) in 2019. However, conducting an economic evaluation study for a broad set of health interventions simultaneously is challenging in terms of cost, timeliness, input data demanded, and analytic competency. Therefore, this study aimed to synthesize and contextualize cost-effectiveness evidence for the Ethiopian EHSP interventions from the literature.

Methods
The evidence synthesis was conducted in five key steps: search, screen, evaluate, extract, and contextualize. We searched MEDLINE and EMBASE research databases for peer-reviewed published articles to identify average cost-effectiveness ratios (ACERs). Only studies reporting cost per disability-adjusted life year (DALY), quality-adjusted life year (QALY), or life years gained (LYG) were included. All the articles were evaluated using the Drummond checklist for quality, and those with a score of at least 7 out of 10 were included. Information on cost, effectiveness, and ACER was extracted. All the ACERs were converted into 2019 US dollars using appropriate exchange rates and the GDP deflator.

Results
In this study, we synthesized ACERs for 382 interventions from seven major program areas, ranging from US$3 per DALY averted (for the provision of hepatitis B vaccination at birth) to US$242,880 per DALY averted (for late-stage liver cancer treatment). Overall, 56% of the interventions have an ACER of less than US$1000 per DALY, and 80% of the interventions have an ACER of less than US$10,000 per DALY.

Conclusion
We conclude that it is possible to identify relevant economic evaluations using evidence from the literature, even if transferability remains a challenge. The present study identified several cost-effective candidate interventions that could, if scaled up, substantially reduce Ethiopia’s disease burden.
Cancer derived exosomes induce macrophages immunosuppressive polarization to promote bladder cancer progression
Authors: Jiang Ziming , Zhang Yiming , Zhang Yu , Jia Zhankui , Zhang Zhengguo , Yang Jinjian 
Published: September 2021

Abstract
Background
Exosomes mediated crosstalk between tumor cells and other stromal cells including tumor associated macrophages plays an essential role in reprogramming tumor microenvironment (TME) to facilitate tumor progression. However, the mechanism of tumor derived exosomes promotes bladder cancer progression have not been defined.

Methods
Exosomes were extracted from bladder cancer cells MB49 conditioned medium by ultracentrifugation. The effects of MB49-derived exosomes on macrophages polarization were analyzed by qPCR, flow cytometry, and Western blot. The immunosuppressive phenotype and function of MB49-derived exosomes stimulated macrophages were verified by tumor xenograft assays and T cell co-culture experiments. Exosomal miRNAs were analyzed by microarray to identify potential targets regulating macrophage polarization.

Results
MB49-derived exosomes could be ingested by macrophages, consequently promoting macrophages immunosuppressive polarization. Mechanically, the MB49-derived exosomes induced macrophage M2 polarization was mediated by down-regulation of PTEN and activation of AKT/STAT3/6 signaling. Moreover, hindrance of the generation or secretion of exosomes by GW4869 inhibited macrophages differentiation into immunosuppressive phenotype and function, thereby suppressed tumor growth in a mouse subcutaneous tumor model.

Conclusion
Our study confirmed the contribution of bladder cancer derived exosomes on the establishment of immunosuppressive TME and provided a potential therapeutic target for bladder cancer treatment.
Reasons for canakinumab initiation among patients with periodic fever syndromes: a retrospective medical chart review from the United States
Authors: Hur Peter , Lomax Kathleen G. , Ionescu-Ittu Raluca , Manceur Ameur M. , Xie Jipan , Cammarota Jordan , Gautam Raju , Sanghera Navneet , Kim Nina , Grom Alexei A. 
Published: September 2021

Abstract
Background
Although canakinumab has demonstrated efficacy in multiple trials in patients with periodic fever syndromes (PFS), the evidence on initiation of canakinumab among PFS patients in real world setting is not well understood. We aimed to characterize the reasons for canakinumab initiation among patients with PFS, specifically, cryopyrin-associated periodic syndrome (CAPS), hyperimmunoglobulin D syndrome/mevalonate kinase deficiency (HIDS/MKD), TNF receptor-associated periodic syndrome (TRAPS) and familial Mediterranean fever (FMF).

Methods
Physicians retrospectively reviewed the medical charts of PFS patients prescribed canakinumab between 2016 and 2018. Information collected included patient clinical characteristics, reasons for previous treatment discontinuation and canakinumab initiation. The results were summarized for overall patients, and by children (< 18 years) and adults and by subtype of PFS.

Results
Fifty-eight physicians in the US (rheumatologists, 44.8 %; allergists/immunologists, 29.3 %; dermatologists, 25.9 %) abstracted information for 147 patients (children, 46.3 %; males, 57.1 %; CAPS, 36.7 %; TRAPS, 26.5 %; FMF, 26.5 %; HIDS/MKD, 6.8 %; Mixed, 3.4 %). Overall, most patients (90.5 %) received treatment directly preceding canakinumab (NSAIDs, 27.8 % [40.0 % in HIDS/MKD]; anakinra, 24.1 % [32.7 % in CAPS]; colchicine, 21.8 % [35.9 % in FMF]), which were discontinued due to lack of efficacy/effectiveness (39.5 %) and availability of a new treatment (36.1 %). The common reasons for canakinumab initiation were physician perceived efficacy/effectiveness (81.0 %; children, 75.0 %; adults, 86.1 %), lack of response to previous treatment (40.8 %; children, 38.2 %; adults, 43.0 %) and favorable safety profile/tolerability (40.1 %; children, 42.6 %; adults, 38.0 %). Within subtypes, efficacy/effectiveness was the most stated reason for canakinumab initiation in HIDS/MKD (90.9 %), lack of response to previous treatment in FMF (52.4 %) and convenience of administration/dosing in CAPS (27.1 %).

Conclusions
This study provided insights into how canakinumab is initiated in US clinical practice among PFS patients, with physician perceived efficacy/effectiveness of canakinumab, lack of response to previous treatment and favorable safety profile/tolerability of canakinumab being the dominant reasons for canakinumab initiation in all patients and in children and adults and PFS subtypes. Notably, the favorable safety profile/tolerability of canakinumab was more often the reason for initiation among children versus adults.
Cholbam® and Zellweger spectrum disorders: treatment implementation and management
Authors: Anderson Janaina Nogueira , Ammous Zineb , Eroglu Yasemen , Hernandez Erick , Heubi James , Himes Ryan , Palle Sirish 
Published: September 2021

Abstract
Background
Zellweger spectrum disorders (ZSDs) are a rare, heterogenous group of autosomal recessively inherited disorders characterized by reduced peroxisomes numbers, impaired peroxisomal formation, and/or defective peroxisomal functioning. In the absence of functional peroxisomes, bile acid synthesis is disrupted, and multisystem disease ensues with abnormalities in the brain, liver, kidneys, muscle, eyes, ears, and nervous system.

Main body
Liver disease may play an important role in morbidity and mortality, with hepatic fibrosis that can develop as early as the postnatal period and often progressing to cirrhosis within the first year of life. Because hepatic dysfunction can have numerous secondary effects on other organ systems, thereby impacting the overall disease severity, the treatment of liver disease in patients with ZSD is an important focus of disease management. Cholbam® (cholic acid), approved by the U.S. Food and Drug Administration in March 2015, is currently the only therapy approved as adjunctive treatment for patients with ZSDs and single enzyme bile acid synthesis disorders. This review will focus on the use of CA therapy in the treatment of liver disease associated with ZSDs, including recommendations for initiating and maintaining CA therapy and the limitations of available clinical data supporting its use in this patient population.

Conclusions
Cholbam is a safe and well-tolerated treatment for patients with ZSDs that has been shown to improve liver chemistries and reduce toxic bile acid intermediates in the majority of patients with ZSD. Due to the systemic impacts of hepatic damage, Cholbam should be initiated in patients without signs of advanced liver disease.
The non-canonical mechanism of ER stress-mediated progression of prostate cancer
Authors: Pachikov Artem N. , Gough Ryan R. , Christy Caroline E. , Morris Mary E. , Casey Carol A. , LaGrange Chad A. , Bhat Ganapati , Kubyshkin Anatoly V. , Fomochkina Iryna I. , Zyablitskaya Evgeniya Y. , Makalish Tatiana P. , Golubinskaya Elena P. , Davydenko Kateryna A. , Eremenko Sergey N. , Riethoven Jean-Jack M. , Maroli Amith S. , Payne Thomas S. , Powers Robert , Lushnikov Alexander Y. , Macke Amanda J. , Petrosyan Armen 
Published: September 2021

Abstract
Background
The development of persistent endoplasmic reticulum (ER) stress is one of the cornerstones of prostate carcinogenesis; however, the mechanism is missing. Also, alcohol is a physiological ER stress inducer, and the link between alcoholism and progression of prostate cancer (PCa) is well documented but not well characterized. According to the canonical model, the mediator of ER stress, ATF6, is cleaved sequentially in the Golgi by S1P and S2P proteases; thereafter, the genes responsible for unfolded protein response (UPR) undergo transactivation.

Methods
Cell lines used were non-malignant prostate epithelial RWPE-1 cells, androgen-responsive LNCaP, and 22RV1 cells, as well as androgen-refractory PC-3 cells. We also utilized PCa tissue sections from patients with different Gleason scores and alcohol consumption backgrounds. Several sophisticated approaches were employed, including Structured illumination superresolution microscopy, Proximity ligation assay, Atomic force microscopy, and Nuclear magnetic resonance spectroscopy.

Results
Herein, we identified the trans-Golgi matrix dimeric protein GCC185 as a Golgi retention partner for both S1P and S2P, and in cells lacking GCC185, these enzymes lose intra-Golgi situation. Progression of prostate cancer (PCa) is associated with overproduction of S1P and S2P but monomerization of GCC185 and its downregulation. Utilizing different ER stress models, including ethanol administration, we found that PCa cells employ an elegant mechanism that auto-activates ER stress by fragmentation of Golgi, translocation of S1P and S2P from Golgi to ER, followed by intra-ER cleavage of ATF6, accelerated UPR, and cell proliferation. The segregation of S1P and S2P from Golgi and activation of ATF6 are positively correlated with androgen receptor signaling, different disease stages, and alcohol consumption. Finally, depletion of ATF6 significantly retarded the growth of xenograft prostate tumors and blocks production of pro-metastatic metabolites.

Conclusions
We found that progression of PCa associates with translocation of S1P and S2P proteases to the ER and subsequent ATF6 cleavage. This obviates the need for ATF6 transport to the Golgi and enhances UPR and cell proliferation. Thus, we provide the novel mechanistic model of ATF6 activation and ER stress implication in the progression of PCa, suggesting ATF6 is a novel promising target for prostate cancer therapy.
Descriptive study on subjective experience of genetic testing with respect to relationship, family planning and psychosocial wellbeing among women with lynch syndrome
Authors: Kalamo Mari , Mäenpää Johanna , Seppälä Toni , Mecklin Jukka-Pekka , Pylvänäinen Kirsi , Staff Synnöve 
Published: September 2021

AbstractBackgroundDue to increased risk of endometrial and ovarian cancer, women belonging to known Lynch Syndrome (LS) families are recommended to undergo germline testing. Current practice in Finland is to offer counselling to women with pathogenic variant and advocate risk-reducing surgery (RRS) after completion of childbirth. The present study aimed to clarify the impacts of positive germline testing on family planning and reproductive decisions of these women, which are relatively unknown.MethodsSeventy-nine carriers of germline MMR gene pathogenic variant (path_MMR)were identified from the Finnish LS Registry as having genetic testing performed before the age of 45 years and not having undergone hysterectomy or oophorectomy. These women were sent a questionnaire concerning family planning, intimate relationships and psychosocial wellbeing.ResultsThirty-five women (44.3%) responded. Parity ofpath_MMRcarriers (2.1) was slightly higher than parity among Finnish women in general (1.8). No significant differences were found between parity, number of induced abortions or sterilizations before and after genetic testing. Only minority of subjects reported any influence on family planning (20%) or negative impact on feminine self and body image (14%).ConclusionsThe positive germline testing does not seem to have a major negative impact on family planning, intimate relationships or feminine self and body image. According to the open comments, counselling, supportive and empathic attitude of the professionals seem to have a significant impact on this. These results are a valuable addition to the counselling of LS women at reproductive age.
Regulatory regions in natural transposable element insertions drive interindividual differences in response to immune challenges in Drosophila
Authors: Ullastres Anna , Merenciano Miriam , González Josefa 
Published: September 2021

Abstract
Background
Variation in gene expression underlies interindividual variability in relevant traits including immune response. However, the genetic variation responsible for these gene expression changes remains largely unknown. Among the non-coding variants that could be relevant, transposable element insertions are promising candidates as they have been shown to be a rich and diverse source of cis-regulatory elements.

Results
In this work, we use a population genetics approach to identify transposable element insertions likely to increase the tolerance of Drosophila melanogaster to bacterial infection by affecting the expression of immune-related genes. We identify 12 insertions associated with allele-specific expression changes in immune-related genes. We experimentally validate three of these insertions including one likely to be acting as a silencer, one as an enhancer, and one with a dual role as enhancer and promoter. The direction in the change of gene expression associated with the presence of several of these insertions is consistent with an increased survival to infection. Indeed, for one of the insertions, we show that this is the case by analyzing both natural populations and CRISPR/Cas9 mutants in which the insertion is deleted from its native genomic context.

Conclusions
We show that transposable elements contribute to gene expression variation in response to infection in D. melanogaster and that this variation is likely to affect their survival capacity. Because the role of transposable elements as regulatory elements is not restricted to Drosophila, transposable elements are likely to play a role in immune response in other organisms as well.
Trycycler: consensus long-read assemblies for bacterial genomes
Authors: Wick Ryan R. , Judd Louise M. , Cerdeira Louise T. , Hawkey Jane , Méric Guillaume , Vezina Ben , Wyres Kelly L. , Holt Kathryn E. 
Published: September 2021

AbstractWhile long-read sequencing allows for the complete assembly of bacterial genomes, long-read assemblies contain a variety of errors. Here, we present Trycycler, a tool which produces a consensus assembly from multiple input assemblies of the same genome. Benchmarking showed that Trycycler assemblies contained fewer errors than assemblies constructed with a single tool. Post-assembly polishing further reduced errors and Trycycler+polishing assemblies were the most accurate genomes in our study. As Trycycler requires manual intervention, its output is not deterministic. However, we demonstrated that multiple users converge on similar assemblies that are consistently more accurate than those produced by automated assembly tools.
Prevalence of malaria and scrub typhus co-infection in febrile patients: a systematic review and meta-analysis
Authors: Wilairatana Polrat , Kuraeiad Saruda , Rattaprasert Pongruj , Kotepui Manas 
Published: September 2021

AbstractBackgroundLittle information is available about malaria and scrub typhus co-infection. This study aimed to investigate the pooled prevalence of malaria and scrub typhus co-infection in febrile patients. Further, it aimed to estimate the prevalence of scrub typhus infection among patients with malaria and the odds of co-infection. This will aid the diagnosis and management of co-infected patients in endemic areas.MethodsWe searched for relevant studies in three databases: PubMed, Scopus, and Web of Science. We assessed the quality of the included studies using the Joanna Briggs Institute checklist for analytical cross-sectional studies. We estimated (1) the pooled prevalence of malaria and scrub typhus co-infection, (2) the pooled prevalence of scrub typhus infection in malaria-positive patients, and (3) the pooled odds of co-infection using the DerSimonian–Laird method for random-effects models. The study results and summary estimates were visualized on a forest plot as point estimates (effect size, prevalence) and 95% confidence intervals (CI). We assessed the heterogeneity of the studies by Cochrane Q orI2statistics. We performed subgroup analyses of countries and scrub typhus diagnostic tests to explore the sources of heterogeneity of the included studies. We assessed publication bias if more than 10 studies were used to estimate the outcome. All data analyses were conducted using Stata version 14 (StataCorp, College Station, TX, USA).ResultsOf the 542 studies retrieved from three databases, we included 14 meeting the inclusion criteria in the systematic review and meta-analysis. The pooled prevalence of malaria and scrub typhus co-infection (56 cases) among febrile patients (7920 cases) was 1% (95% CI: 0–1%,I2: 78.28%), while the pooled prevalence of scrub typhus infection (321 cases) in patients with malaria (1418 cases) was 21% (95% CI: 12–30%,I2: 98.15%). Subgroup analysis showed that the pooled prevalence of scrub typhus infection among patients with malaria in India was 8% (95% CI: 4–13%,I2: 85.87%, nine studies with 59/794 cases), while the pooled prevalence of scrub typhus infection among patients with malaria in Thailand was 35% (95% CI: 7–64%,I2: 98.9%, four studies with 262/624 cases). The co-infections did not occur by chance (P = 0.013, odds: 0.43, 95% CI: 0.22–0.84%,I2: 60.9%). In the sensitivity analysis, the pooled prevalence of malaria and scrub typhus co-infection among febrile patients was 0% (95% CI: 0–1%,I2: 59.91%).ConclusionsThe present study showed the pooled prevalence and a significant association between malaria and scrub typhus. The results show the status of co-infection. Further research into co-infection in endemic areas is needed, in particular, to determine whether co-infection can accelerate disease progression or protect against severe disease.Graphical abstract