bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of low-dose hydrocortisone and hydrocortisone plus fludrocortisone in adults with septic shock: a protocol for a systematic review and meta-analysis of individual participant data
Authors: Annane Djillali , Pirracchio Romain , Billot Laurent , Waschka Andre , Chevret Sylvie , Cohen Jeremy , Finfer Simon , Gordon Anthony , Hammond Naomi , Myburgh John , Venkatesh Balasubramanian , Delaney Anthony 
Published: December 2020

IntroductionThe benefits and risks of low-dose hydrocortisone in patients with septic shock have been investigated in numerous randomised controlled trials and trial-level meta-analyses. Yet, the routine use of this treatment remains controversial. To overcome the limitations of previous meta-analyses inherent to the use of aggregate data, we will perform an individual patient data meta-analysis (IPDMA) on the effect of hydrocortisone with or without fludrocortisone compared with placebo or usual care on 90-day mortality and other outcomes in patients with septic shock.Methods and analysisTo assess the benefits and risks of hydrocortisone, with or without fludrocortisone for adults with septic shock, we will search major electronic databases from inception to September 2020 (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and Latin American Caribbean Health Sciences Literature), complimented by a search for unpublished trials. The primary analysis will compare hydrocortisone with or without fludrocortisone to placebo or no treatment in adult patients with septic shock. Secondary analyses will compare hydrocortisone to placebo (or usual care), hydrocortisone plus fludrocortisone to placebo (or usual care), and hydrocortisone versus hydrocortisone plus fludrocortisone. The primary outcome will be all cause mortality at 90 days. We will conduct both one-stage IPDMA using mixed-effect models and machine learning with targeted maximum likelihood analyses. We will assess the risk of bias related to unshared data and related to the quality of individual trial.Ethics and disseminationThis IPDMA will use existing data from completed randomised clinical trials and will comply with the ethical and regulatory requirements regarding data sharing for each of the component trials. The findings of this study will be submitted for publication in a peer-review journal with straightforward policy for open access.PROSPERO registration numberCRD42017062198.
Values informing the development of an indicator of appropriate diabetes therapy: qualitative study
Authors: LaVecchia Christina M , Montori Victor M , Shah Nilay D , McCoy Rozalina G 
Published: December 2020

ObjectivesDespite increasing focus on individualised diabetes management, current diabetes quality measures are based on meeting generic haemoglobin A1c thresholds and do not reflect considerations of clinical complexity, hypoglycaemic susceptibility or treatment burden. Our team observed a multidisciplinary stakeholder panel tasked with informing an appropriate diabetes therapy indicator (ADTI) and analysed their deliberations, seeking to understand what constitutes appropriate diabetes therapy and how it can be captured using an operational quality indicator. We focused specifically on factors the panel valued in an ideal indicator, how they defined appropriateness and how they thought an indicator of appropriateness could be operationalised.DesignQualitative study examining Delphi panel deliberations as it iteratively refined the ADTI.Participants and methodsThe 12-member panel was comprised of clinicians (endocrinology, primary care, geriatrics), pharmacists, nurses, researchers, and representatives of public and private health plans. It met for four teleconference calls and deliberated asynchronously using semi-structured questionnaires following each call to develop the ADTI. These semistructured questionnaires, as well as the meeting minutes, were then analysed using an inductive thematic approach.ResultsWe identified three themes in panellist discussions that represented the core value systems underpinning the indicator and its formation: (1) promoting individualised, evidence-based and equitable care; (2) balancing autonomy and prescriptiveness in clinical decision-making; and (3) ensuring an accurate, reliable and practical indicator. These three principles were operationalised into definitions of treatment intensity and clinical complexity, and yielded an indicator that participants judged both fair and effective.ConclusionsBetter understanding of what multidisciplinary stakeholders perceive as appropriate diabetes management can help develop quality indicators that are patient-centred, evidence-based, equitable and pragmatic across a range of clinical settings.
Publication of inspection frameworks: a qualitative study exploring the impact on quality improvement and regulation in three healthcare settings
Authors: Weenink Jan-Willem , Wallenburg Iris , Leistikow Ian , Bal Roland A 
Published: December 2020

BackgroundThe Dutch healthcare inspectorate publishes its inspection frameworks to inform both the public and healthcare providers about regulatory procedures and in the hope that publication will motivate healthcare providers to improve quality and comply with standards. This study explores the consequences of publishing these frameworks for the regulation of quality and safety in healthcare.MethodsWe selected recently published inspection frameworks used in three healthcare settings: nursing home care, dental care and hospital care. We conducted 37 interviews with 39 respondents (healthcare professionals, managers, quality officers, policy advisers and inspectors) and explored their awareness of and experiences with these frameworks. We held a group interview with three inspectors to reflect on our findings. All data underwent thematic content analysis.ResultsWe found that the institutional infrastructure of a sector plays an important role in how an inspection framework is used after publication; particularly the presence and maturity of quality improvement work in the sector and the inspectorate’s grip on a sector matter. Respondents mentioned differences in framework use in organisational contexts, particularly relating to scale. In some organisations, the framework served as an accountability mechanism to check if quality meets basic standards, while in other organisations professionals adopted it to stimulate discussion and learning across teams.ConclusionPublication of inspection frameworks might result in quality improvement work, and in particular contexts could be used as a regulatory strategy to target quality improvement in a healthcare sector. For this, it is important that regulators consider the capabilities and possibilities for learning and improving within a sector.
Palliative care in critically ill COVID-19 patients: the early New York City experience
Authors: Sheehan Jacqueline , Ho Kam Sing , Poon Joseph , Sarosky Kimberly , Fung Jennifer Y 
Published: December 2020

ObjectivesThe COVID-19 pandemic in the USA has been accompanied by high rates of mortality and an unprecedented need for palliative care delivery. Little is known about the use of palliative care services in intensive care unit (ICU) settings during the COVID-19 pandemic.MethodsThis is a retrospective cohort study of critically ill COVID-19 patients requiring ICU admission, between 7 March and 14 April 2020 to two academic teaching hospitals in New York City. Palliative care consultation included a one-time telemedicine consultation or continued telemedicine consultation and follow-up with multidisciplinary team involvement. Patient information was collected from the electronic health record and analyses were conducted with Stata V.15.1 (StataCorp) statistical software.ResultsA total of 151 critically ill patients with COVID-19 pneumonia requiring ICU admission were identified, of whom 59 (39.07%) received an inpatient palliative care consultation. More than half of patients died (n=85/151, 56.29%), with 57.65% (n=49/85) of these patients receiving palliative care services during their hospitalisation. Patients who received palliative care consultation were more likely to be older, sicker and receive mechanical ventilation than their counterparts. Patients who died and did not receive palliative care were younger and required non-invasive ventilation support.ConclusionThere is a lack of utilisation of palliative care in COVID-19 patients admitted to the ICU. Further research into predictors of poor outcomes in critically ill COVID-19 patients may help identify patients that would benefit from early palliative care involvement going forward.
Antibody Peptides as Cancer Vaccine—Turning Weapons to Targets
Authors: Seiffert Martina 
Published: December 2020

Abstract
Stereotyped B-cell receptors (BCR) are frequent in patients with chronic lymphocytic leukemia (CLL). In cell culture and in mouse models of CLL, immunogenic epitopes of these BCRs were shown to trigger specific T-cell responses and to control leukemia development. These results suggest vaccination with autologous BCR-derived peptides as a novel therapy for CLL.
See related article by Rovida et al., p. 729
The Origins of the Biblical Aramaic Reading Tradition
Authors: Suchard Benjamin D. 
Published: December 2020

Abstract
The many qere notes in the Aramaic passages of the Hebrew Bible show that the Biblical Aramaic reading tradition goes back to a different variety of Aramaic than the consonantal texts. While this qere dialect differs in important respects from every well-attested dialect of Aramaic, it closely resembles a small number of documents from first- and second-century CE Palestine. This suggests that this was the time and place at which the reading tradition was fixed, not just of the Biblical Aramaic portions of the Hebrew Bible, but of the Hebrew Bible in its entirety.
Long‐term outcomes of acute severe ulcerative colitis in the rescue therapy era: A multicentre cohort study
Authors: Festa Stefano , Scribano Maria L. , Pugliese Daniela , Bezzio Cristina , Principi Mariabeatrice , Ribaldone Davide G. , Allocca Mariangela , Mocci Giammarco , Bodini Giorgia , Spagnuolo Rocco , Vernia Piero , Mazzuoli Silvia , Costa Francesco , Barberio Brigida , Cosintino Rocco , Zerboni Giulia , Aratari Annalisa , Armuzzi Alessandro , Papi Claudio 
Published: December 2020

AbstractBackgroundThe long‐term course of ulcerative colitis after a severe attack is poorly understood. Second‐line rescue therapy with cyclosporine or infliximab is effective for reducing short‐term colectomy but the impact in the long‐term is controversial.ObjectiveThe purpose of this study was to evaluate the long‐term course of acute severe ulcerative colitis patients who avoid early colectomy either because of response to steroids or rescue therapy.MethodsThis was a multicentre retrospective cohort study of adult patients with acute severe ulcerative colitis admitted to Italian inflammatory bowel disease referral centres from 2005 to 2017. All patients received intravenous steroids, and those who did not respond received either rescue therapy or colectomy. For patients who avoided early colectomy (within 3 months from the index attack), we recorded the date of colectomy, last follow‐up visit or death. The primary end‐point was long‐term colectomy rate in patients avoiding early colectomy.ResultsFrom the included 372 patients with acute severe ulcerative colitis, 337 (90.6%) avoided early colectomy. From those, 60.5% were responsive to steroids and 39.5% to the rescue therapy. Median follow‐up was 44 months (interquartile range, 21–85). Colectomy‐free survival probability was 93.5%, 81.5% and 79.4% at 1, 3 and 5 years, respectively. Colectomy risk was higher among rescue therapy users than in steroid‐responders (log‐rank test, p = 0.02). At multivariate analysis response to steroids was independently associated with a lower risk of long‐term colectomy (adjusted odds ratio = 0.5; 95% confidence interval, 0.2–0.8), while previous exposure to antitumour necrosis factor‐α agents was associated with an increased risk (adjusted odds ratio = 3.0; 95% confidence interval, 1.5–5.7). Approximately 50% of patients required additional therapy or new hospitalisation within 5 years due to a recurrent flare. Death occurred in three patients (0.9%).ConclusionsPatients with acute severe ulcerative colitis avoiding early colectomy are at risk of long‐term colectomy, especially if previously exposed to antitumour necrosis factor‐α agents or if rescue therapy during the acute attack was required because of steroid refractoriness.
Immune phenotype of patients with stage IV metastatic inflammatory breast cancer
Authors: Fernandez Sandra V. , MacFarlane Alexander W. , Jillab Mowafaq , Arisi Maria F. , Yearley Jennifer , Annamalai Lakshmanan , Gong Yulan , Cai Kathy Q. , Alpaugh R. Katherine , Cristofanilli Massimo , Campbell Kerry S. 
Published: December 2020

AbstractBackgroundInflammatory breast cancer (IBC) is a rare but aggressive carcinoma characterized by severe erythema and edema of the breast, with many patients presenting in advanced metastatic disease. The “inflammatory” nature is not due to classic immune-mediated inflammation, but instead results from tumor-mediated blockage of dermal lymphatic ducts. Previous work has shown that expression of PD-L1 on tumor cells can suppress T cell activation in triple-negative (TN) non-IBC breast cancer. In the present work, we investigated immune parameters in peripheral blood of metastatic IBC patients to determine whether cellular components of the immune system are altered, thereby contributing to pathogenesis of the disease. These immune parameters were also compared to PD-1 and PD-L1 expression in IBC tumor biopsies.MethodsFlow cytometry-based immune phenotyping was performed using fresh peripheral blood from 14 stage IV IBC patients and compared to 11 healthy age-similar control women. Immunohistochemistry for CD20, CD3, PD-1, and PD-L1 was performed on tumor biopsies of these metastatic IBC patients.ResultsIBC patients with Stage IV disease had lymphopenia with significant reductions in circulating T, B, and NK cells. Reductions were observed in all subsets of CD4+T cells, whereas reductions in CD8+T cells were more concentrated in memory subsets. Immature cytokine-producing CD56brightNK cells expressed higher levels of FcγRIIIa and cytolytic granule components, suggesting accelerated maturation to cytolytic CD56dimcells. Immunohistochemical analysis of tumor biopsies demonstrated moderate to high expression of PD-1 in 18.2% of patients and of PD-L1 in 36.4% of patients. Interestingly, a positive correlation was observed between co-expression levels of PD-L1 and PD-1 in tumor biopsies, and higher expression of PD-L1 in tumor biopsies correlated with higher expression of cytolytic granule components in blood CD4+T cells and CD56dimNK cells, and higher numbers of CD8+effector memory T cells in peripheral blood. PD-1 expression in tumor also correlated with increased infiltration of CD20+B cells in the tumor.ConclusionsOur results suggest that while lymphocyte populations are severely compromised in stage IV IBC patients, an immune response toward the tumor had occurred in some patients, providing biological rationale to evaluate PD-1/PD-L1 immunotherapies for IBC.
Primary and secondary infertility in Africa: systematic review with meta-analysis
Authors: Abebe Melese Shenkut , Afework Mekbeb , Abaynew Yeshiwas 
Published: December 2020

Abstract
BACKGROUND
Infertility is a practical concern of Africans due to social disgrace and exclusion. This meta-analysis aims to analyze the proportion of primary and secondary infertility and identify the etiologic factors based on the studies conducted in Africa.

METHODS
An internet-based search was conducted on the following databases; PubMed/Medline, EMBASE, Cochrane library, and google scholar. Both population and institution-based studies conducted among African couples, males, and females were included. Data extraction and critical appraisal of the articles were done by two independent investigators. Meta-analysis using a random effect model was conducted by Stata version 14. Forest plot, heterogeneity test, and funnel plot for publication bias were performed.

RESULTS
The pooled proportion of primary and secondary infertility in Africa was 49.91% (I2 = 98.7, chi-square = 1509.01, degree of freedom = 19 and p < 0.001) and 49.79% (I2 = 98.7, chi-square = 1472.69, degree of freedom = 19 and p < 0.001) respectively. The pooled prevalence of the causes of infertility indicated that 54.01% and 22.26% of the infertility cases were respectively due to female and male-related problems. In 21.36% of infertility cases, both sexes were affected, while 10.4% of the causes of infertility were unexplained. The pooled prevalence of mostly reported causes of male infertility was 31% (oligospermia), 19.39% (asthenozoospermia), and 19.2% (varicocele). The most commonly identified causes of female infertility were pelvic inflammatory disease, tubal factors, and abortion with a pooled prevalence of 39.38%, 39.17%, and 36.41% respectively.

Conclusions
In Africa, the proportion of primary and secondary infertility is approximately equal. Infertility is mostly due to female-related causes like; pelvic inflammatory diseases, uterine tube related problems, and abortion. Oligospermia, asthenozoospermia, and varicocele were the commonest causes of male-related infertility. It is suggested that interpretation and utilization of these findings should consider the presence of substantial heterogeneity between the included studies.
Factors influencing the effectiveness of recombinant human soluble thrombomodulin on disseminated intravascular coagulation: a retrospective study
Authors: Asai Yuki , Yamamoto Takanori , Kito Daisuke , Ichikawa Kazuya , Abe Yasuharu 
Published: December 2020

AbstractBackgroundAlthough recombinant human soluble thrombomodulin (rTM) has been widely used to treat disseminated intravascular coagulation (DIC) in Japan, there is no consensus regarding rTM efficacy. Therefore, if the factors influencing rTM efficacy is revealed, it may be possible to demonstrate the effectiveness of rTM by limiting the patients who use rTM. This study investigated the factors of rTM treatment which influence DIC status.MethodsThis retrospective case-control study enrolled hospitalized adult patients treated with rTM from October 2010 to May 2020. Among these patients, 227 who were diagnosed with DIC according to the Japanese Association for Acute Medicine DIC scoring system were assessed. The primary endpoint was the 28-day mortality after rTM treatment. For Cox-proportional hazards model, explanatory factors determined using univariate analysis withp <  0.1 were used. In addition, some factors considered to affect DIC-related mortality such as age ≥ 75 years, rTM dose ≥380 U/kg, antithrombin III treatment, and diseases with a poor prognosis (sepsis, solid tumors, and trauma) were added as covariates.ResultsUnivariate analyses suggested that male sex (p = 0.029), treatment in intensive care unit (p = 0.061), and prothrombin time-international normalized ratio (PT-INR) (p <  0.001) were the factors influencing DIC-related 28-day mortality after rTM treatment. According to Cox-proportional hazard analysis, the adjusted odds ratio for DIC-related 28-day mortality in patients with PT-INR ≥ 1.67 was 2.23 (95% confidence interval: 1.451–3.433,p <  0.001), age ≥ 75 years was 1.57 (95% confidence interval: 1.009–2.439,p = 0.046), and male sex was 1.66 (95% confidence interval: 1.065–2.573,p = 0.025), respectively. As life-threatening bleeding events were not observed, prolonged PT-INR might directly or indirectly affect DIC-related mortality caused by rTM treatment.ConclusionrTM treatment for DIC was less effective in male patients with PT-INR ≥ 1.67 and age ≥ 75 years.
Recent developments of tools for genome and metabolome studies in basidiomycete fungi and their application to natural product research
Authors: Alberti Fabrizio , Kaleem Saraa , Weaver Jack A. 
Published: December 2020

ABSTRACT
Basidiomycota are a large and diverse phylum of fungi. They can make bioactive metabolites that are used or have inspired the synthesis of antibiotics and agrochemicals. Terpenoids are the most abundant class of natural products encountered in this taxon. Other natural product classes have been described, including polyketides, peptides, and indole alkaloids. The discovery and study of natural products made by basidiomycete fungi has so far been hampered by several factors, which include their slow growth and complex genome architecture. Recent developments of tools for genome and metabolome studies are allowing researchers to more easily tackle the secondary metabolome of basidiomycete fungi. Inexpensive long-read whole-genome sequencing enables the assembly of high-quality genomes, improving the scaffold upon which natural product gene clusters can be predicted. CRISPR/Cas9-based engineering of basidiomycete fungi has been described and will have an important role in linking natural products to their genetic determinants. Platforms for the heterologous expression of basidiomycete genes and gene clusters have been developed, enabling natural product biosynthesis studies. Molecular network analyses and publicly available natural product databases facilitate data dereplication and natural product characterisation. These technological advances combined are prompting a revived interest in natural product discovery from basidiomycete fungi.
This article has an associated Future Leader to Watch interview with the first author of the paper.
Synthesis of 9-Substituted Fluorenols and Heteroring-fused Analogues by Intramolecular C–H Functionalization
Authors: Kurimoto Yuji , Mitsudo Koichi , Suga Seiji 
Published: December 2020

Abstract
A method for the selective synthesis of 9-substituted fluorenols (FOLs) was developed by suppressing intermolecular cyclization and promoting intramolecular C–H functionalization. This protocol was applied to the synthesis of heteroring-fused FOLs. Further, the obtained FOLs were converted to fulvenes by dehydration.
Should interventional radiology gain speciality status within the royal college of radiologists?
Authors: Kilic Yakup , Illyas Shahzad 
Published: December 2020

Interventional Radiology (IR) medicine’s best kept secret will revolutionise healthcare like never before. The legacy Charles Dotter left behind not only showcases IR’s pursuit of innovative and complex techniques in order to provide better treatment options for patients, it also sparked an opportunity for radiologists to use their imagination and creativity to develop IR into a speciality catering for the 21st century. By utilising imaging as well as clinical and minimal invasive surgical knowledge IRs are able to play an integral role in caring for patients in nearly all specialities.
Over the past few decades, the absence of radiology in the leadership management arena has allowed other specialities to perpetuate turf wars and utilise techniques developed by IR. A concerted effort is required by the wider radiology community to address the problems faced by IR and to recognise its true potential as a speciality to further improve patient care.