bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative analysis reveals within-population genome size variation in a rotifer is driven by large genomic elements with highly abundant satellite DNA repeat elements
Authors: Stelzer C. P. , Blommaert J. , Waldvogel A. M. , Pichler M. , Hecox-Lea B. , Mark Welch D. B. 
Published: September 2021

Abstract
Background
Eukaryotic genomes are known to display an enormous variation in size, but the evolutionary causes of this phenomenon are still poorly understood. To obtain mechanistic insights into such variation, previous studies have often employed comparative genomics approaches involving closely related species or geographically isolated populations within a species. Genome comparisons among individuals of the same population remained so far understudied—despite their great potential in providing a microevolutionary perspective to genome size evolution. The rotifer Brachionus asplanchnoidis represents one of the most extreme cases of within-population genome size variation among eukaryotes, displaying almost twofold variation within a geographic population.

Results
Here, we used a whole-genome sequencing approach to identify the underlying DNA sequence differences by assembling a high-quality reference genome draft for one individual of the population and aligning short reads of 15 individuals from the same geographic population including the reference individual. We identified several large, contiguous copy number variable regions (CNVs), up to megabases in size, which exhibited striking coverage differences among individuals, and whose coverage overall scaled with genome size. CNVs were of remarkably low complexity, being mainly composed of tandemly repeated satellite DNA with only a few interspersed genes or other sequences, and were characterized by a significantly elevated GC-content. CNV patterns in offspring of two parents with divergent genome size and CNV patterns in several individuals from an inbred line differing in genome size demonstrated inheritance and accumulation of CNVs across generations.

Conclusions
By identifying the exact genomic elements that cause within-population genome size variation, our study paves the way for studying genome size evolution in contemporary populations rather than inferring patterns and processes a posteriori from species comparisons.
Lung disease network reveals impact of comorbidity on SARS-CoV-2 infection and opportunities of drug repurposing
Authors: Das Asim Bikas 
Published: September 2021

Abstract
Background
Higher mortality of COVID-19 patients with lung disease is a formidable challenge for the health care system. Genetic association between COVID-19 and various lung disorders must be understood to comprehend the molecular basis of comorbidity and accelerate drug development.

Methods
Lungs tissue-specific neighborhood network of human targets of SARS-CoV-2 was constructed. This network was integrated with lung diseases to build a disease–gene and disease-disease association network. Network-based toolset was used to identify the overlapping disease modules and drug targets. The functional protein modules were identified using community detection algorithms and biological processes, and pathway enrichment analysis.

Results
In total, 141 lung diseases were linked to a neighborhood network of SARS-CoV-2 targets, and 59 lung diseases were found to be topologically overlapped with the COVID-19 module. Topological overlap with various lung disorders allows repurposing of drugs used for these disorders to hit the closely associated COVID-19 module. Further analysis showed that functional protein–protein interaction modules in the lungs, substantially hijacked by SARS-CoV-2, are connected to several lung disorders. FDA-approved targets in the hijacked protein modules were identified and that can be hit by exiting drugs to rescue these modules from virus possession.

Conclusion
Lung diseases are clustered with COVID-19 in the same network vicinity, indicating the potential threat for patients with respiratory diseases after SARS-CoV-2 infection. Pathobiological similarities between lung diseases and COVID-19 and clinical evidence suggest that shared molecular features are the probable reason for comorbidity. Network-based drug repurposing approaches can be applied to improve the clinical conditions of COVID-19 patients.
The opportunities and challenges of social media in interstitial lung disease: a viewpoint
Authors: Grewal Japnam S. , Kawano-Dourado Leticia , Ryerson Christopher J. 
Published: September 2021

AbstractSocial media is an increasingly popular source of health information, and the rarity and complexity of interstitial lung disease (ILD) may particularly draw patients with ILD to social media for information and support. The objective of this viewpoint is to provide an overview of social media, explore the benefits and limitations of ILD-related social media use, and discuss future development of healthcare information on social media. We describe the value of integrating social media into the practice of ILD health professionals, including its role in information dissemination, patient engagement, knowledge generation, and formation of health policy. We also describe major challenges to expanded social media use in ILD, including limited access for some individuals and populations, abundance of misinformation, and concerns about patient privacy. Finally, for healthcare professionals looking to join social media, we provide practical guidance and considerations to optimize the potential benefits and minimize the potential pitfalls of social media.
Circ-SFMBT2 drives the malignant phenotypes of esophageal cancer by the miR-107-dependent regulation of SLC1A5
Authors: Chang Zhiwei , Fu Yang , Jia Yongxu , Gao Ming , Song Lijie , Zhang Weijie , Zhao Ruihua , Qin Yanru 
Published: September 2021

Abstract
Background
Increasing studies focused on the regulatory roles of circular RNAs (circRNAs) in diverse cancers. This study was to evaluate the function and mechanism of circRNA Scm-like with four malignant brain tumor domains 2 (circ-SFMBT2) in esophageal cancer (EC).

Methods
The circ-SFMBT2, microRNA-107 (miR-107) and solute-linked carrier family A1 member 5 (SLC1A5) levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was evaluated by 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay, colony formation assay and EdU assay. Cell apoptosis and invasion were detected by flow cytometry and transwell assay. Glutamine metabolism was assessed by the corresponding kits for glutamine consumption, α-ketoglutarate production and glutamate production. Western blot was used for protein quantification. The binding analysis was performed using dual-luciferase reporter assay, RNA immunoprecipitation (RIP) and pull-down assays. The functional research of circ-SFMBT2 in vivo was performed by xenograft tumor assay. Exosomes were identified by morphological observation and protein detection.

Results
Circ-SFMBT2 was overexpressed in EC samples and cells. Circ-SFMBT2 downregulation inhibited EC cell proliferation, invasion and glutamine metabolism. Circ-SFMBT2 targeted miR-107 and the regulation of circ-SFMBT2 was achieved by sponging miR-107. SLC1A5 was a target of miR-107, and it worked as an oncogene in EC cells. MiR-107 retarded the EC progression by downregulating SLC1A5. Circ-SFMBT2 could affect the SLC1A5 expression by targeting miR-107. Circ-SFMBT2 regulated EC progression in vivo by miR-107/SLC1A5 axis. Circ-SFMBT2 was transferred by exosomes in EC cells.

Conclusion
These results suggested that circ-SFMBT2 upregulated the SLC1A5 expression to promote the malignant development of EC by serving as a miR-107 sponge.
Investigation on heroin and cocaine quality in Luxembourg
Authors: Bourmaud Adèle , Dahm Georges , Meys François , Gengler Nicolas , Origer Alain , Schneider Serge 
Published: September 2021

Abstract
Background
Heroin and cocaine are among the most dangerous illicit drugs available and their presence on the market is increasing. These facts have led to the investigation of the quality of heroin and cocaine samples seized in Luxembourg by police and customs but also collected at the national supervised drug consumption facilities.

Methods
Samples obtained from 2019 to 2020 were analyzed to determine their composition and content using GC–MS, HPLC-UV and LC-Q-ToF. The statistical evaluation of concentration changes depending on the source of collection is based on an ANOVA single factor test and a two-tailed t test.

Results
Results showed important differences between seizure and collection sources. For both drugs, customs samples had significantly higher concentrations than police samples and the latter had significantly higher concentrations than samples from drug consumption facilities, whereas for heroin two cutting steps were identified, for cocaine samples only one appears to occur on the local market. Indeed, cocaine samples seized by police consisted of a mixture of low and high concentration samples.

Conclusion
The results show that extensive adulteration with pharmacological active and inactive compounds takes place at local levels, which, however, are different for heroin and cocaine. This knowledge on variability of quality of drugs should be considered in the elaboration of drug and harm prevention strategies.
De-escalation strategies for non-pharmaceutical interventions following infectious disease outbreaks: a rapid review and a proposed dynamic de-escalation framework
Authors: El Bcheraoui Charbel , Müller Sophie Alice , Vaughan Eleanor C , Jansen Andreas , Cook Robert , Hanefeld Johanna 
Published: September 2021

Abstract
Background
The severity of COVID-19, as well as the speed and scale of its spread, has posed a global challenge. Countries around the world have implemented stringent non-pharmaceutical interventions (NPI) to control transmission and prevent health systems from being overwhelmed. These NPI have had profound negative social and economic impacts. With the timeline to worldwide vaccine roll-out being uncertain, governments need to consider to what extent they need to implement and how to de-escalate these NPI. This rapid review collates de-escalation criteria reported in the literature to provide a guide to criteria that could be used as part of de-escalation strategies globally.

Methods
We reviewed literature published since 2000 relating to pandemics and infectious disease outbreaks. The searches included Embase.com (includes Embase and Medline), LitCovid, grey literature searching, reference harvesting and citation tracking. Over 1,700 documents were reviewed, with 39 documents reporting de-escalation criteria included in the final analysis. Concepts retrieved through a thematic analysis of the included documents were interlinked to build a conceptual dynamic de-escalation framework.

Results
We identified 52 de-escalation criteria, the most common of which were clustered under surveillance (cited by 43 documents, 10 criteria e.g. ability to actively monitor confirmed cases and contact tracing), health system capacity (cited by 30 documents, 11 criteria, e.g. ability to treat all patients within normal capacity) and epidemiology (cited by 28 documents, 7 criteria, e.g. number or changes in case numbers).
De-escalation is a gradual and bi-directional process, and resurgence of infections or emergence of variants of concerns can lead to partial or full re-escalation(s) of response and control measures in place. Hence, it is crucial to rely on a robust public health surveillance system.

Conclusions
This rapid review focusing on de-escalation within the context of COVID-19 provides a conceptual framework and a guide to criteria that countries can use to formulate de-escalation plans.
The validity and reliability of Persian version of smartphone addiction questionnaire in Iran
Authors: Shaahmadi Zahra , Jouybari Touraj Ahmadi , Lotfi Bahare , Aghaei Abbas , Gheshlagh Reza Ghanei 
Published: September 2021

Abstract
Background
Smartphone addiction is one of the most important forms of technology addiction that has attracted the attention of all countries around the world. Many studies have been conducted in Iran on cellphone addiction among different groups. There is a necessity to have a native scale for measuring smartphone addiction in particular. Therefore, this study aimed to localize the smartphone addiction questionnaire in Iran (in the Persian language).

Methods
To assess the validity and reliability of the Persian version of the smartphone addiction scale (SAS), the questionnaire was first provided based on the standard back-translation method. Next, content validity ratio (CVR), content validity index (CVI), and face validity was evaluated for translated questionnaire. After making the necessary changes, the questionnaire was given to the community samples and was then reviewed using confirmatory factor analysis of questions grouping. Finally, the reliability of the questionnaire was investigated by the test-retest method.

Results
The CVR and CVI values of all questions were within the acceptable range. Only some of the questions in the original SAS version titled Twitter and Facebook were changed to Instagram and telegram according to experts. Internal consistency and concurrent validity of the questionnaire were confirmed by Cronbach’s alpha of 0.951. The mean correlation coefficient between the responses of the subjects, who received the questionnaire twice, was 0.946 (0.938–0.954). The grouping of questions in the subscales was changed from the original SAS version because the fitting indexes, obtained from the confirmatory factor analysis test (for example CMIN/DF greater than 5 units and RMSEA of approximately 0.07), were not acceptable.

Conclusion
The results showed that the Iranian version of the cellphone addiction questionnaire can be used as a valid, with minimal modification, tool for determining the level of smartphone addiction among Persian speakers.
Sanctioned countries in the global COVID-19 vaccination campaign: the forgotten 70%
Authors: Blanchet Karl , Mallard Grégoire , Moret Erica , Sun Jin 
Published: September 2021

AbstractCOVAX, the global initiative on COVID-19 vaccines, has set the target of achieving a COVID-19 vaccination coverage of up to 30% of the population of 135 countries in 2 years. Here, we argue that COVAX should anticipate important and unforeseen challenges with regard to sanctioned countries. For those, COVAX needs to provide a higher percentage of the vaccines. Otherwise, the problems of vaccination will linger, risking the advent of new variants and preventing an effective global response in reigning the pandemic under control.
Pre-hospital management of penetrating neck injuries: a scoping review of current evidence and guidance
Authors: Simpson Christopher , Tucker Harriet , Hudson Anthony 
Published: September 2021

AbstractPenetrating injuries to the neck pose a unique challenge to clinicians due to the proximity of multiple significant anatomical structures with little protective soft tissue coverage. Injuries to this area, whilst low in incidence, are potentially devastating. Respiratory, vascular, gastro-oesophageal and neurological structures may all be involved, either in isolation or combination. These injuries are particularly difficult to manage in the resource poor, often austere and/or remote, pre-hospital environment. A systematic scoping review of the literature was conducted to evaluate the current available research pertaining to managing this injury profile, prior to the patient arriving in the emergency department. The available research is discussed in sections based on the commonly used trauma management acronym ‘cABCD’ (catastrophic haemorrhage, Airway, Breathing, Circulation, Disability) to facilitate a systematic approach and clinical evaluation familiar to clinicians. Based on the available reviewed evidence, we have proposed a management algorithm for this cohort of patients. From this we plan to instigate a Delphi process to develop a consensus statement on the pre-hospital management of this challenging presentation.
Early versus late awake prone positioning in non-intubated patients with COVID-19
Authors: Kaur Ramandeep , Vines David L. , Mirza Sara , Elshafei Ahmad , Jackson Julie A. , Harnois Lauren J. , Weiss Tyler , Scott J. Brady , Trump Matthew W. , Mogri Idrees , Cerda Flor , Alolaiwat Amnah A. , Miller Amanda R. , Klein Andrew M. , Oetting Trevor W. , Morris Lindsey , Heckart Scott , Capouch Lindsay , He Hangyong , Li Jie 
Published: September 2021

AbstractBackgroundAwake prone positioning (APP) is widely used in the management of patients with coronavirus disease (COVID-19). The primary objective of this study was to compare the outcome of COVID-19 patients who received early versus late APP.MethodsPost hoc analysis of data collected for a randomized controlled trial (ClinicalTrials.gov NCT04325906). Adult patients with acute hypoxemic respiratory failure secondary to COVID-19 who received APP for at least one hour were included. Early prone positioning was defined as APP initiated within 24 h of high-flow nasal cannula (HFNC) start. Primary outcomes were 28-day mortality and intubation rate.ResultsWe included 125 patients (79 male) with a mean age of 62 years. Of them, 92 (73.6%) received early APP and 33 (26.4%) received late APP. Median time from HFNC initiation to APP was 2.25 (0.8–12.82) vs 36.35 (30.2–75.23) hours in the early and late APP group (p < 0.0001), respectively. Average APP duration was 5.07 (2.0–9.05) and 3.0 (1.09–5.64) hours per day in early and late APP group (p < 0.0001), respectively. The early APP group had lower mortality compared to the late APP group (26% vs 45%,p = 0.039), but no difference was found in intubation rate. Advanced age (OR 1.12 [95% CI 1.0–1.95],p = 0.001), intubation (OR 10.65 [95% CI 2.77–40.91],p = 0.001), longer time to initiate APP (OR 1.02 [95% CI 1.0–1.04],p = 0.047) and hydrocortisone use (OR 6.2 [95% CI 1.23–31.1],p = 0.027) were associated with increased mortality.ConclusionsEarly initiation (< 24 h of HFNC use) of APP in acute hypoxemic respiratory failure secondary to COVID-19 improves 28-day survival.Trial registrationClinicalTrials.gov NCT04325906.
Four-factor prothrombin complex concentrate to reduce allogenic blood product transfusion in patients with major trauma, the PROCOAG trial: study protocol for a randomized multicenter double-blind superiority study
Authors: Bouzat Pierre , Bosson Jean-Luc , David Jean-Stéphane , Riou Bruno , Duranteau Jacques , Payen Jean-François ,   on behalf of the PROCOAG study group, Levrat Albrice , Abback Paër-Selim , Duranteau Jacques , Riou Bruno , Garrigue Delphine , Marcotte Guillaume , David Jean-Stéphane , Charbit Jonathan , Asehnoune Karim , Leone Marc , Pottecher Julien , Bouzat Pierre 
Published: September 2021

AbstractBackgroundOptimal management of severe trauma patients with active hemorrhage relies on adequate initial resuscitation. Early administration of coagulation factors improves post-traumatic coagulation disorders, and four-factor prothrombin complex concentrate (PCC) might be useful in this context. Our main hypothesis is that four-factor PCC in addition to a massive transfusion protocol decreases blood product consumption at day 1 in severe trauma patients with major bleeding.MethodsThis is a prospective, randomized, multicenter, double-blind, parallel, controlled superiority trial. Eligible patients are trauma patients with major bleeding admitted to a French level-I trauma center. Patients randomized in the treatment arm receive 1 mL/kg (25 IU/ml of Factor IX/Kg) four-factor PCC within 1-h post-admission while patients randomized in the controlled group receive 1 mL/kg of saline solution 0.9% as a placebo. Treatments are given as soon as possible using syringe pumps (120 mL/h). The primary endpoint is the amount of blood products transfused in the first 24 h post-admission (including red blood cells, frozen fresh plasma, and platelets). The secondary endpoints are the amount of each blood product transfused in the first 24 h, time to achieve prothrombin time ratio < 1.5, time to hemostasis, number of thrombo-embolic events at 28 days, mortality at 24 h and 28 days, number of intensive care unit-free days, number of ventilator-free days, number of hospital-free days within the first 28 days, hospitalization status at day 28, Glasgow outcome scale extended for patients with brain lesions on initial cerebral imaging, and cost of each strategy at days 8 and 28. Inclusions have started in December 2017 and are expected to be complete by June 2021.DiscussionIf PCC reduces total blood consumption at day 1 after severe trauma, this therapy, in adjunction to a classic massive transfusion protocol, may be used empirically on admission in patients at risk of massive transfusion to enhance coagulation. Moreover, this treatment may decrease blood product-related complications and may improve clinical outcomes after post-traumatic hemorrhage.Trial registrationClinicalTrials.govNCT03218722. Registered on July 14, 2017
Improving time to palliative care review with predictive modeling in an inpatient adult population: study protocol for a stepped-wedge, pragmatic randomized controlled trial
Authors: Wilson Patrick M. , Philpot Lindsey M. , Ramar Priya , Storlie Curtis B. , Strand Jacob , Morgan Alisha A. , Asai Shusaku W. , Ebbert Jon O. , Herasevich Vitaly D. , Soleimani Jalal , Pickering Brian W. 
Published: September 2021

Abstract
Background
Palliative care is a medical specialty centered on improving the quality of life (QOL) of patients with complex or life-threatening illnesses. The need for palliative care is increasing and with that the rigorous testing of triage tools that can be used quickly and reliably to identify patients that may benefit from palliative care.

Methods
To that aim, we will conduct a two-armed stepped-wedge cluster randomized trial rolled out to two inpatient hospitals to evaluate whether a machine learning algorithm accurately identifies patients who may benefit from a comprehensive review by a palliative care specialist and decreases time to receiving a palliative care consult in hospital. This is a single-center study which will be conducted from August 2019 to November 2020 at Saint Mary’s Hospital & Methodist Hospital both within Mayo Clinic Rochester in Minnesota. Clusters will be nursing units which will be chosen to be a mix of complex patients from Cardiology, Critical Care, and Oncology and had previously established relationships with palliative medicine. The stepped wedge design will have 12 units allocated to a design matrix of 5 treatment wedges. Each wedge will last 75 days resulting in a study period of 12 months of recruitment unless otherwise specified. Data will be analyzed with Bayesian hierarchical models with credible intervals denoting statistical significance.

Discussion
This intervention offers a pragmatic approach to delivering specialty palliative care to hospital patients in need using machine learning, thereby leading to high value care and improved outcomes. It is not enough for AI to be utilized by simply publishing research showing predictive performance; clinical trials demonstrating better outcomes are critically needed. Furthermore, the deployment of an AI algorithm is a complex process that requires multiple teams with varying skill sets. To evaluate a deployed AI, a pragmatic clinical trial can accommodate the difficulties of clinical practice while retaining scientific rigor.

Trial registration
ClinicalTrials.gov NCT03976297. Registered on 6 June 2019, prior to trial start.