bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of different positive end-expiratory pressure selection strategies with all-cause mortality in adult patients with acute respiratory distress syndrome
Authors: Tisminetzky Manuel , Dianti Jose , Ferreyro Bruno L. , Angriman Federico , Del Sorbo Lorenzo , Sud Sachin , Talmor Daniel , Fan Eddy , Ferguson Niall D. , Serpa Neto Ary , Adhikari Neill K. J. , Goligher Ewan C. 
Published: August 2021

AbstractBackgroundThe acute respiratory distress syndrome (ARDS) has high morbidity and mortality. Positive end-expiratory pressure (PEEP) is commonly used in patients with ARDS but the best method to select the optimal PEEP level and reduce all-cause mortality is unclear. The primary objective of this network meta-analysis is to summarize the available evidence and to compare the effect of different PEEP selection strategies on all-cause mortality in adult patients with ARDS.MethodsWe will search MEDLINE, Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and LILACS from inception onwards for randomized controlled trials assessing the effect of PEEP selection strategies in adult patients with moderate to severe ARDS. We will exclude studies that did not use a lung-protective ventilation approach as part of the comparator or intervention strategy. The primary outcome will be all-cause mortality (at the longest available follow-up and up to 90 days). Secondary outcomes will include barotrauma, ventilator-free days, intensive care unit and hospital length of stay, and changes in oxygenation. Two reviewers will independently screen all citations, full-text articles, and extract study-data. We will assess the risk of bias for each of the outcomes using version 2 of the Cochrane risk of bias tool for randomized controlled trials. If feasible, Bayesian network meta-analyses will be conducted to obtain pooled estimates of all potential head-to-head comparisons. We will report pairwise and network meta-analysis treatment effect estimates as risk ratios and risk differences, together with the associated 95% credible intervals. We will assess certainty in effect estimates using GRADE methodology.DiscussionThe present study will inform clinical decision-making for adult patients with ARDS and will improve our understanding of the limitations of the available literature assessing PEEP selection strategies. Finally, this information may also inform the design of future randomized trials, including the selection of interventions, comparators, and predictive enrichment strategies.Trial registrationPROSPERO 2020CRD42020193302.
Identifying and addressing the anthropogenic drivers of global change in the North Sea: a systematic map protocol
Authors: Moullec Fabien , Asselot Rémy , Auch Dominik , Blöcker Alexandra M. , Börner Gregor , Färber Leonie , Ofelio Claudia , Petzold Jan , Santelia Maria Elisabetta , Schwermer Heike , Sguotti Camilla , Steidle Laurin , Tams Verena , Pellerin Félix 
Published: August 2021

AbstractBackgroundAnthropogenic pressures on marine ecosystems have increased over the last 75 years and are expected to intensify in the future with potentially dramatic cascading consequences for human societies. It is therefore crucial to rebuild marine life-support systems and aim for future healthy ecosystems. Nowadays, there is a reasonable understanding of the impacts of human pressure on marine ecosystems; but no studies have drawn an integrative retrospective analysis of the marine research on the topic. A systematic consolidation of the literature is therefore needed to clearly describe the scientific knowledge clusters and gaps as well as to promote a new era of integrative marine science and management. We focus on the five direct anthropogenic drivers of biodiversity loss defined by the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES): (1) climate change; (2) direct exploitation; (3) pollution; (4) biological invasions; and (5) sea-use change. Our systematic map’s regional focus lies on the North Sea, which is among the most impacted marine ecosystems around the globe. The goal of the present study is to produce the first comprehensive overview of how marine research on anthropogenic drivers in the North Sea has grown and changed over the past 75 years. Ultimately, this systematic map will highlight the most urgent challenges facing the North Sea research domain.MethodsThe search will be restricted to peer-reviewed articles, reviews, meta-analyses, book chapters, book reviews, proceeding papers and grey literature using the most relevant search engines for literature published between 1945 and 2020. All authors will participate in the adjustment of the search in order to consider all relevant studies analyzing the effect of the direct anthropogenic drivers on the North Sea marine ecosystem. The references will be screened for relevance according to a predefined set of eligibility/ineligibility criteria by a pool of six trained reviewers. At stage one, each abstract and title will be independently screened by two reviewers. At stage two, potentially relevant references will be screened in full text by two independent reviewers. Subsequently, we will extract a suite of descriptive meta-data and basic information of the relevant references using the SysRev platform. The systematic map database composed will provide the foundation for an interactive geographical evidence map. Moreover, we will summarize our findings with cross-validation plots, heat maps, descriptive statistics, and a publicly available narrative synthesis. The aim of our visualization tools is to ensure that our findings are easily understandable by a broad audience.
Administration of a selective retinoic acid receptor-γ agonist improves neuromuscular strength in a rodent model of volumetric muscle loss
Authors: Whitely Michael E. , Collins Patrick B. , Iwamoto Masahiro , Wenke Joseph C. 
Published: August 2021

Abstract
Purpose
Volumetric muscle loss is a uniquely challenging pathology that results in irrecoverable functional deficits. Furthermore, a breakthrough drug or bioactive factor has yet to be established that adequately improves repair of these severe skeletal muscle injuries. This study sought to assess the ability of an orally administered selective retinoic acid receptor-γ agonist, palovarotene, to improve recovery of neuromuscular strength in a rat model of volumetric muscle loss.

Methods
An irrecoverable, full thickness defect was created in the tibialis anterior muscle of Lewis rats and animals were survived for 4 weeks. Functional recovery of the tibialis anterior muscle was assessed in vivo via neural stimulation and determination of peak isometric torque. Histological staining was performed to qualitatively assess fibrous scarring of the defect site.

Results
Treatment with the selective retinoic acid receptor-γ agonist, palovarotene, resulted in a 38% improvement of peak isometric torque in volumetric muscle loss affected limbs after 4 weeks of healing compared to untreated controls. Additionally, preliminary histological assessment suggests that oral administration of palovarotene reduced fibrous scarring at the defect site.

Conclusions
These results highlight the potential role of selective retinoic acid receptor-γ agonists in the design of regenerative medicine platforms to maximize skeletal muscle healing. Additional studies are needed to further elucidate cellular responses, optimize therapeutic delivery, and characterize synergistic potential with adjunct therapies.
Institutionalization of transnationalizing political parties: the case of the Conservative People’s Party of Estonia
Authors: Jakobson Mari-Liis , Saarts Tõnis , Kalev Leif 
Published: August 2021

AbstractWhile party institutionalization research has advanced notably in the recent years, the institutionalization of political parties that extend their organizations abroad (i.e. transnationalizing parties) has remained an academically uncharted territory. This article draws on party institutionalization literature and analyses the particularities of institutionalization in transnationalizing parties. The findings suggest that transnational institutionalization takes place simultaneously on multiple levels (local, national and transnational) and is distinctly interactive, placing crucial importance on the activities and responsiveness of both the central party organization as well as the extraterritorial branches. The internal dimensions of institutionalization can be notably affected by the territorially and temporally scattered nature of emigrant communities and by the sense of inclusion provided to the activists. The external dimensions of transnational institutionalization involve a wider variety of actors than institutionalization on the national level and can also be more challenging due to the more contingent socialization patterns and interest in politics of transnational migrants. Transnational institutionalization of political parties is relevant to the parties and their continuous electoral success, but also for transnational migrant communities and impact of their political participation.
Saving lives during the COVID-19 pandemic: the benefits of the first Swiss lockdown
Authors: Gatti Nicolò , Retali Beatrice 
Published: August 2021

AbstractThe implementation of a lockdown to control the spread of the COVID-19 pandemic has led to a strong economic and political debate in several countries. This makes it crucial to shed light on the actual benefits of such kind of policy. To this purpose, we focus on the Swiss lockdown during the first wave of COVID-19 infections and estimate the number of potentially saved lives. To predict the number of deaths in the absence of any restrictive measure, we develop a novel age-structured SIRDC model which accounts for age-specific endogenous behavioral responses and for seasonal patterns in the spread of the virus. Including the additional fatalities which would have materialized because of the shortage of healthcare resources, our estimates suggest that the lockdown prevented more than 11,200 deaths between March and the beginning of September 2020.
The effect of radiation exposure and storage time on the degree of conversion and flexural strength of different resin composites
Authors: Taher Ragia M. , Moharam Lamiaa M. , Amin Amin E. , Zaazou Mohamed H. , El-Askary Farid S. , Ibrahim Mokhtar N. 
Published: August 2021

Abstract
Background
This study was conducted to evaluate the effect of radiation exposure and storage time on the degree of conversion (DC%) and flexural strength (FS) of three different resin composites. In total, 90 disk-shaped, and 360 rod-shaped composite specimens were prepared to evaluate the DC% and FS, respectively. Specimens were divided into 18 groups (DC%: n = 5 and FS: n = 20) according to the three experimental factors of the study: 1—Radiation (no-exposure and exposure), 2—Resin composite material (Herculite XRV Ultra, Z250 XT and Grandio), and 3—Storage time (24 h in distilled water, 3-m and 6-m in 70% ethanol). Fourier transform infrared spectrometer (FTIR) was used to determine the DC%. For FS, the specimens were subjected to a three-point bending test at 1 mm/min crosshead speed. Data were analyzed using three-way ANOVA/Tukey HSD test. Significant level was set at P = 0.05.

Results
For DC%, there was no significant difference between no-radiation exposure and radiation exposure (P > 0.05). Herculite XRV Ultra revealed the highest statistically significant DC% (P < 0.05). The 24-h storage time revealed the least significant DC% (P < 0.05). For FS, radiation exposure showed a statistically significant higher value compared to no-radiation exposure (P < 0.05). Herculite XRV Ultra showed the least FS value (P < 0.05). The 24-h storage time showed the highest significant value (P < 0.05).

Conclusions
Radiation exposure has no significant impact on the DC% of the different resin composites, but it has a significant positive effect on the FS. Storage time had a significant effect on both DC% and FS.
Development, optimization and pharmacokinetic evaluation of biphasic extended-release osmotic drug delivery system of trospium chloride for promising application in treatment of overactive bladder
Authors: Gundu Ramakanth , Pekamwar Sanjay , Shelke Santosh , Kulkarni Deepak , Shep Santosh 
Published: August 2021

Abstract
Background
The research was aimed with an approach to formulate biphasic extended-release system of trospium chloride resulting in controlled release of drug up to 24 h with prospects of better control on urinary frequency, efficacy, tolerability, and improved patient compliance. The push–pull osmotic pump (PPOP) bi-layered tablet of trospium chloride (60 mg) was developed with the use of immediate-release polymers in the pull layer (30 mg drug) and polyethylene oxide in the push layer (remaining 30 mg drug). The tablet was formulated by compression after non-aqueous granulation, seal coating, and semipermeable coating. The tablet prepared was laser drilled to create an orifice for drug release.

Results
Comparative in vitro dissolution and in vivo pharmacokinetic analysis of available marketed formulations demonstrated the complete drug release within 16–18 h; hence the developed biphasic extended-release system has its great importance as it provides zero-order release up to 24 h.

Conclusions
The developed biphasic extended-release drug delivery system of trospium chloride provides the drug release for 24 h with effective plasma concentration in comparison with the available marketed formulation. Extended release of drug from the developed formulation provides scope for its promising application in the treatment of overactive bladder (OAB).
BDV Syndrome: an Emerging Syndrome With Profound Obesity and Neurodevelopmental Delay Resembling Prader-Willi Syndrome
Authors: Bosch Elisabeth , Hebebrand Moritz , Popp Bernt , Penger Theresa , Behring Bettina , Cox Helen , Towner Shelley , Kraus Cornelia , Wilson William G , Khan Shagufta , Krumbiegel Mandy , Ekici Arif B , Uebe Steffen , Trollmann Regina , Woelfle Joachim , Reis André , Vasileiou Georgia 
Published: August 2021

Abstract

Context
CPE encodes carboxypeptidase E, an enzyme that converts proneuropeptides and propeptide hormones to bioactive forms. It is widely expressed in the endocrine and central nervous system. To date, 4 individuals from 2 families with core clinical features including morbid obesity, neurodevelopmental delay, and hypogonadotropic hypogonadism, harboring biallelic loss-of-function (LoF) CPE variants, have been reported.

Objective
We describe 4 affected individuals from 3 unrelated consanguineous families, 2 siblings of Syrian, 1 of Egyptian, and 1 of Pakistani descent, all harboring novel homozygous CPE LoF variants.

Methods
After excluding Prader-Willi syndrome (PWS), exome sequencing was performed in both Syrian siblings. The variants identified in the other 2 individuals were reported as research variants in a large-scale exome study and in the ClinVar database. Computational modeling of all possible missense alterations allowed assessing CPE tolerance to missense variants.

Results
All affected individuals were severely obese with neurodevelopmental delay and other endocrine anomalies. Three individuals from 2 families shared the same CPE homozygous truncating variant c.361C &gt; T, p.(Arg121*), while the fourth carried the c.994del, p.(Ser333Alafs*22) variant. Comparison of clinical features with previously described cases and standardization according to the Human Phenotype Ontology terms indicated a recognizable clinical phenotype, which we termed Blakemore-Durmaz-Vasileiou (BDV) syndrome. Computational analysis indicated high conservation of CPE domains and intolerance to missense changes.

Conclusion
Biallelic truncating CPE variants are associated with BDV syndrome, a clinically recognizable monogenic recessive syndrome with childhood-onset obesity, neurodevelopmental delay, hypogonadotropic hypogonadism, and hypothyroidism. BDV syndrome resembles PWS. Our findings suggest missense variants may also be clinically relevant.
Vitamin D Levels Are Associated With Blood Glucose and BMI in COVID-19 Patients, Predicting Disease Severity
Authors: di Filippo Luigi , Allora Agnese , Doga Mauro , Formenti Anna Maria , Locatelli Massimo , Rovere Querini Patrizia , Frara Stefano , Giustina Andrea 
Published: August 2021

Abstract

Context
A high prevalence of vitamin D (VD) deficiency in COVID-19 patients has been reported and hypothesized to increase COVID-19 severity likely because of its negative impact on immune and inflammatory responses. Furthermore, clear associations between hypovitaminosis D and fat body mass excess and diabetes, factors associated with COVID-19 severity, have been widely recognized.

Objective
The aim of this study was to evaluate in COVID-19 patients the relationship between VD levels and inflammatory response, body mass index (BMI), blood glucose (GLU), and disease severity.

Methods
Patients admitted to San Raffaele-Hospital for COVID-19 were enrolled in this study, excluding those with comorbidities and therapies influencing VD metabolism. 25-Hydroxyvitamin D levels, plasma GLU levels, BMI, and inflammatory parameters were evaluated at admission.

Results
A total of 88 patients were included. Median VD level was 16.3 ng/mL and VD deficiency was found in 68.2% of patients. VD deficiency was found more frequently in male patients and in those affected by severe COVID-19. Regression analyses showed a positive correlation between VD and PaO2/FiO2 ratio, and negative correlations between VD and plasma GLU, BMI, neutrophil/lymphocyte ratio, C-reactive protein, and interleukin 6. Patients with both hypovitaminosis D and diabetes mellitus, as well those with hypovitaminosis D and overweight, were more frequently affected by a severe disease with worse inflammatory response and respiratory parameters, compared to those without or just one of these conditions.

Conclusion
We showed, for the first-time, a strict association of VD levels with blood GLU and BMI in COVID-19 patients. VD deficiency might be a novel common pathophysiological mechanism involved in the detrimental effect of hyperglycemia and adiposity on disease severity.
Bioluminescent imaging in induced mouse models of endometriosis reveals differences in four model variations
Authors: Dorning Ashley , Dhami Priya , Panir Kavita , Hogg Chloe , Park Emma , Ferguson Gregory D. , Hargrove Diane , Karras James , Horne Andrew W. , Greaves Erin 
Published: August 2021

ABSTRACT
Our understanding of the aetiology and pathophysiology of endometriosis remains limited. Disease modelling in the field is problematic as many versions of induced mouse models of endometriosis exist. We integrated bioluminescent imaging of ‘lesions’ generated using luciferase-expressing donor mice. We compared longitudinal bioluminescence and histology of lesions, sensory behaviour of mice with induced endometriosis and the impact of the gonadotropin-releasing hormone antagonist Cetrorelix on lesion regression and sensory behaviour. Four models of endometriosis were tested. We found that the nature of the donor uterine material was a key determinant of how chronic the lesions were, as well as their cellular composition. The severity of pain-like behaviour also varied across models. Although Cetrorelix significantly reduced lesion bioluminescence in all models, it had varying impacts on pain-like behaviour. Collectively, our results demonstrate key differences in the progression of the ‘disease’ across different mouse models of endometriosis. We propose that validation and testing in multiple models, each of which may be representative of the different subtypes/heterogeneity observed in women, should become a standard approach to discovery science in the field of endometriosis.
Lamin regulates the dietary restriction response via the mTOR pathway in Caenorhabditis elegans
Authors: Charar Chayki , Metsuyanim-Cohen Sally , Bar Daniel Z. 
Published: August 2021

ABSTRACT
Animals subjected to dietary restriction (DR) have reduced body size, low fecundity, slower development, lower fat content and longer life span. We identified lamin as a regulator of multiple dietary restriction phenotypes. Downregulation of lmn-1, the single Caenorhabditis elegans lamin gene, increased animal size and fat content specifically in DR animals. The LMN-1 protein acts in the mTOR pathway, upstream of RAPTOR and S6 kinase β1 (S6K), a key component of and target of the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1), respectively. DR excludes the mTORC1 activator RAGC-1 from the nucleus. Downregulation of lmn-1 restores RAGC-1 to the nucleus, a necessary step for the activation of the mTOR pathway. These findings further link lamin to metabolic regulation.
Whole genome sequencing of colonies derived from cannabis flowers and the impact of media selection on benchmarking total yeast and mold detection tools
Authors: McKernan Kevin , Helbert Yvonne , Kane Liam , Houde Nathan , Zhang Lei , McLaughlin Stephen 
Published: August 2021

Background: Cannabis products are subjected to microbial testing for human pathogenic fungi and bacteria. These testing requirements often rely on non-specific colony forming unit (CFU/g) specifications without clarity on which medium, selection or growth times are required. We performed whole genome sequencing to assess the specificity of colony forming units (CFU) derived from three different plating media: Potato Dextrose Agar (PDA), PDA with chloramphenicol and Dichloran Rose Bengal with chloramphenicol (DRBC). Methods: Colonies were isolated from each medium type and their whole genomes sequenced to identify the diversity of microbes present on each medium selection. Fungal Internal Transcribed Spacer (ITS3) and Bacterial 16S RNA(16S) quantitative polymerase chain reactions (qPCR) were performed, to correlate these CFUs with fungi- and bacterial- specific qPCR. Results: Each plating medium displayed a ten-fold difference in CFU counts. PDA with chloramphenicol showed the highest diversity and the highest concordance with whole genome sequencing. According to ITS3 and 16S qPCR confirmed with whole genome sequencing, DRBC under counted yeast and mold while PDA without chloramphenicol over counted CFUs due to bacterial growth without selection. Conclusions: Colony Forming Unit regulations lack specificity. Each medium produces significant differences in CFU counts. These are further dependent on subjective interpretation, failure to culture most microbes, and poor selection between bacteria and fungi. Given the most human pathogenic microbes found on cannabis are endophytes which culture fails to detect, molecular methods offer a solution to this long-standing quantification problem in the cannabis testing field.