bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upregulation of ERK-EGR1-heparanase axis by HDAC inhibitors provides targets for rational therapeutic intervention in synovial sarcoma
Authors: Lanzi Cinzia , Favini Enrica , Dal Bo Laura , Tortoreto Monica , Arrighetti Noemi , Zaffaroni Nadia , Cassinelli Giuliana 
Published: December 2021

Abstract
Background
Synovial sarcoma (SS) is an aggressive soft tissue tumor with limited therapeutic options in advanced stage. SS18-SSX fusion oncogenes, which are the hallmarks of SS, cause epigenetic rewiring involving histone deacetylases (HDACs). Promising preclinical studies supporting HDAC targeting for SS treatment were not reflected in clinical trials with HDAC inhibitor (HDACi) monotherapies. We investigated pathways implicated in SS cell response to HDACi to identify vulnerabilities exploitable in combination treatments and improve the therapeutic efficacy of HDACi-based regimens.

Methods
Antiproliferative and proapoptotic effects of the HDACi SAHA and FK228 were examined in SS cell lines in parallel with biochemical and molecular analyses to bring out cytoprotective pathways. Treatments combining HDACi with drugs targeting HDACi-activated prosurvival pathways were tested in functional assays in vitro and in a SS orthotopic xenograft model. Molecular mechanisms underlying synergisms were investigated in SS cells through pharmacological and gene silencing approaches and validated by qRT-PCR and Western blotting.

Results
SS cell response to HDACi was consistently characterized by activation of a cytoprotective and auto-sustaining axis involving ERKs, EGR1, and the β-endoglycosidase heparanase, a well recognized pleiotropic player in tumorigenesis and disease progression. HDAC inhibition was shown to upregulate heparanase by inducing expression of the positive regulator EGR1 and by hampering negative regulation by p53 through its acetylation. Interception of HDACi-induced ERK-EGR1-heparanase pathway by cell co-treatment with a MEK inhibitor (trametinib) or a heparanase inhibitor (SST0001/roneparstat) enhanced antiproliferative and pro-apoptotic effects. HDAC and heparanase inhibitors had opposite effects on histone acetylation and nuclear heparanase levels. The combination of SAHA with SST0001 prevented the upregulation of ERK-EGR1-heparanase induced by the HDACi and promoted caspase-dependent cell death. In vivo, the combined treatment with SAHA and SST0001 potentiated the antitumor efficacy against the CME-1 orthotopic SS model as compared to single agent administration.

Conclusions
The present study provides preclinical rationale and mechanistic insights into drug combinatory strategies based on the use of ERK pathway and heparanase inhibitors to improve the efficacy of HDACi-based antitumor therapies in SS. The involvement of classes of agents already clinically available, or under clinical evaluation, indicates the transferability potential of the proposed approaches.
Point-of-care ultrasound in cardiorespiratory arrest (POCUS-CA): narrative review article
Authors: Ávila-Reyes Diana , Acevedo-Cardona Andrés O. , Gómez-González José F. , Echeverry-Piedrahita David R. , Aguirre-Flórez Mateo , Giraldo-Diaconeasa Adrian 
Published: December 2021

AbstractThe POCUS-CA (Point-of-care ultrasound in cardiac arrest) is a diagnostic tool in the Intensive Care Unit and Emergency Department setting. The literature indicates that in the patient in a cardiorespiratory arrest it can provide information of the etiology of the arrest in patients with non-defibrillable rhythms, assess the quality of compressions during cardiopulmonary resuscitation (CPR), and define prognosis of survival according to specific findings and, thus, assist the clinician in decision-making during resuscitation. This narrative review of the literature aims to expose the usefulness of ultrasound in the setting of cardiorespiratory arrest as a tool that allows making a rapid diagnosis and making decisions about reversible causes of this entity. More studies are needed to support the evidence to make ultrasound part of the resuscitation algorithms. Teamwork during cardiopulmonary resuscitation and the inclusion of ultrasound in a multidisciplinary approach is important to achieve a favorable clinical outcome.
Repetitive and restricted behaviours and anxiety in autism spectrum disorder: protocol for a systematic review and meta-analysis
Authors: Sellick Tegan , Ure Alexandra , Williams Katrina 
Published: December 2021

Abstract
Background
Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by persistent deficits in social functioning and the presence of restricted and repetitive behaviours (RRBs). RRBs refer to four subtypes of behaviour including repetitive movements, speech, or use of objects; insistence on sameness; restricted interests; and sensory processing abnormalities. Many individuals with ASD also experience anxiety, which compounds ASD-related difficulties and inhibits daily functioning. RRBs have been found to be positively associated with anxiety; however, our understanding of the interplay between RRB subtypes and anxiety remains unclear. Thus, the current review aims to clarify the association between RRBs and anxiety by conducting a systematic review and meta-analysis.

Methods
To identify relevant studies, we will search five databases: CINAHL Plus, Cochrane Central Register of Controlled Trials, Ovid MEDLINE, PsycINFO, and Scopus. Articles included in the review will have their titles, abstracts, and full texts reviewed by two independent authors and their methodological quality assessed via the modified Newcastle-Ottawa Scale. Random-effects meta-analyses will then be conducted to calculate the pooled association between RRB subtypes and anxiety. Sensitivity analyses will also be conducted to assess the potential impact of bias, missing data, outliers, and methodological differences on this relationship. Additionally, this review will collate the factors which may influence the anxiety-RRB relationship to help identify who is most vulnerable to developing anxiety.

Discussion
This will be the first review to examine the association between the four subtypes of RRBs and anxiety in individuals with ASD. Understanding this relationship, and the factors associated with this, may help clinicians understand the different underpinnings and presentations of anxiety within this population with potential implications for assessment and treatment.

Systematic review registration
PROSPERO CRD42020185434
Appropriate number of observations for determining hand hygiene compliance among healthcare workers
Authors: Park Se Yoon , Park Suyeon , Hwang Beom Seuk , Lee Eunjung , Kim Tae Hyong , Won Sungho 
Published: December 2021

AbstractWe sought to determine the minimum number of observations needed to determine hand hygiene (HH) compliance among healthcare workers. The study was conducted at a referral hospital in South Korea. We retrospectively analyzed the result of HH monitoring from January to December 2018. HH compliance was calculated by dividing the number of observed HH actions by the total number of opportunities. Optimal HH compliance rates were calculated based on adherence to the six-step technique recommended by the World Health Organization. The minimum number of required observations (n) was calculated by the following equation using overall mean value (ρ), absolute precision (d), and confidence interval (CI) (1 − α) [the equation: $${\text{n}} \ge Z_{\alpha /2}^{2} \times \rho \times \left( {1 - \rho } \right)/d^{2}$$

n
≥

Z

α
/
2

2

×
ρ
×

1
-
ρ

/

d
2

]. We considered ds of 5%, 10%, 20%, and 30%, with CIs of 99%, 95%, and 90%. During the study period, 8791 HH opportunities among 1168 healthcare workers were monitored. Mean HH compliance and optimal HH compliance rates were 80.3% and 59.7%, respectively. The minimum number of observations required to determine HH compliance rates ranged from 2 ($$d$$
d
: 30%, CI: 90%) to 624 ($$d$$
d
: 5%, CI: 99%), and that for optimal HH compliance ranged from 5 ($$d$$
d
: 30%, CI: 90%) to 642 ($$d$$
d
: 5%, CI: 99%). Therefore, we found that our hospital required at least five observations to determine optimal HH compliance.
Poultry gut health – microbiome functions, environmental impacts, microbiome engineering and advancements in characterization technologies
Authors: Aruwa Christiana Eleojo , Pillay Charlene , Nyaga Martin M. , Sabiu Saheed 
Published: December 2021

AbstractThe gastrointestinal tract (GIT) health impacts animal productivity. The poultry microbiome has functions which range from protection against pathogens and nutrients production, to host immune system maturation. Fluctuations in the microbiome have also been linked to prevailing environmental conditions. Healthy poultry birds possess a natural resistance to infection. However, the exploration of environmental impacts and other relevant factors on poultry growth and health have been underplayed. Since good performance and growth rate are central to animal production, the host-microbiome relationship remains integral. Prior to the emergence of metagenomic techniques, conventional methods for poultry microbiome studies were used and were low-throughput and associated with insufficient genomic data and high cost of sequencing. Fortunately, the advent of high-throughput sequencing platforms have circumvented some of these shortfalls and paved the way for increased studies on the poultry gut microbiome diversity and functions. Here, we give an up-to-date review on the impact of varied environments on microbiome profile, as well as microbiome engineering and microbiome technology advancements. It is hoped that this paper will provide invaluable information that could guide and inspire further studies on the lingering pertinent questions about the poultry microbiome.
Pharmacists’ perceptions and attitudes toward drug importation into the State of Florida
Authors: Hertig John B. , Jochem Jade M. , Long Allissa M. 
Published: December 2021

Abstract
Background
The Department of Health and Human Services and the Food and Drug Administration released the Safe Importation Action Plan in July 2020 detailing methods to import medicines from Canada to combat increasing drug costs. In November 2020, Florida became the first state in the United States to create and propose an importation plan from Canada. This study examines the proposal submitted by Florida, Florida pharmacists’ perceptions of the program on patient safety, and Florida pharmacists’ thoughts on the pharmacy operational impact.

Methods
This was a cross-sectional study utilizing an electronic questionnaire sent to pharmacist members of the Florida Pharmacy Association. The survey incorporated closed-ended and open-ended questions. The results from the study were reported and analyzed through descriptive statistics, qualitative and quantitative data.

Results
Two-hundred and forty-four pharmacists responded to the survey. Of those respondents, 25% stated they had no knowledge about Florida’s drug importation plan. Less than 12% of respondents stated they would trust the safety and quality of imported medicines. Seventy percent of pharmacists expressed concerns regarding the changes required in pharmacy operations to increase medicine safety. About half of the respondents questioned whether this plan would promote cost-savings as intended.

Conclusion
Florida pharmacists believe the drug importation plan does not address all aspects of patient and medicine safety and expressed concerns regarding logistical operations of a pharmacy. This article highlights those concerns and acts as a summons to action.
The effect of inbreeding, body size and morphology on health in dog breeds
Authors: Bannasch Danika , Famula Thomas , Donner Jonas , Anderson Heidi , Honkanen Leena , Batcher Kevin , Safra Noa , Thomasy Sara , Rebhun Robert 
Published: December 2021

AbstractBackgroundDog breeds are known for their distinctive body shape, size, coat color, head type and behaviors, features that are relatively similar across members of a breed. Unfortunately, dog breeds are also characterized by distinct predispositions to disease. We explored the relationships between inbreeding, morphology and health using genotype based inbreeding estimates, body weight and insurance data for morbidity.ResultsThe average inbreeding based on genotype across 227 breeds was Fadj = 0.249 (95% CI 0.235–0.263). There were significant differences in morbidity between breeds with low and high inbreeding (H = 16.49,P = 0.0004). There was also a significant difference in morbidity between brachycephalic breeds and non-brachycephalic breeds (P = 0.0048) and between functionally distinct groups of breeds (H = 14.95P < 0.0001). Morbidity was modeled using robust regression analysis and both body weight (P < 0.0001) and inbreeding (P = 0.013) were significant (r2 = 0.77). Smaller less inbred breeds were healthier than larger more inbred breeds.ConclusionsIn this study, body size and inbreeding along with deleterious morphologies contributed to increases in necessary health care in dogs.
High level of extra-pair paternity in the socially monogamous Marsh Tits (Poecile palustris)
Authors: Wang Juan , Wei Yanhui , Zhang Lei , Jiang Yiting , Li Keke , Wan Dongmei 
Published: December 2021

Abstract
Background
Extra-pair copulation behavior has been widely studied among socially monogamous birds. Many species revealed high rates of extra-pair paternity. But few of the studies have been carried out in the Asian population.

Methods
From 2012 to 2019, we explored the extra-pair paternity of Marsh Tits (Poecile palustris) in Xianrendong National Nature Reserve, Liaoning Province, China. During the study, adult Marsh Tits were captured with mist nets and parental birds, with nest-box traps. Blood samples were taken from the brachial vein. Parentage analyses were carried out using nine highly variable microsatellite loci through Cervus 3.0 software and maximum likelihood approach.

Results
Forty-nine offspring (15.08%) from 20 nests (45.45%) were the results of extra-pair fertilization out of a total of 325 offspring in 44 nests. The average extra-pair offspring ratio was 33.54%, with a set varying from 11.11 to 71.43%. Nine extra-pair fathers had been successfully identified, four of whom were the close neighbors of the focus nest while the nests of the remaining five were relatively far. No significant difference was found in the genetic similarity between the social and extra-pair mates of the female, nor in the heterozygosis among the maternal half-siblings.

Conclusions
In general, our study proved that the extra-pair paternity in Marsh Tits and its extra-pair mating is independent of the genetic compatibility hypothesis. This complements the understudied bird’s extra-pair paternity in Asian area and contributes to the comprehensive insight of birds’ extra-pair paternity behaviors.
Was Chagas disease responsible for Darwin’s illness? The overlooked eco-epidemiological context in Chile
Authors: Botto-Mahan Carezza , Medel Rodrigo 
Published: December 2021

AbstractThe source of Darwin’s illness has been a contentious issue in the literature for almost 70 years. Different causal factors have been invoked to account for his symptoms, including Chagas disease. The Chagas hypothesis is based upon Darwin’s diary, in which he narrates his experience with kissing bugs, the main vector of the protozoan Trypanosoma cruzi, the etiological agent of Chagas disease. In this contribution, we examine the consistency of the “Chagas disease hypothesis” in the light of current ecological and epidemiological knowledge of the disease in Chile. According to his diary and letters, during his overland trips, Darwin slept in rural houses and outdoors for 128 days in a “hyperendemic” area for Chagas disease, more than exposing him to kissing bugs. This observation conveys a likely additional source of infection than previously considered, which might reinforce the idea that Chagas disease contributed to Darwin’s manifest physical deterioration.
Analysis of childhood overweight and obesity in Namibia using spatio-temporal quantile interval models
Authors: Mtambo Owen Paweni Loss , Debusho Legesse Kassa 
Published: December 2021

AbstractThe global prevalence of overweight (including obesity) in children under 5 years of age was 7% in 2012, and it is expected to rise to 11% by the year 2025. The main objective of this study was to fit spatio-temporal quantile interval regression models for childhood overweight (including obesity) in Namibia from 2000 to 2013 using fully Bayesian inference implemented in R-INLA package in R version 3.5.1. All the available Demographic and Health Survey (DHS) datasets for Namibia since 2000 were used in this study. Significant determinants of childhood overweight (including obesity) ranged from socio-demographic factors to child and maternal factors. Child age and preceding birth interval had significant nonlinear effects on childhood overweight (including obesity). Furthermore, we observed significant spatial and temporal effects on childhood overweight (including obesity) in Namibia between 2000 and 2013. To achieve the World Health Organisation (WHO) global nutrition target 2025 in Namibia, the existing scaling-up nutrition programme and childhood malnutrition policy makers in this country may consider interventions based on socio-demographic determinants, and spatio-temporal variations presented in this paper.
Thinking global health from the perspective of anthropology
Authors: Ji Ruobing , Cheng Yu 
Published: December 2021

AbstractCOVID-19 has brought about political, economic, cultural, and interspecies problems far from medical areas, which challenges academia to rethink global health. For holism principle, anthropology offers valuable insights into these health issues, including the political economy of inequality, cultural diversity, and cultural adaptations, as well as the study of multispecies ethnography. These perspectives indicate that unequal political and economic systems contribute to health problems when people acknowledge disease and illness mechanisms. Moreover, cultural diversity and cultural adaptation are essential for providing appropriate medical solutions. Lastly, as a research method of studying interspecies relationships, multispecies ethnography promotes one health and planetary health from the ultimate perspective of holism. In conclusion, global health is not only a bio-medical concept but also involves political economy, culture, and multispecies factors, for which anthropology proffers inspiring theories and methods.
Characteristics of secondary droplets produced by the impact of drops onto a smooth surface
Authors: Zhang Haixiang , Gao Ye , Zhang Xiwen , Yi Xian , Du Yanxia , He Feng , Jin Zheyan , Hao Pengfei 
Published: December 2021

AbstractThis work investigates the splashing behaviors of droplets impacting on solid surfaces and mainly focuses on the characteristics of secondary droplets. According to the experimental results, two different splashing patterns, corona splash and levitating-lamella breakup, are observed. A new breakup mode, named rim-segmenting, is found during the levitating-lamella breakup. In particular, the detailed information of the splashing secondary droplets, including the size, velocity, angle, and total volume of the splashing secondary droplets is obtained from the experimental data. The size distribution of the splashing secondary droplets obeys the gamma distribution function. The average diameter and splashing angle of the secondary droplets are mainly related to the Reynolds number Re, and can be expressed as functions of Re. High impact velocity and liquid viscosity will result in a wider size distribution range of splashing secondary droplets. We also put forward an empirical model to predict the total splashing volume, which is consistent with the experimental data both in this work and previous studies. This work is believed to provide insights on the prediction of the characteristics of splashing secondary droplets.
Should we vaccinate the better seroconverters or the most vulnerable? Game changing insights for COVID-19 vaccine prioritization policies
Authors: AbdelMassih Antoine , El Shershaby Meryam , Gaber Hanya , Habib Menna , Gamal Nada , Husseiny Reem , AlShehry Nada , Amin Abeer , Heikal Bassant , El-Husseiny Nadine , Moursi Mai , Ismail Habiba-Allah , Senoussy Sara , ElSharkawy Reem , AlZayat Hebat Allah , ElMahdy Ghada , Moawad Hossameldin , Genena Ali , ElKiki Ahmed , Reda Mary , Khalil Mohamed , Al Ramady Reem , Radwan Noran , Khaled-Ibn-ElWalid Mariam , Amin Hager , Hozaien Rafeef , Kamel Aya , Fouda Raghda 
Published: December 2021

Abstract
Background
With the rapid rise in COVID 19 cases incomparable to the number of vaccinations available, there has been a demand to prioritize the older age groups receiving the vaccine as they have more risk of morbidity and mortality and thus better outcome from vaccination.

Main body
Some studies showed a lower seroconversion rate in older group patients; thus, we discuss the necessity to reprioritize vaccinations to younger age groups who have better seroconversion rates, but we may face some ethical dilemma that could hinder our hypothesis. Decreased seroconversion rates in adults are attributable to immuno-senescence which involves a decrease in humoral and cellular-mediated immunity with age. Despite this fact, there remains some ethical dilemma that can hinder widespread vaccination of younger generations, the most important of which is the unknown long-term effects of COVID-19 vaccines due their fast-tracking under the pressure of the pandemic.

Short conclusion
Prioritizing children vaccination against COVID-19 seems an interesting strategy that can help in containing the pandemic. Resolving some ethical dilemma needs to be done before implementing such strategy.
Omental cyst: a case report and review of the literature
Authors: Robbins Keenan J. , Antiel Ryan M. , Shakhsheer Baddr A. 
Published: December 2021

Abstract
Background
Omental cysts are rare, predominantly occur in children, and often initially present with symptoms masquerading as other more common intra-abdominal pathologies. In this case report, we present the case of a child with an omental cyst that originated from the lesser sac. Due to the location of this cyst, resection presented unique technical challenges that have not been described in existing literature.

Case presentation
A 4-year-old male patient presented with symptoms initially concerning for appendicitis. Ultrasound showed a normal appendix but a large volume of complex intraperitoneal fluid. Computed tomography subsequently demonstrated a large cystic structure spanning from the stomach to the bladder. The patient was taken to the operating room where a large omental cyst was found to originate from the lesser sac. The resection was difficult due to the thin wall of the cyst and the intimate association of the superior-most aspect of the cyst with the tail of the pancreas, but was ultimately successful.

Conclusions
Omental cysts are rarely suspected before detection on abdominal imaging. Surgical resection is the treatment of choice, and complete resection can result in a recurrence-free postoperative course. Laparoscopic resection has been reported, but laparotomy is reasonable when a minimally invasive approach may not allow for a safe resection without rupture of the cyst. Anatomical characteristics of the cyst, as demonstrated in our case, can present challenges in the treatment of this otherwise benign entity.