bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of macro-socioeconomic determinants on sustainable perinatal health care in Portugal: a qualitative study on the opinion of healthcare professionals and experts
Authors: Doetsch Julia Nadine , Marques Sandra C. S. , Krafft Thomas , Barros Henrique 
Published: January 2021

Abstract
Background
The WHO identified the importance of macro-socioeconomic determinants and political context as interlinked key factors affecting healthcare quality and health equity. As a response to the recent economic and financial crisis, Portugal approved in 2011 the Economic Adjustment Programme (EAP) to obtain financial assistance from the Troika in order to reduce public debt. This study aims to analyse the impact of the economic crisis and the EAP on perinatal healthcare quality for very preterm (VPT) and/or very low birth weight (VLBW) infants, as perceived by healthcare professionals and experts, within the health administrative regions of the two major metropolitan areas in Portugal.

Methods
A qualitative approach was applied to receive an in-depth understanding and accomplish perspective variability. A purposive sampling technique was used. Semi-structured interviews were conducted with twenty-one healthcare professionals and experts between October 2018–July 2019. Inductive thematic analysis was performed which encompassed a five-step categorization procedure. Data analysis was undertaken by utilizing Nvivo2011 software. Evolved themes were then associated with WHO’s Quality Standards on Maternal and New-born Care. A framework on the impact of macro-socioeconomic determinants on perinatal health care quality was developed.

Results
Although participants did not perceive the quality of perinatal care had deteriorated, the analysis of their accounts on work experience revealed that it was indeed adversely modified in all WHO Quality Standards. Health care provision was perceived as detrimental in five main areas: 1) Availability of human resources; 2) Functional referral systems; 3) Competent and motivated human resources; 4) Emotional support; and 5) Essential physical resources available. Policy reforms by the EAP resulted in reduced timeliness of care, increased waiting times, cuts in sequence and duration of consultations, and deficiencies in follow-up care for VPT/VLBW infants and their mothers. The EAP directly influenced working environment of healthcare professionals by causing stress, burnout, work absence, and brain drain.

Conclusion
An interrelation between macro-socioeconomic determinants and perinatal health care quality was disclosed. The economic crisis and EAP have adversely modified equitable perinatal health care quality for VPT/VLBW infants and their mothers. Our findings underlined the negative impact of austerity policies on vulnerable populations.
The traditional experience strategy (TES) and combined ultrasonography examination (CUE) for the treatment of lateral compression type 1 pelvic fractures: a historical control study
Authors: Huang Hai , Zhang Bin-Fei , Liu Ping , Deng Hong-Li , Wang Peng-Fei , Wang Hu , Li Bao-Feng , Cong Yu-Xuan , Zhuang Yan 
Published: January 2021

Abstract
Background
It is difficult to judge the stability of lateral compression type-1 (LC-1) pelvic fracture, as it is often based on static images of the pelvis. Compared with the traditional experience strategy, ultrasonography examination may be able to distinguish operative and conservative patients before definitive treatment. However, in previous studies, we have not compared the outcomes between traditional experience strategy (TES group) and combined ultrasonography examination (CUE group). Thus, the aim of the study is comparing the differences between TES and CUE strategy, to identify the value of ultrasonography examination.

Methods
Medical records system for patients with LC-1 pelvic fractures who were treated with TES and CUE strategy were included. Patients’ baseline characteristics, treatment strategy, and function were recorded at follow-up. Functional outcomes were evaluated using the Majeed grading system.

Results
In total, 77 patients with LC-1 pelvic fractures were included in the study. There were 42 and 35 patients in TES and CUE group, respectively. Compared to TES group (69 %), there were less proportion patients chosen the operative treatment in CUE group (43 %, P = 0.021). The volume of intraoperative blood loss in CUE operative group was more than TES operative group (P = 0.037). There were more patients with complete sacral fracture in CUE operative group than TES operative group (P = 0.002). The Majeed scores in CUE conservative group was higher than TES conservative group (P = 0.008). The overall Majeed scores in CUE group was higher than that in TES group (P = 0.039).

Conclusions
The ultrasonography examination could relatively accurately identify the unstable LC-1 pelvis than the traditional experience strategy, the operative rate could be reduced and the overall function of LC-1 patients could be improved under the ultrasonography examination.

Level of evidence
Level III.
Struggling to fit the white coat and the role of contextual factors within a hospital organisation - an ethnographic study on the first months as newly graduated doctors
Authors: Klitgaard Tine Lass , Stentoft Diana , Skipper Mads , Grønkjær Mette , Nøhr Susanne Backman 
Published: January 2021

Abstract
Background
Despite increased focus on improving the transition from being a medical student to working as a junior doctor, many newly graduated doctors (NGD) report the process of fitting the white coat as stressful, and burnout levels indicate that they might face bigger challenges than they can handle. During this period, the NGDs are in a process of learning how to be doctors, and this takes place in an organisation where the workflow and different priorities set the scene. However, little is known about how the hospital organisation influences this process. Thus, we aimed to explore how the NGDs experience their first months of work in order to understand 1) which struggles they are facing, and 2) which contextual factors within the hospital organisation that might be essential in this transition.

Methods
An ethnographic study was conducted at a university hospital in Denmark including 135 h of participant observations of the NGDs (n = 11). Six semi-structured interviews (four group interviews and two individual interviews) were conducted (n = 21). The analysis was divided into two steps: Firstly, we carried out a “close-to-data” analysis with focus on the struggles faced by the NGDs. Secondly, we reviewed the struggles by using the theoretical lens of Cultural Historical Activity Theory (CHAT) to help us explore, which contextual factors within the hospital organisation that seem to have an impact on the NGDs’ experiences.

Results
The NGDs’ struggles fall into four themes: Responsibility, local knowhow, time management and collaborators. By using the CHAT lens, we were able to identify significant contextual factors, including a physically remote placement, a missing overlap between new and experienced NGDs, a time limited introduction period, and the affiliation to several departments. These struggles and factors were highly intertwined and influenced by one another.

Conclusion
Contextual factors within the hospital organisation may aggravate the struggles experienced by the NGDs, and this study points to possible elements that could be addressed to make the transition less challenging and overwhelming.
Improving the quality of training paramedics by means of cadavers – a pilot study
Authors: Leszczyński Piotr , Muraczyńska Bożena , Wejnarski Arkadiusz , Baczewska Bożena , Malm Maria , Drop Bartłomiej 
Published: January 2021

AbstractBackgroundParamedics are authorised to perform emergency procedures, including trauma assessment according to global standards. The aim of the study was to answer the question whether the use of cadavers in teaching practical competencies to medical rescue students, in the field of trauma assessment, is necessary as a supplement to learning in simulated conditions with the use of mannequins.MethodsResearch included several stages. The first stage was conduction of classes for 27 students in the field of rapid trauma assessment, in accordance with the guidelines of the International Trauma Life Support. In the second stage, a plan of a test in which students had to perform an analogous procedure of rapid trauma assessment, but with the use of cadavers, human unfixed specimens, was prepared. The Delphi method was used to develop and approve checklists, as well as a scale to assess the global correctness of identification of head, torso and limb injuries by medical rescue students.ResultsThe identification rate was 76.54% in the head area, 67.90% in the torso area, while in the limb area it equalled 44.45%. A significant difference in scores, compared to the examination performed on a mannequin, was observed (Wilcoxon = 4.541;p = 0.000). The most difficult to make a correct diagnosis were injuries related to a fracture of the proximal end of the femur and a dislocated wrist (only 18.52% of correct answers). The students highly rated the usefulness of the examination, by awarding it an average of 4.76 points (SD ± 0.56) on the Likert scale (0–5).ConclusionsThe study shows that the use of cadavers to teach practical competencies in the field of trauma assessment to medical rescue students can be an effective supplement to simulated learning. Students could feel the difference between the human body and the mannequin. More research is needed to assess whether realistic simulation translates into objective endpoints, such as the effectiveness of diagnosis in the examination of trauma patients. However, it should be remembered that the introduction of this teaching method is expensive and requires adequate base, as well as the compliance with a number of formal requirements.
Effect of sodium–glucose cotransporter 2 inhibitors on cardiac structure and function in type 2 diabetes mellitus patients with or without chronic heart failure: a meta-analysis
Authors: Yu Yi-Wen , Zhao Xue-Mei , Wang Yun-Hong , Zhou Qiong , Huang Yan , Zhai Mei , Zhang Jian 
Published: January 2021

Abstract
Background
Although the benefits of sodium–glucose cotransporter 2 inhibitors (SGLT2i) on cardiovascular events have been reported in patients with type 2 diabetes mellitus (T2DM) with or without heart failure (HF), the impact of SGLT2i on cardiac remodelling remains to be established.

Methods
We searched the PubMed, Embase, Cochrane Library and Web of Science databases up to November 16th, 2020, for randomized controlled trials reporting the effects of SGLT2i on parameters of cardiac structure, cardiac function, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) level or the Kansas City Cardiomyopathy Questionnaire (KCCQ) score in T2DM patients with or without chronic HF. The effect size was expressed as the mean difference (MD) or standardized mean difference (SMD) and its 95% confidence interval (CI). Subgroup analyses were performed based on the stage A–B or stage C HF population and HF types.

Results
Compared to placebo or other antidiabetic drugs, SGLT2i showed no significant effects on left ventricular mass index, left ventricular end diastolic volume index, left ventricular end systolic volume index, or left atrial volume index. SGLT2i improved left ventricular ejection fraction only in the subgroup of HF patients with reduced ejection fraction (MD 3.16%, 95% CI 0.11 to 6.22, p = 0.04; I2 = 0%), and did not affect the global longitudinal strain in the overall analysis including stage A–B HF patients. SGLT2i showed benefits in the E/e’ ratio (MD − 0.45, 95% CI − 0.88 to − 0.03, p = 0.04; I2 = 0%), plasma NT-proBNP level (SMD − 0.09, 95% CI − 0.16 to − 0.03, p = 0.004; I2 = 0%), and the KCCQ score (SMD 3.12, 95% CI 0.76 to 5.47, p  = 0.01; I2 = 0%) in the overall population.

Conclusion
The use of SGLT2i was associated with significant improvements in cardiac diastolic function, plasma NT-proBNP level, and the KCCQ score in T2DM patients with or without chronic HF, but did not significantly affect cardiac structural parameters indexed by body surface area. The LVEF level was improved only in HF patients with reduced ejection fraction.
MicroRNA-3613-3p functions as a tumor suppressor and represents a novel therapeutic target in breast cancer
Authors: Chen Chong , Pan Yundi , Bai Lipeng , Chen Huilin , Duan Zhaojun , Si Qin , Zhu Ruizhe , Chuang Tsung-Hsien , Luo Yunping 
Published: January 2021

Abstract
Background
MicroRNAs have been reported to participate in tumorigenesis, treatment resistance, and tumor metastasis. Novel microRNAs need to be identified and investigated to guide the clinical prognosis or therapy for breast cancer.

Method
The copy number variations (CNVs) of MIR3613 from Cancer Genome Atlas (TCGA) or Cancer Cell Line Encyclopedia (CCLE) were analyzed, and its correlation with breast cancer subtypes or prognosis was investigated. The expression level of miR-3613-3p in tumor tissues or serum of breast cancer patients was detected using in situ hybridization and qPCR. Gain-of-function studies were performed to determine the regulatory role of miR-3613-3p on proliferation, apoptosis, and tumor sphere formation of human breast cancer cells MDA-MB-231 or MCF-7. The effects of miR-3613-3p on tumor growth or metastasis in an immunocompromised mouse model of MDA-MB-231-luciferase were explored by intratumor injection of miR-3613-3p analogue. The target genes, interactive lncRNAs, and related signaling pathways of miR-3613-3p were identified by bioinformatic prediction and 3′-UTR assays.

Results
We found that MIR3613 was frequently deleted in breast cancer genome and its deletion was correlated with the molecular typing, and an unfavorable prognosis in estrogen receptor-positive patients. MiR-3613-3p level was also dramatically lower in tumor tissues or serum of breast cancer patients. Gain-of-function studies revealed that miR-3613-3p could suppress proliferation and sphere formation and promote apoptosis in vitro and impeded tumor growth and metastasis in vivo. Additionally, miR-3613-3p might regulate cell cycle by targeting SMS, PAFAH1B2, or PDK3 to restrain tumor progression.

Conclusion
Our findings indicate a suppressive role of miR-3613-3p in breast cancer progression, which may provide an innovative marker or treatment for breast cancer patients.
SequencErr: measuring and suppressing sequencer errors in next-generation sequencing data
Authors: Davis Eric M. , Sun Yu , Liu Yanling , Kolekar Pandurang , Shao Ying , Szlachta Karol , Mulder Heather L. , Ren Dongren , Rice Stephen V. , Wang Zhaoming , Nakitandwe Joy , Gout Alexander M. , Shaner Bridget , Hall Salina , Robison Leslie L. , Pounds Stanley , Klco Jeffery M. , Easton John , Ma Xiaotu 
Published: January 2021

AbstractBackgroundThere is currently no method to precisely measure the errors that occur in the sequencing instrument/sequencer, which is critical for next-generation sequencing applications aimed at discovering the genetic makeup of heterogeneous cellular populations.ResultsWe propose a novel computational method, SequencErr, to address this challenge by measuring the base correspondence between overlapping regions in forward and reverse reads. An analysis of 3777 public datasets from 75 research institutions in 18 countries revealed the sequencer error rate to be ~ 10 per million (pm) and 1.4% of sequencers and 2.7% of flow cells have error rates > 100 pm. At the flow cell level, error rates are elevated in the bottom surfaces and > 90% of HiSeq and NovaSeq flow cells have at least one outlier error-prone tile. By sequencing a common DNA library on different sequencers, we demonstrate that sequencers with high error rates have reduced overall sequencing accuracy, and removal of outlier error-prone tiles improves sequencing accuracy. We demonstrate that SequencErr can reveal novel insights relative to the popular quality control method FastQC and achieve a 10-fold lower error rate than popular error correction methods including Lighter and Musket.ConclusionsOur study reveals novel insights into the nature of DNA sequencing errors incurred on DNA sequencers. Our method can be used to assess, calibrate, and monitor sequencer accuracy, and to computationally suppress sequencer errors in existing datasets.
Behavioral biology of Toxoplasma gondii infection
Authors: Tong Wen Han , Pavey Chris , O’Handley Ryan , Vyas Ajai 
Published: January 2021

AbstractToxoplasma gondii is a protozoan parasite with a complex life cycle and a cosmopolitan host range. The asexual part of its life cycle can be perpetually sustained in a variety of intermediate hosts through a combination of carnivory and vertical transmission. However, T. gondii produces gametes only in felids after the predation of infected intermediate hosts. The parasite changes the behavior of its intermediate hosts by reducing their innate fear to cat odors and thereby plausibly increasing the probability that the definitive host will devour the infected host. Here, we provide a short description of such parasitic behavioral manipulation in laboratory rodents infected with T. gondii, along with a bird’s eye view of underpinning biological changes in the host. We also summarize critical gaps and opportunities for future research in this exciting research area with broad implications in the transdisciplinary study of host–parasite relationships.
Graphical abstract
The role of NbTMP1, a surface protein of sporoplasm, in Nosema bombycis infection
Authors: Zheng Shiyi , Huang Yukang , Huang Hongyun , Yu Bin , Zhou Ni , Wei Junhong , Pan Guoqing , Li Chunfeng , Zhou Zeyang 
Published: January 2021

Abstract
Background
Nosema bombycis is a unicellular eukaryotic pathogen of the silkworm, Bombyx mori, and is an economic and occupational hazard in the silkworm industry. Because of its long incubation period and horizontal and vertical transmission, it is subject to quarantine measures in sericulture production. The microsporidian life-cycle includes a dormant extracellular phase and intracellular proliferation phase, with the proliferation period being the most active period. This latter period lacks spore wall protection and may be the most susceptible stage for control.

Methods
In order to find suitable target for the selective breeding of N. bombycis-resistant silkworm strains, we screen highly expressed membrane proteins from the transcriptome data of N. bombycis. The subcellular localization of the candidate protein was verified by Indirect immunofluorescence analysis (IFA) and immunoelectron microscopy (IEM), and its role in N. bombycis proliferation was verified by RNAi.

Results
The N. bombycis protein (NBO_76g0014) was identified as a transmembrane protein and named NbTMP1. It is homologous with hypothetical proteins NGRA_1734 from Nosema granulosis. NbTMP1 has a transmembrane region of 23 amino acids at the N-terminus. Indirect immunofluorescence analysis (IFA) results suggest that NbTMP1 is secreted on the plasma membrane as the spores develop. Western blot and qRT-PCR analysis showed that NbTMP1 was expressed in all developmental stages of N. bombycis in infected cells and in the silkworm midgut. Downregulation of NbTMP1 expression resulted in significant inhibition of N. bombycis proliferation.

Conclusions
We confirmed that NbTMP1 is a membrane protein of N. bombycis. Reduction of the transcription level of NbTMP1 significantly inhibited N. bombycis proliferation, and this protein may be a target for the selective breeding of N. bombycis-resistant silkworm strains.

Graphical Abstract
Male obesity impacts DNA methylation reprogramming in sperm
Authors: Keyhan Sanaz , Burke Emily , Schrott Rose , Huang Zhiqing , Grenier Carole , Price Thomas , Raburn Doug , Corcoran David L. , Soubry Adelheid , Hoyo Catherine , Murphy Susan K. 
Published: January 2021

Abstract
Background
Male obesity has profound effects on morbidity and mortality, but relatively little is known about the impact of obesity on gametes and the potential for adverse effects of male obesity to be passed to the next generation. DNA methylation contributes to gene regulation and is erased and re-established during gametogenesis. Throughout post-pubertal spermatogenesis, there are continual needs to both maintain established methylation and complete DNA methylation programming, even during epididymal maturation. This dynamic epigenetic landscape may confer increased vulnerability to environmental influences, including the obesogenic environment, that could disrupt reprogramming fidelity. Here we conducted an exploratory analysis that showed that overweight/obesity (n = 20) is associated with differences in mature spermatozoa DNA methylation profiles relative to controls with normal BMI (n = 47).

Results
We identified 3264 CpG sites in human sperm that are significantly associated with BMI (p < 0.05) using Infinium HumanMethylation450 BeadChips. These CpG sites were significantly overrepresented among genes involved in transcriptional regulation and misregulation in cancer, nervous system development, and stem cell pluripotency. Analysis of individual sperm using bisulfite sequencing of cloned alleles revealed that the methylation differences are present in a subset of sperm rather than being randomly distributed across all sperm.

Conclusions
Male obesity is associated with altered sperm DNA methylation profiles that appear to affect reprogramming fidelity in a subset of sperm, suggestive of an influence on the spermatogonia. Further work is required to determine the potential heritability of these DNA methylation alterations. If heritable, these changes have the potential to impede normal development.
Skin regeneration is accelerated by a lower dose of multipotent mesenchymal stromal/stem cells—a paradigm change
Authors: Eylert Gertraud , Dolp Reinhard , Parousis Alexandra , Cheng Richard , Auger Christopher , Holter Magdalena , Lang-Olip Ingrid , Reiner Viola , Kamolz Lars-Peter , Jeschke Marc G. 
Published: January 2021

Abstract
Background
Multipotent mesenchymal stromal/stem cell (MSC) therapy is under investigation in promising (pre-)clinical trials for wound healing, which is crucial for survival; however, the optimal cell dosage remains unknown. The aim was to investigate the efficacy of different low-to-high MSC dosages incorporated in a biodegradable collagen-based dermal regeneration template (DRT) Integra®.

Methods
We conducted a porcine study (N = 8 Yorkshire pigs) and seeded between 200 and 2,000,000 cells/cm2 of umbilical cord mesenchymal stromal/stem cells on the DRT and grafted it onto full-thickness burn excised wounds. On day 28, comparisons were made between the different low-to-high cell dose groups, the acellular control, a burn wound, and healthy skin.

Result
We found that the low dose range between 200 and 40,000 cells/cm2 regenerates the full-thickness burn excised wounds most efficaciously, followed by the middle dose range of 200,000–400,000 cells/cm2 and a high dose of 2,000,000 cells/cm2. The low dose of 40,000 cells/cm2 accelerated reepithelialization, reduced scarring, regenerated epidermal thickness superiorly, enhanced neovascularization, reduced fibrosis, and reduced type 1 and type 2 macrophages compared to other cell dosages and the acellular control.

Conclusion
This regenerative cell therapy study using MSCs shows efficacy toward a low dose, which changes the paradigm that more cells lead to better wound healing outcome.