bluuebunny/crossref_metadata_2025_split huggingface dataset:
Educational assessment of the major lower limb amputations videos on YouTube
Authors: Yammine Kaissar , Assi Chahine 
Published: April 2020

Objective Videos of surgical procedures are viewed by some as potential training resources for surgeons and residents. However, there is little evidence on the effectiveness of surgical videos on learning and understanding complex three-dimensional surgical procedures. Lower extremity amputation is a complex surgery, and many residents and surgeons have low exposure to this type of procedures. This paper investigates the educational quality of lower extremity amputation videos posted on YouTube. Methods The search was limited to the first 100 videos. Full-length videos of any major lower limb amputation or disarticulation were included. Key basic video data such as title, YouTube address (http://), country of origin, channel source, uploading date, video duration time, number of views, number of up-voters and number of down-voters were collected. An educational assessment tool has been developed specifically for limb amputations. It consists in 11 items: three general and eight amputation-specific, each having a maximum score of 2. Results In total, 13 videos met the inclusion criteria for final analysis. Four videos reported the surgical technique of above knee amputation, two reported that of knee disarticulation and the remaining seven videos described below knee amputation. The average score (±SD) was 12.77 ± 5.2 yielding an average grade close to “Fair.” A high level of concordance was found between the two assessors ( κ = 0.79). No correlation was found between educational assessment tool score and the pre-set variables (r = 0.6, R2 = 35.4%, F = 1.09, P = 0.4). Conclusions Most videos describing lower extremity amputation techniques were found to be of low-to-moderate quality. Only 4 out of 13 (30.7%) had an excellent educational and technical quality. Surgeons and surgical residents should be aware that not all posted videos on YouTube are beneficial. High educational quality videos are needed since many surgeons and residents have a low exposure to such surgeries.
Mitochondrial carrier homolog 2 is necessary for AML survival
Authors: Khan Dilshad H. , Mullokandov Michael , Wu Yan , Voisin Veronique , Gronda Marcela , Hurren Rose , Wang Xiaoming , MacLean Neil , Jeyaraju Danny V. , Jitkova Yulia , Xu G. Wei , Laister Rob , Seneviratne Ayesh , Blatman Zachary M. , Ketela Troy , Bader Gary D. , Marhon Sajid A. , De Carvalho Daniel D. , Minden Mark D. , Gross Atan , Schimmer Aaron D. 
Published: April 2020

Abstract
Through a clustered regularly insterspaced short palindromic repeats (CRISPR) screen to identify mitochondrial genes necessary for the growth of acute myeloid leukemia (AML) cells, we identified the mitochondrial outer membrane protein mitochondrial carrier homolog 2 (MTCH2). In AML, knockdown of MTCH2 decreased growth, reduced engraftment potential of stem cells, and induced differentiation. Inhibiting MTCH2 in AML cells increased nuclear pyruvate and pyruvate dehydrogenase (PDH), which induced histone acetylation and subsequently promoted the differentiation of AML cells. Thus, we have defined a new mechanism by which mitochondria and metabolism regulate AML stem cells and gene expression.
The HRI-regulated transcription factor ATF4 activates BCL11A transcription to silence fetal hemoglobin expression
Authors: Huang Peng , Peslak Scott A. , Lan Xianjiang , Khandros Eugene , Yano Jennifer A. , Sharma Malini , Keller Cheryl A. , Giardine Belinda , Qin Kunhua , Abdulmalik Osheiza , Hardison Ross C. , Shi Junwei , Blobel Gerd A. 
Published: April 2020

Abstract
Reactivation of fetal hemoglobin remains a critical goal in the treatment of patients with sickle cell disease and β-thalassemia. Previously, we discovered that silencing of the fetal γ-globin gene requires the erythroid-specific eIF2α kinase heme-regulated inhibitor (HRI), suggesting that HRI might present a pharmacologic target for raising fetal hemoglobin levels. Here, via a CRISPR-Cas9–guided loss-of-function screen in human erythroblasts, we identify transcription factor ATF4, a known HRI-regulated protein, as a novel γ-globin regulator. ATF4 directly stimulates transcription of BCL11A, a repressor of γ-globin transcription, by binding to its enhancer and fostering enhancer-promoter contacts. Notably, HRI-deficient mice display normal Bcl11a levels, suggesting species-selective regulation, which we explain here by demonstrating that the analogous ATF4 motif at the murine Bcl11a enhancer is largely dispensable. Our studies uncover a linear signaling pathway from HRI to ATF4 to BCL11A to γ-globin and illustrate potential limits of murine models of globin gene regulation.
Experimental dyspnoea interferes with locomotion and cognition: a randomised trial
Authors: Lawi David , Dupuis-Lozeron Elise , Berra Gregory , Allali Gilles , Similowski Thomas , Adler Dan 
Published: April 2020

BackgroundChronic respiratory diseases are associated with cognitive dysfunction, but whether dyspnoea by itself negatively impacts on cognition has not been demonstrated. Cortical networks engaged in subjects experiencing dyspnoea are also activated during other tasks that require cognitive input and this may provoke a negative impact through interference with each other.MethodsThis randomised, crossover trial investigated whether experimentally-induced dyspnoea would negatively impact on locomotion and cognitive function among 40 healthy adults. Crossover conditions were unloaded breathing or loaded breathing using an inspiratory threshold load. To evaluate locomotion, participants were assessed by the Timed Up and Go (TUG) test. Cognitive function was assessed by categorical and phonemic verbal fluency tests, the Trail Making Tests (TMTs) A and B (executive function), the CODE test from the Wechsler Adult Intelligence Scale (WAIS)-IV (processing speed) and by direct and indirect digit span (working memory).ResultsThe mean time difference to perform the TUG test between unloaded and loaded breathing was −0.752 s (95% CI −1.012 to −0.492 s) (p<0.001). Executive function, processing speed and working memory performed better during unloaded breathing, particularly for subjects starting first with the loaded breathing condition.ConclusionOur data suggest that respiratory threshold loading to elicit dyspnoea had a major impact on locomotion and cognitive function in healthy adults.
Air pollution and the development of asthma from birth until young adulthood
Authors: Gehring Ulrike , Wijga Alet H. , Koppelman Gerard H. , Vonk Judith M. , Smit Henriette A. , Brunekreef Bert 
Published: April 2020

BackgroundAir pollution is associated with asthma development in children and adults, but the impact on asthma development during the transition from adolescence to adulthood is unclear. Adult studies lack historical exposures and consequently cannot assess the relevance of exposure during different periods of life. We assessed the relevance of early-life and more recent air pollution exposure for asthma development from birth until early adulthood.MethodsWe used data of 3687 participants of the prospective Dutch PIAMA (Prevention and Incidence of Asthma and Mite Allergy) birth cohort and linked asthma incidence until age 20 years to estimated concentrations of nitrogen dioxide (NO2), particulate matter with a diameter <2.5 μm (PM2.5), <10 μm (PM10), and 2.5–10 μm, and PM2.5absorbance (“soot”) at the residential address. We assessed overall and age-specific associations with air pollution exposure with discrete time-hazard models, adjusting for potential confounders.ResultsOverall, we found higher incidence of asthma until the age of 20 years with higher exposure to all pollutants at the birth address (adjusted odds ratio (95% CI) ranging from 1.09 (1.01–1.18) for PM10to 1.20 (1.10–1.32) for NO2) per interquartile range increase) that were rather persistent with age. Similar associations were observed with more recent exposure defined as exposure at the current home address. In two-pollutant models with particulate matter, associations with NO2persisted.ConclusionsExposure to air pollution, especially from motorised traffic, early in life may have long-term consequences for asthma development, as it is associated with an increased risk of developing asthma through childhood and adolescence into early adulthood.
Hierarchical discovery of large-scale and focal copy number alterations in low-coverage cancer genomes
Authors: Khalil Ahmed Ibrahim Samir , Khyriem Costerwell , Chattopadhyay Anupam , Sanyal Amartya 
Published: April 2020

AbstractBackgroundDetection of DNA copy number alterations (CNAs) is critical to understand genetic diversity, genome evolution and pathological conditions such as cancer. Cancer genomes are plagued with widespread multi-level structural aberrations of chromosomes that pose challenges to discover CNAs of different length scales, and distinct biological origins and functions. Although several computational tools are available to identify CNAs using read depth (RD) signal, they fail to distinguish between large-scale and focal alterations due to inaccurate modeling of the RD signal of cancer genomes. Additionally, RD signal is affected by overdispersion-driven biases at low coverage, which significantly inflate false detection of CNA regions.ResultsWe have developed CNAtra framework to hierarchically discover and classify ‘large-scale’ and ‘focal’ copy number gain/loss from a single whole-genome sequencing (WGS) sample. CNAtra first utilizes a multimodal-based distribution to estimate the copy number (CN) reference from the complex RD profile of the cancer genome. We implemented Savitzky-Golay smoothing filter and Modified Varri segmentation to capture the change points of the RD signal. We then developed a CN state-driven merging algorithm to identify the large segments with distinct copy numbers. Next, we identified focal alterations in each large segment using coverage-based thresholding to mitigate the adverse effects of signal variations. Using cancer cell lines and patient datasets, we confirmed CNAtra’s ability to detect and distinguish the segmental aneuploidies and focal alterations. We used realistic simulated data for benchmarking the performance of CNAtra against other single-sample detection tools, where we artificially introduced CNAs in the original cancer profiles. We found that CNAtra is superior in terms of precision, recall and f-measure. CNAtra shows the highest sensitivity of 93 and 97% for detecting large-scale and focal alterations respectively. Visual inspection of CNAs revealed that CNAtra is the most robust detection tool for low-coverage cancer data.ConclusionsCNAtra is a single-sample CNA detection tool that provides an analytical and visualization framework for CNA profiling without relying on any reference control. It can detect chromosome-level segmental aneuploidies and high-confidence focal alterations, even from low-coverage data. CNAtra is an open-source software implemented in MATLAB®. It is freely available athttps://github.com/AISKhalil/CNAtra.
A practical staging atlas to study embryonic development of Octopus vulgaris under controlled laboratory conditions
Authors: Deryckere Astrid , Styfhals Ruth , Vidal Erica A. G. , Almansa Eduardo , Seuntjens Eve 
Published: April 2020

Abstract
Background
Octopus vulgaris has been an iconic cephalopod species for neurobiology research as well as for cephalopod aquaculture. It is one of the most intelligent and well-studied invertebrates, possessing both long- and short-term memory and the striking ability to perform complex cognitive tasks. Nevertheless, how the common octopus developed these uncommon features remains enigmatic. O. vulgaris females spawn thousands of small eggs and remain with their clutch during their entire development, cleaning, venting and protecting the eggs. In fact, eggs incubated without females usually do not develop normally, mainly due to biological contamination (fungi, bacteria, etc.). This high level of parental care might have hampered laboratory research on the embryonic development of this intriguing cephalopod.

Results
Here, we present a completely parameter-controlled artificial seawater standalone egg incubation system that replaces maternal care and allows successful embryonic development of a small-egged octopus species until hatching in a laboratory environment. We also provide a practical and detailed staging atlas based on bright-field and light sheet fluorescence microscopy imaging for precise monitoring of embryonic development. The atlas has a comparative section to benchmark stages to the different scales published by Naef (1928), Arnold (1965) and Boletzky (2016). Finally, we provide methods to monitor health and wellbeing of embryos during organogenesis.

Conclusion
Besides introducing the study of O. vulgaris embryonic development to a wider community, this work can be a high-quality reference for comparative evolutionary developmental biology.
Ionizing radiation modulates the phenotype and function of human CD4+ induced regulatory T cells
Authors: Beauford Samantha S. , Kumari Anita , Garnett-Benson Charlie 
Published: April 2020

Abstract
Background
The use of immunotherapy strategies for the treatment of advanced cancer is rapidly increasing. Most immunotherapies rely on induction of CD8+ tumor-specific cytotoxic T cells that are capable of directly killing cancer cells. Tumors, however, utilize a variety of mechanisms that can suppress anti-tumor immunity. CD4+ regulatory T cells can directly inhibit cytotoxic T cell activity and these cells can be recruited, or induced, by cancer cells allowing escape from immune attack. The use of ionizing radiation as a treatment for cancer has been shown to enhance anti-tumor immunity by several mechanisms including immunogenic tumor cell death and phenotypic modulation of tumor cells. Less is known about the impact of radiation directly on suppressive regulatory T cells. In this study we investigate the direct effect of radiation on human TREG viability, phenotype, and suppressive activity.

Results
Both natural and TGF-β1-induced CD4+ TREG cells exhibited increased resistance to radiation (10 Gy) as compared to CD4+ conventional T cells. Treatment, however, decreased Foxp3 expression in natural and induced TREG cells and the reduction was more robust in induced TREGS. Radiation also modulated the expression of signature iTREG molecules, inducing increased expression of LAG-3 and decreased expression of CD25 and CTLA-4. Despite the disconcordant modulation of suppressive molecules, irradiated iTREGS exhibited a reduced capacity to suppress the proliferation of CD8+ T cells.

Conclusions
Our findings demonstrate that while human TREG cells are more resistant to radiation-induced death, treatment causes downregulation of Foxp3 expression, as well as modulation in the expression of TREG signature molecules associated with suppressive activity. Functionally, irradiated TGF-β1-induced TREGS were less effective at inhibiting CD8+ T cell proliferation. These data suggest that doses of radiotherapy in the hypofractionated range could be utilized to effectively target and reduce TREG activity, particularly when used in combination with cancer immunotherapies.
High post-anthesis temperature effects on bread wheat (Triticum aestivum L.) grain transcriptome during early grain-filling
Authors: Kino Richard I. , Pellny Till K. , Mitchell Rowan A. C. , Gonzalez-Uriarte Asier , Tosi Paola 
Published: April 2020

Abstract
Background
High post-anthesis (p.a) temperatures reduce mature grain weights in wheat and other cereals. However, the causes of this reduction are not entirely known. Control of grain expansion by the maternally derived pericarp of the grain has previously been suggested, although this interaction has not been investigated under high p.a. temperatures. Down-regulation of pericarp localised genes that regulate cell wall expansion under high p.a. temperatures may limit expansion of the encapsulated endosperm due to a loss of plasticity in the pericarp, reducing mature grain weight. Here the effect of high p.a. temperatures on the transcriptome of the pericarp and endosperm of the wheat grain during early grain-filling was investigated via RNA-Seq and is discussed alongside grain moisture dynamics during early grain development and mature grain weight.

Results
High p.a. temperatures applied from 6-days after anthesis (daa) and until 18daa reduced the grain’s ability to accumulate water, with total grain moisture and percentage grain moisture content being significantly reduced from 14daa onwards. Mature grain weight was also significantly reduced by the same high p.a. temperatures applied from 6daa for 4-days or more, in a separate experiment. Comparison of our RNA-Seq data from whole grains, with existing data sets from isolated pericarp and endosperm tissues enabled the identification of subsets of genes whose expression was significantly affected by high p.a. temperature and predominantly expressed in either tissue. Hierarchical clustering and gene ontology analysis resulted in the identification of a number of genes implicated in the regulation of cell wall expansion, predominantly expressed in the pericarp and significantly down-regulated under high p.a. temperatures, including endoglucanase, xyloglucan endotransglycosylases and a β-expansin. An over-representation of genes involved in the ‘cuticle development’ functional pathway that were expressed in the pericarp and affected by high p.a. temperatures was also observed.

Conclusions
High p.a. temperature induced down-regulation of genes involved in regulating pericarp cell wall expansion. This concomitant down-regulation with a reduction in total grain moisture content and grain weight following the same treatment period, adds support to the theory that high p.a. temperatures may cause a reduction in mature grain weight as result of decreased pericarp cell wall expansion.
Misdiagnosis of multiple synchronous small bowel adenocarcinomas as intestinal tuberculosis: a case report
Authors: Li Qiwei , Chen Tao , Cui Hexi , Xiao Xiao , Chen Chunqiu , Shen Zhenyu , Ji Fu , Yin Lu 
Published: April 2020

Abstract
Background
Small bowel adenocarcinoma (SBA) is a rare malignancy that primarily occurs in the duodenum. Multiple synchronous SBA is unique rare and difficult to diagnose due to non-specific disease presentation. Protocols to identify multiple synchronous SBA during early disease stages are urgently required.

Case presentation
An elderly man experienced left lower abdominal pain and melena for 3 months. Abdominal CT showed thickening of the multiple segmental small intestinal walls. As the patient had pulmonary tuberculosis simultaneously, he was misdiagnosis as intestinal tuberculosis and received anti-spasm therapy. The treatment delayed radical resection surgery and the patient underwent palliative segmental resection of the jejunum after 4 months due to intestinal obstruction. Resected specimens showed multiple synchronous SBA (five tumors). The patient accepted chemotherapy postoperatively. Six months postoperatively, the patient died of brain metastasis.

Conclusions
We highlight how multiple synchronous SBA is rare and easily misdiagnosed. We should rule out multiple synchronous SBA when diagnosing intestinal diseases (e.g. inflammatory bowel disease, IBS). Intestinal tuberculosis may also be one of the risk factors for multiple synchronous SBA. High-risk patients should be assessed for known tumor makers, and receive gastroscopy, enteroscopy or capsule endoscopy. Doctors should obtain the pathology under endoscopy to the greatest possible degree. For suspected patients, laparotomy should be performed.
Emergence of carbapenem-resistant and colistin-susceptible Enterobacter cloacae complex co-harboring blaIMP-1 and mcr-9 in Japan
Authors: Kananizadeh Pegah , Oshiro Satoshi , Watanabe Shin , Iwata Shu , Kuwahara-Arai Kyoko , Shimojima Masahiro , Ogawa Miho , Tada Tatsuya , Kirikae Teruo 
Published: April 2020

Abstract
Background
The spread of Enterobacteriaceae producing both carbapenemases and Mcr, encoded by plasmid-mediated colistin resistance genes, has become a serious public health problem worldwide. This study describes three clinical isolates of Enterobacter cloacae complex co-harboring blaIMP-1 and mcr-9 that were resistant to carbapenem but susceptible to colistin.

Methods
Thirty-two clinical isolates of E. cloacae complex non-susceptible to carbapenems were obtained from patients at 14 hospitals in Japan. Their minimum inhibitory concentrations (MICs) were determined by broth microdilution methods and E-tests. Their entire genomes were sequenced by MiSeq and MinION methods. Multilocus sequence types were determined and a phylogenetic tree constructed by single nucleotide polymorphism (SNP) alignment of whole genome sequencing data.

Results
All 32 isolates showed MICs of ≥2 μg/ml for imipenem and/or meropenem. Whole-genome analysis revealed that all these isolates harbored blaIMP-1, with three also harboring mcr-9. These three isolates showed low MICs of 0.125 μg/ml for colistin. In two of these isolates, blaIMP-1 and mcr-9 were present on two separate plasmids, of sizes 62 kb and 280/290 kb, respectively. These two isolates did not possess a qseBC gene encoding a two-component system, which is thought to regulate the expression of mcr-9. In the third isolate, however, both blaIMP-1 and mcr-9 were present on the chromosome.

Conclusion
The mcr-9 is silently distributed among carbapenem-resistant E. cloacae complex isolates, of which are emerging in hospitals in Japan. To our knowledge, this is the first report of isolates of E. cloacae complex harboring both blaIMP-1 and mcr-9 in Japan.
Human Development Index of the maternal country of origin and its relationship with maternal near miss: A systematic review of the literature
Authors: García-Tizón Larroca Santiago , Amor Valera Francisco , Ayuso Herrera Esther , Cueto Hernandez Ignacio , Cuñarro Lopez Yolanda , De Leon-Luis Juan 
Published: April 2020

Abstract
Background
The reduction in maternal mortality worldwide has increased the interest in studying more frequent severe events such as maternal near miss. The Human Development Index is a sociodemographic country-specific variable that includes key human development indicators such as living a long and healthy life, acquiring knowledge, and enjoying a decent standard of living, allowing differentiation between countries. In a globalised environment, it is necessary to study whether the Human Development Index of each patient's country of origin can be associated with the maternal near-miss rate and thus classify the risk of maternal morbidity and mortality.

Methods
A systematic review of the literature published between 2008 and 2019 was conducted, including all articles that reported data about maternal near miss in their sample of pregnant women, in addition to describing the study countries of their sample population. The Human Development Index of the study country, the maternal near-miss rate, the maternal mortality rate, and other maternal-perinatal variables related to morbidity and mortality were used.

Results
After the systematic review, eighty two articles from over thirty countries were included, for a total of 3,699,697 live births, 37,191 near miss cases, and 4029 mortality cases. A statistically significant (p <0.05) inversely proportional relationship was observed between the Human Development Index of the study country and the maternal near-miss and mortality rates. The most common cause of maternal near miss was haemorrhage, with an overall rate of 38.5%, followed by hypertensive disorders of pregnancy (34.2%), sepsis (7.5%), and other undefined causes (20.9%).

Conclusions
The Human Development Index of the maternal country of origin is a sociodemographic variable allowing differentiation and classification of the risk of maternal mortality and near miss in pregnant women. The most common cause of maternal near miss published in the literature was haemorrhage.

Trial registration
PROSPERO ID: CRD 42019133464