bluuebunny/crossref_metadata_2025_split huggingface dataset:
Grade III blunt splenic injury without contrast extravasation - World Society of Emergency Surgery Nijmegen consensus practice
Authors: Amico Francesco , Anning Rebecca , Bendinelli Cino , Balogh Zsolt J. ,   Participants of the 2019 World Society of Emergency Surgery (WSES) Nijmegen splenic injury collaboration group., Leppäniemi Ari , Aparicio-Sánchez Daniel , Hermans Erik , Coccolini Federico , Abu-Zidan Fikri M. , Chiarugi Massimo , Arvieux Catherine , Pirozzolo Giovanni , Khokha Vladimir , Tolonen Matti , Edward Tan , Sugrue Michael , Ceresoli Marco , Muhrbeck Måns , Mohan Rajashekar , Piscioneri Frank , Ietto Giuseppe , Chiara Osvaldo , Catena Fausto 
Published: August 2020

Abstract
Background
Recent trauma guidelines recommend non-operative management for grade III splenic injury without contrast extravasation on computed tomography. Nevertheless, such recommendations rely on low-quality evidence, and practice variation characterizes clinical management for this type of injury. We aimed to identify the role of eleven selected clinical factors influencing the management of grade III splenic injury without contrast extravasation by expert consensus and a modified Delphi approach.

Methods
A questionnaire was developed with the endorsement of the World Society of Emergency Surgery (WSES). This was delivered and answered live by acute care surgeons attending the 6th WSES congress in Nijmegen in 2019. A dedicated mobile phone application was utilized to collect the answers. All answers were evaluated for areas of discrepancy with an 80% threshold for consensus between respondents.

Results
Three factors generated discrepancy in opinion for managing this pattern of injury: the patients’ injury severity, the presence of a bleeding diathesis, and an associated intra-abdominal injury. Agreement was obtained for the other eight factors.

Conclusion
Researchers should focus their efforts on the identified area of discrepancy. Clinicians should use additional care in the presence of the three factors for which discordant opinions were found.
Training to identify red flags in the acute care of trauma: who are the patients at risk for early death despite a relatively good prognosis? An analysis from the TraumaRegister DGU®
Authors: Nolte Philip-C. , Häske David , Lefering Rolf , Bernhard Michael , Casu Sebastian , Frankenhauser Susanne , Gather Andreas , Grützner Paul A. , Münzberg Matthias ,   the TraumaRegister DGU
Published: August 2020

Abstract
Background
In the acute care of trauma, some patients with a low estimated risk of death die suddenly and unexpectedly. In this study, we aim to identify predictors for early death within 24 h following hospital admission in low-risk patients.

Methods
The TraumaRegister DGU® was used to collect records of patients who were primarily treated in a participating hospital between 2004 and 2013 with a RISC II score below 10%.

Results
During the study period, 64,379 patients met the inclusion criteria. The mean RISC II score was 2.0%, and the mean ISS was 16 ± 9. The overall hospital mortality rate was 2.1%, and 0.5% of patients (n = 301) died within the first 24 h. A SPB of ≤ 90 mmHg was associated with an increased risk of death (p < 0.001). An AIS abdomen score of ≥ 3 was associated with increased risk of death within the first 24 h (p < 0.001). A high risk of early death was also seen in patients with an AIS score (thorax) ≥ 3; 51% of those who died died within the first 24 h (p < 0.005). Death in patients over 60 years was more common after 24 h (p < 0.001). Patients with an ASA score of ≥ 3 were more likely to die after the first 24 h (p < 0.001).

Conclusions
Indicators predicting a high risk of early death in patients with a low RISC II score include a SPB ≤ 90 mmHg and severe chest and abdominal trauma. Emergency teams involved in the acute care of trauma patients should be aware of these “red flags” and treat their patients accordingly.
How the clinical dosage of bone cement biomechanically affects adjacent vertebrae
Authors: Chen Xu-shi , Jiang Jian-ming , Sun Pei-dong , Zhang Zhao-fei , Ren Hai-long 
Published: August 2020

Abstract
Objective
This study evaluated the biomechanical changes in the adjacent vertebrae under a physiological load (500 N) when the clinically relevant amount of bone cement was injected into fractured cadaver vertebral bodies.

Methods
The embalmed cadaver thoracolumbar specimens in which each vertebral body (T12–L2) had a BMD of < 0.75 g/cm2 were used for the experiment. For establishing a fracture model, the upper one third of the L1 vertebra was performed wedge osteotomy and the superior endplate was kept complete. Stiffness of specimens was measured in different states. Strain of the adjacent vertebral body and intervertebral disc were measured in pre-fracture, post-fracture, and after augmentation by non-contact optical strain measurement system.

Results
The average amount of bone cement was 4.4 ml (3.8–5.0 ml). The stiffness of after augmentation was significantly higher than the stiffness of post-fracture (p < 0.05), but still lower than pre-fracture stiffness (p < 0.05). After augmentation, the adjacent upper vertebral strain showed no significant difference (p > 0.05) with pre-fracture, while the strain of adjacent lower vertebral body was significantly higher than that before fracture (p < 0.05). In flexion, T12/L1 intervertebral disc strain was significantly greater after augmentation than after the fracture (p < 0.05), but there was no significant difference from that before the fracture (p > 0.05); L1/2 vertebral strain after augmentation was significantly less than that after the fracture (p < 0.05), but there was no significant difference from that before the fracture (p > 0.05).

Conclusions
PVP may therefore have partially reversed the abnormal strain state of adjacent vertebral bodies which was caused by fracture.
Clinical profiles and risk factors of 7-day and 30-day mortality among 160 pediatric patients with hemophagocytic lymphohistiocytosis
Authors: Li Xun , Yan Haipeng , Zhang Xinping , Huang Jiaotian , Xiang Shi-Ting , Yao Zhenya , Zang Ping , Zhu Desheng , Xiao Zhenghui , Lu Xiulan 
Published: August 2020

Abstract
Background
Hemophagocytic lymphohistiocytosis (HLH) is a relatively rare and life-threatening disorder. Early mortality remains significantly high among patients with HLH. Our aim was to investigate clinical features and risk factors associated with 7-day and 30-day mortality among pediatric HLH patients. We retrospectively collected medical records of patients with discharge diagnosis of HLH between August 2014 and October 2018 from a tertiary children’s hospital in China. The main outcome measures were the 7-day and 30-day outcome after hospital admission. The associations between symptoms, concomitant diagnoses, laboratory test results, and the risk of 7-day and 30-day mortality were examined.

Results
Among 160 pediatric HLH patients, 18 (11.3%) patients were deceased within 7 days after admission, and 46 (28.8%) patients were deceased within 30 days. The identified strong risk factors (OR > 10 and p < 0.05) for 30-day mortality were myocardial damage, severe pneumonia, respiratory failure, coagulopathy, gastrointestinal disorder, and multiple organ dysfunction syndrome (MODS). Factors strongly associated with 7-day mortality were sepsis, myocardial damage, shock, and respiratory failure. All patients deceased within 7 days developed hepatic dysfunction, coagulopathy, and MODS.

Conclusions
The identified risk factors could help to stratify patients with high risk of early death, and need to be considered in the development of treatment protocols. As early mortality of HLH remains high, studies are needed to investigate how to initiate adequate HLH-directed treatment strategies for patients at higher risk of early death.
The human microbiome and its link in prostate cancer risk and pathogenesis
Authors: Katongole Paul , Sande Obondo J. , Joloba Moses , Reynolds Steven J. , Niyonzima Nixon 
Published: August 2020

AbstractThere is growing evidence of the microbiome’s role in human health and disease since the human microbiome project. The microbiome plays a vital role in influencing cancer risk and pathogenesis. Several studies indicate microbial pathogens to account for over 15–20% of all cancers. Furthermore, the interaction of the microbiota, especially the gut microbiota in influencing response to chemotherapy, immunotherapy, and radiotherapy remains an area of active research. Certain microbial species have been linked to the improved clinical outcome when on different cancer therapies. The recent discovery of the urinary microbiome has enabled the study to understand its connection to genitourinary malignancies, especially prostate cancer. Prostate cancer is the second most common cancer in males worldwide. Therefore research into understanding the factors and mechanisms associated with prostate cancer etiology, pathogenesis, and disease progression is of utmost importance. In this review, we explore the current literature concerning the link between the gut and urinary microbiome and prostate cancer risk and pathogenesis.
Intact gastro-intestinal tract removal from pig carcasses in a novel Meat Factory Cell approach
Authors: Alvseike Ole , Prieto Miguel , Bjørnstad Per Håkon , Mason Alex 
Published: August 2020

AbstractConventional automated slaughter lines for pigs are organised as disassembly lines with many specialised machines. High costs and capacities make them relevant only for large scale meat production. The ambition with the novel Meat Factory Cell (MFC) concept is to provide the meat industry with a robust and flexible automation platform that is also relevant for smaller scale production. The MFC process deviates radically from conventional processing of pig carcasses after singeing. In MFC, the limbs are removed first. Then the dorsal muscles along the spinal axis from tail to head are removed with the column and rind in one meat cut, followed by removal of the viscera. Finally, the cut ribs and belly are removed. Such approaches to automation in pig abattoirs and cutting plants are highly needed in smaller scale production, and they should produce meat and offal as hygienically as conventional factories. This case study reports the evisceration of 37 pigs in 9 trials performed in 2019. Several approaches were tested with a prototype carcass holding unit. Evisceration could be undertaken without the need to cut through the gastrointestinal tract from tongue to rectum, reducing the probability of accidental faecal contamination of pork carcasses from the gut content. The Meat Factory Cell procedure is an advance towards automated evisceration of pig carcasses which is both simple and hygienic. The traditional separation of internal organs into a pluck set and a set of stomach and bowels was more prone to leakages.
Conditional knockout of leptin receptor in neural stem cells leads to obesity in mice and affects neuronal differentiation in the hypothalamus early after birth
Authors: Ren Zhonggan , Liu Yitong , Hong Wentong , Pan Xinjie , Gong Pifang , Liu Qiong , Zhou Guomin , Qin Song 
Published: August 2020

AbstractLeptin, secreted by peripheral adipocytes, binds the leptin receptor (Lepr) in the hypothalamus, thereby contributing to the regulation of satiety and body weight. Lepr is expressed in the embryonic brain as early as embryonic day 12.5. However, the function of Lepr in neural precursor cells in the brain has not been resolved. To address this issue, we crossed the Leprflox/flox mice with each of Shh-Cre mice (Shh, sonic hedgehog) and Nestin (Nes)-Cre mice. We found that deletion of Lepr specifically in nestin-expressing cells led to extreme obesity, but the conditional null of Lepr in Shh-expressing cells had no obvious phenotype. Moreover, the level of leptin-activated pSTAT3 decreased in the anterior and central subregions of the arcuate hypothalamus of Shh-Cre; Leprflox/flox mice compared with the controls. By contrast, in Nes-Cre; Leprflox/flox mice, the level of leptin-activated pSTAT3 decreased in all subregions including the anterior, central, and posterior arcuate hypothalamus as well as the dorsomedial, ventromedial, and median eminence of the hypothalamus, revealing that the extensive lack of Lepr in the differentiated neurons of the hypothalamus in the conditional null mice. Notably, conditional deletion of Lepr in nestin-expressing cells enhanced the differentiation of neural precursor cells into neurons and oligodendroglia but inhibited differentiation into astrocytes early in postnatal development of hypothalamus. Our results suggest that Lepr expression in neural precursor cells is essential for maintaining normal body weight as well as the differentiation of neural precursor cells to the neural/glial fate in the hypothalamus shortly after birth.
Dendritic cell biology and its role in tumor immunotherapy
Authors: Wang Yingying , Xiang Ying , Xin Victoria W. , Wang Xian-Wang , Peng Xiao-Chun , Liu Xiao-Qin , Wang Dong , Li Na , Cheng Jun-Ting , Lyv Yan-Ning , Cui Shu-Zhong , Ma Zhaowu , Zhang Qing , Xin Hong-Wu 
Published: August 2020

AbstractAs crucial antigen presenting cells, dendritic cells (DCs) play a vital role in tumor immunotherapy. Taking into account the many recent advances in DC biology, we discuss how DCs (1) recognize pathogenic antigens with pattern recognition receptors through specific phagocytosis and through non-specific micropinocytosis, (2) process antigens into small peptides with proper sizes and sequences, and (3) present MHC-peptides to CD4+ and CD8+ T cells to initiate immune responses against invading microbes and aberrant host cells. During anti-tumor immune responses, DC-derived exosomes were discovered to participate in antigen presentation. T cell microvillar dynamics and TCR conformational changes were demonstrated upon DC antigen presentation. Caspase-11-driven hyperactive DCs were recently reported to convert effectors into memory T cells. DCs were also reported to crosstalk with NK cells. Additionally, DCs are the most important sentinel cells for immune surveillance in the tumor microenvironment. Alongside DC biology, we review the latest developments for DC-based tumor immunotherapy in preclinical studies and clinical trials. Personalized DC vaccine-induced T cell immunity, which targets tumor-specific antigens, has been demonstrated to be a promising form of tumor immunotherapy in patients with melanoma. Importantly, allogeneic-IgG-loaded and HLA-restricted neoantigen DC vaccines were discovered to have robust anti-tumor effects in mice. Our comprehensive review of DC biology and its role in tumor immunotherapy aids in the understanding of DCs as the mentors of T cells and as novel tumor immunotherapy cells with immense potential.
Circular RNA circ-CPA4/ let-7 miRNA/PD-L1 axis regulates cell growth, stemness, drug resistance and immune evasion in non-small cell lung cancer (NSCLC)
Authors: Hong Weijun , Xue Min , Jiang Jun , Zhang Yajuan , Gao Xiwen 
Published: August 2020

Abstract
Background
Non-small cell lung cancer (NSCLC) cells derived intracellular and extracellular programmed cell death ligand 1 (PD-L1) promoted cancer progression and drug resistance, and facilitated tumor immune evasion. However, the detailed molecular mechanisms are still largely unknown. In the present study, we aimed to explore the role of circular RNA circ-CPA4/let-7 miRNA/PD-L1 axis in the regulation of NSCLC progression, drug resistance and tumor immune microenvironment.

Methods
Real-Time qPCR and Western Blot analysis were conducted to examine gene expressions at transcriptional and translated levels, respectively. The regulatory mechanisms of circ-CPA4, let-7 miRNA and PD-L1 were validated by dual-luciferase reporter gene system and RNA pull-down assay. Cell growth and apoptosis were determined by CCK-8 assay, colony formation assay and Annexin V-FITC/PI double staining assay. Cell mobility was evaluated by transwell assay.

Results
Circ-CPA4 and PD-L1 were high-expressed, while let-7 miRNA was low-expressed in NSCLC cells and cancer tissues compared to the human bronchial epithelial (HBE) cells and their paired clinical normal adjacent tissues, respectively. Besides, knock-down of circ-CPA4 inhibited cell growth, mobility and epithelial-mesenchymal transition (EMT), and promoted cell death in NSCLC cells by downregulating PD-L1 through serving as a RNA sponge for let-7 miRNA. In addition, the NSCLC cells derived PD-L1-containing exosomes promoted cell stemness and increased resistance of NSCLC cells to cisplatin. Notably, by co-culturing the NSCLC cells with CD8+ T cells isolated from human peripheral blood mononuclear cells (hPBMCs) in a transwell co-culturing system, we found that NSCLC cells inactivated CD8+ T cells in a secreted PD-L1-dependent manner. Further results suggested that circ-CPA4 also positively regulated exosomal PD-L1, and the NSCLC cells with circ-CPA4 ablation re-activated CD8+ T cells in the co-culturing system.

Conclusion
Taken together, circ-CPA4 regulated cell growth, mobility, stemness and drug resistance in NSCLC cells and inactivated CD8+ T cells in the tumor immune microenvironment through let-7 miRNA/PD-L1 axis.
COL4A1 promotes the growth and metastasis of hepatocellular carcinoma cells by activating FAK-Src signaling
Authors: Wang Ting , Jin Haojie , Hu Jingying , Li Xi , Ruan Haoyu , Xu Huili , Wei Lin , Dong Weihua , Teng Fei , Gu Jianren , Qin Wenxin , Luo Xiaoying , Hao Yujun 
Published: August 2020

Abstract
Background
Collagens are the most abundant proteins in extra cellular matrix and important components of tumor microenvironment. Recent studies have showed that aberrant expression of collagens can influence tumor cell behaviors. However, their roles in hepatocellular carcinoma (HCC) are poorly understood.

Methods
In this study, we screened all 44 collagen members in HCC using whole transcriptome sequencing data from the public datasets, and collagen type IV alpha1 chain (COL4A1) was identified as most significantly differential expressed gene. Expression of COL4A1 was detected in HCC samples by quantitative real-time polymerase chain reaction (qRT-PCR), western blot and immunohistochemistry (IHC). Finally, functions and potential mechanisms of COL4A1 were explored in HCC progression.

Results
COL4A1 is the most significantly overexpressed collagen gene in HCC. Upregulation of COL4A1 facilitates the proliferation, migration and invasion of HCC cells through FAK-Src signaling. Expression of COL4A1 is upregulated by RUNX1 in HCC. HCC cells with high COL4A1 expression are sensitive to the treatment with FAK or Src inhibitor.

Conclusion
COL4A1 facilitates growth and metastasis in HCC via activation of FAK-Src signaling. High level of COL4A1 may be a potential biomarker for diagnosis and treatment with FAK or Src inhibitor for HCC.
Development of a Core outcome set for fetal Myelomeningocele (COSMiC): study protocol
Authors: Altoukhi Samar , Whitehead Clare L. , Ryan Greg , Deprest Jan , Joyeux Luc , Gallagher Katie , Drake James , Church Paige , Horn Daphne , Diambomba Yenge , Carvalho Jose C. A. , Van Mieghem Tim 
Published: August 2020

AbstractBackgroundOpen spina bifida (OSB) is one of the most common congenital central nervous system defects and leads to long-term physical and cognitive disabilities. Open fetal surgery for OSB improves neurological outcomes and reduces the need for ventriculoperitoneal shunting, compared to postnatal surgery, but is associated with a significant risk of prematurity and maternal morbidity. Fetoscopic surgery comes with less maternal morbidity, yet the question remains whether the procedure is neuroprotective and reduces prematurity. Comparison of outcomes between different treatment options is challenging due to inconsistent outcome reporting. We aim to develop and disseminate a core outcome set (COS) for fetal OSB, to ensure that outcomes relevant to all stakeholders are collected and reported in a standardised fashion in future studies.MethodsThe COS will be developed using a validated Delphi methodology. A systematic literature review will be performed to identify outcomes previously reported for prenatally diagnosed OSB. We will assess maternal (primary and subsequent pregnancies), fetal, neonatal and childhood outcomes until adolescence. In a second phase, we will conduct semi-structured interviews with stakeholders, to ensure representation of additional relevant outcomes that may not have been reported in the literature. We will include patients and parents, as well as health professionals involved in the care of these pregnancies and children (fetal medicine specialists, fetal surgeons, neonatologists/paediatricians and allied health). Subsequently, an international group of key stakeholders will rate the importance of the identified outcomes using three sequential online rounds of a modified Delphi Survey. Final agreement on outcomes to be included in the COS, their definition and measurement will be achieved through a face-to-face consensus meeting with all stakeholder groups. Dissemination of the final COS will be ensured through different media and relevant societies.DiscussionDevelopment and implementation of a COS for fetal OSB will ensure consistent outcome reporting in future clinical trials, systematic reviews and clinical practice guidelines. This will lead to higher quality research, better evidence-based clinical practice and ultimately improved maternal, fetal and long-term childhood outcomes.Trial registrationInternational Prospective Register of Systematic Reviews (PROSPERO)CRD42018104880. Registered on December 5, 2018. Core Outcome Measures in Effectiveness Trials (COMET):1187
Efficacy, safety and cost-effectiveness of a web-based platform delivering the results of a biomarker-based predictive model of biotherapy response for rheumatoid arthritis patients: a protocol for a randomized multicenter single-blind active controlled clinical trial (PREDIRA)
Authors: Freites-Núñez Dalifer , Baillet Athan , Rodriguez-Rodriguez Luis , Nguyen Minh Vu Chuong , Gonzalez Isidoro , Pablos Jose Luis , Balsa Alejandro , Vazquez Monica , Gaudin Philippe , Fernandez-Gutierrez Benjamín 
Published: August 2020

Abstract
Background
Rheumatoid arthritis (RA) is one of the leading chronic inflammatory rheumatism. First-line therapy with synthetic disease-modifying antirheumatic drugs (sDMARD) is insufficiently effective in 40% of cases and these patients are treated with biotherapies. The increased use of these drugs each year is becoming a public health issue with considerable economic burden. This cost is 20 times higher than that of sDMARD. However, among patients treated with biotherapies, clinical practice shows that about one third will not respond to the selected drug. In nonresponse cases, practitioners currently have no choice but to perform an empirical switching between different treatments, because no tool capable of predicting the response or nonresponse to these molecules is currently available.

Methods
The study is a prospective, phase III, controlled, multicenter, and randomized, single-blind (patient) clinical trial, including RA patients with a previous failure to anti-TNF therapies. The main objective is the analysis of the clinical and pharmacoeconomic impact after 6 months of treatment. Intervention arm: prescription of biotherapy (rituximab, adalimumab, abatacept) using SinnoTest® software, a prediction software based on proteomic biomarkers. Control arm: prescription of biotherapy based on current practice, without the SinnoTest® software (any biotherapy). In addition, a substudy will be carried out within this trial to generate a biobank and further analyze the proteomic profile of the patients and their modification throughout the study.

Discussion
This clinical trial study will be the first validation study of a biotherapy response prediction software, bringing personalized medicine into the management of RA. We expect that the findings from this study will bring several benefits for the patient and the Health Care System.

Trial registration
ClincalTrials.gov NCT04147026. Registered on 31 October, 2019.