bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep reinforcement learning for modeling human locomotion control in neuromechanical simulation
Authors: Song Seungmoon , Kidziński Łukasz , Peng Xue Bin , Ong Carmichael , Hicks Jennifer , Levine Sergey , Atkeson Christopher G. , Delp Scott L. 
Published: August 2021

AbstractModeling human motor control and predicting how humans will move in novel environments is a grand scientific challenge. Researchers in the fields of biomechanics and motor control have proposed and evaluated motor control models via neuromechanical simulations, which produce physically correct motions of a musculoskeletal model. Typically, researchers have developed control models that encode physiologically plausible motor control hypotheses and compared the resulting simulation behaviors to measurable human motion data. While such plausible control models were able to simulate and explain many basic locomotion behaviors (e.g. walking, running, and climbing stairs), modeling higher layer controls (e.g. processing environment cues, planning long-term motion strategies, and coordinating basic motor skills to navigate in dynamic and complex environments) remains a challenge. Recent advances in deep reinforcement learning lay a foundation for modeling these complex control processes and controlling a diverse repertoire of human movement; however, reinforcement learning has been rarely applied in neuromechanical simulation to model human control. In this paper, we review the current state of neuromechanical simulations, along with the fundamentals of reinforcement learning, as it applies to human locomotion. We also present a scientific competition and accompanying software platform, which we have organized to accelerate the use of reinforcement learning in neuromechanical simulations. This “Learn to Move” competition was an official competition at the NeurIPS conference from 2017 to 2019 and attracted over 1300 teams from around the world. Top teams adapted state-of-the-art deep reinforcement learning techniques and produced motions, such as quick turning and walk-to-stand transitions, that have not been demonstrated before in neuromechanical simulations without utilizing reference motion data. We close with a discussion of future opportunities at the intersection of human movement simulation and reinforcement learning and our plans to extend the Learn to Move competition to further facilitate interdisciplinary collaboration in modeling human motor control for biomechanics and rehabilitation research
German-speaking medical students on international electives: an analysis of popular elective destinations and disciplines
Authors: Storz Maximilian Andreas , Lederer Ann-Kathrin , Heymann Eric Pieter 
Published: August 2021

AbstractBackgroundInternational medical electives are a well-established part of the curriculum of many western medical schools. It is widely accepted that these electives contribute to improved clinical examination and communication skills. Overseas electives also exert a strong influence over future career decisions and often pave the way for later international work. Whilst the positive outcomes are known, little information exists regarding elective preferences and destinations overall, information that could help optimise a safe learning experience and maximise the potential for one of the highlights of medical education. In order to obtain analytical data that could assist medical elective framework development, we systematically reviewed the two largest German online databases cataloguing abroad elective testimonies.ResultsWe identified 856 overseas elective reports uploaded within the last five years. European destinations were the most sought-after choice among German-speaking medical students. Interest in abroad electives in the United States (U.S.), a traditionally popular destination, was much lower than expected. U.S. elective reports accounted for only 3 % of long-term electives. Electives in low- and middle-income countries were generally less popular than electives in high-income countries. General surgery was the most popular elective discipline, followed by Emergency Medicine and Gynaecology and Obstetrics.ConclusionsWe observed a large inhomogeneity in German-speaking medical students’ elective choices, potentially influenced by financial and organizational aspects as well as geopolitical developments. This highlights a crucial challenge for medical schools and other organizations involved in elective planning. In light of regional differences, our data suggest that a “one size fits all” preparation is not pertinent to optimize students’ elective experience. Country- or region-specific pre-departure trainings and more individualized elective frameworks might be necessary to address these differences and to ensure a safe learning experience for students.
Reliability and reproducibility of measurements in para-sagittal planes on sub-axial cervical vertebral bodies: a morphometric study of endplates in three-dimensional models
Authors: Wang Long , Luo Hao T. , Lu Wei , Cai Xing Bo , Yu Chen , Lu Sheng 
Published: August 2021

Abstract
Background
Dimensional measurements have been implemented on a variety of entities in morphological studies of the sub-axial cervical vertebral endplate. Despite great progress, little information between the mid-sagittal plane and bilateral uncinate processes has been acquired due to the lack of a reliable method to determine the para-sagittal planes. Also, few studies of this region are available. We proposed a new approach to defining the para-sagittal planes on a 3D cervical vertebral body model; in this approach, dimensions can be measured in a specific plane. The aim of this study was to assess the inter-observer and intra-observer reliability of the measurements in different sagittal planes on sub-axial cervical vertebral endplates of 3D models.

Methods
We established mid-sagittal and bilateral quarter para-sagittal planes on the 3D model of a sub-axial cervical vertebral body based on landmarks labeled on the surface. By intersecting the vertebral body with the planes, three curves located at the three para-sagittal planes were generated. Linear dimensions were measured on every curve by two observers separately, and in total, 24 sub-axial cervical spines were included in the study. The first observer (O1) performed the procedure twice with an interval of 2 weeks. The paired t test, Wilcoxon matched-pairs signed-rank test and the interclass correlation coefficient (ICC) were employed to evaluate the inter- and intra-observer reliability of the proposed method.

Results
There were no significant differences in most intra- and inter-observer comparisons, and higher non-significant proportions were found in the intra-observer comparisons than in comparisons between different observers. The interclass correlation coefficients (ICCs) in the measurements were excellent (> 0.75) in most circumstances, and the values in intra-observer comparisons were higher than those in inter-observer comparisons.

Conclusions
In this study, we proposed an approach to determine the bilateral quarter para-sagittal planes in a 3D cervical vertebral body model; the results demonstrated that the method is reproducible with high intra- and inter-observer agreement.
Is the fusion order of the cranial and caudal levels different in two-level anterior cervical discectomy and fusion for cervical spondylopathy? A retrospective study
Authors: Sheng Xia-Qing , Meng Yang , Liu Hao , Wang Bei-Yu , Yang Yi , Rong Xin , Hong Ying 
Published: August 2021

Abstract
Study design
Retrospective study.

Objective
This study aimed to compare the fusion order between the cranial and caudal levels in two-level anterior cervical discectomy and fusion (ACDF) with a zero-profile device in the treatment of cervical spondylopathy.

Summary of background data
Fusion is the standard used to judge the success of ACDF. However, the fusion order in two-level ACDF remains uncertain. The mechanical environment of different levels is different, which may affect the fusion rate or fusion order.

Methods
From 2014 to January 2019, data of consecutive patients with two-level cervical disk degenerative disease who underwent ACDF were retrospectively reviewed. Radiological assessments were based on the range of motion of the fusion level, segment slope, and disk height, and complications were assessed. Data were analyzed using the paired t, Mann-Whitney U, χ2, Fisher exact, and rank-sum tests and logistic regression analysis.

Results
In total, 118 patients were ultimately enrolled for analysis in the study. The respective fusion rates of the cranial and caudal levels were 26.27% and 10.17% (p < 0.05) at 3 months, 58.47% and 42.37% (p < 0.05) at 6 months, 86.44% and 82.20% (1 0.05) at 1 year, and 92.37% and 89.83% (p > 0.05) at the last follow-up. Multivariate logistic regression analysis indicated that the preoperative segmental slope and cranial level were independent risk factors for non-fusion. The adjacent segment degeneration (ASD) and subsidence rates were comparable between the two levels.

Conclusion
The caudal level had a slower fusion process than the cranial level. A higher preoperative segment slope was a risk factor for fusion. However, the subsidence and ASD rate were comparable between the caudal and cranial levels in the two-level ACDF.
Traditional herbal formula Wu-Mei-Wan alleviates TNBS-induced colitis in mice by inhibiting necroptosis through increasing RIPK3 O-GlcNAcylation
Authors: Wu Fan , Shao Qingqing , Cheng Zhe , Xiong Xinyu , Fang Ke , Zhao Yan , Dong Ruolan , Xu Lijun , Lu Fuer , Chen Guang 
Published: August 2021

AbstractBackgroundAccumulating evidence indicated that necroptosis plays an essential role in the pathogenesis of inflammatory bowel disease (IBD). TheO-linked β-N-acetylglucosaminylation (O-GlcNAcylation) of necroptotic signal molecule receptor-interacting serine-threonine kinase 3 (RIPK3) was reported to exert a protective effect in gut inflammation. Our recent study suggested traditional Chinese herbal formula Wu-Mei-Wan (WMW) as an effective prescription in mouse colitis. However, the potential mechanisms are not fully understood. Considering the crucial role of necroptosis in the pathogenesis of IBD, therefore, this study was designed to explain whether the anti-colitis effect of WMW is mediated by modulating necroptosis and its related mechanisms.MethodsThe protective effects of WMW on colitis have been determined by detecting colitis mice body weight, disease activity index (DAI), survival rate and colon length. Colonic inflammation was examined by inflammatory cells infiltration and local cytokines levels. After then, we measured the levels of necroptosis andO-GlcNAcylation. CO-immunoprecipitation experiments were used to address whether elevatedO-GlcNAcylation can inhibit necroptotic signal transduction in the treatment of WMW. Finally, the key enzymes inO-GlcNAcylation:O-GlcNAc transferase (OGT) andO-GlcNAcase (OGA) were examined and molecular docking analysis was used to determine effective natural compounds in the regulation on OGT and OGA activities.ResultsOur results showed that WMW significantly improved mice body weight, survival rate and colon length, decreased DAI in TNBS-induced colitis. WMW obviously alleviated colonic inflammatory responses with reduced macrophages, neutrophils infiltration and local IL-1β, IL-6, TNF-α and IFN-γ levels. It was found that WMW increased colonicO-GlcNAcylation level and inhibited the activation of RIPK1, RIPK3 and MLKL. Then, further experiments revealed that WMW enhanced OGT activity and suppressed OGA activity, thereby increasing RIPK3O-GlcNAcylation and inhibiting the binding of RIPK3 and MLKL, which led to the inhibition of necroptosis. Additionally, docking analysis demonstrated that hesperidin, coptisine and ginsenoside Rb1 may exert a major role in the regulation on OGT and OGA activities by WMW.ConclusionOur work demonstrated that WMW can alleviate TNBS-induced colitis in mice by inhibiting necroptosis through increasing RIPK3O-GlcNAcylation.
SELP Asp603Asn and severe thrombosis in COVID-19 males
Authors: Fallerini Chiara , Daga Sergio , Benetti Elisa , Picchiotti Nicola , Zguro Kristina , Catapano Francesca , Baroni Virginia , Lanini Simone , Bucalossi Alessandro , Marotta Giuseppe , Colombo Francesca , Baldassarri Margherita , Fava Francesca , Beligni Giada , Di Sarno Laura , Alaverdian Diana , Palmieri Maria , Croci Susanna , Isidori Andrea M. , Furini Simone , Frullanti Elisa ,   GEN-COVID Multicenter Study, Renieri Alessandra , Mari Francesca 
Published: August 2021

AbstractThromboembolism is a frequent cause of severity and mortality in COVID-19. However, the etiology of this phenomenon is not well understood. A cohort of 1186 subjects, from the GEN-COVID consortium, infected by SARS-CoV-2 with different severity was stratified by sex and adjusted by age. Then, common coding variants from whole exome sequencing were mined by LASSO logistic regression. The homozygosity of the cell adhesion molecule P-selectin gene (SELP) rs6127 (c.1807G > A; p.Asp603Asn) which has been already associated with thrombotic risk is found to be associated with severity in the male subcohort of 513 subjects (odds ratio = 2.27, 95% Confidence Interval 1.54–3.36). As the SELP gene is downregulated by testosterone, the odd ratio is increased in males older than 50 (OR 2.42, 95% CI 1.53–3.82). Asn/Asn homozygotes have increased D-dimers values especially when associated with poly Q ≥ 23 in the androgen receptor (OR 3.26, 95% CI 1.41–7.52). These results provide a rationale for the repurposing of antibodies against P-selectin as adjuvant therapy in rs6127 male homozygotes especially if older than 50 or with an impaired androgen receptor.
Altered proTGFα/cleaved TGFα ratios offer new therapeutic strategies in renal carcinoma
Authors: García-Alonso Sara , Romero-Pérez Inés , Gandullo-Sánchez Lucía , Chinchilla Luis , Ocaña Alberto , Montero Juan Carlos , Pandiella Atanasio 
Published: August 2021

Abstract
Background
Treatment of renal cancer has significantly improved with the arrival to the clinic of kinase inhibitors and immunotherapies. However, the disease is still incurable in advanced stages. The fact that several approved inhibitors for kidney cancer target receptor tyrosine kinases (RTKs) suggests that these proteins play a critical role in the pathophysiology of the disease. Based on these precedents, we decided to explore whether RTKs other than those targeted by approved drugs, contribute to the development of kidney cancer.

Methods
The activation status of 49 RTKs in 44 paired samples of normal and tumor kidney tissue was explored using antibody arrays, with validation by western blotting. Genetic and pharmacologic approaches were followed to study the biological implications of targeting the epidermal growth factor receptor (EGFR) and its ligand Transforming Growth Factor-α (TGFα).

Results
Activation of the EGFR was found in a substantial number of tumors. Moreover, kidney tumors expressed elevated levels of TGFα. Down-regulation of EGFR or TGFα using RNAi or their pharmacological targeting with blocking antibodies resulted in inhibition of the proliferation of in vitro cellular models of renal cancer. Importantly, differences in the molecular forms of TGFα expressed by tumors and normal tissues were found. In fact, tumor TGFα was membrane anchored, while that expressed by normal kidney tissue was proteolytically processed.

Conclusions
The EGFR-TGFα axis plays a relevant role in the pathophysiology of kidney cancer. This study unveils a distinctive feature in renal cell carcinomas, which is the presence of membrane-anchored TGFα. That characteristic could be exploited therapeutically to act on tumors expressing transmembrane TGFα, for example, with antibody drug conjugates that could recognize the extracellular region of that protein.
Pathogens distribution and antimicrobial resistance in bloodstream infections in twenty-five neonatal intensive care units in China, 2017–2019
Authors: Liu Jing , Fang Zengyu , Yu Yonghui , Ding Yanjie , Liu Zhijie , Zhang Chengyuan , He Haiying , Geng Hongli , Chen Weibing , Zhao Guoying , Liu Qiang , Wang Baoying , Sun Xueming , Wang Shaofeng , Sun Rongrong , Fu Delong , Liu Xinjian , Huang Lei , Li Jing , Xing Xuexue , Wang Xiaokang , Gao Yanling , Zhu Renxia , Han Meiying , Peng Fudong , Geng Min , Deng Liping 
Published: August 2021

Abstract
Background
Overcrowding, abuse of antibiotics and increasing antimicrobial resistance negatively affect neonatal survival rates in developing countries. We aimed to define pathogens and their antimicrobial resistance (AMR) of early-onset sepsis (EOS), hospital-acquired late-onset sepsis (HALOS) and community-acquired late-onset sepsis (CALOS) in 25 neonatal intensive care units (NICUs) in China.

Study design
This retrospective descriptive study included pathogens and their AMR from all neonates with bloodstream infections (BSIs) admitted to 25 tertiary hospitals in China from January 1, 2017, and December 31, 2019. We defined EOS as the occurrence of BSI at or before 72 h of life and late-onset sepsis (LOS) if BSI occurred after 72 h of life. LOS were classified as CALOS if occurrence of BSI was ≤ 48 h after admission, and HALOS, if occurrence was > 48 h after admission.

Results
We identified 1092 pathogens of BSIs in 1088 infants from 25 NICUs. Thirty-two percent of all pathogens were responsible for EOS, 64.3% HALOS, and 3.7% CALOS. Gram-negative (GN) bacteria accounted for a majority of pathogens in EOS (56.7%) and HALOS (62.2%). The most frequent pathogens causing EOS were Escherichia coli (27.2%) and group B streptococcus (GBS; 14.6%) whereas in CALOS they were GBS (46.3%) and Staphylococcus aureus (41.5%). Klebsiella pneumoniae (27.9%), Escherichia coli (15.7%) and Fungi (12.8%) were the top three isolates in HALOS. Third-generation cephalosporin resistance rates in GN bacteria ranged from 9.7 to 55.6% in EOS and 26% to 63.3% in HALOS. Carbapenem resistance rates in GN bacteria ranged from 2.7 to 31.3% in HALOS and only six isolates in EOS were carbapenem resistant. High rates of multidrug resistance were observed in Klebsiella pneumoniae (60.7%) in HALOS and in Escherichia coli (44.4%) in EOS. All gram-positive bacteria were susceptible to vancomycin except for three Enterococcus faecalis in HALOS. All-cause mortality was higher among neonates with EOS than HALOS (7.4% VS 4.4%, [OR] 0.577, 95% CI 0.337–0.989; P = 0.045).

Conclusions
Escherichia coli, Klebsiella pneumoniae and GBS were the leading pathogens in EOS, HALOS and CALOS, respectively. The high proportion of pathogens and high degree of antimicrobial resistance in HALOS underscore understanding of the pathogenesis and emphasise the need to devise effective interventions in developing countries.
Atezolizumab plus bevacizumab combination enables an unresectable hepatocellular carcinoma resectable and links immune exclusion and tumor dedifferentiation to acquired resistance
Authors: Wang Yulei , Lu Li-Chun , Guan Yinghui , Ho Ming-Chih , Lu Shan , Spahn Jessica , Hsu Chih-Hung 
Published: August 2021

AbstractWe reported a patient with unresectable hepatocellular carcinoma (HCC) who initially received 15 cycles of atezolizumab plus bevacizumab combination and had best tumor response of partial response, but later experienced disease progression. After subsequent surgical resection, the patient enjoyed long-term disease-free status at the last follow-up 19 months after surgery. By investigating paired tumor tissues (pretreatment and post-progression samples) with immunohistochemistry, multiplex immunofluorescence, RNA sequencing, and DNA sequencing, we explored the dynamic changes in the tumor microenvironment (TME) and potential mechanisms underlying acquired resistance to the combination. In the post-progression HCC tissue compared with the baseline tissue, the expression of PD-L1 in tumor-infiltrating immune cells and the abundance of CD8+ T cells in the tumor area had decreased, and an immune-excluded TME had emerged. Transcriptomic analysis revealed a gene expression signature representing progenitor/hepatoblast features in the post-progression tumor tissue, with an increased expression of imprinted genes and decreased expression of cytochrome P450 family genes. Finally, tumor mutational burden and MHC class I expression in tumor cells were both increased in the post-progression tissue, suggesting that neoantigen depletion or loss-of-antigen presentation were unlikely causes of acquired resistance in this patient. Atezolizumab plus bevacizumab combination therapy enabled our patient to receive hepatectomy and achieve long-term remission. A comparison of paired tumor tissues suggested that immune-excluded TME and tumor dedifferentiation may have contributed to acquired resistance to the combination.
High-resolution flow simulation in Typhoon 21, 2018: massive loss of submerged macrophytes in Lake Biwa
Authors: Nakada Satoshi , Haga Hiroki , Iwaki Maho , Mabuchi Kohji , Takamura Noriko 
Published: August 2021

AbstractThe global activities of typhoons and hurricanes are gradually changing, and these storms can drastically affect lake ecosystems through the recession of submerged macrophytes that regulate the water quality in lakes. Using an echosounder, we captured the short-term, massive loss of submerged macrophytes attributed to the abnormal fluctuation of the water level induced by the approach of a catastrophic super typhoon in the southern basin of Lake Biwa, Japan. This paper investigates the physical processes responsible for the loss of vegetation using a high-resolution circulation model in Lake Biwa as a pilot study area. The circulation model was coupled with dynamical models of the fluid force and erosion acting on the vegetation. Our simulation successfully reproduced the water level fluctuation and high-speed current (torrent) generated by the typhoon gale. The simulated results demonstrated that the fluid force driven by the gale-induced torrent uprooted submerged macrophytes during the typhoon approach and that this fluid force (rather than erosion) caused the outflow of vegetation. As a result, this uprooting attributed to the fluid force induced the massive loss of submerged macrophytes in a large area of the southern basin, which might have increased primary production and reduced the stock of fish such as bluegill in the lake. Our model can estimate the reduction in the macrophyte height within the range of − 1.3 to − 0.4 m, suggesting that fluid forces greater than the time-averaged value (1.24 × 10−4 N) were available. Flow speeds of approximately 0.8 m/s might be the critical value that induces the fluid force acting on the uprooting of the submerged macrophytes. Our approach is practical for evaluating changes in lake environments attributed to the massive outflow of submerged macrophytes under various climate change scenarios.