bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of High Hydrostatic Pressure on Human Trabecular Bone Regarding Cell Death and Matrix Integrity
Authors: Waletzko-Hellwig Janine , Pohl Christopher , Riese Janik , Schlosser Michael , Dau Michael , Engel Nadja , Springer Armin , Bader Rainer 
Published: August 2021

The reconstruction of critical size bone defects is still clinically challenging. Even though the transplantation of autologous bone is used as gold standard, this therapy is accompanied by donor site morbidities as well as tissue limitations. The alternatively used allografts, which are devitalized due to thermal, chemical or physical processing, often lose their matrix integrity and have diminished biomechanical properties. High Hydrostatic Pressure (HHP) may represent a gentle alternative to already existing methods since HHP treated human osteoblasts undergo cell death and HHP treated bone cylinders maintain their mechanical properties. The aim of this study was to determine the biological effects caused by HHP treatment regarding protein/matrix integrity and type of cell death in trabecular bone cylinders. Therefore, different pressure protocols (250 and 300 MPa for 10, 20 and 30 min) and end point analysis such as quantification of DNA-fragmentation, gene expression, SDS-PAGE, FESEM analysis and histological staining were performed. While both protein and matrix integrity was preserved, molecular biological methods showed an apoptotic differentiation of cell death for lower pressures and shorter applications (250 MPa for 10 and 20 min) and necrotic differentiation for higher pressures and longer applications (300 MPa for 30 min). This study serves as a basis for further investigation as it shows that HHP successfully devitalizes trabecular bone cylinders.
Difference of Intrahost Dynamics of the Second Human Pegivirus and Hepatitis C Virus in HPgV-2/HCV-Coinfected Patients
Authors: Liang Yuanhao , Hu Fengyu , Fan Hang , Li Linghua , Wan Zhengwei , Wang Haiying , Shui Jingwei , Zhou Yuanping , Tong Yigang , Cai Weiping , Tang Shixing 
Published: August 2021

BackgroundThe second human pegivirus (HPgV-2) and hepatitis C virus (HCV) belong to the Flaviviridae family and share some common genome features. However, the two viruses exhibit significantly different genetic diversity. The comparison of intrahost dynamics of HPgV-2 and HCV that mainly reflect virus-host interactions is needed to elucidate their intrahost difference of genetic diversity and the possible mechanisms.MethodsIntrahost single nucleotide variations (iSNVs) were identified by means of next-generation sequencing from both cross-sectional and longitudinal samples from HPgV-2- and HCV-coinfected patients. The levels of human cytokines were quantified in the patient before and after HCV elimination by the treatment of direct-acting antivirals (DAA).ResultsUnlike HCV, the viral sequences of HPgV-2 are highly conserved among HPgV-2-infected patients. However, iSNV analysis confirmed the intrahost variation or quasispecies of HPgV-2. Almost all iSNVs of HPgV-2 did not accumulate or transmit within host over time, which may explain the highly conserved HPgV-2 consensus sequence. Intrahost variation of HPgV-2 mainly causes nucleotide transition in particular at the 3rd codon position and synonymous substitutions, indicating purifying or negative selection posed by host immune system. Cytokine data further indicate that HPgV-2 infection alone may not efficiently stimulate innate immune responses since proinflammatory cytokine expression dramatically decreased with elimination of HCV.ConclusionThis study provided new insights into the intrahost genomic variations and evolutionary dynamics of HPgV-2 as well as the impact of host immune selection and virus polymerase on virus evolution. The different genetic diversity of HPgV-2 and HCV makes HPgV-2 a potential new model to investigate RNA virus diversity and the mechanism of viral polymerase in modulating virus replication.
FABP3 Deficiency Exacerbates Metabolic Derangement in Cardiac Hypertrophy and Heart Failure via PPARα Pathway
Authors: Zhuang Lingfang , Mao Ye , Liu Zizhu , Li Chenni , Jin Qi , Lu Lin , Tao Rong , Yan Xiaoxiang , Chen Kang 
Published: August 2021

Background: Cardiac hypertrophy was accompanied by various cardiovascular diseases (CVDs), and due to the high global incidence and mortality of CVDs, it has become increasingly critical to characterize the pathogenesis of cardiac hypertrophy. We aimed to determine the metabolic roles of fatty acid binding protein 3 (FABP3) on transverse aortic constriction (TAC)-induced cardiac hypertrophy.Methods and Results: Transverse aortic constriction or Ang II treatment markedly upregulated Fabp3 expression. Notably, Fabp3 ablation aggravated TAC-induced cardiac hypertrophy and cardiac dysfunction. Multi-omics analysis revealed that Fabp3-deficient hearts exhibited disrupted metabolic signatures characterized by increased glycolysis, toxic lipid accumulation, and compromised fatty acid oxidation and ATP production under hypertrophic stimuli. Mechanistically, FABP3 mediated metabolic reprogramming by directly interacting with PPARα, which prevented its degradation and synergistically modulated its transcriptional activity on Mlycd and Gck. Finally, treatment with the PPARα agonist, fenofibrate, rescued the pro-hypertrophic effects of Fabp3 deficiency.Conclusions: Collectively, these findings reveal the indispensable roles of the FABP3–PPARα axis on metabolic homeostasis and the development of hypertrophy, which sheds new light on the treatment of hypertrophy.
Phalangeal Intra-Articular Osteochondroma Caused a Rare Clinodactyly Deformity in Children: Case Series and Literature Review
Authors: Hao Yun , Guo Jia-Chao , Wang Xiao-Lin , Shao Jing-Fan , Feng Jie-Xiong , He Jin-Peng 
Published: August 2021

BackgroundVarious factors are discovered in the development of clinodactyly. The purpose of this retrospective study was to present a group of children with a rare clinodactyly deformity caused by phalangeal intra-articular osteochondroma and evaluate the efficacy of various treatment methods.MethodsAll child patients that were treated for finger problems in our center between Jan 2017 and Dec 2020 were reviewed. A detailed analysis was made of the diagnosis and treatment methods in eight rare cases. X-rays and histopathology were applied.ResultsA preliminary analysis of 405 patients in total was performed, and we included eight cases in our final analysis. This cohort consisted of 2 girls and 6 boys, with a mean age of 5.74 ± 3.22 years (range: 2y5m to 11y). Overall, four patients had their right hand affected and four patients had their left hand affected. One patient was diagnosed as having hereditary multiple osteochondroma (HMO) while the other seven patients were all grouped into solitary osteochondroma. Osteochondroma was proven in all of them by histopathology examination. Preoperative X-rays were used to allow identification and surgery planning in all cases. All osteochondromas were intra-articular and in the distal end of the phalanges, which is located opposite the epiphyseal growth area. All of the osteochondromas developed in half side of the phalanges. The angulation in the finger long axis was measured, and resulted in a mean angulation of 34.63 ± 24.93 degree (range: 10.16-88.91 degree). All of them received surgery, resulting in good appearance and fingers straightening. No recurrence was recorded.ConclusionsThis retrospective analysis indicates that 10 degrees can be selected as the angulation level for diagnosis of clinodactyly deformities. What’s more important, the abnormal mass proven by X-rays should be included as the classical direct sign for diagnosis. The first choice of treatment is surgery in symptomatic osteochondromas.
Beta Cell Function as a Baseline Predictor of Weight Loss After Bariatric Surgery
Authors: Borges-Canha Marta , Neves João Sérgio , Mendonça Fernando , Silva Maria Manuel , Costa Cláudia , M. Cabral Pedro , Guerreiro Vanessa , Lourenço Rita , Meira Patrícia , Salazar Daniela , Ferreira Maria João , Pedro Jorge , Barkoudah Ebrahim , Sande Ana , Lau Eva , B. Souto Selma , Preto John , Freitas Paula , Carvalho Davide 
Published: August 2021

BackgroundObesity is a multifactorial disease, which is strongly associated to other metabolic disorders. Bariatric surgery is the most effective treatment of morbid obesity. The role of beta cell function in weight loss after bariatric surgery is uncertain.AimTo evaluate the association between beta cell function and percentage of total body weight loss (TBWL%) 1, 2, 3, and 4 years after bariatric surgery in patients with morbid obesity.MethodsRetrospective longitudinal study in patients with morbid obesity followed in our center between January 2010 and July 2018. Patients were excluded if they had diabetes at baseline or missing data on the needed parameters. We evaluated baseline Homeostatic Model Assessment of IR, Homeostatic Model Assessment of β-cell function (HOMA-beta), Quantitative Insulin Sensitivity Check Index, and Matsuda and DeFronzo index, and TBWL% at years 1 to 4. Linear regression models were used to evaluate the association of indexes of insulin resistance with TBWL% (unadjusted and adjusted for age, sex, BMI, and type of surgery).ResultsThere were 1,561 patients included in this analysis. HOMA-beta was negatively associated with TBWL% at second, third, and fourth years post-surgery (β = −1.04 [−1.82 to −0.26], p&lt;0.01; β = −1.16 [−2.13 to −0.19], p=0.02; β = −1.29 [−2.64 to 0.06], p=0.061, respectively). This was not observed in the first year post-surgery nor for the other indexes. Glycemia at baseline was positively associated to EWL% at second and third years post-surgery.Conclusionβ-cell function at baseline seems to be associated to long-term weight loss, explicitly after the first year post bariatric surgery. This might be a helpful predictor of weight loss in clinical practice.
A Systematic Review of Virtual Reality Applications for Automated Driving: 2009–2020
Authors: Riegler Andreas , Riener Andreas , Holzmann Clemens 
Published: August 2021

While virtual reality (VR) interfaces have been researched extensively over the last decades, studies on their application in vehicles have only recently advanced. In this paper, we systematically review 12 years of VR research in the context of automated driving (AD), from 2009 to 2020. Due to the multitude of possibilities for studies with regard to VR technology, at present, the pool of findings is heterogeneous and non-transparent. We investigatedN= 176 scientific papers of relevant journals and conferences with the goal to analyze the status quo of existing VR studies in AD, and to classify the related literature into application areas. We provide insights into the utilization of VR technology which is applicable at specific level of vehicle automation and for different users (drivers, passengers, pedestrians) and tasks. Results show that most studies focused on designing automotive experiences in VR, safety aspects, and vulnerable road users. Trust, simulator and motion sickness, and external human-machine interfaces (eHMIs) also marked a significant portion of the published papers, however a wide range of different parameters was investigated by researchers. Finally, we discuss a set of open challenges, and give recommendation for future research in automated driving at the VR side of the reality-virtuality continuum.
Ultrafine Particulate Matter in Methane-Air Premixed Flames With Oxygen Enrichment
Authors: Dasappa Shruthi , Camacho Joaquin 
Published: August 2021

A complementary computational and experimental study is carried out on the formation of ultrafine particulate matter in premixed laminar methane air flames. Specifically, soot formation is examined in premixed stretch-stabilized flames to observe soot inception and growth at relatively high flame temperatures common to oxygen enriched applications. Particle size distribution functions (PSDF) measured by mobility sizing show clear trends as the equivalence ratio increases from Φ = 2.2 to Φ = 2.4. For a given equivalence ratio, the measured distribution decreases in median mobility particle size as the maximum flame temperature increases from approximately 1,950–2,050 K. The median mobility particle size is 20 nm or less for all flame conditions studied. The volume fraction decreases with increasing flame temperature for all equivalence ratio conditions. The Φ = 2.2 condition is close to the soot inception limit and both number density and volume fraction decrease monotonically with increasing flame temperature. The higher equivalence ratio conditions show a peak in number density at 2,000 K which may indicate competing soot inception processes are optimized at this temperature. Flame structure computations are carried out using detailed gas-phase combustion chemistry of the Appel, Bockhorn, Frenklach (ABF) model to examine the connection of the observed PSDF to soot precursor chemistry. Agreement between measured and computed flame standoff distances indicates that the ABF model could provide a reasonable prediction of the flame temperature and soot precursor formation for the flames currently studied. To the first order, the trends observed in the measured PSDF could be understood in terms of computed trends for the formation of benzene, naphthalene and other soot precursors. Results of the current study inform particulate matter behavior for methane and natural gas combustion applications at elevated temperature and oxygen enriched conditions.
Response to Immune Checkpoint Inhibitor Treatment in Advanced Cervical Cancer and Biomarker Study
Authors: Shieh Kevin R. , Huang Anna , Xu Yiqing 
Published: August 2021

Background: Checkpoint inhibitor immunotherapy or immuno-oncology (IO) treatment in refractory cervical cancer yielded an objective response rate (ORR) of 12% in tumors expressing the programmed cell death ligand-1 (PD-L1) in the KEYNOTE-158 phase II study. We hypothesized that the positive response might be associated with the level of PD-L1 expression and/or the tumor mutation burden (TMB). We also aimed to analyze if responses could be associated with platinum sensitivity.Methods: This is a retrospective study of all consecutive patients with cervical cancer who received pembrolizumab or nivolumab.Results: Ten patients were identified. Median age was 64.5 years old (range 48–80). The response rate was 70% and the median duration of response was 21.0 months (range 1.8–26.7) after 20.7 months of follow-up (range 2.0–31.0). The response rate was 80% in patients with PD-L1 combined positive score (CPS) ≥ 10, and 75% in patients with tumor mutation burden (TMB) ≥ 10 mut/Mb. The mean progression-free survival (PFS) for the entire cohort was 20.2 months (95% CI 12.0–28.5). Seven patients had treatment for &gt;12 months (range 14.6–31.0). Five patients were platinum-sensitive and 5 patients were platinum-resistant at the time of immunotherapy, and the response rate was similar regardless of platinum sensitivity.Conclusions: The positive response to IO treatment in advanced cervical cancer in this study was higher than published, and a possible association with the level of PD-L1 expression and the TMB level was suggested. A PD-L1 CPS score ≥ 10 or TMB ≥ 10 may be biomarkers to correlate with response, which should be explored in large studies.
The Oncogenic Roles of JC Virus T Antigen in Breast Carcinogenesis
Authors: Zheng Hua-chuan , E Ying , Cui Zheng-guo , Zhao Shuang , Zhang Yong 
Published: August 2021

Purpose: JC virus (JCV) infects 80–90% of the population and results in progressive multifocal leukoencephalopathy upon immunodeficiency. The study aimed to pathologically clarify the oncogenic roles of T antigen in human breast cancers.Methods: Breast cancer, dysplasia, and normal tissues were examined for T antigen of JCV by nested and real-time PCR. The positive rate or copy number of T antigen was compared with clinicopathological parameters of breast cancer. JCV existence was morphologically detected by immunohistochemistry and in situ PCR. T antigen was examined by Western blot using frozen samples of breast cancer and paired normal tissues.Results: According to nested PCR, the positive rate of breast ductal or lobular carcinoma was lower than that of normal tissue (p &lt; 0.05). T antigen existence was negatively correlated with E-cadherin expression and triple-negative breast cancer (p &lt; 0.05), but positively correlated with lymph node metastasis and estrogen receptor and progestogen receptor expression (p &lt; 0.05). Quantitative PCR showed that JCV copies were gradually decreased from normal, dysplasia to cancer tissues (p &lt; 0.05). JCV T antigen copy number was lower in ductal adenocarcinoma than in normal tissue (p &lt; 0.05), in line with in situ PCR and immunohistochemistry. JCV copies were negatively correlated with tumor size and E-cadherin expression (p &lt; 0.05), but positively correlated with G grading of breast cancer (p &lt; 0.05). Western blot also indicated weaker T antigen expression in breast cancer than normal tissues (p &lt; 0.05).Conclusion: JCV T antigen might play an important role in breast carcinogenesis. It can be employed as a molecular marker for the differentiation and aggressive behaviors of breast cancer.
Auditory Comprehension Deficits in Post-stroke Aphasia: Neurologic and Demographic Correlates of Outcome and Recovery
Authors: Lwi Sandy J. , Herron Timothy J. , Curran Brian C. , Ivanova Maria V. , Schendel Krista , Dronkers Nina F. , Baldo Juliana V. 
Published: August 2021

Introduction: One of the most challenging symptoms of aphasia is an impairment in auditory comprehension. The inability to understand others has a direct impact on a person's quality of life and ability to benefit from treatment. Despite its importance, limited research has examined the recovery pattern of auditory comprehension and instead has focused on aphasia recovery more generally. Thus, little is known about the time frame for auditory comprehension recovery following stroke, and whether specific neurologic and demographic variables contribute to recovery and outcome.Methods: This study included 168 left hemisphere chronic stroke patients stroke patients with auditory comprehension impairments ranging from mild to severe. Univariate and multivariate lesion-symptom mapping (LSM) was used to identify brain regions associated with auditory comprehension outcomes on three different tasks: Single-word comprehension, yes/no sentence comprehension, and comprehension of sequential commands. Demographic variables (age, gender, and education) were also examined for their role in these outcomes. In a subset of patients who completed language testing at two or more time points, we also analyzed the trajectory of recovery in auditory comprehension using survival curve-based time compression.Results: LSM analyses revealed that poor single-word auditory comprehension was associated with lesions involving the left mid- to posterior middle temporal gyrus, and portions of the angular and inferior-middle occipital gyri. Poor yes/no sentence comprehension was associated almost exclusively with the left mid-posterior middle temporal gyrus. Poor comprehension of sequential commands was associated with lesions in the left posterior middle temporal gyrus. There was a small region of convergence between the three comprehension tasks, in the very posterior portion of the left middle temporal gyrus. The recovery analysis revealed that auditory comprehension scores continued to improve beyond the first year post-stroke. Higher education was associated with better outcome on all auditory comprehension tasks. Age and gender were not associated with outcome or recovery slopes.Conclusions: The current findings suggest a critical role for the posterior left middle temporal gyrus in the recovery of auditory comprehension following stroke, and that spontaneous recovery of auditory comprehension can continue well beyond the first year post-stroke.
Efficacy and Safety of a Novel Thrombectomy Device in Patients With Acute Ischemic Stroke: A Randomized Controlled Trial
Authors: Zhang Yongxin , Hua Weilong , Li Zifu , Peng Ya , Han Zhian , Li Tong , Yin Congguo , Wang Shoucun , Nan Guangxian , Zhao Zhenwei , Yang Hua , Zhou Bin , Li Tianxiao , Cai Yiling , Zhang Jianmin , Li Guifu , Peng Xiaoxiang , Guan Sheng , Zhou Junshan , Ye Ming , Wang Liqin , Zhang Lei , Hong Bo , Zhang Yongwei , Wan Jieqing , Wang Yang , Zhu Qing , Liu Jianmin , Yang Pengfei 
Published: August 2021

Purpose: The Tonbridge stent is a novel retriever with several design improvements which aim to achieve promising flow reperfusion in the treatment of acute ischemic stroke (AIS). We conducted a randomized controlled, multicenter, non-inferiority trial to compare the safety and efficacy of the Tonbridge stent with the Solitaire FR.Methods: AIS patients aged 18–85 years with large vessel occlusion in anterior circulation who could undergo puncture within 6 h of symptom onset were included. Randomization was performed on a 1:1 ratio to thrombectomy with either the Tonbridge stent or the Solitaire FR. The primary efficacy endpoint was successful reperfusion using a modified thrombolysis in cerebral infarction score (mTICI) of 2b/3. Safety outcomes were symptomatic intracranial hemorrhage (sICH) within 24 ± 6 h and all-cause mortality within 90 days. A clinically relevant non-inferiority margin of 12% was chosen as the acceptable difference between groups. Secondary endpoints included time from groin puncture to reperfusion, National Institutes of Health Stroke Scale (NIHSS) score at 24 h and at 7 days, and a modified Rankin Scale (mRS) score of 0–2 at 90 days.Results: A total of 220 patients were enrolled; 104 patients underwent thrombectomy with the Tonbridge stent and 104 were treated with the Solitaire FR. In all test group patients, the Tonbridge was used as a single retriever without rescuing by other thrombectomy devices. Angioplasty with balloon and/or stent was performed in 26 patients in the Tonbridge group and 16 patients in the Solitaire group (p = 0.084). Before angioplasty, 86.5% of those in the Tonbridge group and 81.7% of those in the Solitaire group reached successful reperfusion (p = 0.343). Finally, more patients in the Tonbridge group achieved successful reperfusion (92.3 vs. 84.6%, 95% CI of difference value 0.9–16.7%, p &lt; 0.0001). There were no significant differences on sICH within 24 ± 6 h between the two groups. All-cause mortality within 90 days was 13.5% in the Tonbridge group and 16.3% in the Solitaire group (p = 0.559). We noted no significant differences between groups on the NIHSS at either 24 h or 7 days and the mRS of 0–2 at 90 days.Conclusion: The trial indicated that the Tonbridge stent was non-inferior to the Solitaire FR within 6 h of symptom onset in cases of large vessel occlusion stroke.Clinical Trial Registration:ClinicalTrials.gov, number: NCT03210623.