bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mesh Force Modelling and Parametric Studies for Compound Oscillatory Roller Reducer
Authors: Wei Changxu , Song Chaosheng , Zhu Caichao , Liang Chengcheng , Hu Long 
Published: September 2021

AbstractA compound oscillatory roller reducer (CORR) with a first-stage gear transmission and a second-stage oscillatory roller transmission is presented. The transmission principle of oscillatory roller transmission is introduced, and the tooth profile equation of the inner gear is derived. The analytical model of mesh force considering the installation errors and manufacturing errors is proposed. Then, parametric studies considering different errors on the mesh force are conducted. Results show that the design parameters are significant factors for mesh force. The mesh force is reduced by 17% as the eccentricity of disk cam increases from 2.5 mm to 4 mm. When the radius of the movable roller increases from 7 mm to 20 mm, the mesh force decreases by 8%. As the radius of disk cam increases from 125 mm to 170 mm, the mesh force is decreased by 26.5%. For the impacts of errors, the mesh force has a noticeable fluctuation when these errors exist including the manufacturing error of disk cam, the installation error of disk cam and the manufacturing error of movable roller change. The prototype of the reducer is manufactured and preliminary run-in test proved the feasibility of the transmission principle.
HIF-1α/JMJD1A signaling regulates inflammation and oxidative stress following hyperglycemia and hypoxia-induced vascular cell injury
Authors: Zhao Min , Wang Shaoting , Zuo Anna , Zhang Jiaxing , Wen Weiheng , Jiang Weiqiang , Chen Hong , Liang Donghui , Sun Jia , Wang Ming 
Published: September 2021

Abstract
Background
Endothelial cell (EC) injury accelerates the progression of diabetic macrovascular complications. Hypoxia is an important cause of EC injury. Hypoxia-inducible factor-1 alpha (HIF-1α) is an important hypoxia regulatory protein. Our previous studies showed that high-glucose and hypoxic conditions could upregulate HIF-1α expression and enhance EC inflammatory injury, independently of the nuclear factor kappa-B (NF-κB) pathway. However, it is not clear whether HIF-1α plays a role in vascular disease through epigenetic-related mechanisms.

Methods
We conducted gene expression analysis and molecular mechanistic studies in human umbilical vein endothelial cells (HUVECs) induced by hyperglycemia and hypoxia using RNA sequencing (RNA-seq) and small interfering HIF-1α (si-HIF-1α). We determined HIF-1α and Jumonji domain-containing protein 1 A (JMJD1A) expression by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot, analyzed inflammatory protein secretion in the cell supernatant by enzymelinked immunosorbent assay (ELISA), and assessed protein interaction between HIF-1α and JMJD1A by chromatin immunoprecipitation (Ch-IP). We used the Cell Counting Kit8 (CCK-8) assay to analyze cell viability, and assessed oxidative stress indicators by using a detection kit and flow cytometry.

Results
High glucose and hypoxia up-regulated HIF-1α expression, and down-regulated HIF-1α decreased the level of inflammation and oxidative stress in HUVECs. To determine the downstream pathways, we observed histone demethylases genes and related pathway by RNA-sEq. Among these, JMJD1A was the most upregulated gene in histone demethylases. Moreover, we observed that HIF-1α bound to the promoter of JMJD1A, and the ameliorative effects of si-HIF-1α on oxidative stress and inflammatory cytokines in high-glucose and hypoxia-induced HUVECs were reversed by JMJD1A overexpression. Furthermore, knockdown of JMJD1A decreased inflammatory and oxidative stress injury. To determine the JMJD1A-related factors, we conducted gene expression analysis on JMJD1A-knockdown HUVECs. We observed that downregulation of inflammation and the oxidative stress pathway were enriched and FOS and FOSB might be important protective transcription factors.

Conclusions
These findings provide novel evidence that the HIF-1α/JMJD1A signaling pathway is involved in inflammation and oxidative stress in HUVECs induced by high glucose and hypoxia. Also, this pathway might act as a novel regulator of oxidative stress and inflammatory-related events in response to diabetic vascular injury and thus contribute to the pathological progression of diabetes and vascular disease.
Integrative lncRNA landscape reveals lncRNA-coding gene networks in the secondary cell wall biosynthesis pathway of moso bamboo (Phyllostachys edulis)
Authors: Wang Jiongliang , Hou Yinguang , Wang Yu , Zhao Hansheng 
Published: September 2021

Abstract
Background
LncRNAs are extensively involved in plant biological processes. However, the lack of a comprehensive lncRNA landscape in moso bamboo has hindered the molecular study of lncRNAs. Moreover, the role of lncRNAs in secondary cell wall (SCW) biosynthesis of moso bamboo is elusive.

Results
For comprehensively identifying lncRNA throughout moso bamboo genome, we collected 231 RNA-Seq datasets, 1 Iso-Seq dataset, and 1 full-length cDNA dataset. We used a machine learning approach to improve the pipeline of lncRNA identification and functional annotation based on previous studies and identified 37,009 lncRNAs in moso bamboo. Then, we established a network of potential lncRNA-coding gene for SCW biosynthesis and identified SCW-related lncRNAs. We also proposed that a mechanism exists in bamboo to direct phenylpropanoid intermediates to lignin or flavonoids biosynthesis through the PAL/4CL/C4H genes. In addition, we identified 4 flavonoids and 1 lignin-preferred genes in the PAL/4CL/C4H gene families, which gained implications in molecular breeding.

Conclusions
We provided a comprehensive landscape of lncRNAs in moso bamboo. Through analyses, we identified SCW-related lncRNAs and improved our understanding of lignin and flavonoids biosynthesis.
The augment of regulatory T cells undermines the efficacy of anti-PD-L1 treatment in cervical cancer
Authors: Xu Fengying , Zhang Fengying , Wang Qian , Xu Ying , Xu Shuifang , Zhang Caihong , Wang Lihua 
Published: September 2021

Abstract
Background
Immune checkpoint inhibitors have aroused great expectation of tumor eradication. However, the effect of anti-PD-L1 treatment for cervical cancer is unsatisfactory and the underlying antagonist to anti-PD-L1 efficacy is remained to be studied. Here, we investigated the anti-tumor effect of anti-PD-L1 treatment in cervical tumor model and identified the antagonist to the therapeutic efficacy of anti-PD-L1 treatment.

Results
We found that PD-L1 exhibited a moderate expression in both cervical tumor cell lines and clinical samples compared to other tumor types and the para-tumor tissue respectively. Interestingly, our results showed that the anti-PD-L1 treated mice were dichotomously divided into responsive and unresponsive group after five cycles of anti-PD-L1 treatment although all the mice had the same genome background. In addition, the unresponsive tumors showed less tumor necrosis area and higher immunosuppression activity induced by regulatory T cells (Tregs) population than the responsive ones. Furthermore, we found that anti-PD-L1 treatment autonomously upregulated Tregs proliferation and frequency in multiple immune organs, and, most importantly, Tregs depletion significantly depressed the tumor growth rate and tumor weight compared with either anti-PD-L1 or anti-CD25 treatment alone. Finally, we observed that the upregulating effector CD8+ T cell is associated with the better therapeutic effect of anti-PD-L1 therapy post Tregs depletion.

Conclusions
Anti-PD-L1 treatment upregulates Tregs frequency and proliferation in tumor model, and the depletion of Tregs may be a useful adjuvant strategy for anti-PD-L1 therapy of cervical cancer.
Primary care professionals’ experiences during the first wave of the COVID-19 pandemic in Greece: a qualitative study
Authors: Smyrnakis Emmanouil , Symintiridou Despoina , Andreou Martha , Dandoulakis Michael , Theodoropoulos Elias , Kokkali Stamatia , Manolaki Chrysanthi , Papageorgiou Dimitra Iosifina , Birtsou Charis , Paganas Aristofanis , Stachteas Panagiotis , Vlachopoulos Nikolaos , Pagkozidis Ilias , Zeimbekis Akis , Roka Violeta , Giakoumis Anastasios , Kotsani Marina , Avakian Ioanna , Makridou Efthymia , Gavana Magda , Haidich Anna-Bettina , Avgerinou Christina 
Published: September 2021

Abstract
Background
The coronavirus outbreak (COVID-19) tested health care systems worldwide. This qualitative study aimed to explore and understand the experiences, beliefs and concerns of Primary Care Professionals (PCPs) regarding the preparedness and response of primary care to the first wave of the pandemic in Greece, a country where a public structured primary care system has been developing.

Methods
We conducted semi-structured telephone interviews with 33 PCPs (General Practitioners, community General Internal Medicine Specialists, community Paediatricians and nurses) recruited from all regions of Greece after the first wave of the pandemic (June 2020). Interviews were transcribed verbatim, data were anonymised and analysed. Thematic analysis was applied developing a conceptual framework.

Results
Four main themes were identified: a) Primary care unit adaptation and issues faced during the pandemic; b) Management of suspected COVID-19 cases; c) Management of non-suspected cases; d) Consequences of the pandemic. In the first phase of the pandemic, remote management of suspected cases and their referral to the hospital were preferred as a result of a shortage of personal protective equipment and inaccessibility to coronavirus testing in primary care. Due to the discontinuation of regular medical services and the limited in-person contact between doctors and patients, chronic disease management and prevention programmes were left behind. Social and emotional consequences of the pandemic, such as workplace stigma, isolation and social seclusion, deriving from fear of viral transmission, as well as burnout symptoms and exhaustion were commonly experienced among PCPs. Positive consequences of the pandemic were considered to be the recognition of the importance of an empowered public healthcare system by citizens and the valuable insight, knowledge and experience professionals gained in times of crisis.

Conclusions
Primary care has a key role to play during and after the pandemic by using its information infrastructure to identify at-risk groups, detect new cases of COVID-19, provide care according to needs, and carry out vaccination programmes. Central coordination and empowerment of primary care will increase its effectiveness, via public awareness, holistic patient management, and unburdening of hospitals.
A case report of rhino-facial mucormycosis in a non-diabetic patient with COVID-19: a systematic review of literature and current update
Authors: Mohammadi Faezeh , Badri Milad , Safari Shapoor , Hemmat Nima 
Published: September 2021

AbstractBackgroundCOVID-19 disease may be associated with a wide range of bacterial and fungal infections. We report a patient with COVID-19 infection who developed rhino-facial mucormycosis during treatment with corticosteroids.Case presentationA 59-year-old non-diabetic male patient was admitted with a diagnosis of COVID-19 based on positive RT-PCR and CT of the lungs. Due to sever lung involvement, he was treated with methylprednisolone. The patient was re-admitted to hospital, due to nasal obstruction and left side facial and orbital swelling, several days after discharge. In sinus endoscopic surgery, debridement was performed and the specimens were sent to pathology and mycology laboratories. A nasal biopsy showed wide hyphae without septa. The sequenced PCR product revealedRhizopus oryzae. Despite all medical and surgical treatment, the patient died. In addition, the characteristics of patients with COVID-19-associated mucormycosis were reviewed in 44 available literatures. In most studies, diabetes mellitus was the most common predisposing factor for mucormycosis.ConclusionOur report highlights the need for assessing the presence of mucormycosis in patients with COVID-19 and also it shows that physicians should consider the potential for secondary invasive fungal infections in COVID-19 cases.
Neuronal intranuclear inclusion disease presented with recurrent vestibular migraine-like attack: a case presentation
Authors: Zhao Danhua , Zhu Sha , Xu Qinlan , Deng Jianwen , Wang Zhaoxia , Liu Xianzeng 
Published: September 2021

Abstract
Background
Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disorder characterized by dementia, tremor, episodic encephalopathy and autonomic nervous dysfunction. To date, vestibular migraine (VM)-like attack has never been reported in cases with NIID. Here, we describe an 86-year-old patient with NIID who presented with recurrent vertigo associated with headache for more than 30 years.

Case presentation
An 86-year-old Chinese woman with vertigo, headache, weakness of limbs, fever, and disturbance of consciousness was admitted to our hospital. She had suffered from recurrent vertigo associated with headache since her 50 s,followed by essential tremor and dementia. On this admission, brain magnetic resonance imaging revealed high intensity signals along the corticomedullary junction on diffusion weighted imaging (DWI). Peripheral neuropathy of the extremities was detected through electrophysiological studies. We diagnosed NIID after detecting eosinophilic intranuclear inclusions in the ductal epithelial cells of sweat glands and identifying an abnormal expansion of 81 GGC repeats in the 5’UTR of NOTCH2NLC gene.

Conclusions
VM-like attack may be associated with NIID.
Head and neck squamous cell carcinoma cell lines have an immunomodulatory effect on macrophages independent of hypoxia and toll-like receptor 9
Authors: Ishizu Tamiko , Eichin Dominik , Padzik Artur , Tuominen Sanni , Grénman Reidar , Salmi Marko , Grönroos Tove J. , Tuomela Johanna M. 
Published: September 2021

Abstract
Background
A low tissue oxygen level, < 1% O2, is a typical characteristic inside of solid tumors in head and neck cancer (HNSCC) affecting a wide array of cell populations, such as macrophages. However, the mechanisms of how hypoxia influences macrophages are not yet fully elucidated. Our research aimed to study the effect of soluble mediators produced by hypoxic cancer cells on macrophage polarization. Furthermore, we studied the effect of a hypoxic microenvironment on the expression of tumorigenic toll-like receptor 9 (TLR9) and the consecutive macrophage polarization.

Methods
Conditioned media (CMNOX or CMHOX) from cell lines UT-SCC-8, UT-SCC-74A, FaDu, MDA-MB-231 and HaCat cultured under normoxic (21% O2) and hypoxic (1% O2) conditions were used to polarize human monocyte-derived macrophages. Macrophage polarization was measured by flow cytometry and the production of cytokine mRNA using Taqman qPCR. To study the role of TLR9 in macrophage polarization, the lentiviral CRISPR/Cas9 method was used to establish a stable FaDuTLR9def clone.

Results
Our results demonstrate that the soluble mediators produced by the cancer cells under normoxia polarize macrophages towards a hybridized M1/M2a/M2c phenotype. Furthermore, the results suggest that hypoxia has a limited role in altering the array of cancer-produced soluble factors affecting macrophage polarization and cytokine production. Our data also indicates that increased expression of TLR9 due to hypoxia in malignant cells does not markedly influence the polarization of macrophages. TLR9 transcriptional response to hypoxia is dissimilar to a HIF1-α-regulated LDH-A. This may indicate a context-dependent expression of TLR9 under hypoxia.

Conclusions
HNSCC cell lines affect both macrophage activity (polarization) and functionality (cytokines), but with exception to iNOS expression, the effects appear independent of hypoxia and TLR9.
Cannabinoid exposure as a major driver of pediatric acute lymphoid Leukaemia rates across the USA: combined geospatial, multiple imputation and causal inference study
Authors: Reece Albert Stuart , Hulse Gary Kenneth 
Published: September 2021

AbstractBackgroundAcute lymphoid leukaemia (ALL) is the commonest childhood cancer whose incidence is rising in many nations. In the USA, between 1975 and 2016, ALL rates (ALLRs) rose 93.51% from 1.91 to 3.70/100,000 <  20 years. ALL is more common in Caucasian-Americans than amongst minorities. The cause of both the rise and the ethnic differential is unclear, however, prenatal cannabis exposure was previously linked with elevated childhood leukaemia rates. We investigated epidemiologically if cannabis use impacted nationally on ALLRs, its ethnic effects, and if the relationship was causal.MethodsState data on overall, and ethnic ALLR from the Surveillance Epidemiology and End Results databank of the Centre for Disease Control (CDC) and National Cancer Institute (NCI) were combined with drug (cigarettes, alcoholism, cannabis, analgesics, cocaine) use data from the National Survey of Drug Use and Health; 74.1% response rate. Income and ethnicity data was from the US Census bureau. Cannabinoid concentration was from the Drug Enforcement Agency Data. Data was analyzed in R by robust and spatiotemporal regression.ResultsIn bivariate analyses a dose-response relationship was demonstrated between ALLR and Alcohol Use Disorder (AUD), cocaine and cannabis exposure, with the effect of cannabis being strongest (β-estimate = 3.33(95%C.I. 1.97, 4.68),P = 1.92 × 10− 6). A strong effect of cannabis use quintile on ALLR was noted (Chi.Sq. = 613.79,P = 3.04 × 10− 70). In inverse probability weighted robust regression adjusted for other substances, income and ethnicity, cannabis was independently significant (β-estimate = 4.75(0.48, 9.02),P = 0.0389). In a spatiotemporal model adjusted for all drugs, income, and ethnicity, cannabigerol exposure was significant (β-estimate = 0.26(0.01, 0.52),P = 0.0444), an effect increased by spatial lagging (THC: β-estimate = 0.47(0.12, 0.82),P = 0.0083). After missing data imputation ethnic cannabis exposure was significant (β-estimate = 0.64(0.55, 0.72),P = 3.1 × 10− 40). 33/35 minimum e-Values ranged from 1.25 to 3.94 × 1036indicative of a causal relationship. Relaxation of cannabis legal paradigms had higher ALLR (Chi.Squ.Trend = 775.12,P = 2.14 × 10− 112). Cannabis legal states had higher ALLR (2.395 ± 0.039 v. 2.127 ± 0.008 / 100,000,P = 5.05 × 10− 10).ConclusionsData show that ALLR is associated with cannabis consumption across space-time, is associated with the cannabinoids, THC, cannabigerol, cannabinol, cannabichromene, and cannabidiol, contributes to ethnic differentials, demonstrates prominent quintile effects, satisfies criteria for causality and is exacerbated by cannabis legalization.
A novel tool for predicting the survival of endoprosthesis used for reconstruction of the knee following tumor resection: a retrospective cohort study
Authors: Pang Cheng-gang , Yang Xiong-gang , Zhao Yun-long , Liu Yan-cheng , Hu Yong-cheng 
Published: September 2021

AbstractBackgroundProsthesis-related complications, after knee reconstruction with endoprosthesis during operation for tumors around the knee, remain an unresolved problem which necessitate a revision or even an amputational surgery. The purpose of the current study was to identify significant risk factors associated with implant failure, and establish a novel model to predict survival of the prosthesis in patients operated with endoprostheses for tumor around knee.MethodsWe retrospectively reviewed the clinical database of our institution for patients who underwent knee reconstruction due to tumors. A total of 203 patients were included, including 123 males (60.6%) and 80 (39.4%) females, ranging in age from 14 to 77 years (mean: 34.3 ± 17.3 years). The cohort was randomly divided into training (n = 156) and validation (n = 47) samples. Univariable COX analysis was used for initially identifying potential independent predictors of prosthesis survival with the training group (p < 0.150). Multivariate COX proportional hazard model was selected to identify final significant prognostic factors. Using these significant predictors, a graphic nomogram, and an online dynamic nomogram were generated for predicting the prosthetic survival. C-index and calibration curve were used for evaluate the discrimination ability and accuracy of the novel model, both in the training and validation groups.ResultsThe 1-, 5-, and 10-year prosthetic survival rates were 94.0, 90.8, and 83.0% in training sample, and 96.7, 85.8, and 76.9% in validation sample, respectively. Anatomic sites, length of resection and length of prosthetic stem were independently associated with the prosthetic failure according to multivariate COX regression model (p<0.05). Using these three significant predictors, a graphical nomogram and an online dynamic nomogram model were generated. The C-indexes in training and validation groups were 0.717 and 0.726 respectively, demonstrating favourable discrimination ability of the novel model. And the calibration curve at each time point showed favorable consistency between the predicted and actual survival rates in training and validation samples.ConclusionsThe length of resection, anatomical location of tumor, and length of prosthetic stem were significantly associated with prosthetic survival in patients operated for tumor around knee. A user-friendly novel online model model, with favorable discrimination ability and accuracy, was generated to help surgeons predict the survival of the prosthesis.
Prognostic impact of tumor length in esophageal Cancer: a systematic review and Meta-analysis
Authors: Wang Zhao Yang , Jiang Yuan Zhu , Xiao Wen , Xue Xian Biao , Zhang Xiang Wei , Zhang Lin 
Published: September 2021

Abstract
Background
In clinical studies, it has been observed that esophageal cancer (EC) patient prognosis can be very different even for those patients with tumors of the same TNM stage. Tumor length has been analysed as a possible independent prognostic factor in many studies, but no unanimous conclusion has been reached. Therefore, this review used a meta-analysis to evaluate the association between tumor length and prognosis in EC patients.

Methods
A systematic search for relevant articles was performed in PubMed, Web of Science, and Embase. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used as effective measures to estimate the correlation between tumor length and prognosis, including overall survival, disease-free survival, progression-free survival, disease-specific survival, and cancer-specific survival. STATA 15.0 software was used to perform the meta-analysis and the data synthesis.

Results
Finally, 41 articles with 28,973 patients were included in our study. The comprehensive statistical results showed that long tumors are an independent prognostic parameter associated with poor overall survival (OS) (HR = 1.30; 95% CI: 1.21–1.40, p < .001) and disease-free survival (DFS) (HR = 1.38; 95% CI: 1.18–1.61, p < .001) in EC patients. Subgroup analyses also suggested a significant correlation between long tumors and poor OS. Sensitivity analysis and publication bias evaluation confirmed the reliability and stability of the results. Similar results were obtained in the analyses of progression-free survival (PFS), disease-specific survival (DSS), and cancer-specific survival (CSS).

Conclusion
The results of this meta-analysis showed that long tumors were related to poor OS, DFS, PFS, DSS and CSS in EC patients. Tumor length might be an important predictor of prognosis in EC patients, and it can be used as an independent staging index. Further well-designed and large-scale prospective clinical studies are needed to confirm these findings.