bluuebunny/crossref_metadata_2025_split huggingface dataset:
ACBD3 modulates KDEL receptor interaction with PKA for its trafficking via tubulovesicular carrier
Authors: Yue Xihua , Qian Yi , Zhu Lianhui , Gim Bopil , Bao Mengjing , Jia Jie , Jing Shuaiyang , Wang Yijing , Tan Chuanting , Bottanelli Francesca , Ziltener Pascal , Choi Sunkyu , Hao Piliang , Lee Intaek 
Published: September 2021

Abstract
Background
KDEL receptor helps establish cellular equilibrium in the early secretory pathway by recycling leaked ER-chaperones to the ER during secretion of newly synthesized proteins. Studies have also shown that KDEL receptor may function as a signaling protein that orchestrates membrane flux through the secretory pathway. We have recently shown that KDEL receptor is also a cell surface receptor, which undergoes highly complex itinerary between trans-Golgi network and the plasma membranes via clathrin-mediated transport carriers. Ironically, however, it is still largely unknown how KDEL receptor is distributed to the Golgi at steady state, since its initial discovery in late 1980s.

Results
We used a proximity-based in vivo tagging strategy to further dissect mechanisms of KDEL receptor trafficking. Our new results reveal that ACBD3 may be a key protein that regulates KDEL receptor trafficking via modulation of Arf1-dependent tubule formation. We demonstrate that ACBD3 directly interact with KDEL receptor and form a functionally distinct protein complex in ArfGAPs-independent manner. Depletion of ACBD3 results in re-localization of KDEL receptor to the ER by inducing accelerated retrograde trafficking of KDEL receptor. Importantly, this is caused by specifically altering KDEL receptor interaction with Protein Kinase A and Arf1/ArfGAP1, eventually leading to increased Arf1-GTP-dependent tubular carrier formation at the Golgi.

Conclusions
These results suggest that ACBD3 may function as a negative regulator of PKA activity on KDEL receptor, thereby restricting its retrograde trafficking in the absence of KDEL ligand binding. Since ACBD3 was originally identified as PAP7, a PBR/PKA-interacting protein at the Golgi/mitochondria, we propose that Golgi-localization of KDEL receptor is likely to be controlled by its interaction with ACBD3/PKA complex at steady state, providing a novel insight for establishment of cellular homeostasis in the early secretory pathway.
The effect of CYP7B1 polymorphisms on the risk of coronary heart disease in Hainan Han population
Authors: Liang Tiebiao , Zhang Xianbo , Liang Anshan , Wu Haiqing , Wang Qi , He Jun , Long Ming , Jin Tianbo 
Published: September 2021

Abstract
Background
Coronary heart disease (CHD) is the leading cause of human death worldwide. Genetic factors play an important role in the occurrence of CHD. Our study is designed to investigate the influence of CYP7B1 polymorphisms on CHD risk.

Methods
In this case–control study, 508 CHD patients and 510 healthy individuals were recruited to determine the correlation between CYP7B1 polymorphisms (rs7836768, rs6472155, and rs2980003) and CHD risk. The associations were evaluated by computing odds ratios (OR) and 95% confidence intervals (CI) with logistic regression analysis. The association between SNP-SNP interaction and CHD susceptibility was carried out by multifactor dimensionality reduction analyses.

Results
Our study found that rs6472155 is significantly associated with an increased risk of CHD in age > 60 years (OR 2.20, 95% CI = 1.07–4.49, p = 0.031), women (OR 3.17, 95% CI = 1.19–8.44, p = 0.021), and non-smokers (3.43, 95% CI = 1.16–10.09, p = 0.025). Rs2980003 polymorphism has a lower risk of CHD in drinkers (OR 0.47, 95% CI = 0.24–0.91, p = 0.025). Further analyses based on false-positive report probability validated these significant results. Besides, it was found that rs6472155 polymorphism was associated with uric acid level (p = 0.034).

Conclusion
Our study indicated that CYP7B1 polymorphisms are related to the risk of CHD, which provides a new perspective for prevent of CHD.
Dendritic cells matured with recombinant human sperm associated antigen 9 (rhSPAG9) induce CD4+, CD8+ T cells and activate NK cells: a potential candidate molecule for immunotherapy in cervical cancer
Authors: Dhandapani Hemavathi , Jayakumar Hascitha , Seetharaman Abirami , Singh Shirley Sunder , Ganeshrajah Selvaluxmy , Jagadish Nirmala , Suri Anil , Thangarajan Rajkumar , Ramanathan Priya 
Published: September 2021

Abstract
Background
Dendritic cell (DC)-based immunotherapy is capable of activating the immune system and in particular tumor-specific cytotoxic T lymphocytes (CTLs) to eradicate the tumor. However, major limitations are the availability of autologous tumor cells as antigenic source and the selection of antigen that may have potential to activate both CD4+ and CD8+ T cells in immune-specific manner. Recently, we reported the expression of sperm associated antigen 9 (SPAG9) that is associated with various types of malignancies including cervical cancer. We examined the recombinant human SPAG9 (rhSPAG9) as an antigenic source for generating efficient DCs to stimulate CD4+ and CD8+ T cell responses for future DCs-based vaccine trials in cervical cancer patients.

Methods
Human monocytes derived DCs were pulsed with different concentrations (250 ng/ml to 1000 ng/ml) of recombinant human SPAG9 (rhSPAG9) and evaluated for their phenotypic and functional ability. The efficacy of DCs primed with 750 ng/ml of rhSPAG9 (SPDCs) was compared with DCs primed with autologous tumor lysates (TLDCs), to induce CD4+, CD8+ T cells and activating NK cells. In addition, we investigated the effect of the chemotherapeutic drug cisplatin on phenotypic and functional potential of SPDCs.

Results
Phenotypic and functional characterization of DCs pulsed with 750 ng/ml rhSPAG9 was found to be optimal and effective for priming DCs. SPDCs were also capable of stimulating allogeneic T cells similar to TLDCs. SPDCs showed a statistically insignificant increase in the expression of maturation marker CD83 and migration towards CCL19 and CCL21 compared with TLDCs (CD83; P = 0.4; migration; P = 0.2). In contrast, although TLDCs showed better proliferation and secretion of Th1 cytokines (IL12p40, IL12p70 and IFNγ) compared to SPDCs, this difference was not statistically significant (IL12p40, P = 0.06). Further we also observed that clinical dose of cisplatin (200 µM) treated SPDCs were able to stimulate the proliferation of cytotoxic T lymphocytes without increasing the FOXP3+ Tregs in autologous co-cultures.

Conclusions
In summary, in order to overcome the limitation of the availability of autologous tumor cells as antigenic sources, our present strategy provides an insight to consider rhSPAG9 as a strong immunogen for DC-based immunotherapy for cervical cancer trials and warrants further studies. This is the first report to suggest that rhSPAG9 is an effective antigen for pulsing DCs that are capable of eliciting a potent Th1 response which, in turn, may help in decreasing the tumor burden when used along with a cisplatin based combinatorial regimen for therapeutic intervention.
COVID-19: protocol for observational studies utilizing near real-time electronic Australian general practice data to promote effective care and best-practice policy—a design thinking approach
Authors: Georgiou Andrew , Li Julie , Pearce Christopher , McLeod Adam , Wabe Nasir , Hardie Rae-Anne , Franco Guilherme Saffi , Imai Chisato , Sezgin Gorkem , Thomas Judith , Dai Zhaoli , Sheikh Muhammad Kashif , Proposch Amanda , Weeding Stephen , Wickham Brendon , Badrick Tony , Murgatroyd Darnel 
Published: September 2021

Abstract
Background
Health systems around the world have been forced to make choices about how to prioritize care, manage infection control and maintain reserve capacity for future disease outbreaks. Primary healthcare has moved into the front line as COVID-19 testing transitions from hospitals to multiple providers, where tracking testing behaviours can be fragmented and delayed. Pooled general practice data are a valuable resource which can be used to inform population and individual care decision-making. This project aims to examine the feasibility of using near real-time electronic general practice data to promote effective care and best-practice policy.

Methods
The project will utilize a design thinking approach involving all collaborators (primary health networks [PHNs], general practices, consumer groups, researchers, and digital health developers, pathology professionals) to enhance the development of meaningful and translational project outcomes. The project will be based on a series of observational studies utilizing near real-time electronic general practice data from a secure and comprehensive digital health platform [POpulation Level Analysis and Reporting (POLAR) general practice data warehouse]. The study will be carried out over 1.5 years (July 2020–December 2021) using data from over 450 general practices within three Victorian PHNs and Gippsland PHN, Eastern Melbourne PHN and South Eastern Melbourne PHN, supplemented by data from consenting general practices from two PHNs in New South Wales, Central and Eastern Sydney PHN and South Western Sydney PHN.

Discussion
The project will be developed using a design thinking approach, leading to the building of a meaningful near real-time COVID-19 geospatial reporting framework and dashboard for decision-makers at community, state and nationwide levels, to identify and monitor emerging trends and the impact of interventions/policy decisions. This will integrate timely evidence about the impact of the COVID-19 pandemic related to its diagnosis and treatment, and its impact across clinical, population and general practice levels.
Evaluating predictive factors for toxicities experienced by head & neck cancer patients undergoing radiotherapy
Authors: Ray Xenia , Sumner Whitney , Sutton Leisa , Sanghvi Parag , Deichaite Ida , Moiseenko Vitali 
Published: September 2021

Abstract
Purpose
The purpose of this study was to evaluate if HPV status serves as an independent predictor of early and late dysphagia outcomes when considered alongside standard patient characteristics and dose metrics for head and neck cancer patients treated with radiotherapy.

Methods and materials
The age, sex, smoking history, cancer type (oropharyngeal vs non-oropharyngeal), HPV status, and early and late dysphagia outcomes were obtained for 99 retrospective head and neck cancer patients treated at our clinic with radiotherapy. Additionally for each patient, the mean radiation dose to the pharynx, superior/middle/inferior pharyngeal constrictor muscles, and cricopharyngeus was calculated. The predictive power of these clinical characteristics and radiation metrics was evaluated using chi-square tests for categorical variables and t-tests for continuous variables. Then multi-variate logistic models were built for each outcome using a single dose metric at a time, and either HPV status, cancer type, or both. Multi-variate models were built using both top-down and bottom-up technique to establish the most predictive independent covariates.

Results
In the univariate analysis for early dysphagia, cancer type (p = 0.04) and four dose metrics (p ≤ 0.02) were significantly associated with outcome, while for late dysphagia, only cancer type (p = 0.04) was associated with outcome. In the multivariate analysis for early dysphagia, cancer type, smoking history, and mean dose to the five structures were consistently selected as covariates. For late dysphagia, either HPV status or cancer type was selected in each model and the mean dose to the cricopharyngeus was selected in one model.

Conclusion
While HPV is a known contributing factor for tumor prognosis in oropharyngeal cancers, its role in normal tissue toxicities for head and neck cancers has not previously been evaluated. Our results indicate having an oropharyngeal cancer may increase a patient’s risk of high-grade early and late dysphagia while HPV status was seldom selected.
Long-term oral blonanserin treatment for schizophrenia: a review of Japanese long-term studies
Authors: Murasaki Mitsukuni , Inoue Yoshifumi , Nakamura Hiroshi , Kinoshita Toshihiko 
Published: September 2021

AbstractIn general, the course of schizophrenia is chronic accompanied not only by positive and negative symptoms but also by cognitive dysfunction associated with psychosocial disability, and thus treatment combining antipsychotics and psychological therapy is considered promising. This review focused on two prospective, open-label, multicenter, phase 3 long-term studies for approval of oral blonanserin for the treatment of schizophrenia. These two studies included both inpatients and outpatients with variable disease duration or symptom prominence according to the Positive and Negative Syndrome Scale (PANSS). The selected two studies consisted of almost the same study schedule and eligibility criteria but different protocols regarding prior medications and concomitant antipsychotics. The proportion of patients who had a baseline PANSS negative score higher than the positive score was 82.2 and 67.2% in the two studies. In both studies, patients with an illness duration of ≥ 10 years were the most common. Based on the clinical symptoms at baseline, the physician determined the treatment: blonanserin monotherapy, blonanserin in combination with the existing antipsychotic medication, or therapy simplified to haloperidol together with blonanserin. The 28-week completion rate for long-term blonanserin treatment was high in both studies (82.2 and 78.7%). The types of adverse events in both studies were similar to those in the preceding 8-week randomized, active-controlled studies in Japan, which were included in the application package for the approval of oral blonanserin for patients with schizophrenia. Long-term blonanserin use did not increase the risk of extrapyramidal symptoms but reduced the dose of antiparkinsonian drugs, minimally affecting functioning. In both studies, the PANSS total score, positive score, and negative score were improved at the last observation carried forward compared with those at baseline. In conclusion, blonanserin is useful for long-term treatment of chronic schizophrenic patients when the appropriate management of clinical symptoms and adverse drug reactions are applied. Blonanserin might represent a promising treatment option that partially or completely relieves patients with chronic schizophrenia of polypharmacy. Blonanserin may possibly fit both the current real-world clinical setting and the currently recommended approach to antipsychotic medication.
Recovering genotypes and phenotypes using allele-specific genes
Authors: Gürsoy Gamze , Lu Nancy , Wagner Sarah , Gerstein Mark 
Published: September 2021

AbstractWith the recent increase in RNA sequencing efforts using large cohorts of individuals, surveying allele-specific gene expression is becoming increasingly frequent. Here, we report that, despite not containing explicit variant information, a list of genes known to be allele-specific in an individual is enough to recover key variants and link the individuals back to their genotypes and phenotypes. This creates a privacy conundrum.
Prognostic factors of total hip replacement during a 2-year period in participants enrolled in supervised education and exercise therapy: a prognostic study of 3657 participants with hip osteoarthritis
Authors: Clausen Stine , Hartvigsen Jan , Boyle Eleanor , Roos Ewa M. , Grønne Dorte Thalund , Ernst Martin Thomsen , Arnbak Bodil , Skou Søren T. 
Published: September 2021

Abstract
Background
Evidence on prognostic factors associated with progression to total hip replacement (THR) in hip osteoarthritis (OA) is for the most patient- and disease-specific characteristics either conflicting or inconclusive. Therefore, the objectives of this study of participants with hip OA enrolled in a structured program of supervised education and exercise therapy were to describe the rate of THR and to identify prognostic factors for receiving THR within the following 2 years.

Methods
Participants aged ≥ 45 years with hip OA enrolled in Good Life with osteoArthritis in Denmark (GLA:D®) from July 2014 to March 2017 were included. Potential prognostic factors included demographic and disease-specific baseline characteristics and measures of physical activity and quality of life (QoL). Information on THR was retrieved from The Danish National Patient Registry. A multivariable Cox proportional hazards model was developed.

Results
Of 3657 included participants, 30% received a THR within 2 years. Of the 100 participants already wait-listed for THR, 60% had the procedure. Of 22 candidate prognostic factors, 14 were statistically significant for receiving THR. Factors associated with a faster rate of THR included being “male” (HR 1.43), having “self-reported radiographic hip OA” (HR 2.32), being “wait-listed for THR” (HR 2.17), and having a higher “pain intensity” (HR 1.01). In contrast, faster “walking speed” (HR 0.64), better “hip-related QoL” (HR 0.98), and having “three or more comorbidities” (HR 0.62) were predictive of a slower rate of THR.

Conclusion
During the 2-year follow-up period, 30% of the cohort received a THR. Notably, 40% of those wait-listed for THR when entering the program did not receive THR within 2 years. A number of baseline prognostic factors for receiving THR were identified.
Prognostic factors of head and neck cutaneous squamous cell carcinoma: A systematic review
Authors: Lubov Joshua , Labbé Mathilde , Sioufi Krystelle , Morand Grégoire B. , Hier Michael P. , Khanna Manish , Sultanem Khalil , Mlynarek Alex M. 
Published: September 2021

Background Head and neck cutaneous squamous cell carcinoma (HNCSCC) is a non-melanoma skin cancer that is mostly caused by solar ultraviolet radiation exposure. While it usually has an excellent prognosis, a subset of patients (5%) develops nodal metastasis and has poor outcomes. The aim of this study was to systematically review the literature and evaluate the prognostic factors of HNCSCC in order to better understand which patients are the most likely to develop metastatic disease. Methods A comprehensive literature search was performed on PubMed and EMBASE to identify the studies that evaluated the prognostic factors of HNCSCC. Prognostic factors were deemed significant if they had a reported p-value of < 0.05. Proportions of studies that reported a given factor to be statistically significant were calculated for each prognostic factor. Results The search yielded a total of 958 citations. Forty studies, involving a total of 8535 patients, were included in the final analysis. The pre-operative/clinical prognostic factors with the highest proportion of significance were state of immunosuppression (73.3%) and age (53.3%); while post-operative/pathological prognostic factors of importance were number of lymph nodes involved with carcinoma (70.0%), margins involved with carcinoma (66.7%), and tumor depth (50.0%). Conclusion This systematic review is aimed to aid physicians in assessing the prognosis of HNCSCC and identifying the subsets of patients that are most susceptible to metastasis. It also suggests that immunosuppressed patients with a high-risk feature on biopsy, such as invasion beyond subcutaneous fat, could possibly benefit from a sentinel lymph node biopsy. Graphical Abstract
Biomechanics of a calcar loading and a shortened tapered femoral stem: Comparative in-vitro testing of primary stability and strain distribution
Authors: Freitag Tobias , Bieger Ralf , Kiefer Hartmuth , Dornacher Daniel , Reichel Heiko , Ignatius Anita , Dürselen Lutz 
Published: September 2021

Abstract
Purpose
The most common femoral short stems available on the market can, in principle, be divided with regard to their anchoring concepts into a calcar loading and a shortened tapered design. The purpose of this study was to compare the primary stability and stress-shielding of two short stems, which correspond to these two different anchoring concepts.

Methods
Using seven paired fresh frozen human cadaver femurs, primary axial and rotational stabilities under dynamic load (100–1600 N) were evaluated by miniature displacement transducers after 100,000 load cycles. Changes in cortical strains were measured before and after implantation of both stem types to detect implant-specific load transmission and possible stress-shielding effects.

Results
Reversible and irreversible micromotions under dynamic load displayed no significant differences between the two implants. Implantation of either stem types resulted in a reduction of cortical strains in the proximal femur, which was less pronounced for the calcar loading implant.

Conclusions
Both short stems displayed comparable micromotions far below the critical threshold above which osseointegration may disturbed. Neither short stem could avoid proximal stress-shielding. This effect was less pronounced for the calcar loading short stem, which corresponds to a more physiological load transmission.
MicroRNAs as the critical regulators of protein kinases in prostate and bladder cancers
Authors: Zangoue Malihe , Zangouei Amir Sadra , Mojarrad Majid , Moghbeli Meysam 
Published: September 2021

Abstract
Background
Bladder cancer (BCa) and prostate cancer (PCa) are frequent urothelial and genital malignancies with a high ratio of morbidity and mortality which are more common among males. Since BCa and PCa cases are mainly diagnosed in advanced stages with clinical complications, it is required to introduce the efficient early detection markers. Protein kinases are critical factors involved in various cellular processes such as cell growth, motility, differentiation, and metabolism. Deregulation of protein kinases can be frequently observed through the neoplastic transformation and tumor progression. Therefore, kinases are required to be regulated via different genetic and epigenetic processes. MicroRNAs (miRNAs) are among the critical factors involved in epigenetic regulation of protein kinases. Since miRNAs are noninvasive and more stable factors in serum and tissues compared with mRNAs, they can be used as efficient diagnostic markers for the early detection of PCa and BCa.

Main body
In present review, we have summarized all of the reported miRNAs that have been associated with regulation of protein kinases in bladder and prostate cancers.

Conclusions
For the first time, this review highlights the miRNAs as critical factors in regulation of protein kinases during prostate and bladder cancers which paves the way of introducing a noninvasive kinase-specific panel of miRNAs for the early detection of these malignancies. It was observed that the class VIII receptors of tyrosine kinases and non-receptor tyrosine kinases were the most frequent targets for the miRNAs in bladder and prostate cancers, respectively.