bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Mitochondria in Physiology of Chondrocytes and Diseases of Osteoarthritis and Rheumatoid Arthritis
Authors: Kan Shiyi , Duan Mengmeng , Liu Yang , Wang Chunli , Xie Jing 
Published: December 2021

Purpose of Review Mitochondria are recognized to be one of the most important organelles in chondrocytes for their role in triphosphate (ATP) generation through aerobic phosphorylation. Mitochondria also participate in many intracellular processes involving modulating reactive oxygen species (ROS), responding to instantaneous hypoxia stress, regulating cytoplasmic transport of calcium ion, and directing mitophagy to maintain the homeostasis of individual chondrocytes. Designs To summarize the specific role of mitochondria in chondrocytes, we screened related papers in PubMed database and the search strategy is ((mitochondria) AND (chondrocyte)) AND (English [Language]). The articles published in the past 5 years were included and 130 papers were studied. Results In recent years, the integrity of mitochondrial structure has been regarded as a prerequisite for normal chondrocyte survival and defect in mitochondrial function has been found in cartilage-related diseases, such as osteoarthritis (OA) and rheumatoid arthritis (RA). However, the understanding of mitochondria in cartilage is still largely limited. The mechanism on how the changes in mitochondrial structure and function directly lead to the occurrence and development of cartilage-related diseases remains to be elusive. Conclusion This review aims to summarize the role of mitochondria in chondrocytes under the physiological and pathological changes from ATP generation, calcium homeostasis, redox regulation, mitophagy modulation, mitochondria biogenesis to immune response activation. The enhanced understanding of molecular mechanisms in mitochondria might offer some new cues for cartilage remodeling and pathological intervention.
Inequality trends in the distribution of healthcare human resources in eastern Iran
Authors: Sotodeh Manesh Sam , Hedayati Zafarghandi Mahsa , Merati Zahra , Ebrahimzadeh Javad , Delpasand Mansoor 
Published: December 2021

Background Inequitable distribution of human resources in healthcare is one of the main obstacles to improve any health system. This study aimed to evaluate inequalities in the distribution of human resources in healthcare in South Khorasan Province, Iran. Methods We have investigated three types of health staff (i.e. nurses, general practitioners, and specialists) from 2013 to 2018. Data were collected from the annual reports of the Statistical Centre of Iran. The Gini coefficient and time trend regression were applied to measure the inequality. Results The distribution of specialists and general practitioners were the highest and lowest inequality, respectively. Inequalities in the distribution of nurses and specialists have decreased from 2013 to 2018, while the Gini coefficients of the general practitioners have increased from 0.31 to 0.38. According to the regression analysis, inequality in the distribution of nurses and specialists was decreasing over the time; however, the decline was only significant for specialists. While the coefficient B for general practitioners is positive, this indicates raised inequality, but the observed increase was not significant. Conclusions This study revealed that Iran, similar to several other low- and middle-income countries, is with faced the challenge of inequitable distribution of human resources in healthcare, which in turn indicates the necessity of reforms at national and regional levels to address inequalities in the distribution of healthcare human resources, particularly in South Khorasan Province. Hence, the main policy recommendation is to focus on continuous monitoring and evaluation of resource allocation in South Khorasan Province to reduce inequalities.
Features associated with SARS-COV-2 positivity among people presenting with acute respiratory tract infections to public Hospitals in Harari region, Ethiopia
Authors: Birhanu Abdi , Ayana Galana Mamo , Bayu Miesso , Mohammed Ahmed , Dessie Yadeta 
Published: December 2021

Background: Despite investigating coronavirus among respiratory tract infected cases is a top priority to prevent further transmission, severe acute respiratory syndrome coronavirus 2 positivity among this group of patients remains unexplored in resource-limited settings. Therefore, this study intended to assess the severe acute respiratory syndrome coronavirus 2 positivity among patients presenting with acute respiratory tract infection from 1 July to 31 December 2020 in Harar Region, Ethiopia, from 15 February to 10 March 2021. Methods: A facility-based cross-sectional study design was used. Severe acute respiratory syndrome coronavirus 2 was tested by assaying oropharyngeal swabs using reverse transcriptase–polymerase chain reaction among patients presenting with acute respiratory tract infection in Harari Public Hospitals. A binary logistic regression was used to identify factors associated with severe acute respiratory syndrome coronavirus 2 positivity with an adjusted odds ratio at a 95% confidence interval. Results: Out of a total of 1692 study participants, 388 (22.9%) of them tested positive for severe acute respiratory syndrome coronavirus 2. Of these severe acute respiratory syndrome coronavirus 2 positive patients, 364 (21.6%) patients presented with lower respiratory tract infection, while the rest only 24 (1.4%) presented with upper respiratory tract infection. Independent variables included separated/divorced in marital status (AOR = 0.53, 95% CI: 0.29–0.95), presenting with cough, fever, and difficulty of breathing (AOR = 2.5, 95% CI: 1.22–4.7), age group of 30–39 years (AOR = 0.35, 95% CI: 0.15–0.79), 40–49 years (AOR = 0.37, 95% CI: 0.14–0.94), and 50–59 years (AOR = 0.31, 95% CI: 0.13–0.76) compared to patients with the age of ⩾ 60 years, had statistically significant association with severe acute respiratory syndrome coronavirus 2 positivity. Conclusion: Severe acute respiratory syndrome coronavirus 2 was positive among 388 (22.9%) acute respiratory tract infected people. Elder age, particular symptoms, such as cough, fever, and difficulty of breathing, and married marital status were associated with a severe acute respiratory syndrome coronavirus 2 positive test. In resource-limited setups, where a shortage of testing equipment is common, these findings could contribute to boosting targeted symptom-oriented screening schemes. Moreover, this study could have paramount clinical importance for further studies in the country.
Clinical characteristics of patients with undergoing unplanned excisions of malignant soft tissue tumors
Authors: Morinaga Sei , Miwa Shinji , Yamamoto Norio , Hayashi Katsuhiro , Takeuchi Akihiko , Igarashi Kentaro , Tada Kaoru , Langit Mickhael B , Yonezawa Hirotaka , Araki Yoshihiro , Asano Yohei , Tsuchiya Hiroyuki 
Published: December 2021

Introduction Malignant soft tissue tumors are rare tumors representing <1% of all malignancies. As these tumors are rare, it is not uncommon that malignant soft tissue tumor excision is performed without the required preoperative imaging, staging, or wide resection margins for sarcomas. The purpose of this study was to investigate the characteristics of patients with undergoing unplanned excisions. Risk factors for tumor recurrence and mortality in patients treated with unplanned excisions were also analyzed. Methods Forty-nine patients who underwent unplanned excision at other hospitals and additional wide excision at our hospital between January 2002 and December 2018 were identified. Among them, 42 patients with follow-up for more than 1 year were included in this retrospective study. The relationships between sex, age, tumor depth, histological grade, location, size, surgical margin at additional wide excision, residual tumor, reconstruction, kind of hospital where the primary excision was done (sarcoma vs non-sarcoma center), preoperative examination, chemotherapy, radiation therapy, and oncological outcomes were statistically analyzed. Results Mean patient age was 57.3 years (15–85 years) and the mean observation period was 72.5 months (14–181 months). This analysis showed 53.8% tumors that underwent unplanned excisions were small (<5 cm) and 70.7% tumors were superficial. Multivariate analysis revealed that a positive margin during additional wide excision was significantly associated with a lower 5-year LRFS ( p < 0.01). Conclusion Most of the tumors underwent unplanned excisions were small (<5 cm) and superficial. Surgeons should be aware that a positive margin during additional wide excision is an independent risk factor for local recurrence.
Repurposing Statin Drugs to Decrease Toxicity and Improve Survival Outcomes in Head and Neck Cancer
Authors: Bourguillon Richard O. , Stokes William A. , Dorth Jennifer , Schmitt Nicole C. 
Published: December 2021

ObjectiveThe rising incidence of head and neck squamous cell carcinoma (HNSCC) calls for the assessment and improvement of currently available therapies that may enhance the therapeutic ratio in these patients. Statin drugs are one of the most widely used drug classes in the world for their lipid‐lowering properties. As such, statins have been widely studied and found to possess pleiotropic effects that may make them effective in cancer treatment and toxicity mitigation. The aim of this review is to examine the potential use of statin drugs as adjunctive therapy in patients with HNSCC.Data SourcesPubMed.Review MethodsAny preclinical or clinical articles pertaining to the effects of statin drugs on treatment‐related toxicity or survival outcomes in patients with head and neck cancer were included in this narrative review.ConclusionsEmerging data suggest that statins may improve survival and reduce toxicities associated with chemotherapy and radiotherapy in patients with head and neck cancer, by mechanisms that are poorly understood at present.Implications for PracticeGiven their affordability and safety, statins deserve further study as a tool to improve oncologic outcomes and enhance survivorship in patients with HNSCC.
Altered brain functional network dynamics in classic trigeminal neuralgia: a resting-state functional magnetic resonance imaging study
Authors: Zhang Pengfei , Jiang Yanli , Liu Guangyao , Han Jiao , Wang Jun , Ma Laiyang , Hu Wanjun , Zhang Jing 
Published: December 2021

Abstract
Background
Accumulating studies have indicated a wide range of brain alterations with respect to the structure and function of classic trigeminal neuralgia (CTN). Given the dynamic nature of pain experience, the exploration of temporal fluctuations in interregional activity covariance may enhance the understanding of pain processes in the brain. The present study aimed to characterize the temporal features of functional connectivity (FC) states as well as topological alteration in CTN.

Methods
Resting-state functional magnetic resonance imaging and three-dimensional T1-weighted images were obtained from 41 CTN patients and 43 matched healthy controls (HCs). After group independent component analysis, sliding window based dynamic functional network connectivity (dFNC) analysis was applied to investigate specific FC states and related temporal properties. Then, the dynamics of the whole brain topological organization were estimated by calculating the coefficient of variation of graph-theoretical properties. Further correlation analyses were performed between all these measurements and clinical data.

Results
Two distinct states were identified. Of these, the state 2, characterized by complicated coupling between default mode network (DMN) and cognitive control network (CC) and tight connections within DMN, was expressed more in CTN patients and presented as increased fractional windows and dwell time. Moreover, patients switched less frequently between states than HCs. Regarding the dynamic topological analysis, disruptions in global graph-theoretical properties (including network efficiency and small-worldness) were observed in patients, coupled with decreased variability in nodal efficiency of anterior cingulate cortex (ACC) in the salience network (SN) and the thalamus and caudate nucleus in the subcortical network (SC). The variation of topological properties showed negative correlation with disease duration and attack frequency.

Conclusions
The present study indicated disrupted flexibility of brain topological organization under persistent noxious stimulation and further highlighted the important role of “dynamic pain connectome” regions (including DMN/CC/SN) in the pathophysiology of CTN from the temporal fluctuation aspect. Additionally, the findings provided supplementary evidence for current knowledge about the aberrant cortical-subcortical interaction in pain development.
Age- and frequency-dependent changes in dynamic contrast perception in visual snow syndrome
Authors: Eren Ozan E. , Straube Andreas , Schöberl Florian , Ruscheweyh Ruth , Eggert Thomas , Schankin Christoph J. 
Published: December 2021

Abstract
Objective
Patients with visual snow syndrome (VSS) suffer from a debilitating continuous (“TV noise-like”) visual disturbance. They report problems with vision at night and palinopsia despite normal visual acuity. The underlying pathophysiology of VSS is largely unknown. Currently, it is a clinical diagnosis based on the patient’s history, an objective test is not available. Here, we tested the hypothesis that patients with VSS have an increased threshold for detecting visual contrasts at particular temporal frequencies by measuring dynamic contrast detection-thresholds.

Methods
Twenty patients with VSS were compared to age-, gender-, migraine- and aura-matched controls in this case-control study. Subjects were shown bars randomly tilted to the left or right, flickering at six different frequencies (15 Hz, 20 Hz, 25 Hz, 30 Hz, 35 Hz, 40 Hz). The contrast threshold (CT) for detection of left or right tilt was measured in a two-alternative adaptive forced-choice procedure (QUEST). The threshold was defined as the Michelson contrast necessary to achieve the correct response in 75% of the cases.

Results
The CT increased for higher flicker frequencies (ANOVA: main effect frequency: F (5,180) = 942; p < 0.001), with an additional significant frequency*diagnosis interaction (ANOVA: F (5,180) = 5.00; p < 0.001). This interaction effect was due to an increased CT at a flicker frequency of 15 Hz in the VSS cohort (VSS: MC = 1.17%; controls: MC = 0.77%). At the other frequencies, group comparisons revealed no differences. Furthermore, in the VSS cohort we observed an increase of CT with higher age (r = 0.69; p < 0.001), which was not seen in controls (r = 0.30; p = 0.20).

Conclusions
This study demonstrates a lower visual contrast sensitivity exclusively at 15 Hz in VSS patients and demonstrates frequency-dependent differences in dynamic contrast vision. The peak sensitivities of both parvo- and magnocellular visual pathways are close to a frequency of about 10 Hz. Therefore, this frequency seems to be of crucial importance in everyday life. Thus, it seems plausible that the impairment of contrast sensitivity at 15 Hz might be an important pathophysiological correlate of VSS. Furthermore, the overall age-related decrease in contrast sensitivity only in VSS patients underscores the vulnerability of dynamic contrast detection in VSS patients. Dynamic CT detection seems to be a promising neurophysiological test that may contribute to the diagnosis of VSS.
Sources, spatial distribution, and abundance of marine debris on Thondi coast, Palk Bay, Southeast coast of India
Authors: Perumal Karthikeyan , Boopathi Vishwanath , Chellaiyan Stella , Muthuramalingam Subagunasekar , Raja Prakash 
Published: December 2021

Abstract
Background
The Thondi coast is rich in valuable natural marine resources and socio-economically significant activities like agriculture, aquaculture, and fishing. The area receives an excess of untreated solid and liquid waste as a result of these activities. The study focuses on the abundance, distribution, and status of the Clean-Coast Index (CCI) of marine debris from the Thondi coast, Palk Bay, Southeast coast of India. This is the first research work focused on assessing the type and quantity of marine debris on the Thondi coast.

Results
A total of 1636 marine debris items/m2 and their 4.09 concentration of the items/m2 were determined in the marine debris: plastics (77.49%), cotton swabs (8.62%), cigarette butts (10.15%), and food containers (3.73%). From the result, the CCI had ranged between 4.25 (clean) and 20.4 (extremely dirty) with a mean of 8.92 (moderate) in the Thondi coast assessed.

Conclusion
This study was conducted for the first time in this region. Finally, the high CCI value of 20.4 on the coast indicated that the marine debris pollution levels were high at the time of sampling in the middle part of the Thondi coast (most of the beaches are covered with plastic) due to land-based marine debris (62.45%), sea-originated marine debris (21.14%), and unknown sources (16.41%) of the items. Our findings served as a baseline for potential evaluations of the marine environment. Input prevention should be the goal of management efforts, including proper waste management, plastic recycling, and stringent penalties for illegal waste dumping.
MCKAT: a multi-dimensional copy number variant kernel association test
Authors: Maus Esfahani Nastaran , Catchpoole Daniel , Khan Javed , Kennedy Paul J. 
Published: December 2021

AbstractBackgroundCopy number variants (CNVs) are the gain or loss of DNA segments in the genome. Studies have shown that CNVs are linked to various disorders, including autism, intellectual disability, and schizophrenia. Consequently, the interest in studying a possible association of CNVs to specific disease traits is growing. However, due to the specific multi-dimensional characteristics of the CNVs, methods for testing the association between CNVs and the disease-related traits are still underdeveloped. We propose a novel multi-dimensional CNV kernel association test (MCKAT) in this paper. We aim to find significant associations between CNVs and disease-related traits using kernel-based methods.ResultsWe address the multi-dimensionality in CNV characteristics. We first design a single pair CNV kernel, which contains three sub-kernels to summarize the similarity between two CNVs considering all CNV characteristics. Then, aggregate single pair CNV kernel to the whole chromosome CNV kernel, which summarizes the similarity between CNVs in two or more chromosomes. Finally, the association between the CNVs and disease-related traits is evaluated by comparing the similarity in the trait with kernel-based similarity using a score test in a random effect model. We apply MCKAT on genome-wide CNV datasets to examine the association between CNVs and disease-related traits, which demonstrates the potential usefulness the proposed method has for the CNV association tests. We compare the performance of MCKAT with CKAT, a uni-dimensional kernel method. Based on the results, MCKAT indicates stronger evidence, smallerp-value, in detecting significant associations between CNVs and disease-related traits in both rare and common CNV datasets.ConclusionA multi-dimensional copy number variant kernel association test can detect statistically significant associated CNV regions with any disease-related trait. MCKAT can provide biologists with CNV hot spots at the cytogenetic band level that CNVs on them may have a significant association with disease-related traits. Using MCKAT, biologists can narrow their investigation from the whole genome, including many genes and CNVs, to more specific cytogenetic bands that MCKAT identifies. Furthermore, MCKAT can help biologists detect significantly associated CNVs with disease-related traits across a patient group instead of examining each subject’s CNVs case by case.
Comparative analysis of aneurysm subtypes associated genes based on protein–protein interaction network
Authors: Sun Ruya , Zhou Yuan , Cui Qinghua 
Published: December 2021

AbstractThe arterial aneurysm refers to localized dilation of blood vessel wall and is common in general population. The majority of aneurysm cases remains asymptomatic until a sudden rupture which is usually fatal and of extremely high mortality (~ 50–60%). Therefore, early diagnosis, prevention and management of aneurysm are in urgent need. Unfortunately, current understanding of disease driver genes of various aneurysm subtypes is still limited, and without appropriate biomarkers and drug targets no specialized drug has been developed for aneurysm treatment. In this research, aneurysm subtypes were analyzed based on protein–protein interaction network to better understand aneurysm pathogenesis. By measuring network-based proximity of aneurysm subtypes, we identified a relevant closest relationship between aortic aneurysm and aortic dissection. An improved random walk method was performed to prioritize candidate driver genes of each aneurysm subtype. Thereafter, transcriptomes of 6 human aneurysm subtypes were collected and differential expression genes were identified to further filter potential driver genes. Functional enrichment of above driver genes indicated a general role of ubiquitination and programmed cell death in aneurysm pathogenesis. Especially, we further observed participation of BCL-2-mediated apoptosis pathway and caspase-1 related pyroptosis in the development of cerebral aneurysm and aneurysmal subarachnoid hemorrhage in corresponding transcriptomes.