bluuebunny/crossref_metadata_2025 huggingface dataset:
Clonal diversity determines persistence of SARS-CoV-2 epitope-specific T cell response.
Authors: Zornikova Ksenia , Khmelevskaya Alexandra , Sheetikov Savely , Kiryukhin Dmitry , Shcherbakova Olga , Titov Aleksei , Zvyagin Ivan , Efimov Grigory
Published: June 2022

T cells play a pivotal role in reducing disease severity during SARS-CoV-2 infection and formation of long-term immune memory. We studied 50 COVID-19 convalescent patients and found that T cell response was induced more frequently and persisted longer than circulating antibodies. We identified 756 clonotypes specific to nine CD8+ T cell epitopes. Some epitopes were recognized by highly similar public clonotypes. Receptors for other epitopes were extremely diverse, suggesting alternative modes of recognition. We tracked persistence of epitope-specific response and individual clonotypes for a median of eight months after infection. The number of recognized epitopes per patient and quantity of epitope-specific clonotypes decreased over time, but the studied epitopes were characterized by uneven decline in the number of specific T cells. Epitopes with more clonally diverse TCR repertoires induced more pronounced and durable responses. In contrast, the abundance of specific clonotypes in peripheral circulation had no influence on their persistence.
Clinical features and risk factors of surgical site infections in HIV-negative patients with cryptococcal meningitis undergoing ventriculoperitoneal shunt operations: a retrospective study
Authors: Xu Lejia , Zhu Jianyun , Wang Xiaoyun , Zeng Guofen , Gao Zhiliang , Liu Jing
Published: June 2022

Background: To investigate the clinical features and risk factors of ventriculoperitoneal shunt (VPS) associated surgical site infections (SSIs) in HIV-negative patients with cryptococcal meningitis (CM).Methods: We retrospectively reviewed the medical records of HIV-negative patients with CM underwent VPS operation admitted to The Third Affiliated Hospital of Sun Yat-sen University in Southwest China over the past 7 years.Results: 193 patients were included, of whom 25 (12.95%) had SSIs in 6 (median duration, 1-48 days) days after operation. Compared with patients without SSIs, patient with SSIs tended to be shorter preoperative preparation time. 52% patients in SSIs group and 25% patients in no-SSIs group underwent VPS operations within 3 days after admission (p=0.017). Although body temperature and infectious indicators slightly elevated postoperative in both groups. The patients with SSIs experienced more fever; more central nervous system symptoms; higher PCT value and lower cerebrospinal fluid (CSF) glucose in contrast to the no-SSIs group. Multivariate regression analysis found a 2.653 fold increase in the risk of infection for every 1℃ increase in postoperative body temperature. The most prevalent organisms were oxacillin resistant coagulase-negative Staphylococci (found in 33% of positive specimens).Conclusions: SSIs was one of the serious surgical complications after VPS operation. High body temperature, the occurrence of dizziness and headache, low postoperative hemoglobin are risk factors. Postoperative patients with high fever, high PCT and low CSF glucose should be paid more attention to.
Time to use modern contraceptives and associated factors among women of reproductive age in Ethiopia: survival analysis of the 2016 Ethiopian demographic and health survey data
Authors: Bekere Shibabaw , Asena Tilahun , Tesfaw Dejen , Wube Asmare , Alemayehu Meseret
Published: June 2022

Background: Contraceptive methods are one of the most important health interventions of the twenty-first century, and they are critical in slowing population growth and improving women's and family health. Contraceptive methods are now a global issue in general, and in developing countries in particular. Method: This study sought to identify the factors associated with the timing of the use of modern contraceptive methods among Ethiopian women. The study's data were based on EDHS (2016) obtained from CSA. To identify the risk factors associated with when to use modern contraceptive methods, a parametric survival model with frailty was used and compared using AIC and log-likelihood ratio test. Result: The study found that out of a total of 7,890 women, approximately 1,061 (13.45 percent) used modern contraceptive methods, while 6829 (86.55 percent) did not. Conclusion: The Weibull regression survival model with Gamma frailty model was an appropriate fit of time to use modern contraceptive methods among the fitted frailty models. In comparison to the non-frailty survival models, the estimated frailty model, which accounts for unobservable regional heterogeneity, was found to be more appropriate for fitting time to use modern contraceptive methods across Ethiopian regions. Furthermore, using the selected frailty model results, the independent variables age, place of residence, wealth index, educational status, and television awareness information were identified as factors associated with the time to use modern contraceptive methods at a 5% level of significance.
Activation of the Akt signaling pathway alleviates ropivacaine-induced myelination impairment of the spinal cord and hypoalgesia in neonatal rats
Authors: Wu Lei , Wei Siwei , Pei Dongjie , Yao Yiyi , Xiang Zhen , Yu Eryou , Chen Zhen , Du Zhen , Qu Shuangquan
Published: June 2022

Prolonged exposure to local anesthetics (LAs) or intrathecal administration of high doses of LAs can cause spinal cord damage. Intraspinal administration of LAs is increasingly being used in children and neonates. Therefore, it is important to study LA-related spinal cord damage and the underlying mechanism in developmental models. First, neonatal Sprague–Dawley rats received three intrathecal injections of 0.5%, 1%, or 2% ropivacaine or saline (90 min interval) on postnatal day (P)7. The electron microscopy and behavioral tests were performed to evaluate the neurotoxic effects of ropivacaine at different concentrations on spinal cord in rats. Western blot analysis was performed to measure the expression levels of p-Akt, Akt, myelin gene regulatory factor (MYRF) and myelin basic protein (MBP) in the spinal cord following administration of 2% ropivacaine. Our results showed that ropivacaine impaired myelination in the spinal cord and induced hypoalgesia in a dose-dependent, whereas 0.5% ropivacaine did not cause spinal cord damage in neonatal rats. Moreover, 2% ropivacaine decreased the expression of p-Akt, MYRF and MBP in the spinal cord. Then, the Akt-specific activator (SC79) was intraperitoneally injected 30 min before 2% ropivacaine treatment. Interestingly, SC79-mediated activation of the Akt signaling pathway alleviated ropivacaine-induced the impairment of myelination in the spinal cord and hypoalgesia. Overall, the results showed that ropivacaine caused spinal cord damage in a dose-dependent manner in neonatal rats and that activation of the Akt signaling pathway alleviated these ropivacaine-induced changes. These data provide insight into the damage to the developing spinal cord caused by LAs.
Effects of nystatin oral rinse on oral Candida species and Streptococcus mutans among healthy adults
Authors: Aljaffary Mohammed , Jang Hoonji , Alomeir Nora , Zeng Yan , Alkhars Naemah , Vasani Shruti , Almulhim Abdullah , Wu Tong Tong , Quataert Sally , Bruno Jennifer , Xiao Jin
Published: June 2022

Objectives
To examine the effect of nystatin oral rinse on oral Candida species and Streptococcus mutans carriage.
Materials and Methods
Twenty healthy adults with oral candidiasis participated in the single-arm clinical trial and received Nystatin oral rinse for 7 days, 4 applications/day, 600,000 International Units/application. Demographic-socioeconomic-oral-medical conditions were obtained. Salivary and plaque Candida species and Streptococcus mutans were assessed at baseline, 1-week and 3-month follow-ups. Twenty-four salivary cytokines were assessed. Candida albicans isolates underwent Nystatin susceptibility test.
Results
Half of participants (10/20) were free of salivary C. albicans after using Nystatin rinse. Salivary S. mutans was significantly reduced at 3-month follow-up (p < 0.05). Periodontal status reflected by bleeding-on-probing was significantly improved at 1-week and 3-month follow-ups (p < 0.05). Plaque accumulation was significantly reduced at 1-week follow-up (p < 0.05). Interestingly, the responses to Nystatin oral rinse were not associated with race, gender, age, oral hygiene practice, adherence to Nystatin rinse, or sweets consumption (p > 0.05). No C. albicans isolates were resistant to Nystatin. Furthermore, salivary cytokines Eotaxin and Fractalkine were significantly reduced at 3 months follow-up among participants responded to Nystatin rinse (p < 0.05).
Conclusions
The study results indicate that oral antifungal treatment had an effect on S. mutans salivary carriage. Future clinical trials are warranted to comprehensively assess the impact of antifungal treatment on the oral flora other than S. mutans and Candida.
Clinical Relevance
: Due to the potential cariogenic role of oral Candida species, antifungal approaches shed new light on the prevention and management of dental caries from a fungal perspective.
Fatigue Reliability Assessment Method for Aero-engine Compressor Blade-disk System with Failure Dependency between Components Based on Response Surface Method
Authors: Qian Wenxue , Zeng Xianhai , Huang Shuanghui , Yin Xiaowei
Published: June 2022

The compressor blade-disk system of an aero-engine is a complicated system with numerous components, and the failures of components are related. To evaluate its reliability accurately and efficiently, a fatigue reliability assessment method to handle the issues with failure dependency between components was proposed. Firstly, the finite element analysis was carried out considering the dispersion of load and material; secondly, the probabilistic distributions of stress, strain, and fatigue life of components were fitted by the response surface method; finally, the multi-component failure-dependent reliability model (MCFDM) of the compressor blade-disk system was established based on the dependent failure system reliability theory. Based on this model, the fatigue life of the blade-disk system at varying reliability levels and the reliability and failure probability at varying specified life levels were calculated. The results of MCFDM are compared with those of the independent failure reliability assessment model(IFM) and the traditional Monte Carlo method(MCM). It is demonstrated that the system reliability calculated by IFM is too optimistic, while MCM requires a large number of samples based on the finite element model directly. In comparison, MCFDM can offer results with sufficient accuracy and higher efficiency.
Chronic diseases, multi-morbidity and COVID-19 in persons experiencing homelessness: results from a cross-sectional study conducted at three humanitarian clinics in Germany in 2020
Authors: Lutchmun Wandini , Gach Janina , Borup Christiane , Froeschl Guenter
Published: June 2022

Background
Persons experiencing homelessness (PEH) suffer a high burden of chronic diseases and multi-morbidity, yet face significant barriers in accessing healthcare services. These health inequalities were further aggravated during the COVID-19 pandemic. While there is a lack of comprehensive health data on PEH, even less is known about populations experiencing housing exclusion, a hidden form of homelessness. This study examines and compares chronic diseases and multi-morbidity in PEH, persons experiencing housing exclusion, and persons with secure housing who lacked access to regular healthcare services in the wake of the COVID-19 pandemic in Germany.
Methods
Study participants were adults who sought medical care at clinics of the humanitarian organisation “Ärzte der Welt” in Munich, Hamburg and Berlin in 2020. The patients were categorised into three housing groups according to the ETHOS classification of homelessness and housing exclusion. Socio-demographic characteristics, self-rated health, chronic diseases, multi-morbidity and SARS-COV-2 rates were described in each group. Logistic regression analysis was used to identify socio-demographic factors associated with higher odds of chronic diseases and multi-morbidity in each housing group.
Results
Of the 695 study participants, 333 experienced homelessness, 292 experienced housing exclusion and 70 had secure housing. 92.3% of all patients had either no or limited health coverage, and 96.7% were below the poverty line. Males and EU/EEA citizens were highly represented among PEH (74.2% and 56.8% respectively). PEH had lower self-rated health (47.8%, p = 0.04), and higher rates of psychiatric illness (20.9%, p = 0.04). In adjusted analyses, belonging to the age group 35–49 and ≥ 50 years were associated with greater odds of chronic disease (AOR = 2.33, 95% CI = 1.68–3.24; AOR = 3.57, 95% CI = 2.55–5.01, respectively) while being male was associated with lower odds of multi-morbidity (AOR = 0.602, 95% CI = 0.38–0.9). Of the 18 symptomatic participants tested for SARS-COV-2, 15 were PEH, 1 of whom tested positive.
Conclusions
Housing status was not an independent risk factor for chronic disease and multi-morbidity in our study population. However, PEH reported poorer self-rated and psychiatric health. Strategies to improve access to healthcare services amongst persons experiencing homelessness and housing exclusion are needed in Germany.
Circulating microvesicles correlate with radiation proctitis complication after radiotherapy
Authors: Ribault Alexandre , Benadjaoud Mohamed Amine , Squiban Claire , Arnaud Laurent , Judicone Coralie , Leroyer Aurélie S. , Rousseau Alexandra , Huet Christelle , Guha Chandan , Benderitter Marc , Lacroix Romaric , FLAMANT Stephane , Chen Emily I. , Simon Jean-Marc , Tamarat Radia
Published: June 2022

In a large retrospective study, we assessed the putative use of circulating microvesicles (MVs), as innovative biomarkers of radiation toxicity in a cohort of 208 patients with prostate adenocarcinoma overexposed to radiation. The level of platelet (P)-, monocyte (M)- and endothelial (E)-derived MVs were assessed by flow cytometry. Rectal bleeding toxicity scores were collected at the time of blood sampling and during the routine follow-up and were tested for association with MVs using a multivariate logistic regression. MVs dosimetric correlation was investigated using dose volume histograms information from a subset of 36 patients. The number of PMVs was significantly increased in patients with highest toxicity grades compared to lower grades. Risk prediction analysis revealed that increased numbers of PMVs, and an increased amount of MMVs relative to EMVs, were associated with worst rectal bleeding grade compared to the time of blood sampling. Moreover, a significant correlation was found between PMV and MMV numbers, with the range of doses up to the median exposure (40Gy) of bladder/rectum and anterior rectal wall, respectively. MVs could be considered as new biomarkers to improve the identification of patients with high toxicity grade and may be instrumental for the prognosis of radiation therapy complications.
Inhibition of voltage-gated sodium ion channel by corannulene and computational inversion blockage underlying mechanisms
Authors: Li Xinyu , Yin Hongqiang , Zuo Xiang , Jia Zhenzhen , Wang Yanlei , Yang Zhuo , Feng Xizeng
Published: June 2022

Corannulene (Cor), a special carbon materials, have been evidenced have strong protein binding capacity to regulate lysozyme crystallization and controlling reactive oxygen species (ROS) generation. Ion channel functions are controlled by ion channel protein thus affecting on physiological functions. However, the interaction between Cor and ion channel protein have not been studied. In this study, we used mPEG-DSPE to encapsulate Cor and prepare PEG/Cor complexes. The prepared PEG/Cor complexes distributed in cytoplasm and produced cytotoxicity at high concentration. Whole cell patch clamp examined ion channel functions after PEG/Cor complexes administration. we found that PEG/Cor Nps administration inhibited voltage-gated Na+ ion channels in a dose-and time-dependent manner but did not act on voltage-gated K+ ion channels. The potential mechanisms were revealed by all-atom molecular dynamic (MD) simulations. Briefly, Cor could block the pore of sodium ion channel protein due to accumulation of Cor on the pore of ion channel protein. Besides, the orientation angle (θ) configuration of Cor will be inverted with the accumulation to generate two blocking mechanisms. Different from other carbon nanomaterials, the blockage mechanism of Cor provides novel insights into the mechanisms of interaction between carbon nanomaterials and ion channel protein.
TREM2/β-catenin attenuates NLRP3 inflammasome-mediated macrophage pyroptosis to promote bacterial clearance of pyogenic bacteria
Authors: Wang Yi , Cao Can , Zhu Yanting , Fan Huifeng , Liu Qiaojuan , Liu Yiting , Chen Kang , Wu Yongjian , Liang Siping , Li Meiyu , Li Lexi , Liu Xi , Zhang Yuanqing , Wu Chenglin , Lu Gen , Wu Minhao
Published: June 2022

Triggering receptors expressed on myeloid cells 2 (TREM2) is considered a protective factor to protect host from bacterial infection, while how it elicits this role is unclear. In the present study, we demonstrate that deficiency of triggering receptors expressed on myeloid cells 2 (TREM2) significantly enhanced macrophage pyroptosis induced by four common pyogenic bacteria including Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae and Escherichia coli. TREM2 deficiency also decreased bacterial killing ratio of macrophage, while Caspase-1 or GSDMD inhibition promoted macrophage-mediated clearance to these bacteria. Further study demonstrated that the effect of TREM2 on macrophage pyroptosis and bacterial eradication mainly dependents on the activated status of NLRP3 inflammasome. Moreover, as the key downstream of TREM2, b-catenin phosphorylated at Ser675 by TREM2 signal and accumulated in nucleus and cytoplasm. b-catenin mediated the effect of TREM2 on NLRP3 inflammasome and macrophage pyroptosis by reducing NLRP3 expression, and inhibiting inflammasome complex assembly by interacting with ASC. Collectively, TREM2/b-catenin inhibits NLRP3 inflammasome to regulate macrophage pyroptosis, and enhances macrophage-mediated pyogenic bacterial clearance.
Gene duplication and cellular divergence in crops
Authors: Birnbaum Kenneth , Guillotin Bruno , Rahni Ramin , Passalacqua Michael , Mohammed Mohammed , Xu Xiaosa , Jackson David , Groen Simon , Gillis Jesse
Published: June 2022

Different plant species within the grasses were parallel targets of domestication, giving rise to crops with distinct evolutionary histories and traits. Key traits that distinguish these species are mediated by specialized cell types within organs. Here, we compare the transcriptomes of all cells within roots in three grasses—Zea mays (maize), Sorghum bicolor (sorghum), and outgroup Setaria viridis (Setaria). We first show that single-cell and single-nucleus RNA-seq provide complementary readouts of cell identity, warranting a combined analysis. Comparative cellular analysis shows that the transcriptomes of some cell types diverged more rapidly than others, in part by recruiting gene modules from other cell types. Furthermore, examining the whole genome duplication in maize, we detect extensive dosage compensation in surviving co-expressed homeologs, reinforcing genomic balance1. Homeolog pairs that underwent subfunctionalization2, partitioning their expression among cell types, represented a minor pattern but showed the highest rate of acquiring a novel (non-ancestral) domain. These results fit a conjecture in which mechanisms that maintain stoichiometric balance at the molecular level aid in homeolog retention for extended periods to allow new functions to arise. An unexpected synergy between spatial sub- and neo-functionalization then contributes to changes in transcriptional cell identity.
Two cases of dupilumab-associated conjunctivitis with high expression of IL-8 mRNA on the ocular surface: a case report
Authors: Adachi Rumi , Shoji Jun , Akira Hirota , Tomioka Akiko , Tonozuka Yukiko , Inada Noriko , Yamagami Satoru
Published: June 2022

Background: Dupilumab-induced ocular surface disease (DIOSD) has been reported in patients with atopic dermatitis treated with dupilumab, and has been recognized as an adverse event of dupilumab. Our objective was to describe two cases of DIOSD with alterations in eotaxin-2 and interleukin (IL)-8 messenger ribonucleic acid (mRNA) expression on the ocular surface. Case presentation: In the ocular surface test, specimens were collected from the patient's ocular surface, and eotaxin-2 and IL-8 mRNA levels in the specimens were measured using real-time polymerase chain reaction. The clinical score of ocular surface findings was quantified using a 5-5-5 exacerbation grading scale for allergic conjunctivitis. The first case was of a 27-year-old man who developed DIOSD 3 months after starting treatment with dupilumab injection for atopic dermatitis. After 5 weeks of topical instillation of tacrolimus ophthalmic suspension, the clinical score of ocular surface findings improved and IL-8 and eotaxin-2 mRNA expression levels gradually decreased. The second patient was a 55-year-old man who developed DIOSD 11 weeks after the start of treatment with dupilumab injection for atopic dermatitis. Four weeks after starting ophthalmological treatment with tacrolimus ophthalmic suspension, his clinical scores on ocular surface findings improved and IL-8 mRNA expression levels decreased. The ocular surface test in this case revealed increased expression levels of IL-8 mRNA on the ocular surface at the onset of DIOSD, which decreased with the improvement of objective findings. Conclusions: DIOSD, which has been successfully treated with tacrolimus ophthalmic suspension, may involve IL-8-related inflammation in addition to type 2 inflammation.
What is the impact of Light Curing Modes of High-Powered LED on Temperature rise in Primary Teeth Dentin: an in-vitro study
Authors: Jabbour Obada , Alfares Reem
Published: June 2022

Background: Temperature rise in the pulp chamber is a severe stress that can cause irreversible damage to the pulp. The objective of this study was to compare the temperature rise under primary teeth dentin induced by Light Emitting Diode (LED) with different light curing modes. Methods: sixty dentin discs of 0.5- 1- 1.5- and 2-mm thickness were prepared from human primary molars. Resin composite placed in an Teflon cavity was cured using a high-powered LED (Foshan JERRY Medical Apparatus CO., LTD, Foshan, China) for 20s. The different modes tested in this study were standard mode, ramp mode, and pulse mode (n=5). Temperature was recorded using a k-type thermocouple in direct contact with the dentin disc. Temperature change data were subjected to analysis of variance (ANOVA) and Tukey's test. Results: The highest temperature rise was observed under 0.5 mm thick dentin disc with standard mode (4.7 ± 0.42), whereas the lowest values were recorded with pulse mode under 2 mm thick dentin (2.5 ± 0.23). Pulse mode produced significant lower temperature rise compared to standard mode in all dentin thicknesses (P < 0.05). Ramp mode gave significantly lower values compared to standard mode in 0.5 mm group (P < 0.05). For standard and ramp modes, 0.5 mm thick group exhibit higher temperature rise than 2 mm thick group (P < 0.05). Conclusions: Maximum temperature rise induced by high-powered LED was not critical for pulpal health. Temperature rise related to dentin thickness and curing modes. Pulse mode gave the lowest values.
Sex-dependent migration of eastern great bustard (Otis tarda dybowskii) in Northeast Asia
Authors: Wang Yingjun , Purev-Ochir Gankhuyag , Gungaa Amarkhuu , Erdenechimeg Baasansuren , Terbish Oyunchimeg , Khurelbaatar Dashdorj , Wang Zijian , Mi Chunrong , Guo Yumin
Published: June 2022

Background
The great bustard (Otis tarda) holds the distinction of the heaviest bird to undergo migration as well as the greatest degree of sexual size dimorphism among living birds. Though the migration of the species has been widely discussed in the literature, researchers know little about the migration patterns of the subspecies in Asia (Otis tarda dybowskii), especially the males.
Methods
In 2018 and 2019, we captured six O. t. dybowskii (five males and one female) at their breeding sites in eastern Mongolia and tagged them with GPS-GSM satellite transmitters. This constitutes the first time that male great bustards of the eastern subspecies have been tracked. We combined the tracking data of our only female with other three females from central Mongolia, which was published in previous study for analysis.
Results
We found notable differences between the sexes: 1) males started migration later but arrived early than females in the spring, but not in autumn; 2) males had 1/3 of the migration duration of females (16.44 ± 14.68 days vs. 49.34 ± 21.28 days); 3) males migrated about 1/2 the distance of females (945.13 ± 79.00 km vs. 1922.88 ± 87.08 km). Additionally, we found bustards exhibited high fidelity to their breeding, post-breeding and wintering sites. Indeed, most of the wintering sites found by GPS tracking in this study were also utilized 70 years earlier, according to previous work. For conservation, we found only 22.20% of GPS location fixes of bustards were within protected areas and less than 5.0% for wintering sites and during migration.
Conclusions
Our findings suggest that the migration patterns of eastern great bustards are sex-specific and more conservation effort is needed for the Asian populations of this threatened species.
Drift-Diffusion Modeling Reveals that Masked Faces are Preconceived as Unfriendly
Authors: Mulder Martijn J. , Prummer Franziska , Terburg David , Kenemans J. Leon
Published: June 2022

During the COVID-19 pandemic, the use of face masks has become a daily routine. Studies have shown that face masks increase the ambiguity of facial expressions which not only affects (the development of) emotion recognition, but also interferes with social interaction and judgement. To disambiguate facial expressions, we rely on perceptual (stimulus-driven) as well as judgmental (preconception) processes. However, it is unknown which of these two mechanisms accounts for the misinterpretation of masked expressions. To investigate this, we asked participants (N = 136) to decide whether ambiguous (morphed) facial expressions, with or without a mask, were perceived as friendly or unfriendly. To test for the independent effects of perceptual and judgmental biases we fitted a drift-diffusion model (DDM) to the behavioral data of each participant. Results show that face masks induce a clear loss of information leading to a slight perceptual bias towards friendly choices, but also a clear judgmental bias towards unfriendly choices for masked faces. These results suggest that, although face masks can increase the perceptual friendliness of faces, people have the prior preconception to interpret masked faces as unfriendly.
FarGen: Elucidating the distribution of coding variants in the isolated population of the Faroe Islands
Authors: Gregersen Noomi , Mortensen Ólavur , Thomsen Elisabet , Lydersen Leivur , Apol Katrin , Weihe Pál , Steig Bjarni á , Andorsdóttir Guðrið , Als Thomas
Published: June 2022

Here we present results from FarGen Phase I exomes. This dataset is based on the FarGen cohort, which consists of 1,541 individuals from the isolated population of the Faroe Islands. The purpose of this cohort is to serve as a reference catalog of coding variants, and to conduct population genetic studies to better understand the genetic contribution to various diseases in the Faroese population.
Out of the 536 sequenced samples, 465 were chosen to represent the final dataset, and a total of 148,267 variants were discovered. Principle Component Analysis indicates that the population is isolated and weakly structured. The distribution of variants in various functional classes was compared with populations in the gnomAD dataset; the results indicated that the proportions were consistent across the cohorts, but probably due to a small sample size, the FarGen dataset contained relatively few rare variants. We identified 19 variants that are classified as pathogenic or likely pathogenic in ClinVar; several of these variants are associated with monogenetic diseases with increased prevalence in the Faroe Islands.
The results support previous studies, which indicate that the Faroe Islands is an isolated and weakly structured population. Future studies may elucidate the significance of the 19 pathogenic variants that were identified. The FarGen Phase I dataset is an important step for genetic research in the Faroese population, and the next phase of FarGen will increase the sample size and broaden the scope.
Classified Dynamic Hierarchical Load Balancer for Cloud Data Centers
Authors: Chhabra Sakshi chhabra , Saxena Deepika , Kumar Jitendra , Kumar Ashutosh
Published: June 2022

The performance and operational cost of a cloud data center may worsen due to degenerative resource allocation. A novel scheme ’C-DHLB’ Classified Dynamic Hierarchical Load Balancer is introduced to address this issue by the means of resource requirement analysis and allocating an optimized number of computing resources to every application. We formulate the traffic scalability issue as a virtual machine placement optimization with multi-dimensional resource constraints. The model allocates the exact amount of resources and pick out the most optimal host to achieve immediate load balancing effect. Performance evaluation demonstrates that proposed model achieves high throughput, avoid traffic overflow and reduce upto 72.58% of the traffic in the network.
Construct validity of the Amharic version perceived stress scale (PSS-10) among Defense University students
Authors: Tsegaye Bitew Sintayehu , Andegiorgish Amanuel Kidane , Amhare Abebe Feyissa , Belay Habtamu
Published: June 2022

Background: Perceived stress scale (PSS) is the most widely used tool for assessing stressful life events and its management. However, its validity in Ethiopian Amharic language is not assessed. Objective: To translate the perceived stress scale (version PSS-10) and assess its validity among Defense University students in Bishoftu, Ethiopia.Method: From March to May 2020, an anonymous, self-managed questionnaire was used to collect the data on 758 undergraduate students of Defense University in Bishoftu, Ethiopia. Exploratory and Confirmatory factor analyses were employed to assess the factor structure and construct validity of Amharic version of the PSS-10. Cronbach alpha and Item total correlation were calculated to assess the internal consistency of Amharic version of the PSS-10.Result: Exploratory factor analysis resulted in a two-dimensional PSS-10 with Eigenvalues of 3.4 and 1.5, which explained 49.8% of the variance. Confirmatory factor analysis indicates a good model fit of the two correlated factors (Comparative fit index (CFI) = 0.94 with root mean square error of approximation (RMSEA) = 0.05[0.04-0.07] and standardize root mean residual (SRMR) = 0.042). The internal consistency of PSS-10 and the Negative factor were in acceptable range, whereas the Positive factor was marginally acceptable (alpha =0.78, 0.78, and 0.68) respectively.Conclusion: The Amharic translated version of PSS-10 was found to be a valid and reliable instrument to measure the perceived stress level among university students.
Active participation of people with spinal cord injury in the design of scientific research
Authors: Faleiros Fabiana , Braga Deyse , Schoeller Soraia Dornelles , Henriques Sílvia Helena , Cunha Naira Beatriz Favoretto , Videira Lorena Gomes Neves , Grillo Adriana Cordeiro Leandro Silva
Published: June 2022

Scientists are concerned with conducting research that accurately portrays the needs of people with spinal cord injury (SCI). As such, the main difficulties and desires for research according to people with SCI were investigated. This is a quantitative, exploratory, analytical, and cross-sectional study carried out online with a non-probabilistic sample of 618 Brazilian adults with SCI, who registered voluntarily to participate in the research of the Neurorehab group. The questionnaire consisted of 22 questions based on Data Sets from ISCOS. The response rate was 64%, with an average time of 11 minutes to complete the form. The mean age of the participants was 38.04 years (SD=9.85). The majority (68.9%) were male with higher education or a post-graduate qualification (49.5), and 58.7% were paraplegic. The main difficulties after SCI were locomotion/accessibility (70.9%), neurogenic bladder (68.8%), neurogenic bowel (48.2%), and sexuality (36.1%). The most desired studies were stem cell experiments (22.5%), rehabilitation (14.2%), and studies aiming at a cure (13.9%). Most (84.3%) of those who reported problems with sexuality after SCI were men (p=0.013). The obtained results empowered the people with SCI by enabling their participation in the future design of scientific investigations considering their desires and difficulties.
Go beyond “abundance”: cross-cohort single-nucleotide-variant profiling of gut microbiota suggests a novel gut-health assessment approach
Authors: Ma Chenchen , Zhang Yufeng , Jiang Shuaiming , Teng Fei , Huang Shi , Zhang Jiachao
Published: June 2022

Background: The adaptive evolutionary changes can precede the ecological changes in the gut microbial communities under constant host selection pressure, yet their association with host diseased status was underexplored. Results: Herein, we performed a meta-analysis of 1711 gut metagenomic samples from 16 case-control studies spanning 12 human diseases to systematically explored shared disease-associated single nucleotide variants (SNVs) in gut microbes, and included an additional 446-member cohort for validation. Overall, healthy individuals carried more mutated resident gut microbes, and more SNVs, mainly involving the short-chain fatty acids (SCFAs) producing bacteria. Furthermore, the widespread differences in base mutation bias of gut microbes were observed between health and nonhealthy subjects suggesting divergent gut microbial evolutionary directions under different host medical conditions. We further found that nonsynonymous SNVs can lead to functional inactivation of five SCFA-production genes in non-healthy populations, among of which two genes (i.e., ack, and scpC) from Faecalibacterium prausnitzii C, and Bacteroides stercoris respectively were externally validated. Subsequently, we developed a novel gut microbiome health index (GMHI) based on the SNV rate of all mutated strains, classifying host health states with 74.23% accuracy, validated with high accuracy (AUROC=69.28%). Conclusions: Collectively, our study highlights the importance of employing the genetic variability in gut microbiome to characterize the gut microbial adaptation that can also predict human chronic diseases.
Geometry of Mus-gradient Metric and Bi-harmonicity
Authors: zegga kaddour , othmane Reda kada ben
Published: June 2022

In this paper we study the geometry of the Mus-gradient metric in Riemannian manifolds. We establish a necessary and sufficient conditions under which a map is harmonic or bi-harmonic with respect to the Mus-gradient metric.
COVID-19 vaccination uptake and safety profile among germline BRCA1 and BRCA2 pathogenic variant carriers in Singapore
Authors: Zhang Zewen , Ishak Nur Diana Binte , Chan Sock Hoai , Que Frances Victoria Fajardo , Chua Zi Yang , Chiang Jianbang , Ngeow Joanne
Published: June 2022

Background: Cancer patients infected with the Coronavirus disease 2019 (COVID-19) have demonstrated increased mortality rates compared to non-cancer patients. While COVID-19 vaccination remains voluntary in Singapore, it remains highly encouraged to provide better protection at the community level. At our Cancer Genetics Service, we see patients with germline genetic alterations, with the majority being BRCA1/2 pathogenic/likely pathogenic variant (PV/LPV) carriers. Currently, there is insufficient data to suggest if this group should be managed differently from others.Methods: We conducted a survey of COVID-19 vaccination uptake rates and toxicity in a prospective cohort of 189 participants with germline BRCA1/2 PV/LPV between 1st Sept 2021 and 30th Sept 2021. Results: Our study demonstrated that the vaccination rates in our cohort is consistent with the general population and has a similar side effects profile. Conclusion: Recommendations with regards to vaccination for eligible individuals should not differ from non-carriers and be encouraged by their healthcare providers.
AN EFFICIENT HYBRID TEXTURE DESCRIPTOR FOR PULMONARY EMPHYSEMA CLASSIFICATION
Authors: Ramadoss R. , Vimala C.
Published: June 2022

Chronic obstructive pulmonary disease (COPD), a common lung disease is caused due to damages in small air sacs at the end of lung airways that affects both genders. Detecting and treating pulmonary emphysema at earlier stage can reduce the mortality. The lung Computer Tomography (CT) images obtained from Computed Tomography Emphysema Database (CTED) is utilized for emphysema classification. In this paper, the automated Neural Networks (NN) based Pulmonary Emphysema Classification System (PECS) is proposed to identify and classify the emphysema lung diseases using three phases. The preprocessing phase employs the Contrast Limited Adaptive Histogram Equalization (CLAHE) technique for contrast enhancement of images. Then the image feature extraction phase uses the Laws Local Binary Pattern (L2BP) for extracting the texture descriptor images. Finally, the classification is done using two stage Neural Network classifiers (NN-1 and NN-2) to classify the emphysema images. The NN-1 classifier is used to classify the as Normal Tissue (NT), or abnormal (CLE & PLE) class and then NN-2 classifier identify the abnormal CT images into either CLE or PLE.
Systematic dissection of key factors governing recombination outcomes by GCE-SCRaMbLE
Authors: Zhang Huiming , Fu Xian , Gong Xuemei , Wang Yun , Zhang Haolin , Zhao Yu , Shen Yue
Published: June 2022

With the completion of Sc2.0 chromosomes, SCRaMbLE becomes more critical for in-depth investigation of fundamental biological questions and screening of industrially valuable characteristics. Further applications, however, are hindered due to the lack of facile and tight regulation of the SCRaMbLE process, and limited understanding of key factors that may affect the rearrangement outcomes. Here we propose a new approach to precisely regulate SCRaMbLE recombination in a dose-dependent manner using genetic code expansion (GCE) technology with low basal activity. By systematically analyzing 1380 derived strains and six yeast pools subjected to GCE-SCRaMbLE, we find that Cre enzyme abundance, genome ploidy and chromosome conformation play key roles in recombination frequencies and determine the SCRaMbLE outcomes. With these insights, the GCE-SCRaMbLE system will serve as a powerful tool in the future exploitation and optimization of the Sc2.0-related technologies.
Hsa_circ_0084904 drives cervical cancer advancement by modulating the miR- 578/AURAK pathway
Authors: Wang Ying , Liang Lingxia , Jin Canhui , Yu Juanjuan , Tian Xiaoyu , Wang Aihong
Published: June 2022

Cervical cancer (CC) is associated with elevated prevalent rates. Circular RNAs (circRNAs) play vital functions in the pathogenesis of various cancers, such as CC. Here, we evaluated the function and associated molecular mechanisms of hsa_circ_0084904 (circKIAA1429) in CC progression. Analysis of dataset GSE102686 showed that hsa_circ_0084904 expressions were elevated. Function assays found that hsa_circ_0084904 knockdown repressed cell proliferation, formation of colonies, as well as invasion capacities in vitro. In vivo, it reduced tumor progression. Furthermore, in CC cells, hsa_circ_0084904 was shown to upregulate AURKA by sponging miR-578. MiR-578 silencing or AURKA overexpression reversed the effects associated with hsa_circ_0084904 silencing. In conclusion, hsa_circ_0084904 is a potential regulator of CC tumorigenesis via modulation of miR-578/AURKA axis and highlight a therapeutic potential for hsa_circ_0084904 against CC.
Reconstruction of 3D topographic landscape in soft X- ray Fluorescence microscopy through an inverse X- ray-tracing approach based on multiple detectors
Authors: Ippoliti Matteo , Billè Fulvio , Karydas Andreas G. , Gianoncelli Alessandra , Kourousias George
Published: June 2022

The study of X-Ray fluorescence (XRF) emission spectra is a powerful technique used in applications that range from biology to cultural heritage. Key objectives of this technique include identification and quantification of elemental traces composing the analyzed sample. However, precise derivation of elemental concentration is often hampered by self-absorption of the XRF signal emitted by light constituents. This attenuation depends on the amount of sample present between the radiation source and detection system and allows for the exploitation of self-absorption in order to recover a sample topography. In this work, an x-ray-tracing application based on the use of multiple silicon drift detectors, is introduced to inversely reconstruct a 3D sample with correct topographical landscape, from 2D XRF count rates maps obtained from spectroscopy. The reconstruction was tested on the XRF maps of a simulated sample, which is composed of three cells with different size but similar composition. We propose to use the recovered 3D sample topography in order to numerically compute the self-absorption effects on the X-ray fluorescence radiation, thereby showing that a quantitative correction is possible. Lastly, we present a web application which implements the suggested methodology, in order to demonstrate its feasibility and applicability, available at: https://github.com/ElettraSciComp/xrfstir.
Robotic Liver Resection For Hepatocellular Carcinoma. Analysis of Surgical Margins and Clinical Outcomes From A Western Tertiary Hepatobiliary Center
Authors: Shapera Emanuel , Crespo Kaitlyn , Syblis Cameron , Ross Sharona , Rosemurgy Alexander , Sucandy Iswanto
Published: June 2022

Background
This study was undertaken to determine surgical outcomes of patients undergoing robotic hepatectomy for hepatocellular carcinoma (HCC) and to investigate the correlation between tumor distance to margin and perioperative outcomes, as well as overall survival (OS). To our knowledge, this study represents the largest series of robotic liver resection for HCC in North America.
Methods
We retrospectively analyzed 58 consecutive patients who underwent robotic liver resection for HCC. Patients were further stratified by tumor distance to margin (≤ 1mm, 1.1-9.9mm, ≥ 10mm) and their clinical outcomes including OS were compared.
Results
A majority of patients attained a greater than 1mm tumor distance to margin (81%). There were no differences in tumor size between patient cohorts who attained ≤ 1mm, 1.1-9.9mm, and ≥ 10mm margins. There were no differences in pre-, intra-, and postoperative outcomes among the three cohorts. Cost variables of interest were also similar. OS was highest in the > 10mm margin cohort, and this was statistically significant at 3 and 5 years.
Conclusion
Robotic HCC resection was associated with adequate tumor distance to margin. Wide margins ≥ 10mm is associated with the best OS.
Carbonic anhydrase IX inhibitor S4 triggers immunogenic cell death in glioma cells via endoplasmic reticulum stress pathway
Authors: Cui Jing , Xu Huizhe , Shi Ji , Fang Kun , Liang Dapeng , Liu Feng , Wang Jing , Xie Chunrui , Xia Zhiyu , Meng Songshu , Yan Yumei , Piao Haozhe
Published: June 2022

Purpose: Immunogenic cell death (ICD), which releases danger-associated molecular patterns (DAMP) that induce potent anticancer immune response, has emerged as a key component of therapy-induced anti-tumor immunity. The aim of this work was to analyze whether the carbonic anhydrase IX inhibitor S4 can elicit ICD in glioma cells. Methods: The effects of S4 on glioma cell growth were evaluated using the CCK-8, clonogenic and sphere assays. Glioma cell apoptosis was determined by flow cytometry. Surface-exposed calreticulin (CRT) was inspected by confocal imaging. The supernatants of S4-treated cells were concentrated for the determination of HMGB1and HSP70/90 expression by immunoblotting. RNA-seq was performed to compare gene expression profiles between S4-treated and control cells. Pharmacological inhibition of apoptosis, autophagy, necroptosis and endoplasmic reticulum (ER) stress was achieved by inhibitors. In vivo effects of S4 were evaluated in glioma xenografts. Immunohistochemistry (IHC) was performed to stain Ki67 and CRT.Results: S4 significantly decreased the viability of glioma cells and induced apoptosis and autophagy. Moreover, S4 triggered CRT exposure and the release of HMGB1 and HSP70/90. Inhibition of either apoptosis or autophagy significantly reversed S4-induced release of DAMP molecules. RNA-seq analysis indicated that the ER stress pathway was deregulated upon exposure to S4. Both PERK-eIF2α and IRE1α- XBP1 axis were activated in S4-treated cells. Furthermore, pharmacological inhibition of PERK significantly suppressed S4-triggered ICD markers and autophagy. In glioma xerografts, S4 significantly reduced tumor growth. Conclusions: Altogether, these findings suggest S4 as a novel ICD inducer in glioma and might have implications for S4-based immunotherapy.
Salubrinal suppresses cadmium-induced cell death by affecting endoplasmic reticulum stress/autophagy in SH-SY5Y human neuroblastoma cells
Authors: Miyayama Takamitsu , Matsuoka Masato
Published: June 2022

Background: Salubrinal, inhibits the dephosphorylation of eukaryotic translation initiation factor 2 subunit α (eIF2α), provides protection against cadmium toxicity. However, underlying mechanisms of salubrinal for ER stress/autophagy remain unknown in SH-SY5Y human neuroblastoma cells following exposure to cadmium.Methods: Cells were exposed to 1.0 µM CdCl2 and 10 µM salubrinal for 24 h. Cytotoxicities and viabilities were evaluated by using a WST-8 assay. The expression of ER stress– and autophagy–related genes was analyzed by immunoblotting. To evaluate lysosomal pH and autophagosomal formation, fluorescence signals of LysoTracker and Cyto-ID were determined by confocal laser scanning microscopy, respectively. To discriminate autophagic impairment or autophagic activation, flux assay was performed with bafilomycin A1.Results: Salubrinal suppressed cadmium-induced cell death. Treatment with salubrinal led to increased levels of phosphorylated eIF2α and 78-kDa glucose-regulated protein and a decrease in mRNA level of CCAAT/enhancer-binding protein homologous protein (CHOP) in cells exposed to cadmium. p62 protein and microtubule-associated protein light chain 3B-II (LC3B-II) was increased in cells treated with both cadmium and salubrinal. Flux assays showed that the increase in LC3B-II expression was enhanced by treatment with salubrinal and bafilomycin A1.Conclusions: Salubrinal suppresses cadmium-induced CHOP expression and activates autophagic flux, thereby promoting cell survival.