bluuebunny/crossref_metadata_2025 huggingface dataset:
The burden of BRCA1 and BRCA2 gene mutations among Vietnamese women and their associated factors: A protocol for a systematic review and meta-analysis
Authors: Tran Phuc , Tran Duc , Vu Chi , Phan Quang , Nguyen Anh
Published: July 2022

Background: BReast CAncer gene (BRCA)1 and BRCA2 (also known as BRCA) mutation carriers are now frequently provided genetic counselling. A precise estimation of the prevalence of BRCA gene mutations is essential for the counsellor to provide an appropriate risk prediction. However, the data in Vietnam is ambiguous and unreliable risk factors from individual studies. Hence, the objective of this systematic review with meta-analysis protocol is to provide a method used to synthesize evidence pertaining to the proportion of BRCA mutations among Vietnamese women and their risk factors for cancers.Methods: Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P), a set of criteria for conducting systematic reviews, was followed in developing and reporting this protocol. From the databases' inception till June 2023, a comprehensive search will be undertaken in electronic PubMed and Scopus databases. In two stages, title/abstract screening and full-text screening, two independent authors will assess all retrieved articles for inclusion. This review includes papers providing the relevant results reflecting the prevalence of BRCA gene mutations in Vietnamese women who are at least 18 years old with or without cancer. Predefined selection criteria will be used to establish each publication's eligibility. Using the Newcastle-Ottawa Scale and Cochrane Risk of Bias tools, the quality of included studies will be assessed, and overall evidence quality will be appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Initially, all pertinent data from the included articles will be entered into an online MS Excel spreadsheet for meta-analysis, which will thenbe imported into Rstudio. Meta-analyses using random effects will be used to obtain the pooled percentages. The chi-squared test and I2 parameter will be used to evaluate heterogeneity. Publication bias will be investigated visually using funnel plots for asymmetry and Egger's statistical tests.Conclusions:Based on the prevalence of BRCA muations and its comprehensive and specific risk factors for Vietnamese women, we hope our findings will be able to provide a reference for a future strategy to build an effective treatment plan and manage the risk of subsequent cancer development.Registration: PROSPERO (CRD42022340152; 30 June 2022).
Consistent responses to moisture stress within diverse mountain fynbos communities revealed by multi-year in situ physiological measurements
Authors: Skelton Robert Paul , West Adam Gerrard , Buttner Daniel , Dawson Todd
Published: July 2022

● Understanding climate change impacts on the Cape Floristic Region requires improved knowledge of plant physiological responses to the environment. Prior studies examining physiological responses of fynbos species have consisted of campaign-based measurements, capturing snapshots in time of plant water relations and photosynthesis. We examine conclusions drawn from these studies by tracking in situ physiological responses of three species, representing three dominant growth forms (proteoid, ericoid, restioid), over two years using miniature continuous sap flow technology, in combination with long-term observations of xylem water potentials, gas exchange and assessments of xylem vulnerability to embolism. ● We observed considerable inter-specific variation in the timing and extent of dehydration-induced declines in productivity. Erica monsoniana (a shallow-rooted ericoid) exhibited steep within-season declines in sap flow and water potentials, and pronounced inter-annual variability in total daily sap flux (Js). Protea repens showed steady reductions in Js across both years, despite maintaining less negative water potentials. Cannomois congesta - a shallow-rooted restioid - was least negatively impacted. Following rehydrating rain at the end of summer we compared gas exchange recovery in the representative dry year with the normal year, finding significant seasonal, but not species, effects. Loss of function in the drier year was partially accounted for by loss of stem xylem transport capacity, but only in E. monsoniana and C. congesta. ● Hitherto unseen water-use patterns, including inter-annual variability of gas exchange that were driven by contrasting water uptake properties, reveal that mountain fynbos species use different mechanisms to cope with summer dry periods.
Bayesian and evolutionary temperature dependent genome-scale models display alternative optima due to insufficient constraints
Authors: Pettersen Jakob Peder , Almaas Eivind
Published: July 2022

The metabolism of all living organisms is dependent on temperature, and therefore, having a good method to predict temperature effects at a systems level is of importance. Here, we investigate the properties and robustness of a recently developed computational framework for enzyme and temperature constrained genome-scale models (etcGEM). The approach predicts the temperature dependence of an organism's metabolic network from thermodynamic properties of the metabolic enzymes, markedly expanding the scope and applicability of constraint-based metabolic modelling. We show that the existing Bayesian algorithm for fitting an etcGEM converges under a range of different priors and random seeds, yet the solutions differ both in parameter space and on a phenotypic level. We quantified the phenotypic consequences by studying the impact of different solutions on six metabolic network signature reactions. While two of these reactions showed little phenotype variation between the solutions, the remainder displayed huge variation in flux-carrying capacity. Furthermore, we made software improvements to reduce the running time of the compute-intensive Bayesian algorithm by a factor of 8.5. In addition, we develop an evolutionary algorithm as an alternative to the Bayesian parameter fitting algorithm. Our analysis shows that it also gives decent convergence, but it yields solutions with lower variability.
Clinical Evaluation of Single Posterior Long-segment Fixation for Severe Thoracolumbar Fracture (AO type B)
Authors: Chen Yuanyuan , Lian Xiaofeng , Zhang Tao , Cai Bin , Xu Jianguang
Published: July 2022

Background Acute thoracolumbar fracture is a common spine injury in clinical practice, and AO type B injury is a severe fracture based on the morphology of distraction. Controversy remains in approach selection and few studies focused on this type alone. We evaluated the radiologic and clinical results of 56 cases from our university hospital data bases, and aim to provide some ideas during the surgical planning for this patient cohort.Methods From January 2015 to December 2019, fifty-six patients with AO type B thoracolumbar fractures were treated in spine unit of this tertiary hospital. Patient demographics, surgical details, and follow-up data were reviewed. Clinical outcome were analyzed using the Oswestry Disability Index (ODI), Patient Health Questionnaire-9 (PHQ-9), and Visual Analogue Scale (VAS) system. Results All patients received a single posterior approach and an average of 5.7±2.6 segments was instrumented. 41 patients received consecutive, long-segment pedicle screw fixation, while 15 patients were treated by satellite rod due to pedicle fractures. Average preoperative focal kyphotic angle was 26.2±5.6 degrees, which improved significantly to 13.8±7.2 degrees after the procedure (p<0.05). Similar improvements were found in anterior vertebral height (AVH). At the final follow up, no significant loss of correction angle and AVH was detected compared to postoperation. Pain scores had improved over the postoperative months as well as ODI and PHQ-9 scores. No proximal junction kyphotic change was noted, and none of the patients had any implant failure at the final follow-up.Conclusion AO type B thoracolumbar fractures are severely unstable and associated with complicated injuries. Single posterior consecutive, long-segment instrumentation for AO type B thoracolumbar fracture achieved and maintained satisfactory outcome. For patients with broken pedicles at the fractured level, satellite rod enhancement may be a feasible choice of a supplementary procedure.
A plant regeneration protocol from callus cultures of medicinal and ornamental shrub Rhodomyrtus tomentosa
Authors: Yang Ling , Wu Kunlin , Qiu Shengxiang , Cao Honglin , Deng Shulin
Published: July 2022

Rhodomyrtus tomentosa (Ait.) Hask is a multifunctional shrub of the Myrtaceae, which uniquely combines ornamental, medicinal and health purposes. In this study, for the first time, a regeneration system was established in R. tomentosa. At least three types of calli varied in color, shape and texture were induced from explants of leaf, stem, petal or stamen, among which, the light yellow-green, rigidity and granule calli had great potential for differentiation. Adventitious shoots were steady obtained when the calli were grown on 1/2 MS medium with 6-BA 1 mg/L and NAA 0.1 mg/L at 26 °C and 120 µmol m−2s−1 light intensity. Unexpectedly, two types of adventitious roots initiated from the stems above the cutting sites were observed within 15 d when the regenerated plantlets were transferred to PGR-free 1/2 MS medium. When rooted plantlets were transferred to a sandy soil, over 90% survived within 2 months. The established in vitro regeneration system provided a solution for the germplasm preservation and large-scale clonal propagation of elite lines of R. tomentosa.
Interactive effects of intrinsic capacity and obesity on the risk of chronic kidney disease in older patients with type 2 diabetes mellitus
Authors: Tang Wei-Hua , Yu Teng-Hung , Lee Hui-Lan , Lee Yau-Jiunn
Published: July 2022

Background: Intrinsic capacity (IC) is a novel concept focusing on normal and healthy aging. The effect of IC on the risk of chronic kidney disease (CKD) in older type 2 diabetes mellitus (T2DM) patients has rarely been studied. We investigated whether a decline in IC is associated with the risk of CKD.Methods: This is a cross-sectional study. A total of 2482 older subjects with T2DM managed through a disease care program were enrolled. The five domains of IC, namely locomotion, cognition, vitality, sensory, and psychological capacity were assessed. Based on these domains, the IC composite score was calculated. CKD risk was classified according to the KDIGO 2012 CKD definition. Univariate and multivariate analyses were used to assess the association between IC score and CKD risk. Results: The risk of CKD increased in parallel with IC score (p for trend<0.0001). In multivariate analysis, compared to those with an IC score 0, the odds ratio of having a moderately increased and very high risk stage of CKD was 1.76 (1.31-2.37) times higher for those with an IC score of 2-5. Furthermore, an increased IC score was associated with a higher prevalence of moderate and severe obesity. Moreover, there was a synergistic interaction between IC score and obesity on the risk of CKD (synergy index=1.683; 95% CI: 0.630-3.628), and the proportion of the CKD risk caused by this interaction was 25.6% (attributable proportion of interaction=0.256). Conclusions: Our findings indicate that IC score may be closely related to the risk of CKD. In addition, there may be a synergistic interaction between IC score and obesity, and this synergistic interaction may increase the risk of CKD.
Merging Graphic Organizer in 7Es Model to Enhance Online Learning
Authors: Bucayong Cecilia O.
Published: July 2022

The startling shift in the teaching and learning approach due to the COVID-19 pandemic also redirected the researcher's focus on effective pedagogy. Thus, this study merged the Know, Wonder, and Learn (KWL) graphic organizer and 7Es models to develop a learning material for online classes. The model's cognitive origin and constructivist implications inspired material development. This learning intervention material was implemented online and tested using a pretest-posttest design. Statistical results proved this intervention's effectiveness by improving the students' conceptual understanding of force and motion concepts, t = 3.53, p = 0.001. Further investigation was conducted to determine the variances of performance among students. Results showed that the learning intervention, aside from positively affecting the student's learning gains, implies a more significant impact on the initially low-performing students.
Biomedical term extraction using fuzzy association
Authors: Das Bidyut , Majumder Mukta , Phadikar Santanu , Sekh Arif Ahmed
Published: July 2022

Automatic term extraction from a biomedical text is a well-known problem in the area of natural language processing. It is carried out by employing four kinds of measures: linguistic and rule-based, dictionary-based, statistical, and machine learning. Automatic term extraction indicates whether or not two or more words come together in the text more often than by chance to form a biomedical term that automatically extracted using an automated system. A fuzzy set-theoretic approach is presented in this article that compares with the existing statistical measures. The experimental result shows that the fuzzy-measure offers better precision than the popular statistical-measures for extracting biomedical terms, especially when we have compared more than 60% ranked list of extracted terms.
Early echocardiographic evaluation in children with anorexia nervosa in the emergency department of a tertiary level children's hospital.
Authors: Spina Giulia , Clemente Anna , Roversi Marco , Marchili Maria Rosaria , Silvestri Paola , Mascolo Cristina , Zanna Valeria , Diamanti Antonella , Reale Antonino , Villani Alberto , Raucci Umberto , Ammirati Antonio
Published: July 2022

Purpose Anorexia nervosa (AN) is the most frequent eating disorder (ED), whose cardiac complications may have life-threatening consequences for both the physical and psychological health of affected children. In this study we reported and analysed the echocardiographic anomalies found in pediatric patients diagnosed with AN. Methods We reported the demographic and clinical characteristics of children aged 8 to 18 years, who were diagnosed with AN and underwent a complete cardiological evaluation at the Emergency Department of the Bambino Gesù Children's Hospital, IRCCS, Rome between the 1st January 2021 and the 30th June 2021. Furthermore, we compared the patients according to the presence of pericardial effusion and a BMI (Body Mass Index) cut-off 14.5 kg/m2. Results Forty-nine patients were included in the study. The mean age was 15.1 years. Most patients were female (89.8%). The mean length of hospitalisation was 18 days. The mean BMI at admission was 14.8 kg/m2, with a median weight loss of 9 kg in the last year. Eleven patients (22.4%) presented with cardiovascular signs or symptoms at admission. Most patients had pericardial effusion on heart ultrasound, with a mean thickness of 6 mm (SD ± 4). The LV (left ventricle) thickness over age was significantly higher in patients with pericardial effusion, with a Z score of -2.0 vs -1.4 (p = 0.014). The administration of psychiatric drugs was significantly more frequent in patients with a lower BMI (37.5% vs 12%, p = 0.038). Conclusion Our results suggest that it is reasonable, in patients presenting with AN, to perform complete cardiologic work-up to early identify and manage cardiac complications and their life-threatening consequences. Prospective and multi-center studies are required in order to characterise the cardiovascular abnormalities in patients with AN and to describe the evolution of these abnormalities after weight recovery.
Beneficial effects of tannic acid on comorbid anxiety in cecal ligation and puncture-induced sepsis in rats and potential underlying mechanisms
Authors: Ranjbaran Mina , Kianian Farzaneh , Ashabi Ghorbangol , Lorian Keivan , Azizi Fateme
Published: July 2022

Sepsis-associated encephalopathy (SAE), a neurological dysfunction caused by sepsis, is the most common complication among septic ICU patients. Given the major role of inflammation in the pathophysiology of sepsis-induced anxiety, an extreme and early manifestation of SAE, the present study examined whether tannic acid, as an anti-inflammatory agent, has anxiolytic effects in cecal ligation and puncture (CLP)-induced sepsis.Thirty male Wistar rats were assigned to three groups: 1) Sham; 2) Sepsis and 3) Tannic acid. Sepsis was induced by cecal ligation and puncture model. Animals in the Tannic acid group received tannic acid (20 mg/kg, i.p.), 6, 12 and 18 h after the sepsis induction. Twenty four hours after the sepsis induction, systolic blood pressure and sepsis score were assessed. Anxiety-related behaviors were evaluated using elevated plus-maze and dark-light transition tests. Moreover, inflammatory markers (TNF-α and IL-6), oxidative stress parameters (MDA and SOD) and protein levels (GABAA receptors and IL-1β) were measured in the brain tissue samples. Administration of tannic acid significantly improved sepsis score and hypotension which induced by sepsis. Anxiety-related behaviors showed a significant decrease in the Tannic acid group compared to the Sepsis group. Tannic acid caused a significant decrease in the brain inflammatory markers and a remarkable improvement in the brain oxidative status compared to the septic rats. Tannic acid prevented animals from decreasing GABAA receptors and increasing IL-1β protein levels in the brain tissue samples compared to the Sepsis group. This study indicated that tannic acid mitigated anxiety-related behaviors through decreasing inflammation and oxidative stress and positive modifying IL-1β/GABAA receptors pathway. Therefore, tannic acid shows promise as an efficacious treatment for comorbid anxiety in septic patients.
Myeloid cells protect corneal nerves against sterile injury through negative- feedback regulation of TLR2-IL-6 axis
Authors: Lee Hyun Ju , Kim Hyeon Ji , Ko Jung Hwa , Oh Joo Youn
Published: July 2022

Background: Mounting evidence suggests that the immune system plays detrimental or protective roles in nerve injury and repair. Main body: Herein we report that both CD11bhiLy6Ghi and CD11bhiLy6ChiLy6Glo myeloid cells are required to protect corneal nerves against sterile corneal injury. Selective depletion of CD11bhiLy6Ghi or CD11bhiLy6ChiLy6Glo cells resulted in aggravation of corneal nerve loss, which correlated with IL-6 upregulation. IL-6 neutralization preserved corneal nerves while reducing myeloid cell recruitment. IL-6 replenishment exacerbated corneal nerve damage while recruiting more myeloid cells. In mice lacking Toll-like receptor 2 (TLR2), the levels of IL-6 and myeloid cells were decreased and corneal nerve loss attenuated, as compared to wild-type and TLR4 knockout mice. Corneal stromal fibroblasts produced IL-6 in response to TLR2 stimulation. Conclusion: Collectively, our data suggest that CD11bhiLy6Ghi and CD11bhiLy6ChiLy6Glo myeloid cells confer corneal nerve protection under injury by creating a negative-feedback loop to suppress the upstream TLR2-IL-6 axis that drives corneal nerve loss.
Effectiveness of pharmacological thrombolysis on clinical outcomes in high-risk pulmonary embolism patients with extracorporeal membrane oxygenation: a nationwide inpatient database study
Authors: Nishimoto Yuji , Ohbe Hiroyuki , Matsui Hiroki , Nakajima Mikio , Sasabuchi Yusuke , Watanabe Tetsuya , Yamada Takahisa , Fukunami Masatake , Yasunaga Hideo
Published: July 2022

Background
Current guidelines recommend systemic thrombolysis as the first-line reperfusion treatment for patients with high-risk pulmonary embolism (PE) who present cardiogenic shock but do not require extracorporeal membrane oxygenation (ECMO). However, little is known about the optimal reperfusion treatment in high-risk PE patients requiring ECMO. We aimed to evaluate whether pharmacological thrombolysis improved high-risk PE patients’ outcomes who received ECMO.
Methods
This was a retrospective cohort study using the Japanese Diagnosis Procedure Combination inpatient database from April 2010 to March 2021. We identified patients who were diagnosed with PE and received ECMO on the day of admission. Patients who received pharmacological thrombolysis on the same day of ECMO initiation were defined as the thrombolysis group, and the remaining patients as the control group. The primary outcome was in-hospital mortality and secondary outcomes were favourable neurological outcomes, length of the hospital stay, length of the ECMO, total hospitalization cost, major bleeding, and blood transfusion volume. Propensity-score inverse probability of treatment weighting (IPTW) was performed to compare the outcomes between the groups.
Results
Of 1,248 eligible patients, 391 (31%) received pharmacological thrombolysis on the same day of ECMO initiation. Among the unweighted cohort, patients in the thrombolysis group were less likely to have poor consciousness at admission, out-of-hospital cardiac arrest, and left heart catheterization. After IPTW, the patient characteristics were well-balanced between the two groups The crude in-hospital mortality was 52% in the thrombolysis group and 59% in the control group. After IPTW, in-hospital mortality did not differ significantly between the two groups (risk difference: -2.1%, 95% confidence interval: -8.6–4.3%). There were also no significant differences in the secondary outcomes including the favourable neurological outcomes, length of hospital stay, length of ECMO, total hospitalization cost, major bleeding, and blood transfusion volume.
Conclusions
Pharmacological thrombolysis was not associated with a reduced in-hospital mortality or increased major bleeding in the high-risk PE patients receiving ECMO.
‘Something that facilitates our work…rather than a hindrance’: Clinical pharmacist perspectives on the use of data analytics to support polypharmacy medication reviews in primary care.
Authors: Ruth Hurley , Jury Francine , Tjeerd P. van Staa , Palin Victoria , Christopher J. Armitage
Published: July 2022

Background
Polypharmacy and overprescribing is a growing concern due to increased risk of drug interaction and inefficient use of resources. Historical patient records offer a wealth of knowledge that could inform safer prescribing and deprescribing, but it is unclear how these complex data should be summarised and displayed to clinicians. The current study evaluated the perspectives of clinical pharmacists (CPs), a newly expanding workforce of primary care medication specialists, on ways that novel big data analytics could be used to improve health outcomes for frail and elderly (> 65yrs) patients.
Methods
Primary care clinical pharmacists (n = 14) took part in an exploratory participative design workshop to discuss examples and uses of novel analytics (including risk of negative outcomes for frail and elderly patients following treatment with a variety of medication combinations). Participant contributions (verbal and textual) were analysed using the framework method of exploratory content analysis.
Results
Overarching themes of data uses, reservations and digital tools acceptance factors were identified. Uses of polypharmacy analytics valued by CPs included the clinical effects of drug: drug interactions and patient risk scores to highlight patients at increased risk of harm from medication combinations (including cumulative risks). CPs were also positive about the creation of a dedicated online community of practice to enable wider peer support. CP’s current digital systems do not adequately facilitate patient medication reviews and contribute to cognitive overload. Experiencing these existing barriers mean that CPs’ acceptance of digital analytics tools is heavily contingent on ease of use, clear targeting and ability to support clinicians’ understanding and confidence in the strengths, limitations and validity of the analytics in the patient care context.
Conclusions
CPs would benefit from bespoke digital systems designed to meet the needs of their role. Analytics from patient records could help address a concerning deficit in wider knowledge of the real world clinical effects of polypharmacy medication interactions and help clinicians prioritise medication reviews. Based on the user acceptance themes identified, five criteria are suggested to inform user focused development of analytics tools for primary healthcare.
Cohort Study Assessing the Predictive Value of a Research Year vs Additional Degree in Dermatology
Authors: Fritsche Madelaine , King Tonya , Miller Jeffrey , Lam Charlene
Published: July 2022

Taking a gap year to obtain an additional degree or for research is becoming increasingly popular among medical students pursuing dermatology to bolster residency application competitiveness. The purpose of this study was to determine whether doing so influences future academic achievement and career trajectory. A list of dermatologists who achieved board certification in 2010 was obtained from the American Board of Dermatology. Information regarding additional post-graduate degrees, research years, fellowship specialization, practice setting, publication number, and H-index were obtained using publicly available data. Additional degrees were associated with higher research productivity, higher H-index, and practicing at teaching hospitals, while taking a research year was only associated with a higher H-index. This data can be used to further inform medical students wishing to achieve high levels of research productivity and careers at teaching institutions and residency programs wishing to recruit such applicants.
Comparing Pre-Operative Versus Post-Operative Single and Fractionated Stereotactic Radiotherapy for Patients with Resectable Brain Metastases
Authors: Perlow Haley K. , Ho Cindy , Matsui Jennifer K. , Prasad Rahul N. , Klamer Brett G. , Wang Joshua , Damante Mark , Upadhyay Rituraj , Thomas Evan , Blakaj Dukagjin M. , Beyer Sasha , Lonser Russell , Hardesty Douglas , Raval Raju R. , Prabhu Roshan , Elder James B. , Palmer Joshua D.
Published: July 2022

BackgroundThe standard treatment for patients with large brain metastases and limited intracranial disease is surgical resection and post-operative stereotactic radiosurgery (SRS). However, post-operative SRS still has elevated rates of local failure (LF) and is complicated by radiation necrosis (RN), and meningeal disease (MD). Pre-operative SRS may reduce the risk of RN and MD, while fractionated therapy may improve local control through delivering a higher biological effective dose. We hypothesize that pre-operative fractionated stereotactic radiation therapy (FSRT) will have less toxicity compared to patients who receive post-operative SRS or FSRT. MethodsA multi-institutional analysis was conducted and included patients who had surgical resection and stereotactic radiation therapy to treat at least one brain metastasis. Pertinent demographic, clinical, radiation, surgical, and follow up data were collected for each patient. The primary outcome was a composite endpoint defined inclusive of events of 1) LF, 2) MD, and/or 3) Grade 2 or higher (symptomatic) RN. Results279 patients were eligible for analysis. The median follow-up time was 9 months. 87% of patients received fractionated treatment. 29% of patients received pre-operative treatment. The composite endpoint incidences for post-operative SRS (n = 10), post-operative FSRT (n = 189), pre-operative SRS (n = 27), and pre-operative FSRT (n = 53) were 0%, 17%, 15%, and 7.5%, respectively. ConclusionsIn our study, the composite endpoint of 7.5% for pre-operative FSRT compares favorably to our post-operative FSRT rate of 17%. Pre-operative FSRT was observed to have low rates of LF, MD, and RN. Prospective validation is needed.
MxA for differentiating viral and bacterial infections in adults – a prospective, exploratory study
Authors: Metz Matthäus , Gualdoni Guido A. , Winkler Heide-Maria , Warenits Alexandra-Maria , Stöckl Johannes , Burgmann Heinz , Winkler Stefan , Oesterreicher Zoe Anne
Published: July 2022

Purpose
Inappropriate antibiotic prescription in patients with viral infections contributes to the surge of antibiotic resistance. Viral infections induce the expression of the antiviral protein MxA in monocytes, which is a promising biomarker to differentiate between viral and bacterial diseases. In this prospective, exploratory study, we aimed to determine the diagnostic value of monocyte MxA expression in adults with viral, bacterial or co-infections.
Methods
We measured monocyte MxA expression using flow cytometry in a cohort of 61 adults with various viral, bacterial and co-infections including patients receiving immunosuppressive therapy.
Results
Monocyte MxA expression in virus-infected patients was significantly higher compared to bacterial infections (83.3 [66.8, 109.4] vs. 33.8 [29.3, 47.8] mean fluorescence intensity [MFI]; p < 0.0001) but not co-infections (53.1 [33.9, 88.9] MFI). At a threshold of 62.2 MFI, the area under the ROC curve (AUC) to differentiate between viral and bacterial infections was 0.9, with a sensitivity and specificity of 92.3% and 84.6%, respectively. Immunosuppressive therapy did not affect monocyte MxA expression in virus-infected patients.
Conclusion
Our findings corroborate the diagnostic performance of MxA in differentiating viral and bacterial infections but also point to an important caveat of MxA in viral-bacterial co-infections. This study extends previous reports and indicates that MxA is also a useful biomarker in immunocompromised patients.
Thymic microfold and endocrine cells regulate thymus homeostasis and self-tolerance
Authors: Abramson Jakub , Givony Tal , Castillo Diana del , Nevo Shir , Leshkowitz Dena , Kadouri Noam , Dassa Bareket , Ben-Nun Osher , Gruper Yael , Gome Tom , Dobeš Jan , Ben-Dor Shifra , Kedmi Merav , Keren-Shaul Hadas , Haffner-Krausz Rebecca , Porat Ziv , Lo David , Goldfarb Yael
Published: July 2022

Thymic epithelial cells (TEC) play an indispensable role in the development and selection of immunocompetent, yet self-tolerant T cells. To provide further insights into TEC functional and developmental diversity, we utilized multiome analysis, which revealed a detailed atlas of the TEC compartment based on their transcriptional states and chromatin landscapes. The analysis also highlighted numerous unconventional TEC subsets, which shared striking similarities with functionally well-defined parenchymal populations, including endocrine cells, microfold cells or myocytes. Moreover, our fate mapping experiments revealed that most of these rare TEC “parenchymal analogues” differentiated from Csnb+ MHCIIhi mTEC precursors, with varying impacts of Aire on their development. By further focusing on the endocrine- and the microfold-TEC populations, we found that both subsets play different and non-redundant functional roles and require different transcription factors for their terminal differentiation. Specifically, while the endocrine-TEC required Insm1 for their development, and were critical for induction of self-tolerance to various endocrine tissues, the microfold-TEC required Spib for their development, and were essential for the generation of thymic IgA+ plasma cells. Collectively, our study reveals that MHCIIhi mTEC have the potential to differentiate into various types of molecularly functionally defined cells, which not only contribute to the induction of central tolerance, but also regulate homeostasis of other thymus-resident populations.
Frequency and reasons of bypassing lower health care facilities in Lira district- Northern Uganda
Authors: Okori Samuel , Besigye Innocent Kabahena , Namatovu Jane Francis
Published: July 2022

BackgroundTo improve access to health care for all who need, the government of Uganda increased the number of lower level health facilities across the country. However, many patients prefer to bypass the lower level facilities in favour of the high level facilities. Bypass of health care is the situation that patients seek care at a high level facility farther away than the nearby lower facility. Lira district has 42 lower health facilities and one referral hospital that received all referrals from the region. The ratio between patients with and without referral and the reason for bypass are unknown.The study aims to get insight into the frequency of and the reasons why patients visit Lira hospital thereby bypassing lower health facilities.Methods We performed a one-month descriptive cross-sectional study among patients visiting the outpatient department of Lira hospital after written informed consent: qualitatively with four focus group discussions (FGD) of ten participants each and quantitatively using validated questionnaires. The questionnaire included socio-demographic questions, their complaints and the reason(s) to visit the hospital, In the FGD the reasons of bypass were discussed. The topic list includes the patients’ expectations and experience with the lower facility. Thematic analysis of transcripts was performed. Codes and categories were developed and interrogated following an iterative process. The results of the questionnaires were entered in Epidata 3.1 and analysed with SPSS18. Results 387 out of 481(80.5%) respondents recruited by systematic random sampling, bypassed lower health care facilities and were associated with marital status, distance travelled of >10 km from the home town to the hospital and tertiary education. Lack of trust in health care providers, lack of medicines and diagnostic equipment and poor quality of health services at lower health facilities were the main reasons to bypass.ConclusionImprovement of the lack of trust in health care providers and of the poor quality of health services in the lower health care facilities is essential to reduce the bypass problem and to realize health care for all who need within 5 km of the place where they live.
Expression of hormone receptors is associated with specific immunological profiles of the breast cancer microenvironment
Authors: Hanamura Toru , Kitano Shigehisa , Kagamu Hiroshi , Yamashita Makiko , Terao Mayako , Okamura Takuho , Kumaki Nobue , Hozumi Katsuto , Iwamoto Takayuki , Honda Chikako , Kurozumi Sasagu , Niikura Naoki
Published: July 2022

Background
Elucidating the unique immunoregulatory mechanisms in breast cancer microenvironment may help develop new therapeutic strategies. Some studies have suggested that hormone receptors also have immune regulatory functions, but their mechanisms are not fully understood. In this study, we have comprehensively analyzed the relationship between the expressions of estrogen (ER), progesterone (PgR), and androgen receptors (AR), and the immunological profile in breast cancer.
Methods
Using publicly available gene expression profile datasets, METABRIC and SCAN-B, the associations between the expressions of hormone receptors and the immune cell compositions in breast cancer tissue, estimated by CIBERSORTx algorithm, were analyzed. We histologically evaluated tumor infiltrating lymphocytes (hTIL), PD-L1 (hPD-L1) expression, and the infiltration of 11 types of immune cells by flow cytometry (FCM) for 45 breast cancer tissue samples. The relationships between them and the expressions of ER, PgR, and AR of tumor tissues, evaluated immunohistochemically, were analyzed.
Results
Expressions of ESR1, PGR, and AR were negatively correlated with overall immune composition. Expressions of ER and AR, but not that of PgR, were inversely associated with hTIL and hPD-L1 expression. FCM analysis showed that the expressions of ER and AR, but not that of PgR, were associated with decreased total leukocyte infiltration. Both CIBERSORTx and FCM analysis showed that ER expression was associated with reduced infiltration of macrophages and CD4 + T cells, and that of AR with reduced macrophage infiltration.
Conclusion
Hormone receptor expression correlates with specific immunological profiles in the breast cancer microenvironment both at the gene and protein expression levels.
WITHDRAWN: Implementation of soft computing techniques in forecasting compressive strength and permeability of pervious concrete blended with GGBS
Authors: kumar Sudhir
Published: July 2022

Due to the associated economic, environmental, and performance advantages, using natural pozzolans as a substitute for cement is regarded as a standard guidelines in the construction sector. In order to achieve, it is beneficial to use GGBS in the production of concrete, which was identified as the most effective supplementary cementitious material in resisting environmental threats. According to the literature review, GGBS concrete is more impermeable than PPC concrete (concrete with fly ash) or pure OPC concrete. However, it has the potential to increase the strength of concrete, which is a significant disadvantage of pervious concrete. Hence this study investigates the variation of strength and permeability of pervious concrete in order to obtain the optimal proportion of GGBS inclusion in concrete production. Along with that, the research uses artificial neural networks to estimate the compressive strength, water permeability, and porosity of pervious concrete blended with several proportions of GGBS. The study results showed that the inclusion of larger aggregate sizes significantly increased the strength but the effect of adding GGBS in partial replacement of cement could not. As a result, GGBS might replace some of the cement in concrete without significantly altering its mechanical qualities. Further, the developed ANN models outperformed the conventional MLR model and it can act as a useful alternative to analytical models for predicting strength and permeability values in pervious concrete.
Disordered network structure and function in dystonia: Pathological connectivity vs. adaptive responses
Authors: Vo An , Nguyen Nha , Fujita Koji , Schindlbeck Katharina A. , Rommal Andrea , Bressman Susan B. , Niethammer Martin , Eidelberg David
Published: July 2022

Primary dystonia is thought to emerge through abnormal functional relationships between basal ganglia and cerebellar motor circuits. These interactions may differ across disease subtypes and provide a novel biomarker for diagnosis and treatment. Using a network mapping algorithm based on resting-state functional MRI (rs-fMRI), a method that is readily implemented on conventional MRI scanners, we identified similar disease topographies in hereditary dystonia associated with the DYT1 or DYT6 mutations and in sporadic patients lacking these mutations. Both networks were characterized by contributions from the basal ganglia, cerebellum, thalamus, sensorimotor areas, as well as cortical association regions. Expression levels for the two networks were elevated in hereditary and sporadic dystonia, and in non-manifesting carriers of dystonia mutations. Nonetheless, the distribution of abnormal functional connections differed across groups, as did metrics of network organization and efficiency in key modules. Despite these differences, network expression correlated with dystonia motor ratings, significantly improving the accuracy of predictions based on thalamocortical tract integrity obtained with diffusion tensor MRI (DTI). Thus, in addition to providing unique information regarding the anatomy of abnormal brain circuits, rs-fMRI functional networks may provide a widely accessible method to help in the objective evaluation of new treatments for this disorder.
Assessment of Workplace Discrimination against Individuals with Autism Spectrum Disorder (ASD)
Authors: Cooper Ashley-Ann , Mujtaba Bahaudin G.
Published: July 2022

Autism, also known as autism spectrum disorder (ASD), is a genetic / neurological condition, impacting about 2% of young children in the United States, which causes certain challenges in one’s communication, learning, socialization, and even stress management coping skills. Children with autism tend to demonstrate the presence of constrained, confined, or repetitive patterns of behaviors, activities, and interests. People with ASD learn differently than others, and their attention can be gained and maintained through repetition and routine. Individuals who have a mild or extreme form of ASD often experience more difficulty adjusting to changes in the work environment and society in general. Consequently, even though many individuals with ASD can perform their jobs successfully, they are often discriminated against and not afforded reasonable accommodations for them to gain and maintain steady employment. In this paper, we provide an overview of ASD to create awareness, along with recommendations so that more autistic adults can be employed in the workplace. Employers and manager should know that autism spectrum disorder involves a range of symptoms that cause difficulty communicating, such as flat affect (or diminished emotional expression), poor eye contact, and difficulty understanding nonverbal cues. These symptoms make it difficult to find and maintain employment, and people with autism regularly deal with discrimination and prejudice, both in and out of the workplace. Employers show less interest in hiring neurodivergent employees even if they are qualified and capable of performing the required work, and many do not provide sufficient accommodations to those that they do hire.
Analyses Of Demographic Changes, Labor Market Trends, And Challenges In Albania
Authors: Hoxhaj Meleq , Muharremi Oltiana , Nushi Erkinela
Published: July 2022

Albania has seen significant political and socioeconomic changes in the last 30 years, owing mostly to its participation in democratization and the transition to an open market economy. The purpose of this study is to investigate demographic dynamics in Albania to better understand the country’s current population situation and the near future projection for the period 2025-2031. The relevance of analyzing this topic is to better understand actual demographic changes in Albania and to have a detailed projection of the situation in the near future. The article begins by analyzing important demographic changes and their effects on a country’s economy, specifically the labor market. Furthermore, we demonstrated the trajectory of demographic changes in Albania for various main demographic parameters such as births, deaths, natural increase, marriage, divorces, and numbers of foreigners in Albania, using data from the Institute of Statistics in Albania (INSTAT). The following are presented population projections for ten coming years. The changes that have happened in the labor market are presented here to better comprehend the effects and repercussions of these demographic changes. The descriptive analysis of the main demographic indicators shows that the population is rapidly declining, posing a serious problem with numerous consequences, particularly in the labor market, necessitating the implementation of immediate policies to mitigate this phenomenon and its consequences. It makes a technical contribution by employing an approach that allows for fresh estimations of the amount of internal migration, demographic changes, and labor market issues in Albania. The results of the research can be useful for policymakers to initiate social, fiscal, and incentive policies to mitigate the decline and aging of the population.
The History, Culture and Architecture as a Potential of Urban Tourism Development: Evidence from Armenia
Authors: Tovmasyan Gayane , Gevorgyan Marine
Published: July 2022

The article presents a brief history of the founding of the capital Yerevan, some examples of the history and architecture of Armenia, which has a tourist attraction. Yerevan is rich in historical, cultural and scientific monuments, which together with hotels, restaurants, clubs, and various places of entertainment are tourist resources․ The paper is dedicated to urban tourism development issues. The main purpose of the research is to explore urban tourism development opportunities and main challenges in Yerevan, the capital of Republic of Armenia. Investigation of the topic is carried out in the following logical sequence: presentation of historical-cultural monuments, museums of scientific, and cultural interest visited by tourists, the main touristic assets, the main social-economic indicators and tourism infrastructures of Yerevan are discussed, then the main obstacles are analyzed. Yerevan is 2803 years old; it is rich with cultural-historical monuments. Yerevan has all the opportunities for historical, cultural, religious, gastronomic, entertainment, adventure, educational, medical, festival, and MICE tourism development. The methodological tools of the research methods are historical description, historical analysis, statistical methods, also SWOT analysis. The object of the research is Yerevan city and the subject of the research is tourism development issues in Yerevan. The results of the analysis shows that correlation coefficient is high in Yerevan between volume of tourism services and GDP, volume of tourism services and GDP per capita, volume of tourism services and employment. Also, SWOT analysis reveals the main strengths, weaknesses, opportunities and threats of tourism development in Yerevan. The research theoretically proves and empirically confirms that tourism has a significance role for sustainable development of the city. Based on the main analysis, some recommendations are carried out towards creating sustainable tourism development plans, improving marketing, statistical recording, increasing touristic information in the city, developing infrastructures, investing in more sustainable and smart solutions in city development. The main sustainable solutions should be connected with the transport system, water and waste recycling mechanisms, energy efficiency, construction, increasing green areas, and-so-on. The results of the research can be useful for municipalities for elaborating urban tourism development plans which will lead to sustainable development.
Some Economic Issues concerning the Loss of the Special Status Relationship between the United States and Hong Kong
Authors: Gentle Paul
Published: July 2022

The demonstrations in 2019, 2020 and thereabouts for the preservation of certain civil rights in Hong Kong, led to some suppression by the Chinese National central government. As a result, some of the special trade advantages between Hong Kong and the U.S. were lost. The economics and cultural special traits helped Hong Kong thrive. Having a judicial system separate from that of Mainland China, allowed for a more commerce producing judiciary. A key requirement for Hong Kong to be treated differently than Mainland China was for Hong Kong to have some independent autonomy, sufficient for the U.S. to see Hong Kong as a separate area politically from Mainland China. In July 2020, the U.S. made the formal decision to take away Hong Kong’s special status, because a sufficiently independent Hong Kong no longer exists. This article examines the history of this phenomena and the results of having that special trade policy changed. Data from recent years show how the economy with Hong Kong and trade with Hong Kong has changed. Unfortunately, some cultural ties and exchanges between the United States and Hong Kong have also been curtailed. These changes regarding cultural ties are beyond the scope of this article. In regard to Chinese support for the United States, Ukraine and NATO, Ukraine in the war between Ukraine and Russia, this should be pointed out. China should support Ukraine, since it is in China’s best interest, and it is the right action to take.