bluuebunny/crossref_metadata_2025 huggingface dataset:
Global Health in Undergraduate Education: Knowledge, Attitude, and Practice of Sudanese Medical Students towards Global Health Education: a cross-sectional study
Authors: Malik Sawazen , Alkoronky Asi , Elmahi Mugahid , Alsafi Safaa , Shehada Fares , Rahma Rawasi , Alam Elhuda Daffalla
Published: April 2023

Introduction

Globalization and other relevant phenomena such as healthcare workforce, ageing of the population, brain drain etc. all necessitate medical curricula to transcend national medicine and encompass a more global approach. This is especially true in the context of developing countries which currently act as passive recipients of ongoing global decisions, health inequities or pandemics. The aim of this research was to study the Knowledge, Attitude, and Practice of Sudanese medical students towards global health education and the impact of extra-curricular activities on their knowledge and attitudes.

Methods

This was a descriptive cross-sectional institutional based study. The study was conducted in five Sudanese Universities and participants were selected using systematic random sampling. An online-based, self-administered questionnaire was used, samples were collected between November 2019 until April 2020 and data was analyzed using SPSS version 25.

Results

1176 medical students were involved. The study revealed a poor level of knowledge among 72.4%, and only 2.3% of respondents revealed a good level of knowledge. Mean knowledge scores between Universities slightly vary and have shown positive correlation according to the grade of the medical student. Regarding attitude, the results demonstrated the high level of interest of medical students in global health, their agreement in including global health in their official medical education curriculum (64.8%) and their consideration of including global health as part of their future career (46.8%).

Conclusion

The study concluded that there is a knowledge gap among Sudanese medical students regarding global health education, although students showed good attitudes and willingness to include global health in their official curriculum.

Recommendations

Global health education should be implemented in the official curriculums of Sudanese Universities, and Universities should do global partnerships and increase the learning and teaching opportunities in this interesting field.
The P2X3 receptor antagonist filapixant in patients with refractory chronic cough: a randomized controlled trial
Authors: Friedrich Christian , Francke Klaus , Birring Surinder S. , van den Berg Jan Willem K. , Marsden Paul A. , McGarvey Lorcan , Turner Alice M. , Wielders Pascal , Gashaw Isabella , Klein Stefan , Morice Alyn H.
Published: April 2023

Background

P2X3 receptor antagonists seem to have a promising potential for treating patients with refractory chronic cough. In this double-blind, randomized, placebo-controlled study, we investigated the efficacy, safety, and tolerability of the novel selective P2X3 receptor antagonist filapixant (BAY1902607) in patients with refractory chronic cough.

Methods

Following a crossover design, 23 patients with refractory chronic cough (age: 60.4 ± 9.1 years) received ascending doses of filapixant in one period (20, 80, 150, and 250 mg, twice daily, 4-days-on/3-days-off) and placebo in the other. The primary efficacy endpoint was the 24-h cough frequency on Day 4 of each dosing step. Further, subjective cough severity and health-related quality of life were assessed.

Results

Filapixant at doses ≥ 80 mg significantly reduced cough frequency and severity and improved cough health-related quality of life. Reductions in 24-h cough frequency over placebo ranged from 17% (80 mg dose) to 37% (250 mg dose), reductions over baseline from 23% (80 mg) to 41% (250 mg) (placebo: 6%). Reductions in cough severity ratings on a 100-mm visual analog scale ranged from 8 mm (80 mg) to 21 mm (250 mg). No serious or severe adverse events or adverse events leading to discontinuation of treatment were reported. Taste-related adverse events occurred in 4%, 13%, 43%, and 57% of patients treated with filapixant 20, 80, 150, and 250 mg, respectively, and in 12% treated with placebo.

Conclusions

Filapixant proved to be efficacious, safe, and—apart from the occurrence of taste disturbances, especially at higher dosages—well tolerated during the short therapeutic intervention.

Clinical trial registrationEudraCT, eudract.ema.europa.eu, 2018-000129-29; ClinicalTrials.gov, NCT03535168
Development of an antibody-ligand fusion protein scFvCD16A-sc4-1BBL in Komagataella phaffii with stimulatory activity for Natural Killer cells
Authors: Li Yangyang , Xie Siqi , Chen Minhua , Li Hao , Wang Yehai , Fan Yan , An Kang , Wu Yu , Xiao Weihua
Published: April 2023

Background

Natural killer (NK) cell-based immunotherapies have demonstrated substantial potential for the treatment of hematologic malignancies. However, its application is limited due to the difficulty in the production of a large number of NK cells in vitro and the insufficient therapeutic efficacy against solid tumors in vivo. Engineered antibodies or fusion proteins targeting activating receptors and costimulatory molecules of NK cells have been developed to encounter these problems. They are mostly produced in mammalian cells with high cost and long processing times. Yeast systems, such as Komagataella phaffii, present a convenient manipulation of microbial systems with the key advantages of improved folding machinery and low cost.

Results

In this study, we designed an antibody fusion protein scFvCD16A-sc4-1BBL, composed of the single chain variant fragment (scFv) of anti-CD16A antibody and the three extracellular domains (ECDs) of human 4-1BBL in a single-chain format (sc) with the GS linker, aiming to boost NK cell proliferation and activation. This protein complex was produced in the K. phaffii X33 system and purified by affinity chromatography and size exclusion chromatography. The scFvCD16A-sc4-1BBL complex showed comparable binding abilities to its two targets human CD16A and 4-1BB as its two parental moieties (scFvCD16A and monomer ECD (mn)4-1BBL). scFvCD16A-sc4-1BBL specifically stimulated the expansion of peripheral blood mononuclear cell (PBMC)-derived NK cells in vitro. Furthermore, in the ovarian cancer xenograft mouse model, adoptive NK cell infusion combined with intraperitoneal (i.p) injection of scFvCD16A-sc4-1BBL further reduced the tumor burden and prolonged the survival time of mice.

Conclusion

Our studies demonstrate the feasibility of the expression of the antibody fusion protein scFvCD16A-sc4-1BBL in K. phaffii with favourable properties. scFvCD16A-sc4-1BBL stimulates PBMC-derived NK cell expansion in vitro and improves the antitumor activity of adoptively transferred NK cells in a murine model of ovarian cancer and may serve as a synergistic drug for NK immunotherapy in future research and applications.
MiR-3180 inhibits hepatocellular carcinoma growth and metastasis by targeting lipid synthesis and uptake
Authors: Hong Jie , Liu Jie , Zhang Yanan , Ding Lihua , Ye Qinong
Published: April 2023

Purpose

Reprogrammed lipid metabolism is a hallmark of cancer that provides energy, materials, and signaling molecules for rapid cancer cell growth. Cancer cells acquire fatty acids primarily through de novo synthesis and uptake. Targeting altered lipid metabolic pathways is a promising anticancer strategy. However, their regulators have not been fully investigated, especially those targeting both synthesis and uptake.

Methods

Immunohistochemistry was performed on samples from patients with hepatocellular carcinoma (HCC) to establish the correlation between miR-3180, stearoyl-CoA desaturase-1 (SCD1), and CD36 expression, quantified via qRT-PCR and western blotting. The correlation was analyzed using a luciferase reporter assay. Cell proliferation, migration, and invasion were analyzed using CCK-8, wound healing, and transwell assays, respectively. Oil Red O staining and flow cytometry were used to detect lipids. Triglycerides and cholesterol levels were analyzed using a reagent test kit. CY3-labeled oleic acid transport was analyzed using an oleic acid transport assay. Tumor growth and metastasis were detected in vivo in a xenograft mouse model.

Results

MiR-3180 suppressed de novo fatty acid synthesis and uptake by targeting the key lipid synthesis enzyme SCD1 and key lipid transporter CD36. MiR-3180 suppressed HCC cell proliferation, migration, and invasion in an SCD1- and CD36-dependent manner in vitro. The mouse model demonstrated that miR-3180 inhibits HCC tumor growth and metastasis by inhibiting SCD1- and CD36-mediated de novo fatty acid synthesis and uptake. MiR-3180 expression was downregulated in HCC tissues and negatively correlated with SCD1 and CD36 levels. Patients with high miR-3180 levels showed better prognosis than those with low levels.

Conclusions

Our investigation indicates that miR-3180 is a critical regulator involved in de novo fatty acid synthesis and uptake, which inhibits HCC tumor growth and metastasis by suppressing SCD1 and CD36. Therefore, miR-3180 is a novel therapeutic target and prognostic indicator for patients with HCC.
A rare metastatic mesenteric malignant PEComa with TSC2 mutation treated with palliative surgical resection and nab-sirolimus: a case report
Authors: Meredith Luke , Chao Timothy , Nevler Avinoam , Basu Mallick Atrayee , Singla Rajan K. , McCue Peter A. , Bowne Wilbur B. , Jiang Wei
Published: April 2023

Background

Malignant perivascular epithelioid cell tumors (PEComas) are exceedingly rare malignant mesenchymal neoplasms with characteristic morphological and immunohistochemical (IHC) patterns. However, some malignant PEComas are poorly differentiated with atypical histopathological features, making a definitive diagnosis difficult. PEComas are most commonly found in females and often show either TSC1 or TSC2 alterations, which result in the activation of the mTOR pathway, or TFE3 fusions. Given these molecular characteristics, mTOR inhibitors have recently been approved by the FDA in the treatment of malignant PEComas, particularly in those with TSC1/2 alterations. Therefore, molecular analyses may be helpful for both the diagnostic workup of and predicting response to mTOR inhibitors in cases of malignant PEComas.

Case presentation

Here, we report a case of an aggressive, 23 cm mesenteric malignant PEComa with multiple peritoneal metastases in a young male patient. Pathological examination of the initial biopsy showed a malignant epithelioid neoplasm with high-grade morphology and atypical immunoprofile, which precluded a definitive diagnosis. Because of the patient’s excessive transfusion requirements due to intra-tumoral hemorrhage, a palliative R2 resection was performed. Histopathological examination of the tumor revealed focal immunoreactivity for Melan-A, HMB-45, desmin, and CD117. Although a diagnosis of malignant PEComa was favored, other entities such as epithelioid gastrointestinal stromal tumor (GIST) or melanoma could not be definitively ruled out. Given the favored diagnosis, the patient was started on sirolimus, an mTOR inhibitor, rather than chemotherapy. Molecular analyses were performed and the tumor was found to harbor mutations in TP53 and TSC2, supporting a definitive diagnosis of malignant PEComa. The patient was then switched to nab-sirolimus, with initial stabilization of the disease.

Conclusions

This report details a multidisciplinary approach for the diagnosis and management of a highly aggressive, metastatic malignant PEComa in a young male patient. The basis for the treatment of malignant PEComas with the recently FDA-approved mTOR inhibitor, nab-sirolimus, is also reviewed. In summary, this case highlights the importance of molecular analysis, particularly TSC1/2 alterations, for both the definitive diagnosis of malignant PEComas and predicting their response to nab-sirolimus.
Low-grade papillary Schneiderian carcinoma with TP53 mutation: a case report and review of the literature
Authors: Yuzawa Sayaka , Michizuka Tomohiko , Kakisaka Rika , Ono Yusuke , Hayashi Manami , Takahara Miki , Katada Akihiro , Mizukami Yusuke , Tanino Mishie
Published: April 2023

Background

Low-grade papillary Schneiderian carcinoma (LGPSC) is a relatively new entity of the sinonasal tract and is characterized by a bland morphology simulating sinonasal papilloma, invasive growth pattern with pushing borders, and aggressive clinical behavior with multiple recurrences and metastatic potential. Recently, DEK::AFF2 fusions were identified in LGPSC. However, some LPGSCs lack DEK::AFF2 fusion, and the molecular features of these tumors have not been clarified.

Case presentation

A 69-year-old man presented with a discharge of pus from his left cheek. Computed tomography revealed a mass involving the left maxillary sinus, ethmoid sinus, and nasal cavity with the destruction of the orbital wall. The biopsy specimens showed that the tumor had a predominantly exophytic, papillary growth and did not have an apparent stromal invasion. The tumor was composed of multilayered epithelium that showed bland morphology with a round to polygonal shape, abundant eosinophilic cytoplasm, and uniform nuclei. Dense neutrophilic infiltrates were focally present. Immunohistochemically, CK5/6 was strongly and diffusely positive, and p16 was negative. p63 was mainly positive in the basal layer, and EMA was predominantly expressed in the outermost cell layer. DNA-based targeted sequencing showed TP53 R175H mutation, whereas neither EGFR nor KRAS mutation was identified. Reverse transcription polymerase chain reaction and fluorescence in situ hybridization revealed no DEK::AFF2 fusion.

Conclusions

We describe the first case of TP53-mutant LGPSC and review the literature. LGPSC is a genetically heterogeneous entity, and the recognition of this rare entity and comprehensive assessment of clinicopathological and molecular findings are crucial for the correct pathological diagnosis and clinical management.
Evaluating health information provided to kratom consumers by good manufacturing practice-qualified vendors
Authors: Hill Katherine , Gibson Stephen , Grundmann Oliver , Smith Kirsten E. , Ballard Jonathan , Stanciu Corneliu N.
Published: April 2023

Background

“Kratom” commonly refers to the botanical Mitragyna speciosa, native to Southeast Asia, which is increasingly used globally for its unique pharmacological effects. Motives for using the whole plant material or kratom-derived products include self-management of pain, mental health disorders, symptoms related to substance use disorders, and/or to increase energy. In the United States, kratom products have varying alkaloid content, potencies, and marketing profiles. There is little regulatory oversight over kratom, as it is currently not approved as a dietary supplement by the Food and Drug Administration. This results in substantial variability in labeling of kratom products and the product information provided to consumers.

Methods

In January 2023, we evaluated the American Kratom Association’s Good Manufacturing Practices (GMP) qualified vendors’ websites (n = 42) using the well-established and validated DISCERN instrument to examine the quality of health information provided to consumers. DISCERN contains 15 five-point Likert-scale questions on specific criteria, with the highest possible score being 75, indicating that all the DISCERN criteria have been fulfilled by the website (i.e., the highest quality information is provided to consumers).

Results

The mean DISCERN score for all evaluated online kratom vendors was 32.72 (SD = 6.69; score range 18.00–43.76). Overall, vendors scored higher on DISCERN questions assessing the website’s reliability, as vendors typically provided clear information for consumers about product availability, purchasing, shipping, etc. On average, vendors scored poorly on the DISCERN section pertaining to the quality of the health information provided. Information on kratom’s potential risks and benefits was particularly insufficient.

Conclusions

Consumers require high quality information in order to make informed decisions concerning use, which entails disclosure of known risks and potential benefits. The online kratom vendors evaluated in this study should consider enhancing the quality of health information provided, especially information regarding kratom’s risks and benefits. Further, consumers should be made aware of current knowledge gaps related to kratom’s effects. Clinicians must also be aware of the lack of evidence-based information available to their patients who use kratom or are interested in using kratom products, in order to facilitate educational discussions with them.
Levothyroxine use and longitudinal changes in thigh muscles in at-risk participants for knee osteoarthritis: preliminary analysis from Osteoarthritis Initiative cohort
Authors: Mohajer Bahram , Moradi Kamyar , Guermazi Ali , Mammen Jennifer S. R. , Hunter David J. , Roemer Frank W. , Demehri Shadpour
Published: April 2023

Background

We examined the association between levothyroxine use and longitudinal MRI biomarkers for thigh muscle mass and composition in at-risk participants for knee osteoarthritis (KOA) and their mediatory role in subsequent KOA incidence.

Methods

Using the Osteoarthritis Initiative (OAI) data, we included the thighs and corresponding knees of participants at risk but without established radiographic KOA (baseline Kellgren-Lawrence grade (KL) < 2). Levothyroxine users were defined as self-reported use at all annual follow-up visits until the 4th year and were matched with levothyroxine non-users for potential confounders (KOA risk factors, comorbidities, and relevant medications covariates) using 1:2/3 propensity score (PS) matching. Using a previously developed and validated deep learning method for thigh segmentation, we assessed the association between levothyroxine use and 4-year longitudinal changes in muscle mass, including cross-sectional area (CSA) and muscle composition biomarkers including intra-MAT (within-muscle fat), contractile percentage (non-fat muscle CSA/total muscle CSA), and specific force (force per CSA). We further assessed whether levothyroxine use is associated with an 8-year risk of standard KOA radiographic (KL ≥ 2) and symptomatic incidence (incidence of radiographic KOA and pain on most of the days in the past 12 months). Finally, using a mediation analysis, we assessed whether the association between levothyroxine use and KOA incidence is mediated via muscle changes.

Results

We included 1043 matched thighs/knees (266:777 levothyroxine users:non-users; average ± SD age: 61 ± 9 years, female/male: 4). Levothyroxine use was associated with decreased quadriceps CSAs (mean difference, 95%CI: − 16.06 mm2/year, − 26.70 to − 5.41) but not thigh muscles’ composition (e.g., intra-MAT). Levothyroxine use was also associated with an increased 8-year risk of radiographic (hazard ratio (HR), 95%CI: 1.78, 1.15–2.75) and symptomatic KOA incidence (HR, 95%CI: 1.93, 1.19–3.13). Mediation analysis showed that a decrease in quadriceps mass (i.e., CSA) partially mediated the increased risk of KOA incidence associated with levothyroxine use.

Conclusions

Our exploratory analyses suggest that levothyroxine use may be associated with loss of quadriceps muscle mass, which may also partially mediate the increased risk of subsequent KOA incidence. Study interpretation should consider underlying thyroid function as a potential confounder or effect modifier. Therefore, future studies are warranted to investigate the underlying thyroid function biomarkers for longitudinal changes in the thigh muscles.
Baseline structural MRI and plasma biomarkers predict longitudinal structural atrophy and cognitive decline in early Alzheimer’s disease
Authors: Xie Long , Das Sandhitsu R. , Wisse Laura E. M. , Ittyerah Ranjit , de Flores Robin , Shaw Leslie M. , Yushkevich Paul A. , Wolk David A. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: April 2023

Background

Crucial to the success of clinical trials targeting early Alzheimer’s disease (AD) is recruiting participants who are more likely to progress over the course of the trials. We hypothesize that a combination of plasma and structural MRI biomarkers, which are less costly and non-invasive, is predictive of longitudinal progression measured by atrophy and cognitive decline in early AD, providing a practical alternative to PET or cerebrospinal fluid biomarkers.

Methods

Longitudinal T1-weighted MRI, cognitive (memory-related test scores and clinical dementia rating scale), and plasma measurements of 245 cognitively normal (CN) and 361 mild cognitive impairment (MCI) patients from ADNI were included. Subjects were further divided into β-amyloid positive/negative (Aβ+/Aβ−)] subgroups. Baseline plasma (p-tau181 and neurofilament light chain) and MRI-based structural medial temporal lobe subregional measurements and their association with longitudinal measures of atrophy and cognitive decline were tested using stepwise linear mixed effect modeling in CN and MCI, as well as separately in the Aβ+/Aβ− subgroups. Receiver operating characteristic (ROC) analyses were performed to investigate the discriminative power of each model in separating fast and slow progressors (first and last terciles) of each longitudinal measurement.

Results

A total of 245 CN (35.0% Aβ+) and 361 MCI (53.2% Aβ+) participants were included. In the CN and MCI groups, both baseline plasma and structural MRI biomarkers were included in most models. These relationships were maintained when limited to the Aβ+ and Aβ− subgroups, including Aβ− CN (normal aging). ROC analyses demonstrated reliable discriminative power in identifying fast from slow progressors in MCI [area under the curve (AUC): 0.78–0.93] and more modestly in CN (0.65–0.73).

Conclusions

The present data support the notion that plasma and MRI biomarkers, which are relatively easy to obtain, provide a prediction for the rate of future cognitive and neurodegenerative progression that may be particularly useful in clinical trial stratification and prognosis. Additionally, the effect in Aβ− CN indicates the potential use of these biomarkers in predicting a normal age-related decline.
Implementation of structured reporting in clinical routine: a review of 7 years of institutional experience
Authors: Jorg Tobias , Halfmann Moritz C. , Arnhold Gordon , Pinto dos Santos Daniel , Kloeckner Roman , Düber Christoph , Mildenberger Peter , Jungmann Florian , Müller Lukas
Published: April 2023

Background

To evaluate the implementation process of structured reporting (SR) in a tertiary care institution over a period of 7 years.

Methods

We analysed the content of our image database from January 2016 to December 2022 and compared the numbers of structured reports and free-text reports. For the ten most common SR templates, usage proportions were calculated on a quarterly basis. Annual modality-specific SR usage was calculated for ultrasound, CT, and MRI. During the implementation process, we surveyed radiologists and clinical referring physicians concerning their views on reporting in radiology.

Results

As of December 2022, our reporting platform contained more than 22,000 structured reports. Use of the ten most common SR templates increased markedly since their implementation, leading to a mean SR usage of 77% in Q4 2022. The highest percentages of SR usage were shown for trauma CT, focussed assessment with ultrasound for trauma (FAST), and prostate MRI: 97%, 95%, and 92%, respectively, in 2022. Overall modality-specific SR usage was 17% for ultrasound, 13% for CT, and 6% for MRI in 2022. Both radiologists and referring physicians were more satisfied with structured reports and rated SR better than free-text reporting (FTR) on various attributes.

Conclusions

The increasing SR usage during the period under review and the positive attitude towards SR among both radiologists and clinical referrers show that SR can be successfully implemented. We therefore encourage others to take this step in order to benefit from the advantages of SR.

Key points

Structured reporting usage increased markedly since its implementation at our institution in 2016.

Mean usage for the ten most popular structured reporting templates was 77% in 2022.

Both radiologists and referring physicians preferred structured reports over free-text reports.

Our data shows that structured reporting can be successfully implemented.

We strongly encourage others to implement structured reporting at their institutions.
Research progress of engineered mesenchymal stem cells and their derived exosomes and their application in autoimmune/inflammatory diseases
Authors: Zhu Xueqing , Ma Dan , Yang Baoqi , An Qi , Zhao Jingwen , Gao Xinnan , Zhang Liyun
Published: April 2023

Autoimmune/inflammatory diseases affect many people and are an important cause of global incidence and mortality. Mesenchymal stem cells (MSCs) have low immunogenicity, immune regulation, multidifferentiation and other biological characteristics, play an important role in tissue repair and immune regulation and are widely used in the research and treatment of autoimmune/inflammatory diseases. In addition, MSCs can secrete extracellular vesicles with lipid bilayer structures under resting or activated conditions, including exosomes, microparticles and apoptotic bodies. Among them, exosomes, as the most important component of extracellular vesicles, can function as parent MSCs. Although MSCs and their exosomes have the characteristics of immune regulation and homing, engineering these cells or vesicles through various technical means, such as genetic engineering, surface modification and tissue engineering, can further improve their homing and other congenital characteristics, make them specifically target specific tissues or organs, and improve their therapeutic effect. This article reviews the advanced technology of engineering MSCs or MSC-derived exosomes and its application in some autoimmune/inflammatory diseases by searching the literature published in recent years at home and abroad.
Characterization of an unusual coating on funerary portraits from Roman Egypt circa 100-300AD
Authors: Kirby Daniel P. , Svoboda Marie , Mazurek Joy , Spaabæk Lin Rosa , Southon John
Published: April 2023

This paper details the investigation of a discrete coating observed on a group of Egyptian panel paintings, six mummy portraits and one funerary panel, dating from first-third century CE. Six mummy portraits in this group are encaustic, and the funerary panel is tempera using an animal glue binder. An accretion or coating has been observed on the surface and recesses of the paint layers on these panels. Examination of the portraits using ultraviolet radiation revealed an irregular visible fluorescence on the surface. On the mummy portraits, the fluorescence often extends only as far as where the linen wrappings would have secured the portrait to its mummy. Under magnification, the coating appears as a crizzled encrustation. Material exhibiting these characteristics was sampled from the surface of all seven panels. Initial analysis of samples from four panels by gas chromatography mass spectrometry (GC/MS) and enzyme-linked immunoassay (ELISA) revealed the presence of egg. Subsequent analysis of the coating from all seven portraits by peptide mass fingerprinting (PMF) and liquid chromatography with tandem mass spectrometry (LCMSMS) confirmed egg and further characterized the coating as highly deamidated, whole hen egg, or hen egg white in one instance. Importantly, the 14C date of the coating from two portraits indicates the time of application as approximately 2000 years ago, implying that the coating, at least in those cases, is not a modern addition. This report summarizes the examination and analytical characterization of this unusual coating. Possibly applied as an aesthetic or protective layer, or a symbolic and ritual unguent, the principal function of this coating remains unknown.
Interest rates and real estate prices: a panel study
Authors: Vonlanthen Joël
Published: April 2023

This study examines the connection between interest rates and real estate prices in Switzerland. In considering median prices of six real estate groups consisting of rental apartments, owner-occupied flats, houses, office space, industrial real estate and sales area between the first quarter of 2005 and the fourth quarter of 2018 across 106 Swiss regions, we studied their connection with four interest rate proxies: yields on governmental bonds with 10-year maturity, fixed mortgage rates with 10-year maturity, variable mortgage rates and a newly introduced variable indicating the spread between net initial returns and yields on governmental bonds. Not only do our results show how real estate groups react to specific interest rate representatives, but also how this effect varies between Swiss regions.
The determinants of reliable smart grid from experts’ perspective
Authors: Mashal Ibrahim , Khashan Osama A. , Hijjawi Mohammad , Alshinwan Mohammad
Published: April 2023

A smart grid integrates communication networks with the conventional electrical grid. Due to their potential, smart grids are anticipated to achieve widespread deployment. A key component of the success and adoption of smart grids is reliability. Without knowing users’ impressions of the reliability of the smart grid, users will not easily accept and participate in it or its services. However, very few studies address smart grid reliability from the perspective of users. Thus, there is a urgent need to identify key factors that affect smart grid reliability from the user’s viewpoint. The goal of this paper is to examine user perceptions of smart grid reliability and assess their success factors in an effort to close the gap in the literature. This paper propose a model to investigate and determine the most crucial factors that affect the smart grid's reliability based on the Multiple-criteria decision-making (MCDM) method. Firstly, a comprehensive literature analysis was conducted to determine the criteria and sub-criteria used to construct the model; then, the model is constructed using fifteen sub-criteria covering big data, network systems, and grid efficiency criteria; finally, the Fuzzy Analytic Hierarchy Approach (FAHP) and fuzzy triangular numbers are used to evaluate and prioritize the criteria. Twenty smart grid experts were consulted to collect data. The results indicate the significance of the ‘Big Data’ criterion, closely followed by ‘Grid Efficiency’ criterion. Additionally, it is discovered that the sub-criteria of ‘Privacy’ and ‘Interoperability’ had a significant impact on the reliability of the smart grid. The sensitivity analysis shows the variation of factors ranking and the stability and robustness of the model and the results. The research presented in this study has practical applications for academics, engineers, decision-makers, and stakeholders.
Joint inversion of formation radial shear-velocity profiles by dipole acoustic logging while drilling
Authors: Li Jia-Cheng , He Xiao , Zhao Ao-Song , Jiang Can
Published: April 2023

Formation properties near a borehole are frequently altered by mechanical damage from drilling, leading to variations of formation elastic velocities in the radial direction. Inversions of radial shear profiles are necessary for a real-time evaluation of the drilling conditions. In this study, we investigate acoustic wave propagation in a logging-while-drilling (LWD) model excited by a dipole transducer in cylindrically layered media. It is revealed that the dispersion characteristics of the dipole waves of the LWD are sensitive to the radial formation velocity variation. Accordingly, we develop a joint inversion method that evaluates radial shear-velocity profiles using the dipole modes of the first and second orders. The propagation of these two modes is strongly influenced by formation alterations, but the inversion results obtained using a single dipole mode indicate ambiguity caused by the nonuniqueness problem. Through our joint inversion, the additional second-order dipole wave can effectively help address the nonuniqueness issue in dipole acoustic logging, although its dispersion features differ in fast and slow formations. It is validated that the joint inversion has considerably improved convergence and accuracy in evaluating the thickness and shear velocity of the altered zone, compared with the estimation by a single acoustic mode. Furthermore, we develop numerical results based on synthetic logging data to demonstrate the feasibility of this inversion in a continuously varying profile, regardless of whether the formation surrounding the borehole is fast or slow. Even when strong drilling noises of low frequencies are added to the receiver signal arrays, the means of joint inversion can remain stable, and the shear-velocity profiles can be evaluated with good precision.
Application of Yu’s wavelet and supervirtual seismic refraction interferometry to enhance first arrivals: A case study from Kuche Mountain
Authors: Li Yalin , Liu Lianshen , Lei Ganglin , Duan Wensheng , Zheng Duoming , Wang Chuan
Published: April 2023

The signal-to-noise ratio (S/N) of the 3D seismic data in Kuche Mountain is poor, where the first-arrival events are overlapped with random and coherent noises due to the data set collected within a challenging environment with abrupt changes in the topographical elevation. Therefore, it is difficult to carry out first-arrival picking, which in turn affects the application of tomographic inversion and static correction in this area. To face this challenge, first-arrival filtering using Yu’s wavelet and first-arrival enhancement with supervirtual seismic refraction interferometry are applied in 3D seismic data processing on the data set collected from the Kuche Mountain area. The result finds that, by using these two techniques together, the first-arrival events can be recognized easily, the first-arrival times can be picked accurately, and the amount of picked events increases greatly.
External Validation of a Prognostic Model of Overall Survival in Men With Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer
Authors: Halabi Susan , Yang Qian , Roy Akash , Luo Bin , Araujo John C. , Logothetis Christopher , Sternberg Cora N. , Armstrong Andrew J. , Carducci Michael A. , Chi Kim N. , de Bono Johann S. , Petrylak Daniel P. , Fizazi Karim , Higano Celestia S. , Morris Michael J. , Rathkopf Dana E. , Saad Fred , Ryan Charles J. , Small Eric J. , Kelly William Kevin
Published: April 2023

PURPOSE

We have previously developed and externally validated a prognostic model of overall survival (OS) in men with metastatic, castration-resistant prostate cancer (mCRPC) treated with docetaxel. We sought to externally validate this model in a broader group of men with docetaxel-naïve mCRPC and in specific subgroups (White, Black, Asian patients, different age groups, and specific treatments) and to classify patients into validated two and three prognostic risk groupings on the basis of the model.

METHODS

Data from 8,083 docetaxel-naïve mCRPC men randomly assigned on seven phase III trials were used to validate the prognostic model of OS. We assessed the predictive performance of the model by computing the time-dependent area under the receiver operating characteristic curve (tAUC) and validated the two-risk (low and high) and three-risk prognostic groups (low, intermediate, and high).

RESULTS

The tAUC was 0.74 (95% CI, 0.73 to 0.75), and when adjusting for the first-line androgen receptor (AR) inhibitor trial status, the tAUC was 0.75 (95% CI, 0.74 to 0.76). Similar results were observed by the different racial, age, and treatment subgroups. In patients enrolled on first-line AR inhibitor trials, the median OS (months) in the low-, intermediate-, and high-prognostic risk groups were 43.3 (95% CI, 40.7 to 45.8), 27.7 (95% CI, 25.8 to 31.3), and 15.4 (95% CI, 14.0 to 17.9), respectively. Compared with the low-risk prognostic group, the hazard ratios for the high- and intermediate-risk groups were 4.3 (95% CI, 3.6 to 5.1; P < .0001) and 1.9 (95% CI, 1.7 to 2.1; P < .0001).

CONCLUSION

This prognostic model for OS in docetaxel-naïve men with mCRPC has been validated using data from seven trials and yields similar results overall and across race, age, and different treatment classes. The prognostic risk groups are robust and can be used to identify groups of patients for enrichment designs and for stratification in randomized clinical trials.

[Media: see text]
Chrischonakirche von Bettingen
Authors: Moosbrugger-Leu Rudolf
Published: April 2023

In einem ersten Teil beschreibt der Autor ein frühmittelalterliches Plattengrab aus den Jahrzehnten um 700, das möglicherweise den Anfang dieser christlichen Kultstätte bildete. Ausführlich geht er auf die Legende um die heilige Chrischona sowie das Patrozinium des heiligen Brictius ein, der als Beschützer der Kinder gilt und zu dem er den Friedhof der Kleinkinder im Osten der Kirche in Verbindung bringt.

Den Hauptteil bilden die archäologischen und baugeschichtlichen Befunde. Sie bezeugen eine frühmittelalterliche Anlage, einen romanischen sowie hoch- bis spätgotischen Bau.

In einem dritten Teil werden besondere Kleinfunde vorgelegt. So werden u.a. Werkstücke und Halbfabrikate beschrieben, die über die Herstellung von Beinknöpfen durch den ersten Chrischona-Bruder (Anf. 19. Jh.) berichten. Bei den Fundmünzen handelt es sich vor allem um Opfergaben, die im Mittelalter ins Heiligengrab kamen.
neuzeitlichen Funde
Authors: Matteotti René
Published: April 2023

Den Schwerpunkt der Analyse des neuzeitlichen Fundmaterials stellt die statistische Auswertung der zahlreichen Keramikfunde aus den Gartenhorizonten N 3 bis N 5 dar. Geschirrkeramik, Glasgefässe, Tonpfeifen und industriell hergestellte Baukeramik werden ausführlich besprochen; die übrigen Kleinfunde (sämtliche identifizierbaren Gegenstände, mit Ausnahme von Nägeln) sind im Katalog aufgeführt.
Herrschaftsentwicklung, Christianisierung und Kirchenbau
Authors: Wechsler Kurt
Published: April 2023

Kurt Wechsler arbeitete die schriftlichen Quellen zur Kirchenburg in Riehen auf und beleuchtet die Herrschaftsentwicklung, die Christianisierung und den Kirchenbau. Zudem erstellte er ein Quellenverzeichnis und ein Glossar.
Polygenic Risk Score in African populations: progress and challenges
Authors: Adam Yagoub , Sadeeq Suraju , Kumuthini Judit , Ajayi Olabode , Wells Gordon , Solomon Rotimi , Ogunlana Olubanke , Adetiba Emmanuel , Iweala Emeka , Brors Benedikt , Adebiyi Ezekiel
Published: April 2023

Polygenic Risk Score (PRS) analysis is a method that predicts the genetic risk of an individual towards targeted traits. Even when there are no significant markers, it gives evidence of a genetic effect beyond the results of Genome-Wide Association Studies (GWAS). Moreover, it selects  single nucleotide polymorphisms (SNPs) that  contribute to the disease with low effect size  making it more precise at individual level risk prediction. PRS  analysis addresses the shortfall of GWAS by taking into account the SNPs/alleles with  low effect size but play an indispensable role to the observed phenotypic/trait variance.  PRS analysis has  applications that investigate the genetic basis of several traits, which includes rare diseases. However, the accuracy of PRS analysis depends on the genomic data of the underlying population. For instance, several studies  show   that obtaining higher prediction power of PRS analysis is challenging for non-Europeans. In this manuscript, we review the conventional PRS methods and their application to sub-Saharan African communities. We conclude that  lack of sufficient GWAS data and tools is  the limiting factor of applying PRS analysis to sub-Saharan populations.   We recommend developing Africa-specific PRS methods and tools for estimating and analyzing  African population data   for clinical  evaluation of PRSs of interest and predicting  rare diseases.
DDS: integrating data analytics transformations in task-based workflows
Authors: Mammadli Nihad , Ejarque Jorge , Alvarez Javier , Badia Rosa M.
Published: April 2023

High-performance data analytics (HPDA) is a current trend in e-science research that aims to integrate traditional HPC with recent data analytic frameworks. Most of the work done in this field has focused on improving data analytic frameworks by implementing their engines on top of HPC technologies such as Message Passing Interface. However, there is a lack of integration from an application development perspective. HPC workflows have their own parallel programming models, while data analytic (DA) algorithms are mainly implemented using data transformations and executed with frameworks like Spark. Task-based programming models (TBPMs) are a very efficient approach for implementing HPC workflows. Data analytic transformations can also be decomposed as a set of tasks and implemented with a task-based programming model.

In this paper, we present a methodology to develop HPDA applications on top of TBPMs that allow developers to combine HPC workflows and data analytic transformations seamlessly. A prototype of this approach has been implemented on top of the PyCOMPSs task-based programming model to validate two aspects: HPDA applications can be seamlessly developed and have better performance than Spark. We compare our results using different programs. Finally, we conclude with the idea of integrating DA into HPC applications and evaluation of our method against Spark.
The location and development of Replicon Cluster Domains in early replicating DNA
Authors: da Costa-Nunes José A. , Gierlinski Marek , Sasaki Takayo , Haagensen Emma J. , Gilbert David M. , Blow J. Julian
Published: April 2023

Background: It has been known for many years that in metazoan cells, replication origins are organised into clusters where origins within each cluster fire near-synchronously. Despite clusters being a fundamental organising principle of metazoan DNA replication, the location of origin clusters on the genome has not been documented.

Methods: We synchronised human U2OS by thymidine block and release followed by a brief block with L-mimosine to create a population of cells progressing into S phase with a high degree of synchrony. At different times after release into S phase, cells were pulsed with EdU; the EdU-labelled DNA was then pulled down, sequenced and mapped back onto the human genome.

Results: The early replicating DNA showed features at a range of scales. Wavelet analysis showed that the major feature of the early replicating DNA was at a size of 500 kb, consistent with clusters of replication origins. Over the first two hours of S phase, these Replicon Cluster Domains broadened in width, consistent with their being enlarged by the progression of replication forks at their outer boundaries. The total replication signal associated with each Replicon Cluster Domain varied considerably, and this variation was reproducible and conserved over time. We provide evidence that this variability in replication signal was at least in part caused by Replicon Cluster Domains being activated at different times in different cells in the population. We also provide evidence that adjacent clusters were preferentially activated in sequence across a group, consistent with the ‘domino’ model of replication focus activation observed by microscopy.

Conclusions: We show that early replicating DNA is organised into Replicon Cluster Domains that behave as expected of replicon clusters observed by DNA fibre analysis. The coordinated activation of different Replicon Cluster Domains can generate the replication timing programme by which the genome is duplicated.
Problems of Personal Behavior in the Information Educational Environment
Authors: Tverskoy A.
Published: April 2023

The article analyzes the features of the influence of the information environment on the development of the personality of students, the problems of finding a child in the information space, and also explores the motives and behavioral characteristics of a person in a digital educational environment. The influence of the information educa-tional environment on the development and behavior of the child's personality is con-sidered and the need for children to adapt to the information environment and the formation of the correct model of personality behavior within the digital reality is substantiated.
Optimization of Immersive Blended Learning as the Main Direction of Development of "Education 4.0"
Authors: Shishov Sergey , Kal'ney V. , Ryahimova E.
Published: April 2023

The article discusses blended learning, the ability of which to improve the quality of education in the modern conditions of digital society is no longer in doubt. The authors analyze the relationship and interdependence of blended and immersive learning and evaluate it in terms of such parameters as accessibility and a wide sector of practical use. Modern education, already called "Education 4.0", is associated with virtualization and represents dozens of different pedagogical technologies and areas of pedagogical science. Heutagogy, peeragogy and cybergogy are in focus in modern digital pedagogy. Today they are considered as modern innovative pedagogical approaches that can provide the best technological tools for digital immersive learning. This paper provides a systematic review of the scientific literature that characterizes the methodological approaches of "digital pedagogy".
Features of Developing a Healthy Lifestyle in Preschool Children
Authors: Romanova A. , Kuryatnikova L. , Shmeleva S. , Ragulin S.
Published: April 2023

This work is devoted to the search for effective preventive and therapeutic measures for frequently ill (respiratory diseases) preschool children, improving the health of the younger generation. Possibilities of using therapeutic physical culture, a complex of hardening procedures, physical activity in order to reduce the incidence of diseases and form a healthy lifestyle.
Gender differences in the manifestation of self-control of district police officials with different level of professional burnout
Authors: Titova Mariya
Published: April 2023

the article presents the results of an empirical study of gender differences in the manifestation of self-control of district police officers with different levels of professional burnout.

The empirical study involved employees of internal affairs bodies holding the positions of district and senior district police officers, as well as heads and deputies of the PDMA and PDN. The sample consisted of 192 people (96 women and 96 men

aged 20 to 45 years with service experience in the police department from 5 to 20 years).

An empirical study was conducted on the basis of a set of methods: test questionnaire "Professional burnout for law enforcement officers" (K. Maslach, S. Jackson, adapted by N.E. Vodopyanova); self-control test (A.A. Zolotareva); studies of self-government (Yu. Kul, A. Furman, adapted by O.V. Mitina and E.I. Rasskazova); test questionnaire for self-organization of activity (E.Yu. Mandrikova); SORE (E.I. Rasskazova, T.O. Gordeeva, E.N. Osin); questionnaire of the life position of the individual (D.A. Leontiev, A.E. Shilmanskaya); resilience test questionnaire (S. Maddy, adapted by D.A. Leontiev and E.I. Rasskazova); scale of organizational stress (A. McLean, adapted by N.E. Vodopyanova); identity/marginalism test (E.P. Ermolaeva); test of motivators of socio-psychological activity of a person (N.P. Fetisov, V.V. Kozlov, G.M. Mainulov).

According to the results of the study, gender differences in the manifestation of self-control of district police officers with different levels of professional burnout were established.