Miracle-dz/UniFAR-FTUs huggingface dataset:
Minigene Splicing Assays Identify 20 Spliceogenic Variants of the Breast/Ovarian Cancer Susceptibility Gene RAD51C

Simple Summary Loss-of-function variants of the RAD51C gene are known to confer a risk of breast and ovarian cancers. In this study, we analyzed the impact of RAD51C variants on splicing, a highly regulated gene expression step by which introns are removed and exons are sequentially joined. Exon recognition is guided by specific sequences, the 3′ and 5′ splice sites, which define the exon boundaries. Variants of these sequences of susceptibility genes may lead to aberrant splicing and abnormal transcripts that may trigger a disease. Splicing can be tested using a biotechnological tool called minigenes, which mimic the human gene of interest. Thus, we checked 20 RAD51C splice-site variants using the minigene mgR51C_ex2-8. We found that they all disrupted the splicing mechanism, and 16 variants could be classified as likely pathogenic. Our findings are clinically actionable, and variant carriers may benefit from tailored prevention protocols and therapies. Abstract RAD51C loss-of-function variants are associated with an increased risk of breast and ovarian cancers. Likewise, splicing disruptions are a frequent mechanism of gene inactivation. Taking advantage of a previous splicing-reporter minigene with exons 2-8 (mgR51C_ex2-8), we proceeded to check its impact on the splicing of candidate ClinVar variants. A total of 141 RAD51C variants at the intron/exon boundaries were analyzed with MaxEntScan. Twenty variants were selected and genetically engineered into the wild-type minigene. All the variants disrupted splicing, and 18 induced major splicing anomalies without any trace or minimal amounts (<2.4%) of the minigene full-length (FL) transcript. Twenty-seven transcripts (including the wild-type and r.904A FL transcripts) were identified by fluorescent fragment electrophoresis; of these, 14 were predicted to truncate the RAD51C protein, 3 kept the reading frame, and 8 minor isoforms (1.1–4.7% of the overall expression) could not be characterized. Finally, we performed a tentative interpretation of the variants according to an ACMG/AMP (American College of Medical Genetics and Genomics/Association for Molecular Pathology)-based classification scheme, classifying 16 variants as likely pathogenic. Minigene assays have been proven as valuable tools for the initial characterization of potential spliceogenic variants. Hence, minigene mgR51C_ex2-8 provided useful splicing data for 40 RAD51C variants.
The Validity of Measures of Instructional Alignment With State Standards Based on Surveys of Enacted Curriculum

This paper uses a validity argument approach to examine the validity evidence for measures of instructional alignment based on an instrument adapted from the Surveys of Enacted Curriculum (SEC). Using the instrument, Grade 4 math and Grade 5 English language arts teachers reported the level of emphasis they gave to subject-specific topics and cognitive demands in their instruction, which provided the data for measuring instructional alignment—both overall and by topic and by cognitive demand—with state standards. We found that (a) teachers differentiated topics but not cognitive demands when reporting on the content of their instruction, (b) teachers likely overreported levels of emphasis on topics and cognitive demands, and (c) overall alignment and alignment by cognitive demand were not significantly associated with teachers’ value-added scores. Although this study examined a specific version of the SEC, we believe the findings apply more broadly to SEC-based measures of instructional alignment.
Clinical adolescent decision-making: parental perspectives on confidentiality and consent in Belgium and The Netherlands

ABSTRACT This study investigated Belgian and Dutch parental opinions on confidentiality and consent regarding medical decisions about adolescents. Through an online survey, we presented six cases (three on confidentiality, and three on consent) to 1,382 Belgian and Dutch parents. We studied patterns in parental confidentiality and consent preferences across and between cases through binomial logistic regressions and latent class analysis. Participants often grant the right to consent for a treatment to the adolescent, but the majority diverges from the adolescent’s preferences regarding confidentiality. More educated participants would rather not be informed about cases regarding a sexually transmitted disease or depression than lower educated participants. Further analysis shows that participants’ preferences correspond to authoritative (47%), permissive (30%) and authoritarian (17%) parenting styles. Belgian and Dutch parents are willing to grant some degree of autonomy, but they want to be informed about specific health issues. Parental views on confidentiality and granting consent appear to mirror existing parenting styles.
INSTAGRAM INFLUENCERS AS PREDICTORS OF CONSUMER PURCHASE INTENTION TOWARDS FASHION PRODUCTS IN JAKARTA, INDONESIA

Objective: The objective of this study is to determine the effect of perceived originality, perceived uniqueness, and source credibility of accounts owned by Instagram influencers on consumers’ purchase intention of fashion products in Jakarta, Indonesia Methodology: An online survey was administered to online Instagram users in Jakarta, Indonesia. Descriptive, correlation and regression analysis were used as statistical tools to analyse the data and to test the hypotheses. Results: Perceived originality, perceived uniqueness and source credibility have significant and positive relationship on purchase intention of purchase products in Instagram. Moreover, perceived originality is the best predictor of purchase intention among respondents of this study. Implication: This study presents a conceptually yet empirically supported framework to describe the significance of perceived originality, source credibility and purchase intention in fashion products. The study is specifically useful for Instagram influencers as it helps identify which characteristics that they should show to cultivate purchase intention among people aged 18-34.
Impact of FLT3-ITD Insertion Length on Outcomes in Acute Myeloid Leukemia: A Propensity Score-Adjusted Cohort Study

Simple Summary Acute myeloid leukemia (AML) is a complicated disease with well-studied genetic mutations that have been used in both risk stratification as well as targets for treatment. In this study, we examined the varying prognostic significance of different lengths of the special mutation, named internal tandem duplication or ITD, of a commonly mutated gene in AML named FLT3. We found that the longer the size of the ITD mutation, the better the clinical outcomes. Abstract The prognostic significance of the length of internal tandem duplication (ITD) insertions in mutant FLT3 genes in acute myeloid leukemia (AML) is controversial. We conducted a retrospective study to evaluate the correlation between the ITD base-pair (bp) insertion length and clinical outcomes. The mutational status of the FLT3 gene was evaluated in 402 of 467 consecutive AML patients treated at the University of Maryland Greenebaum Comprehensive Cancer Center between 2013 and 2020; 77 had FLT3-ITD mutations. Patients were divided into three cohorts based on bp insertion length (<30 (0–33rd percentile), 30–53 (34th–66th percentile),and >53 (>66th percentile)). The median overall survival (OS) of patients was 16.5 months (confidence interval (CI) 7.3-NA), 18.5 months (CI 7.3-NA), and 21.9 months (CI 19.1-NA) (p = 0.03) for the <30, 30–53, and >53 bp insertion length cohorts, respectively. The adjusted median event-free survival (EFS) for the ITD insertion lengths >30, 30–53, and >53 bp was 11.1 months (CI 2.8–16.5), 5.2 months (CI 2.9–12.6), and 9.1 months (CI 5.4-NA) (p = 0.5), respectively. Complete remission (CR) rates were 64% (<30 inserted bp), 55% (30–53 inserted bp), and 79% (>53 inserted bp) (p = 0.23). For patients treated with gilteritinib and midostaurin, the unadjusted median OS was not statistically significantly different between cohorts.
The Impact of Computerized Health Information System on Medical & Administrative Decisions, Sana’a Hospitals, Yemen (2017-2020)

Background: Health information systems (HIS) play a major role in decision-making. The aim is to identify the components of computerized HIS and their relationship to administrative decisions at the main referral hospitals for Sana’a city. Method: This applied research is a descriptive, cross-sectional study in which the HIS of 7 hospitals affiliated with Sana’a city hospitals during “2017-2020”, was evaluated based on Self-administered questionnaires. Data were collected by using Self-administered questionnaires and analyzed in SPSS 16 by using descriptive statistics. Results: A total of 626 users (95.7%) had responded. 73%, 75%, 69%, 70%, 71% of users mentioned that resources were available, for physical, software, human, organizational, and decision computerized HIS, respectively. The study showed a strong relationship be-tween computerized information systems with their physical, software, human and organizational components, and medical and administrative decisions. While the study showed the absence of a relationship between demographic factors and computerized information systems with their hardware, software, human and organizational components, medical and administrative decisions, except for gender with organizational components, age, qualification with hardware and
Seasonal to Decadal Western Boundary Current Variability From Sustained Ocean Observations

Subtropical western boundary currents (WBCs) exert a substantial influence on regional climate. To improve WBC observations on seasonal‐to‐decadal timescales, and characterize their subsurface structure to 1975 m depth, we combine high‐resolution expendable bathythermograph, Argo, and satellite altimetry observations in the Agulhas Current, East Australian Current, and Kuroshio. The resulting 16 year time series (2004–2019) show a weakening trend in Kuroshio transport, but no trend in Agulhas transport or East Australian Current transport. All three WBCs have stronger transport in summer, driven mostly by changes in current speed rather than current width. This unique subsurface view of WBC variability reveals changes in the path of the Kuroshio Extension on interannual timescales, and eddy variability in the Agulhas. Our work highlights how this application of a consistent methodology to combine complementary ocean observations allows for an unprecedented direct comparison of variability between WBCs.
Decentralized Dynamic Event-Triggered Adaptive Fuzzy Control for Switched Nonlinear Systems With Unstable Inverse Dynamics

In this article, the problem of decentralized dynamic event-triggered (ET) adaptive fuzzy control for a class of strong interconnected switched uncertain nonlinear systems with unstable inverse dynamics and unknown control gains is studied. By utilizing the adaptive backstepping technique and new fuzzy logic systems, decentralized ET adaptive fuzzy controllers for subsystems and a new type of switching decentralized dynamic event-triggering mechanisms are constructed. Then, the asynchronous switching problem between candidate controllers and subsystems is addressed, and the upper bound of asynchronous time is not directly restricted. Meanwhile, by ensuring that the interexecution times are lower bounded by a positive constant, Zeno behavior is avoided. Furthermore, it is proved by the multiple Lyapunov functions method that all signals in the switched closed-loop system are bounded under a new class of slow switching signals. The validity of the derived result is illustrated using two examples which include a two inverted pendulum system.
Building the Capacity of the Malian Police: Why MINUSMA needs to think outside the box

MINUSMA’s deployment was greeted with goodwill since its aim was to stabilise key population centres and support the re-establishment of state authority. However, the mission is losing its initial popularity among the Malian community given considerable frustration with the lack of MINUSMA achievement. the aim of this policy brief is to outline how the capacity-building aspect of the police component of MINUSMA can be strengthened to achieve the mission goal of assisting the re-establishment of state authority and the rebuilding of the security sector. We argue that MINUSMA not only needs to strengthen its presence in the country, but must also find new ways to approach capacity-building in a more holistic manner.
Knowledge of Malaria and Its Uncomplicated Treatment with Argemone mexicana L. in Selected Districts of Jimma Zone, Oromia Regional State, Ethiopia: A Community-Based Cross Sectional Survey

Background With the problems of increasing levels of drug resistance and difficulties to afford and access effective antimalarial drugs in poor and remote areas, herbal medicines could be an important and sustainable source of treatment. Argemone mexicana L. (AM) is a medicinal plant known long ago in several countries for treatment of numerous diseases including malaria. The aim of this study was to conduct a survey on the use of AM in the prevention and treatment of uncomplicated malaria in selected districts of Jimma Zone, Oromia Regional state, Ethiopia. Methods A community-based cross-sectional study was conducted in two selected districts in Jimma Zone, southwest Ethiopia. In total, 552 participants from 17 kebeles (villages/communities) and 18 traditional healers of the districts were interviewed. Data collection was conducted from April 27 to May 18, 2020 using pre-tested structured questionnaires. The data were analyzed using Epi Info 7.0 and the descriptive statistics were used to summarize the results. Results The study indicated that AM is available, known by 39.8% of the respondents and used for prevention and treatment of malaria by 5.7% of the population. All traditional healers interviewed knew the plant, and 44.4% use it for treatment of malaria. In addition, AM is especially used to treat malaria, amoebiasis, diarrhea, cough, and tuberculosis. Conclusion The availability and use of AM to treat malaria was verified in both community and traditional healers. AM, which was found effective as antimalarial plant in high Plasmodium falciparum endemicity in Mali, is also well known and accepted in these areas of Ethiopia for the treatment of malaria. Further research is needed to assess wether AM is also effective against malaria in Ethiopia where P. vivax and P. falciparum coexist.
SCM-198 Prevents Endometriosis by Reversing Low Autophagy of Endometrial Stromal Cell via Balancing ERα and PR Signals

Background Endometriosis (EMS), an endocrine-related inflammatory disease, is characterized by estrogen and progesterone imbalance in ectopic lesions. However, its pathogenic mechanism has not been fully elucidated. While SCM-198 is the synthetic form of leonurine and has multiple pharmacological activities such as antioxidation and anti-inflammation, it remains unknown whether it could inhibit the progress of EMS by regulating estrogen signaling and inflammation. Methods The therapeutic effects of SCM-198 on EMS and its potential mechanism were analyzed by establishing EMS mouse models and performing an RNA sequencing (RNA-seq) assay. ELISA was performed to detect estrogen and tumor necrosis factor (TNF) -α concentrations in normal endometrial stromal cells (nESCs) and ectopic endometrial stromal cells (eESCs) with or without SCM-198 treatment. Western blotting, RNA silencing, and plasmid overexpression were used to analyze the relationship between inflammation, endocrine factors, and autophagy and the regulatory activity of SCM-198 on the inflammation-endocrine-autophagy axis. Results Increased estrogen-estrogen receptor (ER) α signaling and decreased progesterone receptor isoform B (PRB) expression synergistically led to a hypo-autophagy state in eESCs, which further inhibited the apoptosis of eESCs. The high expression of TNF-α in eESCs enhanced the antiapoptotic effect mediated by low autophagy through the activation of the aromatase-estrogen-ERα signaling pathway. SCM-198 inhibited the growth of ectopic lesions in EMS mice and promoted the apoptosis of eESCs both in vivo and in vitro. The apoptotic effect of SCM-198 on eESCs was attained by upregulating the autophagy level via the inhibition of the TNF-α-activated aromatase-estrogen-ERα signal and the increase in PRB expression. Conclusion Inflammation facilitated the progress of EMS by disrupting the estrogen regulatory axis. SCM-198 inhibited EMS progression by regulating the inflammation-endocrine-autophagy axis.
Pathophysiology of Diverticular Disease: From Diverticula Formation to Symptom Generation

Diverticular disease is a common clinical problem, particularly in industrialized countries. In most cases, colonic diverticula remain asymptomatic throughout life and sometimes are found incidentally during colonic imaging in colorectal cancer screening programs in otherwise healthy subjects. Nonetheless, roughly 25% of patients bearing colonic diverticula develop clinical manifestations. Abdominal symptoms associated with diverticula in the absence of inflammation or complications are termed symptomatic uncomplicated diverticular disease (SUDD). The pathophysiology of diverticular disease as well as the mechanisms involved in the shift from an asymptomatic condition to a symptomatic one is still poorly understood. It is accepted that both genetic factors and environment, as well as intestinal microenvironment alterations, have a role in diverticula development and in the different phenotypic expressions of diverticular disease. In the present review, we will summarize the up-to-date knowledge on the pathophysiology of diverticula and their different clinical setting, including diverticulosis and SUDD.
Optimal Size of Electric Vehicle Charging Stations in Distribution System with Consideration of Bus Voltage and Line Capacity Limits

Currently, the deployment of electric vehicle charging stations (EVCSs) in a distribution system has rapidly increased to encourage the electric vehicle usage of a customer. However, this may inevitably cause the technical issues concerning the distribution system operation criteria, i.e., bus voltage and line capacity limits. Therefore, this paper proposes a method for determining the optimal size of each EVCS without violating the bus voltage limit and the line capacity limit. The proposed method is based on the iterative technique to solve the optimization problem where six patterns of EVCS installation are investigated during off-peak and peak time periods of residential loads. To illustrate the effectiveness of the proposed method, a typical low-voltage distribution system in Thailand is selected to be a test system. Moreover, the fairness of all customers is considered by supposing that the EVCSs are equally installed at each bus, and the loads are equally distributed in the distribution system. The simulation results show that the optimal size of the EVCS during off-peak and peak time periods is mostly limited by the line capacity limit and the bus voltage limit, respectively. This implies that the behavior of customers to charge their electric vehicle should occur during off-peak time period instead of peak time period.
Prestigious early Roman gardens across the Empire: the significance of gardens and horticultural trends evidenced by pollen

Abstract The present study has two main goals. The first is to reconstruct the botanical components that grew in the impressive garden of Villa Arianna (Stabiae). The garden, which was extensively destroyed and covered by tephra ash in 79 CE, is considered the largest peristyle garden in the Vesuvian region. Its plants were revealed based on a unique palynological-archaeological method involving the extraction of pollen from plaster attached to structures that faced the garden. The second aim is to compare this prestigious garden with other early elite Roman gardens, located in the eastern part of the Empire, to trace the importation of plants, horticultural trends, etc. For this purpose, gardens of Herod the Great, the client king of Judaea, which the author recently studied palynologically (in Caesarea, Herodium and Jericho), were compared with the new pollen results of Villa Arianna. The comparison between the gardens’ botanical components and their different landscapes led to the following conclusions: (1) Plants were imported from both ends of the Empire as elite products (rather than cash crops). Hazelnut (Corylus) and cedar (Cedrus) were introduced from west to east, while the date palm (Phoenix dactylifera) was introduced along an east-west axis. (2) The gardening trend of tree dwarfism was observed both at Villa Arianna and Jericho. (3) The gardens flourished in challenging habitats. At Villa Arianna and Caesarea, efforts were devoted to sustaining splendid gardens in the relatively harsh, saline Mediterranean Sea environment; at Herodium and Jericho, special efforts were required for the success of Mediterranean plants in semi-arid climate. (4) Herod’s mausoleum garden in Herodium, whose dark evergreen trees on the whitish slopes of the artificial tumulus could be seen from the Temple in Jerusalem, may have been inspired by the architectural arrangement of the Pantheon and the Mausoleum of Augustus, the patron of Herod.
Office occupants as active actors in assessing and informing comfort: a context-embedded comfort assessment in indoor environmental quality investigations

ABSTRACT The energy and building research community acknowledges the importance of including occupants' wellbeing in the evaluation of building energy performance. Particularly in office buildings, occupants' comfort assessment is not yet a common practice, partially due to the shortcomings of the comfort assessment activities. Contextual factors such as the organizational culture, occupants' personality traits and emotional states, and the building and research measurement infrastructures do interact with occupants' motivation to report and influence their actual reporting behaviour. By means of an in situ mixed method approach combining real-world research and user-centric methods, this study investigates the impact of a reporting-based comfort assessment. Two buildings, representing different organizational cultures, were selected to study the influence of reporting behaviour on comfort assessment. The buildings were equipped with innovative indoor climate monitoring and in situ comfort reporting infrastructure and 2-week field studies were conducted in both buildings. By discussing results from these studies, this paper contributes to the development of building research methodologies of indoor climate and comfort assessment by providing practical experience in embedding comfort reporting behaviour in the analysis of comfort assessment. A contextual typology of reporting behaviour is introduced and its implications regarding the reliability and validity of comfort reporting techniques are discussed.