Miracle-dz/UniFAR-FTUs huggingface dataset:
Selective oestrogen receptor degraders in breast cancer: a review and perspectives.

PURPOSE OF REVIEW Estrogen receptor-positive breast cancer accounts for 70% of all breast cancers. Sequential endocrine treatment in monotherapy or in combination with CDK 4/6 or m-TOR inhibitors is the mainstay of recommended treatment options in the management of metastatic breast cancer even in the presence of visceral metastasis. There is an emerging need to address endocrine resistance, which despite highly efficacious treatment combinations still can develop. RECENT FINDINGS One of the mechanisms of endocrine resistance is molecular alteration of the oestrogen receptor itself, such as ESR1 mutations affecting the ligand-binding domain. These mutations emerge under the selective pressure of aromatase inhibitors. The efficacy of selective oestrogen receptor degraders (SERDs) might not be affected by the presence of molecular alterations of oestrogen receptor. Fulvestrant is the only SERD used in current clinical practice. Numerous novel, nonsteroidal orally available SERDs are currently in clinical development. Efficacious oestrogen receptor target engagement and promising clinical activity was shown in early phase clinical trials. SUMMARY Therefore, a new class of orally available nonsteroidal SERDs gains high interest in tackling endocrine resistance in oestrogen receptor-positive (ER+) advanced breast cancer. Clinical efficacy needs to be confirmed in larger patient populations.
The effects of teacher feedback on multiple-draft compositions in ESL classrooms

Teacher feedback plays a significant role in helping ESL learners acquire the writing skills. However, many research findings indicated that feedback on single draft essays does not help ESL learners much in improving the essays because these learners do not have the opportunity to revise, rewrite, and resubmit their work. Therefore, this study aims at examining the effects of teacher feedback on ESL learners’ compositions in terms of content, language and organization by instituting the multiple draft procedure. The participants of this study wrote a first draft; revised it after getting the feedback on content and further revised it after receiving feedback on language. The findings showed that there were significant mean differences in the content, language, organization and the total marks when the second and the third drafts were compared to the first draft.
A pathological study of Leishmania infantum natural infection in European rabbits (Oryctolagus cuniculus) and Iberian hares (Lepus granatensis).

In this study, we describe the pathology of Leishmania infantum infection in naturally infected wild Leporidae and compare diagnosis of infection using histopathology, direct fluorescent antibody (DFA) assay, immunofluorescence antibody test (IFAT), and quantitative real-time PCR (qPCR). Tissues were analysed from 52 European rabbits (Oryctolagus cuniculus) and 7 Iberian hares (Lepus granatensis) from the Community of Madrid (Spain). Our results show that L. infantum infection is associated with only minimal histopathological lesions and that L. infantum amastigotes can be detected by DFA assay in all tissues types tested, including skin. These results were confirmed by qPCR on fresh frozen tissues in 13% of rabbits and 100% of hares. However, L. infantum DNA could not be detected by qPCR on paraffin-embedded tissue obtained by laser capture microdissection. Using the DFA assay to diagnose L. infantum infection may provide further insights into this disease in wild animals and may allow the precise tissue localization of L. infantum, thereby guiding follow-up tests with more accurate qPCR.
Anti-Angiogenic Effect of Orally Available Pemetrexed for Metronomic Chemotherapy

Metronomic chemotherapy (MCT) is defined as the frequent administration of low-dose chemotherapeutics, without long drug-free periods, with the exertion of antitumor activity exclusively through anti-angiogenic mechanisms. In this study, we have developed an orally available formulation of pemetrexed (PMX) for MCT. PMX was first complexed ionically with Nα-deoxycholyl-l-lysyl-methylester (DCK) as the permeation enhancer. This was followed by dispersion with poloxamer 188 and Labrasol to form the solid oral formulation of PMX (PMX/DCK-OP). PMX/DCK-OP exhibited a 10.6-fold increase in permeability across a Caco-2 cell monolayer compared to PMX alone. This resulted in a 70-fold increase in the oral bioavailability of PMX/DCK-OP in mice over oral PMX alone. In the A549 xenograft model, tumor volume was reduced by 51.1% in the PMX/DCK-OP treated group compared to only 32.8% in the maximum tolerated dose (MTD)-treated group. Furthermore, PMX/DCK-OP exhibited a significant anti-angiogenic effect on the A549 xenograft mice when compared to the MTD-treated group, as indicated by microvessel density quantification for CD-31. In addition, PMX/DCK-OP enhanced the release of an endogenous angiogenesis inhibitor, thrombospondin-1 (TSP-1), into both the blood circulation and the tumor microenvironment. Therefore, due to its oral route of administration, PMX/DCK-OP appears to be a better alternative to the conventional treatment of PMX.
Clinical trials in amyotrophic lateral sclerosis.

PURPOSE OF REVIEW To review new developments in the field of amyotrophic lateral sclerosis (ALS) clinical trial design and to review the implications of the latest ALS clinical trials. RECENT FINDINGS There has been substantial reflection on how clinical trials in ALS are best conducted. The revised Airlie House recommendations are an important milestone and should guide trial design. In addition, innovations using individualized risk-based eligibility criteria, adaptive designs, joint modelling, patient-centred approaches, and remote collection of data show real promise. Edaravone was shown to have benefit on function in a well defined subset of patients with ALS, although there are concerns about the generalizability of the findings. Studies of arimoclomol, inosine, and cellular therapies have demonstrated promising signals in early phase work and are being taken forward into larger studies. Well conducted studies of rasagaline did not show an effect on primary outcome measures. SUMMARY For many decades there has been regular disappointment with the results of clinical trials. With the innovations in trial design and advances in our basic understanding of the biology of ALS, the prospects for a step change in treatments for people affected by ALS are strong.
Do Social Determinants Define “Too Sick” to Transplant in Patients With End-stage Liver Disease?

Background. Delisting for being “too sick” to be transplanted is subjective. Previous work has demonstrated that the mortality of patients delisted for “too sick” is unexpectedly low. Transplant centers use their best clinical judgment for determining “too sick,” but it is unclear how social determinants influence decisions to delist for “too sick. ” We hypothesized that social determinants and Donor Service Area (DSA) characteristics may be associated with determination of “too sick” to transplant. Methods. Data were obtained from the Scientific Registry of Transplant Recipients for adults listed and removed from the liver transplant waitlist from 2002 to 2017. Patients were included if delisted for “too sick. ” Our primary outcome was Model for End-Stage Liver Disease (MELD) score at waitlist removal for “too sick. ” Regression assessed the association between social determinants and MELD at removal for “too sick. ” Results. We included 5250 delisted for “too sick” at 127 centers, in 53 DSAs, over 16 years. The mean MELD at delisting for “too sick” was 25.8 (SD ± 11.2). On adjusted analysis, social determinants including age, race, sex, and education predicted the MELD at delisting for “too sick” (P < 0.05). Conclusions. There is variation in delisting MELD for “too sick” score across DSA and time. While social determinants at the patient and system level are associated with delisting practices, the interplay of these variables warrants additional research. In addition, center outcome reports should include waitlist removal rate for “too sick” and waitlist death ratios, so waitlist management practice at individual centers can be monitored.
Beliefs, Practices and Health Care Seeking Behavior of Parents Regarding Fever in Children

Background and objectives: Fever in children is one of the most common reasons for seeking medical attention. Parents often have misconceptions about the effects to fever, which leads to inappropriate use of medication and nonurgent visits to emergency departments (ED). The aim of this study was to clarify the beliefs on the effects and management of fever and to identify healthcare seeking patterns among parents of febrile children in Latvia. Materials and Methods: Parents and legal guardians of children attending ED with febrile illness were included in the study. Participants were recruited in Children’s Clinical University Hospital (CCUH) in Riga, and in six regional hospitals in Latvia. Data on beliefs about fever, administration of antipyretics, healthcare-seeking behavior, and experience in communication with health care workers were collected via questionnaire. Results: In total, 355 participants were enrolled: 199 in CCUH and 156 in regional hospitals; 59.2% of participants considered fever itself as indicative of serious illness and 92.8% believed it could raise the child’s body temperature up to a dangerous level. Antipyretics were usually administered at median temperature of 38.0 °C, and the median temperature believed to be dangerous was 39.7 °C; 56.7% of parents usually contacted a doctor within the first 24 h of the illness. Parents who believed that lower temperatures are dangerous to a child were more likely to contact a doctor earlier and out-of-hours; 60.1% of participants had contacted their family doctor prior their visit to ED. Parental evaluation of satisfaction with the information and reassurance provided by the doctors at the hospital was higher than of that provided by their family doctor; 68.2% of participants felt safer when their febrile children were treated at the hospital. Conclusions: Fever itself was regarded as indicative of serious illness and potentially dangerous to the child’s life. These misconceptions lead to inappropriate administration of antipyretics and early-seeking of medical attention, even out-of-hours. Hospital environment was viewed as safer and more reassuring when dealing with febrile illness in children. More emphasis must be placed on parental education on proper management of fever, especially in primary care
TiO2 and PEEK Reinforced 3D Printing PMMA Composite Resin for Dental Denture Base Applications

The future of manufacturing applications in three-dimensional (3D) printing depends on the improvement and the development of materials suitable for 3D printing technology. This study aims to develop an applicable and convenient protocol for light-curing resin used in 3D industry, which could enhance antibacterial and mechanical properties of polymethyl methacrylate (PMMA) resin through the combination of nano-fillers of surface modified titanium dioxide (TiO2) and micro-fillers of polyetheretherketone (PEEK). PMMA-based composite resins with various additions of TiO2 and PEEK were prepared and submitted to characterizations including mechanical properties, distribution of the fillers (TiO2 or/and PEEK) on the fractured surface, cytotoxicity, antibacterial activity, and blood compatibility assessment. These results indicated that the reinforced composite resins of PMMA (TiO2-1%-PEEK-1%) possessed the most optimized properties compared to the other groups. In addition, we found the addition of 1% of TiO2 would be an effective amount to enhance both mechanical and antibacterial properties for PMMA composite resin. Furthermore, the model printed by PMMA (TiO2-1%-PEEK-1%) composite resin showed a smooth surface and a precise resolution, indicating this functional dental restoration material would be a suitable light-curing resin in 3D industry.
Radioprotective Effect of Hesperidin: A Systematic Review

Background and objectives: Ionizing radiation (IR) has been of immense benefit to man, especially for medical purposes (diagnostic imaging and radiotherapy). However, the risks of toxicity in healthy normal cells, leading to cellular damage as well as early and late side effects, have been major drawbacks. The aim of this study was to evaluate the radioprotective effect of hesperidin against IR-induced damage. Materials and Methods: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) were applied in reporting this study. A search was conducted using the electronic databases PubMed, Scopus, Embase, Google Scholar, and www.ClinicalTrials. gov for information about completed or ongoing clinical trials. Results: From our search results, 24 studies involving rats, mice, and cultured human and animal cells were included. An experimental case—control design was used in all studies. The studies showed that the administration of hesperidin reduced oxidative stress and inflammation in all investigated tissues. Furthermore, it increased 30-day and 60-day survival rates and protected against DNA damage. The best radioprotection was obtained when hesperidin was administered before irradiation. Conclusions: The results of the included studies support the antioxidant, anti-inflammatory, and antiapoptotic abilities of hesperidin as a potential radioprotective agent against IR-induced damage. We recommend future clinical trials for more insights.
A Brief Measure of Interpersonal Interaction for 2-Player Serious Games: Questionnaire Validation

Background Competitive and cooperative serious games have become increasingly popular in areas such as rehabilitation and education and have several potential advantages over single-player games. However, they are not suitable for everyone, and the user experience in competitive and cooperative serious games depends on many factors. One important factor is the verbal interaction between players, but the effect of this factor has not been extensively studied because of the lack of a validated measurement tool. Objective This paper aimed to validate a brief questionnaire that measures the verbal interaction between 2 players of a serious game. The questionnaire consists of 8 questions pertaining to the amount of conversation, its valence (positive or negative emotion), and its game relatedness. Methods The questionnaire was validated with 30 pairs of participants who played a competitive serious game for 10 min while being recorded with cameras. The questionnaire was filled out by both participants, an in-person observer, and 2 members of our research group who watched the videos. Results from these raters were used to develop questionnaire instructions, and the finalized questionnaire was given to 2 additional raters who were trained on 5 videos and then rated the other 25 videos independently. Results The questionnaire’s interrater reliability is excellent for the amount of conversation and its game relatedness (intraclass correlation coefficients [ICCs] above 0.9). Interrater reliability is fair to good for conversation valence (ICCs between 0.4 and 0.7). We believe that the lower interrater reliability for valence is primarily because of a limited spread of valence values in our sample. Furthermore, questionnaire ratings were significantly correlated with players’ personality characteristics (eg, amount of conversation was correlated with extraversion) and pressure/tension experienced in the competitive game. Conclusions The validated questionnaire has the potential to be a useful tool for studying user experience in competitive and cooperative serious games. Furthermore, it could be adapted for other applications such as entertainment games. However, it has only been validated with unimpaired university students in a 2-player competitive serious game and should next be validated with different target populations (eg, stroke survivors) and different game designs (eg, cooperative games).
Dietary Intake and Its Determinants Among Adults Living in the Metropolitan Area of Puerto Rico

There is scarce information regarding the dietary intake of adults living in Puerto Rico (PR). We aimed to assess intake of nutrients and foods, adherence to recommended intake of nutrients and diet quality, and sociodemographic and lifestyle factors correlated with diet quality among adults in the San Juan metropolitan area of PR. Data were obtained from participants of the cross-sectional convenience-sample Puerto Rico Assessment of Diet, Lifestyle, and Diseases (n = 248; ages 30–75 years). Diet quality was defined using the Alternate Healthy Eating Index 2010 (AHEI; range 0–110 indicating lower–higher quality). Linear regression models were used to relate AHEI to sociodemographic and lifestyle factors. Most participants met the Estimated Average Requirement (EAR) for iron, folate, and vitamins B12 and B6; 61% met the EAR for magnesium and 56% for calcium. Only 4% met the EAR for vitamin D, and 7% met the adequate intake for potassium. The main contributors to total energy intake were sugary beverages (11.8%), sweets/desserts (10.2%), dairy (8.5%), mixed dishes (7.6%), starches (6.3%), fast foods (5.5%), and rice (4.9%). The mean (SD) AHEI score was 59.8 (11.0). The lowest AHEI components for which recommended servings were met were red/processed meats, fruit, sodium, sugary beverages, and polyunsaturated fats, and the highest were nuts/legumes, omega-3 fats, and whole grains. Significantly higher AHEI scores were noted for older adults, other ethnicities (vs. Puerto Rican), being single, having some college or higher education, and never/formerly smoking. Adults living in PR report healthy and unhealthy dietary intakes, providing an opportunity to improve diet at the population level.
Clinical and virological outcomes of TB/HIV co-infected patients treated with dolutegravir-based HIV antiretroviral regimens: Programmatic experience from Botswana

Background: Dolutegravir (DTG) has recently been recommended as a preferred first-line regimen for the treatment of new and treatment experienced HIV infected patients. However, potential drug interactions between DTG and rifampicin remain a clinical and public health concern. Methods: We analyzed HIV and TB treatment outcomes of HIV-infected patients concomitantly receiving rifampicin- and DTG-based regimens under programmatic conditions in Botswana. The outcomes of interest were successful TB treatment and viral load suppression. We used multivariable logistic models to determine predictors for each outcome of interest. Results: A total of 1,225 patients were included in the analysis to evaluate predictors of successful TB outcome. Among patients on DTG and non-DTG regimens, 90.9% and 88.3% achieved favorable TB treatment outcomes, respectively. Of those who received DTG-based regimen; 44% received once-daily dosing and 53% twice-daily dosing. We found that DTG was associated with favorable TB treatment outcome (adjusted odds ratio [aOR] = 1.56; 95% confidence interval [CI] = 1.06, 2.31), after adjusting for age, gender, and CD4 cell counts. High rates of viral load suppression were found across all ART regimen categories (>92% for all). We did not find an independent association between DTG and viral suppression after adjustment of other covariates Conclusions: The use of DTG-based ART regimens in patients coinfected with TB and HIV lead to favorable TB and HIV treatment outcomes, comparable to those achieved with alternative ART regimens. Our results provide reassurance to TB and HIV programs about the overall programmatic concomitant use of these first-line treatment regimens for the management of HIV and TB coinfected patients.
Modelling of Mechanical Behavior of Biopolymer Alginate Aerogels Using the Bonded-Particle Model

A novel mesoscale modelling approach for the investigation of mechanical properties of alginate aerogels is proposed. This method is based on the discrete element method and bonded-particle model. The nanostructure of aerogel is not directly considered, instead the highly porous structure of aerogels is represented on the mesoscale as a set of solid particles connected by solid bonds. To describe the rheological material behavior, a new elastic-plastic functional model for the solids bonds has been developed. This model has been derived based on the self-similarity principle for the material behavior on the macro and mesoscales. To analyze the effectiveness of the proposed method, the behavior of alginate aerogels with different crosslinking degrees (calcium content) was analyzed. The comparison between experimental and numerical results has shown that the proposed approach can be effectively used to predict the mechanical behavior of aerogels on the macroscale.
Initial Dietary Protein Intake Influence Muscle Function Adaptations in Older Men and Women Following High-Intensity Interval Training Combined with Citrulline

Background: This study evaluates whether the initial amount of dietary protein intake could influence the combined effect of high-intensity interval training (HIIT) and citrulline (CIT), or HIIT alone, on body composition, muscle strength, and functional capacities in obese older adults. Methods: Seventy-three sedentary obese older men and women who completed a 12-week elliptical HIIT program with double-blinded randomized supplementation of CIT or placebo (PLA) were divided into four groups according to their initial protein intake (CIT–PROT+: n = 21; CIT–PROT−: n = 19; PLA–PROT+: n = 19; PLA–PROT−: n = 14). Body composition (fat and fat-free masses), handgrip (HSr) strength, knee extensor (KESr) strength, muscle power, and functional capacities were measured pre-intervention and post-intervention. Results: Following the intervention, the four groups improved significantly regarding all the parameters measured. For the same initial amount of protein intake, the CIT–PROT− group decreased more gynoid fat mass (p = 0.04) than the PLA–PROT− group. The CIT–PROT+ group increased more KESr (p = 0.04) than the PLA–PROT+ group. In addition, the CIT–PROT− group decreased more gynoid FM (p = 0.02) and improved more leg FFM (p = 0.02) and HSr (p = 0.02) than the CIT–PROT+ group. Conclusion: HIIT combined with CIT induced greater positive changes than in the PLA groups. The combination seems more beneficial in participants consuming less than 1 g/kg/d of protein, since greater improvements on body composition and muscle strength were observed.
Where did the reference desk go? Transforming staff and space to meet user needs

ABSTRACT A sharp decline in the number of reference queries prompted the library administration at Indiana State University to begin a project to combine the circulation, reference, and IT desks to reduce staffing at a new consolidated service point. All faculty and staff in the reference/instruction and circulation units participated in the project. The new arrangement and subsequent removal of librarians from routine desk duties have expanded instructional opportunities, consistent with the university's goals. Project participants plan further assessments to better determine the impacts of the new service arrangements.