Miracle-dz/UniFAR-FTUs huggingface dataset:
HER2-Targeted Immunotherapy and Combined Protocols Showed Promising Antiproliferative Effects in Feline Mammary Carcinoma Cell-Based Models

Simple Summary Mammary tumors are common in cats, presenting an aggressive behavior with high tumor recurrence. Therefore, new and efficient therapeutic protocols are urgent. Monoclonal antibodies (mAbs; ADC) are widely used in human breast cancer therapy, inhibiting the HER2 dimerization and leading to cell apoptosis. Furthermore, drug combinations, with tyrosine kinase inhibitors (TKi) are valuable in patients’ therapeutic protocols. In this study, two mAbs, and an ADC, as well as combined protocols between mAbs and mAbs plus lapatinib (TKi) were tested to address if the drugs could be used as new therapeutic options in feline mammary tumors. All the compounds and the combined treatments revealed valuable antiproliferative effects, and a conserved cell death mechanism, by apoptosis, in the feline cell lines, where the mutations found in the extracellular domain of the HER2 suggest no immunotherapy resistance. Abstract Feline mammary carcinoma (FMC) is a highly prevalent tumor, showing aggressive clinicopathological features, with HER2-positive being the most frequent subtype. While, in human breast cancer, the use of anti-HER2 monoclonal antibodies (mAbs) is common, acting by blocking the extracellular domain (ECD) of the HER2 protein and by inducing cell apoptosis, scarce information is available on use these immunoagents in FMC. Thus, the antiproliferative effects of two mAbs (trastuzumab and pertuzumab), of an antibody–drug conjugate compound (T-DM1) and of combined treatments with a tyrosine kinase inhibitor (lapatinib) were evaluated on three FMC cell lines (CAT-MT, FMCm and FMCp). In parallel, the DNA sequence of the her2 ECD (subdomains II and IV) was analyzed in 40 clinical samples of FMC, in order to identify mutations, which can lead to antibody resistance or be used as prognostic biomarkers. Results obtained revealed a strong antiproliferative effect in all feline cell lines, and a synergistic response was observed when combined therapies were performed. Additionally, the mutations found were not described as inducing resistance to therapy in breast cancer patients. Altogether, our results suggested that anti-HER2 mAbs could become useful in the treatment of FMC, particularly, if combined with lapatinib, since drug-resistance seems to be rare.
Transition to adult care: Exploring factors associated with transition readiness among adolescents and young people in adolescent ART clinics in Uganda

Background Transition readiness refers to a client who knows about his/her illness and oriented towards future goals and hopes, shows skills needed to negotiate healthcare, and can assume responsibility for his/ her treatment, and participate in decision-making that ensures uninterrupted care during and after the care transition to adult HIV care. There is a paucity of research on effective transition strategies. This study explored factors associated with adolescent readiness for the transition into adult care in Uganda. Methods A cross-sectional study was conducted among 786 adolescents, and young people living with HIV randomly selected from 9 antiretroviral therapy clinics, utilizing a structured questionnaire. The readiness level was determined using a pre-existing scale from the Ministry of Health, and adolescents were categorized as ready or not ready for the transition. Bivariate and multivariate analyses were conducted. Results A total of 786 adolescents were included in this study. The mean age of participants was 17.48 years (SD = 4). The majority of the participants, 484 (61.6%), were females. Most of the participants, 363 (46.2%), had no education. The majority of the participants, 549 (69.8%), were on first-line treatment. Multivariate logistic regression analysis found that readiness to transition into adult care remained significantly associated with having acquired a tertiary education (AOR 4.535, 95% CI 1.243–16.546, P = 0.022), trusting peer educators for HIV treatment (AOR 16.222, 95% CI 1.835–143.412, P = 0.012), having received counselling on transition to adult services (AOR 2.349, 95% CI 1.004–5.495, P = 0.049), having visited an adult clinic to prepare for transition (AOR 6.616, 95% CI 2.435–17.987, P = < 0.001) and being satisfied with the transition process in general (AOR 0.213, 95% CI 0.069–0.658, P = 0.007). Conclusion The perceived readiness to transition care among young adults was low. A series of individual, social and health system and services factors may determine successful transition readiness among adolescents in Uganda. Transition readiness may be enhanced by strengthening the implementation of age-appropriate and individualized case management transition at all sites while creating supportive family, peer, and healthcare environments.
A Decade of Organs-on-a-Chip Emulating Human Physiology at the Microscale: A Critical Status Report on Progress in Toxicology and Pharmacology

Organ-on-a-chip technology has the potential to accelerate pharmaceutical drug development, improve the clinical translation of basic research, and provide personalized intervention strategies. In the last decade, big pharma has engaged in many academic research cooperations to develop organ-on-a-chip systems for future drug discoveries. Although most organ-on-a-chip systems present proof-of-concept studies, miniaturized organ systems still need to demonstrate translational relevance and predictive power in clinical and pharmaceutical settings. This review explores whether microfluidic technology succeeded in paving the way for developing physiologically relevant human in vitro models for pharmacology and toxicology in biomedical research within the last decade. Individual organ-on-a-chip systems are discussed, focusing on relevant applications and highlighting their ability to tackle current challenges in pharmacological research.
Seafood Intake as a Method of Non-Communicable Diseases (NCD) Prevention in Adults

Seafood (fish in particular) is one of the main food groups in nutrition models with proven health benefits. Seafood has long been considered a very valuable dietary component, mainly due to presence of n-3 polyunsaturated fatty acids (n-3 PUFA) but it is also an important source of protein (including collagen), anserine, taurine, iodine, selenium, vitamin A, vitamin K, vitamin D, tocopherols, B vitamins and astaxanthin. Considering the beneficial effects of these ingredients on blood pressure, lipid profile and the inflammatory process, seafood should be an essential component of the diet. Non-communicable diseases (NCD) such as cardiovascular diseases, cancer, diabetes and mental disorder, chronic respiratory diseases are common diseases associated with advanced age. Promotion of a healthy lifestyle (including proper nutritional behavior) and prevention of diseases are the most effective and efficient ways to decrease premature mortality from NCD and to maintain mental health and well-being. This review article shows the potential preventive and therapeutic effects of seafood with an emphasis on fish. Our narrative review presents the results of systematic reviews and meta-analysis.
Estimation of 6D Object Pose Using a 2D Bounding Box

This paper provides an efficient way of addressing the problem of detecting or estimating the 6-Dimensional (6D) pose of objects from an RGB image. A quaternion is used to define an object′s three-dimensional pose, but the pose represented by q and the pose represented by -q are equivalent, and the L2 loss between them is very large. Therefore, we define a new quaternion pose loss function to solve this problem. Based on this, we designed a new convolutional neural network named Q-Net to estimate an object’s pose. Considering that the quaternion′s output is a unit vector, a normalization layer is added in Q-Net to hold the output of pose on a four-dimensional unit sphere. We propose a new algorithm, called the Bounding Box Equation, to obtain 3D translation quickly and effectively from 2D bounding boxes. The algorithm uses an entirely new way of assessing the 3D rotation (R) and 3D translation rotation (t) in only one RGB image. This method can upgrade any traditional 2D-box prediction algorithm to a 3D prediction model. We evaluated our model using the LineMod dataset, and experiments have shown that our methodology is more acceptable and efficient in terms of L2 loss and computational time.
Intelligent Bone Age Assessment: An Automated System to Detect a Bone Growth Problem Using Convolutional Neural Networks with Attention Mechanism

Skeletal bone age assessment using X-ray images is a standard clinical procedure to detect any anomaly in bone growth among kids and babies. The assessed bone age indicates the actual level of growth, whereby a large discrepancy between the assessed and chronological age might point to a growth disorder. Hence, skeletal bone age assessment is used to screen the possibility of growth abnormalities, genetic problems, and endocrine disorders. Usually, the manual screening is assessed through X-ray images of the non-dominant hand using the Greulich–Pyle (GP) or Tanner–Whitehouse (TW) approach. The GP uses a standard hand atlas, which will be the reference point to predict the bone age of a patient, while the TW uses a scoring mechanism to assess the bone age using several regions of interest information. However, both approaches are heavily dependent on individual domain knowledge and expertise, which is prone to high bias in inter and intra-observer results. Hence, an automated bone age assessment system, which is referred to as Attention-Xception Network (AXNet) is proposed to automatically predict the bone age accurately. The proposed AXNet consists of two parts, which are image normalization and bone age regression modules. The image normalization module will transform each X-ray image into a standardized form so that the regressor network can be trained using better input images. This module will first extract the hand region from the background, which is then rotated to an upright position using the angle calculated from the four key-points of interest. Then, the masked and rotated hand image will be aligned such that it will be positioned in the middle of the image. Both of the masked and rotated images will be obtained through existing state-of-the-art deep learning methods. The last module will then predict the bone age through the Attention-Xception network that incorporates multiple layers of spatial-attention mechanism to emphasize the important features for more accurate bone age prediction. From the experimental results, the proposed AXNet achieves the lowest mean absolute error and mean squared error of 7.699 months and 108.869 months2, respectively. Therefore, the proposed AXNet has demonstrated its potential for practical clinical use with an error of less than one year to assist the experts or radiologists in evaluating the bone age objectively.
Fatigue in Women with Fibromyalgia: A Gene-Physical Activity Interaction Study

Fatigue is a cardinal symptom in fibromyalgia. Fatigue is assumed to be the result of genetic susceptibility and environmental factors. We aimed at examining the role of genetic susceptibility for fatigue in southern Spanish women with fibromyalgia, by looking at single nucleotide polymorphisms in 34 fibromyalgia candidate-genes, at the interactions between genes, and at the gene-physical activity interactions. We extracted DNA from saliva of 276 fibromyalgia women to analyze gene-polymorphisms. Accelerometers registered physical activity and sedentary behavior. Fatigue was assessed with the Multidimensional Fatigue Inventory. Based on the Bonferroni’s and False Discovery Rate values, we found that the genotype of the rs4453709 polymorphism (sodium channel protein type 9 subunit alpha, SCN9A, gene) was related to reduced motivation (AT carriers showed the highest reduced motivation) and reduced activity (AA carriers showed the lowest reduced activity). Carriers of the heterozygous genotype of the rs1801133 (methylene tetrahydrofolate reductase, MTHFR, gene) or rs4597545 (SCN9A gene) polymorphisms who were physically active reported lower scores on fatigue compared to their inactive counterparts. Highly sedentary carriers of the homozygous genotype of the rs7607967 polymorphism (AA/GG genotype; SCN9A gene) presented more reduced activity (a dimension of fatigue) than those with lower levels of sedentary behavior. Collectively, findings from the present study suggest that the contribution of genetics and gene-physical activity interaction to fatigue in fibromyalgia is modest.
Repeatability of an automated ETDRS contrast threshold measurement

This technical report presents the repeatability of an automated Early Treatment Diabetic Retinopathy Study (ETDRS) contrast threshold (ETDRS‐CT) test in participants (N = 40) with normal vision as well as in subjects with reduced visual acuity. The automated ETDRS‐CT test showed good test‐retest repeatability between the two administrations in both normal and reduced vision participants. Measurement at the retest yielded 0.05 log higher contrast sensitivity than at the first measurement, which might be due to a learning effect among participants.
Water adsorption behaviour of CAU-10-H: a thorough investigation of its structure–property relationships

Aluminium isophthalate CAU-10-H [Al(OH)(benzene-1,3-dicarboxylate)]·nH2O exhibits water adsorption characteristics which make it a promising adsorbent for application in heat-exchange processes. Herein we prepared a stable coating of this MOF and evaluated its long-term stability under closed-cycle conditions for 10 000 water adsorption and desorption cycles, which are typical lifetimes for adsorption heat storage (AHS) applications. No degradation of the adsorption capacity could be observed which makes CAU-10-H the most stable MOF under these humid cycling conditions reported until now. Moreover, thermophysical properties like thermal conductivity and heat of adsorption were directly measured. In order to identify the structural features associated with the adsorption behaviour, the structural differences between the dry and the water loaded CAU-10-H were studied by Rietveld refinements and second harmonic generation (SHG) microscopy. The observed transition of space group symmetry from I41 to I41/amd between the humid and dry forms is induced by the adsorption/desorption of water into/out of the MOF channels. This originates from a torsional motion around the C–C bond between the carboxylate groups and the aromatic ring in half of the linker molecules. These observations are in excellent agreement with molecular dynamics simulations which confirm the energetic benefit of this transition.
Does Protein Supplementation Support Adaptations to Arduous Concurrent Exercise Training? A Systematic Review and Meta-Analysis with Military Based Applications

We evaluated the impact of protein supplementation on adaptations to arduous concurrent training in healthy adults with potential applications to individuals undergoing military training. Peer-reviewed papers published in English meeting the population, intervention, comparison and outcome criteria were included. Database searches were completed in PubMed, Web of science and SPORTDiscus. Study quality was evaluated using the COnsensus based standards for the selection of health status measurement instruments checklist. Of 11 studies included, nine focused on performance, six on body composition and four on muscle recovery. Cohen’s d effect sizes showed that protein supplementation improved performance outcomes in response to concurrent training (ES = 0.89, 95% CI = 0.08–1.70). When analysed separately, improvements in muscle strength (SMD = +4.92 kg, 95% CI = −2.70–12.54 kg) were found, but not in aerobic endurance. Gains in fat-free mass (SMD = +0.75 kg, 95% CI = 0.44–1.06 kg) and reductions in fat-mass (SMD = −0.99, 95% CI = −1.43–0.23 kg) were greater with protein supplementation. Most studies did not report protein turnover, nitrogen balance and/or total daily protein intake. Therefore, further research is warranted. However, our findings infer that protein supplementation may support lean-mass accretion and strength gains during arduous concurrent training in physical active populations, including military recruits.
Prevalence of Skin Reactions and Self-Reported Allergies in 5 Countries with Their Social Impact Measured through Quality of Life Impairment

Background: The prevalence of allergies increases worldwide. Allergies may increase the risk of skin reactions. Objective: To evaluate the prevalence of allergies and skin reactions in the adult population, the strength of their relationship, and their impact on the quality of life. Methods: An online survey was conducted in a representative population of 11,067 adults from China, USA, Brazil, Russia, and France. Results: Overall, 35.6% of respondents reported having allergies, they were predominantly fair-skinned women, and younger than responders reporting no allergy. Among patients reporting allergies, 68.6% declared that their allergy makes their skin reacts. A strong association between allergy and major skin reactions was observed, which were associated with skin discomforts such as itching, burning, and pain. Skin discomforts were associated with an increased risk of quality of life alteration. Conclusions: Quantifying the prevalence and the association of allergies with skin reactions and discomfort sensations is critical to evaluating the impact on quality of life. Since skin barrier alteration is hypothesized as a risk factor and a route of sensitization for allergy development, the daily use of topical treatments, such as moisturizers, could help prevent allergic skin reactions, discomfort and impaired quality of life in individuals with an altered skin barrier.
Relationship between Brain Tissue Changes and Blood Biomarkers of Cyclophilin A, Heme Oxygenase-1, and Inositol-Requiring Enzyme 1 in Patients with Alzheimer’s Disease

Cyclophilin A (CypA), heme oxygenase-1 (HO-1), and inositol-requiring enzyme 1 (IRE1) are believed to be associated with Alzheimer’s disease (AD). In this study, we investigated the association between gray matter volume (GMV) changes and blood levels of CypA, HO-1, and IRE1 in cognitively normal (CN) subjects and those with amnestic mild cognitive impairment (aMCI) and AD. Forty-five elderly CN, 34 aMCI, and 39 AD subjects were enrolled in this study. The results of voxel-based multiple regression analysis showed that blood levels of CypA, HO-1, and IRE1 were correlated with GMV on brain magnetic resonance imaging (MRI) in the entire population (p = 0.0005). The three serum protein levels were correlated with GMV of signature AD regions in the population as a whole. CypA values increased with increasing GMV in the occipital gyrus (r = 0.387, p < 0.0001) and posterior cingulate (r = 0.196, p = 0.034). HO-1 values increased with increasing GMV at the uncus (r = 0.307, p = 0.0008), lateral globus pallidus and putamen (r = 0.287, p = 0.002), and hippocampus (r = 0.197, p = 0.034). IRE1 values decreased with increasing GMV at the uncus (r = −0.239, p = 0.010) and lateral globus pallidus and putamen (r = −0.335, p = 0.0002). Associations between the three serum protein levels and regional GMV indicate that the blood levels of these biomarkers may reflect the pathological mechanism of AD in the brain.
Single Ingestion of Trehalose Enhances Prolonged Exercise Performance by Effective Use of Glucose and Lipid in Healthy Men

Trehalose increases blood glucose levels slowly and induces a slight insulin response. The present study aimed to study the effect of trehalose on prolonged exercise performance. The participants were 12 healthy men (age: 21.3 ± 0.9 y). After an overnight fast (12 h), they first exercised with a constant load (intensity: 40% V˙O2peak) for 60 min using a bicycle ergometer. They continued to exercise with a constant load (40% V˙O2peak) for 30 min between four sets of the 30-s Wingate test. After the 1st set, each participant ingested 500 mL water (control), 8% glucose, or 8% trehalose in three trials. These three trials were at least one week apart and were conducted in a double-blind and randomized crossover manner. Blood was collected for seven biochemical parameters at 12 time points during the experiment. The area under the curve of adrenaline after ingestion of trehalose was significantly lower than that for water and tended to be lower than that for glucose in the later stage of the exercise. Lower secretion of adrenaline after a single dose of 8% trehalose during prolonged exercise reflected the preservation of carbohydrates in the body in the later stage of the exercise. In conclusion, a single ingestion of trehalose helped to maintain prolonged exercise performance.
Assessing the Impact of a Hilly Environment on Depressive Symptoms among Community-Dwelling Older Adults in Japan: A Cross-Sectional Study

Although some neighborhood environmental factors have been found to affect depressive symptoms, few studies have focused on the impact of living in a hilly environment, i.e., land slope, on depressive symptoms among rural older adults. This cross-sectional study aimed to investigate whether a land slope is associated with depressive symptoms among older adults living in rural areas. Data were collected from 935 participants, aged 65 years and older, who lived in Shimane prefecture, Japan. Depressive symptoms were assessed using the Zung Self-Rating Depression Scale (SDS) and defined on the basis of an SDS score ≥ 40. Land slopes within a 400 m network buffer were assessed using geographic information systems. Odds ratios (ORs) with 95% confidence intervals (CIs) of depressive symptoms were estimated using logistic regression. A total of 215 (23.0%) participants reported depressive symptoms. The land slope was positively associated with depressive symptoms (OR = 1.04; 95% CI = 1.01–1.08) after adjusting for all confounders. In a rural setting, living in a hillier environment was associated with depressive symptoms among community-dwelling older adults in Japan.
Granulomatous Mastitis Due to Non-Tuberculous Mycobacteria: A Diagnostic and Therapeutic Dilemma

Non-tuberculous mycobacterial (NTM) infections of the breast are rare. These infections present as cellulitis of the breast or breast abscess. Their diagnosis poses a challenge as they manifest signs of acute inflammation, unlike tuberculous mycobacterial infections which present in a chronic pattern. However, on aspiration of pus from the site of infection, primary smear may show acid fast bacilli. This poses a diagnostic dilemma. The present case is that of a 34-year-old woman who presented with recurrent mastitis. She had history of right breast swelling, for which surgical excision had been performed three months prior at another facility. Her histopathology had showed cystic granulomatous neutrophilic mastitis (CNGM). The patient again presented with right breast abscess which was confirmed on ultrasonography. Incision and drainage along with removal of necrotic tissue was done. Primary smear of pus showed acid fast bacilli on Ziehl–Neelson staining. Bacterial culture and line probe speciation revealed non-tuberculous mycobacterium M. abscessus, which responded well to prolonged anti-microbial therapy. These rapidly growing NTM require prolonged treatment and are quite often recurrent. M. abscessus is a rare cause of CNGM, with this being only the third reported case in literature. A brief case report with a review of literature is presented.