Miracle-dz/UniFAR-FTUs huggingface dataset:
Complex Modes of Inheritance in Hereditary Red Blood Cell Disorders: A Case Series Study of 155 Patients

Hereditary erythrocytes disorders include a large group of conditions with heterogeneous molecular bases and phenotypes. We analyzed here a case series of 155 consecutive patients with clinical suspicion of hereditary erythrocyte defects referred to the Medical Genetics Unit from 2018 to 2020. All of the cases followed a diagnostic workflow based on a targeted next-generation sequencing panel of 86 genes causative of hereditary red blood cell defects. We obtained an overall diagnostic yield of 84% of the tested patients. Monogenic inheritance was seen for 69% (107/155), and multi-locus inheritance for 15% (23/155). PIEZO1 and SPTA1 were the most mutated loci. Accordingly, 16/23 patients with multi-locus inheritance showed dual molecular diagnosis of dehydrated hereditary stomatocytosis/xerocytosis and hereditary spherocytosis. These dual inheritance cases were fully characterized and were clinically indistinguishable from patients with hereditary spherocytosis. Additionally, their ektacytometry curves highlighted alterations of dual inheritance patients compared to both dehydrated hereditary stomatocytosis and hereditary spherocytosis. Our findings expand the genotypic spectrum of red blood cell disorders and indicate that multi-locus inheritance should be considered for analysis and counseling of these patients. Of note, the genetic testing was crucial for diagnosis of patients with a complex mode of inheritance.
An fMRI Investigation into the Effects of Ketogenic Medium-Chain Triglycerides on Cognitive Function in Elderly Adults: A Pilot Study

Evidence suggests that oral intake of medium-chain triglycerides (MCTs), which promote the production of ketone bodies, may improve cognitive functions in elderly people; however, the underlying brain mechanisms remain elusive. We tested the hypothesis that cognitive improvement accompanies physiological changes in the brain and reflects the use of ketone bodies as an extra energy source. To this end, by using functional magnetic resonance imaging, cerebral blood oxygenation level-dependent (BOLD) signals were measured while 20 healthy elderly subjects (14 females and 6 males; mean age: 65.7 ± 3.9 years) were engaged in executive function tasks (N-back and Go-Nogo) after ingesting a single MCT meal (Ketonformula®) or placebo meal in a randomized, double-blind placebo-controlled design (UMIN000031539). Morphological characteristics of the brain were also examined in relation to the effects of an MCT meal. The MCT meal improved N-back task performance, and this was prominent in subjects who had reduced grey matter volume in the dorsolateral prefrontal cortex (DLPFC), a region known to promote executive functions. When the participants were dichotomized into high/low level groups of global cognitive function at baseline, the high group showed improved N-back task performance, while the low group showed improved Go-Nogo task performance. This was accompanied by decreased BOLD signals in the DLPFC, indicative of the consumption of ketone bodies as an extra energy source.
Quality of Life in European Older Adults of SHARE Wave 7: Comparing the Old and the Oldest-Old

CASP-12 (Control, Autonomy, Self-realization, and Pleasure scale) is one of the most common internationally used measures for quality of life in older adults, although its structure is not clearly established. Current research aims to test the factor structure of the CASP-12, so as to provide evidence on reliability and external validity, and to test for measurement invariance across age groups. Data from 61,355 Europeans (≥60 years old) from the Survey of Health, Ageing and Retirement in Europe wave 7 were used. CASP-12, EURO-D (European depression scale), self-perceived health, and life satisfaction measurements were included. Reliability and validity coefficients, competing confirmatory factor models, and standard measurement invariance routine were estimated. A second-order factor model with the original factor structure was retained. The scale showed adequate reliability coefficients except for the autonomy dimension. The correlation coefficients for external validity were all statistically significant. Finally, CASP-12 is scalar invariant across age. We conclude that the best-fitting factor structure retained allows using CASP-12 either by factors, or as an overall score, depending on the research interests. Findings related to CASP-12 measurement invariance encourage its use in the oldest-old too. When comparing the dimensions across age groups, as people age, autonomy slightly increases and the rest of the dimensions decline.
Clinical and electrophysiological predictors of device-detected new-onset atrial fibrillation during 3 years after cardiac surgery

Abstract Aims Postoperative atrial fibrillation (POAF) after cardiac surgery is an independent predictor of stroke and mortality late after discharge. We aimed to determine the burden and predictors of early (up to 5th postoperative day) and late (after 5th postoperative day) new-onset atrial fibrillation (AF) using implantable loop recorders (ILRs) in patients undergoing open chest cardiac surgery. Methods and results Seventy-nine patients without a history of AF undergoing cardiac surgery underwent peri-operative high-resolution mapping of electrically induced AF and were followed 36 months after surgery using an ILR (Reveal XT™). Clinical and electrophysiological predictors of late POAF were assessed. POAF occurred in 46 patients (58%), with early POAF detected in 27 (34%) and late POAF in 37 patients (47%). Late POAF episodes were short-lasting (mostly between 2 min and 6 h) and showed a circadian rhythm pattern with a peak of episode initiation during daytime. In POAF patients, electrically induced AF showed more complex propagation patterns than in patients without POAF. Early POAF, right atrial (RA) volume, prolonged PR time, and advanced age were independent predictors of late POAF. Conclusions Late POAF occurred in 47% of patients without a history of AF. Patients who develop early POAF, with higher age, larger RA, or prolonged PR time have a higher risk of developing late POAF and may benefit from intensified rhythm follow-up after cardiac surgery. Clinicaltrials.gov number NCT01530750.
Changes in Lithium Levels in Bees and Their Products Following Anti-Varroa Treatment

Simple Summary Varroosis caused by the ectoparasitic mite Varroa destructor has been the biggest threat to managed bee colonies over recent decades. Chemicals available to treat the disease imply problems of resistance, inconsistent efficacy, and residues in bee products. Recently, alongside novel compounds to defeat the pest, lithium chloride has been found to be effective. In this study, we found that lithium treatments leave beeswax residue-free. The possibility of decontamination in adult bees, bee bread, and uncapped honey was revealed. On the other hand, ripe honey was found to be affected by lithium administered via feeding. Case studies are necessary to uncover the level of exposition in harvested honey to estimate its potential risk once it becomes a registered veterinary medicine. Abstract The biggest threat to beekeeping is varroosis caused by the mite Varroa destructor. Chemicals available to treat this fatal disease may present problems of resistance or inconsistent efficacy. Recently, lithium chloride has appeared as a potential alternative. To date, the amount of residue lithium treatments may leave in honeybee products is poorly understood. Honeybees were fed with 25 mM lithiated sugar syrup, which was used in earlier studies. The accumulation and elimination of the lithium were monitored in bees and their products for 22 days. Lithium concentration increased in the entire body of the bees to day 4 post-treatment and then recovered rapidly to the control level. Lithium exposure was found to affect uncapped honey in the short term (<16 days), but ripe (capped) honey measured at the end of the trial remained affected. On the other hand, lithium treatment left beeswax lithium-free. Based on these data, we propose that comprehensive research on harvested honey is needed to decide on the veterinary use of lithium.
Lipofection with Synthetic mRNA as a Simple Method for T-Cell Immunomonitoring

The quantification of T-cell immune responses is crucial for the monitoring of natural and treatment-induced immunity, as well as for the validation of new immunotherapeutic approaches. The present study presents a simple method based on lipofection of synthetic mRNA in mononuclear cells as a method to determine in vitro T-cell responses. We compared several commercially available transfection reagents for their potential to transfect mRNA into human peripheral blood mononuclear cells and murine splenocytes. We also investigated the impact of RNA modifications in improving this method. Our results demonstrate that antigen-specific T-cell immunomonitoring can be easily and quickly performed by simple lipofection of antigen-coding mRNA in complex immune cell populations. Thus, our work discloses a convenient solution for the in vitro monitoring of natural or therapy-induced T-cell immune responses.
Bacterial Distribution, Biogenic Amine Contents, and Functionalities of Traditionally Made Doenjang, a Long-Term Fermented Soybean Food, from Different Areas of Korea

Since doenjang quality depends on the bacterial composition, which ambient bacteria in the environment and production conditions influence, a complete understanding of the bacteria community in traditionally madetraditionally made doenjang (TMD) from different regions is needed. We aimed to investigate the bacteria composition and quality of TMD in the following areas: Chonbuk (CB), Chonnam (CN), Kyungsang (KS), Kangwon (KW), Chungchung (CC) provinces, and Jeju island (JJ) of Korea. Twenty-nine TMD samples from different regions were used to assess biogenic amine contents, bacteria composition using next-generation methods, and metabolic functions of the bacteria using Picrust2. Bacillus spp. were isolated, and their antioxidant and fibrinolytic activities were determined. Most TMD contained high amounts of beneficial bacteria (Bacillus, Lactobacillus, Pediococcus and Weissella). However, some KS samples contained harmful bacteria (Cronobacter, Proteus and Acinetobacter) and less beneficial B. velezensis bacteria. There was no similarity among the regional groups, and each TMD showed a different bacteria composition. Shannon index, α-diversity index, was lower in TMD from JJ and CB than the other areas, but there was no β-diversity among TMD from the six area groups. Picrust2 analysis revealed that the functional potential for arachidonic acid metabolism was lowest in JJ and CN, that for supporting insulin action was highest in KS and JJ, and that for carbohydrate digestion and absorption was lowest in CB and JJ among all groups (p < 0.05) according to the Kyoto Encyclopedia of Genes and Genomes Orthology. Histamine contents were lower in CN and CC, and tyramine contents did not differ significantly. B. velezensis, B. subtilis, B. licheniformis, B. siamensis, and B. amyloliquefaciens were isolated from TMD. None of the isolated Bacillus spp. contained the B. cereus gene. B. subtilis from CN had the highest fibrinolytic activity, and B. velezensis from CB had the highest antioxidant activity. In conclusion, TMD mainly contained various Bacillus spp. , and the predominant one was B. velezensis, which had antioxidant and fibrinolytic activity regardless of the regional origin.
The Perception of Primary School Teachers Regarding the Pharmacotherapy of Attention Deficit Hyperactivity Disorder

Attention Deficit Hyperactivity Disorder (ADHD) is raising concerns across health systems, affecting about 5% of the school-age population. Therapy usually involves psychostimulants, which are prone to adverse drug reactions (ADRs). Teachers have many contact hours with children and can easily detect behavioral changes upon the beginning of medication. However, few studies have focused on the role of teachers in the management of ADHD children and detection of ADRs. The present work aimed to characterize the perception of primary school teachers regarding the impact of ADHD therapeutics. A questionnaire was constructed focused on teachers’ training regarding ADHD and its therapy; experience with students with ADHD; changes upon beginning of medication; and observation of ADRs. A total of 107 completed questionnaires were obtained. The results indicate that more than 40% of the inquired teachers have received training in ADHD, but in most cases, the theme of therapeutics was absent from that training. The vast majority of teachers (91.6%) have had students with ADHD and observed mood alterations associated with medications. More than 60% of the teachers answered that they are aware of the ADRs and of these, 24% have already detected them in their students. The teachers reported the observed ADRs to parents in 93% of the cases and to doctors in 28% of the cases. In conclusion, the results show the need to reinforce teachers’ training in ADHD and its therapeutics.
Long-Term Suppression of c-Jun and nNOS Preserves Ultrastructural Features of Lower Motor Neurons and Forelimb Function after Brachial Plexus Roots Avulsion

Brachial plexus root avulsions cause debilitating upper limb paralysis. Short-term neuroprotective treatments have reported preservation of motor neurons and function in model animals while reports of long-term benefits of such treatments are scarce, especially the morphological sequelae. This morphological study investigated the long-term suppression of c-Jun- and neuronal nitric oxide synthase (nNOS) (neuroprotective treatments for one month) on the motor neuron survival, ultrastructural features of lower motor neurons, and forelimb function at six months after brachial plexus roots avulsion. Neuroprotective treatments reduced oxidative stress and preserved ventral horn motor neurons at the end of the 28-day treatment period relative to vehicle treated ones. Motor neuron sparing was associated with suppression of c-Jun, nNOS, and pro-apoptotic proteins Bim and caspases at this time point. Following 6 months of survival, neutral red staining revealed a significant loss of most of the motor neurons and ventral horn atrophy in the avulsed C6, 7, and 8 cervical segments among the vehicle-treated rats (n = 4). However, rats that received neuroprotective treatments c-Jun JNK inhibitor, SP600125 (n = 4) and a selective inhibitor of nNOS, 7-nitroindazole (n = 4), retained over half of their motor neurons in the ipsilateral avulsed side compared. Myelinated axons in the avulsed ventral horns of vehicle-treated rats were smaller but numerous compared to the intact contralateral ventral horns or neuroprotective-treated groups. In the neuroprotective treatment groups, there was the preservation of myelin thickness around large-caliber axons. Ultrastructural evaluation also confirmed the preservation of organelles including mitochondria and synapses in the two groups that received neuroprotective treatments compared with vehicle controls. Also, forelimb functional evaluation demonstrated that neuroprotective treatments improved functional abilities in the rats. In conclusion, neuroprotective treatments aimed at suppressing degenerative c-Jun and nNOS attenuated apoptosis, provided long-term preservation of motor neurons, their organelles, ventral horn size, and forelimb function.
The time to peak blood bicarbonate (HCO3–), pH, and the strong ion difference (SID) following sodium bicarbonate (NaHCO3) ingestion in highly trained adolescent swimmers

The timing of sodium bicarbonate (NaHCO3) supplementation has been suggested to be most optimal when coincided with a personal time that bicarbonate (HCO3–) or pH peaks in the blood following ingestion. However, the ergogenic mechanisms supporting this ingestion strategy are strongly contested. It is therefore plausible that NaHCO3 may be ergogenic by causing beneficial shifts in the strong ion difference (SID), though the time course of this blood acid base balance variable is yet to be investigated. Twelve highly trained, adolescent swimmers (age: 15.9 ± 1.0 years, body mass: 65.3 ± 9.6 kg) consumed their typical pre-competition nutrition 1–3 hours before ingesting 0.3 g∙kg BM-1 NaHCO3 in gelatine capsules. Capillary blood samples were then taken during seated rest on nine occasions (0, 60, 75, 90, 105, 120, 135, 150, 165 min post-ingestion) to identify the time course changes in HCO3–, pH, and the SID. No significant differences were found in the time to peak of each blood measure (HCO3–: 130 ± 35 min, pH: 120 ± 38 min, SID: 98 ± 37 min; p = 0.08); however, a large effect size was calculated between time to peak HCO3– and the SID (g = 0.88). Considering that a difference between time to peak blood HCO3– and the SID was identified in adolescents, future research should compare the ergogenic effects of these two individualized NaHCO3 ingestion strategies compared to a traditional, standardized approach.
Protein Aggregation Patterns Inform about Breast Cancer Response to Antiestrogens and Reveal the RNA Ligase RTCB as Mediator of Acquired Tamoxifen Resistance

Simple Summary Acquired resistance to antiestrogenic therapy remains the major obstacle to curing luminal subtype breast cancer. While current treatment in acquired endocrine-resistant settings includes combined therapy with receptor tyrosine kinase or cyclin-dependent kinase inhibitors, progression to incurable disease remains possible. In recent years, the antioxidant system and the protein quality control network have been associated with the enhanced resistance of breast cancer cells to hormonal therapy. In this work, we raise the hypothesis that antiestrogen treatment induces the accumulation of protein aggregates in sensitive cells, which in turn could hinder the activation of survival pathways. We present evidence concerning a novel way to identify antiestrogen response and disclose a novel protein, RTBC, that controls acquired antiestrogen resistance. This work opens a new avenue for research towards finding breast cancer prognostic markers and therapeutic targets, where the identification of proteins prone to aggregate could help to identify antiestrogen response and understand mechanisms of disease. Abstract The protein quality control network, including autophagy, the proteasome and the unfolded protein response (UPR), is triggered by stress and is overactive in acquired antiestrogen therapy resistance. We show for the first time that the aggresome load correlates with apoptosis and is increased in antiestrogen-sensitive cells compared to endocrine-resistant variants. LC-MS/MS analysis of the aggregated proteins obtained after 4OH-tamoxifen and Fulvestrant treatment identified proteins with essential function in protein quality control in antiestrogen-sensitive cells, but not in resistant variants. These include the UPR modulators RTCB and PDIA6, as well as many proteasome proteins such as PSMC2 and PSMD11. RTCB is a tRNA and XBP1 ligase and its aggregation induced by antiestrogens correlated with impaired XBP1s expression in sensitive cells. Knock down of RTCB was sufficient to restore sensitivity to tamoxifen in endocrine-resistant cells and increased the formation of aggresomes, leading to apoptotic cell death. Analysis of primary human breast cancer samples and their metastases appearing after endocrine treatment showed that RTCB is only localized to aggresomes in the primary tumors, while total aggresomes, including aggregated RTCB, were significantly reduced in the metastases. Therefore, different protein aggregation patterns may indicate loss of function of essential proteins resulting in enhanced protein aggregation that can be used to identify antiestrogen-resistant breast cancer cells and improve the response to antiestrogenic therapy.
Knowledge and Perception on Animal Welfare in Chilean Undergraduate Students with Emphasis on Dairy Cattle

Simple Summary Consumer perceptions on animal welfare have been assessed, providing results that are necessary for the development of policies and legislation regarding animal welfare standards. In Latin America, societal concerns and specifically consumers’ concerns about animal welfare are increasing but so far, the interest of university students on this subject has received little attention. The objectives of this study were to determine differences on knowledge and perception on animal welfare (with emphasis on dairy cattle) from undergraduate students from two universities with different missions and visions and between students from different faculties. Undergraduate students from the two main Chilean universities were surveyed. Overall, this study showed that University only affected the source of animal welfare information used by undergraduate students and some perceptions on dairy cows’ welfare. On the other hand, Faculty did affect most of the variables on awareness, knowledge and perception towards animal welfare. Thus, the knowledge background provided by the faculty of students has a greater influence on their knowledge and perceptions about animal welfare than their university. Abstract The objectives of this study were to determine differences in knowledge and perception of animal welfare (with emphasis on dairy cattle) among undergraduate students from two universities with different missions and visions and between students from different faculties. One thousand surveys were obtained from Universidad de Chile (UChile; n = 500) and Pontificia Universidad Católica de Chile (PUC; n = 500) students. The students from both universities were from the following faculties: Agronomy, Architecture, Biology, Economic Sciences, Psychology, Law, Philosophy, Basic Education, Civil Engineering and Medicine. The majority (77%) of students from both universities were aware of animal welfare. Most (56%) students understand animal welfare as the ‘mental and physical state of animals’. Regardless of their faculty, around 97% of the total respondents perceived animal welfare as important for production systems. Regarding specific knowledge about cows’ welfare related to milk management and behavior, students from Economic Sciences, Psychology, Law, Philosophy, Basic Education, and Civil Engineering had less (p < 0.001) self-reported knowledge about cows’ basic behavior and specific management practices such as milking and were more negative in their perceptions of dairy production. Overall, results showed that the students’ faculty explained most of the differences among undergraduate students in relation to their perceptions and knowledge about animal welfare. Our data is important, as undergraduate students will make purchasing and power decisions as well as having potential influence on future policies that could modify the animal production industry.