Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased Mortality and Costs Associated with Adverse Events in Intensive Care Unit Patients

Background: Adverse events (AEs) are defined as unintended complications occurring to patients as a result of medical care. AEs are especially prevalent in the intensive care unit (ICU) setting and may lead to negative patient outcomes. Although many studies have examined the impact of AEs on patient outcomes, few have investigated their associated costs. Methods: The study population consisted of 17 173 adult patients (≥18 years of age) who were admitted to the ICU at The Ottawa Hospital (TOH) between 2011 and 2016. AEs were categorized using an established International Classification of Diseases 10th revision (ICD-10) patient safety indicators (PSI) system for AE detection. Logistic regression was performed to determine the association between AEs and in-hospital outcomes, including mortality. In addition, we constructed a generalized linear model to assess the independent association between AEs and total hospital costs. Results: Patients who experienced an AE had longer total hospital and ICU lengths of stay, required more invasive ICU interventions, had more complex discharge plans, and experienced higher rates of in-hospital mortality compared to those who did not experience an AE. Average total hospital costs and ICU-specific costs were higher among patients who experienced an AE ($72 718; $46 715) relative to their counterparts ($20 543; $16 217), but the per day cost was comparable in both groups. After controlling for age, sex, patient comorbidities, and illness severity, AEs were significantly associated with an increased odds of mortality (OR = 1.13, 95% CIs = 1.04, 1.22) and total average costs (Cost Ratio = 1.04, 95% CIs = 1.06, 1.08). The most impactful AE subtypes from a cost- and patient-perspective were hospital-acquired infections (HAI) and cardiac-related AEs. Conclusion: Incidence of AEs among ICU patients is associated with higher patient mortality and elevated costs. Specific causes of these AEs should be investigated, with further protocols and interventions developed to reduce their occurrence.
Generations and Shifting Sexual Identifications Among Flemish Non-Straight Men

ABSTRACT This paper explores age-related differences in non-straight identities, using the concept of “generations” to investigate shared contexts and experiences contributing to processes of sexual identification. The process of identity construction is focused upon, existing research noting a shifting attitude toward identity categories among the youngest generations. Using a mixed-method design, first an exploratory survey of 684 Flemish men was used to determine shifting sexual identifications, which were indeed found among the youngest generation. These insights serve as a background for the analysis of 80 in-depth interviews with non-straight men across four generations: Baby Boomers, Generations X, Millennials and Generation Z. These generational divisions serve as a heuristic to explore shared generational experiences and contexts as well as intergenerational changes in relation to four key moments and themes: first realizations and explorations of same-sex sexuality; sexual identification; coming out; and involvement in the LGBTQ community. The results show clear and positive evolutions across the generations on all accounts, albeit with a lot of variation within generations as well as gradual changes between them. While useful as a heuristic, the notion of generations should be used with caution, as it allows to identify macro level shifts but hides micro level variations.
Research perspectives—Pipelines to human tendon transcriptomics

Tendon transcriptomics is a rapidly growing field in musculoskeletal biology. The ultimate aim of many current tendon transcriptomic studies is characterization of in vitro, ex vivo, or in vivo, healthy, and diseased tendon microenvironments to identify the underlying pathways driving human tendon pathology. The transcriptome interfaces between genomic, proteomic, and metabolomic signatures of the tendon cellular niche and the response of this niche to stimuli. Some of the greatest bottlenecks in tendon transcriptomics relate to the availability and quality of human tendon tissue, hence animal tissues are frequently used even though human tissue is most translationally relevant. Here, we review the variability associated with human donor and procurement factors, such as whether the tendon is cadaveric or a clinical remnant, and how these variables affect the quality and relevance of the transcriptomes obtained. Moreover, age, sex, and health demographic variables impact the human tendon transcriptome. Tendons present tissue‐specific challenges for cell, nuclei, and RNA extraction that include a dense extracellular matrix, low cellularity, and therefore low RNA yield of variable quality. Consideration of these factors is particularly important for single‐cell and single‐nuclei resolution transcriptomics due to the necessity for unbiased and representative cell or nuclei populations. Different cell, nuclei, and RNA extraction methods, library preparation, and quality control methods are used by the tendon research community and attention should be paid to these when designing and reporting studies. We discuss the different components and challenges of human tendon transcriptomics, and propose pipelines, quality control, and reporting guidelines for future work in the field.
Exploring the Role of Occupational Therapy and Forced Migration in Canada

Background. In response to increasing forced migration across the globe, Canadian occupational therapists are returning to the profession's social justice roots by exploring this emergent area of practice. Purpose. This research explores occupational therapy practices with forced migrants in a Canadian context. Method. Grounded in critical epistemologies, the researchers conducted 12 semi-structured interviews with occupational therapists, students, and researchers connected to displacement. Data were analyzed using thematic analysis. Findings. Four themes describe current occupational therapy practices related to forced migration: 1) engaging clients in new environments, 2) translating the everyday, 3) connecting and networking, and 4) advocating for occupational justice. Implications. This research contributes to the advancement of occupational therapy and forced migration by documenting the diverse and fluid nature of occupational therapy roles. Further, the paper outlines promising reflexive practices while forwarding advocacy priorities for (occupational) justice.
Evaluation of diastole by echocardiography for detecting early cardiac dysfunction: an outcome study

Timely detection of subclinical left ventricular diastolic dysfunction (LVDDF) is of importance for precise risk stratification of asymptomatic subjects. Here, we evaluated the prevalence of LVDDF and its prognostic significance in the general population using two grading approaches: the 2016 ASE/EACVI recommendations and population‐derived, age‐specific criteria.
2-Oxoglutarate-Dependent Dioxygenases Drive Expansion of Steroidal Alkaloid Structural Diversity in the Genus Solanum.

Solanum steroidal glycoalkaloids (SGAs) are renowned defense metabolites exhibiting spectacular structural diversity. Genes and enzymes generating SGAs precursor pathway, SGAs scaffold and glycosylated forms have been largely identified. Yet, majority of downstream metabolic steps creating the vast repertoire of SGAs remain untapped. Here, we discovered that members of the 2-OXOGLUTARATE-DEPENDENT DIOXYGENASE (2-ODD) family play a prominent role in SGAs metabolism, carrying out three distinct backbone-modifying oxidative steps in addition to the three formerly reported pathway reactions. The GLYCOALKALOID METABOLISM34 (GAME34) enzyme catalyzes the conversion of core SGAs to habrochaitosides in wild tomato S. habrochaites. Cultivated tomato plants overexpressing GAME34 ectopically accumulates habrochaitosides. These habrochaitosides enriched plants extracts potently inhibits Puccinia spp. spore germination, a significant Solanaceae crops fungal pathogen. Another 2-ODD enzyme, GAME33, acts as a desaturase (via hydroxylation and E/F ring rearrangement) forming unique, yet unreported SGAs. Conversion of bitter α-tomatine to ripe fruit, non-bitter SGAs (e.g. esculeoside A) requires two hydroxylations; while the known GAME31 2-ODD enzyme catalyzes hydroxytomatine formation, we find that GAME40 catalyzes penultimate step in pathway and generates acetoxy-hydroxytomatine towards esculeosides accumulation. Our results highlight the significant contribution of 2-ODD enzymes to the remarkable structural diversity found in plant steroidal specialized metabolism.
Antibiotics for Fever Among Children: Findings From the Surveillance for Enteric Fever in India Cohorts

Abstract Background Acute febrile illness in children is frequently treated with antibiotics. However, the inappropriate use of antibiotics has led to the emergence of multidrug-resistant pathogens. Methods We measured use of antibiotics for fever in 4 pediatric cohorts that were part of the Surveillance for Enteric Fever in India (SEFI) network. In this network, 24 062 children were followed up weekly, capturing information on fever and other morbidity between October 2017 and December 2019. Results An antibiotic was given in 27 183 of the 76 027 (35.8%) episodes of fever. The incidence of fever-related antibiotic use was 58.0 (95% confidence interval [CI], 57.2–58.6) per 100 child-years. The median time to initiation of antibiotics was 4 days, and in 65% of those who received an antibiotic it was initiated by the second day. Antibiotics were continued for <3 days in 24% of the episodes. Higher temperature, younger age, male sex, joint family, higher education, internet access, and availability of personal conveyance were associated with antibiotic treatment for fever. Conclusions In developing countries where antibiotic use is not regulated, broad-spectrum antibiotics are initiated early, and often inappropriately, in febrile illness. Frequent and inappropriate use of antibiotics may increase risk of antimicrobial resistance.
Son preference and sex differentials in receipt of key dimensions of children’s healthcare: Evidence from Pakistan

Almost all research on son preference and the consequent sex differentials in child health has focused on India. Pakistan—a country with the second strongest stated desire for sons, no evidence of sex-selective abortion, and relatively high fertility—offers a different context in which to understand unequal health outcomes for boys and girls. I use three rounds of the Pakistan Demographic and Health Survey to examine sex differentials in child healthcare receipt across different family contexts. I find evidence of generalized discrimination: all girls, regardless of sibling composition or birth order, are less likely to receive full immunization or medical treatment. I do not find evidence that girls with older sisters face greater discrimination than other girls. For boys, I find some evidence of selective preferential treatment: among larger families, first sons are more likely to receive healthcare than other sons or daughters.
The Effects of Uncertainty in Level on Speech-on-Speech Masking

Identification of speech from a "target" talker was measured in a speech-on-speech masking task with two simultaneous "masker" talkers. The overall level of each talker was either fixed or randomized throughout each stimulus presentation to investigate the effectiveness of level as a cue for segregating competing talkers and attending to the target. Experimental manipulations included varying the level difference between talkers and imposing three types of target level uncertainty: 1) fixed target level across trials, 2) random target level across trials, or 3) random target levels on a word-by-word basis within a trial. When the target level was predictable performance was better than corresponding conditions when the target level was uncertain. Masker confusions were consistent with a high degree of informational masking (IM). Furthermore, evidence was found for "tuning" in level and a level "release" from IM. These findings suggest that conforming to listener expectation about relative level, in addition to cues signaling talker identity, facilitates segregation of, and maintaining focus of attention on, a specific talker in multiple-talker communication situations.
Bioactive compounds: Application of albumin nanocarriers as delivery systems

Abstract Enriched products with bioactive compounds (BCs) show the capacity to produce a wide range of possible health effects. Most BCs are essentially hydrophobic and sensitive to environmental factors; so, encapsulation becomes a strategy to solve these problems. Many globular proteins have the intrinsic ability to bind, protect, encapsulate, and introduce BCs into nutraceutical or pharmaceutical matrices. Among them, albumins as human serum albumin (HSA), bovine serum albumin (BSA), ovalbumin (OVA) and α-lactalbumin (ALA) are widely abundant, available, and applied in many industrial sectors, becoming promissory materials to encapsulate BCs. Therefore, this review focuses on researches about the main groups of natural origin BCs (namely phenolic compounds, lipids, vitamins, and carotenoids), the different types of nanostructures based on albumins to encapsulate them and the main fields of application for BCs-loaded albumin systems. In this context, phenolic compounds (catechins, quercetin, and chrysin) are the most extensively BCs studied and encapsulated in albumin-based nanocarriers. Other extensively studied subgroups are stilbenes and curcuminoids. Regarding lipids and vitamins; terpenes, carotenoids (β-carotene), and xanthophylls (astaxanthin) are the most considered. The main application areas of BCs are related to their antitumor, anti-inflammatory, and antioxidant properties. Finally, BSA is the most used albumin to produced BCs-loaded nanocarriers.
The Effects of in-Home Respite Care on the Burden of Caregivers in Taiwan

The utilization rate of respite care in Taiwan is low, and past studies that evaluated the effects of in-home respite care on caregiver burden are few. This two-wave panel study used Taiwan’s long-term care plan 1.0 database and included 2342 care recipient–caregiver dyads who used home services to examine the impact of in-home respite care on caregiver burden. Propensity score matching was used to select 323 in-home respite service users matched with 646 nonusers as control groups (1:2 matching). The mixed effect model was applied to estimate the effects of receiving in-home respite care on caregiver burden. Results showed that compared with those of nonusers, caregiver burden scores of service users decreased significantly after receiving in-home respite care for more than 14 days (adjusted B = −0.14, SE = 0.05). The government should prioritize increasing the number of days of in-home respite care for those in need to reduce the caregiver burden.
Signal peptide peptidase: a potential therapeutic target for parasitic and viral infections

ABSTRACT Introduction Signal peptide peptidase (SPP) is a GxGD-type intramembrane-cleaving aspartyl protease responsible for clearing accumulating signal peptides in the endoplasmic reticulum. SPP is conserved among all kingdoms and is essential for maintaining cell homeostasis. Inhibition of SPP with selective inhibitors and the structurally similar HIV protease inhibitors results in signal peptide accumulation and subsequent cell death. Identification of SPP homologues in major human parasitic infections has opened a new therapeutic opportunity. Moreover, the essentiality of mammalian SPP-mediated viral protein processing during infection is emerging. Areas Covered This review introduces the discovery and biological function of human SPP enzymes and identify parasitic homologues as pharmacological targets of both SPP and HIV protease inhibitors. Later, the role of mammalian SPP during viral infection and how disruption of host SPP can be employed as a novel antiviral therapy are examined and discussed. Expert Opinion Parasitic and viral infections cause severe health and economic burden, exacerbated by the lack of new therapeutics in the pipeline. SPP has been shown to be essential for malaria parasite growth and encouraging evidence in other parasites demonstrates broad essentiality of these proteases as therapeutic targets. As drug resistant parasite and viruses emerge, SPP inhibition will provide a new generation of compounds to counter the growing threat of antimicrobial resistance.
Personalized immunosuppression after kidney transplantation

With advances in immunosuppressive therapy, there have been significant improvements in acute rejection rates and short‐term allograft survival in kidney transplant recipients. However, this success has not been translated into long‐term benefits by the same magnitude. Optimization of immunosuppression is important to improve the clinical outcome of transplant recipients. It is important to note that each patient has unique attributes and immunosuppression management should not be a one‐size‐fits‐all approach. Elderly transplant patients are less likely to develop acute rejection but more likely to die from infectious and cardiovascular causes than younger patients. For those with post‐transplant cancers and BK polyomavirus‐associated nephropathy, reduction of immunosuppression can increase the risk of rejection. Therapeutic drug monitoring (TDM) is routinely used for dosage adjustment of several immunosuppressive drugs. It has been hoped that pharmacogenetics can be used to complement TDM in optimizing drug exposure. Among the various drug‐genotype pairs being investigated, tacrolimus and CYP3A5 gives the most promising results. Different studies have consistently shown that CYP3A5 expressers require a higher tacrolimus dose and take longer time to achieve target blood tacrolimus levels than nonexpressers. However, for pharmacogenetics to be widely used clinically, further trials are necessary to demonstrate the clinical benefits of genotype‐guided dosing such as reduction of rejection and drug‐related toxicities. The development of different biomarkers in recent years may help to achieve true personalized therapy in transplant patients.
Effects of Sarcomere Activators and Inhibitors Targeting Myosin Cross-Bridges on Ca2+-Activation of Mature and Immature Mouse Cardiac Myofilaments

We tested the hypothesis that isoform shifts in sarcomeres of the immature heart modify the effect of cardiac myosin-directed sarcomere inhibitors and activators. Omecamtiv mecarbil (OM) activates tension and is in clinical trials for the treatment of adult acute and chronic heart failure. Mavacamten (Mava) inhibits tension and is in clinical trials to relieve hypercontractility and outflow obstruction in advanced genetic hypertrophic cardiomyopathy (HCM), which is often linked to mutations in sarcomeric proteins. To address the effect of these agents in developing sarcomeres, we isolated heart fiber bundles, extracted membranes with Triton X-100, and measured tension developed over a range of Ca2+ concentrations with and without OM or Mava treatment. We made measurements in fiber bundles from hearts of adult nontransgenic (NTG) controls expressing cardiac troponin I (cTnI), and from hearts of transgenic (TG-ssTnI) mice expressing the fetal/neonatal form, slow skeletal troponin I (ssTnI). We also compared fibers from 7- and 14-day-old NTG mice expressing ssTnI and cTnI. These studies were repeated with 7- and 14-day-old transgenic mice (TG-cTnT-R92Q) expressing a mutant form of cardiac troponin T (cTnT) linked to HCM. OM increased Ca2+-sensitivity and decreased cooperative activation in both ssTnI- and cTnI-regulated myofilaments with a similar effect: reducing submaximal tension in immature and mature myofilaments. Although Mava decreased tension similarly in cTnI- and ssTnI-regulated myofilaments controlled either by cTnT or cTnT-R92Q, its effect involved a depressed Ca2+-sensitivity in the mature cTnT-R92 myofilaments. Our data demonstrate an influence of myosin and thin-filament associated proteins on the actions of myosin-directed agents such as OM and Mava. SIGNIFICANCE STATEMENT The effects of myosin-targeted activators and inhibitors on Ca2+-activated tension in developing cardiac sarcomeres presented here provide novel, ex vivo evidence as to their actions in early-stage cardiac disorders. These studies advance understanding of the molecular mechanisms of these agents, which are important in preclinical studies employing sarcomere Ca2+-response as a screening approach. The data also inform the use of commonly immature cardiac myocytes generated from human-inducible pluripotent stem cells in screening for sarcomere activators and inhibitors.
Retrospective evaluation of operator bias in the performance of high‐resolution anorectal manometry

Measurements obtained during high‐resolution anorectal manometry (HRM) are subject to operator–patient interactions. For example, standardized enhanced instruction delivered by a single operator in a test–retest fashion did not consistently increase pressures generated during dynamic maneuvers. It is probable that factors other than verbal instruction effect communication during the procedure. To investigate this hypothesis, we retrospectively examined inter‐operator variance in HRM results.
A milk-sharing economy allows placental mammals to overcome their metabolic limits

Significance Here, we demonstrate that a naturally evolving behavior (allonursing) has greater effect on reproductive power (mass per unit of time) and output (litter mass at birth) than does artificial selection (domestication). Additionally, we demonstrate the importance of resource optimization afforded by sociality (rather than resource abundance per se) in shaping a species’ life history profile and its ability to overcome its own physiological constraints.
Subclinical hypothyroidism in women’s health: from pre- to post-menopause

Abstract Objective Subclinical hypothyroidism (SCH) is a quite frequent condition among women, affecting 3–12% of the general population. Its consequences on women’s health in reproductive age, pregnancy and menopause have been extensively investigated but data about the effective impact of treatment with levothyroxine (LT4) remain conflicting. Methods This is a narrative review and analysis of the most relevant data until June 2021. Results SCH may affect reproduction. Evidence suggests that women with SCH undergoing assisted reproductive technique (ART) may benefit from LT4 therapy whereas there are no conclusive data regarding women attempting natural conception. SCH may be associated with several negative pregnancy outcomes, that is to say recurrent pregnancy loss (RPL), preterm delivery, preeclampsia and neurocognitive disturbances of offspring. However, the protective role of LT4 treatment has been established in selected cases, for instance in thyroid peroxidase antibody (TPOAb) -positive women with TSH greater than the pregnancy specific reference range and/or in TPOAb-negative women with TSH >10.0 mIU/L. In menopause, SCH can worsen the negative cardio-metabolic effects of hormonal loss and/or aging, by exacerbating dyslipidaemia and hypertension. Nevertheless, robust data about the benefits of LT4 therapy are still lacking and treatment should be encouraged with caution. Conclusions SCH represents a challenging condition during pre- and post- menopause. An aware knowledge of its possible principal consequences could help all clinicians who are involved in women’s health to manage more properly it, preventing its sequelae.