Miracle-dz/UniFAR-FTUs huggingface dataset:
Plasmodium infection and its association with biochemical and haematological parameters in free-living Alouatta guariba clamitans (Cabrera, 1940) (Primates: Atelidae) in Southern Brazil

BACKGROUND The influence of Plasmodium spp. infection in the health of Southern brown howler monkey, Alouatta guariba clamitans, the main reservoir of malaria in the Atlantic Forest, is still unknown. OBJECTIVES The aim of this study was to investigate the positivity rate of Plasmodium infection in free-living howler monkeys in an Atlantic Forest fragment in Joinville/SC and to associate the infection with clinical, morphometrical, haematological and biochemical alterations. METHODS Molecular diagnosis of Plasmodium infection in the captured monkeys was performed by Nested-polymerase chain reaction (PCR) (18S rRNA and coxI). Haematological and biochemical parameters were compared among infected and uninfected monkeys; clinical and morphometrical parameters were also compared. FINDINGS The positivity rate of Plasmodium infection was 70% among forty captured animals, the highest reported for neotropical primates. None statistical differences were detected in the clinical parameters, and morphometric measures comparing infected and uninfected groups. The main significant alteration was the higher alanine aminotransferase (ALT) levels in infected compared to uninfected monkeys. MAIN CONCLUSIONS Therefore, Plasmodium infection in howler monkeys may causes haematological/biochemical alterations which might suggest hepatic impairment. Moreover, infection must be monitored for the eco-epidemiological surveillance of malaria in the Atlantic Forest and during primate conservation program that involves the animal movement, such as translocations.
Degradation of Dynamic Elastic Modulus of Concrete under Periodic Temperature-Humidity Action

Cracks caused by environmental temperature and humidity variation are generally considered one of the most important factors causing durability deterioration of concrete structures. The seasonal or daily variation of ambient temperature and humidity can be considered periodic. The dynamic modulus of elasticity is an important parameter used to evaluate the performance of structural concrete under periodic loads. Hence, in this paper, the dynamic elastic modulus test of concrete under simulating periodic temperature-humidity variation is carried out according to monthly meteorological data of representative areas (Nanjing, China). The dynamic elastic modulus attenuation pattern and a dynamic elastic modulus degradation model of concrete under periodic temperature-humidity are investigated. The test results show that the dynamic elastic modulus of concrete decreases and tends to be stable under the action of periodic temperature-humidity. Comparative analysis shows that the two-parameter dynamic elastic modulus degradation model is more suitable for describing the dynamic elastic modulus attenuation pattern of concrete under periodic temperature-humidity action than the single-parameter one.
Bundled Payment Reform and Dialysis Facility Closures in ESKD.

BACKGROUND In 2011, inclusion of injectable medications into an expanded ESKD payment bundle prompted concerns that dialysis facilities facing higher costs might close, disrupting care delivery and access to care. Whether this policy change influenced dialysis facility closures is unknown. METHODS To examine whether facility closures increased after 2011 and whether factors influencing closures changed, we analyzed US Renal Data System registry data to identify all patients receiving in-center hemodialysis from 2006 through 2015 and to track dialysis facility closures. We used interrupted time series logistic regression models and estimated marginal effects to examine immediate and longer-term changes in the likelihood of being affected by facility closures following payment reform. We also examined whether associations between selected predictors of closures indicating populations at "high risk" of closure (patient characteristics, facility characteristics, and geography-related characteristics) and closures changed after payment reform. RESULTS Dialysis facility closures were uncommon over the study period. In adjusted models, the relative odds of experiencing a closure declined by 37% (odds ratio [OR], 0.63; 95% confidence interval [95% CI], 0.59 to 0.67) immediately after payment reform and declined by an additional 6% (OR, 0.94; 95% CI, 0.91 to 0.97) annually thereafter, corresponding to a 0.3% lower absolute probability of closure in 2015 in association with payment reform. Patients who were black and who dialyzed at small, hospital-based facilities experienced slight increases in closures following payment reform, whereas Hispanic and Medicare/Medicaid dual-eligible patients experienced slight decreases in closures. CONCLUSIONS Expansion of the ESKD payment bundle was not associated with increased closure of dialysis facilities, although the likelihood of closures changed slightly for some higher-risk populations.
PSYCHOLOGY, PSYCHIATRY & BRAIN NEUROSCIENCE SECTION An Open Trial of a Mind–Body Intervention for Young Women with Moderate to Severe Primary Dysmenorrhea

Objective. To evaluate the feasibility, acceptability, and preliminary efficacy of a mind–body intervention for moderate to severe primary dysmenorrhea (PD). Design. Open trial (single arm). Setting. Academic medical school. Subjects. A total of 20 young adult women with moderate to severe primary dysmenorrhea were included across four separate intervention groups. Methods. All participants received five 90-minute sessions of a mind–body intervention and completed self-report measures of menstrual pain, depression, anxiety, somatization, and pain catastrophizing at baseline, post-treatment, and at one-, two-, three-, and 12-month follow-up. Self-report of medication use and use of skills learned during the intervention were also collected at all follow-up points. Results. Participants reported significantly lower menstrual pain over time compared with baseline. No changes in anxiety, depression, or somatization were observed, although pain catastrophizing improved over time. Changes in menstrual pain were not associated with changes in medication use or reported use of skills. Conclusions. A mind–body intervention is a promising nondrug intervention for primary dysmenorrhea, and future research should focus on testing the intervention further as part of a randomized clinical trial.
Cruciate ligament, patellar tendon, and patella formation involves differential cellular sources and dynamics as joint cavitation proceeds

Cruciate ligament (CL) and patellar tendon (PT) are important elements of the knee joint, uniting femur, patella, and tibia into a single functional unit. So far, knowledge on the developmental mechanism of CL, PT, and patella falls far behind other skeletal tissues.
Iron intake is positively associated with viral load in antiretroviral naïve Brazilian men living with HIV

BACKGROUND Iron homeostasis contribute for the human immunodeficiency virus (HIV) pathogenesis. OBJECTIVES We assessed the iron intake pattern in antiretroviral naïve Brazilian men living with HIV correlating with clinical and nutritional parameters. METHODS The iron consumption mean was estimated according to a food frequency questionnaire (FFQ), and a 3-day food record (3dFR) submitted to the patients. HIV viral load, CD4+ T cell counts, serum iron, haematological and anthropometrics parameters were recorded. FINDINGS Fifty-one HIV-infected adult men naïve for antiretroviral therapy (ART) were enrolled. The mean age of participants was 35 (SEM ± 1.28) years old, with mean time of HIV-1 infection of 1.78 (0-16.36, min-max) years. Majority (41.18%) had complete secondary, and 21.57% had tertiary educational level. The income was around 1x (54.90%) to 2x (41.18%) minimum wage. Fifty-four percent showed normal weight, while 40% were overweight. The patients showed normal mean values of haematological parameters, and mean serum iron was 14.40 µM (SEM ± 0.83). The FFQ showed moderate correlation with the 3dFR (ρ = 0.5436, p = 0.0009), and the mean values of iron intake were 10.55(± 0.92) mg/day, recorded by FFQ, and 15.75(± 1.51) mg/day, recorded by 3dFR. The iron intake, recorded by FFQ, negatively correlated with serum iron (ρ = -0.3448, p = 0.0132), and did not have influence in the CD4+ T cell counts [e.B 0.99 (0.97-1.01, 95% confidence interval (CI), p = 0.2]. However, the iron intake showed a positive effect in HIV viral load [e.B 1.12 (1.02-1.25, 95%CI), p < 0.01]. MAIN CONCLUSIONS This study draws attention for the importance of iron intake nutritional counseling in people living with HIV. However, more studies are required to clarify the association between high iron intake and HIV infection and outcome.
Profiling of the viable bacterial and fungal microbiota in fermented feeds using single molecule real-time sequencing.

Fermented concentrated feed has been widely recognized as ideal feed in the animal industry. In this study, we used a powerful method, coupling propidium monoazide (PMA) pre-treatment with single molecule real-time (SMRT) sequencing technology to compare the bacterial and fungal composition of feeds before and after fermentation with four added lactic acid bacteria (LAB) inoculants (one Lactobacillus casei strain and three L. plantarum strains). Five feed samples consisting of corn, soybean meal, and wheat bran were fermented with LAB additives for 3 days. Following anaerobic fermentation, the pH rapidly decreased, and the mean numbers of LAB increased from 106 to 109 colony forming units/g fresh matter. SMRT sequencing results showed that the abundance and diversity of bacteria and fungi in the feed were significantly higher before fermentation than after fermentation. Fifteen bacterial species and eight fungal genera were significantly altered following fermentation, and L. plantarum was the dominant species (relative abundance 88.94%) in the post-fermentation group. PMA treatment revealed that the bacteria Bacillus cereus, B. circulans, Alkaliphilus oremlandii, Cronobacter sakazakii, Paenibacillus barcinonensis, and P. amylolyticus (relative abundance >1%) were viable in raw feed. After fermentation, their relative abundances decreased sharply to < 0.2%; however, viable L. plantarum was still the dominant species post-fermentation. We inferred that our LAB additives grew rapidly and inhibited harmful microorganisms and further improved feed quality. In addition, coupling PMA treatment with the Pacific Biosciences SMRT sequencing technology was a powerful tool for providing accurate live microbiota profiling data in this study.
Optimizing design to estimate genetic correlations between environments with common environmental effects

Abstract Breeding programs for different species aim to improve performance by testing members of full-sib (FS) and half-sib (HS) families in different environments. When genotypes respond differently to changes in the environment, this is defined as genotype by environment (G × E) interaction. The presence of common environmental effects within families generates covariance between siblings, and these effects should be taken into account when estimating a genetic correlation. Therefore, an optimal design should be established to accurately estimate the genetic correlation between environments in the presence of common environmental effects. We used stochastic simulation to find the optimal population structure using a combination of FS and HS groups with different levels of common environmental effects. Results show that in a population with a constant population size of 2,000 individuals per environment, ignoring common environmental effects when they are present in the population will lead to an upward bias in the estimated genetic correlation of on average 0.3 when the true genetic correlation is 0.5. When no common environmental effects are present in the population, the lowest standard error (SE) of the estimated genetic correlation was observed with a mating ratio of one dam per sire, and 10 offspring per sire per environment. When common environmental effects are present in the population and are included in the model, the lowest SE is obtained with mating ratios of at least 5 dams per sire and with a minimum number of 10 offspring per sire per environment. We recommend that studies that aim to estimate the magnitude of G × E in pigs, chicken, and fish should acknowledge the potential presence of common environmental effects and adjust the mating ratio accordingly.
Patients with chronic autoimmune demyelinating polyneuropathies exhibit cognitive deficits which might be associated with CSF evidence of blood-brain barrier disturbance

Background Chronic autoimmune demyelinating polyneuropathies (CADP) result in impaired sensorimotor function. However, anecdotal clinical observations suggest the development of cognitive deficits during the course of disease. Methods We tested 16 patients with CADP (11 patients with chronic inflammatory demyelinating polyneuropathy, 4 patients with multifocal motor neuropathy and 1 patient with multifocal acquired demyelinating sensory and motor neuropathy) and 40 healthy controls (HC) with a neuropsychological test battery. Blood-brain-barrier dysfunction (BBBd) in patients was assessed retrospectively by analysing the cerebral spinal fluid (CSF) status at the time the diagnosis of CAPD was established. Results CADP patients failed on average in 1.7 out of 9 neuropsychological tests (SD ± 1.25, min. 0, max. 5). 50% of the CADP patients failed in at least two neuropsychological tests and 44.3% of the patients failed in at least two different cognitive domains. CADP patients exhibiting BBBd at the time of first diagnosis failed in more neuropsychological tests than patients with intact integrity of the BBB (p < 0.05). When compared directly with the HC group, CADP patients performed worse than HC in tests measuring information processing ability and speed as well as phonemic verbal fluency after adjusting for confounding covariates. Conclusions Our results suggest that mild to moderate cognitive deficits might be present in patients with CAPD. One possible tentative explanation, albeit strong evidence is still lacking for this pathophysiological mechanism, refers to the effect of autoimmune antibodies entering the CNS via the dysfunctional blood-brain barrier typically seen in some of the CADP patients.
Joint analysis of panel count and interval‐censored data using distribution‐free frailty analysis

We propose a joint analysis of recurrent and nonrecurrent event data subject to general types of interval censoring. The proposed analysis allows for general semiparametric models, including the Box–Cox transformation and inverse Box–Cox transformation models for the recurrent and nonrecurrent events, respectively. A frailty variable is used to account for the potential dependence between the recurrent and nonrecurrent event processes, while leaving the distribution of the frailty unspecified. We apply the pseudolikelihood for interval‐censored recurrent event data, usually termed as panel count data, and the sufficient likelihood for interval‐censored nonrecurrent event data by conditioning on the sufficient statistic for the frailty and using the working assumption of independence over examination times. Large sample theory and a computation procedure for the proposed analysis are established. We illustrate the proposed methodology by a joint analysis of the numbers of occurrences of basal cell carcinoma over time and time to the first recurrence of squamous cell carcinoma based on a skin cancer dataset, as well as a joint analysis of the numbers of adverse events and time to premature withdrawal from study medication based on a scleroderma lung disease dataset.
γδ T-cell Receptors Derived from Breast Cancer–Infiltrating T Lymphocytes Mediate Antitumor Reactivity

Proinflammatory γδ T cells infiltrate triple-negative breast cancers and are positioned in close proximity to tumor cells. T cells engineered to express paired TCRγ/TCRδ chains are tumor reactive against an array of tumor types. γδ T cells in human solid tumors remain poorly defined. Here, we describe molecular and functional analyses of T-cell receptors (TCR) from tumor-infiltrating γδ T lymphocytes (γδ TIL) that were in direct contact with tumor cells in breast cancer lesions from archival material. We observed that the majority of γδ TILs harbored a proinflammatory phenotype and only a minority associated with the expression of IL17. We characterized TCRγ or TCRδ chains of γδ TILs and observed a higher proportion of Vδ2+ T cells compared with other tumor types. By reconstructing matched Vδ2– TCRγ and TCRδ pairs derived from single-cell sequencing, our data suggest that γδ TILs could be active against breast cancer and other tumor types. The reactivity pattern against tumor cells depended on both the TCRγ and TCRδ chains and was independent of additional costimulation through other innate immune receptors. We conclude that γδ TILs can mediate tumor reactivity through their individual γδ TCR pairs and that engineered T cells expressing TCRγ and δ chains derived from γδ TILs display potent antitumor reactivity against different cancer cell types and, thus, may be a valuable tool for engineering immune cells for adoptive cell therapies.
The Role of the Clinical Pharmacist in an Irish University Teaching Hospital: A Mixed-Methods Study

Medication review (MR) is a vital part of the pharmacist’s role in hospital. However, in the South Infirmary Victoria University Hospital (SIVUH), Cork, Ireland, this has not been fully implemented due to resource issues. In addition, the cost of providing this service has not been evaluated. Moreover, it is not clear how other members of the multidisciplinary team e.g., Nurses, value any interventions made as a result of the MR. This mixed methods study assessed the impact of MR in terms of (i) potential clinical harm, (ii) cost avoidance and (iii) the views of nursing staff on the role of the pharmacist. The setting is a 192-bed, voluntary, acute hospital, in the Munster region of Ireland. Study I: The pharmacist provided MR to patients conventionally once a week. Any interventions were then assessed for potential clinical harm and to calculate cost avoidance. Study II: Semi-structured interviews, guided by a topic guide were completed with 12 nurses (11 female). Thematic analysis was used to code the main themes. Main outcome measure: To estimate the cost, cost avoidance, and the net cost benefit ratio of MR provided by pharmacists. Study I: Of 128 patients who received the MR, 113 interventions were made. The estimated cost of providing the MR was €2559 (senior pharmacist). Using €1084 as the cost of an adverse drug event (ADE), the cost avoidance was calculated at €42,330. This led to a net cost benefit of €39,771 (senior pharmacist) which equated to a net cost benefit ratio of 16.5:1. Study II: The main themes were (i) perceptions of pharmacy services, (ii) the role of the pharmacist—past, present and future, and (iii) teamwork and communication. Nurses expressed a desire to have more pharmacists present on the wards.
27-Hydroxycholesterol Impairs Plasma Membrane Lipid Raft Signaling as Evidenced by Inhibition of IL6–JAK–STAT3 Signaling in Prostate Cancer Cells

We recently reported that restoring the CYP27A1–27hydroxycholesterol axis had antitumor properties. Thus, we sought to determine the mechanism by which 27HC exerts its anti–prostate cancer effects. As cholesterol is a major component of membrane microdomains known as lipid rafts, which localize receptors and facilitate cellular signaling, we hypothesized 27HC would impair lipid rafts, using the IL6–JAK–STAT3 axis as a model given its prominent role in prostate cancer. As revealed by single molecule imaging of DU145 prostate cancer cells, 27HC treatment significantly reduced detected cholesterol density on the plasma membranes. Further, 27HC treatment of constitutively active STAT3 DU145 prostate cancer cells reduced STAT3 activation and slowed tumor growth in vitro and in vivo. 27HC also blocked IL6-mediated STAT3 phosphorylation in nonconstitutively active STAT3 cells. Mechanistically, 27HC reduced STAT3 homodimerization, nuclear translocation, and decreased STAT3 DNA occupancy at target gene promoters. Combined treatment with 27HC and STAT3 targeting molecules had additive and synergistic effects on proliferation and migration, respectively. Hallmark IL6–JAK–STAT gene signatures positively correlated with CYP27A1 gene expression in a large set of human metastatic castrate-resistant prostate cancers and in an aggressive prostate cancer subtype. This suggests STAT3 activation may be a resistance mechanism for aggressive prostate cancers that retain CYP27A1 expression. In summary, our study establishes a key mechanism by which 27HC inhibits prostate cancer by disrupting lipid rafts and blocking STAT3 activation. Implications: Collectively, these data show that modulation of intracellular cholesterol by 27HC can inhibit IL6–JAK–STAT signaling and may synergize with STAT3-targeted compounds.
Annual Research Review: Defining and treating pediatric treatment-resistant depression.

BACKGROUND Adolescent major depressive disorder (MDD) is a significant health problem, associated with substantial morbidity, cost, and mortality. Depression is a significant risk factor for suicide, which is now the second leading cause of death in young people. Up to twenty per cent of adolescents will experience MDD before adulthood, and while a substantial proportion will improve with standard-of-care treatments (psychotherapy and medication), roughly one third will not. METHODS Here, we have reviewed the literature in order to discuss the concept of treatment-resistant depression (TRD) in adolescence, examine risk factors, diagnostic difficulties, and challenges in evaluating symptom improvement, and providing guidance on how to define adequate medication and psychotherapy treatment trials. RESULTS We propose a staging model for adolescent TRD and review the treatment literature. The evidence base for first- and second-line treatments primarily derives from four large pediatric clinical trials (TADS, TORDIA, ADAPT, and IMPACT). After two medications and a trial of evidence-based psychotherapy have failed to alleviate depressive symptoms, the evidence becomes quite thin for subsequent treatments. Here, we review the evidence for the effectiveness of medication switches, medication augmentation, psychotherapy augmentation, and interventional treatments (i.e., transcranial magnetic stimulation, electroconvulsive therapy, and ketamine) for adolescent TRD. Comparisons are drawn to the adult TRD literature, and areas for future pediatric depression research are highlighted. CONCLUSIONS As evidence is limited for treatments in this population, a careful consideration of the known risks and side effects of escalated treatments (e.g., mood stabilizers and atypical antipsychotics) is warranted and weighed against potential, but often untested, benefits.