Miracle-dz/UniFAR-FTUs huggingface dataset:
PrEP4Love: The Role of Messaging and Prevention Advocacy in PrEP Attitudes, Perceptions, and Uptake Among YMSM and Transgender Women.

BACKGROUND Despite high efficacy, use of pre-exposure prophylaxis (PrEP) remains low among young men who have sex with men (MSM) and transgender women (TW), primarily due to barriers such as stigma and resource awareness. We evaluated a social marketing campaign known as PrEP4Love that works to eliminate PrEP stigma and awareness gaps via targeted advertising. SETTING Chicago, Illinois. METHODS Participants were enrolled within a cohort study of young MSM and TW (RADAR). Data were collected between June 2017 and April 2018 from HIV-negative individuals attending a follow-up visit. Surveys assessed demographics, PrEP attitudes and perceptions, and PrEP4Love campaign awareness. Associations between PrEP4Love awareness and PrEP perceptions, uptake, and behaviors were assessed using multiple logistic regression controlling for age, race/ethnicity, gender, sexual identity, and ever having used PrEP. RESULTS Of 700 participants, the majority (75.9%) indicated seeing PrEP4Love ads in Chicago. Those who had seen ads were more likely to be out to their providers (OR =1.95; 95% CI: 1.17, 3.23) than those who had not, and those who had conversations were significantly more likely to have initiated the conversation themselves. Individuals who had seen ads were more likely to have taken PrEP in the last six months (OR = 1.87; 95% CI: 1.15, 3.16), and more likely to believe their friends and the general public approved of and used PrEP. CONCLUSION Social marketing campaigns are promising interventions that have the potential to alleviate barriers to HIV prevention, particularly among MSM and TW. Future research should evaluate the impact of these initiatives at multiple time points.
Contralateral Prophylactic Mastectomy in Women with Unilateral Breast Cancer Who Are Genetic Carriers, Have a Strong Family History or Are just Young at Presentation

The uptake of contralateral prophylactic mastectomy is rising with increasing trends that are possibly highest in the USA. Whilst its role is generally accepted in carriers of recognized high-risk predisposition genes such as BRCA1 and BRCA2 when the affected individual is premenopausal, controversy surrounds the benefit in less understood risk-profile clinical scenarios. This comprehensive review explores the current evidence underpinning the role of contralateral prophylactic mastectomy and its impact on contralateral breast cancer risk and survival in three distinct at-risk groups affected by unilateral breast cancer: known genetic carriers, those with strong familial risk but no demonstrable genetic mutation and women who are of young age at presentation. The review supports the role of contralateral prophylactic mastectomy in “high risk” groups where the evidence suggests a reduction in contralateral breast cancer risk. However, this benefit is less evident in women who are just young at presentation or those who have strong family history but no demonstrable genetic mutation. A multidisciplinary and personalized approach to support individuals in a shared-decision making process is recommended.
Bone Marrow Clonogenic Myeloid Progenitors from NPM1-Mutated AML Patients Do Not Harbor the NPM1 Mutation: Implication for the Cell-Of-Origin of NPM1+ AML

The cell-of-origin of NPM1- and FLT3-mutated acute myeloid leukemia (AML) is still a matter of debate. Here, we combined in vitro clonogenic assays with targeted sequencing to gain further insights into the cell-of-origin of NPM1 and FLT3-ITD-mutated AML in diagnostic bone marrow (BM) from nine NPM1+/FLT3-ITD (+/−) AMLs. We reasoned that individually plucked colony forming units (CFUs) are clonal and reflect the progeny of a single stem/progenitor cell. NPM1 and FLT3-ITD mutations seen in the diagnostic blasts were found in only 2/95 and 1/57 individually plucked CFUs, suggesting that BM clonogenic myeloid progenitors in NPM1-mutated and NPM1/FLT3-ITD-mutated AML patients do not harbor such molecular lesions. This supports previous studies on NPM1 mutations as secondary mutations in AML, likely acquired in an expanded pool of committed myeloid progenitors, perhaps CD34−, in line with the CD34−/low phenotype of NPM1-mutated AMLs. This study has important implications on the cell-of-origin of NPM1+ AML, and reinforces that therapeutic targeting of either NPM1 or FLT3-ITD mutations might only have a transient clinical benefit in debulking the leukemia, but is unlikely to be curative since will not target the AML-initiating/preleukemic cells. The absence of NPM1 and FLT3-ITD mutations in normal clonogenic myeloid progenitors is in line with their absence in clonal hematopoiesis of indeterminate potential.
Obstetric Ultrasonography to Detect Fetal Abnormalities in a Mouse Model for Zika Virus Infection

In 2015 Zika virus (ZIKV) emerged for the first time in South America. The following ZIKV epidemic resulted in the appearance of a clinical phenotype with microcephaly and other severe malformations in newborns. So far, mechanisms of ZIKV induced damage to the fetus are not completely understood. Previous data suggest that ZIKV may bypass the placenta to reach the fetus. Thus, animal models for ZIKV infection are important to facilitate studies about ZIKV infection during pregnancy. Here, we used ultrasound based imaging (USI) to characterize ZIKV induced pathogenesis in the pregnant Type I interferon receptor-deficient (IFNAR-/-) mouse model. Based on USI we suggest the placenta to be a primary target organ of ZIKV infection enabling ZIKV spreading to the fetus. Moreover, in addition to direct infection of the fetus, the placental ZIKV infection may cause an indirect damage to the fetus through reduced uteroplacental perfusion leading to intrauterine growth retardation (IUGR) and fetal complications as early as embryonic day (ED) 12.5. Our data confirmed the capability of USI to characterize ZIKV induced modifications in mouse fetuses. Data from further studies using USI to monitor ZIKV infections will contribute to a better understanding of ZIKV infection in pregnant IFNAR-/- mice.
Understanding Calcium-Dependent Conformational Changes in S100A1 Protein: A Combination of Molecular Dynamics and Gene Expression Study in Skeletal Muscle

The S100A1 protein, involved in various physiological activities through the binding of calcium ions (Ca2+), participates in several protein-protein interaction (PPI) events after Ca2+-dependent activation. The present work investigates Ca2+-dependent conformational changes in the helix-EF hand-helix using the molecular dynamics (MD) simulation approach that facilitates the understanding of Ca2+-dependent structural and dynamic distinctions between the apo and holo forms of the protein. Furthermore, the process of ion binding by inserting Ca2+ into the bulk of the apo structure was simulated by molecular dynamics. Expectations of the simulation were demonstrated using cluster analysis and a variety of structural metrics, such as interhelical angle estimation, solvent accessible surface area, hydrogen bond analysis, and contact analysis. Ca2+ triggered a rise in the interhelical angles of S100A1 on the binding site and solvent accessible surface area. Significant configurational regulations were observed in the holo protein. The findings would contribute to understanding the molecular basis of the association of Ca2+ with the S100A1 protein, which may be an appropriate study to understand the Ca2+-mediated conformational changes in the protein target. In addition, we investigated the expression profile of S100A1 in myoblast differentiation and muscle regeneration. These data showed that S100A1 is expressed in skeletal muscles. However, the expression decreases with time during the process of myoblast differentiation.
Association between Prurigo Nodularis and Etiologies of Peripheral Neuropathy: Suggesting a Role for Neural Dysregulation in Pathogenesis

Background: Prurigo nodularis (PN) is an intensely pruritic skin condition of considerable morbidity. However, the pathogenesis of PN and its association with underlying neuropathy is unclear. Objective: We sought to investigate the association between PN and etiologies of peripheral neuropathy. Methods: A cross-sectional analysis of adult patients (≥18-year-old) with PN, AD, and Psoriasis at the Johns Hopkins Health System over a six-year period (January 2013–January 2019) was performed. The strength of association with etiologies of peripheral neuropathy were compared to a control cohort of individuals without PN, as well as those with AD or psoriasis. Results: A total of 1122 patients with PN were compared to 10,390 AD patients, 15,056 patients with psoriasis, and a control cohort of 4,949,017 individuals without PN, with respect to 25 comorbidities associated with peripheral neuropathies. Limitations: Comparisons between peripheral neuropathies and PN represent associations but are not causal relationships. Conclusion: Prurigo nodularis is strongly associated with peripheral neuropathies, suggesting a role for neural dysregulation in pathogenesis.
Nisin as a Novel Feed Additive: The Effects on Gut Microbial Modulation and Activity, Histological Parameters, and Growth Performance of Broiler Chickens

Simple Summary In an era with an increasing number of antibiotic-resistant bacteria strains, there is a need to find a novel and efficient alternative to the antibiotics commonly used in animal nutrition. As natural proteins synthesized by most known bacteria, bacteriocins are considered future candidates. To date, nisin (E234), the best-known bacteriocin, is used as a preservative against food-borne pathogens such as Listeria monocytogenes in the food industry. However, there are scarce data about the application of nisin in the diet of livestock, including poultry. In this study, we evaluated the effect of nisin in broiler chicken diets on selected microbial populations, the activities of which are related to gastrointestinal health, growth performance, and gut histomorphology. We found that nisin application positively affects the feed conversion ratio and exerts a similar effect as the ionophore coccidiostat monensin in the case of microbiota modulation. Additionally, nisin supplementation decreased microbial fermentation in the jejunum. No changes in ileal histomorphology or internal organ weights were noted. We conclude that nisin may be considered a natural and safe antimicrobial agent and growth promoter in broiler chicken nutrition. Abstract Two independent experiments were performed to evaluate the effect of nisin alone or with monensin on gut microbiota, gut microbial activities, and histomorphology (exp 1) and the effect of nisin application in a dose‒response manner on the growth performance of broiler chickens (exp 2). A total of 900 one-day-old female Ross 308 chicks (400, exp 1; 500, exp 2) were randomly distributed to four groups (exp 1; 10 replicate pens per treatment with 10 birds each), i.e., NA, no additives; MON, monensin (100 ppm); NIS, nisin (2700 IU/kg diet); and MON + NIS, a mixture of monensin (100 ppm) and nisin (2700 IU/kg diet); or 5 treatments (exp 2), NA, no additives; NIS100, nisin (100 IU/kg diet); NIS200, nisin (200 IU/kg diet); NIS400, nisin (400 IU/kg diet); and NIS800, nisin (800 IU/kg diet). Nisin supplementation positively affected the microbiota of the gut by reducing potentially pathogenic bacterial populations in the jejunum and ceca. The bacterial fermentation in the jejunum was significantly lowered by nisin addition. The addition of nisin from 100 IU to 800 IU decreased the FCR value over the entire experimental period. According to the results, nisin can be considered a natural dietary supplement for broiler chickens.
Assessing performance validity with the TOMM and automatized sequences task in a pediatric psychiatric inpatient setting

ABSTRACT This study examined the performance of children consecutively admitted to an inpatient psychiatric unit on the Test of Memory Malingering (TOMM) (aged 5–12; n = 96) and Automatized Sequences Task (aged 8–12; n = 67). Eighty-three percent of children passed the TOMM Trial 2 (M raw score = 47.7, SD = 4.7) and 76% of children passed the Automatized Sequences Task total time (M = 23.1 seconds; SD = 8.2). The concordance rate between the TOMM and the total time on the Automatized Sequences Task was 73.1%. Receiver operating characteristic curves indicated that of the Automatized Sequences Task subtests, only Counting 1–20 significantly differentiated children who passed Trial 2 of the TOMM from those who did not pass Trial 2 of the TOMM (area under the curve = .756, p = .006). Performance on both PVTs was unrelated to demographic characteristics and measures of psychological and neuropsychological functioning on both the TOMM and Automatized Sequences Task. Further research is needed to determine whether the nearly 1 in 4 children (23.9%) who performed below recommended cutoffs on Automatized Sequences Task reflects genuine suboptimal effort, cognitive difficulties among these children, and/or other factors.
Cardiac mitochondrial function depends on BUD23 mediated ribosome programming

Efficient mitochondrial function is required in tissues with high energy demand such as the heart, and mitochondrial dysfunction is associated with cardiovascular disease. Expression of mitochondrial proteins is tightly regulated in response to internal and external stimuli. Here we identify a novel mechanism regulating mitochondrial content and function, through BUD23-dependent ribosome generation. BUD23 was required for ribosome maturation, normal 18S/28S stoichiometry and modulated the translation of mitochondrial transcripts in human A549 cells. Deletion of Bud23 in murine cardiomyocytes reduced mitochondrial content and function, leading to severe cardiomyopathy and death. We discovered that BUD23 selectively promotes ribosomal interaction with low GC-content 5’UTRs. Taken together we identify a critical role for BUD23 in bioenergetics gene expression, by promoting efficient translation of mRNA transcripts with low 5’UTR GC content. BUD23 emerges as essential to mouse development, and to postnatal cardiac function.
Genome-Wide Association Mapping of Prostrate/Erect Growth Habit in Winter Durum Wheat

By selecting for prostrate growth habit of the juvenile phase of the cycle, durum wheat cultivars could be developed with improved competitive ability against weeds, and better soil coverage to reduce the soil water lost by evaporation. A panel of 184 durum wheat (Triticum turgidum subsp. durum) genotypes, previously genotyped with DArT-seq markers, was used to perform association mapping analysis of prostrate/erect growth habit trait and to identify candidate genes. Phenotypic data of plant growth habit were recorded during three consecutive growing seasons (2014–2016), two different growth conditions (field trial and greenhouse) and two sowing periods (autumn and spring). Genome-wide association study revealed significant marker-trait associations, twelve of which were specific for a single environment/year, 4 consistent in two environments, and two MTAs for the LSmeans were identified across all environments, on chromosomes 2B and 5A. The co-localization of some MTAs identified in this study with known vernalization and photoperiod genes demonstrated that the sensitivity to vernalization and photoperiod response are actually not only key components of spring/winter growth habit, but they play also an important role in defining the magnitude of the tiller angle during the tillering stage. Many zinc-finger transcription factors, such as C2H2 or CCCH-domain zinc finger proteins, known to be involved in plant growth habit and in leaf angle regulation were found as among the most likely candidate genes. The highest numbers of candidate genes putatively related to the trait were found on chromosomes 3A, 4B, 5A and 6A. Moreover, a bioinformatic approach has been considered to search for functional ortholog genes in wheat by using the sequence of rice and barley tiller angle-related genes. The information generated could be used to improve the understanding of the mechanisms that regulate the prostrate/erect growth habit in wheat and the adaptive potential of durum wheat under resource-limited environmental conditions.
Ischemic Stroke and Transient Ischemic Attack Risk Following Vitamin K Antagonist Cessation in Newly Diagnosed Atrial Fibrillation: A Cohort Study

Background In nonvalvular atrial fibrillation (AF), oral anticoagulants prevent ischemic strokes and transient ischemic attacks (TIAs), but nonpersistence with vitamin K antagonist (VKA) oral anticoagulant therapy (20–50% at 1 year) is problematic. The precise risk of stroke/TIA after VKA cessation and its time course during extended follow‐up is unknown. Methods and Results The study cohort of incident AF in patients receiving initial VKA between 2001 and 2013 was identified from the UK Clinical Practice Research Datalink (linked hospitalizations and causes of death). Using a nested case‐control analysis, patients with incident stroke/TIA were matched to patients without stroke/TIA (controls). Relative risk with time since VKA cessation compared with current VKA use was approximated from conditional logistic regression. We studied 16 696 patients with incident AF and initial VKA treatment. There were 489 stroke/TIA cases matched to 2137 controls (mean CHA 2 DS 2‐VASc score 4.3). Compared with current VKA use, the excess incidence rate of stroke/TIA following VKA cessation in the first year after AF diagnosis was 2.29 (95% CI, 0.98–3.90) per 100 person‐years of VKA cessation or 1 additional stroke/TIA per 43 patients per year discontinuing VKA, compared with 1.43 (95% CI, 0.97–1.88) per 100 person‐years corresponding to 1 additional stroke/TIA per 70 patients per year, when VKA was discontinued more than 1 year after AF diagnosis. Conclusions VKA cessation is associated with a continuous excess thromboembolic stroke/TIA risk. Increasing oral anticoagulant persistence, especially in the year after AF diagnosis, should be a therapeutic target to reduce stroke/TIA in AF.
Impact of Vitamin C and Thiamine Administration on Delirium-Free Days in Patients with Septic Shock

Sepsis is a common cause of delirium in the intensive care unit (ICU). Recently, vitamin C and thiamine administration has been gaining interest as a potential adjunct therapy for sepsis. We investigated the impact of early vitamin C and thiamine administration on ICU delirium-free days among critically ill patients in septic shock. We performed a single-center, retrospective study of patients who visited the emergency department (ED) from January 2017 to July 2018. We categorized patients into a treatment (received vitamin C and thiamine) and control group. We compared delirium-free days within 14 days after ICU admission using propensity score matching. Of 435 patients with septic shock, we assigned 89 propensity score-matched pairs to the treatment and control groups. The median delirium-free days did not differ between treatment (11, interquartile range [IQR] 5–14 days) and control (12, IQR 6–14 days) groups (p = 0.894). Secondary outcomes were not different between the two groups, including delirium incidence and 28-day mortality. These findings were consistent after subgroup analysis for patients who met the sepsis-3 definition of septic shock. Vitamin C and thiamine administration showed no association with ICU delirium-free days among patients in septic shock.
The Effects of Surgical Treatment on Retina-Choroidal Findings in Patients With Obstructive Sleep Apnea Syndrome.

BACKGROUND AND OBJECTIVE The purpose of this study was to determine the effect of surgical treatment on ocular findings in obstructive sleep apnea syndrome (OSAS). PATIENTS AND METHODS The authors studied 34 eyes of 34 newly diagnosed OSAS patients. The sleep study was performed before and 6 months after expansion sphincter pharyngoplasty (ESP). Retinal nerve fiber layer (RNFL), choroidal thickness (CT), and retinal arteriolar caliber (RAC) analyses were performed using spectral-domain optical coherence tomography. Intraocular pressure (IOP) and ocular pulse amplitude were performed using the Pascal dynamic contour tonometer. RESULTS The preoperative and postoperative Apnea Hypopnea Index scores and average oxygen saturation values were significantly different (P = .0001 and P = .001, respectively). There was no significant difference between the preoperative and postoperative RNFL thicknesses (P > .05). The preoperative subfoveal, nasal, temporal CT, and IOP were significantly different from the postoperative measurements (P = .006, P = .05, P = .036, and P = .0001, respectively). CONCLUSIONS ESP had a significant influence on CT and IOP in patients with OSAS, maintaining a decrease in CT and IOP 6 months after surgery. The determination of these ocular findings may be useful to show the positive effects of ESP. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:35-42. ].
Physical and functional aspects of persons with multiple sclerosis practicing Tai-Geiko: randomized trial

OBJECTIVES: This study aimed to verify the influence of Tai-Geiko on the physical and functional aspects of people with multiple sclerosis (MS). METHODS: This was a parallel-group, randomized trial with two arms. People with MS were allocated to an experimental group (EG) (n=10) and control group (CG) (n=09). The participants received multidisciplinary care supervised by a physiotherapist in the Tai-Geiko exercise. Participants underwent the assessments after the intervention. The Expanded Disability Status Scale (EDSS-maximum score of 6.0), strength test (kgf) using a dynamometer, Timed Up and Go mobility test (TUG), and stabilometric balance test (Platform EMG system®) were evaluated. Demographic data were recorded, including age, sex, comorbidities, lifestyle and classification of MS. Clinical Trials (ReBeC): RBR-4sty47. RESULTS: The EG group improved in 12 variables, and the CG improved in 3 variables. The following values were obtained for pre/postintervention, respectively: EG: lumbar force (38/52 kgf), TUG (11/9 s), locomotion velocity (519/393 ms); double task two (53/39 s); platform stabilometric trajectory: traversed get up (39/26 s) and sit (45/29 s); anteroposterior (AP) amplitude rise (11/8 cm) and sit (12.40/9.94 cm) and anteroposterior frequency rise (1.00/1.56 Hz) and sit (0.8/1.25 Hz) (p<0.05); CG: right-hand grip force (26/29 kgf); TUG (9.8 /8.7 s) and AP (11.84 /9.53 cm) stabilometric amplitude at the sitting moment (p<0.05), (3.2/5.99 Hz, p=0.01) and sit (3.47/5.01 Hz, p=0.04). CONCLUSION: Tai-Geiko practice can be suggested as complementary exercise in the rehabilitation of persons with MS.