Miracle-dz/UniFAR-FTUs huggingface dataset:
MicroRNA‐145 Antagonism Reverses TGF‐&bgr; Inhibition of F508del CFTR Correction in Airway Epithelia

Rationale: MicroRNAs (miRNAs) destabilize mRNA transcripts and inhibit protein translation. miR‐145 is of particular interest in cystic fibrosis (CF) as it has a direct binding site in the 3′‐untranslated region of CFTR (cystic fibrosis transmembrane conductance regulator) and is upregulated by the CF genetic modifier TGF (transforming growth factor)‐&bgr;. Objectives: To demonstrate that miR‐145 mediates TGF‐&bgr; inhibition of CFTR synthesis and function in airway epithelia. Methods: Primary human CF (F508del homozygous) and non‐CF airway epithelial cells were grown to terminal differentiation at the air‐liquid interface on permeable supports. TGF‐&bgr; (5 ng/ml), a miR‐145 mimic (20 nM), and a miR‐145 antagonist (20 nM) were used to manipulate CFTR function. In CF cells, lumacaftor (3 &mgr;M) and ivacaftor (10 &mgr;M) corrected mutant F508del CFTR. Quantification of CFTR mRNA, protein, and function was done by standard techniques. Measurements and Main Results: miR‐145 is increased fourfold in CF BAL fluid compared with non‐CF (P < 0.01) and increased 10‐fold in CF primary airway epithelial cells (P < 0.01). Exogenous TGF‐&bgr; doubles miR‐145 expression (P < 0.05), halves wild‐type CFTR mRNA and protein levels (P < 0.01), and nullifies lumacaftor/ivacaftor F508del CFTR correction. miR‐145 overexpression similarly decreases wild‐type CFTR protein synthesis (P < 0.01) and function (P < 0.05), and eliminates F508del corrector benefit. miR‐145 antagonism blocks TGF‐&bgr; suppression of CFTR and enhances lumacaftor correction of F508del CFTR. Conclusions: miR‐145 mediates TGF‐&bgr; inhibition of CFTR synthesis and function in airway epithelia. Specific antagonists to miR‐145 interrupt TGF‐&bgr; signaling to restore F508del CFTR modulation. miR‐145 antagonism may offer a novel therapeutic opportunity to enhance therapeutic benefit of F508del CFTR correction in CF epithelia.
Feeding value of methanol-derived single cell protein for broiler chicks.

Abstract Feeding trials were conducted to determine the effects of incorporating a bacterial cell protein product (BCP) produced on methanol substrate into the diet of broiler chicks. The BCP was added to corn-soybean meal type diets at levels of 0, 5, 10 and 15%. In the first trial using all-mash diets, feed consumption and weight gains were reduced as the level of BCP increased. In the second study, pelleting the diets containing the fine, dusty BCP material was effective in improving feed consumption and weight gains. Up to 10% BCP was tolerated without adversely affecting performance when diets were pelleted.
Repeated 177Lu-Labeled PSMA-617 Radioligand Therapy Using Treatment Activities of Up to 9.3 GBq

Current treatment protocols for 177Lu-labeled PSMA-617 therapies were cautiously derived from dosimetry data, but their practical appropriateness has not yet been proven clinically. We retrospectively report our clinical observations using 4 different treatment activities. Methods: Forty patients with advanced prostate cancer and positive uptake in prostate-specific membrane antigen (PSMA) imaging were treated with 4 GBq of 177Lu activity/80 nmol of precursor, 6 GBq of 177Lu activity/120 nmol of precursor, 7.4 GBq of 177Lu activity/150 nmol of precursor, or 9.3 GBq of 177Lu activity/150 nmol of precursor (10 patients per group) every 2 mo. Safety was checked every 2 wk by laboratory tests, the prostate-specific antigen response was checked every 4 wk, and other effects were assessed by anamnesis. Results: The initial prostate-specific antigen response showed no correlation with treatment activity. However, 2 of 10, 4 of 10, 4 of 10, and 7 of 10 patients receiving doses of 4, 6, 7.4, and 9.3 GBq, respectively, were in partial remission 8 wk after completing all 3 cycles. This finding would be in line with but—because of low patient numbers—would not prove a positive dose–response relationship. Acute hematologic toxicity was also not correlated with treatment activity, and no more than 1 patient per group had grade 3/4 toxicity. Nevertheless, in contrast to the findings for the other groups, the mean platelet count in the 9.3-GBq group decreased chronically over time. Conclusion: If patients with diffuse red marrow infiltration and extensive chemotherapeutic pretreatments are excluded, then treatment activities of up to 3 injections of 9.3 GBq of 177Lu-PSMA-617 every 2 mo are tolerated well. Further dose escalation should be conducted with care, as the highest dose seems to be close to the maximum tolerable dose.
Diet dilution and compensatory growth in broilers.

Two experiments were conducted to note the response of broiler chickens to degrees of diet dilution from 4 to 11 days of age. In Experiment 1, broilers were fed conventional broiler diets from 0 to 4 and 11 to 56 days of age. From 4 to 11 days, birds were fed a conventional corn and soybean meal broiler starter, or the same diet in which major nutrients were replaced with 25, 40, or 55% ground rice hulls. Mineral and vitamin sources were not affected by dilution. Each of the three diluted diets together with an undiluted control diet was fed to three replicate floor pen groups of 30 male or 30 female broilers. In a second similar experiment, male birds were fed a regular broiler starter from 4 to 11 days or a diet diluted with 50% rice hulls. In this second experiment, rice hulls were substituted for all ingredients including those providing vitamin and mineral supplements. In Experiment 1, diet dilution resulted in a significant (P less than .05) reduction in body weight at 11 days of age, although by 42 days there was complete recovery of body weight with no change in overall efficiency of feed utilization. This same trend was seen in both sexes. Calculation of energy balance suggests these birds to have used energy very efficiently during the period of undernutrition. Diet dilution had no effect on carcass characteristics at 42 days, although for males at 56 days there was an indication of reduced abdominal fat content (P less than .05). In Experiment 2, compensatory gain was incomplete, although results were confounded due to an outbreak of infectious bronchitis. (ABSTRACT TRUNCATED AT 250 WORDS)
Attachment-Security Prime Effect on Skin-Conductance Synchronization in Psychotherapists: An Empirical Study

Physiological synchronization (PS) is a phenomenon of simultaneous activity between two persons’ physiological signals. It has been associated with empathy, shared affectivity, and efficacious therapeutic relationships. The aim of the present study was to explore the possible connections between PS and the attachment system, seeking preliminary evidence of this link by means of an experimental manipulation of the sense of attachment security in psychotherapists according to a protocol by Mikulincer and Shaver (2001), which has been proven to elicit empathetic behavior. We compared the synchronization of skin-conductance signals in brief psychological interviews between 18 psychodynamic therapists and 18 healthy volunteers. A sense of attachment-security priming was administered to half of the therapists, whereas the other half received a positive-affect control prime. Lag analysis was performed to investigate the “leading” or “following” attitudes of the participants in the two conditions. Mixed-model regressions and evidence-ratio model comparisons were used to investigate the effects of the manipulation on PS. Therapist attachment anxiety and avoidance traits were considered covariates. The attachment-security prime showed a significant effect on PS lag dynamics, but not on overall PS amount. Lag analysis showed that the therapists in the attachment-security condition were significantly more prone to assume a leading attitude in the physiological coupling than the therapists in the control condition. Therapist attachment anxiety and avoidance had no apparent effect. Our result paves the way for further exploration of the clinical relationship from a physiological standpoint.
Chromosomal inversions promote genomic islands of concerted evolution of Hsp70 genes in the Drosophila subobscura species subgroup

Heat‐shock (HS) assays to understand the connection between standing inversion variation and evolutionary response to climate change in Drosophila subobscura found that “warm‐climate” inversion O3+4 exhibits non‐HS levels of Hsp70 protein like those of “cold‐climate” OST after HS induction. This was unexpected, as overexpression of Hsp70 can incur multiple fitness costs. To understand the genetic basis of this finding, we have determined the genomic sequence organization of the Hsp70 family in four different inversions, including OST, O3+4, O3+4+8 and O3+4+16, using as outgroups the remainder of the subobscura species subgroup, namely Drosophila madeirensis and Drosophila guanche. We found (i) in all the assayed lines, the Hsp70 family resides in cytological locus 94A and consists of only two genes, each with four HS elements (HSEs) and three GAGA sites on its promoter. Yet, in OST, the family is comparatively more compact; (ii) the two Hsp70 copies evolve in concert through gene conversion, except in D. guanche; (iii) within D. subobscura, the rate of concerted evolution is strongly structured by inversion, being higher in OST than in O3+4; and (iv) in D. guanche, the two copies accumulated multiple differences, including a newly evolved “gap‐type” HSE2. The absence of concerted evolution in this species may be related to a long‐gone‐unnoticed observation that it lacks Hsp70 HS response, perhaps because it has evolved within a narrow thermal range in an oceanic island. Our results point to a previously unrealized link between inversions and concerted evolution, with potentially major implications for understanding genome evolution.
Gonorrhea in Indonesia: High Prevalence of Asymptomatic Urogenital Gonorrhea but No Circulating Extended Spectrum Cephalosporins-Resistant Neisseria gonorrhoeae Strains in Jakarta, Yogyakarta, and Denpasar, Indonesia

Background Little is known about the epidemiology of asymptomatic urogenital gonorrhea and antimicrobial susceptibility of Neisseria gonorrhoeae (NG) strains circulating in Indonesia. We studied these issues in 3 large Indonesian cities. Methods In 2014, participants were recruited from sexually transmitted infection clinics and through outreach in Jakarta, Yogyakarta, and Denpasar. Neisseria gonorrhoeae detection in genital specimens was performed with NG-qPCR at the Public Health Service in Amsterdam. Antimicrobial susceptibility was investigated using the Etest. Results Among 992 participants, 781 were asymptomatic and included in the risk factors analysis: 439 (56.2%) men, 258 (33.0%) women, and 84 (10.8%) transwomen. They differed significantly in age and were mostly men who have sex with men (35.2%) and female sex workers (29.3%). Overall, 175 (22.4%) asymptomatic participants had a positive NG-qPCR result. Factors positively associated with asymptomatic urogenital gonorrhea were being recruited through outreach (vs clinic-based), inconsistent condom use, and being divorced/widowed (vs single). Among 79 urogenital cultured isolates derived from 27 symptomatic and 52 asymptomatic participants, all isolates were susceptible to ceftriaxone and cefixime, and 98.7% of isolates were susceptible to azithromycin. In contrast, resistance to doxycycline (98.7%) and ciprofloxacin (97.4%) was common. Conclusions Prevalence of asymptomatic urogenital gonorrhea among Indonesian key populations is very high. Little to no resistance against extended spectrum cephalosporins and azithromycin was observed. However, almost all isolates were resistant to doxycycline and ciprofloxacin. Strengthening outreach sexually transmitted infections services, composing guidelines to screen asymptomatic individuals, and implementing periodical antimicrobial resistance surveillance are recommended.
The quality of instruments to assess the process of shared decision making: A systematic review

Objective To inventory instruments assessing the process of shared decision making and appraise their measurement quality, taking into account the methodological quality of their validation studies. Methods In a systematic review we searched seven databases (PubMed, Embase, Emcare, Cochrane, PsycINFO, Web of Science, Academic Search Premier) for studies investigating instruments measuring the process of shared decision making. Per identified instrument, we assessed the level of evidence separately for 10 measurement properties following a three-step procedure: 1) appraisal of the methodological quality using the COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) checklist, 2) appraisal of the psychometric quality of the measurement property using three possible quality scores, 3) best-evidence synthesis based on the number of studies, their methodological and psychometrical quality, and the direction and consistency of the results. The study protocol was registered at PROSPERO: CRD42015023397. Results We included 51 articles describing the development and/or evaluation of 40 shared decision-making process instruments: 16 patient questionnaires, 4 provider questionnaires, 18 coding schemes and 2 instruments measuring multiple perspectives. There is an overall lack of evidence for their measurement quality, either because validation is missing or methods are poor. The best-evidence synthesis indicated positive results for a major part of instruments for content validity (50%) and structural validity (53%) if these were evaluated, but negative results for a major part of instruments when inter-rater reliability (47%) and hypotheses testing (59%) were evaluated. Conclusions Due to the lack of evidence on measurement quality, the choice for the most appropriate instrument can best be based on the instrument’s content and characteristics such as the perspective that they assess. We recommend refinement and validation of existing instruments, and the use of COSMIN-guidelines to help guarantee high-quality evaluations.
Phylogeny of Rosellinia capetribulensis sp. nov. and its allies (Xylariaceae)

A new Rosellinia species, R. capetribulensis isolated from Calamus sp. in Australia is described. R. capetribulensis is characterized by perithecia immersed within a carbonaceous stroma surrounded by subiculum-like hyphae, asci with large, barrel-shaped amyloid apical apparatus and large dark brown spores. Morphologically, R. capetribulensis appears to be similar to R. bunodes, R. markhamiae and R. megalospora. To gain further insights into the phylogeny of this new taxon we analyzed the ITS-5.8S rDNA using maximum parsimony and likelihood methods. In addition, a morphological dataset also was analyzed phylogenetically to investigate possible affinities. ITS rDNA based phylogenies reveal that R. capetribulensis is closely related to other Rosellinia species showing closest affinity to R. arcuata, R. necatrix and R. pepo. However, analysis of R. capetribulensis forms an unsupported branch sister to these taxa. Results from the morphological matrix indicate a close morphological affinity to members of Rosellinia subgenus Rosellinia. Despite that ITS rDNA and morphological analyses present difficulties in constructing a proper phylogenetic framework among Rosellinia and allied genera, there is sufficient evidence to support the establishment of the new taxon in the genus Rosellinia. The morphological similarities and differences between R. capetribulensis and allied genera such as Astrocystis and Entoleuca are also briefly discussed.
Room Temperature Stable PspA-Based Nanovaccine Induces Protective Immunity

Streptococcus pneumoniae is a major causative agent of pneumonia, a debilitating disease particularly in young and elderly populations, and is the leading worldwide cause of death in children under the age of five. While there are existing vaccines against S. pneumoniae, none are protective across all serotypes. Pneumococcal surface protein A (PspA), a key virulence factor of S. pneumoniae, is an antigen that may be incorporated into future vaccines to address the immunological challenges presented by the diversity of capsular antigens. PspA has been shown to be immunogenic and capable of initiating a humoral immune response that is reactive across approximately 94% of pneumococcal strains. Biodegradable polyanhydrides have been studied as a nanoparticle-based vaccine (i.e., nanovaccine) platform to stabilize labile proteins, to provide adjuvanticity, and enhance patient compliance by providing protective immunity in a single dose. In this study, we designed a room temperature stable PspA-based polyanhydride nanovaccine that eliminated the need for a free protein component (i.e., 100% encapsulated within the nanoparticles). Mice were immunized once with the lead nanovaccine and upon challenge, presented significantly higher survival rates than animals immunized with soluble protein alone, even with a 25-fold reduction in protein dose. This lead nanovaccine formulation performed similarly to protein adjuvanted with Alum, however, with much less tissue reactogenicity at the site of immunization. By eliminating the free PspA from the nanovaccine formulation, the lead nanovaccine was efficacious after being stored dry for 60 days at room temperature, breaking the need for maintaining the cold chain. Altogether, this study demonstrated that a single dose PspA-based nanovaccine against S. pneumoniae induced protective immunity and provided thermal stability when stored at room temperature for at least 60 days.
Productivity and Misallocation in General Equilibrium

This paper develops a general theory of aggregation in inefficient economies. We provide nonparametric formulas for aggregating microeconomic shocks in economies with distortions such as taxes, markups, frictions to resource reallocation, financial frictions, and nominal rigidities. We allow for arbitrary elasticities of substitution, returns to scale, factor mobility, and input-output network linkages. We show how to separately measure changes in technical and allocative efficiency. We also show how to compute the social cost of distortions. We pursue applications focusing on firm-level markups in the United States. We find that improvement in allocative efficiency, due to the reallocation over time of market share to high-markup firms, accounts for about half of aggregate TFP growth over the period 1997–2015. We also find that eliminating the misallocation resulting from the large and dispersed markups estimated in the data would raise aggregate TFP by about 15%, increasing the economy-wide cost of monopoly distortions by two orders of magnitude compared with the famous 0.1% estimate by Harberger (1954). These exact numbers should be interpreted with care because the data are imperfect and require substantial imputation.
Lower Extremity Stiffness Changes after Concussion in Collegiate Football Players

Purpose Recent research indicates that a concussion increases the risk of musculoskeletal injury. Neuromuscular changes after concussion might contribute to the increased risk of injury. Many studies have examined gait postconcussion, but few studies have examined more demanding tasks. This study compared changes in stiffness across the lower extremity, a measure of neuromuscular function, during a jump-landing task in athletes with a concussion (CONC) to uninjured athletes (UNINJ). Methods Division I football players (13 CONC and 26 UNINJ) were tested pre- and postseason. A motion capture system recorded subjects jumping on one limb from a 25.4-cm step onto a force plate. Hip, knee, and ankle joint stiffness were calculated from initial contact to peak joint flexion using the regression line slopes of the joint moment versus the joint angle plots. Leg stiffness was (peak vertical ground reaction force [PVGRF]/lower extremity vertical displacement) from initial contact to peak vertical ground reaction force. All stiffness values were normalized to body weight. Values from both limbs were averaged. General linear models compared group (CONC, UNINJ) differences in the changes of pre- and postseason stiffness values. Results Average time from concussion to postseason testing was 49.9 d. The CONC group showed an increase in hip stiffness (P = 0.03), a decrease in knee (P = 0.03) and leg stiffness (P = 0.03), but no change in ankle stiffness (P = 0.65) from pre- to postseason. Conclusion Lower extremity stiffness is altered after concussion, which could contribute to an increased risk of lower extremity injury. These data provide further evidence of altered neuromuscular function after concussion.
TARGETED LEVOTHYROXINE THERAPY FOR TREATMENT OF CONGENITAL HYPOTHYROIDISM.

OBJECTIVE The purpose of this study was to determine if infants with congenital hypothyroidism (CH) whose initial dose of levothyroxine (LT4) is based on thyroid gland anatomy require fewer dose adjustments in the first 6 months of life than those who were started empirically on LT4. METHODS Newborns with CH who had a thyroid ultrasound performed at diagnosis were eligible for this prospective, historical case-controlled study. The daily LT4 dose prescribed was based on results on the thyroid ultrasound as follows: 15 mcg/kg for athyreosis, 12 mcg/kg for a dysgenetic thyroid, and 10 mcg/kg for an anatomically normal gland. Routine labs according to standard guidelines were obtained, and the number of dose adjustments over the first 6 months of therapy was recorded. Each study participant was matched with 2 historical controls with CH based on sex and thyroid anatomy. RESULTS Twenty-two subjects (10 with athyreosis, 4 with dysgenetic glands, and 8 with anatomically normal glands) were matched to 44 controls. There was no significant difference in the overall number of adjustments in the study group compared to controls (P = .74). However, there were significantly fewer adjustments made for undertreatment (P = .03) and significantly more adjustments made for overtreatment (P = .006) in subjects with athyreosis compared to controls. CONCLUSION Targeted LT4 therapy does not appear to decrease the overall frequency of dose adjustments for infants with CH. However, 15 mcg/kg/day appears to exceed thyroid hormone requirements in infants with CH due to athyreosis. ABBREVIATIONS CH = congenital hypothyroidism LT4 = levothyroxine OT = overtreatment T4 = thyroxine TSH = thyroid-stimulating hormone UT = undertreatment.