Miracle-dz/UniFAR-FTUs huggingface dataset:
Higher 25-hydroxyvitamin D concentrations are associated with better lower-extremity function in both active and inactive persons aged > or =60 y.

BACKGROUND Vitamin D may improve muscle strength through a highly specific nuclear receptor in muscle tissue. OBJECTIVES We investigated whether there is an association between 25-hydroxyvitamin D [25(OH)D] concentrations and lower-extremity function in ambulatory older persons, whether that association differs by activity level, and, if so, whether there is an identifiable threshold in the association. DESIGN The study was a population-based survey of the ambulatory US population aged 60 to > or =90 y (n = 4100). Lower-extremity function according to serum 25(OH)D concentrations was assessed by linear regression analyses and regression plots after control for activity level (inactive or active) and several other potential confounders. Separate analyses were performed for the timed 8-foot (ie, 2.4 m) walk test and a repeated sit-to-stand test. RESULTS The 8-foot walk test compared subjects in the lowest and highest quintiles of 25(OH)D; the latter group had an average decrease of 0.27 s [95% CI: -0.44, -0.09 s (or 5.6%); P for trend < 0.001]. The sit-to-stand test compared subjects in the lowest and highest quintiles of 25(OH)D; the latter group had an average decrease of 0.67 s [95% CI: -1.11, -0.23 s (or 3.9%); P for trend = 0.017]. In the 25(OH)D reference range of 22.5-94 nmol/L, most of the improvement occurred in subjects with 25(OH)D concentrations between 22.5 and approximately 40 nmol/L, and further improvement was seen in the range of 40-94 nmol/L. Stratification by activity level showed no significant effect modification. CONCLUSION In both active and inactive ambulatory persons aged > or =60 y, 25(OH)D concentrations between 40 and 94 nmol/L are associated with better musculoskeletal function in the lower extremities than are concentrations < 40 nmol/L.
The unique epigenetic features of Pack-MULEs and their impact on chromosomal base composition and expression spectrum

Acquisition and rearrangement of host genes by transposable elements (TEs) is an important mechanism to increase gene diversity as exemplified by the ∼3000 Pack-Mutator-like TEs in the rice genome which have acquired gene sequences (Pack-MULEs), yet remain enigmatic. To identify signatures of functioning Pack-MULEs and Pack-MULE evolution, we generated transcriptome, translatome, and epigenome datasets and compared Pack-MULEs to genes and other TE families. Approximately 40% of Pack-MULEs were transcribed with 9% having translation evidence, clearly distinguishing them from other TEs. Pack-MULEs exhibited a unique expression profile associated with specificity in reproductive tissues that may be associated with seed traits. Expressed Pack-MULEs resemble regular protein-coding genes as exhibited by a low level of DNA methylation, association with active histone marks and DNase I hypersensitive sites, and an absence of repressive histone marks, suggesting that a substantial fraction of Pack-MULEs are potentially functional in vivo. Interestingly, the expression capacity of Pack-MULEs is independent of the local genomic environment, and the insertion and expression of Pack-MULEs may have altered the local chromosomal expression pattern as well as counteracted the impact of recombination on chromosomal base composition, which has profound consequences on the evolution of chromosome structure.
Effect of early infant feeding practices on infection-specific neonatal mortality: an investigation of the causal links with observational data from rural Ghana.

BACKGROUND Strong associations between delayed initiation of breastfeeding and increased neonatal mortality (2-28 d) were recently reported in rural Ghana. Investigation into the biological plausibility of this relation and potential causal pathways is needed. OBJECTIVE The objective was to assess the effect of early infant feeding practices (delayed initiation, prelacteal feeding, established neonatal breastfeeding) on infection-specific neonatal mortality in breastfed neonates aged 2-28 d. DESIGN This prospective observational cohort study was based on 10 942 breastfed singleton neonates born between 1 July 2003 and 30 June 2004, who survived to day 2, and whose mothers were visited in the neonatal period. Verbal autopsies were used to ascertain the cause of death. RESULTS One hundred forty neonates died from day 2 to day 28; 93 died of infection and 47 of noninfectious causes. The risk of death as a result of infection increased with increasing delay in initiation of breastfeeding from 1 h to day 7; overall late initiation (after day 1) was associated with a 2.6-fold risk [adjusted odds ratio (adj OR): 2.61; 95% CI: 1.68, 4.04]. Partial breastfeeding was associated with a 5.7-fold adjusted risk of death as a result of infectious disease (adj OR: 5.73; 95% CI: 2.75, 11.91). No obvious associations were observed between these feeding practices and noninfection-specific mortality. Prelacteal feeding was not associated with infection (adj OR: 1.11; 95% CI: 0.66, 1.86) or noninfection-specific (adj OR: 1.33; 95% CI: 0.55, 3.22) mortality. CONCLUSIONS This study provides the first epidemiologic evidence of a causal association between early breastfeeding and reduced infection-specific neonatal mortality in young human infants.
Sphingosine kinase 2 inhibition synergises with bortezomib to target myeloma by enhancing endoplasmic reticulum stress

The proteasome inhibitor bortezomib has proven to be invaluable in the treatment of myeloma. By exploiting the inherent high immunoglobulin protein production of malignant plasma cells, bortezomib induces endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), resulting in myeloma cell death. In most cases, however, the disease remains incurable highlighting the need for new therapeutic targets. Sphingosine kinase 2 (SK2) has been proposed as one such therapeutic target for myeloma. Our observations that bortezomib and SK2 inhibitors independently elicited induction of ER stress and the UPR prompted us to examine potential synergy between these agents in myeloma. Targeting SK2 synergistically contributed to ER stress and UPR activation induced by bortezomib, as evidenced by activation of the IRE1 pathway and stress kinases JNK and p38MAPK, thereby resulting in potent synergistic myeloma apoptosis in vitro. The combination of bortezomib and SK2 inhibition also exhibited strong in vivo synergy and favourable effects on bone disease. Therefore, our studies suggest that perturbations of sphingolipid signalling can synergistically enhance the effects seen with proteasome inhibition, highlighting the potential for the combination of these two modes of increasing ER stress to be formally evaluated in clinical trials for the treatment of myeloma patients.
Congenital Vomer Agenesis: A Rare and Poorly Understood Condition Revealed by Cone Beam CT

Isolated congenital vomer agenesis is a very rare and poorly understood condition. In the context of dental work-up by cone-beam computed tomography (CBCT), the explored volume of the facial bones occasionally reveals incidental abnormalities. We report the case of a 13-year old Caucasian female who underwent CBCT for the pre-treatment evaluation of primary failure of tooth eruption affecting the permanent right upper and inferior molars. CBCT depicted a large defect of the postero-inferior part of the nasal septum without associated soft tissue abnormality and without cranio-facial malformation or cleft palate. In the absence of a history of trauma, chronic inflammatory sinonasal disease, neoplasia and drug abuse, a posterior nasal septum defect warrants the diagnosis of vomer agenesis. A discussion of this condition and of salient CBCT features is provided.
Gene Expression Classifier vs Targeted Next-Generation Sequencing in the Management of Indeterminate Thyroid Nodules

Context Molecular testing has reduced the need for diagnostic hemithyroidectomy for indeterminate thyroid nodules. No studies have directly compared molecular testing techniques. Objective Compare the diagnostic performance of Afirma Gene Expression Classifier (GEC) with that of ThyroSeq v2 next-generation sequencing assay. Design Parallel randomized trial, monthly block randomization of patients with Bethesda III/IV cytology to GEC or ThyroSeq v2. Setting University of California, Los Angeles. Participants Patients who underwent thyroid biopsy (April 2016 to June 2017). Intervention Testing with GEC or ThyroSeq v2. Main Outcome Measure Molecular test performance. Results Of 1372 thyroid nodules, 176 (13%) had indeterminate cytology and 149 of 157 eligible indeterminate nodules (95%) were included in the study. Of nodules tested with GEC, 49% were suspicious, 43% were benign, and 9% were insufficient. Of nodules tested with ThyroSeq v2, 19% were mutation positive, 77% were mutation negative, and 4% were insufficient. The specificities of GEC and ThyroSeq v2 were 66% and 91%, respectively (P = 0.002); the positive predictive values of GEC and ThyroSeq v2 were 39% and 57%, respectively. Diagnostic hemithyroidectomy was avoided in 28 patients tested with GEC (39%) and 49 patients tested with ThyroSeq v2 (62%). Surveillance ultrasonography was available for 46 nodules (45 remained stable). Conclusions ThyroSeq v2 had higher specificity than Afirma GEC and allowed more patients to avoid surgery. Long-term surveillance is necessary to assess the false-negative rate of these particular molecular tests. Further studies are required for comparison with other available molecular diagnostics and for newer tests as they are developed.
Obstructive sleep apnoea of mild severity: should it be treated?

Purpose of review To provide guidance in the management of mild obstructive sleep apnoea syndrome (OSAS) in the context of a very high prevalence, poor correlation with symptom profile, and lack of evidence that mild OSAS significantly contributes to comorbidity or early mortality. Recent findings Mild obstructive sleep apnoea defined by hourly frequency of apnoeas or hypopnoeas (AHI) between 5 and 15 affects up to 35% of the general adult population but is much less prevalent when associated daytime symptoms are included. The poor correlation between symptoms and AHI complicates diagnosis and reports that mild OSAS is not significantly associated with comorbidity casts doubt on clinical significance. The diagnosis is complicated by night-to-night variability and by underestimation of AHI in ambulatory sleep studies that do not include sleep assessment. Active management of mild OSAS can be symptom-driven and offers a broad range of options. Lifestyle measures may be sufficient in many cases and mandibular advancement devices or positional therapy may be more effective in mild OSAS. Sleepy patients with low AHI may warrant a trial of continuous positive airway pressure therapy to establish the relationship between sleep disordered breathing and symptoms. Summary Management of mild OSAS can focus on symptom relief to the individual patient.
Bibliotelemetry of information and environment: Evaluation of an IoT‐powered recommender system

Internet of Things (IoT) infrastructure within the physical library environment is the basis for an integrative, hybrid approach to digital resource recommenders. The IoT infrastructure provides mobile, dynamic wayfinding support for items in the collection, which includes features for location‐based recommendations. A modular evaluation and analysis herein clarified the nature of users' requests for recommendations based on their location and describes subject areas of the library for which users request recommendations. The modular mobile design allowed for deep exploration of users' bibliographic identifiers throughout the global module system, serving to provide context to the browsing data that are the focus of this study. Bibliotelemetry is introduced as an evaluation method for IoT middleware within library collections.
Threonine requirements of healthy Indian men, measured by a 24-h indicator amino acid oxidation and balance technique.

BACKGROUND We previously questioned the validity of the 1985 FAO/WHO/UNU upper requirement value for threonine (7 mg x kg(-1) x d(-1)) and proposed a tentative mean requirement of 15 mg x kg(-1) x d(-1). OBJECTIVE In this study we used a 24-h indicator amino acid oxidation and balance technique, with [1-(13)C]leucine as the indicator amino acid, to assess threonine adequacy at 6 test intakes (7, 11, 15, 19, 22, and 27 mg x kg(-1) x d(-1)) with a 6-d dietary adaptation phase in healthy, well-nourished Indian men. DESIGN Sixteen men were randomly allocated to 3 of 6 test intakes and were studied after 6 d of adaptation to the experimental diets. Diets were based on an L-amino acid mixture in which the threonine content was varied. At 1800 on day 6, a 24-h intravenous [(13)C]leucine tracer infusion protocol was conducted to assess 24-h leucine oxidation and daily leucine balances. RESULTS Leucine balances differed significantly (P = 0.02) between the different intakes of threonine. Two-phase linear regression analysis from 12-h and 24-h leucine oxidation and 24-h leucine balance gave a breakpoint at a threonine intake of 15 mg x kg(-1) x d(-1), with 95% CIs ranging from 11 to 27 mg x kg(-1) x d(-1). There was no significant effect of threonine intake on 24-h leucine flux. CONCLUSION The results of the 24-h indicator amino acid oxidation and balance experiments indicate that the current FAO/WHO/UNU threonine recommendation of 7 mg x kg(-1) x d(-1) is inadequate. A mean threonine intake of 15 mg x kg(-1) x d(-1) is sufficient to achieve the indicator (leucine) amino acid balance in healthy Indian men.
Plasma leptin influences gestational weight gain and postpartum weight retention.

BACKGROUND Leptin, a product of the obese (ob) gene, is released from adipocytes. At the same body mass index, women have higher concentrations than men. Thus, during pregnancy, leptin may influence gestational weight gain and retention of a portion of that gain postpartum. OBJECTIVE We examined the relation between plasma leptin at entry to prenatal care and subsequent changes in weight from entry to prenatal care (at 17 wk gestation, baseline) until 6 mo postpartum. DESIGN This was an observational study of leptin, gestational weight gain, and postpartum weight retention (at 6 wk and 6 mo postpartum) in 103 low-income pregnant women from Camden, NJ, with a pregravid body mass index (in kg/m2) in the normal range (19.8-26). RESULTS After potential confounding variables were controlled for, leptin at entry significantly (P < 0.05) predicted weight gain in pregnancy, including measured rate of weight gain (x +/- SEE: 0.25 +/- 0.13 kg x unit log leptin(-1) x wk(-1)), measured rate of third-trimester weight gain (0.37 +/- 0.15 kg x unit log leptin(-1) x wk(-1)), rate of weight gain from recalled pregravid weight (0.23 +/- 0.09 kg x unit log leptin(-1) x wk(-1)), and net rate of gestational weight gain (0.22 +/- 0.09 kg x unit log leptin(-1) x wk(-1)). The leptin concentration at entry also significantly predicted retained weight in the postpartum period (at 6 mo: 7.29 +/- 3.33 kg/unit log leptin at entry) and marginally predicted changes in the sum of skinfold thicknesses (at 6 mo: 14.7 +/- 7.5 mm/unit log leptin at entry). CONCLUSION These results suggest that a high leptin concentration at entry to prenatal care may predict an increased risk of overweight and obesity in vulnerable women.
Metabolic and cardiorespiratory responses to hypoxia in fetal sheep: adenosine receptor blockade.

8-Phenyltheophylline (PT), a potent and specific inhibitor of adenosine receptors, was infused intra-arterially into unanesthetized fetal sheep to determine the role of adenosine in hypoxic inhibition of fetal breathing. PT in normoxic fetuses increased heart rate and the incidence of low-voltage electrocortical activity, rapid eye movements (REM), and breathing. Mean breath amplitude increased by 44%. Hypoxia (preductal arterial[Formula: see text] = 14 Torr) induced a metabolic acidemia, a transient bradycardia, and hypertension while virtually eliminating REM and breathing. PT administration during hypoxia enhanced the metabolic acidemia, blocked the bradycardia and hypertension, increased the incidence of REM and breathing, and elevated mean breath amplitude. The results indicate that 1) adenosine is involved in fetal glycolytic and cardiovascular responses to hypoxia, 2) activation of central adenosine receptors mediates about one-half the inhibitory effects of hypoxia on REM and breathing, and 3) the depression of breathing may critically depend on a hypoxia-induced reduction in phasic REM sleep.
Synergistic effect of zinc and vitamin A on the biochemical indexes of vitamin A nutrition in children.

BACKGROUND Zinc deficiency limits the bioavailability of vitamin A. Because zinc and vitamin A deficiency often coexist in malnourished children, simultaneous zinc and vitamin A supplementation may improve the vitamin A deficiency in these children. OBJECTIVE A randomized, double-blind, placebo-controlled intervention trial was conducted to evaluate whether combining zinc and vitamin A supplementation would improve the biochemical indexes of vitamin A nutriture. DESIGN Children aged 12-35 mo were randomly assigned to 1 of 4 intervention groups: 20 mg Zn/d for 14 d (Z group), 60000 retinol equivalents (200000 IU) vitamin A on day 14 (A group), zinc plus vitamin A (ZA group), or placebo syrup and placebo capsule (placebo group). Venous blood was drawn at enrollment and on day 21. RESULTS Mean serum retinol concentrations were not significantly different between the A and ZA groups. Among vitamin A-deficient children, the proportion of children who remained vitamin A deficient (serum retinol <0.7 micromol/L) after supplementation was 40.6% in the Z group, 37.5% in the A group, and 47.0% in the placebo group; only 13.3% in the ZA group remained vitamin A deficient (P < 0.05 compared with the placebo group). The proportion of children whose retinol binding protein concentrations remained low was significantly lower in the ZA group than in the other groups (P < 0.05). CONCLUSION Combined zinc and vitamin A supplementation improves vitamin A nutriture in vitamin A-deficient children.
Tissue distribution of lycopene in ferrets and rats after lycopene supplementation.

To determine lycopene uptake and tissue distribution in ferrets (Mustela putorius furo) and F344 rats, we supplemented orally 4.6 mg/(kg body wt.d) lycopene in a tomato oleoresin-corn oil mixture (experimental groups). After 9 wk of supplementation, the animals were killed and blood and organs were collected. Plasma and tissue carotenoids were extracted and measured using HPLC. Mean concentrations of lycopene (nmol/kg wet tissue) in saponified tissues of ferrets were as follows: liver 933, intestine 73, prostate 12.7 and stomach 9.3. Levels of lycopene (nmol/kg wet tissue) in saponified tissue of rats were as follows: liver 14213, intestine 3125, stomach 78.6, prostate 24 and testis 3.9. When these organs were extracted without saponification, the lycopene levels were lower, except for rat testis. All-trans-lycopene was the predominant isomer found in tomato oleoresin and in the majority of rat tissues, whereas cis-lycopenes were predominant in rat prostate and plasma. This pattern was reversed in ferrets. The results show the following: 1) lycopene from tomato oleoresin is absorbed and stored primarily in the liver of both animals; 2) saponification generally improves the extraction of lycopene from most tissues of both animals; 3) cis-lycopene and all-trans-lycopene are the predominant isomers in ferret and rat tissues, respectively; and 4) rats absorb lycopene more effectively than ferrets.
Low vitamin B-12 status and risk of cognitive decline in older adults.

BACKGROUND Elevated total homocysteine (tHcy) concentrations have been associated with cognitive impairment, but it is unclear whether low vitamin B-12 or folate status is responsible for cognitive decline. OBJECTIVE We examined the associations of cognitive decline with vitamin B-12 and folate status in a longitudinal cohort study performed from 1993 to 2003 in Oxford, United Kingdom. DESIGN Cognitive function was assessed with the Mini-Mental State Examination on >/=3 occasions during 10 y and related to serum concentrations of vitamin B-12, holotranscobalamin (holoTC), tHcy, methylmalonic acid (MMA), and folate with the use of linear mixed models in 1648 participants who provided blood in 1995. RESULTS Cognitive function declined abruptly at younger ages in some participants but remained intact in others until very old age. In multivariate regression analyses after adjustment for established risk factors, concentrations of holoTC (a marker of reduced vitamin B-12 status), tHcy, and MMA predicted cognitive decline, but folate did not. A doubling in holoTC concentrations (from 50 to 100 pmol/L) was associated with a 30% slower rate of cognitive decline (-0.137 to -0.083), whereas a doubling in tHcy (from 10 to 20 micromol/L) or MMA (from 0.25 to 0.50 micromol/L) was associated with >50% more rapid cognitive decline (-0.090 to -0.169) and (-0.104 to -0.169), respectively. After adjustment for all vitamin markers simultaneously, the associations of cognitive decline with holoTC and MMA remained significant. CONCLUSIONS Low vitamin B-12 status was associated with more rapid cognitive decline. Randomized trials are required to determine the relevance of vitamin B-12 supplementation for prevention of dementia.
Mitochondrial ASncmtRNA-1 and ASncmtRNA-2 as potent targets to inhibit tumor growth and metastasis in the RenCa murine renal adenocarcinoma model

Knockdown of antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptosis in several human and mouse tumor cell lines, but not normal cells, suggesting this approach for a selective therapy against different types of cancer. Here we show that in vitro knockdown of murine ASncmtRNAs induces apoptotic death of mouse renal adenocarcinoma RenCa cells, but not normal murine kidney epithelial cells. In a syngeneic subcutaneous RenCa model, treatment delayed and even reversed tumor growth. Since the subcutaneous model does not reflect the natural microenviroment of renal cancer, we used an orthotopic model of RenCa cells inoculated under the renal capsule. These studies showed inhibition of tumor growth and metastasis. Direct metastasis assessment by tail vein injection of RenCa cells also showed a drastic reduction in lung metastatic nodules. In vivo treatment reduces survivin, N-cadherin and P-cadherin levels, providing a molecular basis for metastasis inhibition. In consequence, the treatment significantly enhanced mouse survival in these models. Our results suggest that the ASncmtRNAs could be potent and selective targets for therapy against human renal cell carcinoma.