Miracle-dz/UniFAR-FTUs huggingface dataset:
Ageing is associated with brown adipose tissue remodelling and loss of white fat browning in female C57BL/6 mice

Fat storage changes throughout life and affects body metabolism. Ageing impact on brown (BAT) and white adipose tissue (WAT) deserves attention, especially in females, because they are less prone to age‐induced weight gain. While in male mice the impact of ageing on adipose tissue remodelling is well characterized, the effects in female mice remain largely unclear. Thus, we investigated BAT and WAT remodelling during ageing in female C57BL/6 mice. At 3 months, body weight was 24 ± 0.3 g (mean±SD), and it increased from 6 to 9 months of age (+20%, P < 0.0001). Oral glucose tolerance test showed no disturbance of glucose metabolism. All WAT depots became heavier, and white adipocytes hypertrophied. The subcutaneous and visceral WAT had clusters of beige cells in younger mice, but they were progressively lost by ageing, indicating loss of WAT browning. Older mice had hypertrophied classic brown adipocytes that had larger cytoplasmic lipid droplets than younger mice. Pearson's correlation showed that WAT mass has a weak correlate with BAT mass, although white adipocyte diameter has a strong correlation with classic brown adipocyte size. In conclusion, our results indicate that female C57BL/6 mice have a progressive age‐dependent loss of subcutaneous and visceral WAT browning, and this process runs in parallel with BAT morphological changes towards a fat storer phenotype, independent of cycling or disturbances in glucose metabolism.
Characteristics Associated with Home Health Care Referrals at Hospital Discharge: Results from the 2012 National Inpatient Sample

OBJECTIVE To assess patient- and hospital-level factors associated with home health care (HHC) referrals following nonelective U.S. patient hospitalizations in 2012. DATA SOURCE The 2012 National Inpatient Sample (NIS). STUDY DESIGN Retrospective, cross-sectional multivariable logistic regression modeling to assess patient- and hospital-level variables in patient discharges with versus without HHC referrals. DATA COLLECTION Analysis included 1,109,905 discharges in patients ≥65 years with Medicare. PRINCIPAL FINDINGS About 29.2 percent of discharges were referred to HHC, which were more likely with older age, female sex, urban location, low income, longer length of stay, higher severity of illness scores, diagnoses of heart failure or sepsis, and hospital location in New England (referent: Pacific). CONCLUSIONS As health policy changes influence postacute HHC, defining specific diagnoses and regional patterns associated with HHC is a first step to optimize postacute HHC services.
Atheroprotective vaccination with MHC-II-restricted ApoB peptides induces peritoneal IL-10-producing CD4 T cells.

Although immunization with major histocompatibility complex (MHC) class II-restricted apolipoprotein B (ApoB) peptides has been shown to be atheroprotective, the mechanism is unclear. Here, we investigated CD4+ T cell populations in immunized atherosclerotic mice. Peptides (16-mers) from mouse ApoB, the core protein of low-density lipoprotein (LDL), were screened for binding to I-Ab by computer prediction and confirmed by radiolabeled peptide competition. Three new peptides, P101 (FGKQGFFPDSVNKALY, 5.5 nM IC50), P102 (TLYALSHAVNSYFDVD, 6.8 nM), and P103 (LYYKEDKTSLSASAAS, 95 nM), were tested in an atherosclerosis model (Apoe-/- mice on Western diet). Immunization with each of the three peptides (1 time in complete Freund's adjuvant subcuntaneously and 4 time in incomplete Freund's adjuvant intraperitoneally) but not with adjuvant alone showed significantly reduced atherosclerotic plaques in the aortic root by serial sections and in the whole aorta by en face staining. There were no differences in body weight, LDL cholesterol, or triglycerides. Peritoneal leukocytes from ApoB peptide-immunized mice, but not control mice, secreted significant amounts of IL-10 (150 pg/ml). Flow cytometry showed that peptide immunization induced IL-10 in 10% of peritoneal CD4+ T cells, some of which also expressed chemokine (C-C motif) receptor 5 (CCR5). Vaccination with ApoB peptides expanded peritoneal FoxP3+ regulatory CD4+ T cells and more than tripled the number of CCR5+FoxP3+ cells. Similar trends were also seen in the draining mediastinal lymph nodes but not in the nondraining inguinal lymph nodes. We conclude that vaccination with MHC class II-restricted autologous ApoB peptides induces regulatory T cells (Tregs) and IL-10, suggesting a plausible mechanism for atheroprotection.NEW & NOTEWORTHY Vaccination against apolipoprotein B (ApoB), the protein of LDL, attracts attention as a novel approach to prevent atherosclerosis. We discovered major histocompatibility complex class II-restricted ApoB peptides, which reduce atherosclerosis and induce IL-10-producing CD4+ T cells and chemokine (C-C motif) receptor 5 expression on regulatory T cells, suggesting that immunization with ApoB peptides inhibits atherosclerosis by inducing anti-inflammatory cytokines.
An Efficient Prevention of Black Hole Problem in AODV Routing Protocol in MANET

Interest in the area of Mobile Ad-hoc Network (MANET) is growing since last few years because of its practical applications and requirement of communication in mobile devices. However, in comparison to wired network or infrastructure-based wireless network, MANET is particularly vulnerable to security attacks due to its fundamental characteristics, e.g., the open medium, dynamic network topology, autonomous terminal, lack of centralized monitoring and management. The black hole attack is one of such security risks. In this attack, a malicious node falsely advertise shortest path to the destination node with an intension to disrupt the communication. In this paper, we propose a solution to the black hole attack in one of the most prominent routing algorithm, ad-hoc on demand distance vector (AODV) routing, for the MANETs. The proposed method uses promiscuous mode to detect malicious node (black hole) and propagates the information of malicious node to all the other nodes in the network. The simulation results show the efficacy of the proposed method as throughput of the network does not deteriorate in presence of the back holes.
The experience of beauty derived from sorrow

We studied the neural mechanisms that are engaged during the experience of beauty derived from sorrow and from joy, two experiences that share a common denominator (beauty) but are linked to opposite emotional valences. Twenty subjects viewed and rerated, in a functional magnetic resonance imaging scanner, 120 images which each had classified into the following four categories: beautiful and sad; beautiful and joyful; neutral; ugly. The medial orbito‐frontal cortex (mOFC) was active during the experience of both types of beauty. Otherwise, the two experiences engaged different parts of the brain: joyful beauty engaged areas linked to positive emotions while sorrowful beauty engaged areas linked to negative experiences. Separate regions of the cerebellum were engaged during experience of the two conditions. A functional connectivity analysis indicated that the activity within the mOFC was modulated by the supplementary motor area/middle cingulate cortex, known to be engaged during empathetic experiences provoked by other peoples' sadness. Hum Brain Mapp 38:4185–4200, 2017. © 2017 Wiley Periodicals, Inc.
Rectal Indomethacin Does Not Prevent Post-ERCP Pancreatitis in Consecutive Patients.

BACKGROUND & AIMS Rectal indomethacin, a nonsteroidal anti-inflammatory drug, is given to prevent pancreatitis in high-risk patients undergoing endoscopic retrograde cholangiopancreatography (ERCP), based on findings from clinical trials. The European Society for Gastrointestinal Endoscopy guidelines recently recommended prophylactic rectal indomethacin for all patients undergoing ERCP, including those at average risk for pancreatitis. We performed a randomized controlled trail to investigate the efficacy of this approach. METHODS We performed a prospective, double-blind, placebo-controlled trial of 449 consecutive patients undergoing ERCP at Dartmouth Hitchcock Medical Center, from March 2013 through December 2014. Approximately 70% of the cohort were at average risk for PEP. Subjects were assigned randomly to groups given either a single 100-mg dose of rectal indomethacin (n = 223) or a placebo suppository (n = 226) during the procedure. The primary outcome was the development of post-ERCP pancreatitis (PEP), defined by new upper-abdominal pain, a lipase level more than 3-fold the upper limit of normal, and hospitalization after ERCP for 2 consecutive nights. RESULTS There were no differences between the groups in baseline clinical or procedural characteristics. Sixteen patients in the indomethacin group (7.2%) and 11 in the placebo group (4.9%) developed PEP (P = .33). Complications and the severity of PEP were similar between groups. Per a priori protocol guidelines, the study was stopped owing to futility. CONCLUSIONS In a randomized controlled study of consecutive patients undergoing ERCP, rectal indomethacin did not prevent post-ERCP pancreatitis. ClincialTrials.gov no: NCT01774604.
Urinary chromium as a biological marker of environmental exposure: what are the limitations?

Public concern has mounted recently about environmental exposures to chromium in soil, tap water, and ambient air. In response, agencies charged with protecting public health have attempted to study exposure by monitoring urinary chromium levels among potentially exposed populations. While urinary biomonitoring of occupationally exposed workers has been successfully used to assess high-level inhalation exposures in the workplace, evaluating low-level environmental exposures has been problematic. Due to these problems, before an extensive biological monitoring study is conducted of those exposed to low levels of environmental chromium, several issues must be resolved. First, exposures to chromium must occur at the same time as sampling, because the biological half-life of chromium in urine is very short (less than 2 days). Second, reduced bioavailability and bioaccessibility via the oral and dermal routes of exposure limit the capacity of urinary monitoring to measure environmental exposures (e.g., systemic dose is too small to be measured). Third, the dose of chromium must be sufficient such that it may be reliably measured above background levels in urine (range of 0.2 to 2 microg/liter) and above the analytical limit of detection (0.2 microg/liter). Fourth, the inter- and intrapersonal variability in background levels of urinary chromium is known to be significant and influenced by food and beverage intake, smoking, and exercise. Thus, the role of each factor must be carefully understood. Finally, it is imperative to have developed a complete understanding of the clinical significance of elevated urinary chromium levels before a study is performed, because higher than background levels, in and of themselves, are not indicative of a significant health concern. The route of exposure, valence of chromium to which people were exposed, exposure time, and duration must all be understood before the biological data can be implemented. We have conducted a total of nine human exposure studies over the past 3 years in an attempt to understand the kinetics of chromium and the impact on urinary, red blood cell (RBC), and plasma biomonitoring programs. The results of these studies are described here and our recommendations are offered for how to design and implement a urinary chromium biomonitoring study. In our view, given some evidence that the dose of hexavalent chromium [Cr(VI)] is sufficient to be measurable above background concentrations of total chromium [Cr(III) and Cr(VI)], duplicated measurements of chromium in plasma and RBCs are, in most cases, a more definitive gauge of environmental exposure than urinary biomonitoring.
Use of Federally Qualified Health Centers and Potentially Preventable Hospital Utilization Among Older Medicare-Medicaid Enrollees

Using Medicare claims data from 2007 to 2010, we sought to determine whether dual eligibles 65 years and older who utilize federally qualified health centers (FQHCs) have lower rates of ambulatory care-sensitive hospitalizations and emergency department visits compared with nonusers. We found that FQHC use is associated with increased ambulatory care-sensitive hospitalization rates for whites and other races, but a decrease among blacks. Depending on race, FQHC use is associated with an increase of 24 to 43 ambulatory care-sensitive emergency department visits per thousand persons annually. More research is needed to understand why FQHC use is associated with these outcomes among dual eligibles.
Achondroplasia: Development, pathogenesis, and therapy

Autosomal dominant mutations in fibroblast growth factor receptor 3 (FGFR3) cause achondroplasia (Ach), the most common form of dwarfism in humans, and related chondrodysplasia syndromes that include hypochondroplasia (Hch), severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN), and thanatophoric dysplasia (TD). FGFR3 is expressed in chondrocytes and mature osteoblasts where it functions to regulate bone growth. Analysis of the mutations in FGFR3 revealed increased signaling through a combination of mechanisms that include stabilization of the receptor, enhanced dimerization, and enhanced tyrosine kinase activity. Paradoxically, increased FGFR3 signaling profoundly suppresses proliferation and maturation of growth plate chondrocytes resulting in decreased growth plate size, reduced trabecular bone volume, and resulting decreased bone elongation. In this review, we discuss the molecular mechanisms that regulate growth plate chondrocytes, the pathogenesis of Ach, and therapeutic approaches that are being evaluated to improve endochondral bone growth in people with Ach and related conditions. Developmental Dynamics 246:291–309, 2017. © 2016 Wiley Periodicals, Inc.
Beam‐commissioning methodology for a three‐dimensional convolution/superposition photon dose algorithm

Commissioning beam data for the convolution/superposition dose‐calculation algorithm used in a commercial three‐dimensional radiation treatment planning (3D RTP) system (PINNACLE3, ADAC Laboratories, Milpitas, CA) can be difficult and time consuming. Sixteen adjustable parameters, as well as spectral weights representing a discrete energy spectrum, must be fit to sets of central‐axis depth doses and off‐axis profiles for a large number of field sizes. This paper presents the beam‐commissioning methodology that we used to generate accurate beam models. The methodology is relatively rapid and provides physically reasonable values for beam parameters. The methodology was initiated by using vendor‐provided automodeling software to generate a single set of beam parameters that gives an approximate fit to relative dose distributions for all beams, open and wedged, in a data set. A limited number of beam parameters were adjusted by small amounts to give accurate beam models for four open‐beam field sizes and three wedged‐beam field sizes. Beam parameters for other field sizes were interpolated and validated against measured beam data. Using this methodology, a complete set of beam parameters for a single energy can be generated and validated in approximately 40 h. The resulting parameter values yielded calculated relative doses that matched measured relative doses in a water phantom to within 0.5–1.0% along the central axis and 2% along off‐axis beam profiles for field sizes from 4cm×4cm to the largest field size available. While the methodology presented is specific to the ADAC PINNACLE3 treatment planning system, the approach should apply to other implementations of the dose model in other treatment planning system. PACS number(s): 87.53. –j, 87.66. –a
TGFβ1‐induced leucine limitation uncovered by differential ribosome codon reading

Cancer cells modulate their metabolic networks to support cell proliferation and a higher demand of building blocks. These changes may restrict the availability of certain amino acids for protein synthesis, which can be utilized for cancer therapy. However, little is known about the amino acid demand changes occurring during aggressive and invasive stages of cancer. Recently, we developed diricore, an approach based on ribosome profiling that can uncover amino acid limitations. Here, we applied diricore to a cellular model in which epithelial breast cells respond rapidly to TGFβ1, a cytokine essential for cancer progression and metastasis, and uncovered shortage of leucine. Further analyses indicated that TGFβ1 treatment of human breast epithelial cells reduces the expression of SLC3A2, a subunit of the leucine transporter, which diminishes leucine uptake and inhibits cell proliferation. Thus, we identified a specific amino acid limitation associated with the TGFβ1 response, a vulnerability that might be associated with aggressiveness in cancer.
Impact on Hip Fracture Mortality After the Establishment of an Orthogeriatric Care Program in a Colombian Hospital

Objective: The aim of this study is to evaluate mortality and survival rates of patients aged 65 years or older who sustained a hip fracture and were treated at a hospital in Bogotá, Colombia, after the establishment of an Orthogeriatric Program. Method: In total, 298 patients were treated according to the program’s protocol. The primary outcome was 1-year mortality. Mortality predictors were estimated using Cox proportional hazards model, and survival was measured with Kaplan–Meier analysis. Results: The annual survival rate increased from 80% to 89% (p = .039) 4 years after its implementation. There was a significant decrease in mortality risk (Hazard Ratio = 0.54, p = .049). Arrhythmia, valvular heart disease, history of myocardial infarction, and age greater than 85 years were predictors of mortality. Discussion: This is the first study in Latin America to show decreased mortality rates 1 year after the implementation of an Orthogeriatric Program. Our rates were lower than developed countries, suggesting the existence of additional factors that influence long-term outcomes.
Association between health-related physical fitness and body mass index status in children

The purpose of this study was to investigate the association between body mass index (BMI) status and physical performance in Brazilian children. The analyzed sample was composed of 978 children of both sexes (518 boys and 460 girls), aged 7 to 11 years. BMI and skinfolds were measured, and three motor tests were applied (flexibility, cardiorespiratory fitness, and muscular strength/endurance). In both sexes, overweight/obese children presented poor performance in all motor tests, except flexibility. In general, overweight/obese children have an increased odds ratio (OR) to present poor physical performance (boys: OR = 3.64 for cardiorespiratory fitness, OR = 1.94 for muscular strength/endurance, OR = 1.52 for flexibility; girls: OR = 5.03 for cardiorespiratory fitness and OR = 2.62 for muscular strength/endurance). In conclusion, for both sexes, a poor physical performance in the tests measuring cardiorespiratory fitness and muscular strength/ endurance was associated with the presence of overweight/obesity.
Heritability of white matter microstructure in late middle age: A twin study of tract‐based fractional anisotropy and absolute diffusivity indices

There is evidence that differences among individuals in white matter microstructure, as measured with diffusion tensor imaging (DTI), are under genetic control. However, little is known about the relative contribution of genetic and environmental effects on different diffusivity indices among late middle‐aged adults. Here, we examined the magnitude of genetic influences for fractional anisotropy (FA), and mean (MD), axial (AD), and radial (RD) diffusivities in male twins aged 56–66 years old. Using an atlas‐based registration approach to delineate individual white matter tracts, we investigated mean DTI‐based indices within the corpus callosum, 12 bilateral tracts and all these regions of interest combined. All four diffusivity indices had high heritability at the global level (72%–80%). The magnitude of genetic effects in individual tracts varied from 0% to 82% for FA, 0% to 81% for MD, 8% to 77% for AD, and 0% to 80% for RD with most of the tracts showing significant heritability estimates. Despite the narrow age range of this community‐based sample, age was correlated with all four diffusivity indices at the global level. In sum, all diffusion indices proved to have substantial heritability for most of the tracts and the heritability estimates were similar in magnitude for different diffusivity measures. Future studies could aim to discover the particular set of genes that underlie the significant heritability of white matter microstructure. Hum Brain Mapp 38:2026–2036, 2017. © 2017 Wiley Periodicals, Inc.
Prolyl dihydroxylation of unassembled uS12/Rps23 regulates fungal hypoxic adaptation

The prolyl-3,4-dihydroxylase Ofd1 and nuclear import adaptor Nro1 regulate the hypoxic response in fission yeast by controlling activity of the sterol regulatory element-binding protein transcription factor Sre1. Here, we identify an extra-ribosomal function for uS12/Rps23 central to this regulatory system. Nro1 binds Rps23, and Ofd1 dihydroxylates Rps23 P62 in complex with Nro1. Concurrently, Nro1 imports Rps23 into the nucleus for assembly into 40S ribosomes. Low oxygen inhibits Ofd1 hydroxylase activity and stabilizes the Ofd1-Rps23-Nro1 complex, thereby sequestering Ofd1 from binding Sre1, which is then free to activate hypoxic gene expression. In vitro studies demonstrate that Ofd1 directly binds Rps23, Nro1, and Sre1 through a consensus binding sequence. Interestingly, Rps23 expression modulates Sre1 activity by changing the Rps23 substrate pool available to Ofd1. To date, oxygen is the only known signal to Sre1, but additional nutrient signals may tune the hypoxic response through control of unassembled Rps23 or Ofd1 activity.
Initial UK experience with transversus abdominis muscle release for posterior components separation in abdominal wall reconstruction of large or complex ventral hernias: a combined approach by general and plastic surgeons

INTRODUCTION Large, complicated ventral hernias are an increasingly common problem. The transversus abdominis muscle release (TAMR) is a recently described modification of posterior components separation for repair of such hernias. We describe our initial experience with TAMR and sublay mesh to facilitate abdominal wall reconstruction. METHODS The study is a retrospective review of patients undergoing TAMR performed synchronously by gastrointestinal and plastic surgeons. RESULTS Twelve consecutive patients had their ventral hernias repaired using the TAMR technique from June 2013 to June 2014. Median body mass index was 30.8kg/m2 (range 19.0‐34.4kg/m2). Four had a previous ventral hernia repair. Three had previous laparostomies. Four had previous stomas and three had stomas created at the time of the abdominal wall reconstruction. Average transverse distance between the recti was 13cm (3‐20cm). Median operative time was 383 minutes (150‐550 minutes) and mesh size was 950cm2 (532‐2400cm2). Primary midline fascial closure was possible in all cases, with no bridging. Median length of hospital stay was 7.5 days (4‐17 days). Three developed minor abdominal wall wound complications. At median review of 24 months (18‐37 months), there have been no significant wound problems, mesh infections or explants, and none has developed recurrence of their midline ventral hernia. Visual analogue scales revealed high patient satisfaction levels overall and with their final aesthetic appearance. CONCLUSIONS We believe that TAMR offers significant advantages over other forms of components separation in this patient group. The technique can be adopted successfully in UK practice and combined gastrointestinal and plastic surgeon operating yields good results.