Miracle-dz/UniFAR-FTUs huggingface dataset:
The Full Expression of Fasting-Induced Torpor Requires β3-Adrenergic Receptor Signaling

Torpor, a controlled rapid drop in metabolic rate and body temperature (Tb), is a hypometabolic adaptation to stressful environmental conditions, which occurs in many small mammals, marsupials, and birds. To date, signaling pathways required for torpor have not been identified. We examined the role of the sympathetic nervous system (SNS) in mediating the torpor adaptation to fasting by telemetrically monitoring the Tb of dopamine β-hydroxylase knock-out (Dbh–/–) mice, which lack the ability to produce the SNS transmitters, norepinephrine (NE), and epinephrine. Control (Dbh+/–) mice readily reduced serum leptin levels and entered torpor after a fast in a cool environment. In contrast, Dbh–/– mice failed to reduce serum leptin and enter torpor under fasting conditions, whereas restoration of peripheral but not central NE lowered serum leptin levels and rescued the torpor response. Torpor was expressed in fasted Dbh–/– mice immediately after administration of either the nonselective β-adrenergic receptor agonist isoproterenol or the β3-adrenergic receptor (AR)-specific agonist CL 316243 [disodium (RR)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino]propyl]-1,3-benzodioxazole-2,2-dicarboxylate], but not after administration of β1, β2, or α1 agonists. Importantly, the β3-specific antagonist SR 59230A [3-(2-ethylphenoxy)-1-[(1,S)-1,2,3,4-tetrahydronapth-1-ylamino]-2S-2-propanol oxalate] severely blunted fasting-induced torpor in control mice, whereas other AR antagonists were ineffective. These results define a critical role of peripheral SNS activity at β3-AR-containing tissues in the torpor adaptation to limited energy availability and cool ambient temperature.
Interactions between Ifenprodil and the NR2B Subunit of the N-Methyl-D-aspartate Receptor (*)

Ifenprodil is an atypical noncompetitive modulator of the N-methyl-D-aspartate (NMDA) receptor (NR) which demonstrates a 140-fold preference for NR2B over NR2A subunits, although the molecular basis for this subunit specificity is unknown. We have made chimeric receptors by fusing the murine forms of NR2A () and NR2B () to localize the high affinity determinants of ifenprodil inhibition on the 2B subunit. Binding experiments with I-MK-801 implicated the region between amino acids 198 and 356 of NR2B for high affinity ifenprodil interaction. Site-directed mutants at Arg-337 showed that this residue is absolutely required for high affinity ifenprodil inhibition. Polyamines also modulate the NMDA receptor with a preference for NR2B subunits, and the pharmacology of these agents overlaps with ifenprodil. Although the determinants of the polyamine enhancement of iodo-MK-801 binding also localize to the NH terminus of NR2B, the point mutants at Arg-337 form receptors that are polyamine-stimulated at wild type levels. In addition, polyamine stimulation depends on the expression of NR1 splice variants, whereas high affinity ifenprodil inhibition is independent of NR1 isoform expression. These studies provide evidence that ifenprodil and polyamines interact at discrete sites on the NR2B subunit.
Heat shock‐induced necrosis and apoptosis in osteoblasts

Damage to bone tissue due to heat shock is one of the main causes of the failure of osseointegration at the bone‐implant interface. To investigate the effect of heat shock on regeneration of bone tissue, osteoblasts were exposed to heat shock for 10 minutes at 42, 45, or 48°C or kept at 37°C as a control. After 10 minutes of heat shock, disruption of actin filaments was seen in the cells and the degree of disruption increased with the temperature. The cytoskeleton reassembled after a 12‐hour incubation at 37°C in the cells treated at 42 or 45°C, but this reversible recovery did not occur in the cells treated at 48°C. Flow cytometric analysis showed that heat shock at 48°C increased the number of necrotic cells to 15‐20% within minutes (p < 0.05 compared with 37°C). Apoptosis, evidenced by annexin V staining, DNA laddering, and caspase 3 activation, started after 6‐8 hours of incubation, reached a peak at 12 hours, and gradually declined (p < 0.05). Pretreatment with the antioxidant N‐acetyl‐L‐cysteine reduced the necrosis induced at 48°C of heat shock by one‐half (p < 0.05) but had no significant effect on caspase 3 activation induced by heat shock, suggesting that reactive oxygen species were critical in heat shock‐induced necrosis but not in apoptosis. Heat shock at 48°C induced a sustained translocation of p53 into the nucleus and a sustained activation of c‐jun N‐terminal kinase, whereas that at 42 and 45°C induced only transient p53 translocation and c‐jun N‐terminal kinase activation. These results suggest that the sustained activation of p53 and c‐jun N‐terminal kinase pathways may contribute to heat shock‐induced apoptosis. On the other hand, heat shock protein 70 increased dramatically in the cells treated at 45 or 48°C, suggesting that the protecting mechanism in the cells was also activated. Such protection was able to prevent apoptosis in cells treated at 45°C but not in those treated at 48°C.
Clinical effectiveness of orthogeriatric and fracture liaison service models of care for hip fracture patients: population-based longitudinal study

Objectives: to evaluate orthogeriatric and nurse-led fracture liaison service (FLS) models of post-hip fracture care in terms of impact on mortality (30 days and 1 year) and second hip fracture (2 years). Setting: Hospital Episode Statistics database linked to Office for National Statistics mortality records for 11 acute hospitals in a region of England. Population: patients aged over 60 years admitted for a primary hip fracture from 2003 to 2013. Methods: each hospital was analysed separately and acted as its own control in a before–after time-series design in which the appointment of an orthogeriatrician or set-up/expansion of an FLS was evaluated. Multivariable Cox regression (mortality) and competing risk survival models (second hip fracture) were used. Fixed effects meta-analysis was used to pool estimates of impact for interventions of the same type. Results: of 33,152 primary hip fracture patients, 1,288 sustained a second hip fracture within 2 years (age and sex standardised proportion of 4.2%). 3,033 primary hip fracture patients died within 30 days and 9,662 died within 1 year (age and sex standardised proportion of 9.5% and 29.8%, respectively). The estimated impact of introducing an orthogeriatrician on 30-day and 1-year mortality was hazard ratio (HR) = 0.73 (95% CI: 0.65–0.82) and HR = 0.81 (CI: 0.75–0.87), respectively. Following an FLS, these associations were as follows: HR = 0.80 (95% CI: 0.71–0.91) and HR = 0.84 (0.77–0.93). There was no significant impact on time to second hip fracture. Conclusions: the introduction and/or expansion of orthogeriatric and FLS models of post-hip fracture care has a beneficial effect on subsequent mortality. No evidence for a reduction in second hip fracture rate was found.
W From Machine-to-Machine Communications towards Cyber-Physical Systems

In recent years, cyber-physical systems (CPS) have emerged as a promising direction to enrich the interactions between physical and virtual worlds. In this article, we first present the correlations among machine-to-machine (M2M), wireless sensor networks (WSNs), CPS and internet of things (IoT), and introduce some research activities in M2M, including M2M architectures and typical applications. Then, we review two CPS platforms and systems that have been proposed recently, including a novel prototype platform for multiple unmanned vehicles with WSNs navigation and cybertransportation systems. Through these reviews, we propose CPS is an evolution of M2M by the introduction of more intelligent and interactive operations, under the architecture of IoT. Also, we especially hope to demonstrate how M2M systems with the capabilities of decisionmaking and autonomous control can be upgraded to CPS and identify the important research challenges related to CPS designs.
Visual Findings in Chiasmal Syndromes

The optic chiasm is an important neuroanatomic landmark, in particular as it relates to the pituitary gland and endocrinologic syndromes. Pathology that affects the chiasm helps emphasize key principles of neuroanatomy. The most common visual consequence of pituitary tumors is chiasmal compression, and visual findings remain important indicators of central nervous system pathology in many patients with sellar/suprasellar lesions. In this review, I have illustrated several different clinical syndromes that ensue from pathology involving the optic chiasm and discussed the various etiologies of chiasmal pathology. In addition, I have provided several examples of the neuroimaging findings that highlight the anatomy and pathology involving the optic chiasm. I hoped to provide a logical basis for the practicing ophthalmologist in approaching chiasmal disorders.
Novel mutations of the ferroportin gene (SLC40A1): analysis of 56 consecutive patients with unexplained iron overload

The aim of this study was to search for SLC40A1 mutations in iron overloaded patients, which tested negative for HFE mutations and other iron‐related genes. After a careful differential diagnosis, we selected 56 patients with unexplained iron overload whose phenotype could suggest the ferroportin disease. Iron overload was assessed by liver biopsy or by superconducting quantum interference device. SLC40A1 exons and intron–exon boundaries were amplified by polymerase chain reaction and sequenced. We also evaluated the presence of the insulin‐resistance hepatic iron overload and of non‐alcoholic fatty liver disease. Iron status was assessed in 44 families. We identified two novel mutations (D157N and V72F) at the heterozygous state in two probands. Phenotype heterogeneity was observed in both families, suggesting variable penetrance and expression. Including the two affected ones, 25 of the 44 families (57%) available for the iron study had one or more relatives with increased serum iron indices. Our findings not only suggest that the presence of major alterations of serum iron parameters in probands’ relatives is a main criteria to improve the power of the genetic testing for ferroportin disease but also indicate that a number of patients exists in which the etiology of iron overload remains still undefined.
Microbial Analysis of Biofilms on Cement Surfaces: An Investigation in Cement-Associated Peri-Implantitis

The cementation of implant-supported restorations always poses the risk of excess cement retained in the peri-implant sulcus despite careful clinical control. Excess cement can become the basis of colonization by oral microorganisms. As a result of the biofilm formation peri-mucositis or peri-implantitis may develop. Complications were observed in the routine prosthetic restoration of implants when a methacrylate-based cement was used. These developed a few weeks after cementation of the suprastructure and caused bleeding on probing as well as suppuration from the peri-implant tissue. In the revision therapy, excess cement in the peri-implant sulcus was found in many cases. This excess cement was sampled from ten patients and investigated for biofilm formation. For this purpose, the cement samples were collected and analyzed for bacterial in situ colonization by 16S rDNA-based methods. In laboratory experiments, the methacrylate-based cement and two other dental cements were then investigated for their proneness to form biofilm. The results of the in situ and in vitro investigations revealed a strong tendency towards bacterial invasion of the methacrylate-based cement by opportunistic species and pathogens.
An empirical research on relationships between subjective judgement, technology acceptance tendency and knowledge transfer

The purpose of this study was to explore the relationships among employees' usage intention pertaining to mobile information devices, focusing on subjective judgement, technology acceptance tendency, information sharing behavior and information transfer. A research model was established to verify several hypotheses. The research model based on integrated concepts of knowledge management and technology acceptance modeling. Participants were employees of enterprises in Taiwan, selected by combining snowball and convenience sampling. Data obtained from 779 e-surveys. Multiple-regression analysis was employed for hypothesis verification. The results indicate that perceived ease-of-use of mobile devices was affected by computer self-efficacy and computer playfulness directly; meanwhile, perceived ease-of-use directly affects perceived usefulness. In addition, perceived ease-of-use and perceived usefulness can predict information-sharing behavior in a positive manner, and impact knowledge transfer as well. Based on the research findings, it suggested that enterprises should utilize mobile information devices to create more contact with customers and enrich their service network. In addition, it is recommended that managers use mobile devices to transmit key information to their staff and that they use these devices for problem-solving and decision-making. Further, the staff’s skills pertaining to the operation of mobile information devices and to fully implement their features are reinforced in order to inspire the users' knowledge transfer. Enhancing the playfulness of the interface is also important. In general, it is useful to promote knowledge transfer behavior within an organization by motivating members to share information and ideas via mobile information devices. In addition, a well-designed interface can facilitate employees' use of these devices.
Menopausal Symptoms and Treatment-Related Effects of Estrogen and Progestin in the Women's Health Initiative

OBJECTIVE: To estimate the effects of estrogen plus progestin (E+P) therapy on menopausal symptoms, vaginal bleeding, gynecologic surgery rates, and treatment-related adverse effects in postmenopausal women. METHODS: Randomized, double-blind, placebo-controlled trial of 16,608 postmenopausal women, ages 50–79 (mean ± standard deviation 63.3 ± 7.1) years, with intact uterus, randomized to one tablet per day containing 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate (n = 8,506) or placebo (n = 8,102), and followed for a mean of 5.6 years. Change in symptoms and treatment-related effects were analyzed at year 1 in all participants. Bleeding and gynecologic surgery rates were analyzed through study close-out. RESULTS: Baseline symptoms did not differ between the treatment groups. More women assigned to E+P than placebo reported relief of hot flushes (85.7% versus 57.7%, respectively; odds ratio 4.40; 95% confidence interval 3.40–5.71), night sweats (77.6% versus 57.4%; 2.58; 2.04–3.26), vaginal or genital dryness (74.1% versus 54.6%; 2.40; 1.90–3.02), joint pain or stiffness (47.1% versus 38.4%; 1.43; 1.24–1.64), and general aches or pains (49.3% versus 43.7%; 1.25; 1.08–1.44). Women asymptomatic at baseline who were assigned to E+P more often developed breast tenderness (9.3% versus 2.4%, respectively; 4.26; 3.59–5.04), vaginal or genital discharge (4.1% versus 1.0%; 4.47; 3.44–5.81), vaginal or genital irritation (4.2% versus 2.8%; 1.52; 1.27–1.81), and headaches (5.8% versus 4.7%; 1.26; 1.08–1.46) than women on placebo. Estrogen plus progestin treatment prevented the onset of new musculoskeletal symptoms. Vaginal bleeding was reported by 51% of women on E+P and 5% of women on placebo at 6 months; most bleeding was reported as spotting. Gynecologic surgeries (hysterectomy and dilation and curettage) were performed more frequently in women assigned to E+P (3.1% versus 2.5% for hysterectomy, hazard ratio = 1.23, P = .026; 5.4% versus 2.4% for dilation and curettage, hazard ratio = 2.23, P < .001). CONCLUSION: Estrogen plus progestin relieved some menopausal symptoms, such as vasomotor symptoms and vaginal or genital dryness, but contributed to treatment-related effects, such as bleeding, breast tenderness, and an increased likelihood of gynecologic surgery. LEVEL OF EVIDENCE: I
10 Posttransplant Lymphoproliferative Disorders Following Solid Organ Transplantation

Posttrasplant lymphoproliferative disorders (PTLD) represent a wide spectrum of pathologic and clinical manifestations that occur in the setting of depressed T-cell function and altered immune surveillance, such as is observed in the setting of solid organ transplantation (SOT). PTLD is a major contributor to long-term morbidity and mortality in this population and is the most common cancer observed in children following SOT. (Webber et al., 2006) Many cases are associated with Epstein-Barr virus (EBV) infection and most, but not all, are of host origin. (Petit et al., 2002, Taylor et al., 2005) This article reviews the pathology, epidemiology, risk factors, and clinical aspects of PTLD, and identifies the need for ongoing systematic study of complex biologic and therapeutic questions.
Treatment of urticaria pigmentosa using interferon alpha

Long‐term treatment with interferon alpha (IFN‐α) has recently been shown to reduce the bone marrow infiltrate and cutaneous lesions in systemic mast cell disease. We therefore administered this cytokine to six patients with urticaria pigmentosa for up to 12 months, using subcutaneous injections of 5×106U, initially five times, and subsequently three times a week. The generally well‐tolerated therapy resulted in marked improvement of the cutaneous symptoms, especially in three of the patients who suffered from very severe pruritus. Two of the patients with bone marrow infiltration showed normal findings after treatment. However, in none of the patients was there any change in the skin lesions, or decrease in the degree of cutaneous mast cell infiltration, as evidenced by light and electron microscopic examination. These findings indicate that IFN‐α is highly effective in the control of symptoms, but otherwise does not influence the cutaneous lesions of urticaria pigmentosa.
Adaptive Tracking for Stochastic Nonlinear Systems With Markovian Switching  $ $

The problem of the adaptive tracking for a class of stochastic nonlinear systems with stationary Markovian switching is considered in this note. An Ito formula is proposed for stochastic integral equations with an integral about martingale measure. An adaptive backstepping controller is designed such that the closed-loop system has a unique solution that is globally bounded in probability and L4-norm of the tracking error converges to an arbitrarily small neighborhood of zero. A simulation example demonstrates the efficiency of the proposed scheme.
Development and Validation of a Patient Satisfaction Survey for Comprehensive Medication Management

BACKGROUND: Comprehensive medication management (CMM) services are a relatively new standard for clinical practice. A patient satisfaction tool for pharmacists providing comparable pharmacy services is essential for measuring quality and sustainability. OBJECTIVE: To develop a psychometrically valid questionnaire for measuring patient satisfaction for CMM services. METHODS: A patient satisfaction survey tool was developed through a multiphase development process. Validation studies were conducted across 2 urban ambulatory care health system settings providing CMM services. The survey consisted of 10 items related to 3 domains: medication-related needs, pharmacist-patient engagement, and overall satisfaction. Using a 4-point scale, the surveys were mailed, collected, and analyzed for descriptive statistics, internal consistency, and factorial composition. RESULTS: Total surveys returned for analysis numbered 195, with an overall survey response rate of 19.2%. Factor analysis and item analysis identified 1 factor of pharmacists’ patient care services. The factor was named “patient satisfaction. ” CONCLUSIONS: The instrument that was developed provided 1 factor of CMM services. This brief patient satisfaction tool appears to be reliable and valid and may serve other CMM providers to assess 1 measure of quality assurance upon further evaluation.
Urinary neutrophil gelatinase-associated lipocalin and clinical outcomes in chronic kidney disease patients

Abstract Background: Tubulointerstitial damage is a final common pathway of most renal diseases. Whether urinary neutrophil gelatinase-associated lipocalin (uNGAL), a biomarker for renal tubular damage, is of prognostic value for clinical outcomes in chronic kidney disease (CKD) patients has not been well investigated. Methods: The uNGAL and proteinuria levels were measured among a cohort of 473 advanced CKD patients of various etiologies recruited during 2002–2009. Results: The estimated glomerular filtration rate (eGFR) was 32.3±22.0 mL/min/1.73 m2 with a urine protein-to-creatinine ratio (UPCR) 680 (255–1248) mg/g and 132 (27.9%) participants had diabetes. The baseline uNGAL level was significantly associated with male gender, eGFR, UPCR, and hemoglobin. The hazard ratio (HR) of the highest uNGAL tertile for end-stage renal disease (ESRD) was 3.44 (95% CI 1.47–8.06, p=0.004). With the adjustment of urine creatinine and urine protein, HR of the highest urine NGAL-to-creatinine ratio (UNCR) tertile and the highest urine NGAL-to-protein ratio (UNPR) tertile was 3.06 (95% CI 1.19–7.90, p=0.02) and 2.10 (95% CI 1.13–3.89, p=0.02), respectively. UNPR increased the prediction of survival model for ESRD. HR of the highest UNCR tertile and UNPR tertile for cardiovascular (CV) events was 2.21 (95% CI 0.81–5.98, p=0.08) and 2.79 (95% CI 1.25–6.26, p=0.01), respectively. None of these were associated with all-cause mortality. Conclusions: Elevated uNGAL in CKD patients is associated with risks for ESRD and probably CV events. UNPR could improve the prediction for ESRD.
A Rapid-Cycle Quality Improvement Initiative to Increase Compliance with Infection Control Precautions in a Pediatric Ward

To the Editor—We read with interest the study by Fries et al on the best way to sample hand hygiene compliance using human observers. They explored how hand hygiene observer scheduling influences the number of events and unique individuals observed and found that short observation periods of 15 minutes each provided the best estimator of compliance for the shift. They also found that the first hour of each day shift, which corresponded with morning rounds, provided the best overall estimator of the entire shift. These results support the methods used in our quality improvement (QI) project, conducted on a much smaller scale, where observations were carried out for short periods and concentrated during the day shift, particularly morning rounds. We sought to measure rates of compliance with infection control precautions in a 36-bed pediatric ward in a 496-bed urban academic medical center. Although intervention studies to increase hand hygiene compliance have not provided conclusive results, QI methods, including rapid improvement approaches, have been shown to result in sustained improvement. Therefore, our secondary aim was to determine whether a focused educational program with feedback would improve these rates.