Miracle-dz/UniFAR-FTUs huggingface dataset:
Albiglutide for treating type 2 diabetes: an evaluation of pharmacokinetics/pharmacodynamics and clinical efficacy

Introduction: Albiglutide is a once-weekly, glucagon-like peptide-1 receptor agonist approved during 2014 in both the US and Europe for the treatment of adults with type 2 diabetes. The recommended dose is 30 mg with the possibility of uptitration to 50 mg based on individual glycemic response. Areas covered: Here, we outline the pharmacokinetics, pharmacodynamics and clinical efficacy data originating from the Phase I – III studies carried out to obtain market authorization for albiglutide. Expert opinion: The eight Phase III clinical trials have provided evidence that albiglutide in monotherapy and as an add-on to different background therapies confers placebo-corrected reductions in glycemia with changes in glycated hemoglobin of −0.8 to −1.0%. Albiglutide did not cause significant weight loss compared to placebo, but the adverse events profile was favorable with gastrointestinal adverse events occurring only slightly more with albiglutide than placebo. There is no clinical evidence of an effect of albiglutide on major cardiovascular outcomes.
The Manchester Triage System (MTS): a score for emergency management of patients with acute gastrointestinal bleeding

Abstract Background Suspected gastrointestinal (GI) bleeding is a common initial diagnosis in emergency departments. Despite existing endoscopic scores to estimate the risk of GI bleeding, the primary clinical assessment of urgency can remain challenging. The 5-step Manchester Triage System (MTS) is a validated score that is often applied for the initial assessment of patients presenting in emergency departments. Methods All computer-based records of patients who were admitted between January 2014 and December 2014 to our emergency department in a tertiary referral hospital were analyzed retrospectively. The aim of our retrospective analysis was to determine if patient triage using the MTS is associated with rates of endoscopy and with presence of active GI bleeding. Results In summary, 5689 patients with a GI condition were treated at our emergency department. Two hundred eighty-four patients (4.9 %) presented with suspected GI bleeding, and 165 patients (58 %) received endoscopic diagnostic. Endoscopic intervention for hemostasis was needed in 34 patients (21 %). In patients who underwent emergency endoscopy, triage into MTS categories with higher urgency was associated with higher rates of endoscopic confirmation of suspected GI bleeding (79 % of patients with MTS priority levels 1 or 2, 53 % in level 3 patients, and 40 % in levels 4 or 5 patients; p = 0.024). Conclusions The MTS is an established tool for triage in emergency departments and could have a potential to guide early clinical decision-making with regards to urgency of endoscopic evaluation in patients with suspected GI bleeding.
Investigation of Adaptive Matching Methods for Near-Field Wireless Power Transfer

Adaptive matching methods for a wireless power transfer system in the near-field region are investigated. The impedance and resonant frequency characteristic of a near-field power transfer system are analyzed according to coupling distance. In the near-field region, adaptive matching is necessary to achieve an effective power transfer. We compare the power transfer efficiencies of several schemes including simultaneous conjugate matching and frequency tracking. It is found that effective adaptive matching can be easily achieved by tracking the split resonant frequency. In addition, a modified frequency tracking method is proposed to extend the range over which the power is transmitted with high efficiency. The experimental results are in agreement with the theoretical results.
Effect of in utero wi-fi exposure on the pre- and postnatal development of rats.

BACKGROUND The increase in exposure to the Wireless Fidelity (Wi-Fi) wireless communication signal has raised public health concerns especially for young people. Animal studies looking at the effects of early life and prenatal exposure to this source of electromagnetic fields, in the radiofrequency (RF) range, on development and behavior have been considered as high priority research needs by the World Health Organization. METHODS For the first time, our study assessed the effects of in utero exposure to a 2450 MHz Wi-Fi signal (2 hr/day, 6 days/week for 18 days) on pregnant rats and their pups. Three levels in terms of whole-body specific absorption rate were used: 0.08, 0.4, and 4 W/kg. The prenatal study on fetuses delivered by caesarean (P20) concerned five females/group. The dams and their offspring were observed for 28 days after delivery (15 females/group). RESULTS For all test conditions, no abnormalities were noted in the pregnant rats and no significant signs of toxicity were observed in the pre- and postnatal development of the pups, even at the highest level of 4 W/kg. CONCLUSIONS In the present study, no teratogenic effect of repeated exposures to the Wi-Fi wireless communication signal was demonstrated even at the highest level of 4 W/kg. The results from this screening study aimed at investigating Wi-Fi effects, strengthen the previous conclusions that teratology and development studies have not detected any noxious effects of exposures to mobile telephony-related RF fields at exposure levels below standard limits.
Relationships Among Neurocognitive Status, Medication Adherence Measured by Pharmacy Refill Records, and Virologic Suppression in HIV-Infected Persons

Background:Optimal antiretroviral therapy (ART) effectiveness depends on medication adherence, which is a complex behavior with many contributing factors, including neurocognitive function. Pharmacy refill records offer a promising and practical tool to assess adherence. Methods:A substudy of the CHARTER (CNS HIV Anti-Retroviral Therapy Effects Research) study was conducted at the Johns Hopkins University (JHU) and the University of Washington. Pharmacy refill records were the primary method to measure ART adherence, indexed to a “sentinel” drug with the highest central nervous system penetration–effectiveness score. Standardized neuromedical, neuropsychological, psychiatric, and substance use assessments were performed at enrollment and at 6 months. Regression models were used to determine factors associated with adherence and relationships between adherence and changes in plasma and cerebrospinal fluid HIV RNA concentrations between visits. Results:Among 80 (33 at JHU and 47 at University of Washington) participants, the mean adherence score was 86.4%, with no difference between sites. In the final multivariable model, better neurocognitive function was associated with better adherence, especially among participants who were at JHU, male, and HIV infected for a longer period of time. Worse performance in working memory tests was associated with worse adherence. Better adherence predicted greater decreases in cerebrospinal fluid HIV RNA between visits. Conclusions:Poorer global neurocognitive functioning and deficits in working memory were associated with lower adherence defined by a pharmacy refill record measure, suggesting that assessments of cognitive function, and working memory in particular, may identify patients at risk for poor ART adherence who would benefit from adherence support.
The occurrence of xerostomia and salivary gland hypofunction in a population-based sample of older South Australians.

This paper examines the prevalence of and concurrence between the symptoms of dry mouth (xerostomia) and reduced salivary flow (SGH) among a population-based sample of older South Australians. Participants in a longitudinal dental study of older people were asked a global question about their experience of dry mouth ("How often does your mouth feel dry? "), and those who responded "Always" or "Frequently" were categorized as xerostomic. Unstimulated whole salivary flow rate was measured, and individuals whose flow rate was less than 0.1 mL/min were categorized as SGH cases. Saliva samples were collected from 700 individuals, of whom 683 (97.7%) answered the dry-mouth question. The mean unstimulated salivary flow rate was 0.27 mL/min (SD 0.22). The prevalence of SGH was 22.1%, and the prevalence of xerostomia was 20.5%, but only 5.7% of participants had both conditions. Almost two-thirds of the sample had neither condition. Males and females differed in the degree of concurrence between the two conditions. It appears that, in the group studied, xerostomia and SGH were largely discrete conditions, supporting the assertion by other workers that low salivary flow may not be the key factor in the etiology of xerostomia among older people.
Communication-Delay-Distribution-Dependent Networked Control for a Class of T–S Fuzzy Systems

This paper investigates a robust networked control for a class of Takagi-Sugeno (T-S) fuzzy systems. The controller design specifically takes probabilistic interval distribution of the communication delay into account. A general framework of networked control is first proposed. The two main features are 1) the zero-order hold can choose the latest control input signal when the packets received are out-of-order, and 2) as the result of 1), the models of the all kinds of uncertainties in networked signal transfer-including network-induced delay and data packet dropout-are under a unified framework. Next, if the probability distribution of communication delay is known or specified in a design process, sufficient stability conditions for networked T-S fuzzy systems are derived, which are based on the Lyapunov theory. Following this, a stabilizing controller design method is developed, which shows that the solvability of the design depends not only on the upper and lower bounds of the delay but on its probability distribution as well. Finally, a numerical example is used to show the application of the theoretical results obtained in this paper.
Autophagy, senescence and tumor dormancy in cancer therapy

The relationships between autophagy and apoptosis have been examined quite extensively and have often been shown to be reciprocally regulated responses to stresses such as exposure of the tumor cells to chemotherapeutic drugs and radiation. However, there is now evidence that autophagy may also play a role in tumor dormancy. Given that tumor dormancy and disease recurrence are poorly understood phenomenon which are nevertheless critical elements of patient morbidity and mortality, this commentary develops the postulate that autophagy and senescence may be related responses that influence the capacity of the tumor cell to maintain a prolonged state of growth arrest that can be succeeded by tumor regrowth and disease recurrence.
Groin Injuries (Athletic Pubalgia) and Return to Play

Context: Groin pain is a common entity in athletes involved in sports that require acute cutting, pivoting, or kicking such as soccer and ice hockey. Athletic pubalgia is increasingly recognized as a common cause of chronic groin and adductor pain in athletes. It is considered an overuse injury predisposing to disruption of the rectus tendon insertion to the pubis and weakness of the posterior inguinal wall without a clinically detectable hernia. These patients often require surgical therapy after failure of nonoperative measures. A variety of surgical options have been used, and most patients improve and return to high-level competition. Evidence Acquisition: PubMed databases were searched to identify relevant scientific and review articles from January 1920 to January 2015 using the search terms groin pain, sports hernia, athletic pubalgia, adductor strain, osteitis pubis, stress fractures, femoroacetabular impingement, and labral tears. Study Design: Clinical review. Level of Evidence: Level 4. Results and Conclusion: Athletic pubalgia is an overuse injury involving a weakness in the rectus abdominis insertion or posterior inguinal wall of the lower abdomen caused by acute or repetitive injury of the structure. A variety of surgical options have been reported with successful outcomes, with high rates of return to the sport in the majority of cases.
Therapeutic vaccination with epidermal growth factor (EGF) in advanced lung cancer: Analysis of pooled data from three clinical trials.

2548 Background: During the last 10 years we have studied the effect of vaccination against self EGF, both in the preclinical setting, and in several pilot clinical trials in advanced non-small cell lung cancer (NSCLC) patients. Here, we undertake the analysis of aggregated data from these trials, addressing particularly the issue of the relationship between immunization and survival. METHODS Pooled data from 3 pilot clinical trials in 75 patients, considered not amenable to any other modality of onco-specific treatment, were used. For survival analysis, 27 NSCLC patients were considered as a non-randomized concurrent control group. This group of patients has features which make it adequate for comparison: compliance with inclusion criteria, simultaneity in time, and treatment in the same hospital by the same physician staff. Vaccination using different adjuvants (alum and Montanide ISA51), cyclophosphamide pre-treatment or not, as well as different dosages of the Vaccine were compared. RESULTS On vaccinated patients, 80% showed seroconversion, of which 47% developed a good antibody (Ab) response. Geometric mean of maximal Ab titers was 1:3949 (sera dilution). Adjuvant, vaccine dose and cyclophosphamide pre-treatment significantly influenced immunogenicity whereas the other analyzed variables (sex, age, clinical stage, previous treatment) did not. The immune response was short lasting (2.64 +/- 1.89 months) and non-boostable. To maintain Ab titers continuous re-immunizations were required. No serious adverse events were registered. Vaccinated patients survived significantly more (mean: 9.13 months; median: 8 months) than the control group (mean: 4.85 months; median: 4.53 months) (p=0.0003). Patients who seroconverted survived significantly more than patients who did not. Patients with good Ab response showed a significant improvement in survival as compared with those with poor Ab response. CONCLUSIONS Vaccination with EGF was safe, immunogenic and improved survival in advanced NSCLC patients as compared with concurrent controls. These results are currently being verified in a randomized trial. No significant financial relationships to disclose.
Dead time correction in the DP5 digital pulse processor

All X-ray and gamma-ray spectroscopy systems exhibit pulse pile-up and dead time losses arising in the signal processing electronics. To accurately determine the true incoming count rate and spectrum, one must determine and correct for these losses. Many correction methods were developed using analog shaping amplifiers and multichannel analyzers, providing the concepts and terms traditionally used to describe these losses and correction factors. Digital pulse processors have a much higher throughput due to fundamental differences in their deadtime and pile-up characteristics. They also permit improved variations of the traditional correction methods. This paper will highlight key distinctions between analog and digital approaches, the implementation used in Amptek’s DP5 digital pulse processor, and show measured results. The DP5 was designed to support Amptek’s silicon drift diodes, operating at input count rates up to 106 s−1 at a peaking time of 0.6 μs with an accurate determination of input spectrum and count rate. Several different deadtime correction algorithms and pile-up rejection algorithms were tested for the DP5 and their measured performance will be presented.
Radiation treatment of acute inflammation in mice

Purpose: Low-dose radiotherapy (RT) has often been used effectively for the treatment of a variety of benign diseases, particularly those with acute inflammatory features. Here we report findings on radiation treatment of acute inflammation using a murine carrageenin air pouch model. Materials and methods: Air pouches raised on the dorsal surface of mice were injected with λ carrageenin and were irradiated 6 h later with doses ranging from 0 – 5 Gy. Treatment success was evaluated at various times thereafter by volume of exudate and number of inflammatory cells, and levels of inflammation-related cytokines tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and transforming growth factor beta-1 (TGFβ-1), and expression of inducible nitric oxide synthase (iNOS), heme oxygenase-1 (HO-1), cyclooxygenase-2 (COX-2) and inducible heat shock protein 70 (HSP70) as determined by enzyme-linked immunosorbent assay (ELISA) and Western blotting, respectively. Results: Crude inflammatory parameters such as the amount of exudates and number of inflammatory cells remained largely unaffected by radiation or were even a slightly and transiently increased. However, the expression of iNOS was attenuated by radiation concomitant with an increase in the levels of HO-1 and HSP70. Cytokine levels varied with the radiation dose and the time point. Conclusions: Ionizing radiation, even at low doses, functionally modulates inflammatory cells. Our findings indicate possible mechanisms as to how low-dose radiation may exert anti-inflammatory effects and provide the first evidence that heat shock proteins may be involved in this response.
Posttraumatic Stress, Coping Flexibility, and Risky Drinking Among Trauma-Exposed Male and Female College Students: The Mediating Effect of Delay of Gratification

ABSTRACT Background: The co-occurence of posttraumatic stress (PTS) and risky drinking has been demonstrated in diverse populations, including college students. However, the mechanisms underlying this co-occurrence, as well as the protective factors that may reduce risky drinking among trauma-exposed college students have yet to be fully understood in the literature. Objectives: The present study builds upon self-regulation theories and previous empirical work to determine whether the effects of PTS and coping flexibility on risky drinking were mediated by delay of gratification among trauma-exposed college students. In addition, the potential moderating effect of gender on these relationships was examined. Methods: Participants included 624 trauma-exposed college students (68.4% female) attending a public university in the southeast region of the United States. Data were collected through an online survey. The hypothesized model was examined using a multigroup structural equation modeling approach. Results: As hypothesized, PTS had a significant, positive indirect effect on risky drinking through delay of gratification; however, the effect of PTS on delay of gratification was stronger for males than for females. Results also indicated that the indirect effect of coping flexibility on risky drinking through delay of gratification was significant and negative for males and females. Conclusions/Importance: The findings of this study suggest that delay of gratification might be an important mechanism underlying the co-occurrence of PTS and risky drinking. In addition, our results highlight the potential benefits of coping flexibility for college students coping with PTS.
Percutaneous endoscopic gastrostomy in patients with ventriculoperitoneal shunts

Percutaneous endoscopic gastrostomy (PEG) may be required in neurosurgical patients with a persistently depressed neurological status or severe lower cranial nerve palsies. Such patients may have a coexisting hydrocephalus requiring cerebrospinal fluid (CSF) diversion. Despite the risk of infection resulting from exposure to oropharyngeal flora by the pull‐through PEG technique and the secondary pneumoperitoneum seen in one‐third of patients, simultaneous peritoneal placement of CSF shunt catheters with PEG is the current practice. The aim of the study was to determine the frequency of CSF diversionary procedures in neurosurgical patients undergoing PEG insertion and the occurrence of infective complications in patients with simultaneous placement of a PEG and a ventriculoperitoneal (VP) shunt.
Panobinostat for the treatment of acute myelogenous leukemia

ABSTRACT Introduction: Therapeutic strategies in patients with acute myeloid leukemia (AML) have not changed significantly over the last decades. Appropriate strategies are ultimately driven by the assessment of patients’ fitness to define suitability for intensive induction chemotherapy, which produces high initial remission rates but, increased likelihood of relapse. Old/unfit AML patients still represent an urgent and unmet therapeutic need. Epigenetic deregulation represents a strategic characteristic of AML pathophysiology whereby aberrant gene transcription provides an advantage to leukemic cell survival. Efforts to re-establish impaired epigenetic regulation include hypomethylating agents and histone deacetylase inhibitors (HDACi). Areas covered: The review discusses the underlying mechanisms leading to disruption of lysine acetyltransferases (KAT or HAT)/deacetylase (KDAC or HDAC) balance and the rationale for using the HDACi panobinostat (LBH-589) in AML. Expert opinion: Although panobinostat has produced significant results in myeloma, its efficacy remains limited in AML. Panobinostat exerts pleiotropic activity and lack of specificity, which likely contributes to its inadequate safety in elderly AML patients. Phase I-II trials, utilizing panobinostat associated with well-known chemotherapeutic agents are ongoing and combinations with other druggable targets may likely be evaluated in future trials. The clinical use of this HDACi in AML the near future does not appearing promising.
The Effect of Nonphysiologically High Initial Tension on the Mechanical Properties of in Situ Frozen Anterior Cruciate Ligament in a Canine Model

An experimental study was performed in 32 adult beagle dogs to clarify the effect of nonphysiologically high initial tension on the mechanical and histologic properties of in situ frozen anterior cruciate ligaments. Both anterior cruciate ligaments in each dog underwent the in situ freeze-thaw treatment. The tibial insertion of the ligament was then made free from the tibia along with a cylindrical bone block. In the right knee, an initial tension of 20 N was applied on the anterior cruciate ligament by translocating the bone block in the distal direction. In the left knee, this bone block was anatomically reduced. Each bone block was firmly fixed with an interference screw. Ten animals were sacrificed at 6 weeks and 10 at 12 weeks. The tensile strength and the tangent modulus in the highly tensioned knee were significantly less than those in the physiologically tensioned knee at 12 weeks. Histologically, cell nuclei appeared to be spindle-shaped in the physiologically tensioned knee, while oval nuclei and focal degenerative changes with a number of vacuoles were occasionally found in the matrix in the highly tensioned knee. This study demonstrated that a nonphysiologically high tension significantly deteriorates the mechanical properties of the in situ frozen anterior cruciate ligament compared with physiologic tension.
Immune Recovery After Starting ART in HIV-Infected Patients Presenting and Not Presenting With Tuberculosis in South Africa

Abstract:We studied the immune response after starting antiretroviral treatment (ART) in 15,646 HIV-infected patients with or without tuberculosis (TB) at presentation in 3 ART programs in South Africa between 2003 and 2010. Patients presenting with TB had similar increases in CD4 cells compared with all other patients (adjusted difference 4.9 cells/µL per 6 months, 95% confidence interval: 0.2 to 9.7). Younger age, advanced clinical stage, female sex, and lower CD4 cell count at ART start were all associated with steeper CD4 slopes. In South Africa, HIV-infected patients presenting with TB experience immune recovery after starting ART that is no worse than in other patients.