Miracle-dz/UniFAR-FTUs huggingface dataset:
L-Histidinol Attenuates Fanconi Syndrome Induced by Ifosfamide in Rats

The effect of L-histidinol (LHL), a structural analogue of the essential amino acid L-histidine, on ifosfamide (IFO) induced nephrotoxicity was investigated in the rat. The aim of this study was to assess whether oral supplementation of LHL could attenuate Fanconi syndrome (FS) induced by IFO. Male Wistar albino rats received daily injections of IFO (50 mg/kg) for 5 days with or without oral supplementation of 0.5% LHL in the drinking water. LHL was supplemented for 3 days before IFO administration and daily thereafter. Control rats were injected with saline with or without oral LHL. The results demonstrated that IFO induces a FS characterized by wasting of glucose, electrolytes, and organic acids, along with elevated serum creatinine and urea levels and decreased creatinine clearance. IFO-induced FS was associated with significant renal nonprotein sulfhydryl depletion and lipid peroxide (malondialdehyde) accumulation. LHL strongly ameliorated the severity of renal dysfunction induced by IFO, with significant decreases in total and fractional excretions of Na+, K+, PO43–, and glucose. Also, LHL significantly decreased the elevated serum creatinine and urea levels and significantly increased the creatinine clearance. Moreover, the beneficial effects of LHL were associated with a significant improvement of IFO-induced nonprotein sufhydry depletion and lipid peroxide accumulation. These results demonstrate that oral supplementation of LHL can partially protect against IFO-induced FS in rats.
Anesthesia drugs, immunity, and long-term outcome

Purpose of review We provide an overview of the immunological effects of commonly used anesthetic drugs and highlight their potential impact on long-term outcome after surgery. Recent findings Clinical trials provide preliminary evidence that the perioperative process can influence long-term patient outcome. Immunology may begin to elucidate the biology of this safety concern and open new therapeutic opportunities. In this context, awareness of the immunological properties of drugs administered in the perioperative period may assist in their deliberate use to modulate this risk. Statins, β-blockers, and clonidine can potentially improve long-term cardiac risk. Volatile anesthetics appear to suppress effector functions of both the innate and adaptive immunity, assist tumor growth in animal models, and facilitate aggregation of certain neurodegenerative disease proteins. Local anesthetics block neurons, but are also potent antiinflammatory drugs. Morphine has recognized immunosuppressive functions, which the newer, synthetic opioids don't seem to share. The cholinergic nervous system has antiinflammatory control functions that are largely unexploited. Summary Long-term outcome after surgery is a new safety concern in perioperative care. We are faced with enormous challenges in healthcare and research. As providers, tailoring an anesthetic plan to patients' needs will become increasingly critical, and immunology should help in this pursuit.
Cholinergic Overstimulation Attenuates Rule Selectivity in Macaque Prefrontal Cortex

Acetylcholine is released in the prefrontal cortex (PFC) and is a key modulator of cognitive performance in primates. Cholinergic stimulation has been shown to have beneficial effects on performance of cognitive tasks, and cholinergic receptors are being actively explored as promising targets for ameliorating cognitive deficits in Alzheimer's disease. We hypothesized that cholinergic stimulation of PFC during performance of a cognitive task would augment neuronal activity and neuronal coding of task attributes. We iontophoretically applied the general cholinergic receptor agonist carbachol onto neurons in dorsolateral PFC (DLPFC) of male rhesus macaques performing rule-guided prosaccades and antisaccades, a well established oculomotor task for testing cognitive control. Carbachol application had heterogeneous effects on neuronal excitability, with both excitation and suppression observed in significant proportions. Contrary to our prediction, neurons with rule-selective activity exhibited a reduction in selectivity during carbachol application. Cholinergic stimulation disrupted rule selectivity regardless of whether it had suppressive or excitatory effects on these neurons. In addition, cholinergic stimulation excited putative pyramidal neurons, whereas the activity of putative interneurons remained unchanged. Moreover, cholinergic stimulation attenuated saccade direction selectivity in putative pyramidal neurons due to nonspecific increases in activity. Our results suggest excessive cholinergic stimulation has detrimental effects on DLPFC representations of task attributes. These findings delineate the complexity and heterogeneity of neuromodulation of cerebral cortex by cholinergic stimulation, an area of active exploration with respect to the development of cognitive enhancers. SIGNIFICANCE STATEMENT The neurotransmitter acetylcholine is known to be important for cognitive processes in the prefrontal cortex. Removal of acetylcholine from prefrontal cortex can disrupt short-term memory performance and is reminiscent of Alzheimer's disease, which is characterized by degeneration of acetylcholine-producing neurons. Stimulation of cholinergic receptors is being explored to create cognitive enhancers for the treatment of Alzheimer's disease and other psychiatric diseases. Here, we stimulated cholinergic receptors in prefrontal cortex and examined its effects on neurons that are engaged in cognitive behavior. Surprisingly, cholinergic stimulation decreased neurons' ability to discriminate between rules. This work suggests that overstimulation of acetylcholine receptors could disrupt neuronal processing during cognition and is relevant to the design of cognitive enhancers based on stimulating the cholinergic system.
Overview of the KTH rule system for musical performance.

The KTH rule system models performance principles used by musicians when performing a musical score, within the realm of Western classical, jazz and popular music. An overview is given of the major rules involving phrasing, micro-level timing, metrical patterns and grooves, articulation, tonal tension, intonation, ensemble timing, and performance noise. By using selections of rules and rule quantities, semantic descriptions such as emotional expressions can be modeled. A recent real-time implementation provides the means for controlling the expressive character of the music. The communicative purpose and meaning of the resulting performance variations are discussed as well as limitations and future improvements.
Biventricular pacing for congestive heart failure: early experience in surgical epicardial versus coronary sinus lead placement.

OBJECTIVE Biventricular pacing (BVP) has recently been introduced for the treatment of refractory congestive heart failure. Coronary sinus lead placement for left ventricular pacing is technically difficult, has a risk of lead dislodgement, and has long procedure times. Surgical epicardial lead placement has the potential advantage of the visual selection of an optimal pacing site, does not need exposure to ionic radiation, and allows lead multiplicity, but it does require a thoracotomy and general anesthesia. We report our early experience of BVP with both modalities. METHODS BVP was performed in 12 patients with New York Heart Association (NYHA) class IV congestive heart failure (10 men, 2 women). Mean patient age was 68.7 years (range, 41-83 years). Surgical epicardial leads were placed through a 2- to 3-inch incision via a left fourth or fifth intercostal thoracotomy in 4 patients with single lung ventilation under general anesthesia. The other 8 patients underwent transvenous coronary sinus lead placement under conscious sedation. RESULTS Postoperative NYHA class status improved from class IV to class II in 8 patients and to class III in 3 patients. In 5 of the 8 patients who had undergone follow-up echocardiography with mitral regurgitation, the severity of the mitral regurgitation improved. The mean left ventricular ejection fractions before and after BVP were 18.3% +/- 8.3% and 20.5% +/- 8.0%, respectively (P =.16). Mean fluoroscopy and total procedure times for transvenous lead placement were 77 +/- 19 minutes and 266 +/- 117 minutes, respectively. The mean surgery time for epicardial lead placement was 122 +/- 13 minutes. There were no differences between the 2 methods in pacing threshold or in lead dislodgement. There were no complications related to the surgery or the laboratory procedure. CONCLUSION In patients with NYHA class IV congestive heart failure, epicardial lead placement through a minithoracotomy for BVP was performed safely with benefits equivalent to those of coronary sinus lead placement and with a shorter procedure time.
What factors are predictive of benefit finding in women treated for non‐metastatic breast cancer? A prospective study

Patients with breast cancer are able to gain psychological benefits from cancer diagnosis and treatment, such as a greater purpose of life and closer relationships, termed as ‘benefit finding’ (BF). The objective of this study was to determine the effects of sociodemographic, pathological, and psychological variables on BF in women with non‐metastatic breast cancer.
In vivo near-infrared fluorescence targeting of T cells: comparison of nanobodies and conventional monoclonal antibodies.

The large size of conventional antibodies impedes tissue penetration and renal elimination, resulting in suboptimal in vivo targeting. Here we assess the utility of nanobodies and nanobody-Fc-fusion proteins as alternatives to monoclonal antibodies as theranostics, using T cell ADP-ribosyltransferase 2 (ART2) as a model antigen for specific targeting of lymph nodes. ART2-specific monovalent nanobody s + 16a (17 kDa), a bivalent Fc-fusion protein of s + 16a (s + 16-mFc, 82 kDa), and conventional antibody Nika102 (150 kDa) were labeled with AlexaFluor680. In vitro binding and inhibitory properties of the three AF680 conjugates were assessed by flow cytometry. For in vivo imaging experiments, AF680 conjugates were intravenously injected in mice lacking (KO) or overexpressing (TG) ART2. We monitored circulating and excreted AF680 conjugates in plasma and urine and performed in vivo near-infrared fluorescence imaging. Nanobody s + 16a(680) and s + 16mFc(680) labeled and inhibited ART2 on T cells in lymph nodes within 10 min. In contrast, mAb Nika102(680) required 2 h for maximal labeling without inhibition of ART2. In vivo imaging revealed specific labeling of ART2-positive lymph nodes but not of ART2-negative lymph nodes with all AF680 conjugates. Even though bivalent s + 16mFc(680) showed the highest labeling efficiency in vitro, the best lymph node imaging in vivo was achieved with monovalent nanobody s + 16a(680) , since renal elimination of unbound s + 16a(680) significantly reduced background signals. Our results indicate that small single-domain nanobodies are best suited for short-term uses, such as noninvasive imaging, whereas larger nanobody-Fc-fusion proteins are better suited for long-term uses, such as therapy of inflammation and tumors.
Personalised mobile learning content delivery: a learner centric approach

This research proposes a context-aware framework that automatically adapts learning content designed for personal computers for mobile learners. The framework is a web application plug-in that captures access patterns and uses the patterns with trained configurations, learner preferences and device profiles to tailor learning content to the learners' needs. Learners can switch devices without losing learning context, and the framework would use Semantic technology to search and make content learners may eventually need available to them. The framework is in line with the surveys recently conducted on mobile learning and uses only proven technologies to guarantee a successful implementation.
A time delay model for control of malignant tumor growth

We present a delay induced three dimensional deterministic system, consisting of malignant tumor cells, hunting and resting immune cells. Stability analysis is performed along with numerical simulations. We obtain certain thresholds which are helpful to control the malignant cell growth. Estimation of time delay factor from our study gives suitable preventive strategy. Our analysis is supported through experimental results available from literature. Keywords—Malignant tumor cells, immune cells, time delay, differential equation, stability, control
Management and Treatment of Temporomandibular Disorders: A Clinical Perspective

Abstract A temporomandibular disorder (TMD) is a very common problem affecting up to 33% of individuals within their lifetime. TMD is often viewed as a repetitive motion disorder of the masticatory structures and has many similarities to musculoskeletal disorders of other parts of the body. Treatment often involves similar principles as other regions as well. However, patients with TMD and concurrent cervical pain exhibit a complex symptomatic behavior that is more challenging than isolated TMD symptoms. Although routinely managed by medical and dental practitioners, TMD may be more effectively cared for when physical therapists are involved in the treatment process. Hence, a listing of situations when practitioners should consider referring TMD patients to a physical therapist can be provided to the practitioners in each physical therapist's region. This paper should assist physical therapists with evaluating, treating, insurance billing, and obtaining referrals for TMD patients.
New Approaches to Prevent LEOPARD Syndrome-associated Cardiac Hypertrophy by Specifically Targeting Shp2-dependent Signaling*

Background: In LEOPARD syndrome, hypertrophic cardiomyopathy develops because of hyperactivated prohypertrophic signaling. Results: Pharmacological inhibition of Shp2, focal adhesion kinase, Akt, or mammalian target of rapamycin counteracts the disease mechanism. Conclusion: Interventions at multiple levels of the signaling cascade effectively prevent cardiomyocyte hypertrophy. Significance: Identification of these novel targets will facilitate the development of highly specific therapies for LEOPARD syndrome. In LEOPARD syndrome (LS) patients, mutations in the protein tyrosine phosphatase Shp2 cause hypertrophic cardiomyopathy. The prohypertrophic effects of mutant Shp2 are mediated downstream by hyperactivation of mammalian target of rapamycin. Our goal was to further define the signaling cascade that is essential for the underlying pathomechanism, thus expanding the list of potential future therapeutic targets. Using cultured neonatal rat cardiomyocytes with adenoviral gene delivery and pharmacological inhibitors, we found that hypertrophy induced by a particularly aggressive LS mutation in Shp2 depends on hyperactivation of Akt and focal adhesion kinase as well as mammalian target of rapamycin. Dissecting domain-specific functions of Shp2 using double and truncation mutants, we determined that the hypertrophic effects of mutant Shp2 depend on the two SH2 domains and on an intact catalytic center. The latter finding prompted us to test the efficacy of a Shp2 inhibitor targeted directly at the catalytic pocket. This compound, PHPS1, effectively prevented mutant Shp2-induced hypertrophy. In summary, we identified three novel targets for pharmacological therapy of LS-associated cardiac hypertrophy. Of particular importance is the finding that intervention directly at the mutant Shp2 protein is effective because this would facilitate custom-tailored therapeutic approaches for patients carrying LS mutations in Shp2.
Readiness of US General Surgery Residents for Independent Practice

Objective: This study evaluates the current state of the General Surgery (GS) residency training model by investigating resident operative performance and autonomy. Background: The American Board of Surgery has designated 132 procedures as being “Core” to the practice of GS. GS residents are expected to be able to safely and independently perform those procedures by the time they graduate. There is growing concern that not all residents achieve that standard. Lack of operative autonomy may play a role. Methods: Attendings in 14 General Surgery programs were trained to use a) the 5-level System for Improving and Measuring Procedural Learning (SIMPL) Performance scale to assess resident readiness for independent practice and b) the 4-level Zwisch scale to assess the level of guidance (ie, autonomy) they provided to residents during specific procedures. Ratings were collected immediately after cases that involved a categorical GS resident. Data were analyzed using descriptive statistics and supplemented with Bayesian ordinal model-based estimation. Results: A total of 444 attending surgeons rated 536 categorical residents after 10,130 procedures. Performance: from the first to the last year of training, the proportion of Performance ratings for Core procedures (n = 6931) at “Practice Ready” or above increased from 12.3% to 77.1%. The predicted probability that a typical trainee would be rated as Competent after performing an average Core procedure on an average complexity patient during the last week of residency training is 90.5% (95% CI: 85.7%–94%). This falls to 84.6% for more complex patients and to less than 80% for more difficult Core procedures. Autonomy: for all procedures, the proportion of Zwisch ratings indicating meaningful autonomy (“Passive Help” or “Supervision Only”) increased from 15.1% to 65.7% from the first to the last year of training. For the Core procedures performed by residents in their final 6 months of training (cholecystectomy, inguinal/femoral hernia repair, appendectomy, ventral hernia repair, and partial colectomy), the proportion of Zwisch ratings (n = 357) indicating near-independence (“Supervision Only”) was 33.3%. Conclusions: US General Surgery residents are not universally ready to independently perform Core procedures by the time they complete residency training. Progressive resident autonomy is also limited. It is unknown if the amount of autonomy residents do achieve is sufficient to ensure readiness for the entire spectrum of independent practice.
Fault-tolerant optimised tracking control for unknown discrete-time linear systems using a combined reinforcement learning and residual compensation methodology

ABSTRACT This paper considers the fault-tolerant optimised tracking control (FTOTC) problem for unknown discrete-time linear system. A research scheme is proposed on the basis of data-based parity space identification, reinforcement learning and residual compensation techniques. The main characteristic of this research scheme lies in the parity-space-identification-based simultaneous tracking control and residual compensation. The specific technical line consists of four main contents: apply subspace aided method to design observer-based residual generator; use reinforcement Q-learning approach to solve optimised tracking control policy; rely on robust H∞ theory to achieve noise attenuation; adopt fault estimation triggered by residual generator to perform fault compensation. To clarify the design and implementation procedures, an integrated algorithm is further constructed to link up these four functional units. The detailed analysis and proof are subsequently given to explain the guaranteed FTOTC performance of the proposed conclusions. Finally, a case simulation is provided to verify its effectiveness.
Cryolipolysis for safe and effective inner thigh fat reduction

While cryolipolysis initially received FDA clearance for fat reduction in the abdomen and flanks, there was significant interest in non‐surgical fat reduction for other sites, such as the inner and outer thighs. This article reports the results of an inner thigh study which contributed to FDA clearance of cryolipolysis for treatment of thighs.
Renal sodium handling and haemodynamics are equally affected by hyperinsulinaemia in salt-sensitive and salt-resistant hypertensives

Objective It is well-known that insulin induces renal sodium retention. It is not yet known whether insulin's renal effects are involved in the development of salt-sensitive hypertension. We assessed the effects of insulin on renal sodium handling and haemodynamics in 10 salt-sensitive (SS) and 10 salt-resistant (SR) essential hypertensives. Design After a baseline period of 90 min, all subjects underwent a euglycaemic clamp with sequential infusion of a physiological and supraphysiological dose of insulin (50 and 150 mU/kg per h) during 90 min periods each. Time-control studies were performed in the same subjects. Clearances of 131I-hippuran, 125I-iothalamate, sodium and lithium were used to evaluate renal plasma flow (RPF), CNa/glomerular filtration rate (GFR) and fractional proximal and distal sodium reabsorption. Results Plasma insulin levels and insulin-mediated glucose uptake did not differ between both groups. RPF and GFR showed similar increases during both insulin infusions in both groups. During physiological hyperinsulinaemia, fractional sodium excretion decreased 38% (P = 0.009) in the SS group and 36% (P = 0.002) in the SR group. During supraphysiological hyperinsulinaemia, fractional sodium excretion decreased 49% (P = 0.01) in the SS group and 19% (P = 0.2) in the SR group, not statistically different between both groups. Fractional proximal sodium reabsorption was unaffected and fractional distal sodium reabsorption increased to a similar magnitude in both groups. Conclusion The comparable renal effects of acute exogenous hyperinsulinaemia in SS and SR hypertensives do not support a role for insulin in the development of salt-sensitive hypertension. However, the results do not yet exclude a role for chronic hyperinsulinaemia.
Decline and Rise of the Antimicrobial Susceptibility of Streptococcus pneumoniae Isolated from Middle Ear Fluid in Children: Influence of Changes in Circulating Serotypes

ABSTRACT Changes in the antimicrobial susceptibility of Streptococcus pneumoniae causing otitis media were studied in 916 isolates from children <5 years old between 1999 and 2010 in a region of northern Spain. The rate of antimicrobial resistance decreased between the period before the introduction of the heptavalent pneumococcal conjugate vaccine (from 1999 to 2001) and the period from 2005 to 2007. However, in 2008 to 2010, resistance rates increased again due to the spread of serotype 19A, especially the multidrug-resistant ST320 and ST276 clones.
Prevalence and characteristics of polycystic ovarian syndrome in a sample of infertile Kurdish women attending IVF infertility center in maternity teaching hospital of Erbil City

Objective: To estimate the prevalence of polycystic ovarian syndrome (PCOS), and to compare the clinical, hormonal and ultrasonography features between infertile women with or without PCOS. Design: A descriptive, comparative study. Materials and Methods: This study was conducted from May 1, 2007 to August 1, 2008, in the Infertility Care and IVF center in Maternity Teaching Hospital, Erbil city, Kurdistan region, North ofIraq. A total of 320 infertile women aged 18 - 45 years, were evaluated for clinical features (oligo-/amenorrhea, hirsutism), body mass index, waist-hip ratio (WHR) and hormonal measures. Transvaginal ultrasonography was used to assess the ovarian morphology. The Rotterdam 2003 criteria adopted by the European Society for Human reproduction and Embryology and the American Society for Reproductive Medicine were used to diagnose cases of PCOS. Data analysis was performed using the SPSS version 15. Results: The prevalence of PCOS was 33%. There were a significant differences between the two groups in terms of oligo-/amenorrhea, hirsutism, WHR, and ovarian ultrasound features. There were no significant differences between the two groups in correlations between the level of obesity with the incidences of anovulation, hyperandrogenemia and hirsutism or with hormonal features. Conclusions: A high prevalence rate of PCOS was observed among infertile women attending IVF center using the Rotterdam 2003 criteria for diagnosis.