Miracle-dz/UniFAR-FTUs huggingface dataset:
Dysfunctional arteriovenous anastomoses in hands of systemic sclerosis patients with digital ulcers.

OBJECTIVES Previous studies indicate that the arteriovenous anastomoses (AVAs) and the arterioles with the nutritive flow are involved in the pathophysiologic process disturbing hand blood flow in systemic sclerosis (SSc). However, impact of different part of the microvascular system involved in digital ulcers (DU) is not well known. Here, we aimed to assess the vasomotor activity of the AVAs in the hands of patients with and without DU in SSc. METHODS Simultaneous recordings were made of laser Doppler flux in the finger pulp and thenar eminence, together with ipsilateral radial artery blood velocity and mean arterial blood pressure (MAP) in 22 non-smoking SSc patients and 13 aged-matched healthy controls. RESULTS AVA responses in the finger pulp to spontaneous vasoconstrictor nerve impulses were abolished in 64% of the SSc patients. Correlation and cross-spectra analysis showed positive correlation between blood flow changes and MAP changes, indicating a passive vascular bed in the SSc finger pulp with blood flow variations depending on short-term variability in MAP. Dysfunctional AVAs were identified in all the patients with a history of DU (n=8), while none of the patients with normal AVA function had episodes of DU (n=8) (p= 0.017). CONCLUSIONS We found that in SSc patients with DU there is a dysfunction of the AVAs of the finger pulp. This proof-of-concept study supports the notion that AVA dysfunction may play a critical role in SSc related DU. AVA dysfunction may be a part of autonomic dysfunction in SSc.
Neurologic and motor dysfunctions in APP transgenic mice

Abstract The discovery of gene mutations underlying autosomal dominant Alzheimer’s disease has enabled researchers to reproduce several hallmarks of this disorder in transgenic mice, notably the formation of Aβ plaques in brain and cognitive deficits. APP transgenic mutants have also been investigated with respect to survival rates, neurologic functions, and motor coordination, which are all susceptible to alteration in Alzheimer dementia. Several transgenic lines expressing human mutated or wild-type APP had higher mortality rates than non-transgenic controls with or without the presence of Aβ plaques. Mortality rates were also elevated in APP transgenic mice with vascular amyloid accumulation, thereby implicating cerebrovascular factors in the precocious death observed in all APP transgenic models. In addition, myoclonic jumping has been described in APP mutants, together with seizure activity, abnormal limb-flexion and paw-clasping reflexes, and motor coordination deficits. The neurologic signs resemble the myoclonic movements, epileptic seizures, pathological reflexes, and gait problems observed in late-stage Alzheimer’s disease.
Toward a mechanistic psychology of dialogue

Traditional mechanistic accounts of language processing derive almost entirely from the study of monologue. Yet, the most natural and basic form of language use is dialogue. As a result, these accounts may only offer limited theories of the mechanisms that underlie language processing in general. We propose a mechanistic account of dialogue, the interactive alignment account, and use it to derive a number of predictions about basic language processes. The account assumes that, in dialogue, the linguistic representations employed by the interlocutors become aligned at many levels, as a result of a largely automatic process. This process greatly simplifies production and comprehension in dialogue. After considering the evidence for the interactive alignment model, we concentrate on three aspects of processing that follow from it. It makes use of a simple interactive inference mechanism, enables the development of local dialogue routines that greatly simplify language processing, and explains the origins of self-monitoring in production. We consider the need for a grammatical framework that is designed to deal with language in dialogue rather than monologue, and discuss a range of implications of the account.
Effects of Strongman Training on Salivary Testosterone Levels in a Sample of Trained Men

Abstract Ghigiarelli, JJ, Sell, KM, Raddock, JM, and Taveras, K. Effects of strongman training on salivary testosterone levels in a sample of trained men. J Strength Cond Res 27(3): 738–747, 2013—Strongman exercises consist of multi-joint movements that incorporate large muscle mass groups and impose a substantial amount of neuromuscular stress. The purpose of this study was to examine salivary testosterone responses from 2 novel strongman training (ST) protocols in comparison with an established hypertrophic (H) protocol reported to acutely elevate testosterone levels. Sixteen men (24 ± 4.4 years, 181.2 ± 6.8 cm, and 95.3 ± 20.3 kg) volunteered to participate in this study. Subjects completed 3 protocols designed to ensure equal total volume (sets and repetitions), rest period, and intensity between the groups. Exercise sets were performed to failure. Exercise selection and intensity (3 sets × 10 repetitions at 75% 1 repetition maximum) were chosen as they reflected commonly prescribed resistance exercise protocols recognized to elicit a large acute hormonal response. In each of the protocols, subjects were required to perform 3 sets to muscle failure of 5 different exercises (tire flip, chain drag, farmers walk, keg carry, and atlas stone lift) with a 2-minute rest interval between sets and a 3-minute rest interval between exercises. Saliva samples were collected pre-exercise (PRE), immediate postexercise (PST), and 30 minutes postexercise (30PST). Delta scores indicated a significant difference between PRE and PST testosterone level within each group (p ⩽ 0.05), with no significant difference between the groups. Testosterone levels spiked 136% (225.23 ± 148.01 pg·ml−1) for the H group, 74% (132.04 ± 98.09 pg·ml−1) for the ST group, and 54% (122.10 ± 140.67 pg·ml−1) for the mixed strongman/hypertrophy (XST) group. A significant difference for testosterone level occurred over time (PST to 30PST) for the H group p ⩽ 0.05. In conclusion, ST elicits an acute endocrine response similar to a recognized H protocol when equated for duration and exercise intensity.
Familial Dysfunction of Protein S

Summary We describe a previously unreported defect of protein S characterized by low levels of cofactor activity for activated protein C contrasting with low normal levels of total and free protein S antigen. The distribution of protein S between the free form and the form complexed with the complement component C4b-binding protein was normal on two-dimensional immunoelectrophoresis. The proband developed juvenile deep-vein thrombosis while taking oral contraceptives. Her defect was transmitted in an autosomal dominant fashion from her asymptomatic mother. Other relatives carrying the same laboratory abnormality (mother, maternal uncle, two sisters and one brother) were also asymptomatic. We postulate that the defect is due to a dysfunctional protein S present in plasma in normal amounts and with normal proportions of the free and complexed forms of the protein.
Posterior Tibial Tendon Insufficiency: Which Ligaments are Involved?

Background: The pathology manifested in posterior tibial tendon insufficiency (PTTI) is not limited to the posterior tibial tendon. The association of ligament failure with deformity has been discussed in numerous publications, but extensive documentation of the structures involved has not been performed. The purpose of this observational study was to identify the pattern of ligament involvement using standarized, high-resolution magnetic resonance imaging (MRI) in a series of 31 consecutive patients diagnosed with PTTI compared to an age matched control group without PTTI. Method: The structures evaluated by MRI were the posterior tibial tendon, superomedial and inferomedial components of the spring ligament complex, talocalcaneal interosseous ligament, long and short plantar ligaments, plantar fascia, deltoid ligament, plantar naviculocuneiform ligament, and tarsometatarsal ligaments. Structural derangement was graded on a five-part scale (0 to IV) with level 0 being normal and level IV indicating a tear of more than 50% of the cross-sectional area of the ligament. Standard flatfoot measurements taken from preoperative plain standing radiographs were correlated with the MRI grading system. Results: Statistically significant differences in frequency of pathology in the PTTI group and controls were found for the superomedial calcaneonavicular ligament (p < 0.0001), inferomedial calcaneonavicular ligament (p < 0.0001), interosseous ligament (p = 0.0009), anterior component of the superficial deltoid (p < 0.0001), plantar metatarsal ligaments (p = 0.0002) and plantar naviculocuneiform ligament (p = 0.0006). The ligaments with the most severe involvement were the spring ligament complex (superomedial and inferomedial calcaneonavicular ligaments) and the talocalcaneal interosseous ligament. Conclusion: Ligament involvement is extensive in PTTI, and the spring ligament complex is the most frequently affected. Because ligament pathology in PTTI is nearly as common as posterior tibial tendinopathy, treatment should seek to protect or prevent progressive failure of these ligaments.
Renal Calyceal Microlithiasis: Clinical Presentation May Precede Sonographic Evidence

Calyceal microlithiasis (CM) is characterized by the sonographic finding of hyperechogenic spots less than 3 mm in diameter in renal calyces, and it may be the first step in calculus formation. From January 1992 to January 1998, we have observed 216 children with CM. The present report deals with 34 of them in whom renal sonography was negative at first observation and the diagnosis of CM was made only on repeated sonographic examinations. The presenting symptoms were recurrent abdominal pain, dysuria, and hematuria occuring alone or in combination. Half of the patients had hypercalciuria. A history of urolithiasis in at least one first- or second-degree relative was present in 85% of patients. Renal sonography was repeated after 6-22 months (mean 11) and showed unilateral CM in 16 subjects and bilateral in18. The finding of CM may be preceded by a period of time when symptoms and/or signs are present while microcalculi are not yet detectable. Repeated ultrasound examinations may be needed not only in patients with hypercalciuria but also in those with recurrent abdominal pain, dysuria, and/or hematuria not associated with hypercalciuria. Clin Pediatr. 1999;38:521-524
Posterior vitreous detachment – prevalence of and risk factors for retinal tears

Purpose The present study aimed to describe clinical characteristics of patients with posterior vitreous detachment (PVD), to determine the prevalence of retinal tears in PVD patients, and to find predictors for retinal tears in this patient group. Methods Retrospective analysis of medical records on patients diagnosed with PVD, retinal tears, or vitreous hemorrhage at the Department of Ophthalmology at Sahlgrenska University Hospital, a tertiary eye center. Results Between February and July 2009, 365 patients consulted the Department of Ophthalmology for PVD-related symptoms. The incidence of retinal tears was 14.5% (n=53) and that of vitreous and/or retinal hemorrhage was 22.7% (n=83). For analysis of possible predictors for complications to PVD, patients diagnosed with retinal tears or vitreous hemorrhage between May and July 2009 were also included in the study, resulting in a total of 426 patients. Predictors of a retinal tear were symptoms of visual impairment (P=0.024), the presence of vitreous or retinal hemorrhage at examination (P<0.001), and a duration of symptoms for <24 hours (P=0.004). Symptoms of flashes did not constitute an extra risk of retinal tears (P=0.135). Subsequent retinal pathology (follow-up time 4.5 years), including vitreous detachment/hemorrhage or retinal tears/detachment, occurred more often in patients presenting with a retinal tear. For patients with a retinal tear, the relative risk of having a retinal detachment in the same eye during the follow-up time was 17.7 when compared to patients without a retinal tear (risk ratio 17.7, 95% confidence interval 2.2–145). Conclusion Patients seeking care on the first day have a higher risk of retinal tears. Also, symptoms of visual loss or a history of previous PVD-related pathology and vitreous/retinal hemorrhage at examination indicate a substantially higher risk of retinal complications. These findings may lead to better management and order of priority among these patients.
Dose-response relationships and mineralocorticoid activity in cortisol-induced hypertension in humans.

OBJECTIVE This study was designed to define the dose-response relationships for cortisol-induced hypertension in humans and to test the hypothesis that cortisol-induced hypertension is a consequence of classical mineralocorticoid actions using the mineralocorticoid antagonist spironolactone. METHODS In study 1, six normal men were given cortisol orally every 6 h for 5 days at doses of 40, 80 and 200 mg per day. In study 2, six normal men were given spironolactone at 400 mg/day for 6 days and cortisol at 80 mg/day for 5 days, commencing on the second day of spironolactone treatment. RESULTS Systolic blood pressure increased significantly with cortisol at 80 and 200 but not 40 mg/day. There was no difference between 80 and 200 mg/day. Weight increases were seen at the two higher doses and serum potassium concentration fell with each dose. Spironolactone prevented the increase in body weight and the decrease in serum potassium but did not affect the increase in blood pressure produced by cortisol. CONCLUSIONS Cortisol at 80 and 200 mg per day produces similar blood pressure and metabolic effects. Spironolactone blocked the mineralocorticoid effects of cortisol but not the blood pressure rise, suggesting that these mineralocorticoid effects are not responsible for cortisol-induced hypertension.
A Finite Control Set Model Predictive Control Method for Matrix Converter With Zero Common-Mode Voltage

In this paper, a novel finite control set model predictive control (FCS-MPC)-based solution is proposed to eliminate the common-mode voltage (CMV) in matrix converters. Different from the existing MPC-based CMV reduction methods, which usually utilize all the possible switching configurations, in the proposed method, only the six rotating vectors, which produce no CMV, are included in the FCS to synthesize the output voltage and the input current. Therefore, zero CMV can be achieved naturally and no CMV related term needs to be included in the cost function. In addition, compared with other zero CMV methods, e.g., the enhanced space-vector modulation using rotating vectors, the proposed MPC-based method can significantly reduce the computational complexity without detracting the CMV elimination performance. Moreover, a modified four-step commutation strategy is proposed to effectively mitigate the CMV spikes due to the dead time, which usually exists when using the conventional current-based four-step commutation strategy. Finally, the feasibility and effectiveness of the proposed method are validated by using experimental studies.
CD30 expression in de novo diffuse large B‐cell lymphoma: a population‐based study from British Columbia

Diffuse large B‐cell lymphoma (DLBCL) is a heterogeneous disease with variable therapeutic responses and alternative therapies are needed for patients with unfavourable treatment outcomes after standard treatment with R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). One promising candidate is brentuximab vedotin, an antibody‐drug conjugate targeting CD30‐expressing cells. However, CD30 (TNFRSF8) expression patterns in DLBCL are not well described thus far. Here, we examined CD30 expression in a population‐based cohort of immunocompetent patients from British Columbia with de novo DLBCL using immunohistochemistry. 385 cases of formalin‐fixed paraffin‐embedded DLBCL in tissue microarrays were evaluated. 95 cases (25%) harboured CD30+ tumour cells. Using a > 0% cut‐off, CD30 expression was predictive of superior 5‐year progression‐free survival within R‐CHOP treated germinal centre B‐cell‐like (GCB) DLBCL (86% vs. 64%, P = 0·020), which was independent of the International Prognostic Index. Epstein‐Barr virus (EBV) was identified in 11 (3%) cases, all of which were non‐GCB (P = 0·001) and almost exclusively positive for CD30 expression (10/11) (P < 0·001). We conclude CD30 is expressed in a substantial proportion of DLBCL and CD30 immunohistochemistry may be a useful prognostic marker in R‐CHOP treated GCB‐DLBCL. The significant association of CD30 with EBV‐positive non‐GCB DLBCL suggests a distinct pathobiology for these cases.
The mitochondrial genome of the Mediterranean fruit fly, Ceratitis capitata

The complete sequence of the mitochondrial genome of Ceratitis capitata has been determined. The circular genome is 15 980 bp long and contains a standard gene complement, i.e. the large and small ribosomal RNA subunits, twenty‐two transfer RNA (tRNA) genes and thirteen genes encoding mitochondrial proteins. When comparing the sequence to fragments previously sequenced from other isolates it becomes apparent that interstrain polymorphisms are not rare. These differences are potentially useful for the development of diagnostic tools for population analysis applications, such as determining the source of recent introductions. Moreover, they could help obtain a solution to the long‐lasting controversy on the possible eradication of the Medfly from certain locations.
Neuro-genetic truck backer-upper controller

The precise docking of a truck at a loading dock has been proposed in (Nguyen and Widrow, 1990) as a benchmark problem for non-linear control by neural-nets. The main difficulty is that backpropagation is not a priori suitable as a learning paradigm, because no set of training vectors is available: It is non-trivial to find solution trajectories that dock the truck from anywhere in the loading yard. In this paper we show how a genetic algorithm can evolve the weights of a feedforward 3-layer neural net that solves the control problem for a given starting state, achieving a short trajectory from starting point to goal. The fitness of a net in the population is a function of both the nearest position from the goal and the distance travelled. The influence of input data renormalisation on trajectory precision is also discussed. <<ETX>>
Co‐stimulatory pathways in lymphocyte regulation: the immunoglobulin superfamily

The controlled orchestration of immune responses is a vital feature of cellular immunity in a system that must be able to reliably distinguish self from non‐self. Contrary to early beliefs, peptide recognition by T cells exhibits a relatively high level of promiscuity. The requirement for a second signalling event to be present in addition to that provided by T cell receptor ligation for T cell activation to proceed helps to prevent inappropriately directed responses. An expanding array of co‐stimulatory or inhibitory signalling receptors and ligands are now recognised to be involved in the control of the crucial decisions made determining the activation, expansion, and effector functions of responding cells, and ultimately the final targeting and execution of these functions. Tight regulation of the temporal and spatial organisation of receptor/ligand expression, combined with both forward and reverse signalling, endows an extraordinary elegance to these co‐stimulatory pathways. The immunoglobulin superfamily occupies a central importance in this coordination of immune responses. The understanding of its relevance in a variety of physio‐pathological circumstances is now yielding a number of potential targets for therapeutic manipulation, and such immunological molecular adjuvants are beginning to enter clinical trials.
Drug monitoring of biologics in inflammatory bowel disease

Purpose of review The monoclonal antibodies currently used for the treatment of inflammatory bowel disease (IBD) have been thoroughly studied with regard to efficacy and safety. Their pharmacokinetics and the considerable inter-individual variability of clearance and immunogenicity have attracted a great deal of attention recently. Knowledge about their properties carries the potential to optimize efficacy and durability of therapeutics that is a mainstay in the medical management of IBD. Recent findings Based on population-based pharmacokinetics models, factors impacting the clearance of infliximab have been identified, antidrug antibodies (ADA) being one of them. Trough levels have been shown to correlate with clinical response and steroid-free remission. Initial insights have recently been gained into the individual course of ADA with a potential impact on future therapeutic strategies. Summary We briefly review the current state of the literature and propose an algorithm for the use of serum trough levels and ADA as basis for monitoring of biologics in patients with IBD.
Docetaxel administered on a weekly basis for metastatic breast cancer.

PURPOSE To evaluate the safety and efficacy of weekly docetaxel in women with metastatic breast cancer. PATIENTS AND METHODS Twenty-nine women were enrolled onto a study of weekly docetaxel given at 40 mg/m(2)/wk. Each cycle consisted of 6 weeks of therapy followed by a 2-week treatment break, repeated until disease progression or removal from study for toxicity or patient preference. Fifty-two percent of patients had been previously treated with adjuvant chemotherapy; 21% had received prior chemotherapy for metastatic breast cancer, and 31% had previously received anthracyclines. All patients were assessable for toxicity; two patients were not assessable for response but are included in an intent-to-treat analysis. RESULTS Patients received a median of 18 infusions, with a median cumulative docetaxel dose of 720 mg/m(2). There were no complete responses. Twelve patients had partial responses (overall response rate, 41%; 95% confidence interval, 24% to 61%), all occurring within the first two cycles. Similar response rates were observed among subgroups of patients previously treated either with any prior chemotherapy or with anthracyclines. An additional 17% of patients had stable disease for at least 6 months. The regimen was generally well tolerated. There was no grade 4 toxicity. Only 28% of patients had any grade 3 toxicity, most commonly neutropenia and fatigue. Acute toxicity, including myelosuppression, was mild. Fatigue, fluid retention, and eye tearing/conjunctivitis became more common with repetitive dosing, although these side effects rarely exceeded grade 2. Dose reductions were made for eight of 29 patients, most often because of fatigue (n = 5). CONCLUSION Weekly docetaxel is active in treating patients with metastatic breast cancer, with a side effect profile that differs from every-3-weeks therapy.