Miracle-dz/UniFAR-FTUs huggingface dataset:
Suppression of voluntary motor activity revealed using transcranial magnetic stimulation of the motor cortex in man.

1. Suppression of voluntary muscle activity of hand and arm muscles in response to transcranial magnetic stimulation (TMS) of the motor cortex has been investigated in man. 2. Suppression could be elicited by low levels of TMS without any prior excitatory response. The latency of the suppression was 3‐8 ms longer than the excitation observed at a higher stimulus intensity. The duration of the suppression ranged from 8 to 26 ms. 3. A circular stimulating coil was used to determine threshold intensity for excitation and suppression of contraction of thenar muscles in response to TMS at different locations over the motor cortex. The locations for lowest threshold excitation coincided with those for lowest threshold suppression. Suppression was elicited at a lower threshold than excitation at all locations. 4. A figure‐of‐eight stimulating coil was positioned over the left motor cortex at the lowest threshold point for excitation of the right thenar muscles. The orientation for the lowest threshold excitatory and inhibitory responses was the same for all subjects. That orientation induced a stimulating current travelling in an antero‐medial direction. Suppression was invariably elicited at lower thresholds than excitation. 5. When antagonistic muscles (second and third dorsal interosseus) were co‐contracted, TMS evoked coincident suppression of voluntary EMG in the two muscles without prior excitation of either muscle. This suggests that the suppression is not mediated via corticospinal activation of spinal interneurones. 6. Test responses to electrical stimulation of the cervical spinal cord were evoked in both relaxed and activated thenar muscles. In the relaxed muscle, prior TMS at an intensity that would suppress voluntary activity failed to influence the test responses, suggesting absence of inhibition at a spinal level. However, in the activated muscle, prior TMS could reduce the test response. This may be explained by disfacilitation of motoneurones due to inhibition of corticospinal output. 7. We propose that suppression of voluntary muscle activity by TMS is due in large part to activation of a mechanism within the motor cortex that reduces the corticospinal output to the muscle. It is concluded that TMS evokes excitation and inhibition via neuronal structures lying close to one another and having similar orientations.
KLEE: A long‐term multi‐species herbivore exclusion experiment in Laikipia, Kenya

Abstract Livestock and wildlife share much of their respective ranges throughout the semi‐arid ecosystems of the world. As the profitability of livestock production becomes more marginal and wildlife values increase, there is a need to understand the interactions between livestock and wild large mammalian herbivores (and other indigenous biodiversity). To address this, we have established a long‐term multi‐species herbivore exclusion experiment in the Laikipia ecosystem in Kenya. Using a series of semi‐permeable barriers, we are differentially excluding various combinations of cattle, large wild mammalian herbivores, and mega‐herbivores (giraffes and elephants) from a series of replicated four‐hectare plots. We are monitoring soil, plant, and animal responses to these treatment characteristics. This multi‐disciplinary project is one of the first to include controlled, replicated exclusion of combinations of multiple guilds of rangeland herbivores in the same place at the same time. We report here (1) the .
[Results and experiences after 1000 IVF cycles at the Clinic for Gynecology and Obstetrics in Novi Sad].

INTRODUCTION Infertility affects 15-17% of reproductive age couples in our country, and 10-15% of couples worldwide. The aim of this paper was to present results and experience gained after the first 1000 cycles of the national In Vitro Fertilization (IVF) program, to offer professional standard of work in our country and to compare it with results obtained in Europe and worldwide. MATERIAL AND METHODS The study prospectively included 1000 women who had undergone national In Vitro Fertilization program from October 2006 until November 2009 at the Department of Gynecology and Obstetrics, Clinical Center of Vojvodina, Novi Sad. RESULTS The analysis included 1000 in vitro fertilization cycles. Male factor infertility was the leading cause (56.9%) followed by tubal factor (45.9%). The classic method of in vitro fertilization constituted 72.3% of all cycles, while intracytoplasmic sperm injection (ICSI) method was used in 27.7% of all cycles. The average number of embryos transferred was 2.67. The cycle cancellation rate was 14.10% and the aspiration rate was 94.40%. The clinical pregnancy and live birth rate were 33.41% and 26.78% per embryo transfer respectively. DISCUSSION AND CONCLUSION The results in our study showed that in our setting there are far less intracytoplasmic sperm injection cycles compared with the European average of 66.5% of all fresh cycles, and that we transferred more embryos on average. Our success rates are comparable with those in other European countries where the clinical pregnancy rates per aspiration and per transfer for in vitro fertilization were 29 and 32.4%, respectively in the period of observation. For intracytoplasmic sperm injection, the corresponding rates were 29.9 and 33%.
Comparing Electronic Health Record Usability of Primary Care Physicians by Clinical Year

Objectives: To examine usability gaps among primary care resident physicians by clinical year: year 1 (Y1), year 2 (Y2), and year 3 (Y3) when using electronic health record (EHR). Methods: Twenty-nine usability tests with video analysis were conducted involving triangular method approach. Performance metrics of percent task success rate, time on task, and mouse activities were compared along with subtask analysis among the three physician groups. Results: Our findings showed comparable results for physicians of all three years in mean performance measures, specifically task success rate (Y1: 95%, Y2: 98%, Y3: 95%). However, varying usability issues were identified among physicians from all three clinical years. Twenty-nine common usability issues across five themes emerged during sub task analysis: inconsistencies, user interface issues, structured data issues, ambiguous terminologies, and workarounds. Discussion and Conclusion: This study identified varying usability issues for users of the EHR with different experience level, which may be used to potentially increase physicians’ performance when using an EHR. While three physician groups showed comparable performance metrics, these groups encountered numerous usability issues that should be addressed for effective EHR training and patient care.
Gram-Schmidt M-Wave Canceller for the EMG Controlled FES

To use the voluntary electromyogram (EMG) as a control signal of the EMG controlled functional electrical stimulator (FES), it is required to reduce the stimulation artifact and non-voluntary contribution (M-wave). In this study, a Gram-Schmidt (GS) prediction error filter (PEF) that can effectively eliminates the M-wave from voluntary EMG is presented. Also, the presented GS PEF is implemented on the field the programmable gate array (FPGA) for real-time processing and the performance is tested with simulated and real signals. Experimental results showed that GS-PEF was effective in reducing M-wave and preserving voluntary EMG.
Bioequivalence Study with Two Naproxen Sodium Tablet Formulations in Healthy Subjects

The purpose of this study was to find out whether the bioavailability of a 550 mg naproxen sodium (CAS 22204-53- 1 ) tablet (Sunprox, test) produced by Sunward Pharmaceutical Sdn Bhd was equivalent to that produced by the innovator. The pharmacokinetic parameters assessed in this study were area under the plasma concentration-time curve from time zero to 72 hours (AUC t ), area under the plasma concentration-time curve from time zero to infinity (AUC inf ), the peak plasma concentration of the drug (C max ), time needed to achieve the peak plasma concentration (t max ), and the elimination half life (t 1/2 ). This was a randomized, single blind, two-period, cross-over study which included 26 healthy adult male and female subjects under fasting conditions. In each of the two study periods (separated by a washout of one week) single dose of test or reference drug was administered. Blood samples were taken up to 72 h post dose, the plasma was separated and the concentration of naproxen were determined by HPLC-UV method. In this study, the mean AUC t , AUC inf , C max , and t ½ of naproxen from the test drug were 936.11 μg. h.mL -1 , 977.03 μg. h.mL -1 , 76.55 μg/mL, and 15.11 h, respectively. The mean AUC t , AUC inf , C max , and t ½ of naproxen from the reference drug were 969.77 μg. h.mL -1 , 1013.72 μg. h.mL -1 , 75.92 μg/mL, and 15.11 h, respectively. The median t max of he test drug and reference drug were 3.0 h and 2.0 h, respectively. The geometric mean ratios (90% CI) of the test drug/ reference drug for naproxen were 96.46% (94.30 – 98.66%) for AUC t , 96.33% (94.03 – 98.69%) for AUC inf , and 100.37% (95.90 – 105.05%) for C max . Based on this study, it can be concluded that the two naproxen sodium tablets (test and drug reference drug) were bioequivalent in term of the rate and extent of absorption.
Disconnect between inflammation and joint destruction after treatment with etanercept plus methotrexate: results from the trial of etanercept and methotrexate with radiographic and patient outcomes.

OBJECTIVE To determine the relationship between disease activity and radiographic progression of joint destruction in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX), those treated with etanercept, and those treated with the combination of MTX plus etanercept. METHODS Baseline, 12-month, and 24-month data from the Trial of Etanercept and Methotrexate with Radiographic and Patient Outcomes database were analyzed. The dependent variable was the 1-year change in the modified Sharp/van der Heijde score (Sharp score); therefore, 2 interval changes per patient were available. Interval change in the Sharp score was modeled by time (years), treatment, disease activity, and the interaction (disease activity x treatment). Disease activity was reflected by the time-averaged Disease Activity Score (taDAS) and the time-averaged C-reactive protein (taCRP) level, which were calculated per 1-year interval. Generalized mixed linear modeling (GMLM) was used to adjust for within-patient correlation. RESULTS GMLM confirmed a significant interaction between treatment and the taCRP level and taDAS with respect to the change in Sharp score (P = 0.012 and P = 0.03, respectively). In patients treated with MTX alone, radiographic progression increased with an increasing taCRP level or taDAS, although progression rates were low in patients whose disease was in remission and in those with low-to-moderate disease activity. This relationship was less clear in patients treated with etanercept and was absent in those who received combination therapy. CONCLUSION Combination therapy with MTX plus etanercept uncouples the classic relationship between disease activity and radiographic progression in patients with RA.
Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: the M.D. Anderson Cancer Center experience.

PURPOSE To evaluate the cardiac safety of long-term trastuzumab therapy in patients with human epidermal growth receptor 2 (HER2) -overexpressing metastatic breast cancer (MBC) treated at The University of Texas M.D. Anderson Cancer Center (Houston, TX). PATIENTS AND METHODS Among 218 MBC patients treated with trastuzumab-based therapy for at least 1 year, 173 patients were assessable for cardiac toxicity. Cardiac events (CEs) were defined as follows: asymptomatic decrease of left ventricular ejection fraction (LVEF) below 50%; decrease of 20 percentage points in LVEF compared with the baseline; or signs or symptoms of congestive heart failure (CHF). RESULTS The median cumulative time for trastuzumab administration was 21.3 months. The median follow-up was 32.6 months (range, 11.8 to 79.0 months). Forty-nine patients (28%) experienced a CE: three patients (1.7%) had an asymptomatic decrease in the LVEF of 20 percentage points, 27 patients (15.6%) experienced grade 2 cardiac toxicity, and 19 patients (10.9%) experienced grade 3 cardiac toxicity. All but three patients had improved LVEF or symptoms of CHF with trastuzumab discontinuation and appropriate therapy. There was one cardiac-related death (0.5%). Baseline LVEF was significantly associated with CE (hazard ratio, 0.94; P = .001). The hazard of a CE among patients taking concomitant taxanes was higher early in the follow-up period but declined during the course of follow-up. CONCLUSION The risk of cardiac toxicity of long-term trastuzumab-based therapy is acceptable in this population, and this toxicity is reversible in the majority of the patients. In patients who have experienced a CE, additional treatment with trastuzumab can be considered after recovery of cardiac function.
ULTRASTRUCTURAL DIFFERENCES IN HUMAN MALIGNANT MELANOMATA

Summary. — Thirty‐two human malignant melanomata have been investigated with the electron microscope. On the basis of the fine structure of the melano‐mata and melanosomes we have distinguished 2 different tumour forms (Type A and Type B). The melanosomes of Type A appear cigar‐shaped, whereas the premelanosomes have an internal helical structure exhibiting periodicity. Most of the mitochondria of this tumour type show an elongated from and numerous cristae. The nucleolus is usually very large and exhibits some vacuole‐like structures which contain a fine granular substance. The nucleus is distinguished by the different extent of heteropyknotic chromatin and fre‐quently has “nuclear bodies”. The tumour cells of the other melanoma form (Type B) contain only spherical melanosomes, whereas the premelanosomes show no internal fibrillar structure. The mitochondria mostly appear spherical as well; their matrix is slightly electron dense. There is no marked difference between the nuclei of these 2 melanoma forms. Their pathogenesis is discussed.
Clinical Outcome of Patients Who Develop PAF After CABG Surgery

KOWEY, P.R. , et al.: Clinical Outcome of Patients Who Develop PAF After CABG Surgery. This was a retrospective analysis of patients who had CABG surgery at our hospital over a 12‐month period to determine the intermediate‐term prognosis of those who had developed PAF after their operation before hospital discharge. Of 317 patients who were operated by a single surgical group, 116 (37%) had AF postoperatively of whom 112 had the paroxysmal form. Of these, 36 were treated with class I or III antiarrhythmic drugs and rate control drugs (group 1) and 76 were treated with rate control alone (group 2). Group 3 consisted of 151 randomly selected patients who did not have AF. All patients were reevaluated at 6 weeks to determine their rhythm and clinical status. Only one patient each in groups 1 and 2 was in AF 6 weeks after discharge. There was a trend toward a higher mortality and morbidity in group 2 patients. PAF after coronary surgery appears to be a self‐limited disease process. In this cohort of patients, the rate of recurrence of AF after discharge was similar in patients receiving class I or class III antiarrhythmic drugs together with rate control agents compared to those receiving rate control drugs alone.
Antioxidants Inhibit Angiogenesis In Vivo through Down-regulation of Nitric Oxide Synthase Expression and Activity

Although reactive oxygen species (ROS) participate in many cellular mechanisms, only few data exist concerning their involvement in physiological angiogenesis. The aim of the present work was to elucidate possible mechanisms through which ROS affect angiogenesis in vivo, using the model of the chicken embryo chorioallantoic membrane (CAM). Superoxide dismutase (SOD) and its membrane permeable mimetic tempol, dose dependently decreased angiogenesis and down-regulated inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production. The NADPH oxidase inhibitors, 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF) and apocynin, but not allopurinol, also had a dose dependent inhibitory effect on angiogenesis and NO production in vivo. Catalase and the intracellular hydrogen peroxide (H2O2) scavenger sodium pyruvate decreased, while H2O2 increased in a dose-dependent manner the number of CAM blood vessels, as well as the expression and activity of iNOS. Dexamethasone, which down-regulated NO production by iNOS and l-NAME, but not d-NAME, dose dependently decreased angiogenesis in vivo. These data suggest that antioxidants affect physiological angiogenesis in vivo, through regulation of NOS expression and activity.
Causal inference in outcome‐dependent two‐phase sampling designs

Summary. We consider estimation of the causal effect of a treatment on an outcome from observational data collected in two phases. In the first phase, a simple random sample of individuals is drawn from a population. On these individuals, information is obtained on treatment, outcome and a few low dimensional covariates. These individuals are then stratified according to these factors. In the second phase, a random subsample of individuals is drawn from each stratum, with known stratum‐specific selection probabilities. On these individuals, a rich set of covariates is collected. In this setting, we introduce five estimators: simple inverse weighted; simple doubly robust; enriched inverse weighted; enriched doubly robust; locally efficient. We evaluate the finite sample performance of these estimators in a simulation study. We also use our methodology to estimate the causal effect of trauma care on in‐hospital mortality by using data from the National Study of Cost and Outcomes of Trauma.
Functional Analysis of the Guanylyl Cyclase Type D Signaling System in the Olfactory Epithelium

The mammalian olfactory system recognizes a wide range of chemical stimuli. The majority of cells in the main olfactory epithelium (MOE) use a cAMP‐mediated signaling system to transduce odor signals. However, a subset of MOE neurons instead expresses components of a cGMP signaling cascade, including the receptor guanylyl cyclase GC‐D and the cyclic nucleotide‐gated channel subunit CNGA3. We used a combination of molecular biological, physiological, and imaging approaches to characterize this neuronal population. Neurons expressing GC‐D show excitatory responses to the natriuretic peptide hormones uroguanylin and guanylin, as well as to stimuli present in urine, that are dependent on both GC‐D and CNGA3. Though all GC‐D‐expressing neurons are highly sensitive to these stimuli, individual cells are differentially tuned to either one or both of the peptides. Together, these findings suggest that neurons expressing GC‐D are part of a specialized olfactory subsystem that is responsive to semiochemicals.
Redefining and Improving Patient Safety

Summary Objectives: The Institute of Medicine (IOM) has focused attention on patient safety in the united States. Other countries share these concerns. Methods: Governmental agencies and professional organizations are redefining approaches to safety, calling upon the use of information and communication technology as an enabler and expanding the range of evidence admissible in documenting success. Results: Efforts to understand medical errors have used retrospective chart review, incident reporting, and computerized surveillance; the result is an evolving picture of the number, nature, and cause of errors. Approaches used to prevent errors include computerized physician order entry, decision support tools, computerized monitoring, and evidence-based practice; varying levels of evidence document their success. Conclusions: Technology offers challenging capabilities, not simple solutions. New evidence and new tools demand new approaches and attention to human factors.
Pressure-Free Phenomenon in Top Layer of Chip Body Under Local Pressure and Design of Channel-Free Flat-Packaged IGBT

This letter investigates the magnitude and direction distributions of stress on an insulated gate bipolar transistor (IGBT) die when local pressure is applied to the chip surface. The results show that the pressure needs a certain thickness to spread uniformly all over the entire chip area. At the top of the chip, the stress concentrates right below the pressure contact region while the other region is pressure-free. Deeper into the die, the pressure becomes uniform vertical stress. This phenomenon is used to design the channel-free flat-packaged IGBT with little stress in the channel region by keeping the pressure contact region a safe distance away from the channel region. This improves the effective area of flat-packaged IGBT without destroying the reliability.
Three Forms of Somatization in Primary Care: Prevalence, Co‐occurrence, and Sociodemographic Characteristics

Three definitions of somatization were operationalized: (a) high levels of functional somatic distress, measured by the Somatic Symptom Index (SSI) of the Diagnostic Interview Schedule; (b) hypochondriasis measured by high scores on a measure of illness worry in the absence of evidence for serious illness; and (c) exclusively somatic clinical presentations among patients with current major depression or anxiety. Of 685 patients attending two family medicine clinics, 26.3% met criteria for one or more forms of somatization. While DSM-III somatization disorder had a prevalence of only 1% in this population, 16.6% of the patients met abridged criteria for subsyndromal somatization disorder (SSI 4,6). Hypochondriacal worry had a prevalence of 7.7% in the clinic sample. Somatized presentations of current major depression or anxiety disorder had a prevalence of 8%. The three forms of somatization were associated with different sociodemographic and illness behavior characteristics. A majority of patients met criteria for only one type of somatization, suggesting that distinct pathogenic processes may be involved in each of the three types.
Decitabine and Vorinostat Cooperate To Sensitize Colon Carcinoma Cells to Fas Ligand-Induced Apoptosis In Vitro and Tumor Suppression In Vivo

The death receptor Fas and its physiological ligand (FasL) regulate apoptosis of cancerous cells, thereby functioning as a critical component of the host cancer immunosurveillance system. To evade Fas-mediated apoptosis, cancer cells often downregulate Fas to acquire an apoptosis-resistant phenotype, which is a hallmark of metastatic human colorectal cancer. Therefore, targeting Fas resistance is of critical importance in Fas-based cancer therapy and immunotherapy. In this study, we demonstrated that epigenetic inhibitors decitabine and vorinostat cooperate to upregulate Fas expression in metastatic human colon carcinoma cells. Decitabine also upregulates BNIP3 and Bik expression, whereas vorinostat decreased Bcl-xL expression. Altered expression of Fas, BNIP3, Bik, and Bcl-xL resulted in effective sensitization of the metastatic human colon carcinoma cells to FasL-induced apoptosis. Using an experimental metastasis mouse model, we further demonstrated that decitabine and vorinostat cooperate to suppress colon carcinoma metastasis. Analysis of tumor-bearing lung tissues revealed that a large portion of tumor-infiltrating CD8+ T cells are FasL+, and decitabine and vorinostat-mediated tumor-suppression efficacy was significantly decreased in Fasgld mice compared with wild-type mice, suggesting a critical role for FasL in decitabine and vorinostat-mediated tumor suppression in vivo. Consistent with their function in apoptosis sensitization, decitabine and vorinostat significantly increased the efficacy of CTL adoptive transfer immunotherapy in an experimental metastasis mouse model. Thus, our data suggest that combined modalities of chemotherapy to sensitize the tumor cell to Fas-mediated apoptosis and CTL immunotherapy is an effective approach for the suppression of colon cancer metastasis.