Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of a pre‐existing neuropathy on the course of bortezomib‐induced peripheral neurotoxicity

Abstract We investigated a series of bortezomib‐treated patients and correlated the course of bortezomib‐induced peripheral neurotoxicity with the presence or absence of peripheral neuropathy at baseline. Forty‐eight patients were examined with the total neuropathy score reduced version (TNSr), visual analogue score (VAS) for pain, and nerve conduction studies at baseline and after two and four cycles of chemotherapy. Twenty‐three patients had a baseline TNSr = 0–2, and 25 patients had a baseline TNSr >2 (median = 6, range 3–13). The course of bortezomib‐induced peripheral neurotoxicity was generally more severe in those patients with the highest baseline TNSr. However, among those subjects with a normal baseline TNSr, two patients developed a clinically relevant peripheral neuropathy with a marked increase in TNSr as early as after two cycles of bortezomib treatment (TNSr = 10 and 15, respectively), while after four cycles, three other patients with normal baseline TNSr had a TNSr of 11, 12, and 13. VAS reporting confirmed that painful neuropathy is frequent after bortezomib administration. Our results indicate that the course of bortezomib‐induced peripheral neurotoxicity can be severe in subjects with normal neurological examination at baseline, and therefore, careful monitoring during treatment is suggested in these patients.
Enhanced trabecular-bone calcium deposition in female rats with a high physiological dose of prolactin diminishes after ovariectomy.

Although an increase in trabecular-bone calcium deposition has been shown to be regulated by prolactin during lactation, the physiological significance of prolactin in bone calcium metabolism in nonlactating rats remains unclear. This investigation sought to demonstrate the effects of endogenous prolactin and a high physiological dose of exogenous prolactin on bone turnover and bone calcium deposition in normal female rats, using the 45Ca-labeling technique. Our results showed that suppression of endogenous prolactin with 6 mg/kg bromocriptine for 15 days significantly enhanced bone formation, but not bone resorption, in primarily trabecular sites, resulting in a significant increase in calcium deposition in the sternum and vertebrae, from -0.20+/-0.07 to 0.40+/-0.09 (p<0.05) and -0.07+/-0.11 to 0.34+/-0.06 (p<0.05) mmol Ca. (g dry mass)-1, respectively. Similarly, 2.5 mg/kg prolactin, a high physiological dose, increased sternal and vertebral calcium deposition, from -0.20+/-0.07 to 0.24+/-0.09 (p<0.05) and -0.07+/-0.11 to 0.25+/-0.18 (p<0.05) mmol Ca. (g dry mass)-1, respectively, by increasing bone formation more than bone resorption. However, as expected, prolactin had no effect on the tibia or femur, which are primarily cortical sites. Because several actions of prolactin have been known to be estradiol-dependent, we further investigated the dependence of prolactin action on 17beta-estradiol. We found that 2.5 mg/kg prolactin did not increase sternal calcium deposition in ovariectomized rats. However, 10 microg/kg 17beta-estradiol supplementation restored the action of prolactin. Ovariectomized rats given 17beta-estradiol plus prolactin also manifested slightly but significantly higher sternal total calcium content than sham-operated rats, (4.58+/-0.12 vs. 4.36+/-0.11 mmol Ca.(g dry mass)-1 (p<0.05)). We concluded that a high physiological dose of prolactin promoted calcium deposition in primarily trabecular sites of nonlactating rats. This effect was diminished after ovariectomy. In addition, we showed that basal endogenous prolactin played a role in the maintenance of normal trabecular-bone turnover.
Structural Logic of Intraorganizational Networks

In this study we examine the structural logic underlying complex intraorganizational networks. Drawing on different propositions about structural regularities in networks and using a comparative case study, we empirically investigate the structural logic of collaborative networks for the strategic decision process in two German corporations. In both organizations, data were gathered on cooperative relationships between all managers belonging to the top two management levels. We model structural regularities at the dyadic and the extradyadic level by applying a class of multivariate exponential random graph models. Our findings contribute to the existing literature in three ways: (1) Although networks are particularly likely to exhibit some types of structural regularities (e.g., reciprocity and transitivity), there are other relational forms such as cycles that seem to be of limited relevance. (2) Structural regularities are not limited to a single type of relation but may comprise instrumental and affective relational ties simultaneously. (3) An organization's formal cooperation structure has surprisingly limited influence on the structural patterns of cooperation, whereas friendship ties are embedded in managers' regular interaction patterns in many different ways.
Protective Effect of L-Arginine in Experimentally Induced Myocardial Ischemia: Comparison With Aspirin

Objective: Coronary artery diseases including myocardial ischemia (MI) remain one of the leading causes of death worldwide. This study was designed to compare the protective effect of L-arginine versus aspirin from the biochemical changes associated with MI injury. Experimental design: Four groups of male New Zealand white rabbits were investigated. Normal group (n = 8) rabbits were fed standard chow pellets, untreated MI group (n = 16), where hypercholesterolemia was induced by feeding the animals with a diet containing 2% cholesterol for 28 days, L-arginine group (n = 12) rabbits were fed a 2% cholesterol-enriched diet in conjunction with L-arginine (2.25 g %) in drinking water for 28 days, and aspirin group (n = 12) rabbits were fed 2% cholesterol-enriched diet in conjunction with aspirin administered orally (0.7 mg/kg per d) for 28 days. After 28 days, MI was induced in all groups, except the normal group, by a single subcutaneous (sc) injection of isoproterenol hydrochloride (0.2 mg/kg body weight [bw]). Animals were sacrificed 6 hours later. Results: Our results showed that L-arginine was more effective than aspirin in reducing platelet aggregation, reducing low-density lipoprotein (LDL) oxidizability, preventing aortic intimal thickening, and maintaining histological architecture of the myocardium. Both drugs, however, had similar positive effects on plasma fibrinogen levels and on the prevention of myocardial release of cardiac troponin I and creatine kinase-MB. The effect on hypercholesterolemia was insignificant for both drugs. Aspirin was more effective than L-arginine in prolonging prothrombin time. Conclusion: L-arginine supplementation represents a potentially novel nutritional strategy for preventing and treating coronary artery diseases especially in cases of aspirin resistance and/or hypersensitivity.
Effect of quercitrin on acute and chronic experimental colitis in the rat.

Quercitrin was tested for acute and chronic anti-inflammatory activity in trinitrobenzenesulfonic acid-induced rat colitis. The inflammatory status was evaluated by myeloperoxidase, alkaline phosphatase and total glutathione levels, leukotriene B4 synthesis, in vivo colonic fluid absorption, macroscopical damage and occurrence of diarrhea and adhesions. Treatment with 1 or 5 mg/kg of quercitrin by the oral route reduced myeloperoxidase and alkaline phosphatase levels, preserved normal fluid absorption, counteracted glutathione depletion and ameliorated colonic damage at 2 days. Increasing or lowering the dose of the flavonoid resulted in marked loss of effect. The acute anti-inflammatory effect of quercitrin is unrelated to impairment of neutrophil function or lipoxygenase inhibition, and it may be caused by mucosal protection or enhancement of mucosal repair secondary to increased defense against oxidative insult and/or preservation of normal colonic absorptive function. When tested in chronic colitis (2 and 4 weeks), quercitrin treatment (1 or 5 mg/kg.day) decreased colonic damage score and the incidence of diarrhea, and normalized the colonic fluid transport. All other parameters were unaffected. The chronic effect of the flavonoid is apparently related to its action on colonic absorption, although it can be partly secondary to its acute beneficial effect.
A leadership primer for software engineers

The principles of leadership resemble the life lessons we (are supposed to) learn as children: introduce yourself first, accentuate the positive, and set an example for others. Everyone knows most of them, already. The hard part of leading (the secret of leading) is that you have to do it, and do it consistently. This essay is intended for career software engineers who want to help their friends and colleagues in the SE community to succeed, whether helping their teams to complete projects or helping the SE profession to thrive.
Matrix remodeling stimulates stromal autophagy, “fueling” cancer cell mitochondrial metabolism and metastasis

We have previously demonstrated that loss of stromal caveolin-1 (Cav-1) in cancer-associated fibroblasts is a strong and independent predictor of poor clinical outcome in human breast cancer patients. However, the signaling mechanism(s) by which Cav-1 downregulation leads to this tumor-promoting microenvironment are not well understood. To address this issue, we performed an unbiased comparative proteomic analysis of wild-type (WT) and Cav-1-/- null mammary stromal fibroblasts (MSFs). Our results show that plasminogen activator inhibitor type 1 and type 2 (PAI-1 and PAI-2) expression is significantly increased in Cav-1-/- MSFs. To establish a direct cause-effect relationship, we next generated immortalized human fibroblast lines stably overexpressing either PAI-1 or PAI-2. Importantly, PAI-1/2(+) fibroblasts promote the growth of MDA-MB-231 tumors (a human breast cancer cell line) in a murine xenograft model, without any increases in angiogenesis. Similarly, PAI-1/2(+) fibroblasts stimulate experimental metastasis of MDA-MB-231 cells using an in vivo lung colonization assay. Further mechanistic studies revealed that fibroblasts overexpressing PAI-1 or PAI-2 display increased autophagy (“self-eating”) and are sufficient to induce mitochondrial biogenesis/activity in adjacent cancer cells, in co-culture experiments. In xenografts, PAI-1/2(+) fibroblasts significantly reduce the apoptosis of MDA-MB-231 tumor cells. The current study provides further support for the “Autophagic Tumor Stroma Model of Cancer” and identifies a novel “extracellular matrix”-based signaling mechanism, by which a loss of stromal Cav-1 generates a metastatic phenotype. Thus, the secretion and remodeling of extracellular matrix components (such as PAI-1/2) can directly regulate both (1) autophagy in stromal fibroblasts and (2) epithelial tumor cell mitochondrial metabolism.
A Phase I and Pharmacologic Trial of Two Schedules of the Proteasome Inhibitor, PS-341 (Bortezomib, Velcade), in Patients with Advanced Cancer

Purpose: To define the toxicities, pharmacodynamics, and clinical activity of the proteasome inhibitor, PS-341 (bortezomib), in patients with advanced malignancies. Patients and Methods: Twenty-eight patients (14 male and 14 female) received PS-341 twice weekly for 4 of 6 weeks (schedule I). Because toxicity necessitated dose omissions on this schedule, 16 additional patients (12 male and 4 female) received PS-341 twice weekly for 2 of every 3 weeks (schedule II). A total of 73 courses of treatment was given (median, 2; range, 1-4). Inhibition of 20S proteasome activity in peripheral blood mononuclear cells (PBMC) and accumulation of proteasome-targeted polypeptides in tumor tissue were evaluated as pharmacodynamic markers of PS-341 activity. Results: The most common toxicity was thrombocytopenia, which was dose limiting at 1.7 mg/m2 (schedule I) and 1.6 mg/m2 (schedule II), respectively. Sensory neuropathy was dose-limiting in a patient in schedule I. Grade ≥3 toxicities for schedule I were constipation, fatigue, myalgia, and sensory neuropathy. Grade ≥3 toxicities for schedule II were dehydration resulting from diarrhea, nausea and vomiting, fatigue, hypoglycemia, and hypotension. The maximum tolerated dose was 1.5 mg/m2 for both schedules. Reversible dose-dependent decreases in 20S proteasome activity in PBMCs were observed, with 36% inhibition at 0.5 mg/m2, 52% at 0.9 mg/m2, and 75% at 1.25 mg/m2. Accumulation of proteasome-targeted polypeptides was detected in tumor samples after treatment with PS-341. A patient with multiple myeloma had a partial response. Conclusion: PS-341 given 1.5 mg/m2 twice weekly for 2 of every 3 weeks is well tolerated and should be further studied.
Comparing Deficits Following Excitotoxic and Contusion Injuries in the Thoracic and Lumbar Spinal Cord of the Adult Rat

The majority of human spinal cord injuries involve gray matter loss from the cervical or lumbar enlargements. However, the deficits that arise from gray matter damage are largely masked by the severe deficits due to associated white matter damage. We have developed a model to examine gray matter-specific deficits and therapeutic strategies that uses intraspinal injections of the excitotoxin kainic acid into the T9 and L2 regions of the spinal cord. The resulting deficits have been compared to those from standard contusion injuries at the same levels. Injuries were assessed histologically and functional deficits were determined using the Basso, Beattie, and Bresnahan (BBB) 21-point open field locomotor scale and transcranial magnetic motor evoked potentials (tcMMEPs). Kainic acid injections into T9 resulted in substantial gray matter damage; however, BBB scores and tcMMEP response latencies were not different from those of controls. In contrast, kainic acid injections into L2 resulted in paraplegia with BBB scores similar to those following contusion injuries at either T9 or L2, without affecting tcMMEP response latencies. These observations demonstrate that gray matter loss can result in significant functional deficits, including paraplegia, in the absence of a disruption of major descending pathways.
Fixed-point free circle actions on 4-manifolds

on orientable 4‐manifolds. We show that the fundamental group plays a predominant role in the equivariant classification of such 4‐manifolds. In particular, it is shown that for any finitely presented group with infinite center there are at most finitely many distinct smooth (resp. topological) 4‐manifolds which support a fixed-point free smooth (resp. locally linear) S 1 ‐action and realize the given group as the fundamental group. A similar statement holds for the number of equivalence classes of fixedpoint free S 1 ‐actions under some further conditions on the fundamental group. The connection between the classification of the S 1 ‐manifolds and the fundamental group is given by a certain decomposition, called a fiber-sum decomposition, of the S 1 ‐ manifolds. More concretely, each fiber-sum decomposition naturally gives rise to a Z‐splitting of the fundamental group. There are two technical results in this paper which play a central role in our considerations. One states that the Z‐splitting is a canonical JSJ decomposition of the fundamental group in the sense of Rips and Sela. Another asserts that if the fundamental group has infinite center, then the homotopy class of principal orbits of any fixed-point free S 1 ‐action on the 4‐manifold must be infinite, unless the 4‐manifold is the mapping torus of a periodic diffeomorphism of some elliptic 3‐manifold. 57S15; 57M07, 57M50
Race, Sex, Ordinal Position of Birth, and Self-Disclosure in High School Students

The Jourard and Lasakow (1958) Self-disclosure Questionnaire was administered to 120 high school students in order to examine relationships of birth order, race, and sex to self-disclosure. Results indicated that later borns disclosed more than firstborns, whites disclosed more than Negroes, and mother was the favorite target person. Further, firstborn Negroes disclosed less than any other group, females disclosed most to mother and female friend while males disclosed least to female friend, firstborns disclosed most to mother, and whites disclosed more to father than Negroes. Results were discussed in relation to possible child-rearing practices affecting the meaningfulness of interpersonal relationships established by the various birth ranks.
Developing a Minimum Data Set for an Information Management System to Study Traffic Accidents in Iran

Background: Each year, around 1.2 million people die in the road traffic incidents. Reducing traffic accidents requires an exact understanding of the risk factors associated with traffic patterns and behaviors. Properly analyzing these factors calls for a comprehensive system for collecting and processing accident data. Objectives: The aim of this study was to develop a minimum data set (MDS) for an information management system to study traffic accidents in Iran. Materials and Methods: This descriptive, cross-sectional study was performed in 2014. Data were collected from the traffic police, trauma centers, medical emergency centers, and via the internet. The investigated resources for this study were forms, databases, and documents retrieved from the internet. Forms and databases were identical, and one sample of each was evaluated. The related internet-sourced data were evaluated in their entirety. Data were collected using three checklists. In order to arrive at a consensus about the data elements, the decision Delphi technique was applied using questionnaires. The content validity and reliability of the questionnaires were assessed by experts’ opinions and the test-retest method, respectively. Results: An (MDS) of a traffic accident information management system was assigned to three sections: a minimum data set for traffic police with six classes, including 118 data elements; a trauma center with five data classes, including 57 data elements; and a medical emergency center, with 11 classes, including 64 data elements. Conclusions: Planning for the prevention of traffic accidents requires standardized data. As the foundation for crash prevention efforts, existing standard data infrastructures present policymakers and government officials with a great opportunity to strengthen and integrate existing accident information systems to better track road traffic injuries and fatalities.
Gastric Cancer Screening by Combined Assay for Serum Anti-Helicobacter pylori IgG Antibody and Serum Pepsinogen Levels - The ABC Method

Background:Helicobacter pylori (Hp) infection and gastric atrophy are both risk factors for gastric cancer. Recently it has been found that X-ray examination for gastric cancer screening does not have much effect on the detection rate for gastric cancer in Japan. A candidate for a new mass screening for gastric cancer, the ABC method, using the combination assay of Hp and serum pepsinogen, was useful for identifying the development of gastric cancer in high-risk and low-risk populations. People with higher cancer risk are recommended to receive endoscopy. The ABC method was carried out as a gastric cancer mass-screening on the initiative of Nishitokyo Medical Association in Nishitokyo city from 2011. This paper reviewed the present status of gastric cancer screening using the ABC method, including the latest results of our ongoing screening. Summary: We report results for 36,627 individuals from 2011 to 2013. Among them, 16,965 received blood examination for the ABC method. Of those, 8,083 planned to undergo endoscopic examination according to stratification of the risk for the development of gastric cancer. In fact, a total of 2,911 individuals underwent endoscopic examination. Gastric cancer was detected in 65 patients, including 52 (80%) diagnosed with early gastric cancer. The ABC method was not organized screening but opportunistic screening. X-ray examination was the organized screening that was ongoing during the same period. Detection cost for 1 gastric cancer case using the ABC method was cheaper than the conventional X-ray screening method (¥1,267,452 vs. ¥2,807,763). Key Messages: Although further large epidemiological studies are required, the ABC method might be positioned as an effective mass screening for gastric cancer.
Population Dynamics of Streptococcus mitis in Its Natural Habitat

ABSTRACT The purpose of this study was to examine the genetic structure of the typical commensal Streptococcus mitisbiovar 1 in its natural habitat in the human oral cavity and pharynx and to investigate the role that selected microbial properties and host, spatial, and temporal factors play in determining the structure of the bacterial population. Consecutive samples were collected from buccal and pharyngeal mucosal surfaces of two infants, their four parents, and two elderly individuals over a period of approximately 1 year. A total of 751 isolates identified as S. mitisbiovar 1 were typed by restriction endonuclease analysis (REA) and representative clones were typed by multilocus enzyme electrophoresis (MLEE). The genetic diversity of the S. mitis biovar 1 isolates collected from single infant hosts over a period of 9 to 10 months was found to be between 0.69 and 0.76, which is considerably higher than that previously observed for intestinal populations ofEscherichia coli. The study provides evidence of the existence of both transient and persistent clones in adult individuals. In the two infants, however, none of 42 demonstrated clones were detected on more than a single occasion. Statistical calculations showed that the ability to persist was not distributed at random in theS. mitis biovar 1 population. However, neither immunoglobulin A1 protease activity nor the ability to bind α-amylase from saliva was a preferential characteristic of persistent genotypes. In contrast to current concepts of climax ecosystems, the species niche in the habitat appears to be maintained predominantly by a succession of clones rather than by stable strains. Several lines of evidence suggest that the major origin of “new” clones is the many other habitats in the respiratory tract that are occupied by this species.
Perception of Effort in Female and Male Competitive Swimmers1

The primary purpose of this investigation was to compare 31 competitive female swimmers with 31 competitive male swimmers on their perceptual responses to submaximal swimming. A secondary purpose was to evaluate the relationship between heart rate (HR) and perceived exertion (RPE) in swimming. Each swimmer completed a 200-yd swim in his/her specialty stroke at 90% of the swimmer's current best time. Underwater and overhead pace lights were used to achieve an even pace during the swims, and HR was monitored by means of radiotelemetry. Ratings of overall and local perceived exertion were assessed immediately following each swim with Borg's 6-20 scale. ANOVA revealed no RPE differences across stroke classifications for the female or male swimmers, but local and overall RPE were lower (p less than 0.01) in the females. Mean HR, however, was significantly higher (p less than 0.05) for the female swimmers. Unlike research with other exercise modes, correlational analyses revealed that overall and local RPE were unrelated to HR (p greater than 0.05). Based on these findings, it is concluded that 1) female swimmers judged a paced swim to be less effortful than did male swimmers despite a greater objective strain in the females, and 2) HR was not correlated with perception of effort.