Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment With Carfilzomib-Lenalidomide-Dexamethasone With Lenalidomide Extension in Patients With Smoldering or Newly Diagnosed Multiple Myeloma.

IMPORTANCE Carfilzomib-lenalidomide-dexamethasone therapy yields deep responses in patients with newly diagnosed multiple myeloma (NDMM). It is important to gain an understanding of this combination's tolerability and impact on minimal residual disease (MRD) negativity because this end point has been associated with improved survival. OBJECTIVE To assess the safety and efficacy of carfilzomib-lenalidomide-dexamethasone therapy in NDMM and high-risk smoldering multiple myeloma (SMM). DESIGN, SETTING, AND PARTICIPANTS Clinical and correlative pilot study at the National Institutes of Health Clinical Center. Patients with NDMM or high-risk SMM were enrolled between July 11, 2011, and October 9, 2013. Median follow-up was 17.3 (NDMM) and 15.9 months (SMM). INTERVENTIONS Eight 28-day cycles were composed of carfilzomib 20/36 mg/m2 on days 1, 2, 8, 9, 15, and 16; lenalidomide 25 mg on days 1 through 21; and dexamethasone 20/10 mg (cycles 1-4/5-8) on days 1, 2, 8, 9, 15, 16, 22, and 23. Patients who achieved at least stable disease subsequently received 24 cycles of lenalidomide extended dosing. MAIN OUTCOMES AND MEASURES Primary end points were neuropathy of grade 3 or greater (NDMM) and at least very good partial response rates (SMM). Minimal residual disease was also assessed. RESULTS Of 45 patients with NDMM, none had neuropathy of grade 3 or greater. Of 12 patients with high-risk SMM, the most common of any-grade adverse events were lymphopenia (12 [100%]) and gastrointestinal disorders (11 [92%]). All patients with SMM achieved at least a very good partial response during the study period. Among the 28 patients with NDMM and the 12 with SMM achieving at least a near-complete response, MRD negativity was found in 28 of 28 (100% [95% CI, 88%-100%]), 11 of 12 (92% [95% CI, 62%-100%]) (multiparametric flow cytometry), 14 of 21 (67% [95% CI, 43%-85%]), and 9 of 12 (75% [95% CI, 43%-94%]) (next-generation sequencing), respectively. In patients with NDMM, 12-month progression-free survival for MRD-negative vs MRD-positive status by flow cytometry and next-generation sequencing was 100% vs 79% (95% CI, 47%-94%; P < .001) and 100% vs 95% (95% CI, 75%-99%; P = .02), respectively. CONCLUSIONS AND RELEVANCE Carfilzomib-lenalidomide-dexamethasone therapy is tolerable and demonstrates high rates of MRD negativity in NDMM, translating into longer progression-free survival in patients achieving MRD negativity. Carfilzomib-lenalidomide-dexamethasone therapy also demonstrates efficacy in high-risk SMM.
Increased availability of family donors for hematopoietic stem cell transplantation in a population with increased incidence of consanguinity

Balcı YI, Tavil B, Tan CS, Ozgur TT, Bulum B, Cetin M, Balcı M, Yalcın S, Tezcan I, Uckan D. Increased availability of family donors for hematopoietic stem cell transplantation in a population with increased incidence of consanguinity. Clin Transplant 2011: 25: 475–480. © 2010 John Wiley & Sons A/S.
Optimistic Disclosure Tone and Conservative Debt Policy

We examine the relationship between managerial optimism and debt conservatism (i.e. the low-leverage puzzle). Our analysis demonstrates that optimistic tone, our time-varying optimism measure, significantly decreases leverage. This evidence supports the proposition that optimistic managers who consider external financing as unduly costly use debt conservatively. This reduced reliance on external financing can be explained by our further evidence that optimistic tone significantly increases cash holdings and decreases dividend payment. The negative tone-leverage relation is stronger in the presence of high insider purchase of own stocks which confirms that optimistic tone reflects managerial optimism. This study suggests that managerial optimism can help explain the low-leverage puzzle.
Oral Chinese herbal medicine for improvement of quality of life in patients with stable chronic obstructive pulmonary disease: a systematic review.

PURPOSE This study evaluates published clinical trials of Chinese herbal medicine (CHM) for chronic obstructive pulmonary disease (COPD) that employ a health-related quality of life (HRQoL) outcome measure. METHODS Searches were conducted in April 2011 on MEDLINE, Embase, the Cochrane Controlled Trials Register, CINAHL, Scopus, and Chinese databases (CNKI, CQVIP, WANFANG). Randomized controlled trials involving oral administration of CHM formulae or single herb, with or without blinding, compared to placebo, no treatment, routine pharmacotherapy control, or CHM plus routine pharmacotherapy versus routine pharmacotherapy, with a HRQoL questionnaire as an outcome measure were identified. The methodological quality was assessed using the Cochrane risk of bias assessment. RESULTS A total of 27 studies involving 1966 patients were identified. St. George Respiratory Questionnaire (SGRQ) or Cai's QoLQ were used in 13 and 14 studies, respectively. Assessment of the Cochrane risk of bias revealed adequate sequence of generation in 10 studies and adequate allocation concealment in 1 study; double blinding was not described adequately in any studies. Seventeen (17) studies addressed incomplete outcome data, and 17 studies were free of selective reporting. The main results of meta-analysis showed improvement of total HRQoL scores (SGRQ and Cai's QoLQ) when CHM was compared to no treatment (-6.07 [-9.21, -2.93] and -0.20 [-32, -0.07], respectively) and for CHM plus routine pharmacotherapy versus routine pharmacotherapy (-5.15 [-7.26, -3.05]) and (-0.25 [-0.37, -0.13]). CONCLUSIONS While the results of CHM on HRQoL for stable COPD sufferers were promising, they need to be interpreted with caution due to methodological problems, which should be addressed in future trials.
Clinical efficacy and safety of gabapentin

Article abstract The challenges of treating patients with partial seizures soon will be met, in part, by a number of new additions (felbamate, gabapentin, lamotrigine) to existing treatment options. Gabapentin, has shown significant promise in the treatment of patients with refractory partial seizures and secondarily generalized tonic-clonic seizures. Three large, randomized, multicenter, double-blind, placebo-controlled, parallel-group clinical trials have established its efficacy and safety as add-on therapy in patients with refractory partial seizures. Gabapentin is well tolerated. Although adverse events occur in most patients receiving gabapentin as adjunctive therapy, they are transient and mild to moderate in severity. To date, serious adverse events have been rare. Long-term safety data are needed. The lack of drug interaction potential between gabapentin and traditional antiepileptic drugs also was confirmed in clinical trials.
Regional variability in secondary remodeling within long bone cortices of catarrhine primates: the influence of bone growth history

Secondary intracortical remodeling of bone varies considerably among and within vertebrate skeletons. Although prior research has shed important light on its biomechanical significance, factors accounting for this variability remain poorly understood. We examined regional patterning of secondary osteonal bone in an ontogenetic series of wild‐collected primates, at the midshaft femur and humerus of Chlorocebus (Cercopithecus) aethiops (n = 32) and Hylobates lar (n = 28), and the midshaft femur of Pan troglodytes (n = 12). Our major objectives were: 1) to determine whether secondary osteonal bone exhibits significant regional patterning across inner, mid‐cortical and outer circumferential cortical rings within cross‐sections; and if so, 2) to consider the manner in which this regional patterning may reflect the influence of relative tissue age and other circumstances of bone growth. Using same field‐of‐view images of 100‐µm‐thick cross‐sections acquired in brightfield and circularly polarized light microscopy, we quantified the percent area of secondary osteonal bone (%HAV) for whole cross‐sections and across the three circumferential rings within cross‐sections. We expected bone areas with inner and middle rings to exhibit higher %HAV than the outer cortical ring within cross‐sections, the latter comprising tissues of more recent depositional history. Observations of primary bone microstructural development provided an additional context in which to evaluate regional patterning of intracortical remodeling. Results demonstrated significant regional variability in %HAV within all skeletal sites. As predicted,%HAV was usually lowest in the outer cortical ring within cross‐sections. However, regional patterning across inner vs. mid‐cortical rings showed a more variable pattern across taxa, age classes, and skeletal sites examined. Observations of primary bone microstructure revealed that the distribution of endosteally deposited bone had an important influence on the patterning of secondary osteonal bone across rings. Further, when present, endosteal compacted coarse cancellous bone always exhibited some evidence of intracortical remodeling, even in those skeletal sites exhibiting comparatively low %HAV overall. These results suggest that future studies should consider the local developmental origin of bone regions undergoing secondary remodeling later in life, for an improved understanding of the manner in which developmental and mechanical factors may interact to produce the taxonomic and intraskeletal patterning of secondary bone remodelling in adults.
Characterization of an anti-glucosyltransferase serum specific for insoluble glucan synthesis by Streptococcus mutans

An anti-glucosyltransferase serum, which synthesized 96% insoluble glucans, was prepared against a purified enzyme preparation from Streptococcus mutans strain HS6 (serotype a). This serum was examined for its effects on glucan synthesis by crude enzyme preparations from eight strains (four serotypes) of S. mutans and for the ability of these preparations to promote adherence of S. mutans to a smooth surface. Glucosyltransferase activity was assayed by measuring the incorporation of glucose from [14C]glucose-labeled sucrose into water-insoluble and water-soluble (ethanol-insoluble) glucans. Anti-glucosyltransferase serum inhibited insoluble glucan synthesis by crude enzyme preparations from cells of the four serotypes of S. mutans. Enzymes from strains of types a, b, and d were inhibited between 70 to 90%; enzymes from type c strains were inhibited from 45 to 60%. The adherence to a glass surface of heat-killed cells from these four serotypes was likewise inhibited. Soluble glucan synthesis was not inhibited by the serum, and in some cases its synthesis increased as insoluble glucan synthesis decreased.
Assessment of left atrial function by MRI myocardial feature tracking

Left atrium (LA) volumes and function are predictors of cardiovascular events. Because LA function cannot be assessed from cardiovascular magnetic resonance imaging (MRI) using the well‐established left ventricular tagging techniques, we hypothesized that adequate feature tracking (FT) applied to conventional cine MRI data could characterize LA function accurately.
Use of an inducible regulatory protein to identify members of a regulon: application to the regulon controlled by the leucine-responsive regulatory protein (Lrp) in Escherichia coli

Procedures were developed to facilitate the identification of genes that belong to a given regulon and characterization of their responses to the regulator. The regulon controlled by the Escherichia coli leucine-responsive regulatory protein (Lrp) was studied by isolating random transcriptional fusions to lacZ, using lambda placMu53 and a strain in which lrp is under isopropylthio-beta-D-galactopyranoside (IPTG)-inducible control. Fusions exhibiting IPTG-responsive beta-galactosidase activity were cloned by integrating the suicide vector pIVET1 via homologous recombination at lacZ, followed by self-ligating digested chromosomal DNA. We verified the patterns of lacZ expression after using the plasmid clones to generate merodiploid strains with interrupted and uninterrupted copies of the same sequence. If the merodiploid expression pattern was unchanged from that shown by the original fusion strain, then the cloned fusion was responsible for the regulatory pattern of interest; a difference in the expression pattern could indicate that the original strain carried multiple fusions or that there were autogenous effects of having interrupted the fused gene. Using these procedures, we generated a fusion library of approximately 5 x 10(6) strains; approximately 3,000 of these strains were screened, yielding 84 Lrp-responsive fusions, and 10 of the 84 were phenotypically stable and were characterized. The responses of different fusions in a given operon to in vivo Lrp titrations revealed variations in expression with the position of insertion. Among the newly identified members of the regulon is an open reading frame (orf3) between rpiA and serA. Also, expression of a fusion just downstream of dinF was found to be Lrp dependent only in stationary phase.
The Compact Mutation of Myostatin Causes a Glycolytic Shift in the Phenotype of Fast Skeletal Muscles

Myostatin is an important negative regulator of skeletal muscle growth. The hypermuscular Compact (Cmpt) mice carry a 12-bp natural mutation in the myostatin propeptide, with additional modifier genes being responsible for the phenotype. Muscle cellularity of the fast-type tibialis anterior (TA) and extensor digitorum longus (EDL) as well as the mixed-type soleus (SOL) muscles of Cmpt and wild-type mice was examined by immunohistochemical staining of the myosin heavy chain (MHC) proteins. In addition, transcript levels of MHC isoforms were quantified by qPCR. Based on our results, all investigated muscles of Cmpt mice were significantly larger compared with that of wild-type mice, as characterized by fiber hyperplasia of different grades. Fiber hypertrophy was not present in TA; however, EDL muscles showed specific IIB fiber hypertrophy while the (I and IIA) fibers of SOL muscles were generally hypertrophied. Both the fast TA and EDL muscles of Cmpt mice contained significantly more glycolytic IIB fibers accompanied by a decreased number of IIX and IIA fibers; however, this was not the case for SOL muscles. In summary, despite the variances found in muscle cellularity between the different myostatin mutant mice, similar glycolytic shifts were observed in Cmpt fast muscles as in muscles from myostatin knockout mice.
Novel approach to fast determination of multiple pesticide residues using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)

A rapid, high-throughput method employing ultra-performance liquid chromatography with tandem quadrupole mass spectrometry (UPLC-MS/MS) was developed and optimized for simultaneous quantification and confirmation of 64 pesticide residues and their toxic metabolites in fruit extracts prepared by a buffered QuEChERS procedure. The total time required for UPLC-MS/MS analysis was 8 min plus 2 min for re-equilibration to the initial UPLC conditions. Performance characteristics were determined for apple extracts spiked at 10 µg kg−1. The repeatability of measurements expressed as relative standard deviations was in the range 1.5–13% at this level for most analytes. Thanks to very low limits of quantification (<10 µg kg−1for the majority of pesticides), an optimized method allows for the reliable control of not only common maximum residue limits (MRLs) set by European Union regulation for various pesticides/fruit combinations, but also of a uniform MRL of 10 µg kg−1endorsed for baby food.
Sinonasal Neoplasia - Clinicopathological Profile And Importance of Computed Tomography.

BACKGROUND Nasal cavity and Paranasal sinus malignancies are very rare, in which maxillary sinus is the commonest, followed by ethmoid, frontal and sphenoid sinus. Computed Tomography (CT) & Magnetic Resonance Imaging (MRI) play a key role in diagnosis, staging and management of paranasal sinuses and nasal pathologies. Multiplanar imaging in CT helps better imaging of critical anatomical areas. Aim of our study was to study the incidence, clinical features, CT features and its importance in the management of sinonasal neoplasms. MATERIALS AND METHODS This prospective study was carried out in a tertiary care hospital of MP, India. Consecutive 40 histologically proven cases of sinonasal neoplasia who visited the Department of Otorhinolaryngology and Radiotherapy are included in our study. Demography and clinical features were recorded. Cases of nasal and paranasal sinus masses diagnosed on CT attending ENT and Radiotherapy OPD or admitted in the Radiotherapy ward forms the material of this study. This included patients of both sexes and all ages. Histopathological examination was asked to confirm the diagnosis made on CT. RESULTS There were total 40 cases of sinonasal neoplasia among which 24 were benign. Almost all the benign cases were seen in the age group <40 y with mean age of 20 y and most of the malignant cases were seen in the age group above 40 y with mean age of 55 y. In our study we found male preponderance with male female ratio of 4:1 in both benign and malignant conditions. The commonest presenting symptoms of the patients with sinonasal masses in our study was nasal obstruction (75%) and nasal discharge (67.5%) followed by nasal mass (65%), epistaxis (62.5%) and headache (60%). Angiofibroma and papilloma were the commonest benign lesions. Commonest malignant lesion was squamous cell carcinoma. Of the malignant Sinonasal tumours studied in our series, maxillary sinus was involved in 13, ethmoid sinuses and nasal cavity in 10 cases each, and frontal sinuses in 2 cases. CONCLUSION Contrast enhanced computed tomography with multiplanar reconstruction is an excellent modality for imaging sinonasal masses. CT can define the character of the sinonasal mass, thus differentiating benign from malignant. CT helps better imaging of critical anatomical areas and helpful in planning treatment procedures such as surgery and radiotherapy.
Why count trees? Volunteer motivations and experiences with tree monitoring in New York City

Volunteer programs can benefit from a deeper understanding of the motivations and experiences of people engaged in citizen science. Research to date has studied motivations of citizen scientists and tree-planting volunteers. Less work has focused on tree-monitoring volunteers, a role that is rapidly increasing as more cities involve the public in monitoring the urban forest. Researchers conducted an assessment of volunteers (n = 636 respondents) of the TreesCount! 2015 street tree census in New York City, New York, U.S., to understand volunteers' demographics, motivations, experiences, and levels of civic engagement. Semistructured interviews (n = 40) were also conducted on a subset of the initial assessment respondents, to deepen understanding of these factors. Like tree-planting volunteers in previous studies, volunteers were more likely to be highly educated, female, white, and with high income levels. Top self-identified motivations for participation included personal values, wanting to contribute, and a desire for education or learning. Demographics correlated with different motivations, suggesting opportunities for targeting recruitment efforts to better reach underrepresented populations. Researchers also found motivations shifted slightly in post-census interviews, also identifying a new theme of exploring the city. Street-tree monitoring presents opportunities for contributing to one's community or city, and for learning about trees and urban nature, suggesting these acts of engagement can both strengthen connections to social-ecological systems and provide personal benefits. At the same time, considering volunteer motivations, experiences, and outcomes when designing programs can positively affect participation turnout, effort, and retention.
INTRAPERITONEAL MICRODIALYSIS (IPM): A NEW TECHNIQUE FOR MONITORING INTESTINAL ISCHEMIA STUDIED IN A PORCINE MODEL

&NA; —Acute mesenteric thrombosis, vascular complications of intestinal transplantation, sepsis, and multiple organ failure are all associated with intestinal ischemia. To improve the outcome of these patients, better monitoring devices are needed. A new technique, intraperitoneal microdialysis (IPM), was evaluated for detection of intestinal ischemia in a porcine model, with the intention of evaluating the technique for future use on humans. Fourteen pigs divided into two studies were used. In a total ischemia study a microdialysis catheter was placed intraperitoneally and the superior mesenteric artery was occluded for 1 h 40 min. In a local ischemia study, the arcus vessels supplying a 30‐cm long small bowel segment were occluded for 3 h 20 min. One IPM catheter was placed next to the ischemic area and another IPM catheter 10 cm caudally as an intraperitoneal reference. In both studies reference catheters were placed subcutaneously. Glucose, lactate, pyruvate, and glycerol were analyzed every 20 min. In both studies vessel occlusion resulted in decreased glucose and increased lactate, glycerol, and lactate/pyruvate ratio. Significant changes were reached after 60 min of ischemia in most analytes, whereas the values from the reference catheter were stable. Our conclusion is that intestinal ischemia is detectable with IPM based on the analysis of well‐documented markers of ischemia (increased lactate/pyruvate ratio) and cell membrane damage (elevated glycerol levels). It allows semi‐continuous monitoring of the intestines with a minimally invasive procedure, which we believe will be possible to apply in human routine clinical use.
Mutations and Polymorphisms Associated with Antiretroviral Drugs in HIV-1C-Infected African Patients

To detect and characterize polymerase gene (pol) polymorphisms and mutation patterns in HIV-1C-infected Batswana patients treated with reverse transcriptase inhibitors, samples from AIDS patients treated with highly active antiretroviral therapy (HAART) were sequenced for the region encompassing the entire HIV-1 protease (PR) and the first 335 amino acids of reverse transcriptase (RT). Amongst the 16 patients treated with antiretroviral (ARV) drugs, eight started HAART regimens containing didanosine, stavudine and nevirapine (ddI/d4T/NVP) or efavirenz (EFV) (arm A) while the others started with zidovudine (AZT) and lamivudine (3TC) given together as combivir (CBV) with either NVP or EFV as arm B. Arm B is the first line regimen currently provided by the Botswana ARV national programme. Greater efficacy, in terms of treatment duration, was observed in patients in arm B (14 months) as compared with patients in arm A (9 months); P<0.05, n=8. Appearance of the M184V mutation in the arm B patients coincided with a rebound of viral load (VL) (4.3 +0.1 log10 RNA copies/ml) and a significantly improved immunological parameter (ΔCD4=207.0 +48.1 cells/μl; P<0.05). Interestingly, patients developing the M184V mutation preferentially harboured polymorphisms Q174K and/or I178L located in close proximity to pol position 184. The M184V mutation occurred following a clear clinical benefit consisting of increased CD4 cell counts and lower plasma viral loads. Primary mutations known to be associated with NNRTI and NRTI resistance for HIV-1B were observed in 10 of the 16 treated patients.