Miracle-dz/UniFAR-FTUs huggingface dataset:
Nivolumab for Newly Diagnosed Advanced-Stage Classic Hodgkin Lymphoma: Safety and Efficacy in the Phase II CheckMate 205 Study.

PURPOSE Nivolumab, an anti-programmed death-1 monoclonal antibody, has demonstrated frequent and durable responses in relapsed/refractory classic Hodgkin lymphoma (cHL). We report results from Cohort D of the CheckMate 205 trial, which assessed nivolumab monotherapy followed by nivolumab plus doxorubicin, vinblastine, and dacarbazine (N-AVD) for newly diagnosed cHL. METHODS Patients 18 years of age or older with untreated, advanced-stage (defined as III to IV and IIB with unfavorable risk factors) cHL were eligible for Cohort D of this multicenter, noncomparative, phase II trial. Patients received nivolumab monotherapy for four doses, followed by 12 doses of N-AVD; all doses were every 2 weeks, and nivolumab was administered at 240 mg intravenously. The primary end point was safety. Efficacy end points included objective response rate and modified progression-free survival, defined as time to disease progression/relapse, death, or next therapy. Chromosome 9p24.1 alterations and programmed death-ligand 1 expression were assessed in Hodgkin Reed-Sternberg cells in evaluable patients. RESULTS A total of 51 patients were enrolled and treated. At diagnosis, 49% of patients had an International Prognostic Score of 3 or greater. Overall, 59% experienced a grade 3 to 4 treatment-related adverse event. Treatment-related febrile neutropenia was reported in 10% of patients. Endocrine immune-mediated adverse events were all grade 1 to 2 and did not require high-dose corticosteroids; all nonendocrine immune-mediated adverse events resolved (most commonly, rash; 5.9%). At the end of therapy, the objective response rate (95% CI) per independent radiology review committee was 84% (71% to 93%), with 67% (52% to 79%), achieving complete remission (five patients [10%] were nonevaluable and counted as nonresponders). With a minimum follow-up of 9.4 months, 9-month modified progression-free survival was 92%. Patients with higher-level Hodgkin Reed-Sternberg programmed death-ligand 1 expression had more favorable responses to N-AVD (P = .041). CONCLUSION Nivolumab followed by N-AVD was associated with promising efficacy and safety profiles for newly diagnosed, advanced-stage cHL.
Corneal Cross-Linking-Induced Stromal Demarcation Line

Purpose: Corneal collagen cross-linking by UVA/riboflavin (X-linking) represents a new method for the treatment of progressive keratoconus and currently is under clinical study. To avoid UVA irradiation damage to the corneal endothelium, the parameters for X-linking are set in a way that effective treatment occurs only in the first 300 μm of the corneal stroma. Here, X-linking not only strengthens the biomechanical properties of the cornea but also induces keratocyte apoptosis. To date, the effectiveness of treatment could be monitored only indirectly by postoperative follow-up corneal topographies or using corneal confocal microscopy. Here we describe a corneal stromal demarcation line indicating the transition zone between cross-linked anterior corneal stroma and untreated posterior corneal stroma. The demarcation line is biomicroscopically detectable in slit-lamp examination as early as 2 weeks after treatment. Methods: X-linking was performed in 16 cases of progressive keratoconus, and corneas were examined biomicroscopically and by means of corneal topography and pachymetry before and after treatment. Results: In 14 of 16 cases, a thin stromal demarcation line was visible at a depth of approximately 300 μm over the whole cornea after X-linking treatment. Conclusion: This newly observed demarcation line may result from differences in the refractive index and/or reflection properties of untreated versus X-linked corneal stroma and represents an effective tool to biomicroscopically easily monitor the depth of effective X-linking treatment in keratoconus.
DRw antisera react with activated T cells.

Nylon wool-purified T cells appear to be nonreactive in a lymphocytotoxicity assay with HLA-DRw antisera and complement before cell activation. However, after activation in mixed lymphocyte culture, responder cells express determinants that are strongly reactive with DRw alloantisera after 6 days and gradually disappear by 16 to 18 days. Restimulation of the primed cells resulted in re-expression of the blast determinants. Mitogenic stimulation with Con A or purified PHA (HA-17) also resulted in temporary expression of these determinants; reactivity usually conformed to DRw genetic restriction; however, occasional extra reactions occurred that were variable depending on the method of activation (i.e., MLC, Con A, or HA-17). The results suggest the presence of additional allospecificities within some of the DRw antisera that react with "Ia-like" antigens on activated cells from unique subsets of T cells. Whether these DRw antisera contain antibodies against T cells or agains activation or differentiation T cell antigens is not as yet clear.
Use of mixed reality for improved spatial understanding of liver anatomy

Abstract Introduction: In liver surgery, medical images from pre-operative computed tomography and magnetic resonance imaging are the basis for the decision-making process. These images are used in surgery planning and guidance, especially for parenchyma-sparing hepatectomies. Though medical images are commonly visualized in two dimensions (2D), surgeons need to mentally reconstruct this information in three dimensions (3D) for a spatial understanding of the anatomy. The aim of this work is to investigate whether the use of a 3D model visualized in mixed reality with Microsoft HoloLens increases the spatial understanding of the liver, compared to the conventional way of using 2D images. Material and methods: In this study, clinicians had to identify liver segments associated to lesions. Results: Twenty-eight clinicians with varying medical experience were recruited for the study. From a total of 150 lesions, 89 were correctly assigned without significant difference between the modalities. The median time for correct identification was 23.5 [4–138] s using the magnetic resonance imaging images and 6.00 [1–35] s using HoloLens (p < 0.001). Conclusions: The use of 3D liver models in mixed reality significantly decreases the time for tasks requiring a spatial understanding of the organ. This may significantly decrease operating time and improve use of resources.
Pre-frontal Cortical Activity During Walking and Turning Is Reliable and Differentiates Across Young, Older Adults and People With Parkinson's Disease

Introduction: Mobility declines with age and further with neurodegenerative disorders, such as Parkinson's disease (PD). Walking and turning ability, in particular, are vital aspects of mobility that deteriorate with age and are further impaired in PD. Such deficits have been linked with reduction in automatic control of movement and the need for compensatory cognitive cortical control via the pre-frontal cortex (PFC), however the underlying neural mechanisms remain unclear. Establishing and using a robust methodology to examine PFC activity during continuous walking and turning via mobile functional near infra-red spectroscopy (fNIRS) may aid in the understanding of mobility deficits and help with development of appropriate therapeutics. This study aimed to: (1) examine test re-test reliability of PFC activity during continuous turning and walking via fNIRS measurement; and (2) compare PFC activity during continuous turning and walking in young, old and Parkinson's subjects. Methods: Twenty-five young (32.3 ± 7.5 years), nineteen older (65.4 ± 7.0 years), and twenty-four PD (69.3 ± 4.1 years) participants performed continuous walking and 360° turning-in-place tasks, each lasting 2 min. Young participants repeated the tasks a second time to allow fNIRS measurement reliability assessment. The primary outcome was PFC activity, assessed via measuring changes in oxygenated hemoglobin (HbO2) concentrations. Results: PFC activity during continuous walking and turning was moderately reproducible (Intra-class correlation coefficient = 0.67). The PD group had higher PFC activation than young and older adults during walking and turning, with significant group differences for bilateral PFC activation (p = 0.025), left PFC activation (p = 0.012), and the early period (first 40 s) of walking (p = 0.007), with greater activation required in PD. Interestingly, older adults had similar PFC activation to young adults across conditions, however older adults required greater activation than young adults during continuous turning, specifically the early period of the turning task (Cohens d = 0.86). Conclusions: PFC activity can be measured during continuous walking and turning tasks with acceptable reliability, and can differentiate young, older and PD groups. PFC activation was significantly greater in PD compared to young and older adults during walking, particularly when beginning to walk.
Tumor‐primed natural killer cells from patients with multiple myeloma lyse autologous, NK‐resistant, bone marrow‐derived malignant plasma cells

Natural killer (NK) cells are cytotoxic lymphocytes able to kill tumor cells and virus‐infected cells. Human‐resting NK cells can be activated by co‐culture with NK‐resistant CTV‐1a cells. These tumor‐activated cells (TaNKs) are cytotoxic to a range of NK‐resistant tumor cells in vitro. This potential, however, has not been explored in multiple myeloma (MM). In this study, we demonstrate that TaNK cells from 21 MM patients lyse a variety of myeloma targets, including primary isolates of autologous and allogeneic CD138+ myeloma cells whilst sparing CD138−ve bone marrow cells. Myeloma patients' TaNK‐induced lysis of the U266 cell line was significantly higher compared to normal controls (median‐specific lysis 79.1% vs. 69.5%) (P = 0.003). In addition, TaNKs induced substantial lysis of autologous and allogeneic CD138+ myeloma cells (median‐specific lysis 52.5% and 37.4%, respectively). The percentage of specific lysis did not correlate with important disease characteristics (ISS, age, and high‐risk molecular abnormalities) or with the disease status and antimyeloma treatment, including novel agents and dexamethasone. In conclusion, tumor‐primed NK cells are able to induce substantial lysis of myeloma targets including autologous and allogeneic CD138+ myeloma plasma cells and could be an additional therapeutic approach in MM, particularly in the era of novel agents. Am. J. Hematol. , 2011. © 2011 Wiley‐Liss, Inc.
Adaptive fuzzy reaching law tracking control of uncertain fully-actuated underwater vehicles with system uncertainties and unknown disturbances

In this paper, an adaptive fuzzy reaching law controller (AFRLC) for robust tracking control of uncertain full-actuated underwater vehicles (FAUV) in the presence of system uncertainties and unknown external disturbances is investigated, where a novel reaching law controller is constructed with a variable speed structure of system states such that the chattering phenomenon in traditional reaching law can be reduced. Moreover, a fuzzy uncertainty observer is employed to online observe the system uncertainties and it is incorporated into the sliding-mode reaching law. Theoretical analysis proves that the proposed AFRLC can ensure the stability of underwater vehicles tracking system and all signals in the closed-loop control system are uniformly ultimately bounded. In addition, the observation error can asymptotically converge to zero. Simulation results demonstrate the effectiveness of the proposed control scheme.
Impact of platinum complexes on dihydropyrimidine dehydrogenase activity in 5-fluorouracil-treated patients.

to control the severe pain in the left chest wall. The patient received oral administration of 80 mg/day of 1 M tegafur–0.4M 5-chloro-2,4-dihydroxypyridine–1 M potassium oxonate (S-1) for 4 weeks as a final line chemotherapy because of hematological toxicity resulting from the previous chemotherapy. Six weeks later, the lesions dried, diminished remarkably in size and showed scab formation (Figure 1B). The left chest pain disappeared, and the administration of morphine sulfate became unnecessary. She was discharged, and is presently enjoying a normal life. Metastasis to the skin is a comparatively rare complication of internal malignancies [1]. The clinical presentations appear as flesh-colored to red-purple or brownish solitary papules or nodules. Although carcinoma erysipeloides are frequently observed in patients affected by breast carcinoma, they are rarely observed during the course of other malignant tumors. These metastases are the clinical representation of the rapid spread of tumor cells along subepidermal lymphatic vessels. As a consequence of lymphatic blockage, edema, erythema and vesicles can appear [2]. Although both the appearance of tumors from gastric cancer and their successful treatment are very rare, S-1 was an effective anticancer drug in the present case. S-1 is a newly developed oral anticancer drug, which consists of tegafur, gimeracil and oteracil potassium at a molecular ratio of 1:0.4:1, based on the biochemical modulation of 5-FU [3]. S-1 was more effective for lymph node metastasis than for the primary lesion, lung metastasis or liver metastasis in a phase II study [4]. Moreover, this oral anticancer drug has the advantage of not requiring hospitalization for patients with good performance status, because of its mild toxicity. The prognosis of gastric cancer with skin metastasis is generally poor, thus treatment preserving the quality of life of cancer patients should be considered positively.
A port-Hamiltonian approach to the control of nonholonomic systems

In this paper a method of controlling nonholonomic systems within the port-Hamiltonian (pH) framework is presented. It is well known that nonholonomic systems can be represented as pH systems without Lagrange multipliers by considering a reduced momentum space. Here, we revisit the modelling of these systems for the purpose of identifying the role that physical damping plays. Using this representation, a geometric structure generalising the well known chained form is identified as \textit{chained structure}. A discontinuous control law is then proposed for pH systems with chained structure such that the configuration of the system asymptotically approaches the origin. The proposed control law is robust against the damping and inertial of the open-loop system. The results are then demonstrated numerically on a car-like vehicle.
The effects of the use of single task-oriented maintenance concept and more accurate letter check alternatives on the reduction of scheduled maintenance downtime of aircraft

This paper provides a connection between an industrial problem of the maximization of aircraft utilization and maintenance cost savings. A more flexible structure is proposed to perform the maintenance not only during scheduled periodic checks but also whenever the aircraft is on the ground for any reason. The proposed method is the use of the single task-oriented maintenance concept. The results obtained from a case study performed in an airline company by using classical maintenance approach — rigid letter check system and the single task-oriented maintenance concept are compared to emphasize the benefits of the proposed concept. To help to reduce scheduled maintenance downtime of aircraft, a software has been developed to support the single-task oriented maintenance concept by calculating more accurate and appropriate letter check alternatives for the related maintenance task.
A TWO-WAREHOUSE EOQ MODEL FOR DETERIORATING ITEMS AND STOCK DEPENDENT DEMAND UNDER CONDITIONALLY PERMISSIBLE DELAY IN PAYMENT IN IMPRECISE ENVIRONMENT

In this paper, a two-warehouse inventory model for deteriorating items is considered with stock demand under conditionally permissible delay in payment in imprecise environment.The capacity of any warehouse is limited, it has to rent warehouse (RW) for storing the excess units over the fixed capacity W of the own warehouse (OW) in practice. The RW is assumed to offer better preserving facilities than the OW resulting in a lower rate of deterioration and is assumed to charge higher holding cost than the OW. The purpose of this study is to find the optimal replenishment policies for minimizing the total relevant inventory costs. Here, the purchasing cost, holding cost for RW and OW and earning interest are taken fuzzy in nature. Useful Algorithms to characterize the optimal solutions have been derived. Furthermore,Graphical representation and numerical examples are provided to illustrate the proposed model.
A novel Design of a z-axis MEMS vibratory Gyroscope

This paper presents a novel design and principle of operation of a one-axis micro machined vibratory gyroscope base on resonant sensing of Coriolis force. Two layer of polysilicon wafer is developed and bonded to create the actuating and sensing layers and electrodes. A rotary fluctuation with electrostatic actuation is used to vibrate the outer gimbal. The rotary motion is detected by capacitive sensing between inner gimbal and doped electrodes. The noise of system is considered and the resolution of sensor is reported. The design has several advantages over similar products include simpler dynamic and mechanism, high resolution and ability of fabrication via wet etching and RIE method. With high quality factor, the gyroscope is able to work on ambient pressure with high resolution about 0.5 / / s Hz . Finally the fabrication steps based on available techniques are presented.
Methadone-Drug * Interactions ( * Medications , illicit drugs , & other substances )

Prior Publication History 3rd Edition: November 2005 Revision/Update, Addiction Treatment Forum Special Report, see ATForum.com. Researcher/Writer: Stewart B. Leavitt, PhD, Editor, Addiction Treatment Forum Medical Reviewers: R. Douglas Bruce, MD, MA; Yale AIDS Program, Yale University School of Medicine; New Haven, CT. ; Chin B. Eap, PhD, Biochemistry and Clinical Psychopharmacology, University Department of Adult Psychiatry; Cery Hospital, Prilly-Lausanne, Switzerland; Evan Kharasch, MD, PhD; Professor and Director, Clinical Research Division, Department of Anesthesiology; Washington University, St. Louis, MO; Lee Kral, PharmD, BCPS; Center for Pain Medicine and Regional Anesthesia; University of Iowa Hospitals and Clinics; Iowa City, IA; Elinore McCance-Katz, MD, PhD, Chair, Addiction Psychiatry; Medical College of Virginia, Virginia Commonwealth University, Richmond, VA; J. Thomas Payte, MD; Corporate Medical Director; Colonial Management Group; Orlando, FL. 2nd Edition: January 2004, Addiction Treatment Forum Special Report. Researcher/Writer: Stewart B. Leavitt, PhD, Editor, Addiction Treatment Forum Medical Reviewers: Chin B. Eap, PhD, Prilly-Lausanne, Switzerland; John J. Faragon, PharmD, RPh, Albany, NY; Gerald Friedland, MD, New Haven, CT; Marc Gourevitch, MD, Bronx, NY; Elinore McCance-Katz, MD, Richmond, VA; J. Thomas Payte, MD, Orlando, FL. 1st Edition: Published as, Leavitt SB. Methadone at work. Addiction Treatment Forum. 1997(Spring);6(2). Sponsored by an educational grant from.
An Outlier Detection Algorithm for Incremental Data and its Application in Auditing of Social Security

It is an important direction to detect outliers efficiently from the incremental data. The method can be widely applied in auditing, stream media analysis etc. Since the network-based auditing system can extract data from the audited enterprise or government in real time, it is crucial to discover outliers efficiently as conditates of audit doubts from the incremental data. However, most of the outlier analysis algorithms are designed to handle the static data sets. The paper presents a density-based local outlier analysis algorithm which is based on the clustering result of historical data and can efficiently detect outliers from the incremental data. The algorithm is applied to audit the real social security data. The experiments show the effectiveness and the efficiency of the proposed method.
Adhesion of Human Hematopoietic Progenitor Cells to Mesenchymal Stromal Cells Involves CD44

Background: Direct cell-cell contact between hematopoietic progenitor cells (HPC) and their cellular microenvironment is essential for maintenance of ‘stemness’. We have previously demonstrated that a feeder layer of human mesenchymal stromal cells (MSC) could provide a surrogate model as a niche for human HPC. Maintenance of long-term culture-initiating cells was significantly lower on fibroblasts. Methods: Adhesion of HPC to MSC was further analyzed using our recently described adhesion assay based on gravitational force upon inversion and in combination with specific antibodies against CD44. Results: Adhesion of KG1a and CD34+ cells was significantly reduced by administration of a monoclonal CD44 antibody and for KG1a to a greater extent than for CD34+ cells. Interaction of HPC and MSC was further analyzed by laser scanning confocal microscopy. CD44 was located on the uropod of CD34+ cells at the site of contact with MSC and both cell types were interwoven by a network of fibronectin. Conclusion: Various adhesion proteins, including CD44, are involved in the contact of human HPC and human MSC and further analysis of the relative significance and interaction of these proteins will be crucial for the understanding of the mechanism of this specific cell-cell interaction.
Role of Heat Shock Transcription Factor in Saccharomyces cerevisiae Oxidative Stress Response

ABSTRACT The heat shock transcription factor Hsf1 of the yeast Saccharomyces cerevisiae regulates the transcription of a set of genes that contain heat shock elements (HSEs) in their promoters and function in diverse cellular processes, including protein folding. Here, we show that Hsf1 activates the transcription of various target genes when cells are treated with oxidizing reagents, including the superoxide anion generators menadione and KO2 and the thiol oxidants diamide and 1-chloro-2,4-dinitrobenzene (CDNB). Similar to heat shock, the oxidizing reagents are potent inducers of both efficient HSE binding and extensive phosphorylation of Hsf1. The inducible phosphorylation of Hsf1 is regulated by the intramolecular domain-domain interactions and affects HSE structure-specific transcription. Unlike the heat shock, diamide, or CDNB response, menadione or KO2 activation of Hsf1 is inhibited by cyclic-AMP-dependent protein kinase (PKA) activity, which negatively regulates the activator functions of other transcriptional regulators implicated in the oxidative stress response. These results demonstrate that Hsf1 is a member of the oxidative stress-responsive activators and that PKA is a general negative regulator in the superoxide anion response.
Probabilistic Analysis of the Plain Algorithm

This paper provides a probabilistic analysis of an algorithm which computes the gcd of ` inputs (with ` ≥ 2), with a succession of ` − 1 phases, each of them being the Euclid algorithm on two entries. This algorithm is both basic and natural, and two kinds of inputs are studied: polynomials over the finite field Fq and integers. The analysis exhibits the precise probabilistic behaviour of the main parameters, namely the number of iterations in each phase and the evolution of the length of the current gcd along the execution. We first provide an average-case analysis. Then we make it even more precise by a distributional analysis. Our results rigorously exhibit two phenomena: (i) there is a strong difference between the first phase, where most of the computations are done and the remaining phases; (ii) there is a strong similarity between the polynomial and integer cases.