Miracle-dz/UniFAR-FTUs huggingface dataset:
Awareness, understanding, attitude and barriers toward prescribing modern cancer immunotherapies in the Arabian Gulf countries.

INTRODUCTION The use of modern immunotherapy has been evolving over the past few years, and various new agents have been developed for new indications at multiple primary sites in oncology. It is important for physicians who are involved in cancer care to be aware and updated about new therapeutic agents and their indications, potential benefits, and side effects. PATIENTS AND METHODS From October to November 2017, we conducted a survey on the awareness, understanding, attitude, and barriers associated with prescribing modern cancer immunotherapies among physicians in the Arabian Gulf countries. The study included practicing physicians who delivered chemotherapy; trainees were not eligible. A total of 460 physicians were contacted and invited to complete an online survey, of which approximately 74.8% did not respond, and 4 (3.4%) were excluded because they had not recently treated patients with cancer. 112 (24.3%) physicians completed the survey (completion rate = 25.2%). An online electronic survey questionnaire was developed via Planet Surveys. The survey was designed with multidisciplinary inputs of the study investigators practicing in the Arabian Gulf countries, piloted, and subsequently revised on the basis of feedback from 10 additional oncologists. The final survey included 23 questions and took 8-10 minutes for completion. RESULTS All respondents were aware of modern immunotherapies, but 62.5% reported having limited experience in implementing them, whereas 31.3% reported good experience. The overall physicians' attitudes toward modern immunotherapy were favorable, with a mean score of 7.4 (scale of 1-10, with 10 being extremely favorable). Efficacy, clear indications, and good safety profile were perceived as key potential benefits. Cost, lack of experience, and lack of access to specific testing were the major barriers. DISCUSSION AND CONCLUSION There was a high level of awareness and an overall positive attitude toward modern cancer immunotherapy among oncologists in the Arabian Gulf countries, but there was a limited experience in prescribing cancer immunotherapeutic agents. Efficacy, clear indications, and good safety profile were perceived as key potential benefits, whereas cost, lack of experience, and lack of access to specific testing prior to prescription were the major barriers. Patients were likely to be receptive to modern immunotherapy as a therapeutic option for cancer treatment. Long-term efficacy data, financial support programs, and educational activities for prescribers may increase the access to modern immunotherapy.
Calcium Channel Blocker-induced Gingival Overgrowth

A 69-year-old man was admitted to the hospital with bacterial pneumonia. He had previously been diagnosed with mild hypertension and treated with oral calcium channel blockers for six months. He denied any history of an allergy or exposure to radiation. An oral examination revealed a pale pink, plaque accumulation and gingival inflammation without pain or bleeding (Picture). Based on the clinical history and physical examination findings, the patient was diagnosed with calcium channel blocker-induced gingival overgrowth. Gingival overgrowth is an enlargement of the gum tissue caused by various factors, including inflammatory conditions, hereditary and metabolic disorders, and adverse drug reactions in patients treated with anticonvulsants, immunosuppressants, and calcium channel blockers (1). Despite the popularity and wide use of calcium channel blockers in the treatment of hypertension, this adverse drug reaction is rarely recognized (2). The most effective treatment for drug-induced gingival overgrowth is the withdrawal or substitution of the causative drug.
Emergent Properties of Microbial Activity in Heterogeneous Soil Microenvironments: Different Research Approaches Are Slowly Converging, Yet Major Challenges Remain

Over the last 60 years, soil microbiologists have accumulated a wealth of experimental data showing that the bulk, macroscopic parameters (e.g., granulometry, pH, soil organic matter, and biomass contents) commonly used to characterize soils provide insufficient information to describe quantitatively the activity of soil microorganisms and some of its outcomes, like the emission of greenhouse gasses. Clearly, new, more appropriate macroscopic parameters are needed, which reflect better the spatial heterogeneity of soils at the microscale (i.e., the pore scale) that is commensurate with the habitat of many microorganisms. For a long time, spectroscopic and microscopic tools were lacking to quantify processes at that scale, but major technological advances over the last 15 years have made suitable equipment available to researchers. In this context, the objective of the present article is to review progress achieved to date in the significant research program that has ensued. This program can be rationalized as a sequence of steps, namely the quantification and modeling of the physical-, (bio)chemical-, and microbiological properties of soils, the integration of these different perspectives into a unified theory, its upscaling to the macroscopic scale, and, eventually, the development of new approaches to measure macroscopic soil characteristics. At this stage, significant progress has been achieved on the physical front, and to a lesser extent on the (bio)chemical one as well, both in terms of experiments and modeling. With regard to the microbial aspects, although a lot of work has been devoted to the modeling of bacterial and fungal activity in soils at the pore scale, the appropriateness of model assumptions cannot be readily assessed because of the scarcity of relevant experimental data. For significant progress to be made, it is crucial to make sure that research on the microbial components of soil systems does not keep lagging behind the work on the physical and (bio)chemical characteristics. Concerning the subsequent steps in the program, very little integration of the various disciplinary perspectives has occurred so far, and, as a result, researchers have not yet been able to tackle the scaling up to the macroscopic level. Many challenges, some of them daunting, remain on the path ahead. Fortunately, a number of these challenges may be resolved by brand new measuring equipment that will become commercially available in the very near future.
Diffuse large B-cell lymphoma: A retrospective study from a regional care center in South India.

Introduction Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma whose outcomes have significantly improved with rituximab in addition to anthracycline-based chemotherapy. Objective This study aimed to study the epidemiology, treatment, and outcomes of patients with DLBCL. Materials and Methods A total of 526 patients diagnosed with DLBCL between 2006 and 2015 were retrospectively analyzed. Results The median age was 50 years with a male preponderance. Two hundred and twenty-three (42.39%) patients presented with B symptoms. A total of 53 (10.07%) patients presented with bulky disease and 202 (31.40%) with extranodal disease. The most common extranodal sites involved were the stomach (20.79%) and the bone marrow (10.89%). Bone marrow involvement was seen in only 22 (4.18%) cases. The distribution of patients presenting in low, low-intermediate, high-intermediate, and high-risk International Prognostic Index (IPI) were 148 (28.13%), 191 (36.31%), 124 (23.57%), and 63 (11.97%), respectively. The median survival of the entire cohort was 22 months. Survival of patients that compared the two groups with respect to the IPI - one having clubbed patients in low and low/intermediate risk and the other clubbing high/intermediate and high risk showed significantly improved survival in the lower risk groups - 24 versus 18 months (P = 0). The survival of those who received chemoimmunotherapy i.e R - CHOP was significantly better than those who received chemotherapy (CHOP) alone - 33 versus 21 months (P = 2.22e-16). Conclusions DLBCL is one of the most common lymphomas seen in our daily practice. Outcomes are significantly inferior compared to western countries. Biological and patient-related factors such as nongerminal center B subtype, higher extranodal involvement, and poor tolerability to treatment could contribute to inferior outcomes.
Renewed interest for low‐dose radiation therapy in follicular lymphomas: From biology to clinical applications

Follicular lymphoma (FL) is the most common subtype of indolent non‐Hodgkin lymphoproliferative disorders. Treatment strategies for FL may include several therapeutic choices, ranging from a “watchful waiting” approach to stem cell transplantation, mostly depending on staging, age, risk factors, and disease burden at diagnosis. The high radiosensitivity of FL compared with other solid tumors has been known since the beginning of radiotherapy treatment in lymphoma patients. Doses of 24 to 40 Gy were considered appropriate in first line curative treatment for localized disease (stages I‐II), but several publications investigating low‐dose radiotherapy (LDRT) of 4Gy (2 × 2Gy) reported an overall response rate surprisingly high. Due to its high local efficacy and negligible toxicity, LDRT might be offered to both early and advanced stage FL patients in combination with new agents, at diagnosis or after several lines of systemic therapy. The aim of this review is to summarize and discuss the current knowledge on LDRT for FL and its potential application in a curative setting in combination with new drugs for both early and advanced disease.
Experimental Reductions of Delay Discounting and Impulsive Choice: A Systematic Review and Meta-Analysis

Many behaviors posing significant risks to public health are characterized by repeated decisions to forego better long-term outcomes in the face of immediate temptations. Steeply discounting the value of delayed outcomes often underlies a pattern of impulsive choice. Steep delay discounting is correlated with addictions (e.g., substance abuse, obesity) and behaviors such as seatbelt use and risky sexual activity. As evidence accumulates suggesting steep delay discounting plays a causal role in these maladaptive behaviors, researchers have begun testing methods for reducing discounting. In this first systematic and comprehensive review of this literature, the findings of 92 articles employing different methodologies to reduce discounting are evaluated narratively and meta-analytically. Although most of the methods reviewed produced significant reductions in discounting, they varied in effect sizes. Most methods were ideal for influencing one-off choices (e.g., framing and priming manipulations), although other successful manipulations, such as episodic future thinking, could be incorporated into existing therapies designed to produce longer-lasting changes in decision-making. The largest and longest-lasting effects were produced by learning-based manipulations, although translational research is needed to determine the generality and clinical utility of these methods. Methodological shortcomings in the existing literature and suggestions for ameliorating these issues are discussed. This review reveals a variety of methods with translational potential, which, through continued refinement, may prove effective in reducing impulsive choice and its associated maladaptive decisions that negatively impact quality of life.
Substate Profiling for Effective Test Suite Reduction

Test suite reduction (TSR) aims at removing redundant test cases from regression test suites. A typical TSR approach ensures that structural profile elements covered by the original test suite are also covered by the reduced test suite. It is plausible that structural profiles might be unable to segregate failing runs from passing runs, which diminishes the effectiveness of TSR in regard to defect detection. This motivated us to explore state profiles, which are based on the collective values of program variables. This paper presents Substate Profiling, a new form of state profiling that enhances existing profile-based analysis techniques such as TSR and coverage-based fault localization. Compared to current approaches for capturing program states, Substate Profiling is more practical and finer grained. We evaluated our approach using thirteen multi-fault subject programs comprising 53 defects. Our study involved greedy TSR using Substate profiles and four structural profiles, namely, basic-block, branch, def-use pair, and the combination of the three. For the majority of the subjects, Substate Profiling detected considerably more defects with a comparable level of reduction. Also, Substate profiles were found to be complementary to structural profiles in many cases, thus, combining both types is beneficial.
Comparative mechanism based study on disinfectants against multidrug‐resistant Acinetobacter baumannii

Acinetobacter baumannii has emerged as a hospital‐acquired pathogen and has spread in the hospital settings, leading to enhanced nosocomial outbreaks associated with high death rates. Therefore, the aim of the current study is to determine the effective concentration of disinfectants like sodium hypochlorite, hydrogen peroxide, and chlorine dioxide, against multidrug‐resistant (MDR) strains of A. baumannii. In this study, we have investigated the effect of disinfectants on different MDR strains i.e. RS307, RS6694, RS7434, RS10953, RS122, and sensitive strain ATCC‐19606 of A. baumannii, via differential growth curves analysis, disc diffusion assay, estimation of reactive oxygen species (ROS), lipid peroxidation, and protein carbonylation. All the results collectively showed that 1% sodium hypochlorite (P value < 0.0027), 2.5% hydrogen peroxide (P value = 0.0032), and 10 mM (P value = 0.017) chlorine dioxide significantly inhibit the growth of MDR strains of A. baumannii. A significant increase in the ROS generations, altered lipid peroxidation, and a decrease in protein carbonylation was also observed after treatment with disinfectants, which confirmed its ROS‐dependent damage mechanism. These disinfectants also enhance the membrane leakage of reducing sugar, protein, and DNA. The current study highlights and recommends the use of 2.5% hydrogen peroxide to control the MDR strains of A. baumannii in the hospital setup. Therefore, the present results will help in selecting concentrations of different disinfectants for regular use in hospital setups to eradicate the multidrug‐resistant A. baumannii from the hospital setup.
Association Between Expression Level of PD1 by Tumor-Infiltrating CD8+ T Cells and Features of Hepatocellular Carcinoma.

BACKGROUND & AIMS T-cell exhaustion, or an impaired capacity to secrete cytokines and proliferate with overexpression of immune checkpoint receptors, occurs during chronic viral infections but has also been observed in tumors, including hepatocellular carcinomas (HCCs). We investigated features of exhaustion in CD8+ T cells isolated from HCC specimens. METHODS We obtained HCC specimens, along with adjacent nontumor tissues and blood samples, from 90 patients who underwent surgical resection at Asan Medical Center (Seoul, Korea) from April 2016 through April 2018. Intrahepatic lymphocytes and tumor-infiltrating T cells were analyzed by flow cytometry. Tumor-infiltrating CD8+ T cells were sorted by flow cytometry into populations based on expression level of programmed cell death 1 (PDCD1 or PD1): PD1-high, PD1-intermediate, and PD1-negative. Sorted cells were analyzed by RNA sequencing. Proliferation and production of interferon gamma (IFNG) and tumor necrosis factor (TNF) by CD8+ T cells were measured in response to anti-CD3 and antibodies against immune checkpoint receptors including PD1, hepatitis A virus cellular receptor 2 (HAVCR2 or TIM3), lymphocyte activating 3 (LAG3), or isotype control. Tumor-associated antigen-specific CD8+ T cells were identified using HLA-A*0201 dextramers. PDL1 expression on tumor tissue was assessed by immunohistochemistry. RESULTS PD1-high, PD1-intermediate, and PD1-negative CD8+ T cells from HCCs had distinct gene expression profiles. PD1-high cells expressed higher levels of genes that regulate T-cell exhaustion than PD1-intermediate cells. PD1-high cells expressed TIM3 and LAG3, and low proportions of TCF1+, TBEThigh/eomesoderminlow, and CD127+. PD1-high cells produced the lowest amounts of IFNG and TNF upon anti-CD3 stimulation. Differences in the PD1 expression patterns of CD8+ T cells led to the identification of 2 subgroups of HCCs: HCCs with a discrete population of PD1-high cells were more aggressive than HCCs without a discrete population of PD1-high cells. HCCs with a discrete population of PD1-high cells had higher levels of predictive biomarkers of response to anti-PD1 therapy. Incubation of CD8+ T cells from HCCs with a discrete population of PD1-high cells with antibodies against PD1 and TIM3 or LAG3 further restored proliferation and production of IFNG and TNF in response to anti-CD3. CONCLUSIONS We found HCC specimens to contain CD8+ T cells that express different levels of PD1. HCCs with a discrete population of PD1-high CD8+ T cells express TIM3 and/or LAG3 and produce low levels of IFNG and TNF in response to anti-CD3. Incubation of these cells with antibodies against PD1 and TIM3 or LAG3 further restore proliferation and production of cytokines; HCCs with a discrete population of PD1-high CD8+ T cells might be more susceptible to combined immune checkpoint blockade-based therapies.
Abnormal neural response to phonological working memory demands in persistent developmental stuttering

Persistent developmental stuttering is a neurological disorder that commonly manifests as a motor problem. Cognitive theories, however, hold that poorly developed cognitive skills are the origins of stuttering. Working memory (WM), a multicomponent cognitive system that mediates information maintenance and manipulation, is known to play an important role in speech production, leading us to postulate that the neurophysiological mechanisms underlying stuttering may be associated with a WM deficit. Using functional magnetic resonance imaging, we aimed to elucidate brain mechanisms in a phonological WM task in adults who stutter and controls. A right‐lateralized compensatory mechanism for a deficit in the rehearsal process and neural disconnections associated with the central executive dysfunction were found. Furthermore, the neural abnormalities underlying the phonological WM were independent of memory load. This study demonstrates for the first time the atypical neural responses to phonological WM in PWS, shedding new light on the underlying cause of stuttering.
Designing a Delinked Incentive for Critical Antibiotics: Lessons from Norway

No country has yet implemented a pilot to ensure access to or the innovation of new antibiotics for multi-drug infections. A team from national health agencies in Norway, with the support of the Innovative Medicine Initiative-funded project DRIVE-AB, designed a model suitable for the national context, including the selection of the antibiotics, the potential value, and the operational model.
Cardiac Autonomic Neuropathy in Diabetes: A Predictor of Cardiometabolic Events

Autonomic nervous system (ANS) imbalance manifesting as cardiac autonomic neuropathy in the diabetic population is an important predictor of cardiovascular events. Symptoms and signs of ANS dysfunction, such as resting heart rate elevations, diminished blood pressure responses to standing, and altered time and frequency domain measures of heart rate variability in response to deep breathing, standing, and the Valsalva maneuver, should be elicited from all patients with diabetes and prediabetes. With the recognition of the presence of ANS imbalance or for its prevention, a rigorous regime should be implemented with lifestyle modification, physical activity, and cautious use of medications that lower blood glucose. Rather than intensifying diabetes control, a regimen tailored to the individual risk of autonomic imbalance should be implemented. New agents that may improve autonomic function, such as SGLT2 inhibitors, should be considered and the use of incretins monitored. One of the central mechanisms of dysfunction is disturbance of the hypothalamic cardiac clock, a consequence of dopamine deficiency that leads to sympathetic dominance, insulin resistance, and features of the metabolic syndrome. An improvement in ANS balance may be critical to reducing cardiovascular events, cardiac failure, and early mortality in the diabetic population.
Primary Leptomeningeal Oligodendroglioma, IDH-Mutant, 1p/19q-Codeleted

We present a case of a 43-year-old woman with a history of headaches and blurry vision. Ophthalmologic examination identified papilledema. MR imaging demonstrated a right parietal region mass with patchy areas of contrast enhancement and focal calcifications. Intraoperative examination and exploration revealed an extra-axial mass with no apparent parenchymal involvement. Microscopic examination revealed solid sheets of tumor cells with clear cell cytologic features and no discernable intra-parenchymal tumor component. Molecular studies demonstrated the presence of IDH1 IDH1 c.395G>A p.R132H and CIC c.601C>T p.R281W mutations and 1p/19q codeletion. The radiographic features, gross appearance, and microscopic and molecular characteristics of the mass support the diagnosis of primary leptomeningeal oligodendroglioma, IDH-mutant, 1p/19-codeleted. This case represents one of a very few reported instances of molecularly-defined solitary, primary, intracranial oligodendroglioma, without definitive involvement of the brain parenchyma.
Sonic Hedgehog Signaling Rises to the Surface: Emerging Roles in Neocortical Development

The mammalian neocortex is composed of a diverse population of neuronal and glial cells that are crucial for cognition and consciousness. Orchestration of molecular events that lead to the production of distinct cell lineages is now a major research focus. Recent studies in mammalian animal models reveal that Sonic Hedgehog (Shh) signaling plays crucial roles in this process. In this review, we will evaluate these studies and provide insights on how Shh signaling specifically influence cortical development, beyond its established roles in telencephalic patterning, by specifically focusing on its impact on cells derived from the cortical radial glial (RG) cells. We will also assess how these findings further advance our knowledge of neurological diseases and discuss potential roles of targeting Shh signaling in therapies.
Advanced Single-Phase Nine-Level Converter for the Integration of Multiterminal DC Supplies

This paper presents a new symmetrical single-phase nine-level dc–ac converter for the applications of distributed generation systems. The proposed multilevel inverter (MLI) utilizes four independent dc sources to generate the nine output voltage levels considering a reduced number of switching devices. The proposed inverter consists of main and auxiliary circuits. The main circuit is a single H-bridge circuit, which is responsible for output voltage polarity. The auxiliary circuit consists of a special combination of switching devices, which are used to synthesize the multilevel output voltage. The merits of the proposed MLI are: increased output voltage levels at reduced number of switching devices, low switching loss, low total harmonic distortion, low dv/dt stress on the switches, and hence, low ratings of the switching devices, and low cost. The effectiveness of the proposed MLI and its pulsewidth modulation switching pattern has been verified experimentally by using a laboratory prototype controlled by DSPACE-1103.
Introducing the Perception-Distortion Tradeoff into the Rate-Distortion Theory of General Information Sources

Blau and Michaeli recently introduced a novel concept for inverse problems of signal processing, that is, the perception-distortion tradeoff. We introduce their tradeoff into the rate distortion theory of lossy source coding in information theory, and clarify the tradeoff among information rate, distortion and perception for general information sources.