Miracle-dz/UniFAR-FTUs huggingface dataset:
Kaposi's Sarcoma-Associated Herpesvirus Induces the ATM and H2AX DNA Damage Response Early during De Novo Infection of Primary Endothelial Cells, Which Play Roles in Latency Establishment

ABSTRACT The DNA damage response (DDR) that evolved to repair host cell DNA damage also recognizes viral DNA entering the nucleus during infections. Here, we investigated the modulation of DDR signaling during de novo infection of primary endothelial cells by Kaposi's sarcoma-associated herpesvirus (KSHV). Phosphorylation of representative DDR-associated proteins, such as ataxia telangiectasia mutated (ATM) and H2AX, was induced as early as 30 min (0.5 h) postinfection and persisted during in vitro KSHV latency. Phosphorylated H2AX (γH2AX) colocalized at 30 min (0.5 h) with the KSHV genome entering the nuclei. Total H2AX protein levels also increased, and the increase was attributed to a decrease in degradative H2AX Lys48-linked polyubiquitination with a concomitant increase in Lys63-linked polyubiquitination that was shown to increase protein stability. ATM and H2AX phosphorylation and γH2AX nuclear foci were also induced by UV-inactivated KSHV, which ceased at later times of infection. Inhibition of ATM kinase activity by KU-55933 and H2AX knockdown by small interfering RNA significantly reduced the expression of the KSHV latency-associated nuclear antigen 1 (LANA-1; ORF73) and LANA-1 nuclear puncta. Knockdown of H2AX also resulted in a >80% reduction in the nuclear KSHV DNA copy numbers. Similar results were also observed in ATM-negative cells, although comparable levels of viral DNA entered ATM-negative and ATM-positive cell nuclei. In contrast, knockdown of CHK1 and CHK2 did not affect ORF73 expression. Collectively, these results demonstrate that KSHV induces ATM and H2AX, a selective arm of the DDR, for the establishment and maintenance of its latency during de novo infection of primary endothelial cells. IMPORTANCE Eukaryotic cells mount a DNA damage response (DDR) to sense and repair different types of cellular DNA damage. In addition, DDR also recognizes exogenous genetic material, such as the viral DNA genome entering the nucleus during infections. The present study was undertaken to determine whether de novo Kaposi's sarcoma-associated herpesvirus (KSHV) infection modulates DDR. Our results demonstrate that early during de novo infection of primary endothelial cells, KSHV induces a selective arm of DDR signaling, such as the ATM kinase and its downstream target, H2AX, which are essential for KSHV's latent gene expression and the establishment of latency. These studies suggest that targeting ATM and H2AX could serve as an attractive strategy to block the establishment of KSHV latent infection and the associated malignancies.
Co-delivery of Vorinostat and Etoposide Via Disulfide Cross-Linked Biodegradable Polymeric Nanogels: Synthesis, Characterization, Biodegradation, and Anticancer Activity

Treatment regimens for cancer patients using single chemotherapeutic agents often lead to undesirable toxicity, drug resistance, reduced uptake etc. Combination of two or more drugs is therefore becoming an imperative strategy to overcome these limitations. A step forward can be taken through delivery of the drugs used in combination via nanoparticles. Co-administration of chemotherapeutic drugs encapsulated in nanoparticles has been shown to result in synergistic effects and enhanced therapeutic efficacy. In present study, we explored the combination treatment of histone deacetylase inhibitor vorinostat (VOR) and topoisomerase II inhibitor etoposide (ETOP). The concurrent combination treatment of VOR and ETOP resulted in synergistic effect on human cervical HeLa cancer cells. VOR and ETOP were encapsulated into poly(ethylene glycol) monomethacrylate (POEOMA)-based disulfide cross-linked nanogels. The nanogels were synthesized using atom transfer radical polymerization (ATRP) via cyclohexane/water inverse mini-emulsion and were degradable in presence of intracellular glutathione (GSH) concentration. Both the drugs were loaded into the nanogels by physical encapsulation method and characterized by Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), X-ray diffraction (XRD), dynamic light scattering (DLS), and differential scanning calorimetry (DSC). Both VOR- and ETOP-loaded nanogels showed sustained release profile. Furthermore, combination treatment drugs encapsulated of POEOMA nanogel demonstrated enhanced synergistic cytotoxic effect compared with combination of free drugs. Enhanced synergistic cell killing efficiency of drug-loaded POEOMA nanogels was due to increased apoptosis via caspase 3/7 activation. Therefore, combination of VOR- and ETOP-loaded PEG-based biodegradable nanogels may provide a promising therapy with enhanced anticancer effect.
Limits of End-to-End Learning

End-to-end learning refers to training a possibly complex learning system by applying gradient-based learning to the system as a whole. End-to-end learning system is specifically designed so that all modules are differentiable. In effect, not only a central learning machine, but also all "peripheral" modules like representation learning and memory formation are covered by a holistic learning process. The power of end-to-end learning has been demonstrated on many tasks, like playing a whole array of Atari video games with a single architecture. While pushing for solutions to more challenging tasks, network architectures keep growing more and more complex. In this paper we ask the question whether and to what extent end-to-end learning is a future-proof technique in the sense of scaling to complex and diverse data processing architectures. We point out potential inefficiencies, and we argue in particular that end-to-end learning does not make optimal use of the modular design of present neural networks. Our surprisingly simple experiments demonstrate these inefficiencies, up to the complete breakdown of learning.
Patellar Tendon Ruptures in National Football League Players

Background: Although knee injuries are common among professional football players, ruptures of the patellar tendon are relatively rare. Predisposing factors, mechanisms of injury, treatment guidelines, and recovery expectations are not well established in high-level athletes. Hypothesis: Professional football players with isolated rupture of the patellar tendon treated with timely surgical repair will return to their sport. Study Design: Case series; Level of evidence, 4. Methods: Twenty-four ruptures of the patellar tendon in 22 National Football League (NFL) players were identified from 1994 through 2004. Team physicians retrospectively reviewed training room and clinic records, operative notes, and imaging studies for each of these players. Player game statistics and draft status were analyzed to identify return to play predictors. A successful outcome was defined as participating in 1 regular-season NFL game. Results: Eleven of the 24 injuries had antecedent symptoms. The most common mechanism of injury was an eccentric overload to a contracting extensor mechanism. Physical examination demonstrated a palpable defect in all players. Twenty-two were complete ruptures, and 2 were partial injuries. Three of the 24 cases had a concomitant anterior cruciate ligament (ACL) injury. In 19 of the 24 injuries, the player returned to participate in at least 1 game in the NFL. Players who returned were drafted, on average, in the fourth round, while those who failed to return to play were drafted, on average, in the sixth round. Of those players who returned to play, the average number of games played was 45.4, with a range of 1 to 142 games. Conclusion: Patellar tendon ruptures can occur in otherwise healthy professional football players without antecedent symptoms or predisposing factors. The most common mechanism of injury is eccentric overload. Close attention should be paid to stability examination of the knee given the not uncommon occurrence of concomitant ACL injury. Although this is usually a season-ending injury when it occurs in isolation, acute surgical repair generally produces good functional results and allows for return to play the following season. Players chosen earlier in the draft are more likely to return to play.
Intraocular pressure and Schirmer tear test results in clinically normal Long-Eared Hedgehogs (Hemiechinus auritus): reference values.

OBJECTIVE The present study was undertaken to establish reference values for Schirmer tear test (STT) and intraocular pressure (IOP) in the long-eared hedgehog (Hemiechinus auritus). ANIMALS Fourteen healthy long-eared hedgehogs (H. auritus) of either sex were studied. PROCEDURES The hedgehogs were individually immobilized with an intramuscular injection of combined Ketamine (20 mg/kg) and Diazepam (0.5 mg/kg), and each animal underwent ophthalmic examinations including: STT, tonometry, biomicroscopy, and indirect ophthalmoscopy. RESULTS No significant effects of animal gender, weight, side (right vs. left eye) were found in this study. Mean (SD) STT values for all eyes (n = 28) were 1.7 ± 1.2 mm/1 min with a range of 0-4 mm/1 min. Mean STT in male animals was 2.2 ± 1.2. Mean STT in female Hedgehogs was 1.3 ± 1.1. Mean (SD) IOP values by applanation tonometry were 20.1 ± 4.0 mmHg (range 11.5-26.5 mmHg). Mean (SD) IOP values by applanation tonometry were 18.2 ± 4.0 and 22.0 ± 3.2 mmHg for males and females, respectively. CONCLUSIONS This study reports STT and IOP findings in long-eared hedgehogs (H. auritus).
Normal-appearing brain tissue MTR histograms in clinically isolated syndromes suggestive of MS

Abstract—Segmented normal-appearing brain tissue (NABT) was investigated in 40 patients with a recent onset and 13 patients with a remote onset of a clinically isolated syndrome (CIS) using magnetization transfer ratio (MTR) histograms. Abnormalities were present in patients with a high risk for MS (recent onset and T2-weighted lesions present) and in those with a low risk for relapse (recent onset without T2-weighted lesions). Similar mild NABT abnormality was present with CIS and no further disease activity 14 years later. NABT MTR abnormality in CIS may indicate susceptibility to demyelination but not to disease progression.
The Impact of Some Family Variables on the Dimension of Social Responsibility

The current study discusses the social and psychological studies conducted on the concept of the social responsibility, as well as the symbolic interactive trend as a theoretical basis for interpretation; moreover, discussing the social responsibility in the light of family variables. The aim of this study is to investigate the family variables, including domicile, parents’ education, their age, the type of work they do, family size, and family income. As to the social responsibility’s dimensions for sample selected for this study; hence, it includes personal, ethical, national, environmental, health, and social responsibility. The current study adopted the descriptive approach along with a demographic data form and the social responsibility’s scale. The sample selected consisted of 330 female students from various colleges within King Abdulaziz University. The results indicated that there was an impact on all the variables, thus such impact was in favor of those living in rural areas as to the ethical dimension and in favor of urban people as to the dimensions of accountability, parents’ level of education, parents’ seniority, working mothers, greater family size, and higher income.
Epilepsy in an Italian community as assessed by a survey for prescriptions of antiepileptic drugs: epidemiology and patterns of care

The prescriptions of antiepileptic drugs in the years 1985 and 1986 were used to identify all possible cases of epilepsy in a population of about 50000 people. The general practitioners of the study area filled out a questionnaire for each user of antiepileptic drugs registered as a patient of theirs. This information was integrated using data obtained by local specialist services or directly collected by visits and/or phone interviews. Two‐hundred and fifty‐six of the 417 antiepileptic drug users proved to be active epileptics with a prevalence rate of 5.2/1000, the annual incidence rate for 1986 being 51.8/100000. The main patterns of the disease appeared to be consistent with those of the literature while the prior history of seizures in the previous five years was generally lower. The health care of epileptic patients involved a wide range of specialists. The general practitioners were responsible for the final diagnosis of epilepsy in 10% of patients and for the management of the disease in 22%, most of the patients being over 50 years old. The calculated mean prescribed daily doses of the antiepileptic drugs suggested that many epileptics were taking therapeutic schedules lower than those of the literature.
Retrieval of autobiographical memory in Alzheimer's disease: Relation to volumes of medial temporal lobe and other structures

The representation of autobiographical memory is distributed over a network of brain structures, with the medial temporal lobe (MTL) at its epicenter. Some believe that, over time, all memories become independent of their MTL component (“consolidation theories”). Others have suggested that this is true only of semantic memory, while episodic aspects of autobiographical memories are dependent on the MTL for as long as they exist, such as multiple trace theory (MTT). In the present study, the volumes of 28 brain regions, including the MTL, and their relation to autobiographical memory were investigated in a group of patients with Alzheimer's disease with varying degrees of retrograde memory loss as assessed by the Autobiographical Memory Interview (AMI). We used the multivariate analysis method of partial least squares (PLS) to assess patterns of atrophy that can lead to retrograde amnesia. We found that different aspects of autobiographical memory were associated with different patterns of tissue loss. Personal semantics were related to a pattern of bilateral anterior and posterior lateral temporal cortex degeneration, more pronounced on the left, as well as right frontal degeneration. Autobiographical event memory (“episodic”) was associated with combined atrophy in bilateral MTL and anterior lateral temporal neocortex, more pronounced on the right. This pattern was invariant for memories from childhood, early adulthood, and recent memories, in line with the predictions of MTT, suggesting that MTL tissue is crucial for retrieval of episodic memories regardless of their age. © 2005 Wiley‐Liss, Inc.
In vivo leukocyte cytokine mRNA responses to biomaterials are dependent on surface chemistry.

An in vivo mouse cage implant system was used to determine whether leukocyte cytokine mRNA responses to implanted biomaterials were dependent on surface chemistry. Surfaces displaying various chemistries (hydrophobic, hydrophilic, anionic, and cationic) were placed into stainless steel cages and implanted subcutaneously. Semiquantitative RT-PCR analyses revealed that hydrophilic surfaces showed a decreased expression of proinflammatory cytokines, IL-6 and IL-8, and pro-wound healing cytokines, IL-10 and TGF-beta by adherent cells, and mRNA levels of the proinflammatory cytokine, IL-1beta, and the pro-wound healing cytokine IL-13 were decreased in surrounding, exudate cells. Cytokine responses by adherent and exudate cells to hydrophobic, anionic and cationic surfaces were similar and indicative of a strong inflammatory response at the earliest time point followed by a wound healing response at later time points. However, no differences in the types or levels of exudate cells for any of the surfaces or the empty cage at each of the respective time points were observed, indicating their respective biocompatibility. These studies identify hydrophilic surface chemistries as having significant effects on leukocyte cytokine responses in vivo by decreasing the expression of inflammatory and wound healing cytokines by inflammatory cells adherent to the biomaterial as well as present in the surrounding exudate.
A 3E typology of visitors at an electronic dance music festival

Purpose The purpose of this paper is to determine the motives of visitors to an electronic dance music (EDM) festival in South Africa and clustered the participants according to these motives. Design/methodology/approach Based on a visitor survey at the oldest EDM festival in South Africa, namely, H2O, five motives for attending H2O were identified (fun and dance; novelty; excitement, group identity and entertainment; lifestyle and well-being; and travel and escape), while the results revealed three clusters of EDM festival visitors: enthusiasts, energizers and electros. The results demonstrated that clustering EDM festival visitors based on their motives is a useful market segmentation tool as it yields a clear and direct profile and understanding of different types of attendees and their preferences. Findings The results as well as findings emphasize how EDM events can play a role in expanding tourism, especially youth travel, by hosting more EDM festivals in the country. Originality/value The study proposes a 3E typology of EDM festival visitors that could be applied to other EDM festival and event markets. This research, therefore, makes a clear contribution to the literature on EDM festivals and events and the market that this distinct music genre attracts.
Epinephrine impairs splanchnic perfusion in septic shock.

OBJECTIVE To assess the effects of epinephrine on splanchnic perfusion and splanchnic oxygen uptake in patients with septic shock. DESIGN Prospective, controlled trial. SETTING University hospital intensive care unit (ICU). PATIENTS Eight patients with septic shock, according to the criteria of the 1992 American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference, requiring treatment with vasopressors. INTERVENTIONS We compared in crossover design a 2-hr infusion of epinephrine with dobutamine plus norepinephrine in eight ICU patients with septic shock. Systemic and splanchnic hemodynamics and oxygen transport were measured before and during treatment with epinephrine. MEASUREMENTS AND MAIN RESULTS There was essentially no effect of epinephrine on the global parameters, except for increased lactate concentrations. There were marked effects on the regional variables; epinephrine caused lower splanchnic flow and oxygen uptake, lower mucosal pH, and higher hepatic vein lactate. CONCLUSION We conclude that undesirable splanchnic effects on patients in whom that region is particularly fragile should be considered when using epinephrine for septic shock treatment.
EXPERIENCE WITH MANAGING SOLID KIDNEY TUMOURS IN COTONOU, BENIN REPUBLIC.

BACKGROUND Kidney cancer is the third most common urological tumour. Diagnosis is made in most cases at an advanced stage of the disease in our setting. AIM & OBJECTIVES The aim of this work was to describe the management of solid tumors of the kidney and the outcome at the National University Hospital, Cotonou, Benin Republic, from January 2008 to December 2014. PATIENTS & METHODS This is a retrospective, descriptive study conducted at the Clinic of Urology and Andrology at the National University Hospital CNHU-Hubert Koutoukou MAGA in Cotonou, Benin Republic. We included patients managed for solid kidney tumours from January 2008 to December 2014. The demographics, clinical presentations, management and outcome were recorded and the data obtained were analyzed using Epi info 3.2. 2. RESULTS Hospital frequency of solid renal mass was 1.9% with a mean age of 54 years and sex ratio of men to women of 1.6. Hematuria, back pain and lumbar mass were the most frequent clinical presentation found in 79.5% of cases. In all, 5% presented at an early stage while 95% presented at a late stage. Diagnosis was based on imaging; histopathological examination was requested in all the case though some could not afford the cost. Radical nephrectomy was performed in 51.5% of cases.The non- operated cases were those whose poor general condition as well as those who could not afford the procedure. Undifferentiated adenocarcinoma was the predominant pathological type found in 78% of operated cases. No patients underwent other treatments such as radiation therapy, immunotherapy or chemotherapy. Mortality occured in 10 cases including 1 intra operative death, 3 patients died in the early post operative period due to respiratory distress and 7 patients died from metatstasis discovered post operatively. CONCLUSION This study has shown that majority of patients with solid renal tumours in this environment present late with advanced stages of the disease. The absence of the necessary investigative equipment, poverty and absence of adjuvant and adjunct therapeutic facilities make the treatment outcome poor.
The impact of cognitive challenges in major depression: the role of the primary care physician

ABSTRACT Nearly 1 in 5 Americans will struggle with major depression in their lives; some will have recurring bouts. Recent psychiatric research has given new attention to the prevalence of cognitive deficits in major depression and the impact such deficits have on remission and overall life functioning. When depression is partially treated i.e., leaving residual symptoms, patients have higher rates of relapse and lower functional outcomes. Impaired cognitive functioning is a frequent residual symptom, persisting in about 45% of patients even when emotional symptoms have improved, and results in a disproportionate share of the functional impairment, particularly in the workplace. Patients with depression have disrupted circuitry in brain regions responsible for cognition and it is therefore important to screen depressed patients for cognitive as well as emotional symptoms. Cognitive dysfunction should be evaluated in every mood disordered patient with validated self-report scales such as the Patient Health Questionnaire-9 or the Beck Depression Inventory and objective measures of cognitive function are also very very useful. Two easily administered tests are the Trails B Test and the Digit Symbol Substitution Test. Each take less than two minutes and measure working memory, executive function, and processing speed and can track cognitive improvement in depressed patients. Treatment of cognitive dysfunction in major depression is complicated by the ‘serotonin conundrum’: SSRI’s frequently do not treat to full remission, and can cause cognitive blunting—actually adding to cognitive problems. Based on recent data including results from a recently completed meta-analysis by McIntyre and colleagues, an evidence-based algorithm for treating cognitive symptoms in depression is presented. A hierarchy of antidepressants and augmentation strategies based on the best available evidence is discussed. In conclusion, cognitive symptoms in major depressive disorder have been recognized as a target of therapeutic improvement by the FDA and have become a focus of clinical importance.