Miracle-dz/UniFAR-FTUs huggingface dataset:
A Comprehensive Literature Review on the Clinical Presentation, and Management of the Pandemic Coronavirus Disease 2019 (COVID-19)

Coronavirus disease 2019 (COVID-19) is a declared global pandemic. There are multiple parameters of the clinical course and management of the COVID-19 that need optimization. A hindrance to this development is the vast amount of misinformation present due to scarcely sourced manuscript preprints and social media. This literature review aims to presents accredited and the most current studies pertaining to the basic sciences of SARS-CoV-2, clinical presentation and disease course of COVID-19, public health interventions, and current epidemiological developments. The review on basic sciences aims to clarify the jargon in virology, describe the virion structure of SARS-CoV-2 and present pertinent details relevant to clinical practice. Another component discussed is the brief history on the series of experiments used to explore the origins and evolution of the phylogeny of the viral genome of SARS-CoV-2. Additionally, the clinical and epidemiological differences between COVID-19 and other infections causing outbreaks (SARS, MERS, H1N1) are elucidated. Emphasis is placed on evidence-based medicine to evaluate the frequency of presentation of various symptoms to create a stratification system of the most important epidemiological risk factors for COVID-19. These can be used to triage and expedite risk assessment. Furthermore, the limitations and statistical strength of the diagnostic tools currently in clinical practice are evaluated. Criteria on rapid screening, discharge from hospital and discontinuation of self-quarantine are clarified. Epidemiological factors influencing the rapid rate of spread of the SARS-CoV-2 virus are described. Accurate information pertinent to improving prevention strategies is also discussed. The penultimate portion of the review aims to explain the involvement of micronutrients such as vitamin C and vitamin D in COVID19 treatment and prophylaxis. Furthermore, the biochemistry of the major candidates for novel therapies is briefly reviewed and a summary of their current status in the clinical trials is presented. Lastly, the current scientific data and status of governing bodies such as the Center of Disease Control (CDC) and the WHO on the usage of controversial therapies such as angiotensin-converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs) (Ibuprofen), and corticosteroids usage in COVID-19 are discussed. The composite collection of accredited studies on each of these subtopics of COVID-19 within this review will enable clarification and focus on the current status and direction in the planning of the management of this global pandemic.
HIV-negative plasmablastic lymphoma: report of 8 cases and a comprehensive review of 394 published cases

Background Human immunodeficiency virus (HIV)-negative plasmablastic lymphoma (PBL) is a rare entity of diffuse large B-cell lymphoma (DLBCL). The clinicopathological features of and optimal treatment for HIV-negative PBL remain largely unknown. Methods To gain insight into this distinct lymphoma, we summarized the clinicopathologic characteristics of 8 unpublished HIV-negative PBLs and performed a comprehensive review of 394 published cases. Results Of the 8 unpublished PBLs, the median patient age was 53.0 years. Four patients presented with stage IV disease. All 8 patients showed a plasma cell-like immunophenotype. Of the six patients who received anthracycline-based chemotherapy, including two who received bortezomib, three patients achieved a continuous complete response, two patients died due to disease progression, and one patient was lost to follow-up. The other two patients achieved continuous complete response after receiving chemotherapy combined with radiotherapy and surgery. Of the 402 patients, the majority were male, with a mean age of 58.0 years. EBV infection was detected in 55.7% of the patients. The median survival times of the patients who received CHOP or CHOP-like regimens and intensive regimens were not reached and 23.0 months, respectively, and the intensive regimen did not improve the survival outcome (P=0.981). Multivariate analysis showed that EBER remained the only independent factor affecting overall survival (OS). Conclusion HIV-negative PBL is a distinct entity with a predilection for elderly and immunosuppressed individuals. Intensive chemotherapy had no apparent survival benefits over the CHOP regimen in terms of OS; the prognosis of this disease is poor with current chemotherapy methods, and treatment remains a challenge.
A chemically unmodified agonistic DNA with growth factor functionality for in vivo therapeutic application

This study identifies an oligonucleotide that activates a growth factor receptor and exerts its antiapoptotic activity in vivo. Although growth factors have great therapeutic potential because of their regenerative functions, they often have intrinsic drawbacks, such as low thermal stability and high production cost. Oligonucleotides have recently emerged as promising chemical entities for designing synthetic alternatives to growth factors. However, their applications in vivo have been recognized as a challenge because of their susceptibility to nucleases and limited distribution to a target tissue. Here, we present the first example of oligonucleotide-based growth factor mimetics that exerts therapeutic effects at a target tissue after systemic injection. The aptamer was designed to dimerize a growth factor receptor for its activation and mitigated the progression of Fas-induced fulminant hepatitis in a mouse model. This unprecedented functionality of the aptamer can be reasonably explained by its high nuclease stability and migration to the liver parenchyma. These mechanistic analyses provided insights for the successful application of aptamer-based receptor agonists.
B cell Sirt1 deacetylates histone and non-histone proteins for epigenetic modulation of AID expression and the antibody response

Sirt1 mediates epigenetic modulation of B cell AID expression and antibody response by deacetylating histones, Dnmt1 and NF-κB p65. Activation-induced cytidine deaminase (AID) mediates immunoglobulin class switch DNA recombination (CSR) and somatic hypermutation (SHM), critical processes for maturation of the antibody response. Epigenetic factors, such as histone deacetylases (HDACs), would underpin B cell differentiation stage–specific AID expression. Here, we showed that NAD+-dependent class III HDAC sirtuin 1 (Sirt1) is highly expressed in resting B cells and down-regulated by stimuli inducing AID. B cell Sirt1 down-regulation, deprivation of NAD+ cofactor, or genetic Sirt1 deletion reduced deacetylation of Aicda promoter histones, Dnmt1, and nuclear factor–κB (NF-κB) p65 and increased AID expression. This promoted class-switched and hypermutated T-dependent and T-independent antibody responses or led to generation of autoantibodies. Genetic Sirt1 overexpression, Sirt1 boost by NAD+, or allosteric Sirt1 enhancement by SRT1720 repressed AID expression and CSR/SHM. By deacetylating histone and nonhistone proteins (Dnmt1 and NF-κB p65), Sirt1 transduces metabolic cues into epigenetic changes to play an important B cell–intrinsic role in modulating antibody and autoantibody responses.
Neferine treatment enhances the TRAIL-induced apoptosis of human prostate cancer cells via autophagic flux and the JNK pathway

Prostate cancer (PCa) is a common type of cancer among males, with a relatively high mortality rate. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a member of the tumor necrosis factor (TNF) family, initiates the apoptosis of certain cancer cells. Neferine, a primary ingredient of bisbenzylisoquinoline alkaloids, has various antitumor activities. The present study examined the effects of neferine treatment on human PCa cells. Human prostate cancer (DU145) cells were treated with neferine for 18 h, and subsequently treated with TRAIL for 2 h. Combined treatment with neferine and TRAIL significantly decreased cell viability compared to treatment with TRAIL alone. Furthermore, neferine treatment decreased the expression of p62 and increased LC3B-II expression, as assessed by western blot analysis and immunocytochemistry. It was alsp demonstrated that neferine and TRAIL act synergistically to trigger autophagy in PCa cells, as revealed by autophagosome formation, LC3B-II accumulation demonstrated by transmission electron microscopy (TEM) analysis and phosphorylated c-Jun N-terminal kinase (p-JNK) upregulation. When the autophagic flux was attenuated by the inhibitor, chloroquine, or by genetically modified ATG5 siRNA, the enhancement of TRAIL-induced autophagy by neferine-induced was also attenuated. Furthermore, treatment with the JNK inhibitor, SP600125, distinctly increased the viability of the cells treated with neferine and TRAIL. On the whole, the findings of the present study demonstrate that neferine treatment effectively promotes TRAIL-mediated cell death and this effect likely occurs via the autophagic flux and the JNK pathway.
Testicular cancer in men with undescended testis: Insights from the Thames Valley Testicular Cancer database

Objective: Undescended testis (UDT) increases the risk of testicular cancer (TCa) development. Historical evidence suggests that malignant transformation of uncorrected UDT primarily results in seminomas, whereas mixed germ cell tumours predominate in corrected UDT; however, the risk of malignancy in the ‘normal’ contralateral testis is unclear. We investigated the contemporary Oxford TCa cohort to report the frequency of prior UDT and types of tumours developing in the prior UDT and normal contralateral testis. Patients and Methods: A 607 patient contemporary TCa cohort within the Thames Valley Testicular Cancer database. Results: Of men with new TCa, 8% had a history of UDT. Of men with TCa and prior UDT, 61% developed seminomas, whereas 56% of men with TCa without previous UDT developed this subtype. Among men with prior UDT, 77% developed tumours in the UDT, whilst 23% developed TCa in the contralateral normal testis. Conclusion: Seminoma was the most frequent malignancy following UDT, with a greater frequency than without prior UDT. Around one in four TCa patients with UDT developed contralateral tumours, emphasising the need for self-examination of both testes. Advice should be given to any patient with a history of UDT stressing the importance of ongoing self-examination of both testes. Level of evidence: Level 4.
The Role of Id Proteins in the Development and Function of T and B Lymphocytes

The Role of Id Proteins in the Development and Function of T and B Lymphocytes by Yen-Yu Lin Department of Immunology Duke University Date:_______________________ Approved: ___________________________ Yuan Zhuang, Supervisor ___________________________ Michael S. Krangel, Chair ___________________________ Qi-Jing Li ___________________________ Mari L. Shinohara ___________________________ Christopher D. Kontos An abstract of a dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Immunology in the Graduate School of Duke University 2014 Copyright by Yen-Yu Lin 2014
Moving on: A survey of Canadian nurses’ self-reported transition practices for young people with chronic pain

ABSTRACT Background Practices to support the transition of a young person from the pediatric to the adult health care setting have been examined for many chronic illness populations. However, specific transition practices to support young people with chronic pain have not been examined. Aim The aim of this study was to describe the current nursing practices used in the pediatric and the adult health care to support transition of young people with chronic pain in Canada. Methods An online survey of pediatric and adult chronic pain nurses’ self-reported transition practices was conducted. Results Twenty-two nurses completed the survey, 10 (45.5%) from the pediatric chronic pain setting and 12 (54.4%) from the adult chronic pain setting. Of the pediatric nurses surveyed none reported using a psychometrically valid tool to assess a young person’s readiness of general transition skills; however, one reported using a tool to assess understanding of chronic pain. Most health care facilities in which these pediatric nurses worked offered a general transition clinic, but only one of these facilities also had a chronic pain transition clinic. Nurses in both settings perceived that young people experience increased levels of distress during transition yet most did not report using formal transition practices in their care. Conclusion Nursing practices and clinic resources to support the transition of young people with chronic pain may not meet the needs of this population. Practices may benefit from the use of psychometrically validated tools to assess general transition preparedness. Research is needed to adapt tools and determine best transition practices for the chronic pain population.
Evolution de l'agressivité des champignons phytopathogènes, couplage des approches théorique et empirique

Les organismes vivants puisent leurs ressources de l'environnement pour les allouer aux differentes fonctions biologiques assurant leur developpement (croissance, survie, reproduction). La quantite de ressources disponibles dans un environnement etant finie voire limitante, les individus doivent faire des compromis lors de l'allocation de ces ressources a leurs differentes fonctions biologiques. Ces compromis contraignent le developpement des individus et entrainent l'apparition d'autres compromis entre leurs traits d'histoire de vie (âge et taille a maturite, nombre de descendants), conditionnant ainsi les capacites d'adaptation des individus a leur environnement. Au cours de cette these, nous avons etudie l'evolution de traits d'histoire de vie des pathogenes relatifs a la virulence, par une approche de modelisation. Nous avons centre notre approche sur l'etude des strategies d'allocation des ressources entre la croissance (ou multiplication intra-hote) et la production de spores au cours d'une infection par un unique genotype pathogene. Nous avons determine, les strategies optimales d'allocation des ressources ponctionnees a l'hote, entre la multiplication intra-hote et la production de spores dans differentes conditions ecologiques. Le resultat principal de ces travaux de modelisation est qu'il n'est jamais optimal d'allouer un pourcentage fixe des ressources exploitees a la croissance et a la production de spores tout au long de l'infection. Au contraire, la strategie optimale comporte generalement une periode de latence, c'est-a-dire un temps au cours duquel toute l'energie est investie dans la croissance et ou aucune spore n'est produite. Apres la periode de latence, toutes les ressources consommees sont utilisees pour la production de spores si le pathogene a un acces limite aux ressources de l'hote. Au contraire, si le pathogene a un acces illimite aux ressources de l'hote, une partie fixe des ressources consommees est reservee pour la maintenance des formes de multiplication intra-hote. Ces modeles mathematiques fournissent non seulement des predictions qualitatives sur les dynamiques intra-hote des agents pathogenes mais permettent egalement de quantifier la variation attendue de certains traits couramment mesures lors d'experimentation d'infection en conditions controlees. Dans un deuxieme volet de ces travaux, des elements de validation empirique de ces modeles ont ete recherches au travers d'experimentations menees sur les deux modeles biologiques couramment manipules par les equipes d'accueil : l'agent de la pyriculariose du riz (Magnaporthe oryzae) et l'agent de la rouille du peuplier (Melampsora larici-populina). Les observations realisees sont en adequation avec les predictions theoriques et confirment la pertinence des hypotheses et de la demarche de modelisation. (Resume d'auteur)
SNP‐SCALE: SNP scoring by colour and length exclusion

Here we present SNP-SCALE, a new single nucleotide polymorphism genotyping protocol based on allele-specific polymerase chain reaction (AS-PCR), but with two critical modifications designed to maximize accuracy, efficiency and throughput and minimize costs. The first is the addition of a locked nucleic acid (LNA) at the 3′-SNP position of each of the two allele-specific forward primers. The second is the addition of size-differentiating M13 tails at the 5′ end of each primer, which facilitates the use of universal fluorescent primers. The use of LNAs makes SNP-SCALE significantly more sensitive and specific than standard AS-PCR. Moreover, SNP-SCALE is ideally suited to a touchdown-like PCR protocol, such that PCRs can be standardized, PCR optimization is straightforward, and medium-high throughput can be readily achieved. We anticipate that the SNP-SCALE protocol will be useful to molecular ecologists for a broad range of studies.
Portrait

Born in 1944, I grew up in a world in which polio was both a gripping fear and real threat. Then in a matter of a few years—polio was eradicated by a vaccine developed by Jonas Salk. Later I learned that Salk’s efforts were built on pioneering work of many others, including John Enders, Thomas Weller and Frederick Robbins (Nobelists, 1954), and David Bodian, who pioneered studies of polio pathogenesis and immunity. Bodian became my teacher in medical school, and Robbins became a colleague. Later, Salk, Robbins and I shared a platform at an infectious diseases symposium, and I was privileged to speak at Robbins’ retirement. But that gets ahead of my story. In January 1956, at age 12 y, I received my first of dose of the “Salk” vaccine. Other kids had pictures of athletes in their rooms; I had a picture of Jonas Salk.
Intraspecific somatic hybridization of mango (Mangifera indica L.) through protoplast fusion

Somatic hybridization of mango via protoplast fusion was attempted at cultivar level. Enzymatically isolated protoplasts from leaves of greenhouse-grown seedlings of cvs. 'Tommy Atkins', 'Keitt' and 'Haden' and from proembryonic masses (PEMs) of cv. 'Kensington Pride' were used. Protoplasts were fused by polyethylene glycol (PEG), embedded in Ca-alginate beads and cultured in shallow liquid culture on shaker (30 rpm). After 4 weeks, Ca-alginate beads were depolymerized and released microcolonies of PEMs were plated onto the solid culture media. After two consecutive subcultures, fast growing large clumps of PEMs were picked up and cultured as PEMs line for analyses. Flow cytometry analysis of 242 PEMs lines revealed 41 tetraploid lines. DNA fingerprinting of the regenerated embryos from the tetraploid lines showed that only four lines were somatic hybrids, all resulting from 'Haden' + 'Kensington Pride' protoplast fusions. By contrast, the tetraploid lines from 'Keitt' + 'Kensington Pride' and 'Tommy Atkins' + 'Kensington Pride' were autotetraploids. Root-tip chromosome counts on resulting germinated cotyledonary embryos confirmed that somatic hybrid embryo lines had a chromosome number of 2n=4x=80 compared to diploid parents (2n=2x=40). Of 50 deflasked somatic-hybrid, in vitro plantlets with true leaves only 3 plantlets formed the healthy apical bud (meristem) in the soil and grew normally.
Pituicytoma

Background: Pituicytomas originate from pituicytes, modified glial cells derived from ependymal lineage that are found in the stalk and posterior lobe of pituitary gland. The clinical presentation is similar to other pituitary tumors and imaging exams may suggest pituitary adenoma. The diagnostic is based on histopathological analysis. Surgical treatment can be performed by transsphenoidal approach with good results. The prognostic is good after total tumor resection. Case Description: We describe here the case of a 17-year-old patient with a history of persistent headache and visual disturbances. Magnetic resonance imaging demonstrated an enhancing solid sellar mass suggestive of pituitary adenoma. The intrasellar mass was resected through a transsphenoidal approach and the diagnosis of pituicytoma was made after histopathological analysis. Conclusion: Pituicytomas are rare tumors of the neurohypophysis derived from pituicytes. Their clinical presentation resembles that of non-functional pituitary adenomas, but these two types of tumors are histologically well distinct.
Pathogénie comparée de 4 espèces d'Helminthosporium Obtenues à Partir des Plantes Malades du Riz au Maroc

Resume L'etude du comportement de quatre especes d'Helminthosporium sur neuf varietes de riz largement cultivees au Maroc, a permis de classer ces especes selon leur virulence. L'Helminthosporium oryzae et l'Helminthosporium sativum sont les plus virulents et sont les mieux equipes a sporuler sur les lesions developpees sur toutes les varietes de riz testees. Le niveau de pathogenie de l'H. spiciferum et de l'H. australiensis et leur aptitude a sporuler sur l'hote depend de la variete du riz etudiee. De meme, chaque Helminthosporium induit sur les feuilles de riz des symptomes caracteristiques.
Altered resting state EEG in chronic pancreatitis patients: toward a marker for chronic pain

Objectives Electroencephalography (EEG) may be a promising source of physiological biomarkers accompanying chronic pain. Several studies in patients with chronic neuropathic pain have reported alterations in central pain processing, manifested as slowed EEG rhythmicity and increased EEG power in the brain’s resting state. We aimed to investigate novel potential markers of chronic pain in the resting state EEG of patients with chronic pancreatitis. Participants Resting state EEG data from 16 patients with persistent abdominal pain due to chronic pancreatitis (CP) were compared to data from healthy controls matched for age, sex and education. Methods The peak alpha frequency (PAF) and power amplitude in the alpha band (7.5–13 Hz) were compared between groups in four regions of interest (frontal, central, parietal, and occipital) and were correlated with pain duration. Results The average PAF was lowered in CP patients compared with that in healthy controls, observed as a statistically significant between-group effect (mean 9.9 versus 9.5 Hz; P=0.049). Exploratory post hoc analysis of average PAF per region of interest revealed a significant difference, particularly in the parietal and occipital regions. In addition, we observed a significant correlation between pain duration and PAF and showed increased shifts in PAF with longer pain durations. No significant group differences were found in peak power amplitudes. Conclusion CP pain is associated with alterations in spontaneous brain activity, observed as a shift toward lower PAF. This shift correlates with the duration of pain, which demonstrates that PAF has the potential to be a clinically feasible biomarker for chronic pain. These findings could be helpful for assisting diagnosis, establishing optimal treatment, and studying efficacy of new therapeutic agents in chronic pain patients.