Miracle-dz/UniFAR-FTUs huggingface dataset:
Determination of feasibility and utility of microscope-integrated optical coherence tomography during ophthalmic surgery: the DISCOVER Study RESCAN Results.

IMPORTANCE Optical coherence tomography (OCT) has transformed the clinical management of a myriad of ophthalmic conditions. Applying OCT to ophthalmic surgery may have implications for surgical decision making and patient outcomes. OBJECTIVE To assess the feasibility and effect on surgical decision making of a microscope-integrated intraoperative OCT (iOCT) system. DESIGN, SETTING, AND PARTICIPANTS Report highlighting the 1-year results (March 2014-February 2015) of the RESCAN 700 portion of the DISCOVER (Determination of Feasibility of Intraoperative Spectral Domain Microscope Combined/Integrated OCT Visualization During En Face Retinal and Ophthalmic Surgery) study, a single-site, multisurgeon, prospective consecutive case series regarding this investigational device. Participants included patients undergoing ophthalmic surgery. Data on clinical characteristics were collected, and iOCT was performed during surgical milestones, as directed by the operating surgeon. A surgeon questionnaire was issued to each surgeon and was completed after each case to evaluate the role of iOCT during surgery and its particular role in select surgical procedures. MAIN OUTCOMES AND MEASURES Percentage of cases with successful acquisition of iOCT (ie, feasibility). Percentage of cases in which iOCT altered surgical decision making (ie, utility). RESULTS During year 1 of the DISCOVER study, a total of 227 eyes (91 anterior segment cases and 136 posterior segment cases) underwent imaging with the RESCAN 700 system. Successful imaging (eg, the ability to acquire an OCT image of the tissue of interest) was obtained for 224 of 227 eyes (99% [95% CI, 98%-100%]). During lamellar keratoplasty, the iOCT data provided information that altered the surgeon's decision making in 38% of the cases (eg, complete graft apposition when the surgeon believed there was interface fluid). In membrane peeling procedures, iOCT information was discordant with the surgeon's impression of membrane peel completeness in 19% of cases (eg, lack of residual membrane or presence of occult membrane), thus affecting additional surgical maneuvers. CONCLUSIONS AND RELEVANCE The DISCOVER study demonstrates the feasibility of real-time iOCT with a microscope-integrated iOCT system for ophthalmic surgery. The information gained from iOCT appears to allow surgeons to assess subtle details in a unique perspective from standard en face visualization, which can affect surgical decision making some of the time, although the effect of these changes in decision making on outcomes remains unknown. A prospective randomized masked trial is needed to confirm these results.
Emergence of divergent Zaire ebola virus strains in Democratic Republic of the Congo in 2007 and 2008.

BACKGROUND Zaire ebolavirus was responsible for 2 outbreaks in Democratic Republic of the Congo (DRC), in 1976 and 1995. The virus reemerged in DRC 12 years later, causing 2 successive outbreaks in the Luebo region, Kasai Occidental province, in 2007 and 2008. METHODS Viruses of each outbreak were isolated and the full-length genomes were characterized. Phylogenetic analysis was then undertaken to characterize the relationships with previously described viruses. RESULTS The 2 Luebo viruses are nearly identical but are not related to lineage A viruses known in DRC or to descendants of the lineage B viruses encountered in the Gabon-Republic of the Congo area, with which they do, however, share a common ancestor. CONCLUSIONS Our findings strongly suggest that the Luebo 2007 outbreak did not result from viral spread from previously identified foci but from an independent viral emergence. The previously identified epidemiological link with migratory bat species known to carry Zaire ebolavirus RNA support the hypothesis of viral spillover from this widely dispersed reservoir. The high level of similarity between the Luebo2007 and Luebo2008 viruses suggests that local wildlife populations (most likely bats) became infected and allowed local viral persistence and reemergence from year to year.
Protein tyrosine phosphatases – from housekeeping enzymes to master regulators of signal transduction

There are many misconceptions surrounding the roles of protein phosphatases in the regulation of signal transduction, perhaps the most damaging of which is the erroneous view that these enzymes exert their effects merely as constitutively active housekeeping enzymes. On the contrary, the phosphatases are critical, specific regulators of signalling in their own right and serve an essential function, in a coordinated manner with the kinases, to determine the response to a physiological stimulus. This review is a personal perspective on the development of our understanding of the protein tyrosine phosphatase family of enzymes. I have discussed various aspects of the structure, regulation and function of the protein tyrosine phosphatase family, which I hope will illustrate the fundamental importance of these enzymes in the control of signal transduction.
The six amino acid antimicrobial peptide bLFcin6 penetrates cells and delivers siRNA

Cell‐penetrating peptides (CPPs) are a new class of vectors with high pharmaceutical potential to deliver bioactive cargos into cells. Here, we characterized bLFcin6, a six amino acid peptide derived from bovine lactoferricin, as a CPP. Uptake of bLFcin6 was measured by flow cytometry. The ability to delivery siRNA was analyzed in HeLa cells. bLFcin6 exhibited concentration‐dependent uptake and intracellular distribution. Below 7.5 μm, uptake of bLFcin6 was significantly lower than uptake of TAT (P < 0.05) because bLFcin6 has fewer cationic amino acids. Compared to CPP5 (RLRWR) and CPP6 (PFVYLI), bLFcin6 had a significantly higher internalization ratio above 2.5 μm because it has two tryptophan residues. Uptake of bLFcin6 starts with an ionic cell‐surface interaction. It is then rapidly internalized by lipid raft‐dependent macropinocytosis, followed by release from macropinosomes into the cytosol and nucleus. Moreover, bLFcin6 formed stable electrostatic complexes with siRNA and delivered siRNA into cells, resulting in significant knockout activity at both the mRNA and protein levels. The knockout activity of siRNA delivered by bLFcin6 was similar to that mediated by TAT, although knockout by bLFcin6 required a higher molar ratio. In this study, bLFcin6 was tested for its ability to act as an siRNA‐delivering CPP.
A peptide derived from the C‐terminus of PB1 inhibits influenza virus replication by interfering with viral polymerase assembly

Efficient assembly of the influenza virus RNA‐dependent RNA polymerase, a heterotrimeric complex formed by three subunits (PA, PB1 and PB2) is critical for virus replication and pathogenicity. Therefore, interfering with the assembly of the RNA‐dependent RNA polymerase complex could offer novel and effective anti‐influenza therapeutics. In the present study, we show that a short peptide derived from amino acids 731–757 of PB1 (PB1731–757) can disrupt the interaction between the C‐terminal part of PB1 (denoted as PB1c corresponding to PB1676–757) and the N‐terminal part of PB2 (denoted as PB2n corresponding to PB21–40). We further show that PB1731–757 is capable of inhibiting viral polymerase activity and viral replication. Interestingly, we find that PB1731–757 interacts with PB1c rather than PB2n. Furthermore, mutational analyses show that the hydrophobic sites of PB1c play an essential role in the PB1c–PB1731–757 interaction. The characterization of the inhibitory effect of PB1731–757 on viral polymerase activity and viral replication could offer a potential target for anti‐influenza drug development.
Monocyte/macrophage interactions with myogenic precursor cells during skeletal muscle regeneration

Adult skeletal muscle has the remarkable property of regenerating after damage, owing to satellite cells and myogenic precursor cells becoming committed to adult myogenesis to rebuild the muscle. This process is accompanied by the continuing presence of macrophages, from the phagocytosis of damaged myofibres to the full re‐formation of new myofibres. In recent years, there has been huge progress in our understanding of the roles of macrophages during skeletal muscle regeneration, notably concerning their effects on myogenic precursor cells. Here, we review the most recent knowledge acquired on monocyte entry into damaged muscle, the various macrophage subpopulations, and their respective roles during the sequential phases of muscle repair. We also discuss the role of macrophages after exercise‐induced muscle damage, notably in humans.
Effect of the Expanded Program on Immunization Contact Method of data collection on health behaviors in Mali.

BACKGROUND The Expanded Program on Immunization Contact Method (EPI-CM) is a proposed monitoring and program management tool for developing countries. The method involves health workers tallying responses to questions about health behaviors during routine immunizations and providing targeted counseling. We evaluated whether asking caretakers about health behaviors during EPI visits led to changes in those behaviors. METHODS We worked in 2 districts in Mali: an intervention district where during immunization visits workers asked about 4 health behaviors related to bed net use, fever, respiratory disease, and diarrhea, and a control district where workers conducted routine immunization activities without health behavior questions. To evaluate the effect of EPI-CM, we conducted a cross-sectional household survey at baseline and 1 year postintervention. We used multivariate logistic regression to compare between districts the change over 1 year in 4 health behaviors: use of insecticide-treated nets, appropriate fever treatment, care-seeking for respiratory complaints, and appropriate diarrhea treatment. RESULTS There were no significant differences between the 2 districts in the change in the 4 health behaviors when controlling for age, sex, maternal education and occupation, immunization history, and wealth. CONCLUSIONS We found no evidence that EPI-CM increases healthy behaviors. Further evaluation of other potential benefits and costs of EPI-CM is warranted.
Aceptación del aprendizaje basado en problemas y de la evaluación entre pares por los estudiantes de medicina

RESUMEN Objetivo: Conocer el grado en el que los estudiantes aceptan y consideran utiles las tecnicas de aprendizaje basado en problemas (ABP) y de evaluacion entre pares. Analizar la asociacion entre el numero de casos clinicos de ABP revisados en el curso con la percepcion de los estudiantes acerca de su aprendizaje, en un modulo de los ciclos basicos de la carrera de medico cirujano. Metodos: Se aplico un cuestionario en forma anonima y voluntaria a 334 estudiantes de 12 grupos que cursaron un modulo predominantemente teorico del tercer ciclo de la carrera de medico cirujano en la Facultad de Estudios Superiores Iztacala, para evaluar su aceptacion y percepcion de la utilidad del ABP y de la evaluacion entre pares, despues de haber usado estas tecnicas durante el curso semestral. La opinion sobre el grado de utilidad del ABP, la percepcion del propio aprendizaje y el grado de aceptacion de la nocion de que las actividades de evaluacion entre pares son justas y formativas se midieron mediante escalas ordinales tipo Likert; la asociacion de estas variables con el numero de casos clinicos revisados en el semestre se analizo mediante el coeficiente de correlacion por rangos de Spearman. Resultados: La mayoria de los estudiantes considero que el metodo de ABP es util (82%) y que las actividades de evaluacion entre pares son justas y formativas (70%). Los estudiantes que revisaron un numero mayor de casos de ABP consideraron mas utiles las actividades de ABP (rho = 0.489, p  0.0001) y percibieron que habian tenido un mejor aprendizaje sobre inmunologia (rho = 0.200, p  0.0001). Conclusiones: Los resultados muestran una buena aceptacion del metodo de ABP y de la evaluacion entre pares por parte de los estudiantes. El numero de casos de ABP revisados durante el semestre correlaciono con que se consideraran utiles las actividades de ABP y con la percepcion de un mejor aprendizaje. Los resultados apoyan la aplicacion de las tecnicas de ABP y evaluacion entre pares en cursos futuros. Palabras clave: Educacion medica, aprendizaje basado en problemas, evaluacion entre pares.
Dental pulp progenitor-derived neuronal- and oligodendrocyte-like cells for spinal cord repair

Spinal cord regeneration following injury represents a major clinical challenge. Over recent years, stem cells have demonstrated promise for promoting spinal repair in the lab and in early stage clinical trials through functional replacement of neuronal and glial cells and through secondary trophic mechanisms to promote endogenous regeneration. Research has primarily focused on the use of embryonic tissue-derived stem cells of potentially limited therapeutic application due to related ethical concerns. The dental pulp harbours a source of easily accessible progenitor cells that have demonstrated early promise in improving functional outcome of experimental models of spinal cord injury via growth factor release. This thesis explores the potential of dental pulp progenitor cells (DPPCs) to promote spinal repair through direct cellular replacement. Progenitor cells isolated from murine incisors were found to express early stage neural and glial markers. Specific protocols were developed demonstrating the ability of DPPCs to differentiate in vitro into neuronal-like and oligodendrocyte-like cells with appropriate morphology and expression of mature markers. Electrophysiological testing revealed that DPPC-derived neuronal-like cells were of an immature non-functional phenotype. Undifferentiated DPPCs injected into an ex vivo spinal cord slice model showed signs of proliferation, migration and spontaneous differentiation within spinal tissue. DPPCs pre-differentiated into oligodendrocyte-like cells failed to survive transplantation but neuronally pre-differentiated cells survived, showing signs of integration into endogenous neuronal pathways. In a small scale pilot study, neuronally pre-differentiated DPPCs were transplanted into a clinically relevant in vivo model of spinal cord injury. DPPCs maintained expression of neuronal markers four weeks after grafting into the injured spinal cord. Axonal projections towards grafted cells and synaptic protein expression suggested possible integration into neuronal pathways, albeit without an associated statistical functional improvement. The results presented in this thesis provide a strong case for the potential of DPPCs to facilitate functional recovery through direct cell replacement mechanisms.
Host gene expression changes correlating with anti-HIV-1 effects in human subjects after treatment with peginterferon Alfa-2a.

We investigated whether interferon-inducible genes (IFIGs) with known anti-human immunodeficiency virus (HIV) activity in vitro were associated with in vivo virological response in HIV infection. Nine untreated HIV-1-infected volunteers were treated for 12 weeks with peginterferon alfa-2a. A subset of IFIGs (23 of 47) increased compared with baseline through 6 weeks beyond therapy, and 10 of the 23 IFIGs significantly inversely correlated (r = -0.7; P < .05) with virological response. The strength of peginterferon alfa-2a-induced IFIG response significantly correlated with declines in HIV load during treatment (r(2) = 0.87, p = . 003). This study links HIV virological response to a specific IFIG subset, a potential prognostic indicator in peginterferon alfa-2a-treated patients with HIV infection.
Impact of human immunodeficiency virus on the natural history of human papillomavirus genital infection in South African men and women.

BACKGROUND This study investigated genital human papillomavirus (HPV) incidence and clearance in 278 human immunodeficiency virus (HIV)-seropositive (HIV-positive) women, 208 HIV-negative women, 161 HIV-positive men, and 325 HIV-negative men, followed at 6-month intervals for up to 24 months. METHODS HPV types were determined by the Roche Reverse Linear Array HPV genotyping assay. RESULTS The rate of new HPV detection at the cervix and penis were 33.83 events/1000 person-months (95% confidence interval [CI], 26.39-43.46) and 55.68 events/1000 person-months (95% CI, 43.59-69.19), respectively. HIV infection was associated with increased risk of new HPV detection in women (relative risk [RR], 2.98; 95% CI, 2.07-4.29) and men (RR, 2.00; 95% CI, 1.49-2.69). The risk of new HPV detection increased in women (RR, 5.25; 95% CI, 3.52-7.81) and men (RR, 8.71; 95% CI, 6.19-12.24) when the sexual partner was infected with the same HPV type. The rate of clearing any HPV infection was 95.1 events/1000 person-months (95% CI, 83.3-108.1) in men and 66.9 events/1000 person-months (95% CI, 57.0-78.5) in women. HIV infection reduced the rate of HPV clearance in women (RR, 0.46; 95% CI, .34-.62) and men (RR, 0.71; 95% CI, .55-.93). CONCLUSIONS HIV infection increases the risk of new HPV detection and decreases the rate of HPV clearance in both women and men.
Molecular dynamics simulations of the interactions of medicinal plant extracts and drugs with lipid bilayer membranes

Several small drugs and medicinal plant extracts, such as the Indian spice extract curcumin, have a wide range of useful pharmacological properties that cannot be ascribed to binding to a single protein target alone. The lipid bilayer membrane is thought to mediate the effects of many such molecules directly via perturbation of the plasma membrane structure and dynamics, or indirectly by modulating transmembrane protein conformational equilibria. Furthermore, for bioavailability, drugs must interact with and eventually permeate the lipid bilayer barrier on the surface of cells. Biophysical studies of the interactions of drugs and plant extracts are therefore of interest. Molecular dynamics simulations, which can access time and length scales that are not simultaneously accessible by other experimental methods, are often used to obtain quantitative molecular and thermodynamic descriptions of these interactions, often with complementary biophysical measurements. This review considers recent molecular dynamics simulations of small drug‐like molecules with membranes, and provides a biophysical description of possible routes of membrane‐mediated pharmacological effects of drugs. The review is not exhaustive, and we focus on molecules containing aromatic ring‐like structures to develop our hypotheses. We also show that some drugs and anesthetics may have an effect on the lipid bilayer analogous to that of cholesterol.
An epidemiological study and risk factor analysis of irritable bowel syndrome in a Chinese naval force

Objective To investigate the prevalence and related factors of irritable bowel syndrome (IBS) in a Chinese navy unit according to Rome Ⅲ classification and diagnostic criteria. Methods The questionnaire survey based on Rome Ⅲ criteria was conducted in 8600 officers and soldiers in Chinese naval force using multistage, stratified, cluster random sampling method. The difference was compared in influence of the criteria on the diagnosis of IBS between Rome Ⅲ and Rome Ⅲ criteria. Analyses were performed for related influencing factors. Results The incidence of IBS meeting Rome Ⅲ criteria was 15.91% (1205/7574), and higher in female than in male (20.37% vs 15.73%, P=0.009), and most of them were in the 41-45 year age bracket (34.6%). Defecation difficulty, abdominal pain/discomfort and abdominal bloating were the main symptoms. Drinking, frequent drug-taking, history of dysentery, family history, and feeling of fatigue might be the most important risk factors (P<0.01). The incidence of IBS based on Rome Ⅱ criteria was significantly lower than that of Rome Ⅲ (1.75% vs 15.91%, P=0.000). Conclusion The incidence of IBS in Chinese naval force is high, and it should be highly regarded. Rome Ⅲ process gives a higher incidence of IBS compared with Rome Ⅱ.
A myogenic precursor cell that could contribute to regeneration in zebrafish and its similarity to the satellite cell

The cellular basis for mammalian muscle regeneration has been an area of intense investigation over recent decades. The consensus is that a specialized self‐renewing stem cell, termed the satellite cell, plays a major role during the process of regeneration in amniotes. How broadly this mechanism is deployed within the vertebrate phylogeny remains an open question. A lack of information on the role of cells analogous to the satellite cell in other vertebrate systems is even more unexpected given the fact that satellite cells were first designated in frogs. An intriguing aspect of this debate is that a number of amphibia and many fish species exhibit epimorphic regenerative processes in specific tissues, whereby regeneration occurs by the dedifferentiation of the damaged tissue, without deploying specialized stem cell populations analogous to satellite cells. Hence, it is feasible that a cellular process completely distinct from that deployed during mammalian muscle regeneration could operate in species capable of epimorphic regeneration. In this minireview, we examine the evidence for the broad phylogenetic distribution of satellite cells. We conclude that, in the vertebrates examined so far, epimorphosis does not appear to be deployed during muscle regeneration, and that analogous cells expressing similar marker genes to satellite cells appear to be deployed during the regenerative process. However, the functional definition of these cells as self‐renewing muscle stem cells remains a final hurdle to the definition of the satellite cell as a generic vertebrate cell type.
Prolonged myalgia in Sindbis virus infection: case description and in vitro infection of myotubes and myoblasts.

BACKGROUND Sindbis virus (SINV) is a mosquito-borne alphavirus found in Eurasia, Africa, and Oceania. Clinical SINV infection is characterized by febrile rash and arthritis and sometimes prolonged arthralgia and myalgia. The pathophysiological mechanisms of musculoskeletal and rheumatic disease caused by SINV are inadequately understood. METHODS We studied the muscle pathology of SINV infection ex vivo by examining a unique muscle biopsy obtained from a patient with chronic myalgia and arthralgia 6 months after acute SINV infection and assessed potential genetic predisposing factors by determining the human leukocyte antigen (HLA) and complement factor C4 genes and proteins. In addition, we performed in vitro SINV infections of primary human myoblasts and myotubes. RESULTS In the muscle biopsy we found evidence of muscle regeneration due to previous necrotic lesions likely caused by earlier SINV infection. We showed that human myoblasts and myotubes were susceptible in vitro for SINV infection as the cells became immunoreactive for viral antigens and cytopathic effect was observed. The patient was homozygous for HLA-B*35 alleles and heterozygous for HLA-DRB1*01 and HLA-DRB1*03 alleles and had total deficiency of C4B protein. CONCLUSIONS This study provides new insights concerning pathological processes leading to chronic symptoms in SINV infection and demonstrates for the first time the susceptibility of human myogenic cells to SINV infection.