Miracle-dz/UniFAR-FTUs huggingface dataset:
Herpes Simplex Virus Type 1 Evades the Effects of Antibody and Complement In Vivo

ABSTRACT Herpes simplex virus type 1 (HSV-1) encodes a complement-interacting glycoprotein, gC, and an immunoglobulin G (IgG) Fc binding glycoprotein, gE, that mediate immune evasion by affecting multiple aspects of innate and acquired immunity, including interfering with complement components C1q, C3, C5, and properdin and blocking antibody-dependent cellular cytotoxicity. Previous studies evaluated the individual contributions of gC and gE to immune evasion. Experiments in a murine model that examines the combined effects of gC and gE immune evasion on pathogenesis are now reported. Virulence of wild-type HSV-1 is compared with mutant viruses defective in gC-mediated C3 binding, gE-mediated IgG Fc binding, or both immune evasion activities. Eliminating both activities greatly increased susceptibility of HSV-1 to antibody and complement neutralization in vitro and markedly reduced virulence in vivo as measured by disease scores, virus titers, and mortality. Studies with C3 knockout mice indicated that other activities attributed to these glycoproteins, such as gC-mediated virus attachment to heparan sulfate or gE-mediated cell-to-cell spread, do not account for the reduced virulence of mutant viruses. The results support the importance of gC and gE immune evasion in vivo and suggest potential new targets for prevention and treatment of HSV disease.
Diagnostic and Prognostic Values of Single Photon Emission Computed Tomography in Neuropsychiatric Manifestations of Systemic Lupus Erythematosus : An Egyptian Study

Although systemic lupus erythematosus (SLE) with involvement of central nervous system (CNS), which is often called neuropsychiatric SLE (NPSLE), is one of the most important manifestations of SLE, yet there is no single test to date that serves as the gold standard for its diagnosis. So, the aim of this work was to study the diagnostic value of SPECT in CNS affection in SLE patients as well as to study its prognostic value in these patients. Also, we set out to study the role of prolactin and anti-ribosomal antibodies (anti-P) in CNS affection in SLE patients. Moreover, we aimed to detect the possible relationship between findings using SPECT and the different disease parameters. We studied 30 Egyptian SLE female patients diagnosed according to the American College of Rheumatology (ACR) criteria for the classification of SLE (1999). Ten normal healthy subjects were also included as a control group. SLE patients were categorized into 3 groups: Group I with major NPSLE (n=7); Group II with only minor NPSLE (n=3); and Group Ill without NPSLE (n=20). They had undergone physical as well as neurological history and examination; followed by assessment of disease activity using SLE Disease Activity Index (SLEDAI). Assessment for psychiatric morbidity using General Health Questionnaire (GHQ), followed by ICD-10 Symptom Checklist for those exceeding the cutoff point on the GHQ. Then they were psychometrically assessed using Beck Depression Inventory (BDI), Hamilton Anxiety Scale (HAS), and Wechsler Memory Scale (WMS). Also, they had undergone laboratory investigations including prolactin and anti-ribosomal antibodies (anti-P); EEG; CT; as well as SPECT. On the other hand, controls were subjected to GHQ to ensure that they were free from psychiatric morbidity, laboratory investigations, and SPECT. Abnormal SPECT scan was found in 83% of group I as compared to 33% of group II. However, normal SPECT scan was found in 72% of group III and in 100% of the control group. Moreover, prolactin and anti-P antibody level were the only disease parameters that showed a significant association with cerebral hypoperfusion detected on SPECT. It was also found that SPECT findings were correlated with changes that occur within the six months follow-up period in neuropsychiatric symptoms as well as with follow-up SPECT findings. So, it might be promising as a prognostic tool in NPSLE. These results confirm that SPECT is a sensitive tool both for the diagnosis as well as the prognosis of CNS involvement in SLE.
Determining the Tumorigenicity of Dental Materials

It has been known for more than a hundred years that certain arsenicals can induce cancer. Literally hundreds of carcinogens have since been recognized. In the early 1930's chromates and nickel carbonyl in metal refineries and asbestos were indicted as carcinogens, prompting a surge of interest in industrial medicine. In recent years, experimental studies involving connective tissue implants of various solids, e.g., films, foils, or powders, and injected liquids, and inhalation tests of many materials have resulted in the development of malignant neoplasms in a variety of animals, including mice, rats, rabbits, dogs, and guinea pigs. ' Since 1942 the following metals have been used to induce experimental sarcomas: beryllium, selenium, chromium, cobalt, nickel, gold, silver, platinum, and alloys such as vitallium, tantalum, and stainless steel. Most of the tumors developing around such implants, after many months, have been fibrosarcomas; but other forms such as rhabdomyo-, osteo-, lipo-, and reticulum-cell sarcomas have also occurred, sometimes depending on the anatomical site of the implant.2 Likewise, since 1948, more than a dozen different plastic materials have been shown to induce sarcoma when implanted in rats or mice.3 In 1954 a study of methyl methacrylate (acrylic resin) demonstrated that small disks of this dental material implanted subdermally in mice resulted in the formation of sarcomas in 25 per cent of the animals which survived for 469 days.4 One might gain the impression that any material implanted in rodents would cause sarcomas after long periods of time; however, the following materials have been so tested without demonstrating a tumorigenic effect: fiberglass, cotton, paraffin, wood, mica, glass, fetal fingernails (keratin), and a number of metal foils.3 The clinical practice of imbedding metals as substitutes for lost bone due to trauma or surgical excision was not used on a large scale until the years of World War I. Most metallic and plastic implants of this nature have been placed more recently, during and after World War II. Little is known regarding tumorigenesis associated with such implants in human beings.5 Because of the increasing popularity of implantation techniques in dentistry (e.g., implant dentures, magnets, materials implanted for fracture fixation, metals placed in root apexes after endodontic procedures), the possible tumorigenic qualities of these materials after long periods of time must be considered.
Associations Between Diurnal Changes in Goldmann Tonometry, Corneal Geometry, and Ocular Response Analyzer Parameters

Purpose: To investigate the possible covariations between diurnal changes in Goldmann applanation tonometry (GAT) estimates of intraocular pressure (IOP), central corneal thickness (CCT), central corneal radius, and ocular response analyzer measures of corneal hysteresis and corneal resistance factor (CRF). Methods: Twenty-five healthy normal subjects (age, 21 ± 2 years) had central corneal radius, ocular response analyzer, GAT, and CCT measurements performed in 1 eye at multiple times for more than 24 hours. Measurements were taken at 17:00 and repeated every 2 hours until 23:00. Subjects then slept uninterrupted overnight for approximately 8 hours. On awakening, readings were taken at a 20-minute frequency from 7:00 to 9:00 inclusive, followed by 2 hourly intervals until 17:00. Results: The maximum variation in GAT for more than 24 hours was 2.5 mm Hg, and these fluctuations were predicted by the diurnal variations of CCT (0.37 mm Hg &Dgr;GAT/10 &mgr;m CCT, P < 0.01) and CRF (0.68 mm Hg &Dgr;GAT/mm Hg CRF, P < 0.01). The diurnal changes in corneal hysteresis and CRF both covaried with those of CCT (0.16 and 0.30 mm Hg/10 &mgr;m &Dgr;CCT, respectively, both Ps < 0.01). None of these associations was statistically different during and after the nominal period of resolution from overnight corneal swelling (2-way interactions, all Ps > 0.05). Conclusions: If the IOP is assumed to be independent of corneal parameters, the clinically significant 24-hour variation in GAT being partially predicted by the changes in CCT and CRF suggests that the diurnal variation in corneal parameters affects tonometry measurements. CRF may also be dependent on the level of IOP.
Activation of annexin A1 signalling in renal fibroblasts exerts antifibrotic effects

The anti‐inflammatory protein annexin A1 (AnxA1) and its formyl peptide receptor 2 (FPR2) have protective effects in organ fibrosis. Their role in chronic kidney disease (CKD) has not yet been elucidated. Our aim was to characterize the AnxA1/FPR2 system in models of renal fibrosis.
Modeling time-series with deep networks

Electronic nose (e-nose) data represents multivariate time-series from an array of chemical gas sensors exposed to a gas. This data is a new data set for usewith deep learning methods, and is highly suitable since e-nose data is complexand difficult to interpret for human experts. Furthermore, this data set presentsa number of interesting challenges for deep learning architectures per se. In this work we present a first study of e-nose data classification using deep learningwhen testing for the presence of bacteria in blood and agar solutions. We showin this study that deep learning outperforms hand-selected strategy based methods which has been previously tried with the same data set.
Final results of a phase II randomized trial of neoadjuvant anthracycline-taxane chemotherapy plus lapatinib, trastuzumab, or both in HER2-positive breast cancer (CHER-LOB trial).

507 Background: This is a randomized phase II trial of preoperative taxane-anthracycline in combination with trastuzumab, lapatinib, or combined trastuzumab and lapatinib in HER2 positive, stage II-IIIA breast cancer patients. Primary aim of the study is the percentage pathological complete response (pCR), defined as complete disappearance of invasive tumor in breast and axillary nodes. METHODS chemotherapy (CT) consists of weekly paclitaxel x 12 followed by FE75C x 4. Pts randomized to arm A receive CT plus weekly trastuzumab; in arm B pts receive CT plus lapatinib 1250 mg po daily; in arm C pts receive CT plus weekly trastuzumab and lapatinib 750 mg po daily. The study sample size has been calculated according to the two-step Simon's design. The overall planned accrual was 120 pts. P95HER2 expression will be measured by bioTheranostics, Inc (San Diego) to explore if there is a clinically relevant difference in the pCR rate according to p-95 status. Gene expression profile analysis to identify a predictive signature is ongoing. RESULTS 121 pts have been randomized as of November 2010. Pts characteristics are the following: median age 49 yrs (26-68 yrs); stage IIA 32%, IIB 50%; IIIA 18%; ER and or PgR positivity: 59%. Eighty pts have completed surgery and are evaluable for response: 50 pts (62.5%) received breast conservation (BCS). A conversion from mastectomy to BCS was observed in 23/44 pts initially candidate to mastectomy (conversion rate: 52%). The pCR rate is 36.2% (28% in arm A, 32% in arm B, and 48% in arm C). By using a 30% cutoff for p95 positivity, in a preliminary analysis on 48 cases, 57% resulted as p-95 positive. In this preliminary analysis, the pCR rate in 15 trastuzumab treated pts is 86% in p-95-negative and 13% in p-95-positive cases. Mean Left ventricular ejection fraction (range) at baseline was 62% (52%-77%), 61% (44%-78%) after 12-13 weeks, and 61% (44%-74%) at the end of therapy. No patient had symptomatic cardiac events. CONCLUSIONS Preliminary activity data are promising, and cardiac safety data are reassuring. Final results per treatment arm, along with definitive biomarker correlations will be presented at the meeting.
Risk factors for domestic sporadic campylobacteriosis among young children in Sweden

A case-control study was conducted in Sweden to study risk factors for domestically acquired Campylobacter jejuni/coli infections among children aged less than 6 y. A total of 126 cases, reported to the national surveillance system were recruited over 1 y. Controls, selected from the population register, were matched to the cases by age, gender, place of residence and time of infection of the case. Information was gathered by posted questionnaires. Two separate conditional regression models were developed including and excluding ‘protective’ factors. Two of the factors significantly associated with Campylobacter infection were water-related: having a well in the household (OR=2.6) and drinking water from a lake/river (OR=7.4; 6.0). Other exposures associated with increased risk were: having a dog (OR=8.4; 3.8) and eating grilled meat (OR=5.5; 2.1). Drinking unpasteurized milk was borderline significant in 1 model (OR=3.7). Eating sausage was protective (OR=0.05). Eating chicken was not a significant risk. Exposures such as eating grilled meat and drinking water from a lake or a river were more common in the warm months, a factor that may partly explain the observed seasonality. The authors suggest that differences between risk factors across studies may reflect geographical and age-specific differences in the sources of infection.
Thrombocytopenia and prognosis in intensive care

Objective To study the incidence and prognosis of thrombocytopenia in adult intensive care unit (ICU) patients. Design Prospective observational cohort study. Setting The medical ICU of a university hospital and the combined medical-surgical ICU of a regional hospital. Patients All patients consecutively admitted during a 5-month period. Interventions Patient surveillance and data collection. Measurements and Main Results The primary outcome measure was ICU mortality. Data of 329 patients were analyzed. Overall ICU mortality rate was 19.5%. A total of 136 patients (41.3%) had at least one platelet count <150 × 109/L. These patients had higher Multiple Organ Dysfunction Score (MODS), Simplified Acute Physiology Score (SAPS) II, and Acute Physiology and Chronic Health Evaluation (APACHE) II scores at admission, longer ICU stay (8 [4–16] days vs. 5 [2–9] days) (median [interquartile range]), and higher ICU mortality (crude odds ratio [OR], 5.0; 95% confidence interval [CI], 2.7–9.1) and hospital mortality than patients with daily platelet counts >150 × 109/L (p < .0005 for all comparisons). Bleeding incidence rose from 4.1% in nonthrombocytopenic patients to 21.4% in patients with minimal platelet counts between 101 × 109/L and 149 × 109/L (p = .0002) and to 52.6% in patients with minimal platelet counts <100 × 109/L (p < .0001). In all quartiles of admission APACHE II and SAPS II scores, a nadir platelet count <150 × 109/L was related with a substantially poorer vital prognosis. Similarly, a drop in platelet count to ≤50% of admission was associated with higher death rates (OR, 6.0; 95% CI, 3.0–12.0;p < .0001). In a logistic regression analysis with ICU mortality as the dependent variable, the occurrence of thrombocytopenia had more explanatory power than admission variables, including APACHE II, SAPS II, and MODS scores (adjusted OR, 4.2; 95% CI, 1.8–10.2). Conclusions Thrombocytopenia is common in ICUs and constitutes a simple and readily available risk marker for mortality, independent of and complementary to established severity of disease indices. Both a low nadir platelet count and a large fall of platelet count predict a poor vital outcome in adult ICU patients.
Transplantation of bone marrow genetically engineered to express proinsulin II protects against autoimmune insulitis in NOD mice

Type 1 diabetes (T1D) is a T‐cell‐dependent autoimmune disease resulting from destructive inflammation (insulitis) of the insulin‐producing pancreatic β‐cells. Transgenic expression of proinsulin II by a MHC class II promoter or transfer of bone marrow from these transgenic mice protects NOD mice from insulitis and diabetes. We assessed the feasibility of gene therapy in the NOD mouse as an approach to treat T1D by ex vivo genetic manipulation of normal hematopoietic stem cells (HSCs) with proinsulin II followed by transfer to recipient mice.
Enterococcus faecalis Resistant to Linezolid: Case Series and Review of the Literature

Reports of linezolid resistance among Enterococcus faecalis have been relatively rare. We describe three patients with linezolid‐resistant strains of E. faecalis, discovered after the patients had received long courses (> 30 days) of linezolid therapy. All strains contained the G2576U mutation in 23S rRNA. A literature review revealed one other case in the United States and three cases in Europe; all involved patients who had received long courses of therapy. It appears that recent or extended linezolid therapy may be a risk factor for development of resistant E. faecalis. In patients who have recently been treated with linezolid and have an identified new systemic enterococcal isolate, linezolid sensitivity should be verified as soon as possible to guide therapy. This strategy also should be considered for patients with a breakthrough enterococcal isolate during linezolid therapy.
Changes in Motor Strategies Across Age Performing a Longswing on the High Bar

Purpose: Improvements in motor performance and coordination may be impacted by the interaction of practice and organismic constraints. It has been proposed that these aspects of motor learning are achieved at a different time rate: first, during placement of the events (performance), and second, segmental spatiotemporal relationships (coordination). We focused on the acquisition of the longswing in high bar as one basic skill in gymnastics. The aim of this study was to determine how longswing performance and coordination change to increase swing amplitude as age and expertise increase. Method: One hundred and thirteen male gymnasts were classified into 5 distinct age groups (G1, G2, G3, G4, and G5) on the basis of the national competition rules. Longswing performance (swing amplitude and event placements) and coordination (positive and negative areas in the continuous relative phase) were measured for each group. Results: Analyses of variance revealed that the adequate placement and coordination of the earlier events were achieved in younger groups (G1, G2), while later events and their coordination were accomplished by the older groups (G3 through G5). Conclusion: Our results suggested that the process of longswing acquisition, as age and expertise increase, follows a progression parallel to the temporal occurrence of the task events, instead of the proposed learning sequence of event placement first and then coordination.
Cervical cancer risk perception and predictors of human papilloma virus vaccine acceptance among female university students in northern Nigeria

Cancer of the cervix is the most common cancer and the leading cause of cancer mortality among women in sub-Saharan Africa. Although a vaccine against human papilloma virus (HPV) is now available, its acceptance among vulnerable women in developing countries islargely unexplored. We studied cervical cancer awareness and HPV vaccine acceptance among 375 female university students in northern Nigeria. A total of 133 participants knew of HPV (35.5%), 202 (53.9%) had heard of cervical carcinoma and 277 (74.0%) were willing to accept HPV vaccination. After adjusting for potential confounders, age (adjusted odds ratio (AOR) = 2.3, 95% confidence interval (CI), 1.47–6.53); medical education (AOR = 3.4, 95% CI, 1.74–6.93); HPV knowledge (AOR = 1.8, 95% CI, 1.38–5.41) and awareness of cervical cancer (AOR = 2.3, 95% CI, 1.52–5.06) were significant predictors of readiness to accept HPV vaccine. Public health education and appropriate communication strategies should be implemented in advance of large scale vaccine introduction to increase awareness and prevent misconceptions about the HPV vaccine.
Changes in the optic disc excavation of children affected by cerebral visual impairment: a tomographic analysis.

PURPOSE To obtain quantitative data on the optic disc excavation in children affected by cerebral visual impairment (CVI) by using the Heidelberg Retinal Tomograph (HRT)-II (Heidelberg Engineering, Heidelberg, Germany). METHODS A total of 24 subjects affected by CVI (mean age, 7.28 years) were examined: 16 in alert conditions and 8 under general anesthesia. The following parameters of the optic nerve head were examined: disc area, cup area, rim area, cup volume, rim volume, cup-to-disc area ratio, mean cup depth, maximum cup depth, cup shape measure, and mean retinal nerve fiber layer (RNFL) thickness. The tomographic results in children with CVI were compared with those of 88 normal, alert subjects of similar age. RESULTS The optic disc of patients with CVI appeared smaller than normal. Its excavation, however, was more pronounced. Several tomographic parameters were altered in CVI-affected subjects. Statistical analysis showed a highly significant probability in cup-to-disc area ratio (P < 0.01, both eyes), rim area (P < 0.01, both eyes), cup shape measure (P < 0.01, right eye; P < 0.01, left eye), and mean RNFL thickness (P < 0.01, right eye; P < 0.01, left eye). A novel observation was temporal atrophy of the optic nerve head in CVI. CONCLUSIONS The data provide a tridimensional, objective evaluation of the anatomic alterations of the optic nerve head in children with CVI. Furthermore, tomographic standards for optic disc shape in normal children are set for the first time.
Characterization of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Trafficking Reveals a Novel Lysosomal Targeting Mechanism via Amyloid Precursor-like Protein 2 (APLP2)

Background: PCSK9 functions to degrade the LDLR by a previously unknown lysosomal sorting mechanism. Results: Here, we discovered and characterized a novel, pH-dependent interaction between PCSK9 and the amyloid precursor-like protein 2 (APLP2). Conclusion: APLP2 plays an integral role in postendocytic PCSK9 lysosomal sorting. Significance: These findings provide key insights into the mechanism by which PCSK9 degrades LDLR and reveal a novel lysosomal transport complex. Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates low density lipoprotein receptor protein levels by diverting it to lysosomes. Monoclonal antibody therapeutics aimed to neutralize PCSK9 have been shown to successfully lower serum LDL levels; however, we previously found that such therapeutic antibodies are subject to PCSK9-mediated clearance. In this study, we discovered that PCSK9 interacts via its C-terminal domain directly and in a pH-dependent manner with amyloid precursor protein as well as its closely related family member, amyloid precursor protein-like protein 2. Furthermore, we determined that amyloid precursor protein-like protein-2, but not amyloid precursor protein, is involved in mediating postendocytic delivery of PCSK9 to lysosomes and is therefore important for PCSK9 function. Based on our data, we propose a model for a lysosomal transport complex by which a soluble protein can target another protein for degradation from the luminal side of the membrane by bridging it to a lysosomally targeted transmembrane protein.