Miracle-dz/UniFAR-FTUs huggingface dataset:
Human papillomavirus genotype distribution in anal cancer in France: The EDiTH V study

Anal cancer is a rare cancer but its incidence is increasing. Human papillomavirus (HPV) infection seems to be associated with the occurrence of most cases. The genotype‐specific prevalence of HPV in anal cancer was estimated to assess the potential benefit of HPV vaccination in France. Anal cancer histological specimens were retrospectively recruited in 2008 from 16 French centres and centrally tested for HPV genotyping using the INNO‐LiPA assay allowing the detection of 28 genotypes. Results were analyzed according to age, gender, HIV status when available and histological diagnosis. A total of 366 anal cancer cases were analyzed among which 62% were females. Mean age at diagnosis was 54.8 years in males and 66.4 years in females (p < 0.001). HPV was found in 96.7% of cases, 72% being infected by a single HPV type. Presence of at least one high‐risk genotype was observed in 91% of cases (96% in females and 83% in males; p < 0.001). HPV16 was by far the most prevalent genotype (75%), followed by HPV18, HPV52, HPV33, and HPV51 (4–6%). HPV16/18 alone or in association were found in 78% of all cases. HIV‐positive cases had a higher proportion of multiple HPV infection than HIV‐negative cases and a slightly different HPV type distribution with an under‐representation of HPV16 and an over‐representation of other types. Our results indicate that anal cancer rarely occurs in the absence of HPV and emphasize the predominant role of HPV16. The potential benefit of HPV vaccine on the occurrence of anal cancer should be further evaluated.
New observations on CD8 cell responses.

Most HIV vaccine development programs target the induction of strong, broad, high-affinity HIV-specific CD8 T-cell responses directed against several HIV antigens. Over the past year, some initial immunogenicity results were reported from human trials. In the first preventative HIV vaccine study to be carried out in Africa, 40 HIV-seronegative Ugandan volunteers were randomly assigned to receive a canarypox vector containing HIV-1 clade B (env and gag-pro) antigens (ALVAC-HIV), control vector containing the rabies virus glycoprotein G gene, or saline placebo. Cytotoxic T lymphocyte (CTL) activity against target cells expressing clade A, B, and D antigens was assessed using chromium-release and enzyme-linked immunospot (ELISPOT) assays. Twenty per cent of vaccine recipients generated detectable cytolytic responses to either Gag or Env, and 45% had vaccine-induced HIVspecific CD8 T-cell responses, as measured using the ELISPOT assay. Although the immunogenicity of this clade B-based vaccine was low, ALVAC-HIV elicited CD8 T-cell responses with detectable cross-reactivity against clade A and D antigens in a significant proportion of vaccine recipients [1]. In another study using ALVAC-HIV vaccine with or without rgp120/SF-2 [2], HIV-1-specific CTL were detected in the blood of 71% and, importantly, in the rectum of 57% of the volunteers. This shows that parenteral administration of this vaccine candidate can lead to the presence of HIVspecific T cells at a mucosal site. Over the next year anticipated results from trials involving adenovirus vectors and modified vaccine Ankara will be announced. Other recent reports of early phase candidate vaccines are not so promising. In one study of a DNA vaccine [3], no CD8 T-cell responses were generated in human volunteers. Therapeutic immunization approaches are also currently under active development, and new information on the role of different antigen presenting cells may lead to better immunogenicity. In one study, plasmacytoid dendritic cells were able to activate influenzaspecific T cells in vitro. Plasmacytoid dendritic cells were compared with CD11c+ dendritic cells, the most potent antigen-presenting cells, for their capacity to activate T-cell responses. After influenza virus exposure, both dendritic cell types showed an equivalent efficiency to expand anti-influenza virus CTL [4]. Other agents that could be used to potentiate virusspecific CD8 T cells are under active investigation. Over the past year, it was reported that thalidomide analogues have potent co-stimulatory activity for virusspecific CD8 T cells, and thus could help function as a novel immune-adjuvant therapy [5]. In addition, structured treatment interruption was shown in a large Swiss Spanish study to boost HIV-specific CD8 T-cell responses [6].
Secure file storage and retrieval in cloud

Security in cloud storage is an important aspect of cloud computing. In this paper, a novel multi-level encryption scheme which ensures security in cloud is introduced. In this scheme, a modified RSA MRSA key generation algorithm is used to generate the phase keys. The file is first subjected to encryption using MRSA with phase public keys. For secure transmission, a modified Vernam cipher MVC is applied to the file and stored in the cloud. Upon request, the file is obtained by applying inverse MVC followed by MRSA decryption using the phase private keys. This scheme was tested on different types of input files. The proposed algorithms protect the system from brute force attack. The MRSA's computational time is significantly less compared to the traditional RSA algorithm. Frequency and spectral analysis proves that MVC is strong and effective. Thus the new scheme ensures both confidentiality and integrity.
Impact of the NREGS on Children’s Intellectual Human Capital

Abstract This paper uses panel data from the Young Lives Survey to examine the effect of the world’s largest public works program and India’s flagship social protection program, the National Rural Employment Guarantee Scheme (NREGS), on children’s learning outcomes such as grade progression, reading comprehension test scores, writing test scores, math test scores, and Peabody Picture Vocabulary Test (PPVT) scores. We find that the program has strong positive effects on these outcomes in both the short-and-medium run. Finally, the impact estimates reported here are robust to a number of econometric concerns such as – program placement, selective attrition, and type I error.
Case report and seeded blood culture study of Brucella bacteremia

Diagnosis of brucellosis requires prompt detection and identification of the coccobacillus for appropriate patient management, as the organism is associated with a potentially severe outcome. In a recent experience, an 18-year-old migrant farm worker presented at a local hospital with nonspecific symptoms. A significant Brucella titer of 2,560 was followed by the recovery of a gram-negative coccobacillus, subsequently identified as Brucella abortus, from subcultured 5-day-old BACTEC NR730 negative blood cultures. The organism proved to be susceptible to a variety of antimicrobial agents and resistant to nitrofurantoin. The patient was administered antimicrobial therapy for Brucella spp. consisting of tetracycline and streptomycin for 21 days. During the course of therapy the patient experienced defervescence and was discharged with the recommendation for periodic follow-up examinations. Seeded culture studies of this isolate with fresh human blood and target inocula of 5 and 500 CFU/ml indicated that the larger (500-CFU/ml) inoculum produced positive instrument detection within 2 days, whereas the smaller (5-CFU/ml) inoculum required 5.5 to 7.5 days for detection, depending on the medium used. These findings underscore the potential for Brucella bacteremia to escape instrument detection given a low bacterial inoculum.
Gait analysis and functional outcomes following ankle arthrodesis for isolated ankle arthritis.

BACKGROUND The functional outcomes following ankle arthrodesis are not known. The purpose of the present study was to compare the intermediate-term clinical results for a group of patients in whom an ankle arthrodesis had been performed with use of modern surgical techniques with the findings for a group of healthy gender and age-matched controls on the basis of validated outcome measures and gait analysis. METHODS Twenty-six patients who had undergone ankle arthrodesis for the treatment of isolated unilateral ankle arthritis were identified and retrospectively assessed clinically and radiographically. The mean age at the time of surgery was fifty-four years, and the mean interval between surgery and assessment was forty-four months. A gender and age-matched control group of twenty-seven individuals was recruited for comparison. All subjects were evaluated with gait analysis, the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot scale, the Musculoskeletal Outcomes Data Evaluation and Management Systems (MODEMS) questionnaire, and the Ankle Osteoarthritis Scale (AOS). RESULTS On preliminary review, twenty of the twenty-six patients were completely satisfied or satisfied with their surgical outcome. All patients but one stated that they would undergo the surgery again. Five patients stated that they did not notice a gait abnormality. Twelve patients wore orthotics, and all believed that the use of the orthotics improved their gait. When the functional outcome scores in the arthrodesis group were compared with those in the control group, specific scores assessing hindfoot pain and satisfaction were similar. However, scores focusing on ankle-hindfoot function and disability revealed significant differences. Gait analysis also identified significant differences between the two groups with regard to cadence and stride length. In addition, there was significantly decreased sagittal, coronal, and transverse range of motion of the hindfoot and midfoot during the stance and swing phases of gait in the arthrodesis group. Radiographic review demonstrated that four of the twenty-six patients had development of moderate to severe arthritis of the subtalar joint. CONCLUSIONS In the intermediate term following an arthrodesis for the treatment of end-stage ankle arthritis, pain is reliably relieved and there is good patient satisfaction. However, there are substantial differences between patients and the normal population with regard to hindfoot function and gait. On the basis of these results, patients should be counseled that an ankle fusion will help to relieve pain and to improve overall function; however, it is a salvage procedure that will cause persistent alterations in gait with a potential for deterioration due to the development of ipsilateral hindfoot arthritis.
Biochemical abnormalities in Huntington's chorea brains

The enzymes glutamic acid decarboxylase, choline acetylase, and succinate dehydrogenase were reduced by 74 to 93 percent in striatum of brains from three patients who died with long-standing Huntington's chorea. Little change was found in acetylcholinesterase or monoamine oxidase activities. In an early case of this disease in a fourth patient, there were no enzymatic changes. A high-molecular-weight soluble protein was present in the striatum of the advanced cases but membrane protein patterns did not differ from those of controls.
Ischemia-Induced Brain Damage Depends on Specific Gap-Junctional Coupling

Ischemic brain injury results in neuronal loss and associated neurologic deficits. Although there is some evidence that intercellular communication via gap junctions can spread oxidative cell injury, the possible role of gap-junctional communication in ischemia-induced cell death is the object of debate. Because gap junctions directly connect the cytoplasms of coupled cells, they offer a way to propagate stress signals from cell to cell. The authors investigated the contribution of gap-junctional communication to cell death using an in vitro ischemia model, which was reproduced by submersion of organotypic hippocampal slices into glucose-free deoxygenated medium. The gap-junctional blocker carbenoxolone significantly decreased the spread of cell death, as measured by propidium iodide staining, over a 48-hour period after the ischemic episode. Carbenoxolone ameliorated the hypoxia-induced impairment of the intrinsic neuronal electrophysiologic characteristics, as measured by whole-cell patch clamp recordings. To determine whether specific connexins were involved in the spread of postischemic cell death, the authors partially reduced the synthesis of specific connexins using antisense oligodeoxynucleotides. Simultaneous knockdown of two connexins localized mostly in neurons, connexins 32 and 26, resulted in significant neuroprotection 48 hours after the hypoxic– hypoglycemic episode. Similarly, partial reduction of the predominant glial connexin 43 significantly decreased cell death. These results indicate that gap-junctional communication contributes to the propagation of hypoxic injury and that specific gap junctions could be a novel target to reduce brain damage.
Common polymorphisms of the growth hormone (GH) receptor do not correlate with the growth response to exogenous recombinant human GH in GH-deficient children.

CONTEXT GH acts through the GH receptor (GHR), whose polymorphisms might affect the growth response to recombinant human GH (rhGH). OBJECTIVE The objective of this study was to investigate possible influences of GHR polymorphisms on the growth response to rhGH in GH-deficient (GHD) children. DESIGN This was a 2-yr study (first year, spontaneous growth; second year, growth during rhGH treatment). SETTING This study was performed at a referral center. PATIENTS Fifty-four prepubertal GHD children (11 females; mean age, 7.8 yr; sd, 3.96) were studied. INTERVENTION Patients were treated with rhGH (0.2 mg/kg.wk) for at least 1 yr after diagnosis. Growth velocity (GV) was measured 1 yr before treatment and during the first treatment year. GHR exons were amplified by PCR using pairs of intronic primers. The presence of single or multiple mismatches in the PCR products was revealed by denaturing high-pressure liquid chromatography. For exons in which mismatches were found by denaturing high-pressure liquid chromatography, direct sequencing was performed by automatic sequencer. MAIN OUTCOME MEASURES Before the start of treatment, the mean height (Ht) sd score was -1.93 (sd, 0.70), and the mean GV sd score was -1.49 (sd, 1.26). RESULTS The posttreatment (first 12 months) mean GV sd score was 3.55 (sd, 3.27). Molecular analysis revealed a high frequency of GHR polymorphisms; in particular: exon 3 deletion (Del 3) in 26 subjects (48%), polymorphism 504 A>G at codon 168 of exon 6 in 44 (82%), and polymorphism 1576 A>C at codon 526 of exon 10 in 35 (65%). In most patients, these different polymorphisms recurred in association. We found no significant differences in GV between the groups of subjects defined by the polymorphic genotypes. CONCLUSION The most common GHR polymorphisms, alone or in association, do not appear to affect the growth response to rhGH in GHD children.
Cepharanthine hydrochloride reverses the mdr1 (P-glycoprotein)-mediated esophageal squamous cell carcinoma cell cisplatin resistance through JNK and p53 signals

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy that is often resistant to therapy. Nowadays, chemotherapy is still one of the main methods for the treatment of ESCC. However, the multidrug resistance (MDR)-mediated chemotherapy resistance is one of the leading causes of death. Exploring agents able to reverse MDR, which thereby increase the sensitivity with clinical first-line chemotherapy drugs, could significantly improve cancer treatment. Cepharanthine hydrochloride (CEH) has the ability to reverse the MDR in ESCC and the mechanism involved have not been reported. The aim of the study was to investigate the potential of CEH to sensitize chemotherapeutic drugs in ESCC and explore the underlying mechanisms by in vitro and in vivo studies. Our data demonstrated that CEH significantly inhibited ESCC cell proliferation in a dose-dependent manner, induced G2/M phase cell cycle arrest and apoptosis, and increased the sensitivity of cell lines resistant to cisplatin (cDDP). Mechanistically, CEH inhibited ESCC cell growth and induced apoptosis through activation of c-Jun, thereby inhibiting the expression of P-gp, and enhancing p21 expression via activation of the p53 signaling pathway. In this study, we observed that growth of xenograft tumors derived from ESCC cell lines in nude mice was also significantly inhibited by combination therapy. To our knowledge, we demonstrate for the first time that CEH is a potentially effective MDR reversal agent for ESCC, based on downregulation of the mRNA expression of MDR1 and P-gp. Together, these results reveal emphasize CEH putative role as a resistance reversal agent for ESCC.
In Vivo Analysis of Human T-Cell Leukemia Virus Type 1 Reverse Transcription Accuracy

ABSTRACT Several studies have indicated that the genetic diversity of human T-cell leukemia virus type 1 (HTLV-1), a virus associated with adult T-cell leukemia, is significantly lower than that of other retroviruses, including that of human immunodeficiency virus type 1 (HIV-1). To test whether HTLV-1 variation is lower than other retroviruses, a tractable vector system has been developed to measure reverse transcription accuracy in one round of HTLV-1 replication. This system consists of a HTLV-1 vector that contains a cassette with the neomycin phosphotransferase (neo) gene, a bacterial origin of DNA replication, and the lacZα peptide gene region (the mutational target). The vector was replicated bytrans-complementation with helper plasmids. The in vivo mutation rate for HTLV-1 was determined to be 7 × 10−6 mutations per target base pair per replication cycle. The majority of the mutations identified were base substitution mutations, namely, G-to-A and C-to-T transitions, frameshift mutations, and deletion mutations. Mutation of the methionine residue in the conserved YMDD motif of the HTLV-1 reverse transcriptase to either alanine or valine (i.e., M188A or M188V) led to a factor of two increase in the rate of mutation, indicating the role of this motif in enzyme accuracy. The HTLV-1 in vivo mutation rate is comparable to that of bovine leukemia virus (BLV), another member of the HTLV/BLV genus of retroviruses, and is about fourfold lower than that of HIV-1. These observations indicate that while the mutation rate of HTLV-1 is significantly lower than HIV-1, this lower rate alone would not explain the low diversity in HTLV-1 isolates, supporting the hypothesis that HTLV-1 replicates primarily as a provirus during cellular DNA replication rather than as a virus via reverse transcription.
The Dancing Kudu: women's initiation in the Namib Desert during the second millennium AD

Abstract Although the rock art of southern Africa is overwhelmingly concerned with ritual, there are few depictions of the initiation rites so important to hunter-gatherer identity. This study presents the first definitive evidence of women's initiation based on evidence from rock art and archaeological features at the site of /Ui-//aes in Namibia. The evidence reveals multiple links between initiation, women's work in gathering wild grass seed, and the importance of the female kudu as a metaphor of positive social values. These links show that the beliefs underlying ritual practice also form part of everyday subsistence activity, extending the same precepts from mundane artefacts such as grindstones, to the habits of desert antelope.
Activation of MyD 88 Signaling upon Staphylococcal Enterotoxin Binding to MHC Class II Molecules

Ligands binding to Toll-like receptor (TLR), interleukin 1 receptor (IL-1R), or IFN-cR1 are known to trigger MyD88-mediated signaling, which activates pro-inflammatory cytokine responses. Recently we reported that staphylococcal enterotoxins (SEA or SEB), which bind to MHC class II molecules on APCs and cross link T cell receptors, activate MyD88mediated proinflammatory cytokine responses. We also reported that MyD88 mice were resistant to SEinduced toxic shock and had reduced levels of serum cytokines. In this study, we investigated whether MHC class IISE interaction by itself is sufficient to activate MyD88 in MHC class II cells and induce downstream pro-inflammatory signaling and production of cytokines such as TNF-a and IL-1b. Here we report that human monocytes treated with SEA, SEB, or anti-MHC class II monoclonal antibodies up regulated MyD88 expression, induced activation of NF-kB, and increased expression of IL-1R1 accessory protein, TNF-a and IL-1b. MyD88 immunoprecipitated from cell extracts after SEB stimulation showed a greater proportion of MyD88 phosphorylation compared to unstimulated cells indicating that MyD88 was a component of intracellular signaling. MyD88 downstream proteins such as IRAK4 and TRAF6 were also up regulated in monocytes after SEB stimulation. In addition to monocytes, primary B cells up regulated MyD88 in response to SEA or SEB stimulation. Importantly, in contrast to primary B cells, MHC class II deficient T2 cells had no change of MyD88 after SEA or SEB stimulation, whereas MHC class II-independent activation of MyD88 was elicited by CpG or LPS. Collectively, these results demonstrate that MHC class II utilizes a MyD88-mediated signaling mechanism when in contact with ligands such as SEs to induce pro-inflammatory cytokines. Citation: Kissner TL, Ruthel G, Alam S, Ulrich RG, Fernandez S, et al. (2011) Activation of MyD88 Signaling upon Staphylococcal Enterotoxin Binding to MHC Class II Molecules. PLoS ONE 6(1): e15985. doi:10.1371/journal.pone. 0015985 Editor: Jacques Zimmer, Centre de Recherche Public de la Santé (CRP-Santé), Luxembourg Received November 10, 2010; Accepted December 1, 2010; Published January 20, 2011 This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. Funding: This work was supported by the Defense Threat Reduction Agency (DTRA; WWW.jpras.us) Grant CBM.THRTOX. 03.10. RD.006 to Kamal U. Saikh. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: kamal.saikh@amedd.army. mil
[Review of 209 cases of foreign bodies in the upper gastrointestinal tract and clinical factors for successful endoscopic removal].

BACKGROUND/AIMS Most of ingested foreign bodies pass through the gastrointestinal tract spontaneously, but some of them (about 20%) need endoscopic or surgical removal. The aims of this study were to characterize the clinical features associated with foreign bodies in the upper gastrointestinal tract and to determine the clinical factors for their successful removal by endoscopic techniques. METHODS We analyzed retrospectively 209 cases of foreign bodies in the upper gastrointestinal tract at Chonnam National University Hospital between May 1998 and May 2003. RESULTS Foreign bodies were found in 97.1% (203/209) of the cases during endoscopic procedure. The types were chiefly fish bones (21.2%), coins (14.8%), meats (11.3%), and bezoars (8.9%). The locations were upper esophagus (49.8%), stomach (26.6%), lower esophagus (11.3%), and mid-esophagus (7.4%). Endoscopic removal was successful in 93.1% (189/203) of the cases, and surgical removal was successful in 8/203 (3.9%) of the cases. Age (p=0.015) and short duration of impaction (p=0.015) were the independent factors to predict the successful removal of the foreign bodies by endoscopic techniques. CONCLUSIONS Endoscopic removal of foreign bodies in the upper gastrointestinal tract is an effective and safe procedure. Foreign bodies are more successfully removed by endoscopic techniques in children or in cases of short duration of impaction.