Miracle-dz/UniFAR-FTUs huggingface dataset:
Distribution of human papillomavirus genotypes in Paraguayan women according to the severity of the cervical lesion

The incidence of cervical cancer in Paraguay is among the highest in the world. This study aimed to determine the distribution of human papillomavirus (HPV) genotypes in Paraguayan women, according to the severity of the cervical lesion. This cross‐sectional study included 207 women without a squamous intraepithelial lesion, 164 with low‐grade squamous intraepithelial lesions, 74 with high‐grade squamous intraepithelial lesions, and 41 with cervical cancer. Type‐specific HPV was determined by the polymerase chain reaction with MY9/11 L1 and GP5+/GP6+ L1 primers, followed by restriction fragment length polymorphism and reverse line blotting hybridization, respectively. In total, 12 high‐risk and 24 low‐risk HPVs types were detected. HPV 16 was the most prevalent, followed by HPV 18 in cervical cancer (14.6%), HPV 31 in high‐grade squamous intraepithelial lesions (14.9%), HPVs 58/42 in low‐grade squamous intraepithelial lesions (9.1% each), and HPVs 31/58 (2.4% each) in women without squamous intraepithelial lesions. Among 285 positive samples, 24.2% harbored multiple HPV types, being this more prevalent in women with squamous intraepithelial lesions (30.8% in low‐grade squamous intraepithelial lesions, 22.5% in high‐grade squamous intraepithelial lesions, and 22.0% in cervical cancer) than in women without lesions (9.3%). The higher prevalence of HPV 16 and other high‐risk HPVs in women both with and without cervical lesions may explain the high incidence of cervical cancer in Paraguay. This information may be of importance for local decision makers to improve prevention strategies. In addition, these results may be useful as baseline pre‐vaccination data for a future virological surveillance in Paraguay. J. Med. Virol. 83:1351–1357, 2011. © 2011 Wiley‐Liss, Inc.
Human papillomavirus infection among women with cytological abnormalities in Switzerland investigated by an automated linear array genotyping test

Limited data are available describing human papillomavirus (HPV) genotype distribution among females with cytological abnormalities in Switzerland. Cervical cell specimens obtained from 5,318 women were screened routinely by liquid‐based Pap smear. All specimens with cellular abnormalities were analyzed subsequently for HPV DNA by the Linear Array HPV genotyping test. Cellular abnormalities were found in 202 (3.8%) specimens, of which 150 (74.3%) were positive for high‐risk (HR) HPV. HR‐HPV was detected in 20 (60.6%; 95% CI, 43.7–75.4%) of 33 specimens with atypical squamous cells of undetermined significance compared to 98 (72.1%; 95% CI, 64–78.9%) of 136 low‐grade squamous intraepithelial lesions and 32 (97%; 95% CI, 83.4–99.9%) of 33 high‐grade squamous intraepithelial lesions. The cumulative prevalence of HR‐HPV other than HPV 16 and 18 was significantly higher than HPV 16 and/or 18 lesions with atypical squamous cells and low‐grade lesions and was comparable in high‐grade squamous intraepithelial lesions. The most common HR‐HPV genotypes were HPV 16 (15.2%), HPV 31 (12.1%), HPV 58 (12.1%), HPV 51 (9.1%), and HPV 59 (9.1%) in women with atypical squamous cells, HPV 16 (25%), HPV 51 (16.9%), HPV 52 (11.8%), HPV 31 (9.6%), and HPV 56 (8.1%) in women with low‐grade lesions (LSIL) and HPV 16 (57.6%), HPV 18 (18.2%), HPV 31 (15.2%), HPV 52 (12.1%), and HPV 58 (6.1%) in women with high‐grade lesions (HSIL). J. Med. Virol. 83:1370–1376, 2011. © 2011 Wiley‐Liss, Inc.
Male Breast Cancer In Calabar Nigeria: A Twenty Year Experience (1983-2002)

Male breast cancer is rare worldwide. The highest incidence of 2.1 per 100,000 is recorded in Louisiana USA. The record for Africa varies from 0.2 per 100,000 in Gambia to 0.8 per 100,000 in Mali Breast cancer has been erroneously thought to be entirely a female disease in the tropics. This ignorance makes late presentation almost the rule in Nigeria as reported by authors in various part of the country. Breast cancer is the commonest malignancy in Calabar. From the Calabar cancer registry record, 105 cases of breast cancer were seen in 1995 through 1998. Of these 5 patients (4.7%) were male. A review of 30 cases of male breast cancer seen in UCTH between Jan 1983 to Dec 2002 is being studied to look at the clinical presentation, histological pattern and management. They were aged 19 to 85yrs with mean of 53.1yrs. We observed two peaks at 3rd and 6th decades of life. More than 80% (25 cases) presented with painless lump and palpable axillary lymph nodes. Over 50% were on the right. Three patients also had nipples changes. Gross weight loss was associated with very advanced cases. The interval before presentation ranged from 3 to 84 months. All had mastectomy and axillary nodes dissection. Adjuvant chemotherapy was also used. Diagnosis was confirmed by histopathological examination of removed specimen. The follow up was generally poor. However one patient survived beyond ten years. KEYWORDS: Male Breast Cancer, Calabar, Nigeria
Patient‐reported outcomes in the Swedish National Quality Registers

Patient‐reported outcomes (PROs) are important in the healthcare system to gain understanding of patients' views on the effects of a treatment. There is an abundance of available patient‐reported outcome measures (PROMs), both disease specific and generic. In the Swedish healthcare system, the national quality registers are obliged to incorporate PROs for certification at a high level. A review of the latest annual applications for funding (n = 108) shows that at present, 93 national quality registers include some form of PROM or patient‐reported experience measure (PREM). Half of the registers include some type of generic measure, more than half include disease/symptom‐specific measures, and around 40% include PREMs. Several different measures and combinations of measures are used, the most common of which are the EQ‐5D, followed by the SF‐36/RAND‐36. About one‐fifth of the registers report examples of how patient‐reported data are used for local quality improvement. These examples include enhancing shared decision‐making in clinical encounters (most common), as a basis for care plans, clinical decision aids and treatment guidelines, to improve the precision of indications for surgery (patient and healthcare professional assessments may differ), to monitor complications after the patient has left hospital and to improve patient information. In addition, funding applications reveal that most registers plan to extend their array of PROMs and PREMs in future, and to increase their use of patient‐reported data as a basis for quality improvement.
Densitometric Threshold and Vertebral Fractures in Heart Transplant Patients

Background. Bone disease is one of the major complications of solid organ transplantation, causes considerable morbidity, and most patients are treated with immunosuppressant drugs after graft. The majority of studies reported rapid bone loss and an increased incidence of fractures after transplantation. The aim of our study was to evaluate osteoporosis and fracture prevalence, bone metabolism, and the effect of immunosuppressant agents on bone after heart transplantation. Methods. We planned a cross-sectional study in 180 heart transplant patients recruited from 3 different centers with a less than 10 years from graft. Each patient underwent a densitometric scan, and in 157 of them, an x-ray of the spine was performed to evaluate fractures. Biochemical assessment of bone metabolism was made at the time of the visit. Physical activity, diet, and calcium intake were evaluated using a specific questionnaire. Results. Vertebral fractures were diagnosed in 40% of subjects, but densitometric osteoporosis was observed only in 13% of spine and in 25% of hip scans. Interestingly, increasing T-score threshold up to −1.5 standard deviation, the prevalence of fractured patient improved significantly, reaching 60% in both genders. Bone content was inversely correlated with glucocorticoids, while a positive correlation was found with cyclosporine A. Almost all subjects had vitamin D deficiency. Conclusions. Standard densitometric criteria are unreliable to identify bone fragility after transplantation, and a different threshold (−1.5 standard deviation) should be considered. Transplanted patients should be adequately supplemented with vitamin D, and the effects of immunosuppressant agents on bone need further investigation.
Antibody-Mediated Rejection After Alemtuzumab Induction: Incidence, Risk Factors, and Predictors of Poor Outcome

Background. Antibody-mediated rejection (AMR) is associated with allograft loss. Identification of factors associated with poor outcome has not been extensively studied. Methods. We retrospectively studied 469 patients who received a negative crossmatch renal transplant with alemtuzumab induction. Forty-eight of 469 (10.2%) patients were treated for AMR. Thirty of 48 (62.5%) of the cases fulfilled the Banff criteria for definite AMR, whereas 18 of 48 (37.5%) were categorized as suspicious for AMR (tissue injury with C4d staining or donor-specific antibodies [DSAbs]). Sensitization, high human leukocyte antigen, and -DR mismatch were risk factors for the development of AMR (P=0.0016, 0.001, and 0.012, respectively). Results. Allograft survival was inferior in the AMR group (70.2%) compared with the nonrejector group (97.0%) (P<0.001). Forty-two of 48 (87.5%) of patients with acute AMR had DSAbs. Patients with CII DSAbs at the time of AMR, whether alone or in combination with CI DSAbs had the worst allograft survival (P=0.014). Both the mean cumulative and immunodominant mean fluorescence index were higher in those patients who subsequently lost their grafts (P<0.001). Patients with diffuse C4d staining had inferior allograft survival than those with focal C4d or no staining (P=0.02). There was no significant difference in survival by histological grade but a trend to inferior outcomes in those with vascular involvement (P=0.06). Those patients who met the full Banff criteria had worse survival than those with suspicion for AMR only (P=0.04). Conclusion. This study identifies patients at risk of graft failure from AMR. These patients may benefit from newer therapeutic strategies including the use of eculizumab or bortezomib.
ADP detection technologies.

TO THE EDITOR: This letter is to point out significant errors in experimental results, data interpretation, and technical information in two articles recently published in Assay and Drug Development Technologies that describe Promega’s ADP Glo assay and compare it to other kinase and ADP detection methods. Both articles incorrectly state that antibodybased ADP detection methods cannot be used for applications requiring more than 100mM ATP. However, the protocols for BellBrook’s three Transcreener ADP2 assays and Invitrogen’s Adapta assay, antibody-based ADP detection assays that have been available for >2 years, provide detailed instructions and supporting data for using ATP levels up to 1 mM and 500mM, respectively. Moreover, use of the Transcreener ADP2 assay with ATP concentrations ranging from 0.1mM to 1 mM was published in February 2009 and highlighted in the abstract of that article. The use of signal:background as the basis for comparing the sensitivity of ADP-Glo with the Adapta and Millipore’s PI3-Kinase HTRF assays (Fig. 7 in Zegzouti et al.; Fig. 5 in Vidugiriene et al.) is misleading. Both of these assays are TR-FRET based, and thus the assay range is defined (bounded) by a ratiometric readout, whereas ADP Glo has a linear luminescence readout and thus has no such limitation on signal:background. The common practice for comparing assay formats in an unbiased manner is by the use of the Z¢-factor. The inability to detect inhibition of EGFR with a known inhibitor using the Adapta assay (Fig. 8C of Zegzouti et al.) is unexpected and inconsistent with other results in the same article. On the basis of the enzyme titration in Figure 7A, the amount of EGFR used for the inhibitor experiments (1.77 and 3.75 ng) should have yielded sufficient signal with the Adapta assay (and the emission ratios in Fig. 8C confirm this), yet paradoxically no effect was observed with PD158780. We repeated this experiment and tested additional inhibitors as well (Fig. 1). PD158780 and gefitinib inhibited EGFR with subnanomolar IC50s, and staurosporine inhibited with a IC50 of 60 nM. These results strongly suggest that the lack of EGFR inhibition in Zegzouti et al. was due to experimental error, and not ‘‘due to the low dynamic range and the low SB. ’’ Further, there are no data to support the conclusion that ‘‘it is difficult to get an IC50 values [sic] accurately for potent inhibitors with Adapta unless a large amount of enzyme is used,’’ as the authors suggest.
Lower Malignancy Rates in Renal Allograft Recipients Converted to Sirolimus-Based, Calcineurin Inhibitor-Free Immunotherapy: 24-Month Results From the CONVERT Trial

Background. Long-term immunosuppression imposes increased malignancy risk in renal allograft recipients, significantly contributing to overall morbidity and mortality. This study examined malignancy rates in renal allograft recipients at 2 years after conversion to a sirolimus (SRL)-based, calcineurin inhibitor (CNI)-free regimen. Methods. This open-label, randomized, multicenter study (the CONVERT Trial) randomly assigned 830 patients to SRL conversion (n=555) or CNI continuation (n=275). Patients with history of posttransplant lymphoproliferative disease or known/suspected malignancy within 5 years before screening were excluded. As part of standard safety measurements, subjects were monitored for any malignancy occurrence; both skin and nonskin malignancies were reported, even if the patient discontinued from the therapy. Malignancy rates were analyzed based on exposure time to study drugs (i.e., number of events per 100 person-years of follow-up). Results. At 2 years postconversion, the total number of malignancies per 100 person-years of exposure was significantly lower among SRL conversion patients compared with CNI continuation (2.1 vs. 6.0, P<0.001). Patients undergoing SRL-based, CNI-free therapy had significantly lower rates of the subset of nonmelanoma skin carcinomas through 2 years postconversion (1.2 vs. 4.3, P<0.001). This difference persisted after excluding patients with a history of malignancy before randomization. The rate of all other malignancies was not significantly different between treatment groups (P=0.058). Conclusion. In renal allograft recipients, SRL-based immunosuppression was associated with a lower rate of malignancy at 2 years postconversion compared with continuation of CNI-based immunosuppression. This reduction was driven by a significant reduction in nonmelanoma skin carcinoma rates; the rate of all other malignancies was numerically lower but did not achieve statistical significance.
Comparative Analysis of Hepatitis C Recurrence and Fibrosis Progression Between Deceased-Donor and Living-Donor Liver Transplantation: 8-Year Longitudinal Follow-Up

Background. Hepatitis C virus (HCV) recurrence is universal after liver transplantation (LT). Whether the progression of recurrent HCV is faster after live-donor LT (LDLT) compared with deceased-donor LT (DDLT) is debatable. Methods and Results. We retrospectively examined 100 consecutive LTs (65 DDLTs and 35 LDLTs) performed between July 2000 and July 2003. A total of 147 liver biopsies were performed between 6 months post-LT and last follow-up. Mean donor age and model for end-stage liver disease (MELD) score were significantly lower in LDLT (P<0.01). On a mean follow-up of 86.6±6.8 months, overall patient and graft survivals were 61% (51% DDLT vs. 77.1% LDLT; P=0.026) and 56% (46.2% DDLT vs. 71.4% LDLT; P=0.042), respectively. Eight of 39 (20.5%) deaths (7 DDLT and 1 LDLT) and two of nine (22.2%) retransplants (one in each group) were related to recurrent HCV. Mean fibrosis scores for DDLT and LDLT were 1.9±1.7 and 1.6±1.4, respectively (P=0.01). When donor age less than 50 years and MELD score less than 25 were matched among 64 patients (32 DDLT and 32 LDLT), the overall patient and graft survivals were 73.4% (68.8% DDLT vs. 78.1% LDLT; P=0.439) and 71.9% (71.9% DDLT vs. 71.9% LDLT; P=0.978), respectively. Conclusions. Long-term survival rates were better, and fibrosis scores were lower for LDLT. The survivals between LDLT and DDLT were comparable for patients with MELD score less than 25 and donor age less than 50 years.
The Neurology of Vision

The author divides vision into three components. The optical component addresses the eye's ability to properly focus light on the retina. The retinocortical component converts light into neural signals in the retina, transmitting them to the primary visual cortex. Finally, the integrative component converts this simple visual information into more complicated forms. The symptoms and signs, testing methods, and diseases of each part of the visual system are presented using this unique, structural component approach. A final chapter discusses the visual manifestations of psychiatric disturbances.
Multiple intra‐familial transmission patterns of hepatitis B virus genotype D in north‐eastern Egypt

The transmission rate of intra‐familial hepatitis B virus (HBV) and mode of transmission were investigated in north eastern Egypt. HBV infection was investigated serologically and confirmed by molecular evolutionary analysis in family members (N = 230) of 55 chronic hepatitis B carriers (index cases). Hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti‐HBc) prevalence was 12.2% and 23% among family members, respectively. HBsAg carriers were prevalent in the age groups; <10 (16.2%) and 21–30 years (23.3%). The prevalence of HBsAg was significantly higher in the family members of females (19.2%) than males (8.6%) index cases (P = 0.031). HBsAg and anti‐HBc seropositive rates were higher significantly in the offspring of females (23%, 29.8%) than those of the males index cases (4.3%, 9.8%) (P = 0.001, 0.003), as well as higher in the offspring of an infected mother (26.5, 31.8%) than those of an infected father (4.7%, 10.5%) (P = 0.0006, 0.009). No significant difference was found in HBsAg seropositive rates between vaccinated (10.6%) and unvaccinated family members (14.8%). Phylogenetic analysis of the preS2 and S regions of HBV genome showed that the HBV isolates were of subgenotype D1 in nine index cases and 14 family members. HBV familial transmission was confirmed in five of six families with three transmission patterns; maternal, paternal, and sexual. It is concluded that multiple intra‐familial transmission routes of HBV genotype D were determined; including maternal, paternal and horizontal. Universal HBV vaccination should be modified by including the first dose at birth with (HBIG) administration to the newborn of mothers infected with HBV. J. Med. Virol. 84:587–595, 2012. © 2011 Wiley Periodicals, Inc.
Stem-Cell Gene Therapy for the Wiskott-Aldrich Syndrome

K Boztug, M Schmidt, A Schwarzer. N Engl J Med. 2010;363(20):1918–1927 To examine the efficacy of transfusion of autologous genetically modified hematopoietic stem cells for Wiskott-Aldrich syndrome (WAS). WAS is an X-linked recessive primary immunodeficiency disorder associated with thrombocytopenia, eczema, and autoimmunity. Two 3-year-old boys with WAS were included. Inclusion criteria included severe WAS, no evidence of malignancy, and isolation of sufficient numbers of CD34+ cells. Autologous …
Alcohol abuse history and adjustment following spinal cord injury.

Objective: Examined the relation of alcohol abuse history to emo- tional adjustment and pressure sore occurrence during the 1st 3 years following Spinal Cord Injury (SCI). Study Design: Comparisons were made between varying levels of prior abuse and depression and disability acceptance. A model predicting pressure sore occurrence over 3 years was computed. Participants: One hundred seventy-five persons completed the self-report measures; 105 were available for pressure sore evaluations. Main Outcome Measures: The Inventory to Diagnose Depression, the Acceptance of Disability Scales, and pressure sore occurrence. Results: Alcohol abuse was not associated with depression or disability acceptance. Severe alcohol abuse history was associated with pressure sores over the 3 years. Conclusions: Persons with prior history of severe alcohol abuse may be at in- creased risk for pressure sore occurrence during the 1st years of SCI. Many persons who sustain severe physical disabilities have a significant history of alcohol and other substance abuse, and alcohol and substance abuse are often related to adjustment following disability (Bombardier, 2000). Alcohol abuse has been associated with impaired self-care activities up to 18 months following the onset of disability (Bombardier & Rimmele, 1998), and a predisability history of substance abuse has been associated with an increased rate of pressure sores 30 months after the onset of spinal cord injury (SCI; Hawkins & Heinemann, 1998). Persons with a significant preinjury alcohol abuse history may be susceptible to pressure sore development even if they abstain from alcohol following their return to the community (Heinemann & Hawkins, 1995). Alcohol abuse has also been associated with higher levels of depression and life stress and with ratings
Balancing the autonomic nervous system to reduce inflammation in rheumatoid arthritis

Imbalance in the autonomic nervous system (ANS) has been observed in many established chronic autoimmune diseases, including rheumatoid arthritis (RA), which is a prototypic immune‐mediated inflammatory disease (IMID). We recently discovered that autonomic dysfunction precedes and predicts arthritis development in subjects at risk of developing seropositive RA. In addition, RA patients with relatively high vagus nerve tone (higher parasympathetic parameters, measured by heart rate variability) respond better to antirheumatic therapies. Together, these data suggest that the ANS may control inflammation in humans. This notion is supported by experimental studies in animal models of RA. We have found that stimulation of the so‐called cholinergic anti‐inflammatory pathway by efferent electrical vagus nerve stimulation (VNS) or pharmacological activation of the alpha7 subunit of nicotinic acetylcholine receptors (α7nAChR) improves clinical signs and symptoms of arthritis, reduces cytokine production and protects against progressive joint destruction. Conversely, increased arthritis activity was observed in alpha7nAChR knockout mice. These studies together with previous work in animal models of sepsis and other forms of inflammation provided the rationale for an experimental clinical trial in patients with RA. We could for the first time show that an implantable vagus nerve stimulator inhibits peripheral blood cytokine production in humans. VNS significantly inhibited TNF and IL‐6 production and improved RA disease severity, even in some patients with therapy‐resistant disease. This work strongly supports further studies using a bioelectronic approach to treat RA and other IMIDs.