Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular mechanisms regulating the synergism between IL‐32γ and NOD for the activation of eosinophils

IL‐32 is a proinflammatory cytokine associated with infections, autoimmune diseases, and allergic asthma. In the present study, we elucidated the synergistic effect of IL‐32γ and NOD ligand on the activation of human eosinophils, principal effector cells for allergic inflammation, and the underlying mechanisms. Specific IL‐32‐binding protein, PR3, was found to localize on the cell surface and in the cytoplasm of eosinophils. IL‐32γ was more capable of activating eosinophils than its isotype variant IL‐32α and exhibited synergistic effect with NOD1 ligand iE‐DAP and NOD2 ligand MDP on the induction of allergic inflammation‐related IL‐1β, TNF‐α, and chemokines CXCL8, CCL3, and CCL4 (P<0.05). Moreover, IL‐32γ and iE‐DAP or MDP induced the significant up‐regulation of the cell‐surface expression of adhesion molecule CD18 and ICAM‐1 on eosinophils. Synergism between IL‐32γ and NOD ligands was dependent on the activation of intracellular caspase 1, ERKs, p38 MAPK, and NF‐κB pathways in eosinophils. The further‐enhanced CD18 and ICAM‐1 expression and production of cytokines and chemokines were observed in eosinophils cocultured with human bronchial epithelial BEAS‐2B cells. Furthermore, combined treatment of IL‐32γ and NOD ligand could activate the release of eosinophil extracellular DNA traps, thereby implying the pathogen‐defense mechanisms of eosinophils. Together, the above study provides pivotal immunological mechanisms by which bacterial infection‐mediated activation of NOD1,2, together with IL‐32γ, can synergize the activation of eosinophils interacting with bronchial epithelial cells.
Answer to: The possible risk of cancer in multiple sclerosis patients: a controversial issue

Dear Sir, We have to thank Dr Bahreini and co-workers for their interesting commentary on the results of our survey on multiple sclerosis (MS) mortality [1]. In their letter, these authors underlie an important but still controversial issue about MS comorbidity. The possible association between cancer and MS is not a secondary aspect of the disease for many reasons. Mechanisms related to chronic inflammatory processes have been supposed to be related both to MS and to cancer. Patients affected by MS may also change their life styles that may influence cancer risk. These changes include also the exposure to immunomodulatory or immunosuppressive treatments. As reported in the comments, results from previous studies showed some inconsistencies. In general, it seems that MS is not associated with cancer by itself but the association should be limited only to some kind of tumors like leukemia, lymphoma, breast, brain and urinary tract cancers [2–4]. In our opinion, this selective association represents a key point because it could indicate a precise pathogenic mechanism related to clinical aspects of the disease and to some kind of cancers indeed. In our paper, we reported five cancer-related deaths amongst 194 MS patients compared to six amongst 388 referent subjects. The increased risk we reported was not statistically significant (RR = 1.67; CI 0.54–5.07; P = 0.5). We also indicated that these cancer diagnoses were anyway based on death certificate reports, which are prone to several limitations. As we already pointed out, these data may reflect differences in health policies and services across countries, and we underlie now, that the accuracy in death certificates reporting is the main factor responsible for observed differences [5]. In this specific case moreover, even assuming that death certificates are accurate (the fact that it is not necessarily so is argued by the percentage of missing death certificates), reported cancers refers to fatal cancers. For these reasons, we stated that there was only a suggestion for a higher cancer mortality in our MS population needing further confirmation. Finally, the kind of cancer could be another important issue, because as already mentioned it could be supportive for specific mechanisms for disease-related changes in patient s life styles. In the near future, treatments with possible lifethreatening side effects must take into account the basal risk of people affected by MS for comorbid disorders, but there is the risk that this will be difficult to estimate, unless we have not clear the real extent of these conditions. For this reason, it is of outstanding importance to have studies aimed at estimating the real frequency for comorbid disorders and for cancers in particular amongst MS patients, looking also at the specific type of tumor and at their possible association with disease-related treatments.
Students come to medical schools prepared to cheat: a multi-campus investigation

Objectives To investigate high school cheating experiences and attitudes towards academic misconduct of freshmen at all four medical schools in Croatia, as a post-communist country in transition, with intention of raising awareness of academic (dis)honesty. Design and method Students were given an anonymous questionnaire containing 22 questions on the atmosphere of integrity at their high school, self-reported educational dishonesty, their evaluation of cheating behaviour, and on their expectations about the atmosphere of integrity at their university. Setting All schools of medicine of Croatian universities (Zagreb, Rijeka, Split and Osijek). Main measures Descriptive statistics and differences in students' self-reported educational dishonesty, perception of cheating behaviour, and perception of the high school integrity atmosphere. Results Of the 761 freshmen attending the four medical schools, 508 (67%) completed the questionnaire: 481 Croatian and 27 international students. Of the Croatian respondents, almost all (>99%) self-reported engaging in at least one behaviour of educational dishonesty, and 78% of respondents admitted to having frequently cheated in at least one form of assessed academic misconduct. Only three students admitted to having reported another student for cheating. For most of the questions, there was no significant difference in the responses among Croatian students. However, significant differences were found in most responses between Croatian students and their international counterparts, who were significantly less likely to engage in dishonest behaviours. No individual factor was found to correlate with the incidence of self-admitted dishonest behaviour. Frequent cheaters evaluated academic dishonesty significantly more leniently than those who did not cheat. Conclusion Academic dishonesty of university students does not begin in higher education; students come to medical schools ready to cheat.
Salmonella inhibits monocyte differentiation into CD11chiMHC‐IIhi cells in a MyD88‐dependent fashion

Monocytes and DCs originate from a shared precursor in the bone marrow, and steady‐state DCs in lymphoid organs develop directly from the precursor rather than via a monocyte intermediate. However, monocytes can differentiate into DCs in tissues such as the lung and gut mucosa and into macrophages in most tissues. As Ly6Chi monocytes accumulate in lymphoid organs during oral Salmonella infection, we investigated their ability to develop into potential DCs, identified as CD11chiMHC‐IIhi cells, in infected hosts. Ly6Chi monocytes, isolated from the blood of Salmonella‐infected mice, developed into CD11chiMHC‐IIhi cells after culture with GM‐CSF or Flt3L. In contrast, the same monocytes cultured in the presence of GM‐CSF and heat‐killed Salmonella did not differentiate into CD11chiMHC‐IIhi cells. The bacteria‐induced differentiation block was dependent on TLRs, as monocytes from MyD88−/− mice converted into CD11chiMHC‐IIhi cells even in the presence of bacteria. We hypothesized that Salmonella‐activated wild‐type monocytes secreted mediators that inhibited differentiation of MyD88−/−‐derived monocytes. However, IL‐6, IL‐10, TNF‐α, or IL‐12p70 did not account for the inhibition. Finally, monocyte‐derived CD11chiMHC‐IIhi cells pulsed with OVA peptide or protein did not induce proliferation of antigen‐specific CD4+ T cells but rather, suppressed the ability of DCs to activate CD4+ T cells. Overall, the data show that Ly6Chi monocytes from Salmonella‐infected mice develop into CD11chiMHC‐IIhi cells with poor antigen‐presentation capacity when cultured ex vivo, and that monocyte exposure to Salmonella inhibits their differentiation into CD11chiMHC‐IIhi cells in a MyD88‐dependent fashion.
Nonstandard Exception Requests Impact Outcomes for Pediatric Liver Transplant Candidates

Nonstandard exceptions requests (NSERs), in which transplant centers appeal on a case‐by‐case basis for Pediatric End‐Stage Liver Disease/Mayo End‐Stage Liver Disease points, have been highly utilized for pediatric liver transplant candidates. We evaluated whether NSE outcomes are associated with waitlist and posttransplant mortality. United Network for Organ Sharing (UNOS) Scientific Registry of Transplant Recipients data on pediatric liver transplant candidates listed in 2009–2014 were analyzed after excluding those granted automatic UNOS exceptions. Of 2581 pediatric waitlist candidates, 44% had an NSE request. Of the 1134 children with NSERs, 93% were approved and 7% were denied. For children 2–18 years at listing, NSER denial increased the risk of waitlist mortality or removal for being too sick (subhazard ratio 2.99, 95% confidence interval [CI] 1.26–7.07, p = 0.01 in multivariate analysis). For children younger than 2 years, NSER denial did not impact waitlist mortality/removal. Children with NSER approved had reduced risk of graft loss 3 years posttransplant in univariate but not multivariable analysis (odds ratio 0.73, 95% CI 0.53–1.01, p = 06). Those with NSER denial had a higher risk of posttransplant death than those with no NSER (hazard ratio 2.43, 95% CI 0.99–5.95, p = 0.05, multivariable analysis), but NSER approval did not impact posttransplant death. Further research on NSER utilization in pediatric liver transplant is needed to optimize organ allocation and outcomes for children.
The Child with a Handicap

This is an outstanding book. It covers numerous difficult topics usually left out of conventional disease-orientated paediatric textbooks and thus fills an important gap, particularly for clinical medical officers, general practitioners, and paediatricians in training. It is indeed a handbook, centred on 'the assessment of hearing, seeing, thinking and growing' and packed with practical information. It begins with a good chapter on normal growth and a discussion of the factors that may influence growth with, for example, straightforward information about how to evaluate an underweight child or an obese one. This is followed by equally useful chapters on practical medical genetics, nutrition and metabolism, and interviewing children and parents. Three chapters cover normal neurological development, mental handicap, and neurological disorders (divided into eight sections). Especially good are the sections on 'The child who does not walk' and 'The child who fails at school'. There are two chapters on visual and hearing development and assessment, followed by a three section chapter on language and speech containing another excellent contribution by Ruth Day on 'The child who does not talk'. There are chapters on social development, emotional development, behaviour disorders, educational medicine (in three parts), immunisation, epidemiology, the environment (school and physical), and a five part chapter on social paediatrics (with particularly good sections on the law, adoption and child abuse, and on disabled school leavers). There are two chapters on common infections, two on death and cot death, and a final one on malformations and orthopaedic conditions which includes tables of teratogens and their effect; and a table about drugs and breast feeding. The remaining 100 pages contain particularly useful appendices including a huge list of voluntary organisations for children with disabilities; helpful tables of biochemical and haematological normal ranges; growth, head circumference, and puberty staging charts; an innovative table of variations in growth patterns; a timetable of normal milestones and motor developments; details of the Goodenough-Harris drawing test, the Cardiff modifications of the Denver developmental screening test and the Woodside assessment test; information about neonatal reflexes and their possible significance if abnormal, accompanied by details of the Dubowitz score for clinical assessment of gestational age in newborns; a list of anticonvulsants, their dosage, their therapeutic range, and their side effects.
A 4Mb embedded SLC resistive-RAM macro with 7.2ns read-write random-access time and 160ns MLC-access capability

Several emerging nonvolatile memories (NVMs) including phase-change RAM (PCRAM) [1–3], MRAM [4–5], and resistive RAM (RRAM) [6–8] have achieved faster operating speeds than embedded Flash. Among those emerging NVMs, RRAM has advantages in faster write time, a larger resistance-ratio (R-ratio), and smaller write power consumption. However, RRAM cells have large cross-die and within-die resistance variations (R-variations) and require low read-mode bitline (BL) bias voltage (VBL-R) to prevent read disturbance. This work proposes process/resistance variation-insensitive read schemes for embedded RRAM to achieve fast read speeds with high yields. An embedded mega-bit scale (4Mb), single-level-cell (SLC) RRAM macro with sub-8ns read-write random-access time is presented. Multi-level-cell (MLC) operation with 160ns write-ver-ify operation is demonstrated.
Prevalence of Metabolic Syndrome Determined on the Basis of Direct Visceral Fat Area Measurement Using Computed Tomography

Introduction One diagnostic criterion for metabolic syndrome (MS) as a conventional method is the measurement of abdominal circumference size. The aim of this study is to investigate the prevalence of MS precisely based on direct measurement of the visceral fat area (VFA) using computed tomography (CT). Methods The VFAs were assessed by CT in 470 individuals, including 262 men (aged 47.6±10.2: mean±SD) and 208 women (aged 43.9±8.5) during a 3-year period. Blood pressure, fasting blood glucose, and lipid profiles were also measured. For those who had VFA>or=100cm2, MS was defined as the presence of at least two of the following criteria: a triacylglycerol level>or=150mg/dl, high-density lipoprotein cholesterol level<40mg/dl, blood pressure>or=130/85mmHg, and fasting glucose level>or=110mg/dl. Results The mean VFA size was 91.6±43.2 in men and 35.5±29.4 in women respectively. 99 (37.8%) of men and 9 (4.3%) of women demonstrated the VFA of>or=100cm2. As a result, 11.1% (29/262) of men and 1.9% (4/208) of women were diagnosed to have MS, which is lower than previously reported in Japan. Conclusion Our results suggest that prevalence of MS assessed based on the direct measurement of VFA might therefore be lower than previously reported, especially in case of women.
Achieving online consent to participation in large-scale gene-environment studies: a tangible destination

Background Population based genetics studies are dependent on large numbers of individuals in the pursuit of small effect sizes. Recruiting and consenting a large number of participants is both costly and time consuming. We explored whether an online consent process for large-scale genetics studies is acceptable for prospective participants using an example online genetics study. Methods We conducted semi-structured interviews with 42 members of the public stratified by age group, gender and newspaper readership (a measure of social status). Respondents were asked to use a website designed to recruit for a large-scale genetic study. After using the website a semi-structured interview was conducted to explore opinions and any issues they would have. Responses were analysed using thematic content analysis. Results The majority of respondents said they would take part in the research (32/42). Those who said they would decline to participate saw fewer benefits from the research, wanted more information and expressed a greater number of concerns about the study. Younger respondents had concerns over time commitment. Middle aged respondents were concerned about privacy and security. Older respondents were more altruistic in their motivation to participate. Common themes included trust in the authenticity of the website, security of personal data, curiosity about their own genetic profile, operational concerns and a desire for more information about the research. Conclusions Online consent to large-scale genetic studies is likely to be acceptable to the public. The online consent process must establish trust quickly and effectively by asserting authenticity and credentials, and provide access to a range of information to suit different information preferences.
Molecular Assessment of Microcirculation Injury in Formalin‐Fixed Human Cardiac Allograft Biopsies With Antibody‐Mediated Rejection

Precise diagnosis of antibody‐mediated rejection (AMR) in cardiac allograft endomyocardial biopsies (EMBs) remains challenging. This study assessed molecular diagnostics in human EMBs with AMR. A set of 34 endothelial, natural killer cell and inflammatory genes was quantified in 106 formalin‐fixed, paraffin‐embedded EMBs classified according to 2013 International Society for Heart and Lung Transplantation (ISHLT) criteria. The gene set expression was compared between ISHLT diagnoses and correlated with donor‐specific antibody (DSA), endothelial injury by electron microscopy (EM) and prognosis. Findings were validated in an independent set of 57 EMBs. In the training set (n = 106), AMR cases (n = 70) showed higher gene set expression than acute cellular rejection (ACR; n = 21, p < 0.001) and controls (n = 15, p < 0.0001). Anti‐HLA DSA positivity was associated with higher gene set expression (p = 0.01). Endothelial injury by electron microscopy strongly correlated with gene set expression, specifically in AMR cases (r = 0.62, p = 0.002). Receiver operating characteristic curve analysis for diagnosing AMR showed greater accuracy with gene set expression (area under the curve [AUC] = 79.88) than with DSA (AUC = 70.47) and C4d (AUC = 70.71). In AMR patients (n = 17) with sequential biopsies, increasing gene set expression was associated with inferior prognosis (p = 0.034). These findings were confirmed in the validation set. In conclusion, biopsy‐based molecular assessment of antibody‐mediated microcirculation injury has the potential to improve diagnosis of AMR in human cardiac transplants.
Urinary Tract Infections Caused by Staphylococcus saprophyticus and their antimicrobial sensitivity pattern in Young Adult Women

The present study was conducted to observe the antibiotic sensitivity pattern of isolated S. saprophyticus from urine samples of patients admitted in inpatient department or visited the out patient department of Sir Salimullah Medical College & Mitford Hospital (SSMC& MH) Dhaka from October 2002 to September 2003. Among the isolates, Esch.coli was the most predominant (82.61%) urinary pathogens followed by S. saprophyticus (7.01%). 93.10% S.saprophyticus was isolated from females of which highest (44.82%) rate of isolation was among female of 18- 45 years age group. Rate of isolation was also high (41.38%) among female of <18 years age group. All strains of S.saprophyticus (100%) were sensitive to Imipenem. High sensitivity was also observed to gentamicin (86.20%) andceftriaxone (72.41%). Ciprofloxacin was found to be sensitive against 68.96% isolates. Sensitivity of ceftazidime, cephalexin and cloxacillin were 65.51%, 55.17% and 55.17% respectively. However, most of the S. saprophyticus are resistant to ampicillin, nalidixic acid and cotrimoxazole. So, the present study illustrates that physicians and microbiologists must be aware that S. saprophyticus is an important cause of UTIs in young women and there is a need for continuous evaluation of common antibiotics used in the therapy of uropathogens. DOI: http://dx.doi. org/10.3329/bjmm.v5i1. 15817 Bangladesh J Med Microbiol 2011; 05 (01): 21-25
Early Macrophage Infiltration and Sustained Inflammation in Kidneys From Deceased Donors Are Associated With Long‐Term Renal Function

Kidney transplants from living donors (LDs) have a better outcome than those from deceased donors (DDs). Different factors have been suggested to justify the different outcome. In this study, we analyzed the infiltration and phenotype of monocytes/macrophages and the expression of inflammatory and fibrotic markers in renal biopsy specimens from 94 kidney recipients (60 DDs and 34 LDs) at baseline and 4 months after transplantation. We evaluated their association with medium‐ and long‐term renal function. At baseline, inflammatory gene expression was higher in DDs than in LDs. These results were confirmed by the high number of CD68‐positive cells in DD kidneys, which correlated negatively with long‐term renal function. Expression of the fibrotic markers vimentin, fibronectin, and α–smooth muscle actin was more elevated in biopsy specimens from DDs at 4 months than in those from LDs. Gene expression of inflammatory and fibrotic markers at 4 months and difference between 4 months and baseline correlated negatively with medium‐ and long‐term renal function in DDs. Multivariate analysis point to transforming growth factor‐β1 as the best predictor of long‐term renal function in DDs. We conclude that early macrophage infiltration, sustained inflammation, and transforming growth factor‐β1 expression, at least for the first 4 months, contribute significantly to the difference in DD and LD transplant outcome.
A 0.4mW/Gb/s 16Gb/s near-ground receiver front-end with replica transconductance termination calibration

The growing demand for low-power and high-fidelity chip-to-chip data communication has motivated the use of near-ground or low-common-mode voltage (LCM) signaling [1-2]. However, deployment of such signaling for high-speed applications such as graphics memory interfaces has been hampered by complications of the transmitter and receiver designs. Recent techniques have enhanced the performance of source-series terminated transmitters by accommodating impedance and equalization calibration at a low power cost [3]. This work advances LCM receiver high-frequency operation by introducing an accurate termination calibration, taking into account the receiver loading on the data link channel. Our receiver also incorporates common-mode-to-differential-gain cancellation and in-situ equalization calibration for reliable data reception at 16Gb/s over a 3” FR4 PCB memory link with 15dB loss at Nyquist frequency.
Preliminary Single‐Center Canadian Experience of Human Normothermic Ex Vivo Liver Perfusion: Results of a Clinical Trial

After extensive experimentation, outcomes of a first clinical normothermic machine perfusion (NMP) liver trial in the United Kingdom demonstrated feasibility and clear safety, with improved liver function compared with standard static cold storage (SCS). We present a preliminary single‐center North American experience using identical NMP technology. Ten donor liver grafts were procured, four (40%) from donation after circulatory death (DCD), of which nine were transplanted. One liver did not proceed because of a technical failure with portal cannulation and was discarded. Transplanted NMP grafts were matched 1:3 with transplanted SCS livers. Median NMP was 11.5 h (range 3.3–22.5 h) with one DCD liver perfused for 22.5 h. All transplanted livers functioned, and serum transaminases, bilirubin, international normalized ratio, and lactate levels corrected in NMP recipients similarly to controls. Graft survival at 30 days (primary outcome) was not statistically different between groups on an intent‐to‐treat basis (p = 0.25). Intensive care and hospital stays were significantly more prolonged in the NMP group. This preliminary experience demonstrates feasibility as well as potential technical risks of NMP in a North American setting and highlights a need for larger, randomized studies.