Miracle-dz/UniFAR-FTUs huggingface dataset:
The impact of pre-graft serology on the risk of BKPyV infection post-renal transplantation.

OBJECTIVES BK polyomavirus associated nephropathy, is a troublesome disease induced by BK polyomavirus (BKPyV) infection in immunocompromised renal graft recipients with no effective available treatment, making immunosuppression reduction the only management option. Thus, pre-graft predictive BKPyV replication markers are needed for high-risk viremia patient identification. METHODS we conducted a retrospective study to assess the correlation between the BKPyV pre-transplant serostatus and post-transplant BKPyV infection incidence. Sera from 329 recipients and 222 matched donors were tested for anti-BKV antibodies against BKPyV serotypes I and IV by a VLPs-based IgG ELISA, and BKPyV DNA load was monitored for at least 1 year post transplantation. RESULTS 80 recipients were viruric and 59 recipients were viremic post transplantation. In the post-transplant period, the probability of developing viremia for serotype I was increasing from 4.3% for the D-/R + group to 12.1% for the D+/R + group and climbing to 37.5% for the D+/R- group (p < 0.05). When calculating the recipient mean titers for serotypes I and IV, we observed a clear difference in the proportions of viremia passing from 50% for mean titers < 400 to 13.5% for titers ≥ 400 (p < 0.001) with also a higher proportion of presumptive nephropathy (50% vs 23.1%, p < 0.05). In univariate analysis this parameter has an odds ratio of 6.41 for the risk of developing post-transplant BKPyV viremia (95% CI: 3.16-13.07; p < 0.0001). CONCLUSIONS Both donor and recipient BKPyV seropositivity determination before transplantation and antibody titer may serve as a predictive tool to manage clinical BKPyV infection by identification of patients at high risk.
Serum 25‐Hydroxy‐Vitamin D Status and Incident Hip Fractures in Elderly Adults: Looking Beyond Bone Mineral Density

Observational studies have consistently reported a higher risk of fractures among those with low levels of serum 25‐hydroxyvitamin D (25(OH)D). Emerging evidence suggests that low serum 25(OH)D levels may increase the rate of falls through impaired physical function. Examine to what extent baseline measures of volumetric bone mineral density (vBMD), absolute bone mineral content (BMC), and markers of physical function may explain incident hip fractures in older adults with different serum levels of 25(OH)D. A prospective study of 4309 subjects (≥66 years) recruited between 2002 and 2006 into the Age, Gene/Environment Susceptibility‐Reykjavik (AGES‐Reykjavik) study. Hip fractures occurring until the end of 2012 were extracted from hospital records. Prevalence of serum 25(OH)D deficiency (<30 nmol/L), inadequacy (30–<50 nmol/L), and sufficiency (≥50 nmol/L) was 6%, 23%, and 71% for males; and 11%, 28%, and 53% for females, respectively. Female participants had ~30% lower absolute BMC compared to males. Serum 25(OH)D concentrations were positively associated with vBMD and BMC of the femoral neck and markers of physical function, including leg strength and balance. Those who had deficient compared to sufficient status at baseline had a higher age‐adjusted risk of incidence hipfractures with hazard ratios (HRs) of 3.1 (95% confidence interval [CI], 1.9–5.2) and 1.8 (95% CI, 1.3–2.5) among males and females, respectively. When adjusting for vBMD and measures of physical function, the association was attenuated and became nonsignificant for males (1.3; 95% CI, 0.6–2.5) but remained significant for females (1.7; 95% CI, 1.1–2.4). Deficient compared to sufficient serum 25(OH)D status was associated with a higher risk of incident hip fractures. This association was explained by poorer vBMD and physical function for males but to a lesser extent for females. Lower absolute BMC among females due to smaller bone volume may account for these sex‐specific differences. © 2021 American Society for Bone and Mineral Research (ASBMR).
LGR5, HES1 and ATOH1 in Young Rectal Cancer Patients in Egyptian

Objective: The study aimed to delineate the gene expression profile of LGR5, HES1 and ATOH1 in young Egyptian rectal cancer (RC) patients and investigate the correlation between expression profiles and clinical outcome. Methods: The study was conducted on 30 young Egyptian RC patients. Expression study of LGR5, HES1 and ATOH1 were performed by quantitative PCR (QPCR) based on comparative Cq method after normalization to adjacent non tumor tissues and ACTB as a reference gene. Patients were followed up for assessment of response to neoadjuvant chemoradiotherapy (CRT) based on revised RECIST1.1. Result: The study detected overexpression of LGR5 and HES1 and down-regulation of ATOH1 in human RC tissues compared to non- tumor tissues. High expression of LGR5 was correlated with more depth of tumor invasion, lymph node (LN) metastasis, advanced cTNM stage and mesorectal fascia (MRF) involvement. More prominently, high LGR5 expression level was associated with poor response to CRT. LGR5 was suggested as unfavorable prognostic biomarker for RC. Conversely, HES1 and ATOH1 expression did not show significant association with most of the studied clinical criteria nor response to CRT. Still, HES1 and ATOH1 were significantly and inversely associated with presence of mucinous component. Conclusion: High LGR5 expression is indicative of poor prognosis among young Egyptian RC patients and is proposed as a predictive marker of resistance to neoadjuvant CRT. However, HES1 and ATOH1 expressions were not prognostic nor predictive of response to CRT. Overall, LGR5, HES1 and ATOH1 gene expression patterns among young onset RC patients, are in line with patterns encountered in older age groups.
Recovery of Memory B-cell Subsets and Persistence of Antibodies in Convalescent COVID-19 Patients

ABSTRACT. It is essential to examine the longevity of the defensive immune response engendered by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. We examined the SARS-CoV-2-specific antibody responses and ex vivo memory B-cell subsets in seven groups of individuals with COVID-19 classified based on days since reverse-transcription polymerase chain reaction confirmation of SARS-CoV-2 infection. Our data showed that the levels of IgG and neutralizing antibodies started increasing from days 15 to 30 to days 61 to 90, and plateaued thereafter. The frequencies of naive B cells and atypical memory B cells decreased from days 15 to 30 to days 61 to 90, and plateaued thereafter. In contrast, the frequencies of immature B cells, classical memory B cells, activated memory B cells, and plasma cells increased from days 15 to 30 to days 61 to 90, and plateaued thereafter. Patients with severe COVID-19 exhibited increased frequencies of naive cells, atypical memory B cells, and activated memory B cells, and lower frequencies of immature B cells, central memory B cells, and plasma cells when compared with patients with mild COVID-19. Therefore, our data suggest modifications in memory B-cell subset frequencies and persistence of humoral immunity in convalescent individuals with COVID-19.
Tubeless Anesthesia in Subglottic Stenosis: Comparative Review of Apneic Low‐Flow Oxygenation With THRIVE

Managing the shared airway in subglottic stenosis presents a unique challenge. Tubeless anesthesia with apneic oxygenation is increasingly being adopted as it overcomes the limitations of access to and visualization of the narrowed subglottis. Low‐flow oxygenation (LFO) and transnasal humidified rapid‐insufflation ventilatory exchange (THRIVE) are two delivery techniques. We sought to compare their utility in this patient cohort.
In silico integrative analysis for the characterization of LYT1 a unique protein of Trypanosoma cruzi

Abstract Trypanosoma rangeli is the most similar organism to Trypanosoma cruzi. They share distribution areas, hosts, and some vectors. However, there are key differences between them; the first lacks a multiplicative form in the host and does not cause disease, while the second is the etiological agent of the American tripanosomiasis, a tropical disease that still does not have an effective vaccine nor treatment. Aiming to reveal the differences in their gene expression patterns in each life cycle form, the comparison of expression profiles was made parting from the ESTs available in TriTrypDB. We verified that there are no genes unique to T. rangeli in the ESTs. Astonishingly, we determined that T. cruzi has a single copy gene called LYT1, which has no similarity to any other protein of any organism on Earth. LYT1 is involved in invasion, motility, and cell cycle, making it an attractive vaccine target. After its identification, using immunoinformatics programs, we found multiple potential B- and T-cell epitopes in this protein, which is also rich in intrinsically disordered regions. Additionally, an approximation of the 3 D structure was predicted where the B-cell epitopes were located to assess their solvent access. We propose that its particular structural conformation confers the flexibility required for the interactions with multiple proteins, which in part may be performed through N-myristoylation sites. Given its important role in the infectiveness of T. cruzi and its antigenic potential, we highlight the need for future studies focused on its molecular and immunological in vivo characterization. Communicated by Ramaswamy H. Sarma
Ensuring exchangeability in data‐based priors for a Bayesian analysis of clinical trials

In many orphan diseases and pediatric indications, the randomized controlled trials may be infeasible because of their size, duration, and cost. Leveraging information on the control through a prior can potentially reduce sample size. However, unless an objective prior is used to impose complete ignorance for the parameter being estimated, it results in biased estimates and inflated type‐I error. Hence, it is essential to assess both the confirmatory and supplementary knowledge available during the construction of the prior to avoid “cherry‐picking” advantageous information. For this purpose, propensity score methods are employed to minimize selection bias by weighting supplemental control subjects according to their similarity in terms of pretreatment characteristics to the subjects in the current trial. The latter can be operationalized through a proposed measure of overlap in propensity‐score distributions. In this paper, we consider single experimental arm in the current trial and the control arm is completely borrowed from the supplemental data. The simulation experiments show that the proposed method reduces prior and data conflict and improves the precision of the of the average treatment effect.
Seroprevalence, Genotyping, and Monitoring of Hepatitis C Viral Loads in Patients on Antivirals in Burkina Faso

Introduction: Hepatitis C virus (HCV) infection remains a major public health problem worldwide. In Burkina Faso, nearly 720,000 people are living with HCV, and each year about 900 people die from complications of cirrhosis or hepatocellular carcinoma. This study was planned to determine the HCV seroprevalence, characterize circulating genotypes, and monitor HCV viral loads in patients under treatment with antivirals. Methods: A total of 4,124 individuals and 167 patients in the pre-therapy program were recruited. The “SD Bioline HCV” kit was used for rapid screening of anti-HCV antibodies. Viral load and genotyping were performed in 167 HCV patients on antivirals using the “Iontek HCV Quant” and “Iontek genotyping” kits. Results: Prevalence of HCV was 1.65% (68/4,124), and the median viral load of participants was 5.37 log10/mL (1.32–7.67 log10/mL). Genotype 2 was predominant with a frequency of 86.23% (144/167) and appeared to be more active with higher viral load compared to 13.77% (23/167) for genotype 1 (p < 0.001). After 24 weeks of pan-genotypic direct-acting antivirals, such as sofosbuvir/daclatasvir and sofosbuvir/velpatasvir, the viral loads of all patients became undetectable. Conclusion: The responses to antivirals by the circulating genotypes indicate that the results are very satisfactory. Therefore, the prevalence of HCV in the population can be reduced through identification of cases and treatment.
The differences between surface degradation and bulk degradation of FEM on the prediction of the degradation time for poly (lactic-co-glycolic acid) stent

Abstract The degradation time is a crucial factor in evaluating the performance of poly (lactic-co-glycolic acid) (PLGA) stents. Bulk degradation mode was commonly used to analyze the stent degradation behavior by finite element approach. However, the PLGA stents may present surface degradation more than bulk degradation under certain conditions, which will greatly affect the degradation time after implantation. In this study, the degradation processes of the poly (lactic-co-glycolic acid) stent were reproduced utilizing finite element analysis. Both bulk degradation and surface degradation modes were considered. The correlation between tensile stress and degradation rate was investigated. The degradation time was analyzed selectively. The stress distribution, fracture, and mass loss were also compared between bulk degradation mode and surface degradation mode. The simulation results showed that, in both evolution modes, the degradation began at the ‘peak-valley’ region and fracture occurred at the cross of links and rings. Additionally, high levels of Von-Mises stress were observed in these two regions. Compared with bulk degradation, the fracture time of the stent was delayed by 63% in the surface degradation mode. In conclusion, the mass loss rate and scaffolding period showed great differences between surface degradation and bulk degradation. Based on this study, it is suggested that bulk degradation mode is not applicable to the case of inadequate water uptake mode, such as the tracheal stent degradation process. More experimental research should be carried out to accurately predict the scaffolding period after implantation. The mechanical properties of the fracture zone should be strengthened.
The Interaction of Acute‐Phase Reaction and Efficacy for Osteoporosis After Zoledronic Acid: HORIZON Pivotal Fracture Trial

Zoledronic acid (ZOL) as a yearly infusion is effective in reducing fracture risk. An acute‐phase reaction (APR), consisting of flu‐like symptoms within 3 days after infusion, is commonly seen. The objective of this analysis was to investigate whether APR occurrence influences drug efficacy. This analysis uses data from the 3‐year randomized clinical trial, Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly‐Pivotal Fracture Trial (HORIZON‐PFT). APRs were identified as adverse events within 3 days of first infusion with higher frequency in ZOL than placebo. To compare mean 3‐year change in bone mineral density (BMD) in ZOL versus placebo, among women with and without APR, t tests were used. Logistic regression was used to examine the relationship between APR occurrence and odds of incident morphometric vertebral fracture. Cox regression was used to determine the risk of nonvertebral and hip fractures for women with versus without APR. Logistic and Cox models were used to determine the risk of incident fracture in ZOL versus placebo for women with and without an APR. The analysis included 3862 women in the ZOL group and 3852 in placebo, with 42.4% in ZOL versus 11.8% in placebo experiencing an APR. The difference in BMD mean change for ZOL versus placebo was similar for women with and without an APR (all p interaction >0.10). Among ZOL women, those with APR had 51% lower vertebral fracture risk than those without (odds ratio [OR] = 0.49, p < 0.001). A similar but nonsignificant trend was observed for nonvertebral and hip fracture (relative hazard [RH] = 0.82, p = 0.10; RH = 0.70, p = 0.22, respectively). There was a greater treatment‐related reduction in vertebral fracture risk among women with APR (OR = 0.19) than those without (OR = 0.38) (p interaction = 0.01). Our results suggest that women starting ZOL who experience an APR will have a larger reduction in vertebral fracture risk with ZOL. © 2021 American Society for Bone and Mineral Research (ASBMR).
Norovirus diarrhea is significantly associated with higher counts of fecal histo-blood group antigen expressing Enterobacter cloacae among black South African infants

ABSTRACT The study tested the hypothesis that harboring high levels of histo-blood group antigen-expressing Enerobactero cloacae is a risk factor for norovirus diarrhea. The fecal E. cloacae abundance in diarrheic norovirus positive (DNP), non-diarrheic norovirus negative (NDNN), diarrhea norovirus negative (DNN), and non-diarrhea norovirus positive (NDNP) infants was determined by qPCR, and the risk of norovirus diarrhea was assessed by logistical regression. DNP infants contained significantly higher counts of E. cloacae than NDNN and DNN infants, p = . 0294, and 0.0001, respectively. The risk of norovirus diarrhea was significantly high in infants with higher counts of E. cloacae than those with lower counts, p = . 009. Harboring higher counts of E. cloacae is a risk factor for norovirus diarrhea.
Dietary Advanced Glycation End-Products and Mortality after Breast Cancer in the Women's Health Initiative

Background: Advanced glycation end-products (AGE) are formed through nonenzymatic glycation of free amino groups in proteins or lipid. They are associated with inflammation and oxidative stress, and their accumulation in the body is implicated in chronic disease morbidity and mortality. We examined the association between postdiagnosis dietary Nϵ-carboxymethyl-lysine (CML)–AGE intake and mortality among women diagnosed with breast cancer. Methods: Postmenopausal women aged 50 to 79 years were enrolled in the Women's Health Initiative (WHI) between 1993 and 1998 and followed up until death or censoring through March 2018. We included 2,023 women diagnosed with first primary invasive breast cancer during follow-up who completed a food frequency questionnaire (FFQ) after diagnosis. Cox proportional hazards (PH) regression models estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) of association between tertiles of postdiagnosis CML-AGE intake and mortality risk from all causes, breast cancer, and cardiovascular disease. Results: After a median 15.1 years of follow-up, 630 deaths from all causes were reported (193 were breast cancer–related, and 129 were cardiovascular disease–related). Postdiagnosis CML-AGE intake was associated with all-cause (HRT3vsT1, 1.37; 95% CI, 1.09–1.74), breast cancer (HRT3vsT1, 1.49; 95% CI, 0.98–2.24), and cardiovascular disease (HRT3vsT1, 1.91; 95% CI, 1.09–3.32) mortality. Conclusions: Higher intake of AGEs was associated with higher risk of major causes of mortality among postmenopausal women diagnosed with breast cancer. Impact: Our findings suggest that dietary AGEs may contribute to the risk of mortality after breast cancer diagnosis. Further prospective studies examining dietary AGEs in breast cancer outcomes and intervention studies targeting dietary AGE reduction are needed to confirm our findings.
Distribution and daily oscillation of GABA in the circadian system of the cockroach Rhyparobia maderae

Gamma‐aminobutyric acid (GABA) is the prevalent inhibitory neurotransmitter in nervous systems promoting sleep in both mammals and insects. In the Madeira cockroach, sleep‐wake cycles are controlled by a circadian clock network in the brain's optic lobes, centered in the accessory medulla (AME) with its innervating pigment‐dispersing factor (PDF) expressing clock neurons at the anterior‐ventral rim of the medulla. GABA is present in cell clusters that innervate different circuits of the cockroach's AME clock, without colocalizing in PDF clock neurons. Physiological, immunohistochemical, and behavioral assays provided evidence for a role of GABA in light entrainment, possibly via the distal tract that connects the AME's glomeruli to the medulla. Furthermore, GABA was implemented in clock outputs to multiple effector systems in optic lobe and midbrain. Here, GABAergic brain circuits were analyzed further, focusing on the circadian system in search for sleep/wake controlling brain circuits. All GABA‐immunoreactive neurons of the cockroach brain were also stained with an antiserum against the GABA‐synthesizing enzyme glutamic acid decarboxylase. We found strong overlap of the distribution of GABA‐immunoreactive networks with PDF clock networks in optic lobes and midbrain. Neurons in five of the six soma groups that innervate the clock exhibited GABA immunoreactivity. The intensity of GABA immunoreactivity in the distal tract showed daily fluctuations with maximum staining intensity in the middle of the day and weakest staining at the end of the day. Quantification via enzyme‐linked immunosorbent assay and quantitative liquid chromatography coupled to electrospray ionization tandem mass spectrometry, likewise, showed higher GABA levels in the optic lobe during the inactivity phase of the cockroach during the day and lower levels during its activity phase at dusk. Our data further support the hypothesis that light‐ and PDF‐dependently the circadian clock network of the cockroach controls GABA levels and thereby promotes sleep during the day.
Children’s Nutritional Rehabilitation Program in Beira, Mozambique: A Retrospective Study

ABSTRACT. Malnutrition is still a major public health issue in sub-Saharan Africa and Mozambique. The main aim of this study was to evaluate the adherence to the nutritional rehabilitation program (NRP) and its impact on the growth of malnourished children in Beira, Mozambique. The secondary aim was to verify the prevalence of HIV infection in malnourished children at the time of admission to the NRP. A retrospective observational study in Beira Central Hospital and 10 health centers in Beira, Mozambique, was conducted. All children 0 to 5 years of age with acute malnutrition admitted to the outpatient services of the NRP from March 2016 until February 2017 were included in the study. A total of 1,231 children with the following characteristics have been enrolled: 58% female; 33% severely malnourished; and 16.5% HIV-positive. Of the 198 (21.7%) children who completed the program, 177 (89.4%) recovered from malnutrition and 21 (10.6%) did not. Ten (1.1%) were hospitalized and 706 (77.2%) dropped out of the program. Among children who completed the program, the median weight-for-length and weight-for-height z-scores at admission were ≥ −3 and < −2; at discharge, these median z-scores were ≥ −1 (P < 0.001). Children with HIV infection and who were male had a higher prevalence of severe acute malnutrition (P < 0.001). Weight gain was found to be significant after 23 days (P = 0.004) of consuming supplements (ready-to-use therapeutic food). A diagnosis of the degree of malnutrition was accurate at admission for 70.5%; at discharge, this diagnosis was accurate for 67.2%. The NRP seems to be successful if correctly followed, even if it is limited by adherence problems. However, its effectiveness requires further investigation.