Miracle-dz/UniFAR-FTUs huggingface dataset:
Elicited and pre‐existing anti‐Neu5Gc antibodies differentially affect human endothelial cells transcriptome

Humans cannot synthesize N‐glycolylneuraminic acid (Neu5Gc) but dietary Neu5Gc can be absorbed and deposited on endothelial cells (ECs) and diet‐induced anti‐Neu5Gc antibodies (Abs) develop early in human life. While the interaction of Neu5Gc and diet‐induced anti‐Neu5Gc Abs occurs in all normal individuals, endothelium activation by elicited anti‐Neu5Gc Abs following a challenge with animal‐derived materials, such as following xenotransplantation, had been postulated. Ten primary human EC preparations were cultured with affinity‐purified anti‐Neu5Gc Abs from human sera obtained before or after exposure to Neu5Gc‐glycosylated rabbit IgGs (elicited Abs). RNAs of each EC preparation stimulated in various conditions by purified Abs were exhaustively sequenced. EC transcriptomic patterns induced by elicited anti‐Neu5Gc Abs, compared with pre‐existing ones, were analyzed. qPCR, cytokines/chemokines release, and apoptosis were tested on some EC preparations. The data showed that anti‐Neu5Gc Abs induced 967 differentially expressed (DE) genes. Most DE genes are shared following EC activation by pre‐existing or anti‐human T‐cell globulin (ATG)‐elicited anti‐Neu5Gc Abs. Compared with pre‐existing anti‐Neu5Gc Abs, which are normal component of ECs environment, elicited anti‐Neu5Gc Abs down‐regulated 66 genes, including master genes of EC function. Furthermore, elicited anti‐Neu5Gc Abs combined with complement‐containing serum down‐regulated most transcripts mobilized by serum alone. Both types of anti‐Neu5Gc Abs‐induced a dose‐ and complement‐dependent release of selected cytokines and chemokines. Altogether, these data show that, compared with pre‐existing anti‐Neu5Gc Abs, ATG‐elicited anti‐Neu5Gc Abs specifically modulate genes related to cytokine responses, MAPkinase cascades, chemotaxis, and integrins and do not skew the EC transcriptome toward a pro‐inflammatory profile in vitro.
Acute effect of Finnish sauna bathing on brachial artery flow‐mediated dilation and reactive hyperemia in healthy middle‐aged and older adults

Regular Finnish sauna bathing is associated with a reduced risk of all‐cause and cardiovascular mortality in middle‐aged and older adults. Potential acute physiological adaptations induced by sauna bathing that underlie this relationship remain to be fully elucidated. The purpose of this study was to determine if typical Finnish sauna sessions acutely improve brachial artery flow‐mediated dilation (FMD) and reactive hyperemia (RH) in healthy middle‐aged and older adults. Using a randomized crossover design, FMD and RH were evaluated in 21 healthy adults (66 ± 6 years, 10 men/11 women) before and after each of the following conditions: (1) 1 × 10 min of Finnish sauna bathing (80.2 ± 3.2°C, 23 ± 2% humidity); (2) 2 × 10 min of sauna bathing separated by 10 min of rest outside the sauna; (3) a time control period (10 min of seated rest outside the sauna). FMD was taken as the peak change from baseline in brachial artery diameter following 5 min of forearm ischemia, whereas RH was quantified as both peak and area‐under‐the‐curve forearm vascular conductance postischemia. FMD was statistically similar pre to post 1 × 10 min (4.69 ± 2.46 to 5.41 ± 2.64%, P = 0.20) and 2 × 10 min of sauna bathing (4.16 ± 1.79 to 4.55 ± 2.14%, P = 0.58). Peak and area‐under‐the‐curve forearm vascular conductance were also similar following both sauna interventions. These results suggest that typical Finnish sauna bathing sessions do not acutely improve brachial artery FMD and RH in healthy middle‐aged and older adults.
Nicotinamide protects against skeletal muscle atrophy in streptozotocin-induced diabetic mice

Abstract Context: Skeletal muscle atrophy is a complication of diabetes, partially induced by nicotinamide adenine dinucleotide (NAD+) deficiency. Objective: This study investigates the potential of nicotinamide (NAM) supplementation, a precursor of NAD+, against muscle atrophy. Methods: Mice were separated into normal control group, normal control with NAM administration group, diabetic group, and diabetic mice with NAM administration group. Basic characteristics, muscle weight, maximal grip strength, and myofibers cross-sectional area were analysed. Markers reflecting muscle atrophy and hypertrophy, and transforming growth factor β1/Smad2 (TGF-β1/Smad2) pathway were examined. Results: NAM did not influence body weight and blood glucose. In diabetic mice, NAM increased NAD+ level, rescued muscle weight and strength loss, and increased myofibers cross-sectional area. NAM inhibited MuRF1 and Atrogin1, while elevated phosphorylation of Akt. Overactivation of TGF-β1/Smad2 pathway was repressed by NAM. Conclusion: NAM ameliorated diabetic muscle atrophy by rebalancing protein anabolism and catabolism, probably through de-activation of TGF-β1/Smad2 signaling.
A modelling approach for correcting reporting delays in disease surveillance data

One difficulty for real‐time tracking of epidemics is related to reporting delay. The reporting delay may be due to laboratory confirmation, logistical problems, infrastructure difficulties, and so on. The ability to correct the available information as quickly as possible is crucial, in terms of decision making such as issuing warnings to the public and local authorities. A Bayesian hierarchical modelling approach is proposed as a flexible way of correcting the reporting delays and to quantify the associated uncertainty. Implementation of the model is fast due to the use of the integrated nested Laplace approximation. The approach is illustrated on dengue fever incidence data in Rio de Janeiro, and severe acute respiratory infection data in the state of Paraná, Brazil.
Cutting Edge: Protein Arginine Deiminase 2 and 4 Regulate NLRP3 Inflammasome–Dependent IL-1β Maturation and ASC Speck Formation in Macrophages

Key Points Citrullination in macrophages is induced during pyroptosis. The NLRP3 inflammasome is regulated by Ca2+-dependent PAD enzymes. Protein arginine deiminase (PAD) enzymes catalyze the conversion of protein-bound arginine into citrulline, an irreversible posttranslational modification with loss of a positive charge that can influence protein–protein interactions and protein structure. Protein arginine deiminase activity depends on high intracellular calcium concentrations occurring in dying cells. In this study, we demonstrate that protein citrullination is common during pyroptotic cell death in macrophages and that inhibition of PAD enzyme activity by Cl-amidine, a pan-PAD inhibitor, blocks NLRP3 inflammasome assembly and proinflammatory IL-1β release in macrophages. Genetic deficiency of either PAD2 or PAD4 alone in murine macrophages does not impair IL-1β release; however, pharmacological inhibition or small interfering RNA knockdown of PAD2 within PAD4−/− macrophages does. Our results suggest that PAD2 and 4 activity in macrophages is required for optimal inflammasome assembly and IL-1β release, a finding of importance for autoimmune diseases and inflammation.
Climate drivers of malaria at its southern fringe in the Americas

In this work we analyze potential environmental drivers of malaria cases in Northwestern Argentina. We inspect causal links between malaria and climatic variables by means of the convergent cross mapping technique, which provides a causality criterion from the theory of dynamic systems. Analysis is based on 12 years of weekly malaria P. vivax cases in Tartagal, Salta, Argentina—at the southern fringe of malaria incidence in the Americas—together with humidity and temperature time-series spanning the same period. Our results show that there are causal links between malaria cases and both maximum temperature, with a delay of five weeks, and minimum temperature, with delays of zero and twenty two weeks. Humidity is also a driver of malaria cases, with thirteen weeks delay between cause and effect. Furthermore we also determined the sign and strength of the effects. Temperature has always a positive non-linear effect on cases, with maximum temperature effects more pronounced above 25° C and minimum above 17° C, while effects of humidity are more intricate: maximum humidity above 85% has a negative effect, whereas minimum humidity has a positive effect on cases. These results might be signaling processes operating at short (below 5 weeks) and long (over 12 weeks) time delays, corresponding to effects related to parasite cycle and mosquito population dynamics respectively. The non-linearities found for the strength of the effect of temperature on malaria cases make warmer areas more prone to higher increases in the disease incidence. Moreover, our results indicate that an increase of extreme weather events could enhance the risks of malaria spreading and re-emergence beyond the current distribution. Both situations, warmer climate and increase of extreme events, will be remarkably increased by the end of the century in this hot spot of climate change.
Evaluation of the psychometric properties of the HIV Disability Questionnaire among adults living with HIV in the United Kingdom: A cross-sectional self-report measurement study

Objective To evaluate the psychometric properties of the HIV Disability Questionnaire (HDQ) among adults living with HIV in London, United Kingdom (UK). Methods This is a cross-sectional measurement study. We recruited and administered the self-reported HDQ, seven criterion measures, and a demographic questionnaire with adults living with HIV accessing HIV care. We determined median and interquartile ranges (IQR) for disability presence, severity and episodic scores (range 0-100). We calculated Cronbach’s alpha (α) Kuder-Richardson-20 (KR-20) statistics for disability and episodic scores respectively (internal consistency reliability), smallest detectable change (SDC) for each HDQ severity item and domain (precision), and tested 36 a priori hypotheses assessing correlations between HDQ and criterion scores (construct validity). Results Of N=243 participants, all were male, median age 40 years, 94% currently taking antiretroviral therapy, and 22% living with ≥2 concurrent health conditions. Median HDQ domain scores ranged from 0 (IQR: 0,7) (difficulties with day-to-day activities domain) to 27 (IQR: 14, 41) (uncertainty domain). Cronbach’s alpha for the HDQ severity scale ranged from 0.85 (95% Confidence Interval (CI): 0.80-0.90) in the cognitive domain to 0.93 (95%CI: 0.91-0.94) in the mental-emotional domain. The KR-20 statistic for the HDQ episodic scale ranged from 0.74 (95%CI: 0.66-0.83) in the cognitive domain to 0.91 (95%CI: 0.89-0.94) in the uncertainty domain. SDC ranged from 7.3-15.0 points on the HDQ severity scale for difficulties with day-to-day activities and cognitive symptoms domains, respectively. The majority of the construct validity hypotheses (n=30/36, 83%) were confirmed. Conclusions The HDQ possesses internal consistency reliability and construct validity with varied precision when administered to males living with HIV in London, UK. Clinicians and researchers may use the HDQ to measure the nature and extent of disability experienced by PLHIV in the UK, and to inform HIV service provision to address the health-related challenges among PLHIV.
Real-time, embedded fuzzy control of the pioneer3-DX robot for path following

This paper presents a microcontroller implementation of a fuzzy logic control algorithm applied to the mobile robot Pioneer3-DX. The design and implementation of the fuzzy controller is described. Both speed and steering control are achieved using the same real-time fuzzy controller. The description starts with an example for a circular path following, then presents an implementation of the algorithms for following a generalized curve path.
Neuronal integration in the adult mouse olfactory bulb is a non-selective addition process

Adult neurogenesis in the olfactory bulb (OB) is considered as a competition in which neurons scramble during a critical selection period for integration and survival. Moreover, newborn neurons are thought to replace pre-existing ones that die. Despite indirect evidence supporting this model, systematic in vivo observations are still scarce. We used two-photon in vivo imaging to study neuronal integration and survival. We show that loss of new neurons in the OB after arrival at terminal positions occurs only at low levels. Moreover, long-term observations showed that no substantial cell death occurred at later stages. Neuronal death was induced by standard doses of thymidine analogs, but disappeared when low doses were used. Finally, we demonstrate that the OB grows throughout life. This shows that neuronal selection during OB-neurogenesis does not occur after neurons reached stable positions. Moreover, this suggests that OB neurogenesis does not represent neuronal turnover but lifelong neuronal addition.
Optimization of textural and technological parameters using response surface methodology (RSM) for the development of beef products for older consumers.

Red meat has a tougher texture compared with many other food products, therefore consumption is often reduced among older adults. Acidic treatments had a positive effect on WBSF values (reduced the WBSF values from 23.35 N for control to 14.83 N), and texture parameters and a combination with apple fibre and rice starch may improve the health profile of a meat product with benefits for consumers, particularly for older population. A novel meat product with a softer texture (apple fibre 0.15%, rice starch 0.30% and citric acid 0.16 M) was optimized and successfully validated in this study. The results obtained for the objective measurements of tenderness were confirmed by consumers' tenderness results (p < 0.05) moreover texture-optimized beef samples were found to be more acceptable by older consumers compared with control. Meat processors have an important role in increasing the availability of suitable meat products for older consumers, by developing products that will meet their nutritional and textural needs. In this study, a novel meat product with a softer texture was developed, successfully validated and the product was found to be acceptable by older consumers. Meat processors could consider using rice starch, apple fibre and citric acid as feasible alternative to traditional ingredients used for beef injection, in order to obtain a softer product, that appeal to older consumers with difficulties in mastication. This article is protected by copyright. All rights reserved.
Clonal expansion of SIV-infected cells in macaques on antiretroviral therapy is similar to that of HIV-infected cells in humans

Clonal expansion of HIV infected cells plays an important role in the formation and persistence of the reservoir that allows the virus to persist, in DNA form, despite effective antiretroviral therapy. We used integration site analysis to ask if there is a similar clonal expansion of SIV infected cells in macaques. We show that the distribution of HIV and SIV integration sites in vitro is similar and that both viruses preferentially integrate in many of the same genes. We obtained approximately 8000 integration sites from blood samples taken from SIV-infected macaques prior to the initiation of ART, and from blood, spleen, and lymph node samples taken at necropsy. Seven clones were identified in the pre-ART samples; one persisted for a year on ART. An additional 100 clones were found only in on-ART samples; a number of these clones were found in more than one tissue. The timing and extent of clonal expansion of SIV-infected cells in macaques and HIV-infected cells in humans is quite similar. This suggests that SIV-infected macaques represent a useful model of the clonal expansion of HIV infected cells in humans that can be used to evaluate strategies intended to control or eradicate the viral reservoir.
How prepared are we for cross-border outbreaks? An exploratory analysis of cross-border response networks for outbreaks of multidrug resistant microorganisms in the Netherlands and Germany

Background The emergence and spread of multidrug resistant microorganisms is a serious threat to transnational public health. Therefore, it is vital that cross-border outbreak response systems are constantly prepared for fast, rigorous, and efficient response. This research aims to improve transnational collaboration by identifying, visualizing, and exploring two cross-border response networks that are likely to unfold during outbreaks involving the Netherlands and Germany. Methods Quantitative methods were used to explore response networks during a cross-border outbreak of carbapenem resistant Enterobacteriaceae in healthcare settings. Eighty-six Dutch and German health professionals reflected on a fictive but realistic outbreak scenario (response rate ≈ 70%). Data were collected regarding collaborative relationships between stakeholders during outbreak response, prior working relationships, and trust in the networks. Network analysis techniques were used to analyze the networks on the network level (density, centralization, clique structures, and similarity of tie constellations between two networks) and node level (brokerage measures and degree centrality). Results Although stakeholders mainly collaborate with stakeholders belonging to the same country, transnational collaboration is present in a centralized manner. Integration of the network is reached, since several actors are beneficially positioned to coordinate transnational collaboration. However, levels of trust are moderately low and prior-existing cross-border working relationships are sparse. Conclusion Given the explored network characteristics, we conclude that the system has a promising basis to achieve effective coordination. However, future research has to determine what kind of network governance form might be most effective and efficient in coordinating the necessary cross-border response activity. Furthermore, networks identified in this study are not only crucial in times of outbreak containment, but should also be fostered in times of non-crisis.
National Longitudinal Lesbian Family Study - Mental Health of Adult Offspring.

To the Editor: The peak incidence of many psychiatric disorders occurs during emerging adulthood.1 The ongoing, community-based National Longitudinal Lesbian Family Study (NLLFS), which has a 92% retention rate, has followed a cohort of offspring with sexual-minority parents.2 This longitudinal study (from conception into adulthood) provides the opportunity to examine mental health status in these adult offspring. During the first epoch of the study (1986–1992), we recruited 154 prospective mothers from 84 planned lesbian families conceiving through donor insemination in Boston, Washington, D.C., and San Francisco.2 All the callers who responded to study announcements were enrolled. In the sixth epoch, with approval from the institutional review board at Sutter Health (a not-for-profit health system in Northern California) and after obtaining written informed consent from the participants, we administered the standardized Achenbach Adult Self-Report through a protected online software program to assess the psychological health of 77 index offspring (who were 25 years old, 49.4% female, 90.9% white, and 87.0% with a college degree or higher), including one set of twins. The Adult Self-Report is a validated, self-rating form for measuring adaptive functioning and behavioral or emotional problems among adults between the ages of 18 and 59 years.3 The NLLFS offspring sample was matched with the Achenbach normative sample of persons in the United States3 with respect to age, sex, race or ethnic background, and educational level. Case–control matching (random sampling without replacement) was used for all Adult SelfReport demographic variables. A comparison of the NLLFS offspring sample and the matched Achenbach normative sample showed no significant between-group differences with respect to adaptive functioning (family, friends, spouse or partner relationships, and educational or job performance), behavioral or emotional problems, scores on mental health diagnostic scales, or the percentage of participants with a score in the borderline or clinical range (Table 1, and Table S2 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). A limitation of our study is that because of the sample size, the effect sizes and statistical power in the post hoc analyses were low. Thus, the results should be interpreted with caution. Furthermore, the study was conducted with a nonrandom sample. These findings need replication in a larger population that includes participants with more diversity with respect to race, ethnic background, education, income, gender identity, and sexual orientation, with parents in more diverse sexual minorities (i.e., lesbian, gay, bisexual, and transgender). In addition, such a study would ideally be conducted in a longitudinal population with multiple informants. In conclusion, in a large, prospective study involving 25-year-olds with sexual-minority parents, there were no significant differences in measures of mental health between those who were conceived through donor insemination and enrolled
Properties and pitfalls of weighting as an alternative to multilevel multiple imputation in cluster randomized trials with missing binary outcomes under covariate-dependent missingness

The generalized estimating equation (GEE) approach can be used to analyze cluster randomized trial data to obtain population-averaged intervention effects. However, most cluster randomized trials have some missing outcome data and a GEE analysis of available data may be biased when outcome data are not missing completely at random. Although multilevel multiple imputation for GEE (MMI-GEE) has been widely used, alternative approaches such as weighted GEE are less common in practice. Using both simulations and a real data example, we evaluate the performance of inverse probability weighted GEE vs. MMI-GEE for binary outcomes. Simulated data are generated assuming a covariate-dependent missing data pattern across a range of missingness clustering (from none to high), where all covariates are measured at baseline and are fully observed (i.e. a type of missing-at-random mechanism). Two types of weights are estimated and used in the weighted GEE: (1) assuming no clustering of missingness (W-GEE) and (2) accounting for such clustering (CW-GEE). Results show that, even in settings with high missingness clustering, CW-GEE can lead to more bias and lower coverage than W-GEE, whereas W-GEE and MMI-GEE provide comparable results. W-GEE should be considered a viable strategy to account for missing outcomes in cluster randomized trials.