Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Exercise Training in Postoperative Patients With Congenital Heart Disease: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

Background The purpose of this meta‐analysis is to assess the effects of exercise training on quality of life, specific biomarkers, exercise capacity, and vascular function in congenital heart disease (CHD) subjects after surgery. Methods and Results We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE from the date of the inception of the database through April 2019. Altogether, 1161 records were identified in the literature search. Studies evaluating outcomes before and after exercise training among postoperative patients with congenital heart disease were included. The assessed outcomes were exercise capacity, vascular function, serum NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) levels and quality of life. We analyzed heterogeneity by using the I2 statistic and evaluated the evidence quality according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines. Nine randomized controlled trials were included. The evidence indicated that exercise interventions increased the one of the quality of life questionnaire score (mean difference=3.19 [95% CI, 0.23, 6.16]; P=0.03; I2=39%) from the score before the interventions. However, no alterations in exercise capacity, vascular function, NT‐proBNP or quality of life were observed after exercise training. The results of the subgroup analysis showed that NT‐proBNP levels were lower in the group with exercise training than in the group without exercise training over the same duration of follow‐up. The evidence quality was generally assessed to be low. Conclusions In conclusion, there is insufficient evidence to suggest that physical exercise improves long‐term follow‐up outcomes of congenital heart disease, although it has some minor effects on quality of life.
The Surgical Benefit of Hysterolaparoscopy in Endometriosis-Related Infertility: A Single Centre Retrospective Study with a Minimum 2-Year Follow-Up

Aim: This study examined the fertility performance of women after combined hysterolaparoscopic surgical management of endometriosis. Design: This study is a hospital-based retrospective review. Materials and Methods: Data collected from the records of all patients presented with endometriosis-related infertility using a checklist designed for the purpose. Result: A total of 81.3% (370/455) of women who have had the desire to have children became pregnant during the study period after the surgery. Of those who became pregnant, all three-hundred-forty-seven patients were followed to the end of their pregnancies. A successful live birth occurred in 94.2% (327/347) of individuals, and pregnancy loss occurred in 5.8% (20/347). The mean patient age was 34.1 ± 4.1 years, and the average duration of infertility was 3.4 ± 3.3 years. Pregnancy occurred spontaneously in 39.5% (146/370) of patients, after artificial insemination (AIH) in 3.8% (14/370) of women, and after in vitro fertilization-embryo transfer (IVF-ET) in 56.8% (210/370) of cases. Patients aged ≤ 35 years had a higher chance of conception post-surgery—84% versus 77%, respectively (p = 0.039). Based on the modes of pregnancy, the timely introduction of an assisted reproductive technique (ART) demonstrated a significant effect on fertility performance postsurgery. Comparatively, this effect was 91.3% vs. 74.1% among the ≤35- and >35-year-old age groups, respectively. There was no significant difference in reproductive performance based on stages of endometriosis, nor in the other parameters evaluated. Conclusion: Our data are consistent with previous clinical studies regarding the management options of endometriosis-related infertility. Overall, the combined hysterolaparoscopy treatment is a very effective and reliable procedure, and is even more effective when combined with ART. It enhances women’s wellbeing and quality of life, and significantly improves reproductive performance.
Quantitative assessment of diffusion kurtosis imaging depicting deep myometrial invasion: a comparative analysis with diffusion-weighted imaging.

PURPOSE We aimed to investigate histogram analysis of diffusion kurtosis imaging (DKI) and conventional diffusion-weighted imaging (DWI) to distinguish between deep myometrial invasion and superficial myometrial invasion in endometrial carcinoma (EC). METHODS A total of 118 pathologically confirmed EC patients with preoperative DWI were included. The data were postprocessed with a DKI (b value of 0, 700, 1400, and 2000 s/mm2) model for quantitation of apparent diffusion values (D) and apparent kurtosis coefficient values (K) for non-Gaussian distribution. The apparent diffusion coefficient (ADC) was postprocessed with a conventional DWI model (b values of 0 and 800 s/mm2). A whole-tumor analysis approach was used. Comparisons of the histogram parameters of D, K, and ADC were carried out for the deep myometrial invasion and superficial myometrial invasion subgroups. Diagnostic performance of the imaging parameters was assessed. RESULTS The Dmean, D10th, and D90th in deep myometrial invasion group were significantly lower than those in superficial invasion group (P < 0.001, P < 0.001, and P = 0.023, respectively), as well as the ADCmean, ADC10th, and ADC90th (P = 0.001, P = 0.001, and P = 0.042, respectively). The Kmean and K90th were significantly higher in deep invasion group than those in superficial myometrial invasion group (P = 0.002 and P = 0.026, respectively). The D10th, Kmean, and ADC10th had a relatively higher area under the curve (AUC) (0.72, 0.66, and 0.71, respectively) than other parameters for distinguishing deep myometrial invasion of EC. D10th showed a relatively higher AUC than ADC10th for the differentiation of lesions with deep myometrial invasion from those with superficial myometrial invasion (0.72 vs. 0.71), but the variation was not statistically significant (P = 0.35). CONCLUSION Distribution of DKI and conventional DWI parameters characterized by histogram analysis may represent an indicator for deep myometrial invasion in EC. Both DKI and DWI models showed relatively equivalent effectiveness.
Endoplasmic Reticulum-Associated Degradation-Dependent Processing in Cross-Presentation and Its Potential for Dendritic Cell Vaccinations: A Review

While the success of dendritic cell (DC) vaccination largely depends on cross-presentation (CP) efficiency, the precise molecular mechanism of CP is not yet characterized. Recent research revealed that endoplasmic reticulum (ER)-associated degradation (ERAD), which was first identified as part of the protein quality control system in the ER, plays a pivotal role in the processing of extracellular proteins in CP. The discovery of ERAD-dependent processing strongly suggests that the properties of extracellular antigens are one of the keys to effective DC vaccination, in addition to DC subsets and the maturation of these cells. In this review, we address recent advances in CP, focusing on the molecular mechanisms of the ERAD-dependent processing of extracellular proteins. As ERAD itself and the ERAD-dependent processing in CP share cellular machinery, enhancing the recognition of extracellular proteins, such as the ERAD substrate, by ex vivo methods may serve to improve the efficacy of DC vaccination.
Sons accelerate maternal aging in a wild mammal

Significance Do sons and daughters have a differential cost over the long term? Sexual size dimorphism is widespread in animals and offspring of the larger sex commonly require more parental resources. The relationship between offspring sex ratio and maternal longevity has been tested in humans, producing mixed results and debates over the relative influence of biological and sociocultural factors. Meanwhile, links between offspring sex and reproductive aging have been neglected. We used data from a wild ungulate with high male-biased sexual dimorphism but without complicating sociocultural factors to show that females with many sons during early adulthood showed the strongest declines in reproductive success in old age. Our results underline the need to consider offspring sex in studies of aging. Aging, or senescence, is a progressive deterioration of physiological function with age. It leads to age-related declines in reproduction (reproductive senescence) and survival (actuarial senescence) in most organisms. However, senescence patterns can be highly variable across species, populations, and individuals, and the reasons for such variations remain poorly understood. Evolutionary theories predict that increases in reproductive effort in early life should be associated with accelerated senescence, but empirical tests have yielded mixed results. Although in sexually size-dimorphic species offspring of the larger sex (typically males) commonly require more parental resources, these sex differences are not currently incorporated into evolutionary theories of aging. Here, we show that female reproductive senescence varies with both the number and sex ratio of offspring weaned during early life, using data from a long-term study of bighorn sheep. For a given number of offspring, females that weaned more sons than daughters when aged between 2 and 7 y experienced faster senescence in offspring survival in old age. By contrast, analyses of actuarial senescence showed no cost of early-life reproduction. Our results unite two important topics in evolutionary biology: life history and sex allocation. Offspring sex ratio may help explain among-individual variation in senescence rates in other species, including humans.
Global transmission and evolutionary dynamics of the Chikungunya virus

Abstract Chikungunya virus (CHIKV) is a re-emerging pathogen of global importance. We attempted to gain an insight into the organisation, distribution and mutational load of the virus strains reported from different parts of the world. We describe transmission dynamics and genetic characterisation of CHIKV across the globe during the last 65 years from 1952 to 2017. The evolutionary pattern of CHIKV was analysed using the E1 protein gene through phylogenetic, Bayesian and Network methods with a dataset of 265 sequences from various countries. The time to most recent common ancestor of the virus was estimated to be 491 years ago with an evolutionary rate of 2.78 × 10−4 substitutions/site/year. Genetic characterisation of CHIKV strains was carried out in terms of variable sites, selection pressure and epitope mapping. The neutral selection pressure on the E1 gene of the virus suggested a stochastic process of evolution. We identified six potential epitope peptides in the E1 protein showing substantial interaction with human MHC-I and MHC-II alleles. The present study augments global epidemiological and population dynamics of CHIKV warranting undertaking of appropriate control measures. The identification of epitopic peptides can be useful in the development of epitope-based vaccine strategies against this re-emerging viral pathogen.
On Motor Performance in Virtual 3D Object Manipulation

Fitts's law facilitates approximate comparisons of target acquisition performance across a variety of settings. Conceptually, also the index of difficulty of 3D object manipulation with six degrees of freedom can be computed, which allows the comparison of results from different studies. Prior experiments, however, often revealed much worse performance than one would reasonably expect on this basis. We argue that this discrepancy stems from confounding variables and show how Fitts's law and related research methods can be applied to isolate and identify relevant factors of motor performance in 3D manipulation tasks. The results of a formal user study ($\mathrm{n}=21$) demonstrate competitive performance in compliance with Fitts's model and provide empirical evidence that simultaneous 3D rotation and translation can be beneficial.
A female with X‐linked Nephrogenic diabetes insipidus in a family with inherited central diabetes Insipidus: Case report and review of the literature

There are two forms of diabetes insipidus, central (neurohypophyseal), and nephrogenic, caused by pathogenic variants in the AVP gene and the AVPR2 or AQP2 genes, respectively. We report on a four‐generation family, seven individuals had central diabetes insipidus (CDI) and the female index patient seen from age 16 to 26 years had (mild) nephrogenic diabetes insipidus. In her father with CDI, a known pathogenic heterozygous AVP variant c. 232_234del p.(Glu78del) was identified, confirming the diagnosis of CDI in him and the other affected family members. In the proband, molecular analysis disclosed a novel heterozygous AVPR2 gene variant, c.962A > T p.(Asn321Ile) and an extremely skewed X‐inactivation, confirming X‐linked nephrogenic diabetes insipidus (XL‐NDI). Whole exome sequencing showed no further causative mutation. This is the first report on the co‐existence of CDI and NDI in one family. Our review of symptomatic female AVPR2 heterozygotes includes 23 families with at least one affected female (including this study). There were 21 different causative mutations. Mutation types in females did not differ from those in males. Both severe XL‐NDI and mild forms were reported in females. All six females with severe XL‐NDI had complete loss‐of‐function (null) mutations. The remaining 17 female probands had milder XL‐NDI caused by 14 missense variants and three null variants of the AVPR2 gene. X‐inactivation was studied in nine of these females; all showed extreme or slight skewing. The review underlines that XL‐NDI in female AVPR2 heterozygotes is always accompanied by skewed X‐inactivation, emphasizing a need for X‐inactivation studies in these females.
Hydrogen Peroxide-Mediated Oxygen Enrichment Eradicates Helicobacter pylori In Vitro and In Vivo

Helicobacter pylori is an important risk factor for gastric ulcers. However, antibacterial therapies increase the resistance rate and decrease the eradication rate of H. pylori. Inspired by the microaerophilic characteristics of H. pylori, we aimed at effectively establishing an oxygen-enriched environment to eradicate and prevent the recurrence of H. pylori. The effect and the mechanism of an oxygen-enriched environment in eradicating H. pylori and preventing the recurrence were explored in vitro and in vivo. ABSTRACT Helicobacter pylori is an important risk factor for gastric ulcers. However, antibacterial therapies increase the resistance rate and decrease the eradication rate of H. pylori. Inspired by the microaerophilic characteristics of H. pylori, we aimed at effectively establishing an oxygen-enriched environment to eradicate and prevent the recurrence of H. pylori. The effect and the mechanism of an oxygen-enriched environment in eradicating H. pylori and preventing the recurrence were explored in vitro and in vivo. During oral administration and after drug withdrawal, H. pylori counts were evaluated by Giemsa staining in animal cohorts. An oxygen-enriched environment in which H. pylori could not survive was successfully established by adding hydrogen peroxide into several solutions and rabbit gastric juice. Hydrogen peroxide effectively killed H. pylori in Columbia blood agar and special peptone broth. Minimum inhibition concentrations and minimum bactericidal concentrations of hydrogen peroxide were both relatively stable after promotion of resistance for 30 generations, indicating that hydrogen peroxide did not easily promote resistance in H. pylori. In models of Mongolian gerbils and Kunming mice, hydrogen peroxide has been shown to significantly eradicate and effectively prevent the recurrence of H. pylori without toxicity and damage to the gastric mucosa. The mechanism of hydrogen peroxide causing H. pylori death was related to the disruption of bacterial cell membranes. The oxygen-enriched environment achieved by hydrogen peroxide eradicates and prevents the recurrence of H. pylori by damaging bacterial cell membranes. Hydrogen peroxide thus provides an attractive candidate for anti-H. pylori treatment.
Extra‐pair paternity as a strategy to reduce the costs of heterospecific reproduction? Insights from the crow hybrid zone

Within hybrid zones of socially monogamous species, the number of mating opportunities with a conspecific can be limited. As a consequence, individuals may mate with a heterospecific (social) partner despite possible fitness costs to their hybrid offspring. Extra‐pair copulations with a conspecific may thus arise as a possible post hoc strategy to reduce the costs of hybridization. We here assessed the rate of extra‐pair paternity in the hybrid zone between all‐black carrion crows (Corvus (corone) corone) and grey hooded crows (C. (c.) cornix) and tested whether extra‐pair paternity (EPP) was more likely in broods where parents differed in plumage colour. The proportion of broods with at least one extra‐pair offspring and the proportion of extra‐pair offspring were low overall (6.98% and 2.90%, respectively) with no evidence of hybrid broods having higher EPP rates than purebred nests.
Intrathecal Injection in a Rat Model: A Potential Route to Deliver Human Wharton’s Jelly-Derived Mesenchymal Stem Cells into the Brain

Mesenchymal stem cells (MSCs) are considered as promising therapeutic agents for neurodegenerative disorders because they can reduce underlying pathology and also repair damaged tissues. Regarding the delivery of MSCs into the brain, intravenous and intra-arterial routes may be less feasible than intraparenchymal and intracerebroventricular routes due to the blood–brain barrier. Compared to the intraparenchymal or intracerebroventricular routes, however, the intrathecal route may have advantages: this route can deliver MSCs throughout the entire neuraxis and it is less invasive since brain surgery is not required. The objective of this study was to investigate the distribution of human Wharton’s jelly-derived MSCs (WJ-MSCs) injected via the intrathecal route in a rat model. WJ-MSCs (1 × 106) were intrathecally injected via the L2-3 intervertebral space in 6-week-old Sprague Dawley rats. These rats were then sacrificed at varying time points: 0, 6, and 12 h following injection. At 12 h, a significant number of MSCs were detected in the brain but not in other organs. Furthermore, with a 10-fold higher dose of WJ-MSCs, there was a substantial increase in the number of cells migrating to the brain. These results suggest that the intrathecal route can be a promising route for the performance of stem cell therapy for CNS diseases.
The Multifaceted Impact of Education on Entry into Motherhood

This article studies the composite effect of education on young women's entry into motherhood, using longitudinal data from Norway from 1971 to 2001. In line with previous research, we find that school enrolment delays motherhood, but having finished education there is a catching-up effect, as women who have completed at higher levels have their first child sooner than women who have completed at lower levels. Contrasting behaviour between women within various fields of education further indicate a career-adjustment effect related to differences in opportunity costs and/or preference heterogeneity. Finally, increasing educa tional differences in the timing of motherhood among younger cohorts suggest that long parental leaves and generous family benefits may fit better with a career track in some jobs than others.
Lifetime of a structure evolving by cluster aggregation and particle loss, and application to postsynaptic scaffold domains

The dynamics of several mesoscopic biological structures depend on the interplay of growth through the incorporation of components of different sizes laterally diffusing along the cell membrane, and loss by component turnover. In particular, a model of such an out-of-equilibrium dynamics has recently been proposed for postsynaptic scaffold domains which are key structures of neuronal synapses. It is of interest to estimate the lifetime of these mesoscopic structures, especially in the context of synapses where this time is related to memory retention. The lifetime of a structure can be very long as compared to the turnover time of its components and it can be difficult to estimate it by direct numerical simulations. Here, in the context of the model proposed for postsynaptic scaffold domains, we approximate the aggregation-turnover dynamics by a shot-noise process. This enables us to analytically compute the quasi-stationary distribution describing the sizes of the surviving structures as well as their characteristic lifetime. We show that our analytical estimate agrees with numerical simulations of a full spatial model, in a regime of parameters where a direct assessment is computationally feasible. We then use our approach to estimate the lifetime of mesoscopic structures in parameter regimes where computer simulations would be prohibitively long. For gephyrin, the scaffolding protein specific to inhibitory synapses, we estimate a lifetime longer than several months for a scaffold domain when the single gephyrin protein turnover time is about half an hour, as experimentally measured. While our focus is on postsynaptic domains, our formalism and techniques should be applicable to other biological structures that are also formed by a balance of condensation and turnover.
Structure and function of the calcium‐selective TRP channel TRPV6

Epithelial calcium channel TRPV6 is a member of the vanilloid subfamily of TRP channels that is permeable to cations and highly selective to Ca2+; it shows constitutive activity regulated negatively by Ca2+ and positively by phosphoinositol and cholesterol lipids. In this review, we describe the molecular structure of TRPV6 and discuss how its structural elements define its unique functional properties. High Ca2+ selectivity of TRPV6 originates from the narrow selectivity filter, where Ca2+ ions are directly coordinated by a ring of anionic aspartate side chains. Divalent cations Ca2+ and Ba2+ permeate TRPV6 pore according to the knock‐off mechanism, while tight binding of Gd3+ to the aspartate ring blocks the channel and prevents Na+ from permeating the pore. The iris‐like channel opening is accompanied by an α‐to‐π helical transition in the pore‐lining transmembrane helix S6. As a result of this transition, the intracellular halves of the S6 helices bend and rotate by about 100 deg, exposing different residues to the channel pore in the open and closed states. Channel opening is also associated with changes in occupancy of the transmembrane domain lipid binding sites. The inhibitor 2‐aminoethoxydiphenyl borate (2‐APB) binds to TRPV6 in a pocket formed by the cytoplasmic half of the S1‐S4 transmembrane helical bundle and shifts open‐closed channel equilibrium towards the closed state by outcompeting lipids critical for activation. Ca2+ inhibits TRPV6 via binding to calmodulin (CaM), which mediates Ca2+‐dependent inactivation. The TRPV6‐CaM complex exhibits 1:1 stoichiometry; one TRPV6 tetramer binds both CaM lobes, which adopt a distinct head‐to‐tail arrangement. The CaM C‐terminal lobe plugs the channel through a unique cation‐π interaction by inserting the side chain of lysine K115 into a tetra‐tryptophan cage at the ion channel pore intracellular entrance. Recent studies of TRPV6 structure and function described in this review advance our understanding of the role of this channel in physiology and pathophysiology and inform new therapeutic design.