Miracle-dz/UniFAR-FTUs huggingface dataset:
Open Fetal Microneurosurgery for Intrauterine Spina Bifida Repair

Objectives: The aim of the study was to describe the feasibility of open fetal microneurosurgery for intrauterine spina bifida (SB) repair and to compare perinatal outcomes with cases managed using the classic open fetal surgery technique. Methods: In this study, we selected a cohort of consecutive fetuses with isolated open SB referred to our fetal surgery center in Queretaro, Mexico, during a 3.5-year period (2016–2020). SB repair was performed by either classic open surgery (6- to 8-cm hysterotomy with leakage of amniotic fluid, which was replaced before uterine closure) or open microneurosurgery, which is a novel technique characterized by a 15- to 20-mm hysterotomy diameter, reduced fetal manipulation by fixing the fetal back, and maintenance of normal amniotic fluid and uterine volume during the whole surgery. Perinatal outcomes of cases operated with the classic open fetal surgery technique and open microneurosurgery were compared. Results: Intrauterine SB repair with a complete 3-layer correction was successfully performed in 60 cases either by classic open fetal surgery (n = 13) or open microneurosurgery (n = 47). No significant differences were observed in gestational age (GA) at fetal intervention (25.4 vs. 25.1 weeks, p = 0.38) or surgical times (107 vs. 120 min, p = 0.15) between both groups. The group with open microneurosurgery showed a significantly lower rate of oligohydramnios (0 vs. 15.4%, p = 0.01), preterm rupture of the membranes (19.0 vs. 53.8%, p = 0.01), higher GA at birth (35.1 vs. 32.7 weeks, p = 0.03), lower rate of preterm delivery <34 weeks (21.4 vs. 61.5%, p = 0.01), and lower rate of perinatal death (4.8 vs. 23.1%, p = 0.04) than the group with classic open surgery. During infant follow-up, the rate of hydrocephalus requiring ventriculoperitoneal shunting was similar between both groups (7.5 vs. 20%, p = 0.24). All patients showed an intact hysterotomy site at delivery. Conclusion: Intrauterine spina repair by open fetal microneurosurgery is feasible and was associated with better perinatal outcomes than classic open fetal surgery.
Data Sharing Under the General Data Protection Regulation

Supplemental Digital Content is available in the text. The General Data Protection Regulation (GDPR) became binding law in the European Union Member States in 2018, as a step toward harmonizing personal data protection legislation in the European Union. The Regulation governs almost all types of personal data processing, hence, also, those pertaining to biomedical research. The purpose of this article is to highlight the main practical issues related to data and biological sample sharing that biomedical researchers face regularly, and to specify how these are addressed in the context of GDPR, after consulting with ethics/legal experts. We identify areas in which clarifications of the GDPR are needed, particularly those related to consent requirements by study participants. Amendments should target the following: (1) restricting exceptions based on national laws and increasing harmonization, (2) confirming the concept of broad consent, and (3) defining a roadmap for secondary use of data. These changes will be achieved by acknowledged learned societies in the field taking the lead in preparing a document giving guidance for the optimal interpretation of the GDPR, which will be finalized following a period of commenting by a broad multistakeholder audience. In parallel, promoting engagement and education of the public in the relevant issues (such as different consent types or residual risk for re-identification), on both local/national and international levels, is considered critical for advancement. We hope that this article will open this broad discussion involving all major stakeholders, toward optimizing the GDPR and allowing a harmonized transnational research approach.
Profiling plasma‐extracellular vesicle proteins and microRNAs in diabetes onset in middle‐aged male participants in the ELSA‐Brasil study

We measured plasma‐derived extracellular vesicle (EV) proteins and their microRNA (miRNA) cargos in normoglycemic (NG), glucose intolerant (GI), and newly diagnosed diabetes mellitus (DM) in middle‐aged male participants of the Brazilian Longitudinal Study of Adult Health (ELSA‐Brazil). Mass spectrometry revealed decreased IGHG‐1 and increased ITIH2 protein levels in the GI group compared with that in the NG group and higher serotransferrin in EVs in the DM group than in those in the NG and GI groups. The GI group also showed increased serum ferritin levels, as evaluated by biochemical analysis, compared with those in both groups. Seventeen miRNAs were differentially expressed (DEMiRs) in the plasma EVs of the three groups. DM patients showed upregulation of miR‐141‐3p and downregulation of miR‐324‐5p and ‐376c‐3p compared with the NG and GI groups. The DM and GI groups showed increased miR‐26b‐5p expression compared with that in the NG group. The DM group showed decreased miR‐374b‐5p levels compared with those in the GI group and higher concentrations than those in the NG group. Thus, three EV proteins and five DEMiR cargos have potential prognostic importance for diabetic complications mainly associated with the immune function and iron status of GI and DM patients.
Can Double Fortification of Salt with Iron and Iodine Reduce Anemia, Iron Deficiency Anemia, Iron Deficiency, Iodine Deficiency, and Functional Outcomes? Evidence of Efficacy, Effectiveness, and Safety

ABSTRACT Background Anemia, iron deficiency, and iodine deficiency are problems of important public health concern in many parts of the world, with consequences for the health, development, and work capacity of populations. Several countries are beginning to implement double fortified salt (DFS) programs to simultaneously address iodine and iron deficiencies. Objective Our objective was to summarize the evidence for efficacy and effectiveness of DFS on the full range of status and functional outcomes and across different implementation and evaluation designs essential to successful interventions. Methods We conducted a systematic review and meta-analysis of published and gray literature examining the effects of DFS on nutritional status, cognition, work productivity, development, and morbidity of all population groups. We searched for articles in Medline, Embase, CINAHL, Cochrane Central Register, and ProQuest for randomized trials, quasi-randomized trials, and program effectiveness evaluations. Results A total of 22 studies (N individuals = 52,758) were included. Efficacy studies indicated a significant overall positive effect on hemoglobin concentration [standardized mean difference (95% CI): 0.33 (0.18, 0.48)], ferritin [0.42 (0.08, 0.76)], anemia [risk ratio (95% CI): 0.80 (0.70, 0.92)], and iron deficiency anemia [0.36 (0.24, 0.55)]. Effects on urinary iodine concentration were not significantly different between DFS and iodized salt. The impact on functional outcomes was mixed. Only 2 effectiveness studies were identified. They reported programmatic challenges including low coverage, suboptimal DFS quality, and storage constraints. Conclusions Given the biological benefits of DFS across several populations in efficacy research, additional evaluations of robust DFS programs delivered at scale, which consider effective implementation and measure appropriate biomarkers, are needed.
School absenteeism is linked to household food insecurity in school catchment areas in Southern Nevada

Abstract Objectives: Food security and school attendance are both important for health, well-being and academic performance of children and adolescents. However, their intersection remains underexamined, especially in the USA. The current study considered the association between elementary school-level absenteeism and household food insecurity. Design: The current study linked school-level absenteeism and household food insecurity rates using geographic information system mapping and applied the tobit regression model to examine their association. Setting: The Clark County, Nevada, public school district – the fifth largest in the USA and in a state with disproportionate food insecurity and chronic school absenteeism rates. Participants: Data consisted of school-level absenteeism rates from 185 elementary schools and census tract-level household food insecurity rates. Results: Average daily attendance rates were lower for schools with catchment areas that had higher average household food insecurity (FI), decreasing by −0·0232 % per 1 % increase in FI rate (P-value = 0·022). They were also significantly associated with most absenteeism risk factors. Average daily attendance rate was negatively associated with Free and Reduced Lunch eligibility percentage (−0·010 per 1 % increase in FI, P-value < 0·001) and Individualized Education Program participation percentage (−0·039 % per 1 % increase in FI, P-value = 0·033), but positively associated with parent–teacher conference participation rate (0·006 % per 1 % increase in FI, P-value = 0·025) and white student percentage (0·011 % per 1 % increase in FI, P-value = 0·022). Conclusions: The current study suggests a link between household food insecurity and elementary school-level absenteeism. Understanding this link is important for policy and practice because schools are frequent settings for food insecurity mitigation interventions.
Effect of exercise intensity on metabolic responses on combined application of electrical stimulation and voluntary exercise

The combined application of voluntary exercises and neuromuscular electrical stimulation (NMES) has been developed as a new type of exercise that can recruit motor units contributing to both aerobic and anaerobic energy metabolisms. We aimed to investigate the effect of voluntary exercise intensity on metabolic responses on the combination of voluntary exercise and NMES. In 13 volunteers, oxygen consumption and the blood lactate concentration were measured during (1) voluntary pedaling exercise at four different intensities: 50%, 75%, 100%, and 125% of the ventilatory threshold (VT) (VOL), (2) these voluntary exercises with superimposed NMES applied to the gluteus and thigh muscles (VOL+NMES), and (3) NMES only (NMES). Oxygen consumption and the blood lactate concentration in VOL+NMES were significantly greater than VOL at each exercise intensity (p < 0.05). Differences in oxygen consumption between VOL+NMES and VOL decreased with exercise intensity, and that at 125% VT was significantly lower than the net gain in oxygen consumption following NMES (p < 0.05). Differences in the blood lactate concentration between VOL+NMES and VOL increased with exercise intensity, and that at 50% VT was significantly lower than the net gain in the blood lactate concentration following NMES (p < 0.05). Our results suggest that voluntary exercise intensity has a critical impact on metabolic responses during the combined application of voluntary exercises and NMES. Superimposing NMES onto voluntary exercises at high exercise intensities may induce overlapping recruitment of motor units, leading to a markedly reduced benefit of additional metabolic responses on its superimposition.
Laterality of lower extremity deep vein thrombosis after colectomy: A retrospective study using the national inpatient sample

Background and aims Deep venous thrombosis (DVT) is known to occur preferentially on the left lower extremity. The renowned surgeon Denis Burkitt advanced the theory that a heavy sigmoid colon would compress the left pelvic veins and predispose to DVT. Our study aimed to evaluate this hypothesis by comparing the laterality distributions with and without a prior colectomy. Methods We conducted a retrospective analysis of the 2016 National Inpatient Sample database by stratifying the patients at any age with acute DVT of lower extremity by history of prior colectomy, thereby eliminating local gut mechanical factors in the development of DVT. We compared the laterality distribution (i.e., left, right, bilateral, and unspecified) between the patients with and without a prior colectomy. We also conducted a subgroup analysis by the sex category to examine the difference in laterality distribution for male and female patients. Chi-square test for independence was used. P value ≤0.05 was considered statistically significant. Results We found an estimated total of 342,525 cases. Among patients without a prior colectomy, 136,605 (41.6%) were left-sided DVT versus 119,555 (36.4%) right-sided, with 55,555 bilateral and 16,865 unspecified. Among patients with a prior colectomy, 5,750 (41.2%) were left-sided, 5,000 (35.9%) were right-sided, 2,345 were bilateral and 850 were unspecified. The laterality distribution between the two groups was not significantly different (p = .167). The left-side predominance disappeared only in males with a prior colectomy (37.1% for left vs. 38.9% for right, p = .027). Conclusions Our findings did not confirm the Burkitt’s hypothesis. The left-side predominance of lower extremity DVT was attenuated only in male patients with a prior colectomy.
DCT4—A New Member of the Dicarboxylate Transporter Family in C4 Grasses

Abstract Malate transport shuttles atmospheric carbon into the Calvin–Benson cycle during NADP-ME C4 photosynthesis. Previous characterizations of several plant dicarboxylate transporters (DCT) showed that they efficiently exchange malate across membranes. Here, we identify and characterize a previously unknown member of the DCT family, DCT4, in Sorghum bicolor. We show that SbDCT4 exchanges malate across membranes and its expression pattern is consistent with a role in malate transport during C4 photosynthesis. SbDCT4 is not syntenic to the characterized photosynthetic gene ZmDCT2, and an ortholog is not detectable in the maize reference genome. We found that the expression patterns of DCT family genes in the leaves of Zea mays, and S. bicolor varied by cell type. Our results suggest that subfunctionalization, of members of the DCT family, for the transport of malate into the bundle sheath plastids, occurred during the process of independent recurrent evolution of C4 photosynthesis in grasses of the PACMAD clade. We also show that this subfunctionalization is lineage independent. Our results challenge the dogma that key C4 genes must be orthologues of one another among C4 species, and shed new light on the evolution of C4 photosynthesis.
Posttraumatic stress disorder: from gene discovery to disease biology

Abstract Posttraumatic stress disorder (PTSD) is a complex mental disorder afflicting approximately 7% of the population. The diverse number of traumatic events and the wide array of symptom combinations leading to PTSD diagnosis contribute substantial heterogeneity to studies of the disorder. Genomic and complimentary-omic investigations have rapidly increased our understanding of the heritable risk for PTSD. In this review, we emphasize the contributions of genome-wide association, epigenome-wide association, transcriptomic, and neuroimaging studies to our understanding of PTSD etiology. We also discuss the shared risk between PTSD and other complex traits derived from studies of causal inference, co-expression, and brain morphological similarities. The investigations completed so far converge on stark contrasts in PTSD risk between sexes, partially attributed to sex-specific prevalence of traumatic experiences with high conditional risk of PTSD. To further understand PTSD biology, future studies should focus on detecting risk for PTSD while accounting for substantial cohort-level heterogeneity (e.g. civilian v. combat-exposed PTSD cases or PTSD risk among cases exposed to specific traumas), expanding ancestral diversity among study cohorts, and remaining cognizant of how these data influence social stigma associated with certain traumatic events among underrepresented minorities and/or high-risk populations.
Evolution of stomatal closure to optimise water use efficiency in response to dehydration in ferns and seed plants.

Plants control water use efficiency (WUE) by regulating water loss and CO2 diffusion through stomata. Variation in stomatal control has been reported among lineages of vascular plants, thus giving raise to the possibility that different lineages may show distinct WUE dynamics in response to water stress. Here, we compared the response of gas exchange to decreasing leaf water potential among four ferns and nine seed plant species exposed to a gradually intensifying water deficit. The data collected were combined with those from 339 phylogenetically diverse species obtained from previous studies. In well-watered angiosperms, the maximum stomatal conductance was high and greater than that required for maximum WUE, but drought stress caused a rapid reduction in stomatal conductance and an increase in WUE in response to elevated levels of abscisic acid. However, in ferns stomata did not open beyond the optimum point corresponding to maximum WUE and actually exhibited a steady WUE in response to dehydration. Thus, seed plants showed improved photosynthetic WUE under water stress. The ability of seed plants to increase WUE may provide them with an advantage over ferns under drought conditions, thereby, presumably increasing their fitness under selection pressure by drought.
Advances in the optimization of therapeutic drug monitoring using serum, tissue and faecal anti-tumour necrosis factor concentration in patients with inflammatory bowel disease treated with TNF-α antagonists

ABSTRACT Introduction The relationship between clinical outcomes and serum anti-TNF levels is controversial. The aim of this study was to perform simultaneous analyses of serum, mucosal, and fecal anti-TNF-α levels. Methods Consecutive IBD patients who received maintenance anti-TNF-α therapy were enrolled. The number of TNF-α positive cells in the mucosa was detected using immunofluorescent labeling on biopsy samples. Serum, mucosal and fecal anti-TNF-α, serum anti-drug antibody, and fecal calprotectin levels were determined using ELISA. Each patient underwent body composition analysis as well. Results Data of 50 patients were analyzed. The number TNF-α positive cells was significantly higher in the inflamed part of the colon than in the un-inflamed part of the colon. Tissue and fecal drug levels did not show any association with serum drug levels; moreover, serum anti-TNF concentration did not correlate with endoscopic activity. Mucosal anti-TNF levels were higher only in IFX-treated patients in remission and IFX-treated patients with detectable fecal anti-TNF had lower tissue drug levels. Presence of the drug in the feces was significantly different according to disease activity. Conclusion Fecal drug concentration is suggested to be a better predictor of endoscopic activity and loss of response, and fecal drug monitoring may improve the estimation accuracy of tissue drug levels.
Hydrophilicity–Hydrophobicity Characteristics of Solid Surfaces and the State of Water near Surfaces of a Various Nature

Values for the surface tension, π, of 85 mJ/m2 and for the contact angle of wetting by water as its saturated vapour, θV, of 75° are proposed as criteria for distinguishing between hydrophilic and hydrophobic solid surfaces. It is shown that the water boundary layers at hydrophilic surfaces are more ordered while those at hydrophobic surfaces are less ordered relative to the situation in the bulk water structure. The localised model can be used to describe the state of motion of water molecules at a hydrophilic surface, while the motion of water molecules near a hydrophobic surface conforms to the non-localised model.
Human Plasma In‐Cell Western Assays—An In vitro Predictor for In vivo Pharmacology in Oncology Drug Discovery

Evaluation of in vivo potencies plays an important role in drug discovery. Traditionally, the cellular activity and percent of plasma protein binding of a test agent are evaluated separately, with the plasma protein binding−adjusted cellular potency computation used to estimate in vivo potency. This process is costly, takes weeks to complete, and is increasingly unreliable for compounds that bind extensively to plasma proteins. Described in this article is a simple, high‐throughput human plasma in‐cell Western (ICW) assay that directly incorporates plasma protein binding into a cellular pharmacodynamic assay to provide a rapid and accurate estimate of in vivo potencies. The assay is versatile and can be readily employed for various targets that require short treatment periods for displaying maximal biological responses. © 2021 Wiley Periodicals LLC.
Phosphatidylethanol as Blood Biomarker of Alcohol Consumption in Early Pregnancy: An Observational Study in 4067 Pregnant Women.

BACKGROUND The teratogenic effects of alcohol are well documented, but there is a lack of screening methods to detect alcohol use during pregnancy. Phosphatidylethanol 16:0/18:1 (PEth) is a specific and sensitive alcohol marker reflecting alcohol intake up to several weeks after consumption. The aim of this study was to investigate the prevalence of positive PEth values as an indicator of early prenatal alcohol exposure in a general population of pregnant women. METHODS Rhesus typing is routinely performed in Norway in all pregnancies around gestational week 12. Rhesus negative women have an additional test taken around week 24. Blood samples submitted to St. Olav University Hospital in Trøndelag, Norway, for Rhesus typing during the period September 2017 to October 2018, were collected. A total of 4533 blood samples from 4067 women were analysed for PEth (limit of quantification of 0.003 µM) in whole blood. RESULTS A total of 58 women had a positive PEth sample. Of these, 50 women were positive around gestational week 12, three women were positive around week 24, and in five cases the timing was unknown. There were no significant differences in proportions of women with positive PEth values related to age, or rural versus urban residency. CONCLUSION In an unselected pregnant population in Norway 1.4 % had a positive PEth sample around gestational week 12 whereas 0.4% had a positive sample around week 24. The use of PEth as an alcohol biomarker should be further investigated as a possible diagnostic tool in the antenatal setting.
RIC7 plays a negative role in ABA-induced stomatal closure by inhibiting H2O2 production

ABSTRACT When plants encounter environmental stresses, phytohormone abscisic acid (ABA) accumulates quickly and efficiently reduces water loss by inducing stomatal closure. Reactive oxygen species (ROS) is an important regulator in ABA-induced stomatal closure, and ROS generation is modulated by multiple components in guard-cell ABA signaling. ROP interactive CRIB-containing protein 7 (RIC7) has been found to negatively regulate ABA-induced stomatal closure. However, the molecular details of the RIC7 function in this process are unclear. Here, by using two RIC7 overexpressing mutants, we confirmed the negative role of RIC7 in ABA-induced stomatal closure and found that guard cells of RIC7 overexpressing mutants generated less H2O2 than the wild type with ABA treatment, which were consistent with the reduced expression levels of ROS generation related NADPH oxidase genes AtRBOHD and AtRBOHF, and cytosolic polyamine oxidase genes PAO1 and PAO5 in the RIC7 overexpressing mutants. Furthermore, external applied H2O2 failed to rescue the defects of stomatal closure in RIC7 overexpressing mutants. These results suggest that RIC7 affects H2O2 generation in guard cells, and the function of H2O2 is dependent on RIC7 in ABA-induced stomatal closure, indicative of interdependency between RIC7 and H2O2 in ABA guard-cell signaling.