Miracle-dz/UniFAR-FTUs huggingface dataset:
Is empathy change in medical school geo‐socioculturally influenced?

There is convincing evidence that physician empathy leads to better patient care. As a result, there has been considerable research interest in investigating how empathy changes during undergraduate medical studies. Early (generally North American) studies raised concerns that medical training causes a decline in empathy. More recent studies (conducted around the world) have begun to suggest that either a slight increase or decrease in empathy occurs during undergraduate medical training, which has led some to argue that empathy changes indiscriminately (with no discernible pattern). This paper explores whether there is evidence to suggest that empathy changes indiscriminately or with a discernible geo‐sociocultural pattern during undergraduate medical training.
Paediatric reference intervals for plasma anti-Müllerian hormone: comparison of data from the Roche Elecsys assay and the Beckman Coulter Access assay using the same cohort of samples

Background Autoanalyser methods for the measurement of anti-Müllerian hormone have been introduced into clinical laboratories but few reports of paediatric reference intervals using these new assays have been published. Methods After prior evaluation of the Roche Elecsys anti-Müllerian hormone assay against the Beckman Coulter modified second generation anti-Müllerian Hormone enzyme-linked immunosorbent assay using samples from adult females, a cohort of paediatric samples which had previously been assessed using the Beckman Coulter Access anti-Müllerian hormone assay was analysed using the Roche Elecsys anti-Müllerian hormone assay. Results The Roche Elecsys anti-Müllerian hormone assay measured significantly lower than the Beckman Coulter modified second generation anti-Müllerian Hormone enzyme-linked immunosorbent assay. In the paediatric cohort measured with the Roche Elecsys assay, male levels are very high from birth to puberty after which they fall towards postpubertal female levels. Male results were similar to those previously obtained using the Beckman Coulter Access anti-Müllerian hormone assay on the same cohort. Roche Elecsys anti-Müllerian hormone in the females was very low in the neonatal and prepubertal years and the postpubertal trend, with a steady rise from 15 years, was smoother than previously modelled using the Beckman Coulter Access anti-Müllerian hormone assay. Conclusion Anti-Müllerian hormone levels measured with the Roche Elecsys assay were significantly lower than the Beckman Coulter modified second generation enzyme-linked immunosorbent assay suggesting the need for new reference ranges. In the paediatric cohort, Roche Elecsys anti-Müllerian hormone levels between boys and girls showed good prepubertal delineation and small but statistically significant differences to previously measured levels using the Beckman Coulter Access anti-Müllerian hormone assay on the same sample cohort.
Phylogenetic Analyses Comparing HIV Sequences from Plasma at Virologic Failure to Cervix Versus Blood Sequences from Antecedent Antiretroviral Therapy Suppression.

Identifying tissue sources of HIV that rebound following "failure" of antiretroviral therapy (ART) is critical to evaluating cure strategies. To assess the role of the uterine cervix and peripheral blood mononuclear cells (PBMC) as viral reservoirs, nearest-neighbor phylogenetic analyses compared genetic relatedness of tissue sequences during ART suppression to those detected in plasma at viral rebound. Blood and genital tract specimens from a natural history cohort of HIV-infected women were collected over 5 years. HIV DNA sequences extracted from PBMC and cervical biopsies during ART suppression and plasma RNA from rebound (defined as HIV RNA >3 log10 copies/mL) were derived by single-genome amplification. Phylogenetic and nearest-neighbor analyses of HIV env sequences and drug resistance in pol sequences were compared between tissues. Nine instances of plasma viral rebound (median HIV RNA 3.6 log10 c/mL; IQR: 3.1-3.8) were detected in 7 of 57 women. Nearest-neighbor analyses found rebound plasma sequences were closer to uterine cervical sequences in 4/9 (44%), closer to PBMC in 3/9 (33%), and ambiguous in 2/9 (22%) cases. Rebound plasma clades (n = 27) shared identical sequences in seven instances with the cervix versus two with PBMC. Novel drug resistance mutations were detected in 4/9 (44%) rebounds. The observed tendency for greater sharing of identical HIV variants and greater nearest-neighbor association between rebounding plasma and uterine cervical versus PBMC sequences suggests that the uterine cervix may be a relevant HIV reservoir. The cervix, a readily accessible tissue in women that can be repeatedly sampled, could help assess the HIV reservoir when evaluating cure strategies.
Structural maturation of cortical perineuronal nets and their perforating synapses revealed by superresolution imaging

Significance Particular inhibitory neurons containing parvalbumin (PV) play a critical role in determining the time course by which experience shapes developing brain circuits. Embedded deep within cortical gray matter, extracellular matrices enwrapping PV-positive (PV+) cells have remained difficult to study partly due to the small length scale on which they are organized. To overcome such challenges, we used a superresolution fluorescence imaging approach to visualize these perineuronal nets (PNNs), a specialized form of the extracellular matrix critical for maintaining mature PV+ neuron function and their synaptic inputs. We quantified changes that define PNN structure and identified specific synaptic defects in a mouse model lacking MeCP2, the causative gene for Rett syndrome, a regressive neurodevelopmental disorder. Parvalbumin-positive (PV+) interneurons play a pivotal role in orchestrating windows of experience-dependent brain plasticity during development. Critical period closure is marked by the condensation of a perineuronal net (PNN) tightly enwrapping subsets of PV+ neurons, both acting as a molecular brake on plasticity and maintaining mature PV+ cell signaling. As much of the molecular organization of PNNs exists at length scales near or below the diffraction limit of light microscopy, we developed a superresolution imaging and analysis platform to visualize the structural organization of PNNs and the synaptic inputs perforating them in primary visual cortex. We identified a structural trajectory of PNN maturation featuring a range of net structures, which was accompanied by an increase in Synaptotagmin-2 (Syt2) signals on PV+ cells suggestive of increased inhibitory input between PV+ neurons. The same structural trajectory was followed by PNNs both during normal development and under conditions of critical period delay by total sensory deprivation or critical period acceleration by deletion of MeCP2, the causative gene for Rett syndrome, despite shifted maturation levels under these perturbations. Notably, superresolution imaging further revealed a decrease in Syt2 signals alongside an increase in vesicular glutamate transporter-2 signals on PV+ cells in MeCP2-deficient animals, suggesting weaker recurrent inhibitory input between PV+ neurons and stronger thalamocortical excitatory inputs onto PV+ cells. These results imply a latent imbalanced circuit signature that might promote cortical silencing in Rett syndrome before the functional regression of vision.
Impact of germline CTC1 alterations on telomere length in acquired bone marrow failure

Compound heterozygous germline mutations in CTC1 gene have been found in patients with atypical dyskeratosis congenita (DC), whereas heterozygous carriers are unaffected. Through screening of a large cohort of adult patients with acquired bone marrow failure syndromes, in addition to a DC case, we have also found extremely rare or novel heterozygous deleterious germline variants of CTC1 in patients with aplastic anaemia (AA; n = 5), paroxysmal nocturnal haemoglobinuria (PNH; n = 3) and myelodysplastic syndrome (MDS; n = 2). A compound heterozygous case of AA showed clonal evolution. Our results suggest that some of the inherited CTC1 variants may represent predisposition factors for acquired bone marrow failure.
The Transcription Factor ERG Regulates Super-Enhancers Associated With an Endothelial-Specific Gene Expression Program

Rationale: The ETS (E-26 transformation-specific) transcription factor ERG (ETS-related gene) is essential for endothelial homeostasis, driving expression of lineage genes and repressing proinflammatory genes. Loss of ERG expression is associated with diseases including atherosclerosis. ERG’s homeostatic function is lineage-specific, because aberrant ERG expression in cancer is oncogenic. The molecular basis for ERG lineage-specific activity is unknown. Transcriptional regulation of lineage specificity is linked to enhancer clusters (super-enhancers). Objective: To investigate whether ERG regulates endothelial-specific gene expression via super-enhancers. Methods and Results: Chromatin immunoprecipitation with high-throughput sequencing in human umbilical vein endothelial cells showed that ERG binds 93% of super-enhancers ranked according to H3K27ac, a mark of active chromatin. These were associated with endothelial genes such as DLL4 (Delta-like protein 4), CLDN5 (claudin-5), VWF (von Willebrand factor), and CDH5 (VE-cadherin). Comparison between human umbilical vein endothelial cell and prostate cancer TMPRSS2 (transmembrane protease, serine-2):ERG fusion-positive human prostate epithelial cancer cell line (VCaP) cells revealed distinctive lineage-specific transcriptome and super-enhancer profiles. At a subset of endothelial super-enhancers (including DLL4 and CLDN5), loss of ERG results in significant reduction in gene expression which correlates with decreased enrichment of H3K27ac and MED (Mediator complex subunit)-1, and reduced recruitment of acetyltransferase p300. At these super-enhancers, co-occupancy of GATA2 (GATA-binding protein 2) and AP-1 (activator protein 1) is significantly lower compared with super-enhancers that remained constant following ERG inhibition. These data suggest distinct mechanisms of super-enhancer regulation in endothelial cells and highlight the unique role of ERG in controlling a core subset of super-enhancers. Most disease-associated single nucleotide polymorphisms from genome-wide association studies lie within noncoding regions and perturb transcription factor recognition sequences in relevant cell types. Analysis of genome-wide association studies data shows significant enrichment of risk variants for cardiovascular disease and other diseases, at ERG endothelial enhancers and super-enhancers. Conclusions: The transcription factor ERG promotes endothelial homeostasis via regulation of lineage-specific enhancers and super-enhancers. Enrichment of cardiovascular disease-associated single nucleotide polymorphisms at ERG super-enhancers suggests that ERG-dependent transcription modulates disease risk.
Treatment of idiopathic oligozoospermia with combined human chorionic gonadotropin/human menopausal gonadotrophin: A randomised, double‐blinded, placebo‐controlled clinical study

To evaluate whether hCG/hMG therapy has beneficial effects on idiopathic oligozoospermia in Chinese infertility population. The patients were randomly divided into the treatment group receiving hCG/hMG for 3 months and the placebo group receiving placebo for 3 months. Semen and biochemical analysis was performed, and DNA fragmentation as well as spermatid concentration was evaluated. Administration of hCG/hMG for 3 months could significantly improve sperm concentration, rate of forward motile spermatozoa, total motile sperm count, the percentage of sperm with normal morphology and the rate of spontaneous pregnancy in medium‐ and higher‐level inhibin B group respectively. Moreover, in medium‐ and higher‐level inhibin B group, sperm DNA fragmentation index and spermatid concentration were significantly declined respectively at the end of treatment. However, there were no significant differences in lower‐level inhibin B group before and after treatment in term of seminal parameters, DNA fragmentation and spermatid concentration. HCG/hMG therapy for 3 months has a beneficial effect on a part of male with idiopathic oligozoospermia, and the efficacy of hCG/hMG therapy is associated with the inhibin B level.
Sleep duration and blood pressure in children: Analysis of the pan‐European IDEFICS cohort

The present study aims to examine the cross‐sectional and longitudinal association between self‐reported nocturnal sleep duration, blood pressure, and hypertension in European children, aged 2‐9.9 years, participating in the IDEFICS project. Blood pressure (BP) and the main anthropometric indices were measured according to standardized procedures. Childhood elevated BP and hypertension were defined according to the European Society of Hypertension Guidelines for children and adolescents. Parents reported lifestyle and socio‐demographic data. Nocturnal sleep duration was assessed as part of a parental 24‐h recall and categorized as follows: (a) ≤9 hours/night; (b) >9 hours to ≤10 hours/night; (c) >10 hours to ≤11 hours/night; and (d) >11 hours/night. A complete set of variables included in the present analysis was provided by 7974 participants (boys/girls = 4049/3925) at the baseline survey (T0). Of them, 5656 were re‐examined 2 years later at follow‐up (T1). Children reporting shorter sleep duration at T0 had significantly higher BP values (P for trend < 0.001) compared to those who slept more. Prospective analyses showed that shorter sleep duration at baseline predicted, over the 2‐year follow‐up, higher increases in systolic blood pressure and diastolic blood pressure, after adjustment for age, sex, country of origin, BMI z‐score, parental education, physical activity, screen time, and T0 value of the examined outcome variables (P for trend < 0.001). Our findings reveal that shorter sleep duration is associated with higher BP in childhood, suggesting that sleep may be a potential risk factor for hypertension later in life.
Whole genome experimental maps of DNA G-quadruplexes in multiple species

Abstract Genomic maps of DNA G-quadruplexes (G4s) can help elucidate the roles that these secondary structures play in various organisms. Herein, we employ an improved version of a G-quadruplex sequencing method (G4-seq) to generate whole genome G4 maps for 12 species that include widely studied model organisms and also pathogens of clinical relevance. We identify G4 structures that form under physiological K+ conditions and also G4s that are stabilized by the G4-targeting small molecule pyridostatin (PDS). We discuss the various structural features of the experimentally observed G-quadruplexes (OQs), highlighting differences in their prevalence and enrichment across species. Our study describes diversity in sequence composition and genomic location for the OQs in the different species and reveals that the enrichment of OQs in gene promoters is particular to mammals such as mouse and human, among the species studied. The multi-species maps have been made publicly available as a resource to the research community. The maps can serve as blueprints for biological experiments in those model organisms, where G4 structures may play a role.
Recurrent loops: Incorporating prediction error and semantic/episodic theories into Drosophila associative memory models

In 2003, Martin Heisenberg et al. presented a model of how associative memories could be encoded and stored in the insect brain. This model was extremely influential in the Drosophila memory field, but did not incorporate several important mammalian concepts, including ideas of separate episodic and semantic types of memory and prediction error hypotheses. In addition, at that time, the concept of memory traces recurrently entering and exiting the mushroom bodies, brain areas where associative memories are formed and stored, was unknown. In this review, I present a simple updated model incorporating these ideas, which may be useful for future studies.
Galactolipids Are Essential for Internal Membrane Transformation during Etioplast-to-Chloroplast Differentiation

Abstract Etioplasts developed in angiosperm cotyledon cells in darkness rapidly differentiate into chloroplasts with illumination. This process involves dynamic transformation of internal membrane structures from the prolamellar bodies (PLBs) and prothylakoids (PTs) in etioplasts to thylakoid membranes in chloroplasts. Although two galactolipids, monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG), are predominant lipid constituents of membranes in both etioplasts and chloroplasts, their roles in the structural and functional transformation of internal membranes during etioplast-to-chloroplast differentiation are unknown. We previously reported that a 36% loss of MGDG by an artificial microRNA targeting major MGDG synthase (amiR-MGD1) only slightly affected PLB structures but strongly impaired PT formation and protochlorophyllide biosynthesis. Meanwhile, strong DGDG deficiency in a DGDG synthase mutant (dgd1) disordered the PLB lattice structure in addition to impaired PT development and protochlorophyllide biosynthesis. In this study, thylakoid biogenesis after PLB disassembly with illumination was strongly perturbed by amiR-MGD1. The amiR-MGD1 expression impaired the accumulation of Chl and the major light-harvesting complex II protein (LHCB1), which may inhibit rapid transformation from disassembled PLBs to the thylakoid membrane. As did amiR-MGD1 expression, dgd1 mutation impaired the accumulation of Chl and LHCB1 during etioplast-to-chloroplast differentiation. Furthermore, unlike in amiR-MGD1 seedlings, in dgd1 seedlings, disassembly of PLBs after illumination was retarded. Because DGDG but not MGDG prefers to form the bilayer lipid phase in membranes, the MGDG-to-DGDG ratio may strongly affect the transformation of PLBs to the thylakoid membrane during etioplast-to-chloroplast differentiation.
Northern bottlenose whales in a pristine environment respond strongly to close and distant navy sonar signals

Impact assessments for sonar operations typically use received sound levels to predict behavioural disturbance in marine mammals. However, there are indications that cetaceans may learn to associate exposures from distant sound sources with lower perceived risk. To investigate the roles of source distance and received level in an area without frequent sonar activity, we conducted multi-scale controlled exposure experiments (n = 3) with 12 northern bottlenose whales near Jan Mayen, Norway. Animals were tagged with high-resolution archival tags (n = 1 per experiment) or medium-resolution satellite tags (n = 9 in total) and subsequently exposed to sonar. We also deployed bottom-moored recorders to acoustically monitor for whales in the exposed area. Tagged whales initiated avoidance of the sound source over a wide range of distances (0.8–28 km), with responses characteristic of beaked whales. Both onset and intensity of response were better predicted by received sound pressure level (SPL) than by source distance. Avoidance threshold SPLs estimated for each whale ranged from 117–126 dB re 1 µPa, comparable to those of other tagged beaked whales. In this pristine underwater acoustic environment, we found no indication that the source distances tested in our experiments modulated the behavioural effects of sonar, as has been suggested for locations where whales are frequently exposed to sonar.
Changes in pharyngeal airway dimensions following incremental and maximum bite advancement during Herbst-rapid palatal expander appliance therapy in late adolescent and young adult patients: a randomized non-controlled prospective clinical study.

OBJECTIVES This was a parallel, assessor-blinded, randomized, non-controlled prospective trial with the objective to evaluate and compare the effects of maximum advancement (MA) and incremental advancement (IA) of mandible with cast-splint-type Herbst-rapid palatal expander (RPE) appliance on pharyngeal airway dimensions and hyoid bone position in skeletal Class II late adolescents and young adults. MATERIALS AND METHODS A total of 48 patients (19 male and 29 female, mean age: 15.45 ± 1.42 years) with skeletal Class II malocclusion were treated with cast-splint Herbst-RPE appliance. Inclusion criteria were skeletal Class II malocclusion, mandibular retrognathia, bilateral Class II molar and canine relationship, increased overjet, normal or decreased vertical dimensions, minimal crowding, and no missing teeth. Enrolled subjects were randomly allocated into two groups according to mandibular advancement type: IA and MA Herbst-RPE therapy. The outcome assessor was blinded. Advancement in MA group was adjusted until tête-à-tête incisor relationship or super Class I molar relationship was obtained. Initial forward movement in IA group was 4-5 mm and followed by bimonthly 2 mm of subsequent advancements. Skeletal, pharyngeal airway, and hyoid measurements were performed using lateral cephalometric films. Statistical significance was set at P value of less than 0.05. RESULTS Hypopharyngeal airway dimensions (P < 0.000), oropharyngeal airway dimensions (P < 0.001, P < 0.007), and PASmin values (P < 0.010, P < 0.009) were increased and soft palate angle (P < 0.018, P < 0.007) was decreased in MA and IA groups significantly. Hyoid bone measurements revealed a significant difference in H-Cv2 distance (MA: P < 0.002-P < 0.002; IA: P < 0.001-P < 0.043) and H-Cv3 distance (P < 0.005, P < 0.001) for both groups. However, all these changes did not differ among the MA and IA activation groups. ANB°, Wits, overjet, and overbite measurements decreased and SNB°, Co-Gn, Na-Me, ANS-Me, and S-Go increased with the treatment significantly in both mandibular advancement groups (P < 0.000-P < 0.040). CONCLUSIONS Herbst-RPE appliance provided a similar improvement in the oropharyngeal and hypopharyngeal airway dimensions and similar changes in sagittal and vertical hyoid position for both maximum and IA protocols in patients with skeletal Class II malocclusion. TRIAL REGISTRATION ISRCTN69743543.
3D Multi-Resolution Optical Flow Analysis of Cardiovascular Pulse Propagation in Human Brain

The brain is cleaned from waste by glymphatic clearance serving a similar purpose as the lymphatic system in the rest of the body. Impairment of the glymphatic brain clearance precedes protein accumulation and reduced cognitive function in Alzheimer’s disease (AD). Cardiovascular pulsations are a primary driving force of the glymphatic brain clearance. We developed a method to quantify cardiovascular pulse propagation in the human brain with magnetic resonance encephalography (MREG). We extended a standard optical flow estimation method to three spatial dimensions, with a multi-resolution processing scheme. We added application-specific criteria for discarding inaccurate results. With the proposed method, it is now possible to estimate the propagation of cardiovascular pulse wavefronts from the whole brain MREG data sampled at 10 Hz. The results show that on average the cardiovascular pulse propagates from major arteries via cerebral spinal fluid spaces into all tissue compartments in the brain. We present an example, that cardiovascular pulsations are significantly altered in AD: coefficient of variation and sample entropy of the pulse propagation speed in the lateral ventricles change in AD. These changes are in line with the theory of glymphatic clearance impairment in AD. The proposed non-invasive method can assess a performance indicator related to the glymphatic clearance in the human brain.