Miracle-dz/UniFAR-FTUs huggingface dataset:
Sleep strengthens integration of spatial memory systems

Spatial memory comprises different representational systems that are sensitive to different environmental cues, like proximal landmarks or local boundaries. Here we examined how sleep affects the formation of a spatial representation integrating landmark-referenced and boundary-referenced representations. To this end, participants (n = 42) were familiarized with an environment featuring both a proximal landmark and a local boundary. After nocturnal periods of sleep or wakefulness and another night of sleep, integration of the two representational systems was tested by testing the participant's flexibility to switch from landmark-based to boundary-based navigation in the environment, and vice versa. Results indicate a distinctly increased flexibility in relying on either landmarks or boundaries for navigation, when familiarization to the environment was followed by sleep rather than by wakefulness. A second control study (n = 45) did not reveal effects of sleep (vs. wakefulness) on navigation in environments featuring only landmarks or only boundaries. Thus, rather than strengthening isolated representational systems per se, sleep presumably through forming an integrative representation, enhances flexible coordination of representational subsystems.
Collagen IV differentially regulates planarian stem cell potency and lineage progression

Significance Comprehensive assessment of matrisome genes identified collagen IV as one of the many extracellular matrix (ECM) proteins regulating the stem cell pool in planarian tissue homeostasis and regeneration. While collagen IV has been shown to be involved in stem cell biology, our finding links it to pluripotent stem cells in vivo, including self-renewal and differentiation into tissue-specific progenitors. We show a link between the ECM niches in the parenchyma/gut region and EGF/neuregulin-secreting neurons, thus providing mechanistic insight into interactions between cell niches. The conservation of basement membranes between planarian and mammalian gut niches suggests a similar interplay may exist in the mammalian systems, worthy of further investigation. The extracellular matrix (ECM) provides a precise physical and molecular environment for cell maintenance, self-renewal, and differentiation in the stem cell niche. However, the nature and organization of the ECM niche is not well understood. The adult freshwater planarian Schmidtea mediterranea maintains a large population of multipotent stem cells (neoblasts), presenting an ideal model to study the role of the ECM niche in stem cell regulation. Here we tested the function of 165 planarian homologs of ECM and ECM-related genes in neoblast regulation. We identified the collagen gene family as one with differential effects in promoting or suppressing proliferation of neoblasts. col4-1, encoding a type IV collagen α-chain, had the strongest effect. RNA interference (RNAi) of col4-1 impaired tissue maintenance and regeneration, causing tissue regression. Finally, we provide evidence for an interaction between type IV collagen, the discoidin domain receptor, and neuregulin-7 (NRG-7), which constitutes a mechanism to regulate the balance of symmetric and asymmetric division of neoblasts via the NRG-7/EGFR pathway.
Preoperative nutritional status impacts clinical outcome and hospital length of stay in pelvic exenteration patients – a retrospective study

Background: Preoperative malnutrition is common in surgical oncology patients and can have negative effects on postoperative outcomes. Pelvic exenteration is major surgery associated with high morbidity rates. Associations between preoperative malnutrition, determined using the patient-generated subjective global assessment, and postoperative outcomes in this patient cohort has not yet been investigated. Aim: To determine if preoperative nutritional status is associated with postoperative surgical and quality of life (QoL) outcomes after pelvic exenteration surgery. Methods: A retrospective cohort study was conducted at a quaternary hospital investigating 123 patients who had pelvic exenteration surgery from January 2017 to August 2019. Preoperative nutritional status and postoperative surgical and QoL outcomes were collected and analysed to determine any associations. Results: Overall, 49.6% of patients were female with a median age of 59 years. Forty patients (32.5%) were malnourished and 83 (67.5%) were well nourished before surgery. Well-nourished patients had a shorter length of hospital stay (p = 0.034) and at 6 months post-surgery, presented with a significantly better physical and mental QoL score (p = 0.038 and p = 0.001 respectively). The regression analyses showed that intensive care unit (ICU) readmission rates were 7.19 times more likely to occur in malnourished patients (p = 0.022). Conclusions: Preoperative malnutrition is associated with increased length of stay, ICU readmissions and poorer QoL following pelvic exenteration. Nutrition screening, assessment and optimisation of management are essential in this patient cohort to improve patient outcomes. Future studies are needed to measure the effect of interventions and identify the most beneficial model of care for this complex patient group.
Colonization of macroalgal deposits by estuarine nematodes through air and potential for rafting inside algal structures

Dispersal is an important life-history trait. In marine meiofauna, and particularly in nematodes, dispersal is generally considered to be mainly passive, i.e. through transport with water currents and bedload transport. Because nematodes have no larval dispersal stage and have a poor swimming ability, their per capita dispersal capacity is expected to be limited. Nevertheless, many marine nematode genera and even species have near-cosmopolitan distributions, and at much smaller spatial scales, can rapidly colonise new habitat patches. Here we demonstrate that certain marine nematodes, like the morphospecies Litoditis marina, can live inside macroalgal structures such as receptacula and–to a lesser extent–floating bladders, which may allow them to raft over large distances with drifting macroalgae. We also demonstrate for the first time that these nematodes can colonize new habitat patches, such as newly deposited macroalgal wrack in the intertidal, not only through seawater but also through air. Our experimental set-up demonstrates that this aerial transport is probably the result of hitchhiking on vectors such as insects, which visit, and move between, the patches of deposited algae. Transport by wind, which has been observed for terrestrial nematodes and freshwater zooplankton, could not be demonstrated. These results can be important for our understanding of both large-scale geographic distribution patterns and of the small-scale colonization dynamics of habitat patches by marine nematodes.
Delayed Aneurysm Clip Migration from the Posterior Fossa to the Thoracic Spinal Canal

We present the case of an 84-year-old female who presented with a World Federation of Neurosurgical Societies Grade 1 subarachnoid haemorrhage in 2012 when she was 76 years old. CT scan demonstrated a modified Fisher grade 4 subarachnoid haemorrhage with blood centred around the medulla and in the 4th and 3rd ventricles without hydrocephalus. Digital subtraction angiography revealed an irregular, 4 × 2.5 × 2 mm saccular aneurysm on an arterial branch arising from the distal left posterior inferior cerebellar artery (PICA) tonsillar segment (Figure 1C). The left vertebral artery has normal anatomical branching pattern and does not end in PICA. Via a far lateral craniotomy, the aneurysm was clipped with a bayonetted mini-clip (Sugita Elgiloy Non-ferromagnetic) (Figure 1A and B). Post-operative CT scan demonstrated complete exclusion of the aneurysm with the clip in the expected location (Figure 1D and E). The patient was discharged well 10-d post-clipping. One-year post-clipping, the patient underwent a CT head after presenting with a right-sided transient ischaemic attack. The clip at this time was in the same location. Six years after clipping, the patient presented with confusion and a CT head demonstrated the clip now adjacent to the C2 vertebra intradurally (Figure 2A). CTA demonstrated no aneurysm recurrence. Three months after this, a chest X-ray for productive cough demonstrated that the clip had migrated further to the level of the thoracic spine (Figure 2B and C). The patient remained asymptomatic from the clip migration with no signs of radiculopathy or myelopathy clinically. The aneurysm has not been demonstrated to have recurred on CT angiography. A number of case reports have been published describing the
Maternal age at birth and daughter's fecundability.

STUDY QUESTION Do daughters of older mothers have lower fecundability? SUMMARY ANSWER In this cohort study of North American pregnancy planners, there was virtually no association between maternal age ≥35 years and daughters' fecundability. WHAT IS KNOWN ALREADY Despite suggestive evidence that daughters of older mothers may have lower fertility, only three retrospective studies have examined the association between maternal age and daughter's fecundability. STUDY DESIGN, SIZE, DURATION Prospective cohort study of 6689 pregnancy planners enrolled between March 2016 and January 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS Pregnancy Study Online (PRESTO) is an ongoing pre-conception cohort study of pregnancy planners (age, 21-45 years) from the USA and Canada. We estimated fecundability ratios (FR) for maternal age at the participant's birth using multivariable proportional probabilities regression models. MAIN RESULTS AND THE ROLE OF CHANCE Daughters of mothers ≥30 years were less likely to have previous pregnancies (or pregnancy attempts) or risk factors for infertility, although they were more likely to report that their mother had experienced problems conceiving. The proportion of participants with prior unplanned pregnancies, a birth before age 21, ≥3 cycles of attempt at study entry or no follow-up was greater among daughters of mothers <25 years. Compared with maternal age 25-29 years, FRs (95% CI) for maternal age <20, 20-24, 30-34, and ≥35 were 0.72 (0.61, 0.84), 0.92 (0.85, 1.00), 1.08 (1.00, 1.17), and 1.00 (0.89, 1.12), respectively. LIMITATIONS, REASONS FOR CAUTION Although the examined covariates did not meaningfully affect the associations, we had limited information on the participants' mother. Differences by maternal age in reproductive history, infertility risk factors and loss to follow-up suggest that selection bias may partly explain our results. WIDER IMPLICATIONS OF THE FINDINGS Our finding that maternal age 35 years or older was not associated with daughter's fecundability is reassuring, considering the trend towards delayed childbirth. However, having been born to a young mother may be a marker of low fecundability among pregnancy planners. STUDY FUNDING/COMPETING INTEREST(S) PRESTO was funded by NICHD Grants (R21-HD072326 and R01-HD086742) and has received in-kind donations from Swiss Precision Diagnostics, FertilityFriend.com, Kindara.com, and Sandstone Diagnostics. Dr Wise is a fibroid consultant for AbbVie, Inc. TRIAL REGISTRATION NUMBER n/a.
Reliability of Serological Prestin Levels in Humans and its Relation to Otoacoustic Emissions, a Functional Measure of Outer Hair Cells

Objectives: Serological biomarkers, common to many areas of medicine, have the potential to inform on the health of the human body and to give early warning of risk of compromised function or illness before symptoms are experienced. Serological measurement of prestin, a motor protein uniquely produced and expressed in outer hair cells, has recently been identified as a potential biomarker to inform on the health of the cochlea. Before any test can be introduced into the clinical toolkit, the reproducibility of the measurement when repeated in the same subject must be considered. The primary objective of this study is to outline the test-retest reliability estimates and normative ranges for serological prestin in healthy young adults with normal hearing. In addition, we examine the relation between serum prestin levels and otoacoustic emissions (OAEs) to compare this OHC-specific protein to the most common measure of OHC function currently used in hearing assessments. Design: We measured prestin levels serologically from circulating blood in 34 young adults (18 to 24 years old) with clinically normal pure-tone audiometric averages at five different timepoints up to six months apart (average intervals between measurements ranged from <1 week to 7 weeks apart). To guide future studies of clinical populations, we present the standard error of the measurement, reference normative values, and multiple measures of reliability. Additionally, we measured transient evoked OAEs at the same five timepoints and used correlation coefficients to examine the relation between OAEs and prestin levels (pg/mL). Results: Serum prestin levels demonstrated good to excellent reliability between and across the five different time points, with correlation coefficients and intraclass correlations >0.8. Across sessions, the average serum prestin level was 250.20 pg/mL, with a standard error of measurement of 7.28 pg/mL. Moreover, positive correlations (generally weak to moderate) were found between prestin levels and OAE magnitudes and signal-to-noise ratios. Conclusions: Findings characterize serum prestin in healthy young adults with normal hearing and provide initial normative data that may be critical to interpreting results from individuals with sensorineural hearing loss. Our results demonstrate reliability of serum prestin levels in a sample of normal-hearing young adults across five test sessions up to 6 months apart, paving the way for testing larger samples to more accurately estimate test-retest standards for clinical protocols, including those involving serial monitoring. The positive correlations between serum prestin and OAE levels, although weak to moderate, reinforce that the source of serum prestin is likely the outer hair cells in the inner ear, but also that serum prestin and OAEs each may also index aspects of biologic function not common to the other.
Mononitrate Isosorbide as an Adjunctive Therapy in Schizophrenia

Supplemental digital content is available in the text. Abstract Background Schizophrenia is a complex disabling mental disorder, and many patients present poor response to available treatments. Accumulating evidence about the role of the glutamate/nitric oxide pathway in mediating the positive and negative symptoms of schizophrenia suggests potential benefits of drugs that modulate this system. The aim of this study was to test the efficacy of isosorbide mononitrate (ISMN) as an adjunctive therapy for symptomatic outpatients with schizophrenia. Methods This was a 2-month randomized, double-blind, placebo-controlled trial with 24 schizophrenia patients. Participants were treated with ISMN 50 mg for 1 month and placebo for another month in a crossover design. The Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale, Global Assessment of Functioning, and MATRICS Cognitive Consensual Battery were used for symptom assessment and arterial spin labeling was used to assess brain activation patterns. Results We found significant differences in the total, general, and positive subscales of the PANSS, Global Assessment of Functioning scores, and Clinical Global Impression scores during treatment with ISMN relative to placebo. No treatment effects were found comparing scores in the MATRICS Cognitive Consensual Battery and the negative subscale of the PANSS between the active and placebo conditions. A post hoc analysis of neuroimaging data showed reduced activity in the thalamus in subgroup of patients with severe psychopathology. Conclusions Schizophrenia patients with persistent symptoms showed significant improvement after 4 weeks of treatment with ISMN 50 mg/d compared with placebo. Isosorbide mononitrate added beneficial effects to antipsychotic treatment in terms of positive symptoms and functioning.
Hitting the mark: The influence of emotional culture on resilient performance.

Previous research has established the role of positive emotional cultures such as companionate love and joy in predicting team performance. Building on this work, the present study analyzes the role of positive emotional culture variables as predictors of resilient performance by examining patterns of objective team performance in U.S. Army tank crews over time. We also broaden the emotional culture domain by investigating an action-oriented positive emotional culture of optimism and a negative emotional culture of anger. During a high-stakes international military training exercise, 55 U.S. Army tank crews (N = 175) completed a pre-qualification performance event, a final qualification performance event, and surveys at baseline and after both events. The positive emotional culture of optimism predicted a pattern of resilient performance defined as a rebound from poor pre-qualification performance. Emotional cultures of joy and optimism also directly predicted final performance, but neither the emotional culture of companionate love, nor the emotional culture of anger was a significant predictor. Results demonstrate the distinct nature of each of these emotional culture variables, and show that these variables differ from group trait affectivity and cohesion. Teams with a strong emotional culture of optimism were better positioned to rebound in the face of poor performance, suggesting that organizations that promote an optimistic culture develop more resilient teams. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
HY5 regulates light-responsive transcription of microRNA163 to promote primary root elongation in Arabidopsis seedlings.

MicroRNAs (miRNAs) play key roles in the post-transcriptional regulation of gene expression in plants. Many miRNAs are responsive to environmental signals. Light is the first environmental signal perceived by plants after emergence from the soil. However, less is known about the roles and regulatory mechanism of miRNAs in response to light signal. Here, using small RNA sequencing, we determined that miR163 is significantly rapidly induced by light signaling in Arabidopsis thaliana seedlings. The light-inducible response of miR163 functions genetically downstream of LONG HYPOCOTYL 5 (HY5), a central positive regulator of photomorphogenesis. HY5 directly binds to the two G/C-hybrid elements in the miR163 promoter with unequal affinity; one of these elements, which is located next to the transcription start site, plays a major role in light-induced expression of miR163. Overexpression of miR163 rescued the defective primary root elongation of hy5 seedlings without affecting lateral root growth, whereas overexpressing of miR163 target PXMT1 inhibited primary root elongation. These findings provide insight into understanding the post-transcriptional regulation of root photomorphogenesis mediated by the HY5-miR163-PXMT1 network. This article is protected by copyright. All rights reserved.
The Society for Obstetric Anesthesia and Perinatology Interdisciplinary Consensus Statement on Neuraxial Procedures in Obstetric Patients With Thrombocytopenia

Because up to 12% of obstetric patients meet criteria for the diagnosis of thrombocytopenia in pregnancy, it is not infrequent that the anesthesiologist must decide whether to proceed with a neuraxial procedure in an affected patient. Given the potential morbidity associated with general anesthesia for cesarean delivery, thoughtful consideration of which patients with thrombocytopenia are likely to have an increased risk of spinal epidural hematoma with neuraxial procedures, and when these risks outweigh the relative benefits is important to consider and to inform shared decision making with patients. Because there are substantial risks associated with withholding a neuraxial analgesic/anesthetic procedure in obstetric patients, every effort should be made to perform a bleeding history assessment and determine the thrombocytopenia etiology before admission for delivery. Whereas multiple other professional societies (obstetric, interventional pain, and hematologic) have published guidelines addressing platelet thresholds for safe neuraxial procedures, the US anesthesia professional societies have been silent on this topic. Despite a paucity of high-quality data, there are now meta-analyses that provide better estimations of risks. An interdisciplinary taskforce was convened to unite the relevant professional societies, synthesize the data, and provide a practical decision algorithm to help inform risk-benefit discussions and shared decision making with patients. Through a systematic review and modified Delphi process, the taskforce concluded that the best available evidence indicates the risk of spinal epidural hematoma associated with a platelet count ≥70,000 × 106/L is likely to be very low in obstetric patients with thrombocytopenia secondary to gestational thrombocytopenia, immune thrombocytopenia (ITP), and hypertensive disorders of pregnancy in the absence of other risk factors. Ultimately, the decision of whether to proceed with a neuraxial procedure in an obstetric patient with thrombocytopenia occurs within a clinical context. Potentially relevant factors include, but are not limited to, patient comorbidities, obstetric risk factors, airway examination, available airway equipment, risk of general anesthesia, and patient preference.
Leveraging proteomics in orphan disease research: pitfalls and potential

ABSTRACT Introduction: The term ‘orphan diseases’ includes conditions meeting prevalence-based or commercial viability criteria: they affect a small number of individuals and are considered an unviable market for drug development. Proteomics is an important technology to study them, providing information on mechanisms and evolution, biomarkers, and effects of therapeutic interventions. Areas covered: Herein, we review how proteomics and bioinformatic tools could be applied to the study of rare diseases and discuss pitfalls and potential. Expert opinion: Research in the field of rare diseases has to face many challenges, and implementation plans should foresee highly specialized collaborative consortia to create multidisciplinary frameworks for data sharing, advancing research, supporting clinical studies, and accelerating drug development. The integration of different technologies will allow better knowledge of disease pathophysiology, and the inclusion of proteomics and other omics technologies in this context will be pivotal to this aim. Several aspects of rare diseases, often perceived as limiting factors, might actually be advantages for a precision medicine approach: the limited number of patients, the collaboration with patient societies, and the availability of curated clinical registries could allow the development of homogeneous clinical databases and ultimately a better control over the data to be analyzed.