Miracle-dz/UniFAR-FTUs huggingface dataset:
Fetal and neonatal alloimmune thrombocytopenia: a late or missed diagnosis disease in fetal and perinatal health-care settings

Abstract Introduction Even though Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT) has been recognized as the main cause of primary hemorrhagic morbidity and mortality in fetuses and newborns, screening programs to detect pregnancies at risk have not yet been implemented in any country. Moreover, in spite of increased concerns about maternal, fetal and neonatal health care in general, this potentially lethal disease is still underdiagnosed. The aim of this report is to highlight the importance of considering FNAIT in fetal and perinatal health-care settings and show the usefulness of molecular tools in early diagnosis of this clinical entity. Methods DNA was extracted from whole blood from parents and newborns; genotyping was performed by in house PCR using sequence-specific primers for typing Human Platelet Antigens (HPA)-1 to -6, -9, and -15, and with commercial HPA-TYPE (BAG HealthCare, Lich, Germany). Anti-HPA antibodies in the maternal serum were detected by the Monoclonal Antibody Solid Phase Platelet antibody Test (MASPAT). Chloroquine-treated platelets were used for the discrimination of platelet-specific antibodies from anti-HLA antibodies. Results Patients 1 and 2 had severe thrombocytopenia due to incompatibility in HPA-1 and HPA-15, respectively. The third case was a thrombocytopenic neonate with severe bleeding complications other than ICH and in whom differential diagnosis between FNAIT and Von Willebrand congenital disease was necessary; incompatibility in HPA-15 was also demonstrated. Case 4 represents a missed diagnostic opportunity. Conclusion This is the first report of FNAIT cases confirmed by molecular evidence and anti-HPA antibodies detection in Argentina. This report reinforces the relevance of early diagnosis of this clinical entity. Since the delay in FNAIT diagnosis could lead to severe consequences in the fetus and neonates, strategies to approach maternal, fetal, and perinatal health, as well as prevention policies aimed to reduce fetal and neonatal morbidity and mortality should focus on implementing programs to identify high-risk pregnancies and thus reduce thrombocytopenia-related complications in fetuses and newborns.
Regulation of breast cancer resistance protein and P‐glycoprotein by ezrin, radixin and moesin in lung, intestinal and renal cancer cell lines

Ezrin (Ezr), radixin (Rdx) and moesin (Msn) (ERM) proteins anchor other proteins to the cell membrane, serving to regulate their localization and function. Here, we examined whether ERM proteins functionally regulate breast cancer resistance protein (BCRP) and P‐glycoprotein in cell lines derived from lung, intestinal and renal cancers.
A review of thirty‐nine patients diagnosed with necrotising otitis externa over three years: Is CT imaging for diagnosis sufficient?

1.Early necrotising otitis externa (NOE) does not always show osseous destruction on CT imaging; therefore complimentary MRI is superior in evaluating anatomical location and extent of the soft tissue involvement. 2.This study showed a high percentage of CT scans with no obvious radiological appearance of NOE (in a group of patients with NOE confirmed with MRI). 3.CT imaging will evaluate bone erosion and demineralization, but early soft tissue findings in NOE are poorly evaluated by CT and are difficult to appreciate. 4.The most helpful MRI sequences are the post gadolinium T1-Weighted sequences with fat suppression. 5.The most common positive MRI finding in NOE is retrocondylar fat infiltration.
Auditory verbal skills training is a new approach in adult cochlear implant rehabilitation.

INTRODUCTION Outcome after cochlear implantation in adults varies and is affected by many factors. One factor is auditory training after implantation. No national guidelines for adult auditory training currently exist in Denmark. An auditory verbal skills training (AVST) rehabilitation programme was developed and applied at the East Danish Cochlear Implant (CI) Centre (Rigshospitalet, Gentofte Unit). The AVST intervention was inspired by the auditory verbal therapy practice and targeted the paediatric population and their families. The objectives were to document the outcome for first-time adult CI users, to apply and explore the effects of the AVST and to examine CI users' possibly extended need for technical follow-up. METHODS A prospective comparative study design was used. Ten CI users participated in AVST with a relative. Seven CI users were included in a control group. The outcome measures of speech understanding and quality of life (QoL) were recorded pre-implant and post-implant. RESULTS All participants showed improved speech understanding and a higher QoL post-implant. The within-group analyses showed significant improvements in outcome over time. However, no differences were seen in the between-group analyses post-implant. The CI users in the intervention group received more CI fine-tuning. CONCLUSIONS The AVST was successfully implemented at the CI Centre. Improvements in speech understanding and QoL were seen in both groups over time, but no differences were seen between the groups. The CI users in the intervention group received more fine-tuning of their processor. FUNDING Oticon Medical A/S supported the study financially. TRIAL REGISTRATION Not relevant as the study applied a prospective method study design.
Free-Flap Reconstruction of the Tongue

Abstract The tongue is paramount to natural speech and swallowing, and good tongue function is important in the overall quality of life. Autologous free-flap reconstruction of the tongue after glossectomy allows for adequate speech, swallow, and quality-of-life outcomes in a majority of patients. Herein, the authors review autologous free-flap reconstruction of the tongue with a focus on different flap options, speech and swallow outcomes, quality-of-life outcomes, and factors that affect how patients perform after tongue reconstruction.
Intramolecular domain dynamics regulate synaptic MAGUK protein interactions

PSD-95 MAGUK family scaffold proteins are multi-domain organisers of synaptic transmission that contain three PDZ domains followed by an SH3-GK domain tandem. This domain architecture allows coordinated assembly of protein complexes composed of neurotransmitter receptors, synaptic adhesion molecules, cytoskeletal proteins and downstream signalling effectors. Here we show that binding of monomeric PDZ3 ligands to the third PDZ domain of PSD-95 induces functional changes in the intramolecular SH3-GK domain assembly that influence subsequent homotypic and heterotypic complex formation. We identify PSD-95 interactors that differentially bind to the SH3-GK domain tandem depending on its conformational state. Among these interactors we further establish the heterotrimeric G protein subunit Gnb5 as a PSD-95 complex partner at dendritic spines. The PSD-95 GK domain binds to Gnb5 and this interaction is triggered by PDZ3 ligands binding to the third PDZ domain of PSD-95, unraveling a hierarchical binding mechanism of PSD-95 complex formation.
RETINAL TEARS DUE TO PICKLEBALL INJURY

This is the first case series of two instances of retinal tears occurring after a pickleball injury to the eye. Participants should consider wearing eye protection, similar to recommendations of other racquet sports, while playing pickleball to reduce the risk of ocular injury. Purpose: This is the first case series of two instances of retinal tears due to an injury sustained while playing pickleball. Methods: Case series. Results: A 66-year old white man presented with a symptomatic retinal tear, localized retinal detachment, and mild vitreous hemorrhage nine days after he was hit in his left eye while playing pickleball. The patient was not wearing eye protection while playing. The patient was treated with cryotherapy, and after three weeks, the vitreous hemorrhage and retinal detachment resolved. In addition, a 60-year-old woman presented with a posterior vitreous detachment and a symptomatic retinal tear 1 month after blunt trauma to her left eye from a pickleball injury. She underwent successful laser retinopexy treatment. Conclusion: Proper eye protection should be strongly considered while playing pickleball, especially in the elderly population or in individuals who are at higher risk for retinal detachment.
Migratory goose arrival time plays a larger role in influencing forage quality than advancing springs in an Arctic coastal wetland

With warmer springs, herbivores migrating to Arctic breeding grounds may experience phenological mismatches between their energy demands and the availability of high quality forage. Yet, how the timing of the start of the season and herbivore arrival influences forage quality is often unknown. In coastal western Alaska, approximately one million migratory geese arrive each spring to breed, where foliar %N and C:N ratios are linked to gosling survival and population growth. We conducted a three-year experiment where we manipulated the start of the growing season using warming chambers and grazing times using captive Pacific black brant (Branta bernicla nigricans) to examine how the timing of these events influences the quality of an important forage species. Our results suggest that grazing timing plays a much greater role than an advanced growing season in determining forage quality. All top models included grazing timing, and suggested that compared to typical grazing timing, early grazing significantly reduced foliar %C by 6% and C:N ratios by 16%, while late goose grazing significantly reduced foliar %N by 15% and increased foliar C:N ratios by 21%. While second-ranking top models included the effect of season, the advanced growing season effect was not significant and only reduced %N by 4%, increased %C by <1%, and increased C:N ratios by 5% compared to an ambient growing season. In summary, in years where geese arrive early, they will consume higher quality forage when they arrive and throughout the season, while in years that geese arrive late they will consume lower quality forage when they arrive and for the remainder of the season. When the growing season starts has only a minor influence on this pattern. Our findings suggest that cues determining migration and arrival times to breeding areas are important factors influencing forage quality for geese in western Alaska.
Protein Solvent Shell Structure Provides Rapid Analysis of Hydration Dynamics

The solvation layer surrounding a protein is clearly an intrinsic part of protein structure-dynamics-function, and our understanding of how the hydration dynamics influences protein function is emerging. We have recently reported simulations indicating a correlation between regional hydration dynamics and the structure of the solvation layer around different regions of the enzyme Candida antarctica lipase B, wherein the radial distribution function (RDF) was used to calculate the pairwise entropy, providing a link between dynamics (diffusion) and thermodynamics (excess entropy) known as Rosenfeld scaling. Regions with higher RDF values/peaks in the hydration layer (the first peak, within 6 Å of the protein surface) have faster diffusion in the hydration layer. The finding thus hinted at a handle for rapid evaluation of hydration dynamics at different regions on the protein surface in molecular dynamics simulations. Such an approach may move the analysis of hydration dynamics from a specialized venture to routine analysis, enabling an informatics approach to evaluate the role of hydration dynamics in biomolecular function. This paper first confirms that the correlation between regional diffusive dynamics and hydration layer structure (via water center of mass around protein side-chain atom RDF) is observed as a general relationship across a set of proteins. Second, it seeks to devise an approach for rapid analysis of hydration dynamics, determining the minimum amount of information and computational effort required to get a reliable value of hydration dynamics from structural data in MD simulations based on the protein-water RDF. A linear regression model using the integral of the hydration layer in the water-protein RDF was found to provide statistically equivalent apparent diffusion coefficients at the 95% confidence level for a set of 92 regions within five different proteins. In summary, RDF analysis of 10 ns of data after simulation convergence is sufficient to accurately map regions of fast and slow hydration dynamics around a protein surface. Additionally, it is anticipated that a quick look at protein-water RDFs, comparing peak heights, will be useful to provide a qualitative ranking of regions of faster and slower hydration dynamics at the protein surface for rapid analysis when investigating the role of solvent dynamics in protein function.
Chemical Composition and Biological Activities of Lebanese Pentapera Plant

Background Due to their chemical constituents and biological properties, plants have long been used to control life-threatening diseases. The flora of Lebanon includes many plants that have already been demonstrated to have medicinal value, and other species, such as Pentapera sicula libanotica, that are yet to be characterized. The present study characterized the chemical composition, anti-oxidant, anti-inflammatory, and anti-proliferative potential of aqueous, ethanol, and methanol extracts derived from the leaves of the Lebanese Pentapera plant. Material/Methods High-performance liquid chromatography (HPLC) was used to determine the chemical composition. Gas chromatography (GC) coupled with mass spectrometry (MS) was applied to determine the content of essential oil. DPPH radical scavenging assay was performed to evaluate the anti-oxidant potential. The anti-inflammatory potential was assessed using quantitative real-time PCR (qRT-PCR) by measuring TNF-α, IL-6, and CCL4 mRNA levels, and we assessed Cox-2 and iNOS proteins levels using Western blot (WB) analysis. MTT assay was carried out to determine the anti-proliferative potential. Results We identified, mainly in the alcoholic (methanol and ethanol) extracts, distinct bioactive compounds with pharmacological relevance. In parallel, with their phytochemical content, these 2 extracts showed significant anti-oxidant, anti-inflammatory and anti-proliferative capacities. Conclusion Pentapera sicula libanotica appears to be a promising pharmacological tool.
Unbiased pattern analysis reveals highly diverse responses of cytoskeletal systems to cyclic straining

In mammalian cells, actin, microtubules, and various types of cytoplasmic intermediate filaments respond to external stretching. Here, we investigated the underlying processes in endothelial cells plated on soft substrates from silicone elastomer. After cyclic stretch (0.13 Hz, 14% strain amplitude) for periods ranging from 5 min to 8 h, cells were fixed and double-stained for microtubules and either actin or vimentin. Cell images were analyzed by a two-step routine. In the first step, micrographs were segmented for potential fibrous structures. In the second step, the resulting binary masks were auto- or cross-correlated. Autocorrelation of segmented images provided a sensitive and objective measure of orientational and translational order of the different cytoskeletal systems. Aligning of correlograms from individual cells removed the influence of only partial alignment between cells and enabled determination of intrinsic cytoskeletal order. We found that cyclic stretching affected the actin cytoskeleton most, microtubules less, and vimentin mostly only via reorientation of the whole cell. Pharmacological disruption of microtubules had barely any influence on actin ordering. The similarity, i.e., cross-correlation, between vimentin and microtubules was much higher than the one between actin and microtubules. Moreover, prolonged cyclic stretching slightly decoupled the cytoskeletal systems as it reduced the cross-correlations in both cases. Finally, actin and microtubules were more correlated at peripheral regions of cells whereas vimentin and microtubules correlated more in central regions.
Novel displays of patient information in critical care settings: a systematic review

Objective Clinician information overload is prevalent in critical care settings. Improved visualization of patient information may help clinicians cope with information overload, increase efficiency, and improve quality. We compared the effect of information display interventions with usual care on patient care outcomes. Materials and Methods We conducted a systematic review including experimental and quasi‐experimental studies of information display interventions conducted in critical care and anesthesiology settings. Citations from January 1990 to June 2018 were searched in PubMed and IEEE Xplore. Reviewers worked independently to screen articles, evaluate quality, and abstract primary outcomes and display features. Results Of 6742 studies identified, 22 studies evaluating 17 information displays met the study inclusion criteria. Information display categories included comprehensive integrated displays (3 displays), multipatient dashboards (7 displays), physiologic and laboratory monitoring (5 displays), and expert systems (2 displays). Significant improvement on primary outcomes over usual care was reported in 12 studies for 9 unique displays. Improvement was found mostly with comprehensive integrated displays (4 of 6 studies) and multipatient dashboards (5 of 7 studies). Only 1 of 5 randomized controlled trials had a positive effect in the primary outcome. Conclusion We found weak evidence suggesting comprehensive integrated displays improve provider efficiency and process outcomes, and multipatient dashboards improve compliance with care protocols and patient outcomes. Randomized controlled trials of physiologic and laboratory monitoring displays did not show improvement in primary outcomes, despite positive results in simulated settings. Important research translation gaps from laboratory to actual critical care settings exist.
Kuru, the First Human Prion Disease

Kuru, the first human prion disease was transmitted to chimpanzees by D. Carleton Gajdusek (1923–2008). In this review, we summarize the history of this seminal discovery, its anthropological background, epidemiology, clinical picture, neuropathology, and molecular genetics. We provide descriptions of electron microscopy and confocal microscopy of kuru amyloid plaques retrieved from a paraffin-embedded block of an old kuru case, named Kupenota. The discovery of kuru opened new vistas of human medicine and was pivotal in the subsequent transmission of Creutzfeldt–Jakob disease, as well as the relevance that bovine spongiform encephalopathy had for transmission to humans. The transmission of kuru was one of the greatest contributions to biomedical sciences of the 20th century.
Aminated 3D Printed Polystyrene Maintains Stem Cell Proliferation and Osteogenic Differentiation.

As 3D printing becomes more common and the technique is used to build culture platforms, it is imperative to develop surface treatments for specific responses. The advantages of aminating and oxidizing polystyrene (PS) for human mesenchymal stem cell (hMSC) proliferation and osteogenic differentiation are investigated. We find that ammonia (NH3) plasma incorporates amines while oxygen plasma adds carbonyl and carboxylate groups. Across 2D, 3D, and 3D dynamic culture, we find that the NH3- treated surfaces encouraged cell proliferation. Our results show that the NH3-treated scaffold was the only treatment allowing dynamic proliferation of hMSCs with little evidence of osteogenic differentiation. With osteogenic media, particularly in 3D culture, we find the NH3 treatment encouraged greater and earlier expression of RUNX2 and ALP. The NH3-treated PS scaffolds support hMSC proliferation without spontaneous osteogenic differentiation in static and dynamic culture. This work provides an opportunity for further investigations into shear profiling and coculture within the developed culture system toward developing a bone marrow niche model. Impact statement Surface treatment can be leveraged to enhance human mesenchymal stem cell response when transitioning polystyrene from a 2D to a 3D culture substrate. Understanding how the underlying surface chemistry influences the adhered cells could help build complex culture environments, with multiple cell types and work toward more biomimetic models of the bone marrow niche. Toward this goal, it is imperative to establish how the cells respond under static and dynamic culture and ensure the scaffolds support osteogenesis under typical induction conditions.
Ketamine disrupts neuromodulatory control of glutamatergic synaptic transmission

A growing body of literature has demonstrated the potential for ketamine in the treatment of major depression. Sub-anesthetic doses produce rapid and sustained changes in depressive behavior, both in patients and rodent models, associated with reorganization of glutamatergic synapses in the prefrontal cortex (PFC). While ketamine is known to regulate NMDA-type glutamate receptors (NMDARs), the full complement of downstream cellular consequences for ketamine administration are not well understood. Here, we combine electrophysiology with 2-photon imaging and glutamate uncaging in acute slices of mouse PFC to further examine how ketamine alters glutamatergic synaptic transmission. We find that four hours after ketamine treatment, glutamatergic synapses themselves are not significantly affected. However, expression levels of the neuromodulatory Regulator of G-protein Signaling (RGS4) are dramatically reduced. This loss of RGS4 activity disrupts the normal compartmentalization of synaptic neuromodulation. Thus, under control conditions, α2 adrenergic receptors and GABAB receptors selectively inhibit AMPA-type glutamate receptors (AMPARs) and NMDARs, respectively. After ketamine-induced loss of RGS4 activity, this selectivity is lost, with both modulatory systems broadly inhibiting glutamatergic transmission. These results demonstrate a novel mechanism by which ketamine can influence synaptic signaling and provide new avenues for the exploration of therapeutics directed at treating neuropsychiatric disorders, such as depression.
Molecular Phylogeny of Mobatviruses (Hantaviridae) in Myanmar and Vietnam

The discovery of highly divergent lineages of hantaviruses (family Hantaviridae) in shrews, moles, and bats of multiple species raises the possibility that non-rodent hosts may have played a significant role in their evolutionary history. To further investigate this prospect, total RNA was extracted from RNAlater®-preserved lung tissues of 277 bats (representing five families, 14 genera and 40 species), captured in Myanmar and Vietnam during 2013–2016. Hantavirus RNA was detected in two of 15 black-bearded tomb bats (Taphozous melanopogon) and two of 26 Pomona roundleaf bats (Hipposideros pomona) in Myanmar, and in three of six ashy leaf-nosed bats (Hipposideros cineraceus) in Vietnam. Pair-wise alignment and comparison of coding regions of the S, M, and L segments of hantaviruses from Taphozous and Hipposideros bats revealed high nucleotide and amino acid sequence similarities to prototype Láibīn virus (LAIV) and Xuân Sơn virus (XSV), respectively. Phylogenetic analyses, generated by maximum-likelihood and Bayesian methods, showed a geographic clustering of LAIV strains from China and Myanmar, but not of XSV strains from China and Vietnam. These findings confirm that the black-bearded tomb bat is the natural reservoir of LAIV, and that more than one species of Hipposideros bats can host XSV.