Interfacially Enhanced Superconductivity in Fe(Te,Se)/Bi4Te3 Heterostructures.

Realizing topological superconductivity by integrating high-transition-temperature (TC) superconductors with topological insulators can open new paths for quantum computing applications. Here, a new approach is reported for increasing the superconducting transition temperature ( T C onset ) $( {T_{\mathrm{C}}^{{\mathrm{onset}}}} )$ by interfacing the unconventional superconductor Fe(Te,Se) with the topological insulator Bi-Te system in the low-Se doping regime, near where superconductivity vanishes in the bulk. The critical finding is that the T C onset $T_{\mathrm{C}}^{{\mathrm{onset}}}$ of Fe(Te,Se) increases from nominally non-superconducting to as high as 12.5 K when Bi2Te3 is replaced with the topological phase Bi4Te3. Interfacing Fe(Te,Se) with Bi4Te3 is also found to be critical for stabilizing superconductivity in monolayer films where T C onset $T_{\mathrm{C}}^{{\mathrm{onset}}}$ can be as high as 6 K. Measurements of the electronic and crystalline structure of the Bi4Te3 layer reveal that a large electron transfer, epitaxial strain, and novel chemical reduction processes are critical factors for the enhancement of superconductivity. This novel route for enhancing TC in an important epitaxial system provides new insight on the nature of interfacial superconductivity and a platform to identify and utilize new electronic phases.

Generating Clinical-Grade Gene-Disease Validity Classifications Through the ClinGen Data Platforms.

Clinical genetic laboratories must have access to clinically validated biomedical data for precision medicine. A lack of accessibility, normalized structure, and consistency in evaluation complicates interpretation of disease causality, resulting in confusion in assessing the clinical validity of genes and genetic variants for diagnosis. A key goal of the Clinical Genome Resource (ClinGen) is to fill the knowledge gap concerning the strength of evidence supporting the role of a gene in a monogenic disease, which is achieved through a process known as Gene-Disease Validity curation. Here we review the work of ClinGen in developing a curation infrastructure that supports the standardization, harmonization, and dissemination of Gene-Disease Validity data through the creation of frameworks and the utilization of common data standards. This infrastructure is based on several applications, including the ClinGen GeneTracker, Gene Curation Interface, Data Exchange, GeneGraph, and website.

Accelerating P300-based neurofeedback training for attention enhancement using iterative learning control: a randomised controlled trial.

Objective. Neurofeedback (NFB) training through brain-computer interfacing has demonstrated efficacy in treating neurological deficits and diseases, and enhancing cognitive abilities in healthy individuals. It was previously shown that event-related potential (ERP)-based NFB training using a P300 speller can improve attention in healthy adults by incrementally increasing the difficulty of the spelling task. This study aims to assess the impact of task difficulty adaptation on ERP-based attention training in healthy adults. To achieve this, we introduce a novel adaptation employing iterative learning control (ILC) and compare it against an existing method and a control group with random task difficulty variation.Approach. The study involved 45 healthy participants in a single-blind, three-arm randomised controlled trial. Each group underwent one NFB training session, using different methods to adapt task difficulty in a P300 spelling task: two groups with personalised difficulty adjustments (our proposed ILC and an existing approach) and one group with random difficulty. Cognitive performance was evaluated before and after the training session using a visual spatial attention task and we gathered participant feedback through questionnaires.Main results. All groups demonstrated a significant performance improvement in the spatial attention task post-training, with an average increase of 12.63%. Notably, the group using the proposed iterative learning controller achieved a 22% increase in P300 amplitude during training and a 17% reduction in post-training alpha power, all while significantly accelerating the training process compared to other groups.Significance. Our results suggest that ERP-based NFB training using a P300 speller effectively enhances attention in healthy adults, with significant improvements observed after a single session. Personalised task difficulty adaptation using ILC not only accelerates the training but also enhances ERPs during the training. Accelerating NFB training, while maintaining its effectiveness, is vital for its acceptability by both end-users and clinicians.

Online Oncology Careers Events to Attract the Future Oncology Medical Workforce: An Exemplar Event and Review of the Literature.

AIMS: There are too few oncologists to meet the increasing burden imposed by the rising incidence of cancer. This results from issues with the retention of established oncologists and longstanding challenges to the recruitment of adequate numbers of trainees. To counter this, the British Oncology Network for Undergraduate Societies (BONUS) devised an online oncology careers event for medical students and junior doctors who are yet to select a specialty. MATERIALS AND METHODS: An online careers event was devised with a focus on oncology practice and related subspecialties, as well as research. Event attendees were asked to respond to piloted pre- and post-event surveys. Knowledge and attitudes towards a career in oncology were evaluated using Likert scale and multiple-choice questions. A systematic literature search was carried out to contextualise these data. RESULTS: Of the 73 attendees, 44 (60%) participants completed both the pre- and post-event surveys; 79.5% of attendees believed that information on a career in oncology is lacking in medical training. This viewpoint was supported by the systematic review, which highlighted a need for relevant focussed interventions targeted at medical students and fledgling doctors. The education event led to an increase in the median reported understanding of the oncology career pathway from 6.0 to 8.0 (P < 0.05 and P < 0.001), as well as the likelihood of pursuing a career in oncology (8.0-9.0; P < 0.05). It was also associated with a proportional increase in medical and surgical oncology interest, albeit with a fall in interest in clinical and interventional oncology as well as academia. CONCLUSION: A targeted online careers event increases knowledge of and interest in a career in oncology, albeit predominantly for medical and surgical subspecialties. Broader initiatives based on our model should be developed and careers in academia as well as clinical and interventional oncology emphasised.

The impact of genomic context on outcomes of solid cancer patients treated with genotype-matched targeted therapies: a comprehensive review.

INTRODUCTION: A critical need in the field of genotype-matched targeted therapy in cancer is to identify patients unlikely to respond to precision medicines. This will manage expectations of individualised therapies and avoid clinical progression to a point where institution of alternative treatments might not be possible. We examined the evidence base of the impact of genomic context on which targeted alterations are inscribed to identify baseline biomarkers distinguishing those obtaining the expected response from those with less benefit from targeted therapies. METHODS: A comprehensive narrative review was conducted: scoping searches were undertaken in PubMed, Cochrane Database of Systematic Reviews, and PROSPERO. Outcomes included in meta-analysis were progression-free and overall survival. Data were extracted from Kaplan-Meier and used to calculate hazard ratios. Studies presenting data on two molecular subcohorts (e.g. co-mutation versus no co-mutation) were included in fixed meta-analysis. Other studies were used for descriptive purposes. RESULTS: The presence of concomitant driver mutations, higher tumour mutational burden (TMB), greater copy number burden, and APOBEC signatures significantly reduces benefits of targeted therapy in lung cancers in never smokers (LCINS - less than 100 cigarettes per lifetime) and breast cancer, cancers with low TMB. LCINS have significantly poorer outcomes if their cancers harbour p53 co-mutations, an effect also seen in human epidermal growth factor receptor 2-positive (HER2+) breast cancer patients (trastuzumab) and head and neck cancer patients [phosphoinositide 3-kinase (PI3K) inhibition]. PI3K co-alterations have less impact when targeting epidermal growth factor receptor mutations and anaplastic lymphoma kinase fusions, but significantly reduce the impact of targeting HER2 and MET amplifications. SMARCA4 co-mutations predict for poor outcome in patients treated with osimertinib and sotorasib. In BRAF-mutant melanoma, whilst there are no genomic features distinguishing exceptional responders from primary progressors, there are clear transcriptomic features dichotomising these outcomes. CONCLUSION: To our knowledge, this is the most comprehensive review to date of the impact of genomic context on outcomes with targeted therapy. It represents a valuable resource informing progress towards contextualised precision medicine.

Emergent Magnetism with Continuous Control in the Ultrahigh-Conductivity Layered Oxide PdCoO2.

The current challenge to realizing continuously tunable magnetism lies in our inability to systematically change properties, such as valence, spin, and orbital degrees of freedom, as well as crystallographic geometry. Here, we demonstrate that ferromagnetism can be externally turned on with the application of low-energy helium implantation and can be subsequently erased and returned to the pristine state via annealing. This high level of continuous control is made possible by targeting magnetic metastability in the ultrahigh-conductivity, nonmagnetic layered oxide PdCoO2 where local lattice distortions generated by helium implantation induce the emergence of a net moment on the surrounding transition metal octahedral sites. These highly localized moments communicate through the itinerant metal states, which trigger the onset of percolated long-range ferromagnetism. The ability to continuously tune competing interactions enables tailoring precise magnetic and magnetotransport responses in an ultrahigh-conductivity film and will be critical to applications across spintronics.

Effect of Mn doping and charge transfer on LaTi1-xMnxO3.

We report the magnetic and electronic transport properties of Mn-doped LaTi1-xMnxO3(x= 0, 0.1, 0.3, 0.5) as a function of temperature and an applied magnetic field. It was found that the Mn-doped samples show a magnetic transition which is not present in the parent LaTiO3. The Mn-doped samples showed fluctuations in magnetization at low fields below their Néel transition temperature indicating electronic phase separation in the material. Increased Mn content in the sample strengthens the ferromagnetic-like moment while maintaining G-type antiferromagnetic phase by charge transfer from Mn to Ti and influencing orbital ordering of the Ti3+t2gorbitals. The results are discussed in parallel with transport and bulk magnetization measurements detailing the electronic behavior. An additional context for the mechanism is supported by first-principles density-function theory calculations.

High Entropy Oxide Relaxor Ferroelectrics.

Relaxor ferroelectrics are important in technological applications due to strong electromechanical response, energy storage capacity, electrocaloric effect, and pyroelectric energy conversion properties. Current efforts to discover and design materials in this class generally rely on substitutional doping as slight changes to local compositional order can significantly affect the Curie temperature, morphotropic phase boundary, and electromechanical responses. In this work, we demonstrate that moving to the strong limit of compositional complexity in an ABO3 perovskite allows stabilization of relaxor responses that do not rely on a single narrow phase transition region. Entropy-assisted synthesis approaches are utilized to synthesize single-crystal Ba(Ti0.2Sn0.2Zr0.2Hf0.2Nb0.2)O3 [Ba(5B)O] films. The high levels of configurational disorder present in this system are found to influence dielectric relaxation, phase transitions, nanopolar domain formation, and Curie temperature. Temperature-dependent dielectric, Raman spectroscopy, and second-harmonic generation measurements reveal multiple phase transitions, a high Curie temperature of 570 K, and the relaxor ferroelectric nature of Ba(5B)O films. The first-principles theory calculations are used to predict possible combinations of cations to design relaxor ferroelectrics and quantify the relative feasibility of synthesizing these highly disordered single-phase perovskite systems. The ability to stabilize single-phase perovskites with various cations on the B-sites offers possibilities for designing high-performance relaxor ferroelectric materials for piezoelectric, pyroelectric, and electrocaloric applications.

Patterns of oxygen saturation in prolonged recovery from COVID-19 pneumonia.

During the second wave of the COVID-19 pandemic in South Africa, a recurrent pattern of prolonged recovery after acute COVID-19 pneumonia, characterised by low oxygen saturation levels for >2 weeks, was observed in an intermediate-care facility in Cape Town. A case study together with a series of 12 patients is presented to illustrate this phenomenon, and two types of 'sats gap' are described, which were used by physiotherapists and doctors to monitor daily progress. We attempt to explain this prolonged recovery in terms of the possible pathophysiology, and suggest a number of learning points to guide further research.

Safety of Every-Other-Day Fasting in the Treatment of Spinal Cord Injury: A Randomized Controlled Trial.

ABSTRACT: Every-other-day fasting is effective for a variety of major human diseases, but the safety of these interventions is uncertain for patients with spinal cord injury. A randomized controlled study was conducted to investigate the safety of every-other-day fasting in patients with spinal cord injury. Participants who met the diagnostic inclusion and exclusion criteria were randomly divided into the control and every-other-day fasting groups. In the every-other-day fasting group, fasting lasted from 09:00 p.m. on day 1 to 06:00 p.m. on the following day (day 2). Dinner on day 2 was restricted to approximately 30% of the average daily calorie intake. The changes in plasma glucose were recorded daily for 2 days and every other day from the third day after every-other-day fasting intervention. The changes in albumin, prealbumin, plasma potassium, serum sodium, blood calcium, body weight, and body mass index were monitored at the baseline and at the end of the every-other-day fasting intervention. The results showed that compared with the control group, the mean blood glucose levels were significantly decreased from the second week after every-other-day fasting intervention. The body weight of patients in the every-other-day fasting group was notably reduced compared with that at baseline, whereas in body mass index, no obvious differences were observed before and after treatment with every-other-day fasting. In general, every-other-day fasting could be considered as a safe approach for individuals with spinal cord injury.

Species diversity and mycotoxin production by members of the Fusarium tricinctum species complex associated with Fusarium head blight of wheat and barley in Italy.

Fusarium head blight (FHB) is a global cereal disease caused by a complex of Fusarium species. In Europe, the main species responsible for FHB are F. graminearum, F. culmorum and F. poae. However, members of the F. tricinctum species complex (FTSC) have become increasingly important. FTSC fusaria can synthesize mycotoxins such as moniliformin (MON), enniatins (ENNs) and several other biologically active secondary metabolites that could compromise food quality. In this study, FTSC isolates primarily from Italian durum wheat and barley, together with individual strains from four non-graminaceous hosts, were collected to assess their genetic diversity and determine their potential to produce mycotoxins in vitro on rice cultures. A multilocus DNA sequence dataset (TEF1, RPB1 and RPB2) was constructed for 117 isolates from Italy and 6 from Iran to evaluate FTSC species diversity and their evolutionary relationships. Phylogenetic analyses revealed wide genetic diversity among Italian FTSC isolates. Among previously described FTSC species, F. avenaceum (FTSC 4) was the most common species in Italy (56/117 = 47.9%) while F. tricinctum (FTSC 3), and F. acuminatum (FTSC 2) accounted for 11.1% (13/117) and the 8.5% (10/117), respectively. The second most detected species was a new and unnamed Fusarium sp. (FTSC 12; 32/117 = 19%) resolved as the sister group of F. tricinctum. Collectively, these four phylospecies accounted for 111/117 = 94.9% of the Italian FTSC collection. However, we identified five other FTSC species at low frequencies, including F. iranicum (FTSC 6) and three newly discovered species (Fusarium spp. FTSC 13, 14, 15). Of the 59 FTSC isolates tested for mycotoxin production on rice cultures, 54 and 55 strains, respectively, were able to produce detectable levels of ENNs and MON. In addition, we confirmed that the ability to produce bioactive secondary metabolites such as chlamydosporol, acuminatopyrone, longiborneol, fungerin and butanolide is widespread across the FTSC.

Predicting the length of stay at admission for emergency general surgery patients a cohort study.

INTRODUCTION: Predicting length of stay (LOS) is beneficial to patients and the health service. When a prolonged LOS is predicted, it gives the opportunity for focused therapies and allocation of resources to reduce this period. In emergency general surgery (EGS) there has been limited investigation of variables that may be important predictors of LOS. This study examines social characteristics alongside measures of severity of acute illness and co-morbidities in an adult EGS population to establish their contribution to LOS. METHODS: Data were collected prospectively from patients at admission including medical variables, demographics, and therapeutic requirements. The length of hospital admission was measured, and multiple regression analysis was used to identify variables which predicted the LOS. RESULTS: Data were collected from 105 patients. The regression model gave an R2 of 0.34, p = 0.0006. Barthal index (measure of independence in activities of daily living) was a significant predictor of LOS [logworth 1.649, p0.02243]. Housing status and Level of social support both correlated in one-way analysis with LOS. CONCLUSION: There are non-surgical variables, measurable at admission which are of significant value in predicting LOS of EGS patients. This warrants further investigation through a larger study to better quantify the contributions of these variables, and establish potential early interventions to reduce the LOS.

Ketogenic regimens for acute neurotraumatic events.

Dietary modification would be the most translatable, cost-efficient, and, likely, the safest approach available that can reduce the reliance on pharmaceutical treatments for treating acute or chronic neurological disorders. A wide variety of evidence suggests that the ketogenic diet (KD) could have beneficial effects in acute traumatic events, such as spinal cord injury and traumatic brain injury. Review of existing human and animal studies revealed that KD can improve motor neuro-recovery, gray matter sparing, pain thresholds, and neuroinflammation and decrease depression. Although the exact mechanism by which the KD provides neuroprotection is not fully understood, its effects on cellular energetics, mitochondria function and inflammation are likely to have a role.

Epitaxial Stabilization of Single-Crystal Multiferroic YCrO3 Thin Films.

We report on the growth of stoichiometric, single-crystal YCrO3 epitaxial thin films on (001) SrTiO3 substrates using pulsed laser deposition. X-ray diffraction and atomic force microscopy reveal that the films grew in a layer-by-layer fashion with excellent crystallinity and atomically smooth surfaces. Magnetization measurements demonstrate that the material is ferromagnetic below 144 K. The temperature dependence of dielectric permittivity shows a characteristic relaxor-ferroelectric behavior at TC = 375-408 K. A dielectric anomaly at the magnetic transition temperature indicates a close correlation between magnetic and electric order parameters in these multiferroic YCrO3 films. These findings provide guidance to synthesize rare-earth, chromite-based multifunctional heterostructures and build a foundation for future studies on the understanding of magnetoelectric effects in similar material systems.

Profiling cytotoxic microRNAs in pediatric and adult glioblastoma cells by high-content screening, identification, and validation of miR-1300.

MicroRNAs play an important role in the regulation of mRNA translation and have therapeutic potential in cancer and other diseases. To profile the landscape of microRNAs with significant cytotoxicity in the context of glioblastoma (GBM), we performed a high-throughput screen in adult and pediatric GBM cells using a synthetic oligonucleotide library representing all known human microRNAs. Bioinformatics analysis was used to refine this list and the top seven microRNAs were validated in a larger panel of GBM cells using state-of-the-art in vitro assays. The cytotoxic effect of our most relevant candidate was assessed in a preclinical model. Our screen identified ~100 significantly cytotoxic microRNAs with 70% concordance between cell lines. MicroRNA-1300 (miR-1300) was the most potent and robust candidate. We observed a striking binucleated phenotype in miR-1300 transfected cells due to cytokinesis failure followed by apoptosis. This was also observed in two stem-like patient-derived cultures. We identified the physiological role of miR-1300 as a regulator of endomitosis in megakaryocyte differentiation where blockade of cytokinesis is an essential step. In GBM cells, where miR-1300 is normally not expressed, the oncogene Epithelial Cell Transforming 2 (ECT2) was validated as a direct key target. ECT2 siRNA phenocopied the effects of miR-1300, and ECT2 overexpression led to rescue of miR-1300 induced binucleation. We showed that ectopic expression of miR-1300 led to decreased tumor growth in an orthotopic GBM model. Our screen provides a resource for the neuro-oncology community and identified miR-1300 as a novel regulator of endomitosis with translatable potential for therapeutic application.

Neuroprotective effects of a ketogenic diet in combination with exogenous ketone salts following acute spinal cord injury.

We have previously shown that induction of ketosis by ketogenic diet (KD) conveyed neuroprotection following spinal cord injury in rodent models, however, clinical translation may be limited by the slow raise of ketone levels when applying KD in the acute post-injury period. Thus we investigated the use of exogenous ketone supplementation (ketone sodium, KS) combined with ketogenic diet as a means rapidly inducing a metabolic state of ketosis following spinal cord injury in adult rats. In uninjured rats, ketone levels increased more rapidly than those in rats with KD alone and peaked at higher levels than we previously demonstrated for the KD in models of spinal cord injury. However, ketone levels in KD + KS treated rats with SCI did not exceed the previously observed levels in rats treated with KD alone. We still demonstrated neuroprotective effects of KD + KS treatment that extend our previous neuroprotective observations with KD only. The results showed increased neuronal and axonal sparing in the dorsal corticospinal tract. Also, better performance of forelimb motor abilities were observed on the Montoya staircase (for testing food pellets reaching) at 4 and 6 weeks post-injury and rearing in a cylinder (for testing forelimb usage) at 6 and 8 weeks post-injury. Taken together, the findings of this study add to the growing body of work demonstrating the potential benefits of inducing ketosis following neurotrauma. Ketone salt combined with a ketogenic diet gavage in rats with acute spinal cord injury can rapidly increase ketone body levels in the blood and promote motor function recovery. This study was approved by the Animal Care Committee of the University of British Columbia (protocol No. A14-350) on August 31, 2015.

Preserving US microbe collections sparks future discoveries.

Collections of micro-organisms are a crucial element of life science research infrastructure but are vulnerable to loss and damage caused by natural or man-made disasters, the untimely death or retirement of personnel, or the loss of research funding. Preservation of biological collections has risen in priority due to a new appreciation for discoveries linked to preserved specimens, emerging hurdles to international collecting and decreased funding for new collecting. While many historic collections have been lost, several have been preserved, some with dramatic rescue stories. Rescued microbes have been used for discoveries in areas of health, biotechnology and basic life science. Suggestions for long-term planning for microbial stocks are listed, as well as inducements for long-term preservation.