Strongly coupled edge states in a graphene quantum Hall interferometer.

Electronic interferometers using the chiral, one-dimensional (1D) edge channels of the quantum Hall effect (QHE) can demonstrate a wealth of fundamental phenomena. The recent observation of phase jumps in a Fabry-Pérot (FP) interferometer revealed anyonic quasiparticle exchange statistics in the fractional QHE. When multiple integer edge channels are involved, FP interferometers have exhibited anomalous Aharonov-Bohm (AB) interference frequency doubling, suggesting putative pairing of electrons into 2 e quasiparticles. Here, we use a highly tunable graphene-based QHE FP interferometer to observe the connection between interference phase jumps and AB frequency doubling, unveiling how strong repulsive interaction between edge channels leads to the apparent pairing phenomena. By tuning electron density in-situ from filling factor ν < 2 to ν > 7 , we tune the interaction strength and observe periodic interference phase jumps leading to AB frequency doubling. Our observations demonstrate that the combination of repulsive interaction between the spin-split ν = 2 edge channels and charge quantization is sufficient to explain the frequency doubling, through a near-perfect charge screening between the localized and extended edge channels. Our results show that interferometers are sensitive probes of microscopic interactions and enable future experiments studying correlated electrons in 1D channels using density-tunable graphene.

Variability in thermal tolerance of clutches from different mothers indicates adaptation potential to climate warming in sea turtles.

The current climate warming is a challenge to biodiversity that could surpass the adaptation capacity of some species. Hence, understanding the means by which populations undergo an increase in their thermal tolerance is critical to assess how they could adapt to climate warming. Specifically, sea turtle populations could respond to increasing temperatures by (1) colonizing new nesting areas, (2) nesting during cooler times of the year, and/or (3) by increasing their thermal tolerance. Differences in thermal tolerance of clutches laid by different females would indicate that populations have the potential to adapt by natural selection. Here, we used exhaustive information on nest temperatures and hatching success of leatherback turtle (Dermochelys coriacea) clutches over 14 years to assess the occurrence of individual variability in thermal tolerance among females. We found an effect of temperature, year, and the interaction between female identity and nest temperature on hatching success, indicating that clutches laid by different females exhibited different levels of vulnerability to high temperatures. If thermal tolerance is a heritable trait, individuals with higher thermal tolerances could have greater chances of passing their genes to following generations, increasing their frequency in the population. However, the high rate of failure of clutches at temperatures above 32°C suggests that leatherback turtles are already experiencing extreme heat stress. A proper understanding of mechanisms of adaptation in populations to counteract changes in climate could greatly contribute to future conservation of endangered populations in a rapidly changing world.

Optimizing Concussion Care Seeking: Using Machine Learning to Predict Delayed Concussion Reporting.

BACKGROUND: Early medical attention after concussion may minimize symptom duration and burden; however, many concussions are undiagnosed or have a delay in diagnosis after injury. Many concussion symptoms (eg, headache, dizziness) are not visible, meaning that early identification is often contingent on individuals reporting their injury to medical staff. A fundamental understanding of the types and levels of factors that explain when concussions are reported can help identify promising directions for intervention. PURPOSE: To identify individual and institutional factors that predict immediate (vs delayed) injury reporting. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: This study was a secondary analysis of data from the Concussion Assessment, Research and Education (CARE) Consortium study. The sample included 3213 collegiate athletes and military service academy cadets who were diagnosed with a concussion during the study period. Participants were from 27 civilian institutions and 3 military institutions in the United States. Machine learning techniques were used to build models predicting who would report an injury immediately after a concussive event (measured by an athletic trainer denoting the injury as being reported "immediately" or "at a delay"), including both individual athlete/cadet and institutional characteristics. RESULTS: In the sample as a whole, combining individual factors enabled prediction of reporting immediacy, with mean accuracies between 55.8% and 62.6%, depending on classifier type and sample subset; adding institutional factors improved reporting prediction accuracies by 1 to 6 percentage points. At the individual level, injury-related altered mental status and loss of consciousness were most predictive of immediate reporting, which may be the result of observable signs leading to the injury report being externally mediated. At the institutional level, important attributes included athletic department annual revenue and ratio of athletes to athletic trainers. CONCLUSION: Further study is needed on the pathways through which institutional decisions about resource allocation, including decisions about sports medicine staffing, may contribute to reporting immediacy. More broadly, the relatively low accuracy of the machine learning models tested suggests the importance of continued expansion in how reporting is understood and facilitated.

Effect of Hearing Intervention versus Health Education Control on Fatigue: A Secondary Analysis of the ACHIEVE study.

BACKGROUND: Fatigue is a common complaint among older adults with hearing loss. The impact of addressing hearing loss on fatigue symptoms has not been studied in a randomized controlled trial. In a secondary analysis of the ACHIEVE study, we investigated the effect of hearing intervention versus health education control on 3-year change in fatigue in community-dwelling older adults with hearing loss. METHODS: Participants aged 70-84 years old with untreated hearing loss recruited across 4 study sites in the United States (Forsyth County, NC; Jackson, MS; Minneapolis, MN; Washington County, MD) were randomized (1:1) to hearing intervention or health education control and followed for 3 years. Three-year change in fatigue symptoms was measured by 2 instruments (RAND-36 and PROMIS). We estimated the intervention effect as the difference in the 3-year change in fatigue between intervention and control groups using a linear mixed-effects model under the intention-to-treat principle. RESULTS: Participants (n=977) had a mean age (SD) of 76.8 (4.0) years, were 53.5% female and 87.8% White. Over 3 years, a beneficial effect of the hearing intervention versus health education control on fatigue was observed using the RAND-fatigue score (ß= -0.12 [95% CI -0.22, -0.02]). Estimates also suggested beneficial effect of hearing intervention on fatigue when measured by the PROMIS fatigue score (ß= -0.32 [95% CI -1.15, 0.51]). CONCLUSIONS: Our findings suggest that hearing intervention may reduce fatigue over 3 years among older adults with hearing loss.

Differences in coaching in single- versus dual-console robotic cases: a mixed-methods study.

BACKGROUND: A growing importance has been placed on development of trainee robotic surgical skills through simulation curricula and intraoperative experience. However, few studies have examined how console case type impacts learning outcomes. We sought to evaluate how intraoperative coaching and resident autonomy differ based on the use of a single- versus dual-console robot. METHODS: Robotic single- and dual-console cases from February to September 2023 at a single institution were included. Faculty and trainees wore microphones to capture audio during the case. Pre/post surveys were administered, which included metrics on faculty coaching based on the Wisconsin Surgical Coaching Rubric (WiSCoR) and on trainee technical performance based on the Global Evaluative Assessment of Robotic Skills (GEARS). Statistical analysis of survey data was performed using SPSS. Audio from cases was coded by 2 researchers with a deductive approach using WiSCoR as a framework. RESULTS: Data were collected for 7 (38.9%) single and 11 (61.1%) dual-console cases across 9 case types from 4 surgical specialties. Chi-square analysis demonstrated no significant difference in percentage of case trainee spent in the operating surgeon role based on trainee level or console case type. Independent t-tests showed no significant difference in trainee autonomy, trainee performance, or faculty coaching scores based on console case type. Trainees rated faculty highest in WiSCoR Domains 1 (sharing responsibility) and 3 (providing constructive feedback). Qualitative analysis showed that for single-console cases, Domain 4 (goal setting) was most represented (34.0% of comments), while for dual-console cases, Domain 1 was most represented (37.0% of comments). CONCLUSIONS: Qualitative analysis highlights that despite similar survey-based faculty ratings across domains, coaching on self-reflection (Domain 2) is infrequently done, highlighting an opportunity for improvement in this area of coaching during robotic surgery.

Allura Red AC is a xenobiotic. Is it also a carcinogen?

Merriam-Webster and Oxford define a xenobiotic as any substance foreign to living systems. Allura Red AC (a.k.a., E129; FD&C Red No. 40), a synthetic food dye extensively used in manufacturing ultra-processed foods and therefore highly prevalent in our food supply, falls under this category. The surge in synthetic food dye consumption during the 70s, and 80s was followed by an epidemic of metabolic diseases and the emergence of early onset colorectal cancer (EOCRC) in the 1990s. This temporal association raises significant concerns, particularly given the widespread inclusion of synthetic food dyes in ultra-processed products, notably those marketed towards children. Given its interactions with key contributors to colorectal carcinogenesis such as inflammatory mediators, the microbiome, and DNA damage, there is growing interest in understanding Allura Red AC's potential impact on colon health as a putative carcinogen. This review discusses the history of Allura Red AC, current research on its effects on the colon and rectum, potential mechanisms underlying its impact on colon health, and provides future considerations. Indeed, although no governing agencies classify Allura Red AC as a carcinogen, its' interaction with key guardians of carcinogenesis makes it suspect and worthy of further molecular investigation. The goal of this review is to inspire research into the impact of synthetic food dyes on colon health.

Transforming Veteran Rehabilitation Care: Learnings from a Remote Digital Approach for Musculoskeletal Pain.

While musculoskeletal pain (MSP) stands as the most prevalent health condition among Veterans, timely and high-quality care is often hindered due to access barriers. Team Red, White & Blue (Team RWB), a nonprofit organization dedicated to promoting a healthier lifestyle among Veterans, aimed to assess innovative approaches to veteran care. This is a single-arm pilot study investigating the feasibility, clinical outcomes, engagement, and satisfaction of a remote multimodal digital care program among Veterans with MSP. The impact of deployment experience on outcomes was explored as a secondary aim. From 75 eligible Veterans, 61 started the program, reporting baseline pain frequently comorbid with mental distress. Program acceptance was suggested by the high completion rate (82%) and engagement levels, alongside high satisfaction (9.5/10, SD 1.0). Significant improvements were reported in all clinical outcomes: pain (1.98 points, 95%CI 0.13; 3.84, p = 0.036); mental distress, with those reporting at least moderate baseline depression ending the program with mild symptoms (8.50 points, 95%CI: 6.49; 10.51, p = 0.012); daily activity impairment (13.33 points, 95%CI 1.31; 25.34, p = 0.030). Deployed Veterans recovered similarly to their counterparts. Overall, the above results underscore the potential of a remote digital intervention to expand Veterans' access to timely MSP care.

Early-life risperidone alters locomotor responses to apomorphine and quinpirole in adulthood.

An escalating trend of antipsychotic drug use in children with ADHD, disruptive behavior disorder, or mood disorders has raised concerns about the impact of these drugs on brain development. Since antipsychotics chiefly target dopamine receptors, it is important to assay the function of these receptors after early-life antipsychotic administration. Using rats as a model, we examined the effects of early-life risperidone, the most prescribed antipsychotic drug in children, on locomotor responses to the dopamine D1/D2 receptor agonist, apomorphine, and the D2/D3 receptor agonist, quinpirole. Female and male Long-Evans rats received daily subcutaneous injections of risperidone (1.0 and 3.0 mg/kg) or vehicle from postnatal day 14-42. Locomotor responses to one of three doses (0.03, 0.1, and 0.3 mg/kg) of apomorphine or quinpirole were tested once a week for four weeks beginning on postnatal day 76 and 147 for each respective drug. The locomotor activity elicited by the two lower doses of apomorphine was significantly greater in adult rats, especially females, administered risperidone early in life. Adult rats administered risperidone early in life also showed more locomotor activity after the low dose of quinpirole. Overall, female rats were more sensitive to the locomotor effects of each agonist. In a separate group of rats administered risperidone early in life, autoradiography of forebrain D2 receptors at postnatal day 62 revealed a modest increase in D2 receptor density in the medial caudate. These results provide evidence that early-life risperidone administration can produce long-lasting changes in dopamine receptor function and density.

Transcriptomic classification of diffuse large B-cell lymphoma identifies a high-risk activated B-cell-like subpopulation with targetable MYC dysregulation.

Immunochemotherapy has been the mainstay of treatment for newly diagnosed diffuse large B-cell lymphoma (ndDLBCL) yet is inadequate for many patients. In this work, we perform unsupervised clustering on transcriptomic features from a large cohort of ndDLBCL patients and identify seven clusters, one called A7 with poor prognosis, and develop a classifier to identify these clusters in independent ndDLBCL cohorts. This high-risk cluster is enriched for activated B-cell cell-of-origin, low immune infiltration, high MYC expression, and copy number aberrations. We compare and contrast our methodology with recent DLBCL classifiers to contextualize our clusters and show improved prognostic utility. Finally, using pre-clinical models, we demonstrate a mechanistic rationale for IKZF1/3 degraders such as lenalidomide to overcome the low immune infiltration phenotype of A7 by inducing T-cell trafficking into tumors and upregulating MHC I and II on tumor cells, and demonstrate that TCF4 is an important regulator of MYC-related biology in A7.

Best practice in dementia health care: Key clinical practice pointers from a national conference and innovative opportunities for pharmacy practice.

OBJECTIVE: Sub-optimal care of people living with dementia has serious consequences for older populations. The 2021 Australian Royal Commission noted that a large proportion of older adults in aged care live with dementia, yet there are limitations in the knowledge and understanding of staff who care for them. In the pursuit of educating pharmacists, physicians, allied health care professionals, researchers, academics, people living with dementia and their carers, and the public, who are facing the challenges of dementia management, the 'Best Practice in Dementia Health Care' conference was held on November 10, 2022 at Western Health (Sunshine Hospital, Melbourne, Australia). METHODS: Sixteen experts presented on the current practice and challenges associated with delivering best practice dementia health care to older Australians, often highlighting how medication-related challenges impacted on their area of practice. RESULTS: Presenters highlighted the importance of individualised medication management plans, considerations of culture and Indigenous communities, the role of technology, and the impact of exercise and the physical environment on care of people living with dementia. Key clinical practice messages from each expert presenter fit into four main topics: 'navigating complexities of medication management'; 'enhancing wellbeing'; 'supportive settings and environments'; and 'programs and services improving care'. CONCLUSIONS: Pharmacists are crucial members of allied health care teams. They have the necessary medication and comorbidity expertise to review medication regimens, liaise with all health care providers, and provide holistic, pharmacological and non-pharmacological patient education. Towards providing best practice dementia health care, pharmacists can contribute in several ways, such as providing health practitioner education to increase understanding about medications and how they can impact on allied health practice, to ensure that medications are prescribed appropriately and safely. Further, pharmacists can make available resources to ensure people living with dementia receive culturally safe and appropriate care, while advocating for greater understanding of the history and experiences of people living with dementia to ensure care aligns with their day-to-day routines. Finally, pharmacists can provide peer-support to other health care professionals and care staff to ensure optimal management of behavioural and psychological symptoms of dementia. The information and insights shared at the conference can serve as a valuable resource for pharmacists and other health care professionals and researchers working to improve the lives of those living with dementia.

The association between energy-adjusted dietary inflammatory index and 10-year cardiovascular risk: Fasa adult cohort study.

A healthy diet is dominant in cardiovascular disease (CVD) prevention. Inflammation is pivotal for CVD development. This study aimed to evaluate the association between the pro-inflammatory diet and the CVD risk. This cross-sectional study involved 10,138 Fasa adult cohort study participants. After excluding participants with missing data, the Energy-Adjusted Dietary Inflammatory Index (E-DII) was calculated to assess the inflammatory potential of diet using the recorded Food Frequency Questionnaire. Framingham risk score (FRS) was used to predict the 10-year risk of CVD. The association between E-DII and high risk for CVD was investigated using multinominal regression. After exclusion, the mean age of studied individuals (n = 10,030) was 48.6 ± 9.6 years, including 4522 men. Most participants were low risk (FRS <10%) for CVD (87.6%), while 2.7% of them were high risk (FRS ≥20%). The median FRS was 2.80 (1.70, 6.30). The E-DII ranged from -4.22 to 4.49 (mean E-DII = 0.880 ± 1.127). E-DII was significantly associated with FRS. This result persisted after adjusting for confounding factors and in both genders. This study revealed that the pro-inflammatory diet significantly increases the CVD risk. Consequently, reducing the inflammatory potential of diet should be considered an effective dietary intervention in CVD prevention.

Pathfinder experiments with atom interferometry in the Cold Atom Lab onboard the International Space Station.

Deployment of ultracold atom interferometers (AI) into space will capitalize on quantum advantages and the extended freefall of persistent microgravity to provide high-precision measurement capabilities for gravitational, Earth, and planetary sciences, and to enable searches for subtle forces signifying physics beyond General Relativity and the Standard Model. NASA's Cold Atom Lab (CAL) operates onboard the International Space Station as a multi-user facility for fundamental studies of ultracold atoms and to mature space-based quantum technologies. We report on pathfinding experiments utilizing ultracold 87Rb atoms in the CAL AI. A three-pulse Mach-Zehnder interferometer was studied to understand the influence of ISS vibrations. Additionally, Ramsey shear-wave interferometry was used to manifest interference patterns in a single run that were observable for over 150 ms free-expansion time. Finally, the CAL AI was used to remotely measure the Bragg laser photon recoil as a demonstration of the first quantum sensor using matter-wave interferometry in space.

Depressive Symptoms Affect Cognitive Functioning from Middle to Late Adulthood: Ethnoracial Minorities Experience Greater Repercussions.

Cognitive deficits, a diagnostic criterion for depressive disorders, may precede or follow the development of depressive symptoms and major depressive disorder. However, an individual can report an increase in depressive symptoms without any change in cognitive functioning. While ethnoracial minority group differences exist, little is known to date about how the relationship between depressive symptoms and cognitive function may differ by ethnoracial minority status. Utilizing data from the Midlife in the United States (MIDUS) study waves II (M2) and III (M3), this study examines the relationship between depressive symptoms and cognitive functioning concurrently and longitudinally in community-dwelling adults, as well as whether the results differed by ethnoracial minority status. Our participants included 910 adults (43.8% male, 80.8% White, 54.4 ± 11.5 years old at M2). Cross-sectionally, depressive symptoms, ethnoracial minority status, and their interaction had significant effects on cognitive function, consistent with previous investigations. Longitudinally, higher M2 depressive symptoms predicted poorer cognitive function at M3 over and above M2 cognitive functioning, but only within the ethnoracial minority sample. Our finding suggests that depressive symptoms predict cognitive functioning both concurrently and across time, and this relationship is moderated by ethnoracial identity, resulting in greater cognitive deficits among ethnoracial minority groups compared to their non-Hispanic White counterparts.

Modular Baseplate Augmentation: A Simple and Effective Method for Addressing Eccentric Glenoid Wear.

BACKGROUND: Augmented baseplates can be effective at addressing eccentric glenoid wear in reverse total shoulder arthroplasty (rTSA). However, these implants often come in a limited number of predetermined shapes that require additional reaming to ensure adequate glenoid seating. This typically involves complex instrumentation and can have a negative impact on implant stability. Modular baseplate augmentation based on intra-operative measurements may allow for more precise defect filling while preserving glenoid bone. The purpose of this investigation was to assess the stability of a novel ringed baseplate with modular augmentation in comparison to non-augmented standard and ringed baseplate designs. METHODS: In this biomechanical study, baseplate micromotion was tested for three constructs according to American Society for Testing and Materials (ASTM) guidelines. The constructs included a non-augmented curved baseplate, a non-augmented ringed baseplate and ringed baseplate with an 8 mm locking modular augmentation peg. The non-augmented constructs were mounted flush onto polyurethane (PU) foam blocks, while the augmented baseplate was mounted on a PU block with a simulated defect. Baseplate displacement was measured prior to and after 100,000 cycles of cyclic loading. RESULTS: Prior to cyclic loading, the non-augmented and augmented ringed baseplates both demonstrated significantly less micromotion than the non-augmented curved baseplate design (81.1 µm vs 97.2 µm vs 152.7 µm; p=0.009). After cyclic loading, both ringed constructs continued to have significantly less micromotion compared to the curved design (105.5 µm vs 103.2 µm vs 136.6 µm; p<0.001). The micromotion for both ringed constructs remained below the minimum threshold required for bony ingrowth (150 µm) at all time points. CONCLUSION: In the setting of a simulated glenoid defect, locked modular augmentation of a ringed baseplate does not result in increased baseplate micromotion when compared to full contact, non-augmented baseplates. This design offers a simple method for tailored baseplate augmentation that can match specific variations in glenoid anatomy, limiting the need for excessive reaming and ultimately optimizing the environment for long term implant stability. LEVEL OF EVIDENCE: Basic Science Study; Biomechanics.

Chloroformate-mediated ring cleavage of indole alkaloids leads to re-engineered antiplasmodial agents.

Natural product ring distortion strategies have enabled rapid access to unique libraries of stereochemically complex compounds to explore new chemical space and increase our understanding of biological processes related to human disease. Herein is described the development of a ring-cleavage strategy using the indole alkaloids yohimbine, apovincamine, vinburnine, and reserpine that were reacted with a diversity of chloroformates paired with various alcohol/thiol nucleophiles to enable the rapid synthesis of 47 novel small molecules. Ring cleavage reactions of yohimbine and reserpine produced two diastereomeric products in moderate to excellent yields, whereas apovincamine and vinburnine produced a single diastereomeric product in significantly lower yields. Free energy calculations indicated that diastereoselectivity regarding select ring cleavage reactions from yohimbine and apovincamine is dictated by the geometry and three-dimensional structure of reactive cationic intermediates. These compounds were screened for antiplasmodial activity due to the need for novel antimalarial agents. Reserpine derivative 41 was found to exhibit interesting antiplasmodial activities against Plasmodium falciparum parasites (EC50 = 0.50 µM against Dd2 cultures), while its diastereomer 40 was found to be three-fold less active (EC50 = 1.78 µM). Overall, these studies demonstrate that the ring distortion of available indole alkaloids can lead to unique compound collections with re-engineered biological activities for exploring and potentially treating human disease.

Kinetic Trajectories of Glucose Uptake in Single Cancer Cells Reveal a Drug-Induced Cell-State Change Within Hours of Drug Treatment.

The development of drug resistance is a nearly universal phenomenon in patients with glioblastoma multiforme (GBM) brain tumors. Upon treatment, GBM cancer cells may initially undergo a drug-induced cell-state change to a drug-tolerant, slow-cycling state. The kinetics of that process are not well understood, in part due to the heterogeneity of GBM tumors and tumor models, which can confound the interpretation of kinetic data. Here, we resolve drug-adaptation kinetics in a patient-derived in vitro GBM tumor model characterized by the epithelial growth factor receptor (EGFR) variant(v)III oncogene treated with an EGFR inhibitor. We use radiolabeled 18F-fluorodeoxyglucose (FDG) to monitor the glucose uptake trajectories of single GBM cancer cells over a 12 h period of drug treatment. Autocorrelation analysis of the single-cell glucose uptake trajectories reveals evidence of a drug-induced cell-state change from a high- to low-glycolytic phenotype after 5-7 h of drug treatment. Information theoretic analysis of a bulk transcriptome kinetic series of the GBM tumor model delineated the underlying molecular mechanisms driving the cellular state change, including a shift from a stem-like mesenchymal state to a more differentiated, slow-cycling astrocyte-like state. Our results demonstrate that complex drug-induced cancer cell-state changes of cancer cells can be captured via measurements of single cell metabolic trajectories and reveal the extremely facile nature of drug adaptation.

A perioperative study of Safusidenib in patients with IDH1-mutated glioma.

This is a single arm, open label perioperative trial to assess the feasibility, pharmacokinetics and pharmacodynamics of treatment with safusidenib following biopsy, and prior to surgical resection in patients with IDH1 mutated glioma who have not received radiation therapy or chemotherapy. Fifteen participants will receive treatment in two parts. First, biopsy followed by one cycle (28 days) of safusidenib, an orally available, small molecular inhibitor of mutated IDH1, then maximal safe resection of the tumor (Part A). Second, after recovery from surgery, safusidenib until disease progression or unacceptable toxicity (Part B). This research will enable objective measurement of biological activity of safusidenib in patients with IDH1 mutated glioma. Anti-tumor activity will be assessed by progression free survival and time to next intervention.Clinical Trial Registration: NCT05577416 (ClinicalTrials.gov).

Adult low-grade gliomas (aLGG) are primary brain cancers, defined by mutations in IDH1 or IDH2. When the IDH gene becomes abnormal (mutated), production of a metabolite that causes cancer cells to grow is increased. These tumors grow slowly but invade the normal functioning brain, making them nearly impossible to cure. The current standard of care treatment includes surgery, followed by radiation therapy and chemotherapy, the timing of which depends on the risk of cancer regrowth. Some patients may be suitable for monitoring with MRI scans alone, however recurrences will inevitably occur. Recently developed targeted mutant IDH inhibitors for aLGG patients may be beneficial both at diagnosis and recurrence. Notably, early treatment prior to radiation therapy and chemotherapy delays growth of aLGG and the need for subsequent radiation therapy and chemotherapy. Nevertheless, most patients will eventually suffer further tumor growth and the optimal timing and sequencing of these therapies remains an area of active research. This research investigates the mutant IDH1 inhibitor safusidenib. The researchers are conducting an innovative clinical trial where patients with aLGG, who have not received radiation therapy or chemotherapy, are treated with safusidenib following a biopsy and prior to surgical removal of their tumor. In this study they investigate whether this trial design is safe and feasible, and how safusidenib works; with the goal to better understand the optimal use of IDH inhibitors for patients with aLGG.

"Mn3AlN" is Really Mn4N.

We investigate the synthesis of antiperovskite "Mn3AlN" using the published synthesis procedure, as well as several new reaction pathways. In each case, only a combination of antiperovskite Mn4N and Mn5Al8 or precursors is obtained. The identity of the obtained antiperovskite phase is unambiguously determined to be Mn4N via synchrotron powder X-ray diffraction (SPXRD), X-ray absorption spectroscopy (XAS), and magnetometry. The experimental results are further supported by thermochemical calculations informed by density functional theory (DFT), which find Mn3AlN to be metastable versus decomposition into Mn and AlN. The DFT-based calculations also predict an antiferromagnetic ground state for Mn3AlN. This directly contradicts the previously reported ferromagnetic behavior of "Mn3AlN". Instead, the observed magnetic behavior is consistent with ferrimagnetic Mn4N. We examine the data in the original publication and conclude that the compound reported to be Mn3AlN is in fact Mn4N.

Investigation of the association between foot-and-mouth disease clinical signs and abattoir serological data in large ruminants in northern Lao People's Democratic Republic.

Foot-and-mouth disease (FMD) is a highly infectious and endemic disease in Lao PDR. However, surveillance is weak, and outbreaks are not routinely reported. To address this, serum samples were routinely collected from cattle and buffalo from provincial abattoirs between November 2021 and December 2022. A total of 2,663 serum samples were collected from large ruminants (n = 1,625 cattle; n = 1,038 buffalo) from 17 provinces. Samples were tested for specific antibodies directed against FMD non-structural protein (NSP) to determine the proportion of animals exposed to FMD virus. In addition to sampling from abattoirs, further independent data was collected to report clinical signs and outcomes from 94 districts in 12 northern provinces. These incident reports were recorded by district staff using a Google Form and summarised monthly in the National Animal Disease Reporting System. Information was collected on species, incident date, herd size, location and which clinical signs the animals presented. Overall, 46% of the tested animals returned a positive result using ID Screen® FMD NSP Competition ELISA. Results from serological testing were then compared with reported clinical signs from the same district. In districts reporting 'mouth problems' (regardless of other clinical signs) the median FMD seroprevalence was 49.7%, compared to 31.6% in districts not reporting mouth problems (p = 0.021). This finding suggests that reporting clinical cases of 'mouth problems' could be a potential predictor of FMD infection at a district level in cattle and buffalo in Lao PDR. Furthermore, in districts reporting 'fever', 'mouth problems', and 'nose/mouth secretions' together, the median FMD seroprevalence was 46.2%, compared to 24.4% in districts not reporting these signs (p = 0.033). In districts reporting 'mouth problems' and 'nose/mouth secretions' the median FMD seroprevalence was 49.4%, compared to 25.5% in districts not reporting these signs (p = 0.037). In districts reporting both 'fever' and 'mouth problems,' the median FMD seroprevalence was 46.4% compared to 25% in districts not reporting these signs (p = 0.017). Based on serological data generated by abattoir surveillance, this study identified clinical signs most predictive of FMD seroprevalence. These novel findings can be used to guide passive surveillance efforts in the future specifically in northern Laos and help support improved FMD surveillance more broadly in FMD endemic countries in Southeast Asia.