Broad Profile Research Articles

Phenotypic and genotypic insights into rice germplasm resistance against a biotype of the brown planthopper Nilaparvata lugens (stal)

This study explores the resistance of rice landraces, genotypes, and wild rice to the South Asian brown planthopper (BPH) population, a significant pest affecting rice crops. Phenotypic screening identified a few landraces, genotypes, and wild rice varieties with resistance to the South Asian biotype, including, PTB-33, Oryza officinalis, O. nivara, Adukkan, Vellai Kombi Samba and Onamuttan which exhibited damage scores ? 3 Moderate resistance was observed in IR 36, ARC 10550, T12, Manvilayan, Rathu Heenati, CR 2711, Mysore Malli, Swarnalata, Pokkali, Babawee, and ASD 7, while other varieties demonstrated varying levels of susceptibility. Molecular analysis using SSR markers revealed the presence of BPH resistance genes across these genotypes. Notably, Onamuttan and Vellai kombi samba exhibited a broad resistance gene profile, while Adukkan, Manvilayan possess two BPH-resistant genes. Conversely, ASD 7 and Rathu Heenati, despite possessing several resistance gene markers, displayed moderate resistance. This study underscores the potential of integrating resistant genotypes into breeding programs, employing SSR markers for precise gene mapping and marker-assisted selection. The combined phenotypic and genotypic data provide valuable insights for advancing rice breeding strategies for sustainable BPH management and improved pest resistance.

Deoxyvasicinone hybrids in the management of Alzheimer's disease: Recent advances on manmade derivatives, pharmacological activities, and structure-activity relationship.

Alzheimer's disease (AD) is a prevalent neurological illness that affects over 80% of aged adults globally in cases of dementia. Although the exact pathophysiological causes of AD remain unclear, its pathogenesis is primarily driven by several distinct biochemical alterations: (i) the accumulation of toxic Aβ plaques, (ii) the hyperphosphorylation of tau proteins, (iii) oxidative stress resulting in cell death, and (iv) an imbalance between the two main neurotransmitters, glutamate and acetylcholine (ACh). Currently, there are very few medications available and no treatment. Presently marketed medications include memantine, an N-methyl-d-aspartate receptor (NMDA) antagonist, and acetylcholinesterase (AChE) inhibitors: rivastigmine, donepezil, and galantamine. Unfortunately, these medications are only useful in the initial stages of AD. The mentioned medications only provide symptomatic relief and do not slow down the disease progression in the advanced stages. Therefore, there is an urgent need to develop potential candidates to treat AD, symptomatically and therapeutically. Many research groups focus on natural products due to their diverse therapeutic profiles and easy availability. One such natural product is deoxyvasicinone, isolated from Adhatoda vasica. Given its broad pharmacological profile, various researchers have developed semisynthetic hybrids of deoxyvasicinone to address multifaceted diseases like AD. In this review article, we tried to summarize the semisynthetic hybrids of deoxyvasicinone developed over the past decade (2014-2024) for managing AD. We focus on their design, pharmacological activity, and structure-activity relationship (SAR) analysis. We hope this review enhances the reader's understanding of future exploratory options for deoxyvasicinone hybrids in AD management.

Physiologically based pharmacokinetic modeling and simulation of topiramate in populations with renal and hepatic impairment and considerations for drug-drug interactions.

Topiramate (TPM) is a broad-spectrum antiepileptic drug (AED) commonly prescribed for approved and off-label uses. Routine monitoring is suggested for clinical usage of TPM in special population due to its broad side effect profile. Therefore, it is crucial to further explore its pharmacokinetic characteristics. Physio-chemical properties of TPM were initially determined from online database and further optimized while establishing the PBPK model for healthy adults using the PK-Sim software. The model was then extrapolated to patients with renal impairment and patients who were hepatically impaired. A drug-drug interaction (DDI) model was also built to simulate plasma TPM concentrations while concomitantly used with carbamazepine (CBZ). The goodness-of-fit method and average fold error (AFE) method were used to compare the differences between predicted and observed values to assess the accuracy of the PBPK model. Almost all of the predicted concentration fell within twofold error range of corresponding observed concentrations. The AFE ratio of predicted to observed values of Cmax and AUC0-inf was all within 0.5 and 2. It is recommended that the doses be reduced to 70%, 50%, and 40% of the healthy adult dose for the chronic kidney disease (CKD) stage 3, stage 4, and stage 5 patients, respectively, and reduced to ~70%, and 35% for the Child-Pugh-B, and Child-Pugh C scored patient with hepatic impairment, respectively. If TPM is co-administered with CBZ, increasing TPM doses to 150%-175% of the monotherapy dose is recommended according to model simulation.

TIHI Toolkit: A Peak Finder and Analyzer for Spectroscopic Data.

Complex signal vectors, particularly spectra, are integral to many scientific domains. Interpreting these signals often involves decomposing them into contributions from independent components and subtraction or deconvolution of the channel and instrument noise. Despite the fundamental nature of this task, researchers frequently rely on costly commercial tools. To make such tools accessible to all, we present Tihi, interactive, open-source multiplatform software for interpolation, denoising, baseline correction, peak detection, and signal decomposition. Tihi provides a user-friendly graphical interface (GUI) that facilitates the analysis of spectroscopic data and more. It allows researchers to contribute to and freely distribute these tools, ensuring broad accessibility and fostering collaborative improvements. We present examples demonstrating the efficiency of the program using the spectra of different systems acquired by different spectroscopic techniques, including Raman (aspirin), IR (solid ammonia), XRD (anatase), and UV-vis (petal tip from the Puya alpestris flower). These examples showcase a variety of spectra that differ significantly, from signals with narrow profiles to signals with very broad profiles. This demonstrates the versatility of Tihi for peak identification in a wide range of spectroscopic techniques.

First spectropolarimetric observation of the neutron star low-mass X-ray binary GX 3+1

We report the first simultaneous X-ray spectropolarimetric observation of the bright atoll neutron star low-mass X-ray binary GX 3+1, performed by the Imaging X-ray Polarimetry Explorer (IXPE) joint with NICER and NuSTAR. The source does not exhibit significant polarization in the 2–8 keV energy band, with an upper limit of 1.3% at a 99% confidence level on the polarization degree. The observed spectra can be well described by a combination of thermal disk emission, the hard Comptonization component, and reflected photons off the accretion disk. In particular, from the broad Fe Kα line profile, we were able to determine the inclination of the system (i ≈ 36°), which is crucial for comparing the observed polarization with theoretical models. Both the spectral and polarization properties of GX 3+1 are consistent with those of other atoll sources observed by IXPE. Therefore, we may expect a similar geometrical configuration for the accreting system and the hot Comptonizing region. The low polarization is also consistent with the low inclination of the system.

A prognostic molecular signature of hepatic steatosis is spatially heterogeneous and dynamic in human liver.

Hepatic steatosis is a central phenotype in multi-system metabolic dysfunction and is increasing in parallelwith the obesity pandemic. We use a translational approach integrating clinical phenotyping and outcomes, circulating proteomics, and tissue transcriptomics to identify dynamic, functional biomarkers of hepatic steatosis. Using multi-modality imaging and broad proteomic profiling, we identify proteins implicated in the progression of hepatic steatosis that are largely encoded by genes enriched at the transcriptional level in the human liver. These transcripts are differentially expressed across areas of steatosis in spatial transcriptomics, and several are dynamic during stages of steatosis. Circulating multi-protein signatures of steatosis strongly associate with fatty liver disease and multi-system metabolic outcomes. Using a humanized "liver-on-a-chip" model, we induce hepatic steatosis, confirming cell-specific expression of prioritized targets. These results underscore the utility of this approach to identify a prognostic, functional, dynamic "liquid biopsy" of human liver, relevant to biomarker discovery and mechanistic research applications.

A Novel Approach to the Design and Development of a C-Core Sandwich-Type Radial Field Switched Reluctance Motor with On-Shaft Implementation in EV Application

<div>A novel design for a radial field switching reluctance motor with a sandwich-type C-core architecture is proposed. This approach combines elements of both traditional axial and radial field distribution techniques. This motor, similar to an in-wheel construction, is mounted on a shared shaft and is simple to operate and maintain. The rotor is positioned between the two stators in this configuration. The cores and poles of the two stators are separated from one another both magnetically and electrically. Both stators can work together or separately to produce the necessary torque. This adds novelty and improves the design’s suitability for use with electrical vehicles (EVs). A good, broad, and adaptable torque profile is provided by this setup at a modest excitation current. This work presents the entire C-core radial field switched reluctance motor (SRM) design process, including the computation of motor parameters through computer-aided design (CAD). The CAD outputs are verified via finite element (FE) analysis.</div>

Size and kinematics of the low-ionization broad emission line region from microlensing-induced line profile distortions in gravitationally lensed quasars

Microlensing-induced distortions of broad emission line profiles observed in the spectra of gravitationally lensed quasars can be used to probe the size, geometry, and kinematics of the broad-line region (BLR). To this end, single-epoch Mg II or Hα line profile distortions observed in five gravitationally lensed quasars, J1131-1231, J1226-0006, J1355-2257, J1339+1310, and HE0435-1223, have been compared with simulated ones. The simulations are based on three BLR models, a Keplerian disk (KD), an equatorial wind (EW), and a polar wind (PW), with different sizes, inclinations, and emissivities. The models that best reproduce the observed line profile distortions were identified using a Bayesian probabilistic approach. We find that the wide variety of observed line profile distortions can be reproduced with microlensing-induced distortions of line profiles generated by our BLR models. For J1131, J1226, and HE0435, the most likely model for the Mg II and Hα BLRs is either KD or EW, depending on the orientation of the magnification map with respect to the BLR axis. This shows that the line profile distortions depend on the position and orientation of the isovelocity parts of the BLR with respect to the caustic network, and not only on their different effective sizes. For the Mg II BLRs in J1355 and J1339, the EW model is preferred. For all objects, the PW model has a lower probability. As for the high-ionization C IV BLR, we conclude that disk geometries with kinematics dominated by either Keplerian rotation or equatorial outflow best reproduce the microlensing effects on the low-ionization Mg II and Hα emission line profiles. The half-light radii of the Mg II and Hα BLRs are measured in the range of 3 to 25 light-days. We also confirm that the size of the region emitting the low-ionization lines is larger than the region emitting the high-ionization lines, with a factor of four measured between the sizes of the Mg II and C IV emitting regions in J1339. Unexpectedly, the microlensing BLR radii of the Mg II and Hα BLRs are found to be systematically below the radius-luminosity (R − L) relations derived from reverberation mapping, confirming that the intrinsic dispersion of the BLR radii with respect to the R − L relations is large, but also revealing a selection bias that affects microlensing-based BLR size measurements. This bias arises from the fact that, if microlensing-induced line profile distortions are observed in a lensed quasar, the BLR radius should be comparable to the microlensing Einstein radius, which varies only weakly with typical lens and source redshifts.

Administrative Aspects of Molecular Diagnostics-Oversight, Regulatory Approval Process, Clinical and Operational Workflows, and Payment Models.

This paper discusses the administrative aspects of molecular diagnostics in oncology, including US Food and Drug Administration (FDA) oversight, the regulatory approval process, clinical, and operational workflows, and payment models. Comprehensive molecular testing is important to deliver optimal oncology care and improve patient outcomes. Despite the potential benefits of testing, utilization remains low. The FDA regulatory approval process is reviewed for in vitro diagnostic products, which includes classification into three regulatory classes on the basis of risk. Companion diagnostic devices are used to guide treatment decisions. The clinical and operational challenges associated with molecular testing in oncology are also discussed, including the rapidly evolving landscape of precision oncology, the wide range of biomarker testing options, and complexities of test ordering, interpretation, and result delivery. There is a need for a multifaceted support approach involving education, technology enhancements, and workflow support to overcome these challenges. In terms of payment models, coverage policies between Medicare and commercial payers are compared with differences in coverage criteria, with Medicare focusing on FDA approval or clearance, whereas commercial payers consider additional factors such as National Comprehensive Cancer Network and ASCO guidelines. Commercial payers tend to cover smaller panels on the basis of guideline-recommended biomarkers, whereas coverage for broad tumor profiling is limited. Several strategies can increase the utilization of molecular testing, including integrating test results into electronic medical record platforms, standardizing billing practices, increasing clinical trials, and primary literature supporting the use of molecular testing, educating physicians, and using tumor boards for result interpretation and treatment discussions.

Commercialisation, exogenous shocks and nutrition: Evidence from smallholder farmers in Bangladesh

AbstractThis study empirically analyses the effect of agricultural commercialisation on food spending and nutrition outcomes in Bangladesh. We examine whether exposure to exogenous climate shocks moderates these relationships. We construct individual‐level nutrition measures and time‐varying climate extremes using nationally representative panel data. To address endogeneity concerns, we use an instrument variable approach. Results show that commercialisation leads to an improvement in the broad nutritional profile of individuals. However, the commercialisation–nutrition linkage is weaker for households exposed to frequent climate shocks than those in climate‐resilient areas. Importantly, climate shocks dampen the positive nutritional impacts of commercialisation and exacerbate existing inequalities in the nutritional status within the households. Women and girls appear disproportionately vulnerable to the nutrition‐weakening effects of weather stresses in commercialised agricultural households. This highlights twin policy challenges: strengthening smallholders' resilience to escalating climate risks alongside promoting gender‐equitable, nutrition‐sensitive agricultural commercialisation.

ACEIs in high blood pressure: friend or enemy?

Optimal blood pressure control has been one of the fundamental objectives of primary care physicians and other medical specialties for many years. ACEIs (angiotensin-converting enzyme inhibitors) are one of the families of medications with an antihypertensive effect with the greatest experience in their use over decades. A 70-year-old patient previously diagnosed with high blood pressure and treated with ACEI, began in January 2013 with progressive worsening of kidney function.There are several mechanisms by which ACEIs produce an AKF (Acute Kidney Failure), such as efferent arteriolar vasodilatation because of blocking Angiotensin 2 effect or inmunoallergic mechanisms, or even different pathologies that could trigger it (congestive heart failure, liver cirrhosis with ascites and in presence of bilateral renal stenosis or unilateral stenosis of a single functioning kidney). The use of ACEIs as a first-line treatment for high blood pressure is supported by diverse clinical guidelines and by excellent results in a broad profile of patients. In a small percentage of cases, they have shown adverse effects that can affect the functioning of several systems involved in the correct control of the patient's cardiovascular risk, such as the renal system.

Clinical utility of upfront liquid biopsy in non-small cell lung cancer in the community setting.

316 Background: Molecular diagnosis of advanced non-small cell lung cancer (NSCLC) is critical to guide therapeutic decisions. Blood next generation sequencing (NGS) allows for non-invasive screening for targetable genetic abnormalities. Many studies have validated using the liquid biopsies to screen for resistant mutations at the emergence of treatment failure. However, the clinical utility of liquid biopsy for newly diagnosed NSCLC, as part of a comprehensive molecular profiling, is an area of active research. Methods: Retrospective analysis of the molecular landscape and clinical outcomes in NSCLC patients who had liquid biopsy done between December of 2017 to February of 2022. Patients had EGFR, ALK, ROS-1, and BRAF tested in the tissue, and underwent liquid biopsy for broad molecular profiling. The plasma genotyping was conducted using a 73-gene panel by Guardant 360 test. Actionable mutations were stratified accordingly to the OncoKB database based on the level of preclinical and clinical evidence of drug targetability. Survival analysis was conducted by August of 2023. Results: We enrolled 122 NSCLC patients who 84% were treatment-naïve and 78% had the liquid biopsy performed at the initial diagnosis. We found that 86 patients had oncogenic mutations and 43 (35%) had actionable mutations, with 37 (29%) falling under level 1 of evidence mutations. EGFR and KRAS G12C mutations were the two most common level 1 genetic abnormalities (23% and 11% of all actionable mutations, respectively). We identified two germline BRCA carriers who were referred for genetic counselling. 25 patients (20%) received treatment based on the liquid biopsy results, with 15 (12%) achieving partial response. Six patients had liquid biopsy done at progression of EGFR or MET therapies, which identified a resistance mechanism in three of them. Conclusions: Upfront liquid biopsy identified a significant proportion of patients with targetable mutations. Here, we reported actionable mutations in 35% of our patients who 84% had no prior systemic treatment. Our results complement prior literature and shows that blood next generation sequencing can be a useful tool to guide upfront therapeutical options at the community healthcare setting.

Spectroastrometry and Reverberation Mapping of Active Galactic Nuclei. I. The Hβ Broad-line Region Structure and Black Hole Masses of Five Quasars

We conduct a reverberation mapping (RM) campaign to spectroscopically monitor a sample of selected bright active galactic nuclei with large anticipated broad-line region (BLR) sizes adequate for spectroastrometric (SA) observations by the GRAVITY instrument on the Very Large Telescope Interferometer. We report the first results for five objects, IC 4329A, Mrk 335, Mrk 509, Mrk 1239, and PDS 456, among which Mrk 1239 and PDS 456 are for the first time spectroscopically monitored. We obtain multiyear monitoring data and perform multicomponent spectral decomposition to extract the broad Hβ profiles. We detect significant time lags between the Hβ and continuum variations, generally obeying the previously established BLR size–luminosity relation. Velocity-resolved Hβ time lags illustrate diverse, possibly evolving, BLR kinematics. We further measure the Hβ line widths from mean and rms spectra and the resulting virial products show good consistency among different observing seasons. Adopting a unity virial factor and the FWHM of the broad Hβ line from the mean spectra as a measure of velocity, the obtained black hole masses averaged over seasons are logM•/M⊙=8.02−0.14+0.09 , 6.92−0.12+0.12 , 8.01−0.25+0.16 , 7.44−0.14+0.13 , and 8.59−0.11+0.07 for the five objects, respectively. Black hole mass estimations using other line width measures are also reported. For objects with previous RM campaigns, our mass estimates are in agreement with earlier results. In a companion paper, we will employ BLR dynamical modeling to directly infer the black hole mass and thereby determine the virial factors.

Strength of evidence underlying the CMS-FDA parallel review of comprehensive genomic profiling tests in the cancer setting.

Although use of comprehensive genomic profiling was approved by a novel Centers for Medicare & Medicaid Services-US Food and Drug Administration parallel review process, the quality of the supporting evidence is unclear. We evaluated the rigor of the peer-reviewed literature cited in the National Coverage Determination Memorandum for the FoundationOneCDx (Foundation Medicine, Inc, Cambridge, MA). We identified studies cited in the memorandum. Two independent researchers evaluated each study and applied a modified version of the Fryback and Thornbury hierarchy, an established framework for evaluating the efficacy of diagnostic tests. Studies focused on clinical outcomes were then categorized by study design, guided by recommendations from the Center for Medical Technology Policy. The sample included 113 scientific studies. The majority (60/113 [53.1%]) used comprehensive genomic profiling outside the course of clinical care, and there was substantive heterogeneity in the cancer types assessed and the sequencing depth. We found 8 (7.1%) studies that assessed whether clinical care had changed due to comprehensive genomic profiling testing, and 38 (33.6%) assessed clinical outcomes. After excluding studies that tested for 5 or fewer genomic alterations, 25 remained in the clinical outcomes sample: Of these, only 1 included a comparator group that did not receive comprehensive genomic profiling testing. Only 4 studies used FoundationOneCDx as the primary genomic test, none of which compared the outcomes of patients who did vs did not receive the test. The findings indicate gaps in the supporting evidence for broad comprehensive genomic profiling use in patients with solid tumors. More rigorous studies that assess clinical utility would better inform the approval process for novel diagnostic tests.

Saccharification of fructans and simultaneous alcoholic fermentation for sustainable production of agave distillates

ABSTRACT In a world where climate change and sustainability are at the forefront, innovative solutions are more pressing than ever. In the production process of distillates, the critical stage is the cooking of agave for thermal hydrolysis of fructans. This stage determines the efficiency of the process, incurs the highest production cost, and has a detrimental impact on the environment. In this study, we investigate the saccharification of agave fructans in fresh juice using fructanases produced in situ by Kluyveromyces marxianus as an alternative to traditional agave cooking. furthermore, we explore both sequential and simultaneous alcoholic fermentation processes using a native mixed culture to improve the overall yield and obtain a distillate with enjoyable sensory characteristics. The results show that saccharification and simultaneous fermentation allow for obtaining a fermented product containing an average of 7% alcohol. Gas chromatography and mass spectrometry analysis shows that the distillate is essentially an ethanol – water mixture with a broad profile and high concentration of volatile compounds. The composition of the distilled product provides a well-balanced sensory experience that is highly valued by consumers. Hence, for the first time, a novel, efficient, low-cost, and sustainable process for producing agave distillates has been successfully designed.

Human breastmilk memory T cells throughout lactation manifest activated tissue-oriented profile with prominent regulation.

Breastfeeding provides important immunological benefits to the neonate, but how the different immunoactive components in breastmilk contribute to immunity remains poorly understood. Here, we characterized human breastmilk T cells using single-cell RNA-Seq and flow cytometry. Breastmilk contained predominantly memory T cells, with expression of immune signaling genes, high proliferation, and an effector Th1/cytotoxic profile with high cytokine production capacities. Elevated activation was balanced by an enriched Treg population and immune regulatory markers in conventional memory T cells. Gene and surface expression of tissue-residency markers indicate that breastmilk T cells represented tissue-adapted rather than circulatory T cells. In addition, breastmilk T cells had a broad homing profile and higher activation markers in these migratory subsets. The partly overlapping transcriptome profile between breastmilk and breast tissue T cells, particularly cytotoxic T cells, might support a role in local immune defense in the mammary gland. However, unique features of breastmilk, such as Tregs, might imply an additional role in neonatal immune support. We found some correlations between the breastmilk T cell profile and clinical parameters, most notably with maternal and household factors. Together, our data suggest that breastmilk contains an adapted T cell population that exerts their function in specific tissue sites.

Circulating miRNA Signaling for Fatty Acid Metabolism in Response to a Maximum Endurance Test in Elite Long-Distance Runners.

Maximal oxygen uptake (VO2max) is a determining indicator for cardiorespiratory capacity in endurance athletes, and epigenetics is crucial in its levels and variability. This initial study examined a broad plasma miRNA profile of twenty-three trained elite endurance athletes with similar training volumes but different VO2max in response to an acute maximal graded endurance test. Six were clustered as higher/lower levels based on their VO2max (75.4 ± 0.9 and 60.1 ± 5.0 mL.kg-1.min-1). Plasma was obtained from athletes before and after the test and 15 ng of total RNA was extracted and detected using an SYBR-based 1113 miRNA RT-qPCR panel. A total of 51 miRNAs were differentially expressed among group comparisons. Relative amounts of miRNA showed a clustering behavior among groups regarding distinct performance/time points. Significantly expressed miRNAs were used to perform functional bioinformatic analysis (DIANA tools). Fatty acid metabolism pathways were strongly targeted for the significantly different miRNAs in all performance groups and time points (p < 0.001). Although this pathway does not solely determine endurance performance, their significant contribution is certainly achieved through the involvement of miRNAs. A highly genetically dependent gold standard variable for performance evaluation in a homogeneous group of elite athletes allowed genetic/epigenetic aspects related to fatty acid pathways to emerge.

Blood Biomarkers of Long COVID: A Systematic Review.

Long coronavirus disease (COVID; LC) affects millions of people worldwide. The exact mechanisms which result in a broad, undulating and detrimental symptom profile remain unknown. Blood biomarkers associated with LC have been described; however, consensus on these remains elusive, in part due to a lack of continuity between studies on a universally accepted definition of LC. This systematic review aimed to consolidate current knowledge of blood biomarkers associated with the prevalence of LC on the basis of the World Health Organisation (WHO) clinical definition of this condition. Observational, cross-sectional, and randomised control studies published in the English language that studied blood biomarkers associated with the WHO definition of LC. All studies included participants who were ≥ 18 years old and group sizes ≥ 10 participants, and were compared against a control group without any known co-morbidities. A systematic literature search was conducted according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and prospectively registered on Prospero (ID: CRD42022373121). The Cochrane, Embase, PubMed and Web of Science databases were searched from inception to January 2024. Search results were gathered using Rayyan software and data extracted using Microsoft Excel. The reporting recommendations for tumour markers prognostic studies (REMARK) questionnaire was used to assess the quality of the included studies. A total of 45 observational and one interventional study comprising 4415 participants were included in this review which identified 525 blood biomarkers thought to be associated with LC. Three blood biomarker subtypes were associated with the development of LC: (1) immunological and inflammatory dysfunction, (2) endothelial/vascular dysfunction and (3) metabolic and clotting abnormalities. Our data are consistent with previous findings; however, no single biomarker was sufficiently associated with LC prevalence and instead a profile of biomarkers across various physiological systems may be more clinically useful. In all, 196 studies were excluded due to a lack of an adequately healthy comparator group and/or failure to meet the WHO LC definition. This demonstrates a need for further research incorporating a universal LC definition across all disease severity groups and symptom profiles, and longitudinal data reflecting the relapsing and remitting nature of this condition. Further investigation into blood biomarkers of LC, including clear reporting of healthy comparator groups and the investigation of acute and chronic biomarker changes, within the context of medical practice, may support the development of curative/restorative approaches.

The fast transient AT 2023clx in the nearby LINER galaxy NGC 3799 as a tidal disruption of a very low-mass star

We present an extensive analysis of the optical and ultraviolet (UV) properties of AT 2023clx, the closest optical/UV tidal disruption event (TDE) to date ($z=0.01107$), which occurred in the nucleus of the interacting low-ionization nuclear emission-line region (LINER) galaxy, NGC 3799. After correcting for the host reddening ($ h $ = 0.179 mag), we find its peak absolute $g$-band magnitude to be $-18.03 0.07$ mag, and its peak bolometric luminosity to be L_ pk $. AT 2023clx displays several distinctive features: first, it rose to peak within $10.4 days, making it the fastest rising TDE to date. Our SMBH mass estimate of $ M BH ---estimated using several standard methods--- rules out the possibility of an intermediate-mass BH as the reason for the fast rise. Dense spectral follow-up reveals a blue continuum that cools slowly and broad Balmer and He II lines as well as weak He I emission features that are typically seen in TDEs. The early, broad (width $ $) profile of Halpha matches theoretical expectations from an optically thick outflow. A flat Balmer decrement ($L_ H alpha $/$L_ H beta 1.58$) suggests that the lines are collisionally excited rather than being produced via photoionisation, in contrast to typical active galactic nuclei. A second distinctive feature, seen for the first time in TDE spectra, is a sharp, narrow emission peak at a rest wavelength of sim 6353 This feature is clearly visible up to 10\,d post-peak; we attribute it to clumpy material preceding the bulk outflow, which manifests as a high-velocity component of Halpha ($-9\,584 $). Its third distinctive feature is the rapid cooling during the first sim 20 days after peak, reflected as a break in the temperature evolution. Combining these findings, we propose a scenario for AT 2023clx involving the disruption of a very low-mass star ($ with an outflow launched in our line of sight and with disruption properties that led to efficient circularisation and prompt accretion disc formation, observed through a low-density photosphere.

Preparation and Characterization of Zn(II)-Stabilized Aβ42 Oligomers.

Aβ oligomers are being investigated as cytotoxic agents in Alzheimer's disease (AD). Because of their transient nature and conformational heterogeneity, the relationship between the structure and activity of these oligomers is still poorly understood. Hence, methods for stabilizing Aβ oligomeric species relevant to AD are needed to uncover the structural determinants of their cytotoxicity. Here, we build on the observation that metal ions and metabolites have been shown to interact with Aβ, influencing its aggregation and stabilizing its oligomeric species. We thus developed a method that uses zinc ions, Zn(II), to stabilize oligomers produced by the 42-residue form of Aβ (Aβ42), which is dysregulated in AD. These Aβ42-Zn(II) oligomers are small in size, spanning the 10-30 nm range, stable at physiological temperature, and with a broad toxic profile in human neuroblastoma cells. These oligomers offer a tool to study the mechanisms of toxicity of Aβ oligomers in cellular and animal AD models.