A novel NASICON-type Na3MnTi0.5Zr0.5(PO4)3 cathode material with multivalent redox reaction for high performance sodium-ion batteries.

Na3MnZr(PO4)3, a typical manganese-based NASICON-type material, has consistently been at the forefront of research on cathode materials for sodium-ion batteries due to the abundant manganese reserve and high operating voltage. However, the severe Jahn-Teller effect, poor electronic conductivity and kinetic limitation of Na3MnZr(PO4)3 impose constraints on its rate capability and cycling performance, thereby hindering its practical application. To address this challenge, a ternary NASICON-type material Na3MnTi0.5Zr0.5(PO4)3/C, with a multi-metal synergistic effect, is proposed in this study. The substitution of Ti at Zr site significantly mitigates the Jahn-Teller effect induced by Mn3+. Furthermore, the stability of the ZrO bond is enhanced, leading to a more robust crystal structure overall. Cyclic voltammetry and constant-current intermittent titration techniques reveal that the appropriate Ti substitution markedly boosts the electronic conductivity and Na+ diffusion coefficient of the electrode material, thereby mitigating polarization effects and expediting electrode reaction rates. Leveraging the multi-effect of Ti substitution, the prepared Na3MnTi0.5Zr0.5(PO4)3/C presents an improved electrochemical performance. Notably, Na3MnTi0.5Zr0.5(PO4)3/C enables a high discharge capacity of 71.0 mAh g-1 at 10C and maintains 78.8 % capacity after 1000 cycles at 2C rate. This investigation establishes a robust theoretical foundation for comprehending the synergistic effects of multimetal systems in NASICON materials and offers insights into the development of cost-effective, high-performance cathode materials.

12-week melatonin supplementation improved dynamic postural stability and walking performance in persons living with multiple sclerosis: A randomized controlled trial.

BACKGROUND: Persons with multiple sclerosis (PwMS) suffer from sleep disturbances, fatigue and pain, which can be due, at least in part, to decreased levels of endogenous melatonin. These alterations could exacerbate postural instability, gait disorders and fall risk. Acute effects of exogenous melatonin on physical disorders have been studied in PwMS but its long-term effects on these parameters have not been explored yet in this population. This study aimed to determine the impact of chronic melatonin intake on dynamic postural stability, walking performance and fall risk in PwMS. METHODS: This randomized placebo-controlled study included 27 PwMS who were assigned to either melatonin group (MG, n=15) or placebo group (PG, n=12) (3 mg/night for 12 weeks). Dynamic postural balance (force platform), walking performance (locometer) and fall risk (Four Square Step Test) were evaluated pre (T0)- and post (T1)-intervention. Sleep quality (Pittsburgh Sleep Quality Index (PSQI)), fatigue perception (Fatigue Severity Scale (FSS)), neuropathic pain (Neuropathic Pain Questionnaire 4 (DN4)) and quality of life (International Multiple Sclerosis (MS) Quality of Life Questionnaire) were also assessed at T0 and T1. RESULTS: The center of pressure mean velocity decreased in MG compared with PG in the frontal plane (22.98 %, p=0.028). Stride length and walking speed increased in MG comparatively with PG (18.09 %, p=0.036; 9.65 %, p=0.025, respectively). The PSQI (55.89 %, p<0.001), FSS (32.38 %, p=0.003) and DN4 (32.41 %, p=0.035) scores decreased in MG compared with PG. CONCLUSION: 12-week melatonin supplementation can be recommended for managing MS-related gait disorders and dynamic postural imbalance. This therapy may also be prescribed for PwMS due to its anti-fatigue and analgesic effects as well as its benefits on sleep quality. CLINICAL REGISTRATION: This study was prospectively recorded in the Pan African Clinical Trial Registry database (PACTR202007465309582) (https://pactr.samrc.ac.za/.).

Long Chain Base Profiling with Multiple Reaction Monitoring Mass Spectrometry.

Sphingolipids (SLs) are essential lipids with important functions in membrane formation and cell signaling. The presence of a long chain base (LCB) structure is common to all SLs. De novo SL synthesis is initiated by the enzyme serine-palmitoyltransferase (SPT), which forms an LCB by the conjugation from serine and fatty acyl-CoAs. SPT can metabolize a variety of acyl-CoA substrates, which form diverse LCB structures within and across species. The LCB then undergoes further metabolic modifications resulting in an extraordinarily diverse spectrum of sphingolipids formed. SL analysis, using liquid chromatography-mass spectrometry (LC-MS)-based methods, poses challenges due to the diverse range of frequently isobaric species. This complexity complicates the identification of underlying LCB structures using standard lipidomics approaches. Here, we describe a simplified method to analyze the LCB profile in cells, tissue, and blood. The procedure involves chemical hydrolysis to remove the conjugated headgroups and N-acyl chains, allowing to specifically resolve the underlying LCB structures by LC-MS. This method can also be combined with an isotope labeling approach to determine in vivo SPT activity and total SL de novo synthesis over time.

A colorimetric sensor based on multiple elements doped carbon dot nanozyme for rapid detection of 1-naphthol in human urine samples.

The residual carbaryl in crops can cause serious damage to the human kidney and nervous system after entering the human body, which may be metabolized to 1-naphthol (1-NAP) and excreted through urine. 1-NAP is often used as the biomarker for carbaryl exposure, so the intake or leakage of carbaryl can be monitored by detecting the concentration of 1-NAP. Herein, Co, N, P ternary co-doped carbon dots (CoNP-CDs) derived from vitamin B12 were synthesized by a facile hydrothermal method. CoNP-CDs exhibited oxidase-like activity and excellent peroxidase-like activity, which was attributed to the Fenton-like reaction of Co2+/Co3+ and the presence of pyrrole N and P elements, which together provided multiple active sites for chromogenic substrates. Due to the dual enzyme-like activity of CoNP-CDs, hydroxyl radicals (OH) and superoxide radicals (O2-) were generated during the catalytic process, which could rapidly oxidize colorless 3,3',5,5'-tetramethyl benzidine (TMB) to blue oxidation products (oxTMB). The α-carbon in 1-NAP can be attacked by OH, and the catalytic oxidation process of TMB can be inhibited by the consumption of OH, so that the blue color of the solution became lighter. Based on this principle, a smartphone-assisted colorimetric sensing platform was constructed for the detection of 1-NAP, and which resulted in a linear range of 1.07-37.3 µM and a visual detection limit of 0.68 µM. Moreover, the colorimetric sensing system showed satisfactory recoveries in the detection of human urine samples. The colorimetric sensing system owned the advantages of fast response, strong selectivity and simple operation, and provided a potential strategy for the on-site detection of 1-NAP.

Nanoscale octopus guiding telomere entanglement: An innovative strategy for inducing apoptosis in cancer cells.

Telomere length plays a crucial role in cellular aging and the risk of diseases. Unlike normal cells, cancer cells can extend their own survival by maintaining telomere stability through telomere maintenance mechanism. Therefore, regulating the lengths of telomeres have emerged as a promising approach for anti-cancer treatment. In this study, we introduce a nanoscale octopus-like structure designed to induce physical entangling of telomere, thereby efficiently triggering telomere dysfunction. The nanoscale octopus, composed of eight-armed PEG (8-arm-PEG), are functionalized with cell penetrating peptide (TAT) to facilitate nuclear entry and are covalently bound to N-Methyl Mesoporphyrin IX (NMM) to target G-quadruplexes (G4s) present in telomeres. The multi-armed configuration of the nanoscale octopus enables targeted binding to multiple G4s, physically disrupting and entangling numerous telomeres, thereby triggering telomere dysfunction. Both in vitro and in vivo experiments indicate that the nanoscale octopus significantly inhibits cancer cell proliferation, induces apoptosis through telomere entanglement, and ultimately suppresses tumor growth. This research offers a novel perspective for the development of innovative anti-cancer interventions and provides potential therapeutic options for targeting telomeres.

Multiple sclerosis treatments a review of current biomedical engineering approaches.

Multiple Sclerosis (MS) is an autoimmune condition targeting the central nervous system (CNS) characterized by focal demyelination with inflammation, causing neurodegeneration and gliosis. This is accompanied by a refractory period in relapsing MS or chronic progression in primary progressive MS. Current MS treatments target disease relapses and aim to reduce further demyelination and disability. These include the treatment of acute exacerbations through global immunomodulation upon corticosteroid administration, which are accompanied by adverse reactions. Disease modifying therapies (DMTs) which provide targeted immunosuppression of T and B cells, and sequestration of leukocytes out of CNS, have led to further improvements in demyelination prevention and disease burden reduction. Despite their efficacy, DMTs are ineffective in remyelination, pathology reversal and have minimal effects in progressive MS. The advent of modern biomedical engineering approaches in combination with a better understanding of MS pathology, has led to the development of novel, regenerative approaches to treatment. Such treatments utilize neural stem cells (NSCs) and can reduce disease relapses and reverse damage caused by the disease through localized tissue regeneration. While at initial stages, pre-clinical and clinical studies utilizing NSCs and immune modulation have shown promising outcomes in tissue regeneration, creating a potential new era in MS therapy.

Flow Cytometric MRD Detection in Selected Mature B-Cell Malignancies.

The quantification of submicroscopic minimal residual disease (MRD) after therapy proved to have independent prognostic significance in many mature B-cell malignancies. With the advent of routine benchtop cytometers capable of simultaneously analyzing ≥8 colors and with improved standardization, flow cytometry has become the method of choice for MRD assessments in some lymphoma entities. Herein we describe general aspects of flow cytometric standardization. Chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) are used as examples to explain the technical standardization of flow cytometry for MRD detection according to EuroFlow strategies. MRD data acquisition and detailed analysis in MM and CLL is a particular focus of this chapter.

Comparative evaluation of single and multiple exposure to PM2.5 in respirable air on cardiac physiology, structure and function in a Wistar rat model.

Many studies have shown the negative relationship between long term exposure to PM2.5 and cardiac dysfunction. Recently, studies have shown that even a single exposure of PM2.5 from air sample in permissible range can induce very mild cardiac pathological changes. In the present study, we revisited the toxic effect of PM2.5 on rat heart by adopting single and multiple exposure durations. Female Wistar rats were exposed to PM2.5 at a concentration of 250 µg/m3 daily for 3 hr for single (1 day) and multiple (7, 14, 21 days) durations. The major pathological changes noted in 21 days exposed myocardium comprised of an elevated ST segment (the segment between the S wave and the T wave), development of cardiac fibrosis, hypertrophy, cardiac injury, tissue inflammation and declined cardiac function. With 14 days exposed heart, the electrocardiograms (ECG),data showed insignificantly declined heart rate and an increased QT (the time from the start of the Q wave to the end of the T wave) interval along with mild fibrosis, hypertrophy and lesser number of TUNEL positive cells. On the other hand, single- and 7-days exposure to PM2.5 did not impart any significant changes in the myocardium. To determine the reversibility potential of PM2.5 induced cardiotoxicity, a washout period of 24 hours was adopted and all observed changes in the myocardium were reversed till day 7, but not in 14- and 21-days exposed samples. Based on the above findings we concluded that PM2.5 associated cardiac dysfunction is the cumulative outcome of ineffective cardiac adaptive and repair process that accumulate additively over the time due to prolonged exposure durations.

Enfermedad de Von Willebrand adquirida en un Mieloma múltiple: reporte de caso

La Enfermedad de Von Willebrand adquirida (EVW adquirida) es un trastorno hemorrágico adquirido poco frecuente, con características clínicas y de laboratorio similares a la Enfermedad de Von Willebrand congénita. Asociándose con enfermedades hemato-oncológicas, autoinmunes, cardiovasculares y tumores sólidos. Las gammapatías monoclonales constituyen un grupo heterogéneo de trastornos caracterizados por la proliferación de linfocitos B en los últimos estadios madurativos o células plasmáticas que preservan la capacidad de producir una inmunoglobulina (Ig) monoclonal o alguno de sus componentes. Como consecuencia, se produce la aparición de una paraproteína o componente M (CM) en suero y/o orina que estará formado por la misma cadena pesada o ligera, y por regiones variables idénticas. Se presenta el caso de una mujer de 57 años, que se presenta con un síndrome hemorragíparo, alteración de la crasis en su vía intrínseca, donde se diagnostica EVW adq secundaria a Mieloma Múltiple (MM) con CM IgM 5,9 g/dl. El tratamiento tuvo como objetivos detener el sangrado, prevenir complicaciones y abordar precozmente la patología hemato-oncológica causante. Para su abordaje requirió la realización de recambios plasmáticos terapéuticos (RPT) que tuvieron un rol de acción terapéutica temprana y eficaz con excelente tolerancia. Ante el diagnóstico se inició rápidamente poliquimioterapia siendo ésta una paciente candidata a trasplante de progenitores hematopoyéticos. El objetivo de la presentación de este caso clínico es destacar la importancia de un correcto y oportuno diagnóstico ante la sospecha clínica de una coagulopatía secundaria a una enfermedad hemato-oncológica subyacente. Por lo que hacemos énfasis en el abordaje multidisciplinario.

Acquired von Willebrand disease (AVWS) is a rare acquired bleeding disorder with clinical and laboratory features similar to congenital von Willebrand disease. Associated with hemato-oncological, autoimmune, cardiovascular diseases and solid tumors. Monoclonal gammopathies constitute a heterogeneous group of disorders characterized by the proliferation of B lymphocytes in the last stages of maturation or plasma cells that preserve the capacity to produce a monoclonal immunoglobulin (Ig) or one of its components. As a consequence, the appearance of a paraprotein or M component (CM) occurs in serum and/or urine, which will be formed by the same heavy or light chain, and by identical variable regions. We present the case of a 57-year-old woman, who presented with a hemorrhagic parous syndrome, alteration of the crasis in its intrinsic way, where Acquired Von Willebrand Disease secondary to Multiple Myeloma is diagnosed. Treatment was aimed at stopping the bleeding, preventing complications, and promptly addressing the underlying hemato-oncological pathology. For its approach, it required the performance of therapeutic plasma exchanges that had a role of early and effective therapeutic action with excellent tolerance. Given the diagnosis, polychemotherapy was quickly started, this patient being a candidate for hematopoietic stem cell transplantation. The objective of presenting this clinical case is to highlight the importance of a correct and timely diagnosis in the face of clinical suspicion of a coagulopathy secondary to an underlying hemato-oncological disease. Therefore, we emphasize the multidisciplinary approach.

A doença de von Willebrand adquirida (EVW acq, AVWS) é um distúrbio hemorrágico adquirido raro com características clínicas e laboratoriais semelhantes à doença de von Willebrand congênita. Associado a doenças hemato-oncológicas, autoimunes, cardiovasculares e tumores sólidos. As gamopatias monoclonais constituem um grupo heterogêneo de distúrbios caracterizados pela proliferação de linfócitos B nos últimos estágios de maturação ou plasmócitos que preservam a capacidade de produzir uma imunoglobulina monoclonal (Ig) ou um de seus componentes. Como consequência, ocorre o aparecimento de uma paraproteína ou componente M (CM) no soro e/ou na urina, que serão formados pela mesma cadeia pesada ou leve, e por regiões variáveis idênticas. Apresentamos o caso de uma mulher de 57 anos, que apresentava um síndroma hemorrágico, alteração da crase na sua via intrínseca, onde é diagnosticada Doença de Von Willebrand Adquirida secundária a Mieloma Múltiplo. O tratamento visava estancar o sangramento, prevenir complicações e abordar prontamente a patologia hemato-oncológica subjacente. Para sua abordagem, exigiu a realização de plasmaférese terapêutica que teve papel de ação terapêutica precoce e efetiva com excelente tolerância. Diante do diagnóstico, rapidamente foi iniciada poliquimioterapia, sendo este paciente candidato a transplante de células-tronco hematopoiéticas. O objetivo da apresentação deste caso clínico é realçar a importância de um diagnóstico correto e atempado face à suspeita clínica de uma coagulopatia secundária a uma doença hemato-oncológica subjacente. Portanto, enfatizamos a abordagem multidisciplinar.

The Lehigh Valley Health Network narcolepsy cohort: clinical and polysomnographic analysis of 304 cases.

STUDY OBJECTIVE: We aimed to characterize clinical features, comorbidities and polysomnographic characteristics of a large cohort of patients with narcolepsy. METHODS: We undertook a retrospective chart and polysomnographic review of all patients with a diagnosis of narcolepsy type 1 (NT1) or narcolepsy type 2 (NT2) seen within the Lehigh Valley Health Network between 2000 and 2022. RESULTS: We found 304 cases with a diagnosis of narcolepsy (52 NT1, 252 NT2), based on International Classification of Sleep Disorders, third edition criteria. Compared to NT2, patients with NT1 had younger diagnosis age (24.5 versus 27.4 years, p=0.03), shorter diagnostic gap (3.0 versus 4.6 years, p=0.002), more frequent sleep paralysis (55.8% versus 19.4%, p<0.0001) and hypnagogic hallucinations (46.2% versus 25.4%, p=0.003), and higher Epworth Sleepiness Scale (ESS) scores (17.8 versus 16.7, p=0.02). The most common comorbid sleep disorders were breathing disorders (17.4%) and insomnia (15.5%). Migraine was the most common neurological disorder. Depression was more common in NT2 than NT1 [12 (23.1%) versus 94 (37.3%), p=0.05]. On the Multiple Sleep Latency Test, patients with NT1 had more sleep onset REM periods (SOREMPs) than patients with NT2 (≥3 SOREMPs in 59.2% versus 26.9%, p<0.0001). Only in NT2, hypnagogic hallucinations and higher ESS scores were associated with higher numbers of SOREMPs (p=0.0277 and p=0.0179 respectively). CONCLUSION: This is one of the largest monocentric studies to date of patients with narcolepsy and confirms the frequent comorbidities of narcolepsy. Specific clinical characteristics and comorbidities may help differentiate NT1 from NT2.

Corrigendum: Relationship between gut microbiota and multiple sclerosis: a scientometric visual analysis from 2010 to 2023.

[This corrects the article DOI: 10.3389/fimmu.2024.1451742.].

Osteosarcoma Arising from Iliac Bone Lesions of Hereditary Multiple Osteochondromas: A Case Report.

Introduction: Osteochondromas are benign tumors that arise primarily in the metaphyseal region of long bones. The malignant transformation rate is estimated to be less than 1% and 1-3% in solitary and multiple osteochondromas, respectively. Transformation to osteosarcoma is very rare. Little information is available on treatment or outcome. A rare case of osteosarcoma arising from hereditary multiple osteochondromas of the right iliac bone is reported. Case Presentation: A 66-year-old woman presented with recurrent right abdominal pain. Computed tomography (CT) showed a mass protruding into the pelvic cavity, 9 cm × 7 cm × 7 cm, with bone destruction and internal calcification in the right iliac bone. A CT-guided biopsy was performed, and the diagnosis was osteosarcoma. After one course of chemotherapy with doxorubicin and ifosfamide, extensive resection of the tumor was performed. The pathology showed proliferation of highly pleomorphic dysplastic cells with bone formation inside the tumor just below the osteochondroma tissue, which led to the diagnosis of osteosarcoma arising from the osteochondroma. Three years after surgery, there was no evidence of recurrence or metastasis, and the patient was able to walk unassisted. Conclusion: A case of osteosarcoma arising from an iliac lesion of hereditary multiple osteochondromas was described. Although no recurrence or metastasis has been observed 3 years after surgery, further follow-up is necessary due to the short time after surgery.

Exploring Spinal Cord Changes in Multiple Sclerosis Patients Using MRI.

Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system (CNS). The diagnosis of MS is based on clinical signs and symptoms as well as findings in magnetic resonance imaging (MRI) sequences by demonstrating the spatial and temporal dispersion of white matter lesions, which are thought to be typical of MS in distribution, shape, extent, and signal abnormalities. Spinal cord MRI can identify asymptomatic lesions and rule out malignancies or spinal stenosis in patients for whom brain imaging is not helpful in making an MS diagnosis. This study examines the MRI features of Saudi Arabian patients clinically proven to have MS with typical lesions exclusively evident in the spinal cord. This retrospective cross-sectional study was carried out in 151 patients who are confirmed cases of MS based on clinical findings and MRI results. Patients' MRI data were reviewed from the picture archiving and communication system (PACS). The study revealed that MS incidence was higher in females than males and that the number of people diagnosed with MS increased in middle age. Cervical cord plaques and cervical cord curve straightening were the most frequent changes (67% and 56%, respectively), indicating that MRI can complement and even replace clinical data in MS diagnosis, leading to earlier, more precise diagnoses and speedier starts to treatment.

Beyond lines of treatment: embracing early high-efficacy disease-modifying treatments for multiple sclerosis management.

Recent advances in multiple sclerosis (MS) management have shifted perspectives on treatment strategies, advocating for the early initiation of high-efficacy disease-modifying therapies (heDMTs). This perspective review discusses the rationale, benefits, and challenges associated with early heDMT initiation, reflecting on the obsolescence of the traditional "first-line" and "second-line" treatment classifications. The article emerges from the last update of the consensus document of the Spanish Society of Neurology on the treatment of MS. During its development, there was a recognized need to further discuss the concept of treatment lines and the early use of heDMTs. Evidence from randomized controlled trials and real-world studies suggests that early heDMT initiation leads to improved clinical outcomes, including reduced relapse rates, slowed disease progression, and decreased radiological activity, especially in younger patients or those in early disease stages. Despite the historical belief that heDMTs involve more risks and adverse events compared to moderate-efficacy DMTs (meDMTs), some studies have reported comparable safety profiles between early heDMTs and meDMTs, though long-term safety data are still lacking. The review also addresses the need for a personalized approach based on patient characteristics, prognostic factors, and preferences, explores the importance of therapeutic inertia, and highlights the evolving landscape of international and national guidelines that increasingly advocate for early intensive treatment approaches. The article also addresses the challenges of ensuring access to these therapies and the importance of further research to establish long-term safety and effectiveness of DMTs in MS.

Choosing stronger treatments early on for better multiple sclerosis care Recent progress in treating multiple sclerosis (MS) has changed how doctors think about starting treatments, with more support now for using high-efficacy disease-modifying treatments (heDMTs) early on. This article talks about why starting heDMTs early can be good, what benefits it might bring, and what challenges there might be. It also mentions how the old way of categorizing treatments into "first-line" and "second-line" is becoming outdated. This discussion is based on the latest recommendations from the Spanish Society of Neurology. The article explains that starting heDMTs early can lead to better results for patients, like fewer relapses, slower progression of the disease, and less damage seen on magnetic resonance imaging (MRI). This is particularly true for younger patients or those who are in the early stages of MS. Even though there was a concern that these heDMTs might have more side effects compared to other treatments, recent studies show that they could be just as safe, though more research is needed to be sure about their safety in the long run. The review suggests that treatment should be tailored to each patient, considering their specific situation, what they prefer, and the urgency to start treatment. It also discusses the need to overcome delays in starting these treatments and how treatment guidelines are changing to support starting strong treatments earlier. Finally, the article points out that it is still important to make these treatments accessible to everyone who needs them and to keep researching to understand their long-term safety and effectiveness.

Is there a Possible Association between Multiple Myeloma Relapse and Coronavirus Disease 2019 Vaccination? A Case Report.

Due to the high morbidity and mortality of the coronavirus disease 2019 (COVID-19) in patients with malignancy, the necessity of vaccination in this group of patients became particularly important. Although a large number of studies have reported the safety of COVID-19 vaccination in multiple myeloma (MM) patients, the effect of the COVID-19 vaccine on MM relapse has not yet been reported. Here, we report a case of a possible association between relapse of MM and COVID-19 vaccination with Sinopharm®, an inactivated virus vaccine, in a patient with MM who has remained in complete remission for about 4 years. The MM relapse in the patient was diagnosed by both clinical findings and laboratory workup including serum protein electrophoresis, bone marrow aspiration, and biopsy. Despite this possible association between COVID-19 vaccination and MM relapse in the patient, given its importance in reducing mortality and having an acceptable safety profile, the COVID-19 vaccine should be administered to all cancer patients. However, careful monitoring and follow-up are recommended in patients with MM after COVID-19 vaccination.

Fused SDT/IRT Models for Mixed-Format Exams.

A psychological framework for different types of items commonly used with mixed-format exams is proposed. A choice model based on signal detection theory (SDT) is used for multiple-choice (MC) items, whereas an item response theory (IRT) model is used for open-ended (OE) items. The SDT and IRT models are shown to share a common conceptualization in terms of latent states of "know/don't know" at the examinee level. This in turn suggests a way to join or "fuse" the models-through the probability of knowing. A general model that fuses the SDT choice model, for MC items, with a generalized sequential logit model, for OE items, is introduced. Fitting SDT and IRT models simultaneously allows one to examine possible differences in psychological processes across the different types of items, to examine the effects of covariates in both models simultaneously, to allow for relations among the model parameters, and likely offers potential estimation benefits. The utility of the approach is illustrated with MC and OE items from large-scale international exams.

Microstructural alterations of cerebellar peduncles in multiple sclerosis: a diffusion tensor imaging study.

BACKGROUND AND PURPOSE: Ataxia, tremors, dysarthria, and sometimes impaired cognition are the signs of cerebellum involvement in multiple sclerosis (MS). These symptoms affect up to 80% of patients and are usually hard to treat. To find the underlying involvement of the cerebellum in MS, we assessed the microstructural alterations with DTI in the cerebellar peduncles of the affected subjects. MATERIALS AND METHODS: We included 58 relapsing-remitting MS patients and 27 healthy controls. Patients were divided into 18 patients of relapsing-remitting MS with cerebellar impairment (RRMSc) and 40 without cerebellar impairment (RRMSnc). Using Diffusion Tensor Imaging (DTI), we calculated fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) metrics in all subjects. We also checked if there were associations between DTI metrics and clinical cerebellar measures (i.e., tremor severity and the scale for the assessment and rating of ataxia). RESULTS: ANOVA and post-hoc results showed significant differences in DTI metrics between RRMSc and HC and between RRMSnc and HC subjects. Inferior peduncle RD remained the only metric with a significant difference across all pairwise comparisons. The general linear model assessing the effects of the three study groups on the association between DTI metrics and clinical cerebellar measures yielded no significant result. CONCLUSIONS: Our study showed that DTI can mainly reveal significant differences between different MS groups and HCs. Our results imply the role of cerebellar peduncles in the pathophysiology of MS and that this role does not necessarily reflect the severity of cerebellar signs of the patients.

The FGF/FGFR/c-Myc axis as a promising therapeutic target in multiple myeloma.

Among blood cancers, multiple myeloma (MM) represents the second most common neoplasm and is characterized by the accumulation and proliferation of monoclonal plasma cells within the bone marrow. Despite the last few decades being characterized by the development of different therapeutic strategies against MM, at present such disease is still considered incurable. Although MM is highly heterogeneous in terms of genetic and molecular subtypes, about 67% of MM cases are associated with abnormal activity of the transcription factor c-Myc, which has so far revealed a protein extremely difficult to target. We have recently demonstrated that activation of fibroblast growth factor (FGF) signaling protects MM cells from oxidative stress-induced apoptosis by stabilizing the oncoprotein c-Myc. Accordingly, secretion of FGF ligands and autocrine activation of FGF receptors (FGFR) is observed in MM cells and FGFR3 genomic alterations represent some 15-20% MM cases and are associated with poor outcome. Thus, FGF/FGFR blockade may represent a promising strategy to indirectly target c-Myc in MM. On this basis, the present review aims at providing an overview of recently explored connections between the FGF/FGFR system and c-Myc oncoprotein, sustaining the therapeutic potential of targeting the FGF/FGFR/c-Myc axis in MM by using inhibitors targeting FGF ligands or FGF receptors. Importantly, the provided findings may represent the rationale for using FDA approved FGFR TK inhibitors (i.e. Pemigatinib, Futibatinib, Erdafitinib) for the treatment of MM patients presenting with an aberrant activation of this axis.

Estimation of genetic parameters for reproductive traits in Korean dairy cattle.

Objective: In Korea, dairy cattle breeding programs have historically prioritized productive, conformation traits, leading to positive improvements, yet reproductive traits have lagged in development. This study was conducted to develop the breeding program of key reproductive traits in the Korean dairy cattle population. Methods: Utilizing data from 7,596 farms and over seven million observations, we conducted quality control to rectify manual entry errors and selected traits in line with international genetic evaluation standards. Traits analyzed included heifer conception rate (HCR), interval from calving to first insemination (CF), cow conception rate (CCR), interval from first to last insemination (FL), and days open (DO). Genetic parameters were estimated using a single trait animal model for HCR and a multiple lactation animal model for CF, CCR, FL, and DO, considering contemporary group of herd-insemination year, insemination month, and monthly age (MA) as fixed effects. Results: Results showed low heritability estimates, ranging from 0.007 to 0.035 across different traits and lactations. Theoretical reliability appears to be low on average due to the influence of heritability, but it showed sufficiently high reliability in some sires (over 0.8). In terms of genetic and phenotypic trends, capacity for reproductive traits declined for a long time until around 2014. In recent individuals, improved trend can be found. Conclusion: This study addressed the critical need for enhancing reproductive efficiency to complement the existing breeding goals, thereby supporting sustained economic viability in the dairy industry. The results underscore the need for improved data quality and methodological adjustments for reproduction records to enhance the genetic evaluation of dairy cattle in Korea.