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Pile-up and dead-time are two main causes of nonlinearity in the response of a PET scanner as a function of activity in the field of view (FOV). For a given scanner and acquisition system, pile-up effects depend on the material and size of the object being imaged and on the distribution of activity inside and outside the FOV, because these factors change the singles-to-coincidences ratio (SCR). Thus, it is difficult to devise an accurate correction that would be valid for any acquisition. In this work, we demonstrate a linear relationship between SCR and effective dead-time, which measures the effects of both dead-time (losses) and pile-up (gains and losses). This relationship allows us to propose a simple method to accurately estimate dead-time and pile-up corrections using only two calibration acquisitions with, respectively, a high and low SCR. The method has been tested with simulations and experimental data for two different scanner geometries: a scanner with large area detectors and no pile-up rejection, and a scanner composed of two full rings of smaller detectors. Our results show that the SCR correction method is accurate within 7%, even for high activities in the FOV, and avoids the bias of the standard single-parameter method. [ABSTRACT FROM AUTHOR]

Effective medicines exist to treat or alleviate many diseases which predominate in the developing world and cause high mortality and morbidity rates. Price should not be an obstacle preventing access to these medicines. Increasingly, drug donations have been established by drug companies, but these are often limited in time, place or use. Measures exist which are more sustainable and will have a greater positive impact on people's health. Principally, these are encouraging generic competition; adopting into national legislation and implementing TRIPS safeguards to gain access to cheaper sources of drugs; differential pricing; creating high volume or high demand through global and regional procurement; and supporting the production of quality generic drugs by developing countries through voluntary licenses if needed, and facilitating technology transfer. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is a central nervous system disorder marked by progressive neurological impairments. Magnetic resonance imaging (MRI) parameters are key paraclinical measures that play a crucial role in the diagnosis, prognosis, and monitoring of MS-related disability. This study aims to analyze and summarize the existing literature on the correlation between MRI parameters and disability in people with MS (pwMS). Methods: The PubMed/MEDLINE, Embase, Scopus, and Web of Science databases were searched from inception to July 19, 2024, and a meta-analysis was carried out using R software version 4.4.0 and the random effects model used to determine the pooled correlation coefficient, with its 95% confidence interval (CI), between MRI measurements and disability scales. Results: Among 5741 studies, 383 studies with 39707 pwMS were included. The meta-analysis demonstrated that Expanded Disability Status Scale (EDSS) had significant correlations with cervical cord volume (r = -0.51, 95% CI: -0.62 to -0.38, I2 = 0%, p-heterogeneity = 0.86, p-value<0.01), cortical lesion volume (r = 0.45, 95% CI: 0.36 to 0.53, I2 = 68%, p-heterogeneity<0.01, p-value<0.01), brain volume (r = -0.40, 95% CI: -0.47 to -0.33, I2 = 41%, p-heterogeneity = 0.05, p-value<0.05), and grey matter volume (GMV) (r = -0.36, 95% CI: -0.49 to -0.21, I2 = 0%, p-heterogeneity = 0.53, p-value<0.01), respectively. Conclusion: This study offers evidence suggesting that cortical lesion volume, brain volume, GMV, and MRI measurements of the spinal cord may constitute reliable indicators for assessing disability in pwMS. [ABSTRACT FROM AUTHOR]

This comprehensive review aims to explore imaging outcome measures targeting compartmentalized inflammation in Phase 2 clinical trials for multiple sclerosis (MS). The traditional primary imaging outcomes used in Phase 2 MS trials, new or enhancing white matter lesions on MRI, target the effects of peripheral inflammation, but the widespread inflammation behind a mostly closed blood-brain barrier is not captured. This review discusses several emerging imaging technologies that could be used as surrogate markers of compartmentalized inflammation, targeting chronic active lesions, meningeal inflammation, and innate immune activation within the normal-appearing white matter and gray matter. The integration of specific imaging outcomes into Phase 2 trials can provide a more accurate assessment of treatment efficacy, ultimately contributing to the development of more effective therapies for MS. [ABSTRACT FROM AUTHOR]

The principle of immune checkpoint blockade therapy is based on the activation of T cells. Immune checkpoint inhibitors (ICIs), such as anti-PD-1/PD-L1 and anti-CTLA-4 antibodies, have demonstrated effectiveness in treating solid tumors by reinvigorating the immune system to recognize and eliminate malignant cells. In recent years, ICIs have shown promise in certain patients with relapsed or refractory lymphoma and myeloid malignancies. Allogeneic hematopoietic stem cell transplant (allo-HCT) currently remains the only curative immunotherapy option for eligible patients with these hematologic malignancies. An increasing number of patients with indications for allo-HCT have received treatment with ICIs either before the procedure or as a therapy for relapse after allo-HCT. Nevertheless, initial reports suggest that patients exposed to immune checkpoint inhibitors either before or after allo-HCT are at an increased risk of developing severe graft-versus-host disease and other immune-related adverse events, likely due to the persistent effects of immune checkpoint blocking. Maximizing therapeutic benefits while minimizing side effects of the combination of checkpoint blockade immunotherapy and allo-HCT is an active area of research aimed at improving the prognosis of relapsed or refractory hematologic malignancies. However, there is still a lack of rational design strategies to optimize the combined use of these two different types of immunotherapies. In this review, we addressed the scientific rationale behind ICIs for treating lymphoma and myeloid malignancies. We also summarized the evidence supporting the use of ICIs as salvage therapy before and after allo-HCT. Additionally, we offered insights into current approaches for preventing and treating graft-versus-host disease and other immune-related adverse events during the procedure. [ABSTRACT FROM AUTHOR]

Background: 11C-PBR28 positron emission tomography (PET), targeting the translocator protein, and paramagnetic rim lesions (PRL) have emerged as promising imaging markers of MS chronic inflammation. No consensus on which is the optimal marker exists. Objectives: To investigate the ability of 11C-PBR28 PET and PRL assessment to identify chronic inflammation in white matter (WM) MS lesions and their relation to neurological impairment. Methods: Based on 11C-PBR28 uptake, brain WM lesions from 30 MS patients were classified as PET active or inactive. The PRL presence was assessed on 7T phase reconstructions, T1/T2 ratio was calculated to measure WM microstructural integrity. Results: Less than half (44%) of non-PRL WM lesions were active on 11C-PBR28 imaging either throughout the lesion (whole active) or at its periphery. PET peripherally active lesions and PRL did not differ in T1/T2 ratio and 11C-PBR28 uptake. A positive correlation was observed between PRL and active PET lesion count. Whole active PET lesion volume was the strongest predictor (β = 0.97, p < 0.001) of increased Expanded Disability Status Scale scores. Conclusion: 11C-PBR28 imaging reveals more active WM lesions than 7T PRL assessment. Although PRL and PET active lesion counts are related, neurological disability is better explained by PET whole active lesion volume. [ABSTRACT FROM AUTHOR]

This paper investigates the nature of the associations and the potential existence of both short-run and long-run relationships between the stock market indices of Morocco, France, Germany, the United Kingdom, China, and the United States from January 2014 to January 2024. The purpose of analyzing dynamic interconnections and contagion effects is to determine how the stock markets of these countries influence and relate to each other. The study employs a time series Vector Error Correction Model (VECM) approach, incorporating stationarity, cointegration, and Granger causality tests. Additionally, the Impulse Response Function (IRF) is used to analyze the response of variables to shocks. The bivariate Granger causality test reveals significant causal influences: from France, Germany, and the USA to Morocco; from the USA to the DAX and France; and from the UK to Germany. After establishing the Granger causal relationships, long-run and short-run relationships are further examined. Using the Johansen multivariate cointegration approach, the study suggests a long-term equilibrium among the six stock market indices over time. The short-run adjustments are analyzed using the VECM, which reveals that adjustments in the CAC 40, DAX, and MASI tend to correct deviations from equilibrium, indicating a tendency to move towards equilibrium. For the FTSE 100, S&P 500, and SSEC, the VECM captures the speed and direction of adjustments as these indices respond to short-term disruptions and work towards restoring equilibrium. The findings underscore the importance of closely connected global stock markets, which means that international regulators must coordinate their efforts to reduce the risks of contagion. Policymakers should prioritize improving financial stability through integrated frameworks considering short-term disruptions and long-term equilibrium trends. [ABSTRACT FROM AUTHOR]

In the domain of Extended Reality (XR), particularly Virtual Reality (VR), extensive research has been devoted to harnessing this transformative technology in various real-world applications. However, a critical challenge that must be addressed before unleashing the full potential of XR in practical scenarios is to ensure robust security and safeguard user privacy. This paper presents a systematic survey of the utility of biometric characteristics applied in the XR environment. To this end, we present a comprehensive overview of the different types of biometric modalities used for authentication and representation of users in a virtual environment. We discuss different biometric vulnerability gateways in general XR systems for the first time in the literature along with taxonomy. A comprehensive discussion on generating and authenticating biometric-based photorealistic avatars in XR environments is presented with a stringent taxonomy. We also discuss the availability of different datasets that are widely employed in evaluating biometric authentication in XR environments together with performance evaluation metrics. Finally, we discuss the open challenges and potential future work that need to be addressed in the field of biometrics in XR. [ABSTRACT FROM AUTHOR]

Blood oxygen saturation (SpO2) is vital for patient monitoring, particularly in clinical settings. Traditional SpO2 estimation methods have limitations, which can be addressed by analyzing photoplethysmography (PPG) signals with artificial intelligence (AI) techniques. This systematic review, following PRISMA guidelines, analyzed 183 unique references from WOS, PubMed, and Scopus, with 26 studies meeting the inclusion criteria. The review examined AI models, key features, oximeters used, datasets, tested saturation intervals, and performance metrics while also assessing bias through the QUADAS-2 criteria. Linear regression models and deep neural networks (DNNs) emerged as the leading AI methodologies, utilizing features such as statistical metrics, signal-to-noise ratios, and intricate waveform morphology to enhance accuracy. Gaussian Process models, in particular, exhibited superior performance, achieving Mean Absolute Error (MAE) values as low as 0.57% and Root Mean Square Error (RMSE) as low as 0.69%. The bias analysis highlighted the need for better patient selection, reliable reference standards, and comprehensive SpO2 intervals to improve model generalizability. A persistent challenge is the reliance on non-invasive methods over the more accurate arterial blood gas analysis and the limited datasets representing diverse physiological conditions. Future research must focus on improving reference standards, test protocols, and addressing ethical considerations in clinical trials. Integrating AI with traditional physiological models can further enhance SpO2 estimation accuracy and robustness, offering significant advancements in patient care. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is unsurpassed for its clinical and pathological hetherogeneity, but the biological determinants of this variability are unknown. HLA‐DRB1*15, the main genetic risk factor for MS, influences the severity and distribution of MS pathology. This study set out to unravel the molecular determinants of the heterogeneity of MS pathology in relation to HLA‐DRB1*15 status. Shotgun proteomics from a discovery cohort of MS spinal cord samples segregated by HLA‐DRB*15 status revealed overexpression of the extracellular matrix (ECM) proteins, biglycan, decorin, and prolargin in HLA‐DRB*15‐positive cases, adding to established literature on a role of ECM proteins in MS pathology that has heretofore lacked systematic pathological validation. These findings informed a neuropathological characterisation of these proteins in a large autopsy cohort of 41 MS cases (18 HLA‐DRB1*15‐positive and 23 HLA‐DRB1*15‐negative), and seven non‐neurological controls on motor cortical, cervical and lumbar spinal cord tissue. Biglycan and decorin demonstrate a striking perivascular expression pattern in controls that is reduced in MS (−36.5%, p = 0.036 and − 24.7%, p = 0.039; respectively) in lesional and non‐lesional areas. A concomitant increase in diffuse parenchymal accumulation of biglycan and decorin is seen in MS (p = 0.015 and p = 0.001, respectively), particularly in HLA‐DRB1*15‐positive cases (p = 0.007 and p = 0.046, respectively). Prolargin shows a faint parenchymal pattern in controls that is markedly increased in MS cases where a perivascular deposition pattern is observed (motor cortex +97.5%, p = 0.001; cervical cord +49.1%, p = 0.016). Our findings point to ECM proteins and the vascular interface playing a central role in MS pathology within and outside the plaque area. As ECM proteins are known potent pro‐inflammatory molecules, their parenchymal accumulation may contribute to disease severity. This study brings to light novel factors that may contribute to the heterogeneity of the topographical variation of MS pathology. [ABSTRACT FROM AUTHOR]

Fused filament fabrication (FFF) is one of the additive manufacturing processes which has gained more interest because of its simplicity and low-cost. This technology is similar to the conventional metal injection moulding (MIM) process, consisting of the feedstock preparation of metal powder and polymer binders, followed by layer-by-layer 3D printing (FFF) or injection (MIM) to create green parts and, finally, debinding and sintering. Moreover, both technologies provide near-dense parts. This work presents an in-depth study of the processing method's influence. The porosity, microstructure, hardness, corrosion, and tribocorrosion behaviour are compared for 17-4 PH SS samples processed from powder by additive manufacturing using FFF and MIM, as well as conventional powder metallurgy (PM) samples. MIM samples exhibited the highest macro and microhardness, while corrosion behaviour was similar for both MIM and FFF samples, but superior in comparison to conventional PM samples. However, the FFF-as fabricated samples displayed a significant improvement in tribocorrosion resistance that could be explained by the higher proportion of delta ferrite and retained austenite in their microstructure. [ABSTRACT FROM AUTHOR]

High-quality antiferromagnetic Mott insulator thin films of LaTiO3 (LTO) were epitaxially grown onto SrTiO3 (STO) (110) substrates using the pulsed laser deposition. The LTO/STO heterostructures are not only highly conducting and ferromagnetic, but also show Kondo effect, Shubnikov-de Haas (SdH) oscillations with a nonzero Berry phase of π, and low-field hysteretic negative magnetoresistance (MR). Angle-dependent SdH oscillations and a calculation of the thickness of the interfacial conducting layer indicate the formation of a 4-nm high mobility two-dimensional electron gas (2DEG) layer at the interface. Moreover, an amazingly large low-field negative MR of ∼61.8% is observed at 1.8 K and 200 Oe, which is approximately one to two orders of magnitude larger than those observed in other spin-polarized 2DEG oxide systems. All these results demonstrate that the 2DEG is spin-polarized and the 4-nm interfacial layer is ferromagnetic, which are attributed to the presence of magnetic Ti3+ ions due to interfacial oxygen vacancies and the diffusion of La3+ ions into the STO substrate. The localized Ti3+ magnetic moments couple to high mobility itinerant electrons under magnetic fields, giving rise to the observed low-field MR. Our work demonstrates the great potential of antiferromagnetic titanate oxide interface for designing spin-polarized 2DEG and spintronic devices. [ABSTRACT FROM AUTHOR]

CAR-T cell therapy is known as an effective therapy in patients with hematological malignancies. Since 2017, several autologous CAR-T cell (auto-CAR-T) drugs have been approved by the US Food and Drug Administration (FDA) for the treatment of some kinds of relapsed/refractory hematological malignancies. However, some patients fail to respond to these drugs due to high manufacturing time, batch-to-batch variation, poor quality and insufficient quantity of primary T cells, and their insufficient expansion and function. CAR-T cells prepared from allogeneic sources (allo-CAR-Ts) can be an alternative option to overcome these obstacles. Recently, several allo-CAR-Ts have entered into the early clinical trials. Despite their promising preclinical and clinical results, there are two main barriers, including graft-versus-host disease (GvHD) and allo-rejection that may decline the safety and efficacy of allo-CAR-Ts in the clinic. The successful development of these products depends on the starter cell source, the gene editing method, and the ability to escape immune rejection and prevent GvHD. Here, we summarize the gene editing technologies and the potential of various cell sources for developing allo-CAR-Ts and highlight their advantages for the treatment of hematological malignancies. We also describe preclinical and clinical data focusing on allo-CAR-T therapy in blood malignancies and discuss challenges and future perspectives of allo-CAR-Ts for therapeutic applications. [ABSTRACT FROM AUTHOR]

Periarticular calcifications are a common condition for rheumatologists. They are characterized by deposition of carbonated apatite in tendons or connective tissues around joints. It most commonly affects patients between 30 and 60, and the main location is the shoulder (rotator cuff tendons), followed by the hip. Although the disease is frequent, factors associated with the appearance of the deposits or their spontaneous resorption remain unclear. In this review, we will summarize the available data about mechanisms underlying the constitution of the deposits and their resorption and describe the various affected sites and the associated symptoms. In the last part, we will discuss current treatment options. [ABSTRACT FROM AUTHOR]

This study explores the relationship between oil prices and the Human Development Index (HDI) in the Gulf Cooperation Council (GCC) countries. It investigates whether oil prices remain the primary driver of economic growth and development in the region. The analysis employs a Cross-Sectional Autoregressive Distributed Lag (CS-ARDL) approach and Cointegrated Autoregressive Distributed Lag (CCEMG) methods, following unit root and stationarity tests. The findings reveal an insignificant correlation between oil prices and HDI in the overall GCC countries. However, significant relationships are observed at the individual country level. These results suggest that policymakers in the region should prioritize economic diversification and focus on sectors such as tourism in Dubai and the specific policies implemented in Saudi Arabia to foster sustainable development. [ABSTRACT FROM AUTHOR]

The catalyst layers (CLs) electrode is the key component of the membrane electrode assembly (MEA) in proton exchange membrane fuel cells (PEMFCs). Conventional electrodes for PEMFCs are composed of carbon-supported, ionomer, and Pt nanoparticles, all immersed together and sprayed with a micron-level thickness of CLs. They have a performance trade-off where increasing the Pt loading leads to higher performance of abundant triple-phase boundary areas but increases the electrode cost. Major challenges must be overcome before realizing its wide commercialization. Literature research revealed that it is impossible to achieve performance and durability targets with only high-performance catalysts, so the controllable design of CLs architecture in MEAs for PEMFCs must now be the top priority to meet industry goals. From this perspective, a 3D ordered electrode circumvents this issue with a support-free architecture and ultrathin thickness while reducing noble metal Pt loadings. Herein, we discuss the motivation in-depth and summarize the necessary CLs structural features for designing ultralow Pt loading electrodes. Critical issues that remain in progress for 3D ordered CLs must be studied and characterized. Furthermore, approaches for 3D ordered CLs architecture electrode development, involving material design, structure optimization, preparation technology, and characterization techniques, are summarized and are expected to be next-generation CLs for PEMFCs. Finally, the review concludes with perspectives on possible research directions of CL architecture to address the significant challenges in the future. [ABSTRACT FROM AUTHOR]

Background: Recent studies provide increasing evidence for a relevant role of lifestyle factors including diet in the pathogenesis of neuroinflammatory diseases such as multiple sclerosis (MS). While the intake of saturated fatty acids and elevated salt worsen the disease outcome in the experimental model of MS by enhanced inflammatory but diminished regulatory immunological processes, sugars as additional prominent components in our daily diet have only scarcely been investigated so far. Apart from glucose and fructose, galactose is a common sugar in the so-called Western diet. Methods: We investigated the effect of a galactose-rich diet during neuroinflammation using myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-EAE) as a model disease. We investigated peripheral immune reactions and inflammatory infiltration by ex vivo flow cytometry analysis and performed histological staining of the spinal cord to analyze effects of galactose in the central nervous system (CNS). We analyzed the formation of advanced glycation end products (AGEs) by fluorescence measurements and investigated galactose as well as galactoseinduced AGEs in oligodendroglial cell cultures and induced pluripotent stem cellderived primary neurons (iPNs). Results: Young mice fed a galactose-rich diet displayed exacerbated disease symptoms in the acute phase of EAE as well as impaired recovery in the chronic phase. Galactose did not affect peripheral immune reactions or inflammatory infiltration into the CNS, but resulted in increased demyelination, oligodendrocyte loss and enhanced neuro-axonal damage. Ex vivo analysis revealed an increased apoptosis of oligodendrocytes isolated from mice adapted on a galactose-rich diet. In vitro, treatment of cells with galactose neither impaired the maturation nor survival of oligodendroglial cells or iPNs. However, incubation of proteins with galactose in vitro led to the formation AGEs, that were increased in the spinal cord of EAE-diseased mice fed a galactose-rich diet. In oligodendroglial and neuronal cultures, treatment with galactose-induced AGEs promoted enhanced cell death compared to control treatment. Conclusion: These results imply that galactose-induced oligodendrocyte and myelin damage during neuroinflammation may be mediated by AGEs, thereby identifying galactose and its reactive products as potential dietary risk factors for neuroinflammatory diseases such as MS. [ABSTRACT FROM AUTHOR]

Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two neuroprotective and anti-inflammatory molecules of the central nervous system (CNS). Both bind to three G protein-coupled receptors, namely PAC1, VPAC1 and VPAC2, to elicit their beneficial effects in various CNS diseases, including multiple sclerosis (MS). In this study, we assessed the expression and distribution of PACAP/VIP receptors in the normal-appearing white matter (NAWM) of MS donors with a clinical history of either relapsing–remitting MS (RRMS), primary MS (PPMS), secondary progressive MS (SPMS) or in aged-matched non-MS controls. Gene expression studies revealed MS-subtype specific changes in PACAP and VIP and in the receptors' levels in the NAWM, which were partly corroborated by immunohistochemical analyses. Most PAC1 immunoreactivity was restricted to myelin-producing cells, whereas VPAC1 reactivity was diffused within the neuropil and in axonal bundles, and VPAC2 in small vessel walls. Within and around lesioned areas, glial cells were the predominant populations showing reactivity for the different PACAP/VIP receptors, with distinctive patterns across MS subtypes. Together, these data identify the differential expression patterns of PACAP/VIP receptors among the different MS clinical entities. These results may offer opportunities for the development of personalized therapeutic approaches to treating MS and/or other demyelinating disorders. [ABSTRACT FROM AUTHOR]

Introduction: Small-cell lung cancer (SCLC) is an aggressive form of cancer with a poor prognosis. The two-year survival rate is 8% of all cases. Case presentation: We present the case of a male patient who was 50 years old at the time of diagnosis in May 2022. He was diagnosed with extensive-stage small-cell lung cancer, treated with immunotherapy in combination with chemotherapy (Durvalumab in combination with Etoposide plus Carboplatin) as a first-line treatment, followed by maintenance immunotherapy. In December 2023, a PET-CT scan revealed progressive disease with multiple metastases. Chemotherapy was reinitiated with Etoposide plus Cisplatin in January 2024. After two cycles of chemotherapy, the patient developed post-chemotherapy anemia, for which treatment with Epoetinum alpha was initiated. Chemotherapy was continued for another five cycles, until May 2024, with the maintenance of hemoglobin at a level within 9.9 mg/dL–11 mg/dL. Upon assessment at the end of May 2024, the patient presented an ECOG = 2 performance status, with a moderate general state, moderate-intensity fatigue, no pain, no anxiety or depression and no dyspnea. Discussions, Literature Review and Conclusions: Reinitiating chemotherapy after the failure of maintenance immunotherapy may be an option in patients with SCLC. Epoetinum allows oncological treatment by preventing chemotherapy-induced anemia. [ABSTRACT FROM AUTHOR]

Inborn errors of metabolism (IEMs) and immunity (IEIs) are Mendelian diseases in which complex phenotypes and patient rarity have limited clinical understanding. Whereas few genes have been annotated as contributing to both IEMs and IEIs, immunometabolic demands suggested greater functional overlap. Here, CRISPR screens tested IEM genes for immunologic roles and IEI genes for metabolic effects and found considerable previously unappreciated crossover. Analysis of IEMs showed that N-linked glycosylation and the hexosamine pathway enzyme Gfpt1 are critical for T cell expansion and function. Further, T helper (TH1) cells synthesized uridine diphosphate N-acetylglucosamine more rapidly and were more impaired by Gfpt1 deficiency than TH17 cells. Screening IEI genes found that Bcl11b promotes the CD4 T cell mitochondrial activity and Mcl1 expression necessary to prevent metabolic stress. Thus, a high degree of functional overlap exists between IEM and IEI genes, and immunometabolic mechanisms may underlie a previously underappreciated intersection of these disorders. Editor's summary: Inborn errors of metabolism (IEMs) and immunity (IEIs) are two groups of monogenic disorders whose study has offered insights into fundamental human biology. Patterson et al. used CRISPR screens of mouse CD4 T cells disrupting known IEM and IEI genes to test potential overlapping immunometabolic regulators of T cell function. This approach revealed hundreds of previously unappreciated players, including N-linked glycosylation and the de novo hexosamine synthesis enzyme Gfpt1, which were critical for T cell expansion and function. Moreover, Bcl11b, a player in thymic T cell differentiation, promoted mitochondrial activity and prevented metabolic stress in CD4 T cells. —Seth Thomas Scanlon [ABSTRACT FROM AUTHOR]

Background: Autologous stem cell transplantation (ASCT) is a potentially curative strategy for relapse or refractory(r/r) aggressive lymphoma. However, a proportion of lymphoma patients who are at high risk of mobilization failure fail to mobilize stem cells and cannot proceed to ASCT. The aim of this study is to explore the efficacy and safety of Etoposide combined with Cytarabine (EA) plus G-CSF mobilization in poor mobilizers (PMs) with r/r aggressive lymphoma. Methods: This retrospective study analyzed the outcomes of chemomobilization based on EA (Etoposide 0.1 g/m2, qd d1~3; AraC 0.5 g/m2, q12h d1~3) in 98 patients with r/r aggressive lymphoma. Of these, 39 patients met the criteria for predicted PMs as proposed by the Gruppo Italiano Trapianto di Midollo Osseo working group. Results: Of the 39 PMs, 38(97.4%) patents harvested adequate mobilization (=2×106 CD34+ cells/kg), while 31(79.5%) patients achieved optimal mobilization (=5×106 CD34+ cells/kg). Overall, the mean number of CD34+ cells/kg collected was 17.99(range: 1.08~83.07) ×106 with an average of 1.4 apheresis sessions, and the number was 15.86(range: 0.37~83.07) ×106 for the first apheresis, respectively. A single apheresis procedure was sufficient to reach the target yield of adequate mobilization in 35(89.7%) PMs, while 76.9% of PMs achieved optimal collection within two apheresis sessions. We observed acceptable hematological toxicity and antibiotic usage exposure in 26 patients with a mean duration of 3.6 days. No grade 4 infection or mobilization-related mortality was recorded. Most patients underwent ASCT and achieved successful hematopoietic recovery with prompt engraftment duration, except for one NK/T-cell lymphoma patient who succumbed to severe septicemia after receiving conditioning chemotherapy. Conclusion: Our findings indicate that EA plus G-CSF is an effective and tolerable CD34+ stem cell mobilization strategy for patients with r/r lymphoma, including those predicted to be PMs. This regimen could be an option for patients with r/r lymphoma, particularly those undergoing mobilization for salvage ASCT therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: The chemotherapy combination rituximab, gemcitabine, and dexamethasone (R-GDP), followed by high-dose chemotherapy and autologous stem cell transplantation, is one of the standards of care for relapsed or refractory B-cell non-Hodgkin lymphoma (R/R NHL). Complete metabolic response before transplantation is the most important prognosis factor for a long duration of remission. Selinexor is an oral, selective inhibitor of the nuclear export compound (XPO1). For heavily pretreated patients with DLBCL, the single drug selinexor has previously shown an overall response rate of 29%. In this study, we evaluated selinexor in combination with RGDP for patients with R/R B-cell lymphoma. The results from our phase I clinical study indicate that weekly selinexor plus RGDP has a generally tolerable safety profile and durable efficacy in R/R B-NHL. Purpose: Selinexor is an oral selective inhibitor of exportine-1 (XPO1) with efficacy as a single agent in heavily pretreated diffuse large B-cell lymphoma (DLBCL). We conducted a study investigating the combination of selinexor with rituximab and platinum-based chemotherapy in B-cell lymphoma. Patients and methods: We conducted a phase 1b, dose-escalation, and expansion trial, which enrolled patients with relapsed or refractory B-cell non-Hodgkin lymphoma. Patients received oral selinexor according to a 3 + 3 design in combination with rituximab and dexamethasone, high-dose cytarabine, oxaliplatine (DHAOX) or gemcitabine, dexamethasone, and cisplatin (GDP) chemotherapy. Results: A total of 39 patients were enrolled, 27 during the escalation phase and 12 during the expansion phase. Most patients had diffuse large B-cell lymphoma (DLBCL; 77%). Group R-DHAOX was prematurely closed to inclusion due to a recommendation from the French drug agency, independent of this trial. A recommended phase 2 dose (RP2D) of selinexor in association with R-GPD was established at 40 mg on days 1, 8, and 15 of each 21-day cycle. In a population of 18 patients treated at this dose of selinexor, the most frequent grade 3–4 adverse events were hematological. With this regimen, seven obtained a complete metabolic response and five a partial response. The median PFS was 5.8 months. Conclusions: Among the patients with R/R B-cell lymphoma, selinexor at a weekly dose of 40 mg with R-GDP is feasible for outpatients, with a generally acceptable safety profile. [ABSTRACT FROM AUTHOR]

Understanding complex urban systems necessitates untangling the relationships between diverse urban elements such as population, infrastructure, and socioeconomic activities. Scaling laws are basic but effective rules for evaluating a city's internal growth logic and assessing its efficiency by investigating whether urban indicators scale with population. To date, only limited research has empirically explored the scaling relations between variables of urban mobility in mega-cities at an intra-urban scale of a few meters. Using multiple urban-sensed and human-sensed data, this study proposes a thorough framework for quantifying the scaling laws in a city. To begin, urban mobility networks are built by aggregating population flows using large-scale mobile phone tracking data. To demonstrate the spatiotemporal variability of urban mobility, various network-based mobility measures are proposed. Following that, three different features of urban mobility laws are exposed, explaining spatial agglomeration, spatial hierarchical structures, and the temporal growth process. The scaling correlations between urban indicators pertaining to socioeconomic features and infrastructure and a mobility-population measure are then quantified using multi-sourced urban-sensed data. Applying this framework to the case study of Shenzhen, China revealed (a) spatial travel heterogeneity, hierarchical spatial structures, and mobility growth, and (b) not only a robust sub-linear relationship between infrastructure volume and population, but also a sub-linear relationship for socioeconomic activity. The identified scaling laws, both in terms of mobility measures and urban indicators, provide a multi-faceted portrait of the spatio-temporal variations of urban settings, allowing us to better understand intra-urban developments and, consequently, provide critical policy evaluations and suggestions for improving intra-urban efficiency in the future. [ABSTRACT FROM AUTHOR]

Introduction: Microglia (MG) is suggested to play an immunopathological role of in Multiple Sclerosis (MS). Since hyper-reflective foci (HRF) might mark MG activation, in vivo analysis by Optic Coherence Tomography (OCT) in MS patients under disease modifying therapies may help to clarify MS immunopathology as well as drug's mechanism of intrathecal action. Objective: To analyze HRF in patients treated with Natalizumab (NTZ), a high efficacy therapy for MS. Materials and methods: The effect of NTZ on the retina of 36 Relapsing-Remitting MS patients was investigated in a prospective, single-center study. OCT was performed immediately before the first infusion and then between infusion 3 and 4, infusion 6 and 7, infusion 11 and 13. Peripapillary and macular scans were acquired, evaluating peripapillary RNFL thickness, macular volumes (vertical scans), and HRF count (horizontal scan) in Ganglion Cell Layer (GCL), Inner Plexiform Layer (IPL) and Inner Nuclear Layer (INL). Clinical examination was performed every six months. Results: HRF count significantly increased under NTZ therapy (p<0.001) in both GCL (18.85 ± 6.93 at baseline, 28.24 ± 9.55 after 12 months) and IPL (25.73 ± 7.03 at baseline, 33.21 ± 8.50 after 12 months) but remained stable in INL (33.65 ± 7.76 at baseline, 36.06 ± 6.86 after 12 months, p=0.87), while no relevant modification of pRNFL and macular volumes were observed during the study. EDSS remained stable and no clinical relapse was observed between month 6 and 12. Conclusion: In RRMS NTZ affects HRF count in GCL and IPL, but not in INL, suggesting that NTZ does not impact on some aspects of MS immunopathology. [ABSTRACT FROM AUTHOR]

Background: Primary pulmonary myxoid sarcoma (PPMS) is a rare, low-grade malignant tumor, constituting approximately 0.2% of all lung tumors. Despite its rarity, PPMS possesses distinctive histological features and molecular alterations, notably the presence of EWSR1-CREB1 gene fusion. However, its precise tissue origin remains elusive, posing challenges in clinical diagnosis. Case demonstration: A 20-year-old male patient underwent a routine physical examination 6 months prior, revealing a pulmonary mass. Following surgical excision, microscopic evaluation unveiled predominantly short spindle-shaped tumor cells organized in a fascicular, beam-like, or reticular pattern. The stromal matrix exhibited abundant mucin, accompanied by lymphocytic and plasma cell infiltration, with Russell bodies evident in focal areas. Immunophenotypic profiling revealed positive expression of vimentin and epithelial membrane antigen in tumor cells, whereas smooth muscle actin and S-100, among others, were negative. Ki-67 proliferation index was approximately 5%. Subsequent second-generation sequencing identified the characteristic EWSR1-CREB1 gene fusion. The definitive pathological diagnosis established PPMS. The patient underwent no adjuvant chemotherapy or radiotherapy and remained recurrence-free during a 30-month follow-up period. Conclusions: We report a rare case of PPMS located within the left lung lobe interlobar fissure, featuring Russell body formation within the tumor stroma, a novel finding in PPMS. Furthermore, the histomorphological characteristics of this case highlight the diagnostic challenge it poses, as it may mimic inflammatory myofibroblastic tumor, extraskeletal myxoid chondrosarcoma, or hemangiopericytoma-like fibrous histiocytoma. Therefore, accurate diagnosis necessitates an integrated approach involving morphological, immunohistochemical, and molecular analyses. [ABSTRACT FROM AUTHOR]