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Nisha S Joseph,1 Yu-Tzu Tai,2 Kenneth C Anderson,2 Sagar Lonial1 1Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA; 2Dana-Farber Cancer Institute, Harvard University, Boston, MA, USACorrespondence: Kenneth C AndersonDana-Farber Cancer Institute, Blood Compont, D289, 44 Binney St, Boston, MA, 02115, USATel +1 617 632-2569Email kenneth_anderson@dfci.harvard.eduAbstract: Though survival outcomes in multiple myeloma patients have improved drastically over the past few decades, there still remains an ongoing need for effective and tolerable treatment options in the relapsed and refractory space. Encouragingly, there have been three recent FDA approvals for triple-class refractory multiple myeloma, and there is promising ongoing development of additional agents with varying novel mechanisms of action. Here, we will review the most recent data on both belantamab mafodotin, an antibody drug conjugate (ADC) targeting BCMA, and selinexor, a first-in-class selective inhibitor of XPO1, as well as touch on some of the recently published data for other immunotherapies in development, namely bispecific T cell engagers, ADCs, and CAR-T cell therapies.Keywords: belantamab mafodotin, belamaf, selinexor, relapsed/refractory myeloma, myeloma

Omar Nadeem, Yu-Tzu Tai, Kenneth C Anderson Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USACorrespondence: Omar NadeemDana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave, Boston, MA 02215, USATel +1 617-632-3000Email Omar_Nadeem@dfci.harvard.eduAbstract: The multiple myeloma (MM) therapeutic landscape has evolved significantly with the approval of numerous novel agents, including next generation proteasome inhibitors (PIs), immunomodulatory agents (IMIDs), and monoclonal antibodies (MoABs) targeting CD38 and SLAMF7. While these discoveries have led to an unprecedented improval in patient outcomes, the disease still remains incurable. Immunotherapeutic approaches have shown substantial promise in recent studies of chimeric antigen receptor T-cell (CAR T-cell) therapy, bispecific antibodies, and antibody drug conjugates targeting B-cell maturation antigen (BCMA). This review will highlight these novel and targeted therapies in MM, with particular focus on PIs, IMIDs, MoAb and BCMA-directed immunotherapy.Keywords: immunotherapy multiple myeloma, chimeric antigen receptor T-cell therapy; CAR T-cell therapy, bispecific antibodies, immunomodulatory agents; IMID, monoclonal antibodies; MoAB

This study aims to evaluate the impact of transcatheter radiofrequency ablation on quality-of-life (QOL) and exercise capacity in patients with paroxysmal supraventricular tachycardia (SVT) on stable medical therapy and the extent of symptomatic benefits of this treatment in patients with SVT of different clinical severity. A total of 55 patients with SVT on stable medications for 3 months were randomly selected for either radiofrequency ablation treatment (46 patients) or continuation of medical therapy (medical control group, 9 patients). Severity of SVT was classified based on the frequency and duration of SVT episodes, hemodynamic disturbance, and the presence of preexcited atrial fibrillation during an episode. Treadmill exercise capacity (Bruce protocol) and QOL (questionnaire study and interview) were assessed before and at 3-month intervals for 1 year after the radiofrequency procedure and at 3 months in the medical control group. Thirty-six of 46 patients were successfully ablated in one session, and a QOL measure before and at 3 months after ablation in these patients showed an improvement in total scores for 'General Health Questionnaire' (20.3 +/- 6.2 vs 16.9 +/- 5.3, P < 0.01), 'Somatic Symptoms Inventory' (73.0 +/- 6.0 vs 76.1 +/- 4.1, P < 0.02), and 'Sickness Impact Profile' (12.6 +/- 1.7 vs 4.9 +/- 3.9, P < 0.01). This improvement in QOL was progressive and sustained over a 1-year period. Major arrhythmia limitations, such as apprehension of strenuous activities and long distance travel, were alleviated after a successful procedure. The extent of improvement in QOL was significant for patients considered to have 'mild' or 'severe' arrhythmia.(ABSTRACT TRUNCATED AT 250 WORDS) [ABSTRACT FROM AUTHOR]

Presents information on myeloma from citations and notes of clinicians. Therapeutic applications of proteasome inhibitor PS-341; Comparison of the efficacy of intensified chemotherapy followed by myeloablative therapy/autograft with intensified chemotherapy alone; Prognostic impact of cytogenetic and interphase fluorescence in situ hybridization-defined chromosome 13 deletion in multiple myeloma.

Purpose: Manual wheelchair users with spinal cord injury (SCI) face challenges in wheelchair skill training (WSTr) due to the complexity of learning advanced skills and limited access to rehabilitation services. This review aims to summarize existing WSTr methods for individuals with SCI/disabilities and propose the use of Augmented Reality (AR)-enhanced Immediate Visual Feedback (ARe-IVF) learning modules for wheelie and curbing skill training., Methods: The proposed ARe-IVF learning modules will incorporate AR-enhanced visual feedback, allowing users to visualize spatial and temporal aspects of wheelchair skills and assess their performance through computer vision technology. These modules are designed to tailor the learning experience to each user's SCI level, age, gender, body height, and weight. Key features of the ARe-IVF modules include verbal cues, computer graphic indications, and AR-enhanced feedback to support skill acquisition., Results: The anticipated outcomes of the ARe-IVF modules include improved safety and effectiveness in WSTr by providing intuitive and concise guidance for key movements in wheelie and curbing maneuvers. Additionally, these modules offer an accessible alternative WSTr method for manual wheelchair users, caregivers, and rehabilitation therapists, with potential applications in Rehabilitation Centers, Hospitals, or home settings., Conclusion: The ARe-IVF learning modules present an innovative approach to WSTr for manual wheelchair users with SCI, so that the modules provide promising learning outcomes through tailored, AR-supported feedback. This approach may empower wheelchair users to develop advanced skills with increased safety and confidence, ultimately improving rehabilitation outcomes and expanding training accessibility.

Background: The relationship between serum low-density lipoprotein cholesterol (LDL-C) and the risk of relapse in neuromyelitis optica spectrum disorder (NMOSD) remains uncertain. We aimed to examine the association between serum LDL-C level and relapse in NMOSD patients., Methods: We conducted an analysis of the prospective observational NMOSD cohort study with consecutive 184 hospitalized NMOSD patients from department of neurology. Blood samples were collected to measure LDL-C level upon admission. Primary and relapse were evaluated during hospitalization. The relationship between serum LDL-C level and relapse were analyzed by linear curve fitting analyses. Crude and adjusted odds ratios (OR) of LDL-C for relapse with 95% confidence intervals were analyzed using multiple logistic regression models. ROC curve analysis was used to identify the target lipid-lowering value of LDL-C and the probability of relapse was evaluated by the Kaplan-Meier Plot., Results: Over a mean disease course of 100±87 days, 59.24% (n=109) participants developed relapse with higher LDL-C than the primary group (n=75) ( p <0.001). Adjusted smoothed plots suggested that there were linear relationships between serum LDL-C level and relapse ( p < 0.001). The OR (95% CI) between serum LDL-C level and relapse were 2.67 (1.76-4.04, p <0.001), and 2.38 (1.48-3.83, p <0.001) respectively in NMOSD patients before and after adjusting for potential confounders. The target LDL-C lowering values were 2.795 mmol/L with potential benefits to prevent relapse in NMOSD., Conclusion: In this sample of NMOSD patients, we found that the elevated serum LDL-C was independently and positively associated with the relapse, and serum LDL-C should be well-controlled to prevent the relapse of NMOSD., Competing Interests: The authors declare no competing financial interests., (© 2024 Ding et al.)

Metal ions play a pivotal role in maintaining optimal brain function within the human body. Nevertheless, the accumulation of these ions can result in irregularities that lead to brain damage and dysfunction. Disruptions of metal ion homeostasis can result in various pathologies, including inflammation, redox dysregulation, and blood-brain barrier disruption. While research on metal ions has chiefly focused on neurodegenerative diseases, little attention has been given to their involvement in the onset and progression of stroke. Recent studies have identified cuproptosis and confirmed ferroptosis as significant factors in stroke pathology, underscoring the importance of metal ions in stroke pathology, including abnormal ion transport, neurotoxicity, blood-brain barrier damage, and cell death. Additionally, it provides an overview of contemporary metal ion chelators and detection techniques, which may offer novel approaches to stroke treatment., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: Conflicts of interest: The authors declare no conflicts of interest related to the subject matter or materials discussed in this article.

Background: Motor-sparing local infiltration analgesia (LIA) enhances recovery after total hip arthroplasty (THA) and total knee arthroplasty (TKA). However, LIA can induce local anesthetic systemic toxicity (LAST), sometimes necessitating rescue lipid emulsion therapy. Our institute initiated a pilot study to pretreat patients with lipid emulsion (SMOFlipid ® ) to test its efficacy in mitigating LIA-induced LAST events., Methods: This retrospective study enrolled 1,621 adult patients who received LIA with bupivacaine (2-3 mg/kg, maximum 300 mg) for unilateral primary THA or TKA under general anesthesia between January 2020 and April 2022. A total of 439 patients received lipid pretreatment, while 1,182 did not. Demographics, surgical and anesthesia profiles, along with LAST events affecting the neurological, cardiovascular, and respiratory systems, were compared after propensity score matching for age, sex, body mass index (BMI), and surgery type., Results: The incidence of severe LAST events requiring rescue lipid emulsion slightly decreased after lipid pretreatment (from 2.54 to 2.28 per 1000). Lipid pretreatment significantly reduced the incidence of bradycardia and new-onset arrhythmia (odds ratio: 0.13, adjusted p-value: 0.024) but increased postoperative opioid requirement (odds ratio: 1.71, adjusted p-value: 0.032) after Benjamini-Hochberg correction for multiplicity., Conclusions: The efficacy of lipid pretreatment (SMOFlipid ® 1.5 ml/kg, maximum 100 ml) in mitigating LIA-induced LAST remains controversial. While lipid pretreatment reduced the incidence of new-onset arrhythmia, it showed no clear benefits for neurologic and respiratory outcomes. Additionally, lipid pretreatment might hinder postoperative recovery by increasing the need for rescue opioid analgesia. Further prospective pharmacokinetic studies are required to assess plasma bupivacaine concentrations following LIA and lipid pretreatment, examine their relationship to LAST events, and establish the efficacy and safety of lipid pretreatment., (© 2024. The Author(s).)

Background: Nephroureterectomy with bladder cuff excision is the standard treatment for high-risk upper urinary tract urothelial carcinoma (UTUC). The role of minimally invasive surgery in treating locally advanced UTUC remains controversial. This study aimed to compare the outcomes of open, laparoscopic, and robotic surgeries for managing locally advanced UTUC., Methods: We retrospectively reviewed 705 patients with locally advanced UTUC from multiple institutions throughout Taiwan. Perioperative outcomes and oncological outcomes, such as cancer-specific survival, overall survival, disease-free survival and bladder-free survival, were compared between the open, laparoscopic and robotic groups., Results: The minimally invasive group had better overall and cancer-specific survival (CSS) rates. The 2-year CSS rates of the open, laparoscopic and robotic groups were 71%, 83%, and 77% respectively (p < 0.001). The robotic group had similar outcomes to the laparoscopic group. (p = 0.061, 0.825, 0.341 for OS, CSS, DFS respectively.) More lymph node dissections were performed and more lymph nodes were harvested in the robotic group (p = 0.009)., Conclusions: Our results demonstrated that minimally invasive surgery, including laparoscopic and robotic surgery, for locally advanced UTUC resulted in oncological outcomes that are non-inferior to those of open surgery., (© 2024. The Author(s).)

As the global population ages, the incidence of neurodegenerative diseases such as Alzheimer's and Parkinson's is rapidly rising. These diseases present a significant public health challenge, as they severely impair cognitive and motor functions, ultimately leading to a substantial reduction in quality of life and placing a heavy burden on healthcare systems worldwide. Although several therapeutic agents have been developed to manage the symptoms of these diseases, their effectiveness is often limited, and there remains an urgent need for preventive strategies. Growing evidence indicates that bioactive compounds from natural products possess neuroprotective properties through antioxidant and anti-inflammatory effects, modulating key pathways such as phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and brain-derived neurotrophic factor-tropomyosin receptor kinase B-cAMP response element-binding protein (BDNF-TrkB-CREB), which are crucial for neuronal survival. These compounds may also reduce amyloid-beta and tau pathology, as well as enhance cholinergic neurotransmission by inhibiting acetylcholinesterase activity. By targeting oxidative stress, neuroinflammation, and neurodegeneration, natural products offer a promising approach for both prevention and treatment. These findings suggest that natural products may be promising for preventing and treating neurodegenerative diseases. This review aims to explore the pathogenesis of neurodegenerative diseases, the limitations of current therapies, and the potential role of natural products as therapeutic agents.

The prevalence of social media has significantly facilitated the spread and diffusion of online memes. The Clubhouse voice community application, which gained popularity rapidly during the COVID-19 pandemic and became widely used, can be regarded as a form of internet meme. However, the underlying reasons for this phenomenon have been scarcely explored. In this context, the purpose of this study is to understand the dissemination mechanisms of the Clubhouse voice community. Specifically, this research employs the value-attitude-behavior model to investigate the relationships between social value, attitude, immediate response syndrome, and information spread behavior on Clubhouse. To achieve this objective, the snowball sampling technique was used to recruit Clubhouse users to complete a questionnaire. The collected data were assessed for reliability and validity before being analyzed using structural equation modeling for confirmatory factor analysis and model verification. The results indicated that the social value of joining Clubhouse is positively associated with participants' attitudes toward participation. Additionally, attitudes toward participation were found to be positively associated with both immediate response syndrome and information spread behavior, thus showing a positive association between immediate response syndrome and information spread behavior. This study reveals the pathways of internet meme dissemination, offering insights into the factors driving the formation of internet memes., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Yu-Feng Wu reports financial support was provided by 10.13039/100020595National Science and Technology Council, Taiwan, R.O.C. Yu-Feng Wu reports was provided by Ming Chi University of Technology. Yu-Feng Wu reports a relationship with 10.13039/100020595National Science and Technology Council, Taiwan, R.O.C that includes: funding grants. Yu-Feng Wu reports a relationship with 10.13039/501100019786Ming Chi University of Technology that includes: employment and funding grants. Jian-Hong Ye is one of the associate editors of the Applied Psychology section of Heliyon, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Ovarian clear cell carcinoma (OCCC) has a high incidence in Asia, with a frequent occurrence at an early stage, but without sufficient data on molecular stratification for high-risk patients. Recently, immune-hot features have been proposed as indicators of poor prognosis in early stage OCCC. Specific patterns of intratumoral heterogeneity associated with immune-hot features must be defined. NanoString Digital Spatial Profiling technology (Cold spring biotech corp.) was used to decipher the spatial distribution of the 18-plex protein panel. Regions of interest (ROIs) were collected based on the reference hematoxylin and eosin-stained morphology. Areas of illumination (AOIs) were defined according to the ROI segmentation using the fluorescence signals of the visualization markers pan-cytokeratin (PanCK), CD45, or DNA. Unsupervised hierarchical clustering of 595 AOIs from 407 ROIs showed that the PanCK segments expressed different combinations of immune markers, suggestive of immune mimicry. The following 3 immune-hot clusters were identified: granzyme B-high, immune signal-high , and immune-like cells; the following 2 immune-cold clusters were identified: fibronectin-high and immune checkpoint-high cells. In tumor samples at the International Federation of Gynecology and Obstetrics stage IC1/2 experiencing recurrence, there was an increased occurrence of PanCK+ AOIs with immune signal-high and immune-like cell groups in the papillary morphology surrounded by macrophage lineage tumor-infiltrating immune cells (TIIs). In contrast, for tumor samples at the International Federation of Gynecology and Obstetrics stage IC3/II with recurrence, PanCK+ AOIs were prevalent in the fibronectin-high group, particularly in those with a tubulocystic morphology surrounded by lymphoid lineage non-TIIs. Our study on the spatial profiling of early stage OCCC tumors revealed that the immune mimicry of tumor cells, presence of TIIs, and morphologic patterns were associated with recurrence, which switched during tumor progression., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors have no conflicts of interest relevant to this article.

Competing Interests: The authors have no conflicts of interest relevant to this article.

Competing Interests: The authors have no conflicts of interest relevant to this article.

Abstract: The hypothalamic paraventricular nucleus (PVN) plays a central role in regulating cardiovascular activity and blood pressure. We administered hydroxylamine hydrochloride (HA), a cystathionine-β-synthase inhibitor, into the PVN to suppress endogenous hydrogen sulfide and investigate its effects on the mitogen-activated protein kinase (MAPK) pathway in high salt (HS)-induced hypertension. We randomly divided 40 male Dahl salt-sensitive rats into 4 groups: the normal salt (NS) + PVN vehicle group, the NS + PVN HA group, the HS + PVN vehicle group, and the HS + PVN HA group, with 10 rats in each group. The rats in the NS groups were fed a NS diet containing 0.3% NaCl, while the HS groups were fed a HS diet containing 8% NaCl. The mean arterial pressure was calculated after noninvasive measurement using an automatic sphygmomanometer to occlude the tail cuff once a week. HA or vehicle was infused into the bilateral PVN using Alzet osmotic mini pumps for 6 weeks after the hypertension model was successfully established. We measured the levels of H 2 S in the PVN and plasma norepinephrine using enzyme linked immunosorbent assay. In addition, we assessed the parameters of the MAPK pathway, inflammation, and oxidative stress through western blotting, immunohistochemical analysis, or real-time polymerase chain reaction. In this study, we discovered that decreased levels of endogenous hydrogen sulfide in the PVN contributed to the onset of HS-induced hypertension. This was linked to the activation of the MAPK signaling pathway, proinflammatory cytokines, and oxidative stress in the PVN, as well as the activation of the sympathetic nervous system., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Central poststroke pain (CPSP) is a medical complication that arises poststroke and significantly impacts the quality of life and social functioning of affected individuals. Despite ongoing research, the exact pathomechanisms of CPSP remain unclear, and practical treatments are still unavailable. Our review aims to systematically analyse current clinical and preclinical studies on CPSP, which is critical for identifying gaps in knowledge and guiding the development of effective therapies. The review will clarify the clinical characteristics, evaluation scales and contemporary therapeutic approaches for CPSP based on clinical investigations. It will particularly emphasise the CPSP model initiated by stroke, shedding light on its underlying mechanisms and evaluating treatments validated in preclinical studies. Furthermore, the review will not only highlight methodological limitations in animal trials but also offer specific recommendations to researchers to improve the quality of future investigations and guide the development of effective therapies. This review is expected to provide valuable insights into the current knowledge regarding CPSP and can serve as a guide for future research and clinical practice. The review will contribute to the scientific understanding of CPSP and help develop effective clinical interventions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Obesity among adolescents have become a global public health problem. Exercises can effectively improve the bio-physiological factors of obese adolescents. High-intensive interval training (HIIT) has been applied to obese adolescents. Studies have reported that the Aquatic environment may bring the same or more positive exercise effects as the land environment. Therefore, the purpose of this study was to examine the effects of aquatic and land interventions on selected bio-and physiological variables among obese adolescences., Methods: Twenty-eight obese adolescents who met the requirements participated in and completed this study. The participants were randomly assigned to Aquatic HIIT group (n=17) or Land HIIT group (n=11) for a four-week exercise intervention, 3 time/week. Each Intervention program was one-hour long, including 20 minutes of warm-up, 30 minutes of HIIT and 10 minutes of stretching and relaxation. Bio- and physiological variables including Anthropometry and body composition, Physical Function and blood pressure, and Lipid metabolism indexes were collected before and after the Aquatic and Land interventions., Results: After four weeks of exercise interventions, the body mass, BMI, body fat rate, waist circumference, hip circumference and body water content were significantly reduced ( p <0.05), and the lean body mass were significantly increased ( p <0.05) in both groups. Both group exhibited significant effects in decreasing, systolic blood pressure ( p <0.05), diastolic blood pressure ( p <0.01), and increasing vital capacity and total energy consumption ( p <0.05). The Aquatic HIIT group showed significant effects on reducing Rest heart rate ( p <0.05), but no significant changes in Rest heart rate in Land HIIT group ( p =0.364). The low-density lipoprotein cholesterol in both groups was significantly decreased ( p <0.05). Moreover, the Aquatic HIIT group had significant better improvements ( p <0.05) in lean body mass, waist circumference, waist-to-hip ratio, vital capacity and total energy consumption than Land HIIT group did., Conclusions: The results of the present study demonstrated that in a short-term (4 weeks) both Aquatic and Land HIIT interventions may improve the body composition, physical function, blood pressure and low-density lipoprotein cholesterol (LDL-C) of overweight and obese adolescents. Furthermore, the Aquatic HIIT may be superior than the Land HIIT in weight control among the obese adolescents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liao, Zheng, Xue and Wang.)

Competing Interests: Conflicts of interest: The authors declare no conflicts of interest related to the subject matter or materials discussed in this article.

Objective: This case demonstrated the possibility of using GATA3-positive circulating tumor cells (CTCs) to detect early-stage breast cancer (BrC)., Case Report: The 86 years old female patient received a mammographic examination with no evidence of malignancy (Breast Imaging Reporting and Data System, (BI-RADS category 2). However, CTC testing on the same day revealed four GATA3-positive CTCs in 4 ml of peripheral blood. Core needle biopsy was performed in the suspicious area even with no evidence of malignant image on breast ultrasound. Pathologic examination showed invasive carcinoma of no special type of the breast. The patient then received an oncoplastic partial mastectomy of right breast and sentinel lymph node biopsy. The surgical staging was cT1N0M0. Post-operation follow-up examination showed absence of GATA3-positive CTCs and the presence of HER2/ER positive CTCs., Conclusion: The role of GATA3-positive CTCs as a potential biomarker for early-stage BrC should be explored., (Copyright © 2024. Published by Elsevier B.V.)