Mantle cell lymphoma is an aggressive, heterogeneous B-cell malignancy characterized by frequent relapse, therapeutic resistance, and poor long-term survival in advanced disease. Recent advances in targeted therapy, cellular immunotherapy, and molecular profiling have transformed management. This review summarizes emerging strategies, resistance mechanisms, and translational approaches, emphasizing Bruton tyrosine kinase (BTK) inhibitors, CAR T-cell therapy, bispecific antibodies, SOX11-directed therapy, venetoclax regimens, and precision medicine. A comprehensive narrative review analyzed recent preclinical studies, clinical trials, translational research, and real-world evidence on treatment and resistance biology, focusing on targeted therapies, immunotherapy, molecular biomarkers, and cellular engineering. Therapeutic advances have improved outcomes in relapsed/refractory disease: covalent and noncovalent BTK inhibitors, CAR T-cell therapy, bispecific antibodies, and venetoclax combinations demonstrate significant antitumor activity. However, resistance driven by clonal evolution, antigen escape, tumor microenvironment remodeling, and drug-tolerant persister cells limits durable remission. SOX11-targeted approaches, gene-editing technologies, and measurable residual disease monitoring offer translational promise. Molecular profiling and immunotherapeutics are reshaping personalized management. Combination therapies and biomarker-guided selection may overcome resistance and enhance survival, though treatment toxicity, limited accessibility, and high costs pose challenges. Targeted and cellular therapies are redefining paradigms; precision medicine, resistance-directed strategies, and immunotherapeutic combinations could improve long-term control. This review uniquely integrates evidence on resistance biology, SOX11 therapy, CAR T-cell failure mechanisms, and precision strategies. Future studies should prioritize biomarker-driven approaches, CAR T-cell optimization, safer agents, and accessible treatments for refractory cases.

The surgical options for medically refractory trigeminal neuralgia (TN) are diverse, with limited comparative evidence. This study evaluates and compares pain-free period and time to recurrence for patients who underwent microvascular decompression (MVD), gamma knife radiosurgery (GKRS), and radiofrequency ablation (RFA). A retrospective review of patients with medically refractory TN over a 10-year period from 2009 to 2018 at a tertiary neurosurgical center was performed. Patients with at least 1 year of follow-up after the treatment procedure were included. Clinical details, radiological records, intraoperative findings, and treatment details of radiosurgery and ablative procedures were recorded. A total of 189 patients were included, the mean age being 52.54 (± 13.3) years, with a male:female ratio of 1.52:1. The mean duration of symptoms was 70.19 (± 57.6) months, with 86.3% of patients presenting with type 1 neuralgia. The median follow-up duration was 84, 100, and 67 months for MVD, GKRS, and RFA, respectively. The percentages of patients with favorable outcomes (Barrow Neurological Institute Pain Intensity Score [BNI I-IIIa]) were 87.8, 67.3, and 66.5%, respectively, for MVD, GKRS, and RFA. The median pain-free intervals were 65, 59, and 36 months, with recurrence rates of 24.2, 25, and 40.5% for MVD, GKRS, and RFA, respectively. This study reaffirms MVD as the best first-line treatment for medically refractory TN, with GKRS being a useful alternative in patients who are surgically unfit or unwilling, and an optimum second-line treatment for those with recurrences. RFA is useful as an adjunct in patients unfit for surgery, with a high initial efficacy albeit with high recurrence rates.

The objective was to prepare guidelines to perform the current optimum treatment by organizing effective and efficient treatments of hemangiomas and vascular malformations, confirming the safety, and systematizing treatment, employing evidence-based medicine techniques and aimed at improvement of the outcomes. Clinical questions (CQs) were decided based on the important clinical issues. For document retrieval, key words for literature searches were set for each CQ and literature published from 1980 to the end of December 2020 was searched in PubMed, and Japana Centra Revuo Medicina (JCRM). The strengths of evidence and recommendations acquired by systematic reviews were determined following the Medical Information Network Distribution Service (Minds) technique. A total of 38 CQs were used to compile recommendations and the subjects included efficacy of resection, sclerotherapy/embolization, drug therapy, laser therapy, radiotherapy, and other conservative treatment, differences in appropriate treatment due to the location of lesions and among symptoms, appropriate timing of treatment and tests, pathological diagnosis deciding the diagnosis, and causal genes of vascular anomalies. Thus, the Japanese Clinical Practice Guidelines for Vascular Tumors, Vascular Malformations, Lymphatic Malformations, and Lymphangiomatosis 2022 have been prepared as the evidence-based guidelines for the management of vascular anomalies.

The objective was to prepare guidelines to perform the current optimum treatment by organizing effective and efficient treatments of hemangiomas and vascular malformations, confirming the safety, and systematizing treatment, employing evidence-based medicine techniques and aimed at improvement of the outcomes. Clinical questions (CQs) were decided based on the important clinical issues. For document retrieval, key words for literature searches were set for each CQ and literature published from 1980 to the end of December 2020 was searched in PubMed, and Japana Centra Revuo Medicina (JCRM). The strengths of evidence and recommendations acquired by systematic reviews were determined following the Medical Information Network Distribution Service (Minds) technique. A total of 38 CQs were used to compile recommendations and the subjects included efficacy of resection, sclerotherapy/embolization, drug therapy, laser therapy, radiotherapy, and other conservative treatment, differences in appropriate treatment due to the location of lesions and among symptoms, appropriate timing of treatment and tests, pathological diagnosis deciding the diagnosis, and causal genes of vascular anomalies. Thus, the Japanese Clinical Practice Guidelines for Vascular Tumors, Vascular Malformations, Lymphatic Malformations, and Lymphangiomatosis 2022 have been prepared as the evidence-based guidelines for the management of vascular anomalies.

Hybrid additive manufacturing (HAM) of aluminum alloys integrates additive and conventional fabrication routes to achieve complex geometries, design flexibility, and material efficiency. Significant thermal and microstructural variations often occur between the built and substrate regions, despite the advantages of HAM. This can be attributed to differences in heat input, solidification rate, and thermal conductivity. These irregularities introduce residual stresses and uneven phase distributions, often creating weak interfacial zones that compromise strength, corrosion resistance, and dimensional precision. In this study, a critical examination of the origins and implications of thermal mismatch and microstructural heterogeneity in hybrid additively manufactured aluminum alloys is conducted. This study emphasizes the interaction between processing conditions, material composition, and build orientation, significantly influencing heat distribution and interfacial evolution in additively manufactured systems. Consequently, approaches such as substrate preheating, scan path optimization, compositional grading, and postdeposition heat treatments are discussed in relation to their capacity to mitigate these effects, hence promoting improved microstructural uniformity and enhanced interfacial cohesion. Furthermore, emerging modeling tools and advanced characterization techniques, like electron backscatter diffraction (EBSD) and high‐resolution Scanning Electron Microscopy (SEM), are noted for their role in understanding microstructure–property relationships. The review concludes by identifying current challenges and proposing future pathways toward achieving thermal compatibility, enhanced reliability, and consistent performance in hybrid additively manufactured aluminum components.

Rilzabrutinib for patients with moderate-to-severe asthma with uncontrolled symptoms: a double-blind, placebo-controlled, phase 2 study.

Abstract Pleomorphic adenomas are the most common benign tumours of the salivary glands. Pleomorphic adenomas in nasal cavity are extremely rare and are often misdiagnosed, as they have higher myoepithelial cellularity in comparison to myxoid stroma. We present a case of a 45-year-old Nigerian patient with a history of left sided septal swelling slowly growing over 2 years. The patient had a biopsy in Nigeria. Pathology there suggested a squamous cell carcinoma of the nasal septum and he was referred for wide local excision and radiotherapy. The patient presented in London for a second opinion where he had a thorough clinical, endoscopic and radiological assessment. He later went on to have full macroscopic resection of the septal lesion and subsequent histopathological examination was consistent with pleomorphic adenoma with clear margins. Pleomorphic adenomas are rare benign tumours of the nasal septum but should be kept in the differential diagnosis. Review of the literature reveals that optimum treatment for pleomorphic adenoma consists of surgical excision with wide margins to prevent recurrence; the surgical approach used in this patient was end nasal endoscopic resection. We present a further literature review and discussion regarding management.

The objective was to prepare guidelines to perform the current optimum treatment by organizing effective and efficient treatments of hemangiomas and vascular malformations, confirming the safety, and systematizing treatment, employing evidence-based medicine techniques and aimed at improvement of the outcomes. Clinical questions (CQs) were decided based on the important clinical issues. For document retrieval, key words for literature searches were set for each CQ and literature published from 1980 to the end of December 2020 was searched in PubMed, and Japana Centra Revuo Medicina (JCRM). The strengths of evidence and recommendations acquired by systematic reviews were determined following the Medical Information Network Distribution Service (Minds) technique. A total of 38 CQs were used to compile recommendations and the subjects included efficacy of resection, sclerotherapy/embolization, drug therapy, laser therapy, radiotherapy, and other conservative treatment, differences in appropriate treatment due to the location of lesions and among symptoms, appropriate timing of treatment and tests, pathological diagnosis deciding the diagnosis, and causal genes of vascular anomalies. Thus, the Japanese clinical practice guidelines for vascular tumors, vascular malformations, lymphatic malformations, and lymphangiomatosis 2022 have been prepared as the evidence-based guidelines for the management of vascular anomalies.

The objective was to prepare guidelines to perform the current optimum treatment by organizing effective and efficient treatments of hemangiomas and vascular malformations, confirming the safety, and systematizing treatment, employing evidence-based medicine techniques and aimed at improvement of the outcomes. Clinical questions (CQs) were decided based on the important clinical issues. For document retrieval, key words for literature searches were set for each CQ and literature published from 1980 to the end of December 2020 was searched in PubMed, and Japana Centra Revuo Medicina (JCRM). The strengths of evidence and recommendations acquired by systematic reviews were determined following the Medical Information Network Distribution Service (Minds) technique. A total of 38 CQs were used to compile recommendations and the subjects included efficacy of resection, sclerotherapy/embolization, drug therapy, laser therapy, radiotherapy, and other conservative treatment, differences in appropriate treatment due to the location of lesions and among symptoms, appropriate timing of treatment and tests, pathological diagnosis deciding the diagnosis, and causal genes of vascular anomalies. Thus, the Japanese Clinical Practice Guidelines for Vascular Tumors, Vascular Malformations, Lymphatic Malformations, and Lymphangiomatosis 2022 have been prepared as the evidence-based guidelines for the management of vascular anomalies.

In general, particle board uses formaldehyde-based synthetic adhesives. One of the ways of minimizing the use of synthetic adhesives is by using natural adhesives such as citric acid and sucrose. Previous studies on particle board particularly regarding the physical and mechanical properties of particle board made of dregs and bark fiber of sago (Metroxylon spp) based on layer composition and citric acid-sucrose ratio, show that in addition to its physical and mechanical properties, the quality of particle board is also determined by its resistance to attacks by wood destroying organisms such as termites (Coptotermes curvignathus). This study used a completely randomized factorial design (CRD) with two factors, namely layer composition (70/30, 60/40, 50/50) and citric acid- sucrose ratio (0/100, 25/75, 75/ 25, 100/0). The research found that the value of weight loss in the sample that was fed to termites at the end of the test was 7.32-13.22%. The highest average weight loss value was found in the particle layer composition of 50/50 and the citric acid to sucrose ratio of 0/100, which was 13.22%. Meanwhile, the lowest average weight loss value was found in particleboard with the particle layer composition of 70/30 and the citric acid to sucrose ratio of 100/0, which was 7,3207%. The highest percentage of termite mortality, which reached 100%, was found in particle board with the particle layer composition of 70/30 with the citric acid to sucrose ratio of 100/0. Meanwhile, the lowest percentage of termite mortality was 89.81% in a 50/50 layer composition with a 0/100 citric acid to sucrose ratio. Particle board made of sago fiber and bark with a layer composition of 70/30 and a ratio of citric acid to sucrose of 100/0, classified under class 2 durability, is the optimum treatment to resist termite attack.

Multidrug-resistant tuberculosis (MDR-TB) is an urgent public health challenge in Namibia, with profound socioeconomic consequences. The high burden of both tuberculosis and HIV complicates treatment and underscores the need for optimised drug therapies. Precision medicine, which leverages patient-specific genetic and molecular information, offers promise for improving MDR-TB outcomes. However, its effective application relies on population-specific data, particularly understanding how individuals metabolise tuberculosis drugs and how genetic diversity drives variability in treatment response. Currently, no pharmacokinetic (PK) or pharmacogenetic (PG) data on TB treatment exist for Namibian populations. This gap is particularly concerning, given the country's genetic diversity, environmental factors and comorbidities that may uniquely influence drug metabolism. This study aims to generate PK and PG data to inform dose optimisation and support personalised treatment strategies for MDR-TB in Namibia. The findings will contribute to improved patient care and inform health system strengthening based on locally relevant evidence. This cross-sectional study will consist of 100 Namibian participants with matched human DNA and PK data of MDR-TB cases receiving isoniazid, clofazimine, bedaquiline and the fluoroquinolones (levofloxacin or moxifloxacin). PK sampling will be divided as follows: 30 individuals will undergo intensive PK sampling, while the remaining (n=70) will undergo sparse PK sampling. DNA will be extracted at Stellenbosch University (SU), and samples will be genotyped using the H3Africa microarray. Sequences will be aligned to the human reference genome, hg38 (GRCh38p13), using the freely available Burrows-Wheeler Aligner. A subset of the samples (n=20-30) will undergo whole genome sequencing (WGS) to verify imputation results and identify novel genetic variants potentially affecting PK in this population. Quality control and variant call format file generation will be performed using the Genome Analysis Toolkit best practices (V.3.5). Intensive and sparse PK data will be pooled for the development of a population PK (popPK) model using a non-linear mixed-effects modelling approach. The popPK model will characterise the relationship between TB drug dose and exposure, including quantifying covariates, including genetic variation, explaining PK variability, providing a foundation for dose optimisation and personalised treatment strategies. Ethics approval was obtained from the University of Namibia Human Research Ethics Committee for Health (Ref. SOM18/2024), the Ministry of Health and Social Services (Ref. 22/4/2/3), the SU Health Research Ethics Committee (Ref. N21/11/136) and the University of Cape Town Human Research Ethics Committee (Ref. 500/2022).

The choice of appropriate treatment aids holds paramount significance in achieving optimum treatment outcomes. Rehabilitation of large craniofacial defects following conventional workflow is challenging and is influenced by the required material properties, operator's expertise and anatomical complexity. A woman in her early 30s was referred for the prosthetic rehabilitation of an extensive facial defect following traumatic avulsion from a fodder-cutting machine. The defect involved the frontal bone, orbit, cheek and upper lip on the right side, including complete nose. Analogue impressions were unsuccessful in recording the tissue bed accurately and in a resting state.A predominantly digital workflow was employed for prosthesis fabrication. Facial scanning using structured light technology obtained a precise and detailed three-dimensional (3D) model of the entire face including the defect. A computer-aided design software programme was used to duplicate and mirror the normal side of the face on the defect side. A hollow shim and three-part mould were digitally designed and 3D printed. The final prosthesis was processed conventionally using silicone and characterised with extrinsic staining. Eyebrows and eyelashes were sewn in the prosthesis using patient's hair. A combination of medical-grade adhesive and a customised hair wig was employed to achieve both aesthetic integration and functional stability.At 6 months, the prosthesis showed a stable fit and colour, with notable progress in the patient's confidence and social reintegration. The outcome achieved makes a strong case for integrating digital workflow not only for the rehabilitation of extensive facial defects but also in routine clinical practice.

This study examines ultrasonic treatment as an approach to reduce tetracycline and oxytetracycline residues in Acacia honey and its effects on physicochemical properties. An experimental laboratory-based study using a completely randomized design. The study was conducted at the Animal Product Quality Testing and Certification Center (BPMSPH) Laboratory, Bogor City, Indonesia, between October and December 2025. Acacia honey samples artificially contaminated with tetracycline and oxytetracycline were subjected to ultrasonic treatment at a frequency of 40 kHz for 0 (control), 10, 20, and 30 minutes. Antibiotic residues were quantified using high-performance liquid chromatography. Physicochemical parameters including moisture and ash content, water insoluble solids, acidity, hydroxymethyl furfural (HMF) content, and diastase enzyme activity were analyzed using standard analytical methods. Measurements were repeated three times, and the data were subjected to analysis of variance with a significance threshold of P < .05. Ultrasonic treatment reduced tetracycline residues highly significantly (P< .01) and oxytetracycline residues significantly (.01< P < .05), with an optimum treatment duration of 10 minutes. Moisture content, ash content, HMF content, free acidity, reducing sugars, and sucrose were not significantly affected (P > .05), indicating preservation of the main physicochemical characteristics. Water insoluble solids decreased, and diastase enzyme activity remained within acceptable standard limits. Ultrasonic treatment effectively reduced tetracycline and oxytetracycline residues in Acacia honey while maintaining physicochemical quality. Optimization of treatment duration is required to preserve functional properties.

The objective was to prepare guidelines to perform the current optimum treatment by organizing effective and efficient treatments of hemangiomas and vascular malformations, confirming the safety, and systematizing treatment, employing evidence-based medicine techniques and aimed at improvement of the outcomes. Clinical questions (CQs) were decided based on the important clinical issues. For document retrieval, key words for literature searches were set for each CQ and literature published from 1980 to the end of December 2020 was searched in PubMed and Japana Centra Revuo Medicina (JCRM). The strengths of evidence and recommendations acquired by systematic reviews were determined following the Medical Information Network Distribution Service (Minds) technique. A total of 38 CQs were used to compile recommendations and the subjects included efficacy of resection, sclerotherapy/embolization, drug therapy, laser therapy, radiotherapy, and other conservative treatment, differences in appropriate treatment due to the location of lesions and among symptoms, appropriate timing of treatment and tests, pathological diagnosis deciding the diagnosis, and causal genes of vascular anomalies. Thus, the Japanese Clinical Practice Guidelines for Vascular Tumors, Vascular Malformations, Lymphatic Malformations, and Lymphangiomatosis 2022 have been prepared as the evidence-based guidelines for the management of vascular anomalies.

Communities are facing extreme pressure to provide safe water to the fast-growing population, especially in urban regions. Wastewater is a valuable resource which must be used to curb water shortage; otherwise, it would become a lost opportunity. However, the implementation of an effective water reuse scheme faces many techno-economic and social challenges, stressing the need for an integrated approach. This study presents a decision support framework for implementing water reuse in India by synthesizing and evaluating treatment trains for various applications. Compared to previous DSS (Decision Support System) techniques, the study integrates lifecycle cost and performance estimation using MCDM (Multi-Criteria Decision Making) technique and formulates treatment train synthesis to the Indian context. A total of 40 treatment trains have been generated for reuse in agriculture, horticulture, toilet flushing/vehicle washing, environmental, recreational, surface, and groundwater recharge. It can be observed that for agricultural reuse, the optimum treatment train is based on extended aeration followed by the tertiary process with an annual lifecycle cost of USD 3.1 billion (B)/m3/day of wastewater treatment capacity and moderate performance. The results indicate that the treatment requirement and associated life cycle costs vary with the type of reuse application. The evaluation of performance reliability and cost assessment further provides robustness to the developed approach.

Anti-glomerular basement membrane (GBM) disease is a rare autoimmune disease characterized by injury to small blood vessels in the kidneys and/or lungs. IgA nephropathy is the most common primary glomerular disease diagnosed in China. However, the co-occurrence of anti-GBM illness and IgA nephropathy has been infrequently documented in the literature. At present, its mechanism is unknown, the treatment approach is unclear, and the prognosis remains poor. Herein, we report a case of anti-GBM disease complicated with IgA nephropathy, in which renal function returned to normal state following treatment with a combination of prednisone and cyclophosphamide. This case suggests that in patients with anti-GBM disease and IgA nephropathy, the combination of glucocorticoids and cyclophosphamide may serve as an optimum treatment choice.

Vigna unguiculata is the main legume grown in Africa. A major constraint to its production is cowpea mosaic disease (CABMV), transmitted by aphids. This disease can cause yield losses of up to 87%. The objectives of this study were to sanitize contaminated cowpea seeds by thermotherapy and to evaluate agro-morphological parameters in the field. Contaminated seeds from a local accession (Kahkiri) susceptible to CABMV were heat-treated in water baths of 59˚C, 61˚C, 63˚C, 65˚C and 67˚C for 15 minutes. Agronomic parameters were assessed in the field (Pissa, Central African Republic) over a three-month period up to harvest. Overall, although none of the treatment temperatures tested totally eliminated the virus and resulted in 100% CABMV-free seedlings, heat-treated cowpea seeds produced 87.5% plants with a significantly lower incidence and severity of CABMV symptoms than untreated plants. Our results show that 65˚C represents the optimum treatment temperature, with no negative impact on seed regeneration capacity, and for which we observed the highest seed yield (95.77 kg/ha ± 34.71) and biomass (437.98 kg/ha ± 133.7) equivalent to untreated seeds from asymptomatic plants (95.07 kg/ha ± 27.08 and 441.98 kg/ha ± 132.29, respectively), while the yield of seedlings and biomass in plants from contaminated and untreated seeds was the lowest (43.18 kg/ha ± 27.53 and 236.54 kg/ha ± 92.47, respectively).

Spiritual beliefs of many ethnic and religious groups can play a major role in the maintenance of physical and mental health. Integration of spiritual understanding into medical treatment can enhance patient outcomes in many specialties, especially psychiatry. As the Muslim population grows worldwide, the integration of spiritually and culturally sensitive mental healthcare with Islamic principles becomes increasingly important for optimum treatment outcomes. Herein, we discuss the inclusion of spiritual care in the treatment of a young Muslim man with schizophrenia who presented with the belief of being possessed by a jinn, a supernatural being capable of possessing or harming humans. In the context of a biopsychosocial-spiritual model of care, we focus on how Islamic principles augmented our patient's treatment through involvement of an Islamic religious leader (imam) to expertly address this patient's religious-based beliefs. Continuing to integrate spirituality broadly into mental health care should enrich our understanding of human nature and the patient experience and result in better outcomes through holistic medicine.

Periosteal osteosarcomas are rare bone tumors that comprise less than 2% of all bone malignancies. The tumor was previously thought to affect the diaphysis of long bones solely, but Recent case reports have demonstrated its existence in the clavicle, mandible, and scapula. Several factors, including stage, grade, and medullary invasion primarily drive survival and recurrence of periosteal osteosarcomas. Related to its rarity, little data currently exists regarding optimum treatment strategies, including limb amputation, surgical resection, and chemotherapy in the neoadjuvant/adjuvant setting. In this regard, bone pain is the most common manifestation. Pain treatment can include medications such as oral or transdermal opioids. Adjuvant drugs can reduce inflammation and neuropathic pain, including corticosteroids, gabapentinoid agents such as gabapentin or pregabalin, lidocaine patches, tricyclic antidepressants such as amitriptyline, nortriptyline, and desipramine, or selective serotonin-norepinephrine reuptake inhibitors such as duloxetine and venlafaxine. More advanced pain treatment interventions can be provided by interventional pain medicine physicians, such as radiofrequency ablation, peripheral nerve stimulation, spinal cord stimulation, or intrathecal drug delivery systems, when conventional opioids and adjuvants do not adequately provide relief. Molecular workups of case reports have shown common mutations, such as the p53 gene, which may provide utility for future molecular targets. The present investigation aims to synthesize currently available data on periosteal osteosarcomas, including common clinical, histologic, and radiographic presentations. In addition, this review aims to further examine the potential for biomarkers and provide recommendations for treatment and future research direction.

Background: Due to an outbreak of conjunctivitis in Uttarakhand, a large number of cases are being reported to hospitals for management. It was important to document it to learn about its characteristics. Through this study, we put forth the distribution and clinical features of the cases managed at a tertiary care hospital in Dehradun, contributing to the widespread event beyond the state of Uttarakhand. Material and Method: All cases were isolated from other patients and studied. Proper history, clinical features were recorded, managed with the optimum treatment and monitored for the requisite duration to learn the course and resolution. Data was analysed using the Statistical Package for Social Sciences, Chi-square and Fisher test. A P value less than .05 was considered significant. Results: The total number of new patients attending the eye out patient department (OPD) from 1st July to 31st October was 3,381. Out of these 172 patients (5.08%), some presented in one or both eyes. A 5.13% increase was observed in July and August, compared to 0.80% cases and the difference in decline was found to be statistically significant ( P value = .0001). The most significant age group affected was between 20 and 30 years of age. Most common clinical features of presentation were attributed to swelling of the eyes, redness and mucopurulent discharge, found to be statistically significant ( P < .0001). Conclusion: In our study, clinical features are considered to be non-specific for diagnosis, rapid onset and remission with antibiotic therapy could be suggestive of bacterial or even a mixed event of both viral and bacterial aetiology.