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Summary: Radiotherapy (RT) has potential synergistic effects with chimeric antigen receptor (CAR) T but is not widely used as bridging therapy due to logistical challenges and lack of standardised protocols. We analysed RT bridging in a multicentre national cohort of large B‐cell lymphoma patients approved for 3L axicabtagene ciloleucel or tisagenlecleucel across 12 UK centres. Of 763 approved patients, 722 were leukapheresed, 717 had data available on bridging therapy. 169/717 (24%) received RT bridging, 129 as single modality and 40 as combined modality treatment (CMT). Of 169 patients, 65.7% had advanced stage, 36.9% bulky disease, 86.5% elevated LDH, 41.7% international prognostic index (IPI) ≥3 and 15.2% double/triple hit at the time of approval. Use of RT bridging varied from 11% to 32% between centres and increased over time. Vein‐to‐vein time and infusion rate did not differ between bridging modalities. RT‐bridged patients had favourable outcomes with 1‐year progression‐free survival (PFS) of 56% for single modality and 47% for CMT (1‐year PFS 43% for systemic bridging). This is the largest cohort of LBCL patients receiving RT bridging prior to CAR T reported to date. Our results show that RT bridging can be safely and effectively used even in advanced stage and high‐risk disease, with low dropout rates and excellent outcomes. [ABSTRACT FROM AUTHOR]

Summary: The success of CD19 Chimeric antigen receptor (CAR) T‐cell therapy in large B‐cell lymphoma (LBCL) has been partially offset by toxicity and logistical challenges, which off‐the‐shelf agents like CD20xCD3 bispecific antibodies might potentially overcome. However, when using CAR T outcomes as the ʽstandard‐of‐care comparator̕ for relapsed/refractory (r/r) LBCL, a potential learning curve with implementing a novel, complex therapy like CAR T needs to be considered. To address this, we analysed 726 UK patients intended to be treated with CD19 CAR T for r/r LBCL and compared outcomes between the first year of the national CAR T programme (Era 1; 2019) and the more recent treatment era (Era 2; 2020–2022). We identified significant improvements for Era 2 versus Era 1 in dropout rate (17% vs. 27%, p = 0.001), progression‐free survival (1‐year PFS 50% vs. 32%, p < 0.001) and overall survival (1‐year OS 60% vs. 40%, p < 0.001). We also observed increased use of bridging therapy, improvement in bridging outcomes, more tocilizumab/corticosteroid use, reduced high‐grade cytokine release syndrome (4% vs. 9%, p = 0.01) and intensive care unit admissions (20% vs. 32%, p = 0.001). Our results demonstrate significant improvement in CAR T outcomes over time, highlighting the importance of using up‐to‐date clinical data when comparing CAR T against new treatment options for r/r LBCL. [ABSTRACT FROM AUTHOR]

Summary: Large B‐cell lymphoma (LBCL) patients with comorbidities and/or advanced age are increasingly considered for treatment with CD19 CAR T, but data on the clinical benefit of CAR T in the less fit patient population are still limited. We analysed outcomes of consecutive patients approved for treatment with axicabtagene ciloleucel (axi‐cel) or tisagenlecleucel (tisa‐cel) by the UK National CAR T Clinical Panel, according to fitness for autologous stem cell transplant (ASCT). 81/404 (20%) of approved patients were deemed unfit for ASCT. Unfit patients were more likely to receive tisa‐cel versus axi‐cel (52% vs. 48%) compared to 20% versus 80% in ASCT‐fit patients; p < 0.0001. The drop‐out rate from approval to infusion was significantly higher in the ASCT‐unfit group (34.6% vs. 23.5%; p = 0.042). Among infused patients, response rate, progression‐free and overall survival were similar in both cohorts. CAR T was well‐tolerated in ASCT‐unfit patients with an incidence of grade ≥3 cytokine release syndrome and neurotoxicity of 2% and 11%, respectively. Results from this multicentre real‐world cohort demonstrate that CD19 CAR T can be safely delivered in carefully selected older patients and patients with comorbidities who are not deemed suitable for transplant. [ABSTRACT FROM AUTHOR]

B Introduction: b T-cell immunostimulatory antibodies invoke potent anti-tumour responses in murine models but their ability to induce T-cell immunostimulation in the immunosuppressive tumour microenvironment (TME) of patients, or induce clinical responses, is lacking. Determinants of response to T-cell stimulation by CD27 antibody therapy in lymphoma: The RiVa trial Agonistic CD27 antibody stimulation of T cells enhanced tumour killing by anti-CD20 in murine models led to the RiVa trial (NCT3307746): a phase IIa study of rituximab (ritux) and varlilumab (varli, anti-CD27) in relapsed/refractory B-cell lymphoma. [Extracted from the article]

Cadmium is a highly toxic environmental pollutant that is known to show lethal effects on the macro- and microorganisms. The current study is aimed at the isolation and screening of cadmium-resistant bacteria from contaminated soil samples collected from the rhizosphere region wet land paddy fields near Katpadi, Vellore. Cadmium concentration in the rhizosphere soil samples was estimated by atomic absorption spectroscopy (AAS) and was found to be 2.59 mg/kg. A total of four morphologically distinct bacterial colonies were isolated and named VITATJM1, VITATJM2, VITATJM3 and VITATJM4. Maximum tolerable concentration (MTC) studies were also performed to establish the maximum concentration of Cd at which the bacteria can survive. The cultures were able to tolerate a maximum cadmium concentration of up to 500 ppm. PGPR tests such as ammonia production, phosphate solubilization, hydrogen cyanide (HCN) production and indole-3-acetic acid (IAA) were performed, and cultures VITATJM1 and VITATJM4 were found to be strongly effective. Similarly, isolates were also capable of forming biofilms. Pot culture studies were performed using Pennisetum purpureum plants, with different concentrations of cadmium in combination with bacterial culture (VITATJM1 and VITATJM4) for 30 days. From the current study, it can be concluded that application of P. purpureum augmented with bacteria in the rhizosphere could be an effective strategy for the removal of cadmium. [ABSTRACT FROM AUTHOR]

Tender coconut water is not merely served as a hydrating beverage but is also a good source of nutrients when consumed as a natural liquid refreshment. While providing health benefits, the fruit endosperm was considered sterile for generations. The current study was aimed at studying the presence of endophytic bacteria in tender coconut endosperm and exploring their potential role in the production of metabolites present in Tender coconut water. Endophytic bacteria were isolated from the coconut fruit endosperm – both, from liquid and flesh sources. Morphological and biochemical characterization was carried out for the isolates and were screened for antibacterial activity. Further, the effective isolate was mass multiplied, the metabolites synthesized by the isolate were extracted and the presence of compounds such as stigmasterol, oleic acid, and palmitic acid (2-Phenyl-1,3-Dioxolan-4-yl) methyl ester were identified by Gas chromatography–mass spectrometry analysis and were confirmed with Fourier-transform infrared spectroscopy. Scanning electron microscope images revealed the presence of microbial cells in the endoderm flesh. The isolate VITKUJ4 was identified to be the closest neighbor of Staphylococcus cohnii upon 16S rRNA gene sequencing and phylogenetic analysis. The study indicates the presence of endophytic bacteria in coconut fruit tissue that could be responsible for the beneficial metabolite synthesis. Current study is the first report on isolation and identification of bacteria in coconut fruit endosperm. [ABSTRACT FROM AUTHOR]

In the pivotal trial, the addition of polatuzumab vedotin to bendamustine and rituximab (Pola-BR) improved overall survival (OS) for stem cell transplant (SCT)-ineligible patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). B Results: b Pola-BR was administered as stand-alone treatment for 76 of 106 patients who received it via EAMS, treatment intent for the remaining patients was bridge to CAR-T or SCT. INFERIOR OUTCOMES WITH POLATUZUMAB VEDOTIN, BENDAMUSTINE AND RITUXIMAB FOR TREATMENT OF RELAPSED/REFRACTORY LARGE B-CELL LYMPHOMA AFTER >1 PRIOR LINE OF THERAPY. [Extracted from the article]

Internationally it has become increasingly common practice to modify escalated BEACOPP (eBPP) by replacing procarbazine with dacarbazine to reduce haematopoietic stem cell and gonadal toxicity in Hodgkin lymphoma (HL) patients. We show eBPDac patients have a reduced blood transfusion requirement and earlier return of menstrual periods compared with real-world eBPP patients (Figure 1A). We have compared toxicity data with 73 UK patients treated with eBPP and outcome data with 2073 patients treated in the German HD18 trial. [Extracted from the article]

B Methods: b The ACOPP regimen comprises doxorubicin 35 mg/m SP 2 sp and cyclophosphamide 650 mg/m SP 2 sp intravenous infusion day (D) 1, vincristine 1.4 mg/m SP 2 sp intravenous injection D8, oral procarbazine 100 mg/m SP 2 sp D1-7, prednisolone 40 mg/m SP 2 sp D1-14 and subcutaneous G-CSF D9-13. B Introduction: b Patients (pts) aged >=60 years comprise 20%-30% of classical Hodgkin lymphoma (cHL) diagnoses, but are significantly underrepresented in clinical trials and outcomes for this group have not improved in line with advances seen in younger counterparts. Whilst treatment in clinical trials should be considered optimal therapy, enrolment in this group remains challenging and the ACOPP regimen offers promising outcomes in a difficult to treat population. [Extracted from the article]

High-precision, individualised RT protocols allowed successful tumour de-bulking with limited toxicity, providing the basis to develop specific RT bridging protocols in lymphoma. RADIOTHERAPY BRIDGING IN LARGE B-CELL LYMPHOMA PATIENTS RECEIVING CD19 CAR-T - THE UK EXPERIENCE B Background: b Radiotherapy (RT) has potential synergistic effects with CAR T but is not widely used as bridging therapy for lymphoma patients due to logistical challenges, uncertainty about patient selection and lack of standardised protocols. [Extracted from the article]

Heavy metals are the major cause of pollution and cadmium is one among the highly toxic metals discharged into the environment from various industries. The current study was focused on the bioremoval of cadmium by phyto and rhizoremediation approach using Vetiveria zizanioides. The bacterial strains were isolated from wetland paddy rhizosphere soil and the isolate VITJAN13 was found to be a biofilm forming Cd resistant plant growth promoting rhizobacteria (PGPR). The 16S rRNA gene sequencing revealed VITJAN13 to be the closest neighbor of Aeromonas sp. and was submitted to Genbank with the accession number KX770741. Further, pot culture studies indicated that the treatments bioaugmented with VITJAN13 increased the root length and shoot height by 21.4 and 17.36%, respectively as compared to the non-augmented plants. Hence, bioaugmentation of Aeromonas sp. in the rhizosphere of Vetiveria zizanioides enhanced the uptake of cadmium by 67.7% in the soil treated with 15 mg/kg of Cd to that of the phytoremediation setup. [ABSTRACT FROM AUTHOR]

Presents a study that examined impulse coupling to targets in vacuum by potassium fluoride, hydrogen fluoride and carbon dioxide single-pulse lasers. Theory used in the study; Description of the theoretical model used; Discussion.

Seaweeds are known to exhibit various antimicrobial properties, since it harbours an enormous range of indigenous bioactive compounds. The emergence of drug resistant strains has directed to the identification of prospective metabolites from seaweed and its endophytes, thereby exploiting the properties in resisting bacterial diseases. The current study was aimed to assess the antimicrobial activity of extracts obtained from Ulva reticulate, for which metabolites of Ulva reticulata and its endophytes were extracted and assessed against human pathogens like Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, and Bacillus subtilis. It was observed that the hexane extract of isolate VITDSJ2 was effective against all the tested pathogens but a significant inhibition was observed for Staphylococcus aureus and Escherichia coli. Further, Gas chromatography coupled with Mass spectroscopy (GC-MS) revealed the existence of phenol, 3, 5-bis (1, 1-dimethylethyl) in the crude hexane extract which is well-known to possess antibacterial activity. The effective isolate VITDSJ2 was identified to be the closest neighbour of Pseudomonas stutzeri by phenotypic and genotypic methods. The crude extracts of the seaweed Ulva reticulata was also screened for antibacterial activity and the hexane extract was effective in showing inhibition against all the tested pathogens. The compound in the crude extract of Ulva reticulata was identified as hentriacontane using GC-MS. The extracts obtained from dichloromethane did not show significant activity in comparison with the hexane extracts. Hence the metabolites of Ulva reticulata and the bacterial secondary metabolites of the endophytes could be used in the treatment of bacterial infections. [ABSTRACT FROM AUTHOR]

Retrovirus-mediated gene transfer into adult skin fibroblasts has provided measurable amounts of therapeutic proteins in animal models. However, the major problem emerging from these experiments was a limited time of vector encoded gene expression once transduced cells were engrafted. We hypothesized that sustained transduced gene expression in quiescent fibroblasts in vivo might be obtained by using a fibronectin (Fn) promoter. Fibronectin plays a key role in cell adhesion, migration and wound healing and is up-regulated in quiescent fibroblasts. Retroviral vectors containing human adenosine deaminase (ADA) cDNA linked to rat fibronectin promoter (LNFnA) or viral LTR promoter (LASN) were compared for their ability to express ADA from transduced primary rat skin fibroblasts in vivo. Skin grafts formed from fibroblasts transduced with LNFnA showed strong human ADA enzyme activity from 1 week to 3 months. In contrast, skin grafts containing LASN-transduced fibroblasts tested positive for human ADA for weeks 1 and 2, were faintly positive at week 3 and showed no human ADA expression at 1, 2 and 3 months. Thus, a fibronectin promoter provided sustained transduced gene expression at high levels for at least 3 months in transplanted rat skin fibroblasts, perhaps permitting the targeting of this tissue for human gene therapy. [ABSTRACT FROM AUTHOR]

Purine nucleoside phosphorylase (NP; EC 2.4.2.1) deficiency is associated with selective T-celI dysfunction and normal B-cell immunity. In order to create an in vivo model of this immune deficiency, we administered 8-aminoguanosine to rats. This water-soluble nucleoside was rapidly converted by NP to the more potent inhibitor 8-aminoguanine, which has a K1 of 0.19 M. The accumulation of inosine in plasma showed that administration of 8-aminoguanosine was effectively inhibiting NP activity. The administration of 8-aminoguanosine with deoxyguanosine produced increased levels of dGTP only in thymus cells, and increased levels of GTP in cells from thymus, spleen and lymph node and in red cells. This correlated with assays of deoxyguanosine kinase, which showed significantly higher activity in thymus cells than in cells from spleen and lymph node. The intraperitoneal injection of 8-aminoguanosine alone or with deoxyguanosine for 8 consecutive days caused significant decreases in the number of thymus cells (P <0.001) and in lymph node and spleen lymphocytes (P< 0.01). These data showed that the administration of 8-aminoguanosine to rats provided an animal model of NP deficiency that will allow studies of the specific regulation of T-cell function. [ABSTRACT FROM AUTHOR]

Analyzes results of a study to examine the theoretical similarities and differences between the counseling and consulting processes by investigating the characteristics of elementary school counselors who prefer to use one process more than the other. Lack of strong correlates to differentiate counselors who prefer either functions; Tendency of counselors to perform counseling functions.

Reality therapy is a cognitive behavioral approach but has not been developed for, nor associated with, career counseling. This article discusses the role of reality therapy in career counseling, with the aid of a flowchart model to present the particulars of the system. [ABSTRACT FROM AUTHOR]

Some biochemical properties of a new red cell human carbonic anhydrase variant, CA Ih Hiroshima, have been determined. Evidence is presented that the amino acid substitution in the Japanese variant is not the same as the previously characterized CA Ic variant from Guam of similar electrophoretic mobility. Based on a comparison with the normal CA I isoenzyme, a proposal for the site of the amino acid substitution is presented. [ABSTRACT FROM AUTHOR]