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The intestinal microbiota is essential for the fermentation of dietary fiber into short-chain fatty acids (SCFA) such as butyrate, acetate, and propionate. SCFAs can bind to the G-protein-coupled receptors GPR43 and GPR109A (HCAR2), with varying affinities to promote cellular effects in metabolism or changes in immune function. We explored the role of GPR109A as the main receptor for butyrate in mouse models of allogeneic hematopoietic cell transplantation (allo-HCT) and graft-versus-host disease (GVHD). Deletion of GPR109A in allo-HCT recipients did not affect GVHD, but transplantation of T cells from GPR109A knockout (KO) (Gpr109a−/−) mice into allo-HCT recipient mice significantly reduced GVHD morbidity and mortality compared with recipients of wild-type (WT) T cells. Recipients of Gpr109a−/− T cells exhibited less GVHD-associated target organ pathology and decreased proliferation and homing of alloreactive T cells to target tissues. Although Gpr109a−/− T cells did not exhibit immune deficits at a steady state, following allo-activation, Gpr109a−/− T cells underwent increased apoptosis and were impaired mitochondrial oxidative phosphorylation, which was reversible through antioxidant treatment with N-acetylcysteine (NAC). In conclusion, we found that GPR109A expression by allo-activated T cells is essential for metabolic homeostasis and expansion, which are necessary features to induce GVHD after allo-HCT.

Tissue engineering leads to the development of biomaterial scaffolds where its biocompatibility and bioactivity are often improved after performing physical or chemical surface modification treatments. Micropatterning, soft lithography, and biofabrication are also approaches that provide a biomimetic microenvironment but have proven very costly and time consuming. In this concern, an appropriate substrate with suitable sites for cell attachment represents a major factor in cell behavior and biological functions. For this reason, our strategy was to fabricate a standard fibrous biomaterial with reproducible surface topography, incorporating microbeads and nanofeatures, and show the positive outcomes of the new substrate reflected on cell functions of bone cells. The electrospun polycaprolactone (PCL) beads-on-string membranes were obtained by adjusting the spinning solution at different concentrations until continuous beads were formed. Cell adhesion and proliferation, on the PCL scaffold, were analyzed the subsequent 2 days after initial culture. Complementary studies of cytoskeleton spreading and differentiation were analyzed after 7 and 14 days of the initial incubation. The scanning electron microscopy (SEM) images showed evidence of the formation of beads-on-string nanofibers and suggested that as-formed microstructures worked as attachment sites for osteoblasts. We investigated cell proliferation using anti-BrdU fluorescence assay, and results show a similar proliferation rate of cells cultured between PCL scaffolds and control. Finally, Phalloidin TRITC and antisialoprotein antibody were used to analyze cell spreading and differentiation after 7 and 14 days, respectively. This work shows a low-cost fabrication method to produce a biodegradable scaffold with micro/nanostructured characteristics that favor cell adhesion, proliferation, maturation, and subsequent differentiation of osteoblasts. According to the results, the biocompatibility of PCL beads-on-string could be comparable to other complex biomaterials, and we conclude that our scaffold is optimal for applications in bone tissue regeneration.

Drawing on Bronfenbrenner's ecological systems theory, this study investigated child labour experiences of children in Ghana. Using a qualitative research approach, in-depth interviews were conducted with 25 participants who were purposively selected. Data collected were analyzed thematically and the findings indicated that reasons why children engaged in child labour included poverty, parental absence, and poor enforcement of educational and child labour laws. The findings further revealed that children's engagement in selling on the highway could negatively affect their health and education. Based on the findings, we recommend that there should be effective implementation of educational and child labour laws in order to mitigate this menace.

Background Acute graft-versus-host disease (aGVHD) remains a major limitation of allogeneic hematopoietic cell transplantation (allo-HCT) despite prophylactic immunosuppression. Not all patients who develop aGVHD respond to currently available treatment and thus there is a pressing need for novel prophylactic and therapeutic strategies. Interleukin-2-Inducible T-Cell Kinase (ITK) is a Tec-family, non-receptor tyrosine kinase expressed in T-cells, homologous with Bruton's tyrosine kinase (BTK) in B cells and is involved in proximal T-cell receptor (TCR) signaling, activating Phospholipase Cγ1 (PLCγ1) and initiating a signaling cascade that includes the NFAT, NF-κB, and MAPK pathways tuning T-cell activation, proliferation, and differentiation. Targeting ITK (ITK-/- in T cell graft and short-term exposure of donor graft to ITK inhibitor) has been shown to be associated with less GVHD in preclinical studies (Mammadli et al 2020, Kondo et al 2021). CPI-818 is a highly selective irreversible ITK inhibitor that covalently binds to cysteine 442 of ITK and abolishes kinase activity. In vitro assays demonstrate that CPI-818 inhibits phosphorylation of the ITK substrate PLC γ1 (Y783) and downstream signaling molecules ERK and S6, and blocks IL-2 secretion. CPI-818 reduced clinical and histological disease severity in a Th1-driven T cell adoptive transfer model of colitis (not published). CPI-818 is currently being evaluated in a Phase 1/1b study in patients with relapsed/refractory T-cell lymphoma (NCT03952078), and thus far appears well tolerated. Methods and Results We used 2 well established preclinical aGVHD models (MHC-disparate B6 → BALB/c and minor MHC-mismatched B6 → 129) to explore the effects of ITK inhibition by CPI-818. Recipient mice were treated with CPI-818-formulated (300 mg/kg/day) or control diet from day -7 to day 90 relative to allo-HCT. We found significantly improved survival (MHC-disparate: p Conclusion These data in two clinically relevant GVHD models demonstrate that ITK inhibition has potential as a novel targeted approach to prevent aGVHD through a) the suppression of T cell activation and proliferation, b) decreased concentrations of pro-inflammatory cytokines and increased concentration of anti-inflammatory cytokines. CPI-818 is the most potent and selective ITK inhibitor reported to date and these data highlight its promise as a novel agent for the prevention of aGVHD. Figure 1 Figure 1. Disclosures Smith: Janssen: Consultancy, Honoraria. Perales: Celgene: Honoraria; Kite/Gilead: Honoraria, Other; MorphoSys: Honoraria; Merck: Honoraria; Incyte: Honoraria, Other; Cidara: Honoraria; Bristol-Myers Squibb: Honoraria; Omeros: Honoraria; Novartis: Honoraria, Other; Medigene: Honoraria; Karyopharm: Honoraria; Nektar Therapeutics: Honoraria, Other; Equilium: Honoraria; Takeda: Honoraria; Sellas Life Sciences: Honoraria; NexImmune: Honoraria; Miltenyi Biotec: Honoraria, Other; Servier: Honoraria. Buggy: Corvus Pharmaceuticals Inc: Consultancy, Current holder of individual stocks in a privately-held company. Janc: Corvus Pharmaceuticals Inc: Current Employment, Current holder of individual stocks in a privately-held company. van den Brink: Forty-Seven, Inc.: Honoraria; WindMILTherapeutics: Honoraria; Kite Pharmaceuticals: Other; Da Volterra: Other: has consulted, received honorarium from or participated in advisory boards; Notch Therapeutics: Honoraria; Pluto Therapeutics: Current holder of stock options in a privately-held company, Other: has consulted, received honorarium from or participated in advisory boards ; GlaskoSmithKline: Other: has consulted, received honorarium from or participated in advisory boards; Synthekine (Spouse): Other: has consulted, received honorarium from or participated in advisory boards; Priothera: Research Funding; Wolters Kluwer: Patents & Royalties; Pharmacyclics: Other; Rheos: Honoraria; Nektar Therapeutics: Honoraria; Ceramedix: Other: has consulted, received honorarium from or participated in advisory boards ; Novartis (Spouse): Other: has consulted, received honorarium from or participated in advisory boards; Lygenesis: Other: has consulted, received honorarium from or participated in advisory boards ; Frazier Healthcare Partners: Honoraria; DKMS (nonprofit): Other; Juno Therapeutics: Other; MagentaTherapeutics: Honoraria; Merck & Co, Inc: Honoraria; Amgen: Honoraria; Therakos: Honoraria; Jazz Pharmaceuticals: Honoraria; Seres: Other: Honorarium, Intellectual Property Rights, Research Fundingand Stock Options.

Introduction: Cellular immunotherapy with CD19-targeted chimeric antigen receptor (CAR) T cells has provided new therapeutic options for patients with high-risk hematologic malignancies. Following this therapy, patients may experience disease relapse or CAR-mediated toxicity due to cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS). Recent studies have confirmed that the intestinal microbiome can modulate the anti-tumor immune response to chemotherapy, immune checkpoint blockade, graft-versus-host disease after allogeneic hematopoietic cell transplantation, and adoptive cellular therapy. The contribution of the intestinal microbiome on the function of CAR T cells in vivo both with respect to their anti-tumor function and their propensity to induce toxicities is not known. Hence, in a multi-center study we analyzed the association between clinical outcomes and (1) antibiotic exposure prior to CAR T cell infusion and (2) the composition and diversity of the fecal microbiome. Methods and Results: We retrospectively collected clinical data and antibiotic exposures from patients with acute lymphoblastic leukemia (ALL, n=91) and non-Hodgkin lymphoma (NHL, n=137) treated with investigational or commercial CD19 CAR T cells at Memorial Sloan Kettering Cancer Center (MSK) and the University of Pennsylvania (Penn). We considered any antibiotic exposure between day -30 and the day of CAR T cell infusion. We focused our analysis on anaerobe-targeting antibiotics used in the setting of neutropenic fever: piperacillin-tazobactam, imipenem-cilastatin, and meropenem (here referred to as "P-I-M"). We found that forty-seven (20.6%) of 228 patients were exposed to P-I-M in the four weeks before CAR T cell infusion. Patient characteristics at the time of CAR T cell infusion were similar between the P-I-M-exposed and not-exposed groups, although a worse performance status was observed in patients with NHL treated with P-I-M. We found that overall survival (OS) was significantly decreased following CAR T cell infusion in patients exposed to P-I-M (Fig 1A; OS HR, 2.58; 95% CI, 1.68 - 3.98; p= We also prospectively collected baseline fecal samples prior to cell infusion from CD19 CAR T cells recipients (n=48) at MSK and Penn. Samples were submitted for 16S RNA sequencing of the V4-V5 region on the Illumina MiSeq platform and the amplicon sequence variants (ASVs) were annotated according to the NCBI 16S database using BLAST. In comparison to healthy controls (n=30), we found that alpha-diversity was significantly lower in fecal samples from CAR T cell patients (p= 0.0023, Fig 1B) and the composition of fecal samples was significantly different (p= Conclusion: Our results suggest that exposure to antibiotics, in particular P-I-M, in the four weeks before therapy was associated with worse survival. Profiling of the baseline fecal microbiome samples by 16S revealed that CD19 CAR T cell patients presented with evidence of an altered fecal microbiome as measured by lower alpha-diversity and a composition that is distinct from that of healthy controls. Finally, we identified bacterial taxa that were associated with Day 100 CR and CAR-mediated toxicity. Our findings indicate that the intestinal microbiome can affect the efficacy of CD19 CAR T cell therapy and provides a rationale to target the intestinal microbiome to improve clinical outcomes of patients treated with cellular therapies. Figure 1 Figure 1. Disclosures Smith: Janssen: Consultancy, Honoraria. Gomes: Xbiome: Current Employment. Schluter: Postbiotics Plus LLC: Other: cofounder. Park: Kura Oncology: Consultancy; BMS: Consultancy; Servier: Consultancy; Autolus: Consultancy; Curocel: Consultancy; Artiva: Consultancy; Kite Pharma: Consultancy; Amgen: Consultancy; Novartis: Consultancy; Affyimmune: Consultancy; Intellia: Consultancy; Innate Pharma: Consultancy; Minerva: Consultancy; PrecisionBio: Consultancy. Palomba: Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Kite Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Jain: Targeted Healthcare Communications: Consultancy; Bristol Myers Squibb: Other: for advisory board participation; CareDx: Other: for advisory board participation; CTI Biopharma: Research Funding; Syneos Health: Research Funding. Pennisi: Gilead Sciences: Consultancy. Perales: Miltenyi Biotec: Honoraria, Other; Novartis: Honoraria, Other; Omeros: Honoraria; NexImmune: Honoraria; Bristol-Myers Squibb: Honoraria; Merck: Honoraria; Celgene: Honoraria; Takeda: Honoraria; Kite/Gilead: Honoraria, Other; Medigene: Honoraria; Nektar Therapeutics: Honoraria, Other; Cidara: Honoraria; Servier: Honoraria; Sellas Life Sciences: Honoraria; Karyopharm: Honoraria; MorphoSys: Honoraria; Equilium: Honoraria; Incyte: Honoraria, Other. Garfall: Amgen: Honoraria; CRISPR Therapeutics: Research Funding; GlaxoSmithKline: Honoraria; Janssen: Honoraria, Research Funding; Novartis: Research Funding; Tmunity: Research Funding. Landsburg: Triphase: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Other: DSMB member; Incyte: Membership on an entity's Board of Directors or advisory committees; ADCT: Membership on an entity's Board of Directors or advisory committees; Curis: Research Funding; Takeda: Research Funding. Gerson: Kite: Consultancy; Pharmacyclics: Consultancy; Abbvie: Consultancy; TG Therapeutics: Consultancy. Svoboda: Imbrium: Consultancy; Genmab: Consultancy; Astra Zeneca: Consultancy, Research Funding; Atara: Consultancy; BMS: Consultancy, Research Funding; Adaptive: Consultancy, Research Funding; Incyte: Research Funding; Merck: Research Funding; Pharmacyclics: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; TG: Research Funding. Giralt: AMGEN: Membership on an entity's Board of Directors or advisory committees; PFIZER: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; SANOFI: Membership on an entity's Board of Directors or advisory committees; CELGENE: Membership on an entity's Board of Directors or advisory committees; JAZZ: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; JENSENN: Membership on an entity's Board of Directors or advisory committees; Actinnum: Membership on an entity's Board of Directors or advisory committees. Gill: Interius Biotherapeutics: Current holder of stock options in a privately-held company, Research Funding; Novartis: Other: licensed intellectual property, Research Funding; Carisma Therapeutics: Current holder of stock options in a privately-held company, Research Funding. Rivière: FloDesign Sonics: Other: Provision of Services; Centre for Commercialization of Cancer Immunotherapy: Other: Provision of Services; Fate Therapeutics: Other: Provision of Services, Patents & Royalties; The Georgia Tech Research Corporation (GTRC): Other: Provision of Services (uncompensated); Juno Therapeutics: Patents & Royalties. Porter: Kite/Gilead: Membership on an entity's Board of Directors or advisory committees; Wiley and Sons Publishing: Honoraria; Tmunity: Patents & Royalties; Novartis: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; ASH: Membership on an entity's Board of Directors or advisory committees; DeCart: Membership on an entity's Board of Directors or advisory committees; Genentech: Current equity holder in publicly-traded company, Ended employment in the past 24 months; American Society for Transplantation and Cellular Therapy: Honoraria; National Marrow Donor Program: Membership on an entity's Board of Directors or advisory committees. Schuster: Abbvie: Consultancy, Research Funding; Acerta Pharma: Consultancy; AstraZeneca: Consultancy; Adaptive Biotechnologies: Research Funding; BeiGene: Consultancy; Celgene: Consultancy, Honoraria, Research Funding; DTRM: Research Funding; Genetech: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Incyte: Research Funding; Juno Theraputics: Consultancy, Research Funding; Loxo Oncology: Consultancy; Merck: Research Funding; Nordic Nanovector: Consultancy; Novartis: Consultancy, Honoraria, Patents & Royalties, Research Funding; Pharmaclcyclics: Research Funding; Tessa Theraputics: Consultancy; TG Theraputics: Research Funding. Sadelain: NHLBI Gene Therapy Resource Program: Other: Provision of Services (uncompensated); Fate Therapeutics: Other: Provision of Services (uncompensated), Patents & Royalties; Atara Biotherapeutics: Patents & Royalties; Ceramedix: Patents & Royalties; Mnemo Therapeutics: Patents & Royalties; Takeda Pharmaceuticals: Other: Provision of Services, Patents & Royalties; St. Jude Children's Research Hospital: Other: Provision of Services; Juno Therapeutics: Patents & Royalties; Minerva Biotechnologies: Patents & Royalties. Frey: Novartis: Research Funding; Kite Pharma: Consultancy; Sana Biotechnology: Consultancy; Syndax Pharmaceuticals: Consultancy. Brentjens: Gracell Biotechnologies, Inc: Consultancy, Ended employment in the past 24 months; BMS: Consultancy, Patents & Royalties, Research Funding; sanofi: Patents & Royalties; Caribou: Patents & Royalties. June: AC Immune, DeCART, BluesphereBio, Carisma, Cellares, Celldex, Cabaletta, Poseida, Verismo, Ziopharm: Consultancy; Novartis: Patents & Royalties; Tmunity, DeCART, BluesphereBio, Carisma, Cellares, Celldex, Cabaletta, Poseida, Verismo, Ziopharm: Current equity holder in publicly-traded company. Pamer: Diversigen: Other: Advisory board; Bristol Myers Squibb, Celgene, Seres Therapeutics, MedImmune, Novartis and Ferring Pharmaceuticals: Honoraria. Peled: DaVolterra: Consultancy; MaaT Pharma: Consultancy; CSL Behring: Consultancy; Seres Therapeutics: Research Funding. Ruella: BMS, BAYER, GSK: Consultancy; Novartis: Patents & Royalties; AbClon: Consultancy, Research Funding; Tmunity: Patents & Royalties; viTToria biotherapeutics: Research Funding. van den Brink: WindMILTherapeutics: Honoraria; Pluto Therapeutics: Current holder of stock options in a privately-held company, Other: has consulted, received honorarium from or participated in advisory boards ; Priothera: Research Funding; Forty-Seven, Inc.: Honoraria; MagentaTherapeutics: Honoraria; GlaskoSmithKline: Other: has consulted, received honorarium from or participated in advisory boards; Ceramedix: Other: has consulted, received honorarium from or participated in advisory boards ; Merck & Co, Inc: Honoraria; Synthekine (Spouse): Other: has consulted, received honorarium from or participated in advisory boards; Kite Pharmaceuticals: Other; Amgen: Honoraria; Frazier Healthcare Partners: Honoraria; Seres: Other: Honorarium, Intellectual Property Rights, Research Fundingand Stock Options; Rheos: Honoraria; Therakos: Honoraria; Jazz Pharmaceuticals: Honoraria; Notch Therapeutics: Honoraria; Nektar Therapeutics: Honoraria; Wolters Kluwer: Patents & Royalties; Juno Therapeutics: Other; DKMS (nonprofit): Other; Pharmacyclics: Other; Da Volterra: Other: has consulted, received honorarium from or participated in advisory boards; Novartis (Spouse): Other: has consulted, received honorarium from or participated in advisory boards; Lygenesis: Other: has consulted, received honorarium from or participated in advisory boards .

Studies in seven districts of northern Ghana showed that Nephopterix sp., physiological disorders and an unidentified borer caused 16%, 2.6% and 0.8% of fruit losses, respectively. Infestation by borers occurred mainly in April to June, while losses due to physiological disorders were highest in March. Copyright © 2004 Whurr Publishers Ltd

Insect fauna on sheanut tree were surveyed in 28 locations in Northern Ghana. A total of 260 insect species were collected and 53 were identified to the family, generic and/or species level. Copyright © 2003 Whurr Publishers Ltd

BACKGROUND: Cashew (Anacardium occidentale L.) has become a very important non-traditional tree crop in Ghana. The crop is, however, attacked by sap-sucking insects, particularly the mosquito bug, Helopeltis schoutedeni Reuter, the leaf-footed bug, Pseudotheraptus devastans (Dist.), and the coreid bug, Anoplocnemis curvipes (F.), which feed on shoots, panicles and fruits. Their damage is characterised by withering of the latter. In Ghana, Oecophylla longinoda Latr. occurs in large numbers on cashew and other native plants, but little is known about its relationship with insect pests. The relationship between O. longinoda and shoot and panicle damage by sap-sucking bugs and the effectiveness of O. longinoda as a biocontrol agent in the protection of cashew as compared with two chemical insecticides, lambda-cyhalothrin (Karate®) and cypermethrin + dimethoate (Cyperdim®), were therefore investigated at Bole in the northern region of Ghana. RESULTS: There was a negative correlation between numbers of O. longinoda nests and pest damage. Trees treated with cypermethrin + dimethoate (969 mg AI mL−1 tree−1) and lambda-cyhalothrin (100 mg AI mL−1 tree−1) recorded the smallest bug numbers, followed by O. longinoda. Trees infested by Oecophylla longinoda and trees treated with cypermethrin + dimethoate and with lambda-cyhalothrin had less than 6% pest damage to shoots, panicles and fruits, while water-sprayed trees recorded damage as high as 36.8% (shoots) in February, 32.9% (panicles) in February and 37.8% (fruits) in March. Cypermethrin + dimethoate again recorded the highest (485.0 kg ha−1) nut yield, followed by O. longinoda (431.0 kg ha−1), with water recording the lowest (93.0 kg ha−1) nut yield. CONCLUSION: The results indicate that O. longinoda can be used to control some sucking bugs as effectively as some insecticides. Copyright © 2008 Society of Chemical Industry