bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel agents in relapsed/refractory diffuse large B‐cell lymphoma
Authors: Varma Gaurav , Goldstein Jordan , Advani Ranjana H. 
Published: June 2023

AbstractPatients with relapsed or refractory (R/R) diffuse large B‐cell lymphoma (DLBCL), ineligible for or relapsing after autologous stem‐cell transplant or chimeric antigen‐receptor T‐cell therapies have poor outcomes. Several novel agents, polatuzumab vedotin, tafasitamab, loncastuximab tesirine, and selinexor, have been approved and offer new opportunities for this difficult to treat population. Studies are evaluating combination of these agents with chemotherapy and other emerging therapies. Additionally, advances in our understanding of DLBCL biology, genetics, and immune microenvironment have allowed for the identification of new therapeutic targets like Ikaros and Aiolos, IRAK4, MALT1, and CD47 with several agents in ongoing clinical trials. In this chapter we review updated data supporting the use of the approved agents and discuss other emerging novel therapies for patients with R/R DLBCL.
Lymphomas in pregnancy
Authors: Pirosa Maria Cristina , Peccatori Fedro Alessandro 
Published: June 2023

AbstractLymphoma in pregnancy is an uncommon occurrence. This diagnosis is challenging, and a multidisciplinary team of specialists in obstetrics, anesthesiology, neonatology, hematology psychology should participate in the management of this condition. The choice of treatment regimen depends on the histotype and the gestational age. In Hodgkin lymphoma, ABVD is safe if administered after the thirteenth week of pregnancy. In indolent non‐Hodgkin Lymphomas (NHL) a watchful waiting approach is reasonable; in case of aggressive NHLs, if the diagnosis occurs in the first gestational weeks, a termination of the pregnancy might be considered or if it occurs after the thirteenth week of pregnancy, a standard R‐CHOP regimen is safe. Regarding new anti‐lymphoma drugs, available data on the potential fetotoxicity of these agents are limited. Data collection regarding the use of new drugs in pregnant patients is mandatory in order to learn more about their safety and facilitating clinical decision making in this setting of patients.
Reversing vemurafenib‐resistance in primary melanoma cells by combined romidepsin and type I IFN treatment through blocking of tumorigenic signals and induction of immunogenic effects
Authors: Fragale Alessandra , Stellacci Emilia , Romagnoli Giulia , Licursi Valerio , Parlato Stefania , Canini Irene , Remedi Giacomo , Buoncervello Maria , Matarrese Paola , Pedace Lucia , Ascione Barbara , Pizzi Simone , Tartaglia Marco , D'Atri Stefania , Presutti Carlo , Capone Imerio , Gabriele Lucia 
Published: June 2023

AbstractBRAFV600 mutations are the most common oncogenic alterations in melanoma cells, supporting proliferation, invasion, metastasis and immune evasion. In patients, these aberrantly activated cellular pathways are inhibited by BRAFi whose potent antitumor effect and therapeutic potential are dampened by the development of resistance. Here, by using primary melanoma cell lines, generated from lymph node lesions of metastatic patients, we show that the combination of two FDA‐approved drugs, the histone deacetylate inhibitor (HDCAi) romidepsin and the immunomodulatory agent IFN‐α2b, reduces melanoma proliferation, long‐term survival and invasiveness and overcomes acquired resistance to the BRAFi vemurafenib (VEM). Targeted resequencing revealed that each VEM‐resistant melanoma cell line and the parental counterpart are characterized by a distinctive and similar genetic fingerprint, shaping the differential and specific antitumor modulation of MAPK/AKT pathways by combined drug treatment. By using RNA‐sequencing and functional in vitro assays, we further report that romidepsin‐IFN‐α2b treatment restores epigenetically silenced immune signals, modulates MITF and AXL expression and induces both apoptosis and necroptosis in sensitive and VEM‐resistant primary melanoma cells. Moreover, the immunogenic potential of drug‐treated VEM‐resistant melanoma cells results significantly enhanced, given the increased phagocytosis rate of these cells by dendritic cells, which in turn exhibit also a selective down‐modulation of the immune checkpoint TIM‐3. Overall, our results provide evidence that combined epigenetic‐immune drugs can overcome VEM resistance of primary melanoma cells by oncogenic and immune pathways reprogramming, and pave the way for rapidly exploiting this combination to improve BRAFi‐resistant metastatic melanoma treatment, also via reinforcement of immune checkpoint inhibitor therapy.
City‐wide medication use process standardization and implementation of intravenous patient‐controlled analgesia consensus recommendations at an academic medical center
Authors: Brown Michelle E. , Fuller James , Voss Hannah , Walroth Todd A. 
Published: June 2023

AbstractIntroductionIndianapolis Coalition for Patient Safety, Inc. (ICPS) identified practice variation across participating health‐systems related to intravenous Patient‐Controlled Analgesia (PCA) in 2018. No evidence‐based published recommendations were available to provide optimization for the medication use process during this evaluation, leading to development of an ad hoc interdisciplinary group to address gaps.ObjectivesPrimary objectives were to operationalize safe use of PCA and evaluate implementation of ICPS PCA consensus recommendations at an academic medical center by assessing PCA prescribing patterns following policy and electronic health record (EHR) changes. Secondary objectives focused on markers of adoption changes and employee engagement.MethodsICPS formed an interdisciplinary, diverse group of content experts representing six health‐systems to review current PCA processes. Significant variations were identified, and a gap‐analysis was completed to develop consensus recommendations. To evaluate implementation of these recommendations, a retrospective pre‐/post‐analysis was completed of patients at a safety‐net, academic medical center from March 2021 to July 2022 who received an order for PCA. Prescribing patterns and electronic documentation were analyzed.ResultsThe ICPS PCA Safety Summit developed 45 consensus recommendations addressing the following PCA medication use processes: ordering, patient assessment, administration, EHR design, documentation tools, smart pump drug library settings, policies, adverse event monitoring, and education. Evaluation included a total of 155 patients. The ordered total number of morphine milligram equivalent (MME) potentially available per day to a patient from PCA, electronic documentation of opioid tolerance, and PCA smart infusion pump review all significantly improved post‐implementation.ConclusionCity‐wide standardization and development of PCA consensus guidelines filled a gap in practice to provide direction and optimization for the medication use process surrounding these high‐alert medications. Organizational results following implementation provide evidence that using new EHR order sets and incorporating opioid tolerance resulted in more intentional PCA prescribing and more thorough electronic nursing documentation.
Hydroponic phytoremediation of antimony by Tamarix smyrnensis and Nerium oleander
Authors: Seridou Petroula , Fyntrilakis Konstantinos , Syranidou Evdokia , Kalogerakis Nicolas 
Published: June 2023

AbstractBackgroundAntimony (Sb) is considered a priority pollutant and its removal from the environment is of great importance. Among the various treatments, phytoremediation is considered an efficient method when the accumulation of this metalloid in plant tissues is sufficiently high. This work focused on removal of Sb(III) from aqueous solution at two Sb concentrations (5 and 10 ppm) and using salt as stressor (100 mmol L−1) only at the lowest Sb concentration (5 ppm). The response of two salt‐tolerant plant species – Tamarix smyrnensis and Nerium oleander – was monitored when subjected to Sb‐contaminated hydroponic solutions.ResultsPlant growth and water content remained unaltered within the 15‐day experimental period, while the chlorophyll content declined significantly at the higher Sb level (10 ppm) only for N. oleander. The antioxidant enzymatic activity in T. smyrnensis with respect to guaiacol peroxidase (GPOD) and catalase (CAT) was significantly increased in the treatment under Sb and salt stress. In N. oleander there was a strong increase in GPOD activity by the exposure to Sb, whereas the CAT activity was increased considerably with the presence of salinity. Sb concentration was detected on the surface of the leaves, indicating that excretion occurred in both plants. Increased accumulation was observed in N. oleander in the absence of salinity whereas, under salt stress, Sb accumulation was considerably higher (60%) in T. smyrnensis. Notably, both plants could accumulate a high amount of Sb, preferentially in the roots, with the concentrations in the leaves being significantly lower.ConclusionThe experimental results from this study demonstrate that both plants are suitable for phytoremediation due to substantial Sb accumulation without visible Sb toxicity. © 2023 The Authors. Journal of Chemical Technology and Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry (SCI).
Degradation of endocrine‐disrupting chemicals using various sulfate radical activation methods: kinetics and mechanism
Authors: Puri Mehak , Gandhi Kavita , Kumar M Suresh 
Published: June 2023

AbstractBACKGROUNDMost studies have focused on the degradation of endocrine‐disrupting chemicals using persulfate activation processes. Therefore, the current study compares various sulfate radical activation processes in an aqueous solution of a mixture of diethyl phthalate, butylparaben and bisphenol A that are present in water and wastewater. The effects of initial persulfate dose and pH variation, the effect of concentration of target endocrine‐disrupting chemicals and degradation efficiency under various processes were studied. Additionally, the toxicity and cost estimation of the systems were also examined.RESULTSThe results showed pseudo‐first‐order kinetics with maximum degradation efficiency of 99% for 1 mg L−1 at pH 7, 2.5 mmol L−1 persulfate dose, 450 W power in 60 min for UV‐activated persulfate oxidation process. A quenching experiment highlights the dominance of both sulfate and hydroxyl radicals in the degradation of mixtures of diethyl phthalate, butylparaben and bisphenol A in an aqueous solution. The transformative products identified using gas chromatography–mass spectrometry were monohydroxylated structures that decompose to form organic acids, indicating efficient degradation capacity with minimal toxicity. Further, the sono‐activated persulfate oxidation process was found to be cost‐effective at 1 mg L−1 with 95% degradation efficiency.CONCLUSIONIt is concluded that an increase in the concentration of target compounds decreases the efficiency of degradation under various activation processes. pH 3 and pH 7 favor thermal and sono‐activated and UV‐activated processes, respectively. Toxicity evaluation shows minimal harm to non‐target species Daphnia magna for all activation processes. These findings can be useful for on‐field application for the degradation of chemicals in mixtures. © 2023 Society of Chemical Industry.
Co‐trimoxazole prophylaxis for children who are HIV‐exposed and uninfected: a systematic review
Authors: Wedderburn Catherine J. , Evans Ceri , Slogrove Amy L. , Rehman Andrea M. , Gibb Diana M. , Prendergast Andrew J. , Penazzato Martina 
Published: June 2023

AbstractIntroductionCo‐trimoxazole prophylaxis is recommended for children born to women with HIV to protect those who acquire HIV from opportunistic infections, severe bacterial infections and malaria. With scale‐up of maternal antiretroviral therapy, most children remain HIV‐exposed uninfected (HEU) and the benefits of universal co‐trimoxazole are uncertain. We assessed the effect of co‐trimoxazole on mortality and morbidity of children who are HEU.MethodsWe performed a systematic review (PROSPERO number: CRD42021215059). We systematically searched MEDLINE, Embase, Cochrane CENTRAL, Global Health, CINAHL Plus, Africa‐Wide Information, SciELO and WHO Global Index Medicus for peer‐reviewed articles from inception to 4th January 2022 without limits. Ongoing randomized controlled trials (RCTs) were identified through registries. We included RCTs reporting mortality or morbidity in children who are HEU receiving co‐trimoxazole versus no prophylaxis/placebo. The risk of bias was assessed using the Cochrane 2.0 tool. Data were summarized using narrative synthesis and findings were stratified by malaria endemicity.ResultsWe screened 1257 records and included seven reports from four RCTs. Two trials from Botswana and South Africa of 4067 children who are HEU found no difference in mortality or infectious morbidity in children randomized to co‐trimoxazole prophylaxis started at 2–6 weeks of age compared to those randomized to placebo or no treatment, although event rates were low. Sub‐studies found that antimicrobial resistance was higher in infants receiving co‐trimoxazole. Two trials in Uganda investigating prolonged co‐trimoxazole after breastfeeding cessation showed protection against malaria but no other morbidity or mortality differences. All trials had some concerns or a high risk of bias, which limited the certainty of evidence.DiscussionStudies show no clinical benefit of co‐trimoxazole prophylaxis in children who are HEU, except to prevent malaria. Potential harms were identified for co‐trimoxazole prophylaxis leading to antimicrobial resistance. The trials in non‐malarial regions were conducted in populations with low mortality potentially reducing generalizability to other settings.ConclusionsIn low‐mortality settings with few HIV transmissions and well‐performing early infant diagnosis and treatment programmes, universal co‐trimoxazole may not be required.
Screening and identification of high yield tetramethylpyrazine strains in Nongxiangxing liquor Daqu and study on the mechanism of tetramethylpyrazine production
Authors: Liu Yanbo , Li Mengke , Hong Xinfeng , Li Haideng , Huang Runna , Han Suna , Hou Jianguang , Pan Chunmei 
Published: June 2023

AbstractBACKGROUNDThere are few reports on the breeding of high‐yielding tetramethylpyrazine (TTMP) strains in strong‐flavor Daqu. In addition, studies on the mechanism of TTMP production in strains are mostly based on common physiological and biochemical indicators, and there is no report on RNA level. Therefore, in this study, a strain with high production of TTMP was screened out from strong‐flavor liquor, and transcriptome sequencing analysis was performed to analyze its key metabolic pathways and key genes, and to infer the mechanism of TTMP production in the strain.RESULTSIn this study, a strain with a high yield of tetramethylpyrazine (TTMP) was screened out, and the yield was 29.83 μg mL−1. The identified strain was Bacillus velezensis, which could increase the content of TTMP in liquor by about 88%. After transcriptome sequencing, a total of 1851 differentially expressed genes were screened, including 1055 up‐regulated genes and 796 down‐regulated genes. Three pathways related to the production of TTMP were identified by gene ontology (GO) annotation and COG annotation, including carbohydrate metabolism, cell movement and amino acid metabolism. The key genes of TTMP were analyzed, and the factors that might regulate the production of TTMP, such as the transfer of uracil phosphate ribose and glycosyltransferase, were obtained.CONCLUSIONSA strain of B. velezensis with high TTMP production was screened and identified in strong‐flavor Daqu for the first time. The yield of TTMP was 29.83 μg mL−1, which increased the TTMP content in liquor by 88%. The key metabolic pathways of TTMP production in the strain were obtained: carbohydrate metabolism, cell movement and amino acid metabolism, and the key regulatory genes of each pathway were found, which complemented the gap in gene level in the production regulation of the strain, and provided a theoretical basis for the subsequent study of TTMP in liquor. © 2023 Society of Chemical Industry.
Seed storage proteins and seed coat compounds additively influence Callosobruchus maculatus Fab. tolerance in selected cowpea (Vigna unguiculata L. Walp.) varieties
Authors: Amusa Oluwafemi Daniel , Emereuwa Emmanuella Adaeze , Akinyosoye Solomon Tayo , Olayiwola Oreoluwa Ideraoluwa , Osunkojo Omotola Victoria , Adetola Azeezat Adeola , Ugbo Fechi Daniella , Ogunkanmi Liasu Adebayo , Oboh Bolanle Olufunmilayo 
Published: June 2023

AbstractThe cowpea weevil, Callosobruchus maculatus, is a major threat to stable cowpea production, especially in storage, and has been reported to facilitate postharvest losses in cowpea grains. Host resistance has been suggested as the best control method but with conflicting knowledge on the source of resistance. Hence, the study seeks to evaluate seed storage proteins (SSPs) and seed coat compounds (SCCs) associated with tolerance to C. maculatus. SSPs and SCCs were assayed and associated with C. maculatus tolerance in 19 cowpea varieties with varied tolerance levels using a stepwise multiple regression analysis. Top C. maculatus tolerants were TVu‐2027, TVu‐11952, TVu‐11953, and TVu‐145. The protein fraction with a mass of 51 kDa was a significant predictor associated with percentage adult insect emergence (PAE) and host suitability index (H.S.I.), and 57 and 71 kDa were associated with mean development period (MDP) whereas 59 and 131 kDa were associated with seed damage tolerance (TolSD). Several SCCs identified were associated with the C. maculatus tolerant measures used in the study. However, Thiazole, tetrahydro‐ and Undecane were consistently identified with C. maculatus tolerance. Higher phenotypic variability was accounted for by SCC than SSP fractions associated with C. maculatus tolerance in the study indicating that SCCs contributed more to the C. maculatus tolerance than the SSPs identified. These compounds can be incorporated into breeding for C. maculatus tolerant in cowpea and biopesticide formulations whereas cowpea varieties with the high or significant amount of these compounds can also be recommended to the farmers or to the cowpea producers.
Development and Validation of Analytical Methods for the Quantitation of Flavonoid Metabolites in Physiological Fluids via UHPLC‐MS
Authors: Kaiser Michael , Schieber Andreas 
Published: June 2023

This thesis deals with the development and validation of methods for the quantification of flavonoid derivatives from physiological samples in cases of bioavailability research, as there is always a need for valid and reliable methods suitable for a wide variety of analytes. With the enzymatic proteolysis of plasma samples for flavonoid analysis, a completely new approach to sample preparation of plasma samples was investigated. Various enzymes and procedures were tested as part of the research, and the method was thus continuously optimized. The method validation showed the suitability of the developed method for several analytes of different flavonoid classes. It therefore appears to be promising when it comes to extending the application to further classes of analytes. With regard to the analysis of flavonoids in urine samples, an easy to handle method using evaporation was found and validated for anthocyanidins. In routine analysis, however, this method was not suitable for all anthocyanidins but only for the methoxylated ones. Nevertheless, the possibility of extending it to other analytes, especially the metabolically derivatized flavonoids, appears to be promising in the future.Compared to already established methods, both methods presented here showed at least equivalent results with regard to method validation, apart from for hydroxylated anthocyanidins. But, when considering this it should be noted that due to the different validation guidelines used, there is no absolute comparability between the different analytical methods. It is indisputable, however, that with the methods presented here the costs can be blatantly reduced and the amount of material and the resulting waste can be reduced compared to the established methods using SPE. The application of a single sample preparation procedure for different analyte classes can also be used here, whereas different procedures would often be necessary with the classic SPE.The repertory of available valid methods for bioavailability and metabolism research of flavonoids, and possibly other phytochemicals, could thus be expanded by the research work presented here.
Die Enzymologie der C8‐Oxylipinbiosynthese
Authors: Karrer Dominik , Rühl Martin 
Published: June 2023

Based on transcriptomic, volatilomic and metabolomic data of the model organism Cyclocybe aegerita, the endogenous and enzymatic production of the C8‐oxylipins oct‐2‐en‐1‐ol, octan‐ 1‐ol, oct‐2‐enal, octanal, octan‐3‐ol, oct‐1‐en‐3‐ol, oct‐1‐en‐3‐one and octan‐3‐ one via biotransformations with [U‐13C]linoleic acid was compared to the developmental state depending gene expression patterns of putative oxylipin‐associated enzyme classes like lipoxygenases, dioxygenases, ene‐reductases and alcohol dehydrogenases. On closer consideration of these data sets, the C8‐oxylipin production seemed to occur cluster‐like.While one cluster (ketonic‐cycle) consisted of octan‐3‐ol, oct‐1‐en‐3‐one, octan‐3‐one and oct‐1‐en‐3‐ol, which were detected through out all developmental stages, a second cluster (aldehydic‐cycle) primarily active at early developmental stages involved oct‐2‐enal, octanal, oct‐2‐en‐1‐ol and octan‐1‐ol. Studying these clusters revealed that all C8‐oxylipins of the aldehydic‐cycle and ketonic‐cycle can be derived from oct‐2‐enal and oct‐1‐en‐3‐one, respectively. A detailled consideration of the gene expression patterns revealed several enzyme classes putatively involved in the C8‐oxylipin biosynthesis. Especially the two genes AAE3 04864 and AAE3 13549 encoding the lox4‐ and enr1‐gene showed great similarities between their strongly increasing transcript counts with maturation. Subsequent recombinant production of CaeLOX4 and CaeEnR1 revealed that CaeLOX4 showed a preference for C18‐ fatty acids with the highest affinity towards linoleic acid. Analysis of the reaction product revealed that this LOX selectively oxygenated linoleic acid at position 13 to 13‐ hydroperoxyoctadecadienoic acid (13‐HPOD). CaeEnR1 showed high affinities towards the reduction of oct‐1‐en‐3‐one and oct‐2‐enal to their saturated counterparts octan‐3‐one and octanal, respectively. Due to the strong similarities between the expression patterns of CaeLOX4 and CaeEnR1 a coherence between their main reaction products 13‐HPOD and the precursor of the ketonic‐cycle oct‐1‐en‐3‐one seems very likely. This suggests a biosynthetic route from linoleic acid to 13‐HPOD, followed by a subsequent cleavage step to oct‐1‐en‐3‐ one and therefore to C8‐oxylipins of the ketonic‐cycle.