Efficient axonal transport of endolysosomes relies on the balanced ratio of microtubule tyrosination and detyrosination.

In neurons, the microtubule (MT) cytoskeleton forms the basis for long-distance protein transport from the cell body into and out of dendrites and axons. To maintain neuronal polarity, the axon initial segment (AIS) serves as a physical barrier, separating the axon from the somatodendritic compartment and acting as a filter for axonal cargo. Selective trafficking is further instructed by axonal enrichment of MT post-translational modifications, which affect MT dynamics and the activity of motor proteins. Here, we compared two knockout mouse lines lacking the respective enzymes for MT tyrosination and detyrosination, and found that both knockouts led to a shortening of the AIS. Neurons from both lines also showed an increased immobile fraction of endolysosomes present in the axon, whereas mobile organelles displayed shortened run distances in the retrograde direction. Overall, our results highlight the importance of maintaining the balance of tyrosinated and detyrosinated MTs for proper AIS length and axonal transport processes.

PI3Kδ/γ inhibition promotes human CART cell epigenetic and metabolic reprogramming to enhance antitumor cytotoxicity.

Current limitations in using chimeric antigen receptor T(CART) cells to treat patients with hematological cancers include limited expansion and persistence in vivo that contribute to cancer relapse. Patients with chronic lymphocytic leukemia (CLL) have terminally differentiated T cells with an exhausted phenotype and experience low complete response rates after autologous CART therapy. Because PI3K inhibitor therapy is associated with the development of T-cell-mediated autoimmunity, we studied the effects of inhibiting the PI3Kδ and PI3Kγ isoforms during the manufacture of CART cells prepared from patients with CLL. Dual PI3Kδ/γ inhibition normalized CD4/CD8 ratios and maximized the number of CD8+ T-stem cell memory, naive, and central memory T-cells with dose-dependent decreases in expression of the TIM-3 exhaustion marker. CART cells manufactured with duvelisib (Duv-CART cells) showed significantly increased in vitro cytotoxicity against CD19+ CLL targets caused by increased frequencies of CD8+ CART cells. Duv-CART cells had increased expression of the mitochondrial fusion protein MFN2, with an associated increase in the relative content of mitochondria. Duv-CART cells exhibited increased SIRT1 and TCF1/7 expression, which correlated with epigenetic reprograming of Duv-CART cells toward stem-like properties. After transfer to NOG mice engrafted with a human CLL cell line, Duv-CART cells expressing either a CD28 or 41BB costimulatory domain demonstrated significantly increased in vivo expansion of CD8+ CART cells, faster elimination of CLL, and longer persistence. Duv-CART cells significantly enhanced survival of CLL-bearing mice compared with conventionally manufactured CART cells. In summary, exposure of CART to a PI3Kδ/γ inhibitor during manufacturing enriched the CART product for CD8+ CART cells with stem-like qualities and enhanced efficacy in eliminating CLL in vivo.

"HIV has taught us that you can survive anything": findings from auto-ethnographic video diaries exploring resilience among people living with HIV during the Covid pandemic in five countries.

This study aimed to elucidate the intrinsic and extrinsic resilience resources among people living with HIV (PLWH) during the Covid pandemic. Autoethnographic video diaries from 29 PLWH from Argentina, UK, Philippines, Zimbabwe, and Trinidad and Tobago were included. Data were thematically analysed and validated with community partners and a video was co-produced. PLWH displayed a readiness to adopt healthy behaviours and engage in optimistic and constructive thinking about the future. Hobbies and daily activities, supportive relationships with peers living with HIV, family and friends, opportunities to mobilise and contribute to their communities in meaningful ways, supportive healthcare providers and reliable access to antiretroviral treatment helped foster psychological resilience among PLWH. The extrinsic resilience resources also supported positive physical health outcomes among PLWH through improved medication adherence.

Accuracy of patient-reported spell duration: A comparative study.

Clinicians rely heavily on patient histories to make medical diagnoses, most of which are inherently subjective and prone to inaccuracies. The aim of this study is to compare the subjective versus objective duration of spells through a retrospective chart review of patients admitted to the epilepsy monitoring unit at our tertiary care medical center. One hundred patients were analyzed. Differences in the accuracy of subjective estimations versus objective duration were compared by age, sex, focal versus generalized, location (frontal versus non-frontal), and spell type (focal aware versus impaired awareness and epileptic versus non-epileptic). Our data show that patients are poor subjective estimators, with 73% of patients overestimating the duration of their spells. We did not find differences in estimated duration by age, sex, seizure location or spell type. A notable exception was patients with generalized convulsive seizures, who accurately reported spell duration to within 17 s. This is likely because these seizures are stereotypical, and patients/family time them. Moreover, patients with non-epileptic spells were worse estimators of their spell duration than those with epileptic spells. In addition, although the prefrontal lobe plays a role in time estimation, we did not find that patients with frontal lobe seizures were worse estimators than those with non-frontal seizures, but invasive monitoring can more precisely localize seizures within areas of the frontal lobe responsible for time estimation. Our data emphasize the importance of not relying solely on patient-reported time estimation in diagnosing and developing treatment plans and instead instructing patients to time their spells.

Epidemiology and Outcomes of Hospitalized Chimeric Antigen Receptor T-Cell (CAR-T) Therapy Patients Who Developed Acute Respiratory Failure.

Objectives:The aim of the study was to examine the incidence, baseline characteristics, and outcomes of Chimeric Antigen Receptor T-cell (CAR-T) therapy admissions in individuals who developed acute respiratory failure (ARF). The study utilized the National Inpatient Sample (NIS) database for the years 2017 to 2020. Methods: The study identified CAR-T cell therapy hospitalizations through the International Classification of Diseases, Tenth Revision, Procedure Coding System (ICD-10-PCS) codes. Patients with acute respiratory failure (ARF) were further classified using specific International Classification of Disease, Tenth Revision, Clinical Modification (ICD-10-CM) codes. Descriptive statistics were performed to analyze baseline characteristics, comorbidities, complications, and outcomes. Results: Analysis of the NIS Database identified 5545 CAR-T therapy admissions between 2017 and 2020, revealing a rising trend over time. In our study, we found that hypertension (39%), dyslipidemia (21.7%), and venous thromboembolism (13%) were the most frequently observed comorbidities in CAR-T cell therapy admissions. Acute respiratory failure (ARF) was reported in 7.1% of admissions, and they had higher all-cause in-hospital mortality than CAR-T cell therapy admissions without ARF (32.9% vs 1.3%, P < 0.001). ARF admissions that required invasive mechanical ventilation (IMV) also had higher all-cause in-hospital mortality compared to admissions not requiring IMV (48.9% vs 11.8%, P = 0.001). There was no difference in the mortality rate among admissions with non-Hodgkin's Lymphoma, Multiple Myeloma, and Leukemia that utilized CAR-T therapy. Conclusions: In this largest study to date, we illuminate the incidence and outcomes of CAR-T cell therapy admissions with ARF. Higher mortality rates were observed in CAR-T cell therapy admissions with ARF. The study emphasizes the crucial role of interdisciplinary collaboration in CAR-T patient management and calls for additional research to clarify ARF's etiology and inform effective management strategies.

Targeting the vivid facets of apolipoproteins as a cardiovascular risk factor in rheumatoid arthritis.

Mostly, cardiovascular diseases are blamed for casualties in rheumatoid arthritis (RA) patients. Customarily, dyslipidemia is probably the most prevalent underlying cause of untimely demise in people suffering from RA as it hastens the expansion of atherosclerosis. The engagement of inflammatory cytokines like tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), etc., is crucial in the progression and proliferation of both RA and abnormal lipid parameters. Thus, lipid abnormalities should be monitored frequently in patients with both primary and advanced RA stages. An advanced lipid profile examination, i.e., direct role of apolipoproteins associated with various lipid molecules is a more dependable approach for better understanding of the disease and selecting suitable therapeutic targets. Therefore, studying their apolipoproteins is more relevant than assessing RA patients' altered lipid profile levels. Among the various apolipoprotein classes, Apo A1 and Apo B are primarily being focused. In addition, it also addresses how calculating Apo B:Apo A1 ratio can aid in analyzing the disease's risk. The marketed therapies available to control lipid abnormalities are associated with many other risk factors. Hence, directly targeting Apo A1 and Apo B would provide a better and safer option.

Avelumab in the Treatment of Advanced Merkel Cell Carcinoma: A Systematic Review.

BACKGROUND: Avelumab, a programmed death ligand-1 inhibitor, has shown success in providing durable responses for difficult-to-treat Merkel cell carcinomas (MCCs). OBJECTIVE: Evaluate the efficacy and safety of avelumab in the treatment of advanced MCC. METHODS: Studies reporting the use of avelumab as a monotherapy or in combination with other agents in the treatment of stage III or IV (advanced) MCC were included. The primary outcomes were overall response rate, overall survival (OS), and treatment-related adverse events. RESULTS: A total of 48 studies were included, involving 1,565 patients with advanced MCC. Most patients were male (1,051, 67.3%) with stage IV MCC (517, 97.0%). The overall response rate was 46.1% (partial response-25.4% and complete response-20.7%) after a mean follow-up period of 9.5 months. Kaplan-Meier survival curves for the pooled stage III and IV group demonstrated OS rates of 58% at 1 year, 47% at 2 years, and 28% at 5 years after completion of treatment with avelumab (median OS: 23.1 months). The most common treatment-related adverse events consisted of constitutional (44%), gastrointestinal (19%), and dermatologic (12%) symptoms. CONCLUSION: Avelumab monotherapy and combination therapy have shown success in the overall response rate and survival for patients with advanced MCC.

Discovery of photosynthesis genes through whole-genome sequencing of acetate-requiring mutants of Chlamydomonas reinhardtii.

Large-scale mutant libraries have been indispensable for genetic studies, and the development of next-generation genome sequencing technologies has greatly advanced efforts to analyze mutants. In this work, we sequenced the genomes of 660 Chlamydomonas reinhardtii acetate-requiring mutants, part of a larger photosynthesis mutant collection previously generated by insertional mutagenesis with a linearized plasmid. We identified 554 insertion events from 509 mutants by mapping the plasmid insertion sites through paired-end sequences, in which one end aligned to the plasmid and the other to a chromosomal location. Nearly all (96%) of the events were associated with deletions, duplications, or more complex rearrangements of genomic DNA at the sites of plasmid insertion, and together with deletions that were unassociated with a plasmid insertion, 1470 genes were identified to be affected. Functional annotations of these genes were enriched in those related to photosynthesis, signaling, and tetrapyrrole synthesis as would be expected from a library enriched for photosynthesis mutants. Systematic manual analysis of the disrupted genes for each mutant generated a list of 253 higher-confidence candidate photosynthesis genes, and we experimentally validated two genes that are essential for photoautotrophic growth, CrLPA3 and CrPSBP4. The inventory of candidate genes includes 53 genes from a phylogenomically defined set of conserved genes in green algae and plants. Altogether, 70 candidate genes encode proteins with previously characterized functions in photosynthesis in Chlamydomonas, land plants, and/or cyanobacteria; 14 genes encode proteins previously shown to have functions unrelated to photosynthesis. Among the remaining 169 uncharacterized genes, 38 genes encode proteins without any functional annotation, signifying that our results connect a function related to photosynthesis to these previously unknown proteins. This mutant library, with genome sequences that reveal the molecular extent of the chromosomal lesions and resulting higher-confidence candidate genes, will aid in advancing gene discovery and protein functional analysis in photosynthesis.

Human iPSC-Derived Proinflammatory Macrophages cause Insulin Resistance in an Isogenic White Adipose Tissue Microphysiological System.

Chronic white adipose tissue (WAT) inflammation has been recognized as a critical early event in the pathogenesis of obesity-related disorders. This process is characterized by the increased residency of proinflammatory M1 macrophages in WAT. However, the lack of an isogenic human macrophage-adipocyte model has limited biological studies and drug discovery efforts, highlighting the need for human stem cell-based approaches. Here, human induced pluripotent stem cell (iPSC) derived macrophages (iMACs) and adipocytes (iADIPOs) are cocultured in a microphysiological system (MPS). iMACs migrate toward and infiltrate into the 3D iADIPOs cluster to form crown-like structures (CLSs)-like morphology around damaged iADIPOs, recreating classic histological features of WAT inflammation seen in obesity. Significantly more CLS-like morphologies formed in aged and palmitic acid-treated iMAC-iADIPO-MPS, showing the ability to mimic inflammatory severity. Importantly, M1 (proinflammatory) but not M2 (tissue repair) iMACs induced insulin resistance and dysregulated lipolysis in iADIPOs. Both RNAseq and cytokines analyses revealed a reciprocal proinflammatory loop in the interactions of M1 iMACs and iADIPOs. This iMAC-iADIPO-MPS thus successfully recreates pathological conditions of chronically inflamed human WAT, opening a door to study the dynamic inflammatory progression and identify clinically relevant therapies.

Recurrent mutations in Refractory/Relapsed Diffuse Large B cell Lymphoma by targeted gene sequencing.

Introduction-Whole genome sequencing of diffuse large B-cell lymphoma [DLBCL] has identified recurrent mutations involved in pathogenesis and potentially affecting response to therapy. In this pilot study, a targeted gene panel was created to identify mutations associated with relapse/refractoriness. Material and methods- A 14-gene targeted panel was designed to sequence thirteen patients who were in remission and nine eight cases that had relapsed/refractory to treatment. A paired diagnostic biopsy and a relapse biopsy were sequenced to find genes repeatedly altered in relapse. Results- A total of 751 nonsynonymous and truncating mutations were identified. Truncated mutations in NOTCH1, TNFAIP3, and CD58 were associated with poor treatment outcomes. In cases that did not respond to treatment, a high number of mutations were found in the EZH2 gene, followed by the DNA-binding domain of TP53 and MYD88. Termination mutations in the intracellular domain of NOTCH were found in 75% of non-responsive cases. Co-occurrence of loss of function mutations of TNFAIP3 and missense mutations in MYD88 was associated with a non-responsive cohort. Discussion-The study highlights mutations associated with chemotherapeutic response in DLBCL with implications for initial diagnostic biopsy response prediction.

The effect of hormone replacement therapy on cognition and mood.

OBJECTIVES: To summarise the available data regarding the effect of hormone replacement therapy (HRT) on cognition and mood in women. BACKGROUND: Complaints of impaired cognition and mood are common in the peri-menopausal and menopausal period. There is debate as to whether HRT can ameliorate this phenomenon. DESIGN: A literature search of studies using electronic databases was conducted. Both randomised control trials and observational studies were included. PATIENTS: Perimenopausal and menopausal women. RESULTS: Due to the heterogenicity of results it is challenging to draw firm conclusions. The preparations used in many of the studies are older regimes no longer routinely used clinically. The notion of a 'critical window' for HRT is compelling, suggesting HRT has a positive impact on cognition when administered in the peri-menopausal or early postmenopausal period but may have negative effects on cognition in the older, postmenopausal woman. The evidence would seem to suggest importance of hormonal replacement in woman undergoing a surgical menopause, especially when young. It remains unclear for how long they ought to continue HRT though until at least the natural age of the menopause seems reasonable. Evidence for a positive effect of HRT on mood is more convincing, though possibly more efficacious in the younger age group. The effect of HRT on anxiety is less clear. CONCLUSIONS: Further study, particularly focusing on the more contemporaneous HRT preparations, is warranted before evidence-based conclusions can be drawn.

Epidemiology and early mortality patterns of acute promyelocytic leukemia in the United States.

There is a lack of contemporary population-based data on the epidemiology of acute promyelocytic leukemia (APL) in the United States. In this study, we aim to elucidate the demographics and early mortality patterns of APL hospitalizations utilizing the National Inpatient Sample database from 2016-2019. APL's annual age-adjusted incidence rate was 0.28/100,000, and the incidence increased with age, with the peak incidence in the 75-79 age group at 0.62/100,000. Whites constituted the majority of admissions at 67.7%, followed by Hispanics at 15.3%, the youngest racial group with a median age of 40 years. The median length of stay was 31 days for patients age < 60 years and 25 days for age ≥ 60 years (p < 0.001). After adjusting for confounders, the mean length of stay was 7 days higher in teaching hospitals compared to non-teaching hospitals (p 0.001). Overall mortality was 12.1% (22.2% for age ≥ 60 and 6.4% for < 60 years {p < 0.001}), and 56.5% of deaths happened before 7 days, with the median time to death being 6 days. The proportion of early deaths (< 7 days) in non-teaching hospitals was higher than late deaths (≥ 7 days) (19.2% vs. 5%; p 0.03), and admission to a teaching hospital was associated with lower mortality (adjusted odds ratio 0.27; p 0.01). Therefore, optimal treatment strategies need to be explored to mitigate this significant early mortality, especially in non-teaching hospitals.

Acidic Calcium-Independent Phospholipase A2 Regulates Eosinophil-Mediated Pathology during Filarial Manifestation of Tropical Pulmonary Eosinophilia.

Eosinophils mediate pathological manifestations during tropical pulmonary eosinophilia (TPE), a potentially fatal complication of lymphatic filariasis, by mechanisms that are incompletely understood. Using two-dimensional gel electrophoresis, mass spectrometry, flow cytometry, and pharmacological and functional studies, we identified acidic calcium-independent phospholipase A2 (aiPLA2) as the master regulator of TPE pathogenesis. FACS-sorted lung eosinophils from TPE mice exhibited aiPLA2-dependent activation characterized by heavy calcium influx, F-actin polymerization, increased degranulation, and heightened reactive oxygen species generation. Interestingly, aiPLA2 also promoted alternative activation in lung macrophages and regulated the release of inflammatory intermediates from them. Treatment of TPE mice with MJ33, a nontoxic pharmacological inhibitor of aiPLA2, lowered eosinophil counts in the bronchoalveolar lavage fluid, reduced eosinophil peroxidase and ß-hexosaminidase activity, increased airway width, improved lung endothelial barrier, and lowered the production of inflammatory lipid intermediates, which significantly improved the pathological condition of the lungs. Importantly, ex vivo reconstitution of arachidonic acid to eosinophils from MJ33-treated TPE mice increased eosinophil degranulation and inflammatory lipid intermediates underlining the pivotal role of aiPLA2 in arachidonic acid metabolism. Mechanistically, phosphorylation of JNK-1 regulated phospholipase activity of aiPLA2, whereas IgG cross-linking mediated pathological activation of eosinophils. Taken together, ours is the first study, to our knowledge, to report hitherto undocumented role of aiPLA2 in regulating TPE pathogenesis.

Clinical features and outcomes of patients with diacylglycerol kinase epsilon nephropathy: a nationwide experience.

BACKGROUND: Thrombotic microangiopathy (TMA) is usually caused due to dysregulation of the alternative complement pathway. Rarely, thrombotic microangiopathy is caused by non-complement mediated mutations in diacylglycerol kinase epsilon (DGKE); information about therapy and outcome of these patients is limited. METHODS: Medical records of patients, younger than 18 years, diagnosed with TMA and variants in DGKE were reviewed to include 12 patients from seven centers. Genetic studies included targeted exome sequencing and multiplex-ligation dependent probe amplification of CFH-CFHR5. RESULTS: Patients presented at a median age of 11 (7.5, 12.3) months; all were younger than 2 years. All patients had an infectious prodrome; enteroinvasive, enteropathogenic, and enterotoxigenic Escherichia coli were detected in two patients with diarrhea. Chief features included those of microangiopathic hemolysis (n = 11), microscopic hematuria (n = 10), nephrotic range proteinuria (n = 10), hypoalbuminemia (n = 6), elevated total cholesterol (n = 6), and hypocomplementemia (n = 4). Histopathology showed thrombotic microangiopathy (n = 4), overlapping with membranoproliferative pattern of injury (n = 1). At median 3.3 years of follow-up, significant hypertension and/or proteinuria (40%), relapses (66.7%), and death or progression to CKD (60%) were common. Genetic sequencing showed 13 homozygous and compound heterozygous variants (7 pathogenic, 3 likely pathogenic) located throughout DGKE; 11 variants were novel. CONCLUSIONS: This case series highlights the need to suspect DGKE nephropathy in young patients with TMA, especially those with severe proteinuria. Medium-term outcomes are unsatisfactory with risk of relapses, progressive kidney failure, and death. A higher resolution version of the Graphical abstract is available as Supplementary information.

Current trends in management of bacterial pathogens infecting plants.

Plants are continuously challenged by different pathogenic microbes that reduce the quality and quantity of produce and therefore pose a serious threat to food security. Among them bacterial pathogens are known to cause disease outbreaks with devastating economic losses in temperate, tropical and subtropical regions throughout the world. Bacteria are structurally simple prokaryotic microorganisms and are diverse from a metabolic standpoint. Bacterial infection process mainly involves successful attachment or penetration by using extracellular enzymes, type secretion systems, toxins, growth regulators and by exploiting different molecules that modulate plant defence resulting in successful colonization. Theses bacterial pathogens are extremely difficult to control as they develop resistance to antibiotics. Therefore, attempts are made to search for innovative methods of disease management by the targeting bacterial virulence and manipulating the genes in host plants by exploiting genome editing methods. Here, we review the recent developments in bacterial disease management including the bioactive antimicrobial compounds, bacteriophage therapy, quorum-quenching mediated control, nanoparticles and CRISPR/Cas based genome editing techniques for bacterial disease management. Future research should focus on implementation of smart delivery systems and consumer acceptance of these innovative methods for sustainable disease management.

Evaluating the Sleep Treatment Education Program (STEP-1): A single-session educational workshop addressing insomnia in cancer survivors.

Insomnia is a common late effect of cancer, affecting as many as 27% of cancer survivors. Although cognitive behavioral therapy for insomnia (CBT-I) is highly effective, treatment-associated burdens and limited availability of providers result in few survivors receiving this treatment. To address this gap, we developed the Sleep Treatment Education Program-1 (STEP-1), a single-session intervention addressing insomnia after cancer. As a preliminary evaluation of STEP-1's potential to improve survivors' insomnia, STEP-1 was delivered to a convenience sample of 34 cancer survivors as an educational workshop in person or by videoconference. Participants completed the Insomnia Severity Index (ISI) at the workshop and at 1-month follow-up; items assessing participants' intentions to implement program suggestions and satisfaction were also collected. At 1-month follow-up, mean insomnia symptoms on the ISI were significantly lower compared to baseline (9.73 vs 15.73; d = 1.38, P < .001); the reduction in mean ISI scores did not significantly differ between in-person and videoconference participants (5.82 vs 6.33; P = .78). These results, along with positive indicators of program engagement and satisfaction, support the potential efficacy of STEP-1 to meet survivors' needs for insomnia care. Particularly when delivered by videoconference, STEP-1 has the potential to dramatically improve access and uptake for insomnia treatment in cancer survivors. Results also more generally support development of low-intensity, self-management insomnia interventions for cancer survivors and potentially other populations.

Integration of biochar with nitrogen in acidic soil: A strategy to sequester carbon and improve the yield of stevia via altering soil properties and nutrient recycling.

The health of agroecosystems is subsiding unremittingly, and the over-use of chemical fertilizers is one of the key reasons. It is hypothesized that integrating biochar, a carbon (C)-rich product, would be an effective approach to reducing the uses of synthetic fertilizers and securing crop productivity through improving soil properties and nutrient cycling. The bamboo biochar at different quantities (4-12 Mg ha-1) and combinations with chemical fertilizers were tested in stevia (Stevia rebaudiana) farming in silty clay acidic soil. The integration of biochar at 8 Mg ha-1 with 100% nitrogen (N), phosphorus (P), and potassium (K) produced statistically (p ≤ 0.05) higher leaf area index, dry leaf yield, and steviol glycosides yield by about 18.0-33.0, 25.8-44.9, and 20.5-59.4%, respectively, compared with the 100% NPK via improving soil physicochemical properties. Soil bulk density was reduced by 5-8% with biochar at ≥ 8 Mg ha-1, indicating the soil porosity was increased by altering the soil macrostructure. The soil pH was significantly (p ≤ 0.05) augmented with the addition of biochar alone or in the combination of N because of the alkaline nature of the used biochar (pH = 9.65). Furthermore, integrating biochar at 8 Mg ha-1 with 100% NPK increased 22.7% soil organic C compared with the sole 100% NPK. The priming effect of applied N activates soil microorganisms to mineralize the stable C. Our results satisfy the hypothesis that adding bamboo biochar would be a novel strategy for sustaining productivity by altering soil physicochemical properties.

Molecular Aspects and Therapeutic Implications of Herbal Compounds Targeting Different Types of Cancer.

Due to genetic changes in DNA (deoxyribonucleic acid) sequences, cancer continues to be the second most prevalent cause of death. The traditional target-directed approach, which is confronted with the importance of target function in healthy cells, is one of the most significant challenges in anticancer research. Another problem with cancer cells is that they experience various mutations, changes in gene duplication, and chromosomal abnormalities, all of which have a direct influence on the potency of anticancer drugs at different developmental stages. All of these factors combine to make cancer medication development difficult, with low clinical licensure success rates when compared to other therapy categories. The current review focuses on the pathophysiology and molecular aspects of common cancer types. Currently, the available chemotherapeutic drugs, also known as combination chemotherapy, are associated with numerous adverse effects, resulting in the search for herbal-based alternatives that attenuate resistance due to cancer therapy and exert chemo-protective actions. To provide new insights, this review updated the list of key compounds that may enhance the efficacy of cancer treatment.

An Insight into Multisystem Inflammatory Syndrome in Adults Associated with Recent SARS-COV-2 Infection: A Case Series.

IMPORTANCE: Multisystem inflammatory syndrome-adults (MIS-A) occur in the postacute coronavirus disease 2019 (COVID-19) period with a diverse clinical presentation. A high index of suspicion, early recognition, diagnosis, and treatment of MIS-A might alleviate COVID-19-related morbidity and mortality. OBJECTIVE: To report seven cases of MIS-A with evidence of recent COVID-19 infection. This is a case series-based study and presents bona fide experiences in terms of main findings and treatment options. MATERIALS AND METHODS: It is a retrospective observational study. We retrospectively collected data on all patients who were diagnosed and treated for MIS-A during the period after the second wave of COVID-19 in India, that is, from June 2021 to November 2021and who were hospitalized in the author's unit. All patients fulfilled the morbidity and mortality weekly report (MMWR) criteria for multisystem inflammatory syndrome in adults. The presenting symptoms, clinical and laboratory parameters, management, and outcome of these seen cases are discussed in this case series-based review.. RESULTS: Data from seven patients were analyzed. Six of them were male, and one patient was female. The median age was 65 years. Four patients had a history of vaccination for COVID-19, three had a history of COVID-19 symptomatic infection in the past, and one patient had contact with COVID-19 in the previous 12 weeks. None of them tested positive for COVID-19 real-time reverse transcription polymerase chain reaction (RT-PCR) test, and all had positive COVID-19 serology. The commonest extrapulmonary organ involved were the cardiovascular and renal systems, followed by the gastrointestinal and central nervous systems (CNS). All had evidence of hyperinflammation. Intravenous immunoglobulin (IVIg) was used in four patients, and steroids were used in all seven patients. The median length of stay (LOS) was 11 days. One patient succumbed to multiorgan failure. CONCLUSIONS: Multisystem inflammatory syndrome (MIS) can affect children (MIS-C) as well as adults (MIS-A). MIS-A is a serious, life-threatening, hyperinflammatory febrile syndrome associated with recent COVID-19 infection and involves multiple organs like the heart, lungs, kidneys, brain, gastrointestinal organs, skin, eyes etc. Clinical suspicion and testing for evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are needed to identify and treat adults suspected to have MIS-A. This case series demonstrates that even the elderly population can be affected and that administration of IVIg and steroids are effective options in management in addition to the usual "standard of care" treatment. Early recognition and prompt treatment of MIS-A could improve clinical outcomes and reduce the mortality rate.

Modelling the ecological impact of invasive weed Verbesina encelioides on vegetation composition across dryland ecosystems of Punjab, northwestern India.

Events of climate change have led to increased aridification, which alters local vegetation patterns and results in the invasion of opportunistic species. Though many studies assess the impact of invasive weeds and aridification at the agronomic level, studies investigating changes in local vegetation are severely lacking. We investigated the impact of the invasive plant Verbesina encelioides (Asteraceae) on the local vegetation composition across different dryland ecosystems in Punjab, northwestern India. Based on the aridity index for the period of 1991-2016, three major dryland ecosystems, i.e., arid, semi-arid, and sub-humid, were found in Punjab. The impact of V. encelioides on local biodiversity was measured in terms of species diversity (using Shannon's diversity index, Simpson's dominance index, Hill's evenness index, and Margalef's richness index), species composition (using non-metric multidimensional scaling based on Bray-Curtis's dissimilarity index), and species proportion in the two invasion classes (uninvaded and invaded) and across the three aridity zones (arid, semi-arid, and sub-humid). The vegetation survey depicted the presence of 53 flowering species belonging to 22 families, including 30 exotics and 23 natives. Verbesina encelioides decreased species diversity and proportion, with a more pronounced impact in arid and semi-arid ecosystems. In contrast, species composition varied between uninvaded and invaded classes only in arid ecosystems. Ecological parameters derived from population statistics (number of individuals) were more drastically affected than those from species abundance data. Since the ecological impacts of V. encelioides were manifested with increased aridification, it is a matter of apprehension under the potential climate change scenario.