Nanomaterial in controlling biofilms and virulence of microbial pathogens.

The escalating threat of antimicrobial resistance (AMR) poses a grave concern to global public health, exacerbated by the alarming shortage of effective antibiotics in the pipeline. Biofilms, intricate populations of bacteria encased in self-produced matrices, pose a significant challenge to treatment, as they enhance resistance to antibiotics and contribute to the persistence of organisms. Amid these challenges, nanotechnology emerges as a promising domain in the fight against biofilms. Nanomaterials, with their unique properties at the nanoscale, offer innovative antibacterial modalities not present in traditional defensive mechanisms. This comprehensive review focuses on the potential of nanotechnology in combating biofilms, focusing on green-synthesized nanoparticles and their associated anti-biofilm potential. The review encompasses various aspects of nanoparticle-mediated biofilm inhibition, including mechanisms of action. The diverse mechanisms of action of green-synthesized nanoparticles offer valuable insights into their potential applications in addressing AMR and improving treatment outcomes, highlighting novel strategies in the ongoing battle against infectious diseases.

TiO2-SiO2 Self-Standing Materials bearing Hierarchical Porosity: MUB-200(x) Series toward 3D-Efficient VOC Photoabatement Properties.

Three-dimensional photoactive self-standing porous materials have been synthesized through the integration of soft chemistry and colloids (emulsions, lyotrope mesophases, and P25 titania nanoparticles). Final multiscale porous ceramics bear 700-1000 m2 g-1 of micromesoporosity depending on the P25 nanoparticle contents. The applied thermal treatment does not affect the P25 anatase/rutile allotropic phase ratio. Photonic investigations correlated with the foams' morphologies suggest that the larger amount of TiO2 that is introduced, the larger the walls' density and the smaller the mean size of the void macroscopic diameters, with both effects inducing a reduction of the photon transport mean free path (lt) with the P25 content increase. A light penetration depth in the range of 6 mm is reached, thus depicting real 3D photonic scavenger behavior. The 3D photocatalytic properties of the MUB-200(x) series, studied in a dynamic "flow-through" configuration, show that the highest photoactivity (concentration of acetone ablated and concentration of CO2 formed) is obtained with the highest monolith height (volume) while providing an average of 75% mineralization. These experimental results validate the fact that these materials, bearing 3D photoactivity, are paving the path for air purification operating with self-standing porous monolith-type materials, which are much easier to handle than powders. As such, the photocatalytic systems can now be advantageously miniaturized, thereby offering indoor air treatment within vehicles/homes while drastically limiting the associated encumbrance. This volumetric counterintuitive acting mode for light-induced reactions may find other relevant advanced applications for photoinduced water splitting, solar fuel, and dye-sensitized solar cells while both optimizing photon scavenging and opening the path for the miniaturization of the processes where encumbrance or a foot-print penalty would be advantageously circumvented.

Platelet response to aspirin in UK and Irish pregnancy cohorts: a genome-wide approach.

A multi-center prospective cross-sectional and genome-wide association study (GWAS) recruited pregnant women taking low dose aspirin. Objectives were to (i) develop pregnancy-specific 95% reference intervals for a range of laboratory based platelet function tests (PFTs); (ii) select an optimal and acceptable PFT that reflected aspirin's COX-1 inhibition in women with confirmed aspirin adherence in pregnancy; and (iii) identify genomic variants that may influence pregnant women's platelet response to aspirin.The study included two independent cohorts of pregnant women. A range of PFTs and matched phenotyping with urinary 11-dehydrothromboxane B2 (11DTXB2) and nuclear magnetic resonance (NMR) spectroscopy detection of urinary salicyluric acid as a measure of aspirin adherence were performed. Genome-wide data was acquired from the UK Biobank Axiom® (Thermo Fisher Scientific). 11DTXB2 in combination with adherence testing with NMR salicyluric acid was an accurate and acceptable testing strategy for detecting biochemical aspirin responsiveness in pregnant women, with the provision of relevant reference ranges. GWAS meta-analysis found no significant single nucleotide polymorphisms in association with response to aspirin in pregnancy. Further evaluation in relation to effective dosing of aspirin in pregnancy and optimizing the benefits to specific subgroups should now be a priority for future research.

Genomic insights into waste valorized extracellular polymeric substances (EPS) produced by Bacillus sp. ISTL8.

The present study discusses the genomic analysis of Bacillus sp. ISTL8 along with the production of EPS (Extracellular polymeric substances) using carbofuran, a toxic carbamate pesticide. Bacillus strain was isolated from landfill soil and evaluated for high growth rates and EPS production. One strain, renamed ISTL8 grew on a broad range of carbon sources, including toxic carbofuran, while producing copious EPS. Growth assays verified the strain to be thermophilic, low salt tolerant, and with a preference for neutral pH. SEM (Scanning Electron Microscopy) was used for morphological characterization of the EPS while the monomeric composition, bonding patterns and functional groups were deduced by GC-MS (Gas Chromatography-Mass Spectrometry), 1H and 13C NMR (Nuclear Magnetic Resonance) and FTIR (Fourier Transform Infrared Spectroscopy). The production of EPS using carbofuran (carbamate pesticide) as a carbon source was found to be 6.20 ± 0.29 g L-1 containing 61.17% w/w carbohydrates, 29.72% w/w proteins and 6.11% w/w lipids (of dry EPS). The potential cytotoxicity of EPS was evaluated with 3- (4,5-dimethyl thiazol-2-Yl) -2,5-diphenyl tetrazolium bromide (MTT) assay and found non-toxic (2.25%). WGS (Whole genome sequencing) was performed for the strain Bacillus sp. ISTL8 producing EPS; an array of genes putatively involved in the EPS production were identified in several different genomic locations, guiding potential genetic manipulation studies in the future. The results highlight the potency of a bacterial isolate Bacillus sp. ISTL8 to produce non-cytotoxic EPS using carbofuran that can be further harnessed for environmental and commercial applications. Additionally, WGS revealed an array of EPS specific genes which can be effectively engineered for much enhanced production.

Psychological and Behavioral Impact of Lockdown and Quarantine Measures for COVID-19 Pandemic on Children, Adolescents and Caregivers: A Systematic Review and Meta-Analysis.

BACKGROUND: During the current ongoing COVID-19 pandemic, psychological problems like anxiety, depression, irritability, mood swings, inattention and sleep disturbance are fairly common among quarantined children in several studies. A systematic review of these publications to provide an accurate burden of these psychiatric/behavioral problems is needed for planning mitigating measures by the health authorities. METHODS: Different electronic databases (MEDLINE, EMBASE, Web of Science, CENTRAL, medRxiv and bioRxiv) were searched for articles describing psychological/behavioral complications in children/adolescents with/without pre-existing behavioral abnormalities and their caregivers related to the COVID-19 pandemic. Only original articles with/without comparator arms and a minimum sample size of 50 were included in the analysis. The pooled estimate of various psychological/behavioral problems was calculated using a random-effect meta-analysis. RESULTS: Fifteen studies describing 22 996 children/adolescents fulfilled the eligibility criteria from a total of 219 records. Overall, 34.5%, 41.7%, 42.3% and 30.8% of children were found to be suffering from anxiety, depression, irritability and inattention. Although the behavior/psychological state of a total of 79.4% of children was affected negatively by the pandemic and quarantine, at least 22.5% of children had a significant fear of COVID-19, and 35.2% and 21.3% of children had boredom and sleep disturbance. Similarly, 52.3% and 27.4% of caregivers developed anxiety and depression, respectively, while being in isolation with children. CONCLUSION: Anxiety, depression, irritability, boredom, inattention and fear of COVID-19 are predominant new-onset psychological problems in children during the COVID-19 pandemic. Children with pre-existing behavioral problems like autism and attention deficit hyperactivity disorder have a high probability of worsening of their behavioral symptoms.

Development of a novel outcome prediction score (PEDSS) for pediatric convulsive status epilepticus: A longitudinal observational study.

OBJECTIVE: The objectives of this study were to evaluate ENDIT score and develop a novel outcome prediction score for outcome of pediatric convulsive status epilepticus (CSE) at the hospital and 3 months postdischarge. METHODS: Children and adolescents aged 1 month to 14 years, presenting with CSE to a tertiary care teaching center in North India from January 2017 to March 2019, were screened for enrollment. In-hospital and 3-month postdischarge outcome were defined as poor if Pediatric Cerebral Performance Category Scale (PCPCS) score dropped by ≥2 levels. RESULTS: Overall, 61 patients were enrolled for final analysis after applying exclusion and inclusion criteria. The area under the receiver operating characteristic (ROC) curve for ENDIT score in predicting mortality and differentiating good from poor outcome at the hospital and at 3 months postdischarge was 0.74 (95% confidence interval [CI] = 0.58-0.89), 0.7 (95% CI = 0.57-0.83), and 0.72 (95% CI = 0.6-0.82), respectively. Based on predictors in the present cohort that were significantly different between good and poor outcome cases at the hospital and 3 months postdischarge, a new six-point score named PEDSS (pre-status epilepticus PCPCS, background electroencephalographic abnormalities, drug refractoriness, semiology, and critical sickness) was developed. The area under ROC curves for PEDSS score in predicting mortality and differentiating good from poor outcome at the hospital and at 3 months postdischarge were 0.93 (95% CI = 0.87-0.99), 0.8 (95% CI = 0.7-0.9), and 0.89 (95% CI = 0.8-0.96), respectively. The best cutoff PEDSS scores for predicting mortality and poor outcome at the hospital and at 3 months postdischarge were ≥4, ≥3, and ≥3, respectively. SIGNIFICANCE: The PEDSS score has high predictive accuracy for mortality and differentiating good from poor outcome at the hospital and 3 months postdischarge in pediatric CSE. Future studies should be planned to validate it in various geographical and health care settings and in adults.

Child Neurology: Allgrove Syndrome: An Intriguing Etiology of Motor Neuron Disease in Children

Motor neuron diseases are a rare group of neurodegenerative disorders with considerable phenotypic heterogeneity and a multitude of etiologies in the pediatric population. In this study, we report 2 unrelated adolescents (a boy and a girl) who presented with 4-6 years of progressive difficulty in walking, thinning of limbs, and gradually progressive darkening of the skin. Examination revealed generalized hyperpigmentation of skin and features suggestive of motor neuron involvement such as tongue atrophy, wasting of distal extremities, and brisk deep tendon reflexes. On detailed exploration for systemic involvement, history of dysphagia, inability to produce tears, and Addisonian crises were evident. An etiologic diagnosis of Allgrove syndrome, which is characterized by a triad of achalasia, alacrimia, and adrenal insufficiency was considered. Next-generation sequencing revealed pathogenic variants in the AAAS gene, confirming the diagnosis. Steroid replacement therapy was initiated along with relevant multidisciplinary referrals. The disease stabilized in the boy and a significant improvement was noted in the girl. These cases highlight the value of non-neurologic cues in navigating the etiologic complexities of motor neuron diseases in children and adolescents. It is imperative for neurologists to develop awareness of the diverse neurologic manifestations associated with Allgrove syndrome because they are often the first to be approached. A multidisciplinary team of experts including neurologists, endocrinologists, gastroenterologists, ophthalmologists, and dermatologists is essential for planning comprehensive care for these patients.

Pregnancy Outcomes and Maternal Periodontal Diseases: The Unexplored Connection.

In the early 20th century, numerous in-vitro studies, animal studies, epidemiological studies, and human trials have attempted to demonstrate the interrelationship between pregnancy outcomes and maternal periodontal disease. This review aims to shed light on the unexplored connections between pregnancy outcomes and maternal periodontal diseases. A literature search was conducted using electronic databases such as PubMed, Scopus, Google Scholar, Web of Science, and Embase. Our research focuses on the role of epigenetics, maternal vitamin D status, stress levels, genetic factors, innate immunity, pattern recognition receptors, and any potential paternal influence, and their possible connections to maternal periodontal disease. Although the precise etiologies and pathogenic mechanisms of the adverse pregnancy outcomes remain obscure, substantial affirmation of the inter-relationship between maternal periodontal diseases and adverse pregnancy outcomes may prove to be of public health relevance as periodontitis can certainly be prevented and treated. Maternal periodontal disease may augment the probability of jeopardizing maternal health causing adverse effects on the pregnancy and neonatal morbidity. Hence, emphasis should be placed on an early diagnosis and management of periodontal diseases. Routine oral health evaluation during prenatal care should be encouraged to combat complications. Ensuing endeavors should be undertaken to help find plausible mechanisms keeping in view the future research domains and new pathways.

Harnessing Nanovaccines for Effective Immunization─A Special Concern on COVID-19: Facts, Fidelity, and Future Prospective.

Nanotechnology has emerged as a transformative pathway in vaccine research and delivery. Nanovaccines, encompassing lipid and nonlipid formulations, exhibit considerable advantages over traditional vaccine techniques, including enhanced antigen stability, heightened immunogenicity, targeted distribution, and the potential for codelivery with adjuvants or immune modulators. This review provides a comprehensive overview of the latest advancements and applications of lipid and non-lipid-based nanovaccines in current vaccination strategies for immunization. The review commences by outlining the fundamental concepts underlying lipid and nonlipid nanovaccine design before delving into the diverse components and production processes employed in their development. Subsequently, a comparative analysis of various nanocarriers is presented, elucidating their distinct physicochemical characteristics and impact on the immune response, along with preclinical and clinical studies. The discussion also highlights how nanotechnology enables the possibility of personalized and combined vaccination techniques, facilitating the creation of tailored nanovaccines to meet the individual patient needs. The ethical aspects concerning the use of nanovaccines, as well as potential safety concerns and public perception, are also addressed. The study underscores the gaps and challenges that must be overcome before adopting nanovaccines in clinical practice. This comprehensive analysis offers vital new insights into lipid and nonlipid nanovaccine status. It emphasizes the significance of continuous research, collaboration among interdisciplinary experts, and regulatory measures to fully unlock the potential of nanotechnology in enhancing immunization and ensuring a healthier, more resilient society.

Association of maternal prenatal copper concentration with gestational duration and preterm birth: a multicountry meta-analysis.

BACKGROUND: Copper (Cu), an essential trace mineral regulating multiple actions of inflammation and oxidative stress, has been implicated in risk for preterm birth (PTB). OBJECTIVES: This study aimed to determine the association of maternal Cu concentration during pregnancy with PTB risk and gestational duration in a large multicohort study including diverse populations. METHODS: Maternal plasma or serum samples of 10,449 singleton live births were obtained from 18 geographically diverse study cohorts. Maternal Cu concentrations were determined using inductively coupled plasma mass spectrometry. The associations of maternal Cu with PTB and gestational duration were analyzed using logistic and linear regressions for each cohort. The estimates were then combined using meta-analysis. Associations between maternal Cu and acute-phase reactants (APRs) and infection status were analyzed in 1239 samples from the Malawi cohort. RESULTS: The maternal prenatal Cu concentration in our study samples followed normal distribution with mean of 1.92 µg/mL and standard deviation of 0.43 µg/mL, and Cu concentrations increased with gestational age up to 20 wk. The random-effect meta-analysis across 18 cohorts revealed that 1 µg/mL increase in maternal Cu concentration was associated with higher risk of PTB with odds ratio of 1.30 (95% confidence interval [CI]: 1.08, 1.57) and shorter gestational duration of 1.64 d (95% CI: 0.56, 2.73). In the Malawi cohort, higher maternal Cu concentration, concentrations of multiple APRs, and infections (malaria and HIV) were correlated and associated with greater risk of PTB and shorter gestational duration. CONCLUSIONS: Our study supports robust negative association between maternal Cu and gestational duration and positive association with risk for PTB. Cu concentration was strongly correlated with APRs and infection status suggesting its potential role in inflammation, a pathway implicated in the mechanisms of PTB. Therefore, maternal Cu could be used as potential marker of integrated inflammatory pathways during pregnancy and risk for PTB.

Comparative Assessment of Periodontal Status in Subjects with and without Polycystic Ovary Syndrome and its Correlation with Body Mass Index: A Cross-Sectional Study.

New avenues for research have opened, which assess the influence of systemic disease on periodontium and vice versa. To find the correlation between polycystic ovary syndrome (PCOS) and periodontium by assessing clinical parameters [plaque index (PI), probing depth, periodontal disease index (PDI)] and the anthropological parameter [body mass index (BMI)] and to find the correlation between body mass index and periodontal disease index in subjects with and without PCOS. Sixty females comprising 30 with PCOS and 30 without PCOS were selected. Clinical, anthropological, and radiological assessment was done. Double blinding was incorporated. There was a statistically highly significant difference in mean age, mean PI, and mean PDI (P < 0.001) in PCOS group when compared to those without PCOS group by unpaired t-test for inter-group analysis. A statistically significant difference was found in mean probing depth and mean BMI (P < 0.05) in PCOS group when compared to those without PCOS group by unpaired t-test for inter-group analysis. No statistically significant correlation was found between mean PDI and mean BMI in PCOS and non-PCOS group subjects using Spearman's rank correlation. Women suffering from PCOS may be at a heightened risk for developing periodontal disease as our study re-establishes this association with respect to some periodontal parameters. With such a result, general practitioners/gynecologists can be encouraged to refer cases of PCOS to periodontists for early detection, prevention of periodontal disease, and maintenance of periodontal health.

The Relationship Between Insufficient Vision and Technology Access and Use Among Hospitalized Adults at an Urban Academic Hospital: Observational Study.

BACKGROUND: The role of sufficient vision in self-management is salient with respect to the growing prevalence of eHealth-based interventions for chronic diseases. However, the relationship between insufficient vision and self-management has been understudied. OBJECTIVE: We aimed to assess differences in access to and use of technology among adults with and without insufficient vision at an academic urban hospital. METHODS: This is an observational study of hospitalized adult general medicine patients that is part of a larger quality improvement study called the hospitalist study. The hospitalist study provided demographic and health literacy data (Brief Health Literacy Screen). Our substudy included several measures. Validated surveys assessed technology access and use, and included benchmarked questions from the National Pew Survey to determine access to, willingness to use, and self-described ability to use technology at home, particularly for self-management, and eHealth-specific questions assessing future willingness to access eHealth post discharge. The eHealth Literacy Scale (eHEALS) was used to assess eHealth literacy. Visual acuity was assessed using the Snellen pocket eye chart with low vision defined as visual acuity ≤20/50 in at least one eye. Descriptive statistics, bivariate chi-square analyses, and multivariate logistic regressions (adjusted for age, race, gender, education level, and eHealth literacy) were performed using Stata. RESULTS: A total of 59 participants completed our substudy. The mean age was 54 (SD 16.4) years. Demographic data from the hospitalist study was missing for several participants. Among those who responded, most identified as Black (n=34, 79%) and female (n=26, 57%), and most reported at least some college education (n=30, 67%). Most participants owned technology devices (n=57, 97%) and had previously used the internet (n=52, 86%), with no significant differences between those with insufficient and sufficient vision (n=34 vs n=25). Though there was a 2x effect size for laptop ownership, with those with sufficient vision more likely to own a laptop, those with insufficient vision versus sufficient vision were less likely to report an ability to perform online tasks without assistance, including using a search engine (n=22, 65% vs n=23, 92%; P=.02), opening an attachment (n=17, 50% vs n=22, 88%; P=.002), and using an online video (n=20, 59% vs n=22, 88%; P=.01). In multivariate analysis, the ability to independently open an online attachment did not remain statistically significant (P=.01). CONCLUSIONS: Technology device ownership and internet use rates are high in this population, yet participants with insufficient vision (vs sufficient vision) reported a reduced ability to independently perform online tasks. To ensure the effective use of eHealth technologies by at-risk populations, the relationship between vision and technology use needs to be further studied.

Primary Hemophagocytic Lymphohistiocytosis With Prolonged Primary Neurologic Presentation.

Primary hemophagocytic lympho-histiocytosis (HLH) is a hyperinflammatory syndrome with devastating consequences. Multisystem involvement is a hallmark of HLH; however, HLH may rarely present with signs and symptoms isolated to the central nervous system (CNS). Within the brain, HLH can mimic demyelination, chronic infection, or vasculitis, leading to a diagnostic delay of months to years. We describe here a 7-year-old boy who presented with a history of prolonged fever and multiple focal neurologic deficits, which were being treated as CNS tuberculosis at the referring hospital. In view of the relapsing course with multiple areas of hemorrhagic tumefactive lesions on neuroimaging, the diagnosis was revised to acquired demyelination, and he received multiple cycles of immunotherapy. A brain biopsy was inconclusive. Subsequently, 13 months after disease onset, the child presented with features of systemic HLH in the form of fever, pancytopenia, splenomegaly, elevated ferritin, and triglycerides. Primary HLH was suspected, and genetic testing revealed a likely pathologic compound heterozygous variation in the PRF1 gene confirming the diagnosis. We planned a hematopoietic stem cell transplant as definitive therapy, but the child succumbed to an episode of sepsis and aspiration pneumonia. We infer from this case that primary HLH is a great mimicker. A high index of suspicion is required to establish a timely diagnosis. Primary HLH may stay isolated to CNS for months and should be considered in the differential diagnosis of all refractory cases of demyelination.

Brain Stimulation and Constraint Induced Movement Therapy in Children With Unilateral Cerebral Palsy: A Randomized Controlled Trial.

BACKGROUND: There is a crucial need to devise optimum rehabilitation programs for children with cerebral palsy (CP). OBJECTIVE: This study aimed to assess the feasibility, safety, and efficacy of combining 6-Hz primed, low-frequency, repetitive transcranial magnetic stimulation (rTMS) with modified constraint-induced movement therapy (mCIMT) in improving upper limb function in children with unilateral CP. METHODS: Children aged 5 to 18 years with unilateral CP were randomized (23 in each arm) to receive 10 sessions of mCIMT with real rTMS (intervention arm) or mCIMT with sham rTMS (control arm), on alternate weekdays over 4 weeks. The primary outcome was the difference in mean change in Quality of Upper Extremity Skills Test (QUEST) scores. Secondary outcomes were changes in QUEST domain scores, speed and strength measures, CP quality of life (CP-QOL) scale scores, and safety of rTMS. RESULTS: All 46 children completed the trial except one. At 4 weeks, the mean change in total QUEST scores was significantly higher in the intervention arm as compared to the control arm (11.66 ± 6.97 vs 6.56 ± 4.3, d = 5.1, 95% CI 1.7-8.5, P = .004). Change in "weight bearing" and "protective extension" domain score was significantly higher for children in the intervention arm. These improvements were sustained at 12 weeks (P = .028). CP-QOL scores improved at 12 weeks. No serious adverse events were seen. CONCLUSION: A 6-Hz primed rTMS combined with mCIMT is safe, feasible, and superior to mCIMT alone in improving the upper limb function of children with unilateral CP. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03792789.

ETV6 Deficiency Unlocks ERG-Dependent Microsatellite Enhancers to Drive Aberrant Gene Activation in B-Lymphoblastic Leukemia.

Distal enhancers play critical roles in sustaining oncogenic gene-expression programs. We identify aberrant enhancer-like activation of GGAA tandem repeats as a characteristic feature of B-cell acute lymphoblastic leukemia (B-ALL) with genetic defects of the ETV6 transcriptional repressor, including ETV6-RUNX1+ and ETV6-null B-ALL. We show that GGAA repeat enhancers are direct activators of previously identified ETV6-RUNX1+/- like B-ALL "signature" genes, including the likely leukemogenic driver EPOR. When restored to ETV6-deficient B-ALL cells, ETV6 directly binds to GGAA repeat enhancers, represses their acetylation, downregulates adjacent genes, and inhibits B-ALL growth. In ETV6-deficient B-ALL cells, we find that the ETS transcription factor ERG directly binds to GGAA microsatellite enhancers and is required for sustained activation of repeat enhancer-activated genes. Together, our findings reveal an epigenetic gatekeeper function of the ETV6 tumor suppressor gene and establish microsatellite enhancers as a key mechanism underlying the unique gene-expression program of ETV6-RUNX1+/- like B-ALL. SIGNIFICANCE: We find a unifying mechanism underlying a leukemia subtype-defining gene-expression signature that relies on repetitive elements with poor conservation between humans and rodents. The ability of ETV6 to antagonize promiscuous, nonphysiologic ERG activity may shed light on other roles of these key regulators in hematolymphoid development and human disease. See related commentary by Mercher, p. 2. This article is highlighted in the In This Issue feature, p. 1.

Selective Enhancer Dependencies in MYC -Intact and MYC -Rearranged Germinal Center B-cell Diffuse Large B-cell Lymphoma.

High expression of MYC and its target genes define a subset of germinal center B-cell diffuse large B-cell lymphoma (GCB-DLBCL) associated with poor outcomes. Half of these high-grade cases show chromosomal rearrangements between the MYC locus and heterologous enhancer-bearing loci, while focal deletions of the adjacent non-coding gene PVT1 are enriched in MYC -intact cases. To identify genomic drivers of MYC activation, we used high-throughput CRISPR-interference (CRISPRi) profiling of candidate enhancers in the MYC locus and rearrangement partner loci in GCB-DLBCL cell lines and mantle cell lymphoma (MCL) comparators that lacked common rearrangements between MYC and immunoglobulin (Ig) loci. Rearrangements between MYC and non-Ig loci were associated with unique dependencies on specific enhancer subunits within those partner loci. Notably, fitness dependency on enhancer modules within the BCL6 super-enhancer ( BCL6 -SE) cluster regulated by a transcription factor complex of MEF2B, POU2F2, and POU2AF1 was higher in cell lines bearing a recurrent MYC::BCL6 -SE rearrangement. In contrast, GCB-DLBCL cell lines without MYC rearrangement were highly dependent on a previously uncharacterized 3' enhancer within the MYC locus itself (GCBME-1), that is regulated in part by the same triad of factors. GCBME-1 is evolutionarily conserved and active in normal germinal center B cells in humans and mice, suggesting a key role in normal germinal center B cell biology. Finally, we show that the PVT1 promoter limits MYC activation by either native or heterologous enhancers and demonstrate that this limitation is bypassed by 3' rearrangements that remove PVT1 from its position in cis with the rearranged MYC gene. Key points: CRISPR-interference screens identify a conserved germinal center B cell MYC enhancer that is essential for GCB-DLBCL lacking MYC rearrangements. Functional profiling of MYC partner loci reveals principles of MYC enhancer-hijacking activation by non-immunoglobulin rearrangements.

Biogeochemical profiling and taxonomic characterization of municipal landfill site by metagenomic sequencing.

Most of the discarded waste material paves their way to the utmost common dumping grounds, Landfills. Despite their widespread use, the landfill microbiomes are still not well characterized. Metagenomics approach provides insight into the identification of operational parameters influencing the microbiome composition and their biodegradation competencies. The metagenomic DNA was prepared to explore taxonomical community structure, phylogenetic relationships, and functional profile at the same time. A total of 100,021,052 high-quality filtered reads were acquired with a GC abundance of 62.59%. Taxonomical abundance revealed the dominance of phylum Proteobacteria and genes involved in biomolecules metabolism, aromatic compound degradation, stress tolerance, xenobiotic biodegradation etc. were revealed functionally. The intricate heterogeneous environment of landfill revealed well flourished biogeochemical metabolic profiles including nitrogen metabolism. This is the first study for the generated metagenome of Ghazipur landfill and the obtained results propose that microbial communities in landfill settings are far more intricate than expected. It remain mostly unexplored which demands the usage of multiple platforms for a better understanding.

A review on advances in removal of endocrine disrupting compounds from aquatic matrices: Future perspectives on utilization of agri-waste based adsorbents.

In the recent past, a class of emerging contaminants particularly endocrine disrupting compounds (EDCs) in the aquatic environment have gained a lot of attention. This is due to their toxic behaviour, affecting endocrine activities in humans as well as among aquatic animals. Presently, there are no regulations and discharge limits for EDCs to preclude their negative impact. Furthermore, the conventional treatment processes fail to remove EDCs efficiently. This necessitates the need for more research aimed at development of advanced alternative treatment methods which are economical, efficient, and sustainable. This paper focusses on the occurrence, fate, toxicity, and various treatment processes for removal of EDCs. The treatment processes (physical, chemical, biological and hybrid) have been comprehensively studied highlighting their advantages and disadvantages. Additionally, the use of agri-waste based adsorption technologies has been reviewed. The aim of this review article is to understand the prospect of application of agri-waste based adsorbents for efficient removal of EDCs. Interestingly, research findings have indicated that the use of these low-cost and abundantly available agri-waste based adsorbents can efficiently remove the EDCs. Furthermore, the challenges and future perspectives on the use of agri-waste based adsorbents have been discussed.

Agro-forestry waste management- A review.

Agroforestry, an integration of farming system with woody perennials leads to the generation of potential agroforestry residues. The conventional treatment of agroforestry waste includes landfilling, thermal management, and decomposition which is accompanied with their own share of disadvantages. The ample amount of residues and products needs effective management to reap the economic and environmental benefits. The channel of waste collection, transportation, and recycle or valorization into products like biofuel, fertilizers, biochar, industrial chemicals is essential to maintain a circular sustainable bioeconomy. Global market value of biowaste to bioenergy (BtB) technology is roughly US $25.32 billion and is projected to enhance to US $40 billion by 2023. Employment of an appropriate pretreatment technology such as fermentation, hydrolysis, gasification etc. is going to elevate the degree of valorization along with surpassing the mobilization barrier. The sustainability assessment of the management process can be achieved with multiple models including technoeconomic analysis, life cycle assessment and multi criteria approach which are dependent on both hard and soft indices. Additionally, the loopholes of the agroforestry sectors would be managed by the introduction of appropriate policies which are undertaken globally by the Orlando and Lugo declarations, food and agriculture organization, Millennium Development Goals, Global Research Alliance and Guidelines for Sustainable Agriculture and Rural Development. The present review envisaged the agroforestry waste management strategy and its sustainability assessment primarily based upon Social, Economic and Environmental parameters without tormenting the future generations.