CD4 T Cell-Derived IL-21 Is Critical for Sustaining Plasmodium Infection-Induced Germinal Center Responses and Promoting the Selection of Memory B Cells with Recall Potential.

Development of Plasmodium-specific humoral immunity is critically dependent on CD4 Th cell responses and germinal center (GC) reactions during blood-stage Plasmodium infection. IL-21, a cytokine primarily produced by CD4 T cells, is an essential regulator of affinity maturation, isotype class-switching, B cell differentiation, and maintenance of GC reactions in response to many infection and immunization models. In models of experimental malaria, mice deficient in IL-21 or its receptor IL-21R fail to develop memory B cell populations and are not protected against secondary infection. However, whether sustained IL-21 signaling in ongoing GCs is required for maintaining GC magnitude, organization, and output is unclear. In this study, we report that CD4+ Th cells maintain IL-21 expression after resolution of primary Plasmodium yoelii infection. We generated an inducible knockout mouse model that enabled cell type-specific and timed deletion of IL-21 in peripheral, mature CD4 T cells. We found that persistence of IL-21 signaling in active GCs had no impact on the magnitude of GC reactions or their capacity to produce memory B cell populations. However, the memory B cells generated in the absence of IL-21 exhibited reduced recall function upon challenge. Our data support that IL-21 prevents premature cellular dissolution within the GC and promotes stringency of selective pressures during B cell fate determination required to produce high-quality Plasmodium-specific memory B cells. These data are additionally consistent with a temporal requirement for IL-21 in fine-tuning humoral immune memory responses during experimental malaria.

A guide to selecting upper thoracic versus lower thoracic uppermost instrumented vertebra in adult spinal deformity correction.

PURPOSE: Operative treatment of adult spinal deformity (ASD) has been shown to improve patient health-related quality of life (HRQOL). Selection of the uppermost instrumented vertebra (UIV) in either the upper thoracic (UT) or lower thoracic (LT) spine is a pivotal decision with effects on operative and postoperative outcomes. This review overviews the multifaceted decision-making process for UIV selection in ASD correction. METHODS: PubMed was queried for articles using the keywords "uppermost instrumented vertebra", "upper thoracic", "lower thoracic", and "adult spinal deformity". RESULTS: Optimization of UIV selection may lead to superior deformity correction, better patient-reported outcomes, and lower risk of proximal junctional kyphosis (PJK) and failure (PJF). Patient alignment characteristics, including preoperative thoracic kyphosis, coronal deformity, and the magnitude of sagittal correction influence surgical decision-making when selecting a UIV, while comorbidities such as poor body mass index, osteoporosis, and neuromuscular pathology should also be taken in to account. Additionally, surgeon experience and resources available to the hospital may also play a role in this decision. Currently, it is incompletely understood whether postoperative HRQOLs, functional and radiographic outcomes, and complications after surgery differ between selection of the UIV in either the UT or LT spine. CONCLUSION: The correct selection of the UIV in surgical planning is a challenging task, which requires attention to preoperative alignment, patient comorbidities, clinical characteristics, available resources, and surgeon-specific factors such as experience.

A comprehensive study on applications of nanomaterials in petroleum upstream and downstream industry.

Nanotechnology has emerged as a revolutionary technology that has been applied in the oil and gas industry for over a decade, spanning the upstream, midstream, and downstream sectors. Nanotechnology has made significant contributions to the exploration of crude oil and natural gas, both in underground and deep-water environments. It has also played a crucial role in improving the drilling process, enabling the extraction of oil and gas resources from beneath the Earth's surface. Nanoparticles, with their unique physical and chemical properties, such as high specific surface area, high pore volume, and small size, have demonstrated considerable potential in the oil industry. Extensive research has been conducted to explore various types of nanoparticles for advanced applications, including oil exploration, drilling, production, and enhanced oil recovery (EOR). Moreover, nanomaterials have found applications in downstream and intermediate sectors, such as crude oil refining, natural gas processing, and transportation and storage of petroleum products. Ongoing advancements in nanomaterial synthesis methods, the exploration of new nanomaterial uses, and understanding the remarkable properties of nanomaterials will continue to make them increasingly valuable in the oil and gas sector. The oil and gas industry recognises the potential of nanotechnology and nanoparticles and is investing significantly in research and development in this area. This comprehensive review aims to summarise successful applications of nanotechnology while addressing associated challenges. It serves as a valuable resource for future research and application endeavours in the field, highlighting the potential of nanotechnology in the oil and gas industry.

miR-365-3p mediates BCL11A and SOX6 erythroid-specific coregulation: A new player in HbF activation.

Hemoglobin switching is a complex biological process not yet fully elucidated. The mechanism regulating the suppression of fetal hemoglobin (HbF) expression is of particular interest because of the positive impact of HbF on the course of diseases such as ß-thalassemia and sickle cell disease, hereditary hemoglobin disorders that affect the health of countless individuals worldwide. Several transcription factors have been implicated in the control of HbF, of which BCL11A has emerged as a major player in HbF silencing. SOX6 has also been implicated in silencing HbF and is critical to the silencing of the mouse embryonic hemoglobins. BCL11A and SOX6 are co-expressed and physically interact in the erythroid compartment during differentiation. In this study, we observe that BCL11A knockout leads to post-transcriptional downregulation of SOX6 through activation of microRNA (miR)-365-3p. Downregulating SOX6 by transient ectopic expression of miR-365-3p or gene editing activates embryonic and fetal ß-like globin gene expression in erythroid cells. The synchronized expression of BCL11A and SOX6 is crucial for hemoglobin switching. In this study, we identified a BCL11A/miR-365-3p/SOX6 evolutionarily conserved pathway, providing insights into the regulation of the embryonic and fetal globin genes suggesting new targets for treating ß-hemoglobinopathies.

Exploring the efficacy of metabarcoding and non-target screening for detecting treated wastewater.

Wastewater treatment processes can eliminate many pollutants, yet remainder pollutants contain organic compounds and microorganisms released into ecosystems. These remainder pollutants have the potential to adversely impact downstream ecosystem processes, but their presence is currently not being monitored. This study was set out with the aim of investigating the effectiveness and sensitivity of non-target screening of chemical compounds, 18S V9 rRNA gene, and full-length 16S rRNA gene metabarcoding techniques for detecting treated wastewater in receiving waters. We aimed at assessing the impact of introducing 33 % treated wastewater into a triplicated large-scale mesocosm setup during a 10-day exposure period. Discharge of treated wastewater significantly altered the chemical signature as well as the microeukaryotic and prokaryotic diversity of the mesocosms. Non-target screening, 18S V9 rRNA gene, and full-length 16S rRNA gene metabarcoding detected these changes with significant covariation of the detected pattern between methods. The 18S V9 rRNA gene metabarcoding exhibited superior sensitivity immediately following the introduction of treated wastewater and remained one of the top-performing methods throughout the study. Full-length 16S rRNA gene metabarcoding demonstrated sensitivity only in the initial hour, but became insignificant thereafter. The non-target screening approach was effective throughout the experiment and in contrast to the metabarcoding methods the signal to noise ratio remained similar during the experiment resulting in an increasing relative strength of this method. Based on our findings, we conclude that all methods employed for monitoring environmental disturbances from various sources are suitable. The distinguishing factor of these methods is their ability to detect unknown pollutants and organisms, which sets them apart from previously utilized approaches and allows for a more comprehensive perspective. Given their diverse strengths, particularly in terms of temporal resolution, these methods are best suited as complementary approaches.

A holistic review on the assessment of groundwater quality using multivariate statistical techniques.

Water is an essential element in nature. It is used in drinking, irrigation, and industry mainly. Human health is directly linked to groundwater quality and is affected by poor groundwater quality caused by excessive fertilizer application and unhygienic circumstances. Because of increased pollution, investigating the water quality became a point of research for many researchers. There are numerous approaches to assessing water quality, and statistical methods are essential among them. This review paper discusses Multivariate Statistical Techniques, including Cluster Analysis, Principal Component Analysis, Factor Analysis, Geographical Information System, and Analysis of Variance, to name a few. We have presented the significance of each method concisely and how it is being used. In addition, an extensive table is prepared to demonstrate the individual technique along with the computational tool, the type of water bodies, and their respective regions. The advantages and disadvantages of the statistical techniques are also discussed therein. It is found that Principal Component Analysis and Factor Analysis are widely explored techniques.

Genomic Index of Sensitivity to Chemotherapy for Triple Negative Breast Cancer.

OBJECTIVE: Patients with triple-negative breast cancer (TNBC) frequently develop resistance to chemotherapy. Studies have shown that microRNAs (miRNAs) are often aberrantly expressed in TNBC and are associated with drug resistance. However, a prognostic strategy that correlates miRNAs with chemotherapy resistance remains largely unknown. METHODS: To identify breast cancer chemoresistance-associated miRNAs, the miRNA microarray dataset GSE71142 was downloaded from the Gene Expression Omnibus database. Differentially expressed miRNAs (DE-miRNAs) in chemoresistant groups were identified using the LIMMA package in R. Potential target genes were predicted using the miRTarBase 9. Functional and pathway enrichment analyses was done using WebGestalt. A protein-protein interaction network was visualized using Cytoscape software. The top six hub genes regulated by DE-miRNAs were identified using the random forest model. The chemotherapy resistance index (CRI) in TNBC was defined as sum of the median expression levels of the top six hub genes. The association of CRI with distant relapse risk was evaluated using point-biserial correlation coefficient in the validation cohorts of patients with TNBC. The correlation between CRI and cumulative hazard rate was estimated using the Cox model, and the predicted rate of distant relapse was obtained from the Breslow-type estimator of the survival function. All statistical computations were performed using Origin2019b. RESULTS: A total of 12 DE-miRNAs were screened, including six upregulated and six downregulated miRNAs in chemoresistant breast cancer tissues compared with chemosensitive tissues. Based on fold changes, miR-214-3p, miR-4758-3p, miR-200c-3p, miR-4254, miR-140-3p, and miR-24-3p were the top six most upregulated miRNAs, whereas miR-142-5p, miR-146-5p, miR-1268b, miR-1275, miR-4447, and miR-4472 were the top six most downregulated miRNAs. The top three hub genes for upregulated miRNAs were RAC1, MYC, and CCND1 and for downregulated miRNAs were IL-6, SOCS1, and PDGFRA. CRI was significantly associated with the risk of distant relapse. CONCLUSION: CRI predicted survival benefits with reduced hazard rate.

Comprehensive molecular profile of primary cutaneous epithelioid rhabdomyosarcoma: A tumor genomically and molecularly related to malignant melanoma.

The histogenesis of the rare primary cutaneous epithelioid rhabdomyosarcoma (PCERMS) remains unclear, with the morphological and immunophenotypic appearance of a rhabdomyosarcoma but a genomic profile consistent with sarcomatoid undifferentiated malignant melanoma (SUMM). Here, we provide comprehensive clinical, histopathological, and genomic analysis of a putative PCERMS presenting in an elderly patient. Histopathologic examination revealed an ulcerative tumefactive lesion with diffuse replacement of the dermis by sheets of malignant epithelioid cells with a rhabdoid appearance. By immunohistochemistry, the tumor cells were strongly and diffusely positive for desmin and myogenin. Comprehensive genomic analysis with a 542 gene DNA-based sequencing panel revealed likely biallelic NF1 inactivation (mutation and deletion), TERT promoter mutation, and a high tumor mutation burden (>100 mutations/mB) with features of a UV-mutational signature, which are all genomic features that can be seen in undifferentiated malignant melanoma. This case provides evidence of a close relationship at a molecular level between PCERMS and SUMM. Molecular genomic characterization of a larger cohort of PCERMS is warranted for further elucidation.

Patient-reported distress at a cancer center during the COVID-19 pandemic.

Assessments of health-related quality of life (HRQOL) are conducted by health systems to improve patient-centered care. Studies have shown that the COVID-19 pandemic poses unique stressors for patients with cancer. This study investigates change in self-reported global health scores in patients with cancer before and during the COVID-19 pandemic. In this single-institution retrospective cohort study, patients who completed the Patient-Reported Outcomes Measurement Information System (PROMIS) at a comprehensive cancer center before and during the COVID-19 pandemic were identified. Surveys were analyzed to assess change in the global mental health (GMH) and global physical health (GPH) scores at different time periods (pre-COVID: 3/1/5/2019-3/15/2020, surge1: 6/17/2020-9/7/2020, valley1: 9/8/2020-11/16/2020, surge2: 11/17/2020-3/2/2021, and valley2: 3/3/2021-6/15/2021). A total of 25,192 surveys among 7209 patients were included in the study. Mean GMH score for patients before the COVID-19 pandemic (50.57) was similar to those during various periods during the pandemic: surge1 (48.82), valley1 (48.93), surge2 (48.68), valley2 (49.19). Mean GPH score was significantly higher pre-COVID (42.46) than during surge1 (36.88), valley1 (36.90), surge2 (37.33) and valley2 (37.14). During the pandemic, mean GMH (49.00) and GPH (37.37) scores obtained through in-person were similar to mean GMH (48.53) and GPH (36.94) scores obtained through telehealth. At this comprehensive cancer center, patients with cancer reported stable mental health and deteriorating physical health during the COVID-19 pandemic as indicated by the PROMIS survey. Modality of the survey (in-person versus telehealth) did not affect scores.

A comprehensive study on Industry 4.0 in the pharmaceutical industry for sustainable development.

The four evolutionary stages have brought us to Industry 4.0. Industry 4.0 is nothing but the 4th Industrial Revolution which will change the production processes. The implementation of Industry 4.0 in the pharmaceutical sector will make the manufacturing of complex drugs easier. The arrival of Industry 4.0 and its advanced technologies such as artificial intelligence (AI), robotics, and the Internet of Things (IoT) makes the processes flexible. Industry 4.0 was introduced to reduce the human workforce and make the complicated processes unchallenging. It is used in all aspects of pharmaceutical sector like analysis, diagnosis, manufacturing, and packaging. The main aim of this paper is to comprehensively elucidate how Industry 4.0 has played a significant role in sustainable development (SD). Industry 4.0 in sustainability decreases the research efforts and examines the research sector's opportunities. This paper also discusses the impact of Industry 4.0 on sustainable development. Industry 4.0 constructs a bridge between industry and sustainability leading to sustainable development. Sustainability can be achieved by adopting innovative techniques of Industry 4.0 in manufacturing. Moreover, Industry 4.0 provides potential benefits for enhancing pharmaceutical production concerning flexibility, expenses, standards, and safety. It is noticed that Industry 4.0 has a beneficial impact on sustainable development by implementing advanced technologies leading to flexible manufacturing processes.

Geothermal energy integrated multi-effect evaporator (MEE) and multi-effect distillation (MED)-based desalination systems: an ecofriendly and sustainable solutions.

Desalination is a tried-and-true method for obtaining clean water from the ocean's brackish waters and recycling and reusing water. It requires a fair amount of energy, so it is necessary to create sustainable energy systems to lessen energy use and environmental impact. For thermal desalination procedures, thermal sources can be great heat sources. This paper's research focuses on thermoeconomically optimized multi-effect distillation and geothermal desalination systems. Collecting hot water from subsurface reservoirs is a well-established method of generating electricity through geothermal sources. Low-temperature geothermal sources, which have a temperature of less than 130 °C, can be utilized for thermal desalination systems, for example, multi-effect distillation (MED). Geothermal desalination is affordable, and it is possible to produce power simultaneously. Because it only uses clean, renewable energy and produces no greenhouse gasses or other pollutants, it is also safe for the environment. The viability of any geothermal desalination plant will be influenced by the location of the geothermal resource, feed water supply, cooling water source, water market, and concentrate disposal site. Geothermal energy can directly supply heat for a thermal desalination system or indirectly give electrical power to reverse the osmosis (RO) membrane-based desalination plant.

Temporal disturbance of a model stream ecosystem by high microbial diversity from treated wastewater.

Microbial communities in freshwater streams play an essential role in ecosystem functioning via biogeochemical cycling. Yet, the impacts of treated wastewater influx into stream ecosystems on microbial strain diversity remain mostly unexplored. Here, we coupled full-length 16S ribosomal RNA gene Nanopore sequencing and strain-resolved metagenomics to investigate the impact of treated wastewater on a mesocosm system (AquaFlow) run with restored river water. Over 10 days, community Bray-Curtis dissimilarities between treated and control mesocosm decreased (0.57 ± 0.058 to 0.26 ± 0.046) based on ribosomal protein S3 gene clustering, finally converging to nearly identical communities. Similarly, strain-resolved metagenomics revealed a high diversity of bacteria and viruses after the introduction of treated wastewater; these microbes also decreased over time resulting in the same strain clusters in control and treatment at the end of the experiment. Specifically, 39.2% of viral strains detected in all samples were present after the introduction of treated wastewater only. Although bacteria present at low abundance in the treated wastewater introduced additional antibiotic resistance genes, signals of naturally occurring ARG-encoding organisms resembled the resistome at the endpoint. Our results suggest that the previously stressed freshwater stream and its microbial community are resilient to a substantial introduction of treated wastewater.

Concurrent Cardio-Cerebral Infarctions in COVID-19: A Systematic Review of Published Case Reports/Series.

Twelve CCI patients were studied with confirmed or suspected COVID-19 infection. The majority of these patients were males (83.3%) with a median age of 55 years from three geographical locations, constituting the Middle East (7), Spain (3), and the USA (1). In 6 patients, IgG/IgM was positive for COVID-19, 4 with high pretest probability and 2 with positive RT-PCR. Type 2 DM, hyperlipidemia, and smoking were the primary risk factors. Right-sided neurological impairments and verbal impairment were the most common symptoms. Our analysis found 8 (66%) synchronous occurrences. In 58.3% of cases, neuroimaging showed left Middle Cerebral Artery (MCA) infarct and 33.3% right. Carotid artery thrombosis (16.6%), tandem occlusion (8.3%), and carotid stenosis (1%) were also reported in imaging. Dual antiplatelet therapy (DAPT) and anticoagulants were conservative therapies (10). Two AMI patients had aspiration thrombectomy, while three AIS patients had intravenous thrombolysis/tissue plasminogen activator (IVT-tPA), 2 had mechanical thrombectomy (MT), and 1 had decompressive craniotomy. Five had COVID-19-positive chest X-rays, whereas 4 were normal. four of 8 STEMI and 3 NSTEMI/UA patients complained chest pain. LV, ICA, and pulmonary embolism were further complications (2). Upon discharge, 7 patients (70%) had residual deficits while 1 patient unfortunately died.

Fuelling the sustainable future: a comparative analysis between battery electrical vehicles (BEV) and fuel cell electrical vehicles (FCEV).

With the advancement of technology in recent decades and the implementation of international norms to minimize greenhouse gas emissions, automakers have focused on new technologies connected to electric/hybrid vehicles and electric fuel cell vehicles. Alternative fuel sources like hydrogen and electricity have been introduced as a sustainable, lower-emission alternative to burning fossil fuel. BEVs or battery electric vehicles are typical electric cars with a battery and electric motor that have to be charged. FCEVs, or fuel cell electric vehicles, have a fuel cell that converts pure hydrogen into electricity via reverse electrolysis to charge a battery connected to an electric motor. The lifecycle costs of the BEV and FCHEV are comparable; however, depending on driving patterns, one may be more advantageous than the other. This study compares the most recent proposed fuel-cell electric car topologies. This paper aims to find out which fuel alternative is more sustainable, looking forward to the future. An analysis was conducted by comparing different fuel cells' and batteries' efficiencies, performance, advantages, and disadvantages.

A comprehensive and systematic study on the techniques used for augmenting the performance of a solar still distillate yield.

One of the biggest problems the globe is currently experiencing is the availability of safe freshwater for drinking, especially in rural and dry regions. Drinking fresh water is among the basic requirements for surviving all life on Earth, along with food and energy. Rapid economic growth and poverty increase the demand for clean water. There are numerous approaches to getting clean water, and a current popular method is the solar distillation of brine water. Solar distillation converts brine water into fresh, usable water using solar radiation. It is a cheap, non-polluting, and greenhouse method. Various methods are used to enhance the distillate output, for instance, using nanoparticles, adding external devices, changing the design, and coupling the solar still. This paper reviews various research work and articles on different approaches used to enrich the distillate yield of solar still, increasing its efficiency and thermal energy, and decreasing the cost of desalination of brine water. Lastly, it contains challenges and the future scope.

A systematic and comparative study of Water Quality Index (WQI) for groundwater quality analysis and assessment.

Water is essential for human survival. Its quality must be maintained to prevent any potential health problems. Pollution and contamination are likely causes of the water quality decline. This may occur if the world's rapidly expanding population and industrial facilities fail to clean their effluent correctly. The Water Quality Index, often known as the WQI, is the indicator most frequently used to characterize surface water quality. This study emphasizes several WQI models that could be of use to us in determining the level of water quality available in the various areas. We have tried to cover multiple essential procedures and their corresponding mathematical counterparts. In this article, we also examine the applications of index models in different types of water bodies, such as lakes, rivers, surface water, and groundwater. The level of contamination in water due to pollution directly affects the overall quality of water. A pollution index is a valuable tool for measuring the level of pollution. Concerning this, we have discussed two approaches, namely, the Overall Index of Pollution and Nemerrow's Pollution Index, which demonstrate the most effective technique to evaluate the water standard. Examining the similarities and differences between these approaches may offer researchers a suitable starting point to delve further into assessing water quality.

Interventions to reduce repetitive ordering of low-value inpatient laboratory tests: a systematic review.

BACKGROUND: Over-ordering of daily laboratory tests adversely affects patient care through hospital-acquired anaemia, patient discomfort, burden on front-line staff and unnecessary downstream testing. This remains a prevalent issue despite the 2013 Choosing Wisely recommendation to minimise unnecessary daily labs. We conducted a systematic review of the literature to identify interventions targeting unnecessary laboratory testing. METHODS: We systematically searched MEDLINE, EMBASE, Cochrane Central and SCOPUS databases to identify interventions focused on reducing daily complete blood count, complete metabolic panel and basic metabolic panel labs. We defined interventions as 'effective' if a statistically significant reduction was attained and 'highly effective' if a reduction of ≥25% was attained. RESULTS: The search yielded 5646 studies with 41 articles that met inclusion criteria. We grouped interventions into one or more categories: audit and feedback, cost display, education, electronic medical record (EMR) change, and policy change. Most interventions lasted less than a year and used a multipronged approach. All five strategies were effective in most studies with EMR change being the most commonly used independent strategy. EMR change and policy change were the strategies most frequently reported as effective. EMR change was the strategy most frequently reported as highly effective. CONCLUSION: Our analysis identified five categories of interventions targeting daily laboratory testing. All categories were effective in most studies, with EMR change being most frequently highly effective. PROSPERO REGISTRATION NUMBER: CRD42021254076.

HER2 Gene Protein Assay: A Robust Tool for Evaluating HER2 Status and Intratumoral Heterogeneity in Endometrial Cancers.

OBJECTIVES: Human epidermal growth factor receptor 2 (HER2) status in endometrial cancer is usually determined by immunohistochemistry and/or in situ hybridization. We employed a novel HER2 gene protein assay (GPA) to simultaneously assesses HER2 gene amplification and protein expression in high-grade endometrial cancers. METHODS: We performed GPA in 180 endometrial cancers, including 106 serous carcinomas, 34 carcinosarcomas, and 40 mixed epithelial carcinomas. HER2 status was determined using the 2018 HER2 guidelines for breast carcinoma, and HER2 intratumoral heterogeneity (ITH) was examined. Clinicopathologic characteristics were collected and correlated with HER2 status. RESULTS: HER2 positivity was noted in 32% of serous carcinomas, significantly higher than in carcinosarcomas (5.9%) and mixed carcinomas (12.5%). HER2 ITH was detected in 32% of serous carcinomas, significantly greater than in carcinosarcomas (8.8%) and mixed carcinomas (10%). Patients with carcinosarcoma had a significantly lower overall survival than patients with serous or mixed epithelial carcinoma, but HER2 status caused no difference in survival in patients with serous carcinoma. CONCLUSIONS: HER2 GPA can be used to accurately determine HER2 status in endometrial cancers and is a highly valuable tool for identifying HER2 heterogeneity.