The Tumor Immune Microenvironment in Primary CNS Neoplasms: A Review of Current Knowledge and Therapeutic Approaches.

Primary CNS neoplasms are responsible for considerable mortality and morbidity, and many therapies directed at primary brain tumors have proven unsuccessful despite their success in preclinical studies. Recently, the tumor immune microenvironment has emerged as a critical aspect of primary CNS neoplasms that may affect their malignancy, prognosis, and response to therapy across patients and tumor grades. This review covers the tumor microenvironment of various primary CNS neoplasms, with a focus on glioblastoma and meningioma. Additionally, current therapeutic strategies based on elements of the tumor microenvironment, including checkpoint inhibitor therapy and immunotherapeutic vaccines, are discussed.

Next-Generation Serology by Mass Spectrometry: Readout of the SARS-CoV-2 Antibody Repertoire.

Methods of antibody detection are used to assess exposure or immunity to a pathogen. Here, we present Ig-MS, a novel serological readout that captures the immunoglobulin (Ig) repertoire at molecular resolution, including entire variable regions in Ig light and heavy chains. Ig-MS uses recent advances in protein mass spectrometry (MS) for multiparametric readout of antibodies, with new metrics like Ion Titer (IT) and Degree of Clonality (DoC) capturing the heterogeneity and relative abundance of individual clones without sequencing of B cells. We applied Ig-MS to plasma from subjects with severe and mild COVID-19 and immunized subjects after two vaccine doses, using the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 as the bait for antibody capture. Importantly, we report a new data type for human serology, that could use other antigens of interest to gauge immune responses to vaccination, pathogens, or autoimmune disorders.

Reexamining the Role of Postoperative ICU Admission for Patients Undergoing Elective Craniotomy: A Systematic Review.

OBJECTIVES: The standard-of-care for postoperative care following elective craniotomy has historically been ICU admission. However, recent literature interrogating complications and interventions during this postoperative ICU stay suggests that all patients may not require this level of care. Thus, hospitals began implementing non-ICU postoperative care pathways for elective craniotomy. This systematic review aims to summarize and evaluate the existing literature regarding outcomes and costs for patients receiving non-ICU care after elective craniotomy. DATA SOURCES: A systematic review of the PubMed database was performed following PRISMA guidelines from database inception to August 2021. STUDY SELECTION: Included studies were published in peer-reviewed journals, in English, and described outcomes for patients undergoing elective craniotomies without postoperative ICU care. DATA EXTRACTION: Data regarding study design, patient characteristics, and postoperative care pathways were extracted independently by two authors. Quality and risk of bias were evaluated using the Oxford Centre for Evidence-Based Medicine Levels of Evidence tool and Risk Of Bias In Non-Randomized Studies-of Interventions tool, respectively. DATA SYNTHESIS: In total, 1,131 unique articles were identified through the database search, with 27 meeting inclusion criteria. Included articles were published from 2001 to 2021 and included non-ICU inpatient care and same-day discharge pathways. Overall, the studies demonstrated that postoperative non-ICU care for elective craniotomies led to length of stay reduction ranging from 6 hours to 4 days and notable cost reductions. Across 13 studies, 53 of the 2,469 patients (2.1%) intended for postoperative management in a non-ICU setting required subsequent care escalation. CONCLUSIONS: Overall, these studies suggest that non-ICU care pathways for appropriately selected postcraniotomy patients may represent a meaningful opportunity to improve care value. However, included studies varied greatly in patient selection, postoperative care protocol, and outcomes reporting. Standardization and multi-institutional collaboration are needed to draw definitive conclusions regarding non-ICU postoperative care for elective craniotomy.

Pre-surgery immune profiles of adult glioma patients.

INTRODUCTION: Although immunosuppression is a known characteristic of glioma, no previous large studies have reported peripheral blood immune cell profiles prior to patient surgery and chemoradiation. This report describes blood immune cell characteristics and associated variables prior to surgery among typical glioma patients seen at a large University practice. METHODS: We analyzed pre-surgery blood samples from 139 glioma patients diagnosed with a new or recurrent grade II/III glioma (LrGG, n = 64) or new glioblastoma (GBM, n = 75) and 454 control participants without glioma. Relative cell fractions of CD4, CD8, B-cells, Natural Killer cells, monocytes, and neutrophils, were estimated via a validated deconvolution algorithm from blood DNA methylation measures from Illumina EPIC arrays. RESULTS: Dexamethasone use at time of blood draw varied by glioma type being highest among patients with IDH wild-type (wt) GBM (75%) and lowest for those with oligodendroglioma (14%). Compared to controls, glioma patients showed statistically significant lower cell fractions for all immune cell subsets except for neutrophils which were higher (all p-values < 0.001), in part because of the higher prevalence of dexamethasone use at time of blood draw for IDHwt GBM. Patients who were taking dexamethasone were more likely to have a low CD4 count (< 200, < 500), increased neutrophils, low absolute lymphocyte counts, higher total cell count and higher NLR. CONCLUSION: We show that pre-surgery blood immune profiles vary by glioma subtype, age, and more critically, by use of dexamethasone. Our results highlight the importance of considering dexamethasone exposures in all studies of immune profiles and of obtaining immune measures prior to use of dexamethasone, if possible.

A Brief History of Machine Learning in Neurosurgery.

The history of machine learning in neurosurgery spans three decades and continues to develop at a rapid pace. The earliest applications of machine learning within neurosurgery were first published in the 1990s as researchers began developing artificial neural networks to analyze structured datasets and supervised tasks. By the turn of the millennium, machine learning had evolved beyond proof-of-concept; algorithms had success detecting tumors in unstructured clinical imaging, and unsupervised learning showed promise for tumor segmentation. Throughout the 2000s, the role of machine learning in neurosurgery was further refined. Well-trained models began to consistently best expert clinicians at brain tumor diagnosis. Additionally, the digitization of the healthcare industry provided ample data for analysis, both structured and unstructured. By the 2010s, the use of machine learning within neurosurgery had exploded. The rapid deployment of an exciting new toolset also led to the growing realization that it may offer marginal benefit at best over conventional logistical regression models for analyzing tabular datasets. Additionally, the widespread adoption of machine learning in neurosurgical clinical practice continues to lag until additional validation can ensure generalizability. Many exciting contemporary applications nonetheless continue to demonstrate the unprecedented potential of machine learning to revolutionize neurosurgery when applied to appropriate clinical challenges.

Endotypes and the Path to Precision in Moderate and Severe Traumatic Brain Injury.

Heterogeneity is recognized as a major barrier in efforts to improve the care and outcomes of patients with traumatic brain injury (TBI). Even within the narrower stratum of moderate and severe TBI, current management approaches do not capture the complexity of this condition characterized by manifold clinical, anatomical, and pathophysiologic features. One approach to heterogeneity may be to resolve undifferentiated TBI populations into endotypes, subclasses that are distinguished by shared biological characteristics. The endotype paradigm has been explored in a range of medical domains, including psychiatry, oncology, immunology, and pulmonology. In intensive care, endotypes are being investigated for syndromes such as sepsis and acute respiratory distress syndrome. This review provides an overview of the endotype paradigm as well as some of its methods and use cases. A conceptual framework is proposed for endotype research in moderate and severe TBI, together with a scientific road map for endotype discovery and validation in this population.

Outcome of post-COVID-19 fungal pyelonephritis: A single Indian tertiary center experience.

Introduction: COVID-19 pandemic is associated with secondary opportunistic fungal infections. These have an aggressive course with a high mortality rate. We present our experience of seven cases of post-COVID-19 fungal pyelonephritis. Methods: An observational study over a period of 8 months of May to December 2021 was carried out at our tertiary care hospital, including all patients with features of fungal pyelonephritis in post-COVID-19 setting. The patient demographics, details of previous COVID-19 infection, details of present admission and management were collected. The endpoints were either discharge from the hospital or death. Results: Seven patients were included. Mean age of presentation was 42 years (range: 20-63 years, standard deviation ± 14.2). Male-to-female ratio was 6:1. One patient was diabetic. Two patients were asymptomatic, one had mild infection, and four patients had severe COVID-19 infection as per National Institute of Health criteria. In the present admission, all patients had symptomatic pyelonephritis with laboratory parameters showing elevated D dimer, C reactive protein, and total leukocyte counts. In all seven patients, ultrasound of kidney ureter bladder region showed bulky kidney, color Doppler showed main renal arterial thrombosis in two patients, segmental arterial thrombosis in another patient. Computed tomography scan was suggestive of changes of pyelonephritis in all patients with multiple renal hypodense areas. All patients required nephrectomy with biopsy suggestive of changes of necrotizing fungal inflammation. Three patients expired. Conclusion: Management of post-COVID-19 fungal pyelonephritis should be aggressive and suspicious laboratory and imaging findings should be treated by early nephrectomy.

A practical approach for gmp-compliant validation of real-time PCR method for mycoplasma detection in human mesenchymal stromal cells as advanced therapy medicinal product.

BACKGROUND: Manufacturing of human Mesenchymal Stromal Cells as advanced therapy medicinal product (ATMP) for clinical use involves an ex vivo expansion, which leads to a risk of contamination by microbiological agents. Even if manufacturing under Good Manufacturing Practice (GMP) license minimizes this risk, contamination of cell cultures by mycoplasmas still represents a widespread problem. Furthermore, the absence of mycoplasma contamination represents one of ATMPs release criteria. Since July 2007, European Pharmacopoeia (EuPh) offers the possibility to replace official mycoplasma detection methods with Nucleic Acid Amplification techniques, after suitable validation. As an Italian authorized Cell Factory, we developed an in-house GMP-compliant validation of real-time PCR method for mycoplasma detection in human Mesenchymal Stromal Cells, according to EuPh sec. 2.6.7 and International Conference on Harmonization Q2. MATERIALS AND METHODS: The study was performed in compliance with GMP international requirements with MycoSEQ™ Mycoplasma Detection Assay (Thermofisher) on QuantStudio5 real-Time PCR (Applied Biosystems). Assay validation was developed to evaluate sensitivity, interferences matrix-related, specificity and robustness. RESULTS: MycoSEQ™ Mycoplasma Detection Assay has been successfully validated on human Mesenchymal Stromal Cells as results comply with validation protocol acceptance criteria. CONCLUSIONS: MycoSEQ™ Mycoplasma Detection Assay is a fast, sensitive and specific PCR-based Nucleic Acid Test assay that can be used as an alternative to official mycoplasma test methods for lot release of human Mesenchymal Stromal Cells as advanced therapy medicinal product (ATMP). Moreover, our study underlines the presence of interference on real-time PCR reaction due to matrix composition, pointing out a practical approach for method validation (i.e interference removal).

A systematic review of tumor treating fields therapy for high-grade gliomas.

INTRODUCTION: Tumor treating fields (TTF) is a unique treatment modality that utilizes alternating electric fields to deliver therapy. Treatment effects have been assessed in patients with newly diagnosed and recurrent glioblastoma in clinical trials and retrospective studies. While the results of these studies led to FDA approval for both populations, a portion of the neuro-oncology and neurosurgery community remains skeptical of TTF. Thus, this review aims to systematically summarize and evaluate prior studies investigating the efficacy and safety of TTF in patients with high-grade gliomas. METHODS: A systematic review of the literature was performed according to PRISMA guidelines from database inception through February 2019. To be included, studies must have investigated the efficacy of TTF in adult high-grade glioma patients. RESULTS: In total, 852 studies were initially identified, 9 of which met final inclusion criteria. In total, 1191 patients were identified who received TTF. Included studies consisted of two pilot clinical trials, two randomized clinical trials, and five retrospective studies. In randomized clinical trials, TTF improved survival for newly diagnosed glioblastoma patients but not for recurrent glioblastoma patients. Adverse skin reactions were the primary adverse effect associated with TTF. CONCLUSION: While TTF has been evaluated for safety and efficacy in a number of studies, concerns remain regarding study design, quality of life, and cost of therapy. Further investigation is needed regarding the therapy, and ongoing trials are already underway to provide more data regarding therapy outcomes and interactions in combination regimens.

The 5-factor modified frailty index predicts health burden following surgery for pituitary adenomas.

PURPOSE: Frailty is known to influence cost-related surgical outcomes in neurosurgery, but quantifying frailty is often challenging. Therefore, we investigated the predictive value of the 5-factor modified frailty index (mFI-5) on total hospital charges, LOS, and 90-day readmission for patients undergoing pituitary surgery. METHODS: The medical records of all patients undergoing endoscopic endonasal resection of pituitary adenomas at an academic medical center between January 2017 and December 2018 were retrospectively reviewed. Bivariate statistical analyses were conducted using Fisher's exact test, chi-square test, and independent samples t-test. Linear and logistic regression models were used for multivariate analysis. RESULTS: Our cohort (n = 234) had a mean age of 53.8 years (standard deviation 14.6 years). Sex distributions were equal, and most patients were Caucasian (59%). On multivariate linear regression, with each one-point increase in mFI-5, total LOS increased by 0.64 days in the overall cohort (p < 0.001), 1.08 days in the Cushing disease cohort (p = 0.045), and 0.59 days in non-functioning tumors cohort (p = 0.004). Total charges increased by $3954 in the whole cohort (p < 0.001), $10,652 in the Cushing disease cohort (p = 0.033), and $2902 in the non-functioning tumors cohort (p = 0.007) with each one-point increase in mFI-5. Greater mFI-5 scores were associated with greater odds of 90-day readmission in both overall and Cushing disease cohorts, but these associations did not reach statistical significance. CONCLUSION: A patient's mFI-5 score is significantly associated with increased length of stay and hospital charges for patients undergoing pituitary surgery. The mFI-5 may hold peri-operative value in patient counseling for pituitary adenoma surgery.

Extracorporeal photopheresis as an immunomodulatory agent: Haematocrit-dependent effects on natural killer cells.

The GvHD is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Extracorporeal photopheresis (ECP) represents an alternative therapeutic strategy to immunosuppressive therapy. Although ECP is used since 1990s, the mechanism of action has not yet been completely clarified. We analyzed cells collected from 20 ECP procedures of 4 patients affected by chronic GvHD and, for comparison, Peripheral Blood Mononuclear Cells (PBMCs) of 10 healthy donors undergoing from same type of photochemiotherapy, evaluating by flow cytometry, the effects before and after photoactivation with 8-MOP. The analysis showed a significant increase in cell death after ECP in particular in CD4 T lymphocytes as described in literature correlated with haematocrit value. Most interesting data emerge from the analysis of cytotoxic activity of NK cells, using flow cytometry analysis of surface expression of CD107a in the presence of target cells (K562). In all analyzed samples it was possible to document a statistically significant reduction of the cytotoxic activity of NK cells after photoactivation. The decrease of the cytotoxic activity was related to hematocrit value of leukoapheresis: in fact, lower HCT values were associated with a more marked reduction of cytotoxic activity. The study confirms literature data about the increase of cellular mortality induce by ECP. Furthermore, for the first time it is demonstrated that the ECP exerts a marked and significant inhibitory effect on the cytotoxic activity of NK cells. Our study suggests that lower values of hematocrit are associated with better treatment outcome.

Mesophilic and thermophilic anaerobic co-digestion of winery wastewater sludge and wine lees: An integrated approach for sustainable wine production.

In this work, winery wastes generated by a cellar producing approximately 300,000 hL of wine per year was monitored for a period of one year. On average, 196 L of wastewater, 0.1 kg of waste activated sludge (dry matter) and 1.6 kg of wine lees were produced per hectoliter of wine produced. Different winery wastes, deriving from different production steps, namely waste activated sludge from wastewater treatment and wine lees, were co-treated using an anaerobic digestion process. Testing was conducted on a pilot scale for both mesophilic and thermophilic conditions. The process was stable for a long period at 37 °C, with an average biogas production of 0.386 m3/kg CODfed. On the other hand, for thermophilic conditions, volatile fatty acids accumulated in the reactor and the process failed after one hydraulic retention time (23 days). In order to fix the biological process, trace elements (iron, cobalt and nickel) were added to the feed of the thermophilic reactor. Metals augmentation improved process stability and yields at 55 °C. The pH ranged between 7.8 and 8.0, and specific gas production was 0.450 m3/kg CODfed, which corresponded to dry matter and COD removals of 34% and 88%, respectively. Although the observed performances in terms of biogas production were good, the thermophilic process exhibited some limitations related to both the necessity of metals addition and the worse dewaterability properties. In fact, while the mesophilic digestates reached a good dewatering quality via the addition of 6.5 g of polymer per kg of dry matter, the required dosage for the thermophilic sludge was greater than 10 g/kg of dry matter.

Essentials of Pediatric Emergency Medicine Fellowship: Part 1: An Overview.

This article is the first in a 7-part series (Table 1) that aims to comprehensively describe the current state and future directions of pediatric emergency medicine fellowship training from the essential requirements to considerations for successfully administering and managing a program to the careers that may be anticipated on program completion. This overview article provides a framework for the series.

Leukapheresis for autologous stem cell transplantation: Comparative study of two different thawing methods WSCFD(®) Stem Cell Fast Thawer KW versus 37 °C thermostatic bath.

BACKGROUND: Leukapheresis for autologous stem cell transplantation represents an efficient technique for the reconstitution of haematopoietic system in patients subjected to a high-dose chemotherapy for the treatment of haematological malignancies. The current regulations emphasise first steps of leukapheresis procedure but do not recommend methods for thawing, only suggesting that it must be performed as soon as possible in a 37 °C thermostatic bath. AIM OF THE STUDY: We compared the classic method of thawing with an innovative and fully traceable method that uses WSCFD(®) Stem Cell Fast Thawer KW. MATERIALS AND METHODS: The first part of the study was focused on the thermodynamic process of the two methods, thawing 6 "simulated" leukapheresis (buffy coats of healthy donors cryopreserved with saline solution, 5% HSA and 5% DMSO) and analysing the thawing curve obtained, by using an inside probe. In the second part, we focused on the recovery of viable CD34+ cells and leukocytes, thawing 20 real leukapheresis from paediatric patients. In this phase we also analyse final core bag temperature, time of procedure, cellular recovery with ISHAGE single platform flow cytometry assay and clonogenic potential performing a CFU assay. RESULTS: We found no significant differences between the two methods, both for thermodynamic aspect and cellular recovery. Thawing curves were similar and the paired Student's-t test used for statistical analysis showed a CD34+ cells recovery of 92.2% ± 11.4 using WSCFD(®) versus 90% ± 11.1 of thermostatic bath. Data were similar even for leukocytes recovery (80.8% ± 9.5 with WSCFD(®) and 79.2% ± 14.4 with thermostatic bath). All thawed products never exceeded the core temperature of 30 °C and no differences were found about the post-thaw clonogenic potential (614 × 10(4) ± 98.3 total CFU using WSCFD(®) versus 592 × 10(4) ± 78.5 using thermostatic bath). The only difference observed was about the thawing time: WSCFD method requires a slightly longer time but, on the other hand, it correlates with reduced mean increase in temperature per minute, as a result of a more linear thawing curve. CONCLUSIONS: WSCFD(®) can replace the 37 °C thermostatic bath thawing procedure for leukapheresis, providing more security and fully traceable process data.

Functional interaction between PML and SATB1 regulates chromatin-loop architecture and transcription of the MHC class I locus.

The function of the subnuclear structure the promyelocytic leukaemia (PML) body is unclear largely because of the functional heterogeneity of its constituents. Here, we provide the evidence for a direct link between PML, higher-order chromatin organization and gene regulation. We show that PML physically and functionally interacts with the matrix attachment region (MAR)-binding protein, special AT-rich sequence binding protein 1 (SATB1) to organize the major histocompatibility complex (MHC) class I locus into distinct higher-order chromatin-loop structures. Interferon gamma (IFNgamma) treatment and silencing of either SATB1 or PML dynamically alter chromatin architecture, thus affecting the expression profile of a subset of MHC class I genes. Our studies identify PML and SATB1 as a regulatory complex that governs transcription by orchestrating dynamic chromatin-loop architecture.

Treatment of waste activated sludge together with agro-waste by anaerobic digestion: focus on effluent quality.

Waste activated sludge production and management plays an important role in wastewater treatment plants (WWTPs), especially from an economic point of view. One possible approach is the anaerobic co-digestion of waste activated sludge with others organic substrates in mesophilic and thermophilic conditions in order to exploit the spare volume of existing reactors, recover energy from biogas production, and obtain a fertilizer as final product. The anaerobic trials were carried out at pilot scale, applying two organic loading rates (2.8 and 4.5 kg chemical oxygen demand (COD)/(m(3)·d)) with a hydraulic retention time of 16 and 21 days. Among agro-wastes, wine lees were chosen because of their continuous availability throughout the year, and their high COD content (up to 200-300 g/l, 70% soluble, on average). The addition of wine lees to activated sludge determined a higher biogas production (best yield was 0.40 Nm(3)/kgCOD(fed)) improving the energetic balance of the sludge line of the WWTP. The characterization of both substrates fed and digester effluents was carried out in terms of heavy metals; comparison with EC proposed limits showed that, due to high content of Cu in wine lees, the loading rate of this agro-waste should be limited to maintain good characteristics of final biosolids.

Internal neurolysis versus intraoperative glycerin rhizotomy for trigeminal neuralgia.

OBJECTIVE: Internal neurolysis (IN) and intraoperative glycerin rhizotomy (ioGR) are emerging surgical options for patients with trigeminal neuralgia without neurovascular contact. The objective of this study was to compare the neurological outcomes of patients who underwent IN with those of patients who underwent ioGR. METHODS: The authors retrospectively reviewed all patients who underwent IN or ioGR for trigeminal neuralgia at our institution. Patient demographic characteristics and immediate postoperative outcomes, as well as long-term neurological outcomes, were compared. RESULTS: Of 1044 patients who underwent open surgical treatment for trigeminal neuralgia, 56 patients underwent IN and 91 underwent ioGR. Of these 147 patients, 37 had no evidence of intraoperative neurovascular conflict. All patients who underwent IN and 96.7% of patients who underwent ioGR had immediate postoperative pain relief. At last follow-up, patients who underwent IN had lower Barrow Neurological Institute (BNI) pain intensity scores (p = 0.05), better BNI facial numbness scores (p < 0.01), and a greater degree of pain improvement (p = 0.05) compared with those who underwent ioGR. Patients who underwent IN also had significantly lower rates of symptomatic pain recurrence (p < 0.01) at last follow-up over an average of 9.5 months. CONCLUSIONS: IN appears to provide patients with a greater degree of pain relief, lower rates of facial numbness, and lower rates of pain recurrence compared with ioGR. Future prospective studies will better characterize long-term pain recurrence and outcomes.

Rapid Development and Testing of a COVID-19 Vaccine Curriculum for Pediatricians.

BACKGROUND AND OBJECTIVES: As the coronavirus disease 2019 (COVID-19) pandemic evolves and vaccines become available to children, pediatricians must navigate vaccination discussions in the setting of rapidly changing vaccine recommendations and approvals. We developed and evaluated an educational curriculum for pediatricians to improve their knowledge about COVID-19 vaccines and confidence in communicating with patients and families about COVID-19 vaccines. METHODS: Five institutions collaborated to develop an online educational curriculum. Utilizing the collaboration's multidisciplinary expertise, we developed a 3-module curriculum focused on the SARS-CoV-2 virus and vaccine basics, logistics and administration of COVID-19 vaccine, and COVID-19 vaccine communication principles. Surveys administered to clinician participants before and after completion of the curriculum assessed knowledge and confidence; a follow-up survey 1 month after the post-survey assessed persistence of initial findings. RESULTS: A total of 152 pediatric providers participated; 72 completed both pre- and post-surveys. The median knowledge score improved from the pre-survey to the post-survey (79%-93%, P < .001). There was an increase in providers' confidence after completing the curriculum, which persisted in the follow-up survey. In the post-survey, 98% of participants had had the opportunity to discuss the COVID-19 vaccine with patients, and most clinicians reported that the modules decreased apprehension some or significantly. CONCLUSIONS: This project demonstrates rapid and feasible deployment of a curriculum providing up-to-date information to front-line clinicians responsible for having complex conversations about COVID-19 vaccine decision-making. Clinicians who completed this curriculum had sustained increased confidence and decreased levels of apprehension when discussing the COVID-19 vaccine.

Autophagy and lysosomal dysfunction as emerging mechanisms of nanomaterial toxicity.

The study of the potential risks associated with the manufacture, use, and disposal of nanoscale materials, and their mechanisms of toxicity, is important for the continued advancement of nanotechnology. Currently, the most widely accepted paradigms of nanomaterial toxicity are oxidative stress and inflammation, but the underlying mechanisms are poorly defined. This review will highlight the significance of autophagy and lysosomal dysfunction as emerging mechanisms of nanomaterial toxicity. Most endocytic routes of nanomaterial cell uptake converge upon the lysosome, making the lysosomal compartment the most common intracellular site of nanoparticle sequestration and degradation. In addition to the endo-lysosomal pathway, recent evidence suggests that some nanomaterials can also induce autophagy. Among the many physiological functions, the lysosome, by way of the autophagy (macroautophagy) pathway, degrades intracellular pathogens, and damaged organelles and proteins. Thus, autophagy induction by nanoparticles may be an attempt to degrade what is perceived by the cell as foreign or aberrant. While the autophagy and endo-lysosomal pathways have the potential to influence the disposition of nanomaterials, there is also a growing body of literature suggesting that biopersistent nanomaterials can, in turn, negatively impact these pathways. Indeed, there is ample evidence that biopersistent nanomaterials can cause autophagy and lysosomal dysfunctions resulting in toxicological consequences.

Predicting performance of in-situ microbial enhanced oil recovery process and screening of suitable microbe-nutrient combination from limited experimental data using physics informed machine learning approach.

Screening of suitable microbe-nutrient combination and prediction of oil recovery at the initial stage is essential for the success of Microbial Enhanced Oil Recovery (MEOR) technique. However, experimental and physics-based modelling approaches are expensive and time-consuming. In this study, Physics Informed Machine Learning (PIML) framework was developed to screen and predict oil recovery at a relatively lesser time and cost with limited experimental data. The screening was done by quantifying the influence of parameters on oil recovery from correlation and feature importance studies. Results revealed that microbial kinetic, operational and reservoir parameters influenced the oil recovery by 50%, 32.6% and 17.4%, respectively. Higher oil recovery is attained by selecting a microbe-nutrient combination having a higher ratio of value between biosurfactant yield and microbial yield parameters, as they combinedly influence the oil recovery by 27%. Neural Network is the best ML model for MEOR application to predict oil recovery (R2≈0.99).