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Oil has become an essential commodity in various fields, including cooking. In India, coconuts are produced abundantly, making it the third-largest coconut-producing nation worldwide. Despite the massive demand for coconut oil, there is a shortage of its production, & the majority of the entities producing the oil are large-scale industries, with only a few operating in local shops. The solution to this problem lies in the "Compact & Cost-Effective Coconut Oil Expeller," which has the potential to increase oil production & address the current gaps. The machine can operate with low quantities of copra, allowing customers to produce oil based on their requirements. Furthermore, it is a zero-waste process that enables the sale of the leftover parts after oil extraction. By facilitating chemical-free oil extraction & reducing space & initial purchase costs, the expeller machine offers an opportunity for small-scale industries to set up a profitable business, similar to flour mills in the area. This project addresses the issues with the currently used oil extractors, leading to the design & fabrication of an automatic portable oil extractor that could enhance the life & functionality of the unit for small-scale industries. The project also incorporates a solar panel for multipurpose use, making it functional even in the absence of electricity. Ultimately, this work contributes to reducing the running cost of an industry & prevents sudden breakdowns on the shop floor, making it a valuable addition to the oil extraction industry

Liver transplantation for end stage liver disease, offers the recipient a near normal life, including pregnancies for women. Successful pregnancies have been reported, but successful second pregnancies are rare. We present our patient with a second successful pregnancy following her liver transplantation. A 22-year-old living donor liver transplant (LT) recipient was enrolled in our unit for antenatal care of her second pregnancy. Her native liver had failed due to autoimmune hepatitis. She had her first planned pregnancy at 19 months post-transplant. The second pregnancy was a spontaneous conception a year later. The obstetric parameters were normal, but she developed signs of suspected graft rejection and hence an emergency cesarean section was done. A preterm baby was delivered with a good APGAR score. The baby was treated in neonatal intensive unit for four days. The mother recovered well and the liver parameters normalized on the sixth postoperative day. Liver transplantation restores fertility in transplant recipients. Pregnancy, the liver graft and the associated medications have a complex interplay. Post LT pregnancy outcome can be optimized with a multidisciplinary approach. Better understanding and close monitoring is essential for a successful outcome.

The aim of present work is to govern and scrutinize the kinetics of drug release from the complex by employing various mathematical models. A study was done with Lagerstroemia speciosa extract-phospholipid complex, 50 mg/200mg by employing anticipation precipitation technique using soya lecithin and cholesterol as complex forming polymer. In-vitro drug release profile was carried out in phosphate buffer saline, pH 7.4 (900mL) using USP dissolution apparatus II (Paddle) at 50 RPM at an extended time period of 0.5, 0.75, 1, 1.5, 2, 2.5, 3 and 4 hours. The drug release data was obtained, quantitatively correlated and interpreted with various mathematical models viz. Zero order model, first order model, Higuchi model and Korsmeyer-Peppas model and evaluated to understand the kinetics of drug release. The criterion for the most suitable model was based on the high degree of coefficient of correlation of drug release profile was best fitted with Korsmeyer-Peppas model and follows drug release kinetics which is diffusion controlled.

AimsStructural analogues of bisphenol A (BPA), including BPS and BPF, are emerging environmental toxicants as their presence in the environment is rising since new regulatory restrictions were placed on BPA-containing infant products. The adipogenesis-enhancing effect of bisphenols may explain the link between human exposure and metabolic disease; however, underlying molecular pathways remain unresolved.ResultsExposure to BPS, BPF, BPA or ROS generators enhanced lipid droplet formation and expression of adipogenic markers after induction of differentiation in adipose-derived progenitors isolated from mice. RNAseq analysis in BPS-exposed progenitors revealed modulation in pathways regulating adipogenesis and responses to oxidative stress. ROS was higher in bisphenol-exposed cells, while co-treatment with antioxidants attenuated adipogenesis and abolished the effect of BPS. There was a loss of mitochondria membrane potential in BPS-exposed cells and mitochondria-derived ROS contributed to potentiation of adipogenesis by BPS and its analogues. Male mice exposed to BPS during gestation had higher whole-body adiposity, as measured by TD-NMR, while postnatal exposure had no impact on adiposity in either sex.InnovationThese findings support existing evidence showing a role for ROS in regulating adipocyte differentiation and are the first to highlight ROS as a unifying mechanism that explains the pro-adipogenic properties of BPA and its structural analogues.ConclusionROS act as signaling molecules in the regulation of adipocyte differentiation and mediate bisphenol-induced potentiation of adipogenesis.

To address the key challenges in the development of next-generation drug delivery systems (DDS) with desired physicochemical properties to overcome limitations regarding safety, in vivo efficacy, and solid tumor penetration, an ultrasmall folate receptor alpha (FRα) targeted silica nanoparticle (C'Dot) drug conjugate (CDC; or folic acid CDC) was developed. A broad array of methods was employed to screen a panel of CDCs and identify a lead folic acid CDC for clinical development. These included comparing the performance against antibody-drug conjugates (ADCs) in three-dimensional tumor spheroid penetration ability, assessing in vitro/ex vivo cytotoxic efficacy, as well as in vivo therapeutic outcome in multiple cell-line-derived and patient-derived xenograft models. An ultrasmall folic acid CDC, EC112002, was identified as the lead candidate out of500 folic acid CDC formulations evaluated. Systematic studies demonstrated that the lead formulation, EC112002, exhibited highly specific FRα targeting, multivalent binding properties that would mediate the ability to outcompete endogenous folate

BackgroundUntil recently there were no genome-directed therapies (GDTs) requiring next-generation sequencing (NGS) in prostate cancer. We examined whether the US approval of poly-(ADP-ribose) polymerase (PARP) inhibitors in May 2020 influenced the actionability and utilization of NGS in patients with prostate cancer.MethodsThis was a single-center, retrospective study including men with prostate cancer who received NGS testing from a single lab between 7/11/2018-7/6/2021. Clinical and testing data were derived from the electronic medical record.ResultsThere were 346 patients with prostate cancer and qualifying NGS testing during the study period. Overall, 55 patients (15.9%) had qualifying homologous recombination repair (HRR) alterations for PARP inhibitor treatment. A greater proportion of alterations were actionable post-approval compared to pre-approval (22.7% vs 0%, Chi-squared pConclusionIn this single-center cohort, the approval of PARP inhibitors for later-line treatment of metastatic prostate cancer increased the actionability of NGS findings but did not lead to earlier use of NGS testing.

A comprehensive experimental and kinetic modeling study of the ignition delay time (IDT) characteristics of some binary blends of C1–C2 gaseous hydrocarbons such as methane/ethylene, methane/ethane, and ethane/ethylene was performed over a wide range of composition (90/10, 70/30, 50/50%), temperature (∼800–2000 K), pressure (∼1–40 bar), equivalence ratio (∼0.5–2.0), and dilution (∼75–90%). An extensive literature review was conducted, and available data were extracted to create a comprehensive database for our simulations. Based on the existing literature data, an experimental matrix was designed using the Taguchi approach (L9) in order to identify and complete the experimental matrix required to generate a comprehensive experimental IDT set necessary for the validation of a chemical kinetic model. The required high- and low-temperature IDTs were collected using low-/high-pressure shock tubes and rapid compression machines, respectively. The predictions of NUIGMech1.0 are examined versus all of the available experimental data, including those taken in the current study using the IDT simulations and a correlation technique. Moreover, the individual effect of the studied parameters, including mixture composition, pressure, equivalence ratio, and dilution on IDT, is investigated over the studied temperature range. Correlations that were developed based on NUIGMech1.0 are presented for each specific blended fuel over the conditions studied. These correlations show an acceptable performance versus the experimental data. The authors would like to express their gratitude to Shell Research Ltd. and Science Foundation Ireland (SFI) for funding via project numbers 15/IA/3177 and 16/SP/3829. The authors from PCFC, RWTH Aachen University, would like to recognize the funding support from the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) through the project number – 322460823 (HE7599/2-1). peer-reviewed 2021-06-03

Antibody-drug conjugates (ADCs) exhibit limited efficacy against brain malignancies due to their inability to cross the blood-brain barrier (BBB) and penetrate into solid tumors. In clinical imaging studies C’Dots readily crossed tumor-disrupted BBB and penetrated across/localized in tumors in the brain avoiding healthy brain. CDCs are ultra-small (6-7 nm) nanoparticles with a silica core coated by short polyethylene glycol chains conjugated to up to 80 small payload and targeting moieties, creating highly potent and avid agents. CDCs’ small size mediates rapid renal clearance leading to limited exposure to healthy tissues. ELU001 is a potent anti-FRα CDC with an average of 21 exatecan topoisomerase-1 inhibitor payload molecules and 13 folic acid targeting molecules on its surface. ELU001 is currently in a dose escalation trial in patients with systemic solid tumor indications that have the potential to overexpress FRα. Early signs of activity with a manageable safety profile have been seen across antigen expression levels. ELU001 exhibits in vitro potency in the sub/low nanomolar range against cancer cell lines that express 3+, 2+ or 1+ levels of FRα. In studies performed in immunodeficient mice bearing intracranial NCI-H2228-luc bioluminescent non-small cell lung cancer tumors, ELU001 was observed to penetrate across disrupted BBB and localize in tumors. Microscopic analysis revealed that ELU001 distributed throughout the tumors but not into the healthy brain. Treatment with a single cycle of ELU001 Q3Dx3 in mice bearing either early (Day 7) or late (Day 14) brain tumors was well tolerated and resulted in significant reduction in tumor burden measured by bioluminescence as well as a prolonged survival benefit. Retreatment of these animals resulted in an additional decrease in tumor burden. These results suggest that ELU001 may have promise for the treatment of metastatic brain tumors that are difficult to treat with currently available agents. Citation Format: Gregory P. Adams, Tin Khor, Feng Chen, Kai Ma, Marion Scocca, Aranapakam Venkatesan, Cathy Reddick, Mary Hilgart, Thomas Gardinier, Fei Wu, Melik Turker, Peiming Chen, Vaibhav Patel, Eliel Bayever. Preclinical development of ELU001: A folate receptor alpha (FRα)-targeted C’Dot drug conjugate (CDC) for the treatment of brain metastases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 837.

Combustion and flame 234, 111626 (2021). doi:10.1016/j.combustflame.2021.111626, Published by Elsevier Science, Amsterdam [u.a.]

Objective: Early knee osteoarthritis in all cases, lead to degenerative medial meniscus lesions which are visible in MRI as chondral defects. As a result, it is difficult to distinguish between unstable meniscus and early osteoarthritis which leads to symptomatic knee pain. Hence, we decided to study improvement athroscopic meniscectomy and injecting Hyaluronic acid or Hydrocortisone in cases of degenerative ruptures of the medial meniscus with changes of early stage medial compartment knee osteoarthritis. Materials and Methods: 60 consecutive cases of early OA Knee of non traumatic origin were studied. They were given treatment of arthroscopic lavage and randomly administered hydrocortisone or hyaluronic acid. The WOMAC score was obtained and compared from immediate post-op period to upto 6 months. Result: In our study on patient undergoing arthroscopic debridement of osteoarthritis knee with Inj. Hydrocortisone improvement in WOMAC score was from 50.97% to 43.81%, totally an improvement of WOMAC score 7.2% while those undergoing arthroscopic debridement of osteoarthritis knee with Inj. Hyaluronic acid improvement in WOMAC score was from 51.25% to 37.1%, totally an improvement in WOMAC score of around 15%. Conclusion: Joint lavage by arthroscopy in combination with either intra-articular steroid injection or intra-articular hyaluronic acid injection provides significant improvement in osteoarthritis knee patient. Data suggests that, those patient who underwent arthroscopic debridement and injection of hydrocortisone had symptomatic improvement at early follow up more than those of the hyaluronic acid, while arthroscopic debridement of osteoarthritis knee and injection of hyaluronic acid performed better at longer follow up. Keywords: WOMAC score, Hyaluronan, Osteoarthritis.

Combustion and flame 228, 401-414 (2021). doi:10.1016/j.combustflame.2021.02.009, Published by Elsevier Science, Amsterdam [u.a.]

While several antibody-drug conjugates (ADCs) have shown efficacy in the treatment of solid tumors ADCs remain limited in their therapeutic efficacy due to long circulatory half-life and limited tumor penetration. Ultra-small (sub-10nm) C’Dot-drug-conjugates (CDCs) directly address this, exhibiting deep penetration and retention in solid tumor models, with limited systemic exposure following rapid renal clearance. CDCs can also achieve greater potency by delivering over 10x more payload and by binding to tumor cells with a higher avidity allowing effective killing of tumors with broader range of moderate to high expression of target antigens. ELU001 is a CDC that targets folate receptor alpha (FRα) overexpressing tumors via folic acid moieties on its surface and delivers an average of 21 exatecan topoisomerase-1 inhibitor molecules as its payload. FRα is overexpressed on a variety of tumors including ovarian, endometrial, triple negative breast and non-small cell lung, but is minimally expressed on normal tissues making it an attractive tumor-associated antigen for targeted drug delivery. ELU001 is highly stable in plasma and elicits antitumor efficacy in a variety of cell line and PDX-derived tumor models both in vitro and in vivo. In 15-day repeat dose toxicology and toxicokinetic studies performed in Wistar Han rats and Beagle dogs, ELU001 was well tolerated at up to 0.87 mg/kg/day in rats and 0.174 mg/kg/day in dogs based upon conjugated exatecan concentration when administered on a QWx3 schedule via a 1-hour infusion. Observed dose-related toxicities for both species were limited to the bone marrow and GI tract - the same organs as those observed when free payload (exatecan) was administered suggesting that the delivery of exatecan conjugated to the CDC did not broaden the tissue toxicity profile. Observed toxicities were recovered or substantially reduced by the end of a two-week recovery period. No drug-related hepatic, renal, pulmonary or ocular toxicities were observed and there were no drug-related deaths in the repeat dose toxicity study. TK parameters, estimated in the 15-day GLP studies revealed similar plasma exposure values in males and females for ELU001, Total Exatecan (conjugated and released) and Released Exatecan for rats and dogs, respectively. ELU001 exhibited an average circulatory half-life ranging from approximately 15 to 20 hrs in rats and 24 to 29 hrs in dogs with no accumulation of ELU001, Total Exatecan or Free Exatecan observed from day 1 to day 15. Based upon AUC0-last (hr*ng/ml) released payload levels in the circulation were less than approximately 0.3% and 0.1% of the total payload levels in the rat and the dog respectively. No ELU001 anti-drug antibodies were induced in either species. In summary, ELU001 has a favorable nonclinical safety/TK profile and is currently under evaluation in a clinical safety study - NCT05001282. Citation Format: Gregory P. Adams, Kai Ma, Feng Chen, Marion Scocca, Aranapakam Venkatesan, Cathy Reddick, Mary Hilgart, Thomas Gardinier, Fei Wu, Melik Turker, Peiming Chen, Tin Khor, Vaibhav Patel, Eliel Bayever. Stability and safety evaluation of ELU001, a targeted C’Dot drug conjugate for the potential treatment of folate receptor alpha-overexpressing cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1077.

Acute myeloid leukemia (AML) in infants is a unique subtype of AML that is driven by oncogenic fusions, resulting in a highly proliferative disease. The CBFA2T3-GLIS2 oncogenic fusion that is seen exclusively in infants and young children Citation Format: Quy Le, Feng Chen, Thao Tang, Cynthia Nourigat McKay, Fei Wu, Melik Turker, Thomas Gardinier, Vaibhav Patel, Aranapakam Venkatesan, Tin Khor, Kai Ma, Gregory P. Adams, Soheil Meshinchi. Therapeutic targeting of CBFA2T3-GLIS2 infant AML with ELU001 - folate receptor alpha-directed C’Dot-drug-conjugate [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1075.

Introduction Clinical behavior, treatment parameters, and prognostic factors are less well defined in older adults with low-grade gliomas (LGG). We conducted a two-institution retrospective review of older patients with LGG to better understand disease characteristics and prognosis in this population. Methods Northwestern University (NU) and The University of Washington (UW) clinical research databases were queried for patients ≥ 50 years of age with a diagnosis of WHO grade II glioma between January 1, 2000 and December 2012 (UW). Medical records were reviewed and data relevant to diagnosis, treatment and outcomes were collected. PFS and OS with respect to prognostic factors were calculated. Log-rank test and multivariate proportional hazards models were calculated for multiple tumor characteristics. Results Thirty-five patients with a diagnosis of LGG (WHO grade II) were identified; 15 women and 20 men had a median age of 55 (range 50-78). Fourteen had astrocytomas, fourteen had oligodendrogliomas and seven had oligoastrocytomas. Eight patients had contrast enhancement on neuroimaging, 9 of 21 tested had 1p19q co-deletion and 5 of 14 tested had an IDH1 mutation. Five year PFS was 21% with median PFS of 17 months; 20 patients had died (5 year OS=43%, median OS=48 months). On univariate analysis There was a statistically significant improvement in OS for patients with mixed histology (p=0.001), no midline shift at diagnosis (p=0.002) and with IDH1 mutation (p=0.003). Conclusion LGG appear more aggressive in older patients. Treatment following surgical resection should be considered; ongoing studies may clarify the most appropriate treatments for this age group.

An experimental and kinetic modeling study of the influence of NOx (i.e. NO2, NO and N2O) addition on the ignition behavior of methane/‘air’ mixtures is performed. Ignition delay time measurements are taken in a rapid compression machine (RCM) and in a shock tube (ST) at temperatures and pressures ranging from 900–1500 K and 1.5–3.0 MPa, respectively for equivalence ratios of 0.5–2.0 in ‘air’. The conditions chosen are relevant to spark ignition and homogeneous charge compression ignition engine operating conditions where exhaust gas recirculation can potentially add NOx to the premixed charge. The RCM measurements show that the addition of 200 ppm NO2 to the stoichiometric CH4/oxidizer mixture results in a factor of three increase in reactivity compared to the baseline case without NOx for temperatures in the range 600–1000 K. However, adding up to 1000 ppm N2O does not show any appreciable effect on the measurements. The promoting effect of NO2 was found to increase with temperature in the range 950–1150 K, while the sensitization effect decreases at higher pressures. The experimental results measured are simulated using NUIGMech1.2 comprising an updated NOx sub-chemistry in this work. A kinetic analysis indicates that the competition between the reactions ĊH3 + NO2 ↔ CH3Ȯ + NO and ĊH3 + NO2 (+M) ↔ CH3NO2 (+M), the former being a propagation reaction and the latter being a termination reaction governs NOx sensitization on CH4 ignition. Recent calculations by Matsugi and Shiina (A. Matsugi, H. Shiina, J. Phys. Chem. A. 121 (2017) 4218–4224) for the nitromethane formation reaction CH3 + NO2 (+M) ↔ CH3NO2 (+M), together with the recently calculated rate constants for HONO/HNO2 reactions significantly improve ignition delay time predictions in the temperature range 600–1000 K. Furthermore, the experiments with NO addition reveal a non-monotonous sensitization impact on CH4 ignition at lower temperatures with NO initially acting as an inhibitor at low NO concentrations and then as a promoter as NO concentrations increase in the mixture. This non-monotonous trend is attributed to the role of the chain-termination reaction ĊH3 + NO2 (+M) ↔ CH3NO2 (+M) and the impact of NO on the transition to the chain-branching steps CH2O + HȮ2 ↔ HĊO + H2O2, H2O2 (+M) ↔ ȮH + ȮH (+M), HĊO ↔ CO + Ḣ followed by CO + O2 ↔ CO2 + O and Ḣ + O2 ↔ O + ȮH. NUIGMech1.2 is systematically validated against the new ignition delay measurements taken here together with species measurements and high temperature ignition delay time data available in the literature for CH4/oxidizer mixtures diluted with NO2/N2O/NO and is observed to accurately capture the sensitization trends.

Liquefied Natural Gas (LNG) has become an increasingly important world energy resource and is a part of the European Union clean fuel strategy launched in 2013. Therefore, there are currently several ongoing measurement strategies considering quality specification of LNG. In this context, for application in gas engines, it is essential to understand the combustion behavior of these natural gas mixtures. The methane number (MN) which represents a scale for the knocking propensity, is one of the main indicators for this combustion behavior. In this study, we investigated the influence of the LNG composition on the ignition delay time and thus the knocking behavior of prototypical LNG Mixtures. Several LNG typical mixtures containing CH4/C2H6/C3H8/n-C4H10/i-C4H10/n-C5H12/i-C5H12/N2 were studied in the temperature range 850–1450 K, with pressures of 20 and 40 bar and at equivalence ratios of 0.4 and 1.2. The use of a shock tube and a rapid compression machine facility allowed us to study the ignition behavior over a wide range of operating conditions relevant to gas engines. We report a detailed investigation of LNG autoignition with respect to temperature, pressure and equivalence ratio thereby providing crucial validation data for chemical kinetic models for real applications.

A comprehensive experimental and modeling study of the ignition delay time (IDT) characteristics of some single prominent C1–C2 hydrocarbons including methane, ethane, and ethylene has been performed over a wide range of temperatures (∼800–2000 K), pressures (∼1–80 bar), equivalence ratios (∼0.5–2.0), and dilutions (∼75–90%). An extensive literature review was conducted, and available data were extracted to create a comprehensive database used in our simulations. Based on existing literature data, an experimental matrix was designed using the Taguchi approach (L9) in order to identify and complete the experimental matrix required to generate a comprehensive validation set necessary for validation of a chemical kinetic model. The required IDTs were recorded using a high-pressure shock tube for shorter IDTs and a rapid compression machine for longer times, which encompass high- and low-temperature ranges, respectively. The predictions of a C3-NUIG mechanism have been compared with all of the available experimental data including those from the current study using the IDT simulations and the correlation technique. Moreover, individual and total effects of the studied parameters including pressure, equivalence ratio, and dilutions on IDT have been studied over a wide temperature range. Moreover, correlations which were developed based on the NUIG mechanism are presented for each specific fuel over the conditions studied. These correlations show acceptable performance versus the experimental Taguchi matrix data. The authors would like to express their gratitude to Shell Research Ltd and Science Foundation Ireland (SFI) via their Research Centre Program through project number 16/SP/3829. The authors from PCFC, RWTH Aachen University would like to recognize the funding support from the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) through the Project Number 322460823 (HE7599/2-1). peer-reviewed 2021-02-03

This paper addresses a novel machine learning approach to classify EEG signals that can be useful for discovering likelihood of suffering from genetic alcoholism. Excessive consumption of alcohol can create genetic cognitive impairment and contribute to alcohol disorder in descendants. Children can inherit it either directly from parents or any ancestors. Revealing chances of AUD would help in deciding preventive intervention efficiently. Major contribution of this work is classification based on input augmentation and automatic feature extraction. Instead of using signal from many spatial nodes proposed classification task relies on EEG signal from only two electrodes, therefore it is computationally efficient. Results are shown for performance comparison between customary and augmented EEG as inputs to the classifier. Input augmentation is confirmed for 15% improvement in accuracy.

Nitric oxide (NO) is a ubiquitous, endogenously produced, water-soluble signaling molecule playing critical roles in physiological processes. Nitric oxide plays pleiotropic roles in cancer and, depending on its local concentration, may lead to either tumor progression or tumor suppression. Addition of NO group to a cysteine residue within a protein, termed as S-nitrosylation, plays diverse regulatory roles and affects processes such as metabolism, apoptosis, protein phosphorylation, and regulation of transcription factors. The process of S-nitrosylation has been associated with development of different cancers, including breast cancer. The present review discusses different mechanisms through which NO acts, with special emphasis on breast cancers, and provides detailed insights into reactive nitrogen species, posttranslational modifications of proteins mediated by NO, dual nature of NO in cancers, and the implications of S-nitrosylation in cancers. Our review will generate interest in exploring molecular regulation by NO in different cancers and will have significant therapeutic implications in the management and treatment of breast cancer.

CDCs are novel ultra-small (6-7 nm) nanoparticle drug conjugates that have been demonstrated to be capable of faster tumor targeting and deeper tumor penetration than antibody drug conjugates in animal models. CDCs are capable of targeting tumors in the brain and pancreas that are difficult to access, while exhibiting limited exposure to normal tissues due their efficient renal elimination. CDCs are composed of a silica core, in which Cy5, a far red dye is covalently encapsulated. The silica core is covalently coated with a layer of polyethylene glycol which is then functionalized with targeting moieties and payloads. ELU001 is a CDC functionalized with ~20 molecules of the topoisomerase-1 inhibitor exatecan linked via a proteolytic cleavable linker as a payload and ~15 folic acids to provide targeting to FRα overexpressing cancers. ELU001 is rapidly internalized into FRα expressing cells and is trafficked to the lysosome where the payload is released from the CDC. ELU001 exhibits potency in the low single digit nanomolar to sub-nanomolar range against cancer cells that express 3+ (KB, IGROV-1) and 2+ (SK-OV-3, HCC827 and OVCAR-3) levels of FRα after a 6-hr exposure in a 7-day viability study. In contrast, an anti-FRα ADC based ADC mirvetuximab soravtansine exhibits lower potency (>100 nM IC50) against SK-OV-3 and HCC827 cells and 40 nM IC50 against OVCAR-3 cells. ELU001 exhibits potent efficacy against established s.c. KB human cervical tumor xenografts in immunodeficient mice with significantly better efficacy and safety than free exatecan payload. It is also effective in treating established SK-OV-3 tumors with lower (2+) FRα expression, a setting where the ADC is again less effective. IND-enabling nonclinical studies are currently underway to prepare for initiation of a first-in-human phase 1 clinical trial in subjects with FRα overexpressing cancers in the second half of 2021. Citation Format: Gregory Paul Adams, Kai Ma, Aranapakam Venkatesan, Feng Chen, Fei Wu, Melik Turker, Thomas Gardinier, Peiming Chen, Vaibhav Patel, Eliel Bayever, Paul Rudick, Geno Germano. ELU001, a targeted C'Dot drug conjugate (CDC) for the treatment of folate receptor alpha (FRα) overexpressing cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 305.

The aim of the present work is to formulate heparin-modified-polycaprolactone (HEP) core shell nanoparticles (NPs) of 5-fluorouracil (5-FU). These NPs were characterized for various in vitro parameters like particle size, zeta potential, etc. HEP NPs were found to maintain comparatively slower drug release pattern (98.9% in 96 h) than PCL NPs. Cytotoxicity studies demonstrated a massive cytotoxic potential of 5-FU-loaded HEP NPs in A549, MDA-MD-435, and SK-OV-3 cancer cell lines. Pharmacokinetic parameters were also determined in blood after IV administration of HEP NPs: AUC, Cmax, MRT, and Tmax values are 6096.075 ± 5.90 μg h/mL, 144.38 ± 1.52 μg/L, 58.71 ± 0.25 h, 96 ± 0.50 h, respectively and 117.92 ± 1.78, 45.35 ± 3.00, 1.2 ± 0.25, 0.5 ± 0.02 in plain 5-FU solution.

Additional file 1: Table S1. Description of all U.S. FDA approvals of immune checkpoint inhibitors including date, drug information, indication, trial information (phase, endpoint leading to approval, PD-L1 cutoff)Â

PURPOSE The utilization of three-dimensional modeling technology in craniomaxillofacial surgery has grown exponentially during the last decade. Future development, however, is hindered by the lack of a normative three-dimensional anatomic dataset and a statistical mean three-dimensional virtual model. The purpose of this study is to develop and validate a protocol to generate a statistical three-dimensional virtual model based on a normative dataset of adult skulls. METHOD Two hundred adult skull CT images were reviewed. The average three-dimensional skull was computed by processing each CT image in the series using thin-plate spline geometric morphometric protocol. Our statistical average three-dimensional skull was validated by reconstructing patient-specific topography in cranial defects. The experiment was repeated 4 times. In each case, computer-generated cranioplasties were compared directly to the original intact skull. The errors describing the difference between the prediction and the original were calculated. RESULTS A normative database of 33 adult human skulls was collected. Using 21 anthropometric landmark points, a protocol for three-dimensional skull landmarking and data reduction was developed and a statistical average three-dimensional skull was generated. Our results show the root mean square error (RMSE) for restoration of a known defect using the native best match skull, our statistical average skull, and worst match skull was 0.58, 0.74, and 4.4 mm, respectively. CONCLUSIONS The ability to statistically average craniofacial surface topography will be a valuable instrument for deriving missing anatomy in complex craniofacial defects and deficiencies as well as in evaluating morphologic results of surgery.