Informatics and Artificial Intelligence-Guided Assessment of the Regulatory and Translational Research Landscape of First-in-Class Oncology Drugs in the United States, 2018-2022.

Purpose: Cancer drug development remains a critical but challenging process that affects millions of patients and their families. Using biomedical informatics and artificial intelligence (AI) approaches, we assessed the regulatory and translational research landscape defining successful first-in-class drugs for patients with cancer.

Methods: This is a retrospective observational study of all novel first-in-class drugs approved by the US Food and Drug Administration (FDA) from 2018 to 2022, stratified by cancer versus noncancer drugs.

Achieving end-to-end success in the clinic: Pfizer's learnings on R&D productivity.

Over the past decade, Pfizer has focused efforts to improve its research and development (R&D) productivity. By the end of 2020, Pfizer had achieved an industry-leading clinical success rate of 21%, a tenfold increase from 2% in 2010 and well above the industry benchmark of ∼11%. The company had also maintained the quality of innovation, because 75% of its approvals between 2016 and 2020 had at least one expedited regulatory designation (e.

Incorporation of Carbon Quantum Dots for Improvement of Supercapacitor Performance of Nickel Sulfide.

A facile hydrothermal method is adopted for the synthesis of hierarchical flowerlike nickel sulfide nanostructure materials and their composite with carbon quantum dot (NiS/C-dot) composite. The composite material exhibited good performance for electrochemical energy-storage devices as supercapacitor with a specific capacity of 880 F g at a current density of 2 A g. The material remained stable up to the tested 2000 charge-discharge cycles.

Action of corilagin on hyperglycemia, hyperlipidemia and oxidative stress in streptozotocin-induced diabetic rats.

Diabetes mellitus is the world's most common endocrine disease involving metabolic disorders of carbohydrate, protein and fat. This study was undertaken to investigate the anti-diabetic activity of corilagin, a member of polyphenolic tannins used against hyperglycemia and many other diseases in well-known animal models. Diabetes was induced chemically by intraperitoneal administration of Streptozotocin (40 mg/kg bw) to albino Wistar rats.

Antidiabetic, antihyperlipidemic and antioxidant effect of Vincamine, in streptozotocin-induced diabetic rats.

Diabetes mellitus is the most common endocrine disorder characterized by hyperglycemia resulting from defects in insulin secretion or insulin action. The present study was designed to investigate the antidiabetic effects of vincamine, one of the monoterpenoid indole alkaloid, in streptozotocin-induced diabetic rat model. Diabetes was induced in rats by an intraperitoneal injection of streptozotocin (40 mg/kg bw).

Ameliorative effect of borneol, a natural bicyclic monoterpene against hyperglycemia, hyperlipidemia and oxidative stress in streptozotocin-induced diabetic Wistar rats.

Diabetes mellitus is a major public health problem worldwide. Oxidative stress plays a pivotal role in the pathogenesis of diabetes as it is one of the inevitable outcomes of the cellular process. The present study aims to investigate the putative antihyperglycemic, antihyperlipidemic and antioxidant efficacy of a monoterpene borneol, in comparison with glibenclamide, a standard drug for therapy of diabetes.

Modulatory effect of garcinol in streptozotocin-induced diabetic Wistar rats.

The objective of the study was to evaluate the efficacy of garcinol as an antidiabetic candidate in streptozotocin-induced diabetic Wistar rats. Diabetic rats showed a significant increase in the biochemical parameters such as fasting blood glucose, glycated haemoglobin, urea, alanine aminotransferase and aspartate aminotransferase, malondialdehyde, total cholesterol, triglycerides, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, atherogenic index and a significant decrease in plasma insulin, HOMA-β-cell functioning index, glycogen, high-density lipoprotein cholesterol, body weight and antioxidant enzyme activities, viz. superoxide dismutase, catalase and reduced glutathione.

Antihyperglycemic, antihyperlipidemic and antioxidant activity of phenolic rich extract of Brassica oleraceae var gongylodes on streptozotocin induced Wistar rats.

Cruciferous vegetables, in particular those included into the Brassica genus, are good sources of a variety of nutrients and health-promoting phytochemicals. Phenolic compounds are the major antioxidants of Brassica; hence the contribution of Brassica vegetables to health improvement has largely been associated to their antioxidant capacity. This study aimed to assess anti-diabetic, antilipidemic, and antioxidant activity of phenolic rich extract of Brassica oleraceae var gongylodes (BOvG) in Wistar rats.

Formation of furan along with HO₂ during the OH-initiated oxidation of 2,5-DHF and 2,3-DHF: an experimental and computational study.

Experimental characterization of products during OH-initiated oxidation of dihydrofurans (DHF) confirms the formation of furan accompanied by the formation of HO2 to be a significant channel in 2,5-DHF (21 ± 3%), whereas it is absent in 2,3-DHF. Theoretical investigations on the reaction of OH with these molecules are carried out to understand this difference. All possible channels of reaction are studied at M06-2X level with 6-311G* basis set, and the stationary points on the potential energy surface are optimized.

Photodissociation dynamics of benzoyl chloride at 235 nm: resonance-enhanced multiphoton ionization detection of Cl and HCl.

The photodissociation dynamics of benzoyl chloride at 235 nm has been investigated and compared with that of 2-furoyl chloride. Atomic Cl and molecular HCl channels have been detected in benzoyl chloride by employing resonance-enhanced multiphoton ionization technique and time-of-flight mass spectrometry. Both the Cl fragments, Cl((2)PJ=3/2, relative quantum yield 0.

Photodissociation dynamics of enolic 1,2-cyclohexanedione at 266, 248, and 193 nm: mechanism and nascent state product distribution of OH.

The photodissociation dynamics of 1,2-cyclohexanedione (CHD), which exists in enolic form in gas phase, is studied using pulsed laser photolysis (LP)-laser induced fluorescence (LIF) "pump-and-probe" technique at room temperature. The nascent state distribution of the OH radical, formed after initial photoexcitation of the molecule to it is (π, π*) and Rydberg states, is determined. The initial (π, π*) and Rydberg states are prepared by excitation with the fourth harmonic output of Nd:YAG (266 nm)/KrF (248 nm) and ArF (193 nm) lasers, respectively.

Photodissociation dynamics of halogenated thiophenes at 235 nm: a resonance enhanced multiphoton ionization-time-of-flight (REMPI-TOF) study.

The photodissociation dynamics of halogen-substituted thiophenes, namely, 2-chlorothiophene and 2-bromo-5-chlorothiophene, has been studied in a supersonic molecular beam around 235 nm, using resonance enhanced multiphoton ionization (REMPI) time-of-flight (TOF) technique, by detecting the nascent state of the primary halogen atoms. A single laser has been used for excitation of halothiophenes, as well as for the REMPI detection of photoproducts, namely, chlorine and bromine atoms, in their spin-orbit states X((2)P(3/2)) and X*((2)P(1/2)). We have determined the translational energy distribution, the recoil anisotropy parameter, β, and the spin-orbit branching ratio, for chlorine and bromine atom elimination channels.

Photodissociation dynamics of 3-bromo-1,1,1-trifluoro-2-propanol and 2-(bromomethyl) hexafluoro-2-propanol at 234 nm: resonance-enhanced multiphoton ionization detection of Br (2P(j)).

The photodissociation dynamics of 3-bromo-1,1,1-trifluoro-2-propanol (BTFP) and 2-(bromomethyl) hexafluoro-2-propanol (BMHFP) have been studied at 234 nm, and the C-Br bond dissociation investigated using resonance-enhanced multiphoton ionization coupled with time-of-flight mass spectrometer (REMPI-TOFMS). Br formation is a primary process and occurs on a repulsive surface involving the C-Br bond of BTFP and BMHFP. Polarization dependent time-of-flight profiles were measured, and the translational energy distributions and recoil anisotropy parameters extracted using forward convolution fits.

Antidiabetic properties of Hibiscus rosa sinensis L. leaf extract fractions on nonobese diabetic (NOD) mouse.

On fractionation the ethanolic extract of H. rosa sinensis leaves, 5 fractions were obtained. Of these, fraction-3 (F3) and fraction-5 (F5) were chosen for detailed investigation on non obese diabetic (NOD) mouse to study anti-diabetic properties because they were more active than others.

Dynamics of Cl (2Pj) atom formation in the photodissociation of fumaryl chloride (ClCO - CH = CH - COCl) at 235 nm: a resonance enhanced multiphoton ionization (REMPI) time-of-flight (TOF) study.

The photodissociation dynamics of fumaryl chloride (ClCO-CH═CH-COCl) has been studied in a supersonic molecular beam around 235 nm using resonance enhanced multiphoton ionization (REMPI) time-of-flight (TOF) technique by detecting the nascent state of the primary chlorine atom. A single laser has been used for excitation of fumaryl chloride and the REMPI detection of chlorine atoms in their spin-orbit states, Cl ((2)P(3/2)) and Cl* ((2)P(1/2)). We have determined the translational energy distribution, the recoil anisotropy parameter, β, and the spin-orbit branching ratio for chlorine atom elimination channels.

Laser-induced UV photodissociation of 2-bromo-2-nitropropane: dynamics of OH and Br formation.

Photoexcitation of 2-bromo-2-nitropropane (BNP) at 248 and 193 nm generates OH, Br, and NO(2) among other products. The OH fragment is detected by laser-induced fluorescence spectroscopy, and its translational and internal state distributions (vibration, rotation, spin-orbit, and Λ-doubling components) are probed. At both 248 and 193 nm, the OH fragment is produced translationally hot with the energy of 10.

Dynamics of N-OH bond dissociation in cyclopentanone and cyclohexanone oxime at 193 nm: laser-induced fluorescence detection of nascent OH (v'', J'').

Cyclohexanone oxime (CHO) and cyclopentanone oxime (CPO) in the vapor phase undergo N-OH bond scission upon excitation at 193 nm to produce OH, which was detected state selectively employing laser-induced fluorescence. The measured energy distribution between fragments for both oximes suggests that in CHO the OH produced is mostly vibrationally cold, with moderate rotational excitation, whereas in CPO the OH fragment is also formed in v'' = 1 (~2%). The rotational population of OH (v'' = 0, J'') from CHO is characterized by a rotational temperature of 1440 ± 80 K, whereas the rotational populations of OH (v'' = 0, J'') and OH (v'' = 1, J'') from CPO are characterized by temperatures of 1360 ± 90 K and 930 ± 170 K, respectively.

Next-generation protein-rich potato expressing the seed protein gene AmA1 is a result of proteome rebalancing in transgenic tuber.

Protein deficiency is the most crucial factor that affects physical growth and development and that increases morbidity and mortality especially in developing countries. Efforts have been made to improve protein quality and quantity in crop plants but with limited success. Here, we report the development of transgenic potatoes with enhanced nutritive value by tuber-specific expression of a seed protein, AmA1 (Amaranth Albumin 1), in seven genotypic backgrounds suitable for cultivation in different agro-climatic regions.

Kinetics of gas-phase reaction of OH with morpholine: an experimental and theoretical study.

Kinetics of reaction of OH radical with morpholine, a heterocyclic molecule with both oxygen and nitrogen atoms, has been investigated using laser photolysis-laser-induced fluorescence technique, in the temperature range of 298-363 K. The rate constant at room temperature (k(298)) is (8.0 +/- 0.

Photodissociation dynamics of phosphorus trichloride (PCl3) at 235 nm using resonance enhanced multiphoton ionization (REMPI) with time-of-flight (TOF) mass spectrometry.

The photodissociation dynamics of phosphorus trichloride (PCl(3)) has been studied in a supersonic beam by resonance enhanced multiphoton ionization (REMPI), using time-of-flight (TOF) mass spectrometry. The study is focused on the nascent state of the primary chlorine atom, formed on excitation of the (n, sigma*) transition of the molecule around 235 nm. Dissociation of PCl(3) and the REMPI detection of chlorine atoms are performed, using the same laser around 235 nm.

Photodissociation of 3-bromo-1,1,1-trifluoro-2-propanol at 193 nm: laser-induced fluorescence detection of OH(nu'' = 0, J'').

Photodissociation of 3-bromo-1,1,1-trifluoro-2-propanol (BTFP) has been investigated at 193 nm, employing the laser photolysis laser-induced fluorescence technique. The nascent OH product was detected state selectively, and the energy released into translation, rotation, and vibration of the photoproducts has been measured. OH is produced mostly vibrationally cold, with a moderate rotational excitation, which is characterized by a rotational temperature of 640 +/- 140 K.

Photodissociation dynamics of 2-nitropropane and 2-methyl-2-nitropropane at 248 and 193 nm.

Dynamics of formation of electronically excited NO2 and formation of OH fragment, during photo dissociation of 2-nitropropane (NP) and 2-methyl-2-nitropropane (MNP), were investigated at 193 and 248 nm. The radiative lifetime of the electronically excited NO2 fragment, observed at 193 nm, was measured to be 1.2 ( 0.

Immunocytochemical detection of glucagon and insulin cells in endocrine pancreas and cyclic disparity of plasma glucose in the turtle Melanochelys trijuga.

The present investigation was carried out to know the seasonal variation in plasma glucose,insulin and glucagon cells during the reproductive cycle of untreated Melanochelys trijuga. Pancreatic endocrine cells were immunochemically localized.Insulin-immunoreactive (IR) cells occurred in groups of 3-20 and were in close apposition, while glucagon-IR cells were distributed individually between the exocrine pancreas or formed anastomosing cords where cells were not intimately attached.

Studies on photodissociation dynamics of butadiene monoxide at 193 nm.

Butadiene monoxide (BMO) undergoes the S(0)-->S(1) transition, involving the excitation of both pi and n electrons to pi(*) orbital, at 193 nm. After relaxing to the ground electronic state via internal conversion, BMO molecules undergo intramolecular rearrangement and subsequently dissociate to form unexpected OH radicals, which were detected state selectively by laser-induced fluorescence technique, and the energy state distribution was measured. OH is produced vibrationally cold, OH(nu(")=0,J(")), with the rotational population characterized by a rotational temperature of 456+/-70 K.

Evaluation of hypoglycemic effect of Morus alba in an animal model.

Objective: The objective of the present investigation was to evaluate the therapeutic efficacy of mulberry leaves in an animal model of diabetes.

Materials And Methods: Animals were treated with mulberry leaf extract 400 mg and 600 mg/kg body weight for 35 days. Blood glucose, glycosylated hemoglobin, triglyceride, LDL, VLDL, HDL, blood urea, cholesterol, number of β cells, and diameter of the islets of Langerhans were measured at the beginning and at the end of the experiment.