Bridging the gap in aberrant root canal systems: Case series.

Endodontic success depends on accurate diagnosis, complete debridement of diseased pulp tissue, and adequate disinfection of the root canal system. It is essential to have a solid grasp of root canal variations. Inadequate knowledge of complex root canal configurations can lead to missed canals, failure to negotiate canal deviations, bifurcations, trifurcations, anastomoses, fins, and isthmuses, thereby complicating treatment.

Influence of internal electrostatics on reduction potentials in amine-ligated bimetallic copper complexes.

The electrostatic modulation of redox potentials of molecular electrocatalysts is a promising strategy to minimize overpotentials without compromising their catalytic activity given their intrinsic correlation. While the introduction of s-block cations to modulate the redox potential of single-site transition metal catalysts is known, the prevalence and nature of such electrostatic interactions in bimetallic complexes deserves further attention. In this work, using density functional theory and electrostatic charged sphere models, we quantify the influence of distance-dependent electrostatic effects on the reduction potentials of a bimetallic Cu(II) model system with a dipicolylamine (DPA) ligand, wherein the Cu(II) centers are bridged by an aliphatic diamine (NH-(CH)-NH) linker of varying chain lengths ( = 0 to 10).

Patient-Derived Xenografts of Triple-Negative Breast Cancer Enable Deconvolution and Prediction of Chemotherapy Responses.

Combination chemotherapy remains essential for clinical management of triple-negative breast cancer (TNBC). Consequently, responses to multiple single agents cannot be delineated at the single patient level, even though some patients might not require all drugs in the combination. Herein, we conduct multi-omic analyses of orthotopic TNBC patient-derived xenografts (PDXs) treated with single agent carboplatin, docetaxel, or the combination.

Independent and Interactive Impacts of Prenatal Exposure to Legal Substances and Childhood Trauma on Emotion Processing in Pre-Adolescents: Preliminary Findings From the ABCD Study.

Objective: This paper investigated the effects of prenatal drug exposure (PDE), childhood trauma (CT), and their interactions on the neurobiological markers for emotion processing.

Method: Here, in a non-clinical sample of pre-adolescents (9-10 years of age) from the Adolescent Brain Cognitive Development (ABCD) Study (N = 6,146), we investigate the impact of PDE to commonly used substances (ie, alcohol, cigarettes, and marijuana), CT, and their interaction on emotion processing. From the Emotional N-back functional magnetic resonance imaging task data, we selected 26 regions of interests, previously implicated in emotion processing, and conducted separate linear mixed models (108 total) and accounted for available environmental risk factors.

Cu-amidobis(phosphine) catalyzed C(sp)-C(sp) direct homo- and hetero-coupling of unactivated alkanes C(sp)-H activation.

Herein, we present a Cu-dimer, [Cu{PhPCHC(O)NCHPPh-}], which catalyzed direct C(sp)-H homocoupling of benzyl and cycloalkane derivatives with excellent yields and regio-selectivity. The method is very simple and tolerates various functionalities. Synergistic metal-ligand cooperativity was observed in Cu-N bond cleavage and protonation of nitrogen, and facilitates a bifunctional pathway, minimising the free energy corrugation for catalytic intermediates.

A novel treatment strategy utilizing panobinostat for high-risk and treatment-refractory hepatoblastoma.

Background & Aims: Patients with metastatic, treatment-refractory, and relapsed hepatoblastoma (HB) have survival rates of less than 50% due to limited treatment options. To develop new therapeutic strategies for these patients, our laboratory has developed a preclinical testing pipeline. Given that histone deacetylase (HDAC) inhibition has been proposed for HB, we hypothesized that we could find an effective combination treatment strategy utilizing HDAC inhibition.

Copper(I) Complexes of Amide Functionalized Bisphosphine: Proximity Enhanced Metal-Ligand Cooperativity and Its Catalytic Advantage in C()-H Bond Activation of Unactivated Cycloalkanes in Dehydrogenative Carboxylation Reactions.

The reactions of amide functionalized bisphosphine, -PhPCHC-(O)N(H)CHPPh- () (BalaHariPhos), with copper salts is described. Treatment of with CuX in a 1:1 molar ratio yielded chelate complexes of the type [CuX{(-PhPCHC(O)N(H)CHPPh-)}-κ] (X = Cl, ; Br, ; and I, ), which on subsequent treatment with KOBu resulted in a dimeric complex [Cu(-PhPCHC(O)(N)CHPPh-)] (). Interestingly, complexes - showed weak N-H···Cu interactions.

Toward Practical Integration of Omic and Imaging Data in Co-Clinical Trials.

Co-clinical trials are the concurrent or sequential evaluation of therapeutics in both patients clinically and patient-derived xenografts (PDX) pre-clinically, in a manner designed to match the pharmacokinetics and pharmacodynamics of the agent(s) used. The primary goal is to determine the degree to which PDX cohort responses recapitulate patient cohort responses at the phenotypic and molecular levels, such that pre-clinical and clinical trials can inform one another. A major issue is how to manage, integrate, and analyze the abundance of data generated across both spatial and temporal scales, as well as across species.

Identifying biomarkers of differential chemotherapy response in TNBC patient-derived xenografts with a CTD/WGCNA approach.

Although systemic chemotherapy remains the standard of care for TNBC, even combination chemotherapy is often ineffective. The identification of biomarkers for differential chemotherapy response would allow for the selection of responsive patients, thus maximizing efficacy and minimizing toxicities. Here, we leverage TNBC PDXs to identify biomarkers of response.

Immunologically "cold" triple negative breast cancers engraft at a higher rate in patient derived xenografts.

TNBC is a heterogeneous subtype of breast cancer, and only a subset of TNBC can be established as PDXs. Here, we show that there is an engraftment bias toward TNBC with low levels of immune cell infiltration. Additionally, TNBC that failed to engraft show gene expression consistent with a cancer-promoting immunological state, leading us to hypothesize that the immunological state of the tumor and possibly the state of the immune system of the host may be essential for engraftment.

Orthorhombic charge density wave on the tetragonal lattice of EuAl.

EuAl possesses the BaAl crystal structure type with tetragonal symmetry 4/. It undergoes a charge density wave (CDW) transition at  = 145 K and features four consecutive antiferromagnetic phase transitions below 16 K. Here we use single-crystal X-ray diffraction to determine the incommensurately modulated crystal structure of EuAl in its CDW state.

Ru complexes of 1,2,3-triazole appended tertiary phosphines, [P(Ph){(-CH)(1,2,3-NC(Ph)CH}] and [P(Ph){-CH(CCH)-(1,2,3-N-Ph)}]: highly active catalysts for transfer hydrogenation of carbonyl/nitro compounds and for α-alkylation of ketones.

The synthesis of two new 1,2,3-triazole appended monophosphines [P(Ph){(-CH)(1,2,3-NC(Ph)CH}] (1) and [P(Ph){-CH(CCH)(1,2,3-N-Ph)}] (2) and their Ru complexes is described. The reactions of 1 and 2 with [Ru(PPh)Cl] in a 1 : 1 molar ratio produced cationic complexes 3 and 4, respectively. Both the complexes showed very high catalytic activity towards transfer hydrogenation, nitro reduction, and α-alkylation reactions and afforded the corresponding products in good to excellent yields.

Knowledge Graph-Based Approaches to Drug Repurposing for COVID-19.

The COVID-19 pandemic has motivated researchers all over the world in trying to find effective drugs and therapeutics for treating this disease. To save time, much effort has focused on repurposing drugs known for treating other diseases than COVID-19. To support these drug repurposing efforts, we built the CAS Biomedical Knowledge Graph and identified 1350 small molecules as potentially repurposable drugs that target host proteins and disease processes involved in COVID-19.

Deletion of a Golgi protein in Trypanosoma cruzi reveals a critical role for Mn2+ in protein glycosylation needed for host cell invasion and intracellular replication.

Trypanosoma cruzi is a protist parasite and the causative agent of American trypanosomiasis or Chagas disease. The parasite life cycle in its mammalian host includes an intracellular stage, and glycosylated proteins play a key role in host-parasite interaction facilitating adhesion, invasion and immune evasion. Here, we report that a Golgi-localized Mn2+-Ca2+/H+ exchanger of T.

VEGF-C mediates tumor growth and metastasis through promoting EMT-epithelial breast cancer cell crosstalk.

It is well established that a subset of cells within primary breast cancers can undergo an epithelial-to-mesenchymal transition (EMT), although the role of EMT in metastasis remains controversial. We previously demonstrated that breast cancer cells that had undergone an oncogenic EMT could increase metastasis of neighboring cancer cells via non-canonical paracrine-mediated activation of GLI activity that is dependent on SIX1 expression in the EMT cancer cells. However, the mechanism by which these SIX1-expressing EMT cells activate GLI signaling remained unclear.

Extended Interfacial Stability through Simple Acid Rinsing in a Li-Rich Oxide Cathode Material.

Layered Li-rich Ni, Mn, Co (NMC) oxide cathodes in Li-ion batteries provide high specific capacities (>250 mAh/g) via O-redox at high voltages. However, associated high-voltage interfacial degradation processes require strategies for effective electrode surface passivation. Here, we show that an acidic surface treatment of a Li-rich NMC layered oxide cathode material leads to a substantial suppression of CO and O evolution, ∼90% and ∼100% respectively, during the first charge up to 4.

Definition of Redox Centers in Reactions of Lithium Intercalation in LiRuO Polymorphs.

Cathodes based on layered LiMO are the limiting components in the path toward Li-ion batteries with energy densities suitable for electric vehicles. Introducing an overstoichiometry of Li increases storage capacity beyond a conventional mechanism of formal transition metal redox. However, the role and fate of the oxide ligands in such intriguing additional capacity remain unclear.

Random Global and Local Optimal Search Algorithm Based Subset Generation for Diagnosis of Cancer.

Background: Data mining algorithms are extensively used to classify the data, in which prediction of disease using minimal computation time plays a vital role.

Objectives: The aim of this paper is to develop the classification model from reduced features and instances.

Methods: In this paper we proposed four search algorithms for feature selection the first algorithm is Random Global Optimal (RGO) search algorithm for searching the continuous, global optimal subset of features from the random population.

Mapping free energy regimes in electrocatalytic reductions to screen transition metal-based catalysts.

The free energy landscape of catalytic intermediates in the two-electron reduction of proton donors and/or CO to H, CO and HCO is mapped with density functional theory to screen catalyst candidates from a library of different transition metals and ligands. The goal is to minimize the free energy corrugations between reactants, catalytic intermediates and each desired product, simultaneously screening against intermediates with low free energy that would be traps, and against necessary intermediates with high free energy. Catalysts are initially screened for those with: (a) standard state free energy of the metal hydride intermediate ergoneutral with HCO , which is the lowest energy product with weak proton donors, and (b) standard free energy of the metal carbonyl intermediate sufficiently high to avoid trapping.

Prediction of cancer using customised fuzzy rough machine learning approaches.

This Letter proposes a customised approach for attribute selection applied to the fuzzy rough quick reduct algorithm. The unbalanced data is balanced using synthetic minority oversampling technique. The huge dimensionality of the cancer data is reduced using a correlation-based filter.

Protonation of a Cobalt Phenylazopyridine Complex at the Ligand Yields a Proton, Hydride, and Hydrogen Atom Transfer Reagent.

Protonation of the Co(I) phenylazopyridine (azpy) complex [CpCo(azpy)] 2 occurs at the azo nitrogen of the 2-phenylazopyridine ligand to generate the cationic Co(I) complex [CpCo(azpyH)] 3 with no change in oxidation state at Co. The N-H bond of 3 exhibits diverse hydrogen transfer reactivity, as studies with a variety of organic acceptors demonstrate that 3 can act as a proton, hydrogen atom, and hydride donor. The thermodynamics of all three cleavage modes for the N-H bond (i.

Evolutionary sequential genetic search technique-based cancer classification using fuzzy rough nearest neighbour classifier.

Cancer is one of the deadly diseases of human life. The patient may likely to survive if the disease is diagnosed in its early stages. In this Letter, the authors propose a genetic search fuzzy rough (GSFR) feature selection algorithm, which is hybridised using the evolutionary sequential genetic search technique and fuzzy rough set to select features.

Membrane Proteins in Trypanosomatids Involved in Ca Homeostasis and Signaling.

Calcium ion (Ca) serves as a second messenger for a variety of cell functions in trypanosomes. Several proteins in the plasma membrane, acidocalcisomes, endoplasmic reticulum, and mitochondria are involved in its homeostasis and in cell signaling roles. The plasma membrane has a Ca channel for its uptake and a plasma membrane-type Ca-ATPase (PMCA) for its efflux.