Mapping in silico genetic networks of the KMT2D tumour suppressor gene to uncover novel functional associations and cancer cell vulnerabilities.

Background: Loss-of-function (LOF) alterations in tumour suppressor genes cannot be directly targeted. Approaches characterising gene function and vulnerabilities conferred by such mutations are required.

Methods: Here, we computationally map genetic networks of KMT2D, a tumour suppressor gene frequently mutated in several cancer types.

Triplet Energy Transfer (EnT)-Promoted 1,3-Dipolar Cycloaddition Reactions of -(Trimethylsilyl)methylphthalimide with Electron-Deficient Alkynes and Alkenes.

Triplet energy transfer (EnT)-promoted photochemical pathways, arisen by visible light and its photosensitizers, have gained significant attention as a complementary strategy for initiating organic transformations in photochemical reactions that are unlikely to occur through a single electron transfer (SET) process. In the present study, we investigated the triplet EnT-promoted 1,3-dipolar cycloaddition reactions of -(trimethylsilyl)methylphthalimide with electron-deficient alkynyl and alkenyl dipolarophiles. The triplet excited state of -(trimethylsilyl)methylphthalimide, promoted by the triplet EnT from thioxanthone (TXA) photosensitizer, underwent sequential intramolecular SET and carbon-to-oxygen migration of the silyl group to form azomethine ylide.

Photocatalytic Conversion of CO to Formate/CO by an (η--Cymene)Ru(II) Half-Metallocene Catalyst: Influence of Additives and TiO Immobilization on the Catalytic Mechanism and Product Selectivity.

The catalytic efficacy of the monobipyridyl (η--Cymene)Ru(II) half-metallocene, [(-Cym)Ru(bpy)Cl] was evaluated in both mixed homogeneous (dye + catalyst) and heterogeneous hybrid systems (dye/TiO/Catalyst) for photochemical CO reduction. A series of homogeneous photolysis experiments revealed that the (-Cym)Ru(II) catalyst engages in two competitive routes for CO reduction (CO to formate conversion via Ru-hydride vs CO to CO conversion through a Ru-COOH intermediate). The conversion activity and product selectivity were notably impacted by the p value and the concentration of the proton source added.

Proactive behaviors and health care workers: A systematic review.

Background: Proactive behaviors at work refer to discretionary actions among workers that are self-starting, change oriented, and future focused. Proactive behaviors reflect the idiosyncratic actions by individual workers that shape the delivery and experience of professional services, highlight a bottom-up perspective on workers' agency and motivation that can influence organizational practices, and are associated with a variety of employee and organizational outcomes.

Purpose: This systematic review aims to understand the various forms of proactive behaviors in health care workers that have been studied, and how these proactive behaviors are associated with employee-level outcomes and quality of care.

Whole genome and transcriptome integrated analyses guide clinical care of pediatric poor prognosis cancers.

The role for routine whole genome and transcriptome analysis (WGTA) for poor prognosis pediatric cancers remains undetermined. Here, we characterize somatic mutations, structural rearrangements, copy number variants, gene expression, immuno-profiles and germline cancer predisposition variants in children and adolescents with relapsed, refractory or poor prognosis malignancies who underwent somatic WGTA and matched germline sequencing. Seventy-nine participants with a median age at enrollment of 8.

Temporomandibular disorder pain in older adolescents-young adults: Interrelationship with somatic burden, mental ill-being, and well-being.

Objectives: The associations of Temporomandibular disorder (TMD) pain with somatic symptoms, mental ill-being/distress, and well-being were explored, along with the mental correlates of TMD (TS) and somatic symptom (SS) burden in older adolescents-young adults.

Methods: TMD/somatic symptoms were appraised with the five quintessential symptoms (5Ts) of the DC/TMD/Somatic Symptom Scale-8, whereas mental distress/well-being was assessed with the Depression, Anxiety, Stress Scales-21/Scales of Psychological Well-being-18. Data were examined using Chi-square/non-parametric tests and multivariate analyses (α = .

Dance Exergames for Older Adults: A Systematic Review and Meta-Analysis With Narrative Synthesis.

Background: A systematic review and meta-analysis with narrative synthesis was conducted to evaluate the impact of dance exergaming on older adults' health-related outcomes and its feasibility, usability, and safety.

Methods: PubMed, Scopus, CINAHL, Web of Science, The Cochrane Library, ProQuest Dissertations and Theses Global, and Google Scholar were searched from inception to December 7, 2023. Interventional studies using immersive or nonimmersive virtual reality platforms conducted on older adults ≥60 years old were eligible.

Reaction-Environment-Dependent Photoaddition Reactions of -Phenyl Amino Acid Esters Possessing a Silyl Group with Fullerene C: Selective Formation of Aminomethyl-1,2-dihydrofullerenes vs Fulleropyrrolidines.

The current study investigates SET-promoted photoaddition reactions of the silyl-group-containing -phenylglycinates and -phenylalaninates, -((trimethylsilyl)methyl)--phenyl-substituted glycinates and alaninates, respectively, with fullerene C to explore how the types of amino acid esters (AAEs) and molecular oxygen affect the photoaddition reaction efficiencies and chemoselectivity of in situ formed radical cations of AAEs. The results showed that under deoxygenated (N-purged) conditions, photoreactions of -phenylglycinates with C produced aminomethyl-1,2-dihydrofullerenes through the addition of α-amino radicals arising by sequential SET and desilylation processes from initially formed secondary anilines to C. In oxygenated conditions, photoreactions of -phenylglycinates with C, albeit less efficient, took place to form fulleropyrrolidines through a pathway involving 1,3-dipolar cycloaddition of azomethine ylides to C assisted by in situ formed O.

Application of creatinine height index in patients with trauma for the evaluation of psoas muscle mass: A clinical validation study.

Background: The creatinine height index (CHI) is an estimate of lean body mass. We hypothesize that a modified CHI estimate using serum creatinine (sCr) levels in patients with normal renal function when performed soon after injury would reflect preinjury protein nutrition status.

Methods: The urine CHI (uCHI) was calculated using the 24-h urine sample.

Systematic radical species control by electron push-pull substitution in the perylene-based D-π-A compounds.

Organic radical materials have been mainly reported on the stabilization of radical species because of their high energy and reactivity, while design strategies for controlling radical species beyond stabilization have remained challenging. Here, we report the electronic push-pull control spanning the neutral to the radical state of a series of perylene-based donor-π-acceptors (D-π-A). By introducing electron-withdrawing and -donating R groups to the donor of D-π-A, the observed intramolecular interactions controllable at the HOMO level led to the exploration of radical species.

Singlet fission dynamics modulated by molecular configuration in covalently linked pyrene dimers, Anti- and Syn-1,2-di(pyrenyl)benzene.

Covalently linked dimers (CLDs) and their structural isomers have attracted much attention as potential materials for improving power conversion efficiencies through singlet fission (SF). Here, we designed and synthesized two covalently ortho-linked pyrene (Py) dimers, anti- and syn-1,2-di(pyrenyl)benzene (Anti-DPyB and Syn-DPyB, respectively), and investigated the effect of molecular configuration on SF dynamics using steady-state and time-resolved spectroscopies. Both Anti-DPyB and Syn-DPyB, which have different Py-stacking configurations, form excimers, which then relax to the correlated triplet pair ((TT)) state, indicating the occurrence of SF.

Silyl Tether-Assisted Photooxygenation of Electron-Deficient Enaminoesters: Direct Access to Oxamate Formation.

Photooxygenation reactions of electron-deficient enaminoesters bearing an oxophilic silyl tether at the α-position of the nitrogen atom using methylene blue (MB) were explored to develop a mild and efficient photochemical strategy for oxidative C-C double bond cleavage reactions via singlet oxygen (O). Photochemically generated O, through energy transfer from the triplet excited state of MB (MB*) to molecular oxygen (O), was added across a C-C double bond moiety of enaminoesters to form perepoxides, which rearranged to form dioxetane intermediates. The cycloreversion of the formed dioxetane via both C-C and O-O bond cleavage processes led to the formation of oxamates.

HYDROCORTISONE, ASCORBIC ACID, AND THIAMINE THERAPY DECREASE RENAL OXIDATIVE STRESS AND ACUTE KIDNEY INJURY IN MURINE SEPSIS.

Background: Acute kidney injury (AKI) occurs frequently in septic patients and correlates with increased mortality. Because clinical studies investigating hydrocortisone, ascorbic acid, and thiamine (HAT) have demonstrated discordant results, studies were performed using mortality stratification for therapy to identify candidates for therapy and determine mechanisms of organ injury. Methods: Sepsis was induced using the cecal ligation and puncture (CLP) model of sepsis with fluid and antibiotic support.

Machine learning and murine models explain failures of clinical sepsis trials.

Background: Multiple clinical trials failed to demonstrate the efficacy of hydrocortisone, ascorbic acid, and thiamine (HAT) in sepsis. These trials were dominated by patients with pulmonary sepsis and have not accounted for differences in the inflammatory responses across varying etiologies of injury/illness. Hydrocortisone, ascorbic acid, and thiamine have previously revealed tremendous benefits in animal peritonitis sepsis models (cecal ligation and puncture [CLP]) in contradiction to the various clinical trials.

Exceptional response to combination ipilimumab and nivolumab in metastatic uveal melanoma: Insights from genomic analysis.

Uveal melanoma is the most common intraocular malignancy and has a poor prognosis compared to other melanoma subtypes with a median overall survival of 6-10 months. With immune checkpoint inhibitor therapy, either PD-1 inhibitor alone or combination ipilimumab/nivolumab (anti-CTLA-4/anti-PD-1), responses are rare and often not durable. We present a case report of a now 66-year-old woman with diffuse metastatic uveal melanoma previously treated with a combination of ipilimumab/nivolumab, followed by maintenance nivolumab.

Whole-genome and transcriptome analysis enhances precision cancer treatment options.

Background: Recent advances are enabling delivery of precision genomic medicine to cancer clinics. While the majority of approaches profile panels of selected genes or hotspot regions, comprehensive data provided by whole-genome and transcriptome sequencing and analysis (WGTA) present an opportunity to align a much larger proportion of patients to therapies.

Patients And Methods: Samples from 570 patients with advanced or metastatic cancer of diverse types enrolled in the Personalized OncoGenomics (POG) program underwent WGTA.

Influence of picolinate ancillary ligands on unique photophysical properties of Ir(ppz)(LX).

Homoleptic -Ir(ppz) (ppz = phenylpyrazole) and a series of heteroleptic Ir(ppz)(LX) complexes consisting of picolinic acid (pic), 3-hydroxypicolinic acid (picOH), and isoquinolinecarboxylic acid (iq) as ancillary ligands (LX) were synthesised to investigate the influence of the ancillary ligands on the photophysical properties of the complexes. Generally, the role of the ancillary ligand is considered insignificant compared to that of the main ligand. Ir(ppz) showed deep-blue emission with a vibronic structure at 77 K, whereas Ir(ppz)(LX) showed a broad and red-shifted emission.

Rapid and low-cost, and disposable electrical sensor using an extended gate field-effect transistor for cardiac troponin I detection.

Field effect transistor (FET) biosensor is based on metal oxide field effect transistor that is gated by changes in the surface charges induced the reaction of biomolecules. In most cases of FET biosensor, FET biosensor is not being reused after the reaction; therefore, it is an important concept of investigate the biosensor with simplicity, cheap and reusability. However, the conventional cardiac troponin I (cTnI) sensing technique is inadequate owing to its low sensitivity and high operational time and cost.

-Terphenyl linked donor-π-acceptor dyads: intramolecular charge transfer controlled by electron acceptor group tuning.

A series of -terphenyl linked donor-π-acceptor (D-π-A) dyads were prepared to understand the electronic effects of a -terphenyl linker according to the electron-accepting ability change. The energy band gaps of the dyads were controlled by tuning the accepting ability, which resulted in emission colors ranging from blue-green to red. In the Lippert-Mataga plots, intramolecular charge transfer (ICT) behavior was observed, which showed gradually increased ICT characteristics as the accepting ability was increased.

Solvent-modulated proton-coupled electron transfer in an iridium complex with an ESIPT ligand.

Proton-coupled electron transfer (PCET), an essential process in nature with a well-known example of photosynthesis, has recently been employed in metal complexes to improve the energy conversion efficiency; however, a profound understanding of the mechanism of PCET in metal complexes is still lacking. In this study, we synthesized cyclometalated Ir complexes strategically designed to exploit the excited-state intramolecular proton transfer (ESIPT) of the ancillary ligand and studied their photoinduced PCET in both aprotic and protic solvent environments using femtosecond transient absorption spectroscopy and density functional theory (DFT) and time-dependent DFT calculations. The data reveal solvent-modulated PCET, where charge transfer follows proton transfer in an aprotic solvent and the temporal order of charge transfer and proton transfer is reversed in a protic solvent.

Visible-Light-Induced Selective C-C Bond Cleavage Reactions of Dimeric β-O-4 and β-1 Lignin Model Substrates Utilizing Amine-Functionalized Fullerene.

Finding a selective and efficient fragmentation process under ambient conditions is pivotal for the generation of fuels and chemical feedstocks from lignoceullosic biomass. In the present study, visible-light and amine-functionalized fullerene-based photocatalyst-promoted photodegradation reactions of dimeric β-O-4 and β-1 lignin model compounds, containing varying numbers of methoxy substituents on the arene ring, were explored to find and develop mild, eco-friendly photochemical techniques for efficient delignification. The results showed that, in contrast to well-known organic photoredox catalysts, amine-functionalized fullerene photocatalyst promoted photochemical reactions of lignin model compounds could lead to more efficient lignin fragmentation reactions through a pathway involving a selective C-C bond cleavage process, and in addition, C-hydroxyl moiety in lignin model compounds played a significant role in the success of the C-C bond cleavage reaction of lignin model substrates.

Work Engagement and Patient Quality of Care: A Meta-Analysis and Systematic Review.

Past research has demonstrated that work engagement among health care professionals influences patient quality of care. There is, however, no estimate of the strength of this relationship, and existing reviews have not always explained conflicting findings. We conduct a meta-analysis and review of 25 articles, and find a small to medium mean effect size ( = .

Splice-Switching Antisense Oligonucleotides as a Targeted Intrinsic Engineering Tool for Generating Armored Redirected T Cells.

Modification of specificity of T cells for the use in adoptive transfer (CAR- or TCR-redirected T cells) has revolutionized the therapy of liquid tumors and some infectious diseases. However, several obstacles are still hampering the efficacy of such potent therapy, hence concurrent modification of the function is also required to obtain successful results. Here we show the use of splice-switching antisense oligonucleotides (SSOs) as a tool to transiently modify T cell function.