Phase angle between dim light melatonin onset and sleep timing during residential treatment prospectively predicts obsessive-compulsive symptoms.

The relation between obsessive-compulsive disorder (OCD) and circadian rhythm disturbance has been increasingly acknowledged in recent years. While prior clinical studies have utilized patients' self-reported sleep behaviors, there is a need to also explore the measurable, biological aspects of circadian rhythms. The current study has two aims: first, to describe the biological circadian rhythms of individuals with OCD seeking intensive residential treatment, including their relationship with self-reported measures of sleep and OCD symptoms; and second, to examine longitudinal associations between biological circadian rhythms and OCD symptom severity during the course of residential treatment.

Covalent Fragments Acting as Tyrosine Mimics for Mutant p53-Y220C Rescue by Nucleophilic Aromatic Substitution.

The tumor suppressor p53 is frequently mutated in human cancers. The Y220C mutant is the ninth most common p53 cancer mutant and is classified as a structural mutant, as it leads to strong thermal destabilization and degradation by creating a solvent-accessible hydrophobic cleft. To identify small molecules that thermally stabilize p53, we employed DSF to screen SAr-type electrophiles from our covalent fragment library (CovLib) for binding to different structural (Y220C, R282W) and DNA contact (R273H) mutants of p53.

Asparagine availability controls germinal center B cell homeostasis.

The rapid proliferation of germinal center (GC) B cells requires metabolic reprogramming to meet energy demands, yet these metabolic processes are poorly understood. By integrating metabolomic and transcriptomic profiling of GC B cells, we identified that asparagine (Asn) metabolism was highly up-regulated and essential for B cell function. Asparagine synthetase (ASNS) was up-regulated after B cell activation through the integrated stress response sensor GCN2.

Frustrated Lewis Pairs from Al-E Bonds (E=Ge, Sn, Pb).

The potassium aluminyl K[Al(NON)] ([NON]=[O(SiMeNDipp)], Dipp=2,6-iPrCH) reacts with group 14 chloroamidinates E(Am)Cl (E=Ge, Sn, Pb. [Am]=[tBuC(NDipp)]) to form (NON)Al-E(Am) Lewis pairs with unsupported Al-E bonds, including the first structurally authenticated Al-Pb bond. Analysis using spectroscopic (NMR, UV-vis and Mössbauer for E=Sn), X-ray diffraction and computational (DFT, QTAIM, TD-DFT) methods conclude an Al-E σ-bond derived from a Lewis basic Al and a Lewis acidic tetrylene, with back-donation from the E s-orbital lone pair donor NBO to acceptor NBOs on Al that are derived from s/p-orbitals.

A longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease.

Precision medicine in immune-mediated inflammatory diseases (IMIDs) requires a cellular understanding of treatment response. We describe a therapeutic atlas for Crohn's disease (CD) and ulcerative colitis (UC) following adalimumab, an anti-tumour necrosis factor (anti-TNF) treatment. We generated ~1 million single-cell transcriptomes, organised into 109 cell states, from 216 gut biopsies (41 subjects), revealing disease-specific differences.

A New Organic Laser Material Design Toward Ultra-Low Amplified Spontaneous Red Emission and Ultra-Bright Electroluminescence.

Significant efforts are dedicated to developing new classes of organic semiconductor materials to achieve electrically pumped lasing. However, further advancements are necessary to understand the relationship between the structure and property for the creation of innovative laser materials with high stability, low triplet yield, ultra-low lasing threshold, and low-efficiency roll-off at ultra-bright electroluminescence. Here, a new design principle is validated for organic semiconductor laser materials, demonstrating simultaneous enhancement in the key figures of merit of low amplified spontaneous emission thresholds (E), efficient electroluminescence, and low triplet yields.

Fueling the Firefighter and Tactical Athlete with Creatine: A Narrative Review of a Key Nutrient for Public Safety.

Firefighters, tactical police officers, and warriors often engage in periodic, intermittent, high-intensity physical work in austere environmental conditions and have a heightened risk of premature mortality. In addition, tough decision-making challenges, routine sleep deprivation, and trauma exacerbate this risk. Therefore, identifying strategies to bolster these personnel's health and occupational performance is critical.

Easy-to-configure zero-dimensional valley-chiral modes in a graphene point junction.

The valley degree of freedom in two-dimensional (2D) materials can be manipulated for low-dissipation quantum electronics called valleytronics. At the boundary between two regions of bilayer graphene with different atomic or electrostatic configuration, valley-polarized current has been realized. However, the demanding fabrication and operation requirements limit device reproducibility and scalability toward more advanced valleytronics circuits.

Evidence for a kinetic FLP reaction pathway in the activation of benzyl chlorides by alkali metal-phosphine pairs.

Kinetic frustrated Lewis pairs (FLP) allow facile cleavage of a number of E-H bonds (E = H, Si, C, B) where both the Lewis base and Lewis acid are involved in the bond activation transition state. More recently, kinetic FLP systems have been extended to the cleavage of C-X (X = F, Cl, Br) bonds. We report on the role of sodium tetrakis(pentafluorophenyl)borate in the benzylation of triarylphosphines, where the sodium cation and phosphine support a kinetic FLP type transition state.

Simultaneous portal vein thrombosis and splenic vein thrombosis in a COVID-19 patient: A case report and review of literature.

Background: It is well-described that the coronavirus disease 2019 (COVID-19) infection is associated with an increased risk of thrombotic complications. While there have been many cases of pulmonary emboli and deep vein thrombosis in these patients, reports of COVID-19 associated portal vein thrombosis (PVT) have been uncommon. We present a unique case of concomitant PVT and splenic artery thrombosis in a COVID-19 patient.

Mixing and matching ,- and ,-chelates in anionic Mg(I) compounds: synthesis and reactivity with RNCNR and CO.

Reduction of [Mg(NON)] ([NON] = [O(SiMeNDipp)], Dipp = 2,6-iPrCH) affords Mg(I) species containing NON- and NNO-ligands ([NNO] = [N(Dipp)SiMeN(Dipp)SiMeO]). The products of reactions with iPrNCNiPr and CO are consistent with the presence of reducing Mg(I) centres. Extraction with THF affords [K(THF)][(NNO)Mg-Mg(NNO)] with a structurally characterised Mg-Mg bond that was examined using density functional theory.

Sleep Disorders, Sleep Medication Use, and Predictors of Sleep Disturbance in Children with Persistent Tic Disorders.

The present study examined rates of sleep disorders and sleep medication use, and predictors of sleep disturbance in children with persistent tic disorders (PTD). Sixty-three parents of children aged 10 to 17 years with PTDs completed an internet survey evaluating sleep patterns and clinical symptoms. Insomnia (19.

Cisgender cellular tissue-based products improve wound healing.

Neither the CTP sex effect of female CTP derived from cryopreserved human placental membranes, nor male CTP bioengineered from living human keratinocytes and foreskin fibroblasts has been described. Healing in wounds was examined to establish the CTP sex' s role in both males and females. Cisgender CTP wounds had better closure.

A single cell atlas of frozen shoulder capsule identifies features associated with inflammatory fibrosis resolution.

Frozen shoulder is a spontaneously self-resolving chronic inflammatory fibrotic human disease, which distinguishes the condition from most fibrotic diseases that are progressive and irreversible. Using single-cell analysis, we identify pro-inflammatory MERTKCD48 macrophages and MERTK + LYVE1 + MRC1+ macrophages enriched for negative regulators of inflammation which co-exist in frozen shoulder capsule tissues. Micro-cultures of patient-derived cells identify integrin-mediated cell-matrix interactions between MERTK+ macrophages and pro-resolving DKK3+ and POSTN+ fibroblasts, suggesting that matrix remodelling plays a role in frozen shoulder resolution.

Three-dimensional, in-vitro approaches for modelling soft-tissue joint diseases.

Diseases affecting the soft tissues of the joint represent a considerable global health burden, causing pain and disability and increasing the likelihood of developing metabolic comorbidities. Current approaches to investigating the cellular basis of joint diseases, including osteoarthritis, rheumatoid arthritis, tendinopathy, and arthrofibrosis, involve well phenotyped human tissues, animal disease models, and in-vitro tissue culture models. Inherent challenges in preclinical drug discovery have driven the development of state-of-the-art, in-vitro human tissue models to rapidly advance therapeutic target discovery.

Aluminyl derived ethene functionalization with heteroallenes, leading to an intramolecular ligand rearrangement.

The aluminacyclopropane K[Al(NON)(η-CH)] ([NON] = [O(SiMeNDipp)], Dipp = 2,6-iPrCH) reacts with CO and iPrNCNiPr to afford ring-expanded products of C-C bond formation. The latter system undergoes a 1,3-silyl retro-Brook rearrangement of the NON-group, to afford the [NNO] ligand ([NNO] = [N(Dipp)SiMeN(Dipp)SiMeO]). The mechanism of transformation was examined by density functional theory (DFT).

Pinacol Cross-Coupling Promoted by an Aluminyl Anion.

A simple sequential addition protocol for the reductive coupling of ketones and aldehydes by a potassium aluminyl grants access to unsymmetrical pinacolate derivatives. Isolation of an aluminium ketyl complex presents evidence for the accessibility of radical species. Product release from the aluminium centre was achieved using an iodosilane, forming the disilylated 1,2-diol and a neutral aluminium iodide, thereby demonstrating the steps required to generate a closed synthetic cycle for pinacol (cross) coupling at an aluminyl anion.

Reductive Coupling of a Diazoalkane Derivative Promoted by a Potassium Aluminyl and Elimination of Dinitrogen to Generate a Reactive Aluminium Ketimide.

The reaction of 9-diazo-9H-fluorene (fluN ) with the potassium aluminyl K[Al(NON)] ([NON] =[O(SiMe NDipp) ] , Dipp=2,6-iPr C H ) affords K[Al(NON)(κN ,N -{(fluN ) })] (1). Structural analysis shows a near planar 1,4-di(9H-fluoren-9-ylidene)tetraazadiide ligand that chelates to the aluminium. The thermally induced elimination of dinitrogen from 1 affords the neutral aluminium ketimide complex, Al(NON)(N=flu)(THF) (2) and the 1,2-di(9H-fluoren-9-yl)diazene dianion as the potassium salt, [K (THF) ][fluN=Nflu] (3).

Characterizing the impact of Enterococcus cecorum infection during late embryogenesis on disease progression, cecal microbiome composition, and early performance in broiler chickens.

Enterococcus cecorum (EC) has been associated with septicemia and early mortality in broiler chickens. There is limited research investigating the pathogenicity of EC field strains obtained from affected birds. The purpose of this study was to evaluate the effect of in-ovo administration into the amnion with different EC field isolates at d 18 of embryogenesis (DOE18).

Assessing the effects of a mixed spp. challenge on performance, intestinal integrity, and the gut microbiome of broiler chickens.

A mixed spp. challenge model was designed to assess the effects of challenge on broiler chicken performance, intestinal integrity, and the gut microbiome for future use to evaluate alternative strategies for controlling coccidiosis in broiler chickens. The experimental design involved broiler chickens divided into two groups: a control group (uninfected) and a positive control group, infected with (EA), (EM), and (ET).

Cellular characterisation of advanced osteoarthritis knee synovium.

Objectives: Osteoarthritis (OA) is increasingly recognised as a whole joint disease, with an important role for synovium. However, the repertoire of immune cells and fibroblasts that constitute OA synovium remains understudied. This study aims to characterise the cellular composition of advanced OA synovium and to explore potential correlations between different cell types and patient demographics or clinical scores.

Isolation, characterization, and experimental infection of Streptococcus gallolyticus subspecies pasteurianus from commercial turkeys with acute septicemia: a pilot study.

Streptococcus gallolyticus (SG) is a Gram-positive cocci found as commensal gut flora in animals and humans. SG has emerged as a cause of disease in young poults between 1 and 3 wk of age. SG is associated with septicemia resulting in acute mortality with no premonitory signs in turkeys.

and evaluation of chlorhexidine salts as potential alternatives to potassium dichromate for M6 oocyst preservation.

Introduction: Coccidiosis caused by the spp., an Apicomplexan protozoon, is a major intestinal disease that affects the poultry industry. Although most cases of coccidiosis are subclinical, infections impair bird health and decrease overall performance, which can result in compromised welfare and major economic losses.

Three Oxidative Addition Routes of Alkali Metal Aluminyls to Dihydridoaluminates and Reactivity with CO.

Three distinct routes are reported to the soluble, dihydridoaluminate compounds, AM[Al(NON )(H) ] (AM=Li, Na, K, Rb, Cs; [NON ] =[O(SiMe NDipp) ] ; Dipp=2,6-iPr C H ) starting from the alkali metal aluminyls, AM[Al(NON )]. Direct H hydrogenation of the heavier analogues (AM=Rb, Cs) produced the first examples of structurally characterized rubidium and caesium dihydridoaluminates, although harsh conditions were required for complete conversion. Using 1,4-cyclohexadiene (1,4-CHD) as an alternative hydrogen source in transfer hydrogenation reactions provided a lower energy pathway to the full series of products for AM=Li-Cs.