Differential contributions of circadian clock genes to cell survival in bipolar disorder patient derived neuronal progenitor cells distinguishes lithium responders and non-responders.

Bipolar disorder (BD) is characterized by disrupted circadian rhythms and neuronal loss. Lithium is neuroprotective and used to treat BD, but outcomes are variable. Past research identified that circadian rhythms in BD patient neurons are associated with lithium response (Li-R) or non-response (Li-NR). However, the underlying cellular mechanisms remain unknown. To study interactions among circadian clock genes and cell survival, and their role in BD and predicting lithium response, we tested selected genes ( PER1 , BMAL1 and REV-ERBα ) and small molecule modulators of ROR/REV-ERB nuclear receptors in models of cell survival using mouse neurons and stem-cell derived neuronal progenitor cells (NPC) from BD patients and controls. In apoptosis assays using staurosporine (STS), lithium was neuroprotective. Knockdown of PER1 , BMAL1 and REV-ERBα modified cell survival across models. In NPCs, reduced expression of PER1 and BMAL1 led to more extensive cell death in Li-NR vs. Li-R. Reduced REV-ERBα expression caused more extensive cell death in BD vs. control NPCs, without distinguishing Li-R and Li-NR. In IMHN, The REV-ERB agonist GSK4112 had strong effects on circadian rhythm amplitude, and was neuroprotective in mouse neurons and control NPCs, but not in BD NPCs. Expression of cell survival genes following STS and GSK4112 treatments revealed BD-associated, and Li-R associated differences in expression profiles. We conclude that the neuroprotective response to lithium is similar in NPCs from Li-R and Li-NR. However, knockdown of circadian clock genes or stimulation of REV-ERBs reveal distinct contributions to cell death in BD patient NPCs, some of which distinguish Li-R and Li-NR.

Rotational Spectrum of the Phenoxy Radical.

We report the hyperfine-resolved rotational spectrum of the gas-phase phenoxy radical in the 8-25 GHz frequency range using cavity Fourier transform microwave spectroscopy. A complete assignment of its complex but well-resolved fine and hyperfine splittings yielded a precisely determined set of rotational constants, spin-rotation parameters, and nuclear hyperfine coupling constants. These results are interpreted with support from high-level quantum chemical calculations to gain detailed insight into the distribution of the unpaired π electron in this prototypical resonance-stabilized radical. The accurate laboratory rest frequencies enable studies of the chemistry of phenoxy in both the laboratory and space. The prospects of extending the present experimental and theoretical techniques to investigate the rotational spectra of isotopic variants and structural isomers of phenoxy and other important gas-phase radical intermediates that are yet undetected at radio wavelengths are discussed.

NTRK3-Rearranged Prostatic Acinar Adenocarcinoma: Report of a Patient and Review of the Literature.

Molecular investigations have led to increased therapeutic options for prostatic adenocarcinoma. A single case report of a PRPSAP1::NTRK3 gene fusion occurring in prostate cancer was previously reported. A review of the literature revealed that NTRK gene rearrangements are exceedingly rare molecular events in prostate cancer. NTRK gene fusions can be oncogenic drivers or develop as resistance mechanisms. The tumor-agnostic approvals of TRK inhibitors by the FDA provide additional rationale for molecular investigations of aggressive prostatic adenocarcinomas. This may prove to be an additional therapeutic option for patients with aggressive prostatic carcinomas refractory to initial therapy. We report a case of an aggressive castrate-resistant prostatic adenocarcinoma with a BMP6::NTRK3 gene fusion.

Greater social jetlag predicts poorer NIH Toolbox crystallized cognitive and academic performance in the Adolescent Brain Cognitive Development (ABCD) study.

Academic performance plays a crucial role in long-term educational attainment and occupational function. Chronotype refers to an individual's daily tendencies for times for waking, activity, and sleep. Social jetlag reflects the mismatch between an individual's chronotype and their social schedule. Because school typically starts early in the morning, later chronotype is often associated with daytime sleepiness, insufficient sleep, and poor academic performance. However, the relationship between academic performance, chronotype, and social jetlag has not been extensively examined in large samples like the Adolescent Brain Cognitive Development (ABCD) study. We hypothesized that greater social jetlag would predict poorer cognitive and academic performance. Year 2 (ages 11-14) cross-sectional data from the ABCD cohort (n = 6,890 adolescents) were used to evaluate academic performance (i.e. self-reported past year grades), NIH Toolbox cognitive performance measures, chronotype, and social jetlag from the Munich Chronotype Questionnaire. We found that later chronotype and greater social jetlag predicted poorer cognitive and academic performance with small effect sizes. Our findings emphasize the importance of individual differences in chronotype and social jetlag when designing class schedules, as aligning school activities with student optimal sleep-wake times may contribute to improved academic performance.

ENGOT-EN20/GOG-3083/XPORT-EC-042 - A phase III, randomized, placebo-controlled, double-blind, multicenter trial of selinexor in maintenance therapy after systemic therapy for patients with p53 wild-type, advanced, or recurrent endometrial carcinoma: rationale, methods, and trial design.

BACKGROUND: Patients with advanced/recurrent endometrial cancer have a poor prognosis and limited treatment options. Biomarkers such as tumor protein 53 (TP53) in endometrial cancer can integrate novel strategies for improved and individualized treatment that could impact patient outcomes. In an exploratory analysis of the phase III ENGOT-EN5/GOG-3055/SIENDO study of selinexor maintenance monotherapy 80 mg in advanced/recurrent endometrial cancer, a pre-specified subgroup of patients with TP53 wild type (wt) endometrial cancer showed preliminary activity at long-term follow-up with a generally manageable safety profile (median progression-free survival 27.4 months vs 5.2 months placebo, HR=0.41). PRIMARY OBJECTIVE: To evaluate the efficacy of selinexor compared with placebo as maintenance therapy in patients with advanced or recurrent TP53wt endometrial cancer. STUDY HYPOTHESIS: Selinexor administered at 60 mg weekly as maintenance therapy will show manageable safety and maintain efficacy in patients with TP53wt advanced/recurrent endometrial cancer after systemic therapy versus placebo. TRIAL DESIGN: This is a prospective, multicenter, double-blind, placebo-controlled, randomized phase III study designed to evaluate the efficacy and safety of selinexor as a maintenance therapy in patients with advanced or recurrent TP53wt endometrial cancer. MAJOR INCLUSION/EXCLUSION CRITERIA: Eligible patients must have histologically confirmed endometrial cancer, TP53wt confirmed by next-generation sequencing, completed at least 12 weeks of platinum-based therapy with or without immunotherapy, with confirmed partial response or complete response, and primary Stage IV disease or at first relapse. PRIMARY ENDPOINT: The primary endpoint is investigator-assessed progression-free survival per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in the intent-to-treat population. SAMPLE SIZE: A total of 220 patients will be enrolled. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Accrual is expected to be completed in 2024 with presentation of results in 2025. TRIAL REGISTRATION: NCT05611931.

Timely Completion of Direct Access Colonoscopy Is Noninferior to Office Scheduled for Screening and Surveillance.

GOALS: We aimed to evaluate whether direct access colonoscopy (DAC) is noninferior to office-scheduled colonoscopy (OSC) for achieving successful colonoscopy. BACKGROUND: DAC may improve access to colonoscopy. We developed an algorithm assessing eligibility, risk for inadequate preparation, and need for nursing/navigator assistance. STUDY: This was a retrospective, single-center study of DAC and OSC patients from June 5, 2018, to July 31, 2019. Patients were 45 to 75 years old with an indication of screening or surveillance. A successful colonoscopy met 3 criteria: complete colonoscopy (cecum, anastomosis, or ileum), adequate preparation (Boston Score ≥2/segment), and performed <90 days from initial patient contact. Unsuccessful colonoscopy did not meet ≥1 criteria. Secondary end points included days to successful colonoscopy, preparation quality, polyp detection, and 10-year recall rate. Noninferiority against risk ratio value of 0.85 was tested using 1-sided alpha of 0.05. RESULTS: A total of 1823 DAC and 828 OSC patients were eligible. DAC patients were younger, with a greater proportion of black patients and screening indications. For the outcome of successful colonoscopy, DAC was noninferior to OSC (DAC vs. OSC: 62.7% vs. 57.1%, RR 1.16, 95% LCL 1.09, P=0.001). For DAC, days to colonoscopy were fewer, and likelihood of 10-year recall after negative screening greater. Boston Score and polyp detection were similar for groups. Black patients were less likely to achieve successful colonoscopy; otherwise, groups were similar. For unsuccessful colonoscopies, proportionally more DAC patients canceled or no-showed while more OSC patients scheduled >90 days. DAC remained noninferior to OSC at 180 days. CONCLUSIONS: DAC was noninferior to OSC for achieving successful colonoscopy, comparing similarly in quality and efficiency outcomes.

Corallococcus senghenyddensis sp. nov., a myxobacterium with potent antimicrobial activity.

AIM: Corallococcus species are diverse in the natural environment with 10 new Corallococcus species having been characterized in just the last 5 years. As well as being an abundant myxobacterial genus, they produce several secondary metabolites, including Corallopyronin, Corramycin, Coralmycin, and Corallorazine. We isolated a novel strain Corallococcus spp RDP092CA from soil in South Wales, UK, using Candida albicans as prey bait and characterized its predatory activities against pathogenic bacteria and yeast. METHODS AND RESULTS: The size of the RDP092CA genome was 8.5 Mb with a G + C content of 71.4%. Phylogenetically, RDP092CA is closely related to Corallococcus interemptor, C. coralloides, and C. exiguus. However, genome average nucleotide identity and digital DNA-DNA hybridization values are lower than 95% and 70% when compared to those type strains, implying that it belongs to a novel species. The RDP092CA genome harbours seven types of biosynthetic gene clusters (BGCs) and 152 predicted antimicrobial peptides. In predation assays, RDP092CA showed good predatory activity against Escherichia coli, Pseudomonas aeruginosa, Citrobacter freundii, and Staphylococcus aureus but not against Enterococcus faecalis. It also showed good antibiofilm activity against all five bacteria in biofilm assays. Antifungal activity against eight Candida spp. was variable, with particularly good activity against Meyerozyma guillermondii DSM 6381. Antimicrobial peptide RDP092CA_120 exhibited potent antibiofilm activity with >50% inhibition and >60% dispersion of biofilms at concentrations down to 1 µg/ml. CONCLUSIONS: We propose that strain RDP092CA represents a novel species with promising antimicrobial activities, Corallococcus senghenyddensis sp. nov. (=NBRC 116490T =CCOS 2109T), based on morphological, biochemical, and genomic features.

Feasibility and utility of mobile health interventions for depression and anxiety in rural populations: A scoping review.

Despite the potential of mobile health (mHealth) to address high rates of depression and anxiety in underserved rural communities, most mHealth interventions do not explicitly consider the realities of rural life. The aim of this scoping review is to identify and examine the available literature on mHealth interventions that consider the needs of rural populations in order to gauge their feasibility and utility for addressing depression and anxiety. Additionally, we provide an overview of rural users' perceptions about and preferences for mHealth-delivered mental health screening and intervention systems. Out of 169 articles identified, 16 met inclusion criteria. Studies were conducted across a wide range of countries, age groups, and rural subpopulations including individuals with bipolar disorder, anxiety, perinatal depression, PTSD, and chronic pain, as well as refugees, veterans, and transgender and LGBTQ+ individuals. All interventions were in the feasibility/acceptability testing stage for rural users. Identified strengths included their simplicity, accessibility, convenience, availability of support between sessions with providers, and remote access to a care team. Weaknesses included problems with charging phone batteries and exceeding data limits, privacy concerns, and general lack of comfort with app-based support. Based upon this review, we provide recommendations for future mHealth intervention development including the value of developer-user coproduction methods, the need to consider user variation in access to and comfort with smartphones, and potential data or connectivity limitations, mental health stigma, and confidentiality concerns in rural communities.

Genomic attributes of prostate cancer across primary and metastatic noncastrate and castrate resistant disease states: a next generation sequencing study of 183 patients.

Primary prostatic adenocarcinoma (pPC) undergoes genomic evolution secondary to therapy-related selection pressures as it transitions to metastatic noncastrate (mNC-PC) and castrate resistant (mCR-PC) disease. Next generation sequencing results were evaluated for pPC (n = 97), locally advanced disease (involving urinary bladder/rectum, n = 12), mNC-PC (n = 21), and mCR-PC (n = 54). We identified enrichment of TP53 alterations in high-grade pPC, TP53/RB1 alterations in HGNE disease, and AR alterations in metastatic and castrate resistant disease. Actionable alterations (MSI-H phenotype and HRR genes) were identified in approximately a fifth of all cases. These results help elucidate the landscape of genomic alterations across the clinical spectrum of prostate cancer.

Direct Probes of π-Delocalization in Prototypical Resonance-Stabilized Radicals: Hyperfine-Resolved Microwave Spectroscopy of Isotopic Propargyl and Cyanomethyl.

Delocalization of the unpaired electron in π-conjugated radicals has profound implications for their chemistry, but direct and quantitative characterization of this electronic structure in isolated molecules remains challenging. We apply hyperfine-resolved microwave rotational spectroscopy to rigorously probe π-delocalization in propargyl, CH2CCH, a prototypical resonance-stabilized radical and key reactive intermediate. Using the spectroscopic constants derived from the high-resolution cavity Fourier transform microwave measurements of an exhaustive set of 13C- and 2H-substituted isotopologues, together with high-level ab initio calculations of zero-point vibrational effects, we derive its precise semiexperimental equilibrium geometry and quantitatively characterize the spatial distribution of its unpaired electron. Our results highlight the importance of considering both spin-polarization and orbital-following contributions when interpreting the isotropic hyperfine coupling constants of π radicals. These physical insights are strengthened by a parallel analysis of the isoelectronic species cyanomethyl, CH2CN, using new 13C measurements also reported in this work. A detailed comparison of the structure and electronic properties of propargyl, cyanomethyl, and other closely related species allows us to correlate trends in their chemical bonding and electronic structure with critical changes in their reactivity and thermochemistry.

Twenty-Year Radiographic Outcomes Following Single-Level Cervical Disc Arthroplasty: Results From a Prospective Randomized Controlled Trial.

STUDY DESIGN: Prospective randomized controlled trial. OBJECTIVE: Compare range of motion (ROM) and adjacent segment degeneration (ASD) following cervical disc arthroplasty (CDA) versus anterior cervical discectomy and fusion (ACDF) at 20-year follow-up. SUMMARY OF BACKGROUND DATA: Anterior cervical discectomy and fusion is the standard of treatment for single-level cervical disc degeneration causing radiculopathy. CDA is claimed to reduce shear strain, and adjacent-level ROM changes are hypothesized to hasten ASD with ACDF. MATERIALS AND METHODS: This study collected data on 47 patients randomized to ACDF or CDA. Lateral cervical spine radiographs were evaluated preoperatively, postoperatively, and at 20 years for alignment, ROM, ASD, and heterotopic ossification. RESULTS: Eighty-two percent (18/22) of CDA patients and 84% (21/25) of ACDF patients followed up at 20 years. At 20 years, total cervical (C2-C7) ROM was statistically different between the CDA and fusion groups (47.8° vs . 33.4°, P =0.005). Total cervical ROM was not significantly different between preoperative and 20-year periods following CDA (45.6° vs . 47.4°, P =0.772) or ACDF (40.6° vs . 33.0°, P =0.192). Differences in postoperative and 20-year index-level ROM following CDA were not significant (10.1° vs . 10.2°, P =0.952). Final ASD grading was statistically lower following CDA versus ACDF at both adjacent levels ( P <0.005). Twenty-year adjacent-level ossification development was increased following ACDF versus CDA ( P <0.001). Polyethylene mean thickness decreased from 9.4 mm immediately postoperatively to 9.1 mm at 20-year follow up ( P =0.013). Differences in adjacent-level ROM from preoperative to 20-year follow-up in both the ACDF and CDA groups did not meet statistical significance ( P >0.05). CONCLUSIONS: Cervical disc arthroplasty maintains index-level and total cervical ROM with very long-term follow-up. Total cervical ROM was higher at 20 years in CDA relative to ACDF. CDA results in lower rates of ASD and adjacent-level ossification development than ACDF.

Impact of compliance to oral cysteamine treatment on the costs of Kidney failure in patients with nephropathic cystinosis in the United Kingdom.

BACKGROUND: Nephropathic Cystinosis (NC), a rare disease characterised by intra-lysosomal accumulation of cystine, results in progressive kidney failure (KF). Compliance to lifelong oral cysteamine, the only therapy, is often compromised. The relationship between compliance and costs of NC has not been previously formally assessed. The present study evaluates the impact of compliance on lifetime (direct) costs of treating KF in NC patients in the United Kingdom. METHODS: A three-state (KF-free, post-KF, death) partitioned survival model was developed for hypothetical 'Good Compliance' (GC) and 'Poor Compliance' (PC) cohorts. Survival in the KF-free state was determined by a published regression function of composite compliance score (CCS). The CCS is a summation of annual compliance scores (ACS) over treatment duration prior to KF. ACSs are indexed on annual (average) leukocyte cystine levels (LCL). The Poor Compliance cohort was defined to reflect NC patients in a previous study with a mean LCL of 2.35 nmols nmol half-cystine/mg protein over the study period - and an estimated mean ACS of 1.64 over a 13.4 year treatment duration. The Good Compliance cohort was assumed to have an ACS of 2.25 for 21 years. Major KF costs were evaluated - i.e., dialysis, kidney transplants, and subsequent monitoring. RESULTS: The mean CCS was 47 for the GC and 22 for the PC cohort respectively, corresponding to estimated lifetime KF costs of £92,370 and £117,830 respectively - i.e., a cost saving of £25,460/patient, or £1,005/patient for every 1-unit improvement in CCS. CONCLUSION: This analysis indicates that lifetime costs of KF in NC can be reduced through improved treatment compliance with oral cysteamine.

The relations between chronotype, stressful life events, and impulsivity in the Adolescent Brain Cognitive Development (ABCD) study.

Circadian rhythm disturbances, especially circadian phase delays are associated with impulsive behaviors and have been implicated in psychiatric disorders. Chronotype is a developmentally regulated proxy measure of circadian phase. Past studies have investigated the relationship between chronotype and trauma and found that trauma is associated with evening chronotypes, suggesting the course of chronotype development may be affected by adverse childhood experiences (ACEs). However, the relationships among chronotype, impulsivity and ACEs have largely been studied in a pairwise manner using small, cross-sectional cohorts. We hypothesized that in a cohort of high-risk youth, childhood trauma would be associated with later chronotype, and later chronotype would be associated with higher rates of impulsivity. We analyzed a cross-sectional sample (n = 966) from Year 2 of adolescents at high risk for psychiatric disorders from the ABCD study who were characterized for chronotype, stressful life events, and impulsivity. We used a hierarchical regression model to examine the relationship between chronotype, stressful life events, and impulsivity using the Munich Chronotype Questionnaire (MCTQ), the Life Events Scale, Urgency, Premeditation, Perseverance and Sensation Seeking (UPPS) Impulsive Behavior scale. We found associations between eveningness, stressful life events, and all dimensions of impulsivity. Increased eveningness was associated with a higher number of stressful life events and increased impulsivity. Understanding the role of stressful life events and impulsivity in those predisposed towards eveningness is useful because it may improve our understanding of the biological mechanisms that contribute to psychiatric disorders, and lead to better prevention and treatment efforts using interventions such as increased lifestyle regularity and daytime light exposure.

Emerging Technologies within Spine Surgery.

New innovations within spine surgery continue to propel the field forward. These technologies improve surgeons' understanding of their patients and allow them to optimize treatment planning both in the operating room and clinic. Additionally, changes in the implants and surgeon practice habits continue to evolve secondary to emerging biomaterials and device design. With ongoing advancements, patients can expect enhanced preoperative decision-making, improved patient outcomes, and better intraoperative execution. Additionally, these changes may decrease many of the most common complications following spine surgery in order to reduce morbidity, mortality, and the need for reoperation. This article reviews some of these technological advancements and how they are projected to impact the field. As the field continues to advance, it is vital that practitioners remain knowledgeable of these changes in order to provide the most effective treatment possible.

Accelerating Cancer Histopathology Workflows with Chemical Imaging and Machine Learning.

Histopathology has remained a cornerstone for biomedical tissue assessment for over a century, with a resource-intensive workflow involving biopsy or excision, gross examination, sampling, tissue processing to snap frozen or formalin-fixed paraffin-embedded blocks, sectioning, staining, optical imaging, and microscopic assessment. Emerging chemical imaging approaches, including stimulated Raman scattering (SRS) microscopy, can directly measure inherent molecular composition in tissue (thereby dispensing with the need for tissue processing, sectioning, and using dyes) and can use artificial intelligence (AI) algorithms to provide high-quality images. Here we show the integration of SRS microscopy in a pathology workflow to rapidly record chemical information from minimally processed fresh-frozen prostate tissue. Instead of using thin sections, we record data from intact thick tissues and use optical sectioning to generate images from multiple planes. We use a deep learning­based processing pipeline to generate virtual hematoxylin and eosin images. Next, we extend the computational method to generate archival-quality images in minutes, which are equivalent to those obtained from hours/days-long formalin-fixed, paraffin-embedded processing. We assessed the quality of images from the perspective of enabling pathologists to make decisions, demonstrating that the virtual stained image quality was diagnostically useful and the interpathologist agreement on prostate cancer grade was not impacted. Finally, because this method does not wash away lipids and small molecules, we assessed the utility of lipid chemical composition in determining grade. Together, the combination of chemical imaging and AI provides novel capabilities for rapid assessments in pathology by reducing the complexity and burden of current workflows. SIGNIFICANCE: Archival-quality (formalin-fixed paraffin-embedded), thin-section diagnostic images are obtained from thick-cut, fresh-frozen prostate tissues without dyes or stains to expedite cancer histopathology by combining SRS microscopy and machine learning.

Prognostic utility of RECIP 1.0 with manual and AI-based segmentations in biochemically recurrent prostate cancer from [68Ga]Ga-PSMA-11 PET images.

PURPOSE: This study aimed to (i) validate the Response Evaluation Criteria in PSMA (RECIP 1.0) criteria in a cohort of biochemically recurrent (BCR) prostate cancer (PCa) patients and (ii) determine if this classification could be performed fully automatically using a trained artificial intelligence (AI) model. METHODS: One hundred ninety-nine patients were imaged with [68Ga]Ga-PSMA-11 PET/CT once at the time of biochemical recurrence and then a second time a median of 6.0 months later to assess disease progression. Standard-of-care treatments were administered to patients in the interim. Whole-body tumour volume was quantified semi-automatically (TTVman) in all patients and using a novel AI method (TTVAI) in a subset (n = 74, the remainder were used in the training process of the model). Patients were classified as having progressive disease (RECIP-PD), or non-progressive disease (non RECIP-PD). Association of RECIP classifications with patient overall survival (OS) was assessed using the Kaplan-Meier method with the log rank test and univariate Cox regression analysis with derivation of hazard ratios (HRs). Concordance of manual and AI response classifications was evaluated using the Cohen's kappa statistic. RESULTS: Twenty-six patients (26/199 = 13.1%) presented with RECIP-PD according to semi-automated delineations, which was associated with a significantly lower survival probability (log rank p < 0.005) and higher risk of death (HR = 3.78 (1.96-7.28), p < 0.005). Twelve patients (12/74 = 16.2%) presented with RECIP-PD according to AI-based segmentations, which was also associated with a significantly lower survival (log rank p = 0.013) and higher risk of death (HR = 3.75 (1.23-11.47), p = 0.02). Overall, semi-automated and AI-based RECIP classifications were in fair agreement (Cohen's k = 0.31). CONCLUSION: RECIP 1.0 was demonstrated to be prognostic in a BCR PCa population and is robust to two different segmentation methods, including a novel AI-based method. RECIP 1.0 can be used to assess disease progression in PCa patients with less advanced disease. This study was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000608561) on 11 June 2015.

Structural and electronic trends of optical cycling centers in polyatomic molecules revealed by microwave spectroscopy of MgCCH, CaCCH, and SrCCH.

The unique optical cycling efficiency of alkaline earth metal-ligand molecules has enabled significant advances in polyatomic laser cooling and trapping. Rotational spectroscopy is an ideal tool for probing the molecular properties that underpin optical cycling, thereby elucidating the design principles for expanding the chemical diversity and scope of these platforms for quantum science. We present a comprehensive study of the structure and electronic properties in alkaline earth metal acetylides with high-resolution microwave spectra of 17 isotopologues of MgCCH, CaCCH, and SrCCH in their 2Σ+ ground electronic states. The precise semiexperimental equilibrium geometry of each species has been derived by correcting the measured rotational constants for electronic and zero-point vibrational contributions calculated with high-level quantum chemistry methods. The well-resolved hyperfine structure associated with the 1,2H, 13C, and metal nuclear spins provides further information on the distribution and hybridization of the metal-centered, optically active unpaired electron. Together, these measurements allow us to correlate trends in chemical bonding and structure with the electronic properties that promote efficient optical cycling essential to next-generation experiments in precision measurement and quantum control of complex polyatomic molecules.

Serum from Myalgic encephalomyelitis/chronic fatigue syndrome patients causes loss of coherence in cellular circadian rhythms.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disabling disorder characterized by disrupted daily patterns of activity, sleep, and physiology. Past studies in ME/CFS patients have examined circadian rhythms, suggested that desynchronization between central and peripheral rhythms may be an important pathological feature, and identified associated changes in post-inflammatory cytokines such as transforming growth factor beta (TGFB). However, no previous studies have examined circadian rhythms in ME/CFS using cellular models or studied the role of cytokines on circadian rhythms. In this study, we used serum samples previously collected from ME/CFS patients (n = 20) selected for the presence of insomnia symptoms and matched controls (n = 20) to determine the effects of serum factors and TGFB on circadian rhythms in NIH3T3 mouse immortalized fibroblasts stably transfected with the Per2-luc bioluminescent circadian reporter. Compared to control serum, ME/CFS serum caused a significant loss of rhythm robustness (decreased goodness of fit) and nominally increased the rate of damping of cellular rhythms. Damping rate was associated with insomnia severity in ME/CFS patients using the Pittsburgh Sleep Quality Index (PSQI). Recombinant TGFB1 peptide applied to cells reduced rhythm amplitude, caused phase delay and decreased robustness of rhythms. However, there was no difference in TGFB1 levels between ME/CFS and control serum indicating the effects of serum on cellular rhythms cannot be explained by levels of this cytokine. Future studies will be required to identify additional serum factors in ME/CFS patients that alter circadian rhythms in cells.

Five-year mortality after traumatic central cord syndrome in Wales.

Aims: Traumatic central cord syndrome (CCS) typically follows a hyperextension injury and results in motor impairment affecting the upper limbs more than the lower, with occasional sensory impairment and urinary retention. Current evidence on mortality and long-term outcomes is limited. The primary aim of this study was to assess the five-year mortality of CCS, and to determine any difference in mortality between management groups or age. Methods: Patients aged ≥ 18 years with a traumatic CCS between January 2012 and December 2017 in Wales were identified. Patient demographics and data about injury, management, and outcome were collected. Statistical analysis was performed to assess mortality and between-group differences. Results: A total of 65 patients were identified (66.2% male (n = 43), mean age 63.9 years (SD 15.9)). At a minimum of five years' follow-up, 32.3% of CCS patients (n = 21) had died, of whom six (9.2%) had died within 31 days of their injury. Overall, 69.2% of patients (n = 45) had been managed conservatively. There was no significant difference in age between conservatively and surgically managed patients (p = 0.062). Kaplan-Meier analysis revealed no significant difference in mortality between patients managed conservatively and those managed surgically (p = 0.819). However, there was a significant difference in mortality between the different age groups (< 50 years vs 50 to 70 years vs > 70 years; p = 0.001). At five years' follow-up, 55.6% of the patient group aged > 70 years at time of injury had died (n = 15). Respiratory failure was the most common cause of death (n = 9; 42.9%). Conclusion: Almost one-third of patients with a traumatic CCS in Wales had died within five years of their injury. The type of management did not significantly affect mortality but their age at the time of injury did. Further work to assess the long-term functional outcomes of surviving patients is needed to generate more reliable prognostic information.

The state of evidence for social and emotional learning: A contemporary meta-analysis of universal school-based SEL interventions.

This article provides a systematic review and meta-analysis of the current evidence for universal school-based (USB) social and emotional learning (SEL) interventions for students in kindergarten through 12th grade available from 2008 through 2020. The sample includes 424 studies from 53 countries, reflecting 252 discrete USB SEL interventions, involving 575,361 students. Results endorsed that, compared to control conditions, students who participate in USB SEL interventions experienced significantly improved skills, attitudes, behaviors, school climate and safety, peer relationships, school functioning, and academic achievement. Significant heterogeneity in USB SEL content, intervention features, context, and implementation quality moderated student experiences and outcomes. Strengths and limitations of this evidence and implications for future USB SEL research, policy, and practice are discussed.