A Well-defined Magnesium Complex of C706.

Controlling and understanding charge state and metal coordination in carbon nanomaterials is crucial to harnessing their unique properties. Here we describe the synthesis of the well-defined fulleride complex [{(Mesnacnac)Mg}6C70], 2, (Mesnacnac) = HC(MeCNMes)2, Mes = 2,4,6-Me3C6H2, from the reaction of the ß-diketiminate magnesium(I) complex [{(Mesnacnac)Mg}2] with C70 in aromatic solvents. The molecular structure of complex 2 was determined, providing the first high-quality structural study of a complex with the C706- ion. In combination with solution state NMR spectroscopic and DFT computational studies, the changes in geometry and charge distribution in the various atom and bond types of the fulleride unit were investigated. Additionally, the influence of the (Mesnacnac)Mg+ cations on the global and local fulleride coordination environment was examined.

Validation of an abbreviated Big Five personality inventory at large population scale: Psychometric structure and associations with common psychiatric and neurological disorders.

BACKGROUND: The five-factor model of personality, as quantified using instruments such as the Big Five Inventory, consists of broad personality domains including Extraversion, Agreeableness, Conscientiousness, Neuroticism (emotional instability), and Openness. Such instruments typically include >40 items. However, instruments with many items can be unwieldly and a cause of measurement error in clinical and cohort studies where multiple scales are sequenced. Conversely, established 5- and 10-item versions of the Big Five Inventory have poor reliability. Here, we developed and validated an abbreviated 18-item Big Five Inventory that balances efficiency, reliability and sensitivity. METHOD: We analysed three datasets (N = 59,797, N = 21,177, and N = 87,983) from individuals who participated in the online Great British Intelligence Test (GBIT) study, a collaborative citizen science project with BBC2 Horizon. We applied factor analyses (FA), predictive normative modelling, and one-sample t-tests to validate the 18-item version of the Big Five and to investigate its associations with psychiatric and neurological conditions. RESULTS: The 18-item version of the Big Five Inventory had higher validity and retest reliability compared to the other previously shortened versions in the literature, with comparable demographic associations to the full Big Five Inventory. It exhibited strong (i.e. large effect size) associations with psychiatric conditions, and moderate (small-medium) associations with neurological conditions. Neuroticism (emotional instability) was substantially higher in all psychiatric conditions, whereas Conscientiousness, Openness and Extraversion showed differential associations across conditions. CONCLUSION: The newly validated 18-item version of the Big Five provides a convenient means of measuring personality traits that is suitable for deployment in a range of studies. It retains psychometric structure, retest reliability and clinical-group sensitivity, as compared to the full original scale.

Outcomes Following the Use of Extracellular Matrix Cartilage Allograft for the Management of Osteochondral Lesions of the Talus: A Systematic Review.

Extracellular matrix cartilage allograft (EMCA) is a novel biological strategy utilized to augment the repair of osteochondral lesions of the talus (OLTs). However, there is no consensus on the precise role and outcomes following its use in the treatment of OLTs. The purpose of this systematic review was to evaluate the clinical and radiological outcomes following the use of EMCA for the treatment of OLT. During July 2023, the PubMed, Embase, and Cochrane Library databases were systematically reviewed to identify clinical studies examining outcomes following EMCA for the management of OLTs. In total, 162 patients (162 ankles) across five studies received EMCA as part of their surgical procedure at a weighted mean follow-up time of 23.8±4.2 months. Across all five studies, there were improvements in subjective clinical outcomes following the use of EMCA, regardless of the clinical scoring tool utilized. Two studies demonstrated superior postoperative magnetic resonance observation of cartilage repair tissue (MOCART) scores in the EMCA cohort compared to the bone marrow stimulation (BMS) cohort alone. In the EMCA-BMS cohort, there were seven complications (9%) and three failures (4.1%). In the autologous osteochondral transplantation (AOT) cohort, there were 10 complications (38.5%), zero failures, and six secondary surgical procedures (23.1%). In the EMCA alone cohort, there were zero complications and three failures (4.3%), all of which underwent an unspecified revision procedure. This current systematic review demonstrated improvements in both clinical and radiological outcomes following the use of EMCA for the treatment of OLTs. Further prospective comparative studies with longer follow-up times are warranted to determine the precise role of EMCA in the management of OLT.

Comparing ventriculoatrial and ventriculopleural shunts in pediatric hydrocephalus: a Hydrocephalus Clinical Research Network study.

OBJECTIVE: When the peritoneal cavity cannot serve as the distal shunt terminus, nonperitoneal shunts, typically terminating in the atrium or pleural space, are used. The comparative effectiveness of these two terminus options has not been evaluated. The authors directly compared shunt survival and complication rates for ventriculoatrial (VA) and ventriculopleural (VPl) shunts in a pediatric cohort. METHODS: The Hydrocephalus Clinical Research Network Core Data Project was used to identify children ≤ 18 years of age who underwent either VA or VPl shunt insertion. The primary outcome was time to shunt failure. Secondary outcomes included distal site complications and frequency of shunt failure at 6, 12, and 24 months. RESULTS: The search criteria yielded 416 children from 14 centers with either a VA (n = 318) or VPl (n = 98) shunt, including those converted from ventriculoperitoneal shunts. Children with VA shunts had a lower median age at insertion (6.1 years vs 12.4 years, p < 0.001). Among those children with VA shunts, a hydrocephalus etiology of intraventricular hemorrhage (IVH) secondary to prematurity comprised a higher proportion (47.0% vs 31.2%) and myelomeningocele comprised a lower proportion (17.8% vs 27.3%) (p = 0.024) compared with those with VPl shunts. At 24 months, there was a higher cumulative number of revisions for VA shunts (48.6% vs 38.9%, p = 0.038). When stratified by patient age at shunt insertion, VA shunts in children < 6 years had the lowest shunt survival rate (p < 0.001, log-rank test). After controlling for age and etiology, multivariable analysis did not find that shunt type (VA vs VPl) was predictive of time to shunt failure. No differences were found in the cumulative frequency of complications (VA 6.0% vs VPl 9.2%, p = 0.257), but there was a higher rate of pneumothorax in the VPl cohort (3.1% vs 0%, p = 0.013). CONCLUSIONS: Shunt survival was similar between VA and VPl shunts, although VA shunts are used more often, particularly in younger patients. Children < 6 years with VA shunts appeared to have the shortest shunt survival, which may be a result of the VA group having more cases of IVH secondary to prematurity; however, when age and etiology were included in a multivariable model, shunt location (atrium vs pleural space) was not associated with time to failure. The baseline differences between children treated with a VA versus a VPl shunt likely explain current practice patterns.

Comparison of a novel expanded social network recruitment intervention with risk network recruitment to HIV testing: locating undiagnosed cases in South Africa.

OBJECTIVE: To ascertain whether a novel expanded social network recruitment to HIV testing (E-SNRHT) intervention recruits men and individuals with previously-undiagnosed HIV at higher rates than risk network recruitment. DESIGN: Initial "seed" participants were prospectively randomly assigned to the E-SNRHT intervention or to risk network recruitment. Their network members were included in the study arm of their recruiter. SETTING: Three Department of Health clinics and two drug treatment centers (DTCs) in the Msunduzi municipality of KwaZulu-Natal, South Africa. PARTICIPANTS: Clinics and DTCs referred 110 newly-HIV-diagnosed adult "seeds" to the study from June 2022-February 2023. E-SNRHT seeds were asked to recruit network members as described below; risk network recruitment arm seeds were asked to recruit recent sex and/or injection partners. Presenting a recruitment coupon (from clinic/DTC staff or another participant) was required for eligibility. INTERVENTION: E-SNRHT seeds were shown educational material about HIV transmission risks and then asked to recruit anyone they know (e.g., friends, family) whom they thought could benefit from HIV testing. MAIN OUTCOME MEASURES: Rates of recruiting men to HIV testing and locating individuals with previously-undiagnosed HIV. RESULTS: E-SNRHT recruited significantly higher proportions of men to HIV testing (70.3% vs. 40.4%; χ2 = 16.33; p < .0005) and located significantly more previously-undiagnosed cases of HIV per seed than risk network recruitment (rate ratio = 9.40; p < .0001). E-SNRHT also recruited significantly higher proportions of women with previously-undiagnosed HIV (29.0% vs. 10.7%; χ2 = 3.87; p = .049). CONCLUSIONS: E-SNRHT is an important strategy to expand the reach of HIV testing among men and undiagnosed cases of HIV in KwaZulu-Natal.

Comparing deposition characteristics of various embolic particles using an in vitro prostate microvasculature model.

PURPOSE: To compare spatial distributions of radiopaque glass (RG) microspheres, trisacryl gelatin (TAG) microspheres, and polyvinyl alcohol (PVA) foam particles within a planar in vitro microvascular model of the hyperplastic hemiprostate. MATERIALS AND METHODS: A microvascular model simulating hyperplastic hemiprostate was perfused with a water-glycerin mixture. A microcatheter was positioned distal to the model's prostatic artery origin and embolic particles (RG: 50 µm, 100 µm, and 150 µm; TAG: 100-300 µm and 300-500 µm; and PVA: 90-180 µm and 180-300 µm) were administered using a syringe pump. Microscopic imaging and subsequent semantic segmentation were performed to quantify particle distributions within the models. Distal penetrations were quantified statistically via modal analysis of the particle distributions. RESULTS: Maximum distal penetration was observed for RG 50, followed by RG 100 and then TAG 100-300 and RG 150. TAG 300-500, PVA 90-180, and PVA 180-300 particles exhibited the lowest distal penetrations. The distal penetration metrics between groups were significantly different (p < 0.05) except between TAG 100-300 and RG 150 and between PVA 90-180 and PVA 180-300. CONCLUSIONS: Comparing the spatial distributions of embolic particles in an in vitro microvascular model simulating the hyperplastic hemiprostate revealed that noncompressible particles and those with narrower size calibrations and smaller relative diameters exhibited higher degrees of distal packing. The embolization front was less distinct for particles with wider size calibrations, which resulted in smaller, more distal emboli along with larger, more proximal emboli. PVA and TAG 300-500 particles both exhibited relatively low overall distal penetration.

Exploring memory-related network via dorsal hippocampus suppression.

Memory is a complex brain process that requires coordinated activities in a large-scale brain network. However, the relationship between coordinated brain network activities and memory-related behavior is not well understood. In this study, we investigated this issue by suppressing the activity in the dorsal hippocampus (dHP) using chemogenetics and measuring the corresponding changes in brain-wide resting-state functional connectivity (RSFC) and memory behavior in awake rats. We identified an extended brain network contributing to the performance in a spatial-memory related task. Our results were cross-validated using two different chemogenetic actuators, clozapine (CLZ) and clozapine-N-oxide (CNO). This study provides a brain network interpretation of memory performance, indicating that memory is associated with coordinated brain-wide neural activities. Significance Statement: Successful memory processes require coordinated activity in a large-scale brain network, extending beyond a few key, well-known brain regions like the hippocampus. However, the specific brain regions involved and how they orchestrate their activity that is pertinent to memory processing remain unclear. Our study, using a chemogenetics-rsfMRI- behavior approach in awake rats, elucidates a comprehensive framework of the extended memory-associated network. This knowledge offers a broader interpretation of memory processes, enhancing our understanding of the neural mechanisms behind memory function, particularly from a network perspective.

Giant diaphragmatic hernia surgical treatment by laparoscopic repair: a case report.

Diaphragmatic hernias occur in up to 10%-50% of the general population. Treatment of hiatal hernias depends on the type of hernia and the severity of the symptoms. We report the case of a 52-year-old woman with no significant history who presented for 1 year with non-specific chest pain, dyspnea, dysphagia, and heartburn. A thoracoabdominal tomography with contrast was performed, showing a diaphragmatic hernia containing the stomach, portions of the duodenum, pancreas, small intestine, and colon with a sac of up to 20 cm, which was successfully repaired laparoscopically.

An active electronic bidirectional interface for high resolution interrogation of the spinal cord.

Epidural electrical stimulation (EES) has shown promise as both a clinical therapeutic tool and research aid in the study of nervous system function. However, available clinical paddles are limited to using a small number of contacts due to the burden of wires necessary to connect each contact to the therapeutic device. Here, we introduce for the first time the integration of a hermetic active electronic multiplexer onto the electrode paddle array itself, removing this interconnect limitation. We evaluated the chronic implantation of an active electronic 60-contact paddle (the HD64) on the lumbosacral spinal cord of two sheep. The HD64 was implanted for 13 months and 15 months, with no device-related malfunctions or adverse events. We identified increased selectivity in EES-evoked motor responses using dense stimulating bipoles. Further, we found that dense recording bipoles decreased the spatial correlation between channels during recordings. Finally, spatial electrode encoding enabled a neural network to accurately perform EES parameter inference for unseen stimulation electrodes, reducing training data requirements. A high-density EES paddle, containing active electronics safely integrated into neural interfaces, opens new avenues for the study of nervous system function and new therapies to treat neural injury and dysfunction.

International Consensus on Standard Outcome Measures for Neurodevelopmental Disorders: A Consensus Statement.

Importance: The use of evidence-based standardized outcome measures is increasingly recognized as key to guiding clinical decision-making in mental health. Implementation of these measures into clinical practice has been hampered by lack of clarity on what to measure and how to do this in a reliable and standardized way. Objective: To develop a core set of outcome measures for specific neurodevelopmental disorders (NDDs), such as attention-deficit/hyperactivity disorder (ADHD), communication disorders, specific learning disorders, and motor disorders, that may be used across a range of geographic and cultural settings. Evidence Review: An international working group composed of clinical and research experts and service users (n = 27) was convened to develop a standard core set of accessible, valid, and reliable outcome measures for children and adolescents with NDDs. The working group participated in 9 video conference calls and 8 surveys between March 1, 2021, and June 30, 2022. A modified Delphi approach defined the scope, outcomes, included measures, case-mix variables, and measurement time points. After development, the NDD set was distributed to professionals and service users for open review, feedback, and external validation. Findings: The final set recommends measuring 12 outcomes across 3 key domains: (1) core symptoms related to the diagnosis; (2) impact, functioning, and quality of life; and (3) common coexisting problems. The following 14 measures should be administered at least every 6 months to monitor these outcomes: ADHD Rating Scale 5, Vanderbilt ADHD Diagnostic Rating Scale, or Swanson, Nolan, and Pelham Rating Scale IV; Affective Reactivity Index; Children's Communication Checklist 2; Colorado Learning Disabilities Questionnaire; Children's Sleep Habits Questionnaire; Developmental-Disability Children's Global Assessment Scale; Developmental Coordination Disorder Questionnaire; Family Strain Index; Intelligibility in Context Scale; Vineland Adaptive Behavior Scale or Repetitive Behavior Scale-Revised and Social Responsiveness Scale; Revised Child Anxiety and Depression Scales; and Yale Global Tic Severity Scale. The external review survey was completed by 32 professionals and 40 service users. The NDD set items were endorsed by more than 70% of professionals and service users in the open review survey. Conclusions and Relevance: The NDD set covers outcomes of most concern to patients and caregivers. Use of the NDD set has the potential to improve clinical practice and research.

Direct computations of viscoelastic moduli of biomolecular condensates.

In vitro facsimiles of biomolecular condensates are formed by different types of intrinsically disordered proteins including prion-like low complexity domains (PLCDs). PLCD condensates are viscoelastic materials defined by time-dependent, sequence-specific complex shear moduli. Here, we show that viscoelastic moduli can be computed directly using a generalization of the Rouse model and information regarding intra- and inter-chain contacts that is extracted from equilibrium configurations of lattice-based Metropolis Monte Carlo (MMC) simulations. The key ingredient of the generalized Rouse model is the Zimm matrix that we compute from equilibrium MMC simulations. We compute two flavors of Zimm matrices, one referred to as the single-chain model that accounts only for intra-chain contacts, and the other referred to as a collective model, that accounts for inter-chain interactions. The single-chain model systematically overestimates the storage and loss moduli, whereas the collective model reproduces the measured moduli with greater fidelity. However, in the long time, low-frequency domain, a mixture of the two models proves to be most accurate. In line with the theory of Rouse, we find that a continuous distribution of relaxation times exists in condensates. The single crossover frequency between dominantly elastic versus dominantly viscous behaviors is influenced by the totality of the relaxation modes. Hence, our analysis suggests that viscoelastic fluid-like condensates are best described as generalized Maxwell fluids. Finally, we show that the complex shear moduli can be used to solve an inverse problem to obtain distributions of relaxation times that underlie the dynamics within condensates.

Worker's compensation and no-fault insurance are associated with decreased patient reported outcomes and higher rates of revision at 2 and 5 years follow-up compared to patients with commercial insurance undergoing hip arthroscopy for femoroacetabular impingement.

PURPOSE: To investigate the patient reported outcomes (PROs) of patients undergoing hip arthroscopy (HA) for femeroacetabular impingement syndrome (FAIS), a condition where irregular bone growth in the hip joint leads to friction and pain during movement, who have worker's compensation (WC) or no-fault insurance (NF) versus commercial insurance (CI) at both 2 year and 5 year follow-up. METHODS: This was a single center, single surgeon, retrospective analysis performed between August 2007 and May 2023 of consecutive patients that underwent HA, a minimally invasive surgical procedure used to diagnose and treat problems inside the hip joint through small incisions, for FAIS. Patients were divided into two cohorts-those with WC/NF and those with commercial insurance (CI). Patient reported outcomes (PROs), which included modified Harris Hip Score (mHHS) and Non-Arthritic Hip Score (NAHS), were collected preoperatively, as well as at least 2-year postoperatively. Additionally, other clinically relevant outcomes variables including prevalence of revision surgery and conversion to total hip arthroplasty were recorded. RESULTS: Three hundred and forty three patients met inclusion criteria. There were 32 patients in the WC/NF cohort and 311 patients in the commercial cohort. When controlling for age, sex, and Body Mass Index (BMI), WC/NF status was associated with lower mHHS at both 2 year (ß = - 8.190, p < 0.01, R2 = 0.092) and 5 year follow-up (ß = - 16.60, p < 0.01, R2 = 0.179) and NAHS at 5 year follow up (ß = - 13.462, p = 0.03, R2 = 0.148). The WC/NF cohort had a lower rate of achieving Substantial Clinical Benefit (SCB) for mHHS at 2-years follow-up (66.7% vs. 84.1%, p = 0.02).The rate of revision hip arthroscopy was significantly higher in the worker's compensation/no fault cohort than the commercial insurance cohort (15.6% vs. 3.5%, p < 0.01). The rate of conversion to total hip arthroplasty (THA) in the WC/NF cohort was not significantly different than the rate of conversion to THA in the commercial insurance cohort (0.0% vs. 3.2%, p = 0.30). CONCLUSION: Patients with WC/NF insurance may expect a significant improvement from baseline mHHS and NAHS following HA for FAIS at short-term follow-up. However, this improvement may not be as durable as those experienced by patients with CI. Additionally, WC/NF patients should be counseled that they have a higher risk of undergoing revision hip arthroscopy than similar CI patients. LEVEL OF EVIDENCE: III, Retrospective Comparative Prognostic Investigation.

Teaching Hospitals and Textbook Outcomes After Major Urologic Cancer Surgery.

OBJECTIVE: To assess textbook outcomes by hospital teaching status following major surgery for urologic cancers. METHODS: We used 100% national Medicare Provider Analysis and Review files from 2017-2020 to assess rates of textbook outcomes in patients undergoing bladder (ie, radical cystectomy), kidney (ie, radical or partial nephrectomy), and prostate (ie, radical prostatectomy) surgery for genitourinary malignancies. The extent of integration of learners into each hospital's workforce-defined as major, minor, and non teaching hospitals-was the primary exposure. A textbook outcome, measured at the patient level, was defined as the absence of in-hospital mortality and mortality within 30days of surgery, no readmission 30days following discharge, no postoperative complication, and no prolonged length of stay. RESULTS: Textbook outcomes were achieved in 51% (8564/16,786) of patients after bladder cancer surgery, 70% (39,938/57,300) of patients after kidney cancer surgery, and 82% (50,408/61,385) of patients after prostate cancer surgery. After adjusting for patient- and hospital-level characteristics, teaching hospitals had higher rates of textbook outcomes in those undergoing bladder (50.7% vs 44.0%; P = .001), kidney (72.0% vs 69.7%; P = .02), and prostate (85.3% vs 81.0%; P <.001) surgery. This effect was attenuated, but not eliminated, by surgical volume in additional sensitivity analyses for bladder (OR: 1.20, 95% CI: 1.00-1.42; P = .04) and prostate (OR: 1.15, 95% CI: 1.00-1.32; P = .04) surgery. There were no significant differences in kidney cancer surgery outcomes after adjusting for hospital volume (OR: 1.03, 95% CI: 0.93-1.14; P = .6). CONCLUSION: Undergoing major cancer surgery at a teaching hospital was associated with an increased likelihood of achieving a textbook outcome. This effect was attenuated by volume but persisted for bladder and prostate surgery.

Association of T-cell subtypes with macrophage-specific arterial infiltration in PWH.

People with human immunodeficiency virus (HIV, PWH) face an increased risk of cardiovascular disease (CVD) compared to the general population. We previously demonstrated that people with (versus without) HIV have higher macrophage-specific arterial infiltration in relation to systemic monocyte activation. We now show that select T lymphocyte subpopulations (naïve CD4+, effector memory CD4+, and central memory CD8+) are differentially associated with macrophage-specific arterial infiltration among participants with versus without HIV, with evidence of interaction by HIV status. Our results suggest that among PWH, circulating T lymphocytes associate with macrophage-specific arterial infiltration, of relevance to atherogenesis and CVD risk. CLINICAL TRIALS REGISTRATION: NCT02542371.

Placebo effects in randomized trials of pharmacological and neurostimulation interventions for mental disorders: An umbrella review.

There is a growing literature exploring the placebo response within specific mental disorders, but no overarching quantitative synthesis of this research has analyzed evidence across mental disorders. We carried out an umbrella review of meta-analyses of randomized controlled trials (RCTs) of biological treatments (pharmacotherapy or neurostimulation) for mental disorders. We explored whether placebo effect size differs across distinct disorders, and the correlates of increased placebo effects. Based on a pre-registered protocol, we searched Medline, PsycInfo, EMBASE, and Web of Knowledge up to 23.10.2022 for systematic reviews and/or meta-analyses reporting placebo effect sizes in psychopharmacological or neurostimulation RCTs. Twenty meta-analyses, summarising 1,691 RCTs involving 261,730 patients, were included. Placebo effect size varied, and was large in alcohol use disorder (g = 0.90, 95% CI [0.70, 1.09]), depression (g = 1.10, 95% CI [1.06, 1.15]), restless legs syndrome (g = 1.41, 95% CI [1.25, 1.56]), and generalized anxiety disorder (d = 1.85, 95% CI [1.61, 2.09]). Placebo effect size was small-to-medium in obsessive-compulsive disorder (d = 0.32, 95% CI [0.22, 0.41]), primary insomnia (g = 0.35, 95% CI [0.28, 0.42]), and schizophrenia spectrum disorders (standardized mean change = 0.33, 95% CI [0.22, 0.44]). Correlates of larger placebo response in multiple mental disorders included later publication year (opposite finding for ADHD), younger age, more trial sites, larger sample size, increased baseline severity, and larger active treatment effect size. Most (18 of 20) meta-analyses were judged 'low' quality as per AMSTAR-2. Placebo effect sizes varied substantially across mental disorders. Future research should explore the sources of this variation. We identified important gaps in the literature, with no eligible systematic reviews/meta-analyses of placebo response in stress-related disorders, eating disorders, behavioural addictions, or bipolar mania.

Bottom-up formulations for the multi-criteria decision analysis of oil and gas pipeline decommissioning in the North Sea: Brent field case study.

Many Oil and Gas (O&G) fields in the North Sea have produced their economically recoverable reserves and have entered the decommissioning phase or are close to cessation of production. The subsequent O&G decommissioning process involves a range of stakeholders with specific interests and priorities. This range of inputs to the process highlights the necessity for the development of multi-criteria decision frameworks to help guide the decision-making process. This study presents bottom-up formulations for the economic, environmental, and safety risk criteria to support the multi-criteria decision analysis within the Comparative Assessment (CA) of O&G pipeline decommissioning projects in the North Sea. The approach adapts current guidelines in the O&G industry and considers a range of parameters to provide estimations for the costs, energy usage, greenhouse gas emissions, and safety risks. To verify the effectiveness of the proposed bottom-up formulations, the longest oil export pipeline in the Brent field, PL001/N0501 is selected as a case study. The numerical results revealed the consistency of the results obtained from the proposed approach with those reported in the technical documents by industry. In most cases, the formulations provide estimates with less than 10% differences for the costs, energy usage, emissions, and safety risks. Based on the proposed multi-criteria formulations, the study also presents the use of an immersive decision-making environment within a marine simulator system to help inform the decision-making process by stakeholders.

Microbiota dictate T cell clonal selection to augment graft-versus-host disease after stem cell transplantation.

Allogeneic T cell expansion is the primary determinant of graft-versus-host disease (GVHD), and current dogma dictates that this is driven by histocompatibility antigen disparities between donor and recipient. This paradigm represents a closed genetic system within which donor T cells interact with peptide-major histocompatibility complexes (MHCs), though clonal interrogation remains challenging due to the sparseness of the T cell repertoire. We developed a Bayesian model using donor and recipient T cell receptor (TCR) frequencies in murine stem cell transplant systems to define limited common expansion of T cell clones across genetically identical donor-recipient pairs. A subset of donor CD4+ T cell clonotypes differentially expanded in identical recipients and were microbiota dependent. Microbiota-specific T cells augmented GVHD lethality and could target microbial antigens presented by gastrointestinal epithelium during an alloreactive response. The microbiota serves as a source of cognate antigens that contribute to clonotypic T cell expansion and the induction of GVHD independent of donor-recipient genetics.

Chiroptical Second-Harmonic Tyndall Scattering from Silicon Nanohelices.

Chirality is omnipresent in the living world. As biomimetic nanotechnology and self-assembly advance, they too need chirality. Accordingly, there is a pressing need to develop general methods to characterize chiral building blocks at the nanoscale in liquids such as water─the medium of life. Here, we demonstrate the chiroptical second-harmonic Tyndall scattering effect. The effect was observed in Si nanohelices, an example of a high-refractive-index dielectric nanomaterial. For three wavelengths of illumination, we observe a clear difference in the second-harmonic scattered light that depends on the chirality of the nanohelices and the handedness of circularly polarized light. Importantly, we provide a theoretical analysis that explains the origin of the effect and its direction dependence, resulting from different specific contributions of "electric dipole-magnetic dipole" and "electric dipole-electric quadrupole" coupling tensors. Using numerical simulations, we narrow down the number of such terms to 8 in forward scattering and to a single one in right-angled scattering. For chiral scatterers such as high-refractive-index dielectric nanoparticles, our findings expand the Tyndall scattering regime to nonlinear optics. Moreover, our theory can be broadened and adapted to further classes where such scattering has already been observed or is yet to be observed.