Ammonium-Binding Bifunctional Aza-Crown Ether Catalysts for Substrate-Selective Hydroxyl Functionalization.

Herein, we describe a new bifunctional macrocyclic catalyst that employs multiple weak noncovalent interactions to enable substrate-selective O-silylation of ammonium alcohols over more reactive aliphatic alcohols with up to >20:1 substrate selectivity. Our catalytic strategy merges (i) the use of crown ethers as ammonium-binding receptors and (ii) the exploitation of N-methyl imidazole as a catalytic motif. Our collective mechanistic studies reveal the importance of receptor size, conformational preorganization, and the number of hydrogen-bonding acceptor units needed to achieve high selectivity within the macrocyclic binding pocket.

Arthroscopic Primary Repair of Proximally Based Anterior Cruciate Ligament Tear With Augmentation and All-Epiphyseal Fixation.

Arthroscopic anterior cruciate ligament (ACL) reconstruction has been the gold standard of care for ACL injuries for many years. Recently, there has been growing literature and interest in arthroscopic primary ACL repair in select patients with predominantly proximally based ACL tears. This Technical Note demonstrates a surgical technique that offers an efficient minimally invasive and physeal-sparing anatomic ACL repair with all-inside internal brace augmentation that in the short term has offered good results for our patients.

Structural Elucidation and Absolute Stereochemistry for Pharma Compounds Using MicroED.

Microcrystal electron diffraction (microED) is an emerging technique for rapid crystallographic analysis of small molecule micro- and nanocrystals. In this report, we evaluate the applicability of microED to pharmaceutical compounds through the analysis of 30 samples obtained from the process and medicinal chemistry groups at Amgen Inc. Using only 40 h of microscope time, 15 of 30 crystal structures were elucidated. From these crystal structures, all chiral compounds had the correct absolute stereochemistry assigned by dynamical refinement of continuous rotation electron diffraction data, confirming dynamical refinement as a promising tool for the absolute stereochemistry determination of pharmaceutically relevant compounds.

GelBox: open-source software to improve rigor and reproducibility when analyzing gels and immunoblots.

GelBox is open-source software that was developed with the goal of enhancing rigor, reproducibility, and transparency when analyzing gels and immunoblots. It combines image adjustments (cropping, rotation, brightness, and contrast), background correction, and band-fitting in a single application. Users can also associate each lane in an image with metadata (for example, sample type). GelBox data files integrate the raw data, supplied metadata, image adjustments, and band-level analyses in a single file to improve traceability. GelBox has a user-friendly interface and was developed using MATLAB. The software, installation instructions, and tutorials, are available at https://campbell-muscle-lab.github.io/GelBox/.NEW & NOTEWORTHY GelBox is open-source software that was developed to enhance rigor, reproducibility, and transparency when analyzing gels and immunoblots. It combines image adjustments (cropping, rotation, brightness, and contrast), background correction, and band-fitting in a single application. Users can also associate each lane in an image with metadata (for example, sample type).

DNA methylation analysis reveals local changes in resistant and susceptible soybean lines in response to Phytophthora sansomeana.

Phytophthora sansomeana is an emerging oomycete pathogen causing root rot in many agricultural species including soybean. However, as of now, only one potential resistance gene has been identified in soybean, and our understanding of how genetic and epigenetic regulation in soybean contributes to responses against this pathogen remains largely unknown. In this study, we performed whole genome bisulfite sequencing (WGBS) on two soybean lines, Colfax (resistant) and Williams 82 (susceptible), in response to P. sansomeana at two time points: 4 and 16 hours post-inoculation to compare their methylation changes. Our findings revealed that there were no significant changes in genome-wide CG, CHG (H = A, T, or C), and CHH methylation. However, we observed local methylation changes, specially an increase in CHH methylation around genes and transposable elements (TEs) after inoculation, which occurred earlier in the susceptible line and later in the resistant line. After inoculation, we identified differentially methylated regions (DMRs) in both Colfax and Williams 82, with a predominant presence in TEs. Notably, our data also indicated that more TEs exhibited changes in their methylomes in the susceptible line compared to the resistant line. Furthermore, we discovered 837 DMRs within or flanking 772 differentially expressed genes (DEGs) in Colfax and 166 DMRs within or flanking 138 DEGs in Williams 82. These DEGs had diverse functions, with Colfax primarily showing involvement in metabolic process, defense response, plant and pathogen interaction, anion and nucleotide binding, and catalytic activity, while Williams 82 exhibited a significant association with photosynthesis. These findings suggest distinct molecular responses to P. sansomeana infection in the resistant and susceptible soybean lines.

Racial and Ethnic Variations in Resilience Factors Among Sexual and Gender Minority Midlife and Older Adults.

BACKGROUND AND OBJECTIVES: This study explores resilience factors among sexual and gender minority (SGM) midlife and older adults, identifying historical/environmental, psychological, social, and behavioral predictors, and examining variations across racial/ethnic subgroups. By adopting a resilience-focused perspective, this research contributes to understanding strengths in the SGM community in the context of aging. RESEARCH DESIGN AND METHODS: Using weighted survey data from Aging with Pride: National Health, Aging, and Sexuality/Gender Study, this research investigates distinct risk and protective factors associated with resilience among SGM midlife and older adults. Subgroup variations were assessed using regression models. Factors moderated by race/ethnicity were integrated into final interaction models. RESULTS: Hispanic and Black individuals showed significantly higher resilience than non-Hispanic Whites. Lifetime victimization and day-to-day discrimination were negatively associated with resilience. Positive associations were found for higher income, identity affirmation, larger network size, greater social participation, increased physical activity, and sufficient food intake. Interaction models revealed nuanced patterns by subgroups; education negatively impacted resilience among Black individuals, while income positively influenced Hispanic individuals' resilience. The Other racial/ethnic group demonstrated unique associations between optimal sleep and resilience. DISCUSSION AND IMPLICATIONS: This study shifts from a deficit-based to a resilience-focused approach among SGM midlife and older adults, revealing key strengths within diverse subgroups. Results underscore the significance of recognizing racial/ethnic differences in factors promoting resilience and posing risks for SGM midlife and older adults. Tailoring interventions to address the intersectional needs of SGM aging populations is essential for enhancing their abilities to bounce back from adverse events.

Transinfection of Wolbachia wAlbB into Culex quinquefasciatus mosquitoes does not alter vector competence for Hawaiian avian malaria (Plasmodium relictum GRW4).

Avian malaria is expanding upslope with warmer temperatures and driving multiple species of Hawaiian birds towards extinction. Methods to reduce malaria transmission are urgently needed to prevent further declines. Releasing Wolbachia-infected incompatible male mosquitoes could suppress mosquito populations and releasing Wolbachia-infected female mosquitoes (or both sexes) could reduce pathogen transmission if the Wolbachia strain reduced vector competence. We cleared Culex quinquefasciatus of their natural Wolbachia pipientis wPip infection and transinfected them with Wolbachia wAlbB isolated from Aedes albopictus. We show that wAlbB infection was transmitted transovarially, and demonstrate cytoplasmic incompatibility with wild-type mosquitoes infected with wPip from Oahu and Maui, Hawaii. We measured vector competence for avian malaria, Plasmodium relictum, lineage GRW4, of seven mosquito lines (two with wAlbB; three with natural wPip infection, and two cleared of Wolbachia infection) by allowing them to feed on canaries infected with recently collected field isolates of Hawaiian P. relictum. We tested 73 groups (Ntotal = 1176) of mosquitoes for P. relictum infection in abdomens and thoraxes 6-14 days after feeding on a range of parasitemias from 0.028% to 2.49%, as well as a smaller subset of salivary glands. We found no measurable effect of Wolbachia on any endpoint, but strong effects of parasitemia, days post feeding, and mosquito strain on both abdomen and thorax infection prevalence. These results suggest that releasing male wAlbB-infected C. quinquefasciatus mosquitoes could suppress wPip-infected mosquito populations, but would have little positive or negative impact on mosquito vector competence for P. relictum if wAlbB became established in local mosquito populations. More broadly, the lack of Wolbachia effects on vector competence we observed highlights the variable impacts of both native and transinfected Wolbachia infections in mosquitoes.

Resiliency Does Not Correlate With Outcome Scores After Meniscectomy.

BACKGROUND: Resilience is a psychometric parameter defined as one's ability to recover or bounce back from stressful events and has been shown to correlate with better outcomes following multiple orthopedic procedures. The purpose of this study was to analyze the correlation between resiliency, as measured using the Brief Resiliency Scale (BRS) and various knee outcome scores, including the International Knee Documentation Committee (IKDC), Lysholm, Single Assessment Numeric Evaluation (SANE), and Return to Work, following isolated partial meniscectomy. METHODS: One hundred patients who had undergone an isolated partial meniscectomy during a 3-year period at a single institution were successfully recruited to participate in the study. The BRS and knee outcome scores (IKDC, Lysholm, SANE, Return to Work) were obtained via phone. Radiographs for each patient were obtained and graded for arthritis severity using the Kellgren-Lawrence classification system. RESULTS: Brief Resiliency Scale scores ranged 15.0 to 23.0 with a mean of 18.2 ± 1.3. Mean knee outcome scores for IKDC, Lysholm, SANE, and Return to Work were 66.3, 77.1, 70.6, and 41.0, respectively. Outcome scores did not correlate with BRS scores. The severe arthritis group significantly correlated (p < 0.05) with worse IKDC, Lysholm, and Return to Work scores compared to mild arthritis scores. Additionally, analysis of the mild arthritis group revealed that resiliency significantly correlated with higher Return to Work scores compared to low resilience groups. CONCLUSION: This study suggests that there is no significant relationship between patient resiliency and outcomes following partial meniscectomy. However, those with poorer outcomes had more severe arthritis.

Prevalence, awareness, treatment, and control of hypertension in community-dwelling older adults with chronic kidney disease: the Irish longitudinal study on ageing.

Background: Hypertension is highly prevalent in chronic kidney disease (CKD), posing a significant but modifiable risk for adverse clinical outcomes. This study explored the prevalence, awareness, treatment, and control of hypertension in older Irish adults with CKD. Methods: Data were analysed from participants in Wave 1 of The Irish Longitudinal Study on Ageing (TILDA) who were aged 50 years and older. CKD was defined as eGFR <60 ml/min/1.72 m2, hypertension defined as systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg and/or self-reported use of antihypertensive medication. Participant awareness and treatment of hypertension was based on self-report and SBP/DBP <140/90 mmHg. Multivariable logistic regression examined relationships with awareness, treatment, and control of hypertension expressed as adjusted odds ratios. Results: Prevalence of hypertension was significantly higher in participants with CKD than without (81.9% vs 59.7%, P < .001). Among hypertensive individuals, 70.1% (95% CI: 65.8-74.1) were aware, 83.5% (95% CI 80.0-86.6) were on treatment, yet blood pressure control <140/90 mmHg and SBP <120 mmHg were achieved in only 49.3% (CI 44.0-54.7%) and 17.9% (CI 14.4-22.1), respectively. In multivariable analysis, advancing age 1.05 (CI 1.01-1.10), obesity 6.23 (CI 2.51-15.5), diabetes 5.78 (CI 1.55-21.5), and cardiovascular disease 9.89 (CI 3.27-29.9) were associated with higher odds of treatment, while cardiovascular disease 2.35 (CI 1.39-3.99) and combination antihypertensive therapy 1.76 (CI 1.03-3.01) were associated with blood pressure control. Conclusion: The prevalence of hypertension is substantial in older Irish adults with CKD; however, control is poor. Approximately, one-third of participants were unaware of their hypertensive status and approximately one-fifth were untreated.

Engineered uterine primary myometrial cells with high-mobility group AT-hook 2 overexpression display a leiomyoma-like transcriptional and epigenomic phenotype.

OBJECTIVE: To determine if engineered high-mobility group AT-hook 2 (HMGA2) overexpressing uterine primary myometrial cells recapitulate the transcriptional and epigenomic features of HMGA2-subtype leiomyomas. DESIGN: Isolated primary, "normal" myometrial cells from three patients were engineered to overexpress HMGA2 to determine how HMGA2 establishes transcriptomic and epigenomic features of HMGA2-overexpressing leiomyoma. SETTING: Academic research laboratory. PATIENT(S): Primary myometrial cells were isolated from normal myometrium obtained from three patients undergoing hysterectomy. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Determined genome-wide transcriptomic and epigenomic features of engineered HMGA2-overexpressing uterine primary myometrial cells. RESULT(S): Engineered HMGA2-V5-overexpressing primary myometrial cells approximated the HMGA2 expression level observed in HMGA2-overexpression subtype leiomyoma. High-mobility group AT-hook 2-V5 expression resulted in differential expression of 1,612 genes (false discovery rate [FDR] < 0.05) that were found to be enriched in pathways associated with leiomyoma formation, including extracellular matrix organization. Comparative gene expression analysis between HMGA2-V5 engineered primary cells and HMGA2-overexpression subtype leiomyoma revealed significant overlap of differentially expressed genes. Mechanistically, HMGA2-V5 overexpression resulted in 41,323 regions with differential H3K27ac deposition (FDR < 0.05) and 205,605 regions of altered chromatin accessibility (FDR < 0.05). Transcription factor binding site analysis implicated the AP-1 family of transcription factors. CONCLUSION(S): High-mobility group AT-hook 2 overexpression induces leiomyoma-like transcriptomic and epigenomic modulations in myometrial cells.

Transcriptomic and epigenetic responses shed light on soybean resistance to Phytophthora sansomeana.

Phytophthora root rot, caused by oomycete pathogens in the Phytophthora genus, poses a significant threat to soybean productivity. While resistance mechanisms against Phytophthora sojae have been extensively studied in soybean, the molecular basis underlying immune responses to Phytophthora sansomeana remains unclear. In this study, we investigated transcriptomic and epigenetic responses of two resistant (Colfax and NE2701) and two susceptible (Williams 82 and Senaki) soybean lines at four time points (2, 4, 8, and 16 h post inoculation [hpi]) after P. sansomeana inoculation. Comparative transcriptomic analyses revealed a greater number of differentially expressed genes (DEGs) upon pathogen inoculation in resistant lines, particularly at 8 and 16 hpi. These DEGs were predominantly associated with defense response, ethylene, and reactive oxygen species-mediated defense pathways. Moreover, DE transposons were predominantly upregulated after inoculation, and more of them were enriched near genes in Colfax than other soybean lines. Notably, we identified a long non-coding RNA (lncRNA) within the mapped region of the resistance gene that exhibited exclusive upregulation in the resistant lines after inoculation, potentially regulating two flanking LURP-one-related genes. Furthermore, DNA methylation analysis revealed increased CHH (where H = A, T, or C) methylation levels in lncRNAs after inoculation, with delayed responses in Colfax compared to Williams 82. Overall, our results provide comprehensive insights into soybean responses to P. sansomeana, highlighting potential roles of lncRNAs and epigenetic regulation in plant defense.

Prioritising Key Concepts for informed health choices in cancer: An evidence-based online educational programme.

Objective: The overabundance of health misinformation has undermined people's capacity to make evidence-based, informed choices about their health. Using the Informed Health Choices (IHC) Key Concepts (KCs), we are developing a two-stage education programme, Informed Health Choices-Cancer (IHC-C), to provide those impacted by cancer with the knowledge and skills necessary to think critically about the reliability of health information and claims and make well-informed choices. Stage 1 seeks to prioritise the most relevant Key Concepts. Methods: A project group and a patient and carer participation group completed a two-round prioritisation process. The process involved disseminating pre-reading materials, training sessions, and a structured judgement form to evaluate concepts for inclusion. Data from each round were analysed to reach a consensus on the concepts to include. Results: Fourteen participants were recruited and completed the first-round prioritisation. Fifteen participants undertook the second-round prioritisation. Nine Key Concepts were selected for the programme across five training sessions and two consensus meetings. Conclusion: The prioritised concepts identified represent the most pertinent aspects of cancer-related information for those impacted by the disease. By incorporating these concepts into educational materials and communication strategies, healthcare providers and organisations can potentially help cancer patients, survivors, and their loved ones to recognise and combat cancer-related misinformation more effectively. Innovation: This study introduces a participatory prioritisation process, which integrates the expertise of healthcare professionals with the insights of patients and carers, thereby enhancing the programme's relevance and applicability.

Dual-Function Alloying Nitrate Additives Stabilize Fast-Charging Lithium Metal Batteries.

Lithium metal is regarded as the "holy grail" of lithium-ion battery anodes due to its exceptionally high theoretical capacity (3800 mAh g-1) and lowest possible electrochemical potential (-3.04 V vs Li/Li+); however, lithium suffers from the dendritic formation that leads to parasitic reactions and cell failure. In this work, we stabilize fast-charging lithium metal plating/stripping with dual-function alloying M-nitrate additives (M: Ag, Bi, Ga, In, and Zn). First, lithium metal reduces M, forming lithiophilic alloys for dense Li nucleation. Additionally, nitrates form ionically conductive and mechanically stable Li3N and LiNxOy, enhancing Li-ion diffusion through the passivation layer. Notably, Zn-protected cells demonstrate electrochemically stable Li||Li cycling for 750+ cycles (2.0 mA cm-2) and 140 cycles (10.0 mA cm-2). Moreover, Zn-protected Li||Lithium Iron Phosphate full-cells achieve 134 mAh g-1 (89.2% capacity retention) after 400 cycles (C/2). This work investigates a promising solution to stabilize lithium metal plating/stripping for fast-charging lithium metal batteries.

Phase 3 randomized COMMODORE 1 trial: Crovalimab versus eculizumab in complement inhibitor-experienced patients with paroxysmal nocturnal hemoglobinuria.

Crovalimab, a novel C5 inhibitor, allows for low-volume, every-4- week, subcutaneous self-administration. COMMODORE 1 (NCT04432584) is a phase 3, global, randomized trial evaluating crovalimab versus eculizumab in C5 inhibitor-experienced patients with paroxysmal nocturnal hemoglobinuria (PNH). Adults with lactate dehydrogenase ≤1.5 × upper limit of normal and receiving approved eculizumab doses for ≥24 weeks were randomized 1:1 to receive crovalimab (weight-based tiered dosing) or continue eculizumab. The original primary study objective was efficacy; however, given the evolving treatment landscape, target recruitment was not met, and all efficacy endpoints became exploratory, with safety as the new primary objective. Exploratory efficacy endpoints included transfusion avoidance, hemolysis control, breakthrough hemolysis, hemoglobin stabilization, FACIT-Fatigue score, and patient preference (crovalimab vs. eculizumab). Eighty-nine patients were randomized (45 to crovalimab; 44 to eculizumab). During the 24-week primary treatment period, adverse events (AEs) occurred in 77% of patients receiving crovalimab and 67% receiving eculizumab. No AEs led to treatment withdrawal or death, and no meningococcal infections occurred. 16% of crovalimab-treated patients had transient immune complex reactions (also known as Type III hypersensitivity events), an expected risk when switching between C5 inhibitors that bind to different C5 epitopes; most were mild/moderate and all resolved without treatment modification. Crovalimab-treated patients had sustained terminal complement activity inhibition, maintained disease control, and 85% preferred crovalimab over eculizumab. Together with phase 3 COMMODORE 2 results in complement inhibitor-naive patients, these data support crovalimab's favorable benefit-risk profile. Crovalimab is a new C5 inhibitor for PNH that is potentially less burdensome than existing therapies for this lifelong disease.

Complete genome sequence of a Pseudomonas fluorescens bacteriophage UNO-G1W1 isolated from freshwater ice in Nebraska.

We provide the complete genome sequence for a novel Pseudomonas fluorescens bacteriophage named UNO-G1W1. This phage was isolated from a single ice cover sampling. The genome was sequenced on the Nanopore MinION, generated with the direct terminal repeat-phage-pipeline and polished with Illumina short reads. Sequence identity classifies the phage as an otagovirus.

Spectroscopy in Nanoscopic Cavities: Models and Recent Experiments.

The ability of nanophotonic cavities to confine and store light to nanoscale dimensions has important implications for enhancing molecular, excitonic, phononic, and plasmonic optical responses. Spectroscopic signatures of processes that are ordinarily exceedingly weak such as pure absorption and Raman scattering have been brought to the single-particle limit of detection, while new emergent polaritonic states of optical matter have been realized through coupling material and photonic cavity degrees of freedom across a wide range of experimentally accessible interaction strengths. In this review, we discuss both optical and electron beam spectroscopies of cavity-coupled material systems in weak, strong, and ultrastrong coupling regimes, providing a theoretical basis for understanding the physics inherent to each while highlighting recent experimental advances and exciting future directions.

Alleviating nanostructural phase impurities enhances the optoelectronic properties, device performance and stability of cesium-formamidinium metal-halide perovskites.

The technique of alloying FA+ with Cs+ is often used to promote structural stabilization of the desirable α-FAPbI3 phase in halide perovskite devices. However, the precise mechanisms by which these alloying approaches improve the optoelectronic quality and enhance the stability have remained elusive. In this study, we advance that understanding by investigating the effect of cationic alloying in CsxFA1-xPbI3 perovskite thin-films and solar-cell devices. Selected-area electron diffraction patterns combined with microwave conductivity measurements reveal that fine Cs+ tuning (Cs0.15FA0.85PbI3) leads to a minimization of stacking faults and an increase in the photoconductivity of the perovskite films. Ultra-sensitive external quantum efficiency, kelvin-probe force microscopy and photoluminescence quantum yield measurements demonstrate similar Urbach energy values, comparable surface potential fluctuations and marginal impact on radiative emission yields, respectively, irrespective of Cs content. Despite this, these nanoscopic defects appear to have a detrimental impact on inter-grains'/domains' carrier transport, as evidenced by conductive-atomic force microscopy and corroborated by drastically reduced solar cell performance. Importantly, encapsulated Cs0.15FA0.85PbI3 devices show robust operational stability retaining 85% of the initial steady-state power conversion efficiency for 1400 hours under continuous 1 sun illumination at 35 °C, in open-circuit conditions. Our findings provide nuance to the famous defect tolerance of halide perovskites while providing solid evidence about the detrimental impact of these subtle structural imperfections on the long-term operational stability.

Addressing Equity and Justice in Age-Friendly Communities: Considerations for LGBTQ+ Older Adults of Color.

BACKGROUND AND OBJECTIVES: This research critically examined the concept of age-friendliness from the perspectives of older Black lesbian women living in New York City (NYC). The primary aim was to extend existing age-friendly frameworks to more inclusively meet the needs of older lesbian, gay, bisexual, transgender, and queer adults of color, promoting greater equity and justice. RESEARCH DESIGN AND METHODS: Applying principles from critical participatory action research, we collected and analyzed data from 5 focus groups consisting of 5 older Black lesbian women. Participants shared their daily experiences living in NYC and proposed ideas to enhance the age-friendliness of the city to better accommodate their unique needs and experiences. RESULTS: Participants called for greater attention to the interaction between identities and structures in relation to age-friendly communities. Historic and contemporary experiences of violence and discrimination, as well as the ever-shifting political context were identified as a key factor shaping their aging experiences. The need for affirming spaces with positive representation of their layered identities was emphasized in the context of age-friendly interventions. DISCUSSION AND IMPLICATIONS: While dominant age-friendly frameworks are universally accepted for improving the health and wellbeing of older adults, the specific challenges of aging with multiple intersecting marginalized identities necessitate a critical perspective. Gerontology needs to take seriously how privilege and oppression operate within society, shaping health and aging trajectories of vulnerable and underserved populations.