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Abstract Background With the rise of the triple burden of malnutrition, the changing nutrition situation in Sub-Saharan Africa may be associated with changes in pubertal timing of adolescents. The purpose of this review was to summarize the association between nutritional status and pubertal milestones among children in SSA. Method A search of publications was conducted in PubMed and Scopus on 1st April 2023. Observational studies with children aged 0 to 22 years, that reported nutritional status and association with pubertal milestones in SSA were selected for review. Risk of bias was assessed using the NOS and results were presented using the PRISMA. Results Twenty-three studies published from 1992 to 2021 reporting data from nine countries and a total of 21,853 children were included in this review. Mean menarche age relative to nutritional status varied from 17.2 years in stunted adolescents in Senegal to 13.3 (in the underweight), 13.9 (in normal weight girls), and 14.1 (in overweight girls) years in adolescents in Ethiopia. Adolescents who were not stunted in Kenya and those with higher height-for-age z-scores (HAZ) and body mass index (BMI) in South Africa had more advanced breast development. Pubic hair development was positively associated with HAZ and BMI z-scores (BMIZ) at 5 years in South Africa and overweight and obesity in adolescents in Nigeria. Attainment of voice break in adolescent boys in Nigeria was associated with lower likelihood of stunting and underweight. In a study in Zambia, earlier onset and more rapid progression of genital development assessed by testicular volume in boys was associated with increased height and arm muscle. Conclusions Higher BMI, height, weight, and triceps skinfolds are significantly associated with advanced pubertal development in SSA. In SSA, less than one-third of the countries have published any research studies on nutritional status and pubertal milestones. Future studies should focus on detailed assessment of pubertal development and associated nutritional factors in both male and female adolescents in SSA. PROSPERO registration CRD42022350048.

Abstract The mental health impacts of climate change are increasingly documented; however, less research has investigated the relationship between climate change-related psychological distress and engagement with the issue. The results from two national probability samples of U.S. adults show that 16% report at least one feature of climate change psychological distress and that certain groups have higher levels of distress than others (e.g., Hispanic/Latinos, lower income adults, younger adults). Importantly, people experiencing distress are more likely to engage in collective action on climate change or express a willingness to do so, even when controlling for several correlates of environmental behavior (e.g., political ideology, collective efficacy beliefs). These findings highlight that many Americans are experiencing psychological distress from climate change, and those who do are more involved in collective climate action. People experiencing such distress may benefit from resources to support mental health and engagement with climate change.

Abstract Background Cancer continues to pose a significant threat to human well-being due to the overwhelming rate of morbidity and mortality associated with it. Hence, the quest for newer, effective and safer anticancer agents has become more crucial. Over the years, some medicinal plants have been used to treat abnormal tissue growths (tumours) in Ghana. Even though sufficient literature points out that people found some relief in their use, there is limited scientific evidence of their antiproliferative activities. Method Ethanolic extracts of nine medicinal plant materials from seven plant species, including the stem bark of Terminalia superba, Talbotiella gentii and Ceiba pentandra and the leaves of Morinda lucida, Dracaena arborea, Dioscorea dumetorum, Thaumatococcus danielli, Ceiba pentandra and Talbotiella gentii, were evaluated for antiproliferative activities against four human cancer cell lines (hepatocellular carcinoma, colorectal adenocarcinoma, cervical carcinoma, and mammary adenocarcinoma) using an MTT-based assay. Results The extract of C. pentandra leaves, exhibited generally higher antiproliferative activity, which was particularly substantial against human hepatocellular carcinoma (HepG2) cells (IC50 = 16.3 µg/mL) and human colorectal adenocarcinoma (RKO) cells (IC50 = 18.7 µg/mL). All the other plant materials demonstrated weak (IC50: 201–500 µg/mL) to moderate (IC50: 21–200 µg/mL) antiproliferative activities against the four cancer cell lines. Conclusion The extracts of the plant materials demonstrated varied antiproliferative activities. Extract of C. pentandra leaves exhibited the highest antiproliferative activity. The IC50 values of C. pentandra leaves met the benchmark to be considered effective against HepG2 and RKO cancer cell lines in particular. Therefore, there is the need to further undertake fractionation work on C. pentandra leaves. The antiproliferative effect of extract of C. pentandra leaves against other cancer cell lines and normal cell line could also be explored in the future to ascertain the anticancer potential of this plant material. Generally, findings from this work support the indigenous use of these plant materials in treating abnormal tissue growth in Ghana.

Abstract Background Trauma can result in systemic inflammation that leads to organ dysfunction, but the impact on the brain, particularly following extracranial insults, has been largely overlooked. Methods Building upon our prior findings, we aimed to understand the impact of systemic inflammation on neuroinflammatory gene transcripts in eight brain regions in rats exposed to (1) blast overpressure exposure [BOP], (2) cutaneous thermal injury [BU], (3) complex extremity injury, 3 hours (h) of tourniquet-induced ischemia, and hind limb amputation [CEI+tI+HLA], (4) BOP+BU or (5) BOP+CEI and delayed HLA [BOP+CEI+dHLA] at 6, 24, and 168 h post-injury (hpi). Results Globally, the number and magnitude of differentially expressed genes (DEGs) correlated with injury severity, systemic inflammation markers, and end-organ damage, driven by several chemokines/cytokines (Csf3, Cxcr2, Il16, and Tgfb2), neurosteroids/prostaglandins (Cyp19a1, Ptger2, and Ptger3), and markers of neurodegeneration (Gfap, Grin2b, and Homer1). Regional neuroinflammatory activity was least impacted following BOP. Non-blast trauma (in the BU and CEI+tI+HLA groups) contributed to an earlier, robust and diverse neuroinflammatory response across brain regions (up to 2–50-fold greater than that in the BOP group), while combined trauma (in the BOP+CEI+dHLA group) significantly advanced neuroinflammation in all regions except for the cerebellum. In contrast, BOP+BU resulted in differential activity of several critical neuroinflammatory-neurodegenerative markers compared to BU. t-SNE plots of DEGs demonstrated that the onset, extent, and duration of the inflammatory response are brain region dependent. Regardless of injury type, the thalamus and hypothalamus, which are critical for maintaining homeostasis, had the most DEGs. Our results indicate that neuroinflammation in all groups progressively increased or remained at peak levels over the study duration, while markers of end-organ dysfunction decreased or otherwise resolved. Conclusions Collectively, these findings emphasize the brain's sensitivity to mediators of systemic inflammation and provide an example of immune-brain crosstalk. Follow-on molecular and behavioral investigations are warranted to understand the short- to long-term pathophysiological consequences on the brain, particularly the mechanism of blood–brain barrier breakdown, immune cell penetration–activation, and microglial activation.

Abstract Impairments in somatosensory function are a common and often debilitating consequence of neurological injury, with few effective interventions. Building on success in rehabilitation for motor dysfunction, the delivery of vagus nerve stimulation (VNS) combined with tactile rehabilitation has emerged as a potential approach to enhance recovery of somatosensation. In order to maximize the effectiveness of VNS therapy and promote translation to clinical implementation, we sought to optimize the stimulation paradigm and identify neural mechanisms that underlie VNS-dependent recovery. To do so, we characterized the effect of tactile rehabilitation combined with VNS across a range of stimulation intensities on recovery of somatosensory function in a rat model of chronic sensory loss in the forelimb. Consistent with previous studies in other applications, we find that moderate intensity VNS yields the most effective restoration of somatosensation, and both lower and higher VNS intensities fail to enhance recovery compared to rehabilitation without VNS. We next used the optimized, moderate intensity to evaluate the mechanisms that underlie recovery. We find that moderate intensity VNS enhances transcription of Arc, a canonical mediator of synaptic plasticity, in the cortex, and that transcript levels were correlated with the degree of somatosensory recovery. Moreover, we observe that blocking plasticity by depleting acetylcholine in the cortex prevents the VNS-dependent enhancement of somatosensory recovery. Collectively, these findings identify neural mechanisms that subserve VNS-dependent somatosensation recovery and provide a basis for selecting optimal stimulation parameters in order to facilitate translation of this potential intervention.

Abstract Background Administrative healthcare databases, such as Medicare, are increasingly used to identify groups at risk of a crash. However, they only contain information on crash-related injuries, not all crashes. If the driver characteristics associated with crash and crash-related injury differ, conflating the two may result in ineffective or imprecise policy interventions. Methods We linked 10 years (2008–2017) of Medicare claims to New Jersey police crash reports to compare the demographics, clinical diagnoses, and prescription drug dispensings for crash-involved drivers ≥ 68 years with a police-reported crash to those with a claim for a crash-related injury. We calculated standardized mean differences to compare characteristics between groups. Results Crash-involved drivers with a Medicare claim for an injury were more likely than those with a police-reported crash to be female (62.4% vs. 51.8%, standardized mean difference [SMD] = 0.30), had more clinical diagnoses including Alzheimer’s disease and related dementias (13.0% vs. 9.2%, SMD = 0.20) and rheumatoid arthritis/osteoarthritis (69.5% vs 61.4%, SMD = 0.20), and a higher rate of dispensing for opioids (33.8% vs 27.6%, SMD = 0.18) and antiepileptics (12.9% vs 9.6%, SMD = 0.14) prior to the crash. Despite documented inconsistencies in coding practices, findings were robust when restricted to claims indicating the injured party was the driver or was left unspecified. Conclusions To identify effective mechanisms for reducing morbidity and mortality from crashes, researchers should consider augmenting administrative datasets with information from police crash reports, and vice versa. When those data are not available, we caution researchers and policymakers against the tendency to conflate crash and crash-related injury when interpreting their findings.

Abstract Learning new skills requires neuroplasticity. Vagus nerve stimulation (VNS) during sensory and motor events can increase neuroplasticity in networks related to these events and might therefore serve to facilitate learning on sensory and motor tasks. We tested if VNS could broadly improve learning on a wide variety of tasks across different skill domains in healthy, female adult rats. VNS was paired with presentation of stimuli or on successful trials during training, strategies known to facilitate plasticity and improve recovery in models of neurological disorders. VNS failed to improve either rate of learning or performance for any of the tested tasks, which included skilled forelimb motor control, speech sound discrimination, and paired-associates learning. These results contrast recent findings from multiple labs which found VNS pairing during training produced learning enhancements across motor, auditory, and cognitive domains. We speculate that these contrasting results may be explained by key differences in task designs, training timelines and animal handling approaches, and that while VNS may be able to facilitate rapid and early learning processes in healthy subjects, it does not broadly enhance learning for difficult tasks.

Accurately predicting a fetus’s gestational age (GA) is crucial in prenatal care. This study aimed to develop an artificial intelligence (AI) model to predict GA using biometric measurements from fetal brain magnetic resonance imaging (MRI). We assessed the significance of using different reference standards for interpreting GA predictions. Measurements of biparietal diameter (BPD), fronto-occipital diameter (FOD), and head circumference (HC) were obtained from 52 normal fetal MRI cases from Rush University. Both manual and AI-based methods were utilized, and comparisons were made using three reference standards (Garel, Freq, and Bio). The AI model showed a strong correlation with manual measurements, particularly for HC, which exhibited the highest correlation with actual values. Differences between GA predictions and picture archiving and communication system (PACS) records varied by reference, ranging from 0.47 to 2.17 weeks for BPD, 0.46 to 2.26 weeks for FOD, and 0.75 to 1.74 weeks for HC. Pearson correlation coefficients between PACS records and GA predictions exceeded 0.97 across all references. In conclusion, the AI model demonstrated high accuracy in predicting GA from fetal brain MRI measurements. This approach offers improved accuracy and convenience over manual methods, highlighting the potential of AI in enhancing prenatal care through precise GA estimation.

Background: The treatment of BRAF V600E gliomas with BRAF inhibitors (BRAFis) and MEK inhibitors (MEKis) has been increasingly integrated into clinical practice for pediatric low-grade gliomas (PLGGs) and pediatric high-grade gliomas (HGGs). However, some questions remain unanswered, such as the best time to start targeted therapy, duration of treatment, and discontinuation of therapy. Given that no clinical trial has been able to address these critical questions, we developed a Canadian Consensus statement for the treatment of BRAF V600E mutated pediatric as well as adolescent and young adult (AYA) gliomas. Methods: Canadian neuro-oncologists were invited to participate in the development of this consensus. The consensus was discussed during monthly web-based national meetings, and the algorithms were revised until a consensus was achieved. Results: A total of 26 participants were involved in the development of the algorithms. Two treatment algorithms are proposed, one for the initiation of treatment and one for the discontinuation of treatment. We suggest that most patients with BRAF V600E gliomas should be treated with BRAFis ± MEKis upfront. Discontinuation of treatment can be considered in certain circumstances, and we suggest a slow wean. Conclusions: Based on expert consensus in Canada, we developed algorithms for treatment initiation of children and AYA with BRAF V600E gliomas as well as a discontinuation algorithm.

Abstract In low- and middle-income countries, indoor air pollution (IAP) is a serious public health concern, especially for women and children who cook with solid fuels. IAP exposure has been linked to a number of medical conditions, including pneumonia, ischemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lung cancer, and anaemia. Around 500 million women of reproductive age (WRA) suffer from anaemia globally, with an estimated 190 million cases in sub-Saharan Africa (SSA). This study, which is based on prior research, investigates the relationship between IAP exposure and anaemia among WRA in Ghana. A diverse sample of 2,406 WRA living in Ghana were interviewed, of which 58.06% were anaemic and used high-pollutant fuels for cooking. Age, place of residence, region, education level, religion, ethnicity, wealth index, type of drinking water, type of toilet facility, and type of cooking fuels were all found to be significantly linked with anaemic state by bivariate analysis. Type of cooking fuels utilized, age, region of residence, and the type of residence were shown to be significant predictors of anaemia status using sequential binary logit regression models. The results emphasise the critical need for efforts to promote the usage of clean cooking fuel in an attempt to lower anaemia prevalence in Ghana. To reduce dependency on solid fuels for cooking, initiatives should promote the use of cleaner cooking fuels and enhance the socioeconomic status of households. These interventions could have significant public health effects by reducing the burden of anaemia and improving maternal and child health outcomes due to the prevalence of anaemia among WRA. Overall, this study sheds light on the relationship between IAP exposure and anaemia in Ghana and highlights the demand for focused public health initiatives to address this serious health problem.

Abstract Background Several studies have been conducted with the 1.0 version of the Hospital Survey on Patient Safety Culture (HSOPSC) in Norway and globally. The 2.0 version has not been translated and tested in Norwegian hospital settings. This study aims to 1) assess the psychometrics of the Norwegian version (N-HSOPSC 2.0), and 2) assess the criterion validity of the N-HSOPSC 2.0, adding two more outcomes, namely ‘pleasure of work’ and ‘turnover intention’. Methods The HSOPSC 2.0 was translated using a sequential translation process. A convenience sample was used, inviting hospital staff from two hospitals (N = 1002) to participate in a cross-sectional questionnaire study. Data were analyzed using Mplus. The construct validity was tested with confirmatory factor analysis (CFA). Convergent validity was tested using Average Variance Explained (AVE), and internal consistency was tested with composite reliability (CR) and Cronbach’s alpha. Criterion related validity was tested with multiple linear regression. Results The overall statistical results using the N-HSOPSC 2.0 indicate that the model fit based on CFA was acceptable. Five of the N-HSOPSC 2.0 dimensions had AVE scores below the 0.5 criterium. The CR criterium was meet on all dimensions except Teamwork (0.61). However, Teamwork was one of the most important and significant predictors of the outcomes. Regression models explained most variance related to patient safety rating (adjusted R2 = 0.38), followed by ‘turnover intention’ (adjusted R2 = 0.22), ‘pleasure at work’ (adjusted R2 = 0.14), and lastly, ‘number of reported events’ (adjusted R2=0.06). Conclusion The N-HSOPSC 2.0 had acceptable construct validity and internal consistency when translated to Norwegian and tested among Norwegian staff in two hospitals. Hence, the instrument is appropriate for use in Norwegian hospital settings. The ten dimensions predicted most variance related to ‘overall patient safety’, and less related to ‘number of reported events’. In addition, the safety culture dimensions predicted ‘pleasure at work’ and ‘turnover intention’, which is not part of the original instrument.

Abstract Excitons in two-dimensional (2D) semiconductors have offered an attractive platform for optoelectronic and valleytronic devices. Further realizations of correlated phases of excitons promise device concepts not possible in the single particle picture. Here we report tunable exciton “spin” orders in WSe2/WS2 moiré superlattices. We find evidence of an in-plane (xy) order of exciton “spin”—here, valley pseudospin—around exciton filling v ex = 1, which strongly suppresses the out-of-plane “spin” polarization. Upon increasing v ex or applying a small magnetic field of ~10 mT, it transitions into an out-of-plane ferromagnetic (FM-z) spin order that spontaneously enhances the “spin” polarization, i.e., the circular helicity of emission light is higher than the excitation. The phase diagram is qualitatively captured by a spin-1/2 Bose–Hubbard model and is distinct from the fermion case. Our study paves the way for engineering exotic phases of matter from correlated spinor bosons, opening the door to a host of unconventional quantum devices.

Abstract Background Prey are more vulnerable during migration due to decreased familiarity with their surroundings and spatially concentrated movements. Predators may respond to increased prey vulnerability by shifting their ranges to match prey. Moose (Alces alces) and white-tailed deer (Odocoileus virginianus) are primary gray wolf (Canis lupus) prey and important subsistence species for Indigenous communities. We hypothesized wolves would increase use of ungulate migration corridors during migrations and predicted wolf distributions would overlap primary available prey. Methods We examined seasonal gray wolf, moose, and white-tailed deer movements on and near the Grand Portage Indian Reservation, Minnesota, USA. We analyzed GPS collar data during 2012–2021 using Brownian bridge movement models (BBMM) in Migration Mapper and mechanistic range shift analysis (MRSA) to estimate individual- and population-level occurrence distributions and determine the status and timing of range shifts. We estimated proportional overlap of wolf distributions with moose and deer distributions and tested for differences among seasons, prey populations, and wolf sex and pack affiliations. Results We identified a single migration corridor through which white-tailed deer synchronously departed in April and returned in October–November. Gray wolf distributions overlapped the deer migration corridor similarly year-round, but wolves altered within-range distributions seasonally corresponding to prey distributions. Seasonal wolf distributions had the greatest overlap with deer during fall migration (10 October–28 November) and greatest overlap with moose during summer (3 May–9 October). Conclusions Gray wolves did not increase their use of the white-tailed deer migration corridor but altered distributions within their territories in response to seasonal prey distributions. Greater overlap of wolves and white-tailed deer in fall may be due to greater predation success facilitated by asynchronous deer migration movements. Greater summer overlap between wolves and moose may be linked to moose calf vulnerability, American beaver (Castor canadensis) co-occurrence, and reduced deer abundance associated with migration. Our results suggest increases in predation pressure on deer in fall and moose in summer, which can inform Indigenous conservation efforts. We observed seasonal plasticity of wolf distributions suggestive of prey switching; that wolves did not exhibit migratory coupling was likely due to spatial constraints resulting from territoriality.

Nonstandard numerical approximation for the study of a competition model for two species that experience nonlocal diffusion, or dispersion, allows for faithful representation of the theoretical solution to the system. Such a scheme may preserve positivity of solutions, be uniquely solvable, and be completely stable. Under appropriate conditions, the error between the scheme and the theoretical solution can be measured. We present such a scheme here and confirm its desirable properties as they reflect the solution to the system.

The appropriateness of branding certain disaster events as a natural disaster continues to be academically debated, given that few disasters are solely the result of uncontrollable forces of nature, and are instead anthropogenic in their creation, or exacerbated by the relationship humans have with actual and potential hazards. Therefore, this socially constructed nature of disasters also makes groups that are marginalized within society, such as queer people, more vulnerable to these disasters. Utilizing a Bourdieusian framework, the field of disaster preparedness, management, and recovery is examined for queer vulnerability, which is deconstructed here as a product of global and local cultures, in their distribution of economic, social, cultural, and symbolic capital away from queer people. The concepts of habitus and subsidiary concepts of ethos and doxa are deployed to understand the ingrained ways of doing and being that perpetuate discrimination against queer individuals through said inequitable distributions of capital. It is argued that the field is privileged for heteronormative lives, thus leading to heteronormative assumptions and actions that further marginalize queer experiences before, during, and after disasters during disasters. In light of this, we call for a more social justice informed approach to disaster risk reduction and relief, in which heteronormativity is consciously decentered to ensure all groups are kept safe from disasters, which can arguably never be natural.

Abstract A combination of improved body armor, medical transportation, and treatment has led to the increased survival of warfighters from combat extremity injuries predominantly caused by blasts in modern conflicts. Despite advances, a high rate of complications such as wound infections, wound failure, amputations, and a decreased quality of life exist. To study the molecular underpinnings of wound failure, wound tissue biopsies from combat extremity injuries had RNA extracted and sequenced. Wounds were classified by colonization (colonized vs. non-colonized) and outcome (healed vs. failed) status. Differences in gene expression were investigated between timepoints at a gene level, and longitudinally by multi-gene networks, inferred proportions of immune cells, and expression of healing-related functions. Differences between wound outcomes in colonized wounds were more apparent than in non-colonized wounds. Colonized/healed wounds appeared able to mount an adaptive immune response to infection and progress beyond the inflammatory stage of healing, while colonized/failed wounds did not. Although, both colonized and non-colonized failed wounds showed increasing inferred immune and inflammatory programs, non-colonized/failed wounds progressed beyond the inflammatory stage, suggesting different mechanisms of failure dependent on colonization status. Overall, these data reveal gene expression profile differences in healing wounds that may be utilized to improve clinical treatment paradigms.

Abstract. Background:. Internal fixation of hip fractures is associated with high reoperation rates. This study investigated the reoperation rates after internal fixation with the femoral neck system (FNS). Materials and Methods:. A single-institution cohort study was conducted on patients aged 18 years or older who sustained intracapsular femoral neck fractures and underwent internal fixation with a fixed-angle implant. Surgeons, patients, and investigators were not blinded. The primary outcome was any hip reoperation at the final follow-up. Secondary outcomes were to characterize a cohort of patients regarding demographics, fracture classification, intraoperative findings, postoperative fracture complications and union rates, and postoperative pain. Results:. This study found that internal fixation with FNS for intracapsular femoral neck fractures was associated with a 23% rate of revision surgery. Of the initial 94 patients who received FNS internal fixation, 44 patients were included for analysis; of those, 10 patients underwent revision surgery. Patients had a 22% rate of in-hospital medical adverse events with a 30-day readmission rate of 9%. Increasing body mass index was associated with increased revision rates (P = 0.037). Patients who sustained displaced femoral neck fractures had a significant decrease in SF-12 Mental Health Composite, SF-12 Physical Health Composite, and quality-of-life subscale scores. Conclusions:. The FNS is a viable alternative for internal fixation of intracapsular femoral neck fractures. The observed rate of revision after internal fixation was comparable with previously published outcomes following fixation with cannulated screws and sliding hip screws. Level of Evidence:. Level IV, Therapeutic Study.

Limb Salvage procedure is now the management of choice for most musculoskeletal malignant tumors. Thanks to advances in imaging and adjuvant modalities, limb salvage has become an oncologically safe option. The purpose of this paper is to demonstrate the use of a new modular titanium nail spanning system designed and developed locally in the Philippines which consists of two interchangeable end-to-end interlocked IM nails in varying sizes and a sliding nail connector that can be locked in place with two set screws. Results have shown good outcomes. Several implants have been used to augment these spacers such as Kuntscher nails, Steinmann pins, plates, and other fixed-angle devices. The challenge lies in increasing the longevity of these constructs as the durability beyond 26 months has not been well established. We present two patients who underwent a knee resection arthrodesis for distal femur osteosarcoma and reconstruction using the Tumor Nail System. The largest and longest possible diameter nails were inserted: one antegrade through the tibia and the other retrograde through the femur. Once the connector was locked, the defect was filled with antibiotic-impregnated cement. Post-operative recovery was unremarkable and patients were able to do pain-free full weight bearing on their affected lower extremity. This implant’s advantages include its modularity, ease of insertion, secure and robust nail connector, and circumventing contamination of the hip unlike traditionally inserted Kuntscher nails. This system is a viable option for primary knee resection-arthrodesis procedures following tumor resection. Long-term follow-up is needed to establish implant durability. Further studies can also show the potential of this implant for use as an initial spacer even in non-oncologic cases.

Abstract Background and Aim Chronic hepatitis B virus (CHB) infection remains a major public health problem. The American Association for the Study of Liver Diseases (AASLD) 2018 Hepatitis B Guidelines provide that CHB individuals not requiring antiviral therapy yet are monitored to determine the need for antiviral therapy in the future; however, these tests do not include measurement of cytokines and immune cell characterization. This case‐control study compared the cytokine and immune checkpoint protein expression profiles between CHB individuals not yet on antiviral treatment and hepatitis B virus (HBV)‐negative individuals. Methods CD4 and CD8 T cells from CHB and HBV‐negative individuals were characterized for immune checkpoint proteins programmed cell death‐1 (PD1), T cell Immunoglobulin domain and mucin domain‐containing protein 3 (TIM‐3), and cytotoxic T lymphocyte‐associated antigen 4 (CTLA‐4) (CD152), and a memory marker CXCR3 (CD183) using flow cytometry. Malaria‐induced cytokine expression levels were determined by stimulating their blood cells with Plasmodium falciparum 3D7 strain antigens (CSP, AMA‐1, and TRAP) in whole blood assays, and cytokine levels were measured using a 13‐plex Luminex kit. Results HBV‐negative and CHB individuals had comparable levels of CD4+ and CD8+ T cells. However, a proportion of the CD4+ and CD8+ populations from both groups, which were CXCR3+, expressed PD‐1 and CD152. The ability to produce cytokines in response to malaria antigen stimulation was not significantly different between the groups. Conclusion These findings support excluding CHB individuals from antiviral therapy at this stage of infection. However, CHB individuals require regular monitoring to determine the need for later antiviral treatment.

Background: Hip dysplasia is considered one of the leading etiologies contributing to hip degeneration and the eventual need for total hip arthroplasty (THA). We validated a deep learning (DL) algorithm to measure angles relevant to hip dysplasia and applied this algorithm to determine the prevalence of dysplasia in a large population based on incremental radiographic cutoffs. Methods: Patients from the Osteoarthritis Initiative with anteroposterior pelvis radiographs and without previous THAs were included. A DL algorithm automated 3 angles associated with hip dysplasia: modified lateral center-edge angle (LCEA), Tönnis angle, and modified Sharp angle. The algorithm was validated against manual measurements, and all angles were measured in a cohort of 3869 patients (61.2 ± 9.2 years, 57.1% female). The percentile distributions and prevalence of dysplastic hips were analyzed using each angle. Results: The algorithm had no significant difference (P > .05) in measurements (paired difference: 0.3°-0.7°) against readers and had excellent agreement for dysplasia classification (kappa = 0.78-0.88). In 140 minutes, 23,214 measurements were automated for 3869 patients. LCEA and Sharp angles were higher and the Tönnis angle was lower (P < .01) in females. The dysplastic hip prevalence varied from 2.5% to 20% utilizing the following cutoffs: 17.3°-25.5° (LCEA), 9.4°-15.6° (Tönnis), and 41.3°-45.9° (Sharp). Conclusions: A DL algorithm was developed to measure and classify hips with mild hip dysplasia. The reported prevalence of dysplasia in a large patient cohort was dependent on both the measurement and threshold, with 12.4% of patients having dysplasia radiographic indices indicative of higher THA risk.

OBJECTIVES Generative artificial intelligence (AI) models such as OpenAI's ChatGPT and Google's Bard have forced educators to consider how these tools will be efficiently utilized to improve medical education. This article investigates current literature on how generative AI is and could be used and implemented in undergraduate medical education (UME). METHODS A rapid review of the literature was performed utilizing a librarian-generated search strategy to identify articles published before June 30, 2023, in 6 databases (Pubmed, EMBASE.com, Scopus, ERIC via EBSCO, Computer Science Database via EBSCO, and CINAHL via EBSCO). Inclusion criteria were (1) a focus on osteopathic and/or allopathic UME and (2) a defined use or implementation strategy for generative AI. Two reviewers screened all articles, and data extraction was performed by 1 reviewer and confirmed by the other reviewer. RESULTS A total of 521 relevant articles were screened during this review. Forty-one articles underwent full-text review and data extraction. The majority of the articles were opinion pieces (9), case reports (8), letters to the editor (5), editorials (5), and commentaries (3) about the use of generative AI while 7 articles used qualitative and/or quantitative methods. The literature is best divided into 5 categories of uses for generative AI in UME: nonclinical learning assistant, content developer, virtual patient interaction, clinical decision-making tutor, and medical writing. The literature indicates generative AI tools’ greatest potential is for use as a virtual patient and clinical decision-making tutor. CONCLUSIONS While the possibilities proliferate for generative AI in UME, there remains a dearth of quantitative evidence of its use for improving learner outcomes. The majority of the literature opines the potential for utilization, but only 7 studies formally evaluated the results of using generative AI. Future research should focus on the effectiveness of incorporating generative AI into preclinical and clinical curricula in UME.

Advancements in the generative AI field have enabled the development of powerful educational avatars. These avatars embody a human and can, for instance, listen to users’ spoken input, generate an answer utilizing a large-language model, and reply by speaking with a synthetic voice. A theoretical introduction summarizes essential steps in developing AI-based educational avatars and explains how they differ from previously available educational technologies. Moreover, we introduce GPTAvatar, an open-source, state-of-the-art AI-based avatar. We then discuss the benefits of using AI-based educational avatars, which include, among other things, individualized and contextualized instruction. Afterward, we highlight the challenges of using AI-based educational avatars. Major problems concern incorrect and inaccurate information provided, as well as insufficient data protection. In the discussion, we provide an outlook by addressing advances in educational content and educational technology and identifying three crucial open questions for research and practice.

Background and Objective Anaemia among pregnant women is a public health challenge in Ghana. Although there is a national programme of routine iron-folic acid (IFA) supplementation, coverage is suboptimal. The current study explored experiences and perceptions of anaemia prevention, and IFA use among pregnant women and antenatal care providers at two hospitals in Accra, Ghana, for enhancing the supplementation programme. Methods Utilizing a qualitative approach, 6 focus group discussions with 48 purposively selected pregnant women, and 10 in-depth interviews with care providers in two hospitals were conducted. Interviews were transcribed verbatim. Using both deductive and inductive approaches, priori themes that informed the design of the interview guides, and emerging codes from transcripts were used in data analysis. Results In both hospitals, pregnant women reported awareness of anaemia and identified poor quality diets and failure to take IFA as the predominant causes. Regular IFA supplementation, and consumption of fruits, vegetables, and animal-source foods were indicated as the main anaemia remedies by the pregnant women. Turkey berry, beetroot, and hibiscus flower were also reported as therapeutic remedies for anaemia. IFA use was linked with improved appetite, haemoglobin, and health status of mothers and their fetus. Both providers and pregnant women indicated that IFA is freely accessible through government facilities but may also be purchased. IFA supplements are recommended to be taken daily but three times for treatment; however, non-adherence to the recommended frequency was reported. This was attributed to adverse reactions including nausea and vomiting, unanticipated cost of increased appetite, forgetfulness to take IFA, misperceptions about adverse effects of IFA, transportation cost to access IFA, and long waiting time at hospitals. Community-level focused antenatal care, follow-up visits, and phone calls were reported by providers as strategies to improve IFA uptake. Community sensitization, enhanced access to IFA, and participatory approach to ANC services were suggested by pregnant women as strategies for improving IFA uptake. Conclusions Food insecurity and misperceptions about IFA should be addressed as part of efforts to address low IFA adherence and high maternal and child anaemia rates in Ghana.

Human regulatory T cells (Treg) suppress other immune cells. Their dysfunction contributes to the pathophysiology of autoimmune diseases, including type 1 diabetes (T1D). Infusion of Tregs is being clinically evaluated as a novel way to prevent or treat T1D. Genetic modification of Tregs, most notably through the introduction of a chimeric antigen receptor (CAR) targeting Tregs to pancreatic islets, may improve their efficacy. We evaluated CAR targeting of human Tregs to monocytes, a human β cell line and human islet β cells in vitro. Targeting of HLA-A2-CAR (A2-CAR) bulk Tregs to HLA-A2+ cells resulted in dichotomous cytotoxic killing of human monocytes and islet β cells. In exploring subsets and mechanisms that may explain this pattern, we found that CD39 expression segregated CAR Treg cytotoxicity. CAR Tregs from individuals with more CD39low/- Tregs and from individuals with genetic polymorphism associated with lower CD39 expression (rs10748643) had more cytotoxicity. Isolated CD39− CAR Tregs had elevated granzyme B expression and cytotoxicity compared to the CD39+ CAR Treg subset. Genetic overexpression of CD39 in CD39low CAR Tregs reduced their cytotoxicity. Importantly, β cells upregulated protein surface expression of PD-L1 and PD-L2 in response to A2-CAR Tregs. Blockade of PD-L1/PD-L2 increased β cell death in A2-CAR Treg co-cultures suggesting that the PD-1/PD-L1 pathway is important in protecting islet β cells in the setting of CAR immunotherapy. In summary, introduction of CAR can enhance biological differences in subsets of Tregs. CD39+ Tregs represent a safer choice for CAR Treg therapies targeting tissues for tolerance induction.

Despite high public stigma towards individuals with borderline personality disorder (BPD), no research has examined whether stigma differs among the various proposed BPD subtypes. The primary purpose of this research was to examine two potential contributors to stigma towards individuals with BPD: 1) gender, and 2) BPD subtype of the individuals. The three subtypes utilized in this study were emotional, low anxiety, and inhibited (Sleuwaegen, 2018). A total of 415 participants read 1 of 6 randomly assigned vignettes about an individual and then completed the Attribution Questionnaire which encompasses 6 aspects of stigma. Male individuals (featured in a vignette) led to greater overall and 5 aspects of stigma than female individuals. Higher public stigma was also expressed towards individuals with the emotional subtype for overall and 4 aspects of stigma than the other subtypes. The aggression portrayed in the emotional subtype may be a particularly worthy area of investigation, given the potential for over-appraisal of threat to one's personal safety. The findings here suggest that accurate portrayals of BPD need to be infused in education or contact anti-stigma interventions.

Abstract The world battled to defeat a novel coronavirus 2019 (SARS-CoV-2 or COVID-19), a respiratory illness that is transmitted from person to person through contacts with droplets from infected persons. Despite efforts to disseminate preventable messages and adoption of mitigation strategies by governments and the World Health Organization (WHO), transmission spread globally. An accurate assessment of the transmissibility of the coronavirus remained a public health priority for many countries across the world to fight this pandemic, especially at the early onset. In this paper, we estimated the transmission potential of COVID-19 across 45 countries in sub-Saharan Africa using three approaches, namely, $$R_{0}$$ R 0 based on (i) an exponential growth model (ii) maximum likelihood (ML) estimation and (iii) a time-varying basic reproduction number at the early onset of the pandemic. Using data from March 14, 2020, to May 10, 2020, sub-Saharan African countries were still grappling with COVID-19 at that point in the pandemic. The region’s basic reproduction number ( $$R_{0}$$ R 0 ) was 1.89 (95% CI: 1.767 to 2.026) using the growth model and 1.513 (95% CI: 1.491 to 1.535) with the maximum likelihood method, indicating that, on average, infected individuals transmitted the virus to less than two secondary persons. Several countries, including Sudan ( $$R_{0}$$ R 0 : 2.03), Ghana ( $$R_{0}$$ R 0 : 1.87), and Somalia ( $$R_{0}$$ R 0 : 1.85), exhibited high transmission rates. These findings highlighted the need for continued vigilance and the implementation of effective control measures to combat the pandemic in the region. It is anticipated that the findings in this study would not only function as a historical record of reproduction numbers during the COVID-19 pandemic in African countries, but can serve as a blueprint for addressing future pandemics of a similar nature.

Aims: Distal femoral resection in conventional total knee arthroplasty (TKA) utilizes an intramedullary guide to determine coronal alignment, commonly planned for 5° of valgus. However, a standard 5° resection angle may contribute to malalignment in patients with variability in the femoral anatomical and mechanical axis angle. The purpose of the study was to leverage deep learning (DL) to measure the femoral mechanical-anatomical axis angle (FMAA) in a heterogeneous cohort. Methods: Patients with full-limb radiographs from the Osteoarthritis Initiative were included. A DL workflow was created to measure the FMAA and validated against human measurements. To reflect potential intramedullary guide placement during manual TKA, two different FMAAs were calculated either using a line approximating the entire diaphyseal shaft, and a line connecting the apex of the femoral intercondylar sulcus to the centre of the diaphysis. The proportion of FMAAs outside a range of 5.0° (SD 2.0°) was calculated for both definitions, and FMAA was compared using univariate analyses across sex, BMI, knee alignment, and femur length. Results: The algorithm measured 1,078 radiographs at a rate of 12.6 s/image (2,156 unique measurements in 3.8 hours). There was no significant difference or bias between reader and algorithm measurements for the FMAA (p = 0.130 to 0.563). The FMAA was 6.3° (SD 1.0°; 25% outside range of 5.0° (SD 2.0°)) using definition one and 4.6° (SD 1.3°; 13% outside range of 5.0° (SD 2.0°)) using definition two. Differences between males and females were observed using definition two (males more valgus; p < 0.001). Conclusion: We developed a rapid and accurate DL tool to quantify the FMAA. Considerable variation with different measurement approaches for the FMAA supports that patient-specific anatomy and surgeon-dependent technique must be accounted for when correcting for the FMAA using an intramedullary guide. The angle between the mechanical and anatomical axes of the femur fell outside the range of 5.0° (SD 2.0°) for nearly a quarter of patients. Cite this article: Bone Jt Open 2024;5(2):101–108.

Abstract The urinary bladder harbors a community of microbes termed the urobiome, which remains understudied. In this study, we present the urobiome of healthy infant males from samples collected by transurethral catheterization. Using a combination of enhanced culture and amplicon sequencing, we identify several common bacterial genera that can be further investigated for their effects on urinary health across the lifespan. Many genera were shared between all samples suggesting a consistent urobiome composition among this cohort. We note that, for this cohort, early life exposures including mode of birth (vaginal vs. Cesarean section), or prior antibiotic exposure did not influence urobiome composition. In addition, we report the isolation of culturable bacteria from the bladders of these infant males, including Actinotignum spp., a bacterial genus that has been associated with urinary tract infections in older male adults. Herein, we isolate and sequence 9 distinct strains of Actinotignum spp. enhancing the genomic knowledge surrounding this genus and opening avenues for delineating the microbiology of this urobiome constituent. Furthermore, we present a framework for using the combination of culture-dependent and sequencing methodologies for uncovering mechanisms in the urobiome.

In the Global South, the COVID-19 crisis has compelled varied efforts to quickly address the pandemic's impact on urban livelihoods. Families, friends as well as public, private, and civil society organizations have mobilized various resources to avert the pandemic's onslaught on the survival of the urban vulnerable. Indeed, there is a burgeoning ‘pandemic urban scholarship’ that shed insights on COVID-19 risks, local responses, and impacts on everyday urban life. Yet, it is unclear how many of these responses are affecting urban livelihoods. This paper thus investigates the impact of COVID-19 on urban livelihood capitals (financial, human, social, and physical) and analyses the moderating role of COVID-19-related support (from families, friends, government agencies, faith-based and non-governmental organizations) to address the pandemic's impact on these capitals. Drawing on a quantitative study in Adenta Municipality of the Greater Accra Region, Ghana, the study finds a negative association between COVID-19 impacts and all urban livelihood capitals. Crucially, COVID-19-related support only reduced the negative impact of the pandemic on financial capital, and not on the other forms of capital. The study suggests that building post-pandemic community resilience warrants the need to transition from the usual reactive, fragmented support to integrated, holistic, and contextually embedded long-term strategies that consider the multi-dimensionality of everyday urban life.

Objective Explore organ-specific SLE burden by assessing health-related quality of life (HRQoL) and fatigue changes associated with Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) organ system response (score improvement) and belimumab treatment.Methods Data from four phase III belimumab trials were pooled for post hoc analysis (GSK Study 217382): BLISS-52 (NCT00424476), BLISS-76 (NCT00410384), BLISS-SC (NCT01484496) and EMBRACE (NCT01632241). Patients with baseline organ system involvement were classed as organ system responders if SELENA-SLEDAI scores for that organ system decreased at any post-baseline visit. HRQoL (36-Item Short Form Health Survey version 2 (SF-36v2)) and fatigue (Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-Fatigue)) changes over 52 weeks were compared between organ system responders and non-responders, and separately between belimumab versus placebo treatment arms among organ system responders. Group-level differences were compared using analysis of variance; differences were interpreted using published group-level minimal important difference (MID).Results In these post hoc analyses, musculoskeletal and mucocutaneous organ system responders had greater SF-36v2 improvements than non-responders across most SF-36v2 domains, but differences were largely MID), with FACIT-Fatigue also improving >MID for renal responders receiving belimumab.Conclusions SLE disease burden differs with the organ system(s) involved. While these analyses are limited by mutual inclusivity of organ system groupings, differing patient numbers between groups and small numbers in some groups, they suggest that mucocutaneous and musculoskeletal organ system response improves SF-36v2 domain scores; cardiovascular and respiratory organ system response may meaningfully improve fatigue; and belimumab may offer additional HRQoL or fatigue benefits beyond standard therapy for musculoskeletal and renal responders.

Abstract This paper has the primary objective of establishing the pragmatic basis for concluding on a present perfect sentence as currently or continuously relevant and the simple past sentence as currently not relevant. This is an attempt to make the concept current relevance as used in relation to present perfect and simple past sentences in Akan determinate for Akan. Three to four formal tests were conducted to reach the following conclusions: The one primary focus or motivation for making a simple past or present perfect sentence in Akan is to indicate the validity/persistence or non-validity/non-persistence of a past event context as at the moment of speech; context is defined here as non-temporal in the form of some evidence of a past event in some space, and/or as temporal such as the period of time within which an event remains/is valid. In summary, in Akan a past event is currently relevant when context(s) of it in focus is/are current (i.e. persists or is valid as at the moment of speech) - present perfect; and currently not relevant when context(s) of it in focus is/are non-current (i.e. not persistent or valid as at the moment of speech) – simple past.

In line with international best practices, countries across the globe are intensifying their teacher education institutions to train world-class teachers to feed their schools. Against this background, this research work tried to determine how robust the admission process at the Presbyterian College of Education, Akropong, is. This is because admitting students into the College of Education is the first step in ensuring a sound teacher training program. The study was quantitative and used secondary data; that is, students' West Africa Senior High School Certificate Examination (WASSCE) entry results against their Final GPA at the College of Education were used for the data analysis. The analysis proved that those who entered the College of Education with good grades from the Senior High School exited with good GPAs, and the inverse was true. The researcher recommends that the college move beyond the regular training and put in measures to ensure that most students can improve their performance to be at par with the current demands of a world-class teacher.

ABSTRACTSensory systems allow pathogens to differentiate between different niches and respond to stimuli within them. A major mechanism through which bacteria sense and respond to stimuli in their surroundings is two-component systems (TCSs). TCSs allow for the detection of multiple stimuli to lead to a highly controlled and rapid change in gene expression. Here, we provide a comprehensive list of TCSs important for the pathogenesis of uropathogenic Escherichia coli (UPEC). UPEC accounts for >75% of urinary tract infections (UTIs) worldwide. UTIs are most prevalent among people assigned female at birth, with the vagina becoming colonized by UPEC in addition to the gut and the bladder. In the bladder, adherence to the urothelium triggers E. coli invasion of bladder cells and an intracellular pathogenic cascade. Intracellular E. coli are safely hidden from host neutrophils, competition from the microbiota, and antibiotics that kill extracellular E. coli. To survive in these intimately connected, yet physiologically diverse niches E. coli must rapidly coordinate metabolic and virulence systems in response to the distinct stimuli encountered in each environment. We hypothesized that specific TCSs allow UPEC to sense these diverse environments encountered during infection with built-in redundant safeguards. Here, we created a library of isogenic TCS deletion mutants that we leveraged to map distinct TCS contributions to infection. We identify—for the first time—a comprehensive panel of UPEC TCSs that are critical for infection of the genitourinary tract and report that the TCSs mediating colonization of the bladder, kidneys, or vagina are distinct.IMPORTANCEWhile two-component system (TCS) signaling has been investigated at depth in model strains of Escherichia coli, there have been no studies to elucidate—at a systems level—which TCSs are important during infection by pathogenic Escherichia coli. Here, we report the generation of a markerless TCS deletion library in a uropathogenic E. coli (UPEC) isolate that can be leveraged for dissecting the role of TCS signaling in different aspects of pathogenesis. We use this library to demonstrate, for the first time in UPEC, that niche-specific colonization is guided by distinct TCS groups.

Summary: Hearing loss can lead to long-lasting effects on the central nervous system, and current therapies, such as auditory training and rehabilitation, show mixed success in improving perception and speech comprehension. Vagus nerve stimulation (VNS) is an adjunctive therapy that can be paired with rehabilitation to facilitate behavioral recovery after neural injury. However, VNS for auditory recovery has not been tested after severe hearing loss or significant damage to peripheral receptors. This study investigated the utility of pairing VNS with passive or active auditory rehabilitation in a rat model of noise-induced hearing loss. Although auditory rehabilitation helped rats improve their frequency discrimination, learn novel speech discrimination tasks, and achieve speech-in-noise performance similar to normal hearing controls, VNS did not enhance recovery of speech sound perception. These results highlight the limitations of VNS as an adjunctive therapy for hearing loss rehabilitation and suggest that optimal benefits from neuromodulation may require restored peripheral signaling.

Background: Food insecurity, lack of consistent access to the food needed for an active, healthy life, harms population health. Although substantial biomedical evidence examines the connections between food insecurity and health, fewer studies examine why food insecurity occurs. Methods: We propose a conceptual understanding of food insecurity risk based on institutions that distribute income—the factor payment system (income distribution stemming from paid labor and asset ownership), transfers within households, and the government tax-and-transfer system. A key feature of our understanding is 'roles' individuals inhabit in relation to the factor payment system: child, older adult, disabled working-age adult, student, unemployed individual, caregiver, or paid laborer. A second feature is that the roles of others in an individual's household also affect an individual's food insecurity risk. We tested hypotheses implied by this understanding, particularly hypotheses relating to role, household composition, and income support programs, using nationally-representative, longitudinal U.S. Current Population Survey data (2016–2019). Results: There were 16,884 participants (year 1 food insecurity prevalence: 10.0%). Inhabiting roles of child (Relative Risk [RR] 1.79, 95% Confidence Interval [95%CI] 1.67 to 1.93), disabled working age-adult (RR 3.74, 95%CI 3.25 to 4.31), or unemployed individual (RR 3.29, 95%CI 2.51 to 4.33) were associated with a greater risk of food insecurity than being a paid laborer. Most food insecure households, 74.8%, had members inhabiting roles of child or disabled working age-adult, and/or contained individuals who experienced job loss. Similar associations held when examining those transitioning from food insecurity to food security in year 2. Conclusions: The proposed understanding accords with the pattern of food insecurity risk observed in the U.S. An implication is that transfer income programs for individuals inhabiting roles, such as childhood and disability, that limit factor payment system participation may reduce food insecurity risk for both those individuals and those in their household.

Abstract Introduction Accurate identification of venous thromboembolism (VTE) is critical to develop replicable epidemiological studies and rigorous predictions models. Traditionally, VTE studies have relied on international classification of diseases (ICD) codes which are inaccurate – leading to misclassification bias. Here, we developed ClotCatcher, a novel deep learning model that uses natural language processing to detect VTE from radiology reports. Methods Radiology reports to detect VTE were obtained from patients admitted to Emory University Hospital (EUH) and Grady Memorial Hospital (GMH). Data augmentation was performed using the Google PEGASUS paraphraser. This data was then used to fine-tune ClotCatcher, a novel deep learning model. ClotCatcher was validated on both the EUH dataset alone and GMH dataset alone. Results The dataset contained 1358 studies from EUH and 915 studies from GMH (n = 2273). The dataset contained 1506 ultrasound studies with 528 (35.1%) studies positive for VTE, and 767 CT studies with 91 (11.9%) positive for VTE. When validated on the EUH dataset, ClotCatcher performed best (AUC = 0.980) when trained on both EUH and GMH dataset without paraphrasing. When validated on the GMH dataset, ClotCatcher performed best (AUC = 0.995) when trained on both EUH and GMH dataset with paraphrasing. Conclusion ClotCatcher, a novel deep learning model with data augmentation rapidly and accurately adjudicated the presence of VTE from radiology reports. Applying ClotCatcher to large databases would allow for rapid and accurate adjudication of incident VTE. This would reduce misclassification bias and form the foundation for future studies to estimate individual risk for patient to develop incident VTE.

Background: End-stage renal disease (ESRD) and renal transplant (RT) patients are known to have more perioperative and postoperative complications after arthroplasty surgeries when compared to patients without. We hypothesize that RT patients undergoing shoulder arthroplasty (SA) have fewer systemic and surgical complications when compared to ESRD patients undergoing SA. Methods: This was a retrospective review from the PearlDiver Patient Record Database. International Classification of Diseases and Current Procedural Terminology codes were used to identify patients who had undergone primary total and reverse shoulder arthroplasty, respectively, and subsequent surgical revisions. Unadjusted univariate analysis of patient demographics, Charlson Cormorbidty Index, and surgical complications at 90 days, 1 year, and 2 years after was performed using chi-squared testing. Multivariate logistic regression analyses were subsequently performed for systemic complications and prosthesis outcomes at all time points. Results: Of 1191 patients with ESRD or previous RT and who underwent either total shoulder arthroplasty or reverse total shoulder arthroplasty, 1042 (87.5%) had ESRD and 149 (12.5%) had a previous RT. ESRD SA patients were more likely to have hypertension, liver disease, coronary artery disease, and hypothyroidism. Interestingly no statistical significance was found in multivariate analysis for systemic complications at 90 days, nor for surgical complications at the 90-day, 1-year, or 2-year mark between ESRD and RT cohorts. Conclusion: SAs have comparable outcomes in ESRD and RT patients. The differing conclusions among studies might be partially accounted for by the demographic differences and comorbidities between these 2 patient populations. Providers should continue to provide appropriate counseling concerning risks, benefits, and timing of SA for these patients.

Abstract Background Black Americans suffer disparities in risk for cardiometabolic and other chronic diseases. Findings from the Adventist Health Study-2 (AHS-2) cohort have shown associations of plant-based dietary patterns and healthy lifestyle factors with prevention of such diseases. Hence, it is likely that racial differences in metabolic profiles correlating with disparities in chronic diseases are explained largely by diet and lifestyle, besides social determinants of health. Methods Untargeted plasma metabolomics screening was performed on plasma samples from 350 participants of the AHS-2, including 171 Black and 179 White participants, using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and a global platform of 892 metabolites. Differences in metabolites or biochemical subclasses by race were analyzed using linear regression, considering various models adjusted for known confounders, dietary and/or other lifestyle behaviors, social vulnerability, and psychosocial stress. The Storey permutation approach was used to adjust for false discovery at FDR

Abstract Functional MRI (fMRI) of the spinal cord is an expanding area of research with potential to investigate neuronal activity in the central nervous system. We aimed to characterize the functional connectivity features of the human lumbar spinal cord using resting-state fMRI (rs-fMRI) at 3T, using region-based and data-driven analysis approaches. A 3D multi-shot gradient echo resting-state blood oxygenation level dependent-sensitive rs-fMRI protocol was implemented in 26 healthy participants. Average temporal signal-to-noise ratio in the gray matter was 16.35 ± 4.79 after denoising. Evidence of synchronous signal fluctuations in the ventral and dorsal horns with their contralateral counterparts was observed in representative participants using interactive, exploratory seed-based correlations. Group-wise average in-slice Pearson’s correlations were 0.43 ± 0.17 between ventral horns, and 0.48 ± 0.16 between dorsal horns. Group spatial independent component analysis (ICA) was used to identify areas of coherent activity¸ and revealed components within the gray matter corresponding to anatomical regions. Lower-dimensionality ICA revealed bilateral components corresponding to ventral and dorsal networks. Additional separate ICAs were run on two subsets of the participant group, yielding two sets of components that showed visual consistency and moderate spatial overlap. This work shows feasibility of rs-fMRI to probe the functional features and organization of the lumbar spinal cord.

Abstract Background although being central for the biology and druggability of hormone-receptor positive, HER2 negative metastatic breast cancer (MBC), ESR1 and PIK3CA mutations are simplistically dichotomized as mutated or wild type in current clinical practice. Methods The study analyzed a multi-institutional cohort comprising 703 patients with luminal-like MBC characterized for circulating tumor DNA through next generation sequencing (NGS). Pathway classification was defined based on previous work (i.e., RTK, RAS, RAF, MEK, NRF2, ER, WNT, MYC, P53, cell cycle, notch, PI3K). Single nucleotide variations (SNVs) were annotated for their oncogenicity through OncoKB. Only pathogenic variants were included in the models. Associations among clinical characteristics, pathway classification, and ESR1/PIK3CA codon variants were explored. Results The results showed a differential pattern of associations for ESR1 and PIK3CA codon variants in terms of co-occurring pathway alterations patterns of metastatic dissemination, and prognosis. ESR1 537 was associated with SNVs in the ER and RAF pathways, CNVs in the MYC pathway and bone metastases, while ESR1 538 with SNVs in the cell cycle pathway and liver metastases. PIK3CA 1047 and 542 were associated with CNVs in the PI3K pathway and with bone metastases. Conclusions The study demonstrated how ESR1 and PIK3CA codon variants, together with alterations in specific oncogenic pathways, can differentially impact the biology and clinical phenotype of luminal-like MBC. As novel endocrine therapy agents such as selective estrogen receptor degraders (SERDS) and PI3K inhibitors are being developed, these results highlight the pivotal role of ctDNA NGS to describe tumor evolution and optimize clinical decision making.

Vagus nerve stimulation (VNS) has gained enormous traction as a promising bioelectronic therapy. In particular, the delivery of VNS paired with training to promote neural changes has demonstrated clinical success for stroke recovery and found far-reaching application in other domains, from autism to psychiatric disorders to normal learning. The success of paired VNS has been extensively documented. Here, we consider a more unusual question: why does VNS have such broad utility, and perhaps more importantly, when does VNS not work? We present a discussion of the concepts that underlie VNS therapy and an anthology of studies that describe conditions in which these concepts are violated and VNS fails. We focus specifically on the mechanisms engaged by implanted VNS, and how the parameters of stimulation, stimulation method, pharmacological manipulations, accompanying comorbidities, and specifics of concurrent training interact with these mechanisms to impact the efficacy of VNS therapy. As paired VNS therapy is increasing translated to clinical implementation, a clear understanding of the conditions in which it does, and critically, does not work is fundamental to the success of this approach.

Esophageal adenocarcinoma typically has a poor prognosis at the time of diagnosis. Consequently, palliation of symptoms is vital to disease management with a cornerstone for palliation being esophageal stent placement. Esophageal stents are associated with a variety of complications that may present immediately or long after stent placement is completed. In this report, we present a 58-year-old male who developed shortness of breath 4 months after metallic esophageal stent placement. After further evaluation with a chest radiograph and CT angiogram of the chest, the patient was found to have obstruction of the left mainstem bronchus secondary to mass effect from the esophageal stent. Airway compromise secondary to metallic esophageal stent placement typically occurs immediately after placement of the stent. There are only a few documented cases of this complication occurring at a delayed interval. This case clearly demonstrates this rare complication of esophageal stent placement in the setting of esophageal adenocarcinoma.

Rapid urbanisation and its associated challenges in Global South countries have necessitated the use of digital technologies in urban management. Key to their successful utilisation for urban management is residents' perceptions and utilisation of these technologies. Yet, little attention has been given to this area of research. Using data gathered from a cross-sectional survey in three suburban communities, the study examined residents' perceptions and utilisation of the digital property address system (DPAS) in Accra, Ghana. The findings revealed that residents understand the benefits of the DPAS. However, residents’ perceived benefits, usage and challenges varied by socio-demographic groups. More importantly, the findings revealed that the use of the DPAS is beset with operational difficulties and non-use by government agencies. To ensure that digital technologies such as the DPAS provide opportunities for sustainable, inclusive, and resilient development trajectories in Ghana and Africa, it is imperative that residents' use and challenges of such technologies inform improvements in their design and implementation.

AbstractThe ideal context for competence-based education (CBE) in the global south appears elusive with negative ramifications on both the teacher and the student. Using Ghana as a case study, this article shines light on the research question: What are the contexts and the implications of the contexts in which agriculture is taught on competence-based education? Drawing on a mixed methods approach involving cross-sectional data on 112 students, 238 teachers, and qualitative enquiries involving key informant interviews, and on-site observations. The findings showed inadequate facilities and low enrolment in agriculture. Specifically, 34% of pre-tertiary schools had less than 5% of the total student population offering agriculture. Theory-based pedagogies still dominate contrary to the core principles of competence-based education, culminating in students limited hands-on exposure that demotivates teachers and learners. We recommend the Ministry of Education focuses on competence-based education by increasing funding allocation to address the inadequate facilities, classrooms, and equipment needed for the effective teaching, learning, and the practice of agriculture. This article argues for sustained investment and conscious efforts directed at addressing challenges constraining CBE to allay the myths, drudgery, and low potentials ascribed to agriculture, with an ultimate aim to motivate the youth to pursue agriculture as a career and game-changer in providing self-employment and resolving the high unemployment phenomenon in the sub-region.

Neurological symptoms associated with COVID-19, acute and long term, suggest SARS-CoV-2 affects both the peripheral and central nervous systems (PNS/CNS). Although studies have shown olfactory and hematogenous invasion into the CNS, coinciding with neuroinflammation, little attention has been paid to susceptibility of the PNS to infection or to its contribution to CNS invasion. Here we show that sensory and autonomic neurons in the PNS are susceptible to productive infection with SARS-CoV-2 and outline physiological and molecular mechanisms mediating neuroinvasion. Our infection of K18-hACE2 mice, wild-type mice, and golden Syrian hamsters, as well as primary peripheral sensory and autonomic neuronal cultures, show viral RNA, proteins, and infectious virus in PNS neurons, satellite glial cells, and functionally connected CNS tissues. Additionally, we demonstrate, in vitro, that neuropilin-1 facilitates SARS-CoV-2 neuronal entry. SARS-CoV-2 rapidly invades the PNS prior to viremia, establishes a productive infection in peripheral neurons, and results in sensory symptoms often reported by COVID-19 patients.

The fundamental optical excitations of correlated transition-metal compounds are typically identified with multielectronic transitions localized at the transition-metal site, such as dd transitions. In this vein, intense interest has surrounded the appearance of sharp, below-band-gap optical transitions, i.e., excitons, within the magnetic phase of correlated Ni^{2+} van der Waals magnets. The interplay of magnetic and charge-transfer insulating ground states in Ni^{2+} systems raises intriguing questions on the roles of long-range magnetic order and of metal-ligand charge transfer in the exciton nature, which inspired microscopic descriptions beyond typical dd excitations. Here we study the impact of charge transfer and magnetic order on the excitation spectrum of the nickel dihalides (NiX_{2}, X=Cl, Br, and I) using Ni-L_{3} edge resonant inelastic x-ray scattering (RIXS). In all compounds, we detect sharp excitations, analogous to the recently reported excitons, and assign them to spin-singlet multiplets of octahedrally coordinated Ni^{2+} stabilized by intra-atomic Hund’s exchange. Additionally, we demonstrate that these excitons are dispersive using momentum-resolved RIXS. Our data evidence a ligand-mediated multiplet dispersion, which is tuned by the charge-transfer gap and independent of the presence of long-range magnetic order. This reveals the mechanisms governing nonlocal interactions of on-site dd excitations with the surrounding crystal or magnetic structure, in analogy to ground-state superexchange. These measurements thus establish the roles of magnetic order, self-doped ligand holes, and intersite-coupling mechanisms for the properties of dd excitations in charge-transfer insulators.