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Immunizing mice with Crimean-Congo hemorrhagic fever virus (CCHFV) nucleoprotein (NP), glycoprotein precursor (GPC), or with the GP38 domain of GPC, can be protective when the proteins are delivered with viral vectors or as a DNA or RNA vaccine. Subunit vaccines are a safe and cost-effective alternative to some vaccine platforms, but Gc and Gn glycoprotein subunit vaccines for CCHFV fail to protect despite eliciting high levels of neutralizing antibodies. Here, we investigated humoral and cellular immune responses and the protective efficacy of recombinant NP, GP38, and GP38 forms (GP85 and GP160) associated with the highly glycosylated mucin-like (MLD) domain, as well as the NP + GP38 combination. Vaccination with GP160, GP85, or GP38 did not confer protection, and vaccination with the MLD-associated GP38 forms blunted the humoral immune responses to GP38, worsened clinical chemistry, and increased viral RNA in the blood compared to the GP38 vaccination. In contrast, NP vaccination conferred 100% protection from lethal outcome and was associated with mild clinical disease, while the NP + GP38 combination conferred even more robust protection by reducing morbidity compared to mice receiving NP alone. Thus, recombinant CCHFV NP alone is a promising vaccine candidate conferring 100% survival against heterologous challenge. Moreover, incorporation of GP38 should be considered as it further enhances subunit vaccine efficacy by reducing morbidity in surviving animals.

Child sex trafficking (CST) is the exchange of something of value for any sexual act with a minor. Public child welfare agencies are responsible for serving CST victims. In response to the critical need for training child welfare workers on engaging survivors of CST, we describe an innovative game-based training model used to train over 1000 workers in Maryland. The "Case-By-Case" game uses case studies to shape small group discussions, role playing, skill drills for child welfare workers to build their capacity to identify and engage survivors. Initial evaluations indicate a significant increase in knowledge and self-efficacy for training participants. The model may hold promise for social work education in this critical area, as well as for other types of professional training for social workers.

BACKGROUND: We sought to review our institutions experience with dental implant placement in free flap jaw reconstruction to determine factors impacting restoration of dental occlusion. METHODS: Exactly 48 patients underwent free flap jaw reconstruction with or without dental restoration from 2017 to 2022. Primary outcome was achievement of restored dental occlusion after jaw free flap reconstruction. RESULTS: A total of 48 patients with a mean age of 59.8 ± 16.4 years underwent jaw reconstruction from 2017 to 2022. Ten patients (20.8%) received osteointegrated dental implants. Two patients received a temporary dental prosthesis, 12 ± 4 months after initial reconstruction. Three patients received a final prosthesis, with a mean time to final prosthesis of 17.7 ± 12.4 months. Five patients did not receive any prosthesis despite placement of implants. CONCLUSION: A minority of patients received dental implant placement with free flap jaw reconstruction and only a small subset of these received a definitive dental prosthesis.

We present six whole community shotgun metagenomic sequencing data sets of two types of biological soil crusts sampled at the ecotone of the Mojave Desert and Colorado Desert in California. These data will help us understand the diversity and function of biocrust microbial communities, which are essential for desert ecosystems.

We present eight metatranscriptomic datasets of light algal and cyanolichen biological soil crusts from the Mojave Desert in response to wetting. These data will help us understand gene expression patterns in desert biocrust microbial communities after they have been reactivated by the addition of water.

Despite decades of study, we still know less than we would like about the association between joint attention (JA) and language acquisition. This is partly because of disagreements on how to operationalise JA. In this study, we examine the impact of applying two different, influential JA operationalisation schemes to the same dataset of child-caregiver interactions, to determine which yields a better fit to children's later vocabulary size. Two coding schemes—one defining JA in terms of gaze overlap and one in terms of social aspects of shared attention—were applied to video-recordings of dyadic naturalistic toy-play interactions (N=45). We found that JA was predictive of later production vocabulary when operationalised as shared focus (study 1), but also that its operationalisation as shared social awareness increased its predictive power (study 2). Our results emphasise the critical role of methodological choices in understanding how and why JA is associated with vocabulary size.

The aerobic hyperthermophile "Fervidibacter sacchari" catabolizes diverse polysaccharides and is the only cultivated member of the class "Fervidibacteria" within the phylum Armatimonadota. It encodes 117 putative glycoside hydrolases (GHs), including two from GH family 50 (GH50). In this study, we expressed, purified, and functionally characterized one of these GH50 enzymes, Fsa16295Glu. We show that Fsa16295Glu is a β-1,3-endoglucanase with optimal activity on carboxymethyl curdlan (CM-curdlan) and only weak agarase activity, despite most GH50 enzymes being described as β-agarases. The purified enzyme has a wide temperature range of 4-95°C (optimal 80°C), making it the first characterized hyperthermophilic representative of GH50. The enzyme is also active at a broad pH range of at least 5.5-11 (optimal 6.5-10). Fsa16295Glu possesses a relatively high kcat/KM of 1.82 × 107 s-1 M-1 with CM-curdlan and degrades CM-curdlan nearly completely to sugar monomers, indicating preferential hydrolysis of glucans containing β-1,3 linkages. Finally, a phylogenetic analysis of Fsa16295Glu and all other GH50 enzymes revealed that Fsa16295Glu is distant from other characterized enzymes but phylogenetically related to enzymes from thermophilic archaea that were likely acquired horizontally from "Fervidibacteria." Given its functional and phylogenetic novelty, we propose that Fsa16295Glu represents a new enzyme subfamily, GH50_3.

Introduction: Despite the inclusion of both diagnostic and procedural ultrasound and regional nerve blocks in the original Model of the Clinical Practice of Emergency Medicine (EM), there is no recommended standardized approach to the incorporation of ultrasound-guided regional anesthesia (UGRA) education in EM training.Methods: We developed and implemented a structured curriculum for both EM residents and faculty to learn UGRA in a four-hour workshop. Each Regional Anesthesia Anatomy and Ultrasound Workshop was four hours in length and followed the same format. Focusing on common UGRA blocks, each workshop began with an anatomist-led cadaveric review of the relevant neuromusculoskeletal anatomy followed by a hands-on ultrasound scanning practice for the blocks led by an ultrasound fellowship-trained EM faculty member, fellow, or a postgraduate year (PGY)-4 resident who had previously participated in the workshop. Learners identified the relevant anatomy on point-of-care ultrasound and reviewed how to conduct the blocks. Learners were invited to complete an evaluation of the workshop with Likert-scale and open-ended questions.Results: In the 2020 academic year, six regional anesthesia anatomy and ultrasound workshops occurred for EM faculty (two sessions, N = 24) and EM residents (four sessions, N = 40, including a total of five PGY4s, 10 PGY3s, 12 PGY2s, and 13 PGY1s). Workshops were universally well-received by both faculty and residents. Survey results found that 100.0% of all responding participants indicated that they were “very satisfied” with the session. All were likely to recommend this session to a colleague and 95.08% of participants believed the session should become a required component of the EM curriculum.Conclusion: The use of UGRA is increasing, and and it critical in EM. An interdisciplinary approach in collaboration with anatomists on an interactive, nerve block workshop incorporating both gross anatomy review and hands-on scanning was shown to be well-received and desired by both EM faculty and residents.

Spatial variability and uncertainties that exist in natural deposits are often modeled in one-dimensional (1D) site response analysis through multiple spatially varied shear wave velocity (VS) profiles. These spatially varied VS profiles usually exhibit VS reversals that might not be observed in the natural deposits. This study investigates the consequences of allowing VS reversals in spatially varied VS on the 1D site response characteristics. Two sets of sixty (60) spatially varied VS profiles, with and without VS reversals, were generated. Results of the 1D site response analysis showed that allowing VS reversals in spatially varied VS profiles can lower the median surface response up to 10% at periods shorter than the fundamental site period. The difference in surface response becomes more significant for the higher intensity input motions. The variability in the median surface response was not significantly influenced by the presence of VS reversals.

Abstract Background Mood disorders, including unipolar and bipolar depression, contribute significantly to the global burden of disease. Psychological therapy is considered a gold standard non-pharmacological treatment for managing these conditions; however, a growing body of evidence also supports the use of lifestyle therapies for these conditions. Despite some clinical guidelines endorsing the application of lifestyle therapies as a first-line treatment for individuals with mood disorders, there is limited evidence that this recommendation has been widely adopted into routine practice. A key obstacle is the insufficient evidence on whether lifestyle therapies match the clinical and cost effectiveness of psychological therapy, particularly for treating those with moderate to severe symptoms. The HARMON-E Trial seeks to address this gap by conducting a non-inferiority trial evaluating whether a multi-component lifestyle therapy program is non-inferior to psychological therapy on clinical and cost-effectiveness outcomes over 8-weeks for adults with major depressive disorder and bipolar affective disorder. Methods This trial uses an individually randomised group treatment design with computer generated block randomisation (1:1). Three hundred and seventy-eight adults with clinical depression or bipolar affective disorder, a recent major depressive episode, and moderate-to-severe depressive symptoms are randomised to receive either lifestyle therapy or psychological therapy (adjunctive to any existing treatments, including pharmacotherapies). Both therapy programs are delivered remotely, via a secure online video conferencing platform. The programs comprise an individual session and six subsequent group-based sessions over 8-weeks. All program aspects (e.g. session duration, time of day, and communications between participants and facilitators) are matched except for the content and program facilitators. Lifestyle therapy is provided by a dietitian and exercise physiologist focusing on four pillars of lifestyle (diet, physical activity, sleep, and substance use), and the psychological therapy program is provided by two psychologists using a cognitive behavioural therapy approach. Data collection occurs at baseline, 8-weeks, 16-weeks, and 6 months with research assistants blinded to allocation. The primary outcome is depressive symptoms at 8 weeks, measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) (minimal clinically important difference = 1.6). A pre-specified within-trial economic evaluation will also be conducted. Discussion Should lifestyle therapy be found to be as clinically and cost effective as psychological therapy for managing mood disorders, this approach has potential to be considered as an adjunctive treatment for those with moderate to severe depressive symptoms. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12622001026718, registered 22nd July 2022. Protocol version: 4.14, 26/06/2024

Abstract Background Ductal carcinoma in situ (DCIS) is a non-obligate precursor to invasive breast cancer (IBC). Studies have indicated differences in DCIS outcome based on race or ethnicity, but molecular differences have not been investigated. Methods We examined the molecular profile of DCIS by self-reported race (SRR) and outcome groups in Black (n = 99) and White (n = 191) women in a large DCIS case-control cohort study with longitudinal follow up. Results Gene expression and pathway analyses suggested that different genes and pathways are involved in diagnosis and ipsilateral breast outcome (DCIS or IBC) after DCIS treatment in White versus Black women. We identified differences in ER and HER2 expression, tumor microenvironment composition, and copy number variations by SRR and outcome groups. Conclusions Our results suggest that different molecular mechanisms drive initiation and subsequent ipsilateral breast events in Black versus White women.

Objective: To develop an artificial intelligence deep neural network (AI-DNN) algorithm to analyze 12-lead electrocardiogram (ECG) for detection of acute pulmonary embolism (PE) and PE categories. Patients and Methods: A cohort of patients seen between January 1, 1999, and December 31, 2020, from across the Mayo Clinic Enterprise with computed tomography pulmonary angiogram (CTPA) and ECG performed ±6 hours was identified. Natural language processing algorithms were applied to radiology reports to determine the diagnosis of acute PE, acute right ventricular strain pulmonary embolism (RVSPE), saddle pulmonary embolism (SADPE), or no PE. Diagnostic performance parameters of the AI-DNN reported were area under the receiver operating characteristics curve (AUROC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: A cohort of patients with CTPA report and ECG consisted of 79,894 patients including 7423 (9.3%) with acute PE, among whom 1138 patients had RVSPE or SADPE. Artificial intelligence deep neural network predicted acute PE with a modest accuracy of AUROC of 0.69 (95% CI, 0.68-0.71), sensitivity of 63.5%, specificity of 64.7%, PPV of 15.6%, and NPV of 94.5%. The AI-DNN prediction using the same algorithm for RVSPE or SADPE was higher (AUROC, 0.84; 95% CI, 0.81-0.86) with a sensitivity of 80.8%, specificity of 64.7.8%, PPV of 3.5%, and NPV of 99.5%. Conclusion: An AI-based analysis of 12-lead ECG shows modest detection power for acute PE in patients who underwent CTPA, with higher accuracy for high-risk PE. Moreover, with the high NPV, it has the clinical potential to exclude high-risk PE quickly and correctly.

Abstract Immunizing mice with Crimean-Congo hemorrhagic fever virus (CCHFV) nucleoprotein (NP), glycoprotein precursor (GPC), or with the GP38 domain of GPC, can be protective when the proteins are delivered with viral vectors or as a DNA or RNA vaccine. Subunit vaccines are a safe and cost-effective alternative to some vaccine platforms, but Gc and Gn glycoprotein subunit vaccines for CCHFV fail to protect despite eliciting high levels of neutralizing antibodies. Here, we investigated humoral and cellular immune responses and the protective efficacy of recombinant NP, GP38, and GP38 forms (GP85 and GP160) associated with the highly glycosylated mucin-like (MLD) domain, as well as the NP + GP38 combination. Vaccination with GP160, GP85, or GP38 did not confer protection, and vaccination with the MLD-associated GP38 forms blunted the humoral immune responses to GP38, worsened clinical chemistry, and increased viral RNA in the blood compared to the GP38 vaccination. In contrast, NP vaccination conferred 100% protection from lethal outcome and was associated with mild clinical disease, while the NP + GP38 combination conferred even more robust protection by reducing morbidity compared to mice receiving NP alone. Thus, recombinant CCHFV NP alone is a promising vaccine candidate conferring 100% survival against heterologous challenge. Moreover, incorporation of GP38 should be considered as it further enhances subunit vaccine efficacy by reducing morbidity in surviving animals.

Abstract Introduction Spinal cord injury (SCI) is a devastating injury and remains one of the largest medical and social burdens because of its intractable nature. According to the recent advances in stem cell biology, the possibility of spinal cord regeneration and functional restoration has been suggested by introducing appropriate stem cells. Multilineage-differentiating stress enduring (Muse) cells are a type of nontumorigenic endogenous reparative stem cell. The positive results of Muse cell transplantation for SCI was shown previously. As a first step for clinical application in human SCI, we conducted a clinical trial aiming to confirm the safety and feasibility of intravenously injected donor-Muse cells. Methods The study design of the current trial was a prospective, multicenter, nonrandomized, nonblinded, single-arm study. The clinical trial registration number was JRCT1080224764. Patients with a cervical SCI with a neurological level of injury C4 to C7 with the severity of modified Frankel classification B1 and B2 were included. A primary endpoint was set for safety and feasibility. Our protocol was approved by the PMDA, and the trial was funded by the Life Science Institute, Tokyo, Japan. The present clinical trial recruited 10 participants (8 males and 2 females) with an average age of 49.3 ± 21.2 years old. All 10 participants received a single dose of allogenic CL2020 (a total of 15 × 106 cells, 2.1–2.7 × 105 cells/kg of body weight), which is a Muse cell-based product produced from human mesenchymal stem cells, by an intravenous drip. Results There were two reported severe adverse events, both of which were determined to have no causal relationship with Muse cell treatment. The change in the ISNCSCI motor score, the activity of daily living and quality of life scores showed statistically significant improvements compared to those data at the time of CL2020 administration. Conclusion In the present trial, no safety concerns were identified, and Muse cell product transplantation demonstrated good tolerability. Future clinical trials with appropriate study designs incorporating a control arm will clarify the definitive efficacy of single-dose allogenic Muse cell treatment with intravenous administration to treat SCI. Trial registration: jRCT, JRCT1080224764. Registered 03 July 2019, https://jrct.niph.go.jp/latest-detail/jRCT1080224764 .

Two decades of growth in dual enrollment, also accelerated during the COVID pandemic, demands attention to equal opportunities available in rural areas. We use the IPEDS database to explore geographic equality of dual enrollment availability offered by two-year public postsecondary institutions in rural America. Shifts in economies and demographic changes across rural America present substantial equity challenges. In this study, we seek to provide a first description of the extent to which dual enrollment offerings in two-year public postsecondary institutions vary in different rural locales, in designated economic regions, and by race enrollment. We conclude students attending smaller two-year postsecondary institutions are less likely to have access to dual enrollment opportunities. Moreover, among all but the largest institutions, students attending institutions with higher minority enrollments are less likely to have access to dual enrollment opportunities. Regardless of locale (city, suburb, town, and rural), two-year postsecondary institutions with the least diversity offer less access to dual enrollment opportunities. Of the 1,164 institutions in the eight Bureau of Economic Analysis (BEA) regions, more than one-fourth (252 or 21.7%) do not offer dual enrollment. Moreover, almost half (115 or 46.6%) of the 252 institutions are in states of the Mid-East and Great Lakes regions. The Southeast region has the lowest (61.1%) dual enrollment availability among the highest minority enrollment institutions. In the most diverse institutions (>63.77% minority enrollment), however, three-fourths or more of the institutions in six of the eight BEA regions offer dual enrollment. Implications for policymakers, practitioners, and researchers are offered.