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Mauricio Arce Villalobos,1 Giorgio Veneziano,1,2 Christopher Iobst,3 Rebecca Miller,2 Ana Gabriela Walch,2 Catherine Roth,2 Graciela Argote-Romero,1,2 David P Martin,1,2 Ralph J Beltran,1,2 Joseph D Tobias1,2 1Department of Anesthesiology & Pain Medicine, The Ohio State University College of Medicine, Columbus, OH, USA; 2Department of Anesthesiology & Pain Medicine, Nationwide Children’s Hospital, Columbus, OH, USA; 3Department of Orthopedic Surgery, Nationwide Children’s Hospital and The Ohio State University College of Medicine, Columbus, OH, USACorrespondence: Mauricio Arce VillalobosDepartment of Anesthesiology & Pain Medicine, Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH 43205, USATel +1614 722-4200Fax +1614 722-4203Email Mauricio.ArceVillalobos@osumc.eduIntroduction: The use of regional anesthesia techniques continues to expand in a wide variety of surgical procedures as the benefits and safety are increasingly appreciated. Limb-lengthening procedures are often associated with significant postoperative pain and high opioid requirements which may impact patient’s recovery and increase risk of chronic pain and long-term opioid use.Methods: The current study retrospectively reviews our experience utilizing a novel peripheral nerve catheter (PNC) protocol for postoperative pain management in patients undergoing elective limb-lengthening procedures. We measure total opioid consumption following 48 hrs in the postoperative period between groups.Results: A total of 70 patients were included from which 41 received general plus regional anesthesia (RA) and 29 were managed with general anesthesia alone (NORA). Postoperative pain needs were calculated as morphine equivalents (ME). There were no differences in the demographic characteristics between the groups. Over the first 48 postoperative hours, opioid use was 0.5 mg/kg ME (IQR 0.3, 0.9) in the RA group versus 1.7 mg/kg ME (IQR 1.1, 3.1) in the NORA group (p< 0.001). Subgroup analysis between femoral lengthening and tibial-fibular lengthening procedures demonstrated the same opioid-sparing effect favoring the RA group compared to the NORA group. Hospital length of stay was significantly shorter in the femoral lengthening RA group compared to NORA group (32 hrs [IQR 29, 35] versus 53 hrs [IQR 33, 55], respectively). There was no significant difference in length of stay between the RA group and NORA group after tibial-fibular lengthening procedures.Discussion: Regional anesthesia via continuous catheter infusions has a clinically significant opioid-sparing effect for postoperative pain management after limb-lengthening procedures and may facilitate earlier hospital discharge.Keywords: peripheral nerve block, pediatric anesthesia, limb-lengthening procedures

Emmanuel Alalade,1 Jena Bilinovic,1 Ana Gabriela Walch,1 Candice Burrier,1,2 Christopher Mckee,1,2 Joseph Tobias1,2 1Department of Anesthesiology & Pain Medicine, Nationwide Children’s Hospital, Columbus, OH, USA; 2Department of Anesthesiology & Pain Medicine, The Ohio State University College of Medicine, Columbus, OH, USACorrespondence: Emmanuel AlaladeDepartment of Anesthesiology & Pain Medicine, Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, Ohio 43205, USATel +1 614 722-4200Fax +1 614 722-4203Email Emmanuel.Alalade@Nationwidechildrens.orgAbstract: The opioid crisis in the United States has been pandemic. As such, anesthesia providers are frequently faced with patients who have a history of opioid abuse or are currently receiving chronic therapy for such disorders. The chronic administration of medications such as buprenorphine-naloxone can impact the choice of perioperative anesthesia and pain control. Furthermore, the postoperative administration of opioids may lead to relapse in patients with a history of opioid abuse. We present a 26-year-old male with a history of opioid abuse on maintenance therapy with buprenorphine-naloxone, who presented for median sternotomy, cardiopulmonary bypass, and pulmonary valve replacement. The perioperative implications of buprenorphine-naloxone and implementation of multimodal analgesia are discussed, along with options to decrease or eliminate the perioperative use of opioids.Keywords: buprenorphine/naloxone, cardiac surgery, opioid use disorder, opioid tolerant patients, addiction

The Trillat procedure, initially described by Albert Trillat, is historically one of the first techniques for addressing recurrent anterior shoulder instability, incorporating fascinating biomechanical mechanisms. After lowering, medializing, and fixing the coracoid process to the glenoid neck, the subcoracoid space is reduced, the subscapularis lowered, and its line of pull changed, accentuating the function of the subscapularis as a humeral head depressor centering the glenohumeral joint. Furthermore, the conjoint tendon creates a ‘seatbelt’ effect, preventing anteroinferior humeral head dislocation. Even though contemporary preferences lean towards arthroscopic Bankart repair with optional remplissage, bone augmentation, and the Latarjet procedure, enduring surgical indications remain valid for the Trillat procedure, which offers joint preservation and superior outcomes in two distinct scenarios: (i) older patients with massive irreparable cuff tears and anterior recurrent instability with an intact subscapularis tendon regardless of the extent of glenoid bone loss; (ii) younger patients with instability associated shoulder joint capsule hyperlaxity without concomitant injuries (glenoid bone loss, large Hill–Sachs lesion). Complications associated with the Trillat procedure include recurrent anterior instability, potential overtightening of the coracoid, leading to pain and a significant reduction in range of motion, risk of subcoracoid impingement, and restriction of external rotation by up to 10°, a limitation that is generally well-tolerated. The Trillat procedure may be an effective alternative technique for specific indications and should remain part of the surgical armamentarium for addressing anterior shoulder instability.

Abstract The growing number of connected vehicles has led to an increased focus on Vehicle-to-Everything (V2X) communication in the field of transport research. This communication paradigm facilitates cooperation between vehicles and infrastructure to address traffic challenges such as efficiency, sustainability and safety. The development and standardisation of such Cooperative Intelligent Transport Systems (C-ITS) has been pursued in several projects. Beyond technical considerations, assessing the effect of these applications in terms of various impact categories is of paramount importance. However, existing research tends to examine impact categories such as efficiency, sustainability, safety, psychological or socioeconomic impacts separately, often overlooking potential interactions and interdependencies. This approach is inadequate as impacts on one category can have both cascading effects on others and rebound effects. To address this gap, this paper proposes a system dynamics approach using Causal Loop Diagrams (CLD) to illustrate the interconnectedness of impact categories and the potential impacts of C-ITS services. By depicting general relationships, interdependencies and feedback loops between impact category elements, the model accommodates the introduction of single or multiple C-ITS services as separate modules, allowing an analysis of their combined effects on the overall system. To this end, two use cases demonstrate the applicability of the developed CLD and illustrate some of the multiple interrelations between the effects of C-ITS services. The results of this paper support road operators and researchers when setting up the impact assessment of C-ITS services by revealing the dynamic and intertwined nature of different impact categories.

Abstract The broadening of accessible methodologies has enabled mechanistic insights into single-pathogen infections, yet the molecular mechanisms underlying co-infections remain largely elusive, despite their clinical frequency and relevance, generally exacerbating symptom severity and fatality. Here, we describe an unbiased in vitro screening of pairwise co-infections in a murine macrophage model, quantifying pathogen proliferation and host cell death in parallel over time. The screen revealed that the majority of interactions are antagonistic for both metrics, highlighting general patterns depending on the pathogen virulence strategy. We subsequently decipher two distinct molecular interaction points: Firstly, murine Adenovirus 3 modifies ASC-dependent inflammasome responses in murine macrophages, altering host cell death and cytokine production, thereby impacting secondary Salmonella infection. Secondly, murine Adenovirus 2 infection triggers upregulation of Mprip, a crucial mediator of phagocytosis, which in turn causes increased Yersinia uptake, specifically in virus pre-infected bone-marrow-derived macrophages. This work therefore encompasses both a first-of-its-kind systematic assessment of host-pathogen-pathogen interactions, and mechanistic insight into molecular mediators during co-infection.

During cervical carcinogenesis, T‐helper (Th)‐17 cells accumulate in the peripheral blood and tumor tissues of cancer patients. We previously demonstrated that Th17 cells are associated with therapy resistance as well as cervical cancer metastases and relapse; however, the underlying Th17‐driven mechanisms are not fully understood. Here, using microarrays, we found that Th17 cells induced an epithelial‐to‐mesenchymal transition (EMT) phenotype of cervical cancer cells and promoted migration and invasion of 2D cultures and 3D spheroids via induction of microRNA miR‐142‐5p. As the responsible mechanism, we identified the subunits C and D of the succinate dehydrogenase (SDH) complex as new targets of miR‐142‐5p and provided evidence that Th17–miR‐142‐5p‐dependent reduced expression of SDHC and SDHD mediated enhanced migration and invasion of cancer cells using small interfering RNAs (siRNAs) for SDHC and SDHD, and miR‐142‐5p inhibitors. Consistently, patients exhibited high levels of succinate in their serum associated with lymph node metastases and diminished expression of SDHD in patient biopsies correlated with increased numbers of Th17 cells. Correspondingly, a combination of weak or negative SDHD expression and a ratio of Th17/CD4+ T cells > 43.90% in situ was associated with reduced recurrence‐free survival. In summary, we unraveled a previously unknown molecular mechanism by which Th17 cells promote cervical cancer progression and suggest evaluation of Th17 cells as a potential target for immunotherapy in cervical cancer.

Abstract The decrease in sperm count and infertility is a global issue that remains unresolved. By screening environmental bacterial isolates, we have found that a novel lactic acid bacterium, Lactiplantibacillus plantarum SNI3, increased testis size, testosterone levels, sperm count, sexual activity and fertility in mice that have consumed the bacteria for four weeks. The abundance of L. plantarum in the colon microbiome was positively associated with sperm count. Fecal microbiota transplantation (FMT) from L. plantarum SNI3-dosed mice improved testicular functions in microbiome-attenuated recipient animals. To identify mediators that confer pro-reproductive effects on the host, untargeted in situ mass spectrometry metabolomics was performed on testis samples of L. plantarum SNI3-treated and control mice. Enrichment pathway analysis revealed several perturbed metabolic pathways in the testis of treated mice. Within the testis, a dipeptide, glutamyl-glutamate (GluGlu) was the most upregulated metabolite following L. plantarum SNI3 administration. To validate the pro-reproductive feature of GluGlu, systemic and local injections of the dipeptide have been performed. γ-GluGlu increased sperm count but had no effect on testosterone. These findings highlight the role of γ-GluGlu in mediating spermatogenetic effects of L. plantarum on the male mouse host and –following relevant human clinical trials- may provide future tools for treating certain forms of male infertility.

Non-thermal plasma, a partially ionized gas, holds significant potential for clinical applications, including wound-healing support, oral therapies, and anti-tumour treatments. While its applications showed promising outcomes, the underlying molecular mechanisms remain incompletely understood. We thus apply non-thermal plasma to mouse auricular skin and conducted non-coding RNA sequencing, as well as single-cell blood sequencing. In a time-series analysis (five timepoints spanning 2 hours), we compare the expression of microRNAs in the plasma-treated left ears to the unexposed right ears of the same mice as well as to the ears of unexposed control mice. Our findings indicate specific effects in the treated ears for a set of five miRNAs: mmu-miR-144-5p, mmu-miR-144-3p, mmu-miR-142a-5p, mmu-miR-223-3p, and mmu-miR-451a. Interestingly, mmu-miR-223-3p also exhibits an increase over time in the right non-treated ear of the exposed mice, suggesting systemic effects. Notably, this miRNA, along with mmu-miR-142a-5p and mmu-miR-144-3p, regulates genes and pathways associated with wound healing and tissue regeneration (namely ErbB, FoxO, Hippo, and PI3K-Akt signalling). This co-regulation is particularly remarkable considering the significant seed dissimilarities among the miRNAs. Finally, single-cell sequencing of PBMCs reveals the downregulation of 12 from 15 target genes in B-cells, Cd4+ and Cd8+ T-cells. Collectively, our data provide evidence for a systemic effect of non-thermal plasma.

Abstract Background Vaccination is one of the greatest tools for individuals to stay healthy. Individuals are, however, often exposed to misinformation via digital and social media, and thus, may miss the opportunity to develop scientific knowledge about vaccines and trust in relevant stakeholders. This has a damaging impact on vaccine confidence. Understanding vaccine confidence is particularly important in North Dakota, where vaccination rates are lower than national averages. Objectives The objectives of this research are to examine the association between vaccine confidence and three potential sources of it, namely, trust, vaccine knowledge, and vaccine information sources and to investigate the relative strength of three vaccine confidence sources, while accounting for covariates. Methods Students (n = 517, 56.6%) and staff and faculty (n = 397, 43.4%) at the University of North Dakota (n = 914) completed an online survey. Logistic regressions estimated odds ratios (OR) and 95% confidence intervals (CI) for associations among trust in doctors, family/friends, government health agencies, charitable organizations, and religious organizations, vaccine knowledge, vaccine information sources as well as vaccine confidence, accounting for gender, race, marital status, age, religion, political ideology, education, and health status. Results The mean age of participants was 29.43 years (SD = 13.48). Most were females (71.6%) and white (91.5%). Great trust in doctors (OR = 3.29, p

PURPOSEGallbladder cancer (GBC) is a biliary tract malignancy characterized by its high lethality. Although the incidence of GBC is low in most countries, specific areas such as Chile display a high incidence. Our collaborative study sought to compare clinical and molecular features of GBC cohorts from Chile and the United States with a focus on ERBB2 alterations.METHODSPatients were accrued at Memorial Sloan Kettering Cancer Center (MSK) or the Pontificia Universidad Católica de Chile (PUC). Clinical information was retrieved from medical records. Genomic analysis was performed by the next-generation sequencing platform MSK-Integrated Mutation Profiling of Actionable Cancer Targets.RESULTSA total of 260 patients with GBC were included, 237 from MSK and 23 from PUC. There were no significant differences in the clinical characteristics between the patients identified at MSK and at PUC except in terms of lithiasis prevalence which was significantly higher in the PUC cohort (85% v 44%; P = .0003). The prevalence of ERBB2 alterations was comparable between the two cohorts (15% v 9%; P = .42). Overall, ERBB2 alterations were present in 14% of patients (8% with ERBB2 amplification, 4% ERBB2 mutation, 1.5% concurrent amplification and mutation, and 0.4% ERBB2 fusion). Notably, patients with GBC that harbored ERBB2 alterations had better overall survival (OS) versus their ERBB2-wild type counterparts (22.3 months v 11.8 months; P = .024).CONCLUSIONThe prevalence of lithiasis seems to be higher in Chilean versus US patients with GBC. A similar prevalence of ERBB2 alterations of overall 14% and better OS suggests that a proportion of them could benefit from human epidermal growth factor receptor type 2–targeted therapies. The smaller cohort of Chile, where the disease prevalence is higher, is a reminder and invitation for the need of more robust next-generation sequencing analyses globally.

IntroductionPancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer-related deaths worldwide with limited treatment options due to extensive radiation and chemotherapy resistance. Monotherapy with immune checkpoint blockade showed no survival benefit. A combination of immunomodulation and radiotherapy may offer new treatment strategies, as demonstrated for non-small cell lung cancer. Radiation-induced anti-tumour immunity is mediated through cytosolic nucleic acid sensing pathways that drive the expression of interferon beta-1 (IFNB1) and proinflammatory cytokines.MethodsHuman PDAC cell lines (PANC-1, MIA PaCa-2, BxPC-3) were treated with X-rays and protons. Immunogenic cell death was measured based on HMGB1 release. Cytosolic dsDNA and dsRNA were analysed by immunofluorescence microscopy. Cell cycle progression, MHC-I and PD-L1 expression were determined by flow cytometry. Galectin-1 and IFNB1 were measured by ELISA. The expression levels and the phosphorylation status of the cGAS/STING and RIG-I/MAVS signalling pathways were analysed by western blotting, the expression of IFNB1 and proinflammatory cytokines was determined by RT-qPCR and genome-wide by RNA-seq. CRISPR-Cas9 knock-outs and inhibitors were used to elucidate the relevance of STING, MAVS and NF-κB for radiation-induced IFNB1 activation.ResultsWe demonstrate that a clinically relevant X-ray hypofractionation regimen (3x8 Gy) induces immunogenic cell death and activates IFNB1 and proinflammatory cytokines. Fractionated radiation induces G2/M arrest and accumulation of cytosolic DNA in PDAC cells, which partly originates from mitochondria. RNA-seq analysis shows a global upregulation of type I interferon response and NF-κB signalling in PDAC cells following 3x8 Gy. Radiation-induced immunogenic response is regulated by STING, MAVS and NF-κB. In addition to immunostimulation, radiation also induces immunosuppressive galectin-1. No significant changes in MHC-I or PD-L1 expression were observed. Moreover, PDAC cell lines show similar radiation-induced immune effects when exposed to single-dose protons or photons.ConclusionOur findings provide a rationale for combinatorial radiation-immunomodulatory treatment approaches in PDAC using conventional photon-based or proton beam radiotherapy.

Cannabidiol (CBD)-containing products are widely marketed as over the counter products. Adverse effects reported in anecdotal consumer reports or during clinical studies were first assumed to be due to acid-catalysed cyclization of CBD to psychotropic Δ9-tetrahydrocannabinol (Δ9-THC) in the stomach after oral consumption. However, research of pure CBD solutions stored in simulated gastric juice or subjected to various storage conditions such as heat and light with specific liquid chromatographic/tandem mass spectrometric (LC/MS/MS) and ultra-high pressure liquid chromatographic/quadrupole time-of-flight mass spectrometric (UPLC-QTOF) analyses was unable to confirm THC formation. Another hypothesis for the adverse effects of CBD products may be residual Δ9-THC concentrations in the products as contamination, because most of them are based on hemp extracts containing the full spectrum of cannabinoids besides CBD. Analyses of 413 hemp-based products of the German market (mostly CBD oils) confirmed this hypothesis: 48 products (12%) contained Δ9-THC above the lowest observed adverse effect level (2.5 mg/day). Hence, it may be assumed that the adverse effects of some commercial CBD products are based on a low-dose effect of Δ9-THC, with the safety of CBD itself currently being unclear with significant uncertainties regarding possible liver and reproductive toxicity. The safety, efficacy and purity of commercial CBD products is highly questionable, and all of the products in our sample collection showed various non-conformities to European food law such as unsafe Δ9-THC levels, hemp extracts or CBD isolates as non-approved novel food ingredients, non-approved health claims, and deficits in mandatory food labelling requirements. In view of the growing market for such lifestyle products, the effectiveness of the instrument of food business operators' own responsibility for product safety and regulatory compliance must obviously be challenged, and a strong regulatory framework for hemp products needs to be devised.

Hash functions are a crucial component in incrementally verifiable computation (IVC) protocols and applications. Among those, recursive SNARKs and folding schemes require hash functions to be both fast in native CPU computations and compact in algebraic descriptions (constraints). However, neither SHA-2/3 nor newer algebraic constructions, such as Poseidon, achieve both requirements. In this work we overcome this problem in several steps. First, for certain prime field domains we propose a new design strategy called Kintsugi, which explains how to construct nonlinear layers of high algebraic degree which allow fast native implementations and at the same time also an efficient circuit description for zeroknowledge applications. Then we suggest another layer, based on the Feistel Type-3 scheme, and prove wide trail bounds for its combination with an MDS matrix. We propose a new permutation design named Monolith to be used as a sponge or compression function. It is the first arithmetization-oriented function with a native performance comparable to SHA3-256. At the same time, it outperforms Poseidon in a circuit using the Merkle tree prover in the Plonky2 framework. Contrary to previously proposed designs, Monolith also allows for efficient constant-time native implementations which mitigates the risk of side-channel attacks.

Abstract Head and Neck Squamous Cell Carcinoma (HNSCC) is a heterogeneous malignancy that remains a significant challenge in clinical management due to frequent treatment failures and pronounced therapy resistance. While metabolic dysregulation appears to be a critical factor in this scenario, comprehensive analyses of the metabolic HNSCC landscape and its impact on clinical outcomes are lacking. This study utilized transcriptomic data from four independent clinical cohorts to investigate metabolic heterogeneity in HNSCC and define metabolic pathway-based subtypes (MPS). In HPV-negative HNSCCs, MPS1 and MPS2 were identified, while MPS3 was enriched in HPV-positive cases. MPS classification was associated with clinical outcome post adjuvant radio(chemo)therapy, with MPS1 consistently exhibiting the highest risk of therapeutic failure. MPS1 was uniquely characterized by upregulation of glycan (particularly chondroitin/dermatan sulfate) metabolism genes. Immunohistochemistry and pilot mass spectrometry imaging analyses confirmed this at metabolite level. The histological context and single-cell RNA sequencing data identified the malignant cells as key contributors. Globally, MPS1 was distinguished by a unique transcriptomic landscape associated with increased disease aggressiveness, featuring motifs related to epithelial-mesenchymal transition, immune signaling, cancer stemness, tumor microenvironment assembly, and oncogenic signaling. This translated into a distinct histological appearance marked by extensive extracellular matrix remodeling, abundant spindle-shaped cancer-associated fibroblasts, and intimately intertwined populations of malignant and stromal cells. Proof-of-concept data from orthotopic xenotransplants replicated the MPS phenotypes on the histological and transcriptome levels. In summary, this study introduces a metabolic pathway-based classification of HNSCC, pinpointing glycan metabolism-enriched MPS1 as the most challenging subgroup that necessitates alternative therapeutic strategies.

Background: In reverse shoulder arthroplasty (RSA), the ideal combination of baseplate lateralization (BL), glenosphere size (GS), and glenosphere overhang (GOH) with a commonly used 145° neck shaft angle (NSA) is unclear. This is the first study evaluating correlations of body height (BH), humeral head size (HS), glenoid height (GH), and association of gender with best glenoid configurations for range of motion (ROM) maintaining anatomic lateralization (aLAT) for optimized muscle length in 145° and less distalized 135° RSA. Methods: In this computer model study, 22 computed tomographies without joint narrowing were analyzed (11 male/female). A standardized semi-inlay 145° platform stem was combined with 20 glenoid configurations (baseplate [B] 25, 25 + 3/+6 lateralized [l], 29, 29 + 3/6l combined with glenosphere 36, 36 + 2 eccentric [e], 36 + 3l, 39, 39 + 3e, 39 + 3l , 42, 42 + 4e). Abduction-adduction, flexion-extension, external rotation-internal rotation, total ROM (TROM), and total notching relevant (TNR) ROM were computed, best TROM models respecting aLAT (-1 mm to +1 mm) and HS/GH recorded. Second, the 145° models (Ascend Flex stem; Stryker, Kalamazoo, MI, USA) were converted and compared to a 135° inlay RSA (New Perform stem; Stryker, Kalamazoo, MI, USA) maintaining GOH (6.5-7 mm) and aLAT. Results: Best 145° models had eccentric glenospheres (mean BL: 3.5 mm, GOH 8.8 mm, GS 38.1 mm, distalization 23 mm). The 135° models had concentric glenospheres, mean BL 3.8 mm, GOH 6.9 mm, GS 39.7 mm, and distalization 14.1 mm. HS showed the strongest positive correlation with BL in 145° and 135° models (0.65/0.79). Despite reduced GOH in smaller females with a 135° NSA, adduction, external rotation, extension, TNR ROM, and TROM were significantly increased (P = .02, P = .005, P = .005, P = .004, P = .003), abduction however reduced (P = .02). The same trends were seen for males. Conclusion: HS is a practical measure in surgery or preoperatively, and the strong positive correlation with BL is a useful planning aid. Despite reduction of GOH, conversion to a less distalized 135° NSAinlay design is powerful to maintain and even significantly increase all components of TNR ROM (extension/external rotation/adduction) in small females with the drawback of reduced abduction which may however be compensated by scapula motion. Lateralization with a less distalized 135° RSA optimizes muscle length, may facilitate subscapularis repair, and maintains highest rigid body motion.

Intracellular bacterial pathogens hijack the protein machinery of infected host cells to evade their defenses and cultivate a favorable intracellular niche. The intracellular pathogen Salmonella enterica subsp. Typhimurium (STm) achieves this by injecting a cocktail of effector proteins into host cells that modify the activity of target host proteins. Yet, proteome-wide approaches to systematically map changes in host protein function during infection have remained challenging. Here we adapted a functional proteomics approach - Thermal-Proteome Profiling (TPP) - to systematically assess proteome-wide changes in host protein abundance and thermal stability throughout an STm infection cycle. By comparing macrophages treated with live or heat-killed STm, we observed that most host protein abundance changes occur independently of STm viability. In contrast, a large portion of host protein thermal stability changes were specific to infection with live STm. This included pronounced thermal stability changes in proteins linked to mitochondrial function (Acod1/Irg1, Cox6c, Samm50, Vdac1, and mitochondrial respiratory chain complex proteins), as well as the interferon-inducible protein with tetratricopeptide repeats, Ifit1. Integration of our TPP data with a publicly available STm-host protein-protein interaction database led us to discover that the secreted STm effector kinase, SteC, thermally destabilizes and phosphorylates the ribosomal preservation factor Serbp1. In summary, this work emphasizes the utility of measuring protein thermal stability during infection to accelerate the discovery of novel molecular interactions at the host-pathogen interface.

ABSTRACTA food assessment questionnaire was completed by Alutiiq and Eyak peoples of the Chugach Region of Alaska in 2016–2017. This questionnaire, conducted by the Chugach Regional Resource Commission, gathered 87 responses from adults residing in seven communities. The questions related to traditional food systems, food security, and food sovereignty and were organised into six sections: Community Food Resources, Diet and Health, Culture, Organisation and Governance, Food Resources, and Natural Resources and Environment. Nine questions directly addressed food sovereignty. Results revealed the importance of traditional food sources in the communities, foods that are not readily available or are difficult to access, resources that are useful to improve traditional food security, health problems that are perceived to be caused or exacerbated by the lack of traditional foods in the area, traditional foods commonly consumed, and barriers from accessing traditional foods. Additionally, recommendations for improving food systems and addressing barriers are provided.

Within higher education, the use of blended learning (BL) is exponentially increased in the 21st century, which poses a number of challenges in designing the process of BL for educators. The aim of this design-based research (DBR) study was to assist an inexperienced educator in teaching and designing a BL course in higher education to convert a face-to-face (F2F) course into a BL course. During the design and delivery of the BL course, what appropriate practices were needed to achieve creating an efficient and effective BL course were determined and the educator's reflections on the first experience of teaching the BL course were documented over three iterative design cycles. Mixed methods including learning environment observations, educator interviews, student surveys were employed. The results demonstrated that BL enabled the educator to adopt active learning approaches, engage students in critical thinking and promote the quality of interactive and collaborative learning assignments. Although the educator indicated the time limitation as an obstacle to teach a more efficient BL course, the educator was contented with teaching and designing the BL course and found it useful and supportive overall. Findings were presented and discussed for future studies and implications.

Abstract Calcium carbonate (CaCO3) is abundant on Earth, is a major component of marine biominerals and thus of sedimentary and metamorphic rocks and it plays a major role in the global carbon cycle by storing atmospheric CO2 into solid biominerals. Six crystalline polymorphs of CaCO3 are known—3 anhydrous: calcite, aragonite, vaterite, and 3 hydrated: ikaite (CaCO3·6H2O), monohydrocalcite (CaCO3·1H2O, MHC), and calcium carbonate hemihydrate (CaCO3·½H2O, CCHH). CCHH was recently discovered and characterized, but exclusively as a synthetic material, not as a naturally occurring mineral. Here, analyzing 200 million spectra with Myriad Mapping (MM) of nanoscale mineral phases, we find CCHH and MHC, along with amorphous precursors, on freshly deposited coral skeleton and nacre surfaces, but not on sea urchin spines. Thus, biomineralization pathways are more complex and diverse than previously understood, opening new questions on isotopes and climate. Crystalline precursors are more accessible than amorphous ones to other spectroscopies and diffraction, in natural and bio-inspired materials.