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Abstract Proteases are promising biomarkers for cancer early detection. Their enzymatic activity against peptide substrates allows for their straightforward detection using low-cost tests. However, the complexity of the human proteome makes it challenging to develop sensitive and selective tests against a specific protease biomarker. Here, we report a different approach by utilizing the total protease activity in plasma samples to detect pancreatic cancer. Instead of targeting a specific protease using a specific peptide substrate, we utilized an array of 360 FRET substrates to screen for cleavage patterns in plasma samples collected from screen negatives and pancreatitis or pancreatic ductal adenocarcinoma cancer (PDAC) patients. In this proof of concept study, we first screened all 360 substrates using a small cohort (n = 13) to identify the top 5 substrates that best separate different conditions. Then, we performed a validation study using a larger cohort (n = 86) and the selected substrates. There was a statistically significant increase in the total protease activity in PDAC samples compared to screen negative and pancreatitis samples. The selected substrates detected PDAC with an area under the curve (AUC) of 0.8. This work represents a novel strategy for identifying peptide substrates for the detection of PDAC and other cancers.

Objective: Selecting the right medication for major depressive disorder (MDD) is challenging, and patients are often on several medications before an effective one is found. Using patient EEG patterns with computer models to select medications is a potential solution, however, it is not widely performed. Therefore, we evaluated a commercially available EEG data analysis system to help guide medication selection in a clinical setting. Methods: Patients with MDD were recruited, and their physicians used their own judgment to select medications (Control; n = 115) or relied on computer-guided selection (PEER n = 165) of medications. Quick Inventory of Depressive Symptomatology (QIDS SR-16) scores were obtained from patients, before the start of the study (day 0) and again at ~90 and ~180 d. Patients in the PEER arm were classified into one of 4 groups depending on if the report was followed throughout (RF/RF), the first 90 days only (RF/RNF), the second 90 days only (RNF/RF), or not at all (RNF/RNF). Outcomes were then compared with controls whose physician performed the EEG and submitted data but did not receive the PEER report. Results: Patients in the controls, RF/RF and RNF/RNF groups had fewer depressive symptoms at 90 and 180 days, but the response was significantly stronger for patients in the RF/RF group. Lower rates of suicidal ideation were also noted in the RF/RF group than the control group at 90 and 180 days of treatment. Conclusion: Computational analysis of EEG patterns may augment physicians’ skills at selecting medications for the patients.

Abstract Objective To review United States chiropractic state boards acceptance of chiropractic residencies and fellowships as continuing education (CE). Methods Between February 2024 and April 2024, board websites and accompanying policy documents for all 50 states and the District of Columbia were manually searched for content related to residencies and fellowships and whether they were considered CE. Information regarding CE credit requirements for new licensees was also collected. Results were tabulated in a spreadsheet and descriptive analysis was performed. Consensus among a minimum of 5 of 6 investigators was sought. Results Four states (Arizona, Indiana, Kansas, and Minnesota) accept residencies or fellowships for CE credit, 6 states possess unclear regulatory language regarding these programs, and 41 states make no mention of these training programs among approved CE. Twenty-one states required CE credits during a licensee’s initial renewal period, 1 state was unclear based on website content alone, and 29 states did not mandate CE for initial license renewal. More than 90% (19/21) of states that require CE for a licensee’s first renewal do not or are unclear if they accept residencies or fellowships for credit. Conclusion Few chiropractic state boards currently accept residencies and fellowships as approved CE. As the number of these postdoctoral training programs for chiropractors grow, more state boards may be asked to determine their CE policies on them.

Aims: Lower limb fractures are common in low- and middle-income countries (LMICs) and represent a significant burden to the existing orthopaedic surgical infrastructure. In high income country (HIC) settings, internal fixation is the standard of care due to its superior outcomes. In LMICs, external fixation is often the surgical treatment of choice due to limited supplies, cost considerations, and its perceived lower complication rate. The aim of this systematic review protocol is identifying differences in rates of infection, nonunion, and malunion of extra-articular femoral and tibial shaft fractures in LMICs treated with either internal or external fixation. Methods: This systematic review protocol describes a broad search of multiple databases to identify eligible papers. Studies must be published after 2000, include at least five patients, patients must be aged > 16 years or treated as skeletally mature, and the paper must describe a fracture of interest and at least one of our primary outcomes of interest. We did not place restrictions on language or journal. All abstracts and full texts will be screened and extracted by two independent reviewers. Risk of bias and quality of evidence will be analyzed using standardized appraisal tools. A random-effects meta-analysis followed by a subgroup analysis will be performed, given the anticipated heterogeneity among studies, if sufficient data are available. Conclusion: The lack of easily accessible LMIC outcome data, combined with international clinical guidelines that are often developed by HIC surgeons for use in HIC environments, makes the clinical decision-making process infinitely more difficult for surgeons in LMICs. This protocol will guide research on surgical management, outcomes, and complications of lower limb shaft fractures in LMICs, and can help guide policy development for better surgical intervention delivery and improve global surgical care. Cite this article: Bone Jt Open 2024;5(11):1020–1026.

Abstract Higher education plays a critical role in driving an innovative economy by equipping students with knowledge and skills demanded by the workforce. While researchers and practitioners have developed data systems to track detailed occupational skills, such as those established by the U.S. Department of Labor (DOL), much less effort has been made to document which of these skills are being developed in higher education at a similar granularity. Here, we fill this gap by presenting Course-Skill Atlas – a longitudinal dataset of skills inferred from over three million course syllabi taught at nearly three thousand U.S. higher education institutions. To construct Course-Skill Atlas, we apply natural language processing to quantify the alignment between course syllabi and detailed workplace activities (DWAs) used by the DOL to describe occupations. We then aggregate these alignment scores to create skill profiles for institutions and academic majors. Our dataset offers a large-scale representation of college education’s role in preparing students for the labor market. Overall, Course-Skill Atlas can enable new research on the source of skills in the context of workforce development and provide actionable insights for shaping the future of higher education to meet evolving labor demands, especially in the face of new technologies.

Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative condition marked by memory impairments and distinct histopathological features such as amyloid-beta (Aβ) accumulations. Alzheimer’s patients experience sleep disturbances at early stages of the disease. APPswe/PS1dE9 (APP) mice exhibit sleep disruptions, including reductions in non-rapid eye movement (NREM) sleep, that contribute to their disease progression. In addition, astrocytic calcium transients associated with a sleep-dependent brain rhythm, slow oscillations prevalent during NREM sleep, are disrupted in APP mice. However, at present it is unclear whether restoration of circuit function by targeting astrocytic activity could improve sleep in APP mice. To that end, APP mice expressing channelrhodopsin-2 (ChR2) targeted to astrocytes underwent optogenetic stimulation at the slow oscillation frequency. Optogenetic stimulation of astrocytes significantly increased NREM sleep duration but not duration of rapid eye movement (REM) sleep. Optogenetic treatment increased delta power and reduced sleep fragmentation in APP mice. Thus, optogenetic activation of astrocytes increased sleep quantity and improved sleep quality in an AD mouse model. Astrocytic activity provides a novel therapeutic avenue to pursue for enhancing sleep and slowing AD progression.

Abstract Background Glioblastoma multiforme (GBM) is an aggressive cancer with poor prognosis, partly due to resistance to the standard chemotherapy treatment, temozolomide (TMZ). Phytocannabinoid cannabidiol (CBD) has exhibited anti-cancer effects against GBM, however, CBD’s ability to overcome common resistance mechanisms to TMZ have not yet been investigated. 4’-Fluoro-cannabidiol (4’-F-CBD, or HUF-101/PECS-101) is a derivative of CBD, that exhibits increased activity compared to CBD during in vivo behavioural studies. Methods This anti-cancer activity of cannabinoids against GBM cells sensitive to and representing major resistance mechanisms to TMZ was investigated. Cannabinoids were also studied in combination with imidazotetrazine agents, and advanced mass spectrometry with the 3D OrbiSIMS was used to investigate the mechanism of action of CBD. Results CBD and 4’-F-CBD were found to overcome two major resistance mechanisms (methylguanine DNA-methyltransferase (MGMT) overexpression and DNA mismatch repair (MMR)-deficiency). Synergistic responses were observed when cells were exposed to cannabinoids and imidazotetrazine agents. Synergy increased with T25 and 4’-F-CBD. 3D OrbiSIMS analysis highlighted the presence of methylated-DNA, a previously unknown anti-cancer mechanism of action of CBD. Conclusions This work demonstrates the anti-cancer activity of 4’-F-CBD and the synergy of cannabinoids with imidazotetrazine agents for the first time and expands understanding of CBD mechanism of action.

Abstract A seed recovered during archaeological excavations of a cave in the Judean desert was germinated, with radiocarbon analysis indicating an age of 993 CE– 1202 calCE. DNA sequencing and phylogenetic analysis identified the seedling as belonging to the angiosperm genus Commiphora Jacq., sister to three Southern African Commiphora species, but unique from all other species sampled to date. The germinated seedling was not closely related to Commiphora species commonly harvested for their fragrant oleoresins including Commiphora gileadensis (L.) C.Chr., candidate for the locally extinct “Judean Balsam” or “Balm of Gilead” of antiquity. GC-MS analysis revealed minimal fragrant compounds but abundance of those associated with multi-target bioactivity and a previously undescribed glycolipid compound series. Several hypotheses are offered to explain the origins, implications and ethnobotanical significance of this unknown Commiphora sp., to the best of our knowledge the first identified from an archaeological site in this region, including identification with a resin producing tree mentioned in Biblical sources and possible agricultural relationship with the historic Judean Balsam.

Abstract Reference genomes of cattle and sheep have lacked contiguous assemblies of the sex-determining Y chromosome. Here, we assemble complete and gapless telomere to telomere (T2T) Y chromosomes for these species. We find that the pseudo-autosomal regions are similar in length, but the total chromosome size is substantially different, with the cattle Y more than twice the length of the sheep Y. The length disparity is accounted for by expanded ampliconic region in cattle. The genic amplification in cattle contrasts with pseudogenization in sheep suggesting opposite evolutionary mechanisms since their divergence 19MYA. The centromeres also differ dramatically despite the close relationship between these species at the overall genome sequence level. These Y chromosomes have been added to the current reference assemblies in GenBank opening new opportunities for the study of evolution and variation while supporting efforts to improve sustainability in these important livestock species that generally use sire-driven genetic improvement strategies.

Summary: This study provides the first empirical evidence of the impact of leaks in natural gas distribution pipelines on nearby home prices. Using high-resolution property transaction data in Massachusetts and a difference-in-differences approach, we find that gas leaks significantly reduce nearby home prices by 2.61% ($11,700) on average. Damage to local greenery likely plays an important role in the negative impact of gas leaks on nearby home prices. The impact is economically and statistically significant for houses with high surrounding tree cover and not significant for houses with low surrounding tree cover. However, we fail to detect a significant difference in the impact before and after an information shock of a deadly natural gas accident. Our estimated benefits of fixing gas leaks are larger than the average costs per repair reported by utilities in Massachusetts, which supports actions by policymakers and environmental organizations to reduce methane emissions from gas distribution pipelines.

Dendritic cells (DCs) have emerged as a promising target for drug delivery and immune modulation due to their pivotal role in initiating the adaptive immune response. Gold nanoparticles (AuNPs) have garnered interest as a platform for targeted drug delivery due to their biocompatibility, low toxicity and precise control over size, morphology and surface functionalization. Our investigation aimed to elucidate the intracellular uptake and trafficking of AuNPs coated with different combinations of monosaccharides (mannose, galactose, and fucose) in DCs. We used 30 unique polymer-tethered monosaccharide combinations to coat 16 nm diameter spherical gold nanoparticles and investigated their effect on DCs phenotype, uptake, and intracellular trafficking.DCs internalized AuNPs coated with 100 % fucose, 100 % mannose, 90 % mannose +10 % galactose, and 80 % mannose +20 % galactose with highest efficiency. Flow cytometry analysis indicated that 100 % fucose-coated AuNPs showed increased lysosomal and endosomal contents compared to other conditions and uncoated AuNPs. Imaging flow cytometry further demonstrated that 100 % fucose-coated AuNPs had enhanced co-localization with lysosomes, while 100 % mannose-coated AuNPs exhibited higher co-localization with endosomes.Furthermore, our data showed that the uptake of carbohydrate-coated AuNPs predominantly occurred through receptor-mediated endocytosis, as evidenced by a marked reduction of uptake upon treatment of DCs with methyl-β-cyclodextrins, known to disrupt receptor-mediated endocytosis. These findings highlight the utility of carbohydrate coatings to enable more targeted delivery of nanoparticles and their payload to distinct intracellular compartments in immune cells with potential applications in drug delivery and immunotherapy.

Abstract Background There are no criteria specifically for evaluating the quality of implementation research and recommending implementation strategies likely to have impact to practitioners. We describe the development and application of the Best Practices Tool, a set of criteria to evaluate the evidence supporting HIV-specific implementation strategies. Methods We developed the Best Practices Tool from 2022–2023 in three phases. (1) We developed a draft tool and criteria based on a literature review and key informant interviews. We purposively selected and recruited by email interview participants representing a mix of expertise in HIV service delivery, quality improvement, and implementation science. (2) The tool was then informed and revised through two e-Delphi rounds using a survey delivered online through Qualtrics. The first and second round Delphi surveys consisted of 71 and 52 open and close-ended questions, respectively, asking participants to evaluate, confirm, and make suggestions on different aspects of the rubric. After each survey round, data were analyzed and synthesized as appropriate; and the tool and criteria were revised. (3) We then applied the tool to a set of research studies assessing implementation strategies designed to promote the adoption and uptake of evidence-based HIV interventions to assess reliable application of the tool and criteria. Results Our initial literature review yielded existing tools for evaluating intervention-level evidence. For a strategy-level tool, additions emerged from interviews, for example, a need to consider the context and specification of strategies. Revisions were made after both Delphi rounds resulting in the confirmation of five evaluation domains – research design, implementation outcomes, limitations and rigor, strategy specification, and equity – and four evidence levels – best, promising, more evidence needed, and harmful. For most domains, criteria were specified at each evidence level. After an initial pilot round to develop an application process and provide training, we achieved 98% reliability when applying the criteria to 18 implementation strategies. Conclusions We developed a tool to evaluate the evidence supporting implementation strategies for HIV services. Although specific to HIV in the US, this tool is adaptable for evaluating strategies in other health areas.

Abstract Background There is a growing demand for fast and reliable plant biomolecular analyses. DNA extraction is the major bottleneck in plant nucleic acid-based applications especially due to the complexity of tissues in different plant species. Conventional methods for plant cell lysis and DNA extraction typically require extensive sample preparation processes and large quantities of sample and chemicals, elevated temperatures, and multiple sample transfer steps which pose challenges for high throughput applications. Results In a prior investigation, an ionic liquid (IL)-based modified vortex-assisted matrix solid phase dispersion approach was developed using the model plant, Arabidopsis thaliana (L.) Heynh. Building upon this foundational study, the present study established a simple, rapid and efficient protocol for DNA extraction from milligram fragments of plant tissue representing a diverse range of taxa from the plant Tree of Life including 13 dicots and 4 monocots. Notably, the approach was successful in extracting DNA from a century old herbarium sample. The isolated DNA was of sufficient quality and quantity for sensitive molecular analyses such as qPCR. Two plant DNA barcoding markers, the plastid rbcL and nuclear ribosomal internal transcribed spacer (nrITS) regions were selected for DNA amplification and Sanger sequencing was conducted on PCR products of a representative dicot and monocot species. Successful qPCR amplification of the extracted DNA up to 3 weeks demonstrated that the DNA extracted using this approach remains stable at room temperature for an extended time period prior to downstream analysis. Conclusions The method presented here is a rapid and simple approach enabling cell lysis and DNA extraction from 1.5 mg of plant tissue across a broad range of plant taxa. Additional purification prior to DNA amplification is not required due to the compatibility of the extraction solvents with qPCR. The method has tremendous potential for applications in plant biology that require DNA, including barcoding methods for agriculture, conservation, ecology, evolution, and forensics.

ABSTRACT Marine pest introductions continue to occur and increase at accelerated rates, threatening the marine environment and blue economy. Environmental DNA (eDNA) is a tool for determining the presence of both indigenous and nonindigenous species, via the detection of genetic material that is shed into the local environment. Although eDNA approaches have gained widespread adoption in the last decade, fundamental knowledge gaps remain around factors that can influence the probability of detection, and how to optimize eDNA sampling in aquatic environments. Here, we partition eDNA research into four major research themes: eDNA concentration (shedding and decay), transport (advection and mixing), sampling design strategies, and the modeling of these dynamics. We review current developments and challenges in each theme with a focus on field sampling strategies and the use of biophysical models for understanding the movement of modeling eDNA in complex aquatic environments. We then introduce three modeling case studies from a large embayment where we (1) quantify the spatial and temporal variability of eDNA dispersion, (2) use biophysical models to inform a field sampling strategy, and (3) demonstrate a backtracking modeling technique to identify upstream DNA sources to an existing sample (monitoring) site. We conclude by identifying specific recommendations to help improve future eDNA studies. This work highlights how biophysical models can be applied to improve early detection and informing response and management decisions.

Abstract Chelating ligands have had a tremendous impact in coordination chemistry and catalysis. Notwithstanding their success as strongly σ-donating and π-accepting ligands, to date no chelating bis[cyclic (alkyl)(amino)carbenes] have been reported. Herein, we describe a chelating, C 2-symmetric bis[cyclic (alkyl)(amino)carbene] ligand, which was isolated as a racemic mixture. The isolation and structural characterization of its isostructural, pseudotetrahedral complexes with iron, cobalt, nickel, and zinc dihalides featuring eight-membered metallacycles demonstrates the binding ability of the bis(carbene). Reduction of the nickel(II) dibromide with potassium graphite produces a dicoordinate nickel(0) complex that features one of the narrowest angles measured in any unsupported dicoordinate transition metal complexes.

Abstract Arbuscular mycorrhizal fungi (AMF) are widespread obligate symbionts of plants. This dynamic symbiosis plays a large role in successful plant performance, given that AMF help to ameliorate plant responses to abiotic and biotic stressors. Although the importance of this symbiosis is clear, less is known about what may be driving this symbiosis, the plant's need for nutrients or the excess of plant photosynthate being transferred to the AMF, information critical to assess the functionality of this relationship. Characterizing the AMF community along a natural plant productivity gradient is a first step in understanding how this symbiosis may vary across the landscape. We surveyed the AMF community diversity at 12 sites along a plant productivity gradient driven by soil nitrogen availability. We found that AMF diversity in soil environmental DNA significantly increased along with the growth of the host plants Acer rubrum and A. saccharum., a widespread tree genus. These increases also coincided with a natural soil inorganic N availability gradient. We hypothesize photosynthate from the increased tree growth is being allocated to the belowground AMF community, leading to an increase in diversity. These findings contribute to understanding this complex symbiosis through the lens of AMF turnover and suggest that a more diverse AMF community is associated with increased host–plant performance.

Summary: Hematopoietic aging is associated with decreased hematopoietic stem cell (HSC) self-renewal capacity and myeloid skewing. We report that culture of bone marrow (BM) HSCs from aged mice with epidermal growth factor (EGF) suppressed myeloid skewing, increased multipotent colony formation, and increased HSC repopulation in primary and secondary transplantation assays. Mice transplanted with aged, EGF-treated HSCs displayed increased donor cell engraftment within BM HSCs and systemic administration of EGF to aged mice increased HSC self-renewal capacity in primary and secondary transplantation assays. Expression of a dominant negative EGFR in Scl/Tal1+ hematopoietic cells caused increased myeloid skewing and depletion of long term-HSCs in 15-month-old mice. EGF treatment decreased DNA damage in aged HSCs and shifted the transcriptome of aged HSCs from genes regulating cell death to genes involved in HSC self-renewal and DNA repair but had no effect on HSC senescence. These data suggest that EGFR signaling regulates the repopulating capacity of aged HSCs.

Abstract Background Alzheimer’s disease (AD) patients exhibit memory disruptions and profound sleep disturbances, including disruption of deep non-rapid eye movement (NREM) sleep. Slow-wave activity (SWA) is a major restorative feature of NREM sleep and is important for memory consolidation. Methods We generated a mouse model where GABAergic interneurons could be targeted in the presence of APPswe/PS1dE9 (APP) amyloidosis, APP-GAD-Cre mice. An electroencephalography (EEG) / electromyography (EMG) telemetry system was used to monitor sleep disruptions in these animals. Optogenetic stimulation of GABAergic interneurons in the anterior cortex targeted with channelrhodopsin-2 (ChR2) allowed us to examine the role GABAergic interneurons play in sleep deficits. We also examined the effect of optogenetic stimulation on amyloid plaques, neuronal calcium as well as sleep-dependent memory consolidation. In addition, microglial morphological features and functions were assessed using confocal microscopy and flow cytometry. Finally, we performed sleep deprivation during optogenetic stimulation to investigate whether sleep restoration was necessary to slow AD progression. Results APP-GAD-Cre mice exhibited impairments in sleep architecture including decreased time spent in NREM sleep, decreased delta power, and increased sleep fragmentation compared to nontransgenic (NTG) NTG-GAD-Cre mice. Optogenetic stimulation of cortical GABAergic interneurons increased SWA and rescued sleep impairments in APP-GAD-Cre animals. Furthermore, it slowed AD progression by reducing amyloid deposition, normalizing neuronal calcium homeostasis, and improving memory function. These changes were accompanied by increased numbers and a morphological transformation of microglia, elevated phagocytic marker expression, and enhanced amyloid β (Aβ) phagocytic activity of microglia. Sleep was necessary for amelioration of pathophysiological phenotypes in APP-GAD-Cre mice. Conclusions In summary, our study shows that optogenetic targeting of GABAergic interneurons rescues sleep, which then ameliorates neuropathological as well as behavioral deficits by increasing clearance of Aβ by microglia in an AD mouse model.

We present a molecular phylogeny for the subtribe Ecliptinae (Asteraceae, Heliantheae) based on three plastid (matK, psbA-trnH, and trnQ-rps16) and two nuclear (nrITS and nrETS) markers. The results of the phylogenetic reconstruction were utilised as a topological constraint for a subsequent divergence dating analysis and ancestral range reconstructions. We sampled 41 species and 40 genera (72%) of Ecliptinae and two species of Montanoa (as outgroups) to elucidate the generic relationships between the genera of this subtribe. The Bayesian inference (BI) and Maximum Likelihood (ML) analyses were performed for the combined molecular dataset. The divergence dating analysis was performed using a relaxed, uncorrelated molecular clock with BEAST v1.8.4 and calibrated using a single secondary calibration point from a recently published chronogram for the family. The ancestral range reconstructions focusing on continents (i.e., South America, North America, Africa, Asia, and Oceania) and biomes (Dry forests, Altitudinal grasslands, Savannas, and Rainforests) were performed on BioGeoBEARS. Our phylogenetic results indicate that the genera of Ecliptinae are grouped into five clades, informally named the Monactis, Oblivia, Blainvillea, Wedelia, and Melanthera clades. The most recent, common ancestor of Ecliptinae was widespread in the North and South American dry forests at 8.16 Ma and mainly radiated in these regions up to the Pleistocene. At least eight dispersal events to South America and four dispersal events from North America to Africa, Asia, and Oceania took place during this period in all five informal clades of Ecliptinae. At least 13 biome shifts from dry forests to rainforests were evidenced, in addition to ten biome shifts from dry forests to altitudinal grasslands and savannas. These results corroborate the mid-late Miocene to early Pleistocene radiation of Ecliptinae in tropical dry forests. Future studies should aim to sample the remaining 14 unsampled genera of Ecliptinae to position them in one of the five informal clades proposed in this study.

Traditional approaches employing natural plant products to treat a wide array of ailments have been documented and described for thousands of years. However, there remains limited scientific study of the therapeutic potential or effectiveness of ethnobotanical applications. Increases in the incidence of cancer and emerging infectious diseases demonstrate a growing need for advances in the development of therapeutic options. In this study, we evaluate the therapeutic potential of aqueous extracts prepared from four plants, purple aster (Symphyotrichum novae-angliae (L.) Nemsom), common sage (Salvia lyrata (L.)), northern spicebush (Lindera benzoin (L.) Blume), and lamb’s ear (Stachys byzantina (K.) Koch)) traditionally used in Native American medicine in Indiana, USA. Using a combination of cytotoxicity assays, immunofluorescence microscopy, and antiviral assays, we found that sage and spicebush extracts exhibit cytotoxic and antiproliferative effects on HeLa cell proliferation and that sage, spicebush, and aster extracts were capable of significantly inhibiting human respiratory syncytial virus (hRSV), a major respiratory pathogen of infants and the elderly. Chemical analysis of the four extracts identified four major compounds which were subsequently evaluated to identify the responsible constituents in the extracts. While none of the identified compounds were shown to induce significant impacts on HeLa cell proliferation, two of the compounds, (1S)-(-)-Borneol and 5-(hydroxymethyl)-furfural, identified in sage and spicebush, respectively, were shown to have antiviral activities. Our data suggest that several of the extracts tested exhibited either anti-proliferative or antiviral activity supporting future further analysis.

Abstract Background Storage of samples may be necessary prior to testing drug levels in certain study designs; however, the effect of storage duration on measured drug levels is not known for all drugs. Objectives The objective of this study was to evaluate the stability of carprofen in canine plasma when stored at −80°C for 6 months. Methods Six healthy dogs were enrolled (1–10 years old, 17–35 kg) and received compounded carprofen at 2.2 mg/kg orally every 12 h for 2 days. On the third day, blood was collected immediately before the morning dose (trough), then 1 and 6 h after the dose (sampling timepoint). Whole blood was immediately centrifuged, and plasma was stored at −80°C. Plasma carprofen concentration was measured at day 2, week 2 and then monthly for 6 months using reversed‐phase high‐performance liquid chromatography. The measured carprofen concentrations were analysed statistically using a linear mixed effects model. Results There was no effect of storage time over 6 months (p = 0.891) on measured carprofen levels. Although there was an effect of sampling timepoint (0, 1 and 6 h) (p

Abstract Complex systems often comprise many kinds of components which vary over many orders of magnitude in size: Populations of cities in countries, individual and corporate wealth in economies, species abundance in ecologies, word frequency in natural language, and node degree in complex networks. Here, we introduce ‘allotaxonometry’ along with ‘rank-turbulence divergence’ (RTD), a tunable instrument for comparing any two ranked lists of components. We analytically develop our rank-based divergence in a series of steps, and then establish a rank-based allotaxonograph which pairs a map-like histogram for rank-rank pairs with an ordered list of components according to divergence contribution. We explore the performance of rank-turbulence divergence, which we view as an instrument of ‘type calculus’, for a series of distinct settings including: Language use on Twitter and in books, species abundance, baby name popularity, market capitalization, performance in sports, mortality causes, and job titles. We provide a series of supplementary flipbooks which demonstrate the tunability and storytelling power of rank-based allotaxonometry.

Abstract The green energy revolution may displace 1.7 million fossil fuel workers in the US but a Just Transition to emerging green industry jobs offers possibilities for re-employing these workers. Here, using 14 years of power plant data from the US Energy Information Administration, job transition data from the Census Bureau, as well as employment and skills data from the Bureau of Labor Statistics, we assess whether people employed in fossil fuel resource extraction today are co-located and have the transferable skills to switch to expected green jobs. We find that these workers could leverage their mobility to other industries and have similar skills to green occupations. However, today’s fossil fuel extraction workers are not co-located with current sources of green energy production. Further, after accounting for federal employment projections, fossil fuel extraction workers are mostly not located in the regions where green employment will grow despite attaining the appropriate skillsets. These results suggest a large barrier to a Just Transition since fossil fuel extraction workers have not historically exhibited geospatial mobility. While stakeholders focus on re-skilling fossil fuel extraction workers, this analysis shows that co-location with emerging green employment will be the larger barrier to a Just Transition.

Abstract Patients with Alzheimer’s disease (AD) exhibit non-rapid eye movement (NREM) sleep disturbances in addition to memory deficits. Disruption of NREM slow waves occurs early in the disease progression and is recapitulated in transgenic mouse models of beta-amyloidosis. However, the mechanisms underlying slow-wave disruptions remain unknown. Because astrocytes contribute to slow-wave activity, we used multiphoton microscopy and optogenetics to investigate whether they contribute to slow-wave disruptions in APP/PS1 mice. The power but not the frequency of astrocytic calcium transients was reduced in APP/PS1 mice compared to nontransgenic controls. Optogenetic activation of astrocytes at the endogenous frequency of slow waves restored slow-wave power, reduced amyloid deposition, prevented neuronal calcium elevations, and improved memory performance. Our findings revealed malfunction of the astrocytic network driving slow-wave disruptions. Thus, targeting astrocytes to restore circuit activity underlying sleep and memory disruptions in AD could ameliorate disease progression.

Trichoderma is a genus of filamentous fungi with several species widely studied and used as biological control agents (BCAs) in agriculture. With respect to fungal disease control, Trichoderma spp. can use different mechanisms of action, including mycoparasitism, antibiosis, competition and/or activation of plant defences. Armillaria spp. are the causal pathogens of Armillaria root rot (ARR) disease, which is widely distributed and of great economic and environmental importance in agriculture and forestry. ARR can be devastating to plant health, through colonisation and rotting of the root system and collar of the infected plant/tree, which can cause a reduction in yield and eventually death. Armillaria can live as a saprophyte that survives on dead plant material, making eradication of ARR extremely difficult. In an exhaustive analysis of work published to date on the control of Armillaria spp. by Trichoderma spp., using the WoS and Scopus databases, we identified 31 papers. We discuss these reports in light of their key findings, including number of publications per year, the countries where they were published, the journals and the citations obtained so far. Although the vast majority do not identify the mechanism of action involved in control, some describe mycoparasitism, antibiosis, competition or modification of the rhizospheric microbiota as being responsible for effective biological control of the pathogen. Further research into these mechanisms and additional in-depth analysis of less studied or currently unidentified mechanisms, such as the activation of plant defences, would be highly beneficial to our understanding of Trichoderma as a BCA of Armillaria.

ABSTRACT Gut microbiota are increasingly being recognized as a contributing factor in the etiology of numerous diseases and as a potential determinant in the immune response to various treatments. Recent work has suggested that the suboptimal immunogenic response to vaccination in low- and middle-income countries may be associated with differences in the gut microbiome, which are known to be substantially different between Western and non-Western countries. However, insufficient consideration has been given to the characterization of non-Western microbiomes and their relationship with well-being and immunity. Humanized gnotobiotic mouse models have been used to better understand the causal associations between the gut microbiota and health outcomes but have largely been limited to the study of Western microbiota. Thus, we were interested in determining the applicability of gavage strategies used to humanize germ-free mice with Western microbiota to the humanization of germ-free mice with rural African fecal samples. Here, we assessed the impact of the number and frequency of gavages and the effect of a donor-matched diet on the colonization of Malian fecal microbiota in germ-free mice. One gavage was insufficient to provide a stable establishment of the Malian microbiome, whereas four weekly gavages resulted in a more consistent colonization of the human donor taxa. Interestingly, the donor-matched diet did not improve colonization over the fixed-formula, grain-based mouse chow. Subsequent phenotypic studies using African gut microbiota-humanized gnotobiotic mouse models will allow for a better understanding of the interaction between African gut microbiota and well-being and potentially aid in developing improved treatments for microbiota-dependent diseases in non-Western populations. IMPORTANCE There is increasing evidence that microbes residing within the intestines (gut microbiota) play important roles in the well-being of humans. Yet, there are considerable challenges in determining the specific role of gut microbiota in human diseases owing to the complexity of diverse internal and environmental factors that can contribute to diseases. Mice devoid of all microorganisms (germ-free mice) can be colonized with human stool samples to examine the specific contribution of the gut microbiota to a disease. These approaches have been primarily focused on stool samples obtained from individuals in Western countries. Thus, there is limited understanding as to whether the same methods used to colonize germ-free mice with stool from Western individuals would apply to the colonization of germ-free mice with stool from non-Western individuals. Here, we report the results from colonizing germ-free mice with stool samples of Malian children.

Abstract The most common malignant brain tumour in children, medulloblastoma (MB), is subdivided into four clinically relevant molecular subgroups, although targeted therapy options informed by understanding of different cellular features are lacking. Here, by comparing the most aggressive subgroup (Group 3) with the intermediate (SHH) subgroup, we identify crucial differences in tumour heterogeneity, including unique metabolism-driven subpopulations in Group 3 and matrix-producing subpopulations in SHH. To analyse tumour heterogeneity, we profiled individual tumour nodules at the cellular level in 3D MB hydrogel models, which recapitulate subgroup specific phenotypes, by single cell RNA sequencing (scRNAseq) and 3D OrbiTrap Secondary Ion Mass Spectrometry (3D OrbiSIMS) imaging. In addition to identifying known metabolites characteristic of MB, we observed intra- and internodular heterogeneity and identified subgroup-specific tumour subpopulations. We showed that extracellular matrix factors and adhesion pathways defined unique SHH subpopulations, and made up a distinct shell-like structure of sulphur-containing species, comprising a combination of small leucine-rich proteoglycans (SLRPs) including the collagen organiser lumican. In contrast, the Group 3 tumour model was characterized by multiple subpopulations with greatly enhanced oxidative phosphorylation and tricarboxylic acid (TCA) cycle activity. Extensive TCA cycle metabolite measurements revealed very high levels of succinate and fumarate with malate levels almost undetectable particularly in Group 3 tumour models. In patients, high fumarate levels (NMR spectroscopy) alongside activated stress response pathways and high Nuclear Factor Erythroid 2-Related Factor 2 (NRF2; gene expression analyses) were associated with poorer survival. Based on these findings we predicted and confirmed that NRF2 inhibition increased sensitivity to vincristine in a long-term 3D drug treatment assay of Group 3 MB. Thus, by combining scRNAseq and 3D OrbiSIMS in a relevant model system we were able to define MB subgroup heterogeneity at the single cell level and elucidate new druggable biomarkers for aggressive Group 3 and low-risk SHH MB.

Interneuron-specific lines reveal that somatostatin interneurons are hyperactive whereas pyramidal neurons and PV interneurons are ‘hypoactive’ in the APP/PS1 mouse model of Alzheimer’s Disease.

Introduction: Human sex trafficking is widespread and a nationally recognized public health crisis. Trafficked individuals and survivors often utilize the healthcare system, yet healthcare professionals cite a lack of formal training to identify and provide appropriate care. This study aims to increase obstetrics/gynecology, emergency medicine, and family medicine residents’ knowledge and confidence when caring for individuals involved in sex trafficking. Methods: Obstetrics/gynecology, emergency medicine, and family medicine residents voluntarily attended an evidence-based education session and received an electronic pre-, immediate post-, and 5-month post-session survey measuring knowledge, attitudes, beliefs, and confidence. Validated survey items were adapted from previous studies. Paired t-tests (p

Abstract Background Prior research has demonstrated bidirectional associations between gestational diabetes mellitus (GDM) and perinatal maternal depression. However, the association between GDM, prenatal depression, and postpartum depression (PPD) has not been examined in a prospective cohort longitudinally. Methods Participants in the current analysis included 5,822 women from the National Institutes of Health’s Environmental influences on Child Health Outcomes (ECHO) Research Program: N = 4,606 with Neither GDM nor Prenatal Maternal Depression (Reference Category); N = 416 with GDM only; N = 689 with Prenatal Maternal Depression only; and N = 111 with Comorbid GDM and Prenatal Maternal Depression. The PROMIS-D scale was used to measure prenatal and postnatal maternal depressive symptoms. Primary analyses consisted of linear regression models to estimate the independent and joint effects of GDM and prenatal maternal depression on maternal postpartum depressive symptoms. Results A higher proportion of women with GDM were classified as having prenatal depression (N = 111; 21%) compared to the proportion of women without GDM who were classified as having prenatal depression (N = 689; 13%), however this finding was not significant after adjustment for covariates. Women with Comorbid GDM and Prenatal Maternal Depression had significantly increased postpartum depressive symptoms measured by PROMIS-D T-scores compared to women with Neither GDM nor Prenatal Maternal Depression (mean difference 7.02, 95% CI 5.00, 9.05). Comorbid GDM and Prenatal Maternal Depression was associated with an increased likelihood of PPD (OR 7.38, 95% CI 4.05, 12.94). However, women with GDM only did not have increased postpartum PROMIS-D T-scores or increased rates of PPD. Conclusions Our findings underscore the importance of universal depression screening during pregnancy and in the first postpartum year. Due to the joint association of GDM and prenatal maternal depression on risk of PPD, future studies should examine potential mechanisms underlying this relation.

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—the causative agent of coronavirus disease 2019 (COVID-19)—has caused a global public health emergency. Personal protective equipment (PPE) is the primary defence against viral exposure in healthcare and community settings. However, the surfaces of PPE materials may trap virus for contact transmission or through laden aerosols generated during removal of PPE, through cleaning or during movement. In this study, the relative efficacy of current PPE materials in terms of virion adsorption to materials and their antiviral potency, has been evaluated on a wide range of PPE for the first time, including four polymer glove types, two types of scrubs, apron material, a mask, visor and a selection of other commercial polymers and products. Although differences in virion adsorption to the test materials were observed, none of the existing polymer-based PPE resulted in more than tenfold reduction in the SARS-CoV-2 titre within either 10 min or 30 min contact period. The wettability and surface chemistry of the test materials were analysed to investigate any correlations with their surface physicochemical properties. While no correlation was found between wettability and viral retention under air flow challenge, one secondary ion of m/z 101.03 (+) and three secondary ions of m/z 31.98 (−), 196.93 (−) and 394.33 (+) in ToF–SIMS data of the test materials showed positive and negative correlations with the viral retention, respectively, which was identified by PLS regression model, suggesting that the surface chemistry plays a role in determining the extent of virion adsorption. Our findings outline the material aspects that influence the efficacy of current PPE against SARS-CoV-2 transmission and give suggestions on the development of novel simple polymer-based PPE for better infection protection.

ObjectiveThe first objective of this study was to describe the type of tarsal injuries sustained, surgery performed, and postoperative complications in greyhounds presenting to a single veterinary hospital. An additional objective of the study was to determine the surgical site infection (SSI) and explantation rate, and if any variables were associated with an increased risk of SSI and/or explantation.Animals116 greyhounds receiving surgical intervention for a tarsal injury.ProceuresMedical records from a single veterinary referral hospital were reviewed retrospectively. Data retrieved included signalment, details regarding the injury, surgical intervention, concurrent castration, surgical/anesthesia times, postoperative management, time to healing, and postoperative complications. In cases that underwent explantation, cause, time from initial surgery, and risk factors were evaluated.ResultsThe most frequently diagnosed tarsal injuries were fracture of the central tarsal bone (CTB; 57.8%), calcaneal fracture (56.9%) and proximal intertarsal subluxation (34.5%). The most common injury combination was a CTB fracture with a calcaneal fracture (31.9%). In total 115 (99.1%) survived to discharge. Of these, 46 (40.0%) were diagnosed with an SSI and 59 (51.3%) underwent explantation. The most common indication for explantation was SSI. Concurrent medial and lateral surgical approaches was found to be associated with an increased likelihood of SSI and explantation.Clinical relevancePractitioners performing surgical intervention for tarsal injuries in greyhounds should be aware of the high SSI rate and likelihood that explantation will be required. This risk is elevated for injuries requiring a bilateral surgical approach.

BACKGROUND Chronic graft-versus-host disease (cGVHD) is a serious complication of allogeneic hematopoietic cell transplantation (HCT). More accurate information regarding the risk of developing cGVHD is required. Bone marrow (BM) grafts contribute to lower cGVHD, which creates a dispute over whether risk biomarker scores should be used for peripheral blood (PB) and BM.METHODS Day 90 plasma proteomics from PB and BM recipients developing cGVHD revealed 5 risk markers that were added to 8 previous cGVHD markers to screen 982 HCT samples of 2 multicenter Blood and Marrow Transplant Clinical Trials Network (BMTCTN) cohorts. Each marker was tested for its association with cause-specific hazard ratios (HRs) of cGVHD using Cox-proportional-hazards models. We paired these clinical studies with biomarker measurements in a mouse model of cGVHD.RESULTS Spearman correlations between DKK3 and MMP3 were significant in both cohorts. In BMTCTN 0201 multivariate analyses, PB recipients with 1-log increase in CXCL9 and DKK3 were 1.3 times (95% CI: 1.1–1.4, P = 0.001) and 1.9 times (95%CI: 1.1–3.2, P = 0.019) and BM recipients with 1-log increase in CXCL10 and MMP3 were 1.3 times (95%CI: 1.0–1.6, P = 0.018 and P = 0.023) more likely to develop cGVHD. In BMTCTN 1202, PB patients with high CXCL9 and MMP3 were 1.1 times (95%CI: 1.0–1.2, P = 0.037) and 1.2 times (95%CI: 1.0–1.3, P = 0.009) more likely to develop cGVHD. PB patients with high biomarkers had increased likelihood to develop cGVHD in both cohorts (22%–32% versus 8%–12%, P = 0.002 and P < 0.001, respectively). Mice showed elevated circulating biomarkers before the signs of cGVHD.CONCLUSION Biomarker levels at 3 months after HCT identify patients at risk for cGVHD occurrence.FUNDING NIH grants R01CA168814, R21HL139934, P01CA158505, T32AI007313, and R01CA264921.

Despite intensive research, effective treatments for many common and devastating diseases are lacking. For example, huge efforts and billions of dollars have been invested in Alzheimer's disease (AD), which affects over 50 million people worldwide. However, there is still no effective drug that can slow or cure AD. This relates, in part, to the absence of an animal model or cellular system that incorporates all the relevant features of the disease. Therefore, large scale studies on human populations and tissues will be key to better understanding dementia and developing methods to prevent or treat it. This is especially difficult because the dementia phenotype can result from many different processes and is likely to be affected by multiple personal and environmental variables. We hypothesize that analyzing massive volumes of demographic data that are currently available and combining this with genomic, proteomic, and metabolomic profiles of AD patients and their families, new insights into pathophysiology and treatment of AD may arise. While this requires much coordination and cooperation among large institutions, the potential for advancement would be life-changing for millions of people. In many ways this represents the next step in the information revolution started by the Human Genome Project.

Abstract Objective To identify and descriptively compare medication recommendations among low back pain (LBP) clinical practice guidelines (CPG). Methods We searched PubMed, Cochrane Database of Systematic Review, Index to Chiropractic Literature, AMED, CINAHL, and PEDro to identify CPGs that described the management of mechanical LBP in the prior five years. Two investigators independently screened titles and abstracts and potentially relevant full text were considered for eligibility. Four investigators independently applied the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument for critical appraisal. Data were extracted for pharmaceutical intervention, the strength of recommendation, and appropriateness for the duration of LBP. Results 316 citations were identified, 50 full-text articles were assessed, and nine guidelines with global representation met the eligibility criteria. These CPGs addressed pharmacological treatments with or without non-pharmacological treatments. All CPGS focused on the management of acute, chronic, or unspecified duration of LBP. The mean overall AGREE II score was 89.3% (SD 3.5%). The lowest domain mean score was for applicability, 80.4% (SD 5.2%), and the highest was Scope and Purpose, 94.0% (SD 2.4%). There were ten classifications of medications described in the included CPGs: acetaminophen, antibiotics, anticonvulsants, antidepressants, benzodiazepines, non-steroidal anti-inflammatory drugs (NSAIDs), opioids, oral corticosteroids, skeletal muscle relaxants (SMRs), and atypical opioids. Conclusions Nine CPGs, included ten medication classes for the management of LBP. NSAIDs were the most frequently recommended medication for the treatment of both acute and chronic LBP as a first line pharmacological therapy. Acetaminophen and SMRs were inconsistently recommended for acute LBP. Meanwhile, with less consensus among CPGs, acetaminophen and antidepressants were proposed as second-choice therapies for chronic LBP. There was significant heterogeneity of recommendations within many medication classes, although oral corticosteroids, benzodiazepines, anticonvulsants, and antibiotics were not recommended by any CPGs for acute or chronic LBP.

Abstract The COVID-19 pandemic has demonstrated the real need for mechanisms to control the spread of airborne respiratory pathogens. Thus, preventing the spread of disease from pathogens has come to the forefront of the public consciousness. This has brought an increasing demand for novel technologies to prioritise clean air. In this study we report on the efficacy of novel biocide treated filters and their antimicrobial activity against bacteria, fungi and viruses. The antimicrobial filters reported here are shown to kill pathogens, such as Candida albicans, Escherichia coli and MRSA in under 15 min and to destroy SARS-CoV-2 viral particles in under 30 s following contact with the filter. Through air flow rate testing, light microscopy and SEM, the filters are shown to maintain their structure and filtration function. Further to this, the filters are shown to be extremely durable and to maintain antimicrobial activity throughout the operational lifetime of the product. Lastly, the filters have been tested in field trials onboard the UK rail network, showing excellent efficacy in reducing the burden of microbial species colonising the air conditioning system.

Abstract Background Plant DNA isolation and purification is a time-consuming and laborious process relative to epithelial and viral DNA sample preparation due to the cell wall. The lysis of plant cells to free intracellular DNA normally requires high temperatures, chemical surfactants, and mechanical separation of plant tissue prior to a DNA purification step. Traditional DNA purification methods also do not aid themselves towards fieldwork due to the numerous chemical and bulky equipment requirements. Results In this study, intact plant tissue was coated by hydrophobic magnetic ionic liquids (MILs) and ionic liquids (ILs) and allowed to incubate under static conditions or dispersed in a suspension buffer to facilitate cell disruption and DNA extraction. The DNA-enriched MIL or IL was successfully integrated into the qPCR buffer without inhibiting the reaction. The two aforementioned advantages of ILs and MILs allow plant DNA sample preparation to occur in one minute or less without the aid of elevated temperatures or chemical surfactants that typically inhibit enzymatic amplification methods. MIL or IL-coated plant tissue could be successfully integrated into a qPCR assay without the need for custom enzymes or manual DNA isolation/purification steps that are required for conventional methods. Conclusions The limited amount of equipment, chemicals, and time required to disrupt plant cells while simultaneously extracting DNA using MILs makes the described procedure ideal for fieldwork and lab work in low resource environments.

Abstract Biofilm formation is a major cause of hospital‐acquired infections. Research into biofilm‐resistant materials is therefore critical to reduce the frequency of these events. Polymer microarrays offer a high‐throughput approach to enable the efficient discovery of novel biofilm‐resistant polymers. Herein, bacterial attachment and surface chemistry are studied for a polymer microarray to improve the understanding of Pseudomonas aeruginosa biofilm formation on a diverse set of polymeric surfaces. The relationships between time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) data and biofilm formation are analyzed using linear multivariate analysis (partial least squares [PLS] regression) and a nonlinear self‐organizing map (SOM). The SOM models revealed several combinations of fragment ions that are positively or negatively associated with bacterial biofilm formation, which are not identified by PLS. With these insights, a second PLS model is calculated, in which interactions between key fragments (identified by the SOM) are explicitly considered. Inclusion of these terms improved the PLS model performance and shows that, without such terms, certain key fragment ions correlated with bacterial attachment may not be identified. The chemical insights provided by the combination of PLS regression and SOM will be useful for the design of materials that support negligible pathogen attachment.

Abstract The impact of COVID-19-related stress on perinatal women is of heightened public health concern given the established intergenerational impact of maternal stress-exposure on infants and fetuses. There is urgent need to characterize the coping styles associated with adverse psychosocial outcomes in perinatal women during the COVID-19 pandemic to help mitigate the potential for lasting sequelae on both mothers and infants. This study uses a data-driven approach to identify the patterns of behavioral coping strategies that associate with maternal psychosocial distress during the COVID-19 pandemic in a large multicenter sample of pregnant women (N = 2876) and postpartum women (N = 1536). Data was collected from 9 states across the United States from March to October 2020. Women reported behaviors they were engaging in to manage pandemic-related stress, symptoms of depression, anxiety and global psychological distress, as well as changes in energy levels, sleep quality and stress levels. Using latent profile analysis, we identified four behavioral phenotypes of coping strategies. Critically, phenotypes with high levels of passive coping strategies (increased screen time, social media, and intake of comfort foods) were associated with elevated symptoms of depression, anxiety, and global psychological distress, as well as worsening stress and energy levels, relative to other coping phenotypes. In contrast, phenotypes with high levels of active coping strategies (social support, and self-care) were associated with greater resiliency relative to other phenotypes. The identification of these widespread coping phenotypes reveals novel behavioral patterns associated with risk and resiliency to pandemic-related stress in perinatal women. These findings may contribute to early identification of women at risk for poor long-term outcomes and indicate malleable targets for interventions aimed at mitigating lasting sequelae on women and children during the COVID-19 pandemic.

Loundras et al. report on the fibril components of the RNA-dependent RNA polymerase RdRp from foot-and-mouth disease virus. They demonstrate that higher-order fibril-based interactions create multiple complex structures within which RNA replication can occur.

As whole genome sequence (WGS) data sets have become abundant and widely available, so has the need for variant detection and scoring. The aim of this study was to compare the accuracy of commonly used variant calling programs, Freebayes and GATK HaplotypeCaller (GATK-HC), and to use U.S. sheep WGS data sets to identify novel breed-associated SNPs. Sequence data from 145 sheep consisting of 14 U.S. breeds were filtered and biallelic single nucleotide polymorphisms (SNPs) were retained for genotyping analyses. Genotypes from both programs were compared to each other and to genotypes from bead arrays. The SNPs from WGS were compared to the bead array data with breed heterozygosity, principal component analysis and identifying breed associated SNPs to analyze genetic diversity. The average sequence read depth was 2.78 reads greater with 6.11% more SNPs being identified in Freebayes compared to GATK-HC. The genotype concordance of the variant callers to bead array data was 96.0% and 95.5% for Freebayes and GATK-HC, respectively. Genotyping with WGS identified 10.5 million SNPs from all 145 sheep. This resulted in an 8% increase in measured heterozygosity and greater breed separation in the principal component analysis compared to the bead array analysis. There were 1,849 SNPs identified in only the Romanov sheep where all 10 rams were homozygous for one allele and the remaining 135 sheep from 13 breeds were homozygous for the opposite allele. Both variant calling programs had greater than 95% concordance of SNPs with bead array data, and either was suitably accurate for ovine WGS data sets. The use of WGS SNPs improved the resolution of PCA analysis and was critical for identifying Romanov breed-associated SNPs. Subsets of such SNPs could be used to estimate germplasm composition in animals without pedigree information.

Higher education is a source of skill acquisition for many middle- and high-skilled jobs. But what specific skills do universities impart on students to prepare them for desirable careers? In this study, we analyze a large novel corpora of over one million syllabi from over eight hundred bachelors’ granting US educational institutions to connect material taught in higher education to the detailed work activities in the US economy as reported by the US Department of Labor. First, we show how differences in taught skills both within and between college majors correspond to earnings differences of recent graduates. Further, we use the co-occurrence of taught skills across all of academia to predict the skills that will be taught in a major moving forward. Our unified information system connecting workplace skills to the skills taught during higher education can improve the workforce development of high-skilled workers, inform educational programs of future trends, and enable employers to quantify the skills of potential workers.

Adoption of electronic identification ear tags (EID) and DNA testing by commercial range sheep producers in the Western United States has been low, despite the availability of these technologies for over a decade. Jointly, these technologies offer an approach to provide individual animal performance data to improve flock health, genetic and reproductive management. This project involved a collaboration with five California sheep producers representing a broad geographic range, varying levels of pre-project EID adoption, and diverse operational practices. Tissue samples were collected from, and ear EIDs were placed in, a total of 2,936 rams and their potential lambs. We partnered with a commercial packing company, Superior Farms, to genotype the animals. Superior Farms used a targeted genotyping panel to assign parentage, and link individual animal identification (ID) to camera-graded carcass measurements. This enabled the collection of individual progeny carcass data and provided insight into sire performance, providing for the within-flock identification of prolific sires that were producing lambs with significantly more saleable meat as compared to their flock mates. Overall, almost 91% of lambs were successfully matched to their sire, and prolificacy ranging from 0–135 lambs per ram. There was as much as an $80 difference in the average edible product from camera-graded carcasses derived from lamb groups sired by different rams. A partial budget analysis modeling investment in an EID system coupled with an autodrafter and scale to collect individual weights and improve labor efficiency during processing, and a sheep flip chute to improve worker safety during foot trimmings, yielded a greater than 7:1 return on investment over a five-year time frame. Ideally, the data collection enabled by EIDs and DNA testing would feed into data-driven genetic evaluation programs to enable selection for more productive and profitable animals, and allow the US sheep industry to accelerate the rate of genetic improvement.

Monkeypox outbreaks were, until recently, mostly confined to Africa but a currently expanding worldwide outbreak has recently been designated a global emergency by the World Health Organization. Genital manifestation is common and can be confused with sexually transmitted infection (STI), posing a diagnostic challenge. We herein report a case of genital monkeypox superimposed on multiple co-incident STIs in a HIV patient and describe characteristic clinical findings and management.

Background:. Although increased cross-sectional area of the median nerve on ultrasound has been associated with carpal tunnel syndrome, there has been little research examining outlier cases with exceedingly large nerves. The purpose of this study was to identify factors associated with these “mega” nerves, and to determine whether these nerves carry with them increased severity of disease. Methods:. Patients who presented to clinic with upper extremity paresthesias over a 4-year period were included in this study. Two groups were created: mega nerves (cross-sectional area >2 SD above average), and nonmega nerves. Statistical analysis was performed to compare demographics, symptom scores, and nerve conduction studies (NCS). Significant variables were then compared between patients with mega nerves and those with ultrasound positive nerves (≥10 mm2), which did not reach mega size (normal nerves were excluded). Results:. The cohort included 425 median nerves with 25 mega nerves. The groups differed significantly in diabetes status, body mass index (BMI), Boston Carpal Tunnel Questionnaire (BCTQ) Symptom Severity Scale scores, and NCS results. When compared only with ultrasound positive but nonmega nerves, mega nerves were still associated with diabetes, higher BMI, and worse NCS results. Conclusions:. Diabetes, BMI, NCS results, and BCTQ Symptom Severity Scale scores are associated with mega nerves. However, BCTQ scores do not differ between mega nerves and other ultrasound positive nerves. In patients with obesity or diabetes, outlier ultrasound measurements may not correlate with worsened clinical symptoms, even in the setting of more significantly altered NCS results.

Transitioning to a sustainable energy system poses a massive challenge to communities, nations, and the global economy in the next decade and beyond. A growing portfolio of satellite data products is available to support this transition. Satellite data complement other information sources to provide a more complete picture of the global energy system, often with continuous spatial coverage over targeted areas or even the entire Earth. We find that satellite data are already being applied to a wide range of energy issues with varying information needs, from planning and operation of renewable energy projects, to tracking changing patterns in energy access and use, to monitoring environmental impacts and verifying the effectiveness of emissions reduction efforts. While satellite data could play a larger role throughout the policy and planning lifecycle, there are technical, social, and structural barriers to their increased use. We conclude with a discussion of opportunities for satellite data applications to energy and recommendations for research to maximize the value of satellite data for sustainable energy transitions.

Prenatal exposure to testosterone is implicated in the etiology of autism spectrum disorder (ASD). Hypertensive disorders of pregnancy and polycystic ovary syndrome are associated with both hyperandrogenism and increased risk for ASD. We examined whether increased maternal testosterone mediates the relationship between these hyperandrogenic disorders (HDs) during pregnancy and child communication and social skills. Maternal plasma was collected during the second trimester and parent-report measures of child communication and social skills were obtained at 4.5-6.5 years of age from 270 participants enrolled in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b). Our retrospective frequency-matched cohort study design identified 58 mothers with one or both of the HDs and 58 matched controls. Women diagnosed with an HD who carried a female had higher testosterone levels compared to those carrying a male (t(56) = -2.70, p = 0.01). Compared to females controls, females born to women with an HD had significantly higher scores on the Social Communication Questionnaire (t(114) = -2.82, p =0.01). Maternal testosterone partially mediated the relationship between a diagnosis of an HD and SCQ scores among females. These findings point to sex-specific associations of two HDs – hypertensive disorders of pregnancy and polycystic ovary syndrome – on child communication and social skills and a mediating effect of maternal testosterone during pregnancy. Further research is needed to understand placental-mediated effects of maternal testosterone on child brain development and neurodevelopmental outcomes.

A key strategy for meeting China’s 2060 carbon neutrality goal and the global 1.5 °C climate goal is to rapidly shift away from unabated coal use. Here, the authors detail how to structure a high-ambition, plant-by-plant coal phaseout in China while balancing multiple national needs.

Recent technological, social, and educational changes are profoundly impacting our work, but what makes labour markets resilient to those labour shocks? Here, the authors show that labour markets resemble ecological systems whose resilience depends critically on the network of skill similarities between different jobs.

OBJECTIVES Low cardiorespiratory fitness, defined as a VO2 max below the 25th percentile for age and sex, is associated with greater body mass index (BMI), blood pressure, and plasma cholesterol values and is an independent risk factor for cardiovascular and metabolic diseases. Given that sedentarism has substantially increased in the U.S. population in the last 20 years and that office workers have the lowest cardiorespiratory fitness of the workforce, we aimed to assess the prevalence of low cardiorespiratory fitness in an corporate wellness program and determine its relationship with associated comorbidities. METHODS For this retrospective observational analysis demographics, height, weight, blood pressure at rest, plasma glucose, lipids, comorbidities, and VO2 max data was extracted from the medical records of 199 participants attending the Executive Health Program at M Health Fairview of the University of Minnesota. Participants were predominantly white, middle-aged men with near-optimal blood pressure values. RESULTS Participants with low cardiorespiratory fitness had a VO2 max [mean (range) of 28 (19.4 - 36.1) mL/kg/min], and was observed in 33% of all participants. Participants with low cardiorespiratory fitness were more likely to have higher BMI, dyslipidemia and hypertension than those in the excellent to superior category of cardiorespiratory fitness, VO2 max [mean (range) 45.6 (31.8 - 61.2) mL/kg/min]. Prevalence of obesity (17%) was lower than in the general U.S. population, and those who were obese were more likely to be of low cardiorespiratory fitness. Those with low cardiorespiratory fitness had a four fold relative risk of belonging to the group at high risk of cardiovascular and metabolic diseases when compared to those with a fair to superior cardiorespiratory fitness. CONCLUSIONS Low cardiorespiratory fitness identified in a third of all participants, is a modifiable risk factor associated with risk for cardiovascular and metabolic disease, should be evaluated in executive health programs.