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Abstract Common and rare alleles are now being annotated across millions of human genomes, and omics technologies are increasingly being used to develop health and treatment recommendations. However, these alleles have not yet been systematically characterized relative to aerospace medicine. Here, we review published alleles naturally found in human cohorts that have a likely protective effect, which is linked to decreased cancer risk and improved bone, muscular, and cardiovascular health. Although some technical and ethical challenges remain, research into these protective mechanisms could translate into improved nutrition, exercise, and health recommendations for crew members during deep space missions.

Abstract Future multi-year crewed planetary missions will motivate advances in aerospace nutrition and telehealth. On Earth, the Human Cell Atlas project aims to spatially map all cell types in the human body. Here, we propose that a parallel Human Cell Space Atlas could serve as an openly available, global resource for space life science research. As humanity becomes increasingly spacefaring, high-resolution omics on orbit could permit an advent of precision spaceflight healthcare. Alongside the scientific potential, we consider the complex ethical, cultural, and legal challenges intrinsic to the human space omics discipline, and how philosophical frameworks may benefit from international perspectives.

Small-cell neuroendocrine carcinoma of the cervix (SCNECC) is a rare cancer with poor prognosis, with limited data to guide its treatment. The objective of this study was to evaluate practice patterns in the management of SCNECC. A 23-question online survey on management of SCNECC was disseminated to Canadian gynecologic oncologists (GO), radiation oncologists (RO) and medical oncologists (MO). In total, 34 practitioners from eight provinces responded, including 17 GO, 13 RO and four MO. During staging and diagnosis, 74% of respondents used a trimodality imaging approach, and 85% tested for neuroendocrine markers. In early-stage (1A1-1B2) SCNECC, 87% of practitioners used a surgical-based approach with various adjuvant and neoadjuvant treatments. In locally advanced (1B3-IVA) SCNECC, 53% favored primary chemoradiation, with cisplatin and etoposide, with the remainder using surgical or radiation-based approaches. In metastatic and recurrent SCNECC, the most common first-line regimen was etoposide and platinum, and 63% of practitioners considered clinical trials in the first line setting or beyond. This survey highlights diverse practice patterns in the treatment of SCNECC. Interdisciplinary input is crucial to individualizing multimodality treatment, and there is a need for prospective trials and intergroup collaboration to define the optimal approach towards managing this rare cancer type.

Background: There is a lack of evidence associating intraoperative transoesophageal echocardiography (TOE) use with improved outcomes among coronary artery bypass graft (CABG) surgery subpopulations. Methods: This matched retrospective cohort study used a US private claims dataset to compare outcomes among different CABG surgery patient populations with vs without TOE. Statistical analyses involved exact matching on pre-selected subgroups (congestive heart failure, single vessel, and multivessel CABG) and used fine and propensity-score balanced techniques to conduct multiple matched comparisons and sensitivity analyses. Results: Of 42 249 patients undergoing isolated CABG surgery, 24 919 (59.0%) received and 17 330 (41.0%) did not receive TOE. After matching, intraoperative TOE was significantly associated with a lower, 30-day mortality: 2.63% vs 3.20% (odds ratio [OR]: 0.81; 95% confidence interval [CI]: 0.71–0.92; P=0.002). In the subgroup matched comparisons, intraoperative TOE was significantly associated with a lower, 30-day mortality rate among those with congestive heart failure: 4.20% vs 5.26% (OR: 0.78; 95% CI: 0.66–0.94; P=0.007) and among those undergoing multivessel CABG with congestive heart failure: 4.23% vs 5.24% (OR: 0.80; 95% CI: 0.65–0.97; P=0.025), but not among those undergoing multivessel CABG without congestive heart failure: 1.83% vs 2.15% (OR: 0.85; 95% CI: 0.70–1.02; P=0.089, nor any of the remaining three subgroups. Conclusions: Among US adults undergoing isolated CABG surgery, intraoperative TOE was associated with improved outcomes in patients with congestive heart failure (vs without) and among patients undergoing multivessel (vs single vessel) CABG. These findings support prioritised TOE allocation to these patient populations at centres with limited TOE capabilities.

Abstract Conifers are long-lived and slow-evolving, thus requiring effective defences against their fast-evolving insect natural enemies. The copy number variation (CNV) of two key acetophenone biosynthesis genes Ugt5/Ugt5b and βglu-1 may provide a plausible mechanism underlying the constitutively variable defence in white spruce (Picea glauca) against its primary defoliator, spruce budworm. This study develops a long-insert sequence capture probe set (Picea_hung_p1.0) for quantifying copy number of βglu-1-like, Ugt5-like genes and single-copy genes on 38 Norway spruce (Picea abies) and 40 P. glauca individuals from eight and nine provenances across Europe and North America respectively. We developed local assemblies (Piabi_c1.0 and Pigla_c.1.0), full-length transcriptomes (PIAB_v1 and PIGL_v1), and gene models to characterise the diversity of βglu-1 and Ugt5 genes. We observed very large copy numbers of βglu-1, with up to 381 copies in a single P. glauca individual. We observed among-provenance CNV of βglu-1 in P. glauca but not P. abies. Ugt5b was predominantly single-copy in both species. This study generates critical hypotheses for testing the emergence and mechanism of extreme CNV, the dosage effect on phenotype, and the varying copy number of genes with the same pathway. We demonstrate new approaches to overcome experimental challenges in genomic research in conifer defences.

Background: Women with a significant family history of breast cancer are often offered more intensive and earlier surveillance than is offered to the general population in the National Breast Screening Programme. Up to now, this strategy has not been fully evaluated. Objective: To evaluate the benefit of mammographic surveillance for women aged 40–49 years at moderate risk of breast cancer due to family history. The study is referred to as FH01. Design: This was a single-arm cohort study with recruitment taking place between January 2003 and February 2007. Recruits were women aged

Abstract Background Estimating arbovirus transmission potential requires a mechanistic understanding of how environmental factors influence the expression of adult mosquito traits. While preimaginal exposure to environmental factors can have profound effects on adult traits, tracking and predicting these effects remains challenging. Methods Using Aedes albopictus and a structural equation modeling approach, we explored how larval nutrition and temperature jointly affect development rate and success, female body size, and whether these metrics capture carry-over effects on adult female longevity. Additionally, we investigated how larval diet and temperature affect the baseline expression of 10 immune genes. Results We found that larval development success was primarily determined by diet, while temperature and diet both affected development rate and female body size. Under a low larval diet, pupal wet weight and wing length both declined with increasing temperature. In contrast, responses of the two morphometric measures to rearing temperature diverged when females were provided higher larval nutrition, with pupal wet weight increasing and wing length decreasing at higher temperatures. Our analyses also revealed opposing relationships between adult female lifespan and the two morphometric measures, with wing length having a positive association with longevity and pupal weight a negative association. Larval diet indirectly affected adult longevity, and the time to pupation was negatively correlated with longevity. The expression of eight immune genes from the toll, JAK-STAT and Imd pathways was enhanced in mosquitoes with higher nutrition. Conclusions Our results highlight deficiencies from using a single body size measure to capture carry-over effects on adult traits. Further studies of larval development rate under varying environmental conditions and its potential for tracking carry-over effects on vectorial capacity are warranted. Graphical Abstract

Summary:. Traditionally, full-thickness wounds with exposed structures are treated with flap coverage or dermal regenerative templates. Most dermal regenerative templates are biologic in origin, but recently synthetic options have become available. One such product is a synthetic hybrid-scale fiber matrix (SHSFM). In this case, SHSFM was used to treat a recalcitrant calcaneal wound. After the wound granulated, it was biopsied, and histopathologic analysis was conducted. A 16-year-old woman involved in a motor vehicle collision sustained multiple traumatic injuries which were stabilized. Postoperatively, she developed a calcaneal infection and associated wound, which developed into a chronic, nonhealing wound. Failed treatments included removal of hardware, multiple debridements, and advanced wound therapies. An SHSFM was then trialed, which led to granulation of the wound without infection. Despite wound healing, the patient subsequently elected to undergo a below-the-knee amputation due to pain and functional disability from posttraumatic ankle arthritis. The heel was biopsied at the time of amputation for analysis. Pathologists noted excellent granulation tissue formation and complete coverage of the wound surface area and 75% of the wound depth, which included epithelialization and decreasing inflammation at wound edges. Collagen deposition and numerous interspersed blood vessels were present. Foreign material and bacteria were absent. No osteomyelitis was observed. This analysis provided the opportunity to investigate the in vivo regenerate from a novel synthetic SHSFM. Given the uniqueness and challenges presented in this case, the usage of this relatively new product warrants further investigation with larger populations and assorted wound etiologies.

Abstract Background Genetic and genomic studies are seeing an increase in sample sizes together with a wider range of species investigated in response to environmental change concerns. In turn, these changes may come with challenges including the time and difficulty to isolate nucleic acids (DNA or RNA), the sequencing cost and environmental impacts of the growing amount of plastic waste generated in the process. Pseudotsuga menziesii var. menziesii (Mirbel) Franco (PM), Tsuga heterophylla (Raf.) Sarg. (TH) and Thuja plicata Donn ex D.Don (TP) are conifer species found in diverse woodlands both as natives and naturalized exotics. Our study was carried out whilst investigating their genetics to understand their population structure and potential for adaptation. Results In the present study, we compared two different DNA isolation methods, i.e., spin-column DNeasy plant mini kit (QIAGEN), and temperature-driven enzymatic cocktail Plant DNA Extraction (MicroGEM). The quantity of recovered DNA and the quality of DNA were assessed along with the plastic footprint and time needed for three tree species. Both methods were optimised and proven to provide enough DNA for each studied species. The yield of DNA for each method depended on the species: QIAGEN showed higher yield in P. menziesii and T. heterophylla, while T. plicata recovered similar amount of DNA for both methods. The DNA quality was investigated using DNA barcoding techniques by confirming species identity and species discrimination. No difference was detected in the PCR amplification of the two barcoding loci, (rbcL and trnH-psbA), and the recovered sequences between DNA isolation methods. Measurement of the plastic use and the processing time per sample indicated that MicroGEM had a 52.64% lower plastic footprint and was 51.8% faster than QIAGEN. Conclusions QIAGEN gave higher yields in two of the species although both methods showed similar quality results across all species. However, MicroGEM was clearly advantageous to decrease the plastic footprint and improve the time efficiency. Overall, MicroGEM recovers sufficient and reliable DNA to perform common downstream analyses such as PCR and sequencing. Our findings illustrate the benefits of research and efforts towards developing more sustainable methods and techniques to reduce the environmental footprint of molecular analyses.

Background: This article presents a previously unpublished technique successfully utilized to treat two neoplastic lesions of the thumb nail bed, while aiming to retain motor and sensory function by maximizing length of the digit. Case report: We present a unique case of concomitant verruca vulgaris and squamous cell carcinoma in the nail bed and surrounding areas of a 75-year-old Caucasian male's thumb. There is not a defined treatment algorithm for this presentation, however, due to its malignant nature and possibility for metastasis, carcinoma must be resected with good margins. Treatment options include amputation at the interphalangeal joint, or resection with adequate margins that would involve the distal phalanx. In this case, we removed the nail bed and used the remainder of the phalanx to create a shortened distal portion of the 1st digit in an attempt to prevent functional loss. Conclusion: Through the utilization of this technique in patients who present with similar findings, the application of this procedure may prove beneficial in returning the patient to normal activity. While Dermatologic and Orthopaedic hand specialties would benefit the most from this technique, there is precedent that this technique may be applied in altered cases.

Patients with advanced cardiogenic shock requiring mechanical circulatory support are uniquely susceptible to clinical deterioration. Limiting physiologic perturbations via avoidance of general anesthesia and endotracheal intubation by awake Impella 5.5 placement is safe and may represent a novel strategy in mechanical circulatory support initiation among patients in cardiogenic shock. (Level of Difficulty: Intermediate.)

Carpometacarpal (CMC) fracture-dislocations are uncommon hand injuries, with few studies available regarding their treatment. The current operative treatment options include fixation with K-wires, mini-screws, or plates, though there is no standardized approach because of varying injury patterns and complications associated with each device. The INnate™ threaded intramedullary nail is a relatively novel treatment option that has shown promise in metacarpal fracture fixation by facilitating faster mobilization and recovery with enhanced rotational stability and no compression to prevent fracture displacement and shortening. This study assesses the efficacy of the INnate™ nail for fixation of CMC fracture-dislocations of the second through fifth joints.Nine patients with fourteen CMC fracture-dislocations treated with the INnate™ nail at the University Medical Center between 2019 and 2021 were enrolled in the study. We evaluated postoperative outcomes in terms of pain, total active range of motion (TAM), and return to normal activities.Of the nine patients, seven returned for follow-up. The average time to radiographic union was 11.5 weeks. At final follow-up, no patient reported pain (n = 6). Four patients had 100% TAM, 1 had 95% TAM, and 1 had 25% TAM. The average percentage of normal activity resumed was 84.0% (n = 5). No significant complications were reported. One patient had a dorsal spanning plate; hence, we were unable to record outcomes measures regarding the CMC injury. An additional patient had diminished ROM of the injured hand, but his last follow-up was only 1 month postop.Our pilot data overall suggest that the INnate™ threaded intramedullary nail has the potential to improve treatment algorithms for CMC fracture-dislocations.

Abstract Background and objectives Phytophthora ramorum severely affects both European larch (EL) and Japanese larch (JL) trees as indicated by high levels of mortality particularly in the UK. Field observations suggested that EL is less severely affected and so may be less susceptible to P. ramorum than JL; however, controlled inoculations have produced inconsistent or non-statistically significant differences. The present study aimed to compare RNA transcript accumulation profiles in EL and JL in response to inoculation with P. ramorum to improve our understanding of their defence responses. Methodology RNA-sequencing was carried out on bark tissues following the inoculation with P. ramorum of potted saplings in both EL and JL carried out under controlled environment conditions, with sampling at 1, 3, 10, and 25 days post inoculation in infected and control plants. Results All of the inoculated trees rapidly developed lesions but no statistically significant differences were found in lesion lengths between EL and JL. RNA-Sequencing comparing control and inoculate saplings identified key differences in differentially expressed genes (DEGs) between the two larch species. European larch had rapid induction of defence genes within 24 hours of infection followed by sustained expression until 25 days after inoculation. Results in JL were more varied; upregulation was stronger but more transient and represented fewer defence pathways. Gene enrichment analyses highlighted differences in jasmonate signalling and regulation including NPR1 upregulation in EL only, and specific aspects of secondary metabolism. Some DEGs were represented by multiple responsive copies including lipoxygenase, chalcone synthase and nucleotide-binding, leucine-rich-repeat genes. Conclusion The variations between EL and JL in responsive DEGs of interest as potentially related to differences seen in the field and should be considered in the selection of trees for planting and future breeding.

The formation and deposition of mineral scales, such as barium sulphate (BaSO4) and calcium carbonate (CaCO3), is a common problem in many industrial and life science processes. This is caused by chemical incompatibility due either to the mixing of incompatible aqueous solutions or due to changes of the physical conditions, usually temperature and pressure. Many laboratory studies have been conducted using techniques broadly classified into batch and flowing tests to understand the reaction and mechanisms which occur in the initial stages of scale formation and its subsequent deposition on a solid surface. In this study we focused on the dynamic (kinetic) deposition of barium sulphate arising from the mixing of two incompatible brines, one containing barium (Ba2+) ions and other containing sulphate (SO42−) ions, suitably charged balanced by other inert anions and cations. The mechanism of barium sulphate (barite) deposition is often assumed to be a one-step reaction in which the ions in the bulk fluid directly deposit onto a surface. However, there is strong evidence in the literature that barium sulphate may deposit through an intermediary nanocrystalline phase which we refer to as BaSO4(aq) in this paper. This initial nucleation species or nanocrystalline material [BaSO4(aq)] may remain suspended in the aqueous system and hence may be transported through the system before it ultimately is deposited on a surface, possibly covered by a previously deposited barite coating. This does not preclude the direct deposition of barite on the surface which may indeed also occur. In this paper, we have formulated a barite formation/deposition model which includes both of these mechanisms noted above, i.e., i) barite formation in solution of a nanocrystalline precursor which may be transported and deposited at an interface and ii) the direct kinetic deposition of barite from the free ions in solution. When only the former mechanism applies (nanocrystal formation, transport and deposition) we refer to the model Model 1 and, when both mechanism occur together it is called Model 2. Although this is a fully kinetic model, it, must honour the known equilibrium state of the system in order to be fully consistent and this is demonstrated in the paper. The kinetic approach is most important in flowing conditions, since the residence time in a given part of the macroscopic system (e.g., in a pipe or duct) may be shorter that the time required to reach the full equilibrium state of the system. The reaction extent can be affected by advection, introduction of viscous dissipation forces, formation of hydrodynamic boundary layers and the mass transport in the boundary layer close to the depositing surface. In this paper, we call the latter the diffusion penetration length, denoted δ, and the relation of this quantity with the hydraulic layer is discussed. In this work, we have coupled the barium sulphate depositional model with a full computation fluid dynamics calculation (CFD) model in order to study the behaviour of this system and demonstrate the importance of non-equilibrium effects. Studied using different kinetic constants. The Navier-Stokes equations are solved to accurately model the local residence time, species transport, and calculate the hydraulic and mass transfer layers. A number of important concepts for barium sulphate kinetic deposition are established and a wide range of sensitivity calculations are performed and analysed. Geometry alteration due to flow constriction in the pipe or duct caused by the depositing scale is also an important phenomenon to consider and model in a flowing system, and this is rarely done, especially with a full kinetic deposition model. The geometry change affects both hydraulic and mass transport layers in the vicinity of the depositing surface and may often change the deposition regime in terms of the balance of dominant mechanism which apply. The change in geometry requires occasional re-gridding of the CFD calculations, which is time consuming but essential in order to study some critical effects I the system. The effect of geometry change on the local residence time is investigated through by performing a “ramping up” of the flow rate and explicitly deforming the geometry as the deposition occurs. The influence of surface roughness on the reaction rates was also studied using different kinetic constants. Our results show that in the laminar flow regime, the extent of deposition on a surface is limited by the diffusion penetration length (δ) referred to above. This means that there will be more deposits at lower flow rates, where the diffusion penetration length is larger. As the deposition reduces the flow path cross-section area near the inlet vicinity, the velocity increases. Thus, the hydraulic layer becomes smaller, resulting in a smaller diffusion penetration length, which causes the deposition location to move towards the end of the flow path, where the velocity is still smaller. The results of this study have the potential to contribute to the development of more effective strategies for preventing scaling in a wide range of industrial processes.

Genomic selection has recently become an established part of breeding strategies in cereals. However, a limitation of linear genomic prediction models for complex traits such as yield is that these are unable to accommodate Genotype by Environment effects, which are commonly observed over trials on multiple locations. In this study, we investigated how this environmental variation can be captured by the collection of a large number of phenomic markers using high-throughput field phenotyping and whether it can increase GS prediction accuracy. For this purpose, 44 winter wheat (Triticum aestivum L.) elite populations, comprising 2,994 lines, were grown on two sites over 2 years, to approximate the size of trials in a practical breeding programme. At various growth stages, remote sensing data from multi- and hyperspectral cameras, as well as traditional ground-based visual crop assessment scores, were collected with approximately 100 different data variables collected per plot. The predictive power for grain yield was tested for the various data types, with or without genome-wide marker data sets. Models using phenomic traits alone had a greater predictive value (R2 = 0.39–0.47) than genomic data (approximately R2 = 0.1). The average improvement in predictive power by combining trait and marker data was 6%–12% over the best phenomic-only model, and performed best when data from one full location was used to predict the yield on an entire second location. The results suggest that genetic gain in breeding programmes can be increased by utilisation of large numbers of phenotypic variables using remote sensing in field trials, although at what stage of the breeding cycle phenomic selection could be most profitably applied remains to be answered.

Global climate model projections suggest that 21st century climate change will bring significant drying in the terrestrial midlatitudes. Recent glacier modeling suggests that runoff from glaciers will continue to provide substantial freshwater in many drainage basins, though the supply will generally diminish throughout the century. In the absence of dynamic glacier ice within global climate models (GCMs), a comprehensive picture of future hydrological drought conditions in glaciated regions has been elusive. Here, we leverage the results of existing GCM simulations and a global glacier model to evaluate glacial buffering of droughts in the Standardized Precipitation-Evapotranspiration Index (SPEI). We compute one baseline version of the SPEI and one version modified to account for glacial runoff changing over time, and we compare the two for each of 56 large-scale glaciated basins worldwide. We find that accounting for glacial runoff tends to increase the multi-model ensemble mean SPEI and reduce drought frequency and severity, even in basins with relatively little ( %) glacier cover. When glacial runoff is included in the SPEI, the number of droughts is reduced in 40 of 56 basins and the average drought severity is reduced in 53 of 56 basins, with similar counts in each time period we study. Glacial drought buffering persists even as glacial runoff is projected to decline through the 21st century. Results are similar under representative concentration pathway (RCP) 4.5 and 8.5 emissions scenarios, though results for the higher-emissions RCP 8.5 scenario show wider multi-model spread (uncertainty) and greater incidence of decreasing buffering later in the century. A k-means clustering analysis shows that glacial drought buffering is strongest in moderately glaciated, arid basins.

Peripheral nerve injuries (PNIs) often present with variable symptoms, making them difficult to diagnose, treat, and monitor. When neurologic compromise is inadequately assessed, suboptimal treatment decisions can result in lasting functional deficits. There are many available tools for evaluating pain and functional status of peripheral nerves. However, the literature lacks a detailed, comprehensive view of the data comparing the clinical utility of these modalities, and there is no consensus on the optimal algorithm for sensory and pain assessment in PNIs. We performed a systematic review of the literature focused on clinical data, evaluating pain and sensory assessment methods in peripheral nerves. We searched through multiple databases, including PubMed/Medline, Embase, and Google Scholar, to identify studies that assessed assessment tools and explored their advantages and disadvantages. A total of 66 studies were selected that assessed various tools used to assess patient's pain and sensory recovery after a PNI. This review may serve as a guide to select the most appropriate assessment tools for monitoring nerve pain and/or sensory function both pre- and postoperatively. As the surgeons work to improve treatments for PNI and dysfunction, identifying the most appropriate existing measures of success and future directions for improved algorithms could lead to improved patient outcomes.

Amputations have been performed with few modifications since the dawn of surgery. Blood vessels are ligated, bones are shortened, and nerves are cut. In a percentage of people, this can result in severe neuropathic, residual limb, and phantom limb pain. Targeted muscle reinnervation is a surgical procedure initially conceived to optimize function for myoelectric prostheses in amputees. Recently, it has been adopted more widely by surgeons for the prevention and treatment of neuropathic pain. Perhaps as a function of its relatively recent development, many authors perform this operation differently, and there has been no overall agreement regarding the principles, indications, technical specifics, and postoperative management guidelines. This article is written as a consensus statement by surgeons focused on the treatment of neuropathic pain and those with extensive experience performing targeted muscle reinnervation. It is designed to serve as a roadmap and template for extremity surgeons to consider when performing targeted muscle reinnervation.

Background:. Revision nerve decompression remains a challenge for surgeons. Avive Soft Tissue Membrane is processed human umbilical cord membrane that may reduce inflammation and scarring, thereby improving tissue gliding. Although synthetic conduits have been reported in revision nerve decompression, the use of Avive has not. Methods:. Prospective study of revision nerve decompression with Avive application. VAS pain, two-point discrimination, Semmes-Weinstein, pinch and grip strength, range of motion, Quick Disability of Arm, Shoulder & Hand (QuickDASH), and satisfaction were recorded. Using a propensity-matched cohort, VAS pain and satisfaction were retrospectively collected to compare with cohort outcomes. Results:. In the Avive cohort, 77 patients (97 nerves) were included. Mean follow-up was 9.0 months. Avive was applied to the median nerve in 47.4%, ulnar nerve in 39.2%, and radial nerve in 13.4%. VAS pain was 4.5 preoperatively and 1.3 postoperatively. S4 sensory recovery was achieved in 58% of patients, S3+ in 33%, S3 in 7%, S0 in 2%, and improvement from baseline in 87%. Strength improved in 92%. Mean total active motion was 94.8%. Mean QuickDASH score was 36.1, and 96% reported improved or resolved symptoms. Preoperative pain was not significantly different between Avive cohort and controls (P = 0.618). Postoperative pain was significantly lower in cohort patients (1.3 ± 2.2 versus 2.7 ± 3.0, P = 0.001). In the Avive cohort, more had improved or resolved symptoms (P < 0.0001). Clinically important improvement in pain was reported in 64.9% of Avive group patients versus 40.8% of controls (P = 0.002). Conclusion:. Avive contributes to improved outcomes in revision nerve decompression.

Background Peripheral nerve function is often difficult to assess given the highly variable presentation and subjective patient experience of nerve injury. If nerve assessment is incomplete or inaccurate, inappropriate diagnosis and subsequent treatment may result in permanent dysfunction. Objective As our understanding of nerve repair and generation evolves, so have tools for evaluating peripheral nerve function, recovery, and nerve-related impact on the quality of life. Provocative testing is often used in the clinic to identify peripheral nerve dysfunction. Patient-reported outcome forms provide insights regarding the effect of nerve dysfunction on daily activities and quality of life. Methods We performed a review of the literature using a comprehensive combination of keywords and search algorithms to determine the clinical utility of different provocative tests and patient-reported outcomes measures in a variety of contexts, both pre- and postoperatively. Results This review may serve as a valuable resource for surgeons determining the appropriate provocative testing tools and patient-reported outcomes forms to monitor nerve function both pre- and postoperatively. Conclusion As treatments for peripheral nerve injury and dysfunction continue to improve, identifying the most appropriate measures of success may ultimately lead to improved patient outcomes.

Abstract Background Selection has dramatically shaped genetic and phenotypic variation in bread wheat. We can assess the genomic basis of historical phenotypic changes, and the potential for future improvement, using experimental populations that attempt to undo selection through the randomizing effects of recombination. Results We bred the NIAB Diverse MAGIC multi-parent population comprising over 500 recombinant inbred lines, descended from sixteen historical UK bread wheat varieties released between 1935 and 2004. We sequence the founders’ genes and promoters by capture, and the MAGIC population by low-coverage whole-genome sequencing. We impute 1.1 M high-quality SNPs that are over 99% concordant with array genotypes. Imputation accuracy only marginally improves when including the founders’ genomes as a haplotype reference panel. Despite capturing 73% of global wheat genetic polymorphism, 83% of genes cluster into no more than three haplotypes. We phenotype 47 agronomic traits over 2 years and map 136 genome-wide significant associations, concentrated at 42 genetic loci with large and often pleiotropic effects. Around half of these overlap known quantitative trait loci. Most traits exhibit extensive polygenicity, as revealed by multi-locus shrinkage modelling. Conclusions Our results are consistent with a gene pool of low haplotypic diversity, containing few novel loci of large effect. Most past, and projected future, phenotypic changes arising from existing variation involve fine-scale shuffling of a few haplotypes to recombine dozens of polygenic alleles of small effect. Moreover, extensive pleiotropy means selection on one trait will have unintended consequences, exemplified by the negative trade-off between yield and protein content, unless selection and recombination can break unfavorable trait-trait associations.

Abstract Introduction The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic revealed a worldwide lack of effective molecular surveillance networks at local, state, and national levels, which are essential to identify, monitor, and limit viral community spread. SARS‐CoV‐2 variants of concern (VOCs) such as Alpha and Omicron, which show increased transmissibility and immune evasion, rapidly became dominant VOCs worldwide. Our objective was to develop an evidenced‐based genomic surveillance algorithm, combining reverse transcription polymerase chain reaction (RT‐PCR) and sequencing technologies to quickly identify highly contagious VOCs, before cases accumulate exponentially. Methods Deidentified data were obtained from 508,969 patients tested for coronavirus disease 2019 (COVID‐19) with the TaqPath COVID‐19 RT‐PCR Combo Kit (ThermoFisher) in four CLIA‐certified clinical laboratories in Puerto Rico (n = 86,639) and in three CLIA‐certified clinical laboratories in the United States (n = 422,330). Results TaqPath data revealed a frequency of S Gene Target Failure (SGTF) > 47% for the last week of March 2021 in both, Puerto Rico and US laboratories. The monthly frequency of SGTF in Puerto Rico steadily increased exponentially from 4% in November 2020 to 47% in March 2021. The weekly SGTF rate in US samples was high (>8%) from late December to early January and then also increased exponentially through April (48%). The exponential increase in SGFT prevalence in Puerto Rico was concurrent with a sharp increase in VOCs among all SARS‐CoV‐2 sequences from Puerto Rico uploaded to Global Influenza Surveillance and Response System (GISAID) (n = 461). Alpha variant frequency increased from

Abstract Burial of nerve allografts in muscle tissue for later use is a novel technique with no prior literature discussions. This may be a safe and effective technique for short‐term preservation of nerve allograft removed from a prior reconstruction.

Abstract Dalbergia cochinchinensis and D. oliveri are classified as vulnerable and endangered, respectively, in the IUCN Red List and under continued threat from deforestation and illegal harvesting for rosewood. Despite emerging efforts to conserve and restore these species, little is known of their responses to drought and heat stress, which are expected to increase in the Greater Mekong Subregion where the species co‐occur and are endemic. In this study of isolated and combined drought and heat effects, we found that D. oliveri had an earlier stomatal closure and more constant midday water potential in response to increasing drought level, suggesting that D. oliveri is relatively isohydric while D. cochinchinensis is relatively anisohydric. Heat shock and drought had synergistic effects on stomatal closure. Our results indicate contrasting relationships in water relations, photosynthetic pigment levels, and total soluble sugars. An increase in chlorophyll a was observed in D. cochinchinensis during drought, and a concomitant increase in carotenoid content likely afforded protection against photo‐oxidation. These physiological changes correlated with higher total soluble sugars in D. cochinchinensis. By contrast, D. oliveri avoided drought by reducing chlorophyll content and compromising productivity. Anisohydry and drought tolerance in D. cochinchinensis are adaptations which fit well with its ecological niche as a pioneering species with faster growth in young trees. We believe this understanding of the stress responses of both species will be crucial to their effective regeneration and conservation in degraded habitats and in the face of climate change.

Abstract Background Clinical trial reports often emphasize efficacy over harms, leading to misinterpretation of the risk‐to‐benefit ratio of new therapies. Clear and sufficiently detailed reporting of methods and results is especially important in the abstracts of trial reports, as readers often base their assessment of a trial on such information. In this study, we evaluated the quality of adverse event (AE) reporting and abstract quality in phase III randomized controlled trials (RCTs) of systemic therapies in breast and colorectal cancer. Methods Medline, EMBASE, Cochrane Database of RCTs, and Cochrane Database of Systematic Reviews were searched from November 2005 to September 2018. Phase III RCTs evaluating systemic therapies in breast or colorectal cancer were included. Each article was independently reviewed by two investigators using a standardized data extraction form based on guidelines developed by the Consolidated Standards of Reporting Trials (CONSORT) group. Descriptive statistics, bivariate analysis, and multivariable linear regression were used to analyze data. All statistical tests were two‐sided. Results Of 166 RCTs identified, 99.4% reported harms in the manuscript body, and 59.6% reported harms in the abstract. Reporting was restricted to severe harms in 15.6% of RCTs. Statistical comparison of AE rates went unreported in 59.0% of studies. Information regarding AEs leading to dose reductions, treatment discontinuations, or study withdrawals went unreported in 59.3%, 18.7%, and 86.8% of studies, respectively. Recently published RCTs (P = .009) and those sponsored at least partially by for‐profit companies (P = .003) had higher abstract quality scores. Conclusions Breast and colorectal cancer phase III RCTs inadequately report CONSORT‐compliant AE data. Improved guideline adherence and abstract reporting is required to properly weigh benefits and harms of new oncologic therapies. Systematic Review Registration Number CRD42019140673.

Background Preoperative oral antibiotics in addition to intravenous antibiotics and mechanical bowel preparation (MBP) may influence the gut microbiome and reduce both the postoperative systemic inflammatory response to surgery and postoperative infective complications following colorectal resection. This propensity score‐matched study compared outcomes of patients undergoing left‐sided colonic or rectal resection with or without a combination of oral antibiotics and MBP. Methods The addition of oral antibiotics and MBP to prophylactic intravenous antibiotics in left‐sided colonic and rectal resections was introduced in 2015–2016 at a single institution. Propensity score matching was undertaken to compare the effects of oral antibiotics plus MBP versus neither oral antibiotics nor MBP on the postoperative systemic inflammatory response and short‐term outcomes in patients undergoing left‐sided colonic or rectal resection between 2013 and 2018. Results Of 396 patients who had propensity score matching for host, anaesthetic and operative factors, 204 matched patients were identified. The addition of oral antibiotics and MBP was associated with a significantly reduced postoperative inflammatory response (reduced postoperative Glasgow Prognostic Score) on day 3 (odds ratio (OR) 0·66, 95 per cent c.i. 0·44 to 0·99; P = 0·013) and day 4 (OR 0·46, 0·30 to 0·71; P = 0·001). Significantly reduced overall complications (OR 0·31, 0·17 to 0·56; P

Penetrating cardiac injury in trauma patients is highly morbid. Most cases do not survive long enough to manifest the severe physiologic consequences of massive blood product resuscitation, namely, thoracic compartment syndrome and right ventricular (RV) failure. This case exhibits a thoracic compartment syndrome and RV failure so severe that the open chest management required mechanical separation of a clamshell thoracotomy. The resuscitation and the techniques utilized to maintain an open chest will be described.

Proliferative Vitreoretinopathy (PVR) is a refractory retinal disease whose primary pathogenesis involves the epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells. At present, there is no effective treatment other than surgery for PVR. The purpose of this study was to investigate the effect of αB crystallin peptide (αBC-P) on EMT in PVR. We have previously shown that this peptide is antiapoptotic and regulates RPE redox status. Subconfluent primary human RPE (hRPE) cells were stimulated by TGFβ2 (10 ng/mL) with or without αBC-P (50 or 75 μg/mL) for 48 h and expression of EMT/mesenchymal to epithelial transition (MET) markers was determined. Mitochondrial ROS (mtROS) generation in hRPE cells treated with TGFβ2 was analyzed. The effect of TGFβ2 and αBC-P on oxidative phosphorylation (OXPHOS) and glycolysis in hRPE was studied. RPE cell migration was also assessed. A PVR-like phenotype was induced by intravitreal dispase injection in C57BL/6J mice. PVR progression and potential therapeutic efficiency of αBC-Elastin-like polypeptides (ELP) was studied using fundus photography, OCT imaging, ERG, and histologic analysis of the retina. αSMA, E-cadherin, Vimentin, Fibronectin and, RPE65, and CTGF were analyzed on Day 28. Additionally, the amount of VEGF-A in retinal cell lysates was measured. The EMT-associated αSMA, Vimentin, SNAIL and SLUG showed a significant upregulation with TGFβ2, and their expression was significantly suppressed by cotreatment with αBC-P. The MET-associated markers, E-cadherin and Sirt1, were significantly downregulated by TGFβ2 and were restored by αBC-P. Incubation of hRPE with TGFβ2 for 24 h showed a marked increase in mitochondrial ROS which was noticeably inhibited by αBC-ELP. We also showed that after TGFβ2 treatment, SMAD4 translocated to mitochondria which was blocked by αBC-ELP. Mitochondrial oxygen consumption rate increased with TGFβ2 treatment for 48 h, and αBC-P co-treatment caused a further increase in OCR. Glycolytic functions of RPE were significantly suppressed with αBC-P (75 μg/mL). In addition, αBC-P significantly inhibited the migration from TGFβ2 treatment in hRPE cells. The formation of proliferative membranes was suppressed in the αBC-ELP-treated group, as evidenced by fundus, OCT, and H&E staining in dispase-induced PVR in mice. Furthermore, ERG showed an improvement in c-wave amplitude. In addition, immunostaining showed significant suppression of αSMA and RPE65 expression. It was also observed that αBC-ELP significantly reduced the expression level of vimentin, fibronectin, and CTGF. Our findings suggest that the antioxidant αBC-P may have therapeutic potential in preventing PVR by reversing the phenotype of EMT/MET and improving the mitochondrial function in RPE cells.

Background: Treatment of patients with traumatic axonotmesis presents challenges. Processed human umbilical cord membrane has been recently developed with improved handling and resorption time compared to other amniotic membrane wraps, and may be beneficial in nerve reconstruction. This study evaluates postoperative outcomes after traumatic peripheral nerve injury after placement of commercially available processed human umbilical cord membrane. Methods: We performed a prospective, single-center pilot study of patients undergoing multi-level surgical reconstruction for exposed, non-transected peripheral nerve. Functional outcomes including pain, range of motion, pinch and grip strength, and the QuickDASH and SF-36 patient-reported outcome measures were recorded, when possible, at the 1-week and 3, 6, and 9 months postop visit. One-tailed paired t -tests were performed to evaluate outcome improvement at final follow-up. Results: Twenty patients had processed human umbilical cord membrane placement without surgical complications. Mean follow-up was 7.5 months (range: 3–10 months) and mean age was 39 years (range: 15–65). Twelve (67%) patients were male, and the majority of placement sites were in the upper extremity (85%). Mean preoperative visual analog scale pain score was significantly reduced at most recent follow-up, as were QuickDASH scores. All patients had improved functional outcomes at the 9-month follow-up, and SF-36 outcomes at 9 months showed improvement across all dimensions. Conclusion: This study indicates that processed human umbilical cord membrane may be a useful adjunct in nerve surgery with noted improvements in postoperative function, pain, and patient-reported outcome measures. Future studies are needed to assess long-term outcomes after traumatic nerve injury treated with processed human umbilical cord membrane.

Abstract Few multifocal hand chondrosarcomas have been reported. To our knowledge, this report is the first to describe multifocal hand chondrosarcoma in a patient with no evidence of prior enchondroma, Ollier's disease, or Maffucci syndrome.

With the emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants that may increase transmissibility and/or cause escape from immune responses, there is an urgent need for the targeted surveillance of circulating lineages. It was found that the B.1.1.7 (also 501Y.V1) variant, first detected in the United Kingdom, could be serendipitously detected by the Thermo Fisher TaqPath COVID-19 PCR assay because a key deletion in these viruses, spike Δ69-70, would cause a "spike gene target failure" (SGTF) result. However, a SGTF result is not definitive for B.1.1.7, and this assay cannot detect other variants of concern (VOC) that lack spike Δ69-70, such as B.1.351 (also 501Y.V2), detected in South Africa, and P.1 (also 501Y.V3), recently detected in Brazil. We identified a deletion in the ORF1a gene (ORF1a Δ3675-3677) in all 3 variants, which has not yet been widely detected in other SARS-CoV-2 lineages. Using ORF1a Δ3675-3677 as the primary target and spike Δ69-70 to differentiate, we designed and validated an open-source PCR assay to detect SARS-CoV-2 VOC. Our assay can be rapidly deployed in laboratories around the world to enhance surveillance for the local emergence and spread of B.1.1.7, B.1.351, and P.1.

Bone and soft tissue sarcomas of the upper extremity are relatively uncommon. In many cases, they are discovered incidentally during evaluation of traumatic injuries or common ailments such as rotator cuff tendonitis or tennis elbow. Thus, it is important for all orthopedic surgeons to understand the differential diagnosis, workup, and treatment for upper extremity lesions. An appreciation of the clinical and radiographic features of primary malignant lesions aids in identifying patients that need referral to an orthopedic oncologist and a multidisciplinary team.

This 3-page document provides an overview of anhidrosis in horses, including symptoms and management tips. Written by Laura Patterson-Rosa, Martha F. Mallicote, Robert J. MacKay, and Samantha A. Brooks, and published by the UF/IFAS Department of Animal Sciences, October 2020.

Abstract Background Outbreaks of spruce budworm (SBW, Choristoneura fumiferana Clem.) cause major recurrent damage in boreal conifers such as white spruce ( Picea glauca [Moench] Voss) and large losses of forest biomass in North America. Although defensive phenolic compounds have recently been linked to chemical resistance against SBW, their genetic basis remains poorly understood in forest trees, especially in conifers. Here, we used diverse association genetics approaches to discover genes and their variants that may control the accumulation of acetophenones, and dissect the genetic architecture of these defence compounds against SBW in white spruce mature trees. Results Out of 4747 single nucleotide polymorphisms (SNPs) from 2312 genes genotyped in a population of 211 unrelated individuals, genetic association analyses identified 35 SNPs in 33 different genes that were significantly associated with the defence traits by using single-locus, multi-locus and multi-trait approaches. The multi-locus approach was particularly effective at detecting SNP–trait associations that explained a large fraction of the phenotypic variance (from 20 to 43%). Significant genes were regulatory including the NAC transcription factor, or they were involved in carbohydrate metabolism, falling into the binding, catalytic or transporter activity functional classes. Most of them were highly expressed in foliage. Weak positive phenotypic correlations were observed between defence and growth traits, indicating little or no evidence of defence-growth trade-offs. Conclusions This study provides new insights on the genetic architecture of tree defence traits, contributing to our understanding of the physiology of resistance mechanisms to biotic factors and providing a basis for the genetic improvement of the constitutive defence of white spruce against SBW.

Information on crop pedigrees can be used to help maximise genetic gain in crop breeding and allow efficient management of genetic resources. We present a pedigree resource of 2,657 wheat (Triticum aestivum L.) genotypes originating from 38 countries, representing more than a century of breeding and variety development. Visualisation of the pedigree enables illustration of the key developments in United Kingdom wheat breeding, highlights the wide genetic background of the UK wheat gene pool, and facilitates tracing the origin of beneficial alleles. A relatively high correlation between pedigree- and marker-based kinship coefficients was found, which validated the pedigree and enabled identification of errors in the pedigree or marker data. Using simulations with a combination of pedigree and genotype data, we found evidence for significant effects of selection by breeders. Within crosses, genotypes are often more closely related than expected by simulations to one of the parents, which indicates selection for favourable alleles during the breeding process. Selection across the pedigree was demonstrated on a subset of the pedigree in which 110 genotyped varieties released before the year 2000 were used to simulate the distribution of marker alleles of 45 genotyped varieties released after the year 2000, in the absence of selection. Allelic diversity in the 45 varieties was found to deviate significantly from the simulated distributions at a number of loci, indicating regions under selection over this period. The identification of one of these regions as coinciding with a strong yield component quantitative trait locus (QTL) highlights both the potential of the remaining loci as wheat breeding targets for further investigation, as well as the utility of this pedigree-based methodology to identify important breeding targets in other crops. Further evidence for selection was found as greater linkage disequilibrium (LD) for observed versus simulated genotypes within all chromosomes. This difference was greater at shorter genetic distances, indicating that breeder selections have conserved beneficial linkage blocks. Collectively, this work highlights the benefits of generating detailed pedigree resources for crop species. The wheat pedigree database developed here represents a valuable community resource and will be updated as new varieties are released at https://www.niab.com/pages/id/501/UK_Wheat_varieties_Pedigree.