X-ray-Sensitive Doped CaF2-Based MRI Contrast Agents for Local Radiation Dose Measurement.

Ionizing radiation has become widely used in medicine, with application in diagnostic techniques, such as computed tomography (CT) and radiation therapy (RT), where X-rays are used to diagnose and treat tumors. The X-rays used in CT and, in particular, in RT can have harmful side effects; hence, an accurate determination of the delivered radiation dose is of utmost importance to minimize any damage to healthy tissues. For this, medical specialists mostly rely on theoretical predictions of the delivered dose or external measurements of the dose. To extend the practical use of ionizing radiation-based medical techniques, such as magnetic resonance imaging (MRI)-guided RT, a more precise measurement of the internal radiation dose internally is required. In this work, a novel approach is presented to measure dose in liquids for potential future in vivo applications. The strategy relies on MRI contrast agents (CAs) that provide a dose-sensitive signal. The demonstrated materials are (citrate-capped) CaF2 nanoparticles (NPs) doped with Eu3+ or Fe2+/Fe3+ ions. Free electrons generated by ionizing radiation allow the reduction of Eu3+, which produces a very small contrast in MRI, to Eu2+, which induces a strong contrast. Oxidative species generated by high-energy X-rays can be measured indirectly using Fe2+ because it oxidizes to Fe3+, increasing the contrast in MRI. Notably, in the results, a strong increase in the proton relaxation rates is observed for the Eu3+-doped NPs at 40 kV. At 6 MV, a significant increase in proton relaxation rates is observed using CaF2 NPs doped with Fe2+/Fe3+ after irradiation. The presented concept shows great promise for use in the clinic to measure in vivo local ionizing radiation dose, as these CAs can be intravenously injected in a saline solution.

Late-life dietary folate restriction reduces biosynthetic processes without compromising healthspan in mice.

Folate is a vitamin required for cell growth and is present in fortified foods in the form of folic acid to prevent congenital abnormalities. The impact of low folate status on life-long health is poorly understood. We found that limiting folate levels with the folate antagonist methotrexate increased the lifespan of yeast and worms. We then restricted folate intake in aged mice and measured various health metrics, metabolites, and gene expression signatures. Limiting folate intake decreased anabolic biosynthetic processes in mice and enhanced metabolic plasticity. Despite reduced serum folate levels in mice with limited folic acid intake, these animals maintained their weight and adiposity late in life, and we did not observe adverse health outcomes. These results argue that the effectiveness of folate dietary interventions may vary depending on an individual's age and sex. A higher folate intake is advantageous during the early stages of life to support cell divisions needed for proper development. However, a lower folate intake later in life may result in healthier aging.

High-Pressure Injection Injuries of the Hand in Community and Industrial Settings: Incidence and Trends.

BACKGROUND: High-pressure injection injuries to the hand have been reported in both the community and industrial setting with varying levels of severity. However, there are little epidemiologic data regarding the prevalence of pressure-injection injuries. The purpose of this study is thus to describe trends in emergency department (ED) encounters associated with pressure injection injuries, thereby informing potential investments in research and education for these injuries. METHODS: The National Electronic Injury Surveillance System (NEISS), a nationally representative database of all ED encounters, was queried for all high-pressure injection injuries from 2012 to 2021. Patient demographic and injury data were collected and analyzed to describe trends in incidence, patient demographics, and sequelae of hand injury associated with an ED encounter for a pressure injection-related injury. RESULTS: There were an estimated 15 307 (95% confidence interval: 15 051-15 562) high-pressure injection hand injuries from 2012 to 2021. Injuries were more frequent on weekends with the highest incidence on Sundays (18.9%) and Saturdays (18.0%) and during late spring and summer months (58.6%), with peak incidence occurring in May (16.8%). High-pressure paint injuries demonstrated a significantly higher rate of infection (23.7% of injuries) than pressure washer injuries (3.7%); however, pressure washer injuries were much more common overall (90% vs 10%). CONCLUSION: High-pressure injection injuries to the hand and upper extremity represent a particularly concerning injury mechanism. Prompt recognition and proper management are crucial for improving outcomes. People that utilize pressure washers for household projects should be aware of the risks associated with these machines and utilize proper safety techniques.

Effect of Soil Temperature on Reproduction of Root-knot Nematodes in Flue-cured Tobacco with Homozygous Rk1 and/or Rk2 Resistance Genes.

Most commercial flue-cured tobacco cultivars contain the Rk1 resistance gene, which provides resistance to races 1 and 3 of Meloidogyne incognita and race 1 of M. arenaria. A number of cultivars now possess a second root-knot resistance gene, Rk2. High soil temperatures have been associated with a breakdown of root-knot resistance genes in a number of crops. Three greenhouse trials were performed from 2014 to 2015 investigate the effect of high soil temperature on the efficacy of Rk1 and/or Rk2 genes in reducing parasitism by a population of M. incognita race 3. Trials were arranged in randomized complete block design in open-top growth chambers set at 25°, 30°, and 35°C. Plants were inoculated with 3,000 eggs and data were collected 35 days post-inoculation. Galling, numbers of egg masses and eggs, and reproductive index were compared across cultivar entries. Nematode reproduction was reduced at 25°C and 30°C on entries possessing Rk1 and Rk1Rk2 compared to the susceptible entry and the entry possessing only Rk2. However, there were often no significant differences in reproduction at 35°C between entries with Rk1 and/or Rk2 compared to the susceptible control, indicating an increase of root-knot nematode parasitism on resistant entries at higher temperatures. Although seasonal differences in nematode reproduction were observed among experiments, relative differences among tobacco genotypes remained generally consistent.

Genetic mapping and prediction for novel lesion mimic in maize demonstrates quantitative effects from genetic background, environment and epistasis.

KEY MESSAGE: A novel locus was discovered on chromosome 7 associated with a lesion mimic in maize; this lesion mimic had a quantitative and heritable phenotype and was predicted better via subset genomic markers than whole genome markers across diverse environments. Lesion mimics are a phenotype of leaf micro-spotting in maize (Zea mays L.), which can be early signs of biotic or abiotic stresses. Dissecting its inheritance is helpful to understand how these loci behave across different genetic backgrounds. Here, 538 maize recombinant inbred lines (RILs) segregating for a novel lesion mimic were quantitatively phenotyped in Georgia, Texas, and Wisconsin. These RILs were derived from three bi-parental crosses using a tropical pollinator (Tx773) as the common parent crossed with three inbreds (LH195, LH82, and PB80). While this lesion mimic was heritable across three environments based on phenotypic ([Formula: see text] = 0.68) and genomic ([Formula: see text] = 0.91) data, transgressive segregation was observed. A genome-wide association study identified a single novel locus on chromosome 7 (at 70.6 Mb) also covered by a quantitative trait locus interval (69.3-71.0 Mb), explaining 11-15% of the variation, depending on the environment. One candidate gene identified in this region, Zm00001eb308070, is related to the abscisic acid pathway involving in cell death. Genomic predictions were applied to genome-wide markers (39,611 markers) contrasted with a marker subset (51 markers). Population structure explained more variation than environment in genomic prediction, but other substantial genetic background effects were additionally detected. Subset markers explained substantially less genetic variation (24.9%) for the lesion mimic than whole genome markers (55.4%) in the model, yet predicted the lesion mimic better (0.56-0.66 vs. 0.26-0.29). These results indicate this lesion mimic phenotype was less affected by environment than by epistasis and genetic background effects, which explain its transgressive segregation.

Horn fly transcriptome data of ten populations from the southern United States with varying degrees and molecular mechanisms of pesticide resistance.

Haematobia irritans irritans (Linnaeus, 1758: Diptera: Muscidae), the horn fly, is an external parasite of penned and pastured livestock that causes a major economic impact on cattle production worldwide. Pesticides such as synthetic pyrethroids and organophosphates are routinely used to control horn flies; however, resistance to these chemicals has become a concern in several countries. To further elucidate the molecular mechanisms of resistance in horn fly populations, we sequenced the transcriptomes of ten populations of horn flies from the southern US possessing varying degrees of pesticide resistance levels to pyrethroids, organophosphates, and endosulfans. We employed an Illumina paired end HiSeq approach, followed by de novo assembly of the transcriptomes using CLC Genomics Workbench 8.0.1 De Novo Assembler using multiple kmers, and annotation using Blast2GO PRO version 5.2.5. The Gene Ontology biological process term Response to Insecticide was found in all the populations, but at an increased frequency in the populations with higher levels of insecticide resistance. The raw sequence reads are archived in the Sequence Read Archive (SRA) and assembled population transcriptomes in the Transcriptome Shotgun Assembly (TSA) at the National Center for Biotechnology Information (NCBI).

Impact of COVID-19 on clinical outcomes following total shoulder arthroplasty.

Background: The coronavirus (COVID-19) pandemic has introduced patient stressors and changes to perioperative protocols in total shoulder arthroplasty (TSA). The purpose of this study is to evaluate the short-term effects of the COVID-19 pandemic on various patient outcomes and satisfaction following elective TSA. Methods: A retrospective review was performed on 147 patients who underwent primary TSA at a single institution between June 2019 and December 2020. Patients were divided into 2 cohorts: pre-COVID (June 2019-March 2020; n = 74) and post-COVID (April 2020-December 2020; n = 73). No elective TSA were performed between 10 March 2020 and 23 April 2020 at our institution. Data were collected prospectively both pre- and postoperatively. Range of motion (ROM) testing included active abduction, internal rotation, and external rotation. Patient reported outcome measures (PROMs) included global shoulder function, Simple Shoulder Test, American Shoulder and Elbow Surgeons, Visual Analog Scale pain scoring systems, and patient satisfaction. ROM and PROMs were compared at preoperative, 3-month follow-up, and 12-month follow-up intervals. Operative time, length of stay (LOS), 90-day readmission, and 90-day reoperation were also compared. Results: There were no differences in baseline patient characteristics. The operative time, LOS, home discharge rate, readmission, and reoperation did not differ between groups. For both cohorts, the PROMs and ROM improved at each follow-up visit postoperatively. While preoperative abduction, internal rotation, and external rotation were significantly greater in the post-COVID group, all ROM measures were similar at 3-month and 12-month follow-up visits. There was no difference in pain, global function, Simple Shoulder Test, American Shoulder and Elbow Surgeons, or patient satisfaction between groups at all time intervals. Conclusions: Patients undergoing elective TSA amidst the COVID-19 pandemic demonstrate excellent PROMs, ROM, and high satisfaction up to 12-months postoperatively that are comparable to pre-pandemic standards. Operative time, LOS, discharge destination, as well as 90-day readmission and reoperation rates were not impacted by the pandemic. Patients can expect similar outcomes for TSA when comparing pre-COVID to post-COVID as the pandemic continues.

Comparative transcriptomic analysis of germinating rice seedlings to individual and combined anaerobic and cold stress.

BACKGROUND: Rice is one of the most important cereals consumed worldwide. Two major abiotic factors affecting rice plants in different growth stages are flooding stress and cold stress. These abiotic stresses can take place independently or simultaneously and significantly affect rice plants during germination and seedling growth. Fortunately, a wide array of phenotypic responses conferring flooding stress and chilling stress tolerance exist within the rice germplasm, indicating the presence of different molecular mechanisms underlying tolerance to these stresses. Understanding these differences may assist in developing improved rice cultivars having higher tolerance to both stresses. In this study, we conducted a comparative global gene expression analysis of two rice genotypes with contrasting phenotypes under cold stress, anaerobic stress, and combined cold and anaerobic stress during germination. RESULTS: The differential gene expression analysis revealed that 5571 differentially expressed genes (DEGs), 7206 DEGs, and 13279 DEGs were identified under anaerobic stress, cold stress, and combined stress, respectively. Genes involved in the carbohydrate metabolic process, glucosyltransferase activity, regulation of nitrogen compound metabolic process, protein metabolic process, lipid metabolic process, cellular nitrogen compound biosynthetic process, lipid biosynthetic process, and a microtubule-based process were enriched across all stresses. Notably, the common Gene Ontology (GO) analysis identified three hub genes, namely Os08g0176800 (similar to mRNA-associated protein mrnp 41), Os11g0454200 (dehydrin), and OS10g0505900 (expressed protein). CONCLUSION: A large number of differentially expressed genes were identified under anaerobic, cold conditions during germination and the combination of the two stress conditions in rice. These results will assist in the identification of promising candidate genes for possible manipulation toward rice crops that are more tolerant under flooding and cold during germination, both independently and concurrently.

Long-Term Oral Steroid Use: A Unique Risk Factor in 4-Corner Fusion Compared With Other Wrist Salvage Operations.

INTRODUCTION: Salvage procedures such as proximal row carpectomy, 4-corner fusion, total wrist arthroplasty, and total wrist arthrodesis are commonly used at the end stages of wrist arthritis. These operations have high complication rates, and significant controversy exists regarding the selection of procedure. Long-term oral glucocorticoid therapy has previously been identified as a risk factor for complications in multiple orthopedic procedures. The purpose of this study is to investigate the effect long-term oral preoperative corticosteroid use has on complications after different salvage operations for wrist arthritis. METHODS: The National Surgical Quality Improvement Program database was queried to identify patients who underwent proximal row carpectomy, 4-corner fusion, total wrist arthroplasty, or total wrist fusion between 2005 and 2020. Patients were classified by steroid use. Univariate analysis and multivariate logistic regression were used to assess the risk of complications. RESULTS: A total of 1298 patients were identified. Overall, steroid use was found to be independently associated with a higher complication rate. On multivariate analysis of patients who underwent 4-corner fusion, steroid use was found to be associated with higher complication rate and surgical site infection rate. Steroid use was not associated with increased complications in patients who underwent proximal row carpectomy, total wrist arthroplasty, or total wrist fusion when examined individually. CONCLUSION: Long-term oral corticosteroid therapy was associated with an increased risk of postoperative infections in patients who underwent 4-corner fusion, which was not found in other wrist salvage operations.

Diversity of Pythium Species Recovered from Float-Bed Tobacco Transplant Production Greenhouses.

Pythium diseases are common in hydroponic crop production and often threaten the greenhouse production of cucumber, tomato, lettuce, and other crops. In tobacco transplant production, where float-bed hydroponic greenhouses are commonly used, Pythium diseases can cause up to 70% seedling loss. However, there have been few comprehensive studies on the composition and diversity of Pythium communities in tobacco greenhouses. In a 2017 survey, 360 Pythium isolates were collected from 41 tobacco greenhouses across four states (VA, MD, GA, and PA). Samples were collected from one to seven sites within each greenhouse. Twelve described Pythium species were identified (P. adhaerens, P. aristosporum, P. attrantheridium, P. catenulatum, P. coloratum, P. dissotocum, P. inflatum, P. irregulare, P. myriotylum, P. pectinolyticum, P. porphyrae, and P. torulosum) among the isolates obtained. Approximately 80% of the surveyed greenhouses harbored Pythium in at least one of four sites (bay water, tobacco seedlings, weeds, and center walkways) within the greenhouse. The structure of Pythium communities was diverse among the surveyed greenhouses: multiple Pythium species coexisted in the same sample, and multiple species were present within the same greenhouse at different sites. This diversity appeared to be influenced by the sampling sites within the surveyed tobacco greenhouses, sample type, and sampling time. Intraspecific variation may also exist among the P. dissotocum populations found in this study. These results uncovered the complexity and diversity of the Pythium communities within float tobacco transplant greenhouses, which could play a role in the variation in Pythium diseases observed in these production systems.

National incidence and trends of bicycle injury.

Bicycle utilization continues to increase annually, and this trend was recently accelerated by the coronavirus disease of 2019 pandemic. There is limited epidemiologic data, however, regarding the prevalence and nature of bicycle-related injuries. Therefore, the purpose of this study is to characterize trends in bicycle-related injuries. The National Electronic Injury Surveillance System was queried for bicycle-related injuries from 2012 to 2021. Patient demographic and injury data were collected and analyzed to describe trends in incidence, patient demographics, and injury patterns associated with an emergency department encounter for a bicycle-related injury. There were an estimated 4,666,491 (95% confidence interval: 4,661,472-4,671,510) bicycle-related injuries from 2012 to 2021. The incidence of these injuries has significantly decreased over time (R = -0.983, R2 = 0.967, p < 0.001). However, the rate of injury in elderly patients increased over time. Injuries occurred most often during summer months (36%) and on weekend days (31.9%). Males and younger patients were more commonly injured. Head injuries were the most commonly affected body part among all age groups. Fractures were the most common injury type overall. Upper extremity injuries were more common than the lower extremity. Despite increased public bicycle utilization, there is a significant downtrend in bicycle-related injuries over the last decade. Injuries among elderly patients are becoming more common, who demonstrate a high rate of fracture and head injury. Fractures and head injuries were the most common injuries among all age groups, highlighting the importance of bicycle safety initiatives and helmet-wearing regardless of age.

Evolution of Molar Mass Distributions Using a Method of Partial Moments: Initiation of RAFT Polymerization.

We describe a method of partial moments devised for accurate simulation of the time/conversion evolution of polymer composition and molar mass. Expressions were derived that enable rigorous evaluation of the complete molar mass and composition distribution for shorter chain lengths (e.g., degree of polymerization, Xn = N < 200 units) while longer chains (Xn ≥ 200 units) are not neglected, rather they are explicitly considered in terms of partial moments of the molar mass distribution, µxN(P)=∑n=N+1∞nx[Pn] (where P is a polymeric species and n is its' chain length). The methodology provides the exact molar mass distribution for chains Xn < N, allows accurate calculation of the overall molar mass averages, the molar mass dispersity and standard deviations of the distributions, provides closure to what would otherwise be an infinite series of differential equations, and reduces the stiffness of the system. The method also allows for the inclusion of the chain length dependence of the rate coefficients associated with the various reaction steps (in particular, termination and propagation) and the various side reactions that may complicate initiation or initialization. The method is particularly suited for the detailed analysis of the low molar mass portion of molar mass distributions of polymers formed by radical polymerization with reversible addition-fragmentation chain transfer (RAFT) and is relevant to designing the RAFT-synthesis of sequence-defined polymers. In this paper, we successfully apply the method to compare the behavior of thermally initiated (with an added dialkyldiazene initiator) and photo-initiated (with a RAFT agent as a direct photo-iniferter) RAFT-single-unit monomer insertion (RAFT-SUMI) and oligomerization of N,N-dimethylacrylamide (DMAm).

Risk Factors for 30-Day Complications and Unplanned Reoperation Following Surgical Treatment of Distal Radius Fractures.

BACKGROUND: The purpose of this study was to identify demographic data, medical comorbidities, and perioperative factors that are associated with increased risk of overall surgical complications, wound complications, and reoperation within 30 days of open reduction and internal fixation (ORIF) of distal radius fractures. METHODS: All adult patients undergoing ORIF of distal radius fractures in the National Surgical Quality Improvement Program database between 2005 and 2020 were identified. Patients were excluded for secondary procedures, open/infected injuries, or inpatient surgical setting. Demographic data, medical comorbidities, and perioperative data were examined for each patient, and patients were grouped by the presence or absence of any surgical complication. Univariate analysis and multivariate logistic regression were used to identify risk factors. RESULTS: A total of 20 301 patients from between 2005 and 2020 met the inclusion criteria, of which 219 complications (1.1% of cases) were identified. Following multivariate analysis, independent risk factors found to be associated with surgical complications included male sex, smoking, heart failure, longer operative time, and American Society of Anesthesiologists (ASA) classification of 3 or higher. CONCLUSION: Male sex, smoking, heart failure, prolonged operative time, and ASA status of 3 or higher are associated with an increased risk of surgical complications following ORIF of distal radius fractures. These complications, with the exception of heart failure, were also associated with an increased risk of wound complications. Finally, male sex, nonwhite race, smoking, dialysis, prolonged operative time, and 3 or higher ASA class were associated with reoperations. Understanding these risk factors allows surgeons to better predict and prevent complications in high-risk populations.

Transcriptome Analysis of Developing Grains from Wheat Cultivars TAM 111 and TAM 112 Reveal Cultivar-Specific Regulatory Networks.

Wheat flour's end-use quality is tightly linked to the quantity and composition of storage proteins in the endosperm. TAM 111 and TAM 112 are two popular cultivars grown in the Southern US Great Plains with significantly different protein content. To investigate regulatory differences, transcriptome data were analyzed from developing grains at early- and mid-filling stages. At the mid-filling stage, TAM 111 preferentially upregulated starch metabolism-related pathways compared to TAM 112, whereas amino acid metabolism and transporter-related pathways were over-represented in TAM 112. Elemental analyses also indicated a higher N percentage in TAM 112 at the mid-filling stage. To explore the regulatory variation, weighted correlation gene network was constructed from publicly available RNAseq datasets to identify the modules differentially regulated in TAM 111 and TAM 112. Further, the potential transcription factors (TFs) regulating those modules were identified using graphical least absolute shrinkage and selection operator (GLASSO). Homologs of the OsNF-Y family members with known starch metabolism-related functions showed higher connectivities in TAM 111. Multiple TFs with high connectivity in TAM 112 had predicted functions associated with ABA response in grain. These results will provide novel targets for breeders to explore and further our understanding in mechanisms regulating grain development.

Pumpkin carving knife injuries: National incidence and trends of hand injury.

INTRODUCTION: Seasonal media reports often describe the dangers of pumpkin carving, yet little data exists regarding the actual incidence of hand injuries resulting from pumpkin carving. The purpose of this study is to describe, quantify, and trend ED encounters associated with pumpkin-related knife injuries. METHODS: The National Electronic Injury Surveillance System (NEISS) was queried for pumpkin-related knife injuries from 2012 to 2021. Patient demographic and injury data was collected and analyzed to describe trends in incidence, patient demographics, and injury patterns associated with an ED encounter for a pumpkin-related knife injury. RESULTS: There were an estimated 20,579 (95% CI: 17,738-23,420) pumpkin-related knife injuries from 2012 to 2021. The incidence of pumpkin-related knife injuries remained stable over time (R2 = 0.195, P = 0.201). Hand injuries comprised 87.6% of all injuries, with the thumb (33.5%) and index finger (25.0%) most commonly affected. Men and women were injured at similar rates (51.6% vs 48.4%). The most common demographic injured were 10 to 19-year olds (31.5%) followed by children <10-years old (19.5%). Women ages 10 to 19-years old were the most commonly injured subgroup (10.0% of all injuries). Most ED presentations occurred on Saturdays (16.5%) or Sundays (23.3%). The large majority occurred during the months of October (83.5%) followed by November (11.2%), with almost half of all cases (45.6%) occurring in the last week of October. Peak incidence of injury occurred on October 30th. CONCLUSION: Pumpkin-related knife injuries are a preventable cause of hand injury with predictably high-incidence in fall months. Additionally, our data suggests further precautions should be taken to prevent injury in pediatric patients. Understanding at-risk populations in addition to implementing public safety initiatives and education on safe pumpkin-carving techniques could prevent serious injuries in the future.

Characterization of triatomine bloodmeal sources using direct Sanger sequencing and amplicon deep sequencing methods.

Knowledge of host associations of blood-feeding vectors may afford insights into managing disease systems and protecting public health. However, the ability of methods to distinguish bloodmeal sources varies widely. We used two methods-Sanger sequencing and amplicon deep sequencing-to target a 228 bp region of the vertebrate Cytochrome b gene and determine hosts fed upon by triatomines (n = 115) collected primarily in Texas, USA. Direct Sanger sequencing of PCR amplicons was successful for 36 samples (31%). Sanger sequencing revealed 15 distinct host species, which included humans, domestic animals (Canis lupus familiaris, Ovis aries, Gallus gallus, Bos taurus, Felis catus, and Capra hircus), wildlife (Rattus rattus, Incilius nebulifer, Sciurus carolinensis, Sciurus niger, and Odocoileus virginianus), and captive animals (Panthera tigris, Colobus spp., and Chelonoidis carbonaria). Samples sequenced by the Sanger method were also subjected to Illumina MiSeq amplicon deep sequencing. The amplicon deep sequencing results (average of 302,080 usable reads per sample) replicated the host community revealed using Sanger sequencing, and detected additional hosts in five triatomines (13.9%), including two additional blood sources (Procyon lotor and Bassariscus astutus). Up to four bloodmeal sources were detected in a single triatomine (I. nebulifer, Homo sapiens, C. lupus familiaris, and S. carolinensis). Enhanced understanding of vector-host-parasite networks may allow for integrated vector management programs focusing on highly-utilized and highly-infected host species.

Brucella activates the host RIDD pathway to subvert BLOS1-directed immune defense.

The phagocytosis and destruction of pathogens in lysosomes constitute central elements of innate immune defense. Here, we show that Brucella, the causative agent of brucellosis, the most prevalent bacterial zoonosis globally, subverts this immune defense pathway by activating regulated IRE1α-dependent decay (RIDD) of Bloc1s1 mRNA encoding BLOS1, a protein that promotes endosome-lysosome fusion. RIDD-deficient cells and mice harboring a RIDD-incompetent variant of IRE1α were resistant to infection. Inactivation of the Bloc1s1 gene impaired the ability to assemble BLOC-1-related complex (BORC), resulting in differential recruitment of BORC-related lysosome trafficking components, perinuclear trafficking of Brucella-containing vacuoles (BCVs), and enhanced susceptibility to infection. The RIDD-resistant Bloc1s1 variant maintains the integrity of BORC and a higher-level association of BORC-related components that promote centrifugal lysosome trafficking, resulting in enhanced BCV peripheral trafficking and lysosomal destruction, and resistance to infection. These findings demonstrate that host RIDD activity on BLOS1 regulates Brucella intracellular parasitism by disrupting BORC-directed lysosomal trafficking. Notably, coronavirus murine hepatitis virus also subverted the RIDD-BLOS1 axis to promote intracellular replication. Our work establishes BLOS1 as a novel immune defense factor whose activity is hijacked by diverse pathogens.

Impact of COVID-19 on the Mode of Presentation and Stage at Diagnosis of Colorectal Cancer.

AIM: This study compares the stage at the presentation of patients with colorectal cancer (CRC) before and after introducing COVID-19 restrictions and the mode of presentation. METHODS: This is a retrospective cohort study comparing the incidence of CRC, TNM stage and mode of presentation in the pre-COVID and COVID cohorts at a single UK Trust. All patients discussed at the CRC multidisciplinary team (MDT) from March 2017 to March 2021 were included and split into two cohorts; the pre-COVID group from 01/03/2017 to 29/02/2020 and the COVID group from 01/03/2020 to 28/02/2021. Percentages were used for descriptive statistics. Student's t-test was used for the comparison of demographic variables. Chi-squared test was used for the difference analysis for the categorical data, such as TNM and mode of presentation. P value ≤0.05 was significant. RESULTS: In total, 1373 patients were diagnosed with CRC during the period from March 2017 to March 2021. The pre-COVID group (2017-2020) included 1104 CRC patients, compared to 269 patients in the COVID one (2020-2021). The mean age was higher in the pre-COVID group (p = 0.001). There was a statistically significant increase in the proportion of cases presenting with T4 disease (p = 0.023) and metastatic disease (p = 0.032) in the COVID group compared to the pre-COVID group. There was also a significant increase in the rate of emergency presentations (p < 0.0001). CONCLUSION: We observed a statistically significant increase in rates of locally advanced (T4) and metastatic (distant) CRC in patients presenting after introducing the COVID-19 lockdown. There was also an increase in emergency presentations. There was no observed difference in nodal status. This may reflect disruption to cancer diagnostic services and the reluctance of patients to access medical care during a pandemic, particularly the elderly.

A new strategy for using historical imbalanced yield data to conduct genome-wide association studies and develop genomic prediction models for wheat breeding.

Using imbalanced historical yield data to predict performance and select new lines is an arduous breeding task. Genome-wide association studies (GWAS) and high throughput genotyping based on sequencing techniques can increase prediction accuracy. An association mapping panel of 227 Texas elite (TXE) wheat breeding lines was used for GWAS and a training population to develop prediction models for grain yield selection. An imbalanced set of yield data collected from 102 environments (year-by-location) over 10 years, through testing yield in 40-66 lines each year at 6-14 locations with 38-41 lines repeated in the test in any two consecutive years, was used. Based on correlations among data from different environments within two adjacent years and heritability estimated in each environment, yield data from 87 environments were selected and assigned to two correlation-based groups. The yield best linear unbiased estimation (BLUE) from each group, along with reaction to greenbug and Hessian fly in each line, was used for GWAS to reveal genomic regions associated with yield and insect resistance. A total of 74 genomic regions were associated with grain yield and two of them were commonly detected in both correlation-based groups. Greenbug resistance in TXE lines was mainly controlled by Gb3 on chromosome 7DL in addition to two novel regions on 3DL and 6DS, and Hessian fly resistance was conferred by the region on 1AS. Genomic prediction models developed in two correlation-based groups were validated using a set of 105 new advanced breeding lines and the model from correlation-based group G2 was more reliable for prediction. This research not only identified genomic regions associated with yield and insect resistance but also established the method of using historical imbalanced breeding data to develop a genomic prediction model for crop improvement. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01287-8.