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Red clover (Trifolium pratense) is a perennial forage legume wildly used in temperate regions, including northern Europe. Its breeders are under increasing pressure to obtain rapid genetic gains to meet the high demand for improved forage yield and quality. One solution to increase genetic gain by reducing time and increasing accuracy is genomic selection. Thus, efficient genomic prediction (GP) models need to be developed, which are unbiased to traits and harvest time points. This study aimed to develop and evaluate single-trait (ST) and multi-trait (MT) models that simultaneously target more than one trait or cut. The target traits were dry matter yield, crude protein content, net energy for lactation, and neutral detergent fiber. The MT models either combined dry matter yield with one forage quality trait, all traits at one cut, or one trait across all cuts. The results show an increase with MT models where the traits had a genetic correlation of 0.5 or above. This study indicates that non-additive genetic effects have significant but varying effects on the predictive ability and reliability of the models. The key conclusion of this study was that these non-additive genetic effects could be better described by incorporating genetically correlated traits or cuts. [ABSTRACT FROM AUTHOR]

Premise: Numerous studies have found a positive association between dioecy and polyploidy; however, this association presents a theoretical conflict: While polyploids are predicted to benefit from self‐reproduction for successful establishment, dioecious species cannot self‐reproduce. We propose a theoretical framework to resolve this apparent conflict. We hypothesize that the inability of dioecious species to self‐reproduce hinders their establishment as polyploids. We therefore expect that genera with many dioecious species have fewer polyploids, leading to a negative association between polyploidy and dioecy across genera. Methods: We used three publicly available databases to determine ploidy and sexual systems for 131 genera and 546 species. We quantified (1) the relationship between the frequency of polyploid species and the frequency of dioecious species across genera, and (2) the proportion of polyploids with hermaphroditism and dioecy across species, adjusting for phylogenetic history. Results: Across genera, we found a negative relationship between the proportion of polyploids and the proportion of dioecious species, a consistent trend across clades. Across all species, we found that sexual system (dioecious or not) was not associated with polyploidy. Conclusions: Polyploids are rare in genera in which the majority of species are dioecious, consistent with the theory that self‐reproduction favors polyploid establishment. The low frequency of polyploidy among dioecious species indicates the association is not as widespread as previously suggested. Our findings are consistent with previous studies identifying a positive relationship between the two traits, but only if polyploidy promotes a transition to dioecy, and not the reverse. [ABSTRACT FROM AUTHOR]

Background: A previous nationwide study from Sweden showed that the rate of permanent hypoparathyroidism is high and under-rated in the Swedish Quality Register. This retrospective population-based study aimed to validate the rate and diagnosis of permanent hypoparathyroidism found in the previous study. A secondary aim was to assess the relationship between the rate of low parathyroid hormone (PTH) levels within 24 h after surgery and the rate of permanent hypoparathyroidism. Methods: All patients who underwent total thyroidectomy from 2005 to 2015 in a region of Sweden were included. Data were retrieved from local health records, the National Patient Registry, the Swedish Prescribed Drug Registry, and the Swedish Quality Register. A strict definition of permanent hypoparathyroidism was used, including biochemical data and attempts to stop the treatment. Results: A total of 1636 patients were included. Altogether, 143 patients (8.7 per cent) developed permanent hypoparathyroidism. Of these, 102 (6.2 per cent) had definitive permanent hypoparathyroidism, whereas 41 (2.5 per cent) had possible permanent hypoparathyroidism, because attempts to stop the treatment were lacking (28) or patients were lost to follow-up (13). The agreement between the Swedish Quality Register and the chart review was 29.3 per cent. A proportion of 23.2 per cent with a PTH level below the reference value corresponded to a 6.7 per cent rate of permanent hypoparathyroidism. Conclusion: The risk of permanent hypoparathyroidism after total thyroidectomy is high. Some patients are overtreated because attempts to stop the treatment are lacking. Quality registers might underestimate the risk of permanent hypoparathyroidism. Approximately one-quarter of all patients with low PTH levels immediately after surgery developed permanent hypoparathyroidism. This retrospective population-based cohort study from Sweden validated the rate and diagnosis of permanent hypoparathyroidism, using a strict definition including both biochemical data and attempts to stop the treatment. The rate of permanent hypoparathyroidism is high, and some patients might be misdiagnosed and overtreated because attempts have not been made to stop the treatment. One-quarter of all patients with an early low PTH level below the reference range develop permanent hypoparathyroidism. Lay summary: The parathyroid glands control calcium levels in the blood. If they do not make enough hormone, calcium levels are low. Parathyroid dysfunction can happen after thyroid surgery, if the glands are hurt or removed by mistake. This is a problem because people with this condition may have symptoms and need ongoing treatment with vitamin D and calcium. They might also face other health issues and need regular visits to their doctor. Finding out how often long-term parathyroid dysfunction happens can be tricky because it requires a full year of follow-up and attempts to stop the treatment. This information is often missing from many studies and registers. Some recent studies have shown that this condition is more common than previously thought. It would be helpful to have a quick way to know how common long-term parathyroid gland dysfunction will be within a unit or hospital, without having to wait for the follow-up. This would help doctors to assess how good they are at taking care of patients. It would also support research on new methods to avoid parathyroid dysfunction. The goal of the study was to see how often long-term parathyroid dysfunction occurs after thyroid surgery, using a strict definition and complete long-term follow-up. Another aim was to assess the link between low parathyroid hormone levels right after surgery and the rate of long-term parathyroid dysfunction. All individuals who had the entire thyroid gland removed for benign disease between 2005 and 2015 in a region of Sweden were included. Data were collected from local health records at six hospitals. Patient information, surgical details, blood tests, and treatment details were gathered from the medical charts. Data were also collected from the national quality register. A high rate of long-term parathyroid dysfunction was seen in this large study of 1636 patients, Some patients may have been overtreated, because no attempts had been made to stop the treatment. The rate of long-term parathyroid dysfunction in patients with a normal early parathyroid hormone level was very low. About 23 per cent of all patients had a low early parathyroid hormone level, which corresponded to a 6.7 per cent rate of long-term parathyroid dysfunction. The authors believe that parathyroid hormone measurement could help predict the rate of permanent hypoparathyroidism, but more studies are needed to be sure. [ABSTRACT FROM AUTHOR]

Diagnostic tests for direct pathogen detection have been instrumental to contain the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic. Automated, quantitative, laboratory-based nucleocapsid antigen (Ag) tests for SARS-CoV-2 have been launched alongside nucleic acid-based test systems and point-of-care (POC) lateral-flow Ag tests. Here, we evaluated four commercial Ag tests on automated platforms for the detection of different sublineages of the SARS-CoV-2 Omicron variant of concern (VoC) (B.1.1.529) in comparison with "non-Omicron" VoCs. A total of 203 Omicron PCR-positive respiratory swabs (53 BA.1, 48 BA.2, 23 BQ.1, 39 XBB.1.5 and 40 other subvariants) from the period February to March 2022 and from March 2023 were examined. In addition, tissue culture-expanded clinical isolates of Delta (B.1.617.2), Omicron-BA.1, -BF.7, -BN.1 and -BQ.1 were studied. These results were compared to previously reported data from 107 clinical "non-Omicron" samples from the end of the second pandemic wave (February to March 2021) as well as cell culture-derived samples of wildtype (wt) EU-1 (B.1.177), Alpha VoC (B.1.1.7) and Beta VoC (B.1.351)). All four commercial Ag tests were able to detect at least 90.9% of Omicron-containing samples with high viral loads (Ct < 25). The rates of true-positive test results for BA.1/BA.2-positive samples with intermediate viral loads (Ct 25–30) ranged between 6.7% and 100.0%, while they dropped to 0 to 15.4% for samples with low Ct values (> 30). This heterogeneity was reflected also by the tests' 50%-limit of detection (LoD50) values ranging from 44,444 to 1,866,900 Geq/ml. Respiratory samples containing Omicron-BQ.1/XBB.1.5 or other Omicron subvariants that emerged in 2023 were detected with enormous heterogeneity (0 to 100%) for the intermediate and low viral load ranges with LoD50 values between 23,019 and 1,152,048 Geq/ml. In contrast, detection of "non-Omicron" samples was more sensitive, scoring positive in 35 to 100% for the intermediate and 1.3 to 32.9% of cases for the low viral loads, respectively, corresponding to LoD50 values ranging from 6181 to 749,792 Geq/ml. All four assays detected cell culture-expanded VoCs Alpha, Beta, Delta and Omicron subvariants carrying up to six amino acid mutations in the nucleocapsid protein with sensitivities comparable to the non-VoC EU-1. Overall, automated quantitative SARS-CoV-2 Ag assays are not more sensitive than standard rapid antigen tests used in POC settings and show a high heterogeneity in performance for VoC recognition. The best of these automated Ag tests may have the potential to complement nucleic acid-based assays for SARS-CoV-2 diagnostics in settings not primarily focused on the protection of vulnerable groups. In light of the constant emergence of new Omicron subvariants and recombinants, most recently the XBB lineage, these tests' performance must be regularly re-evaluated, especially when new VoCs carry mutations in the nucleocapsid protein or immunological and clinical parameters change. [ABSTRACT FROM AUTHOR]

Two studies published in the journal Science have revealed a unique antiphage defense system in bacteria called defense-associated reverse transcriptase 2 (DRT2). This system uses rolling circle reverse transcription to produce a toxic protein called Neo, which arrests bacterial growth and prevents phage replication. The DRT2 system encodes an RNA template that is converted into DNA by reverse transcriptase, and this DNA is transcribed into an mRNA that encodes Neo. The mechanism by which DRT2 senses phage presence and activates the synthesis of the second DNA strand is still unknown. The unconventional protein-encoding mechanism of DRT2 may help solve the problem of autoimmunity caused by transcriptional leakage and allow for the production of Neo even after phage-induced DNA degradation. The researchers suggest that the ability of DRT2 to generate double-stranded DNA through rolling circle reverse transcription could have biotechnological applications. [Extracted from the article]

This article presents the use of phase-change material (PCM) thermal storage within the Horizon 2020 HEART project (Holistic Energy and Architectural Retrofit Toolkit), aimed at decarbonising the European building sector through the retrofitting of existing structures into energy-efficient smart buildings. These buildings not only reduce energy consumption, but also incorporate advanced technologies for harnessing green energy, thereby promoting environmental sustainability. The HEART project employs state-of-the-art technologies for electricity production/dispatching and heat generation/storage, managed by a cloud-based platform for the real-time monitoring of parameters and optimising energy utilisation, enabling users to control their environmental comfort. The article provides a detailed examination of one of the project's demonstration sites in Italy, focusing on various components such as heat pumps, photovoltaic systems (PV), controllers, and particularly emphasising the significance of storage tanks. The study involved the measurement and analysis of three heat storage tanks, each with a total volume of 3000 L. These tanks utilised PCM modules for latent heat storage, significantly enhancing overall heat accumulation. Water served as the heat transfer fluid within the tanks. Through meticulous calculations, the article quantifies the accumulated heat and presents a comparative evaluation between PCM-based storage tanks and conventional water tanks, showcasing the advantages of PCM technology in terms of increased heat retention and efficiency. [ABSTRACT FROM AUTHOR]

Simple Summary: In the past, horses were protected from parasitic infections by routine deworming aimed at keeping harmful worms such as Strongylus vulgaris under control. The emergence of drug-resistant worm populations has stimulated the introduction of alternative control strategies to reduce the frequency of antiparasitic treatments. In Sweden, selective treatment is recommended, and deworming should be based on the results of faecal analyses, where individual horses that contribute substantially to pasture contamination are treated. In our study, horses from equestrian premises across Sweden participated in a parasite monitoring programme during the years 2008–2017. Faecal samples were collected in the spring and in the autumn in order to identify which individuals should be dewormed. According to the results obtained from the spring analyses (March to June), the use of antiparasitic drugs could be greatly reduced when selective treatment is chosen instead of routine treatment. In Sweden, routine deworming has been used for several decades; however, to slow down the development of anthelmintic resistance, selective treatment is currently recommended. As part of a monitoring programme, equestrian premises submitted faecal samples to the National Veterinary Institute (SVA) twice per year between 2008 and 2017. Analyses for strongyles (small and large), tapeworms and ascarids, followed by premise-specific advice regarding deworming and parasite control strategies, were provided. In total, 43,330 faecal samples, collected from 26,625 horses on 935 premises in springtime (March to June), were analysed by quantitative or semi-quantitative flotation. Moreover, Strongylus vulgaris was detected by larval culture or PCR. Between 4 and 11% of individual horses tested positive for S. vulgaris and 3–10% were shedding tapeworm eggs. There were recurrent high and low egg shedders; 75% of horses with S. vulgaris appeared to have been recently introduced into the herd; the proportion of S. vulgaris-positive premises increased when individual samples rather than pooled samples were used. Based on the results of S. vulgaris diagnostics and strongyle egg-shedding level, 59% of the horses did not need to be dewormed. [ABSTRACT FROM AUTHOR]

With an incidence of more than > 1,000,000/day, sexually transmitted diseases remain a major challenge for health care systems worldwide. To reduce disease burden, complications, and spread, rapid diagnosis permitting early therapy is pivotal. The range of pathogens is wide and co-infections are common. This complicates pre-analytics, which are based on different laboratory techniques with potentially long turnaround times, e.g., cultivation and multistep serologies. Multiplex PCR provides the opportunity to overcome these limitations. In this study, we evaluated a novel assay, the Euroarray STI-11 microarray (EA; Euroimmun Medizinische Labordiagnostika), for the detection of eight obligate or facultative pathogens. Three-hundred-thirteen clinical specimens, which had been tested and pre-characterized for STI causing agents as part of routine diagnostics, were used as cases and controls in this retrospective study. The EA detected 34/44 Chlamydia trachomatis, 48/50 HSV-1, 50/50 HSV-2, 48/48 Mycoplasma hominis, 45/47 Neisseria gonorrhoeae, 9/11 Treponema pallidum, 46/46 Ureaplasma parvum, and 49/49 Ureaplasma urealyticum infections, respectively. 293 samples were EA positive, with polymicrobial infections (positive for two to six microbial or viral agents) detected in 130/293 cases. Specificities were 100% in the respective control groups (n = 18–48 depending on targeted pathogen) except for N. gonorrhoeae (25/26) and U. urealyticum (44/45). The broad spectrum of obligate and facultative pathogens targeted by the EA makes it a valuable tool in the setting of STI diagnostics and surveillance. The test has the potential to diagnose diseases neglected or overlooked in routine clinical practice. Besides a low sensitivity for C. trachomatis, the EA demonstrated high performance for all analyzed parameters. Further studies are warranted in order to capture a larger variety of the tested pathogens. [ABSTRACT FROM AUTHOR]

Mason bees (Osmia spp.) are efficient fruit tree pollinators that can be encouraged to occupy and breed in artificial nesting material. In sweet cherry orchards, they are occasionally used as an alternative managed pollinator as a replacement for or in addition to honey bees (Apis mellifera). Yet, the lack of practical guidelines on management practices, for example optimal stocking rates, for both mason bee nesting material and honey bees might compromise pollination service provision. In this study, we assessed the relationship between stocking rates (honey bee hives and mason bee nesting material) and the abundance of honey bees and mason bees in 17 sweet cherry (Prunus avium) orchards in Central Germany. We furthermore performed a pollination experiment to explore the interactive effect of mason bees and honey bees on sweet cherry fruit set. In the orchards, both honey bee and mason bee abundance increased with increasing stocking rates of hives or nesting material, respectively. Honey bee abundance increased linearly with stocking rates. In contrast, mason bee abundance asymptoted at 2–3 nesting boxes per ha, beyond which more boxes resulted in little increase in visitation rate. Our pollination experiment demonstrated that orchards were pollen limited, with only 28% of insect‐pollinated flowers setting fruit versus 39% of optimally hand‐pollinated flowers. Honey bees and mason bees enhanced sweet cherry fruit set, but only when both were present and not when either was present alone in an orchard. Our findings demonstrate that offering nesting material for mason bees and employing honey bee hives can enhance bee abundance in sweet cherry orchards. By increasing honey bee abundance in combination with enhanced mason bee abundance, farmers can substantially boost fruit set and potentially sweet cherry yield. To enhance pollination services, farmers should consider the benefits of increasing pollinator biodiversity as an immediate benefit to improve crop yields. [ABSTRACT FROM AUTHOR]

A complex of soil actinomycetes in the upper horizon of Grumusol (Vertisol) on the western coast of Lake Kinneret in the vicinity of Tiberias (Lower Galilee, Israel) was studied. A high-throughput screening of the antibiotic activity of 26 isolates of the genus Streptomyces using on a dual reporter system revealed the strain 3IZ-6, which had the ability to inhibit protein synthesis. This strain was assigned to Streptomyces rochei according to the polyphase taxonomy approach. The active substance of S. rochei 3IZ-6 was isolated and purified using solid-phase extraction and high-performance liquid chromatography. Toeprint analysis and mass spectrophotometric data allowed us to identify this active compound as borrelidin, a known inhibitor of protein biosynthesis. When co-cultivated on solid media, strain 3IZ-6 is able to suppress the growth of phytopathogenic microorganisms Fusarium solani, F. sambucinum, and Botrytis cinerea, as well as the quarantine object Curtobacterium flaccumfaciens. The cultural liquid of 3IZ-6 had a pronounced phytotoxic effect on the seeds of common wheat (Triticum aestivum L.). Strain Streptomyces rochei 3IZ-6 can find application in biotechnology as a producer of borrelidin, a valuable natural compound with a wide spectrum of antibiotic activity, which can be used as a biocontrol agent for crop protection from phytopathogens and weeds. [ABSTRACT FROM AUTHOR]

During 2022, the COVID-19 pandemic has been dominated by the variant of concern (VoC) Omicron (B.1.1.529) and its rapidly emerging subvariants, including Omicron-BA.1 and -BA.2. Rapid antigen tests (RATs) are part of national testing strategies to identify SARS-CoV-2 infections on site in a community setting or to support layman's diagnostics at home. We and others have recently demonstrated an impaired RAT detection of infections caused by Omicron-BA.1 compared to Delta. Here, we evaluated the performance of five SARS-CoV-2 RATs in a single-centre laboratory study examining a total of 140 SARS-CoV-2 PCR-positive respiratory swab samples, 70 Omicron-BA.1 and 70 Omicron-BA.2, as well as 52 SARS-CoV-2 PCR-negative swabs collected from March 8th until April 10th, 2022. One test did not meet minimal criteria for specificity. In an assessment of the analytical sensitivity in clinical specimen, the 50% limit of detection (LoD50) ranged from 4.2 × 104 to 9.2 × 105 RNA copies subjected to the RAT for Omicron-BA.1 compared to 1.3 × 105 to 1.5 × 106 for Omicron-BA.2. Overall, intra-assay differences for the detection of Omicron-BA.1-containing and Omicron-BA.2-containing samples were non-significant, while a marked overall heterogeneity among the five RATs was observed. To score positive in these point-of-care tests, up to 22-fold (LoD50) or 68-fold (LoD95) higher viral loads were required for the worst performing compared to the best performing RAT. The rates of true-positive test results for these Omicron subvariant-containing samples in the highest viral load category (Ct values < 25) ranged between 44.7 and 91.1%, while they dropped to 8.7 to 22.7% for samples with intermediate Ct values (25–30). In light of recent reports on the emergence of two novel Omicron-BA.2 subvariants, Omicron-BA.2.75 and BJ.1, awareness must be increased for the overall reduced detection rate and marked differences in RAT performance for these Omicron subvariants. [ABSTRACT FROM AUTHOR]

Insect-mediated pollination is crucial for global production of multiple pollinator-dependent crops, including high-value crops like sweet and sour cherry. In the face of increasing agricultural demand and continued pollinator decline, it is essential to identify targeted management strategies to safeguard pollination services. Hence, we performed a systematic review on how cherry pollination is influenced by intrinsic and environmental requirements, flower-visiting insect communities, surrounding landscape and on-farm management practices. We found that most research was conducted in sweet cherry compared to sour cherry, and originated from North America and Europe, disregarding key global production areas. Cherry cultivars can be either self-compatible or self-incompatible, but insect pollination consistently benefits fruit set. Temperature has a strong effect on pollination success by mediating pollen germination, pollen tube growth and ovule longevity. Insect-mediated pollination is essential for adequate fruit set of both crops, whereas pollen limitation was detected for sweet, but not for sour cherry. A great diversity of insects visits cherry blossoms, with 185 species recorded, of which 142 were bees and 36 flies. With a mean relative abundance of 57 % across studies, honeybees were the dominant flower visitor. Little is known about the pollination performance of different taxa, with only one study comparing bees' single-visit efficiency, suggesting that mason bees and mining bees are more efficient pollinators compared to honeybees and bumblebees. This could explain why observational studies detect a positive relationship between wild pollinator visitation and cherry fruit set, which was not detected for honeybee visitation. Studies on managed pollinators focused on honeybees and mason bees, while bumblebee management was neglected. In sum, we conclude that pollination shortages can be improved by the promotion of wild pollinators, managed pollinators, or both, depending on the landscape context and pollination requirements of the cultivars. Wild bee visitation can be enhanced through conserving semi-natural habitats around orchards. Enhancing floral resources as an on-farm measurement has mixed results on pollinators, whereas other management practices such as polytunnels or pesticide effects on pollinators are understudied. Development of targeted guidelines for pollination management practices for farmers to enhance pollination services in cherry orchards should take into account multiple aspects, spanning from horticulture and agronomy (e.g., how to best manage flower strips) to applied entomology and landscape ecology (e.g., adding a landscape perspective to optimize honeybee management). • Research is biased towards North America and Europe, and sweet cherry. • Most cultivars are self-incompatible, yet self-compatible cultivars exist. • Pollen limitation was detected for sweet cherry, but not for sour cherry. • Visitation of wild insects, not honeybees, positively relates to cherry pollination. • Landscape and farm management also impact cherry pollination. [ABSTRACT FROM AUTHOR]

Simple Summary: All grazing horses are exposed to parasites that when ingested have the potential to cause disease. Drugs designed to kill parasites in horses have been used extensively since the 1960s, but this intensive use has led to the development of drug resistance, emphasising the need for more sustainable methods to lessen parasite burdens. The efficacy and suitability of pasture-management methods aiming to reduce the level of parasitic larvae in the herbage are, however, dependent on the prevailing weather conditions. The aim of the present study was therefore to generate data on the effect of regular faecal removal and harrowing of the pasture on reducing the number of parasites in herbage in a Nordic climate. Furthermore, the ability of parasite larvae to migrate from faeces to the herbage and to survive the winter season in Sweden's cold temperate climate was investigated. Twice-weekly faecal removal significantly reduced the number of larvae on the pasture, whereas harrowing on a single occasion in the summer under dry weather conditions did not. Parasite larvae migrated as far as 150 cm from faecal pats and were able to survive one winter season, with two years of rest from grazing horses required to achieve parasite-free pasture. Horses, as grazing animals, are inadvertently exposed to intestinal parasites that, if not controlled, may cause disease. However, the indiscriminate use of anthelmintic drugs has led to drug resistance, highlighting the need for pasture-management practices to reduce the level of parasitic exposure and lessen reliance on drugs. The efficacy of such methods depends both on the epidemiology of the parasites and the prevailing weather conditions. The aim of the study was to investigate the effect of faecal removal and harrowing on reducing the number of parasite larvae in herbage. Moreover, the migratory and survival ability of strongyle larvae in a Nordic climate was studied. Faeces from horses naturally infected with strongyle nematodes were used to contaminate pastures and grass samples were collected to harvest larvae. Twice-weekly faecal removal significantly reduced larval yields, whereas harrowing on a single occasion under dry weather conditions in the summer did not. Strongyle larvae were able to migrate 150 cm from the faecal pats, but most larvae were found within 50 cm. Both Cyathostominae and S. vulgaris survived the winter months with larvae harvested up to 17–18 months after faecal placement. Resting of pastures for one year greatly reduced the parasite level, but two years of rest were required for parasite-free pasture. [ABSTRACT FROM AUTHOR]

Bifidobacteria are early colonizers of the human neonatal gut and provide multiple health benefits to the infant, including inhibiting the growth of enteropathogens and modulating the immune system. Certain Bifidobacterium species prevail in the gut of breastfed infants due to the ability of these microorganisms to selectively forage glycans present in human milk, specifically human milk oligosaccharides (HMOs) and N-linked glycans. Therefore, these carbohydrates serve as promising prebiotic dietary supplements to stimulate the growth of bifidobacteria in the guts of children suffering from impaired gut microbiota development. However, the rational formulation of milk glycan-based prebiotics requires a detailed understanding of how bifidobacteria metabolize these carbohydrates. Accumulating biochemical and genomic data suggest that HMO and N-glycan assimilation abilities vary remarkably within the Bifidobacterium genus, both at the species and strain levels. This review focuses on the delineation and genome-based comparative analysis of differences in respective biochemical pathways, transport systems, and associated transcriptional regulatory networks, providing a foundation for genomics-based projection of milk glycan utilization capabilities across a rapidly growing number of sequenced bifidobacterial genomes and metagenomic datasets. This analysis also highlights remaining knowledge gaps and suggests directions for future studies to optimize the formulation of milk-glycan-based prebiotics that target bifidobacteria. [ABSTRACT FROM AUTHOR]

Topoisomerase V is a unique topoisomerase that combines DNA repair and topoisomerase activities. The enzyme has an unusual arrangement, with a small topoisomerase domain followed by 12 tandem (HhH)2 domains, which include 3 AP lyase repair domains. The uncommon architecture of this enzyme bears no resemblance to any other known topoisomerase. Here, we present structures of topoisomerase V in complex with DNA. The structures show that the (HhH)2 domains wrap around the DNA and in this manner appear to act as a processivity factor. There is a conformational change in the protein to expose the topoisomerase active site. The DNA bends sharply to enter the active site, which melts the DNA and probably facilitates relaxation. The structures show a DNA- binding mode not observed before and provide information on the way this atypical topoisomerase relaxes DNA. In common with type IB enzymes, topoisomerase V relaxes DNA using a controlled rotation mechanism, but the structures show that topoisomerase V accomplishes this in different manner. Overall, the structures firmly establish that type IC topoisomerases form a distinct type of topoisomerases, with no similarities to other types at the sequence, structural, or mechanistic level. They represent a completely different solution to DNA relaxation. [ABSTRACT FROM AUTHOR]

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive head trauma and is characterised by the perivascular accumulation of hyperphosphorylated tau (p-tau) in the depths of cortical sulci. CTE can only be diagnosed postmortem and the cellular mechanisms of disease causation remain to be elucidated. Understanding the full scope of the pathological changes currently identified in CTE is necessary to identify areas requiring further research. This systematic review summarises the current literature on CTE pathology from postmortem human tissue histology studies published until 31 December 2021. Publications were included if they quantitively or qualitatively compared postmortem human tissue pathology in CTE to neuropathologically normal cases or other neurodegenerative diseases such as Alzheimer's disease (AD). Pathological entities investigated included p-tau, beta-amyloid, TDP-43, Lewy bodies, astrogliosis, microgliosis, axonopathy, vascular dysfunction, and cell stress. Of these pathologies, p-tau was the most frequently investigated, with limited reports on other pathological features such as vascular dysfunction, astrogliosis, and microgliosis. Consistent increases in p-tau, TDP-43, microgliosis, axonopathy, and cell stress were reported in CTE cases compared to neuropathologically normal cases. However, there was no clear consensus on how these pathologies compared to AD. The CTE cases used for these studies were predominantly from the VA-BU-CLF brain bank, with American football and boxing as the most frequent sources of repetitive head injury exposure. Overall, this systematic review highlights gaps in the literature and proposes three priorities for future research including: 1. The need for studies of CTE cases with more diverse head injury exposure profiles to understand the consistency of pathology changes between different populations. 2. The need for more studies that compare CTE with normal ageing and AD to further clarify the pathological signature of CTE for diagnostic purposes and to understand the disease process. 3. Further research on non-aggregate pathologies in CTE, such as vascular dysfunction and neuroinflammation. These are some of the least investigated features of CTE pathology despite being implicated in the acute phase response following traumatic head injury. [ABSTRACT FROM AUTHOR]

Background: International guidelines recommend emergency cholecystectomy for acute cholecystitis in patients who are healthy or have mild systemic disease (ASA1-2). Surgery is also an option for patients with severe systemic disease (ASA3) in clinical practice. The study aimed to investigate the risk of complications in ASA3 patients after surgery for acute cholecystitis.Method: 1 634 patients treated for acute cholecystitis at three Swedish centres between 2017 and 2020 were included in the study. Data was gathered from electronic patient records and the Swedish registry for gallstone surgery, Gallriks. Logistic regression was used to assess the risk of complications adjusted for confounding factors: sex, age, BMI, Charlson comorbidity index, cholecystitis grade, smoking and time to surgery.Results: 725 patients had emergency surgery for acute cholecystitis, 195 were ASA1, 375 ASA2, and 152 ASA3. Complications occurred in 9% of ASA1, 13% of ASA2, and 24% of ASA3 patients. There was no difference in 30-day mortality. ASA3 patients stayed on average 2 days longer after surgery. After adjusting for other factors, the risk of complications was 2.5 times higher in ASA3 patients than in ASA1 patients. The risk of complications after elective surgery was 5% for ASA1, 13% for ASA2 and 14% for ASA3 patients. Regardless of ASA 18% of patients treated non-operatively had a second gallstone complication within 3 months.Conclusion: Patients with severe systemic disease have an increased risk of complications but not death after emergency surgery. The risk is lower for elective procedures, but a substantial proportion will have new gallstone complications before elective surgery.Trial Registration: Not applicable. [ABSTRACT FROM AUTHOR]

Peru is probably home to the largest population of Andean bears (Tremarctos ornatus; Peyton 1999); however, no studies have assessed the density and ecology of the species in this region in the past 20 years. Population density estimates are a cornerstone of species conservation because they help guide decision-making and monitoring of species trends. Here, we study Andean bear population density in a small area (i.e., visible area: 352 ha), Copal, in the Amazonas region in Peru between 2015 and 2017. To estimate Andean bear density, we used 3 methods: one based on capture-recapture data of bears, one based on an occupancymodel, and one based on the frequency of a uniquely colored bear compared with the frequency of other black Andean bears. Our results estimated Andean bear densities between 8.85 and 17.39 bears/100 km²; we considered our estimate of 10.38 bears/100 km² from capture-recapture data to be the most reliable. We also recalculated Andean bear density results from Ecuador by Molina et al. (2017), which provided a similar estimate of 11.49 bears/100 km². Additionally, we report a unique finding of a bear with a golden brown pelage, which we suspect to be the first case in Andean bears. During behavioral observations, Andean bears were predominantly feeding. We suggest that, although Andean bears have large home ranges, a few small areas may be of disproportionate importance to a population. Protecting small areas frequently used by a large number of bears could be an effective mean for Andean bear conservation where large reserves are not a feasible option. We also recognize the need for large-scale studies using a spatial capture-recapture framework, and to associate the results of Andean bear density with resource use in order to successfully protect high-value Andean bear habitat. [ABSTRACT FROM AUTHOR]

Since autumn 2020, rapid antigen tests (RATs) have been implemented in several countries as an important pillar of the national testing strategy to rapidly screen for infections on site during the SARS-CoV-2 pandemic. The current surge in infection rates around the globe is driven by the variant of concern (VoC) omicron (B.1.1.529). Here, we evaluated the performance of nine SARS-CoV-2 RATs in a single-centre laboratory study. We examined a total of 115 SARS-CoV-2 PCR-negative and 166 SARS-CoV-2 PCR-positive respiratory swab samples (101 omicron, 65 delta (B.1.617.2)) collected from October 2021 until January 2022 as well as cell culture-expanded clinical isolates of both VoCs. In an assessment of the analytical sensitivity in clinical specimen, the 50% limit of detection (LoD50) ranged from 1.77 × 106 to 7.03 × 107 RNA copies subjected to the RAT for omicron compared to 1.32 × 105 to 2.05 × 106 for delta. To score positive in these point-of-care tests, up to 10-fold (LoD50) or 101-fold (LoD95) higher virus loads were required for omicron- compared to delta-containing samples. The rates of true positive test results for omicron samples in the highest virus load category (Ct values < 25) ranged between 31.4 and 77.8%, while they dropped to 0–8.3% for samples with intermediate Ct values (25–30). Of note, testing of expanded virus stocks suggested a comparable RAT sensitivity of both VoCs, questioning the predictive value of this type of in vitro-studies for clinical performance. Given their importance for national test strategies in the current omicron wave, awareness must be increased for the reduced detection rate of omicron infections by RATs and a short list of suitable RATs that fulfill the minimal requirements of performance should be rapidly disclosed. [ABSTRACT FROM AUTHOR]

In a larger educational building in Slovenia, we examined the efficiency of ventilation systems by analysing the operation of the heating, ventilation, and air conditioning (HVAC) system in several classrooms. Using the Federation of European Heating, Ventilation and Air Conditioning Associations (REHVA) COVID-19 ventilation calculator, the probability of infection due to the spread of coronavirus through aerosol particles and the reproduction number were calculated based on the classroom occupancy, ventilation rates, and other parameters (i.e., classroom characteristics, preventive measures). Firstly, different levels of ventilation capacity (50 % and 80 %) were applied. Considering the distance between occupants 1.5 m and wearing the masks of all participants, the probability of infection during lectures was always lower than 1 %. Secondly, the maximum number of students that can attend lectures is about 30 %, as calculated according to the legal requirements, recommendations, and given conditions. [ABSTRACT FROM AUTHOR]

A versatile portfolio of diagnostic tests is essential for the containment of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic. Besides nucleic acid-based test systems and point-of-care (POCT) antigen (Ag) tests, quantitative, laboratory-based nucleocapsid Ag tests for SARS-CoV-2 have recently been launched. Here, we evaluated four commercial Ag tests on automated platforms and one POCT to detect SARS-CoV-2. We evaluated PCR-positive (n = 107) and PCR-negative (n = 303) respiratory swabs from asymptomatic and symptomatic patients at the end of the second pandemic wave in Germany (February–March 2021) as well as clinical isolates EU1 (B.1.117), variant of concern (VOC) Alpha (B.1.1.7) or Beta (B.1.351), which had been expanded in a biosafety level 3 laboratory. The specificities of automated SARS-CoV-2 Ag tests ranged between 97.0 and 99.7% (Lumipulse G SARS-CoV-2 Ag (Fujirebio): 97.03%, Elecsys SARS-CoV-2 Ag (Roche Diagnostics): 97.69%; LIAISON® SARS-CoV-2 Ag (Diasorin) and SARS-CoV-2 Ag ELISA (Euroimmun): 99.67%). In this study cohort of hospitalized patients, the clinical sensitivities of tests were low, ranging from 17.76 to 52.34%, and analytical sensitivities ranged from 420,000 to 25,000,000 Geq/ml. In comparison, the detection limit of the Roche Rapid Ag Test (RAT) was 9,300,000 Geq/ml, detecting 23.58% of respiratory samples. Receiver-operating-characteristics (ROCs) and Youden's index analyses were performed to further characterize the assays' overall performance and determine optimal assay cutoffs for sensitivity and specificity. VOCs carrying up to four amino acid mutations in nucleocapsid were detected by all five assays with characteristics comparable to non-VOCs. In summary, automated, quantitative SARS-CoV-2 Ag tests show variable performance and are not necessarily superior to a standard POCT. The efficacy of any alternative testing strategies to complement nucleic acid-based assays must be carefully evaluated by independent laboratories prior to widespread implementation. [ABSTRACT FROM AUTHOR]

Prediction models are useful tools in the clinical management of colon cancer patients, particularly when estimating the recurrence rate and, thus, the need for adjuvant treatment. However, the most used models (MSKCC, ACCENT) are based on several decades-old patient series from clinical trials, likely overestimating the current risk of recurrence, especially in low-risk groups, as outcomes have improved over time. The aim was to develop and validate an updated model for the prediction of recurrence within 5 years after surgery using routinely collected clinicopathologic variables. A population-based cohort from the Swedish Colorectal Cancer Registry of 16,134 stage I–III colon cancer cases was used. A multivariable model was constructed using Cox proportional hazards regression. Three-quarters of the cases were used for model development and one quarter for internal validation. External validation was performed using 12,769 stage II–III patients from the Norwegian Colorectal Cancer Registry. The model was compared to previous nomograms. The nomogram consisted of eight variables: sex, sidedness, pT-substages, number of positive and found lymph nodes, emergency surgery, lymphovascular and perineural invasion. The area under the curve (AUC) was 0.78 in the model, 0.76 in internal validation, and 0.70 in external validation. The model calibrated well, especially in low-risk patients, and performed better than existing nomograms in the Swedish registry data. The new nomogram's AUC was equal to that of the MSKCC but the calibration was better. The nomogram based on recently operated patients from a population registry predicts recurrence risk more accurately than previous nomograms. It performs best in the low-risk groups where the risk-benefit ratio of adjuvant treatment is debatable and the need for an accurate prediction model is the largest. [ABSTRACT FROM AUTHOR]

Background: The use of routine immunization data by health care professionals in low- and middle-income countries remains an underutilized resource in decision-making. Despite the significant resources invested in developing national health information systems, systematic reviews of the effectiveness of data use interventions are lacking. Applying a realist review methodology, this study synthesized evidence of effective interventions for improving data use in decision-making.Methods: We searched PubMed, POPLINE, Centre for Agriculture and Biosciences International Global Health, and African Journals Online for published literature. Grey literature was obtained from conference, implementer, and technical agency websites and requested from implementing organizations. Articles were included if they reported on an intervention designed to improve routine data use or reported outcomes related to data use, and targeted health care professionals as the principal data users. We developed a theory of change a priori for how we expect data use interventions to influence data use. Evidence was then synthesized according to data use intervention type and level of the health system targeted by the intervention.Results: The searches yielded 549 articles, of which 102 met our inclusion criteria, including 49 from peer-reviewed journals and 53 from grey literature. A total of 66 articles reported on immunization data use interventions and 36 articles reported on data use interventions for other health sectors. We categorized 68 articles as research evidence and 34 articles as promising strategies. We identified ten primary intervention categories, including electronic immunization registries, which were the most reported intervention type (n = 14). Among the research evidence from the immunization sector, 32 articles reported intermediate outcomes related to data quality and availability, data analysis, synthesis, interpretation, and review. Seventeen articles reported data-informed decision-making as an intervention outcome, which could be explained by the lack of consensus around how to define and measure data use.Conclusions: Few immunization data use interventions have been rigorously studied or evaluated. The review highlights gaps in the evidence base, which future research and better measures for assessing data use should attempt to address. [ABSTRACT FROM AUTHOR]

The completeness and accuracy of the registration of synchronous metastases and recurrences in the Swedish Colorectal Cancer Registry has not been investigated. Knowing how accurate these parameters are in the registry is a prerequisite to adequately measure the current recurrence risk. All charts for patients diagnosed with stage I–III colorectal cancer (CRC) in two regions were reviewed. In one of the regions, all registrations of synchronous metastases were similarly investigated. After the database had been corrected, recurrence risk in colon cancer was calculated stratified by risk group as suggested by ESMO in 2020. In patients operated upon more than five years ago (N = 1235), there were 20 (1.6%) recurrences not reported. In more recent patients, more recurrences were unreported (4.0%). Few synchronous metastases were wrongly registered (3.6%) and, likewise, few synchronous metastases were not registered (about 1%). The five-year recurrence risk in stage II was 6% for low-risk, 11% for intermediate risk, and 23% for high-risk colon cancer patients. In stage III, it was 25% in low- and 45% in high-risk patients. Incorporation of risk factors in stage III modified the risks substantially even if this is not considered by ESMO. Adjuvant chemotherapy lowered the risk in stage III but not to any relevant extent in stage II. The registration of recurrences in the registry after 5 years is accurate to between 1 and 2% but less accurate earlier. A small number of unreported recurrences and falsely reported recurrences were discovered in the chart review. The recurrence risk in this validated and updated patient series matches what has been recently reported, except for the risk of recurrence in stage II low risk colon cancers which seem to be even a few percentage points lower (6 vs. 9%). [ABSTRACT FROM AUTHOR]

Translating 3D resistivity models of the subsurface to relevant hydrogeological parameters such as sediment texture requires applying a rock physics transform that is ideally calibrated using co-located 1D sediment texture logs. It is difficult to select optimal logging sites in the model that span the range of observed resistivity values using expert opinion alone. Instead, we demonstrate a methodology for selecting logging sites using conditioned Latin hypercube sampling (cLHS), a maximally stratified sampling design methodology. cLHS employs simulated annealing to select sampling sites that minimize an objective function by reproducing the statistics of the resistivity model. We implement numerous preprocessing steps to isolate desirable regions within the model for logging, and we use principal component analysis to reduce the dimensionality of the model to aid the convergence of the simulated annealing procedure while preserving the majority of the model variance. Additionally, we impose an additional objective function condition to penalize the selection of sites in the resistivity model that exhibit a high degree of lateral variance. This condition is used to increase the likelihood that the sediment texture logs acquired at the selected sites correlate well with the resistivity model. We tested our approach on a resistivity model obtained using a towed transient EM system in an almond orchard in California's Central Valley, comparing our selected sets of logging sites against the five cone penetrometer testing logs originally acquired at the site, as well as randomly selected logging sites. The sample sets selected with cLHS were consistently able to reproduce the statistics of the resistivity model and did so more effectively than the true sampling locations or the random sampling locations. • A sampling design methodology selects ground-truthing sites for 3D electrical resistivity models. • The statistical moments of the resistivity model are replicated effectively. • The presented sampling design outperforms random sampling and expert opinion at a test site. • The sampling design is modular and adaptable for site-specific challenges. [ABSTRACT FROM AUTHOR]

Purpose: Cancer patients have many medical and psychosocial needs, which may increase during the COVID-19 pandemic. We sought to (1) risk-stratify hematology/oncology patients using general medicine and cancer-specific methods to identify those at high risk for acute care utilization, (2) measure the correlation between two risk stratification methods, and (3) perform a telephone-based needs assessment with intervention for high-risk patients. Methods: Patients were risk-stratified using a general medical health composite score (HCS) and a cancer-specific risk (CSR) stratification based on disease and treatment characteristics. The correlation between HCS and CSR was measured using Spearman's correlation. A multi-disciplinary team developed a focused needs assessment script with recommended interventions for patients categorized as high-risk by either method. The number of patient needs identified and referrals for services made in the first month of outreach are reported. Results: A total of 1697 patients were risk-stratified, with 17% high-risk using HCS and 22% high-risk using CSR. Correlation between HCS and CSR was modest (ρ = 0.41). During the first month of the pilot, 286 patients were called for outreach with 245 contacted (86%). Commonly identified needs were financial difficulties (17%), uncontrolled symptoms (15%), and interest in advance care planning (13%), resulting in referral for supportive services for 33% of patients. Conclusion: There is a high burden of unmet medical and psychosocial needs in hematology/oncology patients during the COVID-19 pandemic. A telephone-based outreach program results in the identification of and intervention for these needs; however, additional cancer-specific risk models are needed to improve targeting to high-risk patients. [ABSTRACT FROM AUTHOR]

Successful containment strategies for the SARS-CoV-2 pandemic will depend on reliable diagnostic assays. Point-of-care antigen tests (POCT) may provide an alternative to time-consuming PCR tests to rapidly screen for acute infections on site. Here, we evaluated two SARS-CoV-2 antigen tests: the STANDARD™ F COVID-19 Ag FIA (FIA) and the SARS-CoV-2 Rapid Antigen Test (RAT). For diagnostic assessment, we used a large set of PCR-positive and PCR-negative respiratory swabs from asymptomatic and symptomatic patients and health care workers in the setting of two University Hospitals in Munich, Germany, i.e. emergency rooms, patient care units or employee test centers. For FIA, overall clinical sensitivity and specificity were 45.4% (n = 381) and 97.8% (n = 360), respectively, and for RAT, 50.3% (n = 445) and 97.7% (n = 386), respectively. For primary diagnosis of asymptomatic and symptomatic individuals, diagnostic sensitivities were 60.9% (FIA) (n = 189) and 64.5% (RAT) (n = 256). This questions these tests' utility for the reliable detection of acute SARS-CoV-2-infected individuals, in particular in high-risk settings. We support the proposal that convincing high-quality outcome data on the impact of false-negative and false-positive antigen test results need to be obtained in a POCT setting. Moreover, the efficacy of alternative testing strategies to complement PCR assays must be evaluated by independent laboratories, prior to widespread implementation in national and international test strategies. [ABSTRACT FROM AUTHOR]

PURPOSE: Because of expanding interoperability requirements, structured patient data are increasingly available in electronic health records. Many oncology data elements (eg, staging, biomarkers, documentation of adverse events and cancer outcomes) remain challenging. The Minimal Common Oncology Data Elements (mCODE) project is a consensus data standard created to facilitate transmission of data of patients with cancer. METHODS: In 2018, mCODE was developed through a work group convened by ASCO, including oncologists, informaticians, researchers, and experts in terminologies and standards. The mCODE specification is organized by 6 high-level domains: patient, laboratory/vital, disease, genomics, treatment, and outcome. In total, 23 mCODE profiles are composed of 90 data elements. RESULTS: A conceptual model was published for public comment in January 2019 and, after additional refinement, the first public version of the mCODE (version 0.9.1) Fast Healthcare Interoperability Resources (FHIR) implementation guide (IG) was presented at the ASCO Annual Meeting in June 2019. The specification was approved for balloting by Health Level 7 International (HL7) in August 2019. mCODE passed the HL7 ballot in September 2019 with 86.5% approval. The mCODE IG authors worked with HL7 reviewers to resolve all negative comments, leading to a modest expansion in the number of data elements and tighter alignment with FHIR and other HL7 conventions. The mCODE version 1.0 FHIR IG Standard for Trial Use was formally published on March 18, 2020. CONCLUSION: The mCODE project has the potential to offer tremendous benefits to cancer care delivery and research by creating an infrastructure to better share patient data. mCODE is available free from www.mCODEinitiative.org. Pilot implementations are underway, and a robust community of stakeholders has been assembled across the oncology ecosystem. [ABSTRACT FROM AUTHOR]

Methylation of nucleotides in rRNA is one of the basic mechanisms of bacterial resistance to protein synthesis inhibitors. The genes for corresponding methyltransferases have been found in producer strains and clinical isolates of pathogenic bacteria. In some cases, rRNA methylation by housekeeping enzymes is, on the contrary, required for the action of antibiotics. The effects of rRNA modifications associated with antibiotic efficacy may be cooperative or mutually exclusive. Evolutionary relationships between the systems of rRNA modification by housekeeping enzymes and antibiotic resistance-related methyltransferases are of particular interest. In this review, we discuss the above topics in detail. [ABSTRACT FROM AUTHOR]

The current coronavirus disease 2019 (COVID-19) pandemic is a challenge for physicians in triaging patients in emergency rooms. We found a potentially dangerous overlap of classical urinary symptoms and the as yet not fully described symptoms of COVID-19. After a patient was primarily triaged as a urosepsis case and then subsequently diagnosed with COVID-19, we focused on an increase in urinary frequency as a symptom of COVID-19 and identified this in seven males out of 57 patients currently being treated in our COVID-19 wards. In the absence of any other causes, urinary frequency may be secondary to viral cystitis due to underlying COVID-19 disease. We propose consideration of urinary frequency as an anamnestic tool in patients with infective symptoms to increase awareness among urologists during the current COVID-19 pandemic to prevent fatal implications of misinterpreting urological symptoms. [ABSTRACT FROM AUTHOR]

To evaluate dietary supplement information needs among collegiate athletes. Three hundred seven (n = 154 male; n = 153 female) student athletes participating in a National Collegiate Athletic Association Division I team completed a dietary supplement survey. Qualitative coding addressed open-ended responses, and chi-square test of independence explored differences among athlete subgroups. Five themes representing athletes' information needs included quality/composition (53.5%; n = 77), general information (31.9%; n = 46), nutrition information (30.6%; n = 44), performance (18.8%; n = 27), and body composition (13.2%; n = 19). Athletes with "no" or "minimal" (n = 63), vs "moderate" or "strong" (n = 195), perceived knowledge of supplement safety were more likely to list a question about supplement quality or composition (34.9% [n = 22/63] vs 21.5% [n= 42/195]; P =.03; chi-square = 4.6). Further research is needed to corroborate findings to inform educational efforts and promote safe and effective use of dietary supplements by student athletes. [ABSTRACT FROM AUTHOR]

This study examines the impact of Big Deal breaks on statewide resource sharing. An analysis within VIVA (Virginia's academic library consortium) for Big Deal publishers showed significant lending of one publisher with low levels of statewide holdings. A closer examination of an individual institution with the most recent cancellations of this publisher's content showed high levels of fulfillment from lending partners outside the consortium. As more groups cancel Big Deals, consideration for alternative access will be increasingly important, and understanding the resource sharing environment should inform a cooperative approach to journal acquisitions in order to minimize negative impacts on researchers. [ABSTRACT FROM AUTHOR]

New targeted therapies to inhibit fibroblast growth factor receptor (FGFR) represent a promising treatment option for patients with metastatic urothelial carcinoma (mUC). Despite significant advances, the optimal combination of drug, disease, genetic alteration, and screening test that together lead to maximal efficacy of FGFR inhibition for patients with mUC remains to be determined. [ABSTRACT FROM AUTHOR]

Recent research suggests that robust predictors of interpersonal forgiveness, such as relationship closeness and offense severity, also predict forgiveness of a parasocial target. We extend this work using an interpersonal forgiveness measure to examine forgiveness of parasocial targets as a function of parasocial closeness and offense perceptions. Across two studies, we found that pre-offense closeness was associated with greater forgiveness and current closeness, and that forgiveness significantly mediated the relationship between pre-offense and current closeness. In Study 2, we additionally found that perceptions of apology sincerity were associated with greater forgiveness and current parasocial closeness. Finally, we found that a brief measure of parasocial closeness was comparable to the Parasocial Interaction Scale in its associations with forgiveness and related outcomes. Implications regarding similarities and differences in interpersonal and parasocial forgiveness are discussed. Additionally, possible benefits of using of a brief, face-valid, and versatile set of items to assess parasocial closeness are suggested. [ABSTRACT FROM AUTHOR]

Background: Human encephalitis can originate from a variety of different aetiologies, of which infection is the most common one. The diagnostic work-up is specifically challenging in patients with travel history since a broader spectrum of unfamiliar additional infectious agents, e. g. tropical disease pathogens, needs to be considered. Here we present a case of encephalitis of unclear aetiology in a female traveller returning from Africa, who in addition developed an atypical herpes simplex virus (HSV) encephalitis in close temporal relation with high-dose steroid treatment.Case Presentation: A previously healthy 48-year-old female presented with confusion syndrome and impaired vigilance which had developed during a six-day trip to The Gambia. The condition rapidly worsened to a comatose state. Extensive search for infectious agents including a variety of tropical disease pathogens was unsuccessful. As encephalitic signs persisted despite of calculated antimicrobial and antiviral therapy, high-dose corticosteroids were applied intravenously based on the working diagnosis of an autoimmune encephalitis. The treatment did, however, not improve the patient's condition. Four days later, bihemispheric signal amplification in the insular and frontobasal cortex was observed on magnetic resonance imaging (MRI). The intracranial pressure rapidly increased and could not be controlled by conservative treatment. The patient died due to tonsillar herniation 21 days after onset of symptoms. Histological examination of postmortem brain tissue demonstrated a generalized lymphocytic meningoencephalitis. Immunohistochemical reactions against HSV-1/2 indicated an atypical manifestation of herpesviral encephalitis in brain tissue. Moreover, HSV-1 DNA was detected by a next-generation sequencing (NGS) metagenomics approach. Retrospective analysis of cerebrospinal fluid (CSF) and serum samples revealed HSV-1 DNA only in specimens one day ante mortem.Conclusions: This case shows that standard high-dose steroid therapy can contribute to or possibly even trigger fulminant cerebral HSV reactivation in a critically ill patient. Thus, even if extensive laboratory diagnostics including wide-ranging search for infectious pathogens has been performed before and remained without results, continuous re-evaluation of potential differential diagnoses especially regarding opportunistic infections or reactivation of latent infections is of utmost importance, particularly if new symptoms occur. [ABSTRACT FROM AUTHOR]

The introduction of national guidelines should eliminate previously observed associations between socioeconomic status (SES) and colorectal cancer treatment. The aim of the study was to investigate whether inequalities remain. CRCBaSe, a register-linkage originating from the Swedish Colorectal Cancer Registry, was used to identify information on patient and tumour characteristics, for 83,460 patients with stage I-III disease diagnosed 2008–2021. SES was measured as disposable income (quartiles) and the highest level of education. Outcomes of interest were emergency surgery, multidisciplinary team (MDT) conference discussion, and oncological treatment. Differences in treatment between SES groups were explored using multivariable logistic regression adjusted for year of diagnosis, age at diagnosis, sex, civil status, comorbidities, tumour location and stage. Patients in the highest income quartile had a lower risk of emergency surgery (OR 0.73 95%CI 0.68–0.80), a higher chance of being discussed at the preoperative (OR 1.39 95%CI 1.28–1.51) and postoperative MDT (OR 1.41 95%CI 1.30–1.53), receiving neoadjuvant (OR 1.15 95%CI 1.06–1.25) and adjuvant treatment (OR 2.04 95%CI 1.88–2.20). Higher education level increased the odds of MDT discussion but was not associated with oncological treatment. The proportion of patients discussed at the MDT increased, with almost all patients discussed since 2016. Despite this, treatment differences remained when patients diagnosed since 2016 were analysed separately. There were significant differences in how patients with different SES were treated for colorectal cancer. Further action is required to investigate the drivers of these differences as well as their impact on mortality and, ultimately, eliminate the inequalities. • Emergency surgery for colorectal cancer is more common in patients most deprived. • Most deprived patients get less oncological treatment for resected colorectal cancer. • Almost all patients were discussed at Multidisciplinary team conferences by 2016. • Despite MDT discussion, differences in treatment remained. [ABSTRACT FROM AUTHOR]

Statistics are presented which shows an overall increase in newborns breastfed between birth and discharge from the hospital in 2022 compared to 2021, with the largest increases observed among younger maternal age groups.

We consider a generalized type of unique factorization of the positive integers with restrictions on the exponents and view them as a family of arithmetic convolutions and divisibility relations, similar to the convolutions defined by Narkewicz [On a class of arithmetical convolutions, Colloq. Math.10 (1963) 81–94]. We introduce special types of multiplicativity corresponding to these convolutions, and discuss algebraic properties of the associated arithmetic convolutions and analogs of the Möbius functions. We also prove asymptotics for analogs of the totient function, totient summatory function, and divisor summatory function. [ABSTRACT FROM AUTHOR]

Background and Aims: Treatment pathways for ulcerative colitis (UC) and Crohn's disease (CD) are shifting to a more individualized, risk-stratified approach. The perception is that insurance policies may not have implemented this paradigm shift, particularly regarding access to newer agents. We evaluated patient access to advanced therapies by analyzing policy information from the Managed Markets Insight and Technology database.Methods: Coverage status as of December 2018 for all US lives was queried for adalimumab, infliximab, infliximab-dyyb, tofacitinib, ustekinumab, and vedolizumab by indication (UC and/or CD) and medical or pharmacy coverage benefit. Coverage status was classified by the number of biologic steps before access to specified drug as "No Biologic," "1 Prior Biologic," "2+ Prior Biologics," "Not Covered." Unknown lives were excluded from the analyses.Results: Coverage analysis was available for approximately 302 million lives under each medical and pharmacy benefit. Our analysis indicates that approximately half of covered lives had access to all agents (except tofacitinib) as first-line therapy; two-thirds had access after one biologic exposure. Among newer agents, vedolizumab had the widest coverage. For indications of UC and CD, 81% of known lives had access to vedolizumab with no prior biologic exposure required ("No Biologic"), 95% after "No Biologic" + "1 prior Biologic." Geographic variations were identified for coverage patterns.Conclusions: This US-based healthcare policy analysis points to an increased access to advanced therapies for UC and CD. An individualized, risk-stratified treatment approach integrating advanced therapies, including those recently approved, into treatment pathways for UC and CD is feasible. [ABSTRACT FROM AUTHOR]

The genome of cells is constantly challenged by DNA damages from endogenous metabolism and environmental agents. These damages could potentially lead to genomic instability and thus to tumorigenesis. To cope with the threats, cells have evolved an intricate network, namely DNA damage response (DDR) system that senses and deals with the lesions of DNA. Although the DDR operates by relatively uniform principles, different tissues give rise to distinct types of DNA damages combined with high diversity of microenvironments across tissues. In this review, we discuss recent findings on specific DNA damage among different tissues as well as the main DNA repair way in corresponding microenvironments, highlighting tissue specificity of DDR and tumorigenesis. We hope the current review will provide further insights into molecular process of tumorigenesis and generate new strategies for cancer treatment. [ABSTRACT FROM AUTHOR]

Case: Recurrent carpal tunnel syndrome is a challenging problem. Nerve wraps have been introduced as a barrier to prevent scar traction neuritis for use during revision carpal tunnel surgery. We present 3 cases of inflammatory responses to bovine collagen and porcine subintestinal mucosal nerve wraps in patients undergoing revision carpal tunnel surgery. No patient had evidence of infection, and pathology revealed acute and chronic inflammation. All 3 patients responded favorably following wrap removal. Conclusions: We recommend caution with the routine use of nerve wraps in the setting of revision carpal tunnel surgery. [ABSTRACT FROM AUTHOR]

The E4 Stockholm Bypass is a new route for the European highway (E4) past the Swedish capital Stockholm. The bypass will connect the southern and northern parts of Stockholm. To reduce the impact on the surroundings, 18 km of the total of 21 km of the Stockholm Bypass are being constructed in tunnels. The Bypass will be one of the longest road tunnels in the world, with a construction cost of 3.1 billion Euro (2009 prices). The challenges have been many, for example how to evaluate the hydraulic rock mass properties for such a vast tunnel stretch and then find the most suitable grouting design, the contractor's ability to deliver proper grout properties and suitable grouting equipment, the time and resources needed for QA/QC of the grouting works and the need for adaption of the grouting works to true geological conditions. Not to mention the complexity of monitoring water ingress during construction for the Client to show that the sealing demands are being met according to the environmental permits for water works operations. The Stockholm Bypass is by far the largest rock fissure grouting operation undertaken for road tunnels in Swedish history. [ABSTRACT FROM AUTHOR]

Libraries have been dealing with chronic, unsustainable journal pricing for many years. In response to this issue, the Virtual Library of Virginia (VIVA), the academic library consortium of Virginia, formed a Sustainable Journal Pricing Task Force in 2018 charged with designing a model built on VIVA's mission and collection development priorities, with special attention given to Open Access (OA). Traditionally, libraries start from publishers' pricing offers and negotiate from that point, but in the envisioned approach, negotiations start with a model proposed by the consortium. VIVA's approach is designed to be a bridge between the past subscription model and an envisioned future of broadened OA options. [ABSTRACT FROM AUTHOR]

Summary: Background: Prospectively designed studies assessing the exposure‐response profile of vedolizumab are lacking. Observational exposure‐response data for vedolizumab are limited and have not been adjusted for potential confounding factors, particularly those that may affect vedolizumab clearance. Aims: To (a) investigate the vedolizumab exposure‐response relationship after adjusting for potential confounding variables; (b) propose potential target serum vedolizumab concentrations for future study; (c) ascertain whether early vedolizumab serum concentrations were associated with short‐ and long‐term clinical outcomes in adults with ulcerative colitis in GEMINI 1. Methods: Propensity‐score‐based case‐matching analysis was performed using data from GEMINI 1 and an earlier large population pharmacokinetic study, with vedolizumab clearance or concentration as predictors of clinical remission and response, adjusted for age, weight, anti‐tumour necrosis factor alpha therapy history, serum albumin and faecal calprotectin concentrations. Potential vedolizumab concentration targets at weeks 6, 14 and steady state were proposed. Association between early vedolizumab concentrations at weeks 2, 4 and 6 and clinical remission at weeks 14 and 52 was evaluated. Results: Among 693 patients with pharmacokinetic data at week 6, potential target vedolizumab concentrations at weeks 6, 14 and steady state were 37.1, 18.4 and 12.7 µg/mL respectively. Week 6 was identified as the earliest time at which vedolizumab concentrations were consistently associated with clinical remission at weeks 14 and 52. Conclusions: In this comprehensively adjusted analysis, vedolizumab concentrations at week 6 were associated with short‐ and long‐term remission. Potential induction and maintenance target concentrations were proposed for further study. [ABSTRACT FROM AUTHOR]

Introduction: There is significant variability in the preparedness of incoming interns at the start of residency training with regard to medical knowledge, procedural skills, and attitudes. Specialty-specific preparatory courses aimed at improving clinical skills exist; however, no preparatory courses targeting wellness promotion or burnout prevention have previously been described. Resident well-being has gained increasing attention from the Accreditation Council for Graduate Medical Education, and numerous studies have demonstrated high levels of burnout among resident physicians. The American Medical Association (AMA) divides resident well-being into the following six categories: nutrition, fitness, emotional health, financial health, preventative care, and mindset and behavioral adaptability. Using the AMA’s conceptual framework for well-being in residency, we performed a targeted needs assessment to support the development of a “pre-residency” well-being curriculum. Our aim was to discover what current residents and faculty felt were the perceived areas of under-preparedness, in relation to resident well-being, for incoming interns at the start of their residency training. Methods: Using a grounded theory approach, we conducted a series of semi-structured, focus group interviews. Focus groups consisted of junior residents (postgraduate years [PGY] 1-3), senior residents (PGY-4), and current faculty members. A standardized interview guide was used to prompt discussion and themes were identified from audio recor ding. We modified theories based on latent and manifest content analysis, and we performed member checking and an external audit to improve validity. Results: Participants noted variable exposure to both formal and informal well-being training prior to residency. Regardless, participants uniformly agreed that their past experiences did not adequately prepare them for the challenges, specific to burn out prevention, faced during residency training. Of the six domains of resident well-being described by the AMA, emotional health, mindset and behavioral adaptability, and financial health were the domains most cited for interns to be underprepared for at the start of residency training. Conclusion: Despite variability in prior medical school and life experiences, incoming interns were underprepared in several domains of well-being, including emotional health, mindset and behavioral adaptability, and financial health. Targeted interventions toward these areas of well-being should be piloted and studied further for their potential to mitigate effects of burnout among resident physicians. [ABSTRACT FROM AUTHOR]

Cyathostominae are ubiquitous to grazing horses and regarded the most prevalent internal parasite in the horse. Unfortunately, decades of indiscriminate use of anthelmintic drugs have resulted in the development of resistance in cyathostomins to all currently available drug groups, the most recent being a documented lack of efficacy to the macrocyclic lactones (ML). In vivo determination of anthelmintic resistance in horses most often utilises the faecal egg count reduction test (FECRT). Further, a shortened egg reappearance period (ERP) can indicate a change in response to the applied treatment and suggest an upcoming reduction of efficacy. Although both true resistance as demonstrated by the FECRT and shorter ERPs after ML treatment have now been shown in cyathostomins worldwide, the efficacy of ML as regards to cyathostomins in Sweden is currently unknown. The aim of the present study was therefore to determine FECRTs and ERPs after ivermectin (IVM) treatment in Swedish horses. Sixteen equestrian establishments with a minimum of six horses excreting at least 150 eggs per gram faeces (EPG) at screening were selected. For each establishment, FECRTs and ERPs were determined by collecting faecal samples prior to and 14 days after IVM treatment (200 µg/kg), and thereafter at weekly intervals for a total of eight weeks. All participants responded to a questionnaire detailing pasture management methods and anthelmintic routines.Questionnaire results showed that the majority of establishments (69%) only treated horses with anthelmintic drugs if indicated by faecal diagnostics and all of the establishments had a mean FECRT exceeding 99.0% and ERPs ranging from six to over eight weeks. The ERP was shown to increase with age as young individuals were shown to excrete cyathostomin eggs earlier after treatment compared with older horses (R = 0.21, p = 0.015). Riding schools, stud farms and those declaring not to use separate summer and winter paddocks had significantly shorter ERPs (p <0.01).In conclusion, retained ERPs and no confirmed resistance to IVM were found in Swedish equine establishments practising selective anthelmintic treatment, and supports the use of selective deworming regimens as a means of reducing the risk of anthelmintic resistance development. [Display omitted] • Routine anthelmintic treatment of horses without prior diagnostics is rare in Sweden. • Ivermectin resulted in FECRs > 99% in all studied horse establishments. • ERPs after ivermectin treatment were 6–8 weeks in all studied horse establishments. • No evidence of resistance in cyathostomins to ivermectin shown in Swedish horses. • Selective treatment regimens can reduce anthelmintic resistance development. [ABSTRACT FROM AUTHOR]

Background: Large B-cell lymphoma (LBCL) is the most common lymphoma and is known to be a biologically heterogeneous disease regarding genetic, phenotypic, and clinical features. Although the prognosis is good, one-third has a primary refractory or relapsing disease which underscores the importance of developing predictive biological markers capable of identifying high- and low-risk patients. DNA methylation (DNAm) and telomere maintenance alterations are hallmarks of cancer and aging. Both these alterations may contribute to the heterogeneity of the disease, and potentially influence the prognosis of LBCL. Results: We studied the DNAm profiles (Infinium MethylationEPIC BeadChip) and relative telomere lengths (RTL) with qPCR of 93 LBCL cases: Diffuse large B-cell lymphoma not otherwise specified (DLBCL, n = 66), High-grade B-cell lymphoma (n = 7), Primary CNS lymphoma (n = 8), and transformation of indolent B-cell lymphoma (n = 12). There was a substantial methylation heterogeneity in DLBCL and other LBCL entities compared to normal cells and other B-cell neoplasms. LBCL cases had a particularly aberrant semimethylated pattern (0.15 ≤ β ≤ 0.8) with large intertumor variation and overall low hypermethylation (β > 0.8). DNAm patterns could not be used to distinguish between germinal center B-cell-like (GC) and non-GC DLBCL cases. In cases treated with R-CHOP-like regimens, a high percentage of global hypomethylation (β < 0.15) was in multivariable analysis associated with worse disease-specific survival (DSS) (HR 6.920, 95% CI 1.499–31.943) and progression-free survival (PFS) (HR 4.923, 95% CI 1.286–18.849) in DLBCL and with worse DSS (HR 5.147, 95% CI 1.239–21.388) in LBCL. These cases with a high percentage of global hypomethylation also had a higher degree of CpG island methylation, including islands in promoter-associated regions, than the cases with less hypomethylation. Additionally, telomere length was heterogenous in LBCL, with a subset of the DLBCL-GC cases accounting for the longest RTL. Short RTL was independently associated with worse DSS (HR 6.011, 95% CI 1.319–27.397) and PFS (HR 4.689, 95% CI 1.102–19.963) in LBCL treated with R-CHOP-like regimens. Conclusion: We hypothesize that subclones with high global hypomethylation and hypermethylated CpG islands could have advantages in tumor progression, e.g. by inactivating tumor suppressor genes or promoting treatment resistance. Our findings suggest that cases with high global hypomethylation and thus poor prognosis could be candidates for alternative treatment regimens including hypomethylating drugs. [ABSTRACT FROM AUTHOR]

The article discusses that the temperature measurement, unvented cavities, loose powder, and direct contact of certain metals must be considered during process development of vacuum heat treatment of additively manufactured parts. It mentions that the rate of layer deposition and cooling kinetics for each layer also has a distinct effect on the internal stress in the build and build plate.