High-level performances following low altitude training and tapering in warm environments in elite racewalkers.

Current guidelines for prolonged altitude exposure suggest altitude levels ranging from 2000 to 2500 m to optimize an increase in total hemoglobin mass (Hbmass). However, natural low altitude locations (<2000 m) remain popular, highlighting the interest to investigate any possible benefit of low altitude camps for endurance athletes. Ten elite racewalkers (4 women and 6 men) underwent a 4-week "live high-train high" (LHTH) camp at an altitude of 1720 m (PIO2 = 121 mmHg; 20.1°C; 67% relative humidity [RH]), followed by a 3-week tapering phase (20 m; PIO2 = 150 mmHg; 28.3°C; 53% RH) in preparation for the World Athletics Championships (WC). Venous blood samples were withdrawn weekly during the entire observation period. In addition, blood volumes were determined weekly by carbon monoxide rebreathing during altitude exposure and 2 weeks after return to sea level. High-level performances were achieved at the WC (five placings among the Top 10 WC races and three all-time career personal bests). A slight but significant increase in absolute (+1.7%, p = 0.03) and relative Hbmass (+2.3%, p = 0.02) was observed after 4-week LHTH. In addition, as usually observed during LHTH protocols, weekly training distance (+28%, p = 0.02) and duration (+30%, p = 0.04) significantly increased during altitude compared to the pre-LHTH period. Therefore, although direct causation cannot be inferred, these results suggest that the combination of increased training load at low altitudes with a subsequent tapering period in a warm environment is a suitable competition-preparation strategy for elite endurance athletes.

Incidence of induced abortion among commercially insured pregnant patients with cancer.

OBJECTIVES: This study aimed to characterize pregnancy outcomes and the incidence of induced abortion among pregnant people with a diagnosis of malignancy. STUDY DESIGN: We conducted a retrospective cohort study among privately insured people aged 12 to 55 years from the fourth quarter of 2015-2020 using US claims data from Merative MarketScan Research Databases. We included pregnancies from seven states with favorable policies for private insurance coverage of abortion. RESULTS: There were 1471 of 183,685 (0.8%) pregnancies with a cancer diagnosis. Among those receiving anticancer therapy, 21.6% (95% CI: 14.4-30.4%) underwent induced abortion compared with 10.9% (95% CI: 10.8-11.1%) of pregnant patients without a cancer diagnosis. CONCLUSIONS: Abortion restrictions may affect many pregnant women requiring cancer treatment in early pregnancy.

Risk calculators for the detection of prostate cancer: a systematic review.

BACKGROUND: Prostate cancer (PCa) (early) detection poses significant challenges, including unnecessary testing and the risk of potential overdiagnosis. The European Association of Urology therefore suggests an individual risk-adapted approach, incorporating risk calculators (RCs) into the PCa detection pathway. In the context of 'The PRostate Cancer Awareness and Initiative for Screening in the European Union' (PRAISE-U) project ( https://uroweb.org/praise-u ), we aim to provide an overview of the currently available clinical RCs applicable in an early PCa detection algorithm. METHODS: We performed a systematic review to identify RCs predicting detection of clinically significant PCa at biopsy. A search was performed in the databases Medline ALL, Embase, Web of Science Core Collection, Cochrane Central Register of Controlled Trials and Google Scholar for publications between January 2010 and July 2023. We retrieved relevant literature by using the terms "prostate cancer", "screening/diagnosis" and "predictive model". Inclusion criteria included systematic reviews, meta-analyses, and clinical trials. Exclusion criteria applied to studies involving pre-targeted high-risk populations, diagnosed PCa patients, or a sample sizes under 50 men. RESULTS: We identified 6474 articles, of which 140 were included after screening abstracts and full texts. In total, we identified 96 unique RCs. Among these, 45 underwent external validation, with 28 validated in multiple cohorts. Of the externally validated RCs, 17 are based on clinical factors, 19 incorporate clinical factors along with MRI details, 4 were based on blood biomarkers alone or in combination with clinical factors, and 5 included urinary biomarkers. The median AUC of externally validated RCs ranged from 0.63 to 0.93. CONCLUSIONS: This systematic review offers an extensive analysis of currently available RCs, their variable utilization, and performance within validation cohorts. RCs have consistently demonstrated their capacity to mitigate the limitations associated with early detection and have been integrated into modern practice and screening trials. Nevertheless, the lack of external validation data raises concerns about numerous RCs, and it is crucial to factor in this omission when evaluating whether a specific RC is applicable to one's target population.

Developing a predictive model for metastatic potential in pancreatic neuroendocrine tumor.

CONTEXT: Pancreatic neuroendocrine tumors (PNETs) exhibit a wide range of behavior from localized disease to aggressive metastasis. A comprehensive transcriptomic profile capable of differentiating between these phenotypes remains elusive. OBJECTIVE: Use machine learning to develop predictive models of PNET metastatic potential dependent upon transcriptomic signature. METHODS: RNA-sequencing data were analyzed from 95 surgically-resected primary PNETs in an international cohort. Two cohorts were generated with equally balanced metastatic PNET composition. Machine learning was used to create predictive models distinguishing between localized and metastatic tumors. Models were validated on an independent cohort of 29 formalin-fixed, paraffin-embedded samples using NanoString nCounter®, a clinically-available mRNA quantification platform. RESULTS: Gene expression analysis identified concordant differentially expressed genes between the two cohorts. Gene set enrichment analysis identified additional genes that contributed to enriched biologic pathways in metastatic PNETs. Expression values for these genes were combined with an additional 7 genes known to contribute to PNET oncogenesis and prognosis, including ARX and PDX1. Eight specific genes (AURKA, CDCA8, CPB2, MYT1L, NDC80, PAPPA2, SFMBT1, ZPLD1) were identified as sufficient to classify the metastatic status with high sensitivity (87.5% - 93.8%) and specificity (78.1% - 96.9%). These models remained predictive of the metastatic phenotype using NanoString nCounter® on the independent validation cohort, achieving a median AUROC of 0.886. CONCLUSIONS: We identified and validated an eight-gene panel predictive of the metastatic phenotype in PNETs, which can be detected using the clinically-available NanoString nCounter® system. This panel should be studied prospectively to determine its utility in guiding operative versus non-operative management.

Missing Value Imputation of Wireless Sensor Data for Environmental Monitoring.

Over the past few years, the scale of sensor networks has greatly expanded. This generates extended spatiotemporal datasets, which form a crucial information resource in numerous fields, ranging from sports and healthcare to environmental science and surveillance. Unfortunately, these datasets often contain missing values due to systematic or inadvertent sensor misoperation. This incompleteness hampers the subsequent data analysis, yet addressing these missing observations forms a challenging problem. This is especially the case when both the temporal correlation of timestamps within a single sensor and the spatial correlation between sensors are important. Here, we apply and evaluate 12 imputation methods to complete the missing values in a dataset originating from large-scale environmental monitoring. As part of a large citizen science project, IoT-based microclimate sensors were deployed for six months in 4400 gardens across the region of Flanders, generating 15-min recordings of temperature and soil moisture. Methods based on spatial recovery as well as time-based imputation were evaluated, including Spline Interpolation, MissForest, MICE, MCMC, M-RNN, BRITS, and others. The performance of these imputation methods was evaluated for different proportions of missing data (ranging from 10% to 50%), as well as a realistic missing value scenario. Techniques leveraging the spatial features of the data tend to outperform the time-based methods, with matrix completion techniques providing the best performance. Our results therefore provide a tool to maximize the benefit from costly, large-scale environmental monitoring efforts.

Serum Biomarkers of Vascular Involvement in Childhood Uveitis.

Purpose: Nonanterior uveitis frequently involves the retinal vasculature; however, no molecular markers associated with the retinal vascular disease are currently known. In this study, we aimed to identify serum biomarker signatures associated with retinal vascular involvement in noninfectious pediatric uveitis. Methods: We performed a 384-plex targeted proteomic analysis of serum samples of 154 noninfectious pediatric uveitis patients diagnosed with nonanterior uveitis (n = 74), idiopathic chronic anterior uveitis (iCAU, n = 36), or juvenile idiopathic arthritis-associated uveitis (JIA-U, n = 44), as well as 22 noninflammatory pediatric controls. Data on retinal vascular involvement (i.e., papillitis, cystoid macular edema, retinal vasculitis, or retinal capillary leakage on optical coherence tomography and/or fluorescein angiography) were used to stratify cases in the nonanterior uveitis group. Results: In the analysis of nonanterior uveitis, we identified nine proteins significantly associated with retinal vascular involvement, including F13B, MYOM3, and PTPN9. These proteins were enriched through pathway enrichment analysis for the coagulation cascade. Comparing cases and controls, we identified 63 differentially expressed proteins, notably proteins involved in platelet biology and complement cascades, which could be primarily attributed to differences in serum proteomes between anterior uveitis and nonanterior uveitis groups. Conclusions: Serum proteins related to the coagulation and complement cascade are associated with retinal vascular involvement in pediatric uveitis patients. Our results indicate involvement of mediators that could interact with the microcirculation in pediatric uveitis and might serve as potential biomarkers in personalized medicine in the future. Translational Relevance: Our targeted proteomics analysis in serum of pediatric uveitis patients indicates involvement of mediators that could interact with the microcirculation in pediatric uveitis and might serve as potential biomarkers in personalized medicine in the future.

Diagnostic interobserver agreement for thyroid fine-needle aspirates: Effects of reviewer experience and molecular diagnostics.

OBJECTIVES: Few cytologically indeterminate thyroid fine-needle aspirations (FNAs) harbor BRAF V600E. Here, we assess interobserver agreement for The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) category III (atypia of undetermined significance [AUS]) FNAs harboring BRAF V600E and contrast their features with those harboring non-BRAF V600E alterations, with attention to cytopathology experience. METHODS: Seven reviewers evaluated 5 AUS thyroid FNAs harboring BRAF V600E. To blind reviewers, cases were intermixed with 19 FNAs falling within other TBSRTC categories and in which genetic alterations other than BRAF V600E had been identified (24 FNAs total). Interobserver agreement against both "index" and most popular ("mode") diagnoses was calculated. Four additional BRAF V600E cases were independently reviewed. RESULTS: Reviewers included 3 trainees and 3 American Board of Pathology (board)-certified cytopathologists. Board-certified cytopathologists, whose experience ranged from 2 to more than 15 subspecialty practice years, had known AUS rates. BRAF V600E was identified in 5 of 260 (2%) AUS FNAs. Interobserver agreement was higher among cytopathologists with more experience. Mode diagnosis differed from index diagnosis in 6 of 11 cases harboring RAS-like alterations; mode diagnosis was AUS in 4 of 5 BRAF V600E FNAs. CONCLUSIONS: Atypia of undetermined significance of thyroid FNAs harboring BRAF V600E is uncommon yet relatively reproducible, particularly among pathologists with experience. It is advisable to sequence BRAF across V600 in such cases.

Changing digital and telecytology practices post COVID-19 comparing ASC survey results from 2016 to 2023.

INTRODUCTION: During the COVID-19 pandemic, the need for digital pathology tools became more urgent. However, there needs to be more knowledge of the use in cytology. We aimed to evaluate current digital cytology practices and attitudes and compare the results with a pre-COVID-19 American Society of Cytopathology (ASC) survey. MATERIALS AND METHODS: Fourteen survey questions assessing current attitudes toward digital cytology were developed from a 2016 ASC Digital Pathology Survey. Ten new survey questions were also created to evaluate telecytology use. The survey was e-mailed to ASC members over 6 weeks in 2023. RESULTS: A total of 123 individuals responded (116 in 2016). Attitudes toward digital cytology were unchanged; most participants stated digital cytology is beneficial (87% 2023 versus 90% 2016). The percentage of individuals using digital cytology was unchanged (56% in 2016 and 2023). However, telecytology for rapid onsite assessment (ROSE) is now considered the best application (55% 2023 versus 31% 2016). Forty-three institutions reported using digital and telecytology tools; 40% made implementations after 2020; most did not feel that COVID-19 affected digital cytology (56%). Telecytology for ROSE is the most common application now (78%) compared with education (30%) in 2016. Limitations for implementing digital imaging in cytology included inability to focus (38%) and expense (33%). CONCLUSIONS: General attitudes toward digital tools by the cytology community have essentially remained the same between 2016 and now. However, telecytology for ROSE is increasingly being used, which supports a need for validation and competency guidelines.

The α4 Nicotinic Acetylcholine Receptor Is Necessary for the Initiation of Organophosphate-Induced Neuronal Hyperexcitability.

Acute intoxication with organophosphorus (OP) cholinesterase inhibitors can produce seizures that rapidly progress to life-threatening status epilepticus. Significant research effort has been focused on investigating the involvement of muscarinic acetylcholine receptors (mAChRs) in OP-induced seizure activity. In contrast, there has been far less attention on nicotinic AChRs (nAChRs) in this context. Here, we address this data gap using a combination of in vitro and in vivo models. Pharmacological antagonism and genetic deletion of α4, but not α7, nAChR subunits prevented or significantly attenuated OP-induced electrical spike activity in acute hippocampal slices and seizure activity in mice, indicating that α4 nAChR activation is necessary for neuronal hyperexcitability triggered by acute OP exposures. These findings not only suggest that therapeutic strategies for inhibiting the α4 nAChR subunit warrant further investigation as prophylactic and immediate treatments for acute OP-induced seizures, but also provide mechanistic insight into the role of the nicotinic cholinergic system in seizure generation.

Not all Medicaid for pregnancy care is delivered equally.

OBJECTIVES: Pregnant beneficiaries in the two primary Medicaid eligibility categories, traditional Medicaid and pregnancy Medicaid, have differing access to care especially in the preconception and postpartum periods. Pregnancy Medicaid has higher income limits for eligibility than traditional Medicaid but only provides coverage during and for a limited time period after pregnancy. Our objective was to determine the association between type of Medicaid (traditional Medicaid and pregnancy Medicaid) on receipt of outpatient care during the perinatal period. METHODS: This retrospective cohort study compared outpatient visits using linked birth certificate and Medicaid claims from all Medicaid births in Oregon and South Carolina from 2014 through 2019. Pregnancy Medicaid ended 60 days postpartum during the study. Our primary outcome was average number of outpatient visits per 100 beneficiaries each month during three perinatal time points: preconceputally (three months prior to conception), prenatally (9 months prior to birthdate) and postpartum (from birth to 12 months). RESULTS: Among 105,808 Medicaid-covered births in Oregon and 141,385 births in South Carolina, pregnancy Medicaid was the most prevelant categorical eligibility. Traditional Medicaid recipients had a higher average number of preconception, prenatal and postpartum visits as compared to those in pregnancy Medicaid. DISCUSSION: In South Carolina, those using traditional Medicaid had 450% more preconception visits and 70% more postpartum visits compared with pregnancy Medicaid. In Oregon, those using traditional Medicaid had 200% more preconception visits and 29% more postpartum visits than individuals using pregnancy Medicaid. Lack of coverage in both the preconception and postpartum period deprive women of adequate opportunities to access health care or contraception. Changes to pregnancy Medicaid, including extended postpartum coverage through the American Rescue Plan Act of 2021, may facilitate better continuity of care.

Lower vs Higher Oxygenation Target and Days Alive Without Life Support in COVID-19: The HOT-COVID Randomized Clinical Trial.

Importance: Supplemental oxygen is ubiquitously used in patients with COVID-19 and severe hypoxemia, but a lower dose may be beneficial. Objective: To assess the effects of targeting a Pao2 of 60 mm Hg vs 90 mm Hg in patients with COVID-19 and severe hypoxemia in the intensive care unit (ICU). Design, Setting, and Participants: Multicenter randomized clinical trial including 726 adults with COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 11 ICUs in Europe from August 2020 to March 2023. The trial was prematurely stopped prior to outcome assessment due to slow enrollment. End of 90-day follow-up was June 1, 2023. Interventions: Patients were randomized 1:1 to a Pao2 of 60 mm Hg (lower oxygenation group; n = 365) or 90 mm Hg (higher oxygenation group; n = 361) for up to 90 days in the ICU. Main Outcomes and Measures: The primary outcome was the number of days alive without life support (mechanical ventilation, circulatory support, or kidney replacement therapy) at 90 days. Secondary outcomes included mortality, proportion of patients with serious adverse events, and number of days alive and out of hospital, all at 90 days. Results: Of 726 randomized patients, primary outcome data were available for 697 (351 in the lower oxygenation group and 346 in the higher oxygenation group). Median age was 66 years, and 495 patients (68%) were male. At 90 days, the median number of days alive without life support was 80.0 days (IQR, 9.0-89.0 days) in the lower oxygenation group and 72.0 days (IQR, 2.0-88.0 days) in the higher oxygenation group (P = .009 by van Elteren test; supplemental bootstrapped adjusted mean difference, 5.8 days [95% CI, 0.2-11.5 days]; P = .04). Mortality at 90 days was 30.2% in the lower oxygenation group and 34.7% in the higher oxygenation group (risk ratio, 0.86 [98.6% CI, 0.66-1.13]; P = .18). There were no statistically significant differences in proportion of patients with serious adverse events or in number of days alive and out of hospital. Conclusion and Relevance: In adult ICU patients with COVID-19 and severe hypoxemia, targeting a Pao2 of 60 mm Hg resulted in more days alive without life support in 90 days than targeting a Pao2 of 90 mm Hg. Trial Registration: ClinicalTrials.gov Identifier: NCT04425031.

Epigenetic control of microglial immune responses.

Microglia, the major population of brain-resident macrophages, are now recognized as a heterogeneous population comprising several cell subtypes with different (so far mostly supposed) functions in health and disease. A number of studies have performed molecular characterization of these different microglial activation states over the last years making use of "omics" technologies, that is transcriptomics, proteomics and, less frequently, epigenomics profiling. These approaches offer the possibility to identify disease mechanisms, discover novel diagnostic biomarkers, and develop new therapeutic strategies. Here, we focus on epigenetic profiling as a means to understand microglial immune responses beyond what other omics methods can offer, that is, revealing past and present molecular responses, gene regulatory networks and potential future response trajectories, and defining cell subtype-specific disease relevance through mapping non-coding genetic variants. We review the current knowledge in the field regarding epigenetic regulation of microglial identity and function, provide an exemplary analysis that demonstrates the advantages of performing joint transcriptomic and epigenomic profiling of single microglial cells and discuss how comprehensive epigenetic analyses may enhance our understanding of microglial pathophysiology.

Temperature-Dependent Kinetics of the Reactions of the Criegee Intermediate CH2OO with Hydroxyketones.

Though there is a growing body of literature on the kinetics of CIs with simple carbonyls, CI reactions with functionalized carbonyls such as hydroxyketones remain unexplored. In this work, the temperature-dependent kinetics of the reactions of CH2OO with two hydroxyketones, hydroxyacetone (AcOH) and 4-hydroxy-2-butanone (4H2B), have been studied using a laser flash photolysis transient absorption spectroscopy technique and complementary quantum chemistry calculations. Bimolecular rate constants were determined from CH2OO loss rates observed under pseudo-first-order conditions across the temperature range 275-335 K. Arrhenius plots were linear and yielded T-dependent bimolecular rate constants: kAcOH(T) = (4.3 ± 1.7) × 10-15 exp[(1630 ± 120)/T] and k4H2B(T) = (3.5 ± 2.6) × 10-15 exp[(1700 ± 200)/T]. Both reactions show negative temperature dependences and overall very similar rate constants. Stationary points on the reaction energy surfaces were characterized using the composite CBS-QB3 method. Transition states were identified for both 1,3-dipolar cycloaddition reactions across the carbonyl and 1,2-insertion/addition at the hydroxyl group. The free-energy barriers for the latter reaction pathways are higher by ∼4-5 kcal mol-1, and their contributions are presumed to be negligible for both AcOH and 4H2B. The cycloaddition reactions are highly exothermic and form cyclic secondary ozonides that are the typical primary products of Criegee intermediate reactions with carbonyl compounds. The reactivity of the hydroxyketones toward CH2OO appears to be similar to that of acetaldehyde, which can be rationalized by consideration of the energies of the frontier molecular orbitals involved in the cycloaddition. The CH2OO + hydroxyketone reactions are likely too slow to be of significance in the atmosphere, except at very low temperatures.

Interobserver agreement and risk of malignancy using the International Academy of Cytology Yokohama System for reporting breast FNA biopsy in a liquid-based exclusive cohort.

BACKGROUND: Per the College of American Pathologist's National Breast Fine Needle Aspiration Biopsy (FNAB) Practice Survey, ∼40% of laboratories use liquid-based cytology (LBC) for breast FNAB. The reproducibility of the International Academy of Cytology Yokohama System (YS) for reporting breast FNAB on LBC was explored. DESIGN: Breast FNAB specimens submitted as LBC only (all ThinPrep) between January 2017 and January 2021 were retrieved. Cases without histopathologic follow-up were excluded. Clinical and radiologic information was collected. One cytologist and six cytopathologists rendered diagnoses per YS. All reviewers were blinded to the original diagnosis and histopathologic follow-up. The risk of malignancy was calculated. Concordance rates were calculated by a weighted Cohen Kappa score (κ). RESULTS: Review of 110 cases demonstrated substantial to near-perfect agreement between each reviewer (κ = 0.73-0.91) and follow-up histopathology (κ = 0.66-0.85). The agreement was lowest in the inadequate (κ = 0.05) and atypical (κ = 0.04) categories. The lack of concordance in the atypical category was common in cases with low cellularity or incomplete structural features. The risk of malignancy for inadequate, benign, atypical, suspicious for malignancy, and malignant categories were 12.5% (2/16), 3% (2/65), 67%, (8/12) 100% (1/1), and 100% (16/16). CONCLUSION: Interobserver agreement is excellent using the five YS categories in LBC. Lack of cellularity and incomplete architectural features were barriers to perfect agreement. Established pitfalls in the interpretation of LBC were cause for atypical diagnoses. Continuous training and education are recommended to avoid misdiagnosis because of the nonconventional cytomorphologic features of LBC and to improve inadequate and atypical rates within YS.

Pan-European survey on current treatment strategies in patients with upfront resectable colorectal liver metastases.

BACKGROUND: There is a lack of consensus on the definition of upfront resectability and use of perioperative systemic therapy for colorectal liver metastases (CRLM). This survey aimed to summarize the current treatment strategies for upfront resectable CRLM throughout Europe. METHODS: A survey was sent to all members of the European-African Hepato-Pancreato-Biliary Association to gain insight into the current views on resectability and the use of systemic therapy for upfront resectable CRLM. RESULTS: The survey was completed by 87 surgeons from 24 countries. The resectability of CRLM is mostly based on the volume of the future liver remnant, while considering tumor biology. Thermal ablation was considered as an acceptable adjunct to resection in parenchymal-sparing CRLM surgery by 77 % of the respondents. A total of 40.2 % of the respondents preferred standard perioperative systemic therapy and 24.1 % preferred standard upfront local treatment. CONCLUSION: Among the participating European hepato-pancreato-biliary surgeons, there is a high degree of consensus on the definition of CRLM resectability. However, there is much variety in the use of adjunctive thermal ablation. Major variations persist in the use of perioperative systemic therapy in cases of upfront resectable CRLM, stressing the need for further evidence and a consensus.

Arthropod diversity in the alpine tundra using metabarcoding: Spatial and temporal differences in alpha- and beta-diversity.

All ecosystems face ecological challenges in this century. Therefore, it is becoming increasingly important to understand the ecology and degree of local adaptation of functionally important Arctic-alpine biomes by looking at the most diverse taxon of metazoans: the Arthropoda. This is the first study to utilize metabarcoding in the Alpine tundra, providing insights into the effects of micro-environmental parameters on alpha- and beta-diversity of arthropods in such unique environments. To characterize arthropod diversity, pitfall traps were set at three middle-alpine sampling sites in the Scandinavian mountain range in Norway during the snow-free season in 2015. A metabarcoding approach was then used to determine the small-scale biodiversity patterns of arthropods in the Alpine tundra. All DNA was extracted directly from the preservative EtOH from 27 pitfall traps. In order to identify the controlling environmental conditions, all sampling locations were equipped with automatic data loggers for permanent measurement of the microenvironmental conditions. The variables measured were: air temperature [°C] at 15 cm height, soil temperature [°C] at 15 cm depth, and soil moisture [vol.%] at 15 cm depth. A total of 233 Arthropoda OTUs were identified. The number of unique OTUs found per sampling location (ridge, south-facing slope, and depression) was generally higher than the OTUs shared between the sampling locations, demonstrating that niche features greatly impact arthropod community structure. Our findings emphasize the fine-scale heterogeneity of arctic-alpine ecosystems and provide evidence for trait-based and niche-driven adaptation. The spatial and temporal differences in arthropod diversity were best explained by soil moisture and soil temperature at the respective locations. Furthermore, our results show that arthropod diversity is underestimated in alpine-tundra ecosystems using classical approaches and highlight the importance of integrating long-term functional environmental data and modern taxonomic techniques into biodiversity research to expand our ecological understanding of fine- and meso-scale biogeographical patterns.

A cis-regulatory element regulates ERAP2 expression through autoimmune disease risk SNPs.

Single-nucleotide polymorphisms (SNPs) near the ERAP2 gene are associated with various autoimmune conditions, as well as protection against lethal infections. Due to high linkage disequilibrium, numerous trait-associated SNPs are correlated with ERAP2 expression; however, their functional mechanisms remain unidentified. We show by reciprocal allelic replacement that ERAP2 expression is directly controlled by the splice region variant rs2248374. However, disease-associated variants in the downstream LNPEP gene promoter are independently associated with ERAP2 expression. Allele-specific conformation capture assays revealed long-range chromatin contacts between the gene promoters of LNPEP and ERAP2 and showed that interactions were stronger in patients carrying the alleles that increase susceptibility to autoimmune diseases. Replacing the SNPs in the LNPEP promoter by reference sequences lowered ERAP2 expression. These findings show that multiple SNPs act in concert to regulate ERAP2 expression and that disease-associated variants can convert a gene promoter region into a potent enhancer of a distal gene.

Effect of fibre fortification of low FODMAP pasta.

Irritable bowel syndrome (IBS) is a condition affecting the digestive system and can be triggered by several different factors, including diet. To ease symptoms of IBS, a diet low in fermentable oligo-, di-, monosaccharides and polyols (FODMAPs) is often recommended. Pasta, as a staple food in the Western World, is naturally high in FODMAPs. This study investigates the impact of insoluble and soluble dietary fibre ingredients in low-FODMAPs pasta. The assessment included physicochemical, sensory, and nutritional quality. Soluble fibre strengthened gluten network, which caused a lower cooking loss and a lower release of sugars during in vitro starch digestion. Insoluble fibre interfered with the gluten network development to a higher extent causing a higher sugar release during digestion. This study reveals the most suitable fibre ingredients for the development of pasta with elevated nutritional value and sensory characteristics compared to commercial products on the market. This type of pasta has a high potential of being suitable for IBS patients.