Significant Increase In Frequency Research Articles

Metal wire embrittlement monitoring by the measurement of wire oscillation frequency

In the process of irradiation of materials by fluxes of heavy particles (protons, neutrons, alpha particles), damage to material structure is often observed. As a result of the accumulation of such damages, there is a subsequent change in the properties of materials, in particular, its embrittlement and hardening. Monitoring of the embrittlement process is important for nuclear reactor vessels exposed to high neutron fluxes. In this work, to observe the effect of heavy irradiation particles on the mechanical properties of metals, we propose to use vibrating wire resonators, in which the natural frequency of oscillations of the wire strongly depends on its tension. The change in the elastic characteristics of the wire alters the value of the natural frequency of wire oscillations. The natural oscillations are generated by a special circuit. Preliminary experiments to study the embrittlement effect of a stretched wire are performed by heating the wire with an electric current. In the case of short pulses, a significant increase in frequency is achieved, which is explained by the process of hardening of the material as a result of the thermal impact on the wire (rapid heating and cooling).

(359) Vasectomy Trends in Western NY Following Dobbs v. Jackson Women’s Health Organization

Abstract Introduction On June 24, 2022, the United States Supreme Court ruled on Dobbs v. Jackson Women’s Health Organization (Dobbs) that the Constitution of the United States does not confer a right to abortion. The court’s decision overruled both Roe v. Wade (1973) and Planned Parenthood v. Casey (1992), giving individual states the full power to regulate any aspect of abortion not protected by federal law. Objective Our study aims to identify the difference, if any, in the number of vasectomies performed in Western NY before and after the ruling on Dobbs v. Jackson Women’s Health Organization. Methods We performed a retrospective chart review of 2428 patients who had vasectomies in Western New York from August 2021 – March 2023. Leveraging a dataset containing de-identified patient information, we compared the rates of all men undergoing vasectomies in the six-month period before and after the ruling. Vasectomy case information collected by urologists in Buffalo dating back to 1996 was collected and tabulated using Excel. Statistical analyses were performed to compare differences in both the overall change in frequency of vasectomies among all men in the six-month period before and after the court decision, as well as by specific demographic groups. Statistical analyses were performed in R and SAS. Results Men with no children had a statistically significant increase (p=0.009) in the number of vasectomies in the six-month period after the Dobbs decision (n=138) compared to before (n=98). Rates of vasectomies pre- and post- Dobbs were organized by age quartiles (<33.20, 33.20-36.65, 36.66-40.59, ≥40.60). In the “No Child” group, men with ages <33.2 (p=0.0137) and ages 33.2-36.65 (p=0.0394) had significant increases in frequency of vasectomy after the court decision. Conclusions Our data demonstrates that in the wake of Dobbs v. Jackson Women’s Health Organization (2022), the number of vasectomies among men with no children significantly increased after the court decision. There were significant increases in the number of vasectomies within different age groups of men without children following the decision. Future aims of this study will seek to create statistical models to determine the underlying reasons that influenced the observed change in frequency of vasectomies following the court decision in men without children. Disclosure No.

Analysis of the Temporal and Spatial Development of Cold Waves in Fujian Province over the Last 58 Years

The escalation in the risk of extreme weather events due to climate system warming has caused a distinct alteration in the frequency and intensity of cold waves in China. Moreover, these changes exhibit distinct regional variations in their altering characteristics. Using daily temperature data from 70 weather stations in Fujian Province of China from 1961 to 2018, this study looks at how cold waves move through the province and how they change over time. It does this by combining linear regression trend, spatial interpolation, and spatial autocorrelation analyses. The findings indicate that the occurrence frequency of cold waves in the designated study area is notably higher in the western and northern regions, while it is comparatively lower in the eastern coastal cities. Furthermore, there is an overall downward trend in the frequency of cold waves, with a declining frequency from 1961 to 2000, followed by a significant increase in frequency after 2000. Furthermore, the number of cold waves in the study area increased significantly after 2010.

Menstrual symptoms and subjective well-being among postmenarchal adolescents

BackgroundMenstrual symptoms are predominantly studied among adults but may occur directly after menarche. Adolescent menstrual health care, however, faces specific obstacles and more research into menstrual symptoms as a determinant of adolescent well-being is therefore advocated. Objective(s)To study menstrual symptoms and their impact on everyday life and well-being among postmenarchal adolescents. Study Design: A survey was delivered to a random sample of 1644 schoolgirls, drawn from a population-based project involving 116 lower secondary education schools (7th-8th grade) in Stockholm, Sweden. Menstrual symptoms (i.e., dysmenorrhea; heavy bleeding; irregular periods; mood disturbance; other general symptoms) were investigated through multiple choice questions and defined according to their impact on everyday life as mild (seldom affected), moderate (affected but possible to cope) and severe (affected and difficult to cope). Subjective well-being was measured with the World Health Organisation Five Well-Being Index (WHO-5). Postmenarchal respondents were eligible for analysis whereas those with incomplete outcome data or using hormonal contraception were excluded. The frequency and severity of symptoms across different postmenarchal years (1st, 2nd, 3rd, 4th, or 5th+ year after menarche) were studied with Chi-square and Kendall's tau statistics. Analysis of variance was used to study the association between menstrual symptoms and WHO-5 scores. A composite Menstrual Health index variable was obtained through principal component analysis and used to study the overall impact of menstrual symptoms on well-being in regression analyses. ResultsOf 1100 postmenarchal girls (mean age 14.1±0.7), 93.2% reported menstrual symptoms, 81.3% had at least one moderate symptom and 31.3% had at least one severe symptom. The most frequent symptoms were dysmenorrhea (80.4%) and mood disturbance (81.1%), followed by irregular periods (67.9%), heavy bleeding (60.4%) and other general symptoms (60.4%). Throughout postmenarchal years, there was a significant increase in frequency and severity (p<.001) of dysmenorrhea (τ=0.148), heavy bleeding (τ=0.134), mood disturbance (τ=0.117) and other general symptoms (τ=0.110), but not irregular periods (τ=-0.0201; p=.434). Girls with menstrual symptoms had significantly lower WHO-5 scores than those without symptoms (mean difference [MD] =17.3; 95%CI 12.3-22.4). Analysis of variance showed significant associations (p<.001) with WHO-5 scores for each of the examined menstrual symptoms. In post-hoc pairwise comparisons with peers without symptoms, the greatest reductions in WHO-5 score were found among girls with severe symptoms (MD for: dysmenorrhea -20.72; heavy bleeding -15.75; irregular periods -13.81; mood disturbance -24.97; other general symptoms -20.29) but significant differences were observed even for moderate or mild symptoms. The composite Menstrual Health index was significantly associated with WHO-5 scores in regression analysis, independently of age, age at menarche, BMI, smoking, physical activity, own and parental country of birth, biparental care, and socioeconomic status. ConclusionsDespite growing awareness about the relevance of menstruation to women's health, unmet menstrual health needs are a potential threat to the well-being of adolescents. Education, screening, and clinical competence are important tools to reduce the burden of menstrual symptoms during adolescence and to prevent long-term consequences. The development of novel person-centered strategies should be a priority for clinical practice and research in adolescent menstrual health.

Augmentation Strategies for Partial or Non-responders to Clozapine in Patients with Schizophrenia: A Bayesian Network Meta-analysis of Randomized Controlled Trials.

Clozapine is the only approved drug for treatment-resistant schizophrenia, but the response to the drug is often inadequate. Augmentation with other antipsychotics, anticonvulsants, and antidepressants is recommended for such patients, but there is a lack of evidence regarding the most effective therapy. This network meta-analysis was conducted to evaluate the efficacy of pharmacological agents used in the augmentation strategies in patients who were partial/ non-responders to clozapine. Relevant data were extracted from 30 randomized controlled trials through searches of electronic databases (MEDLINE/PubMed, Embase, Cochrane, clinical trial registries). PRISMA guidelines were followed for the extraction, management, analysis, and reporting of the data. The outcome measure in this study was a reduction in symptom severity according to total PANSS/BPRS and was reported as the standardized mean difference with a 95% credible interval. Bayesian network meta-analysis with random effects model and uninformative priors was conducted, and the ranking probability of each intervention was done. Meta-regression was done to assess the effect of duration on the reduction in symptom severity scores. Mirtazapine (-5.2 [95%CrI: -7.7, -2.7]) and memantine (-2.1 [95%CrI: -4.0, -0.19]] were more efficacious than placebo for augmentation of clozapine in partial/non-responders and were the most effective adjunctive agents as per SUCRA scores. Both drugs did not cause a significant increase in frequency of adverse events compared to placebo. There was a significant effect of duration on the reduction in symptom severity. There was no evident publication bias. Mirtazapine and memantine may prove beneficial for augmentation of clozapine in non/partial responders to monotherapy.

Intensification of heatwaves in Central Asia from 1981 to 2020 – Role of soil moisture reduction

Heatwaves pose increasing threats on water resources for ecosystems and human consumption especially in arid region, such as Central Asia (CA). As the hinterland of Eurasia, water scarcity and land degradation in CA have increased its vulnerability to heatwaves. While the frequency of heatwaves has been examined, more heatwave metrics such as timing are less known, possible influences of soil moisture on heatwave changes in this region are not fully understood. Using reanalysis and observational datasets, here we examine the spatial–temporal changes of heatwaves in CA during 1981–2020 and the role of various associated factors including soil moisture. The results show that the extreme heatwaves occurred more frequently in northwestern Kazakhstan. Temporally, heatwaves have been intensifying with significant increases in frequency (0.10 events/year), intensity (0.81 °C/year), and duration (0.08 days/year) since the 1980 s, and these trends have accelerated since 1997. The first yearly heatwave event tended to occur earlier in more recent decades, indicating an advanced heatwave season. We also found that the heatwave occurrences were significantly correlated with hydro-meteorological factors. In northwestern of CA, extreme heatwaves are exacerbated by a rapid decrease in soil moisture resulting from reduced precipitation and increased solar net radiation in this area. Our findings provide a scientific basis for understanding the mechanisms and predictions of heatwave in arid regions from the climate change perspective.

Detection and Assessment of Changing Drought Events in China in the Context of Climate Change Based on the Intensity–Area–Duration Algorithm

Drought can have a significant impact on both society and the economy, resulting in issues such as scarcity of water and shortages of food and energy, as well as elevated health risks. However, as global temperatures continue to rise, the impact of drought events is increasingly exacerbated, manifested by an increase in the frequency, intensity, duration, and spatial extent of their effects. Therefore, studying the changing characteristics of drought events with the background of climate change is of great significance. Based on the high-precision and high-resolution CN05.1 dataset, this study obtained the monthly Standardized Precipitation Evapotranspiration Index (SPEI) dataset from 1961 to 2020, and then identified regional drought events in China using the Intensity–Area–Duration (IAD) method, which considers both temporal continuity and spatial dynamics. On this basis, the spatiotemporal variations in frequency, intensity, duration, and affected area of drought events in China and its seven subregions were analyzed. The results showed that the subregions located in the northern region of China generally have lower mean, maximum, and minimum temperatures than those located in the southern region, but the associated interannual change rate of the subregions in the north is higher than that in the south. As for the annual total precipitation, results show a clear pattern of decreasing southeast–northwest gradient, with an increasing trend in the northern subregions and a decreasing trend in the southern subregions except for the subregion south China (SC). The northeast of China (NE), SC, the southwest of China (SW) and north China (NC) are the regions with a high frequency of drought events in China, while the frequency of drought events in NW and Qinghai–Tibetan Plateau (QTP), although lower, is on a significantly increasing trend, and the increasing rate is higher than for the other regions. For drought intensity, Xinjiang (XJ) and QTP had greater drought intensity, and the change rate of these regions with greater drought intensity was also greater. The drought impact area in China showed a significant increasing trend, mainly concentrated in QTP, NW and NE. Particular attention needs to be focused on the southwest of QTP, where drought events in this region show a significant increase in frequency, intensity, duration and impact area.

Effects of in utero exposure to fluoxetine on the gastrointestinal tract of rat offspring.

Perinatal exposure to selective serotonin reuptake inhibitors (SSRIs) has been shown to disrupt the development of serotonergic signaling pathways in the brain and enteric nervous system. Serotonin (5-hydroxytryptamine; 5-HT) signaling is critical for gastrointestinal homeostasis; changes in 5-HT expression and regulation have been associated with gastrointestinal diseases of motility and inflammation. We tested the hypothesis that perinatal exposure to the SSRI fluoxetine can influence the development of the gastrointestinal tract in exposed offspring. Female nulliparous Wistar rats were given fluoxetine (10 mg/kg) or vehicle control from 2 wk before mating until weaning; small and large intestines of female and male offspring were collected at postnatal days 1, 21 (P1, P21, respectively), and 6 mo of age. In histological preparations, the proportion of serotonergic neurons significantly increased in the colons of both female and male fluoxetine-exposed compared with control offspring at P21, a time point that signifies maximal exposure to fluoxetine. At 6 mo of age, male but not female fluoxetine-exposed offspring had a significant increase in circulating 5-HT, with a significant decrease in transcripts encoding the 5-HT2A receptor and monoamine oxidase as compared with control offspring. Measurement of spatiotemporal mapping of contractile activity of the small and large intestine at 6 mo of age revealed no changes in motility in the small bowel of fluoxetine-exposed offspring but revealed a significant increase in the frequency of colonic contractions in the female fluoxetine-exposed compared with control animals. Susceptibility to inflammation was examined at 6 mo using the dextran sulfate sodium model of acute colitis. In utero exposure to fluoxetine was not found to exacerbate colitis severity. These findings suggest that fluoxetine exposure during fetal and early postnatal development can lead to changes in serotonergic neurons at the peak of exposure with sex-specific changes in 5-HT signaling and colonic motility in adulthood.NEW & NOTEWORTHY There is increasing recognition of the relevance of in utero and early postnatal exposures in the developmental programming of the gastrointestinal tract. Perinatal exposure to selective serotonin reuptake inhibitors and antidepressant medications is of particular relevance as they are commonly prescribed during pregnancy, and serotonergic pathways play key roles during gastrointestinal development and in postnatal homeostasis. Here, we provide a comprehensive evaluation of clinically relevant outcomes of gastrointestinal motility and susceptibility to colitis in fluoxetine-exposed offspring and highlight changes in colonic serotonergic neurons at the peak of perinatal fluoxetine exposure with sex-dependent changes in serotonin signaling and colonic motility in adulthood.

Midwife-led pandemic telemedicine services for maternal health and gender-based violence screening in Bangladesh: an implementation research case study

BackgroundThe COVID-19 pandemic disrupted maternal and newborn health services in Bangladesh, exacerbating the large gaps in service utilization that existed prior to the pandemic. As part of its response, Bangladesh initiated remote antenatal and postnatal care telemedicine services led by midwives in 36 sub-district hospitals across five of Bangladesh’s 64 districts. Gender-based violence screening and referral were integrated into the service to address a reported rise in violence following the country’s pandemic lockdown.MethodsMixed-methods implementation research was used to develop an intrinsic case study describing the design and implementation of the telemedicine program. Qualitative analysis comprised document review, key informant interviews, and focus group discussions. Quantitative analysis employed an interrupted time series analysis with segmented multi-variate regression to compare maternity care service use trends before and after implementation. Poisson regression analysis was used to examine the trend in number of gender-based violence remote screenings, sessions held, and cases identified.ResultsA statistically significant change in trend for onsite antenatal and postpartum care as well as women seeking care at the hospital as a result of postpartum hemorrhage arising in the community was observed following the introduction of telemedicine. Facility births and cases of eclampsia appropriately identified and managed also had significant increases. In addition, over 6917 women were screened for GBV, 223 received counseling and 34 referrals were made, showing a statistically significant increase in frequency over time following the implementation of the telemedicine program. Challenges included that not all midwives adopted GBV screening, some women were reluctant to discuss GBV, there was an unanticipated need to introduce a patient visit scheduling system in all intervention hospitals, and many women were not reachable by phone due to lack of access or network coverage.ConclusionsMaternal health and gender-based violence telemedicine led by midwives was an effective, low-cost intervention in Bangladesh for addressing pandemic and pre-pandemic gaps in service use. Other low and middle-income countries planning to implement remote maternal health interventions via midwives should consider whether a patient visit scheduling system needs to be introduced, as well as limitations around mobile phone access and connectivity. Future research should include care quality oversight and improvement, and a more well-informed strategy for facilitating effective GBV screening.

Growing Threats From Swings Between Hot and Wet Extremes in a Warmer World

AbstractThe abrupt alternation between hot and wet extremes can lead to more severe societal impacts than isolated extremes. However, despite an understanding of hot and wet extremes separately, their temporally compounding characteristics are not well examined yet. Our study presents a comprehensive assessment of successive heat‐pluvial and pluvial‐heat events globally. We find that these successive extremes within a week occur every 6–7 years on average within warm seasons during 1956–2015, about 15% more often than would be expected by chance, and that they have a significant increase in frequency of about 22% per decade due to warming. We further investigate the role of vapor pressure deficit (VPD) and find that heat‐pluvial (pluvial‐heat) events are linked to negative (positive) VPD anomalies. Our results are statistically significant based on moving‐blocks bootstrap resampling and field significance tests, highlighting these methods' importance in robustly identifying compound events under autocorrelation and multiple‐testing conditions.

Gastroesophageal reflux disease in conditions of chronic stress. Review with own observation

It is known that 20 to 42% of patients receiving a proton pump inhibitor for the treatment of gastroesophageal reflux disease do not respond satisfactorily to it. This condition is called refractory gastroesophageal reflux disease. To achieve a therapeutic effect, it is advised to use H2‑receptor antagonists, alginates, baclofen or antidepressant therapy in complex treatment. Recent years, solutions containing sodium alginate have been widely used. These drugs reduce the severity and frequency of heartburn when used postprandially as adjunctive therapy to proton pump inhibitors in patients with gastroesophageal reflux disease. The alginates, available in the US and European markets, differ, with the latter containing higher concentrations of alginate, possibly contributing to higher efficiency. This is supported by some researchers reporting rapid efficacy for both postprandial and nocturnal symptoms in patients with refractory gastroesophageal reflux disease. Given the absence of significant side effects, it is advised to use alginates as an addition to proton pump inhibitors, taking into account the availability, as well as the preferences of the doctor and patient.&#x0D; The article presents modern scientific data on a widespread Gastroenterological disease — GERD in the context of the impact of stress factor on its course. The analysis was performed of the recent investigations, aimed at the study of the mechanisms of traumatic effect of psychosocial and psychoemotional stress on the functional activity of the upper gastrointestinal tract. The results of the study of the role of anxiety‑phobic and depressive disorders because of prolonged exposure to stressors were analyzed. The author presented data of his own research, which clearly demonstrated a significant increase of frequency and level of anxiety and depression under wartime stress. It has been established that combination of gastroesophageal reflux disease with anxiety and depression exacerbates the clinical manifestations of the disease and reduces the effectiveness of treatment, which requires an individual approach to the choice of therapeutic measures. It is advisable to use antacids and alginic acid preparations, as well as methods of psychological correction, along with proton pump inhibitors or instead of them.

Skin-to-skin contact and its effect on mothers’ postpartum psychological distress and their full-term neonate in Egypt

A randomized controlled study was conducted on 400 mothers, who were divided into two groups: 200 mothers who applied skin-to-skin infant care (SSC) for at least 1 h daily for 12 weeks and 200 mothers who performed the usual mother-infant care. The mothers were recruited from the Obstetric Department of Al-Zahraa University Hospital in Cairo, Egypt. The enrolled mothers' infants were assessed for body weight. Sleep hours and frequency of breast milk feeding were evaluated by the mother during the day. All of the mothers who took part in the study were assessed for postoperative pain, wound healing, postpartum depression, anxiety, sleep quality and newborn maternal bonding. There was a significant increase in frequencies of breastfeeding and the body weight at 12 weeks' postnatal age and also an increase in sleep hours in the infants who had SSC. The mothers who performed SSC had good sleep quality in comparison with those who performed the usual infant care; in addition, they had less postoperative pain intensity and proper wound healing apart from better maternal-infant bond, decreased anxiety and decreased depression frequency. SSC was associated with better infant breastfeeding, increased sleep hours in infants and less postpartum psychological burden in mothers.

Usage of Heat and Moisture Exchange Devices, Virtual Visits, Masking, and Vaccinations Among People With a Laryngectomy During COVID-19.

This study described the COVID-19 risk mitigation actions of people with a total laryngectomy (TL) during the pandemic. An online survey was completed by 215 people with a TL who lived in the United States. The survey was open from December 1, 2021, to January 15, 2022. There was a significant increase in frequency of heat and moisture exchange (HME) device use during the pandemic compared with pre-COVID-19. Frequency of HME use was significantly greater for those who were vaccinated and those who had at least one clinical visit with their speech-language pathologist (SLP). The use of virtual visits increased from 9% pre-COVID-19 to 37% during the pandemic. Seventy percent of respondents were "satisfied" or "very satisfied" with virtual visits and 51% judged them "as good as in-person." Eighty percent were vaccinated for COVID-19 and 75% received a booster. One third reported that they did not wear mask over the face or over the tracheostoma. Twenty percent had tested positive for COVID-19 with 70% of these people requiring hospitalization. HME use and virtual SLP visits increased during the pandemic and the vaccination rate was high among this group of respondents. Overall, there were still large percentages of people with a TL who were not using an HME, not vaccinated, and did not wear a mask. SLPs should consider reaching out directly to their TL caseload, particularly those not yet seen during the pandemic, to support uptake of COVID-19 mitigation activities specific to people with a TL as the pandemic persists.

Age related immune modulation of experimental autoimmune encephalomyelitis in PINK1 knockout mice.

Recent research has shown that Parkin, an E3 ubiquitin ligase, modulates peripheral immune cells-mediated immunity during experimental autoimmune encephalomyelitis (EAE). Because the PTEN-induced putative kinase 1 (PINK1) protein acts upstream of Parkin in a common mitochondrial quality control pathway, we hypothesized that the systemic deletion of PINK1 could also modify the clinical course of EAE, altering the peripheral and central nervous systems' immune responses. EAE was induced in female PINK1-/- mice of different age groups by immunization with myelin oligodendrocyte glycoprotein peptide. Compared to young wild-type controls, PINK1-/- mice showed earlier disease onset, albeit with a slightly less severe disease, while adult PINK1-/- mice displayed early onset and more severe acute symptoms than controls, showing persistent disease during the recovery phase. In adult mice, EAE severity was associated with significant increases in frequency of dendritic cells (CD11C+, IAIE+), lymphocytes (CD8+), neutrophils (Ly6G+, CD11b+), and a dysregulated cytokine profile in spleen. Furthermore, a massive macrophage (CD68+) infiltration and microglia (TMEM119+) and astrocyte (GFAP+) activation were detected in the spinal cord of adult PINK1-/- mice. PINK1 plays an age-related role in modulating the peripheral inflammatory response during EAE, potentially contributing to the pathogenesis of neuroinflammatory and other associated conditions.

DTX1 Controls Germinal Center B-Cell Development and Lymphomagenesis

DTX1 is highly expressed in germinal center B (GCB)-cells and is targeted by coding mutations in 17% of DLBCL, including 50% of the BN2 genetic subtype that is enriched for the ABC-like cell of origin subtype (Wright et al., Cancer Cell 2020). DTX1 has also been recognized as a prominent target of AID-mediated mutagenesis, with a high rate of non-coding regulatory element (RE) mutations being observed across DLBCL subtypes. The DTX1 gene encodes a ring finger ubiquitin ligase that regulates NOTCH1 recycling. However, the role of DTX1 in GC B-cell development and lymphomagenesis has not been thoroughly investigated. We characterized mutations within the regulatory element of DTX1 using whole genome sequencing data from ICGC and TCGA, together with H3K27Ac ChIP-sequencing data from tonsillar GCB-cells to define active regulatory elements (REs). We observed non-coding mutations of DTX1-proximal REs in 59% of DLBCL tumors. We characterized these putative REs by knocking GFP into the start codon of the endogenous DTX1 gene and performing CRISPR/Cas9 tiling, using reductions of GFP expression as a surrogate for reduced DTX1 RE activity. We observed a significant loss of GFP expression with DTX1 RE-targeted gRNAs compared control gRNAs, confirming these recurrently mutated regions as active REs. We therefore generated a novel floxed Dtx1 genetically engineered mouse model and crossed with Aid-cre for GCB-specific conditional knock-out (cKO). Immunized mice were euthanized at the peak of the GC reaction and analyzed by flow cytometry and multispectral immunofluorescence (mIF) imaging. Mice with monoalleleic (Dtx1+/-) or bialleleic (Dtx1-/-) cKO of Dtx1 had a significant increase in GCB cell frequency compared to wild-type (Dtx1+/+) littermates, with a significant skew of polarization towards the light zone. This was confirmed by mIF analysis, which showed significantly larger and more abundant GCs, and a significantly higher fraction of Ki67+ cells within the GCs, in Dtx1+/- compared to Dtx1+/+ mice. We therefore investigated whether Dtx1 loss may confer a competitive advantage within the GC reaction by generating Dtx1+/+ / Dtx1+/- mixed chimera models in Rag-deficient recipients. Dtx1+/- cells were significantly over-represented within the GCB compartment and showed a significant light-zone skew, and significantly higher frequencies of proliferating (Edu+) GCB cells within the light-zone relative to Dtx1+/+ cells. We therefore investigated changes in GC development using scRNA-sequencing PNA-enriched GCB cells from SRBC-immunized Dtx1+/+ (n=4) and Dtx1+/- littermates (n=4). This confirmed a significant light-zone polarization within GCB cells, and highlighted a dramatic reduction in pre-memory cells within Dtx1+/- mice. Furthermore, differential gene expression analysis identified significant alterations in light-zone gene expression programs within Dtx1+/- GCB cells. To test whether Dtx1 loss may participate in the early stages of lymphomagenesis, we performed serial re-challenge with SRBCs monthly for 3 months and 10 days later euthanized mice. Histological analysis of major organs revealed a significant increase in the frequency of lymphoid aggregates within the lungs, liver and kidneys, indicating extranodal dissemination. In conclusion, these data demonstrate for the first time that highly-recurrent mutations in DLBCL target an active RE for DTX1, resulting in inhibition of DTX1 expression. Dtx1 haploinsufficiency confers a selective advantage to GCB cells that promotes GC hyperplasia with light-zone polarization and alters GCB cell differentiation trajectories, and can result in extranodal dissemination of Dtx1+/- GCB cells following chronic antigen stimulation.

Two different propagation patterns of spatiotemporally contiguous heatwaves in China

Heatwaves detrimentally affect human health and ecosystems. While previous studies focused on either temporal changes or spatial extents of heatwaves, their spatiotemporal contiguity and propagation patterns are unclear. Here, we investigate the climatology, long-term trends, and interannual variations of spatiotemporally contiguous heatwaves across China during 1961 to 2018. Two distinct propagation patterns are identified by introducing a spatiotemporally contiguous events tracking (SCET) method and the k-means clustering. Type 1 contiguous heatwaves mostly generate over eastern China and move southwestward at shorter distances, while Type 2 heatwaves generally initiate over western China and move southeastward at longer distances, with stronger intensity, longer lifetime, and larger coverage. Since the 1960s, both types exhibit significant increases in frequency, intensity, coverage, lifetime, and traveling distances, with relatively larger magnitudes for Type 2, but significant decreases in moving speed only appear for Type 1. On interannual timescale, preceding winter El Niño prolongs the duration and slows down the moving speed of Type 1 through the western North Pacific subtropical high. Type 2 contiguous heatwaves are intensified by the negative spring North Atlantic Oscillation via the upper-atmospheric Rossby wave train.

Emergence of Delta and Omicron variants carrying resistance-associated mutations in immunocompromised patients undergoing sotrovimab treatment with long-term viral excretion

ObjectivesTo monitor the early emergence of genetic mutations related to reduced susceptibility to monoclonal anti-body (mAb)-based treatment in immunocompromised patients with long-term viral excretion using whole-genome sequencing at a tertiary university hospital in Barcelona, Spain. MethodsSerial severe acute respiratory syndrome coronavirus 2-positive samples (mid-December 2021–mid-March 2022) from eight immunosuppressed, fully vaccinated patients (for solid-organ transplantation or haematologic malignancies) with long-term viral excretion despite undergoing mAb therapy (sotrovimab) for coronavirus disease 2019 were selected. Whole-genome sequencing was performed following the ARTIC, version 4.1, protocol on the MiSeq platform. Mutations in the coding sequence of the spike protein with a frequency of ≥5% were studied. ResultsA total of 37 samples from the studied cases were analysed. All the cases, except one, were confirmed to have the Omicron variant BA.1; one had Delta (AY.100). Thirty-four different mutations were detected within the receptor-binding domain of the spike protein in 62.5% of patients, eight of which were not lineage related and located in the sotrovimab target epitope (P337L, E340D, E340R, E340K, E340V, E340Q, R346T and K356T). Except for P337L, all changes showed a significant increase in frequency or fixation after the administration of sotrovimab. Some of them have been associated with either reduced susceptibility to mAb therapy, such as those at position 340, or the acquisition of a new glycosylation site (346 and 356 positions). ConclusionsThis study highlights the importance of monitoring for early in vivo selection of mutations associated with reduced susceptibility to mAb therapy, especially in immunocompromised patients receiving anti-viral drugs, whose immune response is not able to control viral replication, resulting in long-term viral shedding, and those receiving selective evolution pressure. Virologic surveillance of genetically resistant viruses to available anti-viral therapies is considered a priority for both patients and the community.

Tradeoffs of fungal and bacterial residues mediate soil carbon dynamics under persistent drought in subtropical evergreen forests

Global climate change has greatly accelerated hydrological processes, causing significant increases in frequency and intensity of drought events, which may have a great impact on soil carbon (C) dynamics. Microbial residues are frequently represented as the important constituents involved in soil C formation and stability. However, how persistent drought influences microbial residues to regulate soil C cycling remains elusive, especially in forest ecosystems. In this study, we investigated drought effects on microbial (fungal and bacterial) residues and soil C dynamics by a 7-year filed experiment (2013−2020) with a 70 % rainfall reduction in a subtropical evergreen forest of Eastern China. Soil samples (0–10 cm) were collected in 2014, 2015, 2016, and 2020 with drought duration of 1, 2, 3, and 7 years, and soil moisture, soil temperature, soil organic carbon (SOC) and soil nitrogen (N) were measured. The contents of microbial (fungal and bacterial) residues were quantified by amino sugar biomarkers. Our results showed that fungal residues significantly decreased with increasing drought duration, which were mainly induced by the decline of soil N and soil moisture, causing a decrease in soil C under the 7-year persistent drought. In contrast, bacterial residues increased with drought duration due to fast adaption of bacteria to drought and aggregate protection. The retention of bacterial residues might be preserved as a “nutrient reservoir” to cope with the long-term drought in the near future. These results suggest that persistent drought-induced tradeoffs between fungal and bacterial residues mediate soil C dynamics. Fungal residues were the essential prerequisite for soil C sequestration in response to drought, while bacterial residues may mainly regulate soil C cycling under the prolonged drought. Therefore, microbial residues are imperative to understand the responses of microbial-derived C to drought, which could be integrated into terrestrial C models to accurately predict soil C dynamics in unpredictable climate regimes in forest ecosystems.

Impact of the Separation of the Continental Europe Power System on January 8, 2021 on the Work of the Bosnia and Herzegovina Power System

Abstract After the separation of the Continental Europe power system on 8th January 2021 in two synchronous zones, the electric power system of BiH (EPS BiH) shows a significant increase in frequency and voltages and oscillations of active and reactive power. The paper discusses the operation of protective devices in the BiH power system when the system was operating at high frequencies and voltages and had oscillations of active and reactive power. As a consequence of this behaviour in the EPS BiH there was activation of distance protections (DP) in substation (SS) 220/110 kV Prijedor 2 and overhead transmission lines (OHL) 220 kV Prijedor 2 - Međurić and OHL 220 kV Prijedor 2 – Sisak were disconnected. This was followed by activation of generator protections (reverse power protection and under-excitation protection) and outages of generator units in Hydro Power Plant (HPP) Salakovac, Thermal Power Plant (TPP) Kakanj, HPP Mostar, HPP Bočac, HPP Peć Mlini and HPP Jajce 2.

Abstract 5744: Characterization of sideness-related differentiated genetic alterations in stage I-IV colorectal cancer patients by using whole exome sequencing

Abstract Background: Although constituting a single organ, the right colon and left colon arise from midgut and hindgut embryonic precursors respectively. In the context of these embryonic origins, tumor laterality has been associated with differential microsatellite instability (MSI), aneuploidic karyotype, and loss of heterozygosity between the left and right colon. Differential genetic mutation profiles are not fully characterized in the context of left vs right laterality colorectal cancer (CRC). Therefore, we investigated associations between CRC anatomical site and somatic gene mutation patterns using whole exome sequencing. Methods: Whole exome sequencing data were collected from 55 FFPE samples from different stages (stage I: 11, II: 9; III: 19, IV: 16), treatment-naive CRC patients using the Personalis® tumor-only ImmunoID NeXT Platform®, which captures somatic mutations (SNVs), copy number variants (CNVs), percent MSI in the exome, oncovirus detection, etc. The R package maftools was used to identify differential rates of mutation between samples resected from the rectum, left, and right colon respectively. Maftools-derived mutated gene lists, filtered to p&amp;lt;0.5 and odds-ratio&amp;gt;1, were assessed for pathway enrichment with Enrichr. Results: APC and TP53 were the most commonly mutated genes in the entire cohort, with mutations seen in &amp;gt;90% (APC) and &amp;gt;75% (TP53) of samples respectively. Individual gene mutation frequency was not significantly different among the primary tumor locations (left colon; right colon; rectum) after Bonferroni multiple test correction, with FBXW7, APC, trending towards differential mutation between right colon tumors and left/rectal tumors. Maftools-derived mutated gene lists, filtered to p&amp;lt;0.5 and odds-ratio&amp;gt;1, were processed with Enrichr, identifying an enrichment of estrogen-related mutation events in right-sided vs rectal tumors (n=81 genes; Bioplanet 2019; q=5x10-4; WikiPathway 2021 Human; q&amp;lt;5x10-6). In rectal tumors compared to right side, PI3K/AKT signaling mutations were more enriched (n=106 genes; Kyoto Encyclopedia of Genes and Genomes 2021; q&amp;lt;4x10-6; MSigDB Hallmark 2020; q=9x10-3). Conclusion: A statistically significant increase in frequencies of estrogen pathway gene mutations on right-sided tumors, and on PI3K/AKT mutations on rectal tumors, were identified. These are consistent with prior expression-based findings indicating the association of estrogen signaling with right-sided tumors, and increased AKT expression with left-sided CRCs. The whole exome sequencing based laterality associated genetic mutation results provided clinically applicable evidence that patients suffered from left versus right CRC tumors may benefit differential treatment therapies, and further investigation is ongoing to explore the potential correlation between tumor laterality and stage. Citation Format: Danyi Wang, Lee McDaniel, Sean Boyle, Giuseppe Locatelli, Juergen Scheuenpflug, Zheng Feng. Characterization of sideness-related differentiated genetic alterations in stage I-IV colorectal cancer patients by using whole exome sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5744.