bluuebunny/crossref_metadata_2025 huggingface dataset:
Recurrent summer drought affects biomass production and community composition independently of snowmelt manipulation in alpine grassland
Authors: Möhl Patrick , Vorkauf Maria , Kahmen Ansgar , Hiltbrunner Erika
Published: August 2023

Earlier snowmelt and more frequent summer drought due to climate warming are considered particularly influential for extratropical alpine plants, which are adapted to a short growing season and high water availability.

Here, we explored the combined effects of the two drivers with a field experiment in late‐successional alpine grassland in the Swiss Alps (2500 m a.s.l.) over 6–7 years. We advanced and delayed snowmelt by removing and adding snow to experimental plots prior to natural snowmelt for 7 years and combined this treatment with 5 and 10 weeks of summer drought for 6 years. We measured plant biomass formation, community composition and ecosystem respiration, and monitored soil moisture as well as soil temperature.

Natural snowmelt dates varied by 42 days across years. Snow manipulations advanced and delayed snowmelt by 4.6 and 8.0 days on average but did not affect annual growth (peak biomass) above‐ nor below‐ground. Interactions between snowmelt and drought were nonsignificant, implying that drought effects were independent of snowmelt.

Drought reduced total annual above‐ground biomass in the 10‐week treatment by 16 ± 7% across years, while the 5‐week treatment lowered biomass in the last year only. This decline in biomass was accountable to high drought sensitivity of biomass production in a few forb and graminoid species. In contrast, drought did not affect the biomass production of the dominant sedge Carex curvula, whose proportion of total plant cover increased from 36% in controls to 48% in 10‐week drought.

Below‐ground biomass slightly increased under drought (5‐week treatment only), resulting in a higher root mass fraction (both treatments). Despite continued root formation, drought reduced ecosystem respiration by 13%–23% per season, assessed nine times during three growing seasons. Since more than 85% of ecosystem respiration stemmed from below‐ground activities and roots continued growing under drought, we assume that soil microorganisms were heavily constrained by the drought treatments.

Synthesis. We conclude that snowmelt timing is unrelated to productivity, while recurrent drought will shift biomass allocation from shoots to roots in this typical alpine grassland, with potential implications for grazers but also for nutrient and carbon cycling. Species‐specific drought‐sensitivity will considerably alter community composition under more frequent drought.
Phenotypic diversity influenced by a transposable element increases productivity and resistance to competitors in plant populations
Authors: Latzel Vít , Puy Javier , Thieme Michael , Bucher Etienne , Götzenberger Lars , de Bello Francesco
Published: August 2023

An accumulating body of evidence indicates that natural plant populations harbour a large diversity of transposable elements (TEs). TEs, which are especially mobilized under genomic and/or environmental stress, provide genetic and epigenetic variation that can substantially translate into a diversity of plant phenotypes within populations. However, it remains unclear what the potential ecological effects of diversity in TEs within an otherwise genetically uniform population are in terms of phenotypic diversity's effects on coexistence and ecosystem functioning.

Using Arabidopsis thaliana as a proof‐of‐concept model, we assembled populations from individuals differing in the number and positions of ONSEN retrotransposon and tested whether the increasing diversity created by the ONSEN retrotransposon increased the phenotypic diversity of populations and enhanced their functioning under different environmental conditions.

We demonstrate that TE‐generated variation creates differentiation in ecologically important traits connected to different axes of the plant ‘economics’ spectrum. In particular, we show that Arabidopsis populations with increasing diversity of individuals differing in the ONSEN retrotransposon had higher phenotypic and functional diversity in resource use‐related traits. Such increased diversity enhanced population productivity and reduced the performance of interspecific competitors.

Synthesis. We conclude that TE‐generated phenotypic and functional diversity can have similar effects on ecosystems as are usually documented for other biological diversity effects. The results of our experiment open up new fields of investigation, highlighting the ecological relevance of unexplored sources of phenotypic variability and hopefully inspiring functional trait ecologists and evolutionary biologists to begin exploring new questions at the intersection of their fields.
Consequences of affective polarization: Avoidance, intolerance and support for violence in the United Kingdom and Norway
Authors: BERNTZEN LARS ERIK , KELSALL HAYLEE , HARTEVELD EELCO
Published: August 2023

Affective polarization – that is, antipathy towards political opponents – sits high on the academic and political agenda. This is because it is thought to have a multitude of damaging consequences, both for how citizens view and approach each other and for how they relate to the political system. This study investigates some of the most mentioned and worrying potential consequences of affective polarization at the individual level. Zooming in on Europe, it sheds light on the substantive relationship between partisan antipathy and three kinds of norm‐breaking escalation in the form of avoidance, intolerance and support for violence against party supporters. Methodologically, it unpacks the affective component of polarization, testing to what extent the traditional feeling thermometer performs as a predictor of these three potential outcomes. It then tests alternative expectations of the antecedents of such escalation derived from the intergroup emotions’ literature and the study of political radicalization. This is done using a broad range of both established and new survey items fielded in nationally representative panels between May and November 2020 in two contexts that score relatively low (Norway) and high (the United Kingdom) on affective polarization. They reveal that avoidance, intolerance and support for political violence can be validly measured, and are manifest, in these two European countries, but that they are only weakly correlated to mere dislike of the outgroup. Instead, more severe forms of norm‐breaking escalation depend on the specific nature of the discrete emotions induced beyond dislike (anger, fear or disgust) and are rooted in factors such as relative deprivation, Manicheanism, and dark personality traits (psychopathy, Machiavellianism and narcissism). We discuss the implications for the way polarization is theorized and measured.
A multivariate approach to understanding the genetic overlap between externalizing phenotypes and substance use disorders
Authors: Poore Holly E. , Hatoum Alexander , Mallard Travis T. , Sanchez‐Roige Sandra , Waldman Irwin D. , Palmer Abraham A. , Harden K. Paige , Barr Peter B. , Dick Danielle M.
Published: August 2023

Substance use disorders (SUDs) are phenotypically and genetically correlated with each other and with other psychological traits characterized by behavioural under‐control, termed externalizing phenotypes. In this study, we used genomic structural equation modelling to explore the shared genetic architecture among six externalizing phenotypes and four SUDs used in two previous multivariate genome‐wide association studies of an externalizing and an addiction risk factor, respectively. We first evaluated five confirmatory factor analytic models, including a common factor model, alternative parameterizations of two‐factor structures and a bifactor model. We next explored the genetic correlations between factors identified in these models and other relevant psychological traits. Finally, we quantified the degree of polygenic overlap between externalizing and addiction risk using MiXeR. We found that the common and two‐factor structures provided the best fit to the data, evidenced by high factor loadings, good factor reliability and no evidence of concerning model characteristics. The two‐factor models yielded high genetic correlations between factors (rgs ≥ 0.87), and between the effect sizes of genetic correlations with external traits (rg ≥ 0.95). Nevertheless, 21 of the 84 correlations with external criteria showed small, significant differences between externalizing and addiction risk factors. MiXer results showed that approximately 81% of influential externalizing variants were shared with addiction risk, whereas addiction risk shared 56% of its influential variants with externalizing. These results suggest that externalizing and addiction genetic risk are largely shared, though both constructs also retain meaningful unshared genetic variance. These results can inform future efforts to identify specific genetic influences on externalizing and SUDs.
Prelimbic cortex dynorphin/κ opioid receptor system modulates methamphetamine‐induced cognitive impairment
Authors: Cheng Ying‐jie , Deng Ying‐zhi , Deng Di , Wu Man‐qing , Chai Jing‐rui , Wang Yu‐jun , Liu Jing‐gen , Zhao Min
Published: August 2023

Chronic exposure to methamphetamine (METH) causes severe and persistent cognitive impairment. The present study aimed to investigate the role of dynorphin/κ opioid receptor (KOR) system in the development of METH‐induced cognitive impairment. We found that mice showed significant cognitive impairment in the novel object recognition test (NOR) following daily injections of METH (10 mg/kg) for seven consecutive days. Systemic blockade of KOR prevented METH‐induced cognitive impairment by pretreatment of the selective KOR antagonist norBNI (10 mg/kg, i.p.) or KOR deletion. Then, significant increased dynorphin and KOR mRNA were observed exclusively in prelimbic cortex (PL) other than infralimbic cortex. Finally, microinjection with norBNI into PL also improved cognitive memory in METH‐treated mice using NOR and spontaneous alternation behaviour test. Our results demonstrated that dynorphin/KOR system activation in PL may be a possible mechanism for METH‐induced cognitive impairment and shed light on KOR antagonists as a potential neuroprotective agent against the cognitive deficits induced by drug abuse.
Transient increase in platelet counts associated with COVID‐19 infection during TPO‐RA as the second‐line treatment in children with ITP
Authors: Wang Zhifa , Cheng Xiaoling , Wang Nan , Meng Jinxi , Ma Jingyao , Chen Zhenping , Wu Runhui
Published: August 2023

The thrombopoietin receptor agonists (TPO‐RA) were recommended for primary immune thrombocytopenia (ITP) during the pandemic of COVID‐19. However, the incidence of thrombocytosis and thrombosis was sporadically reported in the chronic immune thrombocytopenia (CITP) patients receiving TPO‐RA during the COVID‐19 infection. With the local prevalence of COVID‐19 in December 2022 in the Beijing area, we got more powerful evidence about the change in platelet (Plt) counts associated with COVID‐19 infection. A single‐centre observational cohort study was performed from the beginning of December 2022 to the end of February 2023 to enrol CITP children treated with TPO‐RA alone as the second‐line treatment and suffering from the COVID‐19 infection in December 2022. The Plt counts before, during and after COVID‐19 infection were collected. In total, 67 (34 males and 33 females) patients with 8.10 (2.15, 15.70) years of age were enrolled. Sixty‐three patients who had responded to the TPO‐RA showed a transient increase in Plt counts after the infection of COVID‐19. The time of starting to increase was on Day 3 (2, 7), and to the peak level on Day 14 (7, 19) of infection with the peak Plt count was 289 (88, 1974) × 109/L. With at least 2 months observation period from COVID‐19 infection, the Plt counts of 100% (63/63) patients declined to the baseline on Day 25 (14, 41). The phenomenon of transient increase in Plt counts has been shown in the CITP children who responded to TPO‐RA when suffering from COVID‐19 infection.
Phenotypic subtypes of leukaemic transformation in chronic myelomonocytic leukaemia
Authors: Montalban‐Bravo Guillermo , Kanagal‐Shamanna Rashmi , Li Ziyi , Hammond Danielle , Chien Kelly , Rodriguez‐Sevilla Juan Jose , Sasaki Koji , Jabbour Elias , DiNardo Courtney , Takahashi Koichi , Short Nicholas , Issa Ghayas C. , Pemmaraju Naveen , Kadia Tapan , Ravandi Farhad , Daver Naval , Borthakur Gautam , Loghavi Sanam , Pierce Sherry , Bueso‐Ramos Carlos , Kantarjian Hagop , Garcia‐Manero Guillermo
Published: August 2023

Chronic myelomonocytic leukaemia (CMML) is a haematological disorder with high risk of transformation to acute myeloid leukaemia (AML). To characterize the phenotypic and genomic patterns of CMML progression, we evaluated a cohort of 189 patients with AML evolving from CMML. We found that transformation occurs through distinct trajectories characterized by genomic profiles and clonal evolution: monocytic (Mo‐AML, 53%), immature myeloid (My‐AML, 43%) or erythroid (Ery‐AML, 2%). Mo‐AML, characterized by expansion of monoblasts and promonocytes (low CD34, CD117 expression; high CD14, CD33, CD56 and CD64 expression), were defined by SRSF2, TET2 and RAS pathway mutation co‐dominance and were more likely to evolve from SRSF2‐TET2 co‐mutant CMML through emergence/expansion of RAS pathway mutant clones. Conversely, My‐AML, characterized by expansion of immature myeloid blasts (high frequency of CD34, CD38, CD117; low frequency of CD14, CD64 and CD56 expression) were less likely to exhibit SRSF2‐TET2 co‐mutations or RAS pathway mutations and had higher frequency of CEBPA mutations. Ery‐AML was defined by complex karyotypes and TP53 mutations. A trend towards improved OS and EFS with hypomethylating agent‐venetoclax combination was observed in My‐AML, but not Mo‐AML. These findings define distinct progression of CMML and set the basis for future studies evaluating the role of phenotype‐specific therapeutics.
Cross‐sectional and prospective associations between screen time and childhood neurodevelopment in two Brazilian cohorts born 11 years apart
Authors: de Andrade Leão Otávio Amaral , Bertoldi Andréa Dâmaso , Domingues Marlos Rodrigues , Murray Joseph , Santos Iná Silva , Barros Aluisio J. D. , Matijasevich Alicia , Mielke Gregore Iven
Published: August 2023

Background

The aim of this study was to investigate the associations between screen time from ages 2 to 4 years and child neurodevelopment at age 4.

Methods

The participants were from the 2004 (N = 3787) and 2015 (N = 3604) Pelotas (Brazil) birth cohort studies. Childhood neurodevelopment was assessed at age 4 using the Battelle Development Inventory. The time children spent on screen devices was reported by their guardians at ages 2 and 4 years. Linear regression models were used to investigate the association of: (i) time spent on television at ages 2 and 4 years; (ii) time spent on other screens at age 4; and (iii) total screen time at age 4 (television + other screens) with childhood neurodevelopment at age 4.

Results

Average daily screen time among children born in 2004 and those born in 2005 aged 4 years were 3.4 (SD: 2.4) and 4.4 h (SD: 2.9), respectively. Overall, few associations of very small magnitude between screen time and child neurodevelopment were observed. Television time at 2 years of age was statistically associated with lower neurodevelopment at 4 years of age in the 2015 cohort (β = −0.30, 95%CI = −0.55; −0.05). Conversely, television time (β = 0.17, 95%CI = 0.07, 0.26) and total screen time (β = 0.22, 95%CI = 0.13, 0.31) at age 4 were associated with higher neurodevelopment at age 4 in the 2004 cohort.

Conclusions

The findings of this study suggest that the amount of time spent on screen devices might not be associated with neurodevelopment of children under 5 years of age. The small magnitude and inconsistencies in the direction of associations did not find evidence to support the current guidelines for screen time at this age. Therefore, more studies, especially those with longitudinal data, are important to comprehend the true effect of screen time on neurodevelopment and other health outcomes.
Alcohol relapse prevention health care after alcohol withdrawal in New South Wales prisons, Australia: A patient file review
Authors: Liang Yichao , Roberts Jillian , Conigrave Katherine , Kim Sobi , Doyle Michael F.
Published: August 2023

Introduction

People who enter custody have complex health issues and comorbidities may include alcohol use disorders. We investigated clinical service provision and comorbidities recorded among individuals with a likely alcohol withdrawal syndrome within prison in New South Wales, Australia.

Methods

For this clinical case series review, electronic medical data were used to identify 50 people entering custody between August and November 2018 who likely had a treated alcohol withdrawal syndrome. We aimed for a 3:2 ratio of men and women, and a 1:1 ratio of Aboriginal and non‐Aboriginal individuals. Data were extracted using a purposefully designed tool which included current alcohol withdrawal management, comorbidities and alcohol relapse prevention approaches used or recommended.

Results

Thirty‐eight men and 12 women, of whom 22 were Aboriginal, were included. Twenty‐nine individuals (58%) reported a history of medical comorbidities. Thirty‐five (70%) reported using other substances and over half (60%) had a diagnosis of mental health disorders. Fourteen (28%) individuals had a record of receiving brief intervention and five (10%) of motivational interviewing. Twenty‐three individuals (46%) were referred to and seen by drug and alcohol clinicians. Only seven (14%) of the sample had pre‐release community care plans.

Discussion and Conclusions

Individuals treated for an alcohol withdrawal syndrome in New South Wales prisons have a high prevalence of medical comorbidities and other substance use. Clinical interventions focused on alcohol withdrawal management, and relapse prevention interventions were not recorded for most individuals. Service innovation and expansion are needed to increase the provision of post‐withdrawal management.
Pharmacogenetics of sodium‐glucose co‐transporter‐2 inhibitors: Validation of a sex‐agnostic pharmacodynamic biomarker
Authors: Taylor Simeon I. , Cherng Hua‐Ren , Shahidzadeh Yazdi Zhinous , Montasser May E. , Whitlatch Hilary B. , Mitchell Braxton D. , Shuldiner Alan R. , Streeten Elizabeth A. , Beitelshees Amber L.
Published: August 2023

Aim

To validate pharmacodynamic responses to sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors and test for association with genetic variants in SLC5A4, SLC5A9, and SLC2A9.

Methods

Canagliflozin (300 mg), a SGLT2 inhibitor, was administered to 30 healthy volunteers. Several endpoints were measured to assess clinically relevant responses, including drug‐induced increases in urinary excretion of glucose, sodium and uric acid.

Results

This pilot study confirmed that canagliflozin (300 mg) triggered acute changes in mean levels of several biomarkers: fasting plasma glucose (−4.1 mg/dL; P = 6 × 10−5), serum creatinine (+0.05 mg/dL; P = 8 × 10−4) and serum uric acid (−0.90 mg/dL; P = 5 × 10−10). The effects of sex on glucosuria depended upon how data were normalized. Whereas males' responses were ~60% greater when data were normalized to body surface area, males and females exhibited similar responses when glucosuria was expressed as grams of urinary glucose per gram‐creatinine. The magnitude of glucosuria was not significantly correlated with fasting plasma glucose, estimated glomerular filtration rate or age in those healthy individuals without diabetes with an estimated glomerular filtration rate of more than 60 mL/min/1.73m2.

Conclusions

Normalizing data relative to creatinine excretion will facilitate including data from males and females in a single analysis. Furthermore, because our ongoing pharmacogenomic study (NCT02891954) is conducted in healthy individuals, this will facilitate detection of genetic associations with limited confounding by other factors such as HbA1c and renal function.
Effects of the COVID‐19 pandemic on domestic violence in Los Angeles
Authors: Miller Amalia R. , Segal Carmit , Spencer Melissa K.
Published: August 2023

From the onset of the COVID‐19 pandemic, policymakers and news reports warned that restrictions on individual mobility and commercial activity could lead to a surge in domestic violence (DV). Some initial studies found evidence of greater DV incidence during the pandemic, but findings were inconsistent across locations and DV measures. This paper focuses on a single major city, Los Angeles (LA), to study the impact of the initial pandemic shutdown. We use three DV measures from police data (911 calls, crime incidents and arrests) as well as two measures from non‐police administrative sources (the county DV hotline and hospital records). We find an increase in DV calls to the police and calls to the hotline. However, we find that DV crimes recorded by police and hospital visits by female assault (and DV) victims decreased significantly, suggesting that the increase in calls came from higher reporting rates. The decrease in DV crimes is not attributable to reductions in policing intensity, as the arrest rate for DV crimes was higher during the shutdown. We conclude that the initial LA shutdown increased the rates at which people contacted authorities about DV, but decreased the overall incidence of physical DV crimes in the population.
Does It Matter How the Rigor of High School Coursework Is Measured? Gaps in Coursework Among Students and Across Grades
Authors: Ogut Burhan , Yee Darrick , Circi Ruhan , Dizdari Nevin
Published: August 2023

Research
shows that the intensity of high school course‐taking is related to postsecondary outcomes. However, there are various approaches to measuring the intensity of students’ course‐taking. This study presents new measures of coursework intensity that rely on differing levels of quantity and quality of coursework. We used these new indices to provide a current description of variations in high school course‐taking across grades and student subgroups using a nationally representative dataset, the High School Longitudinal Study of 2009. Results showed that for measures emphasizing the quality of coursework the gaps in coursework among underserved students were larger and there was less upward movement in rigor across grades.
M2CE: Multi‐convolutional neural network ensemble approach for improved multiclass classification of skin lesion
Authors: Gajera Himanshu K. , Nayak Deepak Ranjan , Zaveri Mukesh A.
Published: August 2023

Due to inter‐class homogeneity and intra‐class variability, the classification of skin lesions in dermoscopy images has remained difficult. Although deep convolutional neural networks (DCNNs) have achieved satisfactory performance for binary skin cancer classification, multiclass skin lesion classification is still an open problem due to the limited training samples and class imbalance issues. To tackle these issues, in this article, we propose a multi‐CNN ensemble approach dubbed for multiclass skin lesion classification. The includes three individual CNN models, each helping in extracting different high‐level features from skin images and thereby yielding different prediction results. First, we design a lightweight CNN model to extract prominent features and train it from scratch, which primarily aims at avoiding the data scarcity problem. Then, we ensemble two different pre‐trained CNN models with the lightweight model to improve the performance and generalization capability. The proposed ensemble approach can effectively fuse the predictions of each individual CNN model using the averaging method. The approach is validated using a benchmark data set, HAM10000, which contains skin lesion images of seven different classes. The results demonstrate that the outperforms base CNN models and state‐of‐the‐art approaches without using any external data.
A comparison of spatial and temporal drivers of stream metabolism
Authors: Munn Mark D. , Konrad Christopher P. , Miller Matthew P. , Jaeger Kristin
Published: August 2023

Stream metabolism provides insight into the functional processes that regulate trophic status, biomass, and nutrient cycling in streams. Comparative (spatial) analyses of streams generally do not account for shifting at‐site controls on stream metabolism over time and, thus, may not identify the primary controls on cross‐site differences in trophic status, biomass, and nutrient cycling over longer time scales.

The spatial component included assessing environmental factors controlling stream metabolism (daily values) during a summer low‐flow period (August) at 17 wadable stream sites in four regions of the United States. Explanatory variables for the spatial analysis included discrete nutrients and physical parameters.

The temporal component included assessing 12 of the 17 sites with more than 90 days of stream metabolism values, and continuous nitrate, photosynthetically active radiation (PAR), turbidity, maximum water temperature (°C) and stream stage (water surface elevation).

Spatial analysis at the 17 sites during August (31 days) found that average gross primary production (GPP) ranged from 0.1 to 4 g O2 m−2 day−1 and ecosystem respiration (ER) from 0.37 to 6.4 g O2 m−2 day−1. Sites were primarily heterotrophic; however, some sites varied from autotrophic to heterotrophic daily. Multiple regression indicated that GPP was a function of orthophosphate, percent canopy cover, and the number of days since a high flow (R2 = 0.51), whereas ER was primarily a function of GPP (R2 = 0.40).

Temporal patterns in daily stream metabolism were evaluated using at‐site autoregressive models at 12 streams with relatively complete, continuous records. PAR, nitrate and maximum water temperature were the dominant variables influencing GPP, and water depth and nitrate were the most common explanatory variables for ER models. The autoregressive components (i.e., GPP or ER for the previous day) had a strong influence on both GPP and ER except after spates, indicating that biomass may be the dominant control on metabolism rather than variability in environmental factors during stable‐flow periods.

We found two dominant temporal metabolism regimes: a seasonal pattern with elevated spring metabolism followed by low stable summer metabolism and a temporally disturbed pattern which tended to occur in streams with frequent spates. These patterns were not indicated by differences in metabolism among streams during stable low‐flow conditions.

Because streams are generally heterotrophic with only limited periods when production may be high, comparative analyses must estimate stream metabolism over a time scale representing at‐site spatial variability and account for controls on periods of high production to adequately characterise differences between streams.
Evaluation of the routine use of E‐cadherin immunohistochemistry in the typing of breast carcinomas: results of a randomized diagnostic study
Authors: Cserni Gábor , Kálmán Endre , Udvarhelyi Nóra , Papp Eszter , Grote Isabel , Bartels Stephan , Christgen Matthias , Kreipe Hans , Kulka Janina
Published: August 2023

Aims

Invasive lobular carcinoma (ILC) has distinct morphology and association with loss of E‐cadherin function. It has special clinical and imaging features, and its proper recognition is important. Following a recent proposal, we tested the value of the routine use of E‐cadherin immunohistochemistry (IHC) in recognizing ILC.

Methods and results

Five pathologists with experience in breast pathology from four Hungarian institutions histotyped 1001 breast cancers from diagnostic core biopsies or excision specimens randomly assigned to haematoxylin and eosin (HE) diagnosis first, followed by E‐cadherin IHC; or to immediate HE and E‐cadherin‐based diagnosis. Of 524 cases with HE diagnosis, 73(14%) were deemed uncertain. E‐cadherin made the initial histological type change in 14/524 cases (2.7%), including three with confident HE‐based type allocation. Use of E‐cadherin immunostaining was considered useful in 88/477 cases (18%) with immediate dual assessment, and typing uncertainty went down to 5% (25/477 cases), but was not zero. Collective assessment of 171 uncertain, difficult, nonclassical cases resulted in consensus diagnosis in most cases, but 15 cases were still doubtful as concerns their proper histological type.CDH1gene sequencing was attempted and successful in 13; pathogenic genetic alterations were identified in seven cases.

Conclusions

The routine use of E‐cadherin IHC decreases the uncertainty in typing and improves the typing accuracy at the cost of potentially redundant additional immunostains. Furthermore, this procedure does not exclude uncertainty due to E‐cadherin‐positive ILCs, which are occasionally difficult to confidently label as ILC, especially when the growth pattern is not classic.
Evolution of seroprevalence to SARS‐CoV‐2 in blood donors in Sarajevo Canton, Federation of Bosnia and Herzegovina: Cross‐sectional and longitudinal studies
Authors: Musa Sanjin , Catovic Baralija Elma , Ivey Sawin Veronica , Nardone Anthony , Palo Mirza , Skocibusic Sinisa , Blazevic Mia , Cilovic Lagarija Seila , Ahmetovic‐Karic Gorana , Ljuca Alma , Dostovic‐Halilovic Sanela , Nedic Rozalija , Subissi Lorenzo , Ibrahim Rawi , Boshevska Golubinka , Bergeri Isabel , Pebody Richard , Vaughan Aisling
Published: August 2023

Background

Sarajevo Canton in the Federation of Bosnia and Herzegovina has recorded several waves of high SARS‐CoV‐2 transmission and has struggled to reach adequate vaccination coverage. We describe the evolution of infection‐ and vaccine‐induced SARS‐CoV‐2 antibody response and persistence.

Methods

We conducted repeated cross‐sectional analyses of blood donors aged 18–65 years in Sarajevo Canton in November–December 2020 and 2021. We analyzed serum samples for anti‐nucleocapsid (anti‐N) and anti‐spike (anti‐S) antibodies. To assess immune durability, we conducted longitudinal analyses of seropositive participants at 6 and 12 months.

Results

One thousand fifteen participants were included in Phase 1 (November–December 2020) and 1152 in Phase 2 (November–December 2021). Seroprevalence increased significantly from 19.2% (95% CI: 17.2%–21.4%) in Phase 1 to 91.6% (95% CI: 89.8%–93.1%) in Phase 2. Anti‐S IgG titers were significantly higher among vaccinated (58.5%) than unvaccinated infected participants across vaccine products (p < 0.001), though highest among those who received an mRNA vaccine. At 6 months, 78/82 (95.1%) participants maintained anti‐spike seropositivity; at 12 months, 58/58 (100.0%) participants were seropositive, and 33 (56.9%) had completed the primary vaccine series within 6 months. Among 11 unvaccinated participants who were not re‐infected at 12 months, anti‐S IgG declined from median 770.1 (IQR 615.0–1321.7) to 290.8 (IQR 175.7–400.3). Anti‐N IgG antibodies waned earlier, from 35.4% seropositive at 6 months to 24.1% at 12 months.

Conclusions

SARS‐CoV‐2 seroprevalence increased significantly over 12 months from end of 2020 to end of 2021. Although individuals with previous infection may have residual protection, COVID‐19 vaccination is vital to strengthening population immunity.
Bayesian estimates of genetic effects on calf survival in Hardhenu (Bos taurus × Bos indicus) cattle
Authors: Yadav Devesh Kumar , Malik Zile S. , Dash Spandan Shashwat , Pushpa  , Bangar Yogesh C. , Magotra Ankit
Published: August 2023

The aim of the present study is to carry out a risk analysis and Bayesian estimates of genetic effects on calf survival in Hardhenu cattle using data records of 2593 calves born to 102 sires and 790 dams over 25 years. The Bayesian analysis using Gibbs sampling was employed towards threshold animal models to estimate direct and maternal effects on animal survival of studied population. The results showed that mortality from birth to 3 months of age (S1), birth to 6 months of age (S2) and birth to 12 months of age (S3) was 10.22, 12.88 and 14.65%, respectively. It was revealed from the results of logistic regression analysis that the male animals had greater risk (1.41–1.61 times) of mortality during S1, S2 and S3 as compared to female animals. However, calves born during rainy season had higher risk (1.36 to 1.44 times) of mortality than calves born during winter season. Among died animals, the simultaneous infection of respiratory and digestive diseases had leading contribution (26.84%–30.19%) to deaths while alone of them contributed to 18%–20% only. On evaluation of six threshold animal models, model 1 was found to be most appropriate model and the Bayesian estimates (95% highest posterior density confidence intervals) of direct additive heritability for S1, S2 and S3 under model 1 were 0.15 ± 0.07 (0.04–0.23), 0.23 ± 0.12, (0.02–0.44) and 0.26 ± 0.06 (0.08–0.41), respectively. It was concluded that the inclusion of survival traits in existing selection criteria may be helpful to increase calf survival and ultimately economic gain in the dairy herd.
Challenges in anti‐aging medicine–trends in biomarker discovery and therapeutic interventions for a healthy lifespan
Authors: Popescu Iuliana , Deelen Joris , Illario Maddalena , Adams Jan
Published: August 2023

We are facing a growing aging population, along with increasing pressure on health systems, caused by the impact of chronic co‐morbidities (i.e. cancer, cardiovascular and neurodegenerative diseases) and functional disabilities as people age. Relatively simple preventive lifestyle interventions, such as dietary restriction and physical exercise, are important contributors to active and healthy aging in the general population. However, as shown in model organisms or in 'in vitro' conditions, lifestyle‐independent interventions may have additional health benefits and can even be conceived as possible reversers of the aging process. Thus, pharmaceutical laboratories, research institutes, and universities are putting more and more effort into finding new molecular pathways and druggable targets to develop gerotherapeutics. One approach is to target the driving mechanisms of aging, some of which, like cellular senescence and impaired autophagy, we discussed in an update on the biology of aging at AgingFit 2023 in Lille, France. We underline the importance of carefully and extensively testing senotherapeutics, given the pleiotropism and heterogeneity of targeted senescent cells within different organs, at different time frames. Other druggable targets emerging from new putative mechanisms, like those based on transcriptome imbalance, nucleophagy, protein phosphatase depletion, glutamine metabolism, or seno‐antigenicity, have been evidenced by recent preclinical studies in classical models of aging but need to be validated in humans. Finally, we highlight several approaches in the discovery of biomarkers of healthy aging, as well as for the prediction of neurodegenerative diseases and the evaluation of rejuvenation strategies.
Environmental‐relevant bisphenol A exposure promotes ovarian cancer stemness by regulating microRNA biogenesis
Authors: Lam Sophia S. N. , Shi Zeyu , Ip Carman K. M. , Wong Chris K. C. , Wong Alice S. T.
Published: August 2023

Bisphenol A (BPA) is a ubiquitous environmental xenobiotic impacting millions of people worldwide. BPA has long been proposed to promote ovarian carcinogenesis, but the detrimental mechanistic target remains unclear. Cancer stem cells (CSCs) are considered as the trigger of tumour initiation and progression. Here, we show for the first time that nanomolar (environmentally relevant) concentration of BPA can markedly increase the formation and expansion of ovarian CSCs concomitant. This effect is observed in both oestrogen receptor (ER)‐positive and ER‐defective ovarian cancer cells, suggesting that is independent of the classical ERs. Rather, the signal is mediated through alternative ER G‐protein‐coupled receptor 30 (GPR30), but not oestrogen‐related receptor α and γ. Moreover, we report a novel role of BPA in the regulation of Exportin‐5 that led to dysregulation of microRNA biogenesis through miR‐21. The use of GPR30 siRNA or antagonist to inhibit GPR30 expression or activity, respectively, resulted in significant inhibition of ovarian CSCs. Similarly, the CSCs phenotype can be reversed by expression of Exportin‐5 siRNA. These results identify for the first time non‐classical ER and microRNA dysregulation as novel mediators of low, physiological levels of BPA function in CSCs that may underlie its significant tumour‐promoting properties in ovarian cancer.
Efficacy, safety and tolerability of imeglimin in patients with type 2 diabetes mellitus: A meta‐analysis of randomized controlled trials
Authors: Hagi Katsuhiko , Nitta Masahiro , Watada Hirotaka , Kaku Kohei , Ueki Kohjiro
Published: August 2023

Aims/Introduction

This meta‐analysis aimed to evaluate the efficacy and safety/tolerability of imeglimin, a novel oral antihyperglycemic agent, administered as monotherapy and adjunctive therapy in patients with type 2 diabetes mellitus.

Materials and Methods

Parallel‐group randomized controlled trials comparing imeglimin with placebo in adults with type 2 diabetes mellitus were included. Risk ratios or weighted mean differences (WMD) and 95% confidence intervals (CIs) were calculated using random effects models. The primary outcome for efficacy was the change in glycated hemoglobin (HbA1c). Secondary outcomes included other efficacy‐related outcomes, specific adverse events, and changes in body weight and lipid parameters.

Results

Nine randomized controlled trials (n = 1,655) were included. When analyzed by dose, there was a significant difference in glycated hemoglobin (%) between imeglimin monotherapy and placebo at doses >1,000 mg twice daily (1,000 mg: studies N = 3, patients n = 517, WMD = −0.714, P < 0.001; 1,500 mg: N = 5, n = 448, WMD = −0.531, P = 0.020; 2,000 mg: N = 1, n = 149, WMD = −0.450, P = 0.005). Imeglimin adjunctive therapy significantly improved glycated hemoglobin over placebo at doses of 1,000 mg (N = 1, n = 214, WMD = −0.600, P < 0.001) and 1,500 mg (N = 2, n = 324, WMD = −0.576, P < 0.001). Subgroup analysis of the primary outcome showed that imeglimin was effective regardless of chronic kidney disease category, with studies carried out in Japan and in patients with lower body mass index showing a trend toward improved imeglimin efficacy. There were no significant differences between imeglimin and placebo in the risk of all‐cause discontinuation and the proportion of patients who presented with at least one adverse event.

Conclusions

Imeglimin is efficacious, safe, and well tolerated as monotherapy and adjunctive therapy.
Baseline prevalence of hyperglycemia and its predictors among community clinic users of a selected rural area of Bangladesh: A cross‐sectional study using the WHO PEN Protocol 1
Authors: Faruque Mithila , Barua Lingkan , Rakhshanda Shagoofa , Banik Palash Chandra , Shawon Riffat Ara , Rahman AKM Fazlur , Mashreky Saidur Rahman
Published: August 2023

Aims/Introduction

Our objective was to estimate the prevalence of hyperglycemia at baseline, and identify its predictors among community clinic (CC) users from a selected rural area of Bangladesh.

Materials and Methods

This cross‐sectional study partly used the baseline data of implementation research in which a total of 11,244 adults visited the CC, and their blood glucose, blood pressure and anthropometry were evaluated according to ‘Action 2’ of the World Health Organization (WHO) Package of Essential Noncommunicable Disease Interventions (PEN) protocol 1. Of these, 11,144 had complete information on demography, chronic diseases and their risk factors, which were collected during the implementation of ‘Action 1’ of WHO PEN protocol 1 at the household level. Hyperglycemia, prediabetes (PreD) and type 2 diabetes were diagnosed using the WHO criteria.

Results

Using WHO PEN protocol 1, the estimated baseline prevalence was 12.5% for hyperglycemia, 3.4% for PreD and 9.2% for type 2 diabetes, and was more prevalent among men compared with women. PreD and type 2 diabetes had significantly higher odds ratio (OR >1) of having common risk factors as follows: age ≥40 years (PreD,P < 0.001; type 2 diabetes,P < 0.001), generalized obesity (PreD,P < 0.001; type 2 diabetes,P = 0.005) and hypertension (PreD,P < 0.000; type 2 diabetes,P < 0.001). Furthermore, participants with a family history of diabetes appeared to be a significant predictor of type 2 diabetes (P < 0.001), but not for PreD (P = 0.303).

Conclusions

Hyperglycemia, preD and type 2 diabetes showed a comparatively high prevalence among the CC users of the selected rural area. Obesity and hypertension are the key modifiable risk factors that should be reduced using a CC‐centered risk reduction strategy.
Descriptive and comparative analysis of mucocutaneous manifestations in patients with dengue fever: A prospective study
Authors: Fera C. , Maillard O. , Joly E. , Diallo K. , Mavingui P. , Koumar Y. , Cabié A. , Bertolotti A.
Published: August 2023

Background

Dengue is an arbovirosis affecting nearly 4 billion people worldwide. Since 2018, dengue has been re‐emerging in Reunion Island. The incidence of mucocutaneous manifestations varies according to the studies and is generally called ‘rash’.

Objectives

To assess the prevalence of different mucocutaneous symptoms and describe the characteristics of patients developing these symptoms and the clinical signs associated with severe dengue.

Methods

A prospective study was conducted in 2019 at the University Hospital of La Réunion, in patients presenting a positive PCR for dengue. Descriptive analyses were performed. All cases in the prospective study were examined by a dermatologist.

Results

A total of 163 cases were included. The prevalence of mucocutaneous signs was 80.4%. A pruritus was reported in 33.7% cases, an erythematous rash in 29.4% and a mouth involvement including lip, tongue, cheek, angular cheilitis, pharyngitis, mouth ulcer and gingivitis in 31.3%. Most of symptoms appeared in the first days, but some of them could disappear only after the 3rd week. Mucocutaneous signs were not associated with a severe dengue fever (p = 0.54), but ecchymotic purpura was (p = 0.037). In multivariate analysis, skin involvement was associated with flu‐like syndrome (headache, pharyngitis, rachis pain) and patient required rehydration but not invasive reanimation.

Conclusion

This work confirms the high prevalence of skin symptoms in dengue disease, but also their wide diversity. The mucocutaneous involvement of dengue fever appears to be accompanied by a pronounced flu‐like syndrome in people without severity, but careful examination to identify ecchymotic purpura or sign of dehydration in the mucous membranes would better identify cases that may worsen.
Interactions between egg parasitoids and predatory ants for the biocontrol of the invasive brown marmorated stink bug Halyomorpha halys
Authors: Schifani Enrico , Giannetti Daniele , Costi Elena , Franconi Giulia , Campostrini Arianna , Maistrello Lara , Grasso Donato A.
Published: August 2023

The brown marmorated stink bug Halyomorpha halys is an Asian species that has become a major agricultural pest in North America and Europe. Ants from the genus Crematogaster are predators of H. halys nymphs in Asia, as well as in the Mediterranean, where known native predators are still few. At the same time, ants usually do not harm H. halys eggs, which are the target of the main biological control agents, the scelionid parasitoids of the genus Trissolcus. However, ants, as generalist predators and territorial organisms, may kill or displace a variety of other insects, potentially interfering with parasitoids and biological control programmes. We conducted laboratory experiments to investigate the interactions between the Mediterranean ant Crematogaster scutellaris and the parasitoids T. japonicus and T. mitsukurii, evaluating the possibility that the ants could damage the parasitized eggs, attack the parasitoids during emergence or interfere with the egg‐laying behaviour of female parasitoids. Our results demonstrate that C. scutellaris is not able to damage parasitized eggs and is not aggressive towards adult parasitoids at any stage. The presence of ants can slow down the parasitization rate in T. mitsukurii females in the smallest laboratory setups; however, this has not been observed in a more natural setting. We suggest that ants may play a complementary role together with egg‐parasitoids in the control of H. halys without interfering with each other.
The efficacy and safety of cold snare polypectomy with submucosal injection for the removal of polyps less than 20 mm in size: a systematic review and meta‐analysis
Authors: Liang Zheng , Wei Yongqiu , Zhang Shutian , Li Peng
Published: August 2023

Background and Aim

Neoplastic polyp removal is important for colorectal cancer prevention. Endoscopists have proposed cold snare endoscopic mucosal resection (CS‐EMR) as a solution to solve positive cutting edges and postoperative bleeding. However, many controversies regarding its specific performance in practice have been reported. The aim of this pooled analysis was to report the efficacy and safety of CS‐EMR.

Methods

PubMed/Medline, Embase, Google Scholar, and the Cochrane Library searched up to January 2022 to identify studies in which CS‐EMR was performed for the removal of colorectal polyps measuring less than 20 mm. The primary outcome was the complete resection rate (CRR), and the secondary outcome was the rate of adverse events.

Results

Eleven studies were included in the final analysis, which included 861 colorectal polyps. The overall CRR with CS‐EMR was 96.3% (95% CI, 93.9–98.2%). The early and delayed bleeding rates of CS‐EMR were 3.1% (95% CI, 1.2–5.5%) and 1.4% (95% CI, 0.6–2.4%), respectively. There were no statistical significances between CS‐EMR and cold snare polypectomy (CSP) in terms of the CRR and adverse events, as well as CS‐EMR and hot snare endoscopic mucosal resection (HS‐EMR).

Conclusions

For resecting colorectal polyps measuring ≤20 mm, CS‐EMR is an effective attempt. However, compared with CSP and HS‐EMR, CS‐EMR did not improve the efficiency and safety of polypectomy as expected. Multicenter randomized controlled trials are needed to compare CSP with CS‐EMR in the resection of <10 mm polyps and HSP with CS‐EMR in the resection of ≥10 mm polyps.