bluuebunny/crossref_metadata_2025 huggingface dataset:
Nitrogen pulses increase fungal pathogens in Amazonian lowland tropical rain forests
Authors: Buscardo Erika , Geml József , Schmidt Steven K. , Freitas Helena , Souza Anete P. , Cunha Hillândia B. , Nagy Laszlo
Published: May 2022

Animals represent an overlooked source of horizontal redistribution of primary production and concentration of elements in ecosystems. For example, the high nutrient concentration of excretions by animals creates a mosaic of short‐term nutrient hotspots. However, how this impacts soil microbial communities, especially fungi, and in turn plant species diversity remains little known.

This study quantified the temporal dynamics of soil mineral nitrogen (N) availability and its relationship with soil fungal community and functional group composition in simulated high‐N patches in an Amazonian rain forest. We hypothesised that (H1) changes in local resource dynamics would increase the abundance of pathotrophs and reduce that of saprotrophs and that, (H2) compared with previously reported bacterial community dynamics, fungi would be more resilient after a pulse disturbance event.

A single urea pulse was applied and the relationship between fungal community composition and functional groups and soil N availability were determined before and twice after the urea treatment.

An increase in mineral N availability and soil pH two months after the applied urea pulse was found to be associated with significant changes in fungal community composition and the abundance of functional groups. There was a notable decrease in the relative abundance of saprotrophs, accompanied by an increase in plant pathogenic fungi. Five months after the treatment, no differences were detected either in mineral N availability and soil pH or the composition of fungal communities and functional groups between the control and urea treatment.

Synthesis. By locally favouring the abundance of plant pathogens, temporally short‐lived, but frequent high‐N patches created by animal excretions could potentially be involved in maintaining spatially and temporally variable soil microbial diversity and thus contributing to high plant community diversity in tropical rain forests as predicted by the Janzen–Connell hypothesis. The tendency of soil fungal communities in this study to return to their initial composition after 5 months suggests that they are resilient to perturbation by N pulse, and more so than previously observed in bacterial communities.
Men, suicide, and family and interpersonal violence: A mixed methods exploratory study
Authors: Fitzpatrick Scott J. , Brew Bronwyn K. , Handley Tonelle , Perkins David
Published: May 2022

Research has shown a link between gender, violence, and suicide. This relationship is complex, and few empirical studies have explored suicide and family and interpersonal violence perpetrated by men. Drawing on a coronial dataset of suicide cases and a mixed methods design, this study integrated a quantitative analysis of 155 suicide cases with a qualitative analysis of medico‐legal reports from 32 cases. Findings showed different types and patterns of family and intimate partner violence for men who died by suicide. Men used violence in response to conflict, but also to dominate women. Cumulative, interwoven effects of violence, mental illness, alcohol and other drug use, socioeconomic, and psychosocial circumstances were observed in our study population. However, the use of violence and suicidal behaviour was also a deliberate and calculated response by which some men sought to maintain influence or control over women. Health and criminal justice interventions served as short‐term responses to violence, mental illness, and suicidal behaviour, but were of limited assistance.
Verb Classes in the Resultative Construction in Germanic and Romance Languages
Authors: Métairy Justine
Published: May 2022

The present paper consists of a contrastive corpus‐based study of the (analytical) Resultative Construction (henceforth, RC) in culinary contexts (e.g. cut thin, whisk to a foam, roll into a ball). Four languages are investigated: two Germanic (i.e. Dutch and English) and two Romance languages (i.e. French and Spanish). Based on a sample of 1000 occurrences of the RC (by language) retrieved from our home‐made comparable corpus of cooking recipes, this study shows that: (i) both ‘strong’ (i.e. aspect‐shifting) and ‘weak’ (i.e. non‐aspect‐shifting) RCs are possible in the four languages studied (Washio 1997) – although the latter is said to be the only pattern available in Romance (Fontanals 2000; Mateu 2012; Bigolin & Ausensi 2021); (ii) a greater diversity of verbs occurs in the RC in Dutch and English, which suggests that the construction is still more productive in Germanic languages, even in culinary contexts; and (iii) in Romance, the productivity of the verb slot in the RC depends to a large degree on whether the resultative predicate can be encoded by a prepositional phrase.
Discovering Dwellings
Authors: Fretheim Silje E.
Published: May 2022

This article is based on a study of site formation processes of dwellings, site contexts, and terms relating to dwelling types and attributes. Archaeological evidence discovered during the Ormen Lange project and dated to the Late Mesolithic provides the backdrop for discussion. The project was conducted by the NTNU University Museum in 2003-2004 on the Island of Gossen in Central Norway. Remains of at least 14 dwellings and a large number of dwelling-related features dated to between 6000 and 4000 cal BC were recorded. Based on analyses of several dwelling attributes, the Ormen Lange dwellings are divided into 1) houses for long term or regularly repeated stays (for double and single family units); 2) houses for repeated short-time stays (for task groups); 3) non-permanent dwellings for short time occupation and 4) special-purpose, non-residential shelters.
The Cultural Landscape of the Chinese Bronze Age
Authors: Jinsong Shi
Published: May 2022

The Chinese Bronze Age culture from the 19th to the 1st century BC can be divided into four zones: the Central Plain in the middle and the lower Yellow River region; the Northern zone along the Great Wall; the Southern zone, south to the middle and the lower Yangzi River; the Southwestern zone covering the upper Yangzi River. In each zone, bronzes are not only different in types and styles but also function differently responding to the processes of the early state formation and social development. More precisely, in the first zone, there are mainly ritual bronzes, serving as symbols of the social and political hierarchy. In the second zone, there are mainly utilitarian items such as weapons, tools, bronzes of everyday use, ornaments, as well as horse-chariot fittings. Bronze musical instruments characterise the third zone. And bronzes of the fourth zone are realistic or symbolic in style, depicting scenes of social life. Though having different cultural origins and characteristics, the four zones communicate with and influence each other continuously, creating a dynamic cultural landscape of the Chinese Bronze Age.
1470 Inca Expansion into the Land of the Chachapoya
Authors: Schjellerup Inge
Published: May 2022

Starting from around AD 800, the Chachapoya developed their own culture with monumental architecture. It came to an end in 1470 after the conquest by the Incas. At that time, a different architecture was introduced in the region followed by changes in the landscape. The article summarises the available evidence on architectural and archaeological remains dated to the period following the Inca conquest.
Establishment of Beauveria bassiana as a fungal endophyte in potato plants and its virulence against potato tuber moth, Phthorimaea operculella (Lepidoptera: Gelechiidae)
Authors: Zhang Meng‐Di , Wu Sheng‐Yong , Yan Jun‐Jie , Reitz Stuart , Gao Yu‐Lin
Published: May 2022

The potato tuber moth, Phthorimaea operculella, is the most damaging potato pest in the world and is difficult to control as the larvae are internal feeders in the foliage and tubers. Entomopathogenic fungi that colonize plants as endophytes have lethal and sublethal pathological effects on insect pests. We show that Beauveria bassiana colonizes the aerial parts of potato plants endophytically after inoculation through soil drenching. Endophytic B. bassiana persisted in potato foliage for more than 50 days postinoculation. Bioassays indicated that foliage of B. bassiana‐inoculated potato plants were pathogenic against larvae of P. operculella. Sublethal experiments indicated that B. bassiana negatively affected the growth, development, and reproduction of P. operculella. Development experiments showed that the weight of P. operculella pupae reared on B. bassiana‐colonized potato plants (4.25 mg) was significantly less than that of those reared on uninoculated control plants (8.89 mg). Compared with newly eclosed larvae fed on control plants, those fed on B. bassiana‐inoculated plants had significantly lower survivorship, with only 17.8% developing to the adult stage. Oviposition of P. operculella females reared on B. bassiana endophytically colonized plants was significantly lower (35 eggs/female) than of those reared on uninoculated plants (115 eggs/female). This study demonstrates that endophytic B. bassiana can be a potential biological control agent for the control and management of P. operculella. Comparing pupal weights of P. operculella reared on potato plants inoculated with the B. bassiana strain GZGY‐1‐3 and on untreated control plants, pupae from the control plants were significantly heavier than those from treated plants.
Efficacy of first‐line immune checkpoint inhibitors in patients with advanced NSCLC with KRAS, MET, FGFR, RET, BRAF, and HER2 alterations
Authors: Uehara Yuji , Watanabe Kageaki , Hakozaki Taiki , Yomota Makiko , Hosomi Yukio
Published: May 2022

Background

In patients with non‐small cell lung cancer (NSCLC) harboring driver alterations, the efficacy of immune checkpoint inhibitors (ICIs) remains uncertain. Our study aimed to examine the first‐line ICI efficacy in patients with NSCLC harboring KRAS, MET, FGFR, RET, BRAF, and HER2 alterations in a real‐world setting.

Methods

This single‐center, retrospective cohort study included patients with advanced NSCLC harboring KRAS, MET, FGFR, RET, BRAF, HER2 alterations or driver‐negative, and were treated with first‐line ICI therapy. Best overall response, progression‐free survival (PFS), and overall survival (OS) were evaluated.

Results

Seventy‐eight patients with NSCLC were included (median age, 72 years): 67% were men, 15% were never‐smokers, and 83% had adenocarcinoma. The driver alterations involved KRAS (n = 21), MET (n = 6), FGFR (n = 3), RET (n = 2), BRAF (n = 2), HER2 (n = 1), and driver‐negative (n = 43). The partial responses for KRAS, MET, FGFR, RET, BRAF, HER2, and driver‐negative were 57%, 50%, 100%, 50%, 100%, 0%, and 47%, respectively. The median PFS (months) was 16.2 (95% confidence interval [CI]: 6.3– not reached [NR]) for KRAS, 2.8 (95% CI: 2.7–NR) for MET, 11.7 (95% CI: 5.9–NR) for other alterations (FGFR, RET, BRAF, and HER2), and 10.0 (95% CI: 3.7–14.3) for driver‐negative, respectively. The median OS (months) was 31.3 (95% CI: 9.0–NR) for KRAS, not reached for MET, 23.5 (95% CI: 18.3–NR) for other alterations, and 21.1 (95% CI: 15.2–NR) for driver‐negative, respectively.

Conclusions

The benefit of the first‐line ICI was similar in advanced NSCLC regardless of the driver alterations, except for MET alterations.
Sex‐related differences in pattern of ethanol drinking under the intermittent‐access model and its impact on exploratory and anxiety‐like behavior in Long‐Evans rats
Authors: Pirino Breanne E. , Martin Cydney R. , Carpenter Brody A. , Curtis Genevieve R. , Curran‐Alfaro Christina M. , Samels Shanna B. , Barker Jacqueline M. , Karkhanis Anushree N. , Barson Jessica R.
Published: May 2022

Background

While men in the United States consume more alcohol than women, rates of drinking are converging. Nevertheless, females remain underrepresented in preclinical alcohol research. Here, we examined rats' sex‐related differences in patterns of ethanol (EtOH) drinking and the effects of this drinking on exploratory and anxiety‐like behavior.

Methods

Adult male and female Long‐Evans rats were given 20% ethanol under the intermittent‐access two‐bottle‐choice paradigm. Their intake was measured daily for the first 7 weeks. During the eighth week, intake was measured over the 24 h of daily access. During the ninth week, they, along with EtOH‐naive controls, were tested prior to daily access in a novel chamber, light–dark box, and hole board apparatus. During the tenth week, blood ethanol concentration (BEC) was assessed after 30 to 40 min of access.

Results

Females overall demonstrated higher ethanol intake and preference across all access weeks than males, although only half of females drank significantly more than males. Across 24 h of daily access, both sexes had their highest intake in the first 30 min and their lowest in the middle of the light phase of the light/dark cycle. Despite their greater ethanol intake, females did not show significantly different BECs than males. In behavioral tests, females showed less vertical time in a novel activity chamber, more movement between chambers in a light–dark box, and more nose pokes in a hole‐board apparatus than males. While a history of ethanol drinking led to a trend for lower vertical time in the activity chamber and greater chamber entries in the light–dark box, the effects were not sex‐dependent.

Conclusions

These results suggest that female and male rats could both be tested for acute effects of ethanol after 30 min of daily access, but that nuanced considerations are needed in the design of these experiments and the interpretation of their findings.
Identifying prospective subpopulations of combustible and electronic cigarette dual users in the United States via finite mixture modeling
Authors: Sutton Steven K. , Brandon Karen O. , Harrell Paul T. , Martínez Úrsula , Simmons Vani N. , Gore L. Robert , Bullen Christopher R. , Brandon Thomas H.
Published: May 2022

Aims

To identify subpopulations of dual users of combustible and electronic cigarettes using current smoking and vaping behaviors.

Design

Secondary analysis of baseline data from a randomized controlled trial testing a smoking cessation intervention for dual users. Finite mixture modeling of frequency, quantity, and dependence on combustible and electronic cigarettes was used to identify classes. Demographics and additional smoking and vaping variables were used to further characterize the classes.

Setting

United States.

Participants

A total of 2896 adults who smoked weekly for the past year and vaped weekly for the past month.

Measurements

Self‐report baseline measures assessed demographics and smoking and vaping behaviors and characteristics including days of use per week, frequency of use within a day, time to first use after waking, urges to smoke, smoking cessation motivation, self‐efficacy to abstain from smoking, months since vaping initiation, reasons for initiating and maintaining vaping, and future plans to stop vaping.

Findings

Eight probabilistic classes were identified and well‐defined (relative entropy = 0.95, Lo–Mendell–Rubin adjusted likelihood ratio test P < 0.0001; class probabilities 0.89–0.97). In general, classes crossed two levels of smoking with four levels of vaping. The largest class (31%) had relatively high levels of smoking (72% daily, 56% 11+ cigarettes per day [CPD], 96% within 30 minutes of waking) and vaping (74% daily, 100% 20+ electronic‐CPD, 74%  <30 minutes). The next largest class (27%) had relatively high levels of vaping (93% daily, 100% 20+ electronic‐CPD, 82%  <30 minutes) and very low levels of smoking (28% daily, 12% 11+ CPD, 0%  <30 minutes). The six smaller classes (3%–13%) also had distinct smoking and vaping behaviors. All eight classes exhibited distinguishing characteristics beyond current smoking and vaping behaviors.

Conclusions

Dual users of combustible and electronic cigarettes are not a homogeneous population, having eight well‐defined prospective subpopulations.
Identifying predictors of systemic immunosuppressive treatment of vulvovaginal lichen planus: A retrospective cohort study of 122 women
Authors: Kherlopian Ashod , Fischer Gayle
Published: May 2022

Background

Between 20% and 40% of women with vulvovaginal lichen planus (VLP) fail to respond to first‐line ultra‐potent topical corticosteroid treatment and require systemic immunosuppression to control disease. No data exist regarding risk factors for patients with severe VLP requiring systemic immunosuppression. We aimed to identify clinical features that predict women with VLP who are at risk of severe, recalcitrant disease requiring eventual escalation to systemic treatment.

Methods

A chart review was performed on a cohort of 122 adult women with VLP followed prospectively for 15 years by the same clinician in a private dermatology practice in Australia between 1 January 2004 and 1 October 2021. Uni‐ and multivariable binary logistical regression analyses were performed to identify clinical features distinguishing women eventually requiring systemic treatment of VLP against those whose VLP was controlled with topical corticosteroids alone.

Results

The mean age at diagnosis of VLP was 61 years, with 35 women (28.7%) requiring systemic treatment of VLP. A multivariable regression model utilising ‘Age at Diagnosis’ (adjusted OR = 0.97, 95% CI 0.94–0.99), ‘Non‐Caucasian Ethnicity’ (adjusted OR = 10.3, 95% CI 2.27–73.9) and ‘Vulvar Pruritus’ (adjusted OR = 2.69, 95% CI 1.11–6.86) demonstrated moderate predictive capacity, with specificity and sensitivity for predicting whether a patient will require systemic treatment for VLP of 95.3% and 40.5%, respectively.

Conclusions

Our findings may indicate women with VLP who are younger, of non‐Caucasian ethnicity, and presenting with vulval pruritus are the highest risk of severe disease requiring systemic immunosuppressive treatment and may benefit most from earlier initiation of systemic treatment.
Comparing the levels of CTLA‐4‐dependent biological defects in patients with LRBA deficiency and CTLA‐4 insufficiency
Authors: Catak Mehmet C. , Akcam Bengu , Bilgic Eltan Sevgi , Babayeva Royala , Karakus Ibrahim S. , Akgun Gamze , Baser Dilek , Bulutoglu Alper , Bayram Feyza , Kasap Nurhan , Kiykim Ayca , Hancioglu Gonca , Kokcu Karadag Sefika I. , kendir Demirkol Yasemin , Ozen Selime , Cekic Sukru , Ozcan Dilek , Edeer Karaca Neslihan , Sasihuseyinoglu Ayse S. , Cansever Murat , Ozek Yucel Esra , Tamay Zeynep , Altintas Derya U. , Aydogmus Cigdem , Celmeli Fatih , Cokugras Haluk , Gulez Nesrin , Genel Ferah , Metin Ayse , Guner Sukru N. , Kutukculer Necil , Keles Sevgi , Reisli Ismail , Kilic Sara S. , Yildiran Alisan , Karakoc‐Aydiner Elif , Lo Bernice , Ozen Ahmet , Baris Safa
Published: May 2022

Background

Lipopolysaccharide‐responsive beige‐like anchor protein (LRBA) deficiency and cytotoxic T‐lymphocyte protein‐4 (CTLA‐4) insufficiency are recently described disorders that present with susceptibility to infections, autoimmunity, and lymphoproliferation. Clinical and immunological comparisons of the diseases with long‐term follow‐up have not been previously reported. We sought to compare the clinical and laboratory manifestations of both diseases and investigate the role of flow cytometry in predicting the genetic defect in patients with LRBA deficiency and CTLA‐4 insufficiency.

Methods

Patients were evaluated clinically with laboratory assessments for lymphocyte subsets, T follicular helper cells (TFH), LRBA expression, and expression of CD25, FOXP3, and CTLA4 in regulatory T cells (Tregs) at baseline and 16 h post‐stimulation.

Results

LRBA‐deficient patients (n = 29) showed significantly early age of symptom onset, higher rates of pneumonia, autoimmunity, chronic diarrhea, and failure to thrive compared to CTLA‐4 insufficiency (n = 12). In total, 29 patients received abatacept with favorable responses and the overall survival probability was not different between transplanted versus non‐transplanted patients in LRBA deficiency. Meanwhile, higher probability of survival was observed in CTLA‐4‐insufficient patients (p = 0.04). The T‐cell subsets showed more deviation to memory cells in CTLA‐4‐insufficiency, accompanied by low percentages of Treg and dysregulated cTFH cells response in both diseases. Cumulative numbers of autoimmunities positively correlated with cTFH frequencies. Baseline CTLA‐4 expression was significantly diminished in LRBA deficiency and CTLA‐4 insufficiency, but significant induction in CTLA‐4 was observed after short‐term T‐cell stimulation in LRBA deficiency and controls, while this elevation was less in CTLA‐4 insufficiency, allowing to differentiate this disease from LRBA deficiency with high sensitivity (87.5%) and specificity (90%).

Conclusion

This cohort provided detailed clinical and laboratory comparisons for LRBA deficiency and CTLA‐4 insufficiency. The flow cytometric approach is useful in predicting the defective gene; thus, targeted sequencing can be conducted to provide rapid diagnosis and treatment for these diseases impacting the CTLA‐4 pathway.
A Logic of Care and Black Grassroots Claims to Home in Detroit
Authors: Quizar Jessi
Published: May 2022

This article examines the ways in which Detroit Eviction Defense (DED) and other activist organisations employ a logic of care to argue for Black Detroiters’ right to define who may claim home and place in the city. The article uses the foreclosure case of longtime Detroiter Lela Whitfield to examine the ways in which DED successfully resists eviction by arguing publicly that legitimate claims to land and home should be based on how one cares for it—in terms of stewardship, in terms of relationships on and with places, and based on how one uses it. This essay argues that this logic of care has roots in a Black radical tradition and in the particular conditions of racial capitalism in Detroit. Ultimately, DED and other Detroiters offer care as an alternate logic to resist “racial banishment” and establish alternate place‐claiming logics in the context of urban housing crisis, austerity, and financialisation.
A Compound Decision Approach to Covariance Matrix Estimation
Authors: Xin Huiqin , Zhao Sihai Dave
Published: May 2022

Covariance matrix estimation is a fundamental statistical task in many applications, but the sample covariance matrix is suboptimal when the sample size is comparable to or less than the number of features. Such high-dimensional settings are common in modern genomics, where covariance matrix estimation is frequently employed as a method for inferring gene networks. To achieve estimation accuracy in these settings, existing methods typically either assume that the population covariance matrix has some particular structure, for example, sparsity, or apply shrinkage to better estimate the population eigenvalues. In this paper, we study a new approach to estimating high-dimensional covariance matrices. We first frame covariance matrix estimation as a compound decision problem. This motivates defining a class of decision rules and using a nonparametric empirical Bayes g-modeling approach to estimate the optimal rule in the class. Simulation results and gene network inference in an RNA-seq experiment in mouse show that our approach is comparable to or can outperform a number of state-of-the-art proposals.
Substitution of SERCA2 Cys674 accelerates aortic aneurysm by inducing endoplasmic reticulum stress and promoting cell apoptosis
Authors: Wang Langtao , Yang Zhen , Wang Sai , Que Yumei , Shu Xi , Wu Fuhua , Liu Gang , Li Siqi , Hu Pingping , Chen Hao , Shi Jian , Tong Xiaoyong
Published: May 2022

Background and Purpose

The Cys674 residue (C674) in the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2) is key to maintaining its enzyme activity. The irreversible oxidation of C674 occurs broadly in aortic aneurysms. Substitution of C674 promotes a phenotypic transition of aortic smooth muscle cells (SMCs) and exacerbates angiotensin II‐induced aortic aneurysm. However, its underlying mechanism remains enigmatic.

Experimental Approach

Heterozygous SERCA2 C674S knock‐in (SKI) mice, in which half of C674 was replaced by serine, were used to mimic partially irreversible oxidation of C674 thiol. The aortas of SKI mice and their littermate wild‐type mice under an LDL receptor‐deficient background were collected for histological and immunohistochemical analysis. Cultured aortic SMCs were used for protein expression, apoptosis analysis, and cell function studies.

Key Results

The substitution of SERCA2 C674 caused endoplasmic reticulum (ER) stress and induced SMC apoptosis. The inhibition of ER stress by 4‐phenylbutyric acid (4‐PBA) in SKI aortic SMCs decreased the expression of marker proteins for cell apoptosis as well as phenotypic transition, and prevented cell apoptosis, proliferation, migration, and macrophage adhesion to SMCs. 4‐PBA also ameliorated angiotensin II‐induced aortic aneurysm in SKI mice.

Conclusions and Implications

The irreversible oxidation of SERCA2 C674 promotes the development of aortic aneurysm by inducing ER stress and subsequent SMC apoptosis. Our study illustrates that ER stress caused by oxidative inactivation of C674 is related to the pathogenesis of aortic aneurysm. Therefore, ER stress and SERCA2 are potential therapeutic targets for treating aortic aneurysm.
Association between vitiligo and relevant components of metabolic syndrome: a systematic review and meta‐analysis
Authors: Kang Pan , Zhang Wei‐Gang , Ji Zhao‐Hua , Shao Zhong‐Jun , Li Chun‐Ying
Published: May 2022

Background and objectives

This study aimed to investigate the association of vitiligo with metabolic syndrome (MetS) and its relevant components.

Material and methods

We searched PubMed, Web of Science, Cochrane Library and Embase databases from inception to March 30, 2021, for relevant studies. Cross‐sectional and case‐control studies that reported either the prevalence or odds ratio [OR] of MetS or its components in vitiligo patients were included. Data were pooled using either random‐effects model or fixed‐effects model according to the heterogeneity.

Results

Thirty studies with a total of 28,325 vitiligo patients were included. Significant associations were found between vitiligo and diabetes mellitus (pooled OR, 3.30; 95 % confidence interval [CI], 2.10–5.17) and between vitiligo and obesity (pooled OR, 2.08; 95 % CI, 1.40–3.11). The overall prevalence of hypertension in the patients with vitiligo was 19.0 % (95 % CI, 2.0 %–36.0 %).

Conclusions

Our findings suggest the association of vitiligo with diabetes mellitus, obesity, and hypertension. It is recommended for dermatologists to take these associations into account so as to identify potential comorbidities promptly in vitiligo patients. Additionally, vitiligo patients are advised to monitor the indexes including BMI, blood glucose, and blood pressure levels and the consultation with specialists is necessary upon abnormal changes of these indexes.
Non‐inferiority and clinical superiority of glucagon‐like peptide‐1 receptor agonists and sodium‐glucose co‐transporter‐2 inhibitors: Systematic analysis of cardiorenal outcome trials in type 2 diabetes
Authors: Zaccardi Francesco , Kloecker David E. , Khunti Kamlesh , Davies Melanie J.
Published: May 2022

Aims

Most trials leading to the approval of glucagon‐like peptide receptor agonists (GLP‐1RAs) and sodium‐glucose co‐transporter‐2 inhibitors (SGLT2is) were primarily designed to confirm their non‐inferiority to placebo (commonly using an upper 95% confidence limit threshold of 1.3) and, if confirmed, superiority (threshold 1): this asymmetry of margins (1 vs. 1.3) favours the active intervention. We aimed to quantify the probability of clinical superiority of the active treatment by applying the same threshold used to claim non‐inferiority.

Materials and Methods

We searched PubMed and Cochrane CENTRAL for cardiorenal outcome trials in subjects with type 2 diabetes published before 5 December 2021, to reconstruct from Kaplan‐Meier plots individual‐level data for the primary outcome or all‐cause mortality. We calculated Bayesian posterior densities to obtain the probability for a treatment effect (hazard ratio) <0.769, which is symmetric to the 1.3 threshold (i.e. its reciprocal 1/1.3), emulating a scenario where the active treatment is placebo and placebo is the active treatment.

Results

We extracted data from 27 Kaplan‐Meier plots (18 for the primary outcome, nine for mortality). Probabilities of clinical superiority to placebo varied significantly: for GLP‐1RAs, from a minimum of 0% to a maximum of 69% for the primary outcome and from 0% to 8% for mortality; corresponding estimates for SGLT2is were 0% to 96% and 0% to 93%. Probabilities were on average greater for SGLT2is, particularly in trials investigating kidney or heart failure outcomes.

Conclusions

The probability of clinical superiority to placebo varies widely across trials previously reported as showing superiority of GLP‐1RAs or SGLT2is compared with placebo. These results showed within‐ and between‐class differences, highlight the drawbacks of a binary interpretation of the results, particularly in the context of the current designs of non‐inferiority trials, and have implications for decision makers and future clinical recommendations.
Case–control exercise challenge study on the pathogenesis of high serum gamma‐glutamyl transferase activity in racehorses
Authors: Mann Sabine , Abuelo Angel , Stokol Tracy , Wakshlag Joseph J. , Bayly Warwick , Reed Steven , Gandy Jeff , Ramsay Joshua David , Divers Thomas J.
Published: May 2022

Background

High serum γ‐glutamyl‐transferase (GGT) activity syndrome in racehorses has been associated with maladaption to exercise. Investigation of affected horses before and immediately after standard exercise may provide critical insight into the syndrome's pathophysiology.

Objectives

To investigate blood biomarker changes in actively competing racehorses with high GGT activity associated with an exercise challenge.

Study design

Case–control study.

Methods

High GGT case (age: 2–3 years) and normal GGT control (age: 2–7 years) pairs (3 Thoroughbred, 4 Standardbred pairs) at least 3 months into their training/racing season were included. Horses with a recent history of high GGT activity (≥50 IU/L) without additional biochemical evidence of liver disease were identified by veterinarians. Horses were tested again in the week prior to a planned exercise challenge to confirm persistent increases in GGT activity. Controls from the same stable with similar training/racing intensity and serum GGT activity ≤36 IU/L were matched with each case. Blood samples were obtained immediately before, 15 and 120 min after exercise. Pre‐exercise serum samples were analysed for baseline select serum chemistries, selenium and vitamin E concentrations. Cortisol concentration and markers of oxidative status were measured in serum or plasma for all time points. Individual serum bile acid and coenzyme Q10 concentrations, plasma lipid mediator (fatty acids, oxylipids, isoprostanes) concentrations and targeted metabolomics analyses were performed using liquid chromatography‐mass spectrometry. Serum viral PCR for equine hepaci‐ and parvovirus was performed in each animal.

Results

Cases had higher baseline concentrations of total glutathione, taurocholic acid, cortisol and cholesterol concentrations and higher or lower concentrations of specific oxylipid and isoprostane mediators, but there were no case‐dependent changes after exercise.

Main limitations

Small sample size.

Conclusions

Results indicated that glutathione metabolism was altered in high GGT horses. Enhanced glutathione recycling and mild cholestasis are possible explanations for the observed differences.
5‐α reductase inhibition by Epilobioum fleischeri extract modulates facial microbiota structure
Authors: Sfriso Riccardo , Claypool Joshua , Roche Magalie , Imfeld Dominik
Published: May 2022

Background

Facial skin is a particularly complex environment made of different skin types such as sebaceous (forehead) and dry (cheeks). The skin microbiota composition on different facial sites has not yet been addressed.

Methods

We conducted a 4‐week‐long, single‐centre, randomized and placebo‐controlled clinical study involving 23 Caucasian females. We assessed both bacterial composition on five different facial areas and the microbiome modulatory effects resulting from the topical application of a plant extract (Epilobium fleischeri). Skin microbiome samples were collected before and after 4 weeks of product application. Microbiota profiling was performed via 16S rRNA gene sequencing, and relative abundance data were used to calculate differentials via a multinomial regression model.

Results

Via ‘reference frames’, we observed shifts in microbial composition after 4 weeks of twice‐daily product application and identify certain microbiota species, which were positively associated with the application of the product containing the Epilobium fleischeri extract. Staphylococcus hominis, Staphylococcus epidermidis, and Micrococcus yunnanensis appeared to be significantly enriched in the final microbiota composition of the active treatment group.

Conclusion

Facial skin was found to be colonized by an heterogenous microbiota, and the Epilobium fleischeri extract had a modulatory effect on commensal bacteria on the different facial sites.
Rapid detoxification of Jatropha curcas cake by fermentation with a combination of three microbial strains and characterization of their metabolic profiles
Authors: Zhang Zhenyu , Chang Yaqi , Wen Min , Zhao Hua , Chen Xiaoling , Tian Gang , Liu Guangmang , Cai Jingyi , Jia Gang
Published: May 2022

Aim

Our previous study reported a strain that can detoxify Jatropha curcas L. cake (JCC), but the detoxification duration is long. This study intends to explore the efficient detoxification of JCC through multi-strain collaborative fermentation to accelerate the detoxification process.

Methods and Results

Mucor circinelloides SCYA25 strain that we previously reported can effectively degrade the toxicity of JCC, and the newly screened Bacillus megaterium SCYA10 and Geotrichum candidum SCYA23 strains were used to detoxify JCC. Different solid-state-fermentation (SSF) parameters were optimized by single-factor tests and response surface methodology. A detoxification rate established by zebrafish toxicity of JCC at 96% was achieved under the following optimized conditions: the combination ratio of B. megaterium SCYA10, G. candidum SCYA23 and M. circinelloides SCYA25 at 2:3:1, a total injection amount of 15.25%, a feed to water ratio of 1:0.68, a fermentation temperature of 30.3°C and fermentation duration of 21.5 days. The protein content of fermented JCC (FJCC) increased, while the concentrations of ether extract, crude fibre and toxins were all degraded considerably. Metabolomics analysis revealed that the fermentation increased the contents of neurotransmitter receptor modulator, emulsifier, aromatic substances and insecticidal compounds, as well as decreasing the contents of oxidative stress and neurotoxic substances. A rat feeding trial showed that the growth performance of the rats provided with the FJCC diet was similar to that of the corn-soybean meal group, and no lesions in the liver and kidney were observed.

Conclusion

The co-bio-fermentation process can effectively detoxify JCC and improve its nutritional value, which means it could be served as a protein feed in animal husbandry.

Significance

The combination of three microbial strains can detoxify JCC in a safe and effective manner to provide a great potential alternative to soybean meal. The research also suggests that metabonomics and bioinformatics are useful tools for revealing the bio-detoxification mechanism.
Credit, land and survival work in rural Cambodia: Rethinking rural autonomy through a feminist lens
Authors: Natarajan Nithya , Brickell Katherine
Published: May 2022

This article explores the trajectory of three rural, precarious Cambodian women as they deploy land as a means of undertaking survival work in Cambodia. Using a gendered lens vis‐à‐vis the concept of autonomy, this article rethinks distress sales of land and collateralized land for microfinance borrowing as forms of everyday autonomy. By highlighting women's central role in undertaking social reproductive labour to reproduce the rural household, these acts of distress land sale and debt‐taking are understood as forms of ‘survival work’, acts that ensure the day‐to‐day survival of the household and form the basis for broader projects of autonomy. Although we remain ambivalent about the long‐term prospects for resistance through credit‐taking in particular, we ultimately highlight the need for greater attention to variegated oppositional agency in the path to autonomy to understand the gendered labour of everyday survival in rural life.
Evaluating the prevalence of Hepatitis E virus infection in a large cohort of European blood donors, 2015–2018
Authors: Healy Katie , Freij Urban , Ellerstad Marie , Aulin Linda B. S. , Brückle Lena , Hillmering Helen , Chen Margaret Sällberg , Gustafsson Rasmus
Published: May 2022

Hepatitis E virus (HEV) is endemic in Europe. However, standardized methods for the surveillance of HEV viremia in the general population are lacking. This study aimed to compare the incidence of HEV among blood donors in two European countries, Germany and Portugal, during the period 2015‐2018. The seasonal distribution of HEV infection, as well as host risk factors including age, sex, and blood group phenotype were explored. A total of 191,236 donations from Germany and Portugal were tested for HEV RNA in plasma mini‐pools of up to 96 donations using an internally controlled reverse transcription real‐time PCR (RT‐PCR) assay. The 95% cut‐off of the assay was 15 International Units (IU)/mL (CI 10‐35 IU/mL) as determined by dilution of the WHO International Standard for HEV RNA. Blood type was determined by agglutination and pattern recognition using the Beckmann Coulter PK 7300 AB0‐ and Rhesus‐Assay. The overall positivity rate was 0.09% with significantly more infections observed in the German cohort (p < 0.0001). Infections peaked in the summer months, and investigation of risk factors revealed that incidence was significantly higher amongst males (p = 0.0002), but was not associated with ABO or Rh(D) blood group phenotypes. No significant relationships between risk factors and viral load were observed. Our findings confirm that HEV infections are highly prevalent in Europe, even amongst otherwise healthy blood donors. Increasing awareness of the seasonal spread and risk factors for HEV transmission is of great importance for individuals susceptible to more severe forms of the disease, such as immunocompromised patients.
Second Language Vocabulary Learning through Ecologically Valid Classroom Practice Can Be Indexed by Event‐Related Potentials (ERPs). A Conceptual Replication Study
Authors: Vandenberghe Bert , Montero Perez Maribel , Reynvoet Bert , Desmet Piet
Published: May 2022

Previous research has suggested that Event‐Related Potentials (ERPs) can index form‐, meaning‐, and use‐related aspects of the second language (L2) vocabulary knowledge, through, respectively, a lexical decision task (LDT, targeting N400), a semantic relatedness task (SEMREL, targeting N400), and a grammatical judgment task (GJT, targeting P600/AN). Yet, those findings were established in the context of either laboratory‐based or longitudinal word learning studies. Therefore, this conceptual replication study investigates whether LDT, SEMREL, and GJT could reveal the aforementioned ERP components in the context of an ecologically valid short‐term intervention representative of L2 classroom practice. Twenty Dutch‐speaking participants performed reading and writing tasks in a computer‐assisted learning environment. Target words were 20 real L2 French verbs. ERPs were recorded immediately after the learning sessions. Results showed N400 for form‐ and meaning‐related knowledge and P600 for grammatical use. We conclude that ERPs can index L2 vocabulary knowledge gained through ecologically valid classroom activities.
Stomatal opening ratio mediates trait coordinating network adaptation to environmental gradients
Authors: Xie Jiangbo , Wang Zhongyuan , Li Yan
Published: May 2022

A trait coordination network is constructed through intercorrelations of functional traits, which reflect trait‐based adaptive strategies. However, little is known about how these networks change across spatial scales, and what drivers and mechanisms mediate this change.

This study bridges that gap by integrating functional traits related to plant carbon gain and water economy into the coordination network of Siberian elm (Ulmus pumila), a eurybiont that survives along a 3800 km environmental gradient from humid forest to arid desert.

Our results demonstrated that both stomatal density and stomatal size reached a physiological threshold at which adjustments in these traits were not sufficient to cope with the increased environmental stress. Network analysis further revealed that the mechanism for overcoming this threshold, the stomatal opening ratio, gratio, was represented by the highest values for centrality across different spatial scales, and therefore mediated the changes in the trait coordination network along environmental gradients. The mediating roles manifested as creating the highest maximum theoretical stomatal conductance (gsmax) but lowest possible gratio for pathogen defense in humid regions, while maintaining the gratio ‘sweet spot’ (c. 20% in this region) for highest water use efficiency in semihumid regions, and having the lowest gsmax and highest gratio for gas exchange and leaf cooling in arid regions.

These results suggested that the stomatal traits related to control of stomatal movement play fundamental roles in balancing gas exchange, leaf cooling, embolism resistance and pathogen defense. These insights will allow more accurate model parameterization for different regions, and therefore better predictions of species’ responses to global change.
Long‐term prevalence of taste and olfactory dysfunction in COVID‐19 patients: A cross‐sectional study
Authors: Reis Daiana , Sartoretto Suelen C. , Calasans‐Maia Monica D. , Louro Rafael S. , Moraschini Vittorio
Published: May 2022

Objectives

The objectives of the study were to investigate the long‐term prevalence of taste disorder (TD) and olfactory disorder (OD) and associated risk factors in the non‐hospitalized southeastern Brazil population of COVID‐19 patients.

Methods

This cross‐sectional open survey evaluated possible long‐term OD and TD in non‐hospitalized patients who had been diagnosed with COVID‐19 for more than 30 days, through an online self‐report questionnaire. Demographic data, comorbidities, symptoms, and the intensity of OD and TD at the time of diagnosis and at the time of completing the questionnaire were evaluated.

Results

Three hundred five responses were included. The reported prevalence of OD and TD was 72.9% and 67.4%, respectively, in the moment of diagnosis; after a mean follow‐up period of 179 days, 45% and 50% still had some degree of the symptoms. There was a positive correlation between age and the high prevalence of OD (p = 0.02). However, there was no correlation between age and TD (p = 0.961) and weight in relation to OD/TD (p = 0.500 and p = 0.636, respectively).

Conclusion

This study observed a high long‐term prevalence of OD and TD associated with COVID‐19, with a low recovery rate during the study period. There was a positive association between older participants and the prevalence of OD.
A generalized bird pollination system in Schotia brachypetala (Fabaceae)
Authors: Kiepiel I. , Brown M. , Johnson S. D.
Published: May 2022

Bird pollination systems are diverse, ranging from narrow‐tubed flowers pollinated by specialist nectarivores such as hummingbirds and sunbirds, to relatively open flowers pollinated by opportunistic (i.e. generalist) nectarivores. The role of opportunistic avian nectarivores as pollinators has historically been under‐appreciated. A key aspect to understanding the importance of opportunistic birds as pollinators is to investigate how efficiently they transfer pollen among flowers. Here, we document the pollination and breeding systems of Schotia brachypetala, a southern African tree known as the ‘weeping boer‐bean’ on account of its prolific production of dilute hexose‐dominated nectar. The cup‐shaped flowers of this tree attract a large number of bird species, including both opportunistic and specialist nectarivores.

We identified floral visitors using observations and camera traps and quantified the floral traits responsible for animal attraction. We documented the breeding system, used selective pollinator exclusion to test the contribution of birds to fecundity, and performed supplemental pollination to test for pollen limitation. Single‐visit pollen deposition trials were undertaken to determine the efficacy of bird pollinators.

Controlled hand‐pollination experiments showed that S. brachypetala is genetically self‐incompatible and therefore dependent on pollinators for seed production. Supplemental hand‐pollination experiments showed that natural fecundity is limited by either the amount and/or the quality of pollen on stigmas. Flowers from which birds but not insects were experimentally excluded set fewer seeds than open control flowers. Opportunistic birds deposited more pollen per visit than did specialist sunbirds.

We conclude that S. brachypetala has a generalized bird pollination system that mainly involves opportunistic nectarivores.
Vegetative growth and belowground expansion from transplanted low‐arctic tundra turfs
Authors: Hnatowich Ian G. , Lamb Eric G. , Stewart Katherine J.
Published: May 2022

Whole‐turf transplantation is a restoration method used to restore plant communities within disturbed arctic environments. Transplant expansion and restoration success is often determined based on aboveground characteristics, and to our knowledge, this is the first investigation of belowground expansion from transplanted turfs. In this growth chamber experiment, turfs harvested from undisturbed tundra near Rankin Inlet, Nunavut, Canada, were exposed to fertilized and unfertilized substrates to determine the effect of adjacent nutrient‐enrichment on plant community composition within the turfs and substrates, as well as above and belowground biomass and expansion. Next‐generation sequencing was used to determine the species identity of expanding roots. Our results show that fertilization of substrates surrounding tundra transplants did not alter the community composition of the turfs, but did increase biomass and expansion, as well as biological soil crust cover on the adjacent substrate. Belowground biomass far exceeded aboveground, revealing the importance of evaluating belowground roots and rhizomes that dominate the vegetative biomass within arctic ecosystems. Investigation of belowground development is likely to provide holistic interpretations of restoration success and should not be ignored in future transplantation studies.