bluuebunny/crossref_metadata_2025 huggingface dataset:
Opening the species box: what parsimonious microscopic models of speciation have to say about macroevolution
Authors: Couvert Élisa , Bienvenu François , Duchamps Jean-Jil , Erard Adélie , Miró Pina Verónica , Schertzer Emmanuel , Lambert Amaury
Published: October 2024

In the last two decades, lineage-based models of diversification, where species are viewed as particles that can divide (speciate) or die (become extinct) at rates depending on some evolving trait, have been very popular tools to study macroevolutionary processes. Here, we argue that this approach cannot be used to break down the inner workings of species diversification and that “opening the species box” is necessary to understand the causes of macroevolution, but that too detailed speciation models also fail to make robust macroevolutionary predictions. We set up a general framework for parsimonious models of speciation that rely on a minimal number of mechanistic principles: (a) reproductive isolation is caused by excessive dissimilarity between genotypes; (b) dissimilarity results from a balance between differentiation processes and homogenizing processes; and (c) dissimilarity can feed back on these processes by decelerating homogenization. We classify such models according to the main homogenizing process: (a) clonal evolution models (ecological drift), (b) models of genetic isolation (gene flow), and (c) models of isolation by distance (spatial drift). We review these models and their specific predictions on macroscopic variables such as species abundances, speciation rates, interfertility relationships, or phylogenetic tree structure. We propose new avenues of research by displaying conceptual questions remaining to be solved and new models to address them: the failure of speciation at secondary contact, the feedback of dissimilarity on homogenization, and the emergence in space of breeding barriers.
The joint evolution of separate sexes and sexual dimorphism
Authors: Lesaffre Thomas , Pannell John R , Mullon Charles
Published: October 2024

Dioecious plants are frequently sexually dimorphic. Such dimorphism, which reflects responses to selection acting in opposite directions for male and female components of fitness, is commonly thought to emerge after separate sexes evolved from hermaphroditism. But associations between allocation to male and female function and traits under sexual conflict may well also develop in hermaphroditic ancestors. Here, we show that variation in sex allocation and a trait under sexual conflict inevitably generates an advantage to sexual specialization, fuelling the transition to dioecy. In the absence of constraints, this leads to the joint evolution of separate sexes and sexual dimorphism through the build-up of an association between sex allocation and the conflict trait, such that eventually the population consists of unisexuals expressing their sex-specific optima. We then investigate how such association might materialize genetically, either via recombination suppression or via sex-dependent expression, and show that the genetic architecture of sex allocation and the conflict trait readily evolves to produce the association favoured by selection. Finally and in agreement with previous theory, we demonstrate that limited dispersal and self-fertilization, which are pervasive ecological characteristics of flowering plants, can offset the advantage of sexual specialization generated by sexual conflict and thus maintain hermaphroditism. Taken together, our results indicate that advantages to sexual specialization are inevitable when there is conflict between sexual functions in hermaphrodites, but these advantages can be counterbalanced by ecological benefits of hermaphroditism.
Agroecological importance of smooth brome in managing wheat stem sawfly (Hymenoptera: Cephidae) via associated braconid parasitoids
Authors: Strand Jackson R , Peterson Robert K D , Sterling Tracy M , Weaver David K
Published: October 2024

Wheat stem sawfly (WSS), Cephus cinctus Norton (Hymenoptera: Cephidae), is a major pest of cereal crops throughout the Northern Great Plains of North America. Native parasitoids, Bracon cephi (Gahan) and B. lissogaster Muesebeck (Hymenoptera: Braconidae), play a key role in suppressing WSS populations and limiting associated damage. Smooth brome grass (Bromus inermis Leyss.) serves as a potential trap reservoir for WSS when grown in areas surrounding wheat (Triticum aestivum L.) fields in Montana. Its unique biology allows it to support high WSS infestation while promoting significant larval mortality throughout the growing season. Late-season WSS survivors can then serve as hosts for WSS parasitoids. Our study investigated smooth brome as a host refuge for WSS parasitoids. We measured WSS larval infestation and survival rate inside smooth brome grown within WSS-inclusion cages, finding a maximum infestation of 66.5% and an end-of-year WSS survival of 5.7%. In addition, we collected stems from sites in central and north-central Montana to measure the WSS infestation and parasitoid prevalence in wheat and adjacent smooth brome. WSS infestation was high in both Big Sandy (64.5% smooth brome, 65.7% adjacent wheat) and Moccasin, MT (50.6%, 38.6%). Year-end WSS larval mortality was 43.6% greater in smooth brome compared to adjacent wheat at both field sites, but both hosted similar numbers of WSS parasitoids. This research underscores the importance of smooth brome in providing a sustainable host refuge for WSS parasitoids and highlights its significant role in supporting the economics of wheat cultivation.
Absence of heterosis for hypoxia tolerance in F1 hybrids of Tigriopus californicus
Authors: Deconinck Aimee , Madalone Olivia F , Willett Christopher S
Published: October 2024

Hybridization produces a range of outcomes from advantageous to disadvantageous, and a goal of genetic research is to understand the gene interactions that generate these outcomes. Interactions between cytoplasmic elements, such as mitochondria, and the nucleus may be particularly vulnerable to accruing disadvantageous combinations as a result of their different rates of evolution. Consequently, mitonuclear incompatibilities may play an important role in hybrid outcomes even if their negative impacts could be masked for some fitness measures by heterosis in first-generation (F1) hybrids. We used Tigriopus californicus, a model system for mitonuclear incompatibilities that is also known for exhibiting heterosis in the F1 generation and outbreeding depression in later generations, to test whether heterosis or outbreeding depression would occur when mitonuclear mismatch was paired with a stress that heavily impacts mitochondrial processes—specifically, hypoxia. We generated 284 parental and 436 F1 hybrids from four population crosses (720 total) and compared parental and F1 populations for hypoxia tolerance. We observed that, on average, F1 hybrids were less likely to survive a hypoxia stress test than parental populations, although we did not detect a statistically significant trend (P = 0.246 to 0.614). This suggests that hypoxia may be a particularly intense stressor for mitonuclear coordination and hybridization outcomes vary by trait.
Patient-reported outcome measure (PROM) programs for monitoring symptoms among patients treated with immunotherapy: a scoping review
Authors: Lambert Sylvie D , Soldera Sara , Kazdan Jordana , Frati Francesca , Slominska Anita , Boutin Melina , Samouelian Vanessa , Letendre Caroline , Bilodeau Karine , Howell Doris , Breton Karine Le , Gratton Michel-Olivier
Published: October 2024

Background

Monitoring toxicities among patients receiving immune checkpoint inhibitors using patient-reported outcome measures (PROMs) is relatively recent. This scoping review aims to guide decision making in the development of PROMs programs for patients receiving immune checkpoint inhibitor therapy.

Methods

Four electronic databases were searched from inception to January 2024. Data on PROM programs for patients receiving immune checkpoint inhibitors (eg, PROMs used, frequency) were extracted. Two authors with established interrater reliability screened titles, abstracts, and full texts. A narrative synthesis identified patterns in the data.

Results

A total of 22 articles described 16 unique multicomponent, electronic PROM programs for patients receiving immune checkpoint inhibitor therapy, mainly developed for remote monitoring of toxicities between appointments. Patients typically completed 18-26 items from the Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE) or Common Terminology Criteria for Adverse Events (CTCAE) weekly, with high adherence and satisfaction. Commonly monitored symptoms were diarrhea, fatigue, shortness of breath, cough, nausea, decreased appetite, rash, joint pain, pain, and mood. Other features of PROMs programs included clinician alerts, with some programs only flagging symptoms that had an impact on treatment. Some programs also or only sent alerts to patients to contact their clinicians and gave access to symptom management information. In terms of efficacy, the only consistent finding was an increase in quality of life.

Conclusions

The findings of this scoping review provide some indication as to which components of a PROM program are promising. However, as the evidence base for using PROMs among patients receiving immune checkpoint inhibitors is growing, many questions remain, including which symptoms to monitor, using which PROM, and at what frequency. More trials are needed to answer these questions and to determine how best to implement PROMs among patients receiving immune checkpoint inhibitor in clinical practice.
Multivariate Bayesian variable selection for multi-trait genetic fine mapping
Authors: Canida Travis , Ke Hongjie , Chen Shuo , Ye Zhenyao , Ma Tianzhou
Published: October 2024

Genome-wide association studies (GWAS) have identified thousands of single-nucleotide polymorphisms (SNPs) associated with complex traits, but determining the underlying causal variants remains challenging. Fine mapping aims to pinpoint the potentially causal variants from a large number of correlated SNPs possibly with group structure in GWAS-enriched genomic regions using variable selection approaches. In multi-trait fine mapping, we are interested in identifying the causal variants for multiple related traits. Existing multivariate variable selection methods for fine mapping select variables for all responses without considering the possible heterogeneity across different responses. Here, we develop a novel multivariate Bayesian variable selection method for multi-trait fine mapping to select causal variants from a large number of grouped SNPs that target at multiple correlated and possibly heterogeneous traits. Our new method is featured by its selection at multiple levels, incorporation of prior biological knowledge to guide selection and identification of best subset of traits the variants target at. We showed the advantage of our method over existing methods via comprehensive simulations that mimic typical fine-mapping settings and a real-world fine-mapping example in UK Biobank, where we identified critical causal variants potentially targeting at different subsets of addictive behaviours and risk factors.
Traffic count data analysis using mixtures of Kato–Jones distributions
Authors: Nagasaki Kota , Kato Shogo , Nakanishi Wataru , Jones M C
Published: October 2024

We discuss the modelling of traffic count data that show the variation of traffic volume within a day. For the modelling, we apply mixtures of Kato–Jones distributions in which each component is unimodal and affords a wide range of skewness and kurtosis. We consider two methods for parameter estimation, namely, a modified method of moments and the maximum-likelihood method. These methods were seen to be useful for fitting the proposed mixtures to our data. As a result, the variation in traffic volume was classified into the morning and evening traffic whose distributions have different shapes, particularly different degrees of skewness and kurtosis.
Peritoneal invagination hernia in the virgin abdomen
Authors: Thomas Evan A , Harris Adam S
Published: October 2024

Hernias are a common cause of small bowel obstruction. Many different classifications of hernias exist, all differing by location throughout the abdomen and hernia contents. We present a case report that describes a unique hernia—a peritoneal invagination hernia—which may lead to small bowel obstruction. The peritoneal invagination hernia is a defect in the peritoneum, in this case located on the right anterolateral abdominal wall, allowing small bowel to enter and become incarcerated. In our patient, the peritoneal defect was circular with smooth, rolled borders. The defect contained intact peritoneum overlying intact transversalis fascia. The patient had no prior abdominal surgeries. This hernia differs by location and etiology from preperitoneal interparietal hernias, which are found in the inguinal and femoral regions. This case describes a newly characterized abdominal hernia which is hypothesized to be due to a prior intra-abdominal inflammatory process.
Progressive dysphagia from an esophageal liposarcoma, a complex problem in a challenging setting
Authors: Endara Santiago A , Dávalos Gerardo A , Finke Ana G , Ayala Veronica , Montalvo Nelson A , Munoz-Palomeque Santiago , Molina Gabriel A
Published: October 2024

Esophageal lipomatous tumors are extremely rare, and due to their nonspecific clinical manifestations, distinguishing them is nearly impossible without the aid of histopathology, immunohistochemistry, and molecular analysis. Complete resection with clear margins is the treatment of choice to avert metastasis, improve prognosis, and prevent complex complications due to the polyp growth and location. We present the case of a 70-year-old male who presented in 2023 with dysphagia due to an esophageal polyp; surgery was recommended. However, he did not accept any treatment due to fear. One year later, and since his symptoms worsened, he finally decided to undergo endoscopic treatment at another medical institution. However, during that procedure, he suffered severe asphyxia, which caused a cardiopulmonary arrest. Once he partially recovered and because he continued with dysphagia, surgery was completed, and the polyp was removed. The final diagnosis was esophageal liposarcoma.
“Dispossession”: the movement of hermeneutics and prayer in Paul Ricoeur and Rowan Williams
Authors: Wright O T I
Published: October 2024

In this article, I argue for a constructive relationship between the philosophical discipline of hermeneutics, and the theological practice of prayer. The justification for this claim is the use of the same word “dispossession” and cognate ideas in the arguments of Paul Ricoeur (1913–2005) regarding hermeneutics, and the arguments of Rowan Williams (b.1950) regarding integrity in theological language with its clearest paradigm of prayer. In order to focus this argument, in the first Section, I consider Immanuel Kant’s (1724–1804) idea of prayer, the nearness of the role of hermeneutics to his notion, and reveal how both Ricoeur and Williams can be seen to be reacting—either for or against—Kant’s approach. It is true, as I will discuss, that hermeneutics and prayer have been linked before—but usually prayer only in relation to Scriptural hermeneutics. In affirming and deepening that claim to hermeneutics more generally, therefore, a fresh case is made about the nearness of spiritual practice and philosophical method, and about the contribution of theology to reading more generally.
Comparison of Tuberculosis Cases in Military Personnel Versus Civilians: A Retrospective Descriptive Study
Authors: Sence Étienne , Billhot Magali , Gaspard Wanda , Lorenzi Jean-Noel , Dubourdieu Anne-Pierre , Foissaud Vincent , Bernard Christine , Aletti Marc , Doutrelon Caroline
Published: October 2024

Introduction

Tuberculosis (TB) remains a leading cause of death from infectious diseases worldwide. Military personnel are particularly vulnerable to TB because of the factors like deployments to endemic regions and close-quarters living. This study aims to compare the characteristics and outcomes of symptomatic TB cases between military and civilian patients treated at 2 French military hospitals, with a specific focus on diagnostic delay.

Materials and Methods

This retrospective observational study included patients over 18 years old with culture-confirmed symptomatic TB treated between 2008 and 2021. Military patients (Group A) were compared to civilian patients (Group B), matched by age and sex. Data collected included demographic details, diagnostic delay, clinical presentations, and treatment outcomes. Statistical analyses were performed using chi-squared tests and Mann-Whitney tests, with significance set at P < .05.

Results

A total of 17 military and 38 civilian patients were included in the study. The median diagnostic delay was shorter for military patients at 49 days, compared to 64 days for civilians, although this difference was not statistically significant (P = .42). In the military group, 59% had been deployed to TB endemic regions, with 35% showing symptoms during operational missions. Clinical presentations and microbiological findings were similar between the two groups. Notably, two military patients were infected with Mycobacterium canettii, likely linked to deployments in Djibouti, where this strain is endemic. The military population showed a significant burden of physical sequelae, with 25% experiencing lasting physical impairments post-treatment.

Conclusion

Tuberculosis presentation and outcomes in military and civilian patients were generally comparable. Early diagnosis remains essential to minimize disease severity and operational impact, particularly in military settings.
Evaluating the Diagnostic Inter-rater Reliability Between Virtual and In-person Sick-call Examinations at a Military Dental Treatment Facility
Authors: Vader Vladimir , Kosaraju Amar , Gedge Joseph L , Mitchell Terrell M , Ruff Ryan R , Vandewalle Kraig S
Published: October 2024

Introduction

Teledentistry, also known as “virtual” dental examinations, is an innovative approach to increasing access to care. The objective of this study was to evaluate the diagnostic inter-rater reliability between virtual and in-person examinations for patients seeking emergency dental care (sick call) at a military dental treatment facility.

Materials and Methods

One hundred subjects received both virtual and in-person examinations on the same day, in random order. The virtual examiner and subject were stationed in separate rooms and used only a laptop equipped with a camera, microphone, and speaker to complete the virtual exam. In contrast, the in-person examiner had access to all standard care modalities in a dental treatment room. After the first encounter, the subject proceeded to the corresponding virtual or in-person exam, and both examiners determined a diagnosis. Inter-rater agreement was determined between the two encounters for both diagnosis specialty category and diagnostic code using the Kappa coefficient.

Results

The results of the inter-rater analyses showed a Kappa score of 0.644 for the diagnosis specialty category (P < .001) and a Kappa score of 0.714 for diagnostic codes (P < .001). Both analyses indicated “substantial” agreement.

Conclusions

We conclude that teledentistry can be an effective tool for determining a diagnosis and improving access to care for dental emergencies at military dental treatment facilities.
Optical turbulence in the atmospheric surface layer at the Pamir Plateau Muztagh-ata site
Authors: Gu Wenbo , Esamdin Ali , Bai Chunhai , Zhang Xuan , Feng Guojie , Pu Guangxin , Wang Letian , Sun Gaowen , Wang Haozhi , Shen Lixian
Published: October 2024

In this paper, we conducted a detailed analysis of optical turbulence in the atmospheric surface layer (ASL) at the Muztagh-ata site during on-site testing. We utilized ultrasonic anemometers positioned on a 30-m tower to collect and process data at five height levels, obtaining data from 2021 October 1 to the present. We investigated the behaviour of optical turbulence parameters ($C_n^2$ and seeing $\varepsilon$) in the ASL. Night-time $C_n^2$ primarily fluctuated in the range of $10^{-16}$ to $10^{-14}$, exhibiting an exponential decrease with height. During the day, it showed a $h^{-0.82}$ dependency, while at night, it displayed a $h^{-0.48}$ dependency. Additionally, we presented the distribution of seeing across different layers within the ASL, showing a gradual decrease with increasing height, with a median seeing of 0.24 arcsec at night-time and 0.48 arcsec at daytime between 6 and 30 m. We investigated the relationship between surface temperature inversion, seeing in the ASL, and wind speed at the site. Our results show that under temperature inversion conditions, seeing significantly improves and is often accompanied by low to moderate wind speeds, while high wind speeds are usually associated with poorer seeing. Preliminary calculations and observational results, combined with the high altitude and unique geographical location, suggest that the Muztagh-ata site has the potential to be an outstanding optical astronomical observatory in the western plateau of China.
Global coupling of R-loop dynamics with RNA polymerase II modulates gene expression and early development of Drosophila
Authors: Zhang Xianhong , Liang Shao-Bo , Yi Zhuoyun , Qiao Zhaohui , Xu Bo , Geng Huichao , Wang Honghong , Yin Xinhua , Tang Mingliang , Ge Wanzhong , Xu Yong-Zhen , Liang Kaiwei , Fan Yu-Jie , Chen Liang
Published: October 2024

R-loops are involved in many biological processes in cells, yet the regulatory principles for R-loops in vivo and their impact on development remain to be explored. Here, we modified the CUT&Tag strategy to profile R-loops in Drosophila at multiple developmental stages. While high GC content promotes R-loop formation in mammalian cells, it is not required in Drosophila. In contrast, RNAPII abundance appears to be a universal inducing factor for R-loop formation, including active promoters and enhancers, and H3K27me3 decorated repressive regions and intergenic repeat sequences. Importantly, such a regulatory relationship is dynamically maintained throughout development, and development-related transcription factors may regulate RNAPII activation and R-loop dynamics. By ablating Spt6, we further showed the global R-loop induction coupled with RNAPII pausing. Importantly, depending on the gene length, genes underwent up- or down-regulation, both of which were largely reversed by rnh1 overexpression, suggesting that R-loops play a significant role in the divergent regulation of transcription by Spt6 ablation. DNA damage, defects in survival, and cuticle development were similarly alleviated by rnh1 overexpression. Altogether, our findings indicate that dynamic R-loop regulation is dictated by RNAPII pausing and transcription activity, and plays a feedback role in gene regulation, genome stability maintenance, and Drosophila development.
BGC Atlas: a web resource for exploring the global chemical diversity encoded in bacterial genomes
Authors: Bağcı Caner , Nuhamunada Matin , Goyat Hemant , Ladanyi Casimir , Sehnal Ludek , Blin Kai , Kautsar Satria A , Tagirdzhanov Azat , Gurevich Alexey , Mantri Shrikant , von Mering Christian , Udwary Daniel , Medema Marnix H , Weber Tilmann , Ziemert Nadine
Published: October 2024

Secondary metabolites are compounds not essential for an organism’s development, but provide significant ecological and physiological benefits. These compounds have applications in medicine, biotechnology and agriculture. Their production is encoded in biosynthetic gene clusters (BGCs), groups of genes collectively directing their biosynthesis. The advent of metagenomics has allowed researchers to study BGCs directly from environmental samples, identifying numerous previously unknown BGCs encoding unprecedented chemistry. Here, we present the BGC Atlas (https://bgc-atlas.cs.uni-tuebingen.de), a web resource that facilitates the exploration and analysis of BGC diversity in metagenomes. The BGC Atlas identifies and clusters BGCs from publicly available datasets, offering a centralized database and a web interface for metadata-aware exploration of BGCs and gene cluster families (GCFs). We analyzed over 35 000 datasets from MGnify, identifying nearly 1.8 million BGCs, which were clustered into GCFs. The analysis showed that ribosomally synthesized and post-translationally modified peptides are the most abundant compound class, with most GCFs exhibiting high environmental specificity. We believe that our tool will enable researchers to easily explore and analyze the BGC diversity in environmental samples, significantly enhancing our understanding of bacterial secondary metabolites, and promote the identification of ecological and evolutionary factors shaping the biosynthetic potential of microbial communities.
Tobacco Outlet Availability, Density, and Proximity in Rural Areas in the Netherlands: An Ex ante Evaluation of the Impact of Tobacco Sales Bans
Authors: van Deelen Tessa R D , Belmonte Simona , Veldhuizen Els M , van den Putte Bas , Kunst Anton E , Kuipers Mirte A G
Published: October 2024

Introduction

The Netherlands will ban tobacco sales from supermarkets in 2024 and from petrol stations and small outlets after 2030 (tobacco specialist shops exempted). Previous studies showed that this will reduce outlet availability, density, and proximity in Dutch urban areas.

Aims and Methods

This study assessed the distribution of tobacco outlets in Dutch rural areas, and potential outlet reductions after implementation of these bans. A cross-sectional quantitative audit of tobacco outlets was conducted in seven rural municipalities in the Netherlands. Tobacco outlet availability (N), density (per 10 000 capita and km2), and proximity (average distance of a street or city block to the closest tobacco outlet [meters]) were calculated, as well as predicted changes after implementation of upcoming sales bans.

Results

97 tobacco retailers were identified. There were 5.00 outlets per 10 000 capita and 0.09 per km2. The tobacco sales ban in supermarkets is expected to reduce availability by 57 outlets, and density by 2.94/10 000 per capita and 0.05/km2, while increasing average distance by 824 m. A tobacco sales ban in petrol stations is expected to further reduce availability (−26), density/10 000 capita (−1.34), and density/km2 (−0.02), while increasing distance (+1595 m). For small outlets, these numbers are −12, −0.62, and −0.01, respectively, while the closest tobacco outlet will be mostly outside municipality borders.

Conclusions

Assuming no new tobacco outlets will emerge in response to future tobacco sales bans, the bans could nearly eliminate tobacco outlets in rural areas. To meet the demand for tobacco, there is a risk that new tobacco specialist shops will be established.

Implications

This study shows the potential impact of tobacco sales bans in, sequentially, supermarkets, petrol stations, and small outlets on tobacco outlet density and proximity in rural municipalities in the Netherlands. A ban on tobacco sales in supermarkets, petrol stations, and small outlets could reduce the number of tobacco outlets in rural areas of the Netherlands to nearly zero. As a result, supermarkets may be inspired to open tobacco specialist shops, which are exempt from the bans. To prevent the proliferation of such shops, retail licensing schemes may need to be established.
MIKC*-type MADS transcription factors control JINGUBANG expression and the degree of pollen dormancy in Arabidopsis
Authors: Zhang Liguang , Ma Fei , Duan Guangxing , Ju Yan , Yu Tingqiao , Zhang Quan , Sodmergen
Published: October 2024

While pollen dormancy has been proposed to play a necessary role in sexual reproduction, it remains poorly understood. Here, we used traditional pollen germination assays to characterize dormancy. Our results underscore variation in the degree of dormancy between individual pollen grains. In addition, we provide evidence that JINGUBANG (JGB), previously defined as a negative regulator of pollen germination in Arabidopsis (Arabidopsis thaliana), is responsible for the uneven degrees of pollen dormancy, as asynchronous pollen germination in vitro reflected varied expression levels of JGB. We identified 5 cis-acting elements, including 4 CArG-boxes and the previously uncharacterized element ERE7, as essential for the initiation and enhancement of JGB expression. A 10-bp sequence between CArG-box 3 and ERE7, likely the result of an inverse DNA loop formed between CArG-box 3 and CArG-box 4, was required for robust gene expression. In addition, the pollen-specific AtMIKC*-type MADS transcription factors AGAMOUS-LIKE 30 (AGL30), AGL65, AGL66, AGL94, and AGL104 activated JGB transcription. Notably, the transactivation levels differed among the obligate AtMIKC* heterodimers tested. Our results indicate that distinct AtMIKC* complexes formed in individual pollen grains direct pollen dormancy to uneven degrees, which is likely an adaptive trait that ensures broader pollen dispersal under adverse environmental conditions.
Deciphering acclimation to sublethal combined and sequential abiotic stresses in Arabidopsis thaliana
Authors: Jiang Zhang , Verhoeven Ava , Li Yihong , Geertsma Romy , Sasidharan Rashmi , van Zanten Martijn
Published: October 2024

Plants are frequently exposed to environmental challenges. Responses to sublethal abiotic stress combinations are complex and often distinct from responses to individual stresses and remain poorly understood. Investigating traits and molecular factors mediating acclimation to stress combinations is essential for the development of climate change-resilient field crops. Here, we studied the morphological, physiological, and molecular responses of Arabidopsis thaliana to (i) co-occurring high temperature and drought and (ii) flooding followed by drought, both of which have increased in frequency due to climate change, and the individual component stresses: high temperature, drought, and flooding. A set of 15 physiological and morphological traits were assessed during single and combined stresses. By combining these comprehensive trait analyses with transcriptome characterization, we detected generally additive negative effects of simultaneous or sequential stresses on plant morphology and physiology compared with the corresponding individual stresses. Although drought had a mild effect on various growth, morphological, and physiological traits in both stress combinations, a unique transcriptome signature emerged upon combination with high temperature simultaneously, or flooding sequentially. Molecular processes identified as important for multistress resilience included plastid–nucleus communication, abscisic acid signaling, and photo-acclimation. Based on the RNA-seq data, a set of 39 genes were identified as potential multistress response regulators. Mutants were tested to validate the contribution of these genes to plant survival and phenotypic acclimation under combined stress. We confirmed the involvement of several genes. Among the identified factors were EARLY FLOWERING 6 (ELF6) and ARABIDOPSIS TÓXICOS EN LEVADURA 80 (ATL80), with substantial effects on plant growth, leaf development, and plant survival (wilting) during high-temperature drought and postsubmergence drought, respectively.
Internet-based surveillance to track trends in seasonal allergies across the United States
Authors: Stallard-Olivera Elias , Fierer Noah
Published: October 2024

Over a quarter of adults in the United States suffer from seasonal allergies, yet the broader spatiotemporal patterns in seasonal allergy trends remain poorly resolved. This knowledge gap persists due to difficulties in quantifying allergies as symptoms are seldom severe enough to warrant hospital visits. We show that we can use machine learning to extract relevant data from Twitter posts and Google searches to examine population-level trends in seasonal allergies at high spatial and temporal resolution, validating the approach against hospital record data obtained from selected counties in California, United States. After showing that internet-derived data can be used as a proxy for aeroallergen exposures, we demonstrate the utility of our approach by mapping seasonal allergy-related online activity across the 144 most populous US counties at daily time steps over an 8-year period, highlighting the spatial and temporal dynamics in allergy trends across the continental United States.
Scleroderma renal crisis, an increasingly rare but persistently challenging condition: a retrospective cohort study
Authors: Shah Rushab C , Morrisroe Kathleen , Stevens Wendy , Ferdowsi Nava , Proudman Susanna , Nikpour Mandana , Ross Laura J
Published: October 2024

Objective

Scleroderma renal crisis (SRC) is associated with high morbidity and mortality and there remain unmet needs regarding early identification and treatment. We aimed to assess risk factors for and the outcomes of SRC at a large Australian tertiary hospital.

Methods

Seventeen incident SRC cases were diagnosed between 2012 and 2022. Demographic, SSc manifestations and treatment data were extracted. Using data from the Australian Scleroderma Cohort Study (n = 483), logistic regression analysis was performed to identify risk factors for SRC.

Results

The prevalence of SRC was 3.52%. The median SSc disease duration at SRC onset was 2 years [interquartile range (IQR) 1–4]. Peak creatinine occurred at a median of 11 days (IQR 5–14) post-SRC diagnosis, with a median peak creatinine of 144 µmol/l (IQR 86–306). Nine (52.94%) SRC patients had evidence of acute neurologic and/or cardiac complications. Acute haemofiltration was required in 3 (17.65%) patients. Over the follow-up period, 7 (41.18%) SRC patients died 2.75 years (IQR 0.74–7.25) after SRC onset. Patients with SRC were more likely to be male [odds ratio (OR) 9.73 (95% CI 3.57, 26.56)], have diffuse disease [OR 23.16 (95% CI 5.22, 102.80)] and have antibodies to Scl70 [OR 3.34 (95% CI 1.24, 9.04)] or RNA polymerase III (RNAPIII) [OR 5.15 (95% CI 1.91, 13.89)].

Conclusion

SRC is an uncommon manifestation, but outcomes remain poor. A significant proportion of patients presenting with SRC in Australia are positive for Scl70 or RNAPIII antibody. Despite relatively low peak serum creatinine and rates of renal replacement therapy, SRC was still associated with significant mortality.
Healthcare utilization in general practice and hospitals preceding a diagnosis of systemic sclerosis: a nationwide registry study
Authors: Praastrup Fie J , de Thurah Annette , Hauge Ellen M , Rasmussen Linda A , Næser Esben U
Published: October 2024

Objectives

Irreversible tissue damage is frequently present at the time of diagnosis in systemic sclerosis (SSc), which calls for earlier diagnosis. This study estimated healthcare utilization three years before the diagnosis of SSc.

Methods

We conducted a population-based cohort study using data from Danish national registries. Incident patients diagnosed with SSc between 1 January 2005 and 31 December 2018 were matched by age and gender with 10 references without SSc. The date of diagnosis was the index date. We estimated quarterly rates and adjusted incidence rate ratios (IRRs) with 95% confidence intervals (CI) of healthcare utilization in the three years preceding the diagnosis for patients with SSc and their references.

Results

A total of 1650 SSc patients (1255 women and 395 men) and 16 500 non-SSc references were included. The mean age was 58 years (interquartile range 48–68). Three years before diagnosis, patients with SSc had more contacts with general practice (IRRwomen = 1.43 [95% CI: 1.33; 1.53], IRRmen = 1.47 [95% CI: 1.26; 1.71]) and hospitals (IRRwomen = 1.86 [95% CI: 1.62; 2.14], IRRmen = 2.70 [95% CI: 2.04; 3.58]) compared with their references. In the last three months before diagnosis, patients with SSc had significantly more contacts with general practice (IRRwomen = 2.30 [95% CI: 2.16; 2.44], IRRmen = 2.98 [95% CI: 2.64; 3.35]) and hospitals (IRRwomen = 5.62 [95% CI: 5.08; 6.20], IRRmen = 9.53 [95% CI: 7.81; 11.63]).

Conclusion

The higher use of healthcare services in general practice and hospitals in the three years before diagnosis suggests an opportunity to facilitate earlier diagnosis and treatment of SSc.
Development and intra-renal delivery of renal progenitor organoids for effective integration in vivo
Authors: Lim Diana , Kim Ickhee , Song Qianqian , Kim Ji Hyun , Atala Anthony , Jackson John D , Yoo James J
Published: October 2024

Renal progenitor organoids have been proposed as a source of tissue for kidney regeneration; however, their clinical translatability has not been demonstrated due to an inability to mass-produce comprehensive renal progenitor organoids and the lack of an effective intra-renal delivery platform that facilitates rapid integration into functionally meaningful sites. This study addresses these shortcomings. Human-induced pluripotent stem cells were differentiated into renal progenitor cells using an established protocol and aggregated using a novel assembly method to produce high yields of organoids. Organoids were encapsulated in collagen-based scaffolds for in vitro study and in vivo implantation into mouse renal cortex. In vitro, the organoids demonstrated sustained cell viability and renal structure maturation over time. In vivo delivered organoids showed rapid integration into host renal parenchyma while showing tubular and glomerular-like structure development and maturity markers. This proof-of-concept study presents many promising results, providing a system of renal organoid formation and delivery that may support the development of clinically translatable therapies and the advancement of in vitro renal organoid studies.
Complex Hybridization in a Clade of Polytypic Salamanders (Plethodontidae: Desmognathus) Uncovered by Estimating Higher-Level Phylogenetic Networks
Authors: Pyron R Alexander , O’Connell Kyle A , Myers Edward A , Beamer David A , Baños Hector
Published: October 2024

Reticulation between radiating lineages is a common feature of diversification. We examine these phenomena in the Pisgah clade of Desmognathus salamanders from the southern Appalachian Mountains of the eastern United States. The group contains 4–7 species exhibiting 2 discrete phenotypes, aquatic “shovel-nosed” and semi-aquatic “black-bellied” forms. These ecomorphologies are ancient and have apparently been transmitted repeatedly between lineages through introgression. Geographically proximate populations of both phenotypes exhibit admixture, and at least 2 black-bellied lineages have been produced via reticulations between shovel-nosed parentals, suggesting potential hybrid speciation dynamics. However, computational constraints currently limit our ability to reconstruct network radiations from gene-tree data. Available methods are limited to level-1 networks wherein reticulations do not share edges, and higher-level networks may be non-identifiable in many cases. We present a heuristic approach to recover information from higher-level networks across a range of potentially identifiable empirical scenarios, supported by theory and simulation. When extrinsic information indicates the location and direction of reticulations, our method can successfully estimate a reduced possible set of nonlevel-1 networks. Phylogenomic data support a single backbone topology with up to 5 overlapping hybrid edges in the Pisgah clade. These results suggest an unusual mechanism of ecomorphological hybrid speciation, wherein a binary threshold trait causes some hybrid populations to shift between microhabitat niches, promoting ecological divergence between sympatric hybrids and parentals. This contrasts with other well-known systems in which hybrids exhibit intermediate, novel, or transgressive phenotypes. The genetic basis of these phenotypes is unclear and further data are needed to clarify the evolutionary basis of morphological changes with ecological consequences.
Misadventures and traps in stamp duty dodging in Singapore
Authors: Ooi Vincent
Published: October 2024

As stamp duty rates in Singapore have increased over time, so too have the number of stamp duty avoidance schemes, ranging from simple and straightforward to complex and elaborate. Even when these schemes technically succeed, any potential loopholes are quickly dealt with legislatively. But stamp duty avoidance attempts can also backfire with heavy resulting costs. Changes such as the stamp duty avoidance surcharge discourage aggressive planning. The most severe consequences occur when property buyers go beyond mere avoidance and enter the more dangerous territory like evasion. This article cautions against a range of missteps, each more serious than the last.
Potential protective role of chlorogenic acid against cyclophosphamide-induced reproductive damage in male mice
Authors: Zheng Hong-xing , Xu You-mei , Fan Shu-cong , Qi Shan-shan , Jia Fan-fan , Wu Wei , Chen Chen
Published: October 2024

Background

Cyclophosphamide (CP) is an anticancer drug; however, clinical utilization of CP is limited, resulting from its considerable toxicities. This research was performed to explore the protective effects of Chlorogenic acid (CGA) on reproductive damage induced by CP in mice.

Methods

Blood samples were collected for analysis of hormone content subsequently; semen samples were evaluated for quality, and testis samples were used for histopathological evaluation and analysis of oxidative stress biomarkers, protein and gene expression levels of steroid regulatory factors, and steroid synthase.

Results

The results noted that CGA increased serum testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) activity; increased SOD, GPx, and GSH oxidative stress levels in testis tissue; and decreased MDA content in testis tissue. Testicular cells in the CGA treatment group gradually returned to normal morphology, and CYP11A1 and CYP17A1 levels increased after CGA treatment. The mRNA levels of CYP11A1, CYP17A1, StAR, 3β-HSD, and 17β-HSD were significantly raised in the CGA dose group. In the test dose range, CGA can improve sperm quality, quantitative abnormality, and serum T synthesis disorder caused by CP. This mechanism may be correlated with the inhibition of oxidative stress and antioxidation levels.

Conclusions

Therefore, CGA has a protective impact on testicular injuries arising from CP in mice.
Leaving the Shadows Behind? Effects of Domestic Workers Reform on Mothers’ Formal Employment
Authors: Boruchowicz Cynthia
Published: October 2024

What happens when new labor regulations are implemented and enforced while a welfare cash transfer program is already in place? Argentinean National Law 26.844 of 2013 aimed to increase formalization rates in the domestic work sector by increasing access to benefits for workers and enforcement mechanisms for household employers. Compared to those with older children, a 5 percentage–point lower increase in formalization among domestic workers with children under 18 years of age (a key eligibility criterion for welfare) is found after the introduction of the regulation. Moreover, there is suggestive evidence that this may stem from domestic workers’ concerns about losing welfare payments, although it is unclear whether this fear arises from misunderstanding, lack of information, or distrust in the reform. These findings underscore the importance of policy designs that mitigate potential disincentives and ensure that they do not undermine efforts to increase formal sector participation.
Multicomponent Resistance Responses of Melon to Zucchini Yellow Mosaic Virus
Authors: Bibiano Líllian B. J. , Carvalho Camila P. , Giória Ricardo , Rezende Jorge A. M. , Camargo Luis E. A.
Published: October 2024

A major resistance gene of the melon accession PI414723 to zucchini yellow mosaic virus (ZYMV) is located at the Zym-1 locus on chromosome 2, but the underlying defense mechanisms are poorly understood. The physiological responses and expression of selected genes at Zym-1 were assessed in PI414723 and in the susceptible genotype Védrantais. Viral titers and the expression of genes related to systemic acquired resistance were evaluated in inoculated (Inoc) and noninoculated (Non-Inoc) portions of the cotyledons at 3, 7, and 10 days after inoculation and in apical leaves at 10 days after inoculation. ZYMV was detected in both portions of the cotyledons but not in the apical leaves of PI414723 plants. Also, ZYMV was recovered in a susceptible zucchini only from Inoc portions at 3 days after inoculation. By contrast, in Védrantais, ZYMV was detected and recovered from all tissues at high concentrations. Starchy local lesions and accumulation of transcripts of the systemic acquired resistance marker genes PR1 and PR4 were also detected in the resistant genotype. Plus, transcripts of one candidate resistance gene analog previously located at Zym-1 and of two melon homologs of restricted tobacco etch virus movement 2 genes located close to Zym-1 accumulated only in PI414723. It is proposed that resistance results from the combined action of the R gene involved in restricting ZYMV replication after a supposed recognition event and of the restricted tobacco etch virus movement genes that impact viral systemic movement to distal apical tissues.
BRASH syndrome
Authors: Williams Kaegan G. , Robeck Rachel S.
Published: October 2024

Bradycardia, renal failure, atrioventricular nodal blockade, shock, and hyperkalemia (BRASH) can combine into a vicious cycle that can present as bradycardia refractory to the Advanced Cardiac Life Support bradycardia algorithm. Early identification and treatment of BRASH syndrome are paramount to prevent patient deterioration into multiorgan failure.
Alcohol, Tobacco, and Marijuana Use Among Individuals Receiving Prescription Opioids for Pain Management
Authors: Miller-Matero Lisa R. , Pappas Celeste , Altairi Samah , Sehgal Monica , Chrusciel Timothy , Salas Joanne , Secrest Scott , Wilson Lauren , Carpenter Ryan W. , Sullivan Mark D. , Ahmedani Brian K. , Lustman Patrick J. , Scherrer Jeffrey F.
Published: October 2024

Objective:

Substance use among individuals receiving prescription opioids for pain may be associated with poorer functioning. The purpose of this study was to examine whether the use of substances (ie, alcohol, marijuana, or tobacco) among individuals prescribed opioids for pain management was associated with pain, psychiatric disorders, and opioid misuse.

Methods:

Patients with non-cancer pain and a new opioid prescription were recruited from 2 health systems. Participants (N = 827) completed measures regarding pain severity, pain interference, psychiatric symptoms, and substance use.

Results:

Substance use was common with 58.0%, 26.2%, and 28.9% reporting alcohol, tobacco, and marijuana use, respectively. The use of tobacco or marijuana was associated with poorer functioning. Those with tobacco use had greater pain severity, interference, number of pain sites, and concern for opioid misuse, and were more likely to have probable depression, anxiety, and posttraumatic stress disorders. Participants reporting marijuana use were more likely to have higher concerns for opioid misuse scores and probable depression, anxiety, and posttraumatic stress disorders. Use of alcohol was associated with lower pain severity and interference and fewer number of pain sites.

Conclusion:

Substance use is common among individuals receiving prescription opioids. Some types of substance use may be related to poorer opioid, pain, and psychiatric functioning. Clinicians prescribing opioids for pain management should assess for substance use, including tobacco, and be aware of the association with poorer functioning. Interventions could target pain, psychiatric symptoms, and substance use simultaneously to optimize outcomes for individuals with pain and substance use.