bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmental DNA: The next chapter
Authors: Blackman Rosetta , Couton Marjorie , Keck François , Kirschner Dominik , Carraro Luca , Cereghetti Eva , Perrelet Kilian , Bossart Raphael , Brantschen Jeanine , Zhang Yan , Altermatt Florian
Published: April 2024

Molecular tools are an indispensable part of ecology and biodiversity sciences and implemented across all biomes. About a decade ago, the use and implementation of environmental DNA (eDNA) to detect biodiversity signals extracted from environmental samples opened new avenues of research. Initial eDNA research focused on understanding population dynamics of target species. Its scope thereafter broadened, uncovering previously unrecorded biodiversity via metabarcoding in both well‐studied and understudied ecosystems across all taxonomic groups. The application of eDNA rapidly became an established part of biodiversity research, and a research field by its own. Here, we revisit key expectations made in a land‐mark special issue on eDNA in Molecular Ecology in 2012 to frame the development in six key areas: (1) sample collection, (2) primer development, (3) biomonitoring, (4) quantification, (5) behaviour of DNA in the environment and (6) reference database development. We pinpoint the success of eDNA, yet also discuss shortfalls and expectations not met, highlighting areas of research priority and identify the unexpected developments. In parallel, our retrospective couples a screening of the peer‐reviewed literature with a survey of eDNA users including academics, end‐users and commercial providers, in which we address the priority areas to focus research efforts to advance the field of eDNA. With the rapid and ever‐increasing pace of new technical advances, the future of eDNA looks bright, yet successful applications and best practices must become more interdisciplinary to reach its full potential. Our retrospect gives the tools and expectations towards concretely moving the field forward.
Demand and distribution in a dynamic spatial panel model for the United States: Evidence from state‐level data
Authors: Lima Gilberto Tadeu , Marques André M.
Published: April 2024

We estimate a modified demand‐and‐distribution system for the 48 contiguous US states and the District of Columbia (DC) employing dynamic spatial panel data for 1980–2019. We allow for endogenous regressors, test for the presence, significance, and magnitude of spatial spillovers, and estimate immediate and cumulative effects on our endogenous variables of interest. Without testing for spatial dependence and spillovers, we estimate that output growth and capacity utilization in the sample US states and DC rise in response to an increase in their own wage share. When we test for spatial dependence and spillovers as required by the state‐level nature of the data, and consider that the functional distribution of income and the level of economic activity are jointly determined, we estimate that a higher state wage share raises output growth in the own state and the neighboring states. Yet the effect of a change in the state wage share on capacity utilization in the own state and the neighboring states is not statistically significant. Meanwhile, a higher state output growth raises the wage share in the own state, but its impact on the wage share in the neighboring states is not statistically significant. A higher state capacity utilization raises the wage share in the own state, yet it reduces the wage share in the neighboring states.
The influence of viewing time on visual diagnostic accuracy: Less is more
Authors: Monteiro Sandra , Sherbino Jonathan , LoGiudice Andrew , Lee Mark , Norman Geoff , Sibbald Matthew
Published: April 2024

Background

Understanding the factors that contribute to diagnostic errors is critical if we are to correct or prevent them. Some scholars influenced by the default interventionist dual‐process theory of cognition (dual‐process theory) emphasise a narrow focus on individual clinician's faulty reasoning as a significant contributor. In this paper, we examine the validity of claims that dual process theory is a key to error reduction.

Methods

We examined the relationship between a clinical experience (staff and resident physicians) and viewing time on accuracy for categorising chest X‐rays (CXRs) and electrocardiograms (ECGs). In two studies, participants categorised images as normal or abnormal, presented at viewing times of 175, 250, 500 and 1000 ms, to encourage System 1 processing. Study 2 extended viewing times to 1, 5, 10 and 20 s to allow time for System 2 processing and a diagnosis. Descriptives and repeated measures analysis of variance were used to analyse the proportion of true and false positive rates (TP and FP) as well as correct diagnoses.

Results

In Study 1, physicians were able to detect abnormal CXRs (0.78) and ECGs (0.67) with relatively high accuracy. The effect of experience was found for ECGs only, as staff physicians (0.71, 95% CI = 0.66–0.75) had higher ECG TP than resident physicians (0.63, 95% CI = 0.58–0.68) in Study 1, and staff had lower ECG FP (0.10, 95% CI = 0.03–0.18) than resident physicians (0.27, 95% CI = 0.20–0.33) in Study 2. In other comparisons, experience was equivocal for ECG FPs and CXR TPs and FPs. In Study 2, overall diagnostic accuracy was similar for both ECGs and CXRs, (0.74). There were small interactions between experience and time for TP in ECGs and FP in CXRs, which are discussed further in the discussion and offer insights into the relationship between processing and experience.

Conclusion

Overall, our findings raise concerns about the practical application of models that link processing type to diagnostic error, or to specific diagnostic error reduction strategies.
Intermembrane space‐localized TbTim15 is an essential subunit of the single mitochondrial inner membrane protein translocase of trypanosomes
Authors: von Känel Corinne , Oeljeklaus Silke , Wenger Christoph , Stettler Philip , Harsman Anke , Warscheid Bettina , Schneider André
Published: April 2024

All mitochondria import >95% of their proteins from the cytosol. This process is mediated by protein translocases in the mitochondrial membranes, whose subunits are generally highly conserved. Most eukaryotes have two inner membrane protein translocases (TIMs) that are specialized to import either presequence‐containing or mitochondrial carrier proteins. In contrast, the parasitic protozoan Trypanosoma brucei has a single TIM complex consisting of one conserved and five unique subunits. Here, we identify candidates for new subunits of the TIM or the presequence translocase‐associated motor (PAM) using a protein–protein interaction network of previously characterized TIM and PAM subunits. This analysis reveals that the trypanosomal TIM complex contains an additional trypanosomatid‐specific subunit, designated TbTim15. TbTim15 is associated with the TIM complex, lacks transmembrane domains, and localizes to the intermembrane space. TbTim15 is essential for procyclic and bloodstream forms of trypanosomes. It contains two twin CX9C motifs and mediates import of both presequence‐containing and mitochondrial carrier proteins. While the precise function of TbTim15 in mitochondrial protein import is unknown, our results are consistent with the notion that it may function as an import receptor for the non‐canonical trypanosomal TIM complex.
Higher consumption of ultra‐processed foods is associated with obesity and abdominal obesity in socially vulnerable Brazilian women
Authors: de Medeiros Jocione Mara , Silva‐Neto Luiz Gonzaga Ribeiro , dos Santos Thays Lane Ferreira , dos Santos Neto João Eudes , de Menezes Toledo Florêncio Telma Maria
Published: April 2024

This study aimed to assess the consumption of ultra‐processed foods (UPF) and identify their association with obesity and abdominal obesity in adult women of reproductive age living in situations of social vulnerability in Maceió, Northeastern Brazil. This was a cross‐sectional study carried out between October 2020 and May 2021. An anthropometric evaluation was carried out to assess obesity and abdominal obesity. A dietary assessment was also conducted using a 24‐h food recall to determine the calorie intake from UPF. To estimate intra‐individual variability in food consumption, the probabilistic Multiple Source Method was used. These data in the form of tertiles were used to analyse the association between the consumption of UPF and obesity and abdominal obesity. Logistic regressions were used to analyse the association. A directed acyclic graph (DAG) was created for this analysis. This study included 1702 women of which 53.7% were 31 years old or older, and 74.2% lived in poverty. It identified that 36.5% and 38.1% of the women had obesity and abdominal obesity, respectively, and that an average of 33.8% of calories consumed came from UPF. In the analysis of association guided by the DAG, it was observed that women with a high‐calorie intake from UPF had a 1.3 times higher probability of being obese. It was also observed that women with a moderate and high‐calorie intake from UPF were 1.4 and 1.3 times more likely, respectively, to have abdominal obesity. Thus, it can be concluded that socially vulnerable women in Brazil have a relatively high consumption of UPF and that this condition increases the probability of obesity in this population group.
CPK10 protein kinase regulates Arabidopsis tolerance to boron deficiency through phosphorylation and activation of BOR1 transporter
Authors: Wang Zhangqing , Zhang Yanting , Wu Yaru , Lai Duoduo , Deng Yuan , Ju Chuanfeng , Sun Lv , Huang Panpan , Wang Cun
Published: April 2024

Boron (B) is crucial for plant growth and development. B deficiency can impair numerous physiological and metabolic processes, particularly in root development and pollen germination, seriously impeding crop growth and yield. However, the molecular mechanism underlying boron signal perception and signal transduction is rather limited.

In this study, we discovered that CPK10, a calcium‐dependent protein kinase in the CPK family, has the strongest interaction with the boron transporter BOR1. Mutations in CPK10 led to growth and root development defects under B‐deficiency conditions, while constitutively active CPK10 enhanced plant tolerance to B deficiency.

Furthermore, we found that CPK10 interacted with and phosphorylated BOR1 at the Ser689 residue. Through various biochemical analyses and complementation of B transport in yeast and plants, we revealed that Ser689 of BOR1 is important for its transport activity.

In summary, these findings highlight the significance of the CPK10‐BOR1 signaling pathway in maintaining B homeostasis in plants and provide targets for the genetic improvement of crop tolerance to B‐deficiency stress.
Eco‐evolutionary insights into microbial litter decomposition
Authors: Shao Siya , Sulman Benjamin N.
Published: April 2024

This article is a Commentary on Chakrawal et al. (2024), 243: 866–880.
Transcriptomic features of programmed and inflammatory cell death in gingival tissues
Authors: Ebersole Jeffrey L. , Kirakodu Sreenatha S. , Nguyen Linh M. , Gonzalez Octavio A.
Published: April 2024

The local gingival tissue environment with homeostasis and tissue‐destructive events of periodontitis demonstrates major changes in histological features and biology of the oral/sulcular epithelium, fibroblasts, vascular cells, inflammatory cell infiltration, and alveolar bone.

Objective

This study used an experimental periodontitis model to detail the gingival transcriptome related to cell death processes of pyroptosis, necroptosis, ferroptosis, and cuproptosis.

Materials and Methods

Healthy Macaca mulatta primates stratified by age, ≤3 years (young), 7–12 years (adolescent), 12–15 years (adult), and 17–23 years (aged), provided gingival tissue biopsies for microarray analysis focused on 257 genes representative of the four cell death processes and bacterial plaque samples for 16S rRNA gene analysis.

Results

Age differences in the profiles of gene expression in healthy tissues were noted for cuproptosis, ferroptosis, necroptosis, and pyroptosis. Major differences were then observed with disease initiation, progression, and resolution also related to the age of the animals. Distinct bacterial families/consortia of species were significantly related to the gene expression differences for the cell death pathways.

Conclusions

These results emphasized age‐associated differences in the gingival tissue molecular response to changes in the quality and quantity of bacteria accumulating with the disease process reflected in regulated cell death pathways that are both physiological and pathophysiological.
The roles of 5‐HT in orofacial pain
Authors: Zou Zhishan , Fan Wenguo , Liu Haotian , Liu Qing , He Hongwen , Huang Fang
Published: April 2024

Objectives

Acute and chronic orofacial pain are very common and remain a vexing health problem that has a negative effect on the quality of life. Serotonin (5‐HydroxyTryptamine, 5‐HT) is a kind of monoamine neurotransmitter that is involved in many physiological and pathological processes. However, its role in orofacial pain remains inconclusive. Therefore, this review aims to summarize the recent advances in understanding the effect exerted by 5‐HT on the modulation of orofacial pain.

Subjects and Methods

An extensive search was conducted on PubMed and Web of Science for pertinent studies focusing on the effects of 5‐HT on the modulation of orofacial pain.

Results

In this review, we concisely review how 5‐HT mediates orofacial pain, how 5‐HT is regulated and how we can translate these findings into clinical applications for the prevention and/or treatment of orofacial pain.

Conclusions

5‐HT plays a key role in the modulation of orofacial pain, implying that 5‐HT modulators may serve as effective treatment for orofacial pain. However, further research on the precise mechanisms underlying the modulation of orofacial pain is still warranted.
AN AEGEAN MIRROR FROM HALA SULTAN TEKKE, CYPRUS
Authors: Feldbacher Rainer , Alvarez Laura E. , Miyauchi Yuko , Lorentz Kirsi , Fischer Peter M.
Published: April 2024

This study deals with the results of the 2023 fieldwork at the extramural cemetery of the Late Bronze Age harbour city of Hala Sultan Tekke. One of the three excavated tombs in 2023 was the undisturbed Chamber Tomb XX, which is dated around 1300 BC. It contained a riveted bronze mirror, a rare type in Cyprus at that time, which is part of a mortuary context of four individuals out of a total of 17 individuals and 264 complete objects, many of them imported from a vast area, which includes the Mycenaean, Minoan, Egyptian and Levantine cultures. The current paper presents this mirror and associated contexts. As regards the provenance of the mirror, the Aegean is suggested as the area of manufacture, and more precisely Crete, suggesting potential evidence of direct contact between individuals from Crete and Hala Sultan Tekke.
Long‐term outcomes of two‐dose alemtuzumab induction in pediatric kidney transplantation
Authors: Engen Rachel M. , Bartosh Sharon M.
Published: April 2024

Background

Alemtuzumab is a lymphocyte depleting agent used for induction in kidney transplant, but long‐term information on its use in pediatric recipients remains sparse.

Methods

We performed a single‐center retrospective cohort study of 57 pediatric kidney transplant recipients receiving alemtuzumab 20 mg/m2/dose ×2 doses for induction immunosuppression. All patients underwent surveillance biopsies, and 91.3% underwent steroid withdrawal by day 4 post‐transplant. Outcomes of interest included graft survival, development of donor specific antibodies (DSA), incidence of viremia and PTLD, and duration of lymphopenia.

Results

Median follow‐up time was 7.9 years (IQR 5–13.6 years). Median graft survival was 16.5 years (95% CI 11.6‐unknown). DSA developed in 36.5% at a median of 944 days (IQR 252–2113 days). Incidences of BK polyomavirus DNAemia (BKPyV‐DNAemia), CMV DNAemia, and EBV DNAemia were 38.6%, 22.8%, and 14%, respectively; one patient developed PTLD at 13.3 years post‐transplant. Median duration of lymphopenia was 365 days (IQR 168–713 days); 19.3% of patients remained lymphopenic at 3 years post‐transplant. There was no association between duration of lymphopenia and graft survival, rejection, DSA detection, or viremia.

Conclusions

A two‐dose alemtuzumab induction protocol can have excellent outcomes with a steroid‐free maintenance immunosuppression regimen. More comprehensive, multicenter, comparative studies of pediatric kidney transplant are needed to improve long‐term outcomes.
From intestinal failure to transplantation: Review on the current need for transplant indications under multidisciplinary transplant programs worldwide
Authors: Raghu Vikram K. , Rumbo Carolina , Horslen Simon P.
Published: April 2024

Introduction

Intestinal failure, defined as the loss of gastrointestinal function to the point where nutrition cannot be maintained by enteral intake alone, presents numerous challenges in children, not least the timing of consideration of intestine transplantation.

Objectives

To describe the evolution of care of infants and children with intestinal failure including parenteral nutrition, intestine transplantation, and contemporary intestinal failure care.

Methods

The review is based on the authors' experience supported by an in‐depth review of the published literature.

Results

The history of parenteral nutrition, including out‐patient (home) administration, and intestine transplantation are reviewed along with the complications of intestinal failure that may become indications for consideration of intestine transplantation. Current management strategies for children with intestinal failure are discussed along with changes in need for intestine transplantation, recognizing the difficulty in generalizing recommendations due to the high level of heterogeneity of intestinal pathology and residual bowel anatomy and function.

Discussion

Advances in the medical and surgical care of children with intestinal failure have resulted in improved transplant‐free survival and a significant fall in demand for transplantation. Despite these improvements a number of children continue to fail rehabilitative care and require intestine transplantation as life‐saving therapy or when the burden on ongoing parenteral nutrition becomes too great to bear.
Successful use of eculizumab in immediate ANCA vasculitis recurrence in a pediatric kidney transplant
Authors: Peterson Caitlin G. , Jackson Rachel L.
Published: April 2024

Background

Kidney transplantation is an acceptable therapy end‐stage kidney disease secondary to antineutrophil cytoplasmic antibody‐associated vasculitis with risk of disease recurrence ranging from 3% to 17%. Standard posttransplant immunosuppression is the mainstay of therapy after recurrence. Recently, new medications focused on complement regulation and avoidance of steroids have been shown to be effective in treating antineutrophil cytoplasmic antibody (ANCA) vasculitis with no studies in the pediatric population.

Methods

We report a 5‐year‐old patient with immediate recurrence of positive myeloperoxidase (MPO)‐ANCA vasculitis after deceased donor kidney transplant and the novel use of eculizumab to salvage the graft.

Results

Eculizumab and transition to ravulizumab has been successful in improving graft function and maintenance of disease remission after immediate MPO‐ANCA vasculitis recurrence posttransplant.

Conclusions

Complement inhibitors may be used in addition to standard immunosuppression postkidney transplant in a pediatric patient with MPO‐ANCA vasculitis recurrence without higher rates of infections.
Trait‐dependent plasticity erodes rapidly with repeated intergenerational acclimation in an invasive agricultural pest
Authors: Mlambo Shaw , Machekano Honest , Mvumi Brighton M. , Cuthbert Ross N. , Nyamukondiwa Casper
Published: April 2024

Climate change is associated with increased mean temperatures and amplitudes manifesting both acutely and chronically, triggering organism stress responses that confer fitness costs and/or benefits. The larger grain borer (LGB), Prostephanus truncatus (Horn) (Coleoptera: Bostrichidae) is an invasive postharvest agricultural pest. While host shift is its well‐known potential invasive mechanism, how repeated intergenerational stress environments may influence offspring phenotypes is largely unknown. We thus evaluated physiological and ecological performance of LGB following repeated intergenerational acute heat acclimation to insinuate its likely responses to projected increased bouts of heat stress associated with climate change. Parental colonies were acutely heat‐acclimated separately at 35°C and 38°C; 80% RH for 2 h in climate chambers and released onto sterilized maize grain at optimal conditions (32°C, 80% RH). The F1 progenies were, respectively, acclimated at the same conditions and incubated to F2 generation. We then evaluated physiological and ecological performance under optimal conditions across parental, F1 and F2 generations. Our results showed that plasticity was highly trait dependent, and that acclimation did not affect F1 and F2 critical thermal maxima, but did improve critical thermal minima. However, while acclimation improved heat knockdown time at F1, repeated acclimation significantly reduced heat knockdown times at F2, suggesting plasticity erosion with generational repeated acclimations. Acute acclimation negatively affected ecological performance of F1 generations although this was restored with repeated acclimation in F2 populations. Our results suggest that the LGB may inflict more economic damage with repeated heat stress due to generational adaptation to temperature stress. The results contribute to knowledge on pest forecasting modelling under changing climates and provides a framework for phytosanitary adjustments in heat treatment protocols for international grain trade.
Enhanced visible light photo‐Fenton catalysis by Fe‐doping oligo‐layer natural molybdenite with efficient carrier spatial‐driven Fe3+/Fe2+ cycle
Authors: Zhang Rong , Liu Zhuannian , Chen Taoli
Published: April 2024

Developing cost‐effective and efficient photo‐Fenton catalysts is crucial for advancing photo‐Fenton technology. MoS2 is a representative transition metal disulfide with attractive photoresponsiveness, making it ideal for preparing composite photo‐Fenton catalysts. In this study, natural molybdenite was innovatively utilized as a source of MoS2 (OM) to synthesize a low‐cost and efficient Fe@MoS2 (OMF) composite photo‐Fenton catalyst by comminution and adsorption, which was then applied to the remediation of antibiotic‐contaminated water. The OMF composites exhibited significant catalytic activity, with a kinetic rate constant of 0.022 min−1, which was 3.1 times higher than that of the original OM (0.007 min−1), indicating a 3% increase. This was attributed to the synergistic effect of many photogenerated electrons and reversible Mo4+/Mo6+ redox pairs, which accelerated the regeneration of Fe2+. After three cyclic tests, the concentrations of dissolved Fe2+ and Mo2+ ions remained below 0.38 mg/L and 0.17 mg/L, respectively. This indicates the high reusability of the catalyst in cyclic experiments. Ultimately, the main active species, •OH and •O2−, were generated during the photo‐Fenton process, contributing significantly to TC degradation. This study may serve as a reference for the development and application of natural mineral composite photo‐Fenton catalysts in the treatment of organic wastewater.
Probabilistic risk assessment of residential exposure to electric arc furnace steel slag using Bayesian model of relative bioavailability and PBPK modeling of manganese
Authors: Mittal Liz , Perry Camarie S. , Blanchette Alexander D. , Proctor Deborah M.
Published: April 2024

Electric arc furnace (EAF) slag is a coproduct of steel production used primarily for construction purposes. Some applications of EAF slag result in residential exposures by incidental ingestion and inhalation of airborne dust. To evaluate potential health risks, an EAF slag characterization program was conducted to measure concentrations of metals and leaching potential (including oral bioaccessibility) in 38 EAF slag samples. Arsenic, hexavalent chromium, iron, vanadium, and manganese (Mn) were identified as constituents of interest (COIs). Using a probabilistic risk assessment (PRA) approach, estimated distributions of dose for COIs were assessed, and increased cancer risks and noncancer hazard quotients (HQs) at the 50th and 95th percentiles were calculated. For the residents near slag‐covered roads, cancer risk and noncancer HQs were <1E − 6 and 1, respectively. For residential driveway or landscape exposure, at the 95th percentile, cancer risks were 1E − 6 and 7E − 07 based on oral exposure to arsenic and hexavalent chromium, respectively. HQs ranged from 0.07 to 2 with the upper bound due to ingestion of Mn among children. To expand the analysis, a previously published physiologically based pharmacokinetic (PBPK) model was used to estimate Mn levels in the globus pallidus for both exposure scenarios and further evaluate the potential for Mn neurotoxicity. The PBPK model estimated slightly increased Mn in the globus pallidus at the 95th percentile of exposure, but concentrations did not exceed no‐observed‐adverse‐effect levels for neurological effects. Overall, the assessment found that the application of EAF slag in residential areas is unlikely to pose a health hazard or increased cancer risk.
Preparing safe discharge in a complex practice: A qualitative study of nurses' approach to patients with COPD's hospital discharge from two pulmonary medicinal wards
Authors: Gregersen Nanna Vendelboe , Refsgaard Birgit , Sørensen Dorthe
Published: April 2024

Introduction

It remains unclear why 17% of patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) treated in Danish hospitals are readmitted within 30 days. Hospital discharge is multifaceted. However, the preparation process and nurses' efforts may be essential in ensuring a successful discharge.

Aim

To explore the process of preparing discharge for patients with COPD in a hospital setting.

Method

Using constructivist grounded theory, we observed 11 nurses' work at two pulmonary medical wards using participant observation. Data collection and analysis were conducted using a constant comparative process encompassing three phases: initial, focused and theoretical.

Results

We identified important perspectives influencing nurses when patients with COPD are discharged from two pulmonary medical wards. We generated a substantial theory of how nurses integrate various perspectives into their handling of hospital discharge. The theory contains three discharge approaches: co‐creating, hesitating and socialising. The co‐creating approach focuses on patient and relative involvement and systematic task solution, embedded in a biopsychosocial process, aiming to achieve a safe and sustainable discharge. In contrast, the hesitating approach focuses on discharging patients in line with system requirements and colleagues' expectations. Finally, the socialising approach focuses on creating a pleasant discharge experience for patients and colleagues alike.

Conclusion

This study illuminates three distinct approaches adopted by nurses when discharging a patient with COPD. The co‐creating process encompasses patient involvement and systematic task resolution, incorporating a biopsychosocial process. In contrast, the other approaches are more limited in scope: the hesitating approach aims for harmony and collegial consensus, while the socialising approach focuses on ensuring a pleasant discharge experience for everyone. Nurses should therefore be mindful of the approach they adopt and the values associated with it in order to optimise their management of hospital discharge processes.
Retrospective evaluation of toceranib phosphate (Palladia) in the treatment of canine carcinomatosis and mesothelioma
Authors: Hicks Kelly A. , Leeper Haley J. , Curran Kaitlin M.
Published: April 2024

Canine carcinomatosis (CC) and mesothelioma (CM) are rare but aggressive neoplasms that historically have been associated with poor prognoses. There is limited information regarding treatment for CC and CM. The purpose of this retrospective study was to evaluate the efficacy and tolerability of toceranib phosphate (Palladia) in dogs with CC and CM. Cases were solicited from the American College of Veterinary Internal Medicine (ACVIM) Oncology listserv and retrospectively reviewed. For eligibility, a cytologic and/or histopathologic diagnosis of CC or CM was required. A total of 23 cases were included (CC = 14, CM = 8, both = 1). Eighty‐two percent (19/23) of dogs presented with effusion. The best overall response rate (BORR) was 30.4% (13% complete response [CR], 17.3% partial response [PR]). Stable disease (SD) was appreciated in 14 dogs (60.8%) including the four dogs without effusion. The most common toceranib‐related adverse events were either Grade 1 and 2 diarrhea or hyporexia. The median progression‐free survival (PFS) was 171 days (range, 7–519 days) and overall median survival time (MST) was 301 days (range, 49–875 days) for all dogs. When evaluating dogs solely with effusion, the median PFS and overall MST were 171 days (range, 7–519 days) and 285 days (range, 49–875 days), respectively. This report demonstrates that toceranib is both well tolerated and a potential treatment for CC and CM. A randomised, controlled, prospective study would be needed to objectively assess the survival benefit of toceranib in the management of CC and CM, with and without effusion.
Iron status in Dutch and Finnish blood donor and general populations: A cross‐cohort comparison study
Authors: Karregat Jan H. M. , Ekroos Sofie , Castrén Johanna , Arvas Mikko , van den Hurk Katja
Published: April 2024

Background and Objectives

Blood donors are at risk of developing iron deficiency (ID) (ferritin <15 μg/L, World Health Organization definition). Blood services implement different strategies to mitigate this risk. Although in Finland risk group‐based iron supplementation is in place, no iron supplementation is provided in the Netherlands. We aim to describe differences in ferritin levels and ID prevalence in donor and general populations in these countries.

Materials and Methods

Six cohorts, stratified based on sex, and for women age, in the Netherlands and Finland were used to evaluate differences in ferritin levels and ID between donor populations (Donor InSight‐III and FinDonor 10,000) and general populations (Prevention of Renal and Vascular End‐Stage Disease [PREVEND], FinRisk 1997 and Health 2000) and newly registered Dutch donors. Multivariable logistic regression was used to quantify associations of various explanatory factors with ID.

Results

In total, 13,443 Dutch and 13,933 Finnish subjects were included. Donors, except for women aged ≤50 years old in Finland, had lower median ferritin levels compared with the general population and new donors. Dutch regular blood donors had higher or similar prevalence of ID as compared with the Dutch general population, including new donors. In contrast, Finnish donors showed similar prevalence of ID compared with the general population, except for a markedly lower prevalence in ≤50‐year‐old women who routinely receive iron supplements when donating.

Conclusion

Iron status in blood donors differs from that in the general population. The Finnish blood service donor management policy, for example, iron supplementation for risk groups, seemingly protects young female blood donors from developing ID.
Plasma atomic layer etching of SiO2 with a low global warming potential fluorocarbon precursor (C6F6)
Authors: Seong Inho , You Yebin , Lee Youngseok , Choi Minsu , Sung Dain , Yeom Geunyoung , You ShinJae
Published: April 2024

Reducing greenhouse gas emissions from semiconductor manufacturing has been attracting enormous interest in both industry and academia as global warming issues have increased in significance year by year. Among various strategies, the search for etch precursors that have low global warming potential is actively underway worldwide to reduce the use of conventional precursors with high global warming potential. In this paper, we explore the use of C6F6, a promising candidate to replace the widely utilized perfluorocarbon precursor C4F8, for plasma atomic layer etching (ALE) of SiO2. In situ ellipsometry results indicated that acceptable ALE characteristics were obtained with C4F8 and C6F6 each in their own specific ALE window, while C6F6 showed superior ALE performance. Investigation into the ALE performance with different precursors was then conducted based on plasma diagnostics for radical density, electron density, and plasma potential, and the results of which showed that the difference in the radical composition between precursors significantly affected the resulting ALE trends and also that the excellent ALE performance with C6F6 might originate from its significant polymeric characteristics. We expect the present findings to contribute to the wider adoption of low global warming potential precursors in the etching process.
Barriers to Participation in Organized Physical Activity Among LGBTQ+ Youth: Differences by Sexual, Gender, and Racial Identities
Authors: Parchem Benjamin , Poquiz Jonathan , Rahm-Knigge Ryan L. , Panetta Elizabeth , Watson Ryan J. , Nic Rider G.
Published: April 2024

Background: LGBTQ+ youth engage in organized physical activity to a lesser degree than their cisgender and heterosexual counterparts. Existing literature on this organized physical activity disparity is limited, particularly with LGBTQ+ youth samples. The current analysis examined individual and systemic barriers to organized physical activity for LGBTQ+ youth across sexual, gender, and racial identities. Methods: A subsample of LGBTQ+ students (N = 4566) from the 2021 Dane County Youth Assessment completed items that measured barriers to organized physical activity and systemic factors (ie, family money problems and bias-based bullying) associated with access to organized physical activity. Latent class analysis discerned patterns of individual and systemic barriers to organized physical activity. Latent class regression modeling tested gender, sexual, and racial identities as correlates of latent class membership. Results: More than half of the sample did not participate in organized physical activity. Four profiles of LGBTQ+ youth were discerned based on self-reported barriers: high barrier (8%), bullied (16%), low interest or perceived skills (28%), and low barrier (48%). The low-barrier class included a greater proportion of LGBTQ+ youth who identified as White, or cisgender, or heterosexual as well as youth self-reporting higher organized physical activity. The high-barrier and bullied classes comprised more marginalized gender and sexual identities. Conclusions: LGBTQ+ youth experience individual and systemic barriers to organized physical activity, including inequitable access and bullying, and barriers are uniquely experienced across sexual, gender, and racial identities. Physical activity promotion among LGBTQ+ youth would be strengthened by policies that address inequitable access to opportunities and bias-based bullying.
Dating the Solar System’s giant planet orbital instability using enstatite meteorites
Authors: Avdellidou Chrysa , Delbo’ Marco , Nesvorný David , Walsh Kevin J. , Morbidelli Alessandro
Published: April 2024

The giant planets of the Solar System formed on initially compact orbits, which transitioned to the current wider configuration by means of an orbital instability. The timing of that instability is poorly constrained. In this work, we use dynamical simulations to demonstrate that the instability implanted planetesimal fragments from the terrestrial planet region into the asteroid main belt. We use meteorite data to show that the implantation occurred >60 million years (Myr) after the Solar System began to form. Combining this constraint with a previous upper limit derived from Jupiter’s trojan asteroids, we conclude that the orbital instability occurred 60 to 100 Myr after the beginning of Solar System formation. The giant impact that formed the Moon occurred within this range, so it might be related to the giant planet instability.
Iron starvation increases the production of the
Pseudomonas aeruginosa
RsmY and RsmZ sRNAs in static conditions
Authors: Chourashi Rhishita , Oglesby Amanda G.
Published: April 2024

Pseudomonas aeruginosa
is an opportunistic Gram-negative pathogen that induces virulence gene expression in response to host-mediated iron starvation. Recently, our laboratory showed that some virulence factors are responsive to iron limitation in static but not shaking growth conditions. One of these is the HSI-2-type six secretion system (T6SS), which is also induced during chronic infection. Iron regulation of T6SS was partially impacted by the iron-responsive PrrF sRNA and completely dependent upon the Pseudomonas quinolone signal (PQS) biosynthetic gene
pqsA
. Here, we analyzed the impact of iron on the expression of two small regulatory RNAs (sRNAs), RsmY and RsmZ, that activate the expression of T6SS by sequestering the RsmA translation inhibitor. Our results demonstrate that iron starvation induces the expression of RsmY and RsmZ in static but not shaking cultures. We further show that this induction occurs through the
rsmY
and
rsmZ
promoters and is dependent upon PqsA. Disruption of either the
pqsR
gene also eliminated iron-dependent regulation of
rsmY
and
rsmZ
promoter activity. Taken together, our results show novel targets of iron regulation that are specific to static growth, highlighting the importance of studying regulatory mechanisms in static communities that may be more representative of growth during chronic infection.

IMPORTANCE

Iron is a central component of various bacterial metabolic pathways making it an important host-acquired nutrient for pathogens to establish infection. Previous iron regulatory studies primarily relied on shaking bacterial cultures; while these ensure cultural homogeneity, they do not reflect growth conditions during infection. We recently showed that static growth of
Pseudomonas aeruginosa
promotes iron-dependent regulation of a type six secretion system (T6SS), a virulence factor that is induced during chronic infections. In the current study, we found that static growth also promotes iron-dependent regulation of the RsmY and RsmZ sRNAs, which are global regulators that affect T6SS during chronic
P. aeruginosa
lung infection. Hence, our work demonstrates the Rsm sRNAs as potential effectors of iron regulation during static growth that may also be relevant in chronic infection.
The Hippo kinases control inflammatory Hippo signaling and restrict bacterial infection in phagocytes
Authors: St. Louis Brendyn M. , Quagliato Sydney M. , Su Yu-Ting , Dyson Gregory , Lee Pei-Chung
Published: April 2024

The Hippo kinases MST1 and MST2 initiate a highly conserved signaling cascade called the Hippo pathway that limits organ size and tumor formation in animals. Intriguingly, pathogens hijack this host pathway during infection, but the role of MST1/2 in innate immune cells against pathogens is unclear. In this report, we generated
Mst1/2
knockout macrophages to investigate the regulatory activities of the Hippo kinases in immunity. Transcriptomic analyses identified differentially expressed genes (DEGs) regulated by MST1/2 that are enriched in biological pathways, such as systemic lupus erythematosus, tuberculosis, and apoptosis. Surprisingly, pharmacological inhibition of the downstream components LATS1/2 in the canonical Hippo pathway did not affect the expression of a set of immune DEGs, suggesting that MST1/2 control these genes
via
alternative inflammatory Hippo signaling. Moreover, MST1/2 may affect immune communication by influencing the release of cytokines, including TNFα, CXCL10, and IL-1ra. Comparative analyses of the single- and double-knockout macrophages revealed that MST1 and MST2 differentially regulate TNFα release and expression of the immune transcription factor MAF, indicating that the two homologous Hippo kinases individually play a unique role in innate immunity. Notably, both MST1 and MST2 can promote apoptotic cell death in macrophages upon stimulation. Lastly, we demonstrate that the Hippo kinases are critical factors in mammalian macrophages and single-cell amoebae to restrict infection by
Legionella pneumophila
,
Escherichia coli
, and
Pseudomonas aeruginosa
. Together, these results uncover non-canonical inflammatory Hippo signaling in macrophages and the evolutionarily conserved role of the Hippo kinases in the anti-microbial defense of eukaryotic hosts.

IMPORTANCE

Identifying host factors involved in susceptibility to infection is fundamental for understanding host-pathogen interactions. Clinically, individuals with mutations in the MST1 gene which encodes one of the Hippo kinases experience recurrent infection. However, the impact of the Hippo kinases on innate immunity remains largely undetermined. This study uses mammalian macrophages and free-living amoebae with single- and double-knockout in the Hippo kinase genes and reveals that the Hippo kinases are the evolutionarily conserved determinants of host defense against microbes. In macrophages, the Hippo kinases MST1 and MST2 control immune activities at multiple levels, including gene expression, immune cell communication, and programmed cell death. Importantly, these activities controlled by MST1 and MST2 in macrophages are independent of the canonical Hippo cascade that is known to limit tissue growth and tumor formation. Together, these findings unveil a unique inflammatory Hippo signaling pathway that plays an essential role in innate immunity.
Microbiome properties in the root nodules of
Prosopis cineraria,
a leguminous desert tree
Authors: Ali Rashid , Chaluvadi Srinivasa R. , Wang Xuewen , Hazzouri Khaled M. , Sudalaimuthuasari Naganeeswaran , Rafi Mohammed , Al-Nuaimi Mariam , Sasi Shina , Antepenko Eric , Bennetzen Jeffrey L. , Amiri Khaled M. A.
Published: April 2024

We conducted a comprehensive analysis of the total microbiome and transcriptionally active microbiome communities in the roots and root nodules of
Prosopis cineraria
, an important leguminous tree in arid regions of many Asian countries. Mature
P. cineraria
trees growing in the desert did not exhibit any detected root nodules. However, we observed root nodules on the roots of
P. cineraria
growing on a desert farm and on young plants growing in a growth chamber, when inoculated with rhizosphere soil, including with rhizosphere soil from near desert tree roots that had no nodules. Compared to nearby soil, non-nodulated roots were enriched with Actinobacteria (e.g.,
Actinophytocola
sp.), whereas root nodules sampled from the desert farm and growth chamber had abundant Alphaproteobacteria (e.g.,
Ensifer
sp.). These nodules yielded many microbes in addition to such nitrogen-fixing bacteria as
Ensifer
and
Sinorhizobium
species. Significant differences exist in the composition and abundance of microbial isolates between the nodule surface and the nodule endosphere. Shotgun metagenome analysis of nodule endospheres revealed that the root nodules comprised over 90% bacterial DNA, whereas metatranscriptome analysis showed that the plant produces vastly more transcripts than the microbes in these nodules. Control inoculations demonstrated that four out of six
Rhizobium, Agrobacterium,
or
Ensifer
isolates purified from
P. cineraria
nodules produced nodules in the roots of
P. cineraria
seedlings under greenhouse conditions. The best nodulation was achieved when seedlings were inoculated with a mixture of those bacterial strains. Though root nodulation could be achieved under water stress conditions, nodule number and nodule biomass increased with copious water availability. .

IMPORTANCE

Microbial communities were investigated in roots and root nodules of
Prosopis cineraria
, a leguminous tree species in arid Asian regions that is responsible for exceptionally important contributions to soil fertility in these dramatically dry locations. Soil removed from regions near nodule-free roots on these mature plants contained an abundance of bacteria with the genetic ability to generate nodules and fix nitrogen but did not normally nodulate in their native rhizosphere environment, suggesting a very different co-evolved relationship than that observed for herbaceous legumes. The relative over-expression of the low-gene-density plant DNA compared to the bacterial DNA in the nodules was also unexpected, indicating a very powerful induction of host genetic contributions within the nodule. Finally, the water dependence of nodulation in inoculated seedlings suggested a possible link between early seedling growth (before a deep root system can be developed) and the early development of nitrogen-fixing capability.
Fertility-sparing approach in concurrent gliomatosis peritonei and growing teratoma syndrome in a young woman
Authors: Ahmad Nasfy Siti Nawwal , Abdul Hamid Habibah , Md Khairuddin Azalea , Mohamad Fauzi Maryam Kameelah
Published: April 2024

Gliomatosis peritonei (GP) and Growing Teratoma Syndrome (GTS) are rare and clinically significant conditions often associated with ovarian teratomas. GP involves the development of benign glial implants on the peritoneal surface, while GTS is characterised by the growth of benign, yet enlarging peritoneal implants following chemotherapy for malignant germ cell tumours. These implants are typically histologically mature teratomas devoid of malignancy. Our report documents a unique case where both GP and GTS manifested in a patient undergoing treatment for an immature ovarian teratoma. This dual occurrence is scarcely reported in the existing literature. The patient, a nulliparous woman in her 20s, developed a tumour indicative of GTS immediately after completing three cycles of bleomycin, etoposide and cisplatin therapy. This chemotherapy regimen followed fertility-sparing surgery for a stage IIIb ovarian immature teratoma. Given that total tumour resection is pivotal in positively influencing the prognosis of GTS, early minimally invasive surgical intervention before significant tumour growth is essential. This approach is particularly crucial considering that ovarian germ cell tumours are commonly present in younger patients, necessitating a focus on fertility preservation in most cases.
Extramedullary relapse of multiple myeloma presenting as space-occupying lesion in liver treated with daratumumab, pomalidomide, dexamethasone and bendamustine
Authors: Wadhera Sarthak , Jain Arihant , Mitra Suvradeep , Malhotra Pankaj
Published: April 2024

Extramedullary relapse in patients with multiple myeloma (MM) is often associated with loss of biochemical response and the appearance of measurable residual disease in the bone marrow. Fever is an unusual presenting manifestation of MM. Treatment of extramedullary relapse in patients progressing on proteasome inhibitors, anti-CD38 monoclonal antibodies and immunomodulatory drugs is challenging, as access to chimeric antigen receptor T-cells and bispecific antibodies is limited. We report a case of relapsed MM who presented with fever and hepatic space-occupying lesion mimicking hepatocellular carcinoma. In this case report, we also present our experience of using a novel combination regimen comprising Dara-Pom-Benda-Dexa (daratumumab, pomalidomide, dexamethasone and bendamustine) for relapsed MM.