bluuebunny/crossref_metadata_2025 huggingface dataset:
Silicon and Epichloë‐endophyte defences in a model temperate grass diminish feeding efficiency and immunity of an insect folivore
Authors: Cibils‐Stewart X. , Putra R. , Islam T. , Fanna D. J. , Wuhrer R. , Mace W. J. , Hartley S. E. , Popay A. J. , Johnson S. N.
Published: October 2023

Plants deploy diverse anti‐herbivore defences which reduce feeding and performance of herbivores. Temperate grasses use silicon (Si) accumulation and Epichloë‐endophytes for physical and chemical (i.e. endophytic‐alkaloids) defence against insect herbivores. Recent studies suggest that Epichloë‐endophytes increase Si accumulation in their host grass. It is unknown, however, how this affects Si‐deposition on the leaf surface, their impacts on insect herbivore feeding efficiency and their immunity to potential infection/parasitism.

To address this knowledge gap, we grew tall fescue (Festuca arundinacea) hydroponically with and without Si, in the absence or presence of the novel AR584 Epichloë‐strain. We exposed plants to Helicoverpa armigera (Lepidoptera: Noctuidae) in both in situ (intact leaves) and ex situ (excised leaves) feeding trials and determined the effects of Si and endophyte defences on herbivore feeding efficiency, growth rates and immunity against potential infection/parasitism.

Endophytic plants supplied with Si showed 110% and 143% increases in leaf silica density and leaf Si concentrations, respectively, when exposed to herbivory, compared to non‐endophytic plants that were herbivore‐free. Despite the endophyte‐mediated increases in Si concentrations, H. armigera was only affected by Si supply; growth rates decreased by 87% and most feeding efficiency indices decreased by at least 30%. Si supply also increased mandibular wear by 16%, which was negatively correlated with H. armigera growth rates. Cellular and humoral immunity of H. armigera were negatively affected by both Si and endophytes. Endophytic‐loline alkaloid concentrations were unaffected by Si supply or herbivory, whereas herbivory increased peramine concentrations by 290%.

To our knowledge, this is the first report of Si defences and Epichloë‐endophyte derived alkaloids compromising insect immunity via reduced melanisation response. Using tall fescue and H. armigera, our study suggests that deploying both physical (i.e. Si accumulation) and chemical (i.e. endophytic‐alkaloids) defences acting against multiple insect herbivore traits, including feeding efficiency, growth and immunity, may be a successful defence strategy in temperate grasses. This multi‐faceted defence may be particularly difficult for insect herbivores to overcome.

Read the free Plain Language Summary for this article on the Journal blog.
The competitive effect of neighbouring plants on the growth of two eucalypts is stronger in dry conditions
Authors: Britton Travis G. , Richards Shane A. , Gerwin Melissa R. , Brinkhoff Rose E. , Hovenden Mark J.
Published: October 2023

Plant growth is influenced by interactions with neighbouring plants. The strength and direction of the cumulative neighbourhood effect on growth can depend on neighbour properties, such as their abundance, size and proximity, as well as the degree of similarity between interacting plants and their traits, which can be captured by the species identity of neighbours. Such interactions are also influenced by the local environmental conditions that are largely determined by climate. Because neighbour and climatic effects are typically explored in isolation, particularly in long‐lived species such as trees, it is unclear how the impacts of neighbours on plant growth shift in response to temporal variation in climatic conditions.

Here, we explored how neighbouring plants impact the annual growth of two eucalypts, Eucalyptus delegatensis and Eucalyptus regnans, over three growing seasons in an experimental forest in south‐east Tasmania, Australia. We assessed whether eucalypt growth rates could be described by the number, size, proximity, and species identity of neighbours, and how the strength of this effect was influenced by the growing season climatic conditions.

We found that climate and neighbouring plants had an interactive impact on eucalypt growth. Neighbours had a consistent, competitive effect on the growth of both eucalypts in all three growing seasons which was strongly related to the cumulative neighbourhood biomass. The identity of neighbours was important in determining E. regnans growth only, whereby distinguishing neighbours according to functional group best described growth. Over all three growing seasons, we predicted that, on average, neighbours reduced E. delegatensis and E. regnans mean annual growth by 60.5% and 48.4%, respectively. However, the strength of the competitive effect of neighbours on eucalypt growth was related to growing season climate, being strongest when conditions were hot and dry and weakest in cool, wet conditions.

Synthesis: Given the consistent results observed in two co‐occurring eucalypts, our findings suggest that drier and hotter climatic conditions increase the strength of competitive effects on tree growth. This has implications for future forest productivity given projected increased temperatures and variation in rainfall patterns globally.
Business crisis management in wartime: Insights from Ukraine
Authors: Opatska Sophia , Johansen Winni , Gordon Adam
Published: October 2023

Our research documents the experiences of business crisis management in wartime Ukraine. The goal of the paper is to contribute to our understanding of business crisis management in a conflict zone in wartime conditions, a significantly under‐researched area. Based on interviews with the owners and managers of 20 Ukrainian companies spanning sectors and geography of the country, the paper provides insights into the various elements that characterize and distinguish war as a crisis type, including having an unknown end point, and, furthermore, what we can learn from how Ukrainian managers have approached this crisis. Among the key findings are how war situations appear to be “cosmology episodes” for which it is not possible to adequately prepare and for which the end point is unknown, both of which call for emergent, adaptive crisis management capabilities and leadership skills characterized by improvisation and other forms of resilience. Notwithstanding this, company wartime crisis management experiences have stimulated intention to more structured anticipatory and preparedness practices, as well as narratives of future renewal in communications with staff and stakeholders, which serve both as a guidepost and coping mechanism during the current crisis.
The first chromosome‐level genome assembly and transcriptome sequencing provide insights into cantharidin production of the blister beetles
Authors: ZHOU Chuang , ZHENG Xiaofeng , WANG Lei , YUE Bisong , DU Chao , LIU Xu
Published: October 2023

Blister beetles (Coleoptera: Meloidae) produce a natural defensive toxin cantharidin (CTD), which has been used for various cancer treatments and other diseases. Currently, the lack of chromosome‐level reference genomes in Meloidae limits further understanding of the mechanism of CTD biosynthesis and environmental adaptation. In this study, the chromosome‐level genome assembly of Mylabris phalerata was generated based on PacBio and Hi‐C sequencing. This reference genome was about 136.68 Mb in size with contig N50 of 9.17 Mb and composed of 12 chromosomes. In comparison to six other Coleoptera insects, M. phalerata exhibited multiple expanded gene families enriched in juvenile hormone (JH) biosynthetic process pathway, farnesol dehydrogenase activity, and cytochrome P450, which may be related to CTD biosynthesis. Consistently, the transcriptomic analysis suggested the “terpenoid backbone biosynthesis” pathway and “the juvenile hormone” as putative core pathways of CTD biosynthesis and presented eight up‐regulated differential expression genes in male adults as candidate genes. It is possible that the restricted feeding niche and lifestyle of M. phalerata were the cause of the gene family's contraction of odorant binding proteins. The ABC transporters (ABCs) related to exporting bound toxins out of the cell and the resistance to the self‐secreted toxins (e.g. CTD) were also contracted, possibly due to other self‐protection strategies in M. phalerata. A foundation of understanding CTD biosynthesis and environmental adaptation of blister beetles will be established by our reference genome and discoveries.
Associations of concurrent early‐life famine exposure and adulthood obesity with type 2 diabetes mellitus in middle‐aged Chinese
Authors: Yi Qian , Wu Jing , Shen Yaojia , Zhu Yunying , Zhou Yiyang , Bai He , Hao Jiajun , Song Peige
Published: October 2023

Background

Evidence has shown that early‐life famine exposure and obesity in adulthood are independently associated with the risk of type 2 diabetes mellitus (T2DM). However, few studies had revealed the combined effect of these risk factors.

Methods

Two sets of groups from the China Health and Retirement Longitudinal Study (CHARLS) were selected. The fetal‐exposure group born in 1959–1961 from 2011 wave (N = 958) and nonexposure group born in 1963–1965 from 2015 wave (N = 1540) were selected as Comparison 1. The early childhood‐exposure group born in 1955–1957 from 2011 wave (N = 1510) and fetal‐exposure group born in 1959–1961 from 2015 wave (N = 943) were Comparison 2. Logistic regressions were applied to examine the associations of different famine exposure periods and obesity patterns with T2DM risk.

Results

Compared with nonexposed participants without central overweight/obesity in adulthood, central overweight/obesity in adulthood together with nonexposure (odds ratio [OR]: 1.89, 95% confidence interval [CI]: 1.19–3.00) or fetal‐exposure (OR: 1.99, 95% CI: 1.23–3.23) was associated with higher risks of T2DM. Compared with the early childhood‐exposure group, the fetal‐exposed participants showed higher risks of T2DM (OR: 1.30, 95% CI: 1.02–1.66). The coexistence of fetal famine exposure and central overweight/obesity in adulthood was associated with higher risks of T2DM (OR: 1.82, 95% CI: 1.19–2.79). Consistent associations were observed among males and participants from less severely affected areas.

Conclusions

In conclusion, central overweight/obesity in adulthood is associated with the increased risk of T2DM, but the effect of early‐life famine exposure is not very clear.
FINDeM: A CRISPR‐based, molecular method for rapid, inexpensive and field‐deployable organism detection
Authors: Hoenig Brandon D. , Zegar Jakub , Ohmer Michel E. B. , Chess Macie M. , Porter Brady A. , Madril Myah , Richards‐Zawacki Corinne L.
Published: October 2023

The field of ecology has undergone a molecular revolution, with researchers increasingly relying on DNA‐based methods for organism detection. Unfortunately, these techniques often require expensive equipment, dedicated laboratory spaces and specialized training in molecular and computational techniques; limitations that may exclude field researchers, underfunded programmes and citizen scientists from contributing to cutting‐edge science.

It is for these reasons that we have designed a simplified, inexpensive method for field‐based molecular organism detection—FINDeM (Field‐deployable Isothermal Nucleotide‐based Detection Method). In this approach, DNA is extracted using chemical cell lysis and a cellulose filter disc, followed by two body‐heat inducible reactions—recombinase polymerase amplification and a CRISPR‐Cas12a fluorescent reporter assay—to amplify and detect target DNA, respectively.

Here, we introduce and validate FINDeM in detecting Batrachochytrium dendrobatidis, the causative agent of amphibian chytridiomycosis, and show that this approach can identify single‐digit DNA copies from epidermal swabs in under 1 h using low‐cost supplies and field‐friendly equipment.

This research signifies a breakthrough in ecology, as we demonstrate a field‐deployable platform that requires only basic supplies (i.e. micropipettes, plastic consumables and a UV flashlight), inexpensive reagents (~$1.29 USD/sample) and emanated body heat for highly sensitive, DNA‐based organism detection. By presenting FINDeM in an ecological system with pressing, global biodiversity implications, we aim to not only highlight how CRISPR‐based applications promise to revolutionize organism detection but also how the continued development of such techniques will allow for additional, more diversely trained researchers to answer the most pressing questions in ecology.
Dexamethasone doses in patients with COVID‐19 and hypoxia: A systematic review and meta‐analysis
Authors: Munch Marie Warrer , Granholm Anders , Maláska Jan , Stašek Jan , Rodriguez Pablo O. , Pitre Tyler , Wilson Rebecca , Savović Jelena , Rochwerg Bram , Svobodnik Adam , Kratochvíl Milan , Taboada Manuel , Jha Vivekanand , Vijayaraghavan Bharath Kumar Tirupakuzhi , Myatra Sheila Nainan , Venkatesh Balasubramanian , Perner Anders , Møller Morten Hylander
Published: October 2023

Background

The optimal dose of dexamethasone for severe/critical COVID‐19 is uncertain. We compared higher versus standard doses of dexamethasone in adults with COVID‐19 and hypoxia.

Methods

We searched PubMed and trial registers until 23 June 2023 for randomised clinical trials comparing higher (>6 mg) versus standard doses (6 mg) of dexamethasone in adults with COVID‐19 and hypoxia. The primary outcome was mortality at 1 month. Secondary outcomes were mortality closest to 90 days; days alive without life support; and the occurrence of serious adverse events/reactions (SAEs/SARs) closest to 1 month. We assessed the risk of bias using the Cochrane RoB2 tool, risk of random errors using trial sequential analysis, and certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE).

Results

We included eight trials (2478 participants), of which four (1293 participants) had low risk of bias. Higher doses of dexamethasone probably resulted in little to no difference in mortality at 1 month (relative risk [RR] 0.97, 95% CI: 0.79–1.19), mortality closest to Day 90 (RR 1.01, 95% CI: 0.86–1.20), and SAEs/SARs (RR 1.00, 95% CI: 0.97–1.02). Higher doses of dexamethasone probably increased the number of days alive without invasive mechanical ventilation and circulatory support but had no effect on days alive without renal replacement therapy.

Conclusions

Based on low to moderate certainty evidence, higher versus standard doses of dexamethasone probably result in little to no difference in mortality, SAEs/SARs, and days alive without renal replacement therapy, but probably increase the number of days alive without invasive mechanical ventilation and circulatory support.
Evaluating patterns and drivers of mammal space use and richness in the Angolan savannah woodlands of the Kavango‐Zambezi Transfrontier Conservation Area
Authors: Nieman Willem A. , Botha Alexander E.
Published: October 2023

Large transboundary protected areas such as the Kavango‐Zambezi Transfrontier Conservation Area (KAZA‐TFCA), improve mammal conservation by addressing biodiversity threats on regional and international levels, but an adequate understanding of mammal space use and richness within protected areas is critical for effective management planning. This information has however been missing from the Angolan component of the KAZA‐TFCA, such as areas of Luengue‐Luiana National Park (LLNP), especially compared with neighbouring countries. We used camera trap data from 2021 to 2023 to investigate species richness of medium‐ and large‐sized mammals in two hotspot areas of LLNP, as well as assess the space use patterns of 9 carnivore and 16 herbivore species. A total of 48 species were recorded over 10,781 camera trapping nights, with African elephant (Loxodonta africana) and small antelope (e.g. common duiker Sylvicapra grimmia and steenbok Raphicerus campestris) being the most common. Species composition differed significantly between sites, with 21 species more relatively abundant at Ndunjuru, including cheetah (Acinonyx jubatus) and African wild dog (Lycaon pictus), and eight species more relatively abundant at Bico, including lion (Panthera leo) and hippopotamus (Hippopotamus amphibius). The detection probability of 22 species were affected by one or more ecological (e.g. proximity to rivers) or anthropogenic (e.g. human settlement) covariate. These results are intended to act as a baseline to monitor conservation effort and aid habitat management in LLNP, as well as similar protected areas within the KAZA‐TFCA and elsewhere.
Recurrent pregnancy loss: a male crucial factor—A systematic review and meta‐analysis
Authors: Inversetti Annalisa , Bossi Arianna , Cristodoro Martina , Larcher Alessandro , Busnelli Andrea , Grande Giuseppe , Salonia Andrea , Simone Nicoletta Di
Published: October 2023

Background

Recurrent pregnancy loss (RPL), defined as two or more failed clinical pregnancies, affects 1%–3% of couples trying to conceive. Nowadays up to 50% of cases remain idiopathic. In this context, paternal factors evaluation is still very limited. The aim is to address the topic of the male factor in RPL with a broad approach, analyzing collectively data on sperm DNA fragmentation (SDF) and semen parameters. We systematically searched in Pubmed/MEDLINE and Google Scholar from inception to February 2023. A protocol has been registered on PROSPERO (ID number CRD42022278616). PRISMA guidelines were followed.

Methods

Pooled results from 20 studies revealed a higher DNA fragmentation rate in the RPL group compared to controls (mean difference [MD] 9.21, 95% CI 5.58–12.85, p < 0.00001, I2 98%). Age, body mass index (BMI), smoking, and alcohol intake were not associated with DNA fragmentation. Subgroup analysis by different SDF assays (TUNEL and COMET at a neutral pH vs. indirect assessment with other assays) and ethnicity did not highlight different results (p = 0.25 and 0.44).

Results

Results pooled from 25 studies showed a significant difference comparing RPL and control groups regarding ejaculation volume (MD −0.24, 95% CI −0.43; −0.06, p 0.01, I2 66%), total sperm number (MD −10.03, 95% CI −14.65; −5.41, p < 0.0001, I2 76%), total sperm motility (MD −11.20, 95% CI −16.15; −6.25, p < 0.0001, I2 96%), progressive sperm motility (MD −7.34, 95% CI −10.87; −3.80, p < 0.0001, I2 97%), and normal sperm morphology (MD −5.99, 95% CI −9.08; −2.90, p 0.0001, I2 98%). A sub‐analysis revealed that Asian and Africans, but not white‐European RPL men had lower progressive sperm motility compared to controls.

Conclusion

In conclusion, current review and meta‐analysis findings suggested that SDF and some specific semen parameters were associated with RPL in a multi‐ethnic evaluation. This effort opens future direction on a growing awareness of, first, how the male factor plays a key role and, second, how appropriate would be to establish a direct dialogue between the gynecologist and the urologist.

Patient summary

We performed a systematic review and meta‐analysis on the male component of RPL. We found that sperm DNA fragmentation and some specific sperm parameters are significantly associated with RPL.
Male obesity: Associated effects on fertility and the outcomes of offspring
Authors: Venigalla Greeshma , Ila Vishal , Dornbush James , Bernstein Ari , Loloi Justin , Pozzi Edoardo , Miller David , Ramasamy Ranjith
Published: October 2023

Obesity rates are increasing globally, making it imperative to comprehend the effects of parental obesity on human reproduction. This review aims to highlight the impact of male obesity on reproductive and offspring outcomes. Male obesity has been shown to affect fertility through various mechanisms, including changes in semen quality, difficulty with natural conception, and worsened assisted reproductive technology outcomes. The evidence regarding the impact of male obesity on success of sperm retrieval is conflicting, but all aforementioned adverse effects may be modifiable with weight loss. Moreover, paternal obesity may influence atypical offspring outcomes, such as placental abnormalities and disruptions in fetal development, which may be moderated by epigenetic pathways. Further research is needed to fully understand the complex relationships and underlying mechanisms involved. Gaining more insight into the impact of male obesity on fertility and offspring outcomes can aid in the development of targeted interventions to improve family planning and the health of future generations.
On the qualitative nature of conscious states: Insights from a structuralist theory of mind and meaning
Authors: Salazar Carles
Published: October 2023

The point of departure of this paper is Penrose's definition of conscious action as that in which stimulus and response are linked by a non‐algorithmic relationship, which Penrose defines as ‘understanding’. My purpose is to explore the nature of this understanding by means of a two‐step process. The first step is provided by Tononi's Integrated Information Theory of consciousness. This theory provides us with a quantitative measure of conscious states that we need to transform into qualitative meaning. In the second step, we obtain this qualitative meaning with the help of the structuralist theory of mind. From this perspective, meaning originates in the set of qualitative contrasts that define the alternative courses of action that might have been implemented. Work on the analogy between quantitative bits and qualitative binary oppositions does not solve the hard problem of consciousness, but it might help to reformulate it in a new, productive way.
Evaluation of clinical parameters and biomarkers in older, untreated mantle cell lymphoma patients receiving bendamustine–rituximab
Authors: Ramsower Colleen A. , Rosenthal Allison , Robetorye Ryan S. , Mwangi Raphael , Maurer Matthew , Villa Diego , McDonnell Tim , Feldman Andrew , Cohen Jonathon B. , Habermann Thomas , Campo Elias , Clot Guillem , Bühler Marco M. , Kulis Marta , Martin‐Subero Jose Ignacio , Giné Eva , Cook James R. , Hill Brian , Raess Philipp W. , Beiske Klaus H. , Reichart Alexander , Hartmann Sylvia , Holte Harald , Scott David , Rimsza Lisa
Published: October 2023

Mantle cell lymphoma (MCL) is clinically and biologically heterogeneous. While various prognostic features have been proposed, none currently impact therapy selection, particularly in older patients, for whom treatment is primarily dictated by age and comorbidities. Herein, we undertook a comprehensive comparison of clinicopathological features in a cohort of patients 60 years and older, uniformly treated with bendamustine and rituximab, with a median survival of >8 years. The strongest prognostic indicators in this cohort were a high‐risk call by a simplified MCL international prognostic index (s‐MIPI) (HR: 3.32, 95% CI: 1.65–6.68 compared to low risk), a high‐risk call by MCL35 (HR: 10.34, 95% CI: 2.37–45.20 compared to low risk) and blastoid cytology (HR: 4.21, 95% CR: 1.92–9.22 compared to classic). Patients called high risk by both the s‐MIPI and MCL35 had the most dismal prognosis (HR: 11.58, 95% CI: 4.10–32.72), while those with high risk by either had a moderate but clinically relevant prognosis (HR: 2.95, 95% CI: 1.49–5.82). A robust assay to assess proliferation, such as MCL35, along with stringent guidelines for cytological evaluation of MCL, in combination with MIPI, may be a strong path to risk‐stratify older MCL patients in future clinical trials.
Long‐term clinical performance of short 6‐mm implants supporting single crowns in the posterior region: A 10‐year cohort study
Authors: Bregagnol Raphaela Brambilla , Coltro Maria Paula de Lima , Villarinho Eduardo Aydos , Triches Diego Fernandes , Alonso Fernando Rizzo , Mezzomo Luís André Mendonça , de Macedo Bianca Brandelli , Teixeira Eduardo Rolim , Vigo Alvaro , Shinkai Rosemary Sadami Arai
Published: October 2023

Introduction

Long‐term clinical success of non‐splinted, posterior, and short implants still is unclear. This prospective cohort study reports the 10‐year follow‐up of 6‐mm implants supporting single crowns in the posterior region, and patient‐reported outcomes.

Methods

Baseline sample comprised 20 patients treated with 46 screw‐retained crowns supported by 6‐mm implants with moderately rough implant surface. Participants were recalled for a 10‐year clinical follow‐up to assess survival rates, biologic and mechanic conditions, quality of life (OHIP‐14), and treatment satisfaction. Data were collected with clinical‐radiographic exams and analyzed using descriptive and inferential statistics.

Results

Fourteen patients with 35 implant‐crown units were examined after 127.6 ± 11.8 months. For the entire cohort period, 7/46 implants were lost (survival estimate: 77.7% at 133 months), and mechanic complications occurred in 14/46 units (survival estimate: 66.4% at 116 months). In the Cox models, “maximum occlusal force” had a significant effect for implant loss (p = 0.038) and for prosthetic screw loosening (p = 0.038); “arch” and “bruxism” were not significant. Peri‐implant bone loss was 0.4 ± 0.6 mm at 10 years. For peri‐implant bone level, “crown‐to‐implant ratio” (p < 0.001) and “time” (p = 0.001) were significant. Bone levels differed from baseline to 12, 48, and 120 months. Satisfaction VAS was 94.0 ± 7.9 mm and OHIP‐14 was 2.3 ± 2.2.

Conclusion

Single screw‐retained crowns supported by 6‐mm implants have an acceptable long‐term clinical performance, with stable peri‐implant bone levels after 10 years of function.
Associations between patient factors and successful colon capsule endoscopy – A prospective cohort study
Authors: MacLeod C. , Foxton A. , Wilson P. , Treweek S. , Watson A. J. M.
Published: October 2023

Aim

To establish patient factors associated with a successful colon capsule endoscopy (CCE) test.

Method

This prospective cohort study used data collected from patients who underwent CCE as part of the ScotCap evaluation prior to April 2020. A CCE was defined as successful if the capsule visualized the whole colon and rectum (complete test) with sufficient bowel cleansing to permit assessment of the colonic mucosa (adequate bowel preparation). Factors from patients in symptomatic and surveillance groups were analysed for associations with a successful test, complete test, adequate bowel preparation and requirement for further procedure using univariate, multivariate logistic, least absolute shrinkage and selection operator regression.

Results

Data from 263 symptomatic and 137 surveillance patients were analysed. There was an association between a symptomatic patient's age and a successful test (OR = 0.97, 95% CI: 0.95–0.99), adequate bowel preparation (OR = 0.97, 95% CI: 0.94–1.00) and further procedure requirement (OR = 1.04, 95% CI: 1.02–1.06). An association was found, for symptomatic patients, between a faecal immunochemical test result in the range 10–399 μg/g and a further procedure (OR = 2.32, 95% CI: 1.23–4.48). In patients undergoing surveillance for previous colorectal cancer (OR = 0.42, 95% CI: 0.18–0.97), had previous bowel resection surgery (OR = 0.43, 95% CI: 0.19–0.98) or took a beta blocker medication (OR = 0.32, 95% CI: 0.11–0.88), an association was found with further procedure requirement.

Conclusions

Among symptomatic patients, younger age was associated with obtaining a successful CCE test. Clinicians could consider patient selection based on these results to improve the rate of successful testing in clinical practice.
High sensitivity troponin I as a biomarker for cardiac allograft vasculopathy: Evaluation of diagnostic potential and clinical utility
Authors: Patel Krishan , Yadalam Adithya , DeStefano Robert , Desai Shivang , Almuwaqqat Zakaria , Ko Yi‐An , Alras Zahran , Martini Mohamed Afif , Ejaz Kiran , Alvi Zain , Varounis Christos , Murtagh Gillian , Gupta Divya , Book Wendy , Quyyumi Arshed A.
Published: October 2023

Introduction

Cardiac allograft vasculopathy (CAV) limits long‐term survival in heart transplant (HTx) recipients. The use of biomarkers in CAV surveillance has been studied, but none are used in clinical practice. The predictive value of high‐sensitivity troponin I (hsTnI) has not been extensively investigated in HTx recipients.

Methods

HTx patients undergoing surveillance coronary angiograms and enrolled in the Emory Cardiovascular Biobank had plasma hsTnI measured. CAV grade was assessed using ISHLT nomenclature. Multivariable cumulative link mixed modeling was performed to determine association between hsTnI level and CAV grade. Patients were followed for adverse outcomes over a median 10‐year period. Kaplan‐Meier survival analysis and Cox proportional hazard modeling were performed.

Results

Three hundred and seventy‐two angiograms were analyzed in 156 patients at a median 8.9 years after transplant. hsTnI levels were positively correlated with concurrent CAV grade after adjustment for age, age at transplant, sex, BMI, hypertension, diabetes, hyperlipidemia, estimated glomerular filtration rate, and history of acute cellular rejection (p = .016). In an adjusted Cox proportional hazard model, initial hsTnI level above the median (4.9 pg/mL) remained a predictor of re‐transplantation or death (hazard ratio 1.82; 95% confidence interval 1.16–2.90; p = .01).

Conclusion

An elevated hsTnI level reflects severity of CAV and is associated with poor long‐term outcomes in patients with HTx.
Impact of changes in skeletal muscle mass and quality during the waiting time on outcomes of lung transplantation
Authors: Hagiyama Akikazu , Sugimoto Seiichiro , Tanaka Shin , Matsubara Kei , Miyoshi Kentaroh , Katayama Yoshimi , Hamada Masanori , Senda Masuo , Toyooka Shinichi
Published: October 2023

Introduction

The association of changes in skeletal muscle mass and quality during the waiting time with outcomes of lung transplantation (LT) remains unclear. We aimed to examine the association of changes in skeletal muscle mass and quality during the waiting time, as well as preoperative skeletal muscle mass and quality, with outcomes of LT.

Methods

This study included individuals who underwent LT from brain‐dead donors. Skeletal muscle mass (cm2/m2) and quality (mean Hounsfield units [HU]) of the erector spinae muscle at the 12th thoracic level were evaluated using computed tomography. Preoperative skeletal muscle mass and quality, and their changes during the waiting time were calculated. We evaluated the associations among mechanical ventilation (MV) duration, intensive care unit (ICU) length of stay (LOS), hospital LOS, 6‐minute walk distance at discharge, and 5‐year survival after LT.

Results

This study included 98 patients. The median waiting time was 594.5 days (interquartile range [IQR], 355.0–913.0). The median changes in skeletal muscle mass and quality were −4.4% (IQR, −13.3–3.1) and −2.9% (IQR, −16.0–4.1), respectively. Severe low skeletal muscle mass at LT was associated with prolonged ICU LOS (B = 8.46, 95% confidence interval [CI]: .51–16.42) and hospital LOS (B = 36.00, 95% CI: 3.23–68.78). Pronounced decrease in skeletal muscle mass during the waiting time was associated with prolonged MV duration (B = 7.85, 95% CI: .89–14.81) and ICU LOS (B = 7.97, 95% CI: .83–15.10).

Conclusion

Maintaining or increasing skeletal muscle mass during the waiting time would be beneficial to improve the short‐term outcomes of LT.
CDKL5deficiency disorder: At the intersection between Rett syndrome and developmental epileptic encephalopathies
Authors: Kaufmann Walter E.
Published: October 2023

This commentary is on the original articles by Wong et al. and Daniels et al. on pages469–482and456–468of this issue.
Pharmacokinetic similarity of switching SAR341402 insulin aspart biosimilar and NovoLog insulin aspart versus continuous use of NovoLog in adults with type 1 diabetes: The GEMELLI X trial
Authors: Shah Viral N. , Al‐Karadsheh Amer , Barnes Cathy , Mandry Jose , Nakhle Samer , Wernicke‐Panten Karin , Kramer Daniel , Schmider Wolfgang , Pierre Suzanne , Teichert Lenore , Rotthaeuser Baerbel , Mukherjee Bhaswati , Bailey Timothy S.
Published: October 2023

Aim

To assess whether multiple switches between SAR341402 biosimilar insulin aspart (SAR‐Asp) and the insulin aspart reference product (NovoLog; NN‐Asp) leads to equivalent pharmacokinetic (PK) exposure compared with continuous use of NN‐Asp in adults with type 1 diabetes (T1D).

Materials and Methods

This multicentre, open‐label, phase 3 study randomized (1:1) 210 subjects with T1D treated with once‐daily insulin glargine U100 as basal insulin to four 4‐week periods of alternating multiple daily injections of SAR‐Asp and NN‐Asp (NN‐Asp for the first 4 weeks, SAR‐Asp in the last 4 weeks; switching group) versus 16 weeks of continuous NN‐Asp (non‐switching group). At week 16, a single dose (0.15 U/kg) of SAR‐Asp in the switching group (n = 95) or NN‐Asp in the non‐switching group (n = 105) was given in the morning before breakfast. Primary PK endpoints were area under the plasma concentration curve (AUC) and maximum plasma concentration (Cmax) of SAR‐Asp versus NN‐Asp after the single dose at week 16.

Results

The extent of PK exposure was similar between the two treatments (SAR‐Asp in the switching group and NN‐Asp in the non‐switching group) at week 16, with point estimates of treatment ratios close to 1. The 90% confidence intervals for AUC treatment ratios were contained within 0.8‐1.25. For Cmax in the primary analysis set, the upper confidence limit was 1.32. This was because of the profiles of three participants with implausible high values. A prespecified sensitivity analysis excluding implausible values showed results contained within 0.8‐1.25.

Conclusions

PK exposure of SAR‐Asp (switching group) and reference NN‐Asp (non‐switching group) were similar, supporting interchangeability between these two insulin aspart products.
Slowness as warfare: Towards a relational approach to political violence in the West Bank
Authors: Golańska Dorota
Published: October 2023

Engaging with recent applications of the concept of slow violence to the ongoing political developments in the West Bank, this review article argues that the relational approach offered by feminist geopolitics facilitates the conception of slow violence and warfare as part of a single complex of violence. The article traces feminist geopolitics' contribution to research on geographies of slow violence on the one hand, and to the analyses produced within the fields of critical geopolitics and critical war studies on the other, exposing that scholarly work exploiting the relational approach generated within and across these areas of research enables a broader understanding of political violence's tangled operations. Based on the analysis of the recent scholarly engagement with slow violence in the West Bank, the article proposes that thinking of slowness as a form of warfare captures the complex entanglement of different modalities of violence as they materialize in specific spatio‐temporal circumstances. Moreover, such an approach contributes to the further reinvigoration of feminist geopolitics with insights generated within (settler) colonial studies.
The introduction of the CGRP monoclonal antibodies and their effect on the prescription patterns of chronic migraine preventive medications in a tertiary headache center: A retrospective, observational analysis
Authors: Moskatel Leon S. , Graber‐Naidich Anna , He Zihuai , Zhang Niushen
Published: October 2023

Objective

To determine the effect of the introduction of the calcitonin gene–related peptide monoclonal antibodies (CGRP mAbs) in 2018 on the prescribing of older medications for the prevention of chronic migraine.

Background

Prior to 2018, the preventive treatment of migraine borrowed from medications intended to treat other illnesses with the last medication, onabotulinumtoxinA, receiving Food and Drug Administration (FDA) approval for the prevention of chronic migraine in 2010. The FDA approval of three CGRP mAbs in 2018 provided the ideal natural experiment to assess how the introduction of these medications, and a fourth in 2020, affected the generally stable migraine preventive medications market.

Methods

We performed a retrospective cohort analysis using the aggregated de‐identified data of 6595 patients. The percentage of patients with chronic migraine who had been prescribed one of ten most prescribed oral preventive medications or onabotulinumtoxinA, or any of the four CGRP mAbs, were calculated relative to the total number of patients with chronic migraine who received a prescription for any medication from our clinic during the pre‐CGRP mAb years of 2015–2017 and post‐approval years of 2019–2021.

Results

We observed a statistically significant decrease in the prescription of the top 10 most prescribed medications after the introduction of the CGRP mAbs overall (1456/3144, 46.3%, to 1995/4629, 43.1%, p = 0.001), as well as with most individual medications, including large decreases in verapamil (230/3144, 7.3%, to 125/4629, 2.7%; p < 0.001), the tricyclic antidepressants (494/3144, 15.7%, to 532/4629, 11.5%; p < 0.001), topiramate (566/3144, 18.0%, to 653/4629, 14.1%; p < 0.001), and onabotulinumtoxinA (861/3144, 27.4%, to 1134/4629, 24.5%; p = 0.001).

Conclusion

The introduction of the CGRP mAbs during 2018 resulted in a decrease in utilization of most oral medications and onabotulinumtoxinA for the prevention of migraine. Future work should continue to observe how the prescription patterns of these medications evolve with time.
“A lot of work needs to be done”—Service provider perspectives of mental health services available to Croatia‐ and Bosnia‐born migrants
Authors: Karakas Gabriella , du Plooy Daniel R.
Published: October 2023

Research suggests that migrants have higher rates of mental health disorders but are less likely to access mental health services, which highlights both their vulnerability to mental illness and inequity in service provision. Despite being large and established culturally similar migrant cohorts in Australia, Croatians and Bosnians are invisible in mental health research. This qualitative study collected practice‐based evidence from eight mental health service providers who have had direct professional contact with these communities, in order to understand how they engage with services, barriers to uptake and provide suggestions for service improvements. Thematic analysis was used to identify themes across interviews, which were then compared against Yang and Hwang's Migrant Mental Health Service Utilisation Model. The study identified unique factors specific to Croatia‐ and Bosnia‐born migrants that impact how they engage with services, including mandated/prescribed services, religious resources, knowledge resources, referral pathways and procedures, and service provider competencies. This study will promote a better understanding of the limitations of the current mental health service offerings for Croatia‐ and Bosnia‐born migrants, making it significant to practitioners, mental health organizations, policymakers and the general public.
CD57 T cells associated with immunosenescence in adults living with HIV or AIDS
Authors: Elias Junior Erivaldo , Gubert Vanessa T. , Bonin‐Jacob Camila M. , Puga Marco Antonio M. , Gouveia Cláudia G. , Sichinel Angela H. , Tozetti Inês A.
Published: October 2023

Despite the advancement of human immunodeficiency virus (HIV)‐related discoveries, new HIV infections still persist. With the advent of antiretroviral therapy, prognosis has migrated from acute to chronic HIV infection and inflammation, with the possibility of increased immune aging. We aimed to assess such immunosenescence by analysing CD27 and CD57 expression on the surface of T cells. This cross‐sectional study was conducted between 2017 and 2018 on people living with HIV/AIDS (PLWHA) who attended an outpatient clinic of the Infectious Diseases Service of a university hospital and a geriatric reference service in Brazil. A standardized interview was conducted, and venous peripheral blood was collected for flow cytometry analysis. To assess immunosenescence, we compared CD27 and CD57 expression on the surface of T cells between adult and elderly individuals without HIV and adult PLWHA. All results for cells in terminal senescent stages in adult PLWHA more closely resembled those of elderly than adult participants without HIV (p > 0.05). The presence of CD27+ cells did not differ statistically among the three study groups when comparing immunological responders (IR) and immunological non‐responders (INR); for the entire CD4+ T‐cell population (including CD4 + CD8+ and CD4 + CD8– cells), the median count (25–75th) was higher in the INR (79.6%) than the IR (68.0%) group. HIV‐infected individuals possessed a higher number of T lymphocytes with a molecular phenotype associated with immunosenescence, a lower proportion of T cells in the early stages of senescence (median 25–75th: 27.0%), and a higher proportion of T cells in the intermediate and final stages of senescence (median 25–75th: 16.1%) than adults without HIV (median 25–75th: 42.0% and 18.4%, respectively). Considering the higher number of senescent T lymphocytes, we observed in our PLWHA population—especially in the INR group (CD8CD57+ cells: 39.3% INR vs. 23.4% IR; CD4CD57+ cells: 44.0% INR vs. 27.7% IR)—may indicate a similar mortality risk phenotype from immune‐preventable diseases
Interview With Adrian Raftery
Authors: Alkema Leontine , Murphy Thomas Brendan , Raftery Adrian E.
Published: October 2023

Professor Adrian E. Raftery is the Boeing International Professor of Statistics and Sociology and an adjunct professor of Atmospheric Sciences at the University of Washington in Seattle. He was born in Dublin, Ireland, and obtained a BA in Mathematics (1976) and an MSc in Statistics and Operations Research (1977) at Trinity College Dublin. He obtained a doctorate in mathematical statistics in 1980 from the Université Pierre et Marie Curie in Paris, France, under the supervision of Paul Deheuvels. He was a lecturer in statistics at Trinity College Dublin from 1980 to 1986, and then an associate (1986–1990) and full (1990‐present) professor of statistics and sociology at the University of Washington. He was the founding Director of the Center for Statistics and Social Sciences (1999–2009). Professor Raftery has published over 200 articles in peer‐reviewed statistical, sociological and other journals. His research focuses on Bayesian model selection and Bayesian model averaging, model‐based clustering, inference for deterministic simulation models, and the development of new statistical methods for demography, sociology, and the environmental and health sciences. He is a member of the United States National Academy of Sciences, a Fellow of the American Academy of Arts and Sciences, an Honorary Member of the Royal Irish Academy, a member of the Washington State Academy of Sciences, a Fellow of the American Statistical Association, a Fellow of the Institute of Mathematical Statistics, and an elected Member of the Sociological Research Association. He has won the Population Association of America's Clifford C. Clogg Award, the American Sociological Association's Paul F. Lazarsfeld Award for Distinguished Contribution to Knowledge, the Jerome Sacks Award for Outstanding Cross‐Disciplinary Research from the National Institute of Statistical Sciences, the Parzen Prize for Statistical Innovation, and the Science Foundation Ireland St. Patrick's Day Medal. He is also a former Coordinating and Applications Editor of the Journal of the American Statistical Association and a former Editor of Sociological Methodology. He was identified as the world's most cited researcher in mathematics for the decade 1995–2005 by Thomson‐ISI. Thirty‐three students have obtained PhD's working under Raftery's supervision, of whom 21 hold or have held tenure‐track university faculty positions. He has over 150 academic descendants. This interview took place over two sessions in March 2023.
Think and Feel Country Clusters: A New Approach to International Advertising Standardization
Authors: Zandpour Fred , Harich Katrin R.
Published: October 2023

This article challenges the assumption implicit in regional approaches to international advertising standardization. As such, we address the geographic extent to which advertising can or should be standardized. We develop a model for predicting a country's most prevalent advertising appeals on the basis of cultural and market‐related factors. The model is tested and then utilized to provide a positioning map of twenty‐three countries and their respective predominant advertising appeals. Four country clusters are identified, with each cluster exhibiting a similar preference for emotional and rational advertising appeals. Contrary to the assumptions underlying regional advertising, the results seem to suggest that countries that are not part of a common geographic region may exhibit similar preferences with respect to the same strategic approach, in spite of cultural differences and lack of regional proximity.
Immobilization of beta‐glucosidase from Penicillium funiculosum on nylon powder
Authors: Aguado J. , Romero MD , Rodriguez L.
Published: October 2023

beta‐Glucosidase from Penicillium funiculosum was immobilized on nylon powder previously activated with triethyloxonium tetrafluoroborate, 1,2‐diaminoethane and glutaraldehyde. The activation of the nylon powder and the immobilization processes were studied and optimized for the enzyme and the matrix. A high activity retention (67%) was obtained using the activation and immobilization conditions finally selected.
Recombinant human acetylcholinesterase expressed in Escherichia coli: refolding, purification and characterization
Authors: Fischer M. , Ittah A. , Gorecki M. , MM Werber
Published: October 2023

A large‐scale preparation of a recombinant human acetylcholinesterase (rhAChE) mutant harbouring a CyS580–>Ser substitution, expressed in Escherichia coli, was refolded following solubilization of the inclusion bodies. Refolded active rhAChE was purified by DEAE‐Sepharose and affinity chromatography to apparent homogeneity with a specific activity (4572 units/mg) similar to that of erythrocyte AChE. The stability of the purified enzyme at 22‐37 degrees C was dependent on the presence of 0.5 mg/ml BSA, and the optimum pH for stability was 9.0. rhAChE has a UV‐absorbance spectrum typical of a tryptophan‐rich protein, with a distinct shoulder at 290 nm and a high absorption coefficient at 280 nm (epsilon 1% = 23.1). The tryptophan residues in active rhAChE are located in an apolar environment, characteristic of a globular molecule. The difference in amino acid composition between red‐blood‐cell‐derived and recombinant hAChE is probably reflected in their different pI values, namely 5.5‐5.8 and 4.6‐5.2 respectively. The CD spectrum of rhAChE is typical for an alpha/beta protein, indicating 39% alpha‐helix and 22% beta‐sheet. This secondary structure is similar to that determined for the Torpedo (electric fish) AChE, by both CD and X‐ray crystallography. On the other hand, a purified misfolded and inactive molecule displays a decrease in alpha‐helical content to 24%, accompanied by an increase in beta‐sheet up to 42%, indicative of extensive changes in the conformation of the protein. On the whole, the recombinant enzyme has been refolded into a native‐like conformation possessing full activity, and is thus similar to the naturally occurring red‐blood‐cell‐derived hAChE.