bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of ultra‐low‐dose CT with tin filter for craniosynostosis
Authors: Tao Wilson , Goetti Robert
Published: November 2024

Introduction

CT has replaced skull radiography as the gold standard for assessment of craniosynostosis in children. To minimise the risks of ionising radiation in this radiosensitive population, low‐dose CT protocols are increasingly being adopted. This study evaluates the effectiveness of an ultra‐low‐dose CT protocol with a tin filter in reducing radiation exposure whilst maintaining diagnostic quality for craniosynostosis, and its utility in the evaluation of other findings not appreciable on skull radiography.

Methods

Twenty‐seven patients who underwent ultra‐low‐dose CT for craniosynostosis were compared with an age‐matched control group who received standard‐dose CT for indications other than craniosynostosis. Differences in radiation dosimetry and quantitative image quality parameters were analysed using independent two‐tailed t‐tests. Radiologist reports were also examined for the frequency of other incidental radiological findings.

Results

Mean effective dose for the 27 ultra‐low‐dose CT scans was 0.14 mSv, a 92% reduction compared with the control group. Image quality, measured by contrast‐to‐noise ratio, was significantly lower in the ultra‐low‐dose scans compared with the standard‐dose scans; however, all scans were diagnostic for detecting or excluding craniosynostosis. Hydrocephalus was able to be ruled out in all 27 ultra‐low‐dose scans.

Conclusion

Ultra‐low‐dose CT with a tin filter allows for the diagnosis of craniosynostosis with a 92% dose reduction compared with the standard CT protocol. Despite lower image quality with the ultra‐low‐dose protocol when compared to standard CT, all 27 scans were adequate for craniosynostosis diagnosis. Additionally, it allowed for the assessment of other relevant findings not appreciable with skull radiography, highlighting its advantages as the new clinical standard for craniosynostosis assessment.
The sustainability impacts of a web‐based outpatient booking application
Authors: Yeo Melissa , Nicholls Kane , Shum Pey Ling , Asadi Hamed , Yang Natalie
Published: November 2024

Background

Climate change is a critical global issue, impacting ecosystems, economies and communities worldwide. The shift from paper‐based to digital systems is becoming increasingly prevalent across industries, with downstream positive impacts on sustainability. In 2020, Austin Health, a public tertiary hospital in Victoria, Australia, adopted a web‐based outpatient booking application, which succeeded the prior paper‐based system. The application served as an integrated platform for administrative staff to access various Austin Information Technology platforms and replaced previous mail‐based outpatient appointment notifications with Short Message Service‐based notifications. This study aimed to assess the environmental impact and organisation‐wide economic cost of a web‐based outpatient booking application compared to the prior paper‐based system across the same time period.

Methods

A retrospective environmental and economic assessment was conducted for both the web‐based booking application and the paper‐based system. The evaluation covered 36,925 outpatient diagnostic imaging studies – including CT, MRI, ultrasound and mammography – performed at Austin Health from 1st July 2023 until 30th June 2024. The environmental impact was assessed by calculating the expected carbon dioxide equivalent (CO2e) emissions produced by each system. The economic cost analysis was conducted from the perspective of the hospital and included the direct costs of labour and materials/consumables.

Results

CO2e emissions were significantly reduced using the web‐based outpatient booking application compared to the prior paper‐based system (38.5 tonnes compared to 0.002 tonnes), predominantly attributable to the elimination of postage‐related fuel emissions (27.7 tonnes). The estimated net operating cost savings across the year was at least AUD 175,000 (in 2024 Australian Dollars, adjusted for inflation). This was primarily due to labour savings from the elimination of workflow inefficiencies (at least 2342 h saved) amounting to at least AUD 85,272 in salary, followed by savings from eliminated pathology tests (AUD 57,422) and postage costs (AUD 55,193).

Conclusion

The adoption of the web‐based outpatient booking application led to a substantial reduction in carbon emissions and operating costs, alongside enhanced operational efficiency and productivity. These benefits are anticipated to be enduring, especially in the face of an ever‐increasing demand for medical imaging services.
LuLIPLEX: A Fast, Highly Sensitive, and Multiplexed Method for the Detection of IgE Against Major Allergens
Authors: Leveque Edouard , Pecalvel Cyprien , Casanovas Natacha , Goyard Sophie , Janin Yves L. , Rose Thierry , Trouche‐Estival Benjamin , Apoil Pol André , Michelet Marine , Guilleminault Laurent , Reber Laurent L.
Published: November 2024

Background

Diagnosis of allergies is mostly based on the patient's clinical history and allergen provocation tests. Determination of specific IgE (sIgE) profiles can be performed to support allergy diagnosis. This is commonly done in vivo by the skin prick test or in vitro with automated systems. Several platforms exist to quantify sIgE levels, but all these methods require access to specific instruments, often delaying the test's results. The IgE luciferase‐linked immunosorbent assay (LuLISA) allows bioluminescent quantification of IgE against peanut in microliter samples, but this method awaits extension to other allergens. This study aimed to validate a new method, named LuLIPLEX, for multiplexed bioluminescent detection of sIgE against 20 major molecular allergens.

Methods

Quantification of sIgE against 12 recombinant or purified food allergens and eight aeroallergens was performed by LuLIPLEX versus standard IgE detection methods (ImmunoCAP, ISAC, ALEX, or NOVEOS). Multiplexed detection of IgE against these 20 allergens was performed within 45 min using 50 μL of serum, plasma, or whole blood samples.

Results

A head‐to‐head comparison between LuLIPLEX and standard IgE detection methods showed a high correlation among all allergens tested. sIgE profiles in polysensitized subjects could be determined within 45 min in serum and plasma samples, as well as using a single drop of capillary blood.

Conclusions

LuLIPLEX is a rapid and sensitive method to quantify sIgE levels against multiple allergens. Given that the test is very fast and can be performed on small and inexpensive luminometers, the IgE LuLIPLEX could allow point‐of‐care testing of sIgE profiles in allergic subjects.
Human Pulmonary Neuroendocrine Cells Respond to House Dust Mite Extract With PAR‐1 Dependent Release of CGRP
Authors: Mann‐Nüttel Ritu , Mandal Shivani , Armbruster Marie , Puttagunta Lakshmi , Forsythe Paul
Published: November 2024

Background

Pulmonary neuroendocrine cells (PNEC) are rare airway epithelial cells that have recently gained attention as potential amplifiers of allergic asthma. However, studying PNEC function in humans has been challenging due to a lack of cell isolation methods, and little is known about human PNEC function in response to asthma‐relevant stimuli. Here we developed and characterized an in vitro human PNEC model and investigated the neuroendocrine response to extracts of the common aeroallergen house dust mite (HDM).

Methods

PNEC‐enriched cultures were generated from human induced pluripotent stem cells (iPNEC) and primary bronchial epithelial cells (ePNEC). Characterized PNEC cultures were exposed to HDM extract, a volatile chemical odorant (Bergamot oil), or the bacterial membrane component, lipopolysaccharide (LPS), and neuroendocrine gene expression and neuropeptide release determined.

Results

Both iPNEC and ePNEC models demonstrated similar baseline neuroendocrine characteristics and a stimuli‐specific modulation of gene expression. Most notably, exposure to HDM but not Bergamot oil or LPS, leads to dose‐dependent induction of the CGRP encoding gene, CALCB, and corresponding release of the neuropeptide. HDM‐induced CALCB expression and CGRP release could be inhibited by a protease‐activated receptor 1 (PAR1) antagonist or protease inhibitors and was mimicked by a PAR1 agonist.

Conclusions

We have characterized a novel model of PNEC‐enriched human airway epithelium and utilized this model to demonstrate a previously unrecognized role for human PNEC in mediating a direct neuroendocrine response to aeroallergen exposure.
Artificial intelligence measured 3D lumbosacral body composition and clinical outcomes in rectal cancer patients
Authors: Wei Matthew , Hong Wei , Cao Ke , Loft Matthew , Gibbs Peter , Yeung Justin M.
Published: November 2024

Introduction

Patient body composition (BC) has been shown to help predict clinical outcomes in rectal cancer patients. Artificial intelligence algorithms have allowed for easier acquisition of BC measurements, creating a comprehensive BC profile in patients using data from an entire three‐dimensional (3D) region of the body. This study has utilized AI technology to measure BC from the entire lumbosacral (L1‐S5) region and assessed the associations between BC and clinical outcomes in rectal cancer patients who have undergone neoadjuvant therapy followed by surgery.

Methods

A retrospective, cross sectional analysis was performed on locally advanced rectal cancer (LARC) patients treated with neoadjuvant long‐course chemoradiotherapy followed by curative resection with total mesorectal excision at a tertiary referral centre, Western Health, Melbourne, Australia. A pre‐trained and validated in‐house AI segmentation model was used to automatically segment and measure intramuscular adipose tissue (IMAT), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and skeletal muscle (SM) from CT slices across the entire L1–S5 level of each patient. Multivariate analysis between patient BC and clinical outcomes was performed.

Results

Two hundred and fourteen patients were included in the study. One hundred and fifty‐one (70.6%) patients were male and 63 (29.4%) patients were female. The average age at diagnosis was 62.4 (±12.7) years. SM density, but not volume, was associated with better overall survival (OS) (HR 0.24, P = 0.029), recurrence‐free survival (RFS) (HR 0.45, P = 0.048) and decreased length of stay (LoS) (HR 1.58, P = 0.036). Both IMAT volume (HR 0.13, P = 0.008) and density (HR 0.26, P = 0.006) were associated with better OS.

Conclusion

This study measured 3D BC from the entire lumbosacral region of rectal cancer patients. SM density was the most significant BC parameter, and was associated with improved OS, RFS and LoS. This adds to growing evidence that SM is a key component of BC in cancer patients and should be optimized prior to treatment. IMAT was also a prognostic factor, giving rise to avenues of future research into the role of adiposity on nutrition and tumour immunology.
Does the Productivity of SMEs Affect Poverty Within the EU27? An Empirical Investigation
Authors: Bertsatos Georgios , Missos Vlassis , Rizos Anastasios
Published: November 2024

We examine the relationship between small and medium enterprises’ (SMEs’) productivity and the living standards of low‐income groups in the EU27. To the best of our knowledge, this is the first study that tries to shed light on the link between SMEs’ productivity and poverty in a group of developed economies. Our results from panel estimators suggest a robust positive link between the income—in purchasing power standards (PPS) terms—of the poor population and the productivity (gap) of very small firms, small firms, and SMEs. Such effect also appears to hold true, especially for SMEs, during Covid19. Finally, we explore the same link for the high‐tech, knowledge‐intensive SMEs and confirm a strong positive relationship before Covid19.
Why does GLP‐1 agonist combined with GIP and/or GCG agonist have greater weight loss effect than GLP‐1 agonist alone in obese adults without type 2 diabetes?
Authors: Jiang Yuchen , Zhu Huijuan , Gong Fengying
Published: November 2024

Obesity is a chronic condition demanding effective treatment strategies, among which pharmacotherapy plays a critical role. As glucagon‐like peptide‐1 (GLP‐1) agonist approved by the Food and Drug Administration (FDA) for long‐term weight management in adults with obesity, liraglutide and semaglutide have great weight loss effect through reducing food intake and delaying gastric emptying. The emergence of unimolecular polypharmacology, which utilizes single molecules to simultaneously target multiple receptors or pathways, marked a revolutionary improvement in GLP‐1‐based obesity pharmacotherapy. The dual agonist tirzepatide activates both GLP‐1 and glucose‐dependent insulinotropic polypeptide (GIP) receptors and has shown enhanced potency for weight loss compared to conventional GLP‐1 mono agonist. Furthermore, emerging data suggests that unimolecular GLP‐1/glucagon (GCG) dual agonist, as well as GLP‐1/GIP/GCG triple agonist, may offer superior weight loss efficacy over GLP‐1 agonist. This review summarizes the comprehensive mechanisms underlying the pronounced advantages of GLP‐1/GIP dual agonist, GLP‐1/GCG dual agonist and GLP‐1/GIP/GCG triple agonist over GLP‐1 mono agonist in weight reduction in obese adults without type 2 diabetes. A deeper understanding of these unimolecular multitargeting GLP‐1‐based agonists will provide insights for their clinical application and guide the development of new drugs for obesity treatment.
Evaluation of diagnostic criteria for mild‐to‐advanced stages of Fontan‐associated liver disease: A nationwide epidemiological survey in Japan
Authors: Kogiso Tomomi , Tokuhara Daisuke , Ohfuji Satoko , Tanaka Atsushi , Kanto Tatsuya
Published: November 2024

Aim

Fontan‐associated liver disease (FALD) is a complication after Fontan surgery, and a common cause of liver tumors and cirrhosis. However, no diagnostic criteria for FALD have been established, leading to an underestimation of its prevalence.

Methods

We conducted a national survey to elucidate the characteristics of FALD by collecting data from high‐volume centers managing patients who had undergone the Fontan surgery in Japan. In total, 1168 patients were enrolled in the study. First, we examined typical liver findings on ultrasonography after the Fontan surgery. Next, we proposed diagnostic criteria for FALD and advanced FALD based on blood tests, imaging, liver tumors, and pathological examinations. We investigated the sensitivity of histologically diagnosed FALD and advanced FALD based on criteria for blood or imaging tests.

Results

Hepatomegaly, hepatic venous dilatation, caudate lobe enlargement, splenomegaly, liver atrophy, ascites, hepatocellular carcinoma, and hepatic tumors other than hepatocellular carcinoma were observed in 37.7%, 29.9%, 18.4%, 33.2%, 3.2%, 6.0%, 0.85%, and 10.0% of patients, respectively. Typical ultrasound findings of FALD included hepatomegaly, hepatic vein dilatation, and splenomegaly, reflecting liver congestion. With the progression of fibrosis, caudate lobe enlargement and splenomegaly became more prominent. Based on these findings, we proposed diagnostic criteria for FALD. Using these criteria, FALD was diagnosed in 1014 (86.8%) of the patients, and all patients with a pathological diagnosis of FALD were successfully identified. Eight patients were found to have pathological cirrhosis, and all were diagnosed with advanced FALD using our criteria based on blood tests or imaging.

Conclusion

Our diagnostic criteria facilitate detection of FALD or advanced FALD after the Fontan surgery. The accuracy of these criteria should be further evaluated.
How large is the output cost of disinflation?
Authors: Tetlow Robert J.
Published: November 2024

This paper examines estimates of, and drivers for, the sacrifice ratio, defined as the cumulative sum of foregone annualised output accruing from a disinflation of one percentage point. Three approaches are employed. The first reviews the literature on what sacrifice ratio might be expected. The second studies a generic disinflation experiment using 40 estimated macro models of the U.S. economy, calculating a distribution of sacrifice ratios. Those sacrifice ratios are high by historical standards and the paper discusses some stories for why this is so. The role of expectations formation and the credibility of policy is emphasised. The third approach investigates more closely some drivers of the output cost of disinflation by carrying out a selection of disinflation experiments using the FRB/US model, varying certain characteristics of the model's expectations formation mechanism. Pinning down a precise measure for the output cost of disinflation is challenging. However, the literature and policy experiments do offer some guidance on how the sacrifice ratio can be reduced.
Does a Customer Focus Influence Firms’ Climate‐Change Reporting Decisions? The Role of Market‐Driven Corporate Culture
Authors: Bose Sudipta , Cahan Steven F. , Dhole Sandip , Mishra Sagarika
Published: November 2024

While there is increasing investor demand for climate‐change disclosures, less is known about how a firm's culture influences its decision to provide these disclosures. In this study, we focus on market‐driven or customer‐focused culture. We expect that firms with a market‐driven culture (MDC) will be more likely to provide climate‐change disclosures because such firms are more customer‐oriented. Our results are consistent with this expectation. We also find that the level of carbon emissions is negatively associated with MDC, suggesting that the climate‐change disclosures are not merely greenwash. Further, we find firm value is higher for MDC firms that provide climate‐change disclosures. Overall, we contribute to the literature by identifying MDC as an important determinant of climate‐change disclosure.
Measurement of Physical Activity Divided Into Inside and Outside the Home in People With Parkinson's Disease: A Feasibility Study
Authors: Hirakawa Yuichi , Sakurai Hiroaki , Takeda Kazuya , Koyama Soichiro , Iwai Masanobu , Motoya Ikuo , Kanada Yoshikiyo , Kawamura Nobutoshi , Kawamura Mami , Tanabe Shigeo
Published: November 2024

Rationale

In people with Parkinson's disease (PD), quantitative assessment of activities inside and outside the home is crucial for planning effective rehabilitation tailored to a person's living conditions and characteristics.

Aims and Objectives

We examined the feasibility of combining a physical activity metre and a daily activity diary for people with PD.

Methods

Physical activity was evaluated using a triaxial accelerometer and recorded in a daily activity diary by the participant. The feasibility outcome was the data adoption rate, which was the physical activity rate calculated from the activity metre wearing time and the missing times from the daily activity diary.

Results and Conclusion

Of the 10 participants, nine had a complete data set (adoption rate 90%). The mean physical activity metre wearing time was 14.12 ± 2.26 h/day, with a mean missing time of 25.7 ± 18.1 min/day in the daily activity diary. Combining a physical activity metre and a daily activity diary is feasible in people with PD, particularly when planning rehabilitation protocols to enhance daily physical activity.
What, When, and How of Responsible Leadership: Taking Stock of Eighteen Years of Research and a Future Agenda
Authors: Javed Muzhar , Pless Nicola , Waldman David A. , Garavan Thomas , Gull Ammar Ali , Akhtar Muhammad Waheed , Mouri Nacef , Sengupta Atri , Maak Thomas
Published: November 2024

Because research on responsible leadership has grown significantly in recent years, we conducted a systematic review of research on responsible leadership. Our overall goal was to establish a comprehensive understanding of alternative definitions of responsible leadership, its theoretical foundations, and distinctions from other moral leadership constructs. Drawing from 194 studies, we first clarify the conceptual underpinnings of responsible leadership, and how it differs from other constructs in the moral leadership domain, thus highlighting its value as a construct. Second, we identify and evaluate the prominent theoretical frameworks that underpin responsible leadership. Third, we conceptualize the antecedents, mediating factors, contingency variables and outcomes of responsible leadership. Fourth, we offer important recommendations for future research that will move the field forward. Overall, our review provides insights to advance an understanding of responsible leadership.
Heterogeneity in pediatric resting EEG data processing and analysis: A state of the field
Authors: Troller‐Renfree Sonya V. , Morales Santiago , Buzzell George A. , Sandre Aislinn
Published: November 2024

Developmental, resting electroencephalography (EEG) is gaining rapid popularity with implementation in large‐scale studies as well as a recent WHO report naming resting EEG as a gold standard measure of brain health. With an increased interest in resting EEG as a potential biomarker for neurocognition, it is paramount that resting EEG findings are reliable and reproducible. One of the major threats to replicability and reproducibility stems from variations in preprocessing and analysis. One of the primary challenges facing the field of developmental EEG is that it can be challenging to acquire data from infants and children, which commonly makes data cleaning and analysis difficult and unstandardized. The goal of the present manuscript is to take a state of the field of the methods experts in resting EEG report they would use to clean and analyze a hypothetical data set. Here we report on the responses of 66 self‐identified experts in developmental psychophysiology, none of which submitted identical preregistrations. As expected, there were areas of more and less consensus, but ultimately, we believe our findings highlight opportunities for core methodological work and field‐level efforts to establish consensus.
Marine emissions of methanethiol increase aerosol cooling in the Southern Ocean
Authors: Wohl Charel , Villamayor Julián , Galí Martí , Mahajan Anoop S. , Fernández Rafael P. , Cuevas Carlos A. , Bossolasco Adriana , Li Qinyi , Kettle Anthony J. , Williams Tara , Sarda-Esteve Roland , Gros Valérie , Simó Rafel , Saiz-Lopez Alfonso
Published: November 2024

Ocean-emitted dimethyl sulfide (DMS) is a major source of climate-cooling aerosols. However, most of the marine biogenic sulfur cycling is not routed to DMS but to methanethiol (MeSH), another volatile whose reactivity has hitherto hampered measurements. Therefore, the global emissions and climate impact of MeSH remain unexplored. We compiled a database of seawater MeSH concentrations, identified their statistical predictors, and produced monthly fields of global marine MeSH emissions adding to DMS emissions. Implemented into a global chemistry-climate model, MeSH emissions increase the sulfate aerosol burden by 30 to 70% over the Southern Ocean and enhance the aerosol cooling effect while depleting atmospheric oxidants and increasing DMS lifetime and transport. Accounting for MeSH emissions reduces the radiative bias of current climate models in this climatically relevant region.
Inflammatory cytokines disrupt astrocyte exosomal HepaCAM-mediated protection against neuronal excitotoxicity in the SOD1G93A ALS model
Authors: Jin Shijie , Tian Yang , Hacker Jonathan , Chen Xuan , Bertolio Marcela , Reynolds Caroline , Jarvis Rachel , Hu Jingwen , Promes Vanessa , Halim Dilara , Gao Fen-Biao , Yang Yongjie
Published: November 2024

Astrocyte secreted signals substantially affect disease pathology in neurodegenerative diseases. It remains little understood about how proinflammatory cytokines, such as interleukin-1α/tumor necrosis factor–α/C1q (ITC), often elevated in neurodegenerative diseases, alter astrocyte-secreted signals and their effects in disease pathogenesis. By selectively isolating astrocyte exosomes (A-Exo.) and employing cell type–specific exosome reporter mice, our current study showed that ITC cytokines significantly reduced A-Exo. secretion and decreased spreading of focally labeled A-Exo. in diseased SOD1G93A mice. Our results also found that A-Exo. were minimally associated with misfolded SOD1 and elicited no toxicity to mouse spinal and human iPSC–derived motor neurons. In contrast, A-Exo. were neuroprotective against excitotoxicity, which was completely diminished by ITC cytokines and partially abolished by SOD1G93A expression. Subsequent proteomic characterization of A-Exo. and genetic analysis identified that surface expression of glial-specific HepaCAM preferentially mediates A-Exo’s axon protection effect. Together, our study defines a cytokine-induced loss-of-function mechanism of A-Exo. in protecting neurons from excitotoxicity in amyotrophic lateral sclerosis.
Cesarean delivery and blood DNA methylation at birth and childhood: Meta-analysis in the Pregnancy and Childhood Epigenetics Consortium
Authors: Wang Siwen , Casey Emma , Sordillo Joanne , Aguilar-Lacasaña Sofía , Morales Berstein Fernanda , Biedrzycki Richard J. , Brescianini Sonia , Chen Su , Hough Amy , Isaevska Elena , Kim Woo Jin , Lecorguillé Marion , Li Sebastian Shaobo , Page Christian M. , Park Jaehyun , Röder Stefan , Salontaji Kristina , Santorelli Gillian , Sun Yidan , Won Sungho , Zillich Eric , Zillich Lea , Annesi-Maesano Isabella , Arshad S. Hasan , Bustamante Mariona , Cecil Charlotte A. M. , Elliott Hannah R. , Ewart Susan , Felix Janine F. , Gagliardi Luigi , Håberg Siri E. , Herberth Gunda , Heude Barbara , Holloway John W. , Huels Anke , Karmaus Wilfried , Koppelman Gerard H. , London Stephanie J. , Mumford Sunni L. , Nisticò Lorenza , Popovic Maja , Rusconi Franca , Schisterman Enrique F. , Stein Dan J. , Send Tabea , Tiemeier Henning , Vonk Judith M. , Vrijheid Martine , Wiemels Joseph Leo , Witt Stephanie H. , Wright John , Yeung Edwina H. , Zar Heather J. , Zenclussen Ana C. , Zhang Hongmei , Chavarro Jorge E. , Hivert Marie-France
Published: November 2024

Children born via cesarean delivery have a higher risk of metabolic, immunological, and neurodevelopmental disorders compared to those born via vaginal delivery, although mechanisms remain unclear. We conducted a meta-analysis of epigenome-wide association studies to examine the associations between delivery mode and blood DNA methylation at birth and its persistence in early childhood. Participants were from 19 pregnancy cohorts (9833 term newborns) and 6 pediatric cohorts (2429 children aged 6 to 10 years). We identified six CpGs in cord blood associated with cesarean delivery (effect size range: 0.4 to 0.7%,
P
< 1.0 × 10
−7
):
MAP2K2
(cg19423175),
LIM2
(cg01500140),
CNP
(cg13917614),
BLM
(cg18247172),
RASA3
(cg22348356), and
RUNX3
(cg20674490), independent of cell proportions and other confounders. In childhood, none of these CpGs were associated with cesarean delivery, and no additional CpGs were identified. Delivery mode was associated with cell proportions at birth but not in childhood. Further research is needed to elucidate cesarean delivery’s molecular influence on offspring health.
Fine-scale Southern California Moho structure uncovered with distributed acoustic sensing
Authors: Atterholt James , Zhan Zhongwen
Published: November 2024

Moho topography yields insights into the evolution of the lithosphere and the strength of the lower crust. The Moho reflected phase (PmP) samples this key boundary and may be used in concert with the first arriving P phase to infer crustal thickness. The densely sampled station coverage of distributed acoustic sensing arrays allows for the observation of PmP at fine-scale intervals over many kilometers with individual events. We use PmP recorded by a 100-km-long fiber that traverses a path between Ridgecrest, CA and Barstow, CA to explore Moho variability in Southern California. With hundreds of well-recorded events, we verify that PmP is observable and develop a technique to identify and pick P-PmP differential times with high confidence. We use these observations to constrain Moho depth throughout Southern California, and we find that short-wavelength variability in crustal thickness is abundant, with sharp changes across the Garlock Fault and Coso Volcanic Field.
The antiviral JNJ-A07 significantly reduces dengue virus transmission by
Aedes aegypti
mosquitoes when delivered via blood-feeding
Authors: Rosales-Rosas Ana L. , Goossens Sara , Chiu Winston , Majumder Atreyee , Soto Alina , Masyn Serge , Stoops Bart , Wang Lanjiao , Kaptein Suzanne J. F. , Goethals Olivia , Delang Leen
Published: November 2024

Dengue virus (DENV) is the most widespread mosquito-borne virus worldwide, but no antiviral therapies are available yet. The pan-serotype DENV inhibitor JNJ-A07 has shown potent activity in a mouse model. It remains unknown whether an antiviral drug ingested by mosquitoes could inhibit virus replication and thus reduce transmission to other hosts. Here, we investigated the antiviral activity of JNJ-A07 when administered in the blood meal to
Aedes aegypti
mosquitoes. JNJ-A07 blocked DENV-2 transmission by the mosquitoes in both pre-exposure and post-exposure settings. In addition, JNJ-A07 remained in the mosquito bodies for 7 days after blood meal. Reductions of DENV systemic infection in the mosquitoes suggested a potential for decreased proportions of DENV outbreaks in a simulated environment when the mosquitoes ingested JNJ-A07 via the blood meal.
Synergistic coordination of diphosphine with primary and tertiary phosphorus centers: Ultrastable icosidodecahedral Ag
30
nanoclusters with metallic aromaticity
Authors: Ding Xu-Yang , Zhang Chengkai , Shi Lin-Xi , Wang Jin-Yun , Yang Xin , Zhang Li-Yi , Sun Di , Chen Zhong-Ning
Published: November 2024

As versatile ligands with extraordinary coordination capabilities, RPH
2
(R = alkyl or aryl) are rarely used in constructing metal nanoclusters due to their volatility, toxicity, spontaneous flammability, and susceptibility to oxidation. In this work, we designed a primary and tertiary phosphorus-bound diphosphine chelator (2-Ph
2
PC
6
H
4
PH
2
) to create ultrastable silver nanoclusters with metallic aromaticity. By controlling the deprotonation rate of 2-Ph
2
PC
6
H
4
PH
2
and adjusting the templates, we successfully synthesized two near-infrared emissive nanoclusters,
Ag30
and
Ag32
, which have analogous icosidodecahedral Ag
30
shells with an
I
h
symmetry. Deprotonated ligand (2-Ph
2
P
α
C
6
H
4
P
β
2−
) exhibits a coordination mode of μ
5
-η
1
(P
β
),η
2
(P
α
,P
β
), which endows a unique metallic aromaticity to
Ag30
and
Ag32
. The solution-processed organic light-emitting diodes based on
Ag30
achieve an external quantum efficiency of 15.1%, representing the breakthrough in application of silver nanoclusters to near-infrared–emitting devices. This work represents a special ligand system for synthesizing ligand-protected coinage metal nanoclusters and opens up horizons of creating nanoclusters with distinct geometries and metal aromaticity.
An mRNA-encoded dominant-negative inhibitor of transcription factor RUNX1 suppresses vitreoretinal disease in experimental models
Authors: O’Hare Michael , Miller William P. , Arevalo-Alquichire Said , Amarnani Dhanesh , Apryani Evhy , Perez-Corredor Paula , Marino Claudia , Shu Daisy Y. , Vanderleest Timothy E. , Muriel-Torres Andres , Gordon Harper B. , Gunawan Audrey L. , Kaplan Bryan A. , Barake Karim W. , Bejjani Romy P. , Doan Tri H. , Lin Rose , Delgado-Tirado Santiago , Gonzalez-Buendia Lucia , Rossin Elizabeth J. , Zhao Guannan , Eliott Dean , Weinl-Tenbruck Christine , Chevessier-Tünnesen Frédéric , Rejman Joanna , Montrasio Fabio , Kim Leo A. , Arboleda-Velasquez Joseph F.
Published: November 2024

Messenger RNA (mRNA)–based therapies are a promising approach to medical treatment. Except for infectious diseases, no other disease has mRNA-based therapies available. The eye is an ideal model for mRNA therapeutic development because it requires limited dosing. Proliferative vitreoretinopathy (PVR) is a blinding condition caused by retinal detachment that now lacks available medical treatment, with surgery as the only treatment option. We previously implicated runt-related transcription factor-1 (RUNX1) as a driver of epithelial-to-mesenchymal transition (EMT) in PVR and as a critical mediator of aberrant ocular angiogenesis when up-regulated. On the basis of these findings, an mRNA was designed to express a dominant-negative inhibitor of RUNX1 (RUNX1-Trap). We show that RUNX1-Trap delivered in polymer-lipidoid complexes or lipid nanoparticles sequestered RUNX1 in the cytosol and strongly reduced proliferation in primary cell cultures established from fibrotic membranes derived from patients with PVR. We assessed the preclinical efficacy of intraocular delivery of mRNA-encoded RUNX1-Trap in a rabbit model of PVR and in a laser-induced mouse model of aberrant angiogenesis often used to study wet age-related macular degeneration. mRNA-encoded RUNX1-Trap suppressed ocular pathology, measured as pathological scores in the rabbit PVR model and leakage and lesion size in the laser-induced choroidal neovascularization mouse model. mRNA-encoded RUNX1-Trap also strongly reduced proliferation in a human ex vivo explant model of PVR. These data demonstrate the therapeutic potential of mRNA-encoded therapeutic molecules with dominant-negative properties, highlighting the potential of mRNA-based therapies beyond standard gene supplementation approaches.
Childhood-onset lupus nephritis is characterized by complex interactions between kidney stroma and infiltrating immune cells
Authors: Danaher Patrick , Hasle Nicholas , Nguyen Elizabeth D. , Roberts Jordan E. , Rosenwasser Natalie , Rickert Christian , Hsieh Elena W. Y. , Hayward Kristen , Okamura Daryl M. , Alpers Charles E. , Reed Robyn C. , Baxter Sarah K. , Jackson Shaun W.
Published: November 2024

Children with systemic lupus erythematosus (SLE) are at increased risk of developing kidney disease, termed childhood-onset lupus nephritis (cLN). Single-cell transcriptomics of dissociated kidney tissue has advanced our understanding of LN pathogenesis, but loss of spatial resolution prevents interrogation of in situ cellular interactions. Using a technical advance in spatial transcriptomics, we generated a spatially resolved, single-cell resolution atlas of kidney tissue from eight patients with cLN and four control individuals. Annotated cells were assigned to 30 reference cell types, including major kidney subsets and infiltrating immune cells. Analysis of spatial distribution demonstrated that individual immune lineages localized to specific regions in cLN kidneys, including myeloid cells that trafficked to inflamed glomeruli and B cells that clustered within tubulointerstitial immune hotspots. Gene expression varied as a function of tissue location, demonstrating how incorporation of spatial data can provide new insights into the immunopathogenesis of SLE. Alterations in immune phenotypes were accompanied by parallel changes in gene expression by resident kidney stromal cells. However, there was little correlation between histologic scoring of cLN disease activity and glomerular cell transcriptional signatures at the level of individual glomeruli. Last, we identified modules of spatially correlated gene expression with predicted roles in induction of inflammation and the development of tubulointerstitial fibrosis. Single-cell spatial transcriptomics allowed insights into the molecular heterogeneity of cLN, paving the way toward more targeted and personalized treatment approaches.
Fluid evolution and genesis of the Yidinan granitoid-hosted orogenic gold deposit (China)
Authors: Wang Jie , Yu Hao-Cheng , Petrella Laura , Duo De-Wen , Wang Lei , Yang Fu , Zhou Hao-Yang , Li Chao , Qiu Kun-Feng
Published: November 2024

The metamorphic model explaining orogenic gold ore formation has become widely accepted. However, there has been extensive debate regarding whether a magmatic-hydrothermal system contributes fluids or metals in the source of orogenic gold deposits. The Yidinan gold deposit is hosted by Triassic quartz diorite in the West Qinling Orogen, China, which is controlled by NNE-trending high-angle brittle-ductile faults. The gold mineralization is characterized by vein and disseminated type ores comprising auriferous pyrite and arsenopyrite. Magmatic apatite U-Pb and magmatic biotite Ar-Ar dating pinpoint the emplacement and the cooling of ore-hosting quartz diorite at 241.8 ± 2.8 Ma and 241.7 ± 0.32 Ma, respectively. In situ U-Pb dating of hydrothermal monazite yield an age of 234.6 ± 2.8 Ma for the gold mineralization. Systematic fluid inclusion investigation suggests that the ore-forming fluids belong to a NaCl-H2O-CO2 ± CH4 system with low salinity (5.76−10.09 wt% NaCl equiv.) and medium temperatures (253−395 °C). During fluid evolution, phase separation occurred, with CO2 and other gases preferentially fractionating into the vapor phase. The sulfur isotope data range from 5.50‰ to 7.85‰ and are higher than those from the nearby magmatic-hydrothermal deposits. Such results support that the gold-bearing fluids were sourced from devolatilization of underlying sedimentary rocks during regional metamorphism. Fluid immiscibility caused by fault-valve processes might be the critical mechanism for the gold deposition. Although the geological and geochronological evidence suggested gold mineralization was spatially and temporally associated with the quartz diorite, the ore-forming fluids are not consistent with a magmatic source; therefore, the Yidinan gold deposit is of an orogenic type. This study reveals that despite orogenic gold mineralization and magmatic activities showing a broad temporal or spatial overlap during orogenesis processes, there is no genetic link between gold mineralization and granitic magmatism in many hydrothermal gold deposits. The low-salinity auriferous metamorphic fluid was released from underlying metasedimentary sequences during orogenesis. The rapid cooling of the granitoid after emplacement further prevented it from contributing to gold-bearing fluid formation or creating the necessary pressure-temperature conditions for gold deposition.
Simultaneous, spontaneous and multivessel cervical artery dissection presenting with headache and vertigo
Authors: Jenkins David Matthew , Cowen Jake , Abimanue Nagushan , Bekker Jasper , Ali Riaz
Published: November 2024

Cervical artery dissection (CAD) is a relatively common cause of stroke, particularly in young adults. Typical presentation includes headache, neck pain and neurological signs of ischaemic stroke. More than half of these cases are spontaneous, without a preceding history of trauma, and most commonly affect a single vessel. We report a case of a man in his 20s presenting with spontaneous, non-traumatic multivessel CAD (triple vessel, quadruple dissection), bilateral cerebellar infarcts and concomitant basilar artery thrombus. Triple or quadruple vessel CAD is seldom reported in the absence of trauma. Clinicians should be aware of CAD, and the extent to which it can occur, while appreciating the importance of good clinical examination and appropriate imaging in such cases. Correct characterisation of eye movements is key.
Shotgun injury: don’t forget the wad
Authors: Rahman Shahrose , Patel Ranish K , Sun John X , Brasel Karen
Published: November 2024

While close-range shotgun injuries may clinically appear similar to gunshot wounds from rifles or handguns, they are important to differentiate as they require special consideration. We present a case of a male in his 20s who sustained a close-range shotgun wound to the right lower extremity and was subsequently found to have a retained, radiolucent shotgun wad deep within the wound bed. Identification and removal of shotgun wads are of paramount importance, as failure to do so may lead to downstream secondary infectious complications.
Plasmablastic multiple myeloma presenting as a pleural mass: a diagnostic challenge
Authors: Kabat Maciej , Patel Vanisha , Bhattacharyya Pritish
Published: November 2024

Plasmablastic multiple myeloma (MM) is a rare and highly aggressive variant of MM that presents significant diagnostic and therapeutic challenges. This variant is characterised by a bone marrow infiltration of ≥2% plasmablasts and is distinguished by its atypical pleomorphic morphology, unique immunohistological profile and extensive extramedullary involvement. The anaplastic features of plasmablastic MM can closely mimic those of high-grade lymphomas, leukaemia, non-haematopoietic malignancies and high-grade carcinomas, often leading to initial diagnostic errors. Accurate diagnosis requires a thorough evaluation that integrates clinical history, radiological findings, morphological analysis, immunophenotyping and genetic markers. Here, we present the case of a woman in her early 70s who was diagnosed with high-risk plasmablastic MM. The patient, with no significant neoplastic history, presented with chronic pain and an acute fracture, initially raising suspicion for high-grade metastatic lung carcinoma.
Sieve element traits differ in pulvini and petioles of Mimosa (Leguminosae, Caesalpinioideae) with different types of leaf movement
Authors: Silva Stefany Cristina de Melo , Machado Silvia Rodrigues , Rodrigues Tatiane Maria
Published: November 2024

The vascular system, particularly the phloem, has been considered a key issue in driving the pulvini functioning. Studies comparing phloem in different leaf regions and in plants with different leaf movement types can help clarifying the aspects involved in the pulvini functioning. Here, we investigated the morphological traits of the sieve tube elements in a comparative way between pulvini and petioles of Mimosa pudica L. (a legume with fast leaf movements) and Mimosa caesalpiniifolia Benth. (a legume with slow leaf movements). Pulvini and petioles were analyzed under light and transmission electron microscopy. Sieve elements in pulvini had thicker walls than those of petioles, especially in M. pudica. Nacreous walls occurred in the sieve elements of M. pudica pulvini. Dispersive and non-dispersive P-proteins and P-plastids occurred in the pulvini and petioles of both species. The marked differences in the lumen area and cell wall features of the sieve elements between pulvini and petiole indicate the specialization of the phloem in the pulvinus functioning.
Rock coast geo model: process-response dynamics, resilience and vulnerability
Authors: Moses Cherith A.
Published: November 2024

Geology and geomorphology link starkly in coastal environments, exemplifying the importance of Fookes' geo model approach to understanding site dynamics. Cliffs, and the shore platforms that front them, are subject to both marine and subaerial processes. Throughout his work, Fookes emphasises the role of climate as a weathering agent, influencing material properties and requiring consideration in engineering projects. Comparatively, more is known about the operation of rock weathering processes on shore platforms than on cliffs. Yet, with changing climate, it is becoming apparent that winter salt and frost weathering, and summer salt and wetting-drying weathering contribute to more frequent occurrences of coastal rockfalls. Increasing storm activity and rising sea levels are enhancing marine and subaerial processes. Rock coasts are amongst the most rapidly eroding coastlines in Europe. New applications of technologies, including seismometers, Lidar and InSAR, provide a fuller understanding of rock coast process-response geo model behaviour and the resilience of rock coasts on engineering timescales. Communicating scientific understanding of rock coast dynamics to policy-makers, planners and the public remains a challenge. Assessments of hazard, risk, resilience and vulnerability of rock coasts associated with climate change provide useful communication tools. Databases such as the British Geological Survey GeoCoast geohazard data product, and EMODnet Geology (European Marine Observation and Data Network) coastal behaviour data products integrate and visualise available data and information to communicate situational awareness to a broad audience.
The life and times of Peter George Fookes: 1933–2020
Authors: Charman John
Published: November 2024

This paper is a personal review of the life and career of Peter Fookes, probably the most influential engineering geologist of his time. It includes personal recollections and a review of his 200 technical publications, his professional career and his influence on how geotechnology is viewed and used by the civil engineering profession. Perhaps his greatest epitaph is the development and use of the ground model.
A Compound Data Poisoning Technique with Significant Adversarial Effects on Transformer-based Sentiment Classification Tasks
Authors: Begoli Edmon , Mahbub Maria , Passarella Linsey , Srinivasan Sudarshan
Published: November 2024

Transformer-based models have demonstrated much success in various natural language processing tasks. However, they are often vulnerable to adversarial attacks, such as data poisoning, which can intentionally fool the model into generating incorrect results. In this article, we present a novel, compound variant of a data poisoning attack on a transformer-based model that maximizes the poisoning effect while minimizing the scope of poisoning. We do so by combining the established data poisoning technique (label flipping) with a novel adversarial artifact selection and insertion technique aimed at minimizing detectability and the scope of the poisoning footprint. We find that by using a combination of these two techniques, we achieve a state-of-the-art attack success rate of approximately 90% while poisoning only 0.5% of the original training set, thus minimizing the scope and detectability of the poisoning action. These findings have the potential to advance the development of better data poisoning detection methods.
The index of maximum sweat ion reabsorption rates of sweat glands does not correlate to whole body sweat sodium concentration in exercising young healthy men
Authors: Oshima Shoma , Okamoto Yumi , Otsuka Junto , Yokoyama Shotaro , Hashimoto Yuki , Ishihara Takako , Togo Hiroyoshi , Amano Tatsuro
Published: November 2024

Galvanic skin conductance is influenced by sweat rate and sweat ions, and the sweat rate at which this response begins to increase may reflect the exceeding capacity of sweat ion reabsorption in sweat glands. However, we show that this indirect measure of the sweat gland’s capacity of ion regulation on the forearm and chest does not correlate with whole body sweat sodium concentration during exercise, excluding its role as a determinant of systemic sweat sodium loss.