bluuebunny/crossref_metadata_2025 huggingface dataset:
A lateral organ boundaries domain transcription factor acts downstream of the auxin response factor 2 to control nodulation and root architecture in Medicago truncatula
Authors: Kirolinko Cristina , Hobecker Karen , Cueva Marianela , Botto Florencia , Christ Aurélie , Niebel Andreas , Ariel Federico , Blanco Flavio Antonio , Crespi Martín , Zanetti María Eugenia
Published: April 2024

Legume plants develop two types of root postembryonic organs, lateral roots and symbiotic nodules, using shared regulatory components. The module composed by the microRNA390, the Trans‐Acting SIRNA3 (TAS3) RNA and the Auxin Response Factors (ARF)2, ARF3, and ARF4 (miR390/TAS3/ARFs) mediates the control of both lateral roots and symbiotic nodules in legumes.

Here, a transcriptomic approach identified a member of the Lateral Organ Boundaries Domain (LBD) family of transcription factors in Medicago truncatula, designated MtLBD17/29a, which is regulated by the miR390/TAS3/ARFs module. ChIP‐PCR experiments evidenced that MtARF2 binds to an Auxin Response Element present in the MtLBD17/29a promoter. MtLBD17/29a is expressed in root meristems, lateral root primordia, and noninfected cells of symbiotic nodules.

Knockdown of MtLBD17/29a reduced the length of primary and lateral roots and enhanced lateral root formation, whereas overexpression of MtLBD17/29a produced the opposite phenotype. Interestingly, both knockdown and overexpression of MtLBD17/29a reduced nodule number and infection events and impaired the induction of the symbiotic genes Nodulation Signaling Pathway (NSP) 1 and 2.

Our results demonstrate that MtLBD17/29a is regulated by the miR390/TAS3/ARFs module and a direct target of MtARF2, revealing a new lateral root regulatory hub recruited by legumes to act in the root nodule symbiotic program.
Evaluating free segmentation tools for CBCT‐derived models: Cost‐effective solutions
Authors: Elkersh Noha M. , Abdelrahman Hams H. , Hassan Mohamed G.
Published: April 2024

Objectives

This study evaluated the segmentation accuracy and reliability of free software packages and compared them with commercial alternatives.

Material and Methods

A total of 36 stone models were scanned using a desktop scanner and then imaged by cone beam computed tomography (CBCT). The CBCT volumes were segmented using 2 free software packages (3D Slicer and Blue Sky Plan) and 2 commercial software packages (Mimics and OnDemand3D). Stereolithography (STL) files generated by the desktop scanner were used as the control group (reference models). The accuracy of segmentation was evaluated by (1) comparing 6 linear measurements taken from each STL model generated by the 4 software packages with that obtained by the scanner, and (2) deviation analysis of each STL model generated by the 4 software packages with that obtained by the scanner. Absolute error and percentage error, repeated measures anova and Friedman test followed by post hoc analysis, intraclass correlation coefficient (ICC), and Pearson's r were used to evaluate the accuracy of the tested software packages.

Results

There was no statistically significant difference in all intra‐arch measurements obtained using the four software packages. Measurements obtained using the free software packages and the scanner showed excellent positive correlation, ranging from 0.825 to 0.988, confirming equivalence with commercial software packages.

Conclusion

Within the settings of the current study, accurate and time‐saving segmentations with high positive correlation could be performed using the tested free segmentation software packages (3D Slicer and Blue Sky Plan). Nevertheless, further evaluation is necessary to gage their accuracy using different CBCT modalities.
Development of a one‐step multiplex reverse transcription‐polymerase chain reaction and Luminex xTAG assay for the simultaneous detection of yellowing viruses infecting sugar beet
Authors: Schop Sharella , van den Ham Floor , van Oorschot Ellen , Grapendaal Sander R. , Raaijmakers Elma , van der Vlugt Rene A. A.
Published: April 2024

Yellowing viruses are an increasing threat to sugar beet cultivation, due to limitations on insecticide usage and climate change. Virus detection, monitoring and resistance breeding are key to secure high sugar beet yields in the future. For this research, a one‐step multiplex reverse transcription (mRT)‐PCR method was designed to detect simultaneously beet mild yellowing virus, beet chlorosis virus, beet yellows virus (BYV), beet mosaic virus and turnip yellows virus. The addition of Luminex xTAG array technology was used as a follow‐up method to increase assay specificity. The one‐step mRT‐PCR was evaluated on 22 field samples with single and mixed virus infections. The xTAG assay works as expected both in a simplex and multiplex setting, except that BYV detection needs optimization in the multiplex setting. In the future, the Luminex xTAG assay would be an excellent method for the detection of beet yellowing viruses due to its high specificity and the potential to increase the number of targets.
Unveiling the ecological resilience and industrial potential of Skeletonema marinoi through mixotrophic cultivation in Nordic winter condition
Authors: Villanova Valeria , Engelbrektsson Johan , Strömberg Niklas , Ekendahl Susanne , Spetea Cornelia
Published: April 2024

Mixotrophy, the concurrent use of inorganic and organic carbon in the presence of light for microalgal growth, holds ecological and industrial significance. However, it is poorly explored in diatoms, especially in ecologically relevant species like Skeletonema marinoi. This study strategically employed mixotrophic metabolism to optimize the growth of a strain of Skeletonema marinoi (Sm142), which was found potentially important for biomass production on the west coast of Sweden in winter conditions. The aim of this study was to discern the most effective organic carbon sources by closely monitoring microalgal growth through the assessment of optical density, chlorophyll a fluorescence, and biomass concentration. The impact of various carbon sources on the physiology of Sm142 was investigated using photosynthetic and respiratory parameters. The findings revealed that glycerol exhibited the highest potential for enhancing the biomass concentration of Sm142 in a multi‐cultivator under the specified experimental conditions, thanks to the increase in respiration activity. Furthermore, the stimulatory effect of glycerol was confirmed at a larger scale using environmental photobioreactors simulating the winter conditions on the west coast of Sweden; it was found comparable to the stimulation by CO2‐enriched air versus normal air. These results were the first evidence of the ability of Skeletonema marinoi to perform mixotrophic metabolism during the winter and could explain the ecological success of this diatom on the Swedish west coast. These findings also highlight the importance of both organic and inorganic carbon sources for enhancing biomass productivity in harsh winter conditions.
Are bureaucrats' interactions with politicians linked to the bureaucrats' policy entrepreneurship tendencies?
Authors: Silveira Mariana Costa , Cohen Nissim , Lotta Gabriela
Published: April 2024

Are bureaucrats' interactions with politicians, as well as with other government and non‐government players in the policy arena, linked with the bureaucrats' policy entrepreneurship tendencies? To investigate this question, we sought to identify the factors influencing bureaucrats' willingness to engage in policy entrepreneurship. We also explored the bureaucrats' motivations for doing so in order to better understand if policy entrepreneurship among bureaucrats is a desirable phenomenon. Using national survey data from Brazil, our findings indicate that politician–bureaucrat interactions have a positive relationship with bureaucrats' perceptions about policy entrepreneurship. In addition, there is a positive association between bureaucrats' motivations for engaging in policy entrepreneurship and their social values.
Regulatory mechanism of miR‐20a‐5p in neuronal damage and inflammation in lipopolysaccharide‐induced BV2 cells and MPTP‐HCl‐induced Parkinson's disease mice
Authors: Gao Yanlei , Sheng Dan , Chen Weiguang
Published: April 2024

Background

Parkinson's disease (PD) is a prevailing neurodegenerative disorder increasingly affecting the elderly population. The involvement of microRNAs (miRNAs) in PD has been confirmed. We sought to explore the molecular mechanism of miR‐20a‐5p in PD.

Methods

Lipopolysaccharide (LPS)‐induced BV2 cell model and 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine hydrochloride (MPTP‐HCl)‐induced PD mouse model were established. miR‐20a‐5p, inducible nitric oxide synthase (iNOS), interleukin (IL)‐6, tumour necrosis factor (TNF)‐α, transforming growth factor (TGF)‐β1, and IL‐10 expression in BV2 cells was examined by reverse transcription – quantitative polymerase chain reaction. Cell viability was assessed by MTT assay. The apoptotic rate and levels of Bcl‐2, Bax, cleaved caspase‐3, and signal transducer and activator of transmission (STAT)3 were examined by flow cytometry and Western blot. Bioinformatics software predicted the potential binding sites of miR‐20a‐5p and STAT3. Dual‐luciferase experiment verified the binding relationship. Iba1‐positive and tyrosine hydroxylase (TH)‐positive cell numbers in substantia nigra pars compacta were detected by immunohistochemistry. The effect of miR‐20a‐5p on motor function in MPTP‐induced PD mice was detected by Rota‐rod test, Pole test, Traction test and Beam‐crossing task.

Results

miR‐20a‐5p was under‐expressed in LPS‐induced BV2 cells. Overexpression of miR‐20a‐5p increased the viability of LPS‐induced BV2 cells and reduced apoptosis rates. Moreover, overexpression of miR‐20a‐5p reduced cleaved caspase‐3, Bax, iNOS, IL‐6, and TNF‐α and increased Bcl‐2 and TGF‐β1, and IL‐10. miR‐20a‐5p targeted STAT3. STAT3 overexpression partially reversed miR‐20a‐5p overexpression‐mediated effects on LPS‐induced BV2 cell viability, apoptosis, and inflammatory responses. miR‐20a‐5p overexpression inhibited MPTP‐induced STAT3 and α‐synuclein levels, microglia activation, and inflammatory response, and reduced the loss of TH‐positive cells in mice. miR‐20a‐5p overexpression ameliorated MPTP‐induced dyskinesia in PD model mice.

Conclusion

miR‐20a‐5p alleviates neuronal damage and suppresses inflammation by targeting STAT3 in PD.
Generalizations of the Muller–Schupp theorem and tree‐like inverse graphs
Authors: Rodaro Emanuele
Published: April 2024

We extend the characterization of context‐free groups of Muller and Schupp in two ways. We first show that for a quasi‐transitive inverse graph , being quasi‐isometric to a tree, or context‐free in the sense of Muller–Schupp (finitely many end‐cone up to end‐isomorphism), or having the automorphism group that is virtually free, are all equivalent conditions. Furthermore, we add to the previous equivalences a group theoretic analog to the representation theorem of Chomsky–Schützenberger that is fundamental in solving a weaker version of a conjecture of Brough which also extends Muller and Schupp's result to the class of groups that are virtually finitely generated subgroups of the direct product of free groups. We show that such groups are precisely those whose word problem is the intersection of a finite number of languages accepted by quasi‐transitive, tree‐like inverse graphs.
Crisis estatal en Ecuador: del Estado postneoliberal al Estado predatorio
Authors: Stoessel Soledad
Published: April 2024

El texto aborda el proceso político que derivó en la neoliberalización del Estado y posterior crisis estatal en Ecuador durante el período 2017-2023. Esto se produjo por medio de dos mecanismos: la captura estatal del Estado por los sectores dominantes y la puesta en marcha del lawfare por parte del bloque antipopulista para neutralizar al correísmo como fuerza política, durante el gobierno de L. Moreno. El anticorreísmo operó como identidad política capaz de estructurar el campo político. El texto sostiene que del Estado postneoliberal configurado durante los gobiernos de R. Correa (2007-2017), se pasó a un Estado corporavitizado “hacia arriba”, capturado por las elites y posteriormente durante el gobierno del banquero G. Lasso, a un Estado predatorio al servicio de la apropiación privada y corrupta de las rentas públicas por parte de las elites económicas-financieras.
A Time Headway Control Scheme for Virtually Coupled Heavy Haul Freight Trains
Authors: Wu Qing , Ge Xiaohua , Zhu Shengyang , Cole Colin , Spiryagin Maksym
Published: April 2024

Virtual coupling of railway trains is an emerging technology that has the potential to significantly increase railway operational efficiency by reducing the train following distance from absolute braking distances to relative braking distances. Current research in this topic is mainly focused on passenger trains and uses distance-based headways. This paper studied virtual coupling for heavy haul freight trains and demonstrated that the distance headway scheme was challenging and sometimes impractical for heavy haul trains to achieve virtual coupling. A time-based headway scheme was then proposed to set the follower train to be a certain time behind the schedule of the leader train rather than a distance headway. The time-based headway required the follower train to reproduce the leader train's operational status at the same track location. This also allowed the follower train to copy any optimized train driving strategies from the leader train. Demonstrative simulations were carried out without the consideration of communication errors and train localization errors. The results show that a conventional distance headway simulation had maximum distance and speed errors of 716 m (36%, reference 2 km) and 24 km/h (66%, reference 36 km/h), respectively. A time-based headway simulation reduced the maximum distance and speed errors to 0.07 m (0%, reference 2 km) and 0.1 km/h (9%, reference 1.18 km/h), respectively.
Characteristics of Laminar Separation Bubble With Varying Leading-Edge Shapes and Deflections of the Trailing-Edge Flap
Authors: Sarvankar Sumit S. , Sarkar Drik , Arasu Adrin Issai , Mistry Chetankumar Sureshbhai , Vadlamani Nagabhushana Rao
Published: April 2024

A series of implicit large eddy simulations (ILES) is carried out to examine the characteristics of a leading edge (LE) separation bubble. The test case comprises a flat plate with an elliptic leading edge (ELE), which is equipped with a trailing edge flap. Simulations are carried out (a) at three different flap angles (20 deg, 30 deg, 90 deg) and (b) using two different geometries of ELE where the ratio of the semimajor to semiminor axis is set to either 2:1 or 4:1. The flap is modeled using the immersed boundary method, which is computationally economical as it avoids regenerating the grid for varying flap angles. The results show that (a) the flow separates at lower flap deflection angles with a decrease in the aspect ratio of the ELE from 4:1 to 2:1 (b) an increase in the flap angle promotes separation at the LE due to an increase in the blockage in the bottom passage and a subsequent increase in the flow incidence at the leading edge. Simulations are also carried out using the γ−Reθ transition model and comparisons are drawn against ILES and experiments. Although the qualitative trends predicted using both ILES and Reynolds-Averaged Navier–Stokes (RANS) agree with the experiments, both approaches predict relatively shorter separation bubbles. This is attributed to the excess flow blockage in experiments due to the support plates, which are not modeled in the simulations. Nevertheless, the results demonstrate the superior accuracy of ILES over the RANS model.
Novel surface wave technique for moderate-pressure plasma measurements
Authors: Hussain Shadhin , Goeckner Matthew
Published: April 2024

Most in situ plasma diagnostics are only reliable for low-pressure systems, e.g., systems where the collision frequency, νen, is small compared to the plasma frequency, ωpe. In this article, we describe a novel diagnostic technique for simultaneous measurement of the plasma density, ne; electron temperature, Te; and νen in systems in which νen approaches ωpe. We illustrate the operational setup of our probe system along with an analytical framework for ascertaining ne, Te, and νen. Furthermore, we show experimental results from argon capacitively coupled plasma operating in the 0.5–1 Torr pressure range.
Improving SiO2 to SiNx etch selectivity during atomic layer etching with multiple selective organic pre-functionalization steps
Authors: Wang Xue , Gasvoda Ryan J. , Hudson Eric A. , Kumar Prabhat , Agarwal Sumit
Published: April 2024

Selective thermal pre-functionalization of plasma-deposited SiNx surface with benzaldehyde has been shown to facilitate the formation of a carbon-rich hydrofluorocarbon layer, which retards the etch of SiNx, thereby increasing the etch selectivity of SiO2 to SiNx during atomic layer etching (ALE). However, in technological applications in device manufacturing, the SiNx layer is often buried under the SiO2 layer or has been exposed to the atmosphere. This leads to low uptake of benzaldehyde on the SiNx surface either due to a residual CFx layer or due to the formation of surface SiOxNy. Using in situ attenuated total reflection Fourier transform infrared spectroscopy, we show that the selectivity for benzaldehyde attachment to SiNx over SiO2 is reduced with the slow accumulation of a fluorocarbon residue on both surfaces with an increasing number of ALE cycles. Using in situ ellipsometry, we show that if the two surfaces are dosed with benzaldehyde after the first and fifth ALE cycles, there is a nearly 60% increase in etch selectivity compared to dosing benzaldehyde once after the first ALE cycle. A nearly 100% improvement in etch selectivity was observed compared to the scenario without benzaldehyde pre-functionalization for a target SiO2 etch of ∼20 nm in 20 ALE cycles.
An osteoarthritis pathophysiological continuum revealed by molecular biomarkers
Authors: Kraus Virginia Byers , Sun Shuming , Reed Alexander , Soderblom Erik J. , Moseley M. Arthur , Zhou Kaile , Jain Vaibhav , Arden Nigel , Li Yi-Ju
Published: April 2024

We aimed to identify serum biomarkers that predict knee osteoarthritis (OA) before the appearance of radiographic abnormalities in a cohort of 200 women. As few as six serum peptides, corresponding to six proteins, reached AUC 77% probability to distinguish those who developed OA from age-matched individuals who did not develop OA up to 8 years later. Prediction based on these blood biomarkers was superior to traditional prediction based on age and BMI (AUC 51%) or knee pain (AUC 57%). These results identify a prolonged molecular derangement of joint tissue before the onset of radiographic OA abnormalities consistent with an unresolved acute phase response. Among all 24 protein biomarkers predicting incident knee OA, the majority (58%) also predicted knee OA progression, revealing the existence of a pathophysiological “OA continuum” based on considerable similarity in the molecular pathophysiology of the progression to incident OA and the progression of established OA.
Inputs to the locus coeruleus from the periaqueductal gray and rostroventral medulla shape opioid-mediated descending pain modulation
Authors: Lubejko Susan T. , Livrizzi Giulia , Buczynski Stanley A. , Patel Janki , Yung Jean C. , Yaksh Tony L. , Banghart Matthew R.
Published: April 2024

The supraspinal descending pain modulatory system (DPMS) shapes pain perception via monoaminergic modulation of sensory information in the spinal cord. However, the role and synaptic mechanisms of descending noradrenergic signaling remain unclear. Here, we establish that noradrenergic neurons of the locus coeruleus (LC) are essential for supraspinal opioid antinociception. While much previous work has emphasized the role of descending serotonergic pathways, we find that opioid antinociception is primarily driven by excitatory output from the ventrolateral periaqueductal gray (vlPAG) to the LC. Furthermore, we identify a previously unknown opioid-sensitive inhibitory input from the rostroventromedial medulla (RVM), the suppression of which disinhibits LC neurons to drive spinal noradrenergic antinociception. We describe pain-related activity throughout this circuit and report the presence of prominent bifurcating outputs from the vlPAG to the LC and the RVM. Our findings substantially revise current models of the DPMS and establish a supraspinal antinociceptive pathway that may contribute to multiple forms of descending pain modulation.
Structural insights into the calcium-coupled zinc export of human ZnT1
Authors: Sun Chunqiao , He Bangguo , Gao Yongxiang , Wang Xingbing , Liu Xin , Sun Linfeng
Published: April 2024

Cellular zinc (Zn
2+
) homeostasis is essential to human health and is under tight regulations. Human zinc transporter 1 (hZnT1) is a plasma membrane–localized Zn
2+
exporter belonging to the ZnT family, and its functional aberration is associated with multiple diseases. Here, we show that hZnT1 works as a Zn
2+
/Ca
2+
exchanger. We determine the structure of hZnT1 using cryo–electron microscopy (cryo-EM) single particle analysis. hZnT1 adopts a homodimeric structure, and each subunit contains a transmembrane domain consisting of six transmembrane segments, a cytosolic domain, and an extracellular domain. The transmembrane region displays an outward-facing conformation. On the basis of structural and functional analysis, we propose a model for the hZnT1-mediated Zn
2+
/Ca
2+
exchange. Together, these results facilitate our understanding of the biological functions of hZnT1 and provide a basis for further investigations of the ZnT family transporters.
A vast repertoire of secondary metabolites potentially influences community dynamics and biogeochemical processes in cold seeps
Authors: Dong Xiyang , Zhang Tianxueyu , Wu Weichao , Peng Yongyi , Liu Xinyue , Han Yingchun , Chen Xiangwei , Gao Zhizeng , Xia Jinmei , Shao Zongze , Greening Chris
Published: April 2024

In deep-sea cold seeps, microbial communities thrive on the geological seepage of hydrocarbons and inorganic compounds, differing from photosynthetically driven ecosystems. However, their biosynthetic capabilities remain largely unexplored. Here, we analyzed 81 metagenomes, 33 metatranscriptomes, and 7 metabolomes derived from nine different cold seep areas to investigate their secondary metabolites. Cold seep microbiomes encode diverse and abundant biosynthetic gene clusters (BGCs). Most BGCs are affiliated with understudied bacteria and archaea, including key mediators of methane and sulfur cycling. The BGCs encode diverse antimicrobial compounds that potentially shape community dynamics and various metabolites predicted to influence biogeochemical cycling. BGCs from key players are widely distributed and highly expressed, with their abundance and expression levels varying with sediment depth. Sediment metabolomics reveals unique natural products, highlighting uncharted chemical potential and confirming BGC activity in these sediments. Overall, these results demonstrate that cold seep sediments serve as a reservoir of hidden natural products and sheds light on microbial adaptation in chemosynthetically driven ecosystems.
The role of Piezo1 mechanotransduction in high-grade serous ovarian cancer: Insights from an in vitro model of collective detachment
Authors: Micek Hannah M. , Yang Ning , Dutta Mayuri , Rosenstock Lauren , Ma Yicheng , Hielsberg Caitlin , McCord Molly , Notbohm Jacob , McGregor Stephanie , Kreeger Pamela K.
Published: April 2024

Slowing peritoneal spread in high-grade serous ovarian cancer (HGSOC) would improve patient prognosis and quality of life. HGSOC spreads when single cells and spheroids detach, float through the peritoneal fluid and take over new sites, with spheroids thought to be more aggressive than single cells. Using our in vitro model of spheroid collective detachment, we determine that increased substrate stiffness led to the detachment of more spheroids. We identified a mechanism where Piezo1 activity increased MMP-1/MMP-10, decreased collagen I and fibronectin, and increased spheroid detachment. Piezo1 expression was confirmed in omental masses from patients with stage III/IV HGSOC. Using OV90 and CRISPR-modified
PIEZO1
−/−
OV90 in a mouse xenograft model, we determined that while both genotypes efficiently took over the omentum, loss of Piezo1 significantly decreased ascitic volume, tumor spheroids in the ascites, and the number of macroscopic tumors in the mesentery. These results support that slowing collective detachment may benefit patients and identify Piezo1 as a potential therapeutic target.
Electrochemical oxidation of concentrated benzyl alcohol to high-purity benzaldehyde via superwetting organic-solid-water interfaces
Authors: Shi Run , Zhang Xuerui , Li Chengyu , Zhao Yunxuan , Li Rui , Waterhouse Geoffrey I. N. , Zhang Tierui
Published: April 2024

Organic electrosynthesis in aqueous media is presently hampered by the poor solubility of many organic reactants and thus low purity of liquid products in electrolytes. Using the electrooxidation of benzyl alcohol (BA) as a model reaction, we present a “sandwich-type” organic-solid-water (OSW) system, consisting of BA organic phase, KOH aqueous electrolyte, and porous anodes with Janus-like superwettability. The system allows independent diffusion of BA molecules from the organic phase to electrocatalytic active sites, enabling efficient electrooxidation of high-concentration BA to benzaldehyde (97% Faradaic efficiency at ~180 mA cm
−2
) with substantially reduced ohmic loss compared to conventional solid-liquid systems. The confined organic-water boundary within the electrode channels suppresses the interdiffusion of molecules and ions into the counterphase, thus preventing the hydration and overoxidation of benzaldehyde during long-term electrocatalysis. As a result, the direct production of high-purity benzaldehyde (91.7%) is achieved in a flow cell, showcasing the effectiveness of electrocatalysis over OSW interfaces for the one-step synthesis of high-purity organic compounds.
First documentation of Late Paleozoic conodonts from Argentina: Biostratigraphic and paleoclimatic constraints for the Late Paleozoic Ice Age in SW Gondwana
Authors: Voldman Gustavo G. , Cisterna Gabriela A. , Sterren Andrea F. , Ezpeleta Miguel , Barrick James E.
Published: April 2024

We present the first discovery of Late Paleozoic conodonts in Argentina, marking the southernmost occurrence of this fossil group in the dominantly cold, high latitudes of Gondwana. Recovered from the siliciclastic Río del Peñón (RDP) Formation at the Rincón Blanco section in the northern Precordillera, La Rioja Province, the fossil assemblage includes Neognathodus colombiensis and Neognathodus “pre-colombiensis,” precisely indicating the early Moscovian (late Atokan in North America) N. colombiensis Zone. Furthermore, the conodont fauna establishes a crucial temporal constraint for the brachiopod Tivertonia jachalensis–Streptorhynchus inaequiornatus (TS) Zone, which is a widely employed biostratigraphic unit in southern South America. The warm-water affinity of Neognathodus is in accordance with the record of typical paleoequatorial faunal elements in the TS Zone in several central western Argentinian basins, thus reinforcing the idea of a climatic amelioration in the southern latitudes of Gondwana during the early Moscovian.
steadystate: A MATLAB-based routine for determining steady-state friction conditions in the framework of rate-and-state friction analysis
Authors: Giacomel P. , Faulkner D.R. , Lambert V. , Allen M.J.
Published: April 2024

Reliable determination of rate- and-state friction (RSF) parameters depends on achieving steady-state (SS) friction conditions before and after experimental velocity-stepping friction tests. This operation, through nonlinear least squares fitting, is commonly preceded by the removal of any overall slip weakening/hardening after friction velocity steps (VSs) through a sufficiently large window of slip displacement at SS ( = linear detrend). However, to date, the identification of SS and thus the correct linear detrend is dependent on the user, which potentially results in differing RSF outputs from the same data set. Here, we demonstrate that large errors in the determination of the fitted RSF parameters can result if SS conditions are not reached before and after VSs. Such errors can be particularly relevant for materials characterized by long evolution of frictional resistance with slip, such as clay-rich gouge layers, in which identifying SS after VSs is not always obvious. To this end, we propose a methodology to accurately and consistently identify where SS is achieved after VSs. This methodology is coded into a new MATLAB-based routine, steadystate. We show the key features of the methodology, as well as how to use steadystate and read its output. We also illustrate the broad applicability of the approach to friction data with different noise levels and sampling frequencies referenced to slip velocity, by reviewing observations from synthetic data sets and specific examples of experiments from different laboratories involving various sheared materials.
Experiences and impact of psychiatric inpatient admissions far away from home: a qualitative study with young people, parents/carers and healthcare professionals
Authors: Roe James , Holland Josephine , Burn Anne-Marie , Hopkin Elinor , Wild Lorna , Fisher Michelle , Nazir Saeed , Ford Tamsin , Dubicka Bernadka , James Anthony , Tuomainen Helena , Fung Nicole , Horton Kate , Wagner Adam P , Morriss Richard , Sayal Kapil
Published: April 2024

Background

There are significant clinical, policy and societal concerns about the impact on young people (YP), from admission to psychiatric wards far from home. However, research evidence is scarce.

Aims

To investigate the impact of at-distance admissions to general adolescent units, from the perspectives of YP, parents/carers and healthcare professionals (HCPs) including service commissioners, to inform clinical practice, service development and policy.

Method

Semistructured interviews with purposive samples of YP aged 13–17 years (n=28) and parents/carers (n=19) across five large regions in England, and a national sample of HCPs (n=51), were analysed using a framework approach.

Results

There was considerable agreement between YP, parents/carers and HCPs on the challenges of at-distance admissions. YP and parents/carers had limited or no involvement in decision-making processes around admission and highlighted a lack of available information about individual units. Being far from home posed challenges with maintaining home contact and practical/financial challenges for families visiting. HCPs struggled with ensuring continuity of care, particularly around maintaining access to local clinical teams and educational support. However, some YP perceived separation from their local environment as beneficial because it removed them from unhelpful environments. At-distance admissions provided respite for some families struggling to support their child.

Conclusions

At-distance admissions lead to additional distress, uncertainty, compromised continuity of care and educational, financial and other practical difficulties, some of which could be better mitigated. For a minority, there are some benefits from such admissions.

Clinical implications

Standardised online information, accessible prior to admission, is needed for all Child and Adolescent Mental Health Services units. Additional practical and financial burden placed on families needs greater recognition and consideration of potential sources of support. Policy changes should incorporate findings that at-distance or adult ward admissions may be preferable in certain circumstances.
Incidence and associated in-hospital mortality of myocardial injury characterised by elevated cardiac troponin in adult patients with traumatic brain injury: protocol for a systematic review and meta-analysis
Authors: Tang Jiuning , Yu Jinhui , Zhang Xinhai , He Jun , Chen Minruo , Tang Maoyuan , Ren Qifu , Liu Zhi , Ding Huaqiang
Published: April 2024

Introduction

Myocardial injury is a relatively common complication of traumatic brain injury (TBI). However, the incidence and clinical impact of myocardial injury characterised by elevated cardiac troponin (cTn) levels after TBI are still poorly known. The objective of our study is to assess the global incidence of myocardial injury characterised by elevated cTn in adult patients with TBI and its association with in-hospital mortality.

Methods and analysis

The protocol of our systematic review and meta-analysis is performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. We will search the Medline, Embase, Cochrane Library, Scopus and Web of Science databases from inception to 1 January 2024, for observational studies in any language that reported the incidence of elevated cTn and/or in-hospital mortality associated with elevated cTn among adult patients with TBI. Two reviewers will independently assess study eligibility, extract the data and assess the risk of bias. ORs and 95% CIs will be used with a random-effects or fixed-effects model according to the estimated heterogeneity among studies assessed by the I2index. We will perform a quantitative synthesis for the incidence of elevated cTn and in-hospital mortality data. If sufficient data are available, we will perform subgroup analysis and meta-regression to address the heterogeneity. In addition, we will perform a narrative analysis if quantitative synthesis is not appropriate.

Ethics and dissemination

Ethics approval was not required for this study. We intend to publish our findings in a high-quality, peer-reviewed journal.

PROSPERO registration number

CRD42023454686.
Male involvement in family planning and its association with knowledge and spouse discussion in Ethiopia: a systematic review and meta-analysis
Authors: Adane Bezawit , Kefale Bereket , Damtie Yitayish , Arefaynie Mastewal , Addisu Elsabeth , Dewau Reta , Mitiku Kefale , Tsega Tilahun Degu , Andualem Amare Agmas , Awoke Mahider , Asfaw Tezera , Wasihun Yitbarek , Yalew Melaku
Published: April 2024

Objective

This study aimed to estimate the pooled prevalence of male involvement in family planning (FP) and its association with knowledge and spouse discussion in Ethiopia.

Design

Systematic review and meta-analysis using the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines.

Data sources

The study was conducted by the articles searched from different databases: (PubMed, Cochrane Library, PsycINFO, HINARI and Google Scholar).

Eligibility criteria for selecting studies

This research encompassed investigations carried out within married couples in Ethiopia, specifically focusing on studies where male involvement in FP was the primary outcome. The inclusion criteria comprised studies with an observational study design, encompassing both published and unpublished works, conducted in the English language, with no restrictions on data collection and publication year.

Data extraction and synthesis

Following a systematic search of the articles, two independent authors assessed the quality of the studies, and data extraction was conducted using Microsoft Excel. The data analysis was performed by using STATA V.17. The overall level of male involvement in FP in Ethiopia was calculated using DerSimonian and Liard’s random-effect model, with a significance level set at a p<0.05. Heterogeneity was examined using the I2test, and Egger’s test was employed to assess publication bias.

Results

The pooled prevalence of male involvement in FP in Ethiopia was 59.71% (95% CI (47.68% to 71.73%)). Good knowledge regarding FP (AOR 6.63, 95% CI (2.58 to 17.03)) and spouse discussion on FP (AOR 4.36, 95% CI (2.50 to 7.59)) were significantly associated with male involvement in FP.

Conclusions

The prevalence of male involvement in FP in Ethiopia was low as compared with other literature conducted outside Ethiopia. Both good knowledge and spouse discussion regarding FP were significantly associated with male involvement in FP. So, the government and healthcare providers should focus on interventions that could increase their knowledge through different media. In addition, encouraging couples to have a discussion regarding FP could be a recalled intervention for healthcare providers.
Consensus statements on the utility of defining ARDS and the utility of past and current definitions of ARDS—protocol for a Delphi study
Authors: Nasa Prashant , Bos Lieuwe D , Estenssoro Elisa , van Haren Frank MP , Serpa Neto Ary , Rocco Patricia RM , Slutsky Arthur S , Schultz Marcus J
Published: April 2024

Introduction

Acute respiratory distress syndrome (ARDS), marked by acute hypoxemia and bilateral pulmonary infiltrates, has been defined in multiple ways since its first description. This Delphi study aims to collect global opinions on the conceptual framework of ARDS, assess the usefulness of components within current and past definitions and investigate the role of subphenotyping. The varied expertise of the panel will provide valuable insights for refining future ARDS definitions and improving clinical management.

Methods

A diverse panel of 35–40 experts will be selected based on predefined criteria. Multiple choice questions (MCQs) or 7-point Likert-scale statements will be used in the iterative Delphi rounds to achieve consensus on key aspects related to the utility of definitions and subphenotyping. The Delphi rounds will be continued until a stable agreement or disagreement is achieved for all statements.

Analysis

Consensus will be considered as reached when a choice in MCQs or Likert-scale statement achieved ≥80% of votes for agreement or disagreement. The stability will be checked by non-parametric χ2tests or Kruskal Wallis test starting from the second round of Delphi process. A p-value ≥0.05 will be used to define stability.

Ethics and dissemination

The study will be conducted in full concordance with the principles of the Declaration of Helsinki and will be reported according to CREDES guidance. This study has been granted an ethical approval waiver by the NMC Healthcare Regional Research Ethics Committee, Dubai (NMCHC/CR/DXB/REC/APP/002), owing to the nature of the research. Informed consent will be obtained from all panellists before the start of the Delphi process. The study will be published in a peer-review journal with the authorship agreed as perICMJErequirements.

Trial registration number

NCT06159465.
Neoadjuvant and/or adjuvant chemotherapy for gastric cancer patients with microsatellite instability or deficient mismatch repair: a systematic review and meta-analysis study protocol
Authors: Liu Baike , Yin Xiaonan , Cai Zhaolun , Shen Chaoyong , Jiang Tianxiang , Han Yihui , Yin Yuan , Zhang Bo
Published: April 2024

Introduction

Whether gastric cancer (GC) patients with deficient mismatch repair or microsatellite instability-high (dMMR/MSI-H) benefit from perioperative (neoadjuvant and/or adjuvant) chemotherapy is controversial. This protocol delineates the planned scope and methods for a systematic review and meta-analysis that aims to compare the efficacy of perioperative chemotherapy with surgery alone in resectable dMMR/MSI-H GC patients.

Methods and analysis

This study protocol is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols-P guideline. PubMed, Embase, Cochrane (CENTRAL), and the Web of Science databases will be searched, supplemented by a secondary screening of relevant records. Both randomised controlled trials and non-randomised studies will be included in this study. The primary and secondary outcomes under scrutiny will be overall survival, disease-free survival and progression-free survival. Two reviewers will independently screen studies, extract data and assess the risk of bias. We will analyse different treatment settings (eg, neoadjuvant or adjuvant or combined as perioperative chemotherapies) separately and conduct sensitivity analyses.

Ethics and dissemination

No ethics approval is required for this systematic review and meta-analysis, as no individual patient data will be collected. The findings of our study will be published in a peer-reviewed journal.

Prospero registration number

CRD42023494276.
Trends and projections in fall death in the Netherlands from 1990 to 2045
Authors: van der Naald Niels , Verbeek Frank , Baden David Nico , Verbeek Anna J M , Ham Wietske H W , Verbeek Jan , Brummelkamp Erik , Groenewoud Hans , Stolwijk-van Niekerk Catharina , Verbeek André
Published: April 2024

Background

Increasing life expectancy in high-income countries has been linked to a rise in fall mortality. In the Netherlands, mortality rates from falls have increased gradually from the 1950s, with some indication of stabilisation in the 1990s. For population health and clinical practice, it is important to foresee the future fall mortality trajectories.

Methods

A graphical approach was used to explore trends in mortality by age, calendar period and cohorts born in the periods of 1915–1945. Population data and the numbers of people with accidental fall fatality as underlying cause of death from 1990 to 2021 were derived from Statistics Netherlands. Age-standardised mortality rates of unintentional falls per 100 000 population were calculated by year and sex. A log-linear model was used to examine the separate effects of age, period and cohort on the trend in mortality and to produce estimates of future numbers of fall deaths until 2045.

Results

While the total population increased by 17% between 1990 and 2021, absolute numbers of fall-related deaths rose by 230% (from 1584 to 5234), which was 251% (an increase of 576 deaths in 1990 to 2021 deaths in 2020) for men and 219% (from 1008 to 3213) for women. Age-standardised figures were higher for women than men and increased more over time. In 2020, 79% of those with death due to falls were over the age of 80, and 35% were 90 years or older. From 2020 to 2045, the observed and projected numbers of fall deaths were 2021 and 7073 for men (250% increase) and 3213 and 12 575 for women (291% increase).

Conclusion

Mortality due to falls has increased in the past decades and will continue to rise sharply, mainly caused by growing numbers of older adults, especially those in their 80s and 90s. Contributing risk factors are well known, implementation of preventive measures is a much needed next step. An effective approach to managing elderly people after falls is warranted to reduce crowding in the emergency care and reduce unnecessary long hospital stays.
Axon guidance cue SEMA3A promotes the aggressive phenotype of basal-like PDAC
Authors: Lupo Francesca , Pezzini Francesco , Pasini Davide , Fiorini Elena , Adamo Annalisa , Veghini Lisa , Bevere Michele , Frusteri Cristina , Delfino Pietro , D'agosto Sabrina , Andreani Silvia , Piro Geny , Malinova Antonia , Wang Tian , De Sanctis Francesco , Lawlor Rita Teresa , Hwang Chang-il , Carbone Carmine , Amelio Ivano , Bailey Peter , Bronte Vincenzo , Tuveson David , Scarpa Aldo , Ugel Stefano , Corbo Vincenzo
Published: April 2024

Objective

The dysregulation of the axon guidance pathway is common in pancreatic ductal adenocarcinoma (PDAC), yet our understanding of its biological relevance is limited. Here, we investigated the functional role of the axon guidance cue SEMA3A in supporting PDAC progression.

Design

We integrated bulk and single-cell transcriptomic datasets of human PDAC with in situ hybridisation analyses of patients’ tissues to evaluate SEMA3A expression in molecular subtypes of PDAC. Gain and loss of function experiments in PDAC cell lines and organoids were performed to dissect how SEMA3A contributes to define a biologically aggressive phenotype.

Results

In PDAC tissues, SEMA3A is expressed by stromal elements and selectively enriched in basal-like/squamous epithelial cells. Accordingly, expression of SEMA3A in PDAC cells is induced by both cell-intrinsic and cell-extrinsic determinants of the basal-like phenotype.
In vitro
, SEMA3A promotes cell migration as well as anoikis resistance. At the molecular level, these phenotypes are associated with increased focal adhesion kinase signalling through canonical SEMA3A-NRP1 axis. SEMA3A provides mouse PDAC cells with greater metastatic competence and favours intratumoural infiltration of tumour-associated macrophages and reduced density of T cells. Mechanistically, SEMA3A functions as chemoattractant for macrophages and skews their polarisation towards an M2-like phenotype. In SEMA3A
high
tumours, depletion of macrophages results in greater intratumour infiltration by CD8+T cells and better control of the disease from antitumour treatment.

Conclusions

Here, we show that SEMA3A is a stress-sensitive locus that promotes the malignant phenotype of basal-like PDAC through both cell-intrinsic and cell-extrinsic mechanisms.
Novel transcriptomic panel identifies histologically active eosinophilic oesophagitis
Authors: Gueguen Emilie , Morsy Yasser , Mamie Céline , Schoepfer Alain , Saner Catherine , Biedermann Luc , Straumann Alex , Kreienbühl Andrea ,   Swiss EoE Cohort Study Group, Scharl Michael , Wawrzyniak Marcin
Published: April 2024

Background and aims

Eosinophilic oesophagitis (EoE) is characterised by symptoms of esophageal dysfunction and oesinophil tissue infiltration. The EoE Diagnostic Panel (EDP) can distinguish between active and non-active EoE using a set of 77 genes. Recently, the existence of distinct EoE variants featuring symptoms similar to EoE, such as oesophageal dysfunction but lacking eosinophil infiltration, had been determined.

Methods

We used oesophageal biopsies from patients with histologically active (n=10) and non-active EoE (n=9) as well as from healthy oesophageal controls (n=5) participating in the Swiss Eosinophilic Esophagitis Cohort Study (SEECS) and analysed the gene expression profile in these biopsies by total RNA-sequencing (RNA-seq). Moreover, we employed the publicly accessible RNA-seq dataset (series GSE148381) as reported by Greuter
et al
, encompassing a comprehensive genomic profile of patients presenting with EoE variants.

Results

A novel, diagnostic gene expression panel that can effectively distinguish patients with histologically active conventional EoE from patients with EoE in histological remission and control individuals, and from three newly discovered EoE variants was identified. Histologically Active EoE Diagnostic Panel (HAEDP) consists of 53 genes that were identified based on differential expression between histologically active EoE, histological remission and controls (p≤0.05). By combining the HAEDP with EDP, we expanded our knowledge about factors that may contribute to the inflammation in EoE and improved our understanding of the underlying mechanisms of the disease. Conversely, we suggested a compact group of genes common to both HAEDP and EDP to create a reliable diagnostic tool that might enhance the accuracy of EoE diagnosis.

Conclusion

We identified a novel set of 53 dysregulated genes that are closely associated with the histological inflammatory activity of EoE. In combination with EDP, our new panel might be a valuable tool for the accurate diagnosis of patients with EoE as well as for monitoring their disease course.