bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of wind barriers on the local wind field on a bridge deck
Authors: Chou Chin-Chen , Chung Cheng-Yang , Chung Kung-Ming
Published: January 2024

The adverse effect of crosswinds on road vehicles on a bridge deck or traffic lanes is of increasing concern. Local flow characteristics depend on the bridge's architecture and wind barriers (WBs) are commonly used to alleviate wind-induced instability for vehicles. Terrain orography is another dominant factor. This study uses a terrain model with a coastal bridge (Chen-Kung Bridge, Penghu, Taiwan). The bridge is located between a reservoir and the Taiwan Strait. Numerous accidents have occurred due to strong monsoon winds in autumn and winter. In wind tunnel experiments, an atmosphere boundary layer is established and the test conditions (wind speed and wind incidence) are taken from local meteorological data. The effect of the height of solid WBs on local wind direction and speed is determined. The results can be used to remodel WBs to increase safety for road vehicles.
Patient’s perception of medication and nonadherence to chronic disease treatments. A population-based study in Brazil
Authors: da Silva Menolli Poliana Vieira , Ivama Brummel Adriana Mitsue , Guidoni Camilo Molino , Girotto Edmarlon
Published: January 2024

Objective

To identify the association between patients’ perception of medication for hypertension, diabetes, and dyslipidemia and nonadherence by regions of Brazil.

Methods

This is a cross-sectional study using open data from the urban population-based survey National Survey on Access, Use and Promotion of Rational Use of Medicines in Brazil (PNAUM), conducted from September 2013 to February 2014. Patients’ self-reported perceptions recorded on each of the medicines for hypertension, diabetes, and dyslipidaemia were used for analysis. The dependent variable was nonadherence to treatment, and the patient’s perceptions about medication were the independent variable. Logistic regression was performed to calculate the crude and adjusted odds ratios.

Key findings

Nonadherence was observed in 6.6% of the 16 491 drugs, with missed doses (84.5%) being the main cause. In the adjusted analysis, perception of medication effectiveness considered regular or poor (OR 3.025; 95% CI 1.672–5.473), perception that caused discomfort (OR 2.731; 95% CI 1.464–5.092), and medicines used for <6 months (OR 1.557; 95% CI 1.089–2.227) had higher chances of nonadherence in Brazil (all regions).

Conclusion

Patient perception of the effectiveness, safety, and time of use of medications are key factors associated with nonadherence and can contribute to building medication beliefs that may affect current and future adherence.
Physiological adaptation to irradiance in duckweeds is species and accession specific and depends on light habitat niche
Authors: Smith Kellie E , Cowan Laura , Taylor Beth , McAusland Lorna , Heatley Matthew , Yant Levi , Murchie Erik H
Published: January 2024

Duckweeds span 36 species of free-floating aquatic organisms with body sizes ranging from 2 mm to 10 mm, where each plant body plan is reduced to a largely leaf-like structure. As an emerging crop, their fast growth rates offer potential for cultivation in closed systems. We describe a novel UK collection derived from low light (dLL) or high light (dHL) habitats, profiled for growth, photosynthesis, and photoprotection (non-photochemical quenching, NPQ) responses. Twenty-three accessions of three Lemna species and one Spirodela polyrhiza were grown under relatively low light (LL: 100 μmol m–2 s–1) and high light (HL: 350 μmol m–2 s–1) intensities. We observed broad within- and between-species level variation in photosynthesis acclimation. Duckweeds grown under HL exhibited a lower growth rate, biomass, chlorophyll, and quantum yield of photosynthesis. In HL compared with LL, carotenoid de-epoxidation state and NPQ were higher, whilst PSII efficiency (φPSII) and Chl a:b ratios were unchanged. The dLL plants showed relatively stronger acclimation to HL compared with dHL plants, especially Lemna japonica accessions. These achieved faster growth in HL with concurrent higher carotenoid levels and NPQ, and less degradation of chlorophyll. We conclude that these data support local adaptation to the light environment in duckweed affecting acclimation in controlled conditions.
Structural insights into the Smirnoff–Wheeler pathway for vitamin C production in the Amazon fruit camu-camu
Authors: Vargas Jhon A , Sculaccio Susana A , Pinto Andressa P A , Pereira Humberto D’Muniz , Mendes Luis F S , Flores Jhoao F , Cobos Marianela , Castro Juan C , Garratt Richard C , Leonardo Diego A
Published: January 2024

l-Ascorbic acid (AsA, vitamin C) is a pivotal dietary nutrient with multifaceted importance in living organisms. In plants, the Smirnoff–Wheeler pathway is the primary route for AsA biosynthesis, and understanding the mechanistic details behind its component enzymes has implications for plant biology, nutritional science, and biotechnology. As part of an initiative to determine the structures of all six core enzymes of the pathway, the present study focuses on three of them in the model species Myrciaria dubia (camu-camu): GDP-d-mannose 3',5'-epimerase (GME), l-galactose dehydrogenase (l-GalDH), and l-galactono-1,4-lactone dehydrogenase (l-GalLDH). We provide insights into substrate and cofactor binding and the conformational changes they induce. The MdGME structure reveals a distorted substrate in the active site, pertinent to the catalytic mechanism. Mdl-GalDH shows that the way in which NAD+ association affects loop structure over the active site is not conserved when compared with its homologue in spinach. Finally, the structure of Mdl-GalLDH is described for the first time. This allows for the rationalization of previously identified residues which play important roles in the active site or in the formation of the covalent bond with FAD. In conclusion, this study enhances our understanding of AsA biosynthesis in plants, and the information provided should prove useful for biotechnological applications.
Simultaneous multicolour transit photometry of hot Jupiters HAT-P-19b, HAT-P-51b, HAT-P-55b, and HAT-P-65b
Authors: Kang H , Chen G , Pallé E , Murgas F , García N Abreu , de Leon J , Enoc G , Esparza-Borges E , Fukuda I , Fukui A , Galán D , Hayashi Y , Isogai K , Kagetani T , Kawauchi K , Korth J , Livingston J H , Luque R , Ma Y , Madrigal-Aguado A , Meni P , Rodriguez P Montañes , Mori M , Torres S Muñoz , Narita N , Orell-Miquel J , Parviainen H , Peláez-Torres A , Stangret M , Tamura M , Watanabe N
Published: January 2024

Accurate physical parameters of exoplanet systems are essential for further exploration of planetary internal structure, atmospheres, and formation history. We aim to use simultaneous multicolour transit photometry to improve the estimation of transit parameters, to search for transit timing variations (TTVs), and to establish which of our targets should be prioritized for follow-up transmission spectroscopy. We performed time series photometric observations of 12 transits for the hot Jupiters HAT-P-19b, HAT-P-51b, HAT-P-55b, and HAT-P-65b using the simultaneous four-colour camera MuSCAT2 on the Telescopio Carlos Sánchez. We collected 56 additional transit light curves from TESS photometry. To derive transit parameters, we modelled the MuSCAT2 light curves with Gaussian processes to account for correlated noise. To derive physical parameters, we performed EXOFASTv2 global fits to the available transit and radial velocity data sets, together with the Gaia DR3 parallax, isochrones, and spectral energy distributions. To assess the potential for atmospheric characterization, we compared the multicolour transit depths with a flat line and a clear atmosphere model. We consistently refined the transit and physical parameters. We improved the orbital period and ephemeris estimates, and found no evidence for TTVs or orbital decay. The MuSCAT2 broad-band transmission spectra of HAT-P-19b and HAT-P-65b are consistent with previously published low-resolution transmission spectra. We also found that, except for HAT-P-65b, the assumption of a planetary atmosphere can improve the fit to the MuSCAT2 data. In particular, we identified HAT-P-55b as a priority target among these four planets for further atmospheric studies using transmission spectroscopy.
Reflecting on naked singularities: iron line fitting as a probe of the cosmic censorship conjecture
Authors: Mummery Andrew , Ingram Adam
Published: January 2024

We demonstrate that the X-ray iron line fitting technique can be leveraged as a powerful probe of the cosmic censorship conjecture. We do this by extending existing emission line models to arbitrary spin parameters of the Kerr metric, no longer restricted to black hole metrics with |a•| < 1. We show that the emission lines from naked singularity metrics (|a•| > 1) show significant differences to their black hole counterparts, even for those metrics with identical locations of the innermost stable circular orbit, i.e. emission line fitting does not suffer from the degeneracy which affects continuum fitting approaches. These differences are entirely attributable to the disappearance of the event horizon for |a•| > 1. We highlight some novel emission line features of naked singularity metrics, such as ‘inverted’ emission lines (with sharp red wings and extended blue wings) and ‘triple lines’. The lack of detection of any of these novel features provides support of the cosmic censorship conjecture. We publicly release xspec packages skline and skconv which can now be used to probe the cosmic censorship conjecture in Galactic X-ray binaries and active galactic nuclei. The inclusion of super-extremal space–times can be alternatively posed as a way of stress testing conventional models of accretion.
Accurate halo mass functions from the simplest excursion set theory
Authors: Delos M Sten
Published: January 2024

Excursion set theory is a powerful and widely used tool for describing the distribution of dark matter haloes, but it is normally applied with simplifying approximations. We use numerical sampling methods to study the mass functions predicted by the theory without approximations. With a spherical top-hat window and a constant δ = 1.5 threshold, the theory accurately predicts mass functions with the M200 mass definition, both unconditional and conditional, in simulations of a range of matter-dominated cosmologies. For Λ cold dark matter at the present epoch, predictions lie between the M200m and M200c mass functions. In contrast, with the same window function, a non-constant threshold based on ellipsoidal collapse predicts uniformly too few haloes. This work indicates a new way to simply and accurately evaluate halo mass functions, clustering bias, and assembly histories for a range of cosmologies. We provide a fitting function that accurately represents the predictions of the theory for a wide range of parameters.
Streptococcal toxic shock syndrome due to Streptococcus dysgalactiae subsp. equisimilis from retroperitoneal panniculitis during the treatment with anti-IL-6 receptor antibody: A case report
Authors: Fujimoto Sho , Eriguchi Yoshihiro , Nakamura Rinto , Kamikawa Sota , Yonekawa Akiko , Miyake Noriko , Ono Nobuyuki , Niiro Hiroaki
Published: January 2024

A 53-year-old man with adult-onset Still’s disease developed severe streptococcal toxic shock syndrome (STSS) due to Streptococcus dysgalactiae subsp. equisimilis (SDSE), following retroperitoneal panniculitis. He was receiving tocilizumab (TCZ), an interleukin-6 receptor inhibitor. The modifying effect of TCZ on the immune response and the pathophysiology of SDSE infection may have led to retroperitoneal panniculitis and atypical STSS with delayed shock and flare of soft tissue inflammation.
Target DNA-dependent activation mechanism of the prokaryotic immune system SPARTA
Authors: Finocchio Giada , Koopal Balwina , Potocnik Ana , Heijstek Clint , Westphal Adrie H , Jinek Martin , Swarts Daan C
Published: January 2024

In both prokaryotic and eukaryotic innate immune systems, TIR domains function as NADases that degrade the key metabolite NAD+ or generate signaling molecules. Catalytic activation of TIR domains requires oligomerization, but how this is achieved varies in distinct immune systems. In the Short prokaryotic Argonaute (pAgo)/TIR-APAZ (SPARTA) immune system, TIR NADase activity is triggered upon guide RNA-mediated recognition of invading DNA by an unknown mechanism. Here, we describe cryo-EM structures of SPARTA in the inactive monomeric and target DNA-activated tetrameric states. The monomeric SPARTA structure reveals that in the absence of target DNA, a C-terminal tail of TIR-APAZ occupies the nucleic acid binding cleft formed by the pAgo and TIR-APAZ subunits, inhibiting SPARTA activation. In the active tetrameric SPARTA complex, guide RNA-mediated target DNA binding displaces the C-terminal tail and induces conformational changes in pAgo that facilitate SPARTA-SPARTA dimerization. Concurrent release and rotation of one TIR domain allow it to form a composite NADase catalytic site with the other TIR domain within the dimer, and generate a self-complementary interface that mediates cooperative tetramerization. Combined, this study provides critical insights into the structural architecture of SPARTA and the molecular mechanism underlying target DNA-dependent oligomerization and catalytic activation.
STIM1 translocation to the nucleus protects cells from DNA damage
Authors: Sanchez-Lopez Irene , Orantos-Aguilera Yolanda , Pozo-Guisado Eulalia , Alvarez-Barrientos Alberto , Lilla Sergio , Zanivan Sara , Lachaud Christophe , Martin-Romero Francisco Javier
Published: January 2024

DNA damage represents a challenge for cells, as this damage must be eliminated to preserve cell viability and the transmission of genetic information. To reduce or eliminate unscheduled chemical modifications in genomic DNA, an extensive signaling network, known as the DNA damage response (DDR) pathway, ensures this repair. In this work, and by means of a proteomic analysis aimed at studying the STIM1 protein interactome, we have found that STIM1 is closely related to the protection from endogenous DNA damage, replicative stress, as well as to the response to interstrand crosslinks (ICLs). Here we show that STIM1 has a nuclear localization signal that mediates its translocation to the nucleus, and that this translocation and the association of STIM1 to chromatin increases in response to mitomycin-C (MMC), an ICL-inducing agent. Consequently, STIM1-deficient cell lines show higher levels of basal DNA damage, replicative stress, and increased sensitivity to MMC. We show that STIM1 normalizes FANCD2 protein levels in the nucleus, which explains the increased sensitivity of STIM1-KO cells to MMC. This study not only unveils a previously unknown nuclear function for the endoplasmic reticulum protein STIM1 but also expands our understanding of the genes involved in DNA repair.
Site-specific acetylation of polynucleotide kinase 3′-phosphatase regulates its distinct role in DNA repair pathways
Authors: Islam Azharul , Chakraborty Anirban , Sarker Altaf H , Aryal Uma K , Pan Lang , Sharma Gulshan , Boldogh Istvan , Hazra Tapas
Published: January 2024

Mammalian polynucleotide kinase 3′-phosphatase (PNKP), a DNA end-processing enzyme with 3′-phosphatase and 5′-kinase activities, is involved in multiple DNA repair pathways, including base excision (BER), single-strand break (SSBR), and double-strand break repair (DSBR). However, little is known as to how PNKP functions in such diverse repair processes. Here we report that PNKP is acetylated at K142 (AcK142) by p300 constitutively but at K226 (AcK226) by CBP, only after DSB induction. Co-immunoprecipitation analysis using AcK142 or AcK226 PNKP-specific antibodies showed that AcK142-PNKP associates only with BER/SSBR, and AcK226 PNKP with DSBR proteins. Despite the modest effect of acetylation on PNKP’s enzymatic activity in vitro, cells expressing non-acetylable PNKP (K142R or K226R) accumulated DNA damage in transcribed genes. Intriguingly, in striatal neuronal cells of a Huntington's Disease (HD)-based mouse model, K142, but not K226, was acetylated. This is consistent with the reported degradation of CBP, but not p300, in HD cells. Moreover, transcribed genomes of HD cells progressively accumulated DSBs. Chromatin-immunoprecipitation analysis demonstrated the association of Ac-PNKP with the transcribed genes, consistent with PNKP’s role in transcription-coupled repair. Thus, our findings demonstrate that acetylation at two lysine residues, located in different domains of PNKP, regulates its distinct role in BER/SSBR versus DSBR.
Nucleolar detention of NONO shields DNA double-strand breaks from aberrant transcripts
Authors: Trifault Barbara , Mamontova Victoria , Cossa Giacomo , Ganskih Sabina , Wei Yuanjie , Hofstetter Julia , Bhandare Pranjali , Baluapuri Apoorva , Nieto Blanca , Solvie Daniel , Ade Carsten P , Gallant Peter , Wolf Elmar , Larsen Dorthe H , Munschauer Mathias , Burger Kaspar
Published: January 2024

RNA-binding proteins emerge as effectors of the DNA damage response (DDR). The multifunctional non-POU domain-containing octamer-binding protein NONO/p54nrb marks nuclear paraspeckles in unperturbed cells, but also undergoes re-localization to the nucleolus upon induction of DNA double-strand breaks (DSBs). However, NONO nucleolar re-localization is poorly understood. Here we show that the topoisomerase II inhibitor etoposide stimulates the production of RNA polymerase II-dependent, DNA damage-inducible antisense intergenic non-coding RNA (asincRNA) in human cancer cells. Such transcripts originate from distinct nucleolar intergenic spacer regions and form DNA–RNA hybrids to tether NONO to the nucleolus in an RNA recognition motif 1 domain-dependent manner. NONO occupancy at protein-coding gene promoters is reduced by etoposide, which attenuates pre-mRNA synthesis, enhances NONO binding to pre-mRNA transcripts and is accompanied by nucleolar detention of a subset of such transcripts. The depletion or mutation of NONO interferes with detention and prolongs DSB signalling. Together, we describe a nucleolar DDR pathway that shields NONO and aberrant transcripts from DSBs to promote DNA repair.
Electrospun PCL/gelatin/arbutin nanofiber membranes as potent reactive oxygen species scavengers to accelerate cutaneous wound healing
Authors: Du Mindong , Liu Shuhan , Lan Nihan , Liang Ruiming , Liang Shengde , Lan Maoqiang , Feng Disen , Zheng Li , Wei Qingjun , Ma Ke
Published: January 2024

The presence of excessive reactive oxygen species (ROS) at a skin wound site is an important factor affecting wound healing. ROS scavenging, which regulates the ROS microenvironment, is essential for wound healing. In this study, we used novel electrospun PCL/gelatin/arbutin (PCL/G/A) nanofibrous membranes as wound dressings, with PCL/gelatin (PCL/G) as the backbone, and plant-derived arbutin (hydroquinone-β-d-glucopyranoside, ARB) as an effective antioxidant that scavenges ROS and inhibits bacterial infection in wounds. The loading of ARB increased the mechanical strength of the nanofibres, with a water vapour transmission rate of more than 2500 g/(m2 × 24 h), and the water contact angle decreased, indicating that hydrophilicity and air permeability were significantly improved. Drug release and degradation experiments showed that the nanofibre membrane controlled the drug release and exhibited favourable degradability. Haemolysis experiments showed that the PCL/G/A nanofibre membranes were biocompatible, and DPPH and ABTS+ radical scavenging experiments indicated that PCL/G/A could effectively scavenge ROS to reflect the antioxidant activity. In addition, haemostasis experiments showed that PCL/G/A had good haemostatic effects in vitro and in vivo. In vivo animal wound closure and histological staining experiments demonstrated that PCL/G/A increased collagen deposition and remodelled epithelial tissue regeneration while showing good in vivo biocompatibility and non-toxicity. In conclusion, we successfully prepared a multifunctional wound dressing, PCL/G/A, for skin wound healing and investigated its potential role in wound healing, which is beneficial for the clinical translational application of phytomedicines.
Short-term and long-term outcomes of patients with anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis
Authors: Ida Tomoaki , Furuta Shunsuke , Fujiwara Michio , Hiraguri Masaki , Hirose Koichi , Ikeda Kei , Iwamoto Taro , Kagami Shin-Ichiro , Kobayashi Yoshihisa , Kurasawa Kazuhiro , Nakagomi Daiki , Oya Yoshihiro , Sanayama Yoshie , Shimizu Toshimasa , Tamachi Tomohiro , Umibe Takeshi , Yasui Masahiro , Nakajima Hiroshi
Published: January 2024

Objectives

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (MDA5-DM) is a subtype of dermatomyositis characterized by frequent interstitial lung disease and reduced muscle involvement. This study aimed to determine the short-term and long-term outcomes of patients with MDA5-DM.

Methods

Information on baseline characteristics, treatments and short-term and long-term outcomes of patients with MDA5-DM including survival, relapse and the titre of anti-MDA5 antibody, was retrospectively collected. Descriptive statistics regarding clinical outcomes were calculated, and a comparison of clinical parameters between patients with and without relapse was performed. The short-term survival according to the use of Janus kinase inhibitors (JAKi) was also assessed.

Results

A total of 154 patients with MDA5-DM were included in the study. Forty patients (26.0%) died during the remission induction phase, with respiratory failure being the most common cause of mortality. Among the 114 patients who survived the remission induction phase, the 5-year cumulative survival and relapse-free survival rates were 96.8% and 77.4%, respectively, and 7.9% of patients achieved complete drug-free remission. Fifty-four patients achieved normalization of anti-MDA5 antibody titres and only two of them relapsed after normalization. In the severe patients, the 6-month survival rate became significantly higher after the emergence of the JAKi treatment compared with before its existence (P = 0.03).

Conclusion

Although relapse often occurs, the long-term survival of MDA5-DM patients who survived the remission induction phase is generally favourable. The status of the anti-MDA5 antibody is associated with relapse. JAKi may improve the survival of refractory patients with severe MDA5-DM.
Social support and fear-inhibition: an examination of underlying neural mechanisms
Authors: Hornstein E.A , Leschak C J , Parrish M H , Byrne-Haltom K E , Fanselow M S , Craske M G , Eisenberger N I
Published: January 2024

Recent work has demonstrated that reminders of those we are closest to have a unique combination of effects on fear learning and represent a new category of fear inhibitors, termed prepared fear suppressors. Notably, social-support-figure images have been shown to resist becoming associated with fear, suppress conditional-fear-responding and lead to long-term fear reduction. Due to the novelty of this category, understanding the underlying neural mechanisms that support these unique abilities of social-support-reminders has yet to be investigated. Here, we examined the neural correlates that enable social-support-reminders to resist becoming associated with fear during a retardation-of-acquisition test. We found that social-support-figure-images (vs stranger-images) were less readily associated with fear, replicating prior work, and that this effect was associated with decreased amygdala activity and increased ventromedial prefrontal cortex (VMPFC) activity for social-support-figure-images (vs stranger-images), suggesting that social-support-engagement of the VMPFC and consequent inhibition of the amygdala may contribute to unique their inhibitory effects. Connectivity analyses supported this interpretation, showing greater connectivity between the VMPFC and left amygdala for social-support-figure-images (vs stranger-images).
POSITION STATEMENT: Pass the RESTORE (Re-entry Support Through Opportunities for Resources and Essentials) Act
Authors: LaRowe Lisa R , Frederick Gwyneth , Figueroa Roger , Adams Elizabeth , Bean Melanie , Landry Matthew , Nock Nora
Published: January 2024

Under the Personal Responsibility and Work Opportunity Reconciliation Act (PRWORA), current federal policy mandates a lifetime ban for individuals with a past felony drug conviction from receiving Supplemental Nutrition Assistance Program (SNAP) and Temporary Assistance for Needy Families (TANF) benefits. Denying nutritional and financial assistance to individuals with a past felony conviction will widen existing structural health inequities, set back individuals’ successful re-entry into society, and contribute to recidivism and poorer health outcomes. Therefore, the Society of Behavioral Medicine supports the RESTORE ACT (Re-Entry Support Through Opportunities for Resources and Essentials Act), which would repeal the lifetime ban on receiving SNAP and TANF benefits for individuals convicted of a drug felony.
Equine herpesvirus 4 infected domestic horses associated with Sintashta spoke-wheeled chariots around 4,000 years ago
Authors: Lebrasseur Ophélie , More Kuldeep Dilip , Orlando Ludovic
Published: January 2024

Equine viral outbreaks have disrupted the socio-economic life of past human societies up until the late 19th century and continue to be of major concern to the horse industry today. With a seroprevalence of 60–80 per cent, equine herpesvirus 4 (EHV-4) is the most common horse pathogen on the planet. Yet, its evolutionary history remains understudied. Here, we screen the sequenced data of 264 archaeological horse remains to detect the presence of EHV-4. We recover the first ancient EHV-4 genome with 4.2× average depth-of-coverage from a specimen excavated in the Southeastern Urals and dated to the Early Bronze Age period, approximately 3,900 years ago. The recovery of an EHV-4 virus outside the upper respiratory tract not only points to an animal particularly infected but also highlights the importance of post-cranial bones in pathogen characterisation. Bayesian phylogenetic reconstruction provides a minimal time estimate for EHV-4 diversification to around 4,000 years ago, a time when modern domestic horses spread across the Central Asian steppes together with spoke-wheeled Sintashta chariots, or earlier. The analyses also considerably revise the diversification time of the two EHV-4 subclades from the 16th century based solely on modern data to nearly a thousand years ago. Our study paves the way for a robust reconstruction of the history of non-human pathogens and their impact on animal health.
Complete Genome Resource of a Fungal Antagonistic Strain: Pseudomonas tohonis
Authors: Luo Wan-Zhen , Zhu He , Qi Hong-Yue , Song Jian , Zhang Dan-Dan , Dai Xiao-Feng , Mijiti Maihemuti , Chen Jie-Yin , Han Dongfei , Wang Dan
Published: January 2024

KRS022 was isolated from the rhizosphere soil of a healthy plant in a pathogen-infested cotton field in Xinjiang, China. Previous studies have demonstrated that KRS022 possesses the ability to trigger plant immune responses, inhibit the growth of various pathogenic fungi, including Verticillium dahliae, and promote plant growth. The antagonistic properties of KRS022 primarily stem from its bioactive metabolites. In this study, the high-quality genome of KRS022 was obtained. The KRS022 genome consists of a chromosome of 6,369,026 bp with 67.09% GC content and possesses 5,830 open reading frames, of which 5,186 genes were annotated, and 119 were ncRNA genes. Additionally, 11 gene clusters of secondary metabolites biosynthesis were predicted, involved in polyketide synthase, arylpolyene, NAGGN, beta-lactone, ranthipeptide, PiPP-like, redox cofactor, and non-ribosomal peptide-synthetase clusters. It could be useful to explore the biocontrol potential of P. tohonis, implying promising application of KRS022 to biological control.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Optimizing Management of the Second Stage of Labor: A Multicenter Randomized Controlled Trial
Authors: Saucedo Alexander M. , Cahill Alison G.
Published: January 2024

To review the findings of the Optimizing Management of the Second Stage of Labor randomized controlled trial in the context of prior and subsequent obstetric literature. A multi-database search was performed in addition to a review of the parent trial and secondary studies. Nulliparous patients with neuraxial anesthesia randomized to either immediate or delayed pushing showed no difference in vaginal delivery rates. However, delayed pushing is associated with an increased duration of the second stage and perinatal morbidity. Patients should be appropriately counseled on the timing of second-stage pushing and the risks of prolonged second-stage labor.
Chinese Medicine, Acupuncture and Science
Authors: Eckman Peter
Published: January 2024

Ever since the introduction of Western biomedicine into China, there has been friction between proponents of this new approach, and proponents of the traditional medical practices that had evolved over thousands of years in China. For the most part, this friction has been couched in the unexamined assumption that Western medicine is based on science, while Chinese medicine is not. This article will examine that assumption, which in this author’s opinion is unjustified and incorrect. Having practiced acupuncture for the past 50 years, after receiving my doctoral degrees in medicine and physiology, my thinking on this topic has also evolved over time. I will begin this article with some historical information that bears on the topic under discussion, followed by my personal ideas about how to resolve the conflicts that have arisen.
Effects of COVID-19 mRNA vaccination on HIV viremia and reservoir size
Authors: Duncan Maggie C. , Omondi F. Harrison , Kinloch Natalie N. , Lapointe Hope R. , Speckmaier Sarah , Moran-Garcia Nadia , Lawson Tanya , DeMarco Mari L. , Simons Janet , Holmes Daniel T. , Lowe Christopher F. , Bacani Nic , Sereda Paul , Barrios Rolando , Harris Marianne , Romney Marc G. , Montaner Julio S.G. , Brumme Chanson J. , Brockman Mark A. , Brumme Zabrina L.
Published: January 2024

Objective:

The immunogenic nature of coronavirus disease 2019 (COVID-19) mRNA vaccines led to some initial concern that these could stimulate the HIV reservoir. We analyzed changes in plasma HIV loads (pVL) and reservoir size following COVID-19 mRNA vaccination in 62 people with HIV (PWH) receiving antiretroviral therapy (ART), and analyzed province-wide trends in pVL before and after the mass vaccination campaign.

Design:

Longitudinal observational cohort and province-wide analysis.

Methods:

Sixty-two participants were sampled prevaccination, and one month after their first and second COVID-19 immunizations. Vaccine-induced anti-SARS-CoV-2-Spike antibodies in serum were measured using the Roche Elecsys Anti-S assay. HIV reservoirs were quantified using the intact proviral DNA assay; pVL were measured using the cobas 6800 (lower limit of quantification: 20 copies/ml). The province-wide analysis included all 290 401 pVL performed in British Columbia, Canada between 2012 and 2022.

Results:

Prevaccination, the median intact reservoir size was 77 [interquartile range (IQR): 20–204] HIV copies/million CD4+T-cells, compared to 74 (IQR: 27–212) and 65 (IQR: 22–174) postfirst and -second dose, respectively (all comparisonsP> 0.07). Prevaccination, 82% of participants had pVL <20 copies/ml (max: 110 copies/ml), compared to 79% postfirst dose (max: 183 copies/ml) and 85% postsecond dose (max: 79 copies/ml) (P > 0.4). There was no evidence that the magnitude of the vaccine-elicited anti-SARS-CoV-2-Spike immune response influenced pVL nor changes in reservoir size (P > 0.6). We found no evidence linking the COVID-19 mass vaccination campaign to population-level increases in detectable pVL frequency among all PWH in the province, nor among those who maintained pVL suppression on ART.

Conclusion:

We found no evidence that COVID-19 mRNA vaccines induced changes in HIV reservoir size nor plasma viremia.
Comparative Analysis of Antibacterial and Wound Healing Activities of Chitosan and Povidone-Iodine–Based Hydrogels
Authors: Jeon Sungmi , Kim Iljin , Jeong Yu Jin , Kim Young , Chung Justin J. , Kim Sang Wha
Published: January 2024

Purpose

This study aimed to compare the antibacterial and wound healing efficacies of chitosan hydrogel with povidone-iodine (PI) hydrogel.

Methods

The in vitro antibacterial activities of chitosan and PI hydrogels against Staphylococcus aureus and Escherichia coli were evaluated. Nine 6- to 8-week-old male Sprague-Dawley rats were divided into plain, PI, and chitosan hydrogel groups. Each rat received two 10-mm full-thickness dorsal wounds using an excisional splinting model. Each wound was treated with 0.2 mL of gel thrice over the course of 3 postoperative weeks. Weekly observations were conducted, and at the end of the third postoperative week, the rats were killed for histopathological and quantitative polymerase chain reaction evaluations. Data analysis included both 2- and 1-way analyses of variance.

Results

Chitosan hydrogel exhibited comparable in vitro antibacterial activity and a significantly enhanced in vivo wound closure rate compared with PI hydrogel. Three weeks after the surgery, the chitosan hydrogel group demonstrated marked differences in wound repair (P < 0.01). Histologically, increased collagen deposition was observed with chitosan hydrogel treatment. Immunohistochemistry for CD68 revealed a lower number of macrophages in the wounds treated with chitosan hydrogel. Quantitative polymerase chain reaction analysis indicated a superior collagen 1 to 3 ratio and reduced expression of proinflammatory cytokine mRNAs (interleukin 1b, interleukin 6, tumor necrosis factor α, and interferon γ) in the chitosan hydrogel group.

Conclusion

Chitosan hydrogel demonstrates the potential to serve as an effective alternative to PI hydrogel, providing enhanced wound healing capabilities while maintaining comparable antimicrobial properties.
Is the h-Index Enough? A Comprehensive Bibliometric Analysis of 871 Academic Plastic Surgeons and Their Departments/Divisions
Authors: Persad-Paisley Elijah M. , Gopal Jay R. , Menville Jesse E. , Baranwal Navya , McIntire Damon R. T. , Zeyl Victoria G. , Kalliainen Loree K.
Published: January 2024

Background

In plastic surgery academia, research output is heavily used as a metric of accreditation, from assessing residency applicants to evaluating faculty for promotion. Thehindex, defined as an author'shpapers with at leasthcitations, is commonly used as a measure of academic success. However, the index itself disfavors junior researchers, favors publication quantity, and discounts highly cited works. Given the importance of bibliometrics within plastic surgery, there is a paramount need to adopt additional metrics to measure research productivity. The authors sought to validate the use of time-independent bibliometrics to complement thehindex in measuring citation impact.

Methods

The genders and academic titles of plastic surgeons affiliated with US plastic surgery programs were recorded. Author publications were retrieved from Scopus. Bibliometrics software was used to calculate the following metrics per surgeon:hindex,eindex, andgindex. Time-adjusted versions of these indices were used to correct for the number of years since first publication. Medians and interquartile ranges (IQRs) are reported. Departmental ranks were determined using the cumulative sum of time-corrected indices and compared with Doximity departmental research rankings.P< 0.05 was deemed significant.

Results

Indices were calculated for 871 academic plastic surgeons in 85 departments/divisions. Men had statistically greaterhindex (median, 13.0 [IQR, 7.0–21.0] vs 6.0 [IQR, 3.0–13];P< 0.001),eindex (18.3 [IQR, 10.0–28.7] vs 11.1 [IQR, 5.5–18.4];P< 0.001), andgindex (23.0 [IQR, 11.0–39.0] vs 11.0 [IQR, 5.0–22.0];P< 0.001) than women. Professors had the highest median time-uncorrected indices. After adjusting for the number of years since an author's first publication, there were no significant differences inmquotient (men: 0.66 [IQR, 0.40–0.98] vs women: 0.57 [IQR, 0.33–0.90];P= 0.05) andecindex (men: 0.93 [IQR, 0.62–1.3] vs women: 0.87 [IQR, 0.50–1.3];P= 0.08) between genders. Departmental chairs had significantly higher indices than other faculty after correcting for time. The calculated program rankings were low to moderately correlated with that of Doximity (correlation coefficient τ = 0.49 [95% confidence interval, 0.37–0.59;P< 0.001]).

Conclusions

Men and women have statistically similar citation patterns after correcting for the time. Citation differences between academic levels are less pronounced when controlling for time, suggesting comparable research quality between academic roles.
Shear stress-induced restoration of pulmonary endothelial barrier function following ischaemia reperfusion injury requires VEGFR2 signalling
Authors: Walsh Don , Kostyunina Daria S. , Boylan John , McLoughlin Paul
Published: January 2024

Normal physiological shear stress produced by blood flow is sensed by the vascular endothelium and required for the maintenance of both the normal structure and barrier function of the endothelium. Many common, critical illnesses are characterised by periods of abnormally reduced or absent shear stress e.g. haemorrhagic shock, myocardial infarction and pulmonary embolism and are complicated by oedema formation following restoration of normal perfusion (IRI).

We tested the hypothesis that, in lungs injured by a period of ischaemia and reperfusion (IRI), reduced shear stress contributes to increased endothelial barrier permeability and oedema formation following the restoration of perfusion. Furthermore, we examined the role of VEGFR2 as a mechanosensor in the response of the pulmonary endothelium to altered shear stress in this condition.

Following IRI, we perfused isolated ventilated mouse lungs with a low viscosity solution (LVS) or a higher, physiological viscosity solution (PVS) at constant flow to produce differing shear stresses on the endothelium of the intact pulmonary circulation. Lungs perfused with LVS developed pulmonary oedema due to increased endothelial permeability whereas those perfused with PVS were protected from oedema formation by reduced endothelial permeability. This effect of PVS required normal VEGFR2 tyrosine kinase activity but was unaffected by blocking VEGFA binding to the receptor.

These data show for the first time that shear stress has an important role in restoring endothelial barrier function in the pulmonary circulation following injury and have important implications for the treatment of pulmonary oedema in critically ill patients following ischaemia reperfusion injury.
Elucidating an implicit-statistical learning brain network: Coordinate-based meta-analyses and functional connectivity profiles of artificial grammar learning in healthy adults
Authors: Ramage Amy E. , Cote Kaila , Thorson Jill C. , Lerner Katelyn , Reidel Michael C. , Laird Angela R.
Published: January 2024

Language rehabilitation centers on modifying its use through experience-based neuroplasticity. Implicit statistical learning of language is essential to its acquisition and likely its rehabilitation following brain injury, but its corresponding brain networks remain elusive. Coordinate-based meta-analyses were conducted to identify common and distinct brain activity across 25 studies coded for meta-data and experimental contrasts (grammatical or non-grammatical). The resultant brain regions served as seeds for profiling functional connectivity in large task-independent and task-dependent data sets. Hierarchical clustering of these profiles grouped brain regions into three subnetworks associated with grammatical/non-grammatical processes. Functional decoding clarified the mental operations associated with those subnetworks. Results support a left-dominant language sub-network and two cognitive control networks as scaffolds for grammar rule identification, maintenance, and application in healthy adults. These data suggest that cognitive control is necessary to track regularities across stimuli and imperative for rule identification and application of grammar. Future empirical investigation of these brain networks in language learning in individuals with brain injury will clarify their prognostic role in language recovery.
Spatial interactions modulate tumor growth and immune infiltration
Authors: Marzban Sadegh , Srivastava Sonal , Kartika Sharon , Bravo Rafael , Safriel Rachel , Zarski Aidan , Anderson Alexander , Chung Christine H. , Amelio Antonio L. , West Jeffrey
Published: January 2024

Direct observation of immune cell trafficking patterns and tumor-immune interactions is unlikely in human tumors with currently available technology, but computational simulations based on clinical data can provide insight to test hypotheses. It is hypothesized that patterns of collagen formation evolve as a mechanism of immune escape, but the exact nature of the interaction between immune cells and collagen is poorly understood. Spatial data quantifying the degree of collagen fiber alignment in squamous cell carcinomas indicates that late stage disease is associated with highly aligned fibers. Here, we introduce a computational modeling framework (called Lenia) to discriminate between two hypotheses: immune cell migration that moves 1) parallel or 2) perpendicular to collagen fiber orientation. The modeling recapitulates immune-ECM interactions where collagen patterns provide immune protection, leading to an emergent inverse relationship between disease stage and immune coverage. We also illustrate the capabilities of Lenia to model the evolution of tumor progression and immune predation. Lenia provides a flexible framework for considering a spectrum of local (cell-scale) to global (tumor-scale) dynamics by defining a kernel cell-cell interaction function that governs tumor growth dynamics under immune predation with immune cell migration. Mathematical modeling provides important mechanistic insights into cell interactions. Short-range interaction kernels provide a mechanism for tumor cell survival under conditions with strong Allee effects, while asymmetric tumor-immune interaction kernels lead to poor immune response. Thus, the length scale of tumor-immune interactions drives tumor growth and infiltration.
How many specimens make a sufficient training set for automated 3D feature extraction?
Authors: Mulqueeney James M. , Searle-Barnes Alex , Brombacher Anieke , Sweeney Marisa , Goswami Anjali , Ezard Thomas H. G.
Published: January 2024

Deep learning has emerged as a robust tool for automating feature extraction from 3D images, offering an efficient alternative to labour-intensive and potentially biased manual image segmentation methods. However, there has been limited exploration into the optimal training set sizes, including assessing whether artificial expansion by data augmentation can achieve consistent results in less time and how consistent these benefits are across different types of traits. In this study, we manually segmented 50 planktonic foraminifera specimens from the genus Menardella to determine the minimum number of training images required to produce accurate volumetric and shape data from internal and external structures. The results reveal unsurprisingly that deep learning models improve with a larger number of training images and that data augmentation can enhance network accuracy by up to 8.0%. Notably, predicting both volumetric and shape measurements for the internal structure poses a greater challenge compared to the external structure, due to low contrast between different materials and increased geometric complexity. These results provide novel insight into optimal training set sizes for precise image segmentation of diverse traits and highlight the potential of data augmentation for enhancing multivariate feature extraction from 3D images.

Subject Category

Life Sciences – Computer Science

Subject Areas

computational biology, Artificial Intelligence
A Surgical Technique for Individual Control of the Muscles of the Rabbit Lower Hind-limb
Authors: Baggaley Michael , Sawatsky Andrew , Ross Stephanie A. , Herzog Walter
Published: January 2024

Little is known regarding the precise muscle, bone, and joint actions resulting from individual and simultaneous muscle activation(s) of the lower limb. Anin situexperimental approach is described herein to control the muscles of the rabbit lower hind-limb, including the medial and lateral gastrocnemius, soleus, plantaris, and tibialis anterior. The muscles were stimulated using nerve-cuff electrodes placed around the innervating nerves of each muscle. Animals were fixed in a stereotactic frame with the ankle angle free to rotate in the sagittal plane to quantify the behaviour of the lower hind-limb muscles. To demonstrate the efficacy of the experimental technique, isometric plantarflexion torque was measured at a 90 ° ankle joint angle at a stimulation frequency of 100, 60, and 30 Hz. Individual muscle torque and the torque produced during simultaneous activation of all plantarflexor muscles are presented for four animals. These results demonstrate that the experimental approach was reliable, with insignificant variation in torque between repeated contractions. The experimental approach described herein provides the potential for measuring a diverse array of muscle properties which is important to improve our understanding of musculoskeletal biomechanics.

Highlights

A reliable surgical technique was developed for isolated activation of the plantarflexor muscles and the tibialis anterior in the rabbit. Joint torque data are presented for four rabbits at a single joint angle and three stimulation frequencies.
Assessment of Gene Set Enrichment Analysis using curated RNA-seq-based benchmarks
Authors: Candia Julián , Ferrucci Luigi
Published: January 2024

Pathway enrichment analysis is a ubiquitous computational biology method to interpret a list of genes (typically derived from the association of large-scale omics data with phenotypes of interest) in terms of higher-level, predefined gene sets that share biological function, chromosomal location, or other common features. Among many tools developed so far, Gene Set Enrichment Analysis (GSEA) stands out as one of the pioneering and most widely used methods. Although originally developed for microarray data, GSEA is nowadays extensively utilized for RNA-seq data analysis. Here, we quantitatively assessed the performance of a variety of GSEA modalities and provide guidance in the practical use of GSEA in RNA-seq experiments. We leveraged harmonized RNA-seq datasets available from The Cancer Genome Atlas (TCGA) in combination with large, curated pathway collections from the Molecular Signatures Database to obtain cancer-type-specific target pathway lists across multiple cancer types. We carried out a detailed analysis of GSEA performance using both gene-set and phenotype permutations combined with four different choices for the Kolmogorov-Smirnov enrichment statistic. Based on our benchmarks, we conclude that the classic/unweighted gene-set permutation approach offered comparable or better sensitivity-vs-specificity tradeoffs across cancer types compared with other, more complex and computationally intensive permutation methods. Finally, we analyzed other large cohorts for thyroid cancer and hepatocellular carcinoma. We utilized a new consensus metric, the Enrichment Evidence Score (EES), which showed a remarkable agreement between pathways identified in TCGA and those from other sources, despite differences in cancer etiology. This finding suggests an EES-based strategy to identify a core set of pathways that may be complemented by an expanded set of pathways for downstream exploratory analysis. This work fills the existing gap in current guidelines and benchmarks for the use of GSEA with RNA-seq data and provides a framework to enable detailed benchmarking of other RNA-seq-based pathway analysis tools.