bluuebunny/crossref_metadata_2025 huggingface dataset:
The STF/WOX1 MD is required for physical interaction with MtWOX9 and leaf blade outgrowth in Medicago truncatula
Authors: Li Xue , Wang Tingting , Zhang Yunwei , Tadege Million , Wang Hui
Published: February 2024

Plant‐specific WUSCHEL‐related homeobox (WOX) family transcription factors play critical roles in maintaining meristems and lateral organ development. The WUS clade member STF/LAM1 physically interacts with the intermediate clade member WOX9. This interaction contributes to their antagonistical functions on leaf blade outgrowth by competing for the same cis‐elements in the promoter of their common target in M. truncatula and N. sylvestris. Here, we identified the main interaction domains of STF and MtWOX9 in Medicago, shedding light on the mechanism of WOX gene function. The middle domain of STF and MtWOX9 are both critical for the interaction, while the conserved motif of STF in the C‐terminal domain is also required. Deletion of the middle domain of STF partially rescued the leaf blade phenotypes of the stf null mutant, indicating that the middle domain plays an essential role during leaf blade expansion. This finding provides a new insight that the versatility of WOX function is not only caused by the conserved DNA binding and repression domains but also by the middle domain that recruits different partners.
Monopsony power, offshoring, and a European minimum wage
Authors: Egger Hartmut , Kreickemeier Udo , Wrona Jens
Published: February 2024

This paper sets up a two‐country model of offshoring with monopolistically competitive product and monopsonistically competitive labor markets. In our model, an incentive for offshoring exists even between symmetric countries, because shifting part of the production abroad reduces local labor demand and allows firms to more strongly execute their monopsonistic labor market power. However, offshoring between symmetric countries has negative welfare effects and therefore calls for policy intervention. In this context, we put forward the role of a common minimum wage and show that the introduction of a moderate minimum wage increases offshoring and reduces welfare. In contrast, a sizable minimum wage reduces offshoring and increases welfare. Beyond that, we also show that a sufficiently high common minimum wage cannot only eliminate offshoring but also inefficiencies in the resource allocation due to monopsonistic labor market distortions in closed economies.
Semantic structure and problem posing: Preservice teachers' experience
Authors: Calabrese Julia E. , Capraro Mary Margaret , Viruru Radhika
Published: February 2024

Despite problem posing's prominence in mathematics education research, its implementation in classrooms is limited. Therefore, teacher educators should incorporate problem posing tasks into preparation programs to help prospective teachers gain confidence in their abilities. One approach to teaching problem posing includes providing examples. The Common Core State Standards Initiative provides taxonomies with examples of one‐step word problems for all four basic operations. Through this mixed‐methods study, preservice teachers (N = 44) regularly identified and posed word problems within the addition and subtraction taxonomy. Before and after the intervention, the preservice teachers answered survey questions and posed problems to model given equations. The researchers analyzed the preservice teachers’ abilities to pose logical word problems and to match given equations before and after instruction. They also quantitatively analyzed Likert‐style survey responses on perceptions of posing the various types of word problems and integrated the results with a qualitative analysis of open‐ended responses expanding on the same questions. Results showed participants’ abilities to pose problems increased after the intervention. Additionally, participants felt problems with the unknown information at the beginning or middle were harder to pose than those with the unknown information at the end.
Management of infectious disease syndromes in thoracic organ transplants and mechanical circulatory device recipients: a Delphi panel
Authors: Luong Me‐Linh , Nakamachi Yoshiko , Silveira Fernanda P. , Morrissey Catherine O. , Danziger‐Isakov Lara , Verschuuren Erik A. M , Wolfe Cameron R. , Hadjiliadis Denis , Chambers Daniel C. , Patel Jignesh K. , Dellgren Goran , So Miranda , Verleden Geert M. , Blumberg Emily A. , Vos Robin , Perch Michael , Holm Are M. , Mueller Nicholas J. , Chaparro Cecilia , Husain Shahid
Published: February 2024

Purpose

Antimicrobial misuse contributes to antimicrobial resistance in thoracic transplant (TTx) and mechanical circulatory support (MCS) recipients. This study uses a modified Delphi method to define the expected appropriate antimicrobial prescribing for the common clinical scenarios encountered in TTx and MCS recipients.

Methods

An online questionnaire on managing 10 common infectious disease syndromes was submitted to a multidisciplinary Delphi panel of 25 experts from various disciplines. Consensus was predefined as 80% agreement for each question. Questions where consensus was not achieved were discussed during live virtual live sessions adapted by an independent process expert.

Results

An online survey of 62 questions related to 10 infectious disease syndromes was submitted to the Delphi panel. In the first round of the online questionnaire, consensus on antimicrobial management was reached by 6.5% (4/62). In Round 2 online live discussion, the remaining 58 questions were discussed among the Delphi Panel members using a virtual meeting platform. Consensus was reached among 62% (36/58) of questions. Agreement was not reached regarding the antimicrobial management of the following six clinical syndromes: (1) Burkholderia cepacia pneumonia (duration of therapy); (2) Mycobacterium abscessus (intra‐operative antimicrobials); (3) invasive aspergillosis (treatment of culture‐negative but positive BAL galactomannan) (duration of therapy); (4) respiratory syncytial virus (duration of antiviral therapy); (5) left ventricular assist device deep infection (initial empirical antimicrobial coverage) and (6) CMV (duration of secondary prophylaxis).

Conclusion

This Delphi panel developed consensus‐based recommendations for 10 infectious clinical syndromes seen in TTx and MCS recipients.

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Devaluing personhood: The framing of migrants in the EU's new pact on migration and asylum
Authors: Häkli Jouni , Kudžmaitė Gintarė , Kallio Kirsi Pauliina
Published: February 2024

The latest EU policy initiative to regulate migration to the European Union is called the New Pact on Migration and Asylum. Compared with previous policies, the New Pact promotes and normalises multiple procedures that can have far‐reaching consequences on migrants' agency, dignity, personhood, and vulnerability. As the EU's migration and asylum policies set the parameters for the governance of forced migration and access to asylum in the Member States, they also provide framings for the practical encounters between asylum seekers and the migration regime. These framings legitimise certain approaches to the management of asylum migration and the related interpretations of international human rights treaties both in the Member States and in the EU. By examining how migrants and their encounters with the EU are discussed and represented in the New Pact, we join the critical scholarship that has questioned the EU's supposed turn towards a more humane approach to migration. Examining the official voice of the EU, we conduct a critical policy analysis with a focus on terminology and framing, exploring three major frames through which the New Pact characterises migrants as part of its attempt to transform European asylum and migration governance. These frames relate to human classification, spatial coordination, and temporal control, each of which is linked to the management of encounters between migrants and the migration regime. We conclude by discussing what the New Pact's framing reveals about the EU's approaches to human vulnerability, dignity, agency, and (de)valued personhood.
Imperatives for integrated weed management in vegetable production: Evaluating research and adoption
Authors: Coleman Michael J. , Kristiansen Paul , Sindel Brian M. , Fyfe Christine
Published: February 2024

Weeds have a significant impact on vegetable production worldwide. These intensive cropping systems feature frequent tillage, fertilization and irrigation, providing ideal growing conditions for crops as well as certain weeds. Integrated weed management (IWM) can reduce reliance on herbicides by encouraging a systems approach to weed management. Using insights from global research and industry literature, we investigated the effectiveness of prevailing weed control methods, and evaluated emerging management practices and technologies for ongoing research and adoption. Weed control relies primarily on a relatively narrow range of herbicides as well as frequent tillage. Herbicides have negative impacts on soil, water and human health, while tillage impacts soil quality and function. Intensive cropping on smaller plots facilitates IWM, relying on multiple strategies including hand weeding, mulches, cover crops and cultural methods (e.g., crop rotations, timing). New herbicide options are suggested as an industry priority but are constrained by the lack of new chemistry and potential herbicide resistance. Refinement and adoption of non‐herbicide and emerging precision control methods into farm IWM in vegetables is more likely to be sustainable. This review is relevant to advanced vegetable production systems globally, but also to smallholder vegetable production in developing economies.
Film‐forming polymer solutions containing cholesterol myristate and berberine mediate pressure ulcer repair via the Wnt/β‐catenin pathway
Authors: Li Yu , Huang Haiting , Gu Cuijin , Huang Wenyi , Chen Xianxian , Lu Xiaoting , You Aijia , Ye Sen , Zhong Jun , Zhao Yao , Yan Yu , Li Chun
Published: February 2024

Pressure ulcer (PU) is a worldwide problem that is difficult to address because of the related inflammatory response, local hypoxia, and repeated ischaemia/reperfusion, causing great suffering and financial burden to patients. Traditional Chinese medicine turtle plate powder can treat skin trauma, but its composition is complex and inconvenient to use. Here, we combined cholesterol myristate (S8) with berberine (BBR), with anti‐inflammatory and antibacterial effects, as a drug and used hydroxypropyl methylcellulose and polyvinylpyrrolidone K30 as carriers to construct a novel film‐forming polymeric solution (S8 + BBR FFPS), comprehensively study its reparative effect on PU and explore the potential mechanism in rat PU models. The results showed that S8 + BBR FFPS inhibits excessive inflammatory response, promotes re‐epithelialization, and promotes hair follicle growth during the healing process of PU, which may be related to the activation of the Wnt/β‐catenin signalling pathway by S8 + BBR FFPS to mediate hair follicle stem cell proliferation and maintain skin homeostasis. Therefore, S8 + BBR FFPS may be a potential candidate for the treatment of chronic skin injury, and its association with the Wnt/β‐catenin signalling pathway may provide new ideas to guide the design of biomaterial‐based wound dressings for chronic wound repair.
High moments of theta functions and character sums
Authors: Szabó Barnabás
Published: February 2024

Assuming the Generalised Riemann Hypothesis, we prove a sharp upper bound on moments of shifted DirichletL‐functions. We use this to obtain conditional upper bounds on high moments of theta functions. Both of these results strengthen theorems of Munsch, who proved almost sharp upper bounds for these quantities. The main new ingredient of our proof comes from a paper of Harper, who showed the related result for all under the Riemann Hypothesis. Finally, we obtain a sharp conditional upper bound on high moments of character sums of arbitrary length.
Creencias y prácticas de autocuidado en profesionales de enfermería en UCI durante la pandemia COVID-19
Authors: Gómez Carvajal Andrea Carolina , Rojas Báez Yuri Lizeth , Sánchez Barrera Erika Alexandra
Published: February 2024

Resumen
Para los profesionales de enfermería, la pandemia por COVID-19 agudizó la necesidad de poner en práctica el cuidado y el autocuidado como elementos fundamentales para proteger la vida propia, de los pacientes, allegados, y la salubridad social en general. Objetivo: describir las creencias y las prácticas de autocuidado utilizadas por profesionales de enfermería que trabajan en Unidades de Cuidado Intensivo para mantener el bienestar físico, mental y social durante la atención de la pandemia por COVID-19 entre el segundo semestre del 2020 y primero del 2021. Metodología: enfoque cualitativo tipo etnográfico, basado en el método de la etnoenfermería propuesto por Madeleine Leininger. Muestreo por saturación teórica de 14 informantes clave. Recolección de información mediante entrevistas semiestructuradas presenciales y virtuales grabadas –transcritas en su totalidad– y notas de campo. Análisis de información a través de las fases de la etnoenfermería, categorización, caracterización e identificación de patrones recurrentes. Resultados: se identificaron tres categorías como temas principales, se obtuvo información sobre las creencias y prácticas de autocuidado de los profesionales de enfermería durante la pandemia por COVID-19 que tienen repercusiones en la búsqueda del bienestar individual y colectivo, reconocibles a través de la implementación de diferentes estrategias de protección y las prácticas culturales asociadas. Conclusión: los pensamientos y el consecuente actuar mencionados por la población entrevistada responden de manera directa a las prácticas y creencias relacionadas con sus intenciones de disminuir la probabilidad de contagio y gestionar un autocuidado en la construcción de una resiliencia y un bienestar efectivo de los profesionales de enfermería.
Pseudomonas
effector AvrB is a glycosyltransferase that rhamnosylates plant guardee protein RIN4
Authors: Peng Wei , Garcia Nalleli , Servage Kelly A. , Kohler Jennifer J. , Ready Joseph M. , Tomchick Diana R. , Fernandez Jessie , Orth Kim
Published: February 2024

The plant pathogen
Pseudomonas syringae
encodes a type III secretion system avirulence effector protein, AvrB, that induces a form of programmed cell death called the hypersensitive response in plants as a defense mechanism against systemic infection. Despite the well-documented catalytic activities observed in other Fido (
Fi
c,
Do
c, and AvrB) proteins, the enzymatic activity and target substrates of AvrB have remained elusive. Here, we show that AvrB is an unprecedented glycosyltransferase that transfers rhamnose from UDP-rhamnose to a threonine residue of the
Arabidopsis
guardee protein RIN4. We report structures of various enzymatic states of the AvrB-catalyzed rhamnosylation reaction of RIN4, which reveal the structural and mechanistic basis for rhamnosylation by a Fido protein. Collectively, our results uncover an unexpected reaction performed by a prototypical member of the Fido superfamily while providing important insights into the plant hypersensitive response pathway and foreshadowing more diverse chemistry used by Fido proteins and their substrates.
Nutrient availability regulates the secretion and function of immune cell–derived extracellular vesicles through metabolic rewiring
Authors: Wang Yizhuo , Lou Peng , Xie Yijing , Liu Shuyun , Li Lan , Wang Chengshi , Du Dan , Chen Younan , Lu Yanrong , Cheng Jingqiu , Liu Jingping
Published: February 2024

Extracellular vesicle (EV)–based immunotherapeutics have emerged as promising strategy for treating diseases, and thus, a better understanding of the factors that regulate EV secretion and function can provide insights into developing advanced therapies. Here, we report that nutrient availability, even changes in individual nutrient components, may affect EV biogenesis and composition of immune cells [e.g., macrophages (Mφs)]. As a proof of concept, EVs from M1-Mφ under glutamine-depleted conditions (EV
GLN−
) had higher yields, functional compositions, and immunostimulatory potential than EVs from conventional GLN-present medium (EV
GLN+
). Mechanistically, the systemic metabolic rewiring (e.g., altered energy and redox metabolism) induced by GLN depletion resulted in up-regulated pathways related to EV biogenesis/cargo sorting (e.g., ESCRT) and immunostimulatory molecule production (e.g., NF-κB and STAT) in Mφs. This study highlights the importance of nutrient status in EV secretion and function, and optimizing metabolic states and/or integrating them with other engineering methods may advance the development of EV therapeutics.
Comparative analysis of KRAS4a and KRAS4b splice variants reveals distinctive structural and functional properties
Authors: Whitley Matthew J. , Tran Timothy H. , Rigby Megan , Yi Ming , Dharmaiah Srisathiyanarayanan , Waybright Timothy J. , Ramakrishnan Nitya , Perkins Shelley , Taylor Troy , Messing Simon , Esposito Dominic , Nissley Dwight V. , McCormick Frank , Stephen Andrew G. , Turbyville Thomas , Cornilescu Gabriel , Simanshu Dhirendra K.
Published: February 2024

KRAS
, the most frequently mutated oncogene in human cancer, produces two isoforms, KRAS4a and KRAS4b, through alternative splicing. These isoforms differ in exon 4, which encodes the final 15 residues of the G-domain and hypervariable regions (HVRs), vital for trafficking and membrane localization. While KRAS4b has been extensively studied, KRAS4a has been largely overlooked. Our multidisciplinary study compared the structural and functional characteristics of KRAS4a and KRAS4b, revealing distinct structural properties and thermal stability. Position 151 influences KRAS4a’s thermal stability, while position 153 affects binding to RAF1 CRD protein. Nuclear magnetic resonance analysis identified localized structural differences near sequence variations and provided a solution-state conformational ensemble. Notably,
KRAS4a
exhibits substantial transcript abundance in bile ducts, liver, and stomach, with transcript levels approaching
KRAS4b
in the colon and rectum. Functional disparities were observed in full-length KRAS variants, highlighting the impact of HVR variations on interaction with trafficking proteins and downstream effectors like RAF and PI3K within cells.
Earliest directly dated rock art from Patagonia reveals socioecological resilience to mid-Holocene climate
Authors: Romero Villanueva Guadalupe , Sepúlveda Marcela , Cárcamo-Vega José , Cherkinsky Alexander , de Porras María Eugenia , Barberena Ramiro
Published: February 2024

The timing for the evolution of the capacity to inscribe the landscape with rock art has global relevance. While this was an in-built capacity when
Homo sapiens
first colonized the Americas, the heterogeneous distribution of rock art shows that it was a facultative behavior arising under unknown socioecological conditions. Patagonia was the last region to be explored by humans. While its rock art is globally important, it remains largely undated by absolute methods. We report the earliest set of directly radiocarbon-dated rock art motifs from the archaeological site Cueva Huenul 1 (northwestern Patagonia, Argentina), starting at 8.2 thousand years before the present (ka B.P.), predating previous records by several millennia, and encompassing over 3 ka (~130 human generations). This mid-Holocene “rock art emergence” phase overlaps with extremely arid conditions and a human demographic stasis. We suggest that this diachronic rock art emerged as part of a resilient response to ecological stress by highly mobile and low-density populations.
Skp1 proteins are structural components of the synaptonemal complex in
C. elegans
Authors: Blundon Joshua M. , Cesar Brenda I. , Bae Jung Woo , Čavka Ivana , Haversat Jocelyn , Ries Jonas , Köhler Simone , Kim Yumi
Published: February 2024

The synaptonemal complex (SC) is a zipper-like protein assembly that links homologous chromosomes to regulate recombination and segregation during meiosis. The SC has been notoriously refractory to in vitro reconstitution, thus leaving its molecular organization largely unknown. Here, we report a moonlighting function of two paralogous S-phase kinase-associated protein 1 (Skp1)–related proteins (SKR-1 and SKR-2), well-known adaptors of the Skp1–Cul1–F-box (SCF) ubiquitin ligase, as the key missing components of the SC in
Caenorhabditis elegans
. SKR proteins repurpose their SCF-forming interfaces to dimerize and interact with meiosis-specific SC proteins, thereby driving synapsis independent of SCF activity. SKR-1 enables the formation of the long-sought-after soluble complex with previously identified SC proteins in vitro, which we propose it to represent a complete SC building block. Our findings demonstrate how a conserved cell cycle regulator has been co-opted to interact with rapidly evolving meiotic proteins to construct the SC and provide a foundation for understanding its structure and assembly mechanisms.
Engineered T cells secreting anti-BCMA T cell engagers control multiple myeloma and promote immune memory in vivo
Authors: Díez-Alonso Laura , Falgas Aïda , Arroyo-Ródenas Javier , Romencín Paola A. , Martínez Alba , Gómez-Rosel Marina , Blanco Belén , Jiménez-Reinoso Anaïs , Mayado Andrea , Pérez-Pons Alba , Aguilar-Sopeña Óscar , Ramírez-Fernández Ángel , Segura-Tudela Alejandro , Perez-Amill Lorena , Tapia-Galisteo Antonio , Domínguez-Alonso Carmen , Rubio-Pérez Laura , Jara Maria , Solé Francesc , Hangiu Oana , Almagro Laura , Albitre Ángela , Penela Petronila , Sanz Laura , Anguita Eduardo , Valeri Antonio , García-Ortiz Almudena , Río Paula , Juan Manel , Martínez-López Joaquín , Roda-Navarro Pedro , Martín-Antonio Beatriz , Orfao Alberto , Menéndez Pablo , Bueno Clara , Álvarez-Vallina Luis
Published: February 2024

Multiple myeloma is the second most common hematological malignancy in adults and remains an incurable disease. B cell maturation antigen (BCMA)–directed immunotherapy, including T cells bearing chimeric antigen receptors (CARs) and systemically injected bispecific T cell engagers (TCEs), has shown remarkable clinical activity, and several products have received market approval. However, despite promising results, most patients eventually become refractory and relapse, highlighting the need for alternative strategies. Engineered T cells secreting TCE antibodies (STAb) represent a promising strategy that combines the advantages of adoptive cell therapies and bispecific antibodies. Here, we undertook a comprehensive preclinical study comparing the therapeutic potential of T cells either expressing second-generation anti-BCMA CARs (CAR-T) or secreting BCMAxCD3 TCEs (STAb-T) in a T cell–limiting experimental setting mimicking the conditions found in patients with relapsed/refractory multiple myeloma. STAb-T cells recruited T cell activity at extremely low effector-to-target ratios and were resistant to inhibition mediated by soluble BCMA released from the cell surface, resulting in enhanced cytotoxic responses and prevention of immune escape of multiple myeloma cells in vitro. These advantages led to robust expansion and persistence of STAb-T cells in vivo, generating long-lived memory BCMA-specific responses that could control multiple myeloma progression in xenograft models, outperforming traditional CAR-T cells. These promising preclinical results encourage clinical testing of the BCMA-STAb-T cell approach in relapsed/refractory multiple myeloma.
Aberrant ATM signaling and homology-directed DNA repair as a vulnerability of p53-mutant GBM to AZD1390-mediated radiosensitization
Authors: Chen Jiajia , Laverty Daniel J. , Talele Surabhi , Bale Ashwin , Carlson Brett L. , Porath Kendra A. , Bakken Katrina K. , Burgenske Danielle M. , Decker Paul A. , Vaubel Rachael A. , Eckel-Passow Jeanette E. , Bhargava Rohit , Lou Zhenkun , Hamerlik Petra , Harley Brendan , Elmquist William F. , Nagel Zachary D. , Gupta Shiv K. , Sarkaria Jann N.
Published: February 2024

ATM is a key mediator of radiation response, and pharmacological inhibition of ATM is a rational strategy to radiosensitize tumors. AZD1390 is a brain-penetrant ATM inhibitor and a potent radiosensitizer. This study evaluated the spectrum of radiosensitizing effects and the impact of
TP53
mutation status in a panel of
IDH1
wild-type (WT) glioblastoma (GBM) patient-derived xenografts (PDXs). AZD1390 suppressed radiation-induced ATM signaling, abrogated G
0
-G
1
arrest, and promoted a proapoptotic response specifically in p53-mutant GBM in vitro. In a preclinical trial using 10 orthotopic GBM models, AZD1390/RT afforded benefit in a cohort of
TP53
-mutant tumors but not in
TP53
-WT PDXs. In mechanistic studies, increased endogenous DNA damage and constitutive ATM signaling were observed in
TP53
-mutant, but not in
TP53
-WT, PDXs. In plasmid-based reporter assays, GBM43 (
TP53
-mutant) showed elevated DNA repair capacity compared with that in GBM14 (p53-WT), whereas treatment with AZD1390 specifically suppressed homologous recombination (HR) efficiency, in part, by stalling RAD51 unloading. Furthermore, overexpression of a dominant-negative
TP53
(p53DD) construct resulted in enhanced basal ATM signaling, HR activity, and AZD1390-mediated radiosensitization in GBM14. Analyzing RNA-seq data from TCGA showed up-regulation of HR pathway genes in
TP53
-mutant human GBM. Together, our results imply that increased basal ATM signaling and enhanced dependence on HR represent a unique susceptibility of
TP53
-mutant cells to ATM inhibitor–mediated radiosensitization.
Answer to the Photo Quiz: Were those hyphae or pseudohyphae in blood culture?
Authors: Yeung Eugene Y. H. , Deslandes Vincent , Cowan Juthaporn
Published: February 2024

Read the full article for the answer.
African swine fever virus pH240R enhances viral replication via inhibition of the type I IFN signaling pathway
Authors: Ye Guangqiang , Zhang Zhaoxia , Liu Xiaohong , Liu Hongyang , Chen Weiye , Feng Chunying , Li Jiangnan , Zhou Qiongqiong , Zhao Dongming , Zhang Shuai , Chen Hefeng , Bu Zhigao , Huang Li , Weng Changjiang
Published: February 2024

African swine fever (ASF) is an acute, hemorrhagic, and severe infectious disease caused by ASF virus (ASFV) infection. At present, there are still no safe and effective drugs and vaccines to prevent ASF. Mining the important proteins encoded by ASFV that affect the virulence and replication of ASFV is the key to developing effective vaccines and drugs. In this study, ASFV pH240R, a capsid protein of ASFV, was found to inhibit the type I interferon (IFN) signaling pathway. Mechanistically, pH240R interacted with IFNAR1 and IFNAR2 to disrupt the interaction of IFNAR1-TYK2 and IFNAR2-JAK1. Additionally, pH240R inhibited the phosphorylation of IFNAR1, TYK2, and JAK1 induced by IFN-α, resulting in the suppression of the nuclear import of STAT1 and STAT2 and the expression of IFN-stimulated genes (ISGs). Consistent with these results, H240R-deficient ASFV (ASFV-∆H240R) infection induced more ISGs in porcine alveolar macrophages compared with its parental ASFV HLJ/18. We also found that pH240R enhanced viral replication via inhibition of ISGs expression. Taken together, our results clarify that pH240R enhances ASFV replication by inhibiting the JAK-STAT signaling pathway, which highlights the possibility of pH240R as a potential drug target.

IMPORTANCE

The innate immune response is the host’s first line of defense against pathogen infection, which has been reported to affect the replication and virulence of African swine fever virus (ASFV) isolates. Identification of ASFV-encoded proteins that affect the virulence and replication of ASFV is the key step in developing more effective vaccines and drugs. In this study, we found that pH240R interacted with IFNAR1 and IFNAR2 by disrupting the interaction of IFNAR1-TYK2 and IFNAR2-JAK1, resulting in the suppression of the expression of interferon (IFN)-stimulated genes (ISGs). Consistent with these results, H240R-deficient ASFV (ASFV-∆H240R) infection induces more ISGs’ expression compared with its parental ASFV HLJ/18. We also found that pH240R enhanced viral replication via inhibition of ISGs’ expression. Taken together, our findings showed that pH240R enhances ASFV replication by inhibiting the IFN-JAK-STAT axis, which highlights the possibility of pH240R as a potential drug target.
Complete genome sequence of
Citrobacter braakii
ASE1 generated by PacBio sequencing
Authors: Tran Thao D. , Lee SangIn , Hnasko Robert , McGarvey Jeffery A.
Published: February 2024

We report the complete genome sequence of
Citrobacter braakii
ASE1 generated by the PacBio Sequel II platform. This bacterium was isolated from the soil of a lettuce farm in Salinas, CA, USA, in 2020. The genome consists of a single circular chromosome of 5,021,820 bp with a 52.2% GC content.
Engineering recombinant replication-competent bluetongue viruses expressing reporter genes for
in vitro
and non-invasive
in vivo
studies
Authors: Utrilla-Trigo Sergio , Jiménez-Cabello Luis , Marín-López Alejandro , Illescas-Amo Miguel , Andrés Germán , Calvo-Pinilla Eva , Lorenzo Gema , van Rijn Piet A. , Ortego Javier , Nogales Aitor
Published: February 2024

Bluetongue virus (BTV) is the causative agent of the important livestock disease bluetongue (BT), which is transmitted via Culicoides bites. BT causes severe economic losses associated with its considerable impact on health and trade of animals. By reverse genetics, we have designed and rescued reporter-expressing recombinant (r)BTV expressing NanoLuc luciferase (NLuc) or Venus fluorescent protein. To generate these viruses, we custom synthesized a modified viral segment 5 encoding NS1 protein with the reporter genes located downstream and linked by the Porcine teschovirus-1 (PTV-1) 2A autoproteolytic cleavage site. Therefore, fluorescent signal or luciferase activity is only detected after virus replication and expression of non-structural proteins. Fluorescence or luminescence signals were detected in cells infected with rBTV/Venus or rBTV/NLuc, respectively. Moreover, the marking of NS2 protein confirmed that reporter genes were only expressed in BTV-infected cells. Growth kinetics of rBTV/NLuc and rBTV/Venus in Vero cells showed replication rates similar to those of wild-type and rBTV. Infectivity studies of these recombinant viruses in IFNAR(−/−) mice showed a higher lethal dose for rBTV/NLuc and rBTV/Venus than for rBTV indicating that viruses expressing the reporter genes are attenuated
in vivo
. Interestingly, luciferase activity was detected in the plasma of viraemic mice infected with rBTV/NLuc. Furthermore, luciferase activity quantitatively correlated with RNAemia levels of infected mice throughout the infection. In addition, we have investigated the
in vivo
replication and dissemination of BTV in IFNAR (−/−) mice using BTV/NLuc and non-invasive
in vivo
imaging systems.

IMPORTANCE

The use of replication-competent viruses that encode a traceable fluorescent or luciferase reporter protein has significantly contributed to the
in vitro
and
in vivo
study of viral infections and the development of novel therapeutic approaches. In this work, we have generated rBTV that express fluorescent or luminescence proteins to track BTV infection both
in vitro
and
in vivo
. Despite the availability of vaccines, BTV and other related orbivirus are still associated with a significant impact on animal health and have important economic consequences worldwide. Our studies may contribute to the advance in orbivirus research and pave the way for the rapid development of new treatments, including vaccines.
Isolated left sternocleidomastoid pyomyositis: a rare presentation of cervical sepsis
Authors: Fraser Calum , Thompson Christopher SG , Yeo Justin C L
Published: February 2024

An elderly gentleman self-presented to A+E with a 7-day history of significant and progressive left-sided neck pain, swelling and fevers, despite oral antibiotics from his general practitioner. Examination revealed a large left-sided neck mass involving levels 2–5 of the neck that was firm to palpate, with erythematous overlying skin.

An urgent CT scan demonstrated a large collection throughout the length of the left sternocleidomastoid muscle (SCM), measuring 13×5.5×4 cm, with extensive adjacent inflammatory change. He was subsequently taken to theatre for washout and debridement, during which the collection was found to be loculated and isolated to the SCM, with surrounding structures spared.

Postoperatively, he was managed with intravenous fluids and a total of 2 weeks of intravenous antibiotics. The wound partially dehisced during healing and the cavity was packed with flaminal and regularly dressed with input from the tissue viability team. This was then left to heal by secondary intention and the patient was followed up in clinic over the following weeks to ensure resolution.
Carolyn’s window approach for spontaneous frontal sinus meningoencephalocele
Authors: Akhavan-Mofrad Arshia , Gupta Keshav Kumar , Jolly Karan
Published: February 2024

Spontaneous meningoencephaloceles (MECs) are sparsely documented in the literature. Those occurring in the frontal sinus are an exceedingly rare entity. MECs are commonly associated with cerebrospinal fluid (CSF) rhinorrhoea. CSF rhinorrhoea is frequently misdiagnosed, causing delays in diagnosis and management. The subsequently increased risk of bacterial meningitis can be life-threatening to patients. We report the case of a woman in her late 70s with a spontaneous frontal sinus MEC, presenting with a 6-month history of CSF rhinorrhoea. The patient was successfully treated using the novel Carolyn’s window approach endoscopically; 9-month follow-up revealed no skull-base breach. Our case emphasises the importance of considering MEC as a differential diagnosis for clear rhinorrhoea and demonstrates successful repair through a novel surgical approach.
Infantile hemiparesis and porencephaly due to a COL4A1 mutation: Gould syndrome
Authors: Burns Austin , Hug Jamie
Published: February 2024

Gould syndrome is an autosomal dominant syndrome due to a COL4A1 or COL4A2 mutation that is commonly characterised by familial porencephaly, seizures, intracranial haemorrhages, cataracts, nephropathies and more. There have been up to 137 identified patients based on a review of the literature. In this case, we describe a male infant that presents with hemiparesis, developmental delay and gait abnormalities at his well-child check. Referral to neurology and a subsequent MRI demonstrated porencephaly and ocular lens abnormalities. Genetic sequencing uncovered a mutation to the COL4A1 gene, suggesting Gould syndrome. There are no family members with similar phenotypes. Mutations to the COL4A1 and COL4A2 genes result in disruption of collagen found in most basement membranes, resulting in a variety of phenotypes that can make diagnosis difficult. Genetic identification of these patients is critical as these patients require a multidisciplinary approach to care and specific counselling on risk reduction techniques.
Physical fitness in male adolescents and atherosclerosis in middle age: a population-based cohort study
Authors: Herraiz-Adillo Ángel , Ahlqvist Viktor H , Higueras-Fresnillo Sara , Hedman Kristofer , Hagström Emil , Fortuin-de Smidt Melony , Daka Bledar , Lenander Cecilia , Berglind Daniel , Östgren Carl Johan , Rådholm Karin , Ortega Francisco B , Henriksson Pontus
Published: February 2024

Objectives

To examine the associations between physical fitness in male adolescents and coronary and carotid atherosclerosis in middle age.

Methods

This population-based cohort study linked physical fitness data from the Swedish Military Conscription Register during adolescence to atherosclerosis data from the Swedish CArdioPulmonary bioImage Study in middle age. Cardiorespiratory fitness was assessed using a maximal cycle-ergometer test, and knee extension muscular strength was evaluated through an isometric dynamometer. Coronary atherosclerosis was evaluated via Coronary Computed Tomography Angiography (CCTA) stenosis and Coronary Artery Calcium (CAC) scores, while carotid plaques were evaluated by ultrasound. The associations were analysed using multinomial logistic regression, adjusted (marginal) prevalences and restricted cubic splines.

Results

The analysis included 8986 male adolescents (mean age 18.3 years) with a mean follow-up of 38.2 years. Physical fitness showed a reversed J-shaped association with CCTA stenosis and CAC, but no consistent association was observed for carotid plaques. After adjustments, compared with adolescents in the lowest tertile of cardiorespiratory fitness and muscular strength, those in the highest tertile had 22% (OR 0.78; 95% CI 0.61 to 0.99) and 26% (OR 0.74; 95% CI 0.58 to 0.93) lower ORs for severe (≥50%) coronary stenosis, respectively. The highest physical fitness group (high cardiorespiratory fitness and muscular strength) had 33% (OR 0.67; 95% CI 0.52 to 0.87) lower OR for severe coronary stenosis compared with those with the lowest physical fitness.

Conclusion

This study supports that a combination of high cardiorespiratory fitness and high muscular strength in adolescence is associated with lower coronary atherosclerosis, particularly severe coronary stenosis, almost 40 years later.
Which elements of hospital-based clinical decision support tools for the assessment and management of children with head injury can be adapted for use by paramedics in prehospital care? A systematic mapping review and narrative synthesis
Authors: Proctor Alyesha , Lyttle Mark , Billing Jedd , Shaw Pauline , Simpson Julian , Voss Sarah , Benger Jonathan Richard
Published: February 2024

Objective

Hospital-based clinical decision tools support clinician decision-making when a child presents to the emergency department with a head injury, particularly regarding CT scanning. However, there is no decision tool to support prehospital clinicians in deciding which head-injured children can safely remain at scene. This study aims to identify clinical decision tools, or constituent elements, which may be adapted for use in prehospital care.

Design

Systematic mapping review and narrative synthesis.

Data sources

Searches were conducted using MEDLINE, EMBASE, PsycINFO, CINAHL and AMED.

Eligibility criteria

Quantitative, qualitative, mixed-methods or systematic review research that included a clinical decision support tool for assessing and managing children with head injury.

Data extraction and synthesis

We systematically identified all in-hospital clinical decision support tools and extracted from these the clinical criteria used in decision-making. We complemented this with a narrative synthesis.

Results

Following de-duplication, 887 articles were identified. After screening titles and abstracts, 710 articles were excluded, leaving 177 full-text articles. Of these, 95 were excluded, yielding 82 studies. A further 14 studies were identified in the literature after cross-checking, totalling 96 analysed studies. 25 relevant in-hospital clinical decision tools were identified, encompassing 67 different clinical criteria, which were grouped into 18 categories.

Conclusion

Factors that should be considered for use in a clinical decision tool designed to support paramedics in the assessment and management of children with head injury are: signs of skull fracture; a large, boggy or non-frontal scalp haematoma neurological deficit; Glasgow Coma Score less than 15; prolonged or worsening headache; prolonged loss of consciousness; post-traumatic seizure; amnesia in older children; non-accidental injury; drug or alcohol use; and less than 1 year old. Clinical criteria that require further investigation include mechanism of injury, clotting impairment/anticoagulation, vertigo, length of time of unconsciousness and number of vomits.
Mediation role of perceived social support between recurrence risk perception and health behaviour among patients with stroke in China: a cross-sectional study
Authors: Wang Xiaoxuan , Zhang Zhen-Xiang , Lin Bei-Lei , Jiang Hu , Wang Wenna , Mei Yong-Xia , Zhang Chunhui , Zhang Qiushi , Chen Su-Yan
Published: February 2024

Objectives

To examine whether patients who had a stroke with high recurrence risk perception would have healthier behaviour and to explore whether perceived social support would function as a mediator.

Design

A cross-sectional study.

Setting

The study was conducted in a public tertiary hospital in China.

Participants

A total of 254 patients with stroke were invited to participate, and 250 patients with stroke completed questionnaires validly.

Primary and secondary outcome measures

Questionnaires were administered offline to collect data, consisting of four parts: general demographics and scales related to recurrence risk perception, perceived social support, and health behaviour. A path analysis and correlation analysis were used to analyse the data.

Results

Out of 250 patients with stroke, 78.4% had moderately low health behaviour. The majority (70.8%) of these patients were elderly. High recurrence risk perception and high perceived social support were significantly associated with better health behaviour (all p<0.001). Perceived social support mediated the relationship between recurrence risk perception and health behaviour after controlling for age, gender, education and monthly income in the regression model (95% CI 0.263 to 0.460) and the effect value was 0.360. It was also confirmed that perceived social support had the highest mediation effect with a proportion of mediation up to 59.31%.

Conclusions

Recurrence risk perception and perceived social support were influential factors in promoting health behaviour. Moreover, the impact of recurrence risk perception on health behaviour was partially mediated by perceived social support. Therefore, to enhance the sustainability of health behaviour, it is crucial to inform patients with stroke about the risk of recurrence. Patients with more perception of recurrence risk can improve their recovery confidence and thus perceive more social support.
Multimodality magnetic resonance evaluating the effect of enhanced physical exercise on the growth rate, flow haemodynamics, aneurysm wall and ventricular-aortic coupling of patients with small abdominal aortic aneurysms (AAA MOVE trial): a study protocol for an open-label randomised controlled trial
Authors: Zeng Wen , Weng Chengxin , Yuan Ding , Wang Tiehao , Huang Bin , Zhao Jichun , Xia Chunchao , Li Zhenlin , Wang Jiarong
Published: February 2024

Introduction

The best lifestyle for small abdominal aortic aneurysms (sAAA) is essential for its conservative management. Physical exercise can improve the cardiopulmonary function of the patients, but it remains unclear which specific type of exercise is most beneficial for individuals with sAAA. The current study was designed to investigate the effect of physician-guided enhanced physical exercise programme on the aorto-cardiac haemodynamic environment, aneurysm sac wall, cardiac function and growth rate of sAAA by multimodality MRI.

Methods and analysis

AAA MOVE study is a prospective, parallel, equivalence, randomised controlled trial. Eligible individuals will be recruited if they are diagnosed with sAAA (focal dilation of abdominal aorta with maximum diameter <5 cm), without contraindication for MRI scanning, or severe heart failure, or uncontrolled arrhythmia. Participants will be randomly allocated to intervention group (physician-guided enhanced physical exercise programme: mainly aerobic training) and control group (standard clinical care) separately in a 1:1 ratio. The primary outcome is 12-month growth rate of sAAA. The first set of secondary outcomes involve multimodality MRI parameters covering flow haemodynamics, aortic wall inflammation and cardiac function. The other secondary outcome (safety end point) is a composite of exercise-related injury, aneurysm rupture and aneurysm intervention. Follow-up will be conducted at 6 and 12 months after intervention.

Ethics and dissemination

This study was approved by the Ethics Committee on Biomedical Research of West China Hospital (approval number: 2023-783) on 16 June 2023. Main findings from the trial will be disseminated through presentations at conferences, peer-reviewed publications and directly pushed to smartphone of participants.

Trial registration number

ChiCTR2300073334.
Patient symptoms, self-management, and unscheduled healthcare use during the first 6 months of targeted oral anticancer agent therapy: protocol for a mixed-methods US study
Authors: Rizvi-Toner Amna , Coe Antoinette B , Friese Christopher R , Manojlovich Milisa , Wallner Lauren , Farris Karen B
Published: February 2024

Introduction

Targeted oral anticancer agents (OAAs) are increasingly used to treat cancer, including haematological malignancies and ovarian cancer, but they can cause serious symptomatic side effects such as arrhythmias, hypertension, and hyperglycaemia. Unaddressed OAA symptoms or inadequately managed symptoms may also lead to unnecessary and unscheduled healthcare use that decreases patient quality of life and financially burdens both patients and the healthcare system. Limited information is available about patient symptoms, self-management behaviours, and use of healthcare services over time while taking targeted OAAs, but is needed to ensure successful OAA therapy. The primary objective is to understand patient experiences and behaviours on initiating targeted OAA, and elicit cancer care clinicians’ (ie, physicians, advanced practice practitioners, nurses, and pharmacists) perspectives on supporting patients during therapy. Study results will inform comprehensive and realistic interventions that minimise disruptions to therapy while maximising quality of life.

Methods and analysis

We will conduct a remote single-arm, convergent-parallel mixed-methods cohort study within a large academic medical centre. A minimum of 60 patients will be enrolled. Patients will complete several validated patient-reported outcome measures at six timepoints over 6 months. Mixed-effects logistic regression will be used to predict the primary binary outcome of unscheduled healthcare use by patient self-efficacy for symptom self-management. Semistructured interviews will be conducted with patients and clinicians and thematically analysed. Triangulated quantitative and qualitative results will be reported using cross-case comparison joint display.

Ethics and dissemination

This study protocol is approved by the Institutional Review Board of University of Michigan Medical School (IRBMED). Study results will be published in peer-reviewed journals, presented at conferences, and disseminated to study participants.