bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanoparticle-based inhibition of vascular endothelial growth factor receptors alleviates osteoarthritis pain and cartilage damage
Authors: Ma Kaige , Pham Tiep , Wang Jun , O-Sullivan InSug , DiCamillo Amy , Du Shiyu , Mwale Fackson , Farooqui Zeba , Votta-Velis Gina , Bruce Benjamin , van Wijnen Andre J. , Liu Ying , Im Hee-Jeong
Published: February 2024

Osteoarthritis (OA) is characterized by cartilage damage, inflammation, and pain. Vascular endothelial growth factor receptors (VEGFRs) have been associated with OA severity, suggesting that inhibitors targeting these receptors alleviate pain (via VEGFR1) or cartilage degeneration (via VEGFR2). We have developed a nanoparticle-based formulation of pazopanib (Votrient), an FDA-approved anticancer drug that targets both VEGFR1 and VEGFR2 (Nano-PAZII). We demonstrate that a single intraarticular injection of Nano-PAZII can effectively reduce joint pain for a prolonged time without substantial side effects in two different preclinical OA rodent models involving either surgical (upon partial medial meniscectomy) or nonsurgical induction (with monoiodoacetate). The injection of Nano-PAZII blocks VEGFR1 and relieves OA pain by suppressing sensory neuronal ingrowth into the knee synovium and neuronal plasticity in the dorsal root ganglia and spinal cord. Simultaneously, the inhibition of VEGFR2 reduces cartilage degeneration. These findings provide a mechanism-based disease-modifying drug strategy that addresses both pain symptoms and cartilage loss in OA.
Facet-dependent dispersion and aggregation of aqueous hematite nanoparticles
Authors: Zhou Jianbin , Song Duo , Mergelsberg Sebastian T. , Wang Yining , Adhikari Narendra M. , Lahiri Nabajit , Zhao Yatong , Chen Ping , Wang Zheming , Zhang Xin , Rosso Kevin M.
Published: February 2024

Nanoparticle aggregates in solution controls surface reactivity and function. Complete dispersion often requires additive sorbents to impart a net repulsive interaction between particles. Facet engineering of nanocrystals offers an alternative approach to produce monodisperse suspensions simply based on facet-specific interaction with solvent molecules. Here, we measure the dispersion/aggregation of three morphologies of hematite (α-Fe
2
O
3
) nanoparticles in varied aqueous solutions using ex situ electron microscopy and in situ small-angle x-ray scattering. We demonstrate a unique tendency of (104) hematite nanoparticles to maintain a monodisperse state across a wide range of solution conditions not observed with (001)- and (116)-dominated particles. Density functional theory calculations reveal an inert, densely hydrogen-bonded first water layer on the (104) facet that favors interparticle dispersion. Results validate the notion that nanoparticle dispersions can be controlled through morphology for specific solvents, which may help in the development of various nanoparticle applications that rely on their interfacial area to be highly accessible in stable suspensions.
Unveiling the role of climate in spatially synchronized locust outbreak risks
Authors: Liu Xinyue , Zhang Dongxiao , He Xiaogang
Published: February 2024

Desert locusts threaten crop production and food security. Spatially synchronized locust outbreaks further exacerbate these crises. Continental-scale understanding of such compound locust risks and underlying climatic drivers is crucial to designing coordinated and predictive control strategies but remains elusive. Here, we develop a data-driven framework to assess the compound risk of locust outbreaks in the Middle East and North Africa (MENA) and elucidate the role of climate in locust dynamics. We find that more than one-fifth of high-risk country pairs faced spatially synchronized locust risks from 1985 to 2020, dominated by concurrent winds or inundations. Individual locusts are more prone to infest arid areas punched by extreme rainfall. The spatial prevalence of locusts is strongly modulated by climate variability such as El Niño–Southern Oscillation. A warming climate will lead to widespread increases in locust outbreaks with emerging hotspots in west central Asia, posing additional challenges to the global coordination of locust control.
Uncovering receptor-ligand interactions using a high-avidity CRISPR activation screening platform
Authors: Yang Liping , Sheets Timothy P. , Feng Yang , Yu Guojun , Bajgain Pradip , Hsu Kuo-Sheng , So Daeho , Seaman Steven , Lee Jaewon , Lin Ling , Evans Christine N. , Guest Mary R. , Chari Raj , St. Croix Brad
Published: February 2024

The majority of clinically approved drugs target proteins that are secreted or cell surface bound. However, further advances in this area have been hindered by the challenging nature of receptor deorphanization, as there are still many secreted and cell-bound proteins with unknown binding partners. Here, we developed an advanced screening platform that combines CRISPR-CAS9 guide–mediated gene activation (CRISPRa) and high-avidity bead-based selection. The CRISPRa platform incorporates serial enrichment and flow cytometry–based monitoring, resulting in substantially improved screening sensitivity for well-known yet weak interactions of the checkpoint inhibitor family. Our approach has successfully revealed that siglec-4 exerts regulatory control over T cell activation through a low affinity trans-interaction with the costimulatory receptor 4-1BB. Our highly efficient screening platform holds great promise for identifying extracellular interactions of uncharacterized receptor-ligand partners, which is essential to develop next-generation therapeutics, including additional immune checkpoint inhibitors.
Making immotile sperm motile using high-frequency ultrasound
Authors: Vafaie Ali , Raveshi Mohammad Reza , Devendran Citsabehsan , Nosrati Reza , Neild Adrian
Published: February 2024

Sperm motility is a natural selection with a crucial role in both natural and assisted reproduction. Common methods for increasing sperm motility are by using chemicals that cause embryotoxicity, and the multistep washing requirements of these methods lead to sperm DNA damage. We propose a rapid and noninvasive mechanotherapy approach for increasing the motility of human sperm cells by using ultrasound operating at 800 mW and 40 MHz. Single-cell analysis of sperm cells, facilitated by droplet microfluidics, shows that exposure to ultrasound leads to up to 266% boost to motility parameters of relatively immotile sperm, and as a result, 72% of these immotile sperm are graded as progressive after exposure, with a swimming velocity greater than 5 micrometer per second. These promising results offer a rapid and noninvasive clinical method for improving the motility of sperm cells in the most challenging assisted reproduction cases to replace intracytoplasmic sperm injection (ICSI) with less invasive treatments and to improve assisted reproduction outcomes.
Dexterous helical magnetic robot for improved endovascular access
Authors: Dreyfus R. , Boehler Q. , Lyttle S. , Gruber P. , Lussi J. , Chautems C. , Gervasoni S. , Berberat J. , Seibold D. , Ochsenbein-Kölble N. , Reinehr M. , Weisskopf M. , Remonda L. , Nelson B. J.
Published: February 2024

Treating vascular diseases in the brain requires access to the affected region inside the body. This is usually accomplished through a minimally invasive technique that involves the use of long, thin devices, such as wires and tubes, that are manually maneuvered by a clinician within the bloodstream. By pushing, pulling, and twisting, these devices are navigated through the tortuous pathways of the blood vessels. The outcome of the procedure heavily relies on the clinician’s skill and the device’s ability to navigate to the affected target region in the bloodstream, which is often inhibited by tortuous blood vessels. Sharp turns require high flexibility, but this flexibility inhibits translation of proximal insertion to distal tip advancement. We present a highly dexterous, magnetically steered continuum robot that overcomes pushability limitations through rotation. A helical protrusion on the device’s surface engages with the vessel wall and translates rotation to forward motion at every point of contact. An articulating magnetic tip allows for active steerability, enabling navigation from the aortic arch to millimeter-sized arteries of the brain. The effectiveness of the magnetic continuum robot has been demonstrated through successful navigation in models of the human vasculature and in blood vessels of a live pig.
Decoration of
Burkholderia
Hcp1 protein to virus-like particles as a vaccine delivery platform
Authors: Khakhum Nittaya , Baruch-Torres Noe , Stockton Jacob L. , Chapartegui-González Itziar , Badten Alexander J. , Adam Awadalkareem , Wang Tian , Huerta-Saquero Alejandro , Yin Y. Whitney , Torres Alfredo G.
Published: February 2024

Virus-like particles (VLPs) are protein-based nanoparticles frequently used as carriers in conjugate vaccine platforms. VLPs have been used to display foreign antigens for vaccination and to deliver immunotherapy against diseases. Hemolysin-coregulated proteins 1 (Hcp1) is a protein component of the
Burkholderia
type 6 secretion system, which participates in intracellular invasion and dissemination. This protein has been reported as a protective antigen and is used in multiple vaccine candidates with various platforms against melioidosis, a severe infectious disease caused by the intracellular pathogen
Burkholderia pseudomallei
. In this study, we used P22 VLPs as a surface platform for decoration with Hcp1 using chemical conjugation. C57BL/6 mice were intranasally immunized with three doses of either PBS, VLPs, or conjugated Hcp1-VLPs. Immunization with Hcp1-VLPs formulation induced Hcp1-specific IgG, IgG
1
, IgG
2c
, and IgA antibody responses. Furthermore, the serum from Hcp1-VLPs immunized mice enhanced the bacterial uptake and opsonophagocytosis by macrophages in the presence of complement. This study demonstrated an alternative strategy to develop a VLPs-based vaccine platform against
Burkholderia
species.
Skin dysbiosis and loss of microbiome site specificity in critically ill patients
Authors: Klassert Tilman E. , Zubiria-Barrera Cristina , Denkel Luisa , Neubert Robert , Schneegans Antony , Kulle Aylina , Vester Antje , Bloos Frank , Schulze Christian , Epstude Jörg , Gastmeier Petra , Geffers Christine , Slevogt Hortense
Published: February 2024

An increasing amount of evidence has linked critical illness with dysbiotic microbiome signatures in different body sites. The disturbance of the indigenous microbiota structures has been further associated with disease severity and outcome and has been suggested to pose an additional risk for complications in intensive care units (ICUs), including hospital-acquired infections. A better understanding of the microbial dysbiosis in critical illness might thus help to develop strategies for the prevention of such complications. While most of the studies addressing microbiome changes in ICU patients have focused on the gut, the lung, or the oral cavity, little is known about the microbial communities on the skin of ICU patients. Since the skin is the outermost organ and the first immune barrier against pathogens, its microbiome might play an important role in the risk management for critically ill patients. This observational study characterizes the skin microbiome in ICU patients covering five different body sites at the time of admission. Our results show a profound dysbiosis on the skin of critically ill patients, which is characterized by a loss of site specificity and an overrepresentation of gut bacteria on all skin sites when compared to a healthy group. This study opens a new avenue for further investigations on the effect of skin dysbiosis in the ICU setting and points out the need of strategies for the management of dysbiosis in critically ill patients.

IMPORTANCE

Unbalanced gut microbiota in critically ill patients has been associated with poor outcome and complications during the intensive care unit (ICU) stay. Whether the disturbance of the microbial communities in these patients is extensive for other body sites, such as the skin, is largely unknown. The skin not only is the largest organ of the body but also serves as the first immune barrier against potential pathogens. This study characterized the skin microbiota on five different body sites in ICU patients at the time of admission. The observed disturbance of the bacterial communities might help to develop new strategies in the risk management of critically ill patients.
Lsr2, a pleiotropic regulator at the core of the infectious strategy of
Mycobacterium abscessus
Authors: Gerges Elias , Rodríguez-Ordoñez María del Pilar , Durand Nicolas , Herrmann Jean-Louis , Crémazy Frédéric
Published: February 2024

Mycobacterium abscessus
is a non-tuberculous mycobacterium, causing lung infections in cystic fibrosis patients. During pulmonary infection,
M. abscessus
switches from smooth (Mabs-S) to rough (Mabs-R) morphotypes, the latter being hyper-virulent. Previously, we isolated the
lsr2
gene as differentially expressed during S-to-R transition.
lsr2
encodes a pleiotropic transcription factor that falls under the superfamily of nucleoid-associated proteins. Here, we used two functional genomic methods, RNA-seq and chromatin immunoprecipitation-sequencing (ChIP-seq), to elucidate the molecular role of Lsr2 in the pathobiology of
M. abscessus
. Transcriptomic analysis shows that Lsr2 differentially regulates gene expression across both morphotypes, most of which are involved in several key cellular processes of
M. abscessus
, including host adaptation and antibiotic resistance. These results were confirmed through quantitative real-time PCR, as well as by minimum inhibitory concentration tests and infection tests on macrophages in the presence of antibiotics. ChIP-seq analysis revealed that Lsr2 extensively binds the
M. abscessus
genome at AT-rich sequences and appears to form long domains that participate in the repression of its target genes. Unexpectedly, the genomic distribution of Lsr2 revealed no distinctions between Mabs-S and Mabs-R, implying more intricate mechanisms at play for achieving target selectivity.

IMPORTANCE

Lsr2 is a crucial transcription factor and chromosome organizer involved in intracellular growth and virulence in the smooth and rough morphotypes of
Mycobacterium abscessus
. Using RNA-seq and chromatin immunoprecipitation-sequencing (ChIP-seq), we investigated the molecular role of Lsr2 in gene expression regulation along with its distribution on
M. abscessus
genome. Our study demonstrates the pleiotropic regulatory role of Lsr2, regulating the expression of many genes coordinating essential cellular and molecular processes in both morphotypes. In addition, we have elucidated the role of Lsr2 in antibiotic resistance both
in vitro
and
in vivo
, where
lsr2
mutant strains display heightened sensitivity to antibiotics. Through ChIP-seq, we reported the widespread distribution of Lsr2 on
M. abscessus
genome, revealing a direct repressive effect due to its extensive binding on promoters or coding sequences of its targets. This study unveils the significant regulatory role of Lsr2, intricately intertwined with its function in shaping the organization of the
M. abscessus
genome.
Genetic epidemiology and plasmid-mediated transmission of
mcr-1
by
Escherichia coli
ST155 from wastewater of long-term care facilities
Authors: Feng Jun , Pan Miao , Zhuang Yuan , Luo Jiayuan , Chen Yong , Wu Yitong , Fei Jiayi , Zhu Yanqi , Xu Zhen , Yuan Zhengan , Chen Min
Published: February 2024

Long-term care facilities (LTCFs) for older people play an important and unique role in multidrug-resistant organism transmission. Herein, we investigated the genetic characteristics of mobile colistin resistance gene (
mcr-1
)-carrying
Escherichia coli
strains isolated from wastewater of LTCFs in Shanghai. Antimicrobial susceptibility test was carried out by agar dilution methods. Whole-genome sequencing and plasmid sequencing were conducted, and resistance genes and sequence types of colistin in
E. coli
isolates were analyzed. Core genome multilocus sequence typing (cgMLST) analysis was performed by the Ridom SeqSphere+ software. Phylogenetic tree through the maximum likelihood method was constructed by MEGA X. Out of 306 isolates, only 1
E. coli
named ECSJ33 was found, and the plasmid pECSJ33 from ECSJ33 harbored the
mcr-1
gene that was located with 59,080 bp belonging to IncI2 type. The plasmid pECSJ33 was capable of conjugation with an efficiency of 2.9 × 10
−2
. Bioinformatic analysis indicated pECSJ33 shared backbone with the previously reported
mcr-1
-harboring pHNGDF93 isolated from fish source. Moreover, the cgMLST analysis revealed that ECSJ33 belongs to different lineages from those reported from previous
E. coli
strains but shared high similarity to NCTC11129 in cluster 11. The phylogenetic tree revealed MCR-1 of ECSJ33 in this study was mostly of animal food origin and that they were closely related. Our study firstly reports detection of genome sequence of a multidrug-resistant
mcr-1
-harboring
E. coli
ST155 from wastewater of LTCF source in China. The data may prove that the plasmid pECSJ33 belongs to food origin and help to understand the antimicrobial resistance mechanisms and genomic features of colistin resistance under One Health approach.

IMPORTANCE

One
Escherichia coli
named ECSJ33 was found from wastewater of a long-term care facility (LTCF) and the plasmid pECSJ33 from ECSJ33 harbored the mobile colistin resistance gene (
mcr-1
) that was located with 59,080 bp belonging to IncI2 type, which was capable of conjugation with an efficiency of 2.9 × 10
-2
. This paper firstly reports an
mcr-1
-carrying
E. coli
strain ST155 isolated from LTCF in China. Comparative genomics analysis indicated pECSJ33 shared backbone with the previously reported
mcr-1
-harboring pHNGDF93 isolated from fish source. The phylogenetic tree revealed MCR-1 protein of ECSJ33 in this study was mostly of animal food origin and that they were closely related. Therefore, the pECSJ33 could be considered as food-origin transmission
mcr-1
-harboring plasmid.
Submarine hydrothermal fluids facilitated the accumulation of cadmium in Lower Cambrian black shales, South China
Authors: Zhou Zhengbing , Wen Hanjie , Zhu Yu , Yang Yang
Published: February 2024

The effects of Cd-rich venting fluids on the Cd contents and isotopic compositions of continental margin sediments remain poorly understood. Characterization of the Cd isotopic composition of sediment overprinted by venting fluids is critical, as this may provide insights into how mixing between the venting fluids and bottom waters affects the Cd isotopic composition. Our study determined the Cd isotopic compositions of Lower Cambrian metalliferous sediment deposited on the passive continental margin of the southeastern Yangtze Block, South China. The Cd is predominantly hosted in sphalerite of sulfide-bearing barite sediments, V deposits, and Ni-Mo–platinum group element (PGE) sulfide layers. The Cd isotopic compositions of samples from these three units indicate that the distribution of Cd at this type of continental margin was controlled by submarine hydrothermal activity. Following the venting of hydrothermal fluids onto the seafloor, Cd2+ reacted with a limited amount of H2S generated mainly by thermochemical sulfate reduction near the vents. This resulted in isotopically lighter Cd in the sulfide-bearing barite sediments and V deposits, which have δ114/110Cd values of 0.00‰ ± 0.13‰ and 0.00‰ ± 0.14‰, respectively. The residual dissolved Cd in the fluids migrated with the upwelling seawater and ultimately precipitated almost entirely as sphalerite in the sulfidic wedge, which resulted in Ni-Mo–PGE sulfide layers with a narrow range of high δ114/110Cd values (0.35‰ ± 0.03‰). The presence of Cd-rich venting fluids can alter the Cd contents and isotopic compositions of passive margin sediments, particularly those located within long-term stratified seawater and fault depressions. Previous studies may have underestimated the migration distance and affected areas of hydrothermal activity involving Cd-rich fluids.
Hydrologically driven modulation of cutoff regime in meandering rivers
Authors: Maitan Riccardo , Finotello Alvise , Tognin Davide , D'Alpaos Andrea , Fielding Christopher R. , Ielpi Alessandro , Ghinassi Massimiliano
Published: February 2024

Bend cutoff is a fundamental process shaping meandering rivers. Despite the widely accepted differentiation between neck and chute cutoffs, a significant knowledge gap persists regarding the factors responsible for the occurrence of each cutoff regime and the specific conditions triggering the regime. Here, we used field and photogrammetric data derived from a global set of 22 meandering rivers, stretching more than 5500 km in total river length, to disentangle the controlling factors behind the cutoff regime in meandering rivers. We found that whether a meandering river forms a chute rather than neck meander cutoff depends primarily on the variability of overbank discharges. Short-lived, high-magnitude overbank floods promote the formation of chute cutoffs, aided by (though not required) reduced riparian vegetation density, enhanced stream power, and flow confinement within the river valley. In contrast, neck cutoffs are prevalent in rivers characterized by limited variations in bankfull hydrology, typically associated with low-magnitude, long-lasting overbank floods. Distinct cutoff regimes also discernibly affected floodplain geomorphology, with a chute regime resulting in more frequent cutoff occurrences. Our results suggest that human-induced alterations of river hydrologic regime can potentially cause fundamental shifts in the cutoff behavior of meandering rivers, thus affecting sediment residence time and carbon fluxes in alluvial floodplains.
Supplemental Material: Summer warming during Heinrich Stadial 1 in Northeast China
Authors: Zhu Zeyang , al. et
Published: February 2024

The details about brGDGT-based proxy and Kielguo crater lake; chronological data; the comparison of different calibrations and different seasonal temperatures; and the comparison of TraCE-21ka results among different regions and different single-forcing. Texts S1–S3; Tables S1–S2; and Figures S1–S8.  
Photoinitiated by Red Light (λ 625 nm) Iodosulfonylation of Internal Alkynes to Synthesize β-Iodovinyl Sulfones
Authors: Abramov V. A. , Topchiy M. A. , Malysheva A. S. , Beletskaya I. P. , Asachenko A. F.
Published: February 2024

A number of β-iodovinyl sulfones were synthesized by direct difunctionalization of internal alkynes with arenesulfonyl iodides under irradiation with red light (λmax 625 nm) generated by an economical LED source. The products were obtained in high yields (68–99%) from equimolar amounts of the reactants. The reaction of sulfonyl iodides with internal alkynes follows a radical mechanism and provides a regioselective method of synthesis of β-iodovinyl sulfones.
Rare cause of jaundice in a term newborn
Authors: Costa Inês Silva , Vala Beatriz , Costa Sofia , Henriques Raquel
Published: February 2024

Neonatal jaundice is a frequently observed occurrence in full-term newborns and typically manifests between 48 and 96 hours following birth. Early-onset jaundice is primarily induced by pathological factors, namely sepsis, hemolysis and an excessive accumulation of bilirubin resulting from the breakdown of red blood cells.

We present a case involving a full-term newborn with an uneventful perinatal history, who exhibited jaundice within the initial day of life and was subsequently admitted to the neonatal intensive care unit to commence intensive phototherapy. Initial screenings for sepsis and blood group incompatibility yielded negative results. However, despite 6 hours of phototherapy, the bilirubin levels did not decrease, prompting an investigation into central nervous system haemorrhage, which uncovered the presence of a haemorrhagic stroke.

After a worsening in neurological status with neonatal crisis and need for phenobarbital, a life-saving craniotomy was performed. Clinical evolution was good with no additional crisis detected after the early neonatal period and improvement in motor function at 2-month-old follow-up.
Rapid reviews methods series: guidance on rapid qualitative evidence synthesis
Authors: Booth Andrew , Sommer Isolde , Noyes Jane , Houghton Catherine , Campbell Fiona
Published: February 2024

This paper forms part of a series of methodological guidance from the Cochrane Rapid Reviews Methods Group and addresses rapid qualitative evidence syntheses (QESs), which use modified systematic, transparent and reproducible methodsu to accelerate the synthesis of qualitative evidence when faced with resource constraints. This guidance covers the review process as it relates to synthesis of qualitative research. ‘Rapid’ or ‘resource-constrained’ QES require use of templates and targeted knowledge user involvement. Clear definition of perspectives and decisions on indirect evidence, sampling and use of existing QES help in targeting eligibility criteria. Involvement of an information specialist, especially in prioritising databases, targeting grey literature and planning supplemental searches, can prove invaluable. Use of templates and frameworks in study selection and data extraction can be accompanied by quality assurance procedures targeting areas of likely weakness. Current Cochrane guidance informs selection of tools for quality assessment and of synthesis method. Thematic and framework synthesis facilitate efficient synthesis of large numbers of studies or plentiful data. Finally, judicious use of Grading of Recommendations Assessment, Development and Evaluation approach for assessing the Confidence of Evidence from Reviews of Qualitative research assessments and of software as appropriate help to achieve a timely and useful review product.
Immigrant women’s and families’ views and experiences of routine postnatal care: findings from a qualitative evidence synthesis
Authors: Sacks Emma , Brizuela Vanessa , Javadi Dena , Kim Yoona , Elmi Nika , Finlayson Kenneth , Crossland Nicola , Langlois Etienne V , Ziegler Daniela , Parmar Seema Menon , Bonet Mercedes
Published: February 2024

Background

Uptake of postnatal care (PNC) is low and inequitable in many countries, and immigrant women may experience additional challenges to access and effective use. As part of a larger study examining the views of women, partners, and families on routine PNC, we analysed a subset of data on the specific experiences of immigrant women and families.

Methods

This is a subanalysis of a larger qualitative evidence synthesis. We searched MEDLINE, PUBMED, CINAHL, EMBASE, EBM-Reviews and grey literature for studies published until December 2019 with extractable qualitative data with no language restrictions. For this analysis, we focused on papers related to immigrant women and families. Two reviewers screened each study independently; inclusion was agreed by consensus. Data abstraction and quality assessment were carried out using a study-specific extraction form and established quality assessment tools. Study findings were identified using thematic analysis. Findings are presented by confidence in the finding, applying the GRADE-CERQual approach.

Findings

We included 44 papers, out of 602 full-texts, representing 11 countries where women and families sought PNC after immigrating. All but one included immigrants to high-income countries. Four themes were identified: resources and access, differences from home country, support needs, and experiences of care. High confidence study findings included: language and communication challenges; uncertainty about navigating system supports including transportation; high mental health, emotional, and informational needs; the impact of personal resources and social support; and the quality of interaction with healthcare providers. These findings highlight the importance of care experiences beyond clinical care. More research is also needed on the experiences of families migrating between low-income countries.

Conclusions

Immigrant families experience many challenges in getting routine PNC, especially related to language, culture, and communication. Some challenges may be mitigated by improving comprehensive and accessible information on available services, as well as holistic social support.

Trial registration number

CRD42019139183.
Sialidosis type 1 without cherry-red spots: a case report and literature review
Authors: Zhang Congcong , Liao Zhongkai , Zhou Yanhui , Su Xiaohui
Published: February 2024

Background

Sialidosis is a rare disorder caused by mutations in the NEU1 gene located on chromosome 6p21.3, constituting a group of autosomal recessive diseases. Enzyme activity analysis, electron microscopy examination and genetic testing are reliable methods for diagnosis. Despite previous reports on the disease, its rarity means that its clinical manifestations and prognosis still warrant attention due to the limited amount of information available.

Methods

We report a case of a 40-year-old woman who was admitted to our hospital for worsening dysarthria of 16 years duration and facial and limb twitching that had been present for 2 years. Genetic testing was undertaken.

Results

Genetic testing confirmed type I sialidosis, the first reported instance of this disease in the Hainan Free Trade Port in China. The patient did not have the typical cherry-red spot in the fundus. Despite aggressive treatment, she died of status epilepticus 2 months later. This result indicates that the disease has a poor prognosis.

Discussion

Cherry-red spots in the fundus are characteristic features of type I sialidosis and it has been referred to as the cherry-red spot myoclonus syndrome. We hypothesise that environmental factors may also play a significant role. Overemphasis on the presence of cherry-red spots may mislead clinicians and delay diagnosis. Furthermore, patients presenting with isolated myoclonus should undergo visual evoked potential and somatosensory evoked potential tests, as well as genetic testing to confirm or rule out sialidosis.
Incidence and prevalence of mtDNA-related adult mitochondrial disease in Southwest Finland, 2009–2022: an observational, population-based study
Authors: Martikainen Mika H , Majamaa Kari
Published: February 2024

Background

Mitochondrial diseases are common inherited metabolic disorders. Due to improved case ascertainment and diagnosis methods, the detection of new diagnoses of mitochondrial disease can be expected to increase. In December 2009, the prevalence of mitochondrial DNA (mtDNA)-related mitochondrial disease was 4.6/100 000 (95% CI, 2.7 to 7.2) in the adult population of Southwest Finland. We investigated the number of new diagnoses and the incidence of mitochondrial disease in Southwest Finland between December 2009 and December 2022.

Methods

We collected data on all adult patients from Southwest Finland diagnosed with mitochondrial disease on 31 December 2009 and 31 December 2022. Most patients had been diagnosed at the Turku University Hospital (TUH) neurology outpatient clinic. Patients were also identified by searching the TUH electronic patient database for relevant International Classification of Diseases, Tenth Revision codes and conducted mtDNA analyses.

Results

42 new patients were diagnosed giving a mean annual rate of 3.2 new diagnoses. In 2022, the minimum prevalence estimate of adult mtDNA-related mitochondrial disease was 9.2/100 000 (95% CI, 6.5 to 12.7). The prevalence of adult mtDNA disease associated with m.3243A>G was 4.2/100 000 (95% CI, 2.5 to 6.7), and that with large-scale mtDNA deletions was 1.3/100 000 (95% CI, 0.4 to 2.9). During the 13-year period, the annual incidence of adult mtDNA disease was 0.6/100 000 and that of adult m.3243A>G-related disease 0.3/100 000.

Conclusion

Our results suggest that improved means of diagnostics and dedicated effort increase the detection of mitochondrial disease.
Integrating artificial intelligence into lung cancer screening: a randomised controlled trial protocol
Authors: Benzaquen Jonathan , Hofman Paul , Lopez Stephanie , Leroy Sylvie , Rouis Nesrine , Padovani Bernard , Fontas Eric , Marquette Charles Hugo , Boutros Jacques
Published: February 2024

Introduction

Lung cancer (LC) is the most common cause of cancer-related deaths worldwide. Its early detection can be achieved with a CT scan. Two large randomised trials proved the efficacy of low-dose CT (LDCT)-based lung cancer screening (LCS) in high-risk populations. The decrease in specific mortality is 20%–25%.

Nonetheless, implementing LCS on a large scale faces obstacles due to the low number of thoracic radiologists and CT scans available for the eligible population and the high frequency of false-positive screening results and the long period of indeterminacy of nodules that can reach up to 24 months, which is a source of prolonged anxiety and multiple costly examinations with possible side effects.

Deep learning, an artificial intelligence solution has shown promising results in retrospective trials detecting lung nodules and characterising them. However, until now no prospective studies have demonstrated their importance in a real-life setting.

Methods and analysis

This open-label randomised controlled study focuses on LCS for patients aged 50–80 years, who smoked more than 20 pack-years, whether active or quit smoking less than 15 years ago. Its objective is to determine whether assisting a multidisciplinary team (MDT) with a 3D convolutional network-based analysis of screening chest CT scans accelerates the definitive classification of nodules into malignant or benign. 2722 patients will be included with the aim to demonstrate a 3-month reduction in the delay between lung nodule detection and its definitive classification into benign or malignant.

Ethics and dissemination

The sponsor of this study is the University Hospital of Nice. The study was approved for France by the ethical committee CPP (Comités de Protection des Personnes) Sud-Ouest et outre-mer III (No. 2022-A01543-40) and the Agence Nationale du Medicament et des produits de Santé (Ministry of Health) in December 2023. The findings of the trial will be disseminated through peer-reviewed journals and national and international conference presentations.

Trial registration number

NCT05704920.
Understanding Australian general practice patients’ decisions to deprescribe antidepressants in the WiserAD trial: a realist informed approach
Authors: Coe Amy , Gunn Jane , Allnutt Zoe , Kaylor-Hughes Catherine
Published: February 2024

Objectives

To evaluate how an approach to antidepressant deprescribing works, for whom, and in what contexts by (1) examining the experiences and perceptions of the approach for antidepressant users, (2) identifying the mechanisms of the approach and (3) describing what contexts are associated with antidepressant tapering.

Design

This mixed methods study was informed by the principles of realist evaluation and was conducted in the first 3 months of participation in the WiserAD randomised control trial.

Setting

General practice, Victoria, Australia.

Participants

13 antidepressant users from general practice participating in the WiserAD trial for antidepressant deprescribing.

Intervention

A patient-facing, web-based structured support tool that consists of a personalised tapering schedule, an action plan for managing withdrawal symptoms, a daily mood, sleep and activity tracker and mental health nurse support.

Primary/secondary outcome measures

The outcomes of the study were revealed on data analysis as per a realist evaluation approach which tests and refines an initial programme theory.

Results

The contexts of learnt coping skills, knowledge and perceptions of antidepressants and feeling well were evident. Outcomes were intention to commence, initiation of deprescribing and successful completion of deprescribing. Key mechanisms for antidepressant deprescribing were (1) initiation of the deprescribing discussion; (2) patient self-efficacy; (3) provision of structured guidance; (4) coaching; (5) mood, sleep and activity tracking and (6) feelings of safety during the tapering period.

Conclusions

The WiserAD approach to antidepressant deprescribing supported participants to commence and/or complete tapering. The refined programme theory presents the WiserAD pragmatic framework for the application of antidepressant deprescribing in clinical practice.

Trial registration number

ClinicalTrials.govNCT05355025; ACTRN12622000567729;ISRCTN11562922; Pre-results.
Social media and postsecondary student adoption of mental health labels: protocol for a scoping review
Authors: Alexander Ethan Dylan , Chung Van-Han-Alex , Yacovelli Alexandra , Sarmiento Ivan , Andersson Neil
Published: February 2024

Introduction

Many postsecondary students use social media at an age when mental health issues often arise for the first time. On social media, students describe their mental states or social interactions using psychiatric language. This is a process of mental health labelling as opposed to receiving a formal diagnosis from a psychiatrist. Despite substantial literature on psychiatric labelling effects such as stigma, little research has addressed the mechanisms and effects of labelling through social media. Our objective is to summarise the existing evidence to address this gap.

Methods and analysis

This review includes articles in English published since 1995 on how postsecondary students interact with mental health labels in their use of social media. We will consider empirical studies and theses. The search strategy includes SCOPUS, PubMed, OVID MEDLINE (to access APA PsycINFO), Web of Science and ProQuest Global Dissertations and Theses. This scoping review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extensions for protocols and Scoping Reviews guidelines. The artificial intelligence application, Connected Papers, will assist in identifying additional references. The outcomes of interest are labelling by self or others and changes in self-concept and presentation associated with these labels. Two researchers will independently identify the included studies and extract data, solving disagreements with a third opinion. We will produce tables and narrative descriptions of the operationalisation and measurement methods of labelling and social media use, reported effects and uses of labelling, and explanatory mechanisms for the adoption of labels.

Ethics and dissemination

This literature review does not require ethics approval. The researchers will present their findings for publication in an open-access peer-reviewed journal and at student/scientific conferences. Potential knowledge users include university students, social media users, researchers, mental health professionals and on-campus mental health services.
Changing the liver transplant assessment process from inpatient to a day-case and outpatient approach to reduce inpatient bed utlisation
Authors: Robinson Smith Peter , Richardson Annette , Macdougall Louise , Cross Ellice , Davison Siobhan , Knowles Vanessa
Published: February 2024

The liver transplant assessment process involves a complex set of tests and clinical reviews to determine suitability for liver transplantation. We had an assessment process involving a 3-day inpatient stay and often experienced difficulties admitting patients to the prebooked bed due to a lack of inpatient bed availability.

We aimed to change the process from a 3-day and 2-night inpatient stay to a 1-day day-case stay to reduce the demand for inpatient beds.

Planning the new assessment process involved negotiations with many department staff to establish prebooked timeslots in 1 day. The improvement project was tested and refined through Plan-Do-Study-Act cycles. The liver transplant assessment team used their established once-a-week meeting to learn what went well and to agree on revisions to the process for further testing. The process involved several adaptations, such as the removal and changing of individual time slots, reinforcement of early notification once patients had finished their tests and scheduling a separate outpatient appointment to provide time for junior doctor clerking and blood tests.

The new day-case and outpatient coordinated liver transplant assessment process resulted in a reduction of inpatient hospital bed utilisation from an average of 257–20 inpatient bed days per annum. This reduction in inpatient bed utilisation was maintained for 3 years with a similar level of patient satisfaction. The cost avoidance was calculated at £381.96 per patient, which is a 63% reduction in cost. Assuming an average number of patients being assessed per annum of 110, this would result in an average cost avoidance of £42 016 per annum. The carbon footprint was calculated with an average reduction per patient from 618 kilograms of carbon dioxide equivalent (kgCO2e) to 179 kgCO2e.

This project has highlighted how to change a complex inpatient assessment process to an alternative day-case and outpatient approach and could be considered useful learning for other inpatient assessment services, not just liver transplantation.
Neurological conditions and subsequent divorce risk in the Nordic countries: the importance of gender and both spouses’ education
Authors: Metsä-Simola Niina , Heggebø Kristian , Kjaer Urhoj Stine , Martikainen Pekka , Einiö Elina , Östergren Olof
Published: February 2024

Background

Prior studies suggest that poor physical health, accompanied by functional disability, is associated with increased divorce risk. However, this association may depend on gender, the socioeconomic resources of the couple, as well as the social policy and social (in)equality context in which the illness is experienced. This study focuses on neurological conditions, which often have substantial functional consequences.

Methods

We used longitudinal population-wide register data from the years 2007–2016 (Denmark, Sweden) or 2008–2017 (Finland, Norway) to follow 2 809 209 married couples aged 30–64 for neurological conditions, identified using information on specialised healthcare for diseases of the nervous system and subsequent divorce. Cox regression models were estimated in each country, and meta-analysis used to calculate across-country estimates.

Results

During the 10-year follow-up period, 22.2% of couples experienced neurological conditions and 12.0% of marriages ended in divorce. In all countries, divorce risk was elevated among couples where at least one spouse had a neurological condition, and especially so if both spouses were ill. The divorce risk was either larger or similar for husband’s illness, compared with wife’s illness, in all educational categories. For the countries pooled, the weighted average HR was 1.21 (95% CI 1.20 to 1.23) for wives’ illness, 1.27 (95% CI 1.25 to 1.29) for husbands’ illness and 1.38 (95% CI 1.34 to 1.42) for couples where both spouses were ill.

Conclusions

Despite some variation by educational resources and country context, the results suggest that the social consequences of illness are noticeable even in Nordic welfare states, with the husband’s illness being at least as important as the wife’s.
Targeting oxidative phosphorylation to increase the efficacy of immune-combination therapy in renal cell carcinoma
Authors: Tian Jihua , Luo Jing , Zeng Xing , Ke Chunjin , Wang Yanan , Liu Zhenghao , Li Le , Zhang Yangjun , Hu Zhiquan , Yang Chunguang
Published: February 2024

Background

Immune checkpoint inhibitors (ICIs) are the standard of care for metastatic renal cell carcinoma (RCC); however, most patients develop de novo or acquired resistance to ICIs. Oxidative phosphorylation (OXPHOS) has been rarely explored as a potential target for correcting ICI resistance.

Methods

We systematically analyzed RNA sequencing and clinical data from CheckMate, JAVELIN Renal 101, andNCT01358721clinical trials, and clinicopathological data of 25 patients from Tongji Hospital to investigate the relationship between OXPHOS and ICI resistance. TheNdufb8-knockdown Renca cell line was derived to determine the effect of OXPHOS on RCC immunotherapy in vivo.

Results

An analysis of the CheckMate series data revealed that high OXPHOS levels are risk factors for ICI in patients with RCC, but are affected by thevon Hippel-Lindau protein (VHL) and hypoxia-inducible factor-1α status. This result is consistent with correlation between clinicopathological characteristics and prognostic observations at our institute. Knockdown of the mitochondrial complex I subunitNdufb8of the Renca cell line had no effect on cell growth and migration in vitro, but slowed down cell growth in vivo. Among anti-programmed death ligand 1 (PD-L1)-treated BALB/c mice, shNdufb8Renca tumors grew slower than shControl Renca tumors and the corresponding mice survived longer. Flow cytometry revealed that CD8+T cells in shNdufb8Renca tumors, which were exposed to a lower degree of hypoxia and expressed less programmed death-1 (PD-1) and T-cell immunoglobulin domain and mucin domain 3 (TIM-3), secreted more interferon-γ after stimulation. Immunofluorescence demonstrated that the shNdufb8Renca tumors had a higher proportion of CD8+T cells and the proportion of these cells was lower in the hypoxic area.

Conclusions

OXPHOS is a reliable predictor of immunotherapy response in RCC and is more pronounced in metastatic lesions. RCC cells generate a hypoxic tumor microenvironment and inhibit T-cell function through oxidative metabolism, thereby leading to immunotherapy resistance.
Add-on sirolimus for the treatment of mild or moderate systemic lupus erythematosus via T lymphocyte subsets balance
Authors: Ding Meng , Jin Lu , Zhao Jinwen , Yang Lin , Cui Shaoxin , Wang Xiaoping , He Jingjing , Chang Fei , Shi Min , Ma Jun , Song Shuran , Jin Hongtao , Liu Aijing
Published: February 2024

Objective

The efficacy of sirolimus in treating severe or refractory systemic lupus erythematosus (SLE) has been confirmed by small-scale clinical trials. However, few studies focused on mild or moderate SLE. Therefore, in this study we elucidated clinical efficacy of add-on sirolimus in patients with mild or moderate SLE.

Methods

Data of 17 consecutive patients with SLE were retrospectively collected. SLE Disease Activity Index-2000 (SLEDAI-2K), clinical manifestation, laboratory data and peripheral T lymphocyte subsets with cytokines were collected before and 6 months after sirolimus add-on treatment. T cell subsets were detected by flow cytometry and cytokines were determined by multiplex bead-based flow fluorescent immunoassay simultaneously. Twenty healthy controls matched with age and sex were also included in our study.

Results

(1) The numbers of peripheral blood lymphocytes, T cells, T helper (Th) cells, regulatory T (Treg) cells, Th1 cells, Th2 cells and Treg/Th17 ratios in patients with SLE were significantly lower, while the numbers of Th17 cells were evidently higher than those of healthy control (p<0.05). (2) After 6 months of sirolimus add-on treatment, urinary protein, pancytopenia, immunological indicators and SLEDAI-2K in patients with SLE were distinctively improved compared with those before sirolimus treatment (p<0.05). (3) The numbers of peripheral blood lymphocytes, T cells, Th cells, Treg cells, Th2 cells and the ratios of Treg/Th17 in patients with SLE after treatment were clearly higher than those before (p<0.05). (4) The levels of plasma interleukin (IL)-5, IL-6 and IL-10 in patients with SLE decreased notably, conversely the IL-4 levels increased remarkably compared with pretreatment (p<0.05).

Conclusions

(1) Patients with SLE presented imbalanced T cell subsets, especially the decreased ratio of Treg/Th17. (2) Sirolimus add-on treatment ameliorated clinical involvement, serological abnormalities and disease activity without adverse reactions in patients with SLE. (3) The multi-target therapy facilitates the enhanced numbers of Treg cells, Treg/Th17 imbalance and anti-inflammatory cytokines, simultaneously, reducing inflammatory cytokines.