bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery of a Long Half-Life AURKA Inhibitor to Treat MYC-Amplified Solid Tumors as a Monotherapy and in Combination with Everolimus
Authors: Chang Chun-Ping , Yeh Teng-Kuang , Chen Chiung-Tong , Wang Wan-Ping , Chen Yen-Ting , Tsai Chia-Hua , Chen Yan-Fu , Ke Yi-Yu , Wang Jing-Ya , Chen Ching-Ping , Hsieh Tsung-Chih , Wu Mine-Hsine , Huang Chen-Lung , Chen Ya-Ping , Zhuang Hong , Chi Ya-Hui
Published: April 2024

Aurora kinase inhibitors, such as alisertib, can destabilize MYC-family oncoproteins and have demonstrated compelling antitumor efficacy. In this study, we report 6K465, a novel pyrimidine-based Aurora A inhibitor, that reduces levels of c-MYC and N-MYC oncoproteins more potently than alisertib. In an analysis of the antiproliferative effect of 6K465, the sensitivities of small cell lung cancer (SCLC) and breast cancer cell lines to 6K465 were strongly associated with the protein levels of c-MYC and/or N-MYC. We also report DBPR728, an acyl-based prodrug of 6K465 bearing fewer hydrogen-bond donors, that exhibited 10-fold improved oral bioavailability. DBPR728 induced durable tumor regression of c-MYC- and/or N-MYC-overexpressing xenografts including SCLC, triple-negative breast cancer, hepatocellular carcinoma, and medulloblastoma using a 5-on-2-off or once-a-week dosing regimen on a 21-day cycle. A single oral dose of DBPR728 at 300 mg/kg induced c-MYC reduction and cell apoptosis in the tumor xenografts for more than 7 days. The inhibitory effect of DBPR728 at a reduced dosing frequency was attributed to its uniquely high tumor/plasma ratio (3.6-fold within 7 days) and the long tumor half-life of active moiety 6K465. Furthermore, DBPR728 was found to synergize with the mTOR inhibitor everolimus to suppress c-MYC- or N-MYC-driven SCLC. Collectively, these results suggest DBPR728 has the potential to treat cancers overexpressing c-MYC and/or N-MYC.
Ophthalmic Symptoms of Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency: A Report of Three Cases
Authors: Lange Natalia , Bodetko Aleksandra Maria , Mozrzymas Renata , Kowal-Lange Agnieszka
Published: April 2024

Introduction: Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, typically inherited as a recessive trait, is a genetic condition predominantly observed in Central and Eastern Europe, with birth prevalence in Poland amounting to 1/118,336. In most European countries, e.g., in Poland since 2014, this disorder is included in newborn screening. Case Presentation: This paper presents the ophthalmic symptoms of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency in three pediatric patients. Visual acuity testing, fundus photography, and optical coherence tomography (OCT) were performed and data were collected over several years (2017–2022). In case 1, a female born in 2010, exhibited abnormalities in the central part of the posterior pole, mainly in the macula, and included choriocapillaris atrophy and severe disruption of the outer retinal layer. Case 2, a female born in 2012, presented with progressive shortsightedness and choroid atrophy documented with angio-OCT. Case 3, a male born in 2013, experienced recurrent hospitalizations due to metabolic decompensations and presented with mild myopia, thinning of the choroid layer, and slight pigment dispersion with macular sparing. Conclusion: The main ophthalmic symptoms of LCHAD deficiency were choroidal atrophy, disorganization of the outer retinal layer, and myopia. Choroidal atrophy and pigment dispersion were consistently the earliest signs of LCHAD-associated chorioretinopathy. Although the progression of chorioretinopathy in each case resulted from metabolic decompensation, one documented case revealed that not every metabolic crisis results in ophthalmological changes. Nonetheless, strict adherence to a low-fat, high-carbohydrate diet remains crucial to prevent gradual deterioration and vision loss.
Frailty Influences the Relationship between the Soluble Receptor for Advanced Glycation-End Products and Mortality in Older Adults with Diabetes Mellitus
Authors: Butcher Lee , Carnicero Jose A. , Pérès Karine , Bandinelli Stefania , García-García Francisco Jose , Rodriguez-Artalejo Fernando , Rodriguez-Mañas Leocadio , Erusalimsky Jorge D.
Published: April 2024

Introduction: Frailty is prevalent among older adults with diabetes mellitus. Elevated serum levels of the soluble receptor for advanced glycation-end products (sRAGE) predict mortality in frail older adults. The evidence that sRAGE is also related to higher mortality in older adults with diabetes mellitus is inconsistent. Therefore, this study explored if frailty status influences the relationship between sRAGE and mortality in older adults with this condition. Methods: We analysed data of 391 participants with diabetes mellitus (median age, 76 years) from four European cohorts enrolled in the FRAILOMIC project. Frailty was evaluated at baseline using Fried’s criteria. Serum sRAGE was determined by ELISA. Participants were stratified by frailty status (n = 280 non-frail and 111 frail). Multivariate Cox proportional hazards regression and Kaplan-Meier survival analysis were used to assess the relationship between sRAGE and mortality. Results: During 6 years of follow-up, 98 participants died (46 non-frail and 52 frail). Non-survivors had significantly higher baseline levels of sRAGE than survivors (median [IQR]: 1,392 [962–2,043] pg/mL vs. 1,212 [963–1,514], p = 0.008). High serum sRAGE (>1,617 pg/mL) was associated with increased mortality in the whole diabetes sample after adjustment for relevant confounders (HR 2.06, 95% CI: 1.36–3.11, p < 0.001), and there was an interaction between sRAGE and frailty (p = 0.006). Accordingly, the association between sRAGE and mortality was stronger in the frail group compared to the non-frail group (HR 2.52, 95% CI: 1.30–4.90, p = 0.006 vs. HR 1.71, 95% CI: 0.91–3.23, p = 0.099, respectively). Likewise, Kaplan-Meier curves showed a significant difference in survival rates between frail participants with high sRAGE and those with low sRAGE (p = 0.001), whereas no survival difference was seen in the non-frail group (p = 0.09). Conclusions: Frailty status influences the relationship between sRAGE and mortality in older adults with diabetes mellitus. Determination of sRAGE in this population could be a useful tool for risk stratification.
A repressão franquista na língua galega. A desfeita de uma realidade linguística, cultural e nacional
Authors: Rodríguez da Torre Matías , Baamonde Silva Xosé Manuel
Published: April 2024

A língua galega, originariamente galego-português, é um idioma de grande vitalidade oral, que da segunda metade do século XIX até o primeiro terço do XX começa a recuperar a normalidade de funções duma língua culta e cooficial. A repressão franquista de 1936 submete o povo em uma ditadura de quarenta anos, impõe o castelhano como único idioma obrigatório e oficial e condena a língua própria da Galiza à marginalidade a respeito dos usos escritos, degradando também seus usos orais. Só o exílio, nomeadamente o americano, manteve nessa altura a edição, a literatura e a denúncia da tirania política, social e linguística. Estas décadas totalitárias foram perniciosas para desenvolver o conflito linguístico e a situação de diglossia que há atualmente na Galiza.
Ektaphelenchoides factum n. sp. in Pinus taeda from the USA and E. pini in Pinus koraiensis from China
Authors: Gu Jianfeng , Munawar Maria , Ma Xinxin , Fang Yiwu
Published: April 2024

The genus Ektaphelenchoides is a diverse group of nematodes; they are either inhabitants of trees or present in the rhizosphere of economical plants. Members of the genus have ecological relevance in terms of being associated with insects and predators of other nematodes. In the present study, a new Ektaphelenchoides species, E. factum n. sp., is described and illustrated. The new species was isolated from a log sample of Pinus taeda imported from the USA. It is characterised by the lateral field with three incisures, stylet distinctly tripartite. Females having a vulval flap, the anus and rectum indistinct, and the tail (posterior part of body) filiform. Males having arcuate and 21.5 (19.4-22.9) μm long spicules, the lamina of the spicule is smoothly curved to distal end, condylus well developed with a broadly rounded tip, rostrum triangular with finely rounded tip and cucullus absent, tail arcuate and conical with terminus bearing a sharply pointed mucron. The new species is different from other Ektaphelenchoides species in having a vulval flap. Molecular characterisation and phylogenetic studies also supported its unique status. In addition, a Chinese native population of E. pini, detected in Pinus koraiensis branches from Liaoning province, P.R. China, is described.
Taxonomic review of Aphestia Schiner, 1866 (Diptera: Asilidae: Laphriinae) with description of seven new species
Authors: CAMARGO ALEXSSANDRO , VIEIRA RODRIGO , RAFAEL JOSÉ ALBERTINO
Published: April 2024

A taxonomic review of the Neotropical genus Aphestia Schiner, 1866 was performed and seven new species were described and illustrated: Aphestia amazonica sp. nov., A. dikowi sp. nov., A. fisheri sp. nov., A. fritzi sp. nov., A. nigriseta sp. nov., A. saltuaria sp. nov. and A. spatulata sp. nov. In addition, two species had their status revalidated, Aphestia brasiliensis Schiner, 1866 stat. rev. and A. calceata Schiner, 1867 stat. rev.; together with A. annulipes (Macquart, 1838) and A. nigra Bigot, 1878, increases to 11 the number of known species in the genus. Atomosia affinis Macquart, 1850 stat. rev. et comb. rev. had its status and original combination with Atomosia Macquart, 1838 revalidated. Aphractia andrenoides (Bromley, 1934) stat. rev. et comb. nov. had its status revalidated and a new combination with Aphractia Artigas, Papavero & Serra, 1991 is proposed. Aphestia chalybaea Röder, 1881, is transferred to Cyanonedys Hermann, 1912, becoming Cyanonedys chalybaea (Röder, 1881) comb. nov. with two new synonyms proposed: Cyanonedys leucura Hermann, 1912 syn. nov. and Clariola nigrescens Ricardo, 1912 syn. nov. Descriptions and redescriptions were provided in detail, with characters of male and female terminalia, including detailed illustrations, distribution maps and a key to Aphestia species.
Hydrodynamics and Heat Transfer of Cavitation Bubble in Nanoparticles/Water Nanofluids Based on the Effects of Variable Surface Tension and Viscous Forces
Authors: Abu-Nab Ahmed K. , Mamdouh H. Omran , Mohamed Khaled G. , Abu-Bakr1 Ali F.
Published: April 2024

This paper aims to investigate the unsteady oscillatory flow of water-based nanofluids MoS2 and SiO2 past a parallel plate channel filled with a saturated porous medium. The basic equations are solved analytically using the perturbation technique subject to the
appropriate boundary conditions. A numerical evaluation of the analytical results is performed, and the effects of various physical parameters on velocity, temperature, and concentration profiles within the boundary layer are analyzed. Molybdenum disulfide MoS2 nanoparticles are
well known for their low friction coefficient, good catalytic activity, and excellent physical properties. At the same time, Silicon dioxide (SiO2) nanoparticles are treated to have a porous structure, very high surface activity, and adsorption properties, which makes them suitable
for developing high-capacity antimicrobial agents. Hence these nanoparticles can be considered for Nanoscale elements’ performance to make rigorous thermal quality nano liquids. Thus from engineering curiosity, the skin friction coefficient, Nusselt number, and Sherwood numbers are evaluated
for significant parameters at cold and heated walls by utilizing MoS2 and SiO2 nanoparticles. It would give rise to novel features that can revolutionize biology, medicine, catalysis, and other smart fields. Furthermore, graphs and tables are used to describe a comparative
study of the water-based nanofluids MoS2 and SiO2. It is found that when the radiation parameter Ra is increased by 200%, the average heat transfer rate at the heated channel wall containing MoS2 and SiO2 nanoparticles in the base fluid is
decreased by 6.9% and 8.3%, respectively. Further, it is found that SiO2-water nanofluid has more effectiveness towards heat transfer compared to MoS2-water nanofluid.
Radiation, Dufour, Magnetohydrodynamic and Double Dispersion Influence Over a Nanofluid Flow with Scaling Group Analysis on a Wedge
Authors: Chakraborty Anomitra , Janapatla Pranitha
Published: April 2024

Mixed convection in nanofluids for varying geometries like the vertical sheets, exponentially stretching sheets etc. contributes to various fields of science and technology applicable to nature and natural processes. Based on the wide range of applications of thermal radiation, double
dispersion and magnetohydrodynamic (MHD) flows in the engineering fields, our study focuses on their combined effects on the mixed convection flow over a vertical wedge which has not been studied earlier. Non-dimensional variables have been introduced with scaling group applications for converting
the governing set of partial differential equations to a new set of ordinary differential equations by the help of similarity transformations. Shooting method with bvp4c routine has been used to formulate the equations numerically. Among all the parameters discussed, λ and Peζ
exposes an augmentation in the heat transfer while a decrement in the mass transfer coefficient, which is a reverse trend to the other parameters involved. Nusselt number decreases for the incrementing magnetic parameter while an augmenting Sherwood number is noticeable. The originality of
the current work is to motivate the researchers and emphasize on the awareness of the influences on flow behavior and heat and mass transfer of the nanofluid flow over the vertical wedge geometry.
Unsteady Boundary Layer Heat and Mass Transfer Flow of Nanofluid Over Porous Stretching Sheet with Non-Uniform Heat Generation/Absorption and Double Stratification
Authors: Sreedevi P. , Reddy P. Sudarsana
Published: April 2024

The influence of thermal radiation and stratification process on unsteady MHD flow over stretching sheet embedded in “nanofluid saturated porous medium with non-uniform heat source/sink was analyzed numerically in the present analysis. Proper similarity transformations reduce
the nonlinear partial differential equations into ordinary differential equations and are solved numerically by using Galerkin Finite element method. Impact of different parameters, such as, magnetic parameter (0.1–1.0), buoyancy ratio parameter (0.1–4.5), radiation parameter (0.5–1.7),
Rayleigh number (0.1–0.7), thermophoresis parameter (0.4–1.5), thermal stratification parameter (0.01–1.0), Brownian motion parameter (1.0–2.0), solutal stratification parameter (0.01–1.0), unsteadiness parameter (0.1–0.4), space–dependent (-0.5–0.4)
and temperature dependent (-0.5–0.2) heat source/sink parameters on velocity, temperature and concentration profiles is calculated and are illustrated graphically. Skin-friction coefficient, Nusselt and Sherwood number are calculated and the results are shown in tabular form. It is found
that the thermal stratification parameter deteriorates the temperature of the fluid. The concentration of the fluid diminishes with rising values of solutal stratification parameter. The thermal boundary layer thickness elevates” with higher values of Brownian motion and thermophoresis
parameters.
Variable selection for latent class analysis in the presence of missing data with application to record linkage
Authors: Xu Huiping , Li Xiaochun , Zhang Zuoyi , Grannis Shaun
Published: April 2024

The Fellegi-Sunter model is a latent class model widely used in probabilistic linkage to identify records that belong to the same entity. Record linkage practitioners typically employ all available matching fields in the model with the premise that more fields convey greater information about the true match status and hence result in improved match performance. In the context of model-based clustering, it is well known that such a premise is incorrect and the inclusion of noisy variables could compromise the clustering. Variable selection procedures have therefore been developed to remove noisy variables. Although these procedures have the potential to improve record matching, they cannot be applied directly due to the ubiquity of the missing data in record linkage applications. In this paper, we modify the stepwise variable selection procedure proposed by Fop, Smart, and Murphy and extend it to account for missing data common in record linkage. Through simulation studies, our proposed method is shown to select the correct set of matching fields across various settings, leading to better-performing algorithms. The improved match performance is also seen in a real-world application. We therefore recommend the use of our proposed selection procedure to identify informative matching fields for probabilistic record linkage algorithms.
Use of Daily Web-Based, Real-Time Feedback to Improve Patient and Family Experience
Authors: Remer Lisa M , Line Kristin , Paolella Alyssa , Rozniak Justin M , Alessandrini Evaline A
Published: April 2024

Real-time feedback is a growing trend in patient- and family experience (PFE) work as it allows for immediate service recovery, though it typically requires a significant investment of time and financial resources. We describe a partnership with our “edutainment” system to administer an automated daily experience question (the “Daily Pulse Measure [DPM]”) that allowed targeted just-in-time responses to low scores with minimal administrative cost. Through a series of Plan-Do-Study-Act cycles guided by family feedback, the question was created and modified, and the use of the question spread to all hospital units. The response rate was 23%, similar to our Hospital Consumer Assessment of Healthcare Providers and Systems survey response rate of 24% during the study period. Though the DPM did not have a consistent impact on the results of the 2 PFE survey questions we evaluated, units with improved PFE scores after the DPM roll-out tended to have more robust service recovery than those with low scores.
Predicting inhibitor development using a random peptide phage-display library approach in the SIPPET cohort
Authors: Hassan Shermarke , Baselli Guido , Mollica Luca , Rossi Riccardo L. , Chand Himani , El-Beshlawy Amal , Elalfy Mohsen , Ramanan Vijay , Eshghi Peyman , Karimi Mehran , Palla Roberta , Rosendaal Frits R. , Peyvandi Flora
Published: April 2024

Inhibitor development is the most severe complication of hemophilia A (HA) care and is associated with increased morbidity and mortality. This study aimed to use a novel immunoglobulin G epitope mapping method to explore the factor VIII (FVIII)–specific epitope profile in the SIPPET cohort population and to develop an epitope mapping–based inhibitor prediction model. The population consisted of 122 previously untreated patients with severe HA who were followed up for 50 days of exposure to FVIII or 3 years, whichever occurred first. Sampling was performed before FVIII treatment and at the end of the follow-up. The outcome was inhibitor development. The FVIII epitope repertoire was assessed by means of a novel random peptide phage-display assay. A least absolute shrinkage and selection operator (LASSO) regression model and a random forest model were fitted on posttreatment sample data and validated in pretreatment sample data. The predictive performance of these models was assessed by the C-statistic and a calibration plot. We identified 27 775 peptides putatively directed against FVIII, which were used as input for the statistical models. The C-statistic of the LASSO and random forest models were good at 0.78 (95% confidence interval [CI], 0.69-0.86) and 0.80 (95% CI, 0.72-0.89). Model calibration of both models was moderately good. Two statistical models, developed on data from a novel random peptide phage display assay, were used to predict inhibitor development before exposure to exogenous FVIII. These models can be used to set up diagnostic tests that predict the risk of inhibitor development before starting treatment with FVIII.
Plasma kallikrein supports FXII-independent thrombin generation in mouse whole blood
Authors: Wan Jun , Dhrolia Sophia , Kasthuri Rohan R. , Prokopenko Yuriy , Ilich Anton , Saha Prakash , Roest Mark , Wolberg Alisa S. , Key Nigel S. , Pawlinski Rafal , Bendapudi Pavan K. , Mackman Nigel , Grover Steven P.
Published: April 2024

Plasma kallikrein (PKa) is an important activator of factor XII (FXII) of the contact pathway of coagulation. Several studies have shown that PKa also possesses procoagulant activity independent of FXII, likely through its ability to directly activate FIX. We evaluated the procoagulant activity of PKa using a mouse whole blood (WB) thrombin-generation (TG) assay. TG was measured in WB from PKa-deficient mice using contact pathway or extrinsic pathway triggers. PKa-deficient WB had significantly reduced contact pathway–initiated TG compared with that of wild-type controls and was comparable with that observed in FXII-deficient WB. PKa-deficient WB supported equivalent extrinsic pathway–initiated TG compared with wild-type controls. Consistent with the presence of FXII-independent functions of PKa, targeted blockade of PKa with either small molecule or antibody-based inhibitors significantly reduced contact pathway–initiated TG in FXII-deficient WB. Inhibition of activated FXII (FXIIa) using an antibody-based inhibitor significantly reduced TG in PKa-deficient WB, consistent with a PKa-independent function of FXIIa. Experiments using mice expressing low levels of tissue factor demonstrated that persistent TG present in PKa- and FXIIa-inhibited WB was driven primarily by endogenous tissue factor. Our work demonstrates that PKa contributes significantly to contact pathway–initiated TG in the complex milieu of mouse WB, and a component of this contribution occurs in an FXII-independent manner.
Imaging in pulmonary infections of immunocompetent adult patients
Authors: Pochepnia Svitlana , Grabczak Elzbieta Magdalena , Johnson Emma , Eyuboglu Fusun Oner , Akkerman Onno , Prosch Helmut
Published: April 2024

Pneumonia is a clinical syndrome characterised by fever, cough and alveolar infiltration of purulent fluid, caused by infection with a microbial pathogen. It can be caused by infections with bacteria, viruses or fungi, but a causative organism is identified in less than half of cases. The most common type of pneumonia is community-acquired pneumonia, which is caused by infections acquired outside the hospital.

Current guidelines for pneumonia diagnosis require imaging to confirm the clinical suspicion of pneumonia. Thus, imaging plays an important role in both the diagnosis and management of pneumonia, with each modality having specific advantages and limitations. Chest radiographs are commonly used but have limitations in terms of sensitivity and specificity. Lung ultrasound shows high sensitivity and specificity. Computed tomography scans offer higher diagnostic accuracy but involve higher radiation doses. Radiological patterns, including lobar, lobular and interstitial pneumonia, provide valuable insights into causative pathogens and treatment decisions. Understanding these radiological patterns is crucial for accurate diagnosis. In this review, we will summarise the most important aspects pertaining to the role of imaging in pneumonia and will highlight the imaging characteristics of the most common causative organisms.
Assessment of the FRET-based Teen sensor to monitor ERK activation changes preceding morphological defects in a RASopathy zebrafish model and phenotypic rescue by MEK inhibitor
Authors: Fasano Giulia , Petrini Stefania , Bonavolontà Valeria , Paradisi Graziamaria , Pedalino Catia , Tartaglia Marco , Lauri Antonella
Published: April 2024

Background

RASopathies are genetic syndromes affecting development and having variable cancer predisposition. These disorders are clinically related and are caused by germline mutations affecting key players and regulators of the RAS-MAPK signaling pathway generally leading to an upregulated ERK activity. Gain-of-function (GOF) mutations in PTPN11, encoding SHP2, a cytosolic protein tyrosine phosphatase positively controlling RAS function, underlie approximately 50% of Noonan syndromes (NS), the most common RASopathy. A different class of these activating mutations occurs as somatic events in childhood leukemias.

Method

Here, we evaluated the application of a FRET-based zebrafish ERK reporter, Teen, and used quantitative FRET protocols to monitor non-physiological RASopathy-associated changes in ERK activation. In a multi-level experimental workflow, we tested the suitability of the Teen reporter to detect pan-embryo ERK activity correlates of morphometric alterations driven by the NS-causing Shp2D61G allele.

Results

Spectral unmixing- and acceptor photobleaching (AB)-FRET analyses captured pathological ERK activity preceding the manifestation of quantifiable body axes defects, a morphological pillar used to test the strength of SHP2 GoF mutations. Last, the work shows that by multi-modal FRET analysis, we can quantitatively trace back the modulation of ERK phosphorylation obtained by low-dose MEK inhibitor treatment to early development, before the onset of morphological defects.

Conclusion

This work proves the usefulness of FRET imaging protocols on both live and fixed Teen ERK reporter fish to readily monitor and quantify pharmacologically- and genetically-induced ERK activity modulations in early embryos, representing a useful tool in pre-clinical applications targeting RAS-MAPK signaling.
Chloroplast genomes of Caragana tibetica and Caragana turkestanica: structures and comparative analysis
Authors: Liu LiE , Li HongYan , Li JiaXin , Li XinJuan , Hu Na , Sun Jing , Zhou Wu
Published: April 2024

Background

The genus Caragana encompasses multiple plant species that possess medicinal and ecological value. However, some species of Caragana are quite similar in morphology, so identifying species in this genus based on their morphological characteristics is considerably complex. In our research, illumina paired-end sequencing was employed to investigate the genetic organization and structure of Caragana tibetica and Caragana turkestanica, including the previously published chloroplast genome sequence of 7 Caragana plants.

Results

The lengths of C. tibetica and C. turkestanica chloroplast genomes were 128,433 bp and 129,453 bp, respectively. The absence of inverted repeat sequences in these two species categorizes them under the inverted repeat loss clade (IRLC). They encode 110 and 111 genes (4 /4 rRNA genes, 30 /31tRNA genes, and 76 /76 protein-coding genes), respectively. Comparison of the chloroplast genomes of C. tibetica and C. turkestanica with 7 other Caragana species revealed a high overall sequence similarity. However, some divergence was observed between certain intergenic regions (matK-rbcL, psbD-psbM, atpA-psbI, and etc.). Nucleotide diversity (π) analysis revealed the detection of five highly likely variable regions, namely rps2-atpI, accD-psaI-ycf4, cemA-petA, psbN-psbH and rpoA-rps11. Phylogenetic analysis revealed that C. tibetica’s sister species is Caragana jubata, whereas C. turkestanica’s closest relative is Caragana arborescens.

Conclusions

The present study provides worthwhile information about the chloroplast genomes of C. tibetica and C. turkestanica, which aids in the identification and classification of Caragana species.
Association of ambient air pollution with hemoglobin levels and anemia in the general population of Korean adults
Authors: Hwang Juyeon , Kim Hyun-Jin
Published: April 2024

Background

Emerging evidence has suggested significant associations between ambient air pollution and changes in hemoglobin levels or anemia in specific vulnerable groups, but few studies have assessed this relationship in the general population. This study aimed to evaluate the association between long-term exposure to air pollution and hemoglobin concentrations or anemia in general adults in South Korea.

Methods

A total of 69,830 Korean adults from a large-scale nationwide survey were selected for our final analysis. Air pollutants included particulate matter with an aerodynamic diameter less than or equal to 10 micrometers (PM10), particulate matter with an aerodynamic diameter less than or equal to 2.5 micrometers, nitrogen dioxide, sulfur dioxide (SO2), and carbon monoxide (CO). We measured the serum hemoglobin concentration to assess anemia for each participant.

Results

In the fully adjusted model, exposure levels to PM10, SO2, and CO for one and two years were significantly associated with decreased hemoglobin concentrations (allp < 0.05), with effects ranging from 0.15 to 0.62% per increase in interquartile range (IQR) for each air pollutant. We also showed a significant association of annual exposure to PM10with anemia (p = 0.0426); the odds ratio (OR) [95% confidence interval (CI)] for anemia per each increase in IQR in PM10was estimated to be 1.039 (1.001–1.079). This association was also found in the 2-year duration of exposure (OR = 1.046; 95% CI = 1.009–1.083; adjusted Model 2). In addition, CO exposure during two years was closely related to anemia (OR = 1.046; 95% CI = 1.004–1.091; adjusted Model 2).

Conclusions

This study provides the first evidence that long-term exposure to air pollution, especially PM10, is significantly associated with reduced hemoglobin levels and anemia in the general adult population.
Droplet-based microfluidic platform for detecting agonistic peptides that are self-secreted by yeast expressing a G-protein-coupled receptor
Authors: Asama Ririka , Liu Cher J. S. , Tominaga Masahiro , Cheng Yu-Ru , Nakamura Yasuyuki , Kondo Akihiko , Wang Hsiang-Yu , Ishii Jun
Published: April 2024

Background

Single-cell droplet microfluidics is an important platform for high-throughput analyses and screening because it provides an independent and compartmentalized microenvironment for reaction or cultivation by coencapsulating individual cells with various molecules in monodisperse microdroplets. In combination with microbial biosensors, this technology becomes a potent tool for the screening of mutant strains. In this study, we demonstrated that a genetically engineered yeast strain that can fluorescently sense agonist ligands via the heterologous expression of a human G-protein-coupled receptor (GPCR) and concurrently secrete candidate peptides is highly compatible with single-cell droplet microfluidic technology for the high-throughput screening of new agonistically active peptides.

Results

The water-in-oil microdroplets were generated using a flow-focusing microfluidic chip to encapsulate engineered yeast cells coexpressing a human GPCR [i.e., angiotensin II receptor type 1 (AGTR1)] and a secretory agonistic peptide [i.e., angiotensin II (Ang II)]. The single yeast cells cultured in the droplets were then observed under a microscope and analyzed using image processing incorporating machine learning techniques. The AGTR1-mediated signal transduction elicited by the self-secreted Ang II peptide was successfully detected via the expression of a fluorescent reporter in single-cell yeast droplet cultures. The system could also distinguish Ang II analog peptides with different agonistic activities. Notably, we further demonstrated that the microenvironment of the single-cell droplet culture enabled the detection of rarely existing positive (Ang II-secreting) yeast cells in the model mixed cell library, whereas the conventional batch-culture environment using a shake flask failed to do so. Thus, our approach provided compartmentalized microculture environments, which can prevent the diffusion, dilution, and cross-contamination of peptides secreted from individual single yeast cells for the easy identification of GPCR agonists.

Conclusions

We established a droplet-based microfluidic platform that integrated an engineered yeast biosensor strain that concurrently expressed GPCR and self-secreted the agonistic peptides. This offers individually isolated microenvironments that allow the culture of single yeast cells secreting these peptides and gaging their signaling activities, for the high-throughput screening of agonistic peptides. Our platform base on yeast GPCR biosensors and droplet microfluidics will be widely applicable to metabolic engineering, environmental engineering, and drug discovery.
Impaired proprioception and magnified scaling of proprioceptive error responses in chronic stroke
Authors: Tulimieri Duncan Thibodeau , Semrau Jennifer A.
Published: April 2024

Background

Previous work has shown that ~ 50–60% of individuals have impaired proprioception after stroke. Typically, these studies have identified proprioceptive impairments using a narrow range of reference movements. While this has been important for identifying the prevalence of proprioceptive impairments, it is unknown whether these error responses are consistent for a broad range of reference movements. The objective of this study was to characterize proprioceptive accuracy as function of movement speed and distance in stroke.

Methods

Stroke (N = 25) and controls (N = 21) completed a robotic proprioception test that varied movement speed and distance. Participants mirror-matched various reference movement speeds (0.1–0.4 m/s) and distances (7.5–17.5 cm). Spatial and temporal parameters known to quantify proprioception were used to determine group differences in proprioceptive accuracy, and whether patterns of proprioceptive error were consistent across testing conditions within and across groups.

Results

Overall, we found that stroke participants had impaired proprioception compared to controls. Proprioceptive errors related to tested reference movement scaled similarly to controls, but some errors showed amplified scaling (e.g., significantly overshooting or undershooting reference speed). Further, interaction effects were present for speed and distance reference combinations at the extremes of the testing distribution.

Conclusions

We found that stroke participants have impaired proprioception and that some proprioceptive errors were dependent on characteristics of the movement (e.g., speed) and that reference movements at the extremes of the testing distribution resulted in significantly larger proprioceptive errors for the stroke group. Understanding how sensory information is utilized across a broad spectrum of movements after stroke may aid design of rehabilitation programs.
Effects of bone marrow sparing radiotherapy on acute hematologic toxicity for patients with locoregionally advanced cervical cancer: a prospective phase II randomized controlled study
Authors: Li Wen , Ma Lan , Li Fang , Li Kemin , Zhang Yang , Ren Hongtao , Bao Xing , Guo Yuyan , Guo Ya , Wang Mincong , Li Dan , Duan Yuanqiong , Ma Xiulong , Wang Zhongwei , Wang Yali , Yin Rutie
Published: April 2024

Objective

To evaluate effects of bone marrow sparing (BMS) radiotherapy on decreasing the incidence of acute hematologic toxicity (HT) for locoregionally advanced cervical cancer (LACC) patients treated by pelvic irradiation.

Materials and methods

LACC patients were recruited prospectively from May 2021 to May 2022 at a single center and were evenly randomized into the BMS group and the control group. All patients received pelvic irradiation with concurrent cisplatin (40 mg/m2 weekly), followed by brachytherapy and BM V40 < 25% in the BMS group was additionally prescribed. Acute HT was assessed weekly. Binary logistic regression model and receiver operating characteristic (ROC) curve were used for predictive value analysis. The trial was registered with Chinese clinical trial registry (ChiCTR2200066485).

Results

A total of 242 patients were included in the analysis. Baseline demographic, disease and treatment characteristics were balanced between the two groups. In the intention-to-treat population, BMS was associated with a lower incidence of grade ≥ 2 and grade ≥ 3 acute HT, leukopenia and neutropenia s(72.70% v 90.90%, P < 0.001*; 16.50% vs. 65.30%, P < 0.001*; 66.10% vs. 85.10%, P = 0.001*; 13.20% vs. 54.50%, P < 0.001*; 37.20% vs. 66.10%, P < 0.001*; 10.70% vs. 43.80%, P < 0.001*). BMS also resulted in decreased dose delivered to the organs at risk (OARs) including rectum, bladder and left and right femoral head. Univariate and multivariate analyses showed that BM V40 was an independent risk factor for grade ≥ 3 acute HT (odds ratio [OR] = 2.734, 95% confidence interval [CI] = 1.959–3.815, P < 0.001*). Cutoff value was 25.036% and area under the curve (AUC) was 0.786. The nomogram was constructed, which was rigorously evaluated and internally cross-validated, showing good predictive performance.

Conclusions

Receiving BMS pelvic irradiation could reduce the incidence of acute HT in LACC patients, and BM V40 < 25% may be a significant factor in reducing the risks of acute HT.
Bazi Bushen ameliorates age-related energy metabolism dysregulation by targeting the IL-17/TNF inflammatory pathway associated with SASP
Authors: Shen Xiaogang , Li Mengnan , Li Yawen , Jiang Yuning , Niu Kunxu , Zhang Shixiong , Lu Xuan , Zhang Runtao , Zhao Zhiqin , Zhou Liangxing , Guo Zhifang , Wang Siwei , Wei Cong , Chang Liping , Hou Yunlong , Wu Yiling
Published: April 2024

Background

Chronic inflammation and metabolic dysfunction are key features of systemic aging, closely associated with the development and progression of age-related metabolic diseases. Bazi Bushen (BZBS), a traditional Chinese medicine used to alleviate frailty, delays biological aging by modulating DNA methylation levels. However, the precise mechanism of its anti-aging effect remains unclear. In this study, we developed the Energy Expenditure Aging Index (EEAI) to estimate biological age. By integrating the EEAI with transcriptome analysis, we aimed to explore the impact of BZBS on age-related metabolic dysregulation and inflammation in naturally aging mice.

Methods

We conducted indirect calorimetry analysis on five groups of mice with different ages and utilized the data to construct EEAI. 12 -month-old C57BL/6 J mice were treated with BZBS or β-Nicotinamide Mononucleotide (NMN) for 8 months. Micro-CT, Oil Red O staining, indirect calorimetry, RNA sequencing, bioinformatics analysis, and qRT-PCR were performed to investigate the regulatory effects of BZBS on energy metabolism, glycolipid metabolism, and inflammaging.

Results

The results revealed that BZBS treatment effectively reversed the age-related decline in energy expenditure and enhanced overall metabolism, as indicated by the aging index of energy expenditure derived from energy metabolism parameters across various ages. Subsequent investigations showed that BZBS reduced age-induced visceral fat accumulation and hepatic lipid droplet aggregation. Transcriptomic analysis of perirenal fat and liver indicated that BZBS effectively enhanced lipid metabolism pathways, such as the PPAR signaling pathway, fatty acid oxidation, and cholesterol metabolism, and improved glycolysis and mitochondrial respiration. Additionally, there was a significant improvement in inhibiting the inflammation-related arachidonic acid-linoleic acid metabolism pathway and restraining the IL-17 and TNF inflammatory pathways activated via senescence associated secretory phenotype (SASP).

Conclusions

BZBS has the potential to alleviate inflammation in metabolic organs of naturally aged mice and maintain metabolic homeostasis. This study presents novel clinical therapeutic approaches for the prevention and treatment of age-related metabolic diseases.
Anti-inflammatory therapies are associated with delayed onset of anemia and reduction in transfusion requirements in critically ill patients: results from two studies
Authors: Bolscher Madelief , Koster Stephanie C. E. , Koopmans Matty , Haitsma Mulier Jelle L. G. , Derde Lennie P. G. , Juffermans Nicole P.
Published: April 2024

Background

Anemia is a hallmark of critical illness, which is largely inflammatory driven. We hypothesized that the use of anti-inflammatory agents limits the development of anemia and reduces the need for red blood cell (RBC) transfusions in patients with a hyper-inflammatory condition due to COVID-19.

Methods

An observational cohort (n = 772) and a validation cohort (a subset of REMAP-CAP, n = 119) of critically ill patients with hypoxemic respiratory failure due to COVID-19 were analyzed, who either received no treatment, received steroids or received steroids plus IL-6 blocking agents. The trajectory of hemoglobin (Hb) decline and the need for RBC transfusions were compared using descriptive statistics as well as multivariate modeling.

Results

In both cohorts, Hb level was higher in the treated groups compared to the untreated group at all time points. In the observational cohort, incidence and number of transfused patients were lower in the group receiving the combination treatment compared to the untreated groups. In a multivariate analysis controlling for baseline Hb imbalance and mechanical ventilation, receipt of steroids remained associated with a slower decline in Hb level and the combination treatment remained associated with a slower decline of Hb and with less transfusions. Results remained the same in the validation cohort.

Conclusion

Immunomodulatory treatment was associated with a slower decline in Hb level in critically ill patients with COVID-19 and with less transfusion. Findings point toward inflammation as an important cause for the occurrence of anemia in the critically ill.
Nutrition and movement to improve quality of life in patients with knee osteoarthritis: the NUMOQUA study protocol for a randomised controlled trial
Authors: Höld Elisabeth , Chmelar Sabine , Aubram Tatjana , Leitner Gabriele , Nehrer Stefan , Neubauer Oliver , Wagner Karl-Heinz , Wondrasch Barbara
Published: April 2024

Background

Osteoarthritis (OA) has long been considered as a degenerative disease of cartilage tissue resulting from bodily wear and tear. However, there is accumulating evidence that inflammation plays a key role in the pathogenesis of OA. In knee OA, the most common form of OA, exercise therapy as an effective component of early treatment addresses functional deficits, pain and inflammation. Since inflammation is critical for the development and progress of OA, anti-inflammatory therapies must be combined strategically.

In the course of the NUMOQUA project, an anti-inflammatory therapeutic diet named ‘Austrian Osteoarthritis Cuisine’ was developed. It is based on the framework of the New Nordic Diet combined with the food-based dietary guidelines of Austria, the guidelines for OA, the Austrian food culture and the principles of a sustainable diet. The present study examines the implementation of the ‘Austrian OA Cuisine’ combined with the evidence-based training programme GLA:D® (Good Life with osteoArthritis in Denmark) in Austrian patients with knee OA and the effects on quality of life, nutritional and inflammatory status, as well as oxidative stress parameters.

Methods

A total of 60 participants aged 50 to 75 with knee OA will be included and randomly assigned either to the intervention group or the control group. All participants will undergo the GLA:D® programme in the first 6 weeks. Additionally, the intervention group will receive nutritional group training and individual nutritional counselling on the ‘Austrian OA Cuisine’ over 9 months. The control group will receive general information about a healthy lifestyle. Measurements at baseline and at 4 follow-up dates include nutritional, inflammatory and oxidative stress markers. Furthermore, anthropometric, behavioural and clinical data will be obtained. The recruitment process lasted from autumn 2022 to January 2024, followed by the intervention until October 2024.

Discussion

The prevalence of OA is expected to increase in the future due to ongoing demographic changes and rising obesity rates. The expected results will provide important evidence on whether this interdisciplinary therapeutic approach could be a new, cost-effective and sustainable strategy to address the disease process of OA without negative side effects.

Trial registration

ClinicalTrials.gov NCT05955300. Date of registration: 23rd of October 2023.
Effects of combination of strength and balance training on postural control and functionality in people with chronic ankle instability: a systematic review and meta analysis
Authors: Su Yuying , Li Wei , Pan Changbo , Shi Yu
Published: April 2024

Aim

To identify the effects of strength and balance training on dynamic balance and patient reported outcomes in people with chronic ankle instability(CAI).

Method

Five databases(CNKI, WanFang, Web of Science, EBSCO-SPORTD and PubMed were searched in September 2022. The search was conducted on randomized controlled trials(RCTs) that the effects of strength training, balance training and combination of strength and balance training in people with chronic ankle instability compared to a control group. Using Review Manager 5.3 and Stata-SE 15 to conduct Meta-analysis on the included literature. methodological quality and risk of bias were assessed by using the PEDro scale.

Results

A total of 33 Chinese and English RCTs document were screened and 1154 patients with CAI were included in the study. Compared with control group, strength training, balance training and combination of strength and balance training demonstrated to be more effective in terms of improving patient reported outcomes(strength training: SMD = 0.80, 95%CI = 0.39–1.22; balance training: SMD = 0.79, 95%CI = 0.41–1.17; combination of strength and balance training: SMD = 1.28, 95%CI = 0.57, 1.99). Subgroup analysis: Intervention for 6 weeks, more than 3 times a week and more than 30 min each time were the best rehabilitation programs to improve CAI patientreported outcomes. Compared with control group, balance training demonstrated to be more effective in terms of improving Star Excursion Balance Test (SEBT)((anterior: SMD = 0.71, 95%CI = 0.03–1.40; posterolateral: SMD = 0.84, 95%CI = 0.22–1.46; posteromedial: SMD = 0.88, 95%CI = 0.45–1.32). However, strength training and combination of strength and balance training had no improvement effects on SEBT.

Conclusions

Available evidence showed that, results of the comparison between balance training versus strength training suggest that the combination of strength and balance training achieves greater benefits for patient reported outcomes and balance training could bring greater benefits to dynamic balance. Strength training should be used cautiously in clinic to improve the dynamic balance in individuals with CAI.

Trial registration

(http://www.crd.york.ac.uk/PROSPERO, Registration No. CRD42022371396).