bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide in vivo CRISPR screen identifies TGFβ3 as actionable biomarker of palbociclib resistance in triple negative breast cancer
Authors: Poulet Sophie , Dai Meiou , Wang Ni , Yan Gang , Boudreault Julien , Daliah Girija , Guillevin Alan , Nguyen Huong , Galal Soaad , Ali Suhad , Lebrun Jean-Jacques
Published: June 2024

Triple negative breast cancer (TNBC) remains exceptionally challenging to treat. While CDK4/6 inhibitors have revolutionized HR + breast cancer therapy, there is limited understanding of their efficacy in TNBC and meaningful predictors of response and resistance to these drugs remain scarce. We conducted an in vivo genome-wide CRISPR screen using palbociclib as a selection pressure in TNBC. Hits were prioritized using microarray data from a large panel of breast cancer cell lines to identify top palbociclib sensitizers. Our study defines TGFβ3 as an actionable determinant of palbociclib sensitivity that potentiates its anti-tumor effects. Mechanistically, we show that chronic palbociclib exposure depletes p21 levels, contributing to acquired resistance, and that TGFβ3 treatment can overcome this. This study defines TGFβ3 as an actionable biomarker that can be used to improve patient stratification for palbociclib treatment and exploits the synergistic interaction between CDK4/6 and TGFβ3 to propose a new combinatorial treatment for TNBC.
The association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and the risk of osteoporosis among U.S. adults: analysis of NHANES data
Authors: Wang Jinzhou , Li Shanshan , Pu Hongyu , He Jiangtao
Published: June 2024

Background

Osteoporosis and atherosclerosis frequently afflict older adults, and recent insights suggest a deeper connection between these conditions that surpasses mere aging effects. The ratio of non-high-density to high-density lipoprotein cholesterol (NHHR) has emerged as a novel lipid marker for evaluating the risk of cardiovascular diseases. Nonetheless, investigations into the correlation of the NHHR with the risk of developing osteoporosis remain unexplored.

Methods

We collected NHHR and bone mineral density (BMD) data from 11,024 National Health and Nutrition Examination Survey (NHANES) participants between 2011 and 2018. Multivariate linear regression was employed to examine the correlation between BMD and NHHR. Smooth curves were employed to deal with the nonlinearity. To further account for the nonlinear link, we used a two-part linear regression model. The threshold effects were estimated using two components of a linear regression model. Subgroup and sensitivity analyses were carried out to ascertain the stability of the findings.

Results

We discovered a negative relationship between the NHHR and lumbar spine BMD in all three models. An L-shaped curvilinear association existed between the NHHR and lumbar spine BMD, with a key inflection point of 6.91. The fully adjusted model showed that the BMD of the lumbar spine fell by 0.03 g/cm2 in those who were in the fourth quartile as opposed to the lowest quartile. The sensitivity analysis using unweighted logistic analysis verified the stability of the results. In addition, BMD in the nondiabetic group was more significantly affected by the negative effect of the NHHR in the subgroup analysis.

Conclusions

According to this research, there appears to be a negative correlation between BMD and NHHR in US Adults. To clarify the precise physiological mechanisms by which the NHHR contributes to the onset of osteoporosis, more research is necessary.
Dual-mode nanoprobe strategy integrating ultrasound and near-infrared light for targeted and synergistic arterial thrombolysis
Authors: Wang Zhiwen , Jiang Nan , Jiang Zhixin , Wang Hao , Guo Yuxin , Zhong Fanglu , Gui Bin , Chen Yueying , Deng Qing , Zhou Qing , Hu Bo
Published: June 2024

Efficient thrombolysis in time is crucial for prognostic improvement of patients with acute arterial thromboembolic disease, while limitations and complications still exist in conventional thrombolytic treatment methods. Herein, our study sought to investigate a novel dual-mode strategy that integrated ultrasound (US) and near-infrared light (NIR) with establishment of hollow mesoporous silica nanoprobe (HMSN) which contains Arginine-glycine-aspartate (RGD) peptide (thrombus targeting), perfluoropentane (PFP) (thrombolysis with phase-change and stable cavitation) and indocyanine green (ICG) (thrombolysis with photothermal conversion). HMSN is used as the carrier, the surface is coupled with targeted RGD to achieve high targeting and permeability of thrombus, PFP and ICG are loaded to achieve the collaborative diagnosis and treatment of thrombus by US and NIR, so as to provide a new strategy for the integration of diagnosis and treatment of arterial thrombus. From the in vitro and in vivo evaluation, RGD/ICG/PFP@HMSN can aggregate and penetrate at the site of thrombus, and finally establish the dual-mode directional development and thrombolytic treatment under the synergistic effect of US and NIR, providing strong technical support for the accurate diagnosis and treatment of arterial thrombosis.

Graphical Abstract
Systematic review of fatigue severity in ME/CFS patients: insights from randomized controlled trials
Authors: Park Jae-Woong , Park Byung-Jin , Lee Jin-Seok , Lee Eun-Jung , Ahn Yo-Chan , Son Chang-Gue
Published: June 2024

Background

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating illness medically unexplained, affecting approximately 1% of the global population. Due to the subjective complaint, assessing the exact severity of fatigue is a clinical challenge, thus, this study aimed to produce comprehensive features of fatigue severity in ME/CFS patients.

Methods

We systematically extracted the data for fatigue levels of participants in randomized controlled trials (RCTs) targeting ME/CFS from PubMed, Cochrane Library, Web of Science, and CINAHL throughout January 31, 2024. We normalized each different measurement to a maximum 100-point scale and performed a meta-analysis to assess fatigue severity by subgroups of age, fatigue domain, intervention, case definition, and assessment tool, respectively.

Results

Among the total of 497 relevant studies, 60 RCTs finally met our eligibility criteria, which included a total of 7088 ME/CFS patients (males 1815, females 4532, and no information 741). The fatigue severity of the whole 7,088 patients was 77.9 (95% CI 74.7–81.0), showing 77.7 (95% CI 74.3–81.0) from 54 RCTs in 6,706 adults and 79.6 (95% CI 69.8–89.3) from 6 RCTs in 382 adolescents. Regarding the domain of fatigue, ‘cognitive’ (74.2, 95% CI 65.4–83.0) and ‘physical’ fatigue (74.3, 95% CI 68.3–80.3) were a little higher than ‘mental’ fatigue (70.1, 95% CI 64.4–75.8). The ME/CFS participants for non-pharmacological intervention (79.1, 95% CI 75.2–83.0) showed a higher fatigue level than those for pharmacological intervention (75.5, 95% CI 70.0–81.0). The fatigue levels of ME/CFS patients varied according to diagnostic criteria and assessment tools adapted in RCTs, likely from 54.2 by ICC (International Consensus Criteria) to 83.6 by Canadian criteria and 54.2 by MFS (Mental Fatigue Scale) to 88.6 by CIS (Checklist Individual Strength), respectively.

Conclusions

This systematic review firstly produced comprehensive features of fatigue severity in patients with ME/CFS. Our data will provide insights for clinicians in diagnosis, therapeutic assessment, and patient management, as well as for researchers in fatigue-related investigations.
Whole genome sequencing of HER2-positive metastatic extramammary Paget’s disease: a case report
Authors: Lim Boon Yee , Guo Zexi , Lim Jing Quan , Ko Tun Kiat , Lee Elizabeth Chun Yong , Kannan Bavani , Lee Jing Yi , Lim Abner Herbert , Li Zhimei , Ng Cedric Chuan-Young , Busmanis Inny , Chan Jason Yongsheng
Published: June 2024

Background

Extramammary Paget’s disease (EMPD) is a rare cancer that occurs within the epithelium of the skin, arising predominantly in areas with high apocrine gland concentration such as the vulva, scrotum, penis and perianal regions. Here, we aim to integrate clinicopathological data with genomic analysis of aggressive, rapidly-progressing de novo metastatic EMPD responding to HER2-directed treatment in combination with other agents, to attain a more comprehensive understanding of the disease landscape.

Methods

Immunohistochemical staining on the scrotal wall tumor and bone marrow metastasis demonstrated HER2 overexpression. Whole genome sequencing of the tumor and matched blood was performed.

Results

Notable copy number gains (log2FC > 0.9) on chromosomes 7 and 8 were detected (n = 81), with 92.6% of these unique genes specifically located on chromosome 8. Prominent cancer-associated genes include ZNF703, HOOK3, DDHD2, LSM1, NSD3, ADAM9, BRF2, KAT6A and FGFR1. Interestingly, ERBB2 gene did not exhibit high copy number gain (log2FC = 0.4) although 90% of tumor cells stained HER2-positive. Enrichment in pathways associated with transforming growth factor-beta (TGFβ) (FDR = 0.0376, Enrichment Ratio = 8.12) and fibroblast growth factor receptor (FGFR1) signaling (FDR = 0.0082, Enrichment Ratio = 2.3) was detected. Amplicon structure analysis revealed that this was a simple-linear amplification event.

Conclusion

Whole genome sequencing revealed the underlying copy number variation landscape in HER2-positive metastatic EMPD. The presence of alternative signalling pathways and genetic variants suggests potential interactions with HER2 signalling, which possibly contributed to the HER2 overexpression and observed response to HER2-directed therapy combined with other agents in a comprehensive treatment regimen.
Implementation of a point-of-care ultrasound archiving system and governance framework in a UK physician-paramedic staffed helicopter emergency medical service
Authors: Aziz Shadman , Edmunds Christopher T. , Barratt Jon
Published: June 2024

Introduction

There has been a rapid expansion in the use of point-of-care ultrasonography (POCUS) by emergency medical services (EMS). However, less than a third of UK EMS utilise imaging archiving for POCUS, and fewer review saved images as part of a clinical governance structure. This paper describes the implementation of a novel image archiving system and a robust clinical governance framework in our UK physician-paramedic staffed helicopter emergency medical service (HEMS).

Methods

A retrospective database review was conducted of all patients attended by East Anglian Air Ambulance (EAAA) between the introduction of a new POCUS device and image archiving system on 1 December 2020 to 31 January 2024. All patients with recorded POCUS examinations were included. Images from POCUS examinations at EAAA are archived on a cloud-based server, and retrospectively reviewed within 24 h by an EAAA POCUS supervisor. Image quality is graded using a 5-point Likert-type scale, agreement between reviewer and clinician is recorded and feedback is provided on scanning technique. T-tests were used to assess the difference in image quality between physicians and paramedics. Inter-rater reliability between reviewers and clinicians was assessed using Cohen’s kappa (κ).

Results

During the study period, 5913 patients were attended by EAAA. Of these, 1097 patients had POCUS images recorded. The prevalence of POCUS during the study period was 18.6%. 1061 patient examinations underwent quality assurance (96.7%). The most common POCUS examination was echocardiography (60%), predominantly during cardiac arrest. The primary scanning clinician was a paramedic in 25.4% of POCUS examinations. Across all examination types; image quality was not significantly different between physicians and paramedics and agreement between reviewers and clinicians was strong (κ > 0.85).

Conclusions

In this service evaluation study, we have described outcomes following the introduction of a new POCUS device, image archiving system and governance framework in our HEMS. Paramedics were the primary scanning clinician in a quarter of scans, with image quality comparable to physicians. Almost all scans underwent quality assurance and inter-rater reliability was strong between clinicians and reviewers. Further research is required to investigate the diagnostic accuracy of POCUS and to demonstrate the effect of utilising prehospital POCUS to refine diagnosis on clinical outcomes.
Single-cell and genome-wide Mendelian randomization identifies causative genes for gout
Authors: Yang Yubiao , Hu Ping , Zhang Qinnan , Ma Boyuan , Chen Jinyu , Wang Bitao , Ma Jun , Liu Derong , Hao Jian , Zhou Xianhu
Published: June 2024

Background

Gout is a prevalent manifestation of metabolic osteoarthritis induced by elevated blood uric acid levels. The purpose of this study was to investigate the mechanisms of gene expression regulation in gout disease and elucidate its pathogenesis.

Methods

The study integrated gout genome-wide association study (GWAS) data, single-cell transcriptomics (scRNA-seq), expression quantitative trait loci (eQTL), and methylation quantitative trait loci (mQTL) data for analysis, and utilized two-sample Mendelian randomization study to comprehend the causal relationship between proteins and gout.

Results

We identified 17 association signals for gout at unique genetic loci, including four genes related by protein-protein interaction network (PPI) analysis: TRIM46, THBS3, MTX1, and KRTCAP2. Additionally, we discerned 22 methylation sites in relation to gout. The study also found that genes such as TRIM46, MAP3K11, KRTCAP2, and TM7SF2 could potentially elevate the risk of gout. Through a Mendelian randomization (MR) analysis, we identified three proteins causally associated with gout: ADH1B, BMP1, and HIST1H3A.

Conclusion

According to our findings, gout is linked with the expression and function of particular genes and proteins. These genes and proteins have the potential to function as novel diagnostic and therapeutic targets for gout. These discoveries shed new light on the pathological mechanisms of gout and clear the way for future research on this condition.
Fiscal space for the immunisation program in Zambia– an efficiency analysis approach
Authors: Chompolola Abson , Chama-Chiliba Chitalu Miriam , Simuyemba Moses Chikoti , Sinyangwe Aaron Chisha , Bchir Abdallah , Asiimwe Gilbert , Masiye Felix
Published: June 2024

Objective

The immunisation programme in Zambia remains one of the most effective public health programmes. Its financial sustainability is, however, uncertain. Using administrative data on immunisation coverage rate, vaccine utilisation, the number of health facilities and human resources, expenditure on health promotion, and the provision of outreach services from 24 districts, we used Data Envelopment Analysis to determine the level of technical efficiency in the provision of immunisation services. Based on our calculated levels of technical efficiency, we determined the available fiscal space for immunisation.

Results

Out of the 24 districts in our sample, 9 (38%) were technically inefficient in the provision of immunisation services. The average efficiency score, however, was quite high, at 0.92 (CRS technology) and 0.95 (VRS technology). Based on the calculated level of technical efficiency, we estimated that an improvement in technical efficiency can save enough vaccine doses to supply between 5 and 14 additional districts. The challenge, however, lies in identifying and correcting for the sources of technical inefficiency.
Discrimination sensitivity of visual shapes sharpens in autistic adults but only after explicit category learning
Authors: Van Overwalle Jaana , Geusens Birte , Van der Donck Stephanie , Boets Bart , Wagemans Johan
Published: June 2024

Background

Categorization and its influence on perceptual discrimination are essential processes to organize information efficiently. Individuals with Autism Spectrum Condition (ASC) are suggested to display enhanced discrimination on the one hand, but also to experience difficulties with generalization and ignoring irrelevant differences on the other, which underlie categorization. Studies on categorization and discrimination in ASC have mainly focused on one process at a time, however, and typically only used either behavioral or neural measures in isolation. Here, we aim to investigate the interrelationships between these perceptual processes using novel stimuli sampled from a well-controlled artificial stimulus space. In addition, we complement standard behavioral psychophysical tasks with frequency-tagging EEG (FT-EEG) to obtain a direct, non-task related neural index of discrimination and categorization.

Methods

The study was completed by 38 adults with ASC and 38 matched neurotypical (NT) individuals. First, we assessed baseline discrimination sensitivity by administering FT-EEG measures and a complementary behavioral task. Second, participants were trained to categorize the stimuli into two groups. Finally, participants again completed the neural and behavioral discrimination sensitivity measures.

Results

Before training, NT participants immediately revealed a categorical tuning of discrimination, unlike ASC participants who showed largely similar discrimination sensitivity across the stimuli. During training, both autistic and non-autistic participants were able to categorize the stimuli into two groups. However, in the initial training phase, ASC participants were less accurate and showed more variability, as compared to their non-autistic peers. After training, ASC participants showed significantly enhanced neural and behavioral discrimination sensitivity across the category boundary. Behavioral indices of a reduced categorical processing and perception were related to the presence of more severe autistic traits. Bayesian analyses confirmed overall results.

Limitations

Data-collection occurred during the COVID-19 pandemic.

Conclusions

Our behavioral and neural findings indicate that adults with and without ASC are able to categorize highly similar stimuli. However, while categorical tuning of discrimination sensitivity was spontaneously present in the NT group, it only emerged in the autistic group after explicit categorization training. Additionally, during training, adults with autism were slower at category learning. Finally, this multi-level approach sheds light on the mechanisms underlying sensory and information processing issues in ASC.
Enhanced osteochondral repair by leukocyte-depleted platelet-rich plasma in combination with adipose-derived mesenchymal stromal cells encapsulated in a three-dimensional photocrosslinked injectable hydrogel in a rabbit model
Authors: Iseki Tomoya , Rothrauff Benjamin B. , Kihara Shinsuke , Overholt Kalon J. , Taha Tarek , Lin Hang , Alexander Peter G. , Tuan Rocky S.
Published: June 2024

Introduction

Intra-articular injection of adipose-derived mesenchymal stromal cells (ASCs) and/or platelet-rich plasma (PRP) have been reported to independently and synergistically improve healing of osteochondral lesions in animal models. However, their independent and combined effects when localized to an osteochondral lesion by encapsulation within a photocrosslinkable methacrylated gelatin hydrogel (GelMA) have not been explored. Herein we investigated a unique combination of allogeneic ASCs and PRP embedded in GelMA as a single-stage treatment for osteochondral regeneration in a rabbit model.

Methods

Thirty mature rabbits were divided into six experimental groups: (1) Sham; (2) Defect; (3) GelMA; (4) GelMA + ASCs; (5) GelMA + PRP; and (6) GelMA + ASCs + PRP.At 12 weeks following surgical repair, osteochondral regeneration was assessed on the basis of gross appearance, biomechanical properties, histological and immunohistochemical characteristics, and subchondral bone volume.

Results

In terms of mechanical property reflecting the ability of neotissue to bear stress, PRP only group were significantly lower than the Sham group (p = 0.0098). On the other hand, ASCs only and ASCs combined with PRP groups did not exhibit significantly difference, which suggesting that incorporation of ASCs assists in restoring the ability of the neotissue to bear stresses similarly to native tissue (p = 0.346, p = 0.40, respectively). Safranin O in ASCs combined with PRP group was significantly higher than the Defect and GelMA only groups (p = 0.0009, p = 0.0017, respectively). Additionally, ASCs only and ASCs combined with PRP groups presented especially strong staining for collagen type II. Surprisingly, PRP only and PRP + ASCs groups tended to exhibit higher collagen type I and collagen type X staining compared to ASCs only group, suggesting a potential PRP-mediated hypertrophic effect.

Conclusion

Regeneration of a focal osteochondral defect in a rabbit model was improved by a single-stage treatment of a photocrosslinked hydrogel containing allogenic ASCs and autologous PRP, with the combination of ASCs and PRP producing superior benefit than either alone. No experimental construct fully restored all properties of the native, healthy osteochondral unit, which may require longer follow-up or further modification of PRP and/or ASCs characteristics.
A systematic review and meta-analysis of systematic and topical tranexamic acid administration in aesthetic plastic surgery
Authors: Kolasiński Jerzy , Reysner Tomasz , Kolenda Małgorzata , Kołacz Szymon , Domagalska Małgorzata
Published: June 2024

Introduction

Tranexamic acid has been widely used in plastic surgery. However, its efficacy has yet to be fully established. This meta-analysis aimed to determine its effectiveness in aesthetic plastic surgery.

Methods

Following PRISMA guidelines, we conducted a meta-analysis of prospective randomised clinical trials that compared the effects of topical or systematic administration of tranexamic acid versus the control group in aesthetic plastic surgeries. The study was registered on the International Register of Systematic Reviews (PROSPERO) and is available online (www.crd.york.uk/prospero, CRD42023492585).

Results

Eleven studies encompassing 960 patients were included for the synthesis after critical evaluation. Systematic (MD − 18.05, 95% Cl, − 22.01, − 14.09, p < 0.00001) and topical (MD − 74.93, 95% Cl, − 88.79, − 61.07, p < 0.00001) administration of tranexamic acid reduced total blood loss. Topical tranexamic acid reduced drainage output (p < 0.0006).

Conclusion

Tranexamic acid reduced blood loss in aesthetic plastic surgery. More strictly defined RCTs, using high-quality methodology, are needed to evaluate the advantages and disadvantages of tranexamic acid in aesthetic plastic surgery.
High efficacy of huCD20-targeted AcTaferon in humanized patient derived xenograft models of aggressive B cell lymphoma
Authors: Daneels Willem , Van Parys Alexander , Huyghe Leander , Rogge Elke , De Rouck Steffi , Christiaen Ruben , Zabeau Lennart , Taveirne Sylvie , Van Dorpe Jo , Kley Niko , Cauwels Anje , Depla Erik , Tavernier Jan , Offner Fritz
Published: June 2024

Type I interferon (IFN) is a potent antitumoral drug, with an important history in the treatment of hematologic malignancies. However, its pleiotropic nature leads to severe dose-limiting toxicities that blunt its therapeutic potential. To achieve selective targeting of specific immune or tumor cells, AcTakines (Activity-on-Target Cytokines), i.e., immunocytokines utilizing attenuated cytokines, and clinically optimized A-Kines™ were developed. In syngeneic murine models, the CD20-targeted murine IFNα2-based AcTaferons (AFNs) have demonstrated clear antitumoral effects, with excellent tolerability. The current study explores the antitumoral potential of the humanized huCD20-Fc-AFN in 5 different humanized patient derived xenograft (PDX) models of huCD20+ aggressive B non-Hodgkin lymphomas (B-NHLs). The huCD20-Fc-AFN consists of a huCD20-specific single-domain antibody (VHH) linked through a heterodimeric ‘knob-in-hole’ human IgG1 Fc molecule to an attenuated huIFNα2 sequence. An in vitro targeting efficacy of up to 1.000-fold could be obtained, without detectable in vivo toxicities, except for selective (on-target) and reversible B cell depletion. Treatment with huCD20-Fc-AFN significantly increased the median overall survival (mOS) in both non-humanized (mOS 31 to 45 days; HR = 0.26; p = 0.001), and humanized NSG/NOG mice (mOS 34 to 80 days; HR = 0.37; p < 0.0001). In humanized mice, there was a trend for increased survival when compared to equimolar rituximab (mOS 49 to 80 days; HR = 0.73; p = 0.09). The antitumoral effects of huCD20-Fc-AFN were partly due to direct effects of type I IFN on the tumor cells, but additional effects via the human immune system are essential to obtain long-term remissions. To conclude, huCD20-Fc-AFN could provide a novel therapeutic strategy for huCD20-expressing aggressive B-NHLs.

Graphical Abstract
Discordant conceptualisations of eating disorder recovery and their influence on the construct of terminality
Authors: Elwyn Rosiel , Adams Marissa , Sharpe Sam L. , Silverstein Scout , LaMarre Andrea , Downs James , Burnette C. Blair
Published: June 2024

Eating disorders (EDs) are complex, multifaceted conditions that significantly impact quality-of-life, often co-occur with multiple medical and psychiatric diagnoses, and are associated with a high risk of medical sequelae and mortality. Fortunately, many people recover even after decades of illness, although there are different conceptualisations of recovery and understandings of how recovery is experienced. Differences in these conceptualisations influence categorisations of ED experiences (e.g., longstanding vs. short-duration EDs), prognoses, recommended treatment pathways, and research into treatment outcomes. Within recent years, the proposal of a ‘terminal’ illness stage for a subset of individuals with anorexia nervosa and arguments for the prescription of end-of-life pathways for such individuals has ignited debate. Semantic choices are influential in ED care, and it is critical to consider how conceptualisations of illness and recovery and power dynamics influence outcomes and the ED ‘staging’ discourse. Conceptually, ‘terminality’ interrelates with understandings of recovery, efficacy of available treatments, iatrogenic harm, and complex co-occurring diagnoses, as well as the functions of an individual’s eating disorder, and the personal and symbolic meanings an individual may hold regarding suffering, self-starvation, death, health and life. Our authorship represents a wide range of lived and living experiences of EDs, treatment, and recovery, ranging from longstanding and severe EDs that may meet descriptors of a ‘terminal’ ED to a variety of definitions of ‘recovery’. Our experiences have given rise to a shared motivation to analyse how existing discourses of terminality and recovery, as found in existing research literature and policy, may shape the conceptualisations, beliefs, and actions of individuals with EDs and the healthcare systems that seek to serve them.
Gut microbiota and metabolites signatures of clinical response in anti-PD-1/PD-L1 based immunotherapy of biliary tract cancer
Authors: Zhu Chengpei , Wang Yunchao , Zhu Ruijuan , Wang Shanshan , Xue Jingnan , Zhang Dongya , Lan Zhou , Zhang Chenchen , Liang Yajun , Zhang Nan , Xun Ziyu , Zhang Longhao , Ning Cong , Yang Xu , Chao Jiashuo , Long Junyu , Yang Xiaobo , Wang Hanping , Sang Xinting , Jiang Xianzhi , Zhao Haitao
Published: June 2024

Background

Accumulating evidence suggests that the gut microbiota and metabolites can modulate tumor responses to immunotherapy; however, limited data has been reported on biliary tract cancer (BTC). This study used metagenomics and metabolomics to identify characteristics of the gut microbiome and metabolites in immunotherapy-treated BTC and their potential as prognostic and predictive biomarkers.

Methods

This prospective cohort study enrolled 88 patients with BTC who received PD-1/PD-L1 inhibitors from November 2018 to May 2022. The microbiota and metabolites significantly enriched in different immunotherapy response groups were identified through metagenomics and LC-MS/MS. Associations between microbiota and metabolites, microbiota and clinical factors, and metabolites and clinical factors were explored.

Results

Significantly different bacteria and their metabolites were both identified in the durable clinical benefit (DCB) and non-durable clinical benefit (NDB) groups. Of these, 20 bacteria and two metabolites were significantly associated with survival. Alistipes were positively correlated with survival, while Bacilli, Lactobacillales, and Pyrrolidine were negatively correlated with survival. Predictive models based on six bacteria, four metabolites, and the combination of three bacteria and two metabolites could all discriminated between patients in the DCB and NDB groups with high accuracy. Beta diversity between two groups was significantly different, and the composition varied with differences in the use of immunotherapy.

Conclusions

Patients with BTC receiving immunotherapy have specific alterations in the interactions between microbiota and metabolites. These findings suggest that gut microbiota and metabolites are potential prognostic and predictive biomarkers for clinical outcomes of anti-PD-1/PD-L1-treated BTC.
Biomass yield and metal phytoextraction efficiency of Salix and Populus clones harvested at different rotation lengths in the field experiment
Authors: Prouzová Nikola , Kubátová Pavla , Mercl Filip , Száková Jiřina , Najmanová Jana , Tlustoš Pavel
Published: June 2024

Background

Phytoextraction belongs to environmentally well-accepted remediation technologies to remove metals from contaminated soils. Due to long-time requirement, sufficient data for proper phytoextraction evaluation are missing. Four clones of fast-growing trees: two willow species (S1), Salix viminalis L. (Salix schwerinii E.L.Wolf × S. viminalis) × S. viminalis) and (S2)—Salix smithiana (Salix × smithiana Willd.), and two poplar clones (P1), Populus Max-4 (Populus nigra L. × Populus maximowiczii A. Henry) and (P2) Wolterson (P. nigra L.) were cultivated under field conditions at medium-to-high Cd and Pb, and low Zn soil contamination to assess trees’ long-term ability of biomass production and removal of potentially toxic elements (PTEs). The biomass yield and PTE uptake were measured during 8 years of regular growth under three rotation lengths: four harvests following 2-year periods (4 × 2y), two harvests in 4-year periods (2 × 4y), and one harvest representing 8 years of growth (1 × 8y).

Results

In most cases, the highest annual dry biomass yield was achieved with a 2 × 4y rotation (P1 = 20.9 t ha−1 y−1, S2 = 18.4 t ha−1y−1), and the yield decreased in order 2 × 4y > 1 × 8y > 4 × 2y of harvesting periods. Only clone S1 showed a different pattern. The differences in biomass yield substantially affected the PTE phytoextraction. The greatest amount of Cd and Zn was removed by willow S2, with the highest biomass yield, and the strongest ability to accumulate PTEs. With 2 × 4y rotation, S2 removed a substantial amount of Cd (9.07%) and Zn (3.43%) from the topsoil horizon (0–20 cm) and 5.62% Cd and 2.04% Zn from horizon 20–40 cm; phytoextraction rate was slightly lower for 1 × 8y rotation. The poplar P1 removed the most Pb in the 1 × 8y rotation, but the overall Pb phytoextraction was negligible. The results indicated that lignin and cellulose contents increased, and hemicellulose content decreased with increased concentrations of Cd, Pb and Zn in poplars wood.

Conclusions

The data confirmed that phytoextraction over longer harvest periods offered promising results for removing Cd from medium- to high-level contaminated soils; however, the ability of Pb removal was extremely low. The longer harvest period should be more economically feasible.

Graphical Abstract
[18F]FAPI adds value to [18F]FDG PET/CT for diagnosing lymph node metastases in stage I-IIIA non-small cell lung cancer: a prospective study
Authors: Li Youcai , Zhang Yin , Guo Zhihua , Hou Peng , Lv Jie , Ke Miao , Liu Shaoyu , Li Siwen , Yin Weiqiang , He Jianxing , Wang Xinlu
Published: June 2024

Background

This study investigates the value of fluorine 18 ([18F])-labeled fibroblast activation protein inhibitor (FAPI) for lymph node (LN) metastases in patients with stage I-IIIA non-small cell lung cancer (NSCLC).

Methods

From November 2021 to October 2022, 53 patients with stage I-IIIA NSCLC who underwent radical resection were prospectively included. [18F]-fluorodeoxyglucose (FDG) and [18F]FAPI examinations were performed within one week. LN staging was validated using surgical and pathological findings. [18F]FDG and [18F]FAPI uptake was compared using the Wilcoxon signed-ranks test. Furthermore, the diagnostic value of nodal groups was investigated.

Results

In 53 patients (median age, 64 years, range: 31–76 years), the specificity of [18F]FAPI for detecting LN metastasis was significantly higher than that of [18F]FDG (P < 0.001). High LN risk category, greater LN short-axis dimension(≥ 1.0 cm), absence of LN calcification or high-attenuation, and higher LN FDG SUVmax (≥ 10.1) were risk factors for LN metastasis(P < 0.05). The concurrence of these four risk factors accurately predicted LN metastases (Positive Predictive Value [PPV] 100%), whereas the presence of one to three risk factors was unable to accurately discriminate the nature of LNs (PPV 21.7%). Adding [18F]FAPI in this circumstance improved the diagnostic value. LNs with an [18F]FAPI SUVmax<6.2 were diagnosed as benign (Negative Predictive Value 93.8%), and LNs with an [18F]FAPI SUVmax≥6.2 without calcification or high-attenuation were diagnosed as LN metastasis (PPV 87.5%). Ultimately, the integration of [18F]FDG and [18F]FAPI PET/CT resulted in the highest accuracy for N stage (83.0%) and clinical decision revisions for 29 patients.

Conclusion

In patients with stage I-IIIA NSCLC, [18F]FAPI contributed additional valuable information to reduce LN diagnostic uncertainties after [18F]FDG PET/CT. Integrating [18F]FDG and [18F]FAPI PET/CT resulted in more precise clinical decisions.

Trial registration

The Chinese Clinical Trial Registry: ChiCTR2100044944 (Registered: 1 April 2021, https://www.chictr.org.cn/showprojEN.html?proj=123995).
Research on digital informal learning of sports knowledge of Chinese undergraduates
Authors: Ye Zheng , Zhang Hui
Published: June 2024

With the development of digital technology, the proportion of time spent on digital informal learning in students’ daily lives is increasing. However, digital informal learning behaviors in sports field have not been fully justified and studied. This article aims to investigate the current situation and influencing factors of digital informal learning of sports knowledge (DIL-S) of Chinese undergraduates. As a cross-sectional study, 401 non-sports undergraduate students from six Chinese universities completed the DIL-S measurement questionnaire. The partial least squares structural equation modeling (PLS-SEM) was constructed to explore association among DIL-S, technology expectancy (TE) and digital competence (DC). Results show that (1) Male students’ cognitive learning (CL) was significantly better than that of females; Senior students’ metacognitive learning (MCL) was significantly better than that of junior students; Sports university students’ cognitive learning, metacognitive learning, and social and motivation learning (SML) were significantly better than that of non-sports university students. (2) Digital competence has a significant positive impact on technology expectancy and digital informal learning of sport knowledge, while technology expectancy has a significant negative impact on digital informal learning of sport knowledge. Based on the results, following conclusions can be made (1) Undergraduates have a strong competence to use digital technology and have a high interest in using digital technology to participate in learning. However, they have a low investment in digital informal learning of sports knowledge fields. (2) Males’ sports knowledge learning consciousness and actual performance are better than girls; Compared with freshmen, senior students have stronger monitoring and planning ability for personal sports knowledge learning; The behavior of digital informal learning of sports knowledge in sports university students is better than that of non-sports university students. (3) Digital competence and technological expectancy are key factors influencing digital informal learning of sport knowledge, with digital competence having the most significant impact. These findings underscore the need to enhance the promotion of digital informal learning among undergraduates and to develop assessments that improve their understanding and knowledge of sports.
Advances in the isolation, cultivation, and identification of gut microbes
Authors: Xu Meng-Qi , Pan Fei , Peng Li-Hua , Yang Yun-Sheng
Published: June 2024

The gut microbiome is closely associated with human health and the development of diseases. Isolating, characterizing, and identifying gut microbes are crucial for research on the gut microbiome and essential for advancing our understanding and utilization of it. Although culture-independent approaches have been developed, a pure culture is required for in-depth analysis of disease mechanisms and the development of biotherapy strategies. Currently, microbiome research faces the challenge of expanding the existing database of culturable gut microbiota and rapidly isolating target microorganisms. This review examines the advancements in gut microbe isolation and cultivation techniques, such as culturomics, droplet microfluidics, phenotypic and genomics selection, and membrane diffusion. Furthermore, we evaluate the progress made in technology for identifying gut microbes considering both non-targeted and targeted strategies. The focus of future research in gut microbial culturomics is expected to be on high-throughput, automation, and integration. Advancements in this field may facilitate strain-level investigation into the mechanisms underlying diseases related to gut microbiota.
Rosmarinic acid, a natural polyphenol, has a potential pro-oxidant risk via NADH-mediated oxidative DNA damage
Authors: Kobayashi Hatasu , Hirao Yuichiro , Kawanishi Shosuke , Kato Shinya , Mori Yurie , Murata Mariko , Oikawa Shinji
Published: June 2024

Background

Rosmarinic acid (RA) has a wide range of beneficial effects on human health. On the other hand, RA has been reported to induce metal-mediated reactive oxygen species (ROS) generation and DNA damage. However, its mechanism remains unknown. In this study, to clarify the underlying mechanism, we analyzed metal-mediated DNA damage in isolated DNA treated with RA and its analog isorinic acid.

Results

RA plus Cu(II), but not Fe(III), significantly increased 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG) formation, an indicator of oxidative DNA damage, in calf thymus DNA. Furthermore, a comparison of the 8-oxodG formation induced by RA and its analog isorinic acid suggested that the catechol groups in RA could be associated with their abilities to form 8-oxodG. Interestingly, the 8-oxodG formation induced by RA and isorinic acid plus Cu(II) was markedly enhanced by the addition of NADH, an endogenous reductant. To elucidate the mechanism of RA plus Cu(II)-induced oxidative DNA damage, we examined DNA damage in 32P-labeled DNA treated with RA in the presence of Cu(II). RA plus Cu(II) caused DNA cleavage, which was enhanced by piperidine treatment, suggesting that RA causes not only DNA strand breakage but also base modification. RA plus Cu(II)-induced DNA damage was inhibited by catalase (H2O2 scavenger), bathocuproine (Cu(I) chelator), and methional (scavenger of a variety of ROS other than •OH) but not by typical •OH scavengers and SOD, indicating the involvement of H2O2, Cu(I), and ROS other than •OH. DNA cleavage site analysis showing RA-induced site-specific DNA damage (frequently at thymine and some cytosine residues) supports the involvement of ROS other than •OH, because •OH causes DNA cleavage without site specificity. Based on these results, Cu(I) and H2O2 generation with concomitant RA autoxidation could lead to the production of Cu(I)-hydroperoxide, which induces oxidative DNA damage. o-Quinone and o-semiquinone radicals are likely to be again reduced to RA by NADH, which dramatically increases oxidative DNA damage, particularly at low concentrations of RA.

Conclusions

In this study, physiologically relevant concentrations of RA effectively induced oxidative DNA damage in isolated DNA through redox cycle reactions with copper and NADH.
Assessing nutrition-related knowledge, attitudes, and practices towards breast cancer prevention among female students at the Federal University of Oye-Ekiti, Nigeria
Authors: Kolawole Ibiwumi Damaris , Kunle Oni , Ajayi Kayode , Ong Thomas Prates
Published: June 2024

Background

Breast cancer remains a complex disease and leading cause of cancer-related death in Nigerian women. Recently, the role of nutrition has been highlighted in the etiology of breast cancer.

Methods

The aim of this research was to evaluate the nutrition-related knowledge, attitude, and practices of female university students. We also investigated the correlation between their demographic characteristics and their knowledge and attitudes of the survey participants. A descriptive cross-sectional study was carried out among female students at the Federal University of Oye (FUOYE), Nigeria. Participants completed self-administered questionnaires designed to assess their knowledge, attitude, and practices concerning cancer prevention. Statistical analysis was performed using SPSS 20, and significance was set at p < 0.05.

Results

Out of the 402 students who received the questionnaire, 300 completed it. The average age of the participants was 21.26 years with a standard deviation of 2.68. There was generally limited knowledge regarding breast cancer risk factors, with 45% of participants citing family history as the most recognized risk factor. Overall, knowledge level was influenced by the participants’ permanent place of residence and course of study. Attitudes towards the impact of maternal and paternal nutrition on breast cancer prevention were notably low. Additionally, less than half of the participants demonstrated good dietary practices.

Conclusion

This study revealed low levels of nutrition-related knowledge concerning cancer prevention, accompanied by poor dietary habits among the participants. These results suggest a possible link between inadequate knowledge about breast cancer prevention and the observed poor dietary practices among the participants. The frequent consumption of unhealthy foods among the participants may be a pointer to higher risk of breast cancer in the future, emphasizing a need for health education targeted at this group.
Hunter–Prey Optimization Algorithm: a review
Authors: Lahari Pappu Soundarya , Janamala Varaprasad
Published: June 2024

The Hunter–Prey Optimization Algorithm (HPO) is a nature-inspired optimization technique influenced by the predator–prey relationships observed in nature. Over the years, HPO has gained attention as a promising method for solving complex optimization problems. This review article provides a comprehensive analysis and a bibliographic study of the Hunter–Prey Optimization Algorithm. It explores its origins, underlying principles, applications, strengths, weaknesses, and recent developments in detail. By delving into various facets of HPO, this review aims to shed light on its effectiveness and potential, inspiring the researchers to address real-world optimization challenges.
COVID-19 pandemic, oil prices and Saudi stock market: empirical evidence from ARDL modeling and Bayer–Hanck cointegration approach
Authors: Boukhatem Jamel , Alhazmi Ali M.
Published: June 2024

In 2020, the world experienced several significant events, including the coronavirus (COVID-19) pandemic and the collapse of international crude oil prices. The rapid spread of this pandemic has dramatic impacts on financial markets all over the world, thereby increasing market risk aversion in an unprecedented way since the subprime financial crisis. The decline in stock markets implied volatilities of equity and oil prices, thereby heightening turmoil in global financial markets despite comprehensive and substantial financial reforms. To this end, we investigated the likely effects of this pandemic on the Saudi stock market while controlling for oil prices based on daily data for a period from 1/1/2020 to 19/9/2022. To ascertain the existence of a long-run equilibrium relationship between the variables, we applied autoregressive distributed lag (ARDL) modeling and the error correction model, with this ultimately revealing the existence of strong cointegration in the long run. The ARDL bounds test was found to be robust by combined cointegration tests, thus providing further evidence of a strong relationship in the long run. Granger causality tests also yielded evidence of causality between the variables in both directions. The total COVID-19 confirmed cases and oil prices also caused movements in stock returns in the short run. Our findings have some prominent implications for asset managers and policymakers to improve stock market efficiency and boost global economic activity. Saudi authorities can consequently remove the regulatory and legal obstacles to develop their stock market and better improve the risk management, which will allow to make quick decisions in response to any oil price volatilities. Policymakers should also adopt proactive strategies that can comfort stock investors’ anxieties over the increasing oil price volatilities. Finally, the findings should be treated with some cautions because of the limited sample size and the tests’ statistical inference. Nevertheless, they do open opportunities for further studies to look in more detail at how the COVID-19 pandemic affected, over the short and long run, monetary and fiscal policy coordination, financial stability, and various other macroeconomic indicators in Saudi Arabia.