bluuebunny/crossref_metadata_2025 huggingface dataset:
Amelioration of Atherosclerosis by lycopene is linked to the modulation of gut microbiota dysbiosis and related gut-heart axis activation in high-fat diet-fed ApoE−/− mice
Authors: Tu Tengcan , Liu Hao , Liu Zhenhao , Liang Yunyi , Tan Chujun , Feng Dan , Zou Jun
Published: December 2023

Background

Interplay between gut microbiota and heart, termed “gut-heart” axis, has a crucial role in the pathogenesis of atherosclerosis. Our previous study showed that lycopene possesses anti-inflammatory and anti-atherosclerotic effects, but its link to the gut microbiota is poorly understood. Herein, we surmised that lycopene could regulate the gut microbiota, exert anti-atherosclerotic effect by regulating the “gut-heart” axis.

Methods

Male ApoE−/− mice were fed a high-fat diet (HFD) with or without lycopene (0.1% w/w) for 19 weeks. Gut microbiota was analyzed by 16 S rRNA sequencing, the protein levels of zonula occludens-1 (ZO-1), occludin, toll-like receptor 4 (TLR4) and phospho-nuclear factor-κB (NF-κB) p65 were measured by Western blotting, the levels of serum inflammatory factors including monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 were assayed using ELISA kits. Also, the concentrations of serum lipopolysaccharide (LPS), D-lactic acid (D-LA) and diamine peroxidase (DAO) were measured through ELISA method.

Results

The aortic sinus sections revealed that lycopene supplementation significantly reduced the extent of atherosclerotic lesions and inhibited atherosclerosis development caused by HFD. The analysis of gut microbiota showed that lycopene reduced the ratio of Firmicutes/Bacteroides and increased the relative abundance of Verrucomicrobia, Akkermansia and Alloprevotella, which were related to elevated intestinal barrier function and reduced inflammation. Moreover, lycopene up-regulated the expression of intestinal ZO-1 and occludin and decreased serum LPS, D-LA and DAO levels. In addition, lycopene inhibited the expression of TLR4 and phospho-NF-κB p65 in aortic sinus plaque, serum MCP-1, TNF-α, IL-1β, and IL-6 levels were also lowered by lycopene treatment.

Conclusions

Our results indicated the protective effect of lycopene against atherosclerosis induced by HFD and further revealed that its mechanism might be its prebiotic effect on maintaining gut microbiota homeostasis and improving intestinal barrier function, consequently reducing serum LPS-triggered inflammatory response in the heart.
A novel visual marker to distinguish haploids from doubled haploids in rice (Oryza sativa, L) at early growth stages
Authors: Ghalagi Chaitanya , Namratha Malavalli Rajashekar , Kotyal Kavita , Prakash Shiva , Raju Basavaiah Mohan
Published: December 2023

Doubled haploid technology, which enables the generation of homozygous lines in a single step, is one of the modern tools being employed for accelerating breeding processes in different crops. In rice, a globally important staple food crop, doubled haploid production through androgenesis is increasingly being employed in breeding programs. Amongst the androgenic rice lines, doubled haploids are formed spontaneously at about 50–60%, while the remaining 40–50% of plants remain as haploids. As haploids cannot be easily identified, it is routine to grow all the rice androgenic lines till maturity and harvest the seeds from the fertile doubled haploids. Therefore, the methods that facilitate easy identification of haploids at an early developmental stage in rice would enable treatment of such haploid lines with colchicine, to increase the efficiency of doubled haploid production. Further, it would also help in eliminating the operational cost involved in maintaining them till maturity. In the above context, a systematic study to identify easily observable physiological and morphological differences between haploid and doubled haploid rice lines was undertaken. Rice haploids were found to be noticeably different from doubled haploids in photosynthetic rate, transpiration rate, stomatal conductance, and morphology of lodicules, stigma and style, features which have not been reported before. Most importantly, rice haploids invariably have acute leaf apex which is easily distinguishable from the doubled haploids that have attenuated leaf apex shape. Very high per cent accuracy in the prediction of ploidy level was observed when haploids were identified at an early developmental stage based on leaf apex shape, and the results verified with flow cytometry perfectly matches with leaf apex shape. The study establishes ‘acute leaf apex’ shape as an accurate visual marker to rapidly identify haploid rice lines at an early developmental stage in a cost-effective manner.
New algorithms for structure informed genome rearrangement
Authors: Ozeri Eden , Zehavi Meirav , Ziv-Ukelson Michal
Published: December 2023

We define two new computational problems in the domain of perfect genome rearrangements, and propose three algorithms to solve them. The rearrangement scenarios modeled by the problems consider Reversal and Block Interchange operations, and a PQ-tree is utilized to guide the allowed operations and to compute their weights. In the first problem,$$\mathsf {Constrained \ TreeToString \ Divergence}$$ConstrainedTreeToStringDivergence($$\textsf{CTTSD}{}$$CTTSD), we define the basic structure-informed rearrangement measure. Here, we assume that the gene order members of the gene cluster from which the PQ-tree is constructed are permutations. The PQ-tree representing the gene cluster is ordered such that the series of gene IDs spelled by its leaves is equivalent to that of the reference gene order. Then, a structure-informed genome rearrangement distance is computed between the ordered PQ-tree and the target gene order. The second problem,$$\mathsf {TreeToString \ Divergence}$$TreeToStringDivergence($$\textsf{TTSD}{}$$TTSD), generalizes$$\textsf{CTTSD}{}$$CTTSD, where the gene order members are not necessarily permutations and the structure informed rearrangement measure is extended to also consider up to$$d_S$$dSand$$d_T$$dTgene insertion and deletion operations, respectively, when modelling the PQ-tree informed divergence process from the reference gene order to the target gene order. The first algorithm solves$$\textsf{CTTSD}{}$$CTTSDin$$O(n \gamma ^2 \cdot (m_p \cdot 1.381^\gamma + m_q))$$O(nγ2·(mp·1.381γ+mq))time and$$O(n^2)$$O(n2)space, where$$\gamma $$γis the maximum number of children of a node,nis the length of the string and the number of leaves in the tree, and$$m_p$$mpand$$m_q$$mqare the number of P-nodes and Q-nodes in the tree, respectively. If one of the penalties of$$\textsf{CTTSD}$$CTTSDis 0, then the algorithm runs in$$O(n m \gamma ^2)$$O(nmγ2)time and$$O(n^2)$$O(n2)space. The second algorithm solves$$\textsf{TTSD}{}$$TTSDin$$O(n^2 \gamma ^2 {d_T}^2 {d_S}^2\,m^2 (m_p \cdot 5^\gamma \gamma + m_q))$$O(n2γ2dT2dS2m2(mp·5γγ+mq))time and$$O(d_T d_S m (m n + 5^\gamma ))$$O(dTdSm(mn+5γ))space, where$$\gamma $$γis the maximum number of children of a node,nis the length of the string,mis the number of leaves in the tree,$$m_p$$mpand$$m_q$$mqare the number of P-nodes and Q-nodes in the tree, respectively, and allowing up to$$d_T$$dTdeletions from the tree and up to$$d_S$$dSdeletions from the string. The third algorithm is intended to reduce the space complexity of the second algorithm. It solves a variant of the problem (where one of the penalties of$$\textsf{TTSD}$$TTSDis 0) in$$O(n \gamma ^2 {d_T}^2 {d_S}^2\,m^2 (m_p \cdot 4^{\gamma }\gamma ^2n(d_T+d_S+m+n) + m_q))$$O(nγ2dT2dS2m2(mp·4γγ2n(dT+dS+m+n)+mq))time and$$O(\gamma ^2 n m^2 d_T d_S (d_T+d_S+m+n))$$O(γ2nm2dTdS(dT+dS+m+n))space. The algorithm is implemented as a software tool, denoted MEM-Rearrange, and applied to the comparative and evolutionary analysis of 59 chromosomal gene clusters extracted from a dataset of 1487 prokaryotic genomes.
Inhibition of miR-96-5p alleviates intervertebral disc degeneration by regulating the peroxisome proliferator-activated receptor γ/nuclear factor-kappaB pathway
Authors: Li Xusheng , Hou Qian , Yuan Wenqi , Zhan Xuehua , Yuan Haifeng
Published: December 2023

Background

Intervertebral disc degeneration (IDD) is the main pathogenesis of low back pain. MicroRNAs (miRNAs) have been found to exert regulatory function in IDD. This study aimed to investigate the effect and potential mechanism of miR-96-5p in IDD.

Methods

In vitro cell model of IDD was established by treating human nucleus pulposus cells (HNPCs) with interleukin-1β (IL-1β). The level of peroxisome proliferator-activated receptor γ (PPARγ) was examined in the IDD cell model by Western blot and quantification real-time reverse transcription-polymerase chain reaction (qRT-PCR). The expression level of miR-96-5p was detected by RT-qPCR. Effects of PPARγ or/and PPARγ agonist on inflammatory factors, extracellular matrix (ECM), apoptosis, and nuclear factor-kappaB (NF-κB) nuclear translocation were examined through enzyme-linked immunosorbent assay (ELISA), Western blot, flow cytometry assay, and immunofluorescence staining. The Starbase database and dual luciferase reporter assay were used to predict and validate the targeting relationship between miR-96-5p and PPARγ, and rescue assay was performed to gain insight into the role of miR-96-5p on IDD through PPARγ/NF-κB signaling.

Results

PPARγ expression reduced with concentration and time under IL-1β stimulation, while miR-96-5p expression showed the reverse trend (P < 0.05). Upregulation or/and activation of PPARγ inhibited IL-1β-induced the increase in inflammatory factor levels, apoptosis, degradation of the ECM, and the nuclear translocation of NF-κB (P < 0.05). MiR-96-5p was highly expressed but PPARγ was lowly expressed in IDD, while knockdown of PPARγ partially reversed remission of IDD induced by miR-96-5p downregulation (P < 0.05). MiR-96-5p promoted NF-κB entry into the nucleus but PPARγ inhibited this process.

Conclusion

Inhibition of miR-96-5p suppressed IDD progression by regulating the PPARγ/NF-κB pathway. MiR-96-5p may be a promising target for IDD treatment clinically.
Adaptive evaluation of mHealth and conventional adherence support interventions to optimize outcomes with new treatment regimens for drug-resistant tuberculosis and HIV in South Africa (ADAP-TIV): study protocol for an adaptive randomized controlled trial
Authors: Ross Jesse , Perumal Rubeshan , Wolf Allison , Zulu Mbali , Guzman Kevin , Seepamore Boitumelo , Reis Karl , Nyilana Hlengiwe , Hlathi Senzo , Narasimmulu Radhamoney , Cheung Ying Kuen K. , Amico K. Rivet , Friedland Gerald , Daftary Amrita , Zelnick Jennifer R. , Naidoo Kogieleum , O’Donnell Max R.
Published: December 2023

Background

Highly effective, short-course, bedaquiline-containing treatment regimens for multidrug-resistant tuberculosis (MDR-TB) and integrase strand transfer inhibitor (INSTI)-containing fixed dose combination antiretroviral therapy (ART) have radically transformed treatment for MDR-TB and HIV. However, without advances in adherence support, we may not realize the full potential of these therapeutics. The primary objective of this study is to compare the effect of adherence support interventions on clinical and biological endpoints using an adaptive randomized platform.

Methods

This is a prospective, adaptive, randomized controlled trial comparing the effectiveness of four adherence support strategies on a composite clinical outcome in adults with MDR-TB and HIV initiating bedaquiline-containing MDR-TB treatment regimens and receiving ART in KwaZulu-Natal, South Africa. Trial arms include (1) enhanced standard of care, (2) psychosocial support, (3) mHealth using cellular-enabled electronic dose monitoring, and (4) combined mHealth and psychosocial support. The level of support will be titrated using a differentiated service delivery (DSD)-informed assessment of treatment support needs. The composite primary outcome will include survival, negative TB culture, retention in care, and undetectable HIV viral load at month 12. Secondary outcomes will include individual components of the primary outcome and quantitative evaluation of adherence on TB and HIV treatment outcomes.

Discussion

This trial will evaluate the contribution of different modes of adherence support on MDR-TB and HIV outcomes with WHO-recommended all-oral MDR-TB regimens and ART in a high-burden operational setting. We will also assess the utility of a DSD framework to pragmatically adjust levels of MDR-TB and HIV treatment support.

Trial registration

ClinicalTrials.gov NCT05633056. Registered on 1 December 2022
Effectiveness and mediators of change of an online CBT intervention for students with adjustment disorder—study protocol for a randomized controlled trial
Authors: Juszczyk-Kalina A. , Holas P. , Farchione T. J.
Published: December 2023

Background

Adjustment problems and disorders are highly prevalent among university students worldwide. These problems can cause significant interference in academic and social functioning and increase vulnerability to other mental health disorders. Unfortunately, only half of students in need receive psychological help. Furthermore, few studies have evaluated psychological interventions for adjustment disorders in students. New, more scalable forms of treatment for students with an adjustment disorder need to be developed, evaluated, and implemented. The study aims to determine the effectiveness of an online transdiagnostic cognitive behavioural intervention for students experiencing adjustment disorder and to assess mediators of change.

Method/design

In this three-arm randomized controlled trial, we plan to recruit 214 Polish students diagnosed with an adjustment disorder. Participants who meet initial eligibility criteria will be randomly assigned to one of three 6-week conditions: (1) online cognitive behavioural therapy intervention based on an existing, empirically supported transdiagnostic protocol, the unified protocol; (2) online progressive muscle relaxation training as an active control group; or (3) waiting-list control group. Both interventions are asynchronous, interactive, and include minimal amount of therapist support. Assessments will consist of self-report questionnaires, daily diary measures, and neurocognitive tasks for evaluating cognitive functioning. These will be conducted at baseline, post-treatment, and 1-month follow-up. Daily diary measures will be taken during the first and last week of treatment (or waitlist period). Primary outcome measures will include adjustment disorder severity; secondary outcome measures will consist of other negative (psychopathology: depression, anxiety, and stress) and positive (life satisfaction) indexes of mental health as well as process measures (e.g. mindfulness, experiential avoidance, cognitive fusion).

Discussion

To our knowledge, the current study is the first to evaluate the effectiveness of a psychological intervention for students with adjustment disorder. Therefore, it may have important practical implications for students with this disorder. It can potentially guide the development of a scalable, validated treatment option.

Trial registration

Clinical Trials, NCT05768308, registered 14 March 2023, https://www.clinicaltrials.gov/ct2/show/NCT05768308
Differential interactome mapping of aggregation prone/prion-like proteins under stress: novel links to stress granule biology
Authors: Younas Neelam , Zafar Saima , Saleem Tayyaba , Fernandez Flores Leticia Camila , Younas Abrar , Schmitz Matthias , Zerr Inga
Published: December 2023

Background

Aberrant stress granules (SGs) are emerging as prime suspects in the nucleation of toxic protein aggregates. Understanding the molecular networks linked with aggregation-prone proteins (prion protein, synuclein, and tau) under stressful environments is crucial to understand pathophysiological cascades associated with these proteins.

Methods

We characterized and validated oxidative stress-induced molecular network changes of endogenous aggregation-prone proteins (prion protein, synuclein, and tau) by employing immunoprecipitation coupled with mass spectrometry analysis under basal and oxidative stress conditions. We used two different cell models (SH-SY5Y: human neuroblastoma and HeLa cell line) to induce oxidative stress using a well-known inducer (sodium arsenite) of oxidative stress.

Results

Overall, we identified 597 proteins as potential interaction partners. Our comparative interactome mapping provides comprehensive network reorganizations of three aggregation-prone hallmark proteins, establish novel interacting partners and their dysregulation, and validates that prion protein and synuclein localize in cytoplasmic SGs. Localization of prion protein and synuclein in TIA1-positive SGs provides an important link between SG pathobiology and aggregation-prone proteins. In addition, dysregulation (downregulation) of prion protein and exportin-5 protein, and translocation of exportin-5 into the nucleus under oxidative stress shed light on nucleocytoplasmic transport defects during the stress response.

Conclusions

The current study contributes to our understanding of stress-mediated network rearrangements and posttranslational modifications of prion/prion-like proteins. Localization of prion protein and synuclein in the cytoplasmic SGs provides an important link between stress granule pathobiology and aggregation-prone proteins. In addition, our findings demonstrate nucleocytoplasmic transport defects after oxidative stress via dysregulation and nuclear accumulation of exportin-5.
Predictive and prognostic biomarkers of bone metastasis in breast cancer: current status and future directions
Authors: Wang Shenkangle , Wu Wenxin , Lin Xixi , Zhang Kevin Matthew , Wu QingLiang , Luo Mingpeng , Zhou Jichun
Published: December 2023

The most common site of metastasis in breast cancer is the bone, where the balance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation is disrupted. This imbalance causes osteolytic bone metastasis in breast cancer, which leads to bone pain, pathological fractures, spinal cord compression, and other skeletal-related events (SREs). These complications reduce patients' quality of life significantly and have a profound impact on prognosis. In this review, we begin by providing a brief overview of the epidemiology of bone metastasis in breast cancer, including current diagnostic tools, treatment approaches, and existing challenges. Then, we will introduce the pathophysiology of breast cancer bone metastasis (BCBM) and the animal models involved in the study of BCBM. We then come to the focus of this paper: a discussion of several biomarkers that have the potential to provide predictive and prognostic value in the context of BCBM—some of which may be particularly compatible with more comprehensive liquid biopsies. Beyond that, we briefly explore the potential of new technologies such as single-cell sequencing and organoid models, which will improve our understanding of tumor heterogeneity and aid in the development of improved biomarkers. The emerging biomarkers discussed hold promise for future clinical application, aiding in the prevention of BCBM, improving the prognosis of patients, and guiding the implementation of personalized medicine.
Effective acoustic parameters for automatic classification of performed and synthesized Guzheng music
Authors: Xue Huiwen , Sun Chenxin , Tang Mingcheng , Hu Chenrui , Yuan Zhengqing , Huang Min , Xiao Zhongzhe
Published: December 2023

This study focuses on exploring the acoustic differences between synthesized Guzheng pieces and real Guzheng performances, with the aim of improving the quality of synthesized Guzheng music. A dataset with consideration of generalizability with multiple sources and genres is constructed as the basis of analysis. Classification accuracy up to 93.30% with a single feature put forward the fact that although the synthesized Guzheng pieces in subjective perception evaluation are recognized by human listeners, there is a very significant difference to the performed Guzheng music. With features compensating to each other, a combination of only three features can achieve a nearly perfect classification accuracy of 99.73%, with the essential two features related to spectral flux and an auxiliary feature related to MFCC. The conclusion of this work points out a potential future improvement direction in Guzheng synthesized algorithms with spectral flux properties.
Data extraction and comparison for complex systematic reviews: a step-by-step guideline and an implementation example using open-source software
Authors: Afifi Mohamed , Stryhn Henrik , Sanchez Javier
Published: December 2023

Background

Data extraction (DE) is a challenging step in systematic reviews (SRs). Complex SRs can involve multiple interventions and/or outcomes and encompass multiple research questions. Attempts have been made to clarify DE aspects focusing on the subsequent meta-analysis; there are, however, no guidelines for DE in complex SRs. Comparing datasets extracted independently by pairs of reviewers to detect discrepancies is also cumbersome, especially when the number of extracted variables and/or studies is colossal. This work aims to provide a set of practical steps to help SR teams design and build DE tools and compare extracted data for complex SRs.

Methods

We provided a 10-step guideline, from determining data items and structure to data comparison, to help identify discrepancies and solve data disagreements between reviewers. The steps were organised into three phases: planning and building the database and data manipulation. Each step was described and illustrated with examples, and relevant references were provided for further guidance. A demonstration example was presented to illustrate the application of Epi Info and R in the database building and data manipulation phases. The proposed guideline was also summarised and compared with previous DE guidelines.

Results

The steps of this guideline are described generally without focusing on a particular software application or meta-analysis technique. We emphasised determining the organisational data structure and highlighted its role in the subsequent steps of database building. In addition to the minimal programming skills needed, creating relational databases and data validation features of Epi info can be utilised to build DE tools for complex SRs. However, two R libraries are needed to facilitate data comparison and solve discrepancies.

Conclusions

We hope adopting this guideline can help review teams construct DE tools that suit their complex review projects. Although Epi Info depends on proprietary software for data storage, it can still be a potential alternative to other commercial DE software for completing complex reviews.
PPO-based deployment and phase control for movable intelligent reflecting surface
Authors: Zhao Yikun , Zhou Fanqin , Liu Huaide , Feng Lei , Li Wenjing
Published: December 2023

Intelligent reflecting surface (IRS) stands as a promising technology to revolutionize wireless communication by manipulating incident signal amplitudes and phases to enhance system performance. While existing research primarily centers around optimizing the phase shifts of IRS, the deployment of IRS on movable platforms introduces a new degree of freedom in the design of IRS-assisted systems. Leveraging flexible deployment strategies for IRS holds the potential to further amplify network throughput and extend coverage. This paper addresses the challenging non-convex joint optimization problem of the movable IRS and proposes a dynamic optimization algorithm based on proximal policy optimization (PPO) for dynamically optimizing the aerial position and phase configuration of IRS. Simulation results show the effectiveness of the proposed approach, demonstrating significant performance improvements compared to communication schemes without IRS assistance and conventional static IRS-assisted methods.
A study on a political system for the advance in green hydrogen technology: a South Korea case study
Authors: Yun Minyoung , Jang Wooseok , Lim Jongyeon , Yun Bitnari
Published: December 2023

Background

Hydrogen energy, a type of renewable energy if produced without fossil fuel, has a critical issue in that most of it is still produced from carbon footprint heavy industries such as the fossil fuel industry. It is imperative to produce hydrogen from renewable sources on a global level so that the carbon footprint can be curbed. South Korea, along with other global economies such as the US, the EU, Japan and China, has shown its resolution to build a hydrogen economy with green hydrogen produced only from renewable sources. Since 2017, South Korea has been actively shaping its political actions and policies to develop the necessary technology for this transition. This study focuses on South Korea's actions and policies, using a political system model to better understand the shift towards a green hydrogen economy.

Results

The analysis shows that budgeting for R&D projects has had a significant impact on scientific breakthroughs, advancements, and product development in the field of green hydrogen in South Korea. These actions have also affected market performance, resulting in increased interest and investment in green hydrogen. Although there have been significant advancements in the field of green hydrogen in South Korea, the current state of technology remains in its early stages of development. Most of the breakthroughs have been in water-to-hydrogen and biomass-to-hydrogen technologies. However, these technologies show promise as the foundation of a thriving hydrogen economy in South Korea. The analysis also indicates a strong market demand for green hydrogen technology. To support these efforts, the political system has focused its financial support on water-to-hydrogen technology and projects at the TRL 1–3 stage.

Conclusions

The study concludes that ongoing financial and political support is necessary for areas showing outstanding performance to vitalize the hydrogen economy and facilitate the transition to a green hydrogen society in the future. Additionally, a robust legal framework is crucial to ensure steady growth of the green hydrogen economy, similar to those in other major hydrogen economies such as the US and Germany. This study serves as a case study of South Korea, showcasing the impact of political actions on the advancement of scientific technology.
Conventional versus organic olive farming: which has a better economic performance?
Authors: Martín-García Jaime , Gómez-Limón José A. , Arriaza Manuel
Published: December 2023

The European Green Deal sets a target of at least 25% of the total EU agricultural land under organic farming by 2030. In the case of the Spanish olive sector, organic olive farming accounts for barely 10% of the national agricultural area dedicated to this crop. Within this context, this study compares the economic performance of Spanish conventional and organic olive farms in terms of productivity, profitability, viability, resilience, and independence. To do so, microdata provided by the Spanish Farm Accountancy Data Network have been used, and matching methods have been applied to conduct an unbiased comparative analysis of matched conventional and organic farms. Results show statistically significant differences in productivity, with conventional olive groves being more productive. However, CAP subsidies are shown to be an effective instrument for promoting the conversion to organic farming in olive groves since they cancel out the differences in profitability between these two production systems. There is also evidence of the greater resilience of organic farms. These results could contribute to a more efficient design of instruments promoting the ecological transition of agriculture in line with the aforementioned policy objective.
A bile-based microRNA signature for differentiating malignant from benign pancreaticobiliary disease
Authors: Mato Prado Mireia , Puik Jisce R. , Castellano Leandro , López-Jiménez Elena , Liu Daniel S. K. , Meijer Laura L. , Le Large Tessa Y. S. , Rees Eleanor , Funel Niccola , Sivakumar Shivan , Pereira Stephen P. , Kazemier Geert , Zonderhuis Babs M. , Erdmann Joris I. , Swijnenburg Rutger-Jan , Frilling Andrea , Jiao Long R. , Stebbing Justin , Giovannetti Elisa , Krell Jonathan , Frampton Adam E.
Published: December 2023

Differentiating between pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CCA) is crucial for the appropriate course of treatment, especially with advancements in the role of neoadjuvant chemotherapies for PDAC, compared to CCA. Furthermore, benign pancreaticobiliary diseases can mimic malignant disease, and indeterminate lesions may require repeated investigations to achieve a diagnosis. As bile flows in close proximity to these lesions, we aimed to establish a bile-based microRNA (miRNA) signature to discriminate between malignant and benign pancreaticobiliary diseases. We performed miRNA discovery by global profiling of 800 miRNAs using the NanoString nCounter platform in prospectively collected bile samples from malignant (n = 43) and benign (n = 14) pancreaticobiliary disease. Differentially expressed miRNAs were validated by RT-qPCR and further assessed in an independent validation cohort of bile from malignant (n = 37) and benign (n = 38) pancreaticobiliary disease. MiR-148a-3p was identified as a discriminatory marker that effectively distinguished malignant from benign pancreaticobiliary disease in the discovery cohort (AUC = 0.797 [95% CI 0.68–0.92]), the validation cohort (AUC = 0.772 [95% CI 0.66–0.88]), and in the combined cohorts (AUC = 0.752 [95% CI 0.67–0.84]). We also established a two-miRNA signature (miR-125b-5p and miR-194-5p) that distinguished PDAC from CCA (validation: AUC = 0.815 [95% CI 0.67–0.96]; and combined cohorts: AUC = 0.814 [95% CI 0.70–0.93]). Our research stands as the largest, multicentric, global profiling study of miRNAs in the bile from patients with pancreaticobiliary disease. We demonstrated their potential as clinically useful diagnostic tools for the detection and differentiation of malignant pancreaticobiliary disease. These bile miRNA biomarkers could be developed to complement current approaches for diagnosing pancreaticobiliary cancers.

Graphical Abstract
Interregional and intraregional interaction of the Tianshanbeilu population in eastern Xinjiang from the perspective of pottery analysis
Authors: Zeng Baodong , Ma Tao , Wang Yongqiang , Zhang Jie , Zhang Liangren , Chang Xi’en
Published: December 2023

The beginning of human settlement in the Hami Basin, located in the eastern part of Xinjiang, has been a focal question for the academic community in China. In particular, the thesis that the immigrating population from the Hexi Corridor since the late Neolithic founded the Tianshanbeilu culture has riveted the attention of scholars. Pottery wares, abundantly discovered at the synonymous cemetery of this culture, have played a key role in extrapolating population migration and cultural interaction. This paper aims to test the thesis by characterizing the chemical composition, painting pigment, and carburizing technique of 70 pottery samples from the cemetery with various scientific methods. It shows that the chemical compositions of the coarse pottery in the three colors of red, yellow, and gray, painted and unpainted alike, are remarkably different from those of fine pottery in black and red, indicating that the raw materials for the coarse and fine pottery samples are possibly procured from different sources; the pigments of the red slip and black paint are derived from hematite, black manganese ore, and carbon black; carburizing and polishing techniques are further applied to the gray coarse pottery; In combination with the compositional data of pottery samples from the Yaer cemetery also in the Hami Basin and the Xichengyi settlement in the Hexi Corridor, this paper finds that some pottery wares of the Tianshanbeilu culture were exchanged within the Hami Basin, but each site had its own production facility. No direct exchange of pottery wares with Xichengyi is attested; the similar style of pottery wares between the two sites may have resulted from population migration and technological exchange.
New solidification simulation reveals the secret of the hidden metal cores in ancient Chinese bronzes
Authors: Yang Huan , Fang Minghui , Chang Yihang , Liu Ruiliang , Fang Zhao , Yang Junchang
Published: December 2023

Regardless of the tremendous number of studies on ancient Chinese bronzes and fruitful understanding of the raw materials, technologies and their cultural significance, many related issues have still not been tackled. In particular, it has been known for decades that the legs of Shang and Zhou bronzes have metal cores, but their specific function remains ambiguous. In this work, the Finite Element Method is applied to simulate the pouring and solidification process of bronze cores of different sizes. The findings illustrate that throughout the casting process, the metal core not only maintains the uniformity of the bronze and reducing its’s wall thickness but also lowers the temperature of the surrounding alloy liquid, serving as a casting chill. Specifically, the metal core allows elimination of over 60% of casting defects. In comparison with more widespread clay cores, metal cores help produce less shrinkage porosity, therefore prevent cracking of the legs that is usually caused by different shrinkage rates between the clay core and the metal wall. In summary, the use of metal cores in ancient Chinese bronzes reveals a deep knowledge about the metal properties and the solidification process since the Chinese late Shang period (ca. 1250–1045 BC).
Family social and cultural capital: an analysis of effects on adolescents’ educational outcomes in China
Authors: Tan Gek Ling Claire , Fang Zheng
Published: December 2023

Using a sample of 11,313 students in Grades 7 and 9 from the China Education Panel Survey, this study examines the effects of family social capital and family cultural capital on adolescents’ educational outcomes in the areas of academic effort, educational aspiration, and academic achievement. The results from structural equation modeling analyses showed that family social capital and family cultural capital had significant positive associations with adolescents’ educational aspirations. However, only family cultural capital had a significant positive association with academic effort, while family social capital showed a non-significant negative association, and both forms of family capital had significant negative associations with academic achievement.
Age-Markers on the Red Blood Cell Surface and Erythrocyte Microparticles may Constitute a Multi-parametric Strategy for Detection of Autologous Blood Transfusion
Authors: Biasini Giorgia M. , Botrè Francesco , de la Torre Xavier , Donati Francesco
Published: December 2023

Background

Autologous blood transfusion is one of the illicit strategies, banned by the World Anti-Doping Agency, to increase the levels of hemoglobin, with a consequent improvement in the delivery of oxygen to tissues. At present, this practice is detectable exclusively by the individual, longitudinal monitoring of hematological biomarkers, as in the hematological module of the Athlete Biological Passport; but this indirect approach may suffer from different confounding factors. We are presenting a multi-parametric, analytical strategy to detect autologous blood transfusions by targeting the modification of the red blood cells during storage. We focused on the assessment of “storage lesions”, targeting (i) membrane proteins: Glycophorin-A and Band 3 complex, (ii) biomarkers of oxidative stress: Peroxiredoxin-2, (iii) biomarkers of senescence: CD47 and Phosphatidylserine, (iv) erythrocytes microparticles.

Results

All of the above markers were monitored, by immunological and flow cytofluorimetric methods, on samples of stored whole blood collected at different time intervals, and on fresh blood samples, collected for official doping control tests, mixed “ex vivo” to simulate an autotransfusion. Although anonymized before the delivery to the laboratory, it was possible to mix samples belonging to the same subject based on the “athlete biological passport” code. Our results showed that the irreversible alteration of RBCs morphology, the loss of membrane integrity, the occurrence of hemolysis phenomena, and, more in general, the “aging” of the erythrocytes during storage are closely related to: (i) the reduced concentration, on the erythrocyte membrane, of Band 3 protein (decrease of 19% and of 39% after 20 and 40 days of storage respectively) and of glycophorin A (− 47% and − 63% respectively); (ii) the externalization of phosphatidyl serine (with a five-fold increase after 20 days and a further 2× increase after 40 days); (iii) the reduced concentration of CD47; and (iv) increased levels of erythrocyte microparticles.

Conclusions

The most promising method to detect the presence of transfused blood in whole blood samples can be based on a multi-parametric strategy, considering jointly both protein expression on RBCs membranes and micro-vesiculation phenomena.
Bi-level stackelberg game-based distribution system expansion planning model considering long-term renewable energy contracts
Authors: Gao Hongjun , Wang Renjun , He Shuaijia , Wang Zeqi , Liu Junyong
Published: December 2023

With the deregulation of electricity market in distribution systems, renewable distributed generations (RDG) are being invested in by third-party social capital, such as distributed generations operators (DGOs) and load aggregators (LAs). However, their arbitrary RDG investment and electricity trading behavior can bring great challenges to distribution system planning. In this paper, to reduce distribution system investment, a distribution system expansion planning model based on a bi-level Stackelberg game is proposed for the distribution system operator (DSO) to guide this social capital to make suitable RDG investment. In the proposed model, DSO is the leader, while DGOs and LAs are the followers. In the upper level, the DSO determines the expansion planning scheme including investments in substations and lines, and optimizes the variables provided for followers, such as RDG locations and contract prices. In the lower level, DGOs determine the RDG capacity and electricity trading strategy based on the RDG locations and contract prices, while LAs determine the RDG capacity, demand response and electricity trading strategy based on contract prices. The capacity information of the DRG is sent to the DSO for decision-making on expansion planning. To reduce the cost and risk of multiple agents, two long-term renewable energy contracts are introduced for the electricity trading. Conditional value-at-risk method is used to quantify the RDG investment risk of DGOs and LAs with different risk preferences. The effectiveness of the proposed model and method is verified by studies using the Portugal 54-bus system.
Self S-RNase reduces the expression of two pollen-specific COBRA genes to inhibit pollen tube growth in pear
Authors: Wu Lei , Xu Ying , Qi Kaijie , Jiang Xueting , He Min , Cui Yanbo , Bao Jianping , Gu Chao , Zhang Shaoling
Published: December 2023

Due to self-incompatibility (SI) prevents self-fertilization, natural or artificial cross-pollination has been conducted in many orchards to stabilize fruit yield. However, it is still puzzled which routes of self S-RNase arresting pollen tube growth. Herein, 17 COBRA genes were isolated from pear genome. Of these genes, the pollen-specifically expressed PbCOB.A.1 and PbCOB.A.2 positively mediates pollen tube growth. The promoters of PbCOB.A.1 and/or PbCOB.A.2 were bound and activated by PbABF.E.2 (an ABRE-binding factor) and PbC2H2.K16.2 (a C2H2-type zinc finger protein). Notably, the expressions of PbCOB.A.1, PbCOB.A.2, and PbC2H2.K16.2 were repressed by self S-RNase, suggesting that self S-RNase reduces the expression of PbCOB.A.1 and PbCOB.A.2 by decreasing the expression of their upstream factors, such as PbC2H2.K16.2, to arrest pollen tube growth. PbCOB.A.1 or PbCOB.A.2 accelerates the growth of pollen tubes treated by self S-RNase, but can hardly affect level of reactive oxygen species and deploymerization of actin cytoskeleton in pollen tubes and cannot physically interact with any reported proteins involved in SI. These results indicate that PbCOB.A.1 and PbCOB.A.2 may not relieve S-RNase toxicity in incompatible pollen tube. The information provides a new route to elucidate the arresting pollen tube growth during SI reaction.

Graphical Abstract
Pleural recurrence 21 years after complete resection of thymic mucoepidermoid carcinoma: a case report
Authors: Hayashi Shoko , Matsushima Keigo , Mikubo Masashi , Tochimoto Masataka , Ichinoe Masaaki , Satoh Yukitoshi
Published: December 2023

Background

Thymic mucoepidermoid carcinomas (MECs) are extremely rare malignant neoplasms. We describe a rare case of a MEC with a high histological grade in a patient who survived for more than 20 years after the initial surgery, focusing on the clinical course and recurrence pattern.

Case presentation

A woman underwent surgical resection of a high-grade thymic MEC at another hospital 21 years ago. At the age of 79, she was referred to our hospital with an abnormal opacity incidentally found on her chest radiograph during a health check-up. After the percutaneous biopsy diagnosed thymic MEC, surgical resection was planned based on imaging findings, considering pulmonary metastasis. Intraoperatively, a large tumor and several nodules were detected within the parietal pleura; furthermore, pleural dissemination of the MEC was diagnosed by intraoperative rapid histological evaluation. We completed an exploratory thoracoscopic procedure without performing resection. She did not wish to undergo adjuvant therapy after surgery. Currently, the tumor is growing slowly, but the patient is asymptomatic and is being followed up without treatment intervention.

Conclusion

We encountered a rare case of pleural recurrence 21 years after complete resection of thymic MEC. Whether surgical resection, including volume reduction surgery, should be used as a treatment strategy for thymic carcinoma with dissemination requires further discussion.
The mental health impact of the 2023 earthquakes on the Syrian population: cross-sectional study
Authors: Soqia Jameel , Ghareeb Amjad , Hadakie Rana , Alsamara Kinda , Forbes David , Jawich Kenda , Al-Homsi Alaa , Kakaje Ameer
Published: December 2023

Background

Natural disasters have a significant impact on the mental health of affected populations. The February 2023 earthquakes in Syria and Turkey caused widespread devastation.

Aims

To explore the mental health impact of the earthquakes in Syria on the population across areas differentially damaged by the disaster.

Method

This cross-sectional study conducted in Syria included 1406 adults recruited via social media platforms 1 month after the February 2023 earthquakes. Demographic information, earthquake exposure questions, the PTSD Checklist for DSM-5 (PCL-5: for probable post-traumatic stress disorder, PTSD), the Patient Health Questionnaire-9 (PHQ-9: for probable depression) and the seven-item Generalized Anxiety Disorder scale (GAD-7: for probable anxiety) were included to compare outcomes across areas severely, moderately and slightly damaged by the earthquakes.

Results

Probable PTSD and GAD rates were higher in the severely (57.9 and 57.3% respectively) and moderately damaged regions (55.4 and 56.3% respectively) than in the slightly damaged regions (44.6 and 48.3% respectively) (PTSD: P < 0.001, GAD: P = 0.005). More participants in severely damaged regions (60.6%) reported symptoms of depression compared with moderately (53.1%) and slightly damaged (50.8%) regions (P = 0.003). Poorer mental health outcomes were associated with being female, single, younger, having a damaged or destroyed house, seeing something tragic in person and hearing tragic stories. Seeing something tragic on social media was not statistically significant.

Conclusions

This study highlights the higher prevalence of probable mental disorders in areas with more severe earthquake damage, with over 50% of the population reporting probable PTSD, depression or anxiety. The study also suggests a significant cumulative effect of these earthquakes on an already trauma- and disaster-affected population.
Systemic Therapy for Melanoma: ASCO Guideline Update Q and A
Authors: Sondak Vernon K. , Atkins Michael B. , Messersmith Hans , Provenzano Anthony , Seth Rahul , Agarwala Sanjiv S.
Published: December 2023

This Q&A answers questions regarding ASCO's recent Systemic Therapy for Melanoma guideline.
Successful Treatment of Postprandial Hyperinsulinemic Hypoglycemia After Billroth-II Gastrojejunostomy Using Octreotide
Authors: Hasebe Masashi , Aizawa-Abe Megumi , Shibue Kimitaka , Hamasaki Akihiro
Published: December 2023

Postprandial hyperinsulinemic hypoglycemia, although rare, is a well-documented complication that can manifest after upper gastrointestinal surgery. Despite its potential for severe morbidity, the underlying pathogenesis and optimal treatment strategies for this condition remain insufficiently understood. This report presents a compelling case of postprandial hypoglycemia following Billroth-II gastrojejunostomy, characterized by a marked increase in postprandial insulin levels, accompanied by the exaggerated response of incretin hormones. The incretin effect in this patient was found to be exceptionally high, measuring at approximately 90%. While nutritional interventions proved ineffective in alleviating the patient's symptoms, the administration of octreotide significantly attenuated the exaggerated postprandial insulin and incretin response, substantially ameliorating both the symptoms and postprandial hypoglycemia. Monthly subcutaneous injections of long-acting repeatable octreotide were initiated, resulting in the complete resolution of symptomatic postprandial hypoglycemia. Although the patient developed acalculous cholecystitis and gallstone cholangitis 2 years after commencing octreotide therapy, she has remained free from symptomatic postprandial hypoglycemia for more than 4 years. Our case underscores the efficacy of somatostatin analogs in the management of postprandial hyperinsulinemia after gastrointestinal surgery, shedding light on the potential involvement of incretin hormones in the pathophysiology of this condition.
Deep Imperial Time in Sinophone Poetics of History
Authors: Yeung Wayne C. F.
Published: December 2023

This article examines three Sinophone cultural texts to suggest that Sinophone studies can draw from its affinities with historical and linguistic studies to question the conceptual boundary of “premodern” imperial China. Through case studies of Hou Hsiao-hsien from Taiwan and Saisai (Xi Xi) and Wong Bik-wan from Hong Kong, the article proposes “deep imperial time” as a Sinophone historical poetics and cultural strategy of deimperialization. Artists turn their Sinophone sensibilities into a historiographical method that intervenes in nation-centric history and performs a capacious form of localization. Marginality from the normative nation-state and interimperial positionality compel them to enact decentered visions of historical Chineseness and imagine anti-imperial solidarities with the margins of different imperial formations across history. The article concludes that Sinophone studies can contribute to the conceptual enlargement of decoloniality by incorporating subaltern experiences in contesting non-Western empires.