bluuebunny/crossref_metadata_2025 huggingface dataset:
Applications of Quantum Chemistry in Biomimetic Syntheses of Polycyclic Furanocembrane Derivatives
Authors: Gao Zhanghua , Tang Bencan , Wang Di , Zhou Tao , Ren Jianfeng , Hirst Jonathan D.
Published: January 2024

This account summarizes the guidance provided by quantum chemical calculations towards the biomimetic syntheses of polycyclic marine furanocembrane derivatives. Polycyclic furanocembrane derivatives are a group of structurally complex and biologically important marine natural products isolated from marine corals. Their syntheses are challenging due to their structural complexity. Biomimetic synthetic proposals are made and some are verified via chemical synthesis. Computational chemistry can support these biomimetic syntheses. Hence, we describe herein the synthetic and computational attempts that we have made on the biomimetic syntheses of polycyclic furanocembrane derivatives, including intricarene, bielschowskysin, providencin and plumarellide.

1 Introduction

2 Computational Methodology

3 Introduction to Polycyclic Furanocembrane Derivatives

4 Biomimetic Syntheses of Intricarene, Bielschowskysin and Providencin

5 Computational Studies on the Biomimetic Synthesis of Intricarene

6 Computational Studies on the Biomimetic Synthesis of Bielschowskysin

7 Computational Studies on the Biomimetic Synthesis of Providencin

8 Computational Studies on the Biomimetic Synthesis of Plumarellide

9 Conclusion
Retraction Note: Marriage and Marital Fidelity in Interparental Relationship: A View from Religious Perspective
Authors: Çaksen Hüseyin
Published: January 2024

Retraction

The above article published in Journal of Child Science in Volume 13, Number 01, e58–e61, on May 4, 2023 (DOI: 10.1055/s-0043-1768652), has been retracted as it is lacking scientific base.
Flap Advancement Technique for Scalp Hair Preservation in Massive Cutis Verticis Gyrata
Authors: Javed Bilal , Rao Amina , Abdullah Waleed , Amber Akasha , Amin Mughese
Published: January 2024

Cutis verticis gyrata (CVG) is a rare skin condition characterized by ridges and furrows resembling the brain. CVG falls under three categories: primary essential, primary nonessential, and secondary. This case report focuses on primary essential CVG, where approximately a fourth of the scalp and a significant portion of the forehead and eyelid were involved.

Flap advancement after skin expansion was performed to rectify the disorder. This technique adequately covers the residual defect postexcision and preserves hair growth in affected regions. It is a successful skin expansion technique to cover the exposed scalp, preserve hair growth, and achieve excellent cosmetic results. Our approach demonstrates a promising solution for severe cosmetic disfigurement in primary essential CVG, positively impacting both the physical appearance and psychosocial well-being of the patient.
Updates in the Management of Paraneoplastic Syndrome
Authors: Verma Neha , Jaffer Muhammad H. , Kolli Avinash S. , Mokhtari Sepideh
Published: January 2024

Paraneoplastic neurological syndromes (PNS) are defined as remote neurologic immune-mediated effects triggered by underlying systemic tumors. While recognizing specific syndromes can aid early cancer detection, overutilization of paraneoplastic assays in the absence of a classic syndrome can precipitate overdiagnosis and overtreatment. PNS involve autoantibodies targeting intracellular or extracellular antigens, with variable immunotherapy responses based on antigen type. Diagnosing PNS is challenging, requiring exclusion of other differential diagnoses. New diagnostic criteria classify PNS into high-risk and intermediate-risk phenotypes based on clinical phenotype, neuronal antibodies, and cancer presence. Patients with cell surface antibodies respond better to immunotherapies compared to those with intracellular antigen targets. Understanding PNS syndromes, serological markers, and oncological features guides management, which facilitates initiation of immunosuppression for PNS alongside treatment of the underlying neoplasm, thereby improving neurologic and oncologic outcomes. Initial treatments often include intravenous methylprednisolone, plasma exchange, or intravenous immunoglobulins. Second-line immunosuppressants like rituximab or cyclophosphamide may be necessary if initial treatments fail. Specific therapies vary based on antibody target. Here, we summarize the current approach to the investigation, diagnosis, and treatment of patients with suspected PNS.
Neurologic Complications in Adult Cancer Survivorship
Authors: McGranahan Tresa Michelle , Figuracion Karl Cristie , Goldberg Myron , Sheppard David P.
Published: January 2024

Over the past decade, the improvement in cancer diagnostics and therapeutics has extended the overall survival of patients diagnosed with cancer including brain cancer. However, despite these unprecedented medical successes, patients continue to experience numerous neurologic complications after treatment that interfere with their independence, functionality, and overall quality of life. These include, among others, cognitive impairment, endocrinopathies, peripheral and cranial neuropathies, and vasculopathy. This article describes the long-term neurologic complications cancer survivors commonly experience to increase awareness of these complications and discuss treatments when available. Further research is necessary to understanding of mechanisms of neurologic injury and advance diagnosis and treatment. Effective patient education, monitoring, and managing neurologic issues after cancer treatment may improve independence, functionality, and quality of life during survivorship.
How did you perceive the lifestyle changes caused by the COVID-19 pandemic?
Authors: Tamaki Tetsuya , Nozawa Wataru , Kitsuki Akinori
Published: January 2024

This study did five surveys between April 2020 and March 2021 to look at how lifestyle changes during the pandemic affected well-being. These surveys covered all of Japan and were done both before and after the state of emergency was lifted. Applying the fixed-effects method to the panel data acquired in this manner, the analysis focused on subjective well-being and behavior during the COVID-19 pandemic. The results showed that teleworking during the pandemic may have increased life satisfaction, especially among young people. Although self-restraint behavior reduced well-being among young people, it tended to increase well-being among elderly individuals. On the other hand, self-restraint behavior by partners was found to lead to a decline in well-being among elderly individuals. In addition, it was observed that both the declaration of a state of emergency and the infection status had minimal impact on life satisfaction and happiness across all generational groups. Thus, the results show that lifestyle changes during the pandemic did not necessarily harm well-being, suggesting that the positive or negative impacts of factors differ from generation to generation.
Is cryptocurrency a hedging tool during economic policy uncertainty? An empirical investigation
Authors: He Chengying , Li Yong , Wang Tianqi , Shah Salman Ali
Published: January 2024

In light of the increasing investor interest in cryptocurrencies (CR) as alternative financial assets in financial markets, we sought to examine the connection between economic policy uncertainty (EPU) and cryptocurrencies. To do so, monthly data for Bitcoin (BTC), Ethereum (ETH), and Tether (THT) from January 2021 to April 2023 were employed. We utilized quantile regression and Granger causality analysis to investigate the relationship between EPU and cryptocurrencies. The initial results of this study suggest that EPU has little effect on the cryptocurrency market in the short-term. To enhance the strength and validity of these findings, we performed separate evaluations tailored to the unique contexts of the United States and China. The results revealed that the effects of EPU were adverse and statistically insignificant for China, while the situation differed slightly for the United States. Given that the United States has the most developed economy, its policies have a significant influence globally. As a result, cryptocurrencies have the potential to serve as efficient hedging tools. Furthermore, we incorporated nonlinear autoregressive distributed lag (NARDL) analysis to assess the asymmetric impact of EPU on cryptocurrencies by adopting both short-term and long-term perspectives. The outcomes demonstrated that both Bitcoin and Ethereum can serve as hedging tools in the short-term, although this utility diminishes in the long-term. Conversely, Tether displayed a positive association with EPU in the long-term. The findings of this study hold significance for policy-makers, offering valuable insights related to structuring efficient policies. The recommendations include fostering a rational framework for active participation from various stakeholders, including investors, governmental bodies, central banks, stock exchanges, and financial institutions. This collaborative effort aims to mitigate irrational fluctuations and enhance the acceptability of cryptocurrencies. In essence, this research underscores the potential of cryptocurrencies as a secure hedge against short-term EPU. However, we caution against assuming that any single cryptocurrency can consistently serve as a dependable investment haven.
The community of lactic acid bacteria during kimoto-style seed mash making process and its control
Authors: Takahashi Masayuki
Published: January 2024

Kimoto-style seed mash making processes such as the kimoto and yamahai-moto processes are driven by various microorganisms, and it is very important to make lactic acid bacteria grow stably for the brewing of a sake product with consistent quality. A model of bacterial transition from spherical lactic acid bacteria to rod-shaped lactic acid bacteria during kimoto-making has been advocated, but the model cannot explain all cases of a transition of a bacterial community during kimoto-making at various breweries. Several studies have described unique bacterial transition patterns that differ from those considered in the proposed model, and it is possible that factors such as differences in the initial bacterial community among breweries may cause the diversity of bacterial transitions. In this minireview, I summarize the research concerning the community of lactic acid bacteria during the kimoto-style seed mash making process, and I discuss how stable lactic acid fermentation can be achieved.
Quantification of polyprenyl diphosphates in Escherichia coli cells using high-performance liquid chromatography
Authors: Jitsukawa Tomotaka , Watanabe Soichiro , Shigeri Yasushi , Fujisaki Shingo
Published: January 2024

Dephosphorylation of undecaprenyl diphosphate is a crucial step in the synthesis of undecaprenyl phosphate, which is essential for cell wall synthesis. We have developed a method for the quantification of intracellular polyprenyl diphosphates, which have never before been measured directly. Polyprenyl phosphates and diphosphates prepared by chemical phosphorylation of polyprenols from Staphylococcus aureus were used to establish the conditions for fractionation by ion-exchange chromatography and high-performance liquid chromatography (HPLC). By using an elution solvent containing tetraethylammonium phosphate as an ion-pair reagent for HPLC, polyprenyl phosphate and polyprenyl diphosphate with carbon numbers from 40 to 55 could be detected as separate peaks from the reversed-phase column. This analytical method was applied to lipids extracted from Escherichia coli to determine the intracellular levels of octaprenyl phosphate, undecaprenyl phosphate, octaprenyl diphosphate, and undecaprenyl diphosphate. This is the first report of separate measurement of cellular levels of polyprenyl phosphates and polyprenyl diphosphates.
Predicting drug synergy using a network propagation inspired machine learning framework
Authors: Jin Qing , Zhang Xianze , Huo Diwei , Xie Hongbo , Zhang Denan , Liu Lei , Zhao Yashuang , Chen Xiujie
Published: January 2024

Combination therapy is a promising strategy for cancers, increasing therapeutic options and reducing drug resistance. Yet, systematic identification of efficacious drug combinations is limited by the combinatorial explosion caused by a large number of possible drug pairs and diseases. At present, machine learning techniques have been widely applied to predict drug combinations, but most studies rely on the response of drug combinations to specific cell lines and are not entirely satisfactory in terms of mechanism interpretability and model scalability. Here, we proposed a novel network propagation-based machine learning framework to predict synergistic drug combinations. Based on the topological information of a comprehensive drug–drug association network, we innovatively introduced an affinity score between drug pairs as one of the features to train machine learning models. We applied network-based strategy to evaluate their therapeutic potential to different cancer types. Finally, we identified 17 specific-, 21 general- and 40 broad-spectrum antitumor drug combinations, in which 69% drug combinations were validated by vitro cellular experiments, 83% drug combinations were validated by literature reports and 100% drug combinations were validated by biological function analyses. By quantifying the network relationships between drug targets and cancer-related driver genes in the human protein–protein interactome, we show the existence of four distinct patterns of drug–drug–disease relationships. We also revealed that 32 biological pathways were correlated with the synergistic mechanism of broad-spectrum antitumor drug combinations. Overall, our model offers a powerful scalable screening framework for cancer treatments.
Computational drug repurposing for viral infectious diseases: a case study on monkeypox
Authors: Saha Sovan , Chatterjee Piyali , Nasipuri Mita , Basu Subhadip , Chakraborti Tapabrata
Published: January 2024

The traditional method of drug reuse or repurposing has significantly contributed to the identification of new antiviral compounds and therapeutic targets, enabling rapid response to developing infectious illnesses. This article presents an overview of how modern computational methods are used in drug repurposing for the treatment of viral infectious diseases. These methods utilize data sets that include reviewed information on the host’s response to pathogens and drugs, as well as various connections such as gene expression patterns and protein–protein interaction networks. We assess the potential benefits and limitations of these methods by examining monkeypox as a specific example, but the knowledge acquired can be applied to other comparable disease scenarios.
Comparisons and optimization of two absorption chiller types by considering heat transfer area, exergy and economy as single-objective functions
Authors: Qiu Yida , Wang Jingkun , Han Jing , Chen Yuzhu , Wang Jun , Lund Peter D
Published: January 2024

Absorption cooling technology is an environmentally friendly method to generate continuous chilled water making use of multiple thermal sources, such as waste heat and renewable thermal energy. In this study, two absorption chillers (nominal capacity of 400 kW) with series and parallel connections are evaluated. To research the ideal configuration of chillers after thermodynamic analysis, the structures of the chillers are optimized using the particle swarm optimization algorithm by considering the heat transfer area (HTA), exergy efficiency and total annual cost as single-objective functions. The impact of temperature differences between external and internal flows, heat exchanger efficiencies and the solution allocation ratio is estimated. The optimized HTA, coefficient of performance, exergy efficiency and total annual cost are 149.0 m2, 1.56, 29.44% and $229 119 for the series-connected chiller, and 146.7 m2, 1.59, 31.45% and $234 562 for the parallel-connected type, respectively. Under the lowest HTA condition, compared with the reference simulation results, the energy and exergy performances are improved, while the annual total cost is higher. The annual total cost is highest when maximizing the exergy efficiency, which is attributed to the increase in the HTA. The operating cost accounts for 27.42% (series type) and 26.54% (parallel type) when the annual cost is the lowest.
The links between physical activity and prosocial behavior: an fNIRS hyperscanning study
Authors: Ishihara Toru , Hashimoto Shinnosuke , Tamba Natsuki , Hyodo Kazuki , Matsuda Tetsuya , Takagishi Haruto
Published: January 2024

The prevalence of physically inactive lifestyles in modern society raises concerns about the potential association with poor brain health, particularly in the lateral prefrontal cortex, which is crucial for human prosocial behavior. Here, we explored the relationship between physical activity and prosocial behavior, focusing on potential neural markers, including intra-brain functional connectivity and inter-brain synchrony in the lateral prefrontal cortex. Forty participants, each paired with a stranger, completed two experimental conditions in a randomized order: (i) face-to-face and (ii) face stimulus (eye-to-eye contact with a face stimulus of a fictitious person displayed on the screen). Following each condition, participants played economic games with either their partner or an assumed person displayed on the screen. Neural activity in the lateral prefrontal cortex was recorded by functional near-infrared spectroscopy hyperscanning. Sparse multiset canonical correlation analysis showed that a physically inactive lifestyle was covaried with poorer reciprocity, greater trust, shorter decision-making time, and weaker intra-brain connectivity in the dorsal lateral prefrontal cortex and poorer inter-brain synchrony in the ventral lateral prefrontal cortex. These associations were observed exclusively in the face-to-face condition. Our findings suggest that a physically inactive lifestyle may alter human prosocial behavior by impairing adaptable prosocial decision-making in response to social factors through altered intra-brain functional connectivity and inter-brain synchrony.
Menger-Type Connectivity of Line Graphs of Generalized Hypercubes With Faulty Edges
Authors: Jia Huanshen , Qian Jianguo
Published: January 2024

A connected graph $G$ is called strongly Menger edge connected if $G$ has min{deg$_{G}(x)$, deg$_{G}(y)$} edge-disjoint paths between any two distinct vertices $x$ and $y$ in $G$. In this paper, we consider two types of the strongly Menger edge connectivity of the line graphs of generalized $n$-dimensional hypercubes with faulty edges, namely the $m$-edge-fault-tolerant and $m$-conditional edge-fault-tolerant strongly Menger edge connectivity. We show that the line graphs of all generalized $n$-dimensional hypercubes are $(2n-4)$-edge-fault-tolerant strongly Menger edge connected for $n\geq 3$ and $(4n-10)$-conditional edge-fault-tolerant strongly Menger edge connected for $n\geq 4$. The two bounds for the maximum numbers of faulty edges are best possible.
Association of Bowel Urgency With Quality-of-Life Measures in Patients With Moderately-to-Severely Active Ulcerative Colitis: Results From Phase 3 LUCENT-1 (Induction) and LUCENT-2 (Maintenance) Studies
Authors: Long Millie D , Schreiber Stefan , Hibi Toshifumi , Gibble Theresa Hunter , Fisher Deborah A , Park Gina , Moses Richard E , Higgins Peter D R , Lindsay James O , Lee Scott D , Escobar Rodrigo , Jairath Vipul
Published: January 2024

Background

Improvement in bowel urgency (BU) was associated with better clinical outcomes in phase 3 LUCENT-1 (induction) and LUCENT-2 (maintenance) studies in moderately-to-severely active ulcerative colitis (UC). We assessed association of BU with quality-of-life (QoL) outcomes.

Methods

LUCENT-1: 1162 patients randomized 3:1 to intravenous mirikizumab 300 mg or placebo every 4 weeks (Q4W) for 12 weeks. LUCENT-2: 544 mirikizumab induction responders re-randomized 2:1 to subcutaneous mirikizumab 200 mg or placebo Q4W through Week (W) 40 (W52 of continuous treatment). Patients reported BU severity in the past 24 hours using a validated Urgency Numeric Rating Scale (NRS). In patients with baseline Urgency NRS ≥3, the association between BU Clinically Meaningful Improvement (CMI; ≥3-point decrease) and remission (score 0 or 1) with patient-reported outcomes was assessed at W12 and W52.

Results

A significantly greater proportion of patients with versus without BU Remission achieved IBDQ remission (W12: 87.3% vs 42.7%, P < .0001; W52: 91.4% vs 45.5%, p < .0001). Similarly, BU Remission was associated with more patients achieving CMI in SF-36 Physical Component Summary (W12: 69.0% vs 44.4%, P < .0001; W52: 77.5% vs 42.1%, P < .0001) and Mental Component Summary (W12: 53.5% vs 41.0%, P = .0019; W52: 62.0% vs 38.3%, P < .0001) scores. At W12 and W52, patients with BU CMI or Remission showed significant improvements in EQ-5D-5L and Work Productivity and Activity Impairment:UC scores. Significant improvements were also seen in fatigue, abdominal pain, and nocturnal stool.

Conclusions

In patients with moderately-to-severely active UC, improvement in BU was associated with improved QoL in phase 3 LUCENT-1 and LUCENT-2 studies.

Clinical Studies

LUCENT-1: NCT03518086; LUCENT-2: NCT03524092
Preoperative predictors of successful tumour localization by intraoperative molecular imaging with pafolacianine in lung cancer to create predictive nomogram
Authors: Bou-Samra Patrick , Joffe Jonah , Chang Austin , Guo Emily , Segil Alix , Azari Feredun , Kennedy Gregory , Din Azra , Hwang Wei-Ting , Singhal Sunil
Published: January 2024

OBJECTIVES

Intraoperative molecular imaging (IMI) uses cancer-targeted fluorescent probe to locate nodules. Pafolacianine is a Food and Drug Administration-approved fluorescent probe for lung cancer. However, it has a 8–12% false negative rate for localization. Our goal is to define preoperative predictors of tumour localization by IMI.

METHODS

We performed a retrospective review of patients who underwent IMI using pafolacianine for lung lesions from June 2015 to August 2019. Candidate predictors including sex, age, body mass index, smoking history, tumour size, distance of tumour from surface, use of neoadjuvant therapy and positron emission tomography avidity were included. The outcome was fluorescence in vivo and comprehensively included those who were true or false positives negatives. Multiple imputation was used to handle the missing data. The final model was evaluated using the area under the receiver operating characteristic curve.

RESULTS

Three hundred nine patients were included in our study. The mean age was 64 (standard deviation 13) and 68% had a smoking history. The mean distance of the tumours from the pleural surface was 0.4 cm (standard deviation 0.6). Smoking in pack-years and distance from pleura had an odds ratio of 0.99 [95% confidence interval: 0.98–0.99; P = 0.03] and 0.46 [95% confidence interval: 0.27–0.78; P = 0.004], respectively. The final model had an area under the receiver operating characteristic curve of 0.68 and was used to create a nomogram that gives a probability of fluorescence in vivo.

CONCLUSIONS

Primary tumours that are deeper from the pleural surface, especially in patients with a higher pack-years, are associated with a decreased likelihood of intraoperative localization. We identified a nomogram to predict the likelihood of tumour localization with IMI with pafolacianine.
Characterization of heterogeneities in the sandy facies of the Opalinus Clay (Mont Terri underground rock laboratory, Switzerland)
Authors: Lüth Stefan , Steegborn Florian , Heberling Frank , Beilecke Thies , Bosbach Dirk , Deissmann Guido , Geckeis Horst , Joseph Claudia , Liebscher Axel , Metz Volker , Rebscher Dorothee , Rink Karsten , Ryberg Trond , Schennen Stephan
Published: January 2024

This contribution is presenting a multidisciplinary investigation of heterogeneities in a clay rock formation, based on seismic tomography, logging and core analysis, as a reconnaissance study for a diffusion experiment. Diffusion experiments in clay rock formations provide crucial experimental data on diffusive transport of radionuclides (RN) in extremely low hydraulic conductivity media. Previous diffusion experiments, conducted, for example, in the Mont Terri underground rock laboratory within the relatively homogeneous shaly facies of Opalinus Clay, and modelling studies of these experiments have demonstrated that the clay rock could sufficiently well be described as a homogeneous anisotropic medium. For other lithofacies, characterized by larger heterogeneity, such simplification may be unsuitable, and the description of heterogeneity over a range of scales will be important. The sandy facies of the Opalinus Clay exhibits a significantly more pronounced heterogeneity compared to the shaly facies, and a combined characterization and RN diffusion study has been initiated to investigate various approaches of heterogeneity characterization and subsequent diffusion in a heterogeneous environment. As an initial step, two inclined exploratory boreholes have been drilled to access the margins of the experiment location. These boreholes have been used to acquire a cross-hole tomographic seismic data set. Optical, natural gamma and backscattering logging were applied and rock cores were analysed. The integrated results of these investigations allowed the identification of an anomalous brighter layer within the investigated area of the sandy facies of approximately 1 m thickness and with its upper bound at roughly 10 m depth within the inclined exploratory wells. Mineralogical analyses revealed only slight variations throughout the rock cores and indicated that the anomalous layer exhibited a slightly higher quartz content, and locally significantly higher calcite contents, accompanied by a lower content of clay minerals. The anomalous layer was characterized by reduced natural gamma emissions, due to the lower clay content, and increased neutron backscattering likely indicating an increased porosity. Seismic P-wave velocities, derived from anisotropic tomography, exhibited a maximal gradient near the top of this layer. The transition from the overlaying darker rock matrix into this layer has been identified as an appropriate location for the setup of a tracer diffusion experiment in a heterogeneous environment.
Aftershock forecasts based on incomplete earthquake catalogues: ETASI model application to the 2023 SE Türkiye earthquake sequence
Authors: Hainzl Sebastian , Kumazawa Takao , Ogata Yosihiko
Published: January 2024

The epidemic-type aftershock sequence (ETAS) model is the state-of-the-art approach for modelling short-term earthquake clustering and is preferable for short-term aftershock forecasting. However, due to the large variability of different earthquake sequences, the model parameters must be adjusted to the local seismicity for accurate forecasting. Such an adjustment based on the first aftershocks is hampered by the incompleteness of earthquake catalogues after a mainshock, which can be explained by a blind period of the seismic networks after each earthquake, during which smaller events with lower magnitudes cannot be detected. Assuming a constant blind time, direct relationships based only on this additional parameter can be established between the actual seismicity rate and magnitude distributions and those that can be detected. The ETAS-incomplete (ETASI) model uses these relationships to estimate the true ETAS parameters and the catalogue incompleteness jointly. In this study, we apply the ETASI model to the SE Türkiye earthquake sequence, consisting of a doublet of M 7.7 and M 7.6 earthquakes that occurred within less than half a day of each other on 6 February 2023. We show that the ETASI model can explain the catalogue incompleteness and fits the observed earthquake numbers and magnitudes well. A pseudo-prospective forecasting experiment shows that the daily number of detectable m ≥ 2 can be well predicted based on minimal and incomplete information from early aftershocks. However, the maximum magnitude (Mmax ) of the next day’s aftershocks would have been overestimated due to the highly variable b value within the sequence. Instead, using the regional b value estimated for 2000–2022 would have well predicted the observed Mmax  values.
The lemon genome and DNA methylome unveil epigenetic regulation of citric acid biosynthesis during fruit development
Authors: Yu Hang , Zhang Chao , Lu Chuang , Wang Yana , Ge Congcong , Huang Guixiang , Wang Haifeng
Published: January 2024

Citric acid gives lemons their unique flavor, which impacts their sensory traits and market value. However, the intricate process of citric acid accumulation during lemon fruit growth remains incompletely understood. Here, we achieved a chromosomal-level genome assembly for the ‘Xiangshui’ lemon variety, spanning 364.85 Mb across nine chromosomes. This assembly revealed 27 945 genes and 51.37% repetitive sequences, tracing the divergence from citron 2.85 million years ago. DNA methylome analysis of lemon fruits across different developmental stages revealed significant variations in DNA methylation. We observed decreased CG and CHG methylation but increased CHH methylation. Notably, the expression of RdDM pathway-related genes increased with fruit development, suggesting a connection with elevated CHH methylation, which is potentially influenced by the canonical RdDM pathway. Furthermore, we observed that elevated CHH DNA methylation within promoters significantly influenced the expression of key genes, critically contributing to vital biological processes, such as citric acid accumulation. In particular, the pivotal gene phosphoenolpyruvate carboxykinase (ClPEPCK), which regulates the tricarboxylic acid cycle, was strikingly upregulated during fruit development, concomitant with increased CHH methylation in its promoter region. Other essential genes associated with citric acid accumulation, such as the MYB transcription factor (ClPH1/4/5) and ANTHOCYANIN 1 (ClAN1), were strongly correlated with DNA methylation levels. These results strongly indicate that DNA methylation crucially orchestrates the metabolic synthesis of citric acid. In conclusion, our study revealed dynamic changes in DNA methylation during lemon fruit development, underscoring the significant role of DNA methylation in controlling the citric acid metabolic pathway.
The Compatibility of the Substance over Form Doctrine with Tax and Investment Treaties: A Case Study of Lone Star v the Republic of Korea
Authors: Kuźniacki Błażej
Published: January 2024

In late August 2022, the Lone Star tribunal concluded one of the latest awards in tax-related investment treaty disputes (the tax-related claims account for almost USD 1.5 billion of the total of almost USD 4.7 billion claimed in compensation). It also is the first award in which the tribunal dealt with the application of the substance over form doctrine (SOFD) by tax authorities and courts of the host state to prevent the abuse of a double tax treaty (DTT), and the impact of the refusal to accord the claimants the benefits under the DTT via a domestic (Korean) SOFD on the investment protection standards under the bilateral investment treaty (BIT). The Lone Star tribunal implicitly considered the Korean SOFD to be a suitable rule to prevent abuses of the Korea-Belgium DTT and thus compatible with the BLEU-Korea BIT. This article critically analyses the tribunal’s methodology and reasoning in reaching that conclusion. Notably, the article highlights the need to consider the principle of an abuse of rights while examining the compatibility of a SOFD with a BIT and a DTT. Such an approach could enhance the rule of law in the interpretation of tax and investment treaties in other similar cases. It is also in accordance with the principle of systemic integration. The article argues that it is increasingly more important to properly understand the concept of economic substance insofar as denial of benefits (DoB) clauses in investment treaties and principal purposes test (PPT) in tax treaties appear to specifically prevent abuses of those treaties by arrangements with no or insufficient economic substance. Global and regional tax developments, including the implementation of anti-base erosion and profit shifting (BEPS) rules, as well as Pillar Two rules (global minimum tax of 15%), strengthen the need for a comparative research on economic substance under tax and investment treaties. Such research may reveal that a convergence in denying benefits under DTTs and BITs will enhance the rule of law and increase legal certainty in tax and investment domains.
Cross-Border Disaster Displacement and Non-Refoulement under Article 3 of the ECHR: An Analysis of the European Union and Austria
Authors: Ammer Margit , Mayrhofer Monika
Published: January 2024

Academic literature and policy papers have suggested that the principle of non-refoulement can address the protection gap that exists for people displaced across international borders in the context of disasters and climate change. This article analyses whether non-refoulement under article 3 of the European Convention on Human Rights (ECHR) and subsidiary protection under article 15(b) of the European Union (EU) Qualification Directive could meet this expectation. It assesses their applicability to the cases of individuals who would face difficult living conditions due to the impacts of disasters upon return to their State of origin. This analysis lays the groundwork for a case study focusing on Austria, which as a Council of Europe and an EU Member State has obligations under the ECHR and the Qualification Directive. The case study discusses whether the principle of non-refoulement under article 3 ECHR and the eligibility criteria of subsidiary protection – as incorporated in Austrian law and as interpreted by Austrian courts – address the protection gap at the national level. To this end, the results of a qualitative analysis of 646 decisions on international protection decided by the Austrian appellate court are presented. The article concludes that the ‘livelihood’ approach used by the Austrian courts opens up the possibility of taking disasters and their impacts into account when conducting a real risk assessment under article 3 ECHR. However, the European Court of Human Rights’ suggestion of applying the ‘medical cases’ approach in cases relating to ‘naturally occurring phenomena’ is not adequate to address the protection gap. Against this backdrop, the article reflects on a possible way forward.
The global, regional, and national burden and quality of care index of kidney cancer; a global burden of disease systematic analysis 1990–2019
Authors: Khadembashiri Mohamad Mehdi , Ghasemi Erfan , Khadembashiri Mohammad Amin , Azadnajafabad Sina , Moghaddam Sahar Saeedi , Eslami Mohamad , Rashidi Mohammad-Mahdi , Naderian Mohammadreza , Esfahani Zahra , Ahmadi Naser , Rezaei Nazila , Fateh Sahar Mohammadi , Kompani Farzad , Larijani Bagher , Farzadfar Farshad
Published: January 2024

Kidney cancer (KC) is a prevalent cancer worldwide. The incidence and mortality rates of KC have risen in recent decades. The quality of care provided to KC patients is a concern for public health. Considering the importance of KC, in this study, we aim to assess the burden of the disease, gender and age disparities globally, regionally, and nationally to evaluate the quality and inequities of KC care. The 2019 Global Burden of Disease study provides data on the burden of the KC. The secondary indices, including mortality-to-incidence ratio, disability-adjusted life years -to-prevalence ratio, prevalence-to-incidence ratio, and years of life lost-to-years lived with disability ratio, were utilized. These four newly merged indices were converted to the quality-of-care index (QCI) as a summary measure using principal component analysis. QCI ranged between 0 and 100, and higher amounts of QCI indicate higher quality of care. Gender disparity ratio was calculated by dividing QCI for females by males to show gender inequity. The global age-standardized incidence and mortality rates of KC increased by 29.1% (95% uncertainty interval 18.7–40.7) and 11.6% (4.6–20.0) between 1990 and 2019, respectively. Globally, the QCI score for KC increased by 14.6% during 30 years, from 71.3 to 81.6. From 1990 to 2019, the QCI score has increased in all socio-demographic index (SDI) quintiles. By 2019, the highest QCI score was in regions with a high SDI (93.0), and the lowest was in low SDI quintiles (38.2). Based on the World Health Organization regions, the QCI score was highest in the region of America, with Canada having the highest score (99.6) and the lowest in the African Region, where the Central African Republic scored the lowest (17.2). In 1990, the gender disparity ratio was 0.98, and in 2019, it was 0.97 showing an almost similar QCI score for females and males. Although the quality of care for KC has improved from 1990 to 2019, there is a significant gap between nations and different socioeconomic levels. This study provides clinicians and health authorities with a global perspective on the quality of care for KC and identifies the existing disparities.
Pronounced differentiation on the Z chromosome and parts of the autosomes in crowned sparrows contrasts with mitochondrial paraphyly: implications for speciation
Authors: McCallum Quinn , Askelson Kenneth , Fogarty Finola F , Natola Libby , Nikelski Ellen , Huang Andrew , Irwin Darren
Published: January 2024

When a single species evolves into multiple descendent species, some parts of the genome can play a key role in the evolution of reproductive isolation while other parts flow between the evolving species via interbreeding. Genomic evolution during the speciation process is particularly interesting when major components of the genome—for instance, sex chromosomes vs. autosomes vs. mitochondrial DNA—show widely differing patterns of relationships between three diverging populations. The golden-crowned sparrow (Zonotrichia atricapilla) and the white-crowned sparrow (Zonotrichia leucophrys) are phenotypically differentiated sister species that are largely reproductively isolated despite possessing similar mitochondrial genomes, likely due to recent introgression. We assessed variation in more than 45,000 single nucleotide polymorphisms to determine the structure of nuclear genomic differentiation between these species and between two hybridizing subspecies of Z. leucophrys. The two Z. leucophrys subspecies show moderate levels of relative differentiation and patterns consistent with a history of recurrent selection in both ancestral and daughter populations, with much of the sex chromosome Z and a large region on the autosome 1A showing increased differentiation compared to the rest of the genome. The two species Z. leucophrys and Z. atricapilla show high relative differentiation and strong heterogeneity in the level of differentiation among various chromosomal regions, with a large portion of the sex chromosome (Z) showing highly divergent haplotypes between these species. Studies of speciation often emphasize mitochondrial DNA differentiation, but speciation between Z. atricapilla and Z. leucophrys appears primarily associated with Z chromosome divergence and more moderately associated with autosomal differentiation, whereas mitochondria are highly similar due apparently to recent introgression. These results add to the growing body of evidence for highly heterogeneous patterns of genomic differentiation during speciation, with some genomic regions showing a lack of gene flow between populations many hundreds of thousands of years before other genomic regions.
The role of divergent host use and geography in the evolution of habitat isolation and sexual isolation among sister species of Belonocnema gall wasps
Authors: Zhang Linyi , Hood Glen Ray , Ott James R , Egan Scott P
Published: January 2024

Ecology and geography can play important roles in the evolution of reproductive isolation across the speciation continuum, but few studies address both at the later stages of speciation. This notable gap in knowledge arises from the fact that traditional ecological speciation studies have predominantly focused on the role of ecology in initiating the speciation process, while many studies exploring the effect of geography (e.g., reinforcement) concentrate on species pairs that lack divergent ecological characteristics. We simultaneously examine the strength of habitat isolation and sexual isolation among three closely related species of Belonocnema gall-forming wasps on two species of live oaks, Quercus virginiana and Q. geminata, that experience divergent selection from their host plants and variable rates of migration due to their geographic context. We find that the strength of both habitat isolation and sexual isolation is lowest among allopatric species pairs with the same host plant association, followed by allopatric species with different host plant associations, and highest between sympatric species with different host-plant associations. This pattern suggests that divergent selection due to different host use interacts with geography in the evolution of habitat isolation and sexual isolation during the later stages of speciation of Belonocnema wasps.
An Economic Case against Public Banking, and a Case for It
Authors: Krishnamurthy Prasad , Cochenour Tucker
Published: January 2024

In this article, we examine the economics of public consumer banking in the United States. Public expenditures on consumer banking can take the form of price subsidies or direct provision. The economic case for price subsidies is weak because the evidence suggests most unbanked consumers would prefer a cash grant. The economic case for public provision is also weak because the existing market failures in banking are better remedied by regulation. The exceptions to this rule are check cashing and related payment services, which could be supplied by the US Postal Service (USPS) at a lower cost than private providers. On the other hand, economic arguments for the superiority of cash transfers presume that the institutional infrastructure exists to deliver them. But an effective infrastructure for public transfers does not exist in the United States and is only possible with universal ownership of payment accounts, which in turn requires some form of public subsidy or provision. We suggest one path forward: expand the financial services currently offered to federal beneficiaries—such as Social Security recipients—by the Treasury.
High-order azimuth coherent imaging for microseismic location
Authors: Shi Ying , Guo Xuebao , Yu Youqiang
Published: January 2024

The cross-correlation-based methods, widely used for microseismic monitoring, utilize cross-correlation to extract time differences of signals within station pairs, and subsequently use these time differences for back-projection and localization without the need for triggering moment scanning. The selection of imaging conditions, applied to the spatial projection of all cross-correlation records, determines the noise resistance and resolution of such methods. To fully exploit the azimuthal properties of station pairs for constraining the source imaging, we propose a high-order azimuth coherent imaging condition, which involves the following steps: (i) choosing station pairs that meet specific inter-station distance criteria; (ii) combining station pairs into dual-station pairs that satisfy a certain inter-station pair angle criterion; (iii) further combining station combinations pairwise to form the final set of station pairs; (iv) multiplying the projection results of station pairs within each combination from the third step; and (v) summing the results of all combinations. This method effectively suppresses the hyperboloid in the spatial projection of a single station, enhances the coherence of seismic source imaging, and maintains noise resistance. Compared to the conventional imaging conditions, the method proposed has demonstrated superior resolution and robustness in both theoretical analysis and practical testing.
Biomarkers for immune-related adverse events in cancer patients treated with immune checkpoint inhibitors
Authors: Liang Yao , Maeda Osamu , Ando Yuichi
Published: January 2024

Although immune checkpoint inhibitors have greatly improved cancer therapy, they also cause immune-related adverse events, including a wide range of inflammatory side effects resulting from excessive immune activation. Types of immune-related adverse events are diverse and can occur in almost any organ, with different frequencies and severities. Furthermore, immune-related adverse events may occur within the first few weeks after treatment or even several months after treatment discontinuation. Predictive biomarkers include blood cell counts and cell surface markers, serum proteins, autoantibodies, cytokines/chemokines, germline genetic variations and gene expression profiles, human leukocyte antigen genotype, microRNAs and the gut microbiome. Given the inconsistencies in research results and limited practical utility, there is to date no established biomarker that can be used in routine clinical practice, and additional investigations are essential to demonstrate efficacy and subsequently facilitate integration into routine clinical use.
Recent advances and future perspectives of T-cell engagers in lymphoid malignancies
Authors: Shirouchi Yuko , Maruyama Dai
Published: January 2024

Bispecific antibodies (BsAbs) are monoclonal antibodies that simultaneously bind to a specific antigen on tumors and CD3 on T cells, leading to T cell activation and subsequent tumor cell lysis. Several CD20 × CD3 BsAbs are being developed for B-cell lymphomas. Furthermore, multiple clinical trials to evaluate BsAbs for the treatment of multiple myeloma, with targets including BCMA, GPRC5D and FcRH5, are ongoing. Emerging evidence suggests promising efficacy in heavily pretreated patients with relapsed or refractory lymphoid malignancies, showing an overall response rate of 50–60%, with complete response rates of 30–40% for relapsed or refractory large B-cell lymphoma and 60–70% for relapsed or refractory multiple myeloma. Their toxicity profiles are generally consistent with other T-cell redirecting therapies, including cytokine release syndrome, which may be mitigated with several strategies, such as step-up dosing, pre-mediation with glucocorticoids and a subcutaneous route of administration, and very rare neurotoxicity. Several clinical trials evaluated BsAbs in combination with other agents or in earlier lines of treatment, including in front-line settings. BsAbs have the potential to change the treatment paradigm of lymphoid malignancies in the coming years; however, longer follow-ups are required to assess the durability of responses to these agents. We herein provide an overview of the findings of recent clinical trials on BsAbs, including mechanisms of action, safety profiles, and efficacy, and discuss the role of BsAbs in the treatment of B-cell lymphomas and multiple myeloma.