bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a target concentration intervention to individualize paroxysmal nocturnal hemoglobinuria treatment with pegcetacoplan
Authors: ter Avest Mendy , Langemeijer Saskia M.C , Blijlevens Nicole M.A. , van de Kar Nicole C.A.J. , ter Heine Rob
Published: March 2024

Pegcetacoplan (Aspaveli®/Empaveli™) is a factor C3 inhibitor that is approved for the treatment of paroxysmal nocturnal hemoglobinuria. An individualized dosing strategy might be useful to improve patient-friendliness and cost-effectiveness of this very expensive drug. Therefore, the aim of this study was to develop an individualized treatment regimen for pegcetacoplan based on the pharmacokinetic-pharmacodynamic data of the manufacturer. We conducted a clinical trial simulation with the approved dosing regimen of 1080 mg twice-weekly and a target concentration intervention-based dosing regimen in patients with and without prior eculizumab use. For eculizumab-naïve patients, the target concentration intervention-based dosing regimen resulted in a comparable fraction of patients with LDH normalization (LDH < 226 U/L) and hemoglobulin normalization (> 12 g/dL) compared to the approved regimen (LDH 50.2% and 50.0% respectively and hemoglobulin 45.6% and 44.4%). A modest dose reduction of ~ 5% was possible with target concentration intervention-based dosing. An intensified dosing interval was necessary in 2.3% of the patients however an interval prolongation was possible in 28.2% of the patients. Similar results were obtained for patients prior treated with eculizumab. In this study we show the potential of an individualized dosing regimen of pegcetacoplan with can improve patient friendliness in approximately 30% of the patients and improve therapy in approximately 2% of the patients at slightly reduced costs.
Keep calm and keep rowing: the psychophysical effects of dragon boat program in breast cancer survivors
Authors: Moro Tatiana , Casolo Andrea , Bordignon Veronica , Sampieri Alessandro , Schiavinotto Giorgia , Vigo Lisa , Ghisi Marta , Paoli Antonio , Cerea Silvia
Published: March 2024

Purpose

Dragon Boat discipline has become a popular type of physical exercise among women with breast cancer. The present study aims to investigate the effects of Dragon Boat activity on body composition, physical function, and psychosocial aspects (i.e., body appreciation and quality of life [QoL]) in women operated for breast cancer.

Methods

Thirty-one women (age, 57.88 ± 7.88 years; BMI, 27.86 ± 6.38 kg·m−2) with a previous breast removal surgery were recruited and randomized into two groups: Dragon Boat group (DB, N = 18) or a home-based non-supervised training program (home exercise group; HG, N = 13). All participants underwent body composition, handgrip test, 30-s chair stand test (30CST), 6-min walking test (6MWT), and shoulder mobility measurements at baseline and after 12 weeks of intervention. Participants also filled out the Body Appreciation Scale-2 (BAS-2) and the Short Form Health Survey-12 (SF-12) self-report questionnaires.

Results

Dragon Boat activity significantly improved the 30CST (+ 6%, p = .011) and 6MWT performance (+ 30%, p = .011) compared to a home-based non-supervised training program. Moreover, 20% (3/15 women) of women in the DB group obtained a reliable change from pre- to post-intervention in the BAS-2 and in the mental QoL component of the SF-12 (vs 15% and 0% of the HC group). No reliable change emerged for the physical component of the SF-12.

Conclusion

Dragon Boat activity is efficient to improve lower limb strength in women operated for breast cancer. Furthermore, Dragon Boat activity emerged to improve body appreciation and mental QoL in some of the women assigned to this activity. Importantly, no adverse events were documented during the intervention.

Trial registration

NCT05206526 (10/02/2022)
Microfluidic Diffusional Sizing (MDS) Measurements of Secretory Neutralizing Antibody Affinity Against SARS-CoV-2
Authors: O’Mahoney Cara , Watt Ian , Fiedler Sebastian , Devenish Sean , Srikanth Sujata , Justice Erica , Dover Tristan , Dean Delphine , Peng Congyue
Published: March 2024

SARS-CoV-2 has rampantly spread around the globe and continues to cause unprecedented loss through ongoing waves of (re)infection. Increasing our understanding of the protection against infection with SARS-CoV-2 is critical to ending the pandemic. Serological assays have been widely used to assess immune responses, but secretory antibodies, the essential first line of defense, have been studied to only a limited extent. Of particular interest and importance are neutralizing antibodies, which block the binding of the spike protein of SARS-CoV-2 to the human receptor angiotensin-converting enzyme-2 (ACE2) and thus are essential for immune defense. Here, we employed Microfluidic Diffusional Sizing (MDS), an immobilization-free technology, to characterize neutralizing antibody affinity to SARS-CoV-2 spike receptor-binding domain (RBD) and spike trimer in saliva. Affinity measurement was obtained through a contrived sample and buffer using recombinant SARS-CoV-2 RBD and monoclonal antibody. Limited saliva samples demonstrated that MDS applies to saliva neutralizing antibody measurement. The ability to disrupt a complex of ACE2-Fc and spike trimer is shown. Using a quantitative assay on the patient sample, we determined the affinity and binding site concentration of the neutralizing antibodies.
Pool Fires Within a Large Under-Ventilated Environment: Experimental Analysis and Numerical Simulation Using OpenFOAM
Authors: Cavazzuti Marco , Tartarini Paolo
Published: March 2024

Experimental analyses and numerical simulations are carried out on a test case involving an heptane pool fire within a large under-ventilated environment. During the experiments, the temperature history at several locations within the room is monitored by means of thermocouples, and the fire radiative heat transfer estimated through a plate thermocouple. The experimental layout is then replicated numerically and tested using OpenFOAM CFD code. The study is a preliminary analysis performed for code validation purposes on a full-scale fire scenario. The results of the simulations are compared to the experimental results and critically analysed, finding a reasonable agreement overall. Critical issues in fire modelling are also highlighted. In fact, due to the problem complexity and the limitations of the numerical models available some important aspect that can significantly influence the outcome of the simulations must be calibrated a posteriori, somewhat limiting the general predictive applicability of the fire models. Primarily, these are the heat release rate history, the combustion efficiency, and, to a lesser extent, the convective heat transfer boundary condition at the wall.
Pancreatic adenocarcinoma treated with surgical resection, toceranib phosphate and firocoxib in a dog: a case report
Authors: Fuertes-Recuero Manuel , Vázquez-Fernández Esther , Lizasoain-Sánz Guillermo , Arroba-Alonso Amanda , Sánchez-López Alejandro , Martínez-de-Merlo Elena , Suárez-Redondo María , Ortiz-Diez Gustavo
Published: March 2024

Exocrine pancreatic carcinomas are rarely reported in dogs. A ductal pancreatic adenocarcinoma in a 10-year-old intact beagle is described in this report. The diagnosis was made based on clinical signs, imaging (abdominal ultrasound and CT scan) and histopathology. Treatment consisted of partial right lobe pancreatectomy followed by adjuvant therapy with toceranib phosphate (Palladia®) and firocoxib (Previcox®) for six months. The treatment was well tolerated, and the survival time was 445 days. To our knowledge, this is the longest survival reported in the literature for a dog diagnosed with exocrine pancreatic adenocarcinoma. The results described here may contribute to provide a better understanding about this neoplasia and potential treatment options.
Contextually aware intelligent control agents for heterogeneous swarms
Authors: Hepworth Adam J. , Hussein Aya S. M. , Reid Darryn J. , Abbass Hussein A.
Published: March 2024

An emerging challenge in swarm shepherding research is to design effective and efficient artificial intelligence algorithms that maintain simplicity in their decision models, whilst increasing the swarm’s abilities to operate in diverse contexts. We propose a methodology to design a context-aware swarm control intelligent agent (shepherd). We first use swarm metrics to recognise the type of swarm that the shepherd interacts with, then select a suitable parameterisation from its behavioural library for that particular swarm type. The design principle of our methodology is to increase the situation awareness (i.e. contents) of the control agent without sacrificing the low computational cost necessary for efficient swarm control. We demonstrate successful shepherding in both homogeneous and heterogeneous swarms.
Use of Online Communities among People with Type 2 Diabetes: A Scoping Review
Authors: Bujanda-Sainz de Murieta Arantxa , Soto-Ruiz Nelia , García-Vivar Cristina , San Martín-Rodríguez Leticia , Escalada-Hernández Paula
Published: March 2024

Purpose of Review

People with diabetes require continuous self-monitoring and face numerous decisions in their day-to-day lives. Therefore, on many occasions, they need more support than that provided by health professionals. In this context, peer support in online diabetes communities could be a useful tool. The purpose of the review is to describe, analyze and synthesize the available evidence on the use and health out-comes of online communities for people with type 2 diabetes mellitus. A scoping review was conducted in accordance with the Joanna Briggs Institute guidelines. Searches were performed PubMed, Web of Science, CINHAL, Scopus and Cochrane databases.

Recent Findings

From 1821 identified documents, 6 articles were included. These studies explored the characteristics of diabetes online communities and the population features. Besides, the results were classified according to whether they were clinical, psychosocial, or addressed people's experiences with the online community. The analysis underscores their value in facilitating communication, improving diabetes management, and enhancing psychosocial well-being. Future investigations should prioritize longitudinal assessments to elucidate the sustained impact of community engagement and optimize user participation for enhanced patient outcomes.

The growing relevance of new technologies has led to a significant number of individuals with chronic illnesses seeking peer support. Online health communities have emerged as virtual spaces where individuals with shared health interests interact and form relationships. Within these digital spaces, individuals can engage in peer interaction, observe behaviors, and mutually benefit, potentially leading to improved attitudes toward the disease.
AIH Therapy: Beyond First-Line
Authors: Adao Irina , Klepper Arielle , Tana Michele
Published: March 2024

Purpose of Review

The purpose of the article is to review treatment options for patients with AIH for whom first-line therapy is not successful. We outline recommended approaches for providers and new therapies on the horizon.

Recent Findings

Budesonide, while advantageous in some respects, may not be as effective as predniso(lo)ne. Mycophenolate mofetil is most effective in the setting of azathioprine intolerance and less effective when the response to azathioprine has been inadequate. Infliximab is the biologic agent with the most evidence for use in AIH. Clinical trials studying interleukin 2, regulatory T cells, inhibitors of BAFF signaling, and immunoproteasome inhibitors have been initiated but more research is needed, particularly in Black people, Indigenous people, and People of Color.

While multiple agents have been reported as second- or third-line therapies, the evidence is limited. Future research will require multicenter collaboration and should explore therapeutics supported by molecular studies.
Peripheral artery disease: an underdiagnosed condition in familial hypercholesterolemia? A systematic review
Authors: Acitelli Elisa , Guedon Alexis F. , De Liguori Sara , Gallo Antonio , Maranghi Marianna
Published: March 2024

Purpose

Familial hypercholesterolemia (FH) is one of the most common inherited diseases characterized by elevated LDL-cholesterol levels, leading to early-onset atherosclerosis. While the association between FH and coronary and carotid artery disease is well-established, its association with peripheral artery disease (PAD) is less robust. This systematic review aims at exploring existing evidence on PAD prevalence and incidence in FH individuals.

Methods

A comprehensive search was conducted on MEDLINE and Embase databases, for studies published between January 2013 and December 2023, evaluating prevalence and incidence of PAD in FH patients. Literature reviews, case reports, responses to editors and non-English language articles were excluded.

Results

The initial research provided 53 results. After article screening, 28 articles were fully reviewed and 24 were finally included in the analysis. Among these, 19 reported PAD prevalence, while 5 PAD incidence over a mean follow-up time of 8.7 years. PAD prevalence and incidence ranged from 0.3 to 60% and from 0.5 to 4.2% respectively, probably reflecting the heterogeneity in PAD definition criteria.

Conclusion

This systematic review sheds light on the limited number of studies on PAD in FH patients. Particularly, considering the potential positive effects of newly available lipid-lowering strategies on PAD outcomes, addressing this research gap is pivotal for a more comprehensive understanding of peripheral vascular manifestations in FH patients and for optimal management of this population.
m6A/m1A/m5C-Associated Methylation Alterations and Immune Profile in MDD
Authors: Ren Xin , Feng Zhuxiao , Ma Xiaodong , Huo Lijuan , Zhou Huiying , Bai Ayu , Feng Shujie , Zhou Ying , Weng Xuchu , Fan Changhe
Published: March 2024

Major depressive disorder (MDD) is a prevalent psychiatric condition often accompanied by severe impairments in cognitive and functional capacities. This research was conducted to identify RNA modification-related gene signatures and associated functional pathways in MDD. Differentially expressed RNA modification-related genes in MDD were first identified. And a random forest model was developed and distinct RNA modification patterns were discerned based on signature genes. Then, comprehensive analyses of RNA modification-associated genes in MDD were performed, including functional analyses and immune cell infiltration. The study identified 29 differentially expressed RNA modification-related genes in MDD and two distinct RNA modification patterns. TRMT112, MBD3, NUDT21, and IGF2BP1 of the risk signature were detected. Functional analyses confirmed the involvement of RNA modification in pathways like phosphatidylinositol 3-kinase signaling and nucleotide oligomerization domain (NOD)-like receptor signaling in MDD. NUDT21 displayed a strong positive correlation with type 2 T helper cells, while IGF2BP1 negatively correlated with activated CD8 T cells, central memory CD4 T cells, and natural killer T cells. In summary, further research into the roles of NUDT21 and IGF2BP1 would be valuable for understanding MDD prognosis. The identified RNA modification-related gene signatures and pathways provide insights into MDD molecular etiology and potential diagnostic biomarkers.
Contribution Analysis of Large Language Models and Data Augmentations for Person Names in Solving Legal Bar Examination at COLIEE 2023
Authors: Onaga Takaaki , Fujita Masaki , Kano Yoshinobu
Published: March 2024

This paper describes our system for COLIEE 2023 Task 4, which automatically answers Japanese legal bar exam problems. We propose an extension to our previous system in COLIEE 2022, which achieved the highest accuracy among all submissions using data augmentation. We focus on problems that include mentions of person names. In this paper, we present two main contributions. First, we incorporate LUKE as our deep learning component, which is a named entity recognition model trained on RoBERTa. Second, we fine-tune the pretrained LUKE model in multiple ways, comparing fine-tuning on training datasets that include alphabetical person names and ensembling different fine-tuning models. We confirmed that LUKE and its fine-tuned model on person type problems improve their accuracies. Our formal run results show that LUKE and our fine-tuning approach using alphabetical person names were effective, achieving an accuracy of 0.69 in the COLIEE 2023 Task 4 formal run.
Nano/Micro-Structural Supramolecular Biopolymers: Innovative Networks with the Boundless Potential in Sustainable Agriculture
Authors: Saberi Riseh Roohallah , Hassanisaadi Mohadeseh , Vatankhah Masoumeh , Varma Rajender S. , Thakur Vijay Kumar
Published: March 2024

Sustainable agriculture plays a crucial role in meeting the growing global demand for food while minimizing adverse environmental impacts from the overuse of synthetic pesticides and conventional fertilizers. In this context, renewable biopolymers being more sustainable offer a viable solution to improve agricultural sustainability and production. Nano/micro-structural supramolecular biopolymers are among these innovative biopolymers that are much sought after for their unique features. These biomaterials have complex hierarchical structures, great stability, adjustable mechanical strength, stimuli-responsiveness, and self-healing attributes. Functional molecules may be added to their flexible structure, for enabling novel agricultural uses. This overview scrutinizes how nano/micro-structural supramolecular biopolymers may radically alter farming practices and solve lingering problems in agricultural sector namely improve agricultural production, soil health, and resource efficiency. Controlled bioactive ingredient released from biopolymers allows the tailored administration of agrochemicals, bioactive agents, and biostimulators as they enhance nutrient absorption, moisture retention, and root growth. Nano/micro-structural supramolecular biopolymers may protect crops by appending antimicrobials and biosensing entities while their eco-friendliness supports sustainable agriculture. Despite their potential, further studies are warranted to understand and optimize their usage in agricultural domain. This effort seeks to bridge the knowledge gap by investigating their applications, challenges, and future prospects in the agricultural sector. Through experimental investigations and theoretical modeling, this overview aims to provide valuable insights into the practical implementation and optimization of supramolecular biopolymers in sustainable agriculture, ultimately contributing to the development of innovative and eco-friendly solutions to enhance agricultural productivity while minimizing environmental impact.
MRI quantitative hemodynamic parameter histogram assement of hepatocellular carcinoma development in a rabbit VX2 liver cancer model
Authors: Guo Rui , Song Zhiqiang , Zuo Pengpeng , An Jiajia , Deng Defeng , Li Jinfang , Wu Ying , Ma Jing
Published: March 2024

Background

Nowadays, liver cancer is the second leading cause of cancer death in the world. Therefore, it is very important to understand tumor progression and evaluate tumor microcirculation for treatment strategy.

Objective

To explore the application of MRI quantitative hemodynamic parameter histogram analysis in the development of a rabbit VX2 liver cancer.

Methods

Five New Zealand white rabbits were randomly selected each time for liver Dynamic contrast- enhanced MR perfusion (DCE-MRI) imaging at the 1st, 2nd, 3rd, 4th and 5th weeks after liver tumor implantation. The dynamic changes and the significant differences between the tumor volume and related derived parameters during tumor progression were compared and analyzed.

Results

In the development of the VX2 liver cancer model, the tumor volume between the end of 1 ~ 5w group (F = 44.11; P = 0.000) was statistically significant (P < 0.01), and the significant differences were found between the 5th week and the 1st, 2nd, 3rd, 4th week, the 4th week and the 1st, 2nd week, the 3rd week and the 5th week (P < 0.01), respectively. The skewness and kurtosis of the volume transport constant (Ktrans) value, the maximum, 90th percentile and skewness of the reverse reflux rate constant (Kep) value, and the skewness, kurtosis, 75th and 90th percentiles of the plasma fraction (Vp) value were statistically significant (P < 0.05) at the end of each week. The 10th, 25th, 50th percentiles of the Kep value, the 10th, 25th percentiles of the extracellular space (EES) fraction (Ve) value, the 10th percentile of the Vp value was positively correlated with tumor volume (r > 0, P < 0.05). The expression of α-smooth muscle actin (α-SMA) was negatively correlated with the mean, 75th percentile of the Ktrans value, the 50th, 75th percentiles of the Kep value, the mean, minimum of the Vp value (r < 0, P<0.05). It was positively correlated with the skewness, kurtosis of the Ktrans value, the skewness of the Vp value (r > 0, P<0.05).

Conclusions

MRI quantitative hemodynamic parameter histogram analysis can reflect the progress of the rabbit VX2 liver cancer. In particular, the skewness, kurtosis and percentiles of Ktrans, Kep and Vp can reflect the microvascular information and can be used as biomarkers to assess the development of Hepatocellular Carcinoma(HCC).
CACA guidelines for holistic integrative management of lung cancer
Authors: Wang Jun ,   Society of Lung Cancer of China Anti-Cancer Association
Published: March 2024

Lung cancer (LC) is among the malignant tumors with the highest disease burden in the world, accounting for approximately 11.4% of all cancer cases, and LC was the 2nd most common type of malignant tumor. The editing of the CACA Guidelines for Holistic Integrative Management of Lung Cancer aimed to facilitate the enhancement of lung cancer diagnosis and comprehensive treatment in China.

The CACA Guidelines for Holistic Integrative Management of Lung Cancer include the epidemiology, the early detection, the comprehensive diagnosis, the treatment (including surgical, medical and radiological treatment), rehabilitation, and some general principles for both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC).

The main objective of this guideline is to standardize the clinical diagnosis and treatment process of lung cancer, with a specific focus on enhancing the management of this disease in China.
Invariant measures for -free systems revisited
Authors: DYMEK AURELIA , KUŁAGA-PRZYMUS JOANNA , SELL DANIEL
Published: March 2024

For
$\mathscr {B} \subseteq \mathbb {N} $
, the
$ \mathscr {B} $
-free subshift
$ X_{\eta } $
is the orbit closure of the characteristic function of the set of
$ \mathscr {B} $
-free integers. We show that many results about invariant measures and entropy, previously only known for the hereditary closure of
$ X_{\eta } $
, have their analogues for
$ X_{\eta } $
as well. In particular, we settle in the affirmative a conjecture of Keller about a description of such measures [G. Keller. Generalized heredity in
$\mathcal B$
-free systems. Stoch. Dyn.21(3) (2021), Paper No. 2140008]. A central assumption in our work is that
$\eta ^{*} $
(the Toeplitz sequence that generates the unique minimal component of
$ X_{\eta } $
) is regular. From this, we obtain natural periodic approximations that we frequently use in our proofs to bound the elements in
$ X_{\eta } $
from above and below.
The Role of Judicial Associations in Preventing Rule of Law Decay in Romania: Informal Communication and Strategic Use of Preliminary References
Authors: Doroga Sorina , Bercea Raluca
Published: March 2024

This Article explores the manner in which, faced with the rule of law crisis generated by the 2017–2019 national legislative reforms, the Romanian judicial associations, organized as NGOs, have fulfilled their declared purpose of safeguarding judicial independence. By relying on effective communication tactics—including international networking and lobbying or informal discussions with high-level EU representatives—coupled with a strategic use of preliminary references, they have shed light on some of the most sensitive elements of the Romanian context, garnering both internal and international support in the process. In particular, by taking advantage of the CJEU’s increased willingness to engage with questions concerning the rule of law and the organization of the national judicial systems, the Romanian judicial associations have managed to design strategies capable of triggering preliminary rulings on the most heated and politically charged questions concerning the judiciary. This Article seeks to highlight the specific features and informal elements of such strategies.
Schrödinger’s Judiciary—Formality at the Service of Informality in Hungary
Authors: Vincze Attila
Published: March 2024

There are two contrasting claims regarding the Hungarian judiciary. The Government asserts that it is in the best shape, while many other voices label it as captured or dependent. This article shows how both of these claims can be true, depending on the interplay between formality and informality and shows how a few small loopholes allow some actors to rig the judicial system. Therefore, the Hungarian judiciary is similar to Schrödinger’s cat, which is claimed to be dead and alive at the same time.

The synergy between formality and informality requires a network of a handful of trusted people in managerial positions to administer case allocation, promotion, and disciplinary systems, which seem to be very effective tools. Few small technical loopholes and some special remedies suffice to micromanage important cases precisely because key positions are captured which work as gatekeepers or emergency brakes. Most of these tools are legal in a very formal technical sense of the word because they rely on acts of Parliament. A formal legalism, a very thin understanding of the Rule of law, and a majoritarian mindset serve as a legitimizing ideology for the whole legal system.
Mapping the evidence on psychosocial interventions for migrant populations: Descriptive analysis of a living database of randomized studies
Authors: Cadorin Camilla , Purgato Marianna , Turrini Giulia , Prina Eleonora , Cabral Ferreira Madalena , Cristofalo Doriana , Bartucz Monica B. , Witteveen Anke B. , Sijbrandij Marit , Papola Davide , Barbui Corrado
Published: March 2024

Migrant mental health is a pressing public health issue with wide-ranging implications. Many randomized controlled trials (RCTs) have been conducted in this population to assess the effects of psychosocial interventions. However, the available evidence is characterized by controversy and fragmentation, with studies focusing on different migrant populations, interventions, outcomes, delivery modalities and settings. Aiming to promote systematic reviews of the effectiveness of psychosocial interventions in different migrant groups, we have developed a living database of existing RCTs. The development of the database provides an opportunity to map the existing RCT evidence in this population. A total of 135 studies involving 24,859 participants were included in the living database. The distribution of studies by year of publication aligns with the increasing global migrant population in recent years. Most studies focus primarily on adult participants, with a limited representation of children and adolescents, and a prevalence of female participants, which is consistent with epidemiological data, except for older adults, who are underrepresented in research. Studies predominantly focus on refugees and asylum seekers, likely due to their elevated risk of mental health issues, despite the substantial presence of economic migrants worldwide. While studies mainly involve migrants from the Middle East and East Asia, epidemiological data suggest a broader geographic representation, with migrants coming from Eastern Europe, Latin America and South Asia. The present descriptive analysis of RCTs on mental health and psychosocial interventions for migrant populations provides valuable insights into the existing research landscape. It should be used to inform future research efforts, ensuring that studies are more representative of the global migrant population and more responsive to the mental health needs of migrants in different contexts.
Vulnerability, Recognition, and the Ethics of Pregnancy: A Theological Response
Authors: Kamitsuka Margaret D.
Published: March 2024

Vulnerability is a notion discussed in feminist philosophy as a basis for a morality that widens our sense of those whose deaths are grievable. Vulnerability and grievability also factor in reproductive ethics. This essay employs recognition theory to analyze critically how these notions are mobilized in conservative Christian anti-abortion writings and in feminist philosophy. This analysis exposes weaknesses and misrecognition in both sets of discourses. In response, I offer theological arguments for recognizing fetal value without implying a right to life and for acknowledging how human finitude and the precarity of pregnancy render gestational hospitality a discretionary, not obligatory, moral act.
Documents on the Consequences of the Aggression of the Russian Federation against Ukraine, Namely the Enlarged Partial Agreement on the Register of Damage Caused
Authors: Bowring Bill
Published: March 2024

Following a debate at the Parliamentary Assembly of the Council of Europe (PACE) on January 26, 2023 (7th sitting), under the urgent procedure, a text was adopted by 100 votes in favour, none against, and one abstention: a Resolution on the “Legal and human rights aspects of the Russian Federation's aggression against Ukraine.”
The Innovation Behaviour of Turkish Manufacturing Firms: An Analysis of Additionality
Authors: Öztürk Selcen , Başar Dilek , Çakmak İsmail , Güler Aydin Derya
Published: March 2024

Innovation and R&D activities have significant effects on economic development and firm success. Innovation is a key factor in economic development through productivity gains. However, firms do not perform the socially optimal level of innovation due to market failures. Therefore, innovation activity is largely supported by governments for both developed and developing countries with the aim of creating additionality. While additionality effects from government supports are widely discussed for developed countries, there is scarce evidence for developing countries. The aim of this article is to analyse innovation behaviour of Turkish firms based on firm characteristics. Further, the behavioural additionality of government support is also analysed in order to provide a full picture. For this aim, the innovation structure is analysed using a multinomial logit model and the additionality effects are analysed using the propensity score matching (PSM) technique. Results indicate that firms that are profit-oriented, produce for the internal market and have an internal R&D unit, are more likely to implement organization and/or marketing innovation in comparison with product innovation. In addition, the same pattern is observed in companies that received government support. The results additionality indicate positive effects on behavioural additionality; however, this effect is evaluated to be limited.
AN EFFECTIVE UPPER BOUND FOR ANTI-CANONICAL VOLUMES OF SINGULAR FANO THREEFOLDS
Authors: Jiang Chen , Zou Yu
Published: March 2024

For a real number
$0<\epsilon <1/3$
, we show that the anti-canonical volume of an
$\epsilon $
-klt Fano
$3$
-fold is at most
$3,200/\epsilon ^4$
, and the order
$O(1/\epsilon ^4)$
is sharp.
The Role of Personal Demands and Personal Resources in Enhancing Study Engagement and Preventing Study Burnout
Authors: Zeijen Marijntje E. L. , Brenninkmeijer Veerle , Peeters Maria C. W. , Mastenbroek Nicole J. J. M.
Published: March 2024

Using a 1-year longitudinal design, we examined the role of personal demands and personal resources in long-term health impairment and motivational processes among master students. Based on the job demands-resources theory and transactional model of stress, we hypothesized that students’ personal demands (i.e., irrational performance demands, awfulizing and irrational need for control) predict perceived study demands one year later, and indirectly relate to burnout. Furthermore, we predicted that personal resources indirectly associate with study engagement via students’ perceived study resources one year later. These hypotheses were tested in a sample of Dutch master students (N = 220 at T1 and T2) using structural equation modelling. As hypothesized, personal demands and personal resources at T1 predicted study demands and study resources one year later (T2, β = .25–.42, p <. 05), respectively. Study-home interference [study demand] mediated the association between personal demands and burnout (β = .08, p = .029), whereas opportunities for development [study resource] mediated the association between personal resources and study engagement (β = .08, p = .014). Hence, personal demands and personal resources relate indirectly to students’ burnout and engagement one year later via a heightened level of specific study demands and study resources. Accordingly, the present research expands the propositions of the JD-R Theory by proposing personal demands as a relevant factor for students’ long-term well-being.
Feature of Diurnal Double Maxima in the Topside Ionosphere Observed by ICON
Authors: Du Rongjin , Zhang Ruilong , Liu Libo , Han Tingwei , Li Wenbo , Tariq M. Arslan , Le Huijun , Chen Yiding , Yang Yuyan
Published: March 2024

This study investigates the diurnal variation of topside ionospheric plasma density using the Ionospheric Connection Explorer (ICON) observations from May to July in 2020 and 2021. The total ion density exhibits daytime double‐maxima (DDM) patterns, also known as “bite‐out” at magnetic latitudes from 10°S to 20°N and longitudes of 180°–276°E, but a single peak in other longitudes. The total ion density between 180° and 276°E reaches its first peak around 12 LT (Local Time) in both hemispheres and the second peak at 14–15 LT in the Northern Hemisphere, gradually shifting to around 16–17 LT in the Southern Hemisphere. The formation of the first peak is mainly influenced by vertical plasma drift, while the second peak is associated with both neutral wind and vertical plasma drift. Furthermore, this study provides direct observational evidence for the influence of neutral winds on the longitude and latitude differences of the topside DDM. Stronger southward magnetic meridional winds and vertical plasma drifts are observed at approximately 11–15 LT in the longitude sector with DDM compared to other longitudes, leading to a valley of ion density in the Southern Hemisphere around 15 LT. In the Northern Hemisphere, ion density continues to accumulate to form a second peak at 15 LT.
Agricultural Land‐Use Increases Carbon Yields in Lowland Streams of the Congo Basin
Authors: Drake Travis W. , Baumgartner Simon , Barthel Matti , Bauters Marijn , Alebadwa Serge , Akoko Nadine Bahizire , Haghipour Negar , Eglinton Timothy , Van Oost Kristof , Boeckx Pascal , Six Johan
Published: March 2024

As the dominant mode of deforestation in the Congo Basin, shifting agriculture is expected to increase with the projected four‐fold population growth for the region by 2,100. To assess how this land‐use change will affect the export of carbon (C) to rivers in a typical lowland forest ecosystem, we studied paired watersheds near Kisangani, Democratic Republic of the Congo. Two streams, one draining an intact forest (Forest) and one draining an agricultural landscape (Ag), were gauged, equipped with sensors, and sampled fortnightly for one year. Annual average specific discharge was 1.4 mm d−1 (+76%) higher in the Ag compared to the Forest. Average annual dissolved organic C (DOC) and particulate organic C (POC) concentrations were 5.2 mg L−1 (+163%) and 1.3 mg L−1 (+81%) higher in the Ag stream, which, along with the higher discharge, resulted in 8.3 (+410%) and 2.4 g C m−2 yr−1 (+97%) larger C yields, respectively. Baseflow dissolved inorganic carbon, carbon dioxide, and methane yields were also higher in the Ag stream. Despite the higher yields of organic C (OC), the composition of OC did not differ significantly. Carbon to nitrogen ratios, along with isotopic signatures, revealed that both streams contained young, semi‐degraded organic matter derived from C3 vegetation. Correspondingly, biodegradable DOC (BDOC) proportions did not differ between the streams, although the Ag stream yielded more total BDOC. These results show that agricultural land‐use likely exports a greater proportion of Net Primary Productivity (NPP) to aquatic ecosystems, which may affect both C storage in soils and the proportion of gross PP that is ultimately respired.
Super Tuesday Lays Out Election’s Environmental Stakes
Authors: Cartier Kimberly
Published: March 2024

U.S. elections could pull the country back from several environmental tipping points—or push it beyond them. Scientists are urging people to seek climate action beyond the ballot.
Axicabtagene ciloleucel treatment is more effective in primary mediastinal large B-cell lymphomas than in diffuse large B-cell lymphomas: the Italian CART-SIE study
Authors: Chiappella Annalisa , Casadei Beatrice , Chiusolo Patrizia , Di Rocco Alice , Ljevar Silva , Magni Martina , Angelillo Piera , Barbui Anna Maria , Cutini Ilaria , Dodero Anna , Bonifazi Francesca , Tisi Maria Chiara , Bramanti Stefania , Musso Maurizio , Farina Mirko , Martino Massimo , Novo Mattia , Grillo Giovanni , Patriarca Francesca , Zacchi Giulia , Krampera Mauro , Pennisi Martina , Galli Eugenio , Martelli Maurizio , Ferreri Andrés J. M. , Ferrari Silvia , Saccardi Riccardo , Bermema Anisa , Guidetti Anna , Miceli Rosalba , Zinzani Pier Luigi , Corradini Paolo
Published: March 2024

Axicabtagene ciloleucel showed efficacy for relapsed/refractory large B-cell lymphomas (LBCL), including primary mediastinal B-cell lymphomas (PMBCL); however, only few PMBCLs were reported. Aim was to evaluate efficacy and safety of axicabtagene ciloleucel in patients with PMBCL compared to those with other LBCL, enrolled in the Italian prospective observational CART-SIE study. PMBCLs (n = 70) were younger, with higher percentage of bulky and refractory disease, compared to other LBCLs (n = 190). Median follow-up time for infused patients was 12.17 months (IQR 5.53,22.73). The overall (complete + partial) response rate (ORR,CR + PR) after bridging was 41% for PMBCL and 28% for other LBCL, p = 0.0102. Thirty days ORR was 78% (53/68) with 50% (34) CR in PMBCL, and 75% (141/187) with 53% (100) CR in other LBCL, p = 0.5457. Ninety days ORR was 69% (45/65) with 65% (42) CR in PMBCL, and 54% (87/162) with 47% (76) CR in other LBCL; progressive disease was 21% in PMBCL and 45% in other LBCL, p = 0.0336. Twelve months progression-free survival was 62% (95% CI: 51–75) in PMBCL versus 48% (95% CI: 41–57) in other LBCL, p = 0.0386. Twelve months overall survival was 86% (95% CI: 78–95) in PMBCL versus 71% (95% CI: 64–79) in other LBCL, p = 0.0034. All grade cytokine release syndrome was 88% (228/260); all grade neurotoxicity was 34% (88/260), with 6% of fatal events in PMBCL. Non-relapse mortality was 3%. In conclusion, PMBCLs achieved significantly better response and survival rates than other LBCLs.
Alpha5 nicotine acetylcholine receptor subunit promotes intrahepatic cholangiocarcinoma metastasis
Authors: Fu Yan , Shen Keyu , Wang Hao , Wang Shun , Wang Xufeng , Zhu Le , Zheng Yan , Zou Tiantian , Ci Hongfei , Dong Qiongzhu , Qin Lun-Xiu
Published: March 2024

Neurotransmitter-initiated signaling pathway were reported to play an important role in regulating the malignant phenotype of tumor cells. Cancer cells could exhibit a “neural addiction” property and build up local nerve networks to achieve an enhanced neurotransmitter-initiated signaling through nerve growth factor-mediated axonogenesis. Targeting the dysregulated nervous systems might represent a novel strategy for cancer treatment. However, whether intrahepatic cholangiocarcinoma (ICC) could build its own nerve networks and the role of neurotransmitters in the progression ICC remains largely unknown. Immunofluorescence staining and Enzyme-linked immunosorbent assay suggested that ICC cells and the infiltrated nerves could generate a tumor microenvironment rich in acetylcholine that promotes ICC metastasis by inducing epithelial-mesenchymal transition (EMT). Acetylcholine promoted ICC metastasis through interacting with its receptor, alpha 5 nicotine acetylcholine receptor subunits (CHRNA5). Furthermore, acetylcholine/CHRNA5 axis activated GSK3β/β-catenin signaling pathway partially through the influx of Ca2+-mediated activation of Ca/calmodulin-dependent protein kinases (CAMKII). In addition, acetylcholine signaling activation also expanded nerve infiltration through increasing the expression of Brain-Derived Neurotrophic Factor (BDNF), which formed a feedforward acetylcholine-BDNF axis to promote ICC progression. KN93, a small-molecule inhibitor of CAMKII, significantly inhibited the migration and enhanced the sensitivity to gemcitabine of ICC cells. Above all, Acetylcholine/CHRNA5 axis increased the expression of β-catenin to promote the metastasis and resistance to gemcitabine of ICC via CAMKII/GSK3β signaling, and the CAMKII inhibitor KN93 may be an effective therapeutic strategy for combating ICC metastasis.
Isoform alterations in the ubiquitination machinery impacting gastrointestinal malignancies
Authors: Kasturirangan Srimathi , Nancarrow Derek J. , Shah Ayush , Lagisetty Kiran H. , Lawrence Theodore S. , Beer David G. , Ray Dipankar
Published: March 2024

The advancement of RNAseq and isoform-specific expression platforms has led to the understanding that isoform changes can alter molecular signaling to promote tumorigenesis. An active area in cancer research is uncovering the roles of ubiquitination on spliceosome assembly contributing to transcript diversity and expression of alternative isoforms. However, the effects of isoform changes on functionality of ubiquitination machineries (E1, E2, E3, E4, and deubiquitinating (DUB) enzymes) influencing onco- and tumor suppressor protein stabilities is currently understudied. Characterizing these changes could be instrumental in improving cancer outcomes via the identification of novel biomarkers and targetable signaling pathways. In this review, we focus on highlighting reported examples of direct, protein-coded isoform variation of ubiquitination enzymes influencing cancer development and progression in gastrointestinal (GI) malignancies. We have used a semi-automated system for identifying relevant literature and applied established systems for isoform categorization and functional classification to help structure literature findings. The results are a comprehensive snapshot of known isoform changes that are significant to GI cancers, and a framework for readers to use to address isoform variation in their own research. One of the key findings is the potential influence that isoforms of the ubiquitination machinery have on oncoprotein stability.
Bacillus cereus cereolysin O induces pyroptosis in an undecapeptide-dependent manner
Authors: Wang Yujian , Luo Jingchang , Guan Xiaolu , Zhao Yan , Sun Li
Published: March 2024

Bacillus cereus is a clinically significant foodborne pathogen that causes severe gastrointestinal and non-gastrointestinal disease. Cereolysin O (CLO) is a putative virulence factor of B. cereus, and its function remains to be investigated. In this study, we examined the biological activity of CLO from a deep sea B. cereus isolate. CLO was highly toxic to mammalian cells and triggered pyroptosis through NLRP3 inflammasome-mediated caspase 1 and gasdermin D activation. CLO-induced cell death involved ROS accumulation and K+ efflux, and was blocked by serum lipids. CLO bound specifically to cholesterol, and this binding was essential to CLO cytotoxicity. The structural integrity of the three tryptophan residues in the C-terminal undecapeptide was vital for CLO to interact with membrane lipids and cause membrane perforation. Taken together, these results provided new insights into the molecular mechanism of B. cereus CLO-mediated cytotoxicity.
Regulating ion affinity and dehydration of metal-organic framework sub-nanochannels for high-precision ion separation
Authors: Mo Ri-Jian , Chen Shuang , Huang Li-Qiu , Ding Xin-Lei , Rafique Saima , Xia Xing-Hua , Li Zhong-Qiu
Published: March 2024

Membrane consisting of ordered sub-nanochannels has been pursued in ion separation technology to achieve applications including desalination, environment management, and energy conversion. However, high-precision ion separation has not yet been achieved owing to the lack of deep understanding of ion transport mechanism in confined environments. Biological ion channels can conduct ions with ultrahigh permeability and selectivity, which is inseparable from the important role of channel size and “ion-channel” interaction. Here, inspired by the biological systems, we report the high-precision separation of monovalent and divalent cations in functionalized metal-organic framework (MOF) membranes (UiO-66-(X)2, X = NH2, SH, OH and OCH3). We find that the functional group (X) and size of the MOF sub-nanochannel synergistically regulate the ion binding affinity and dehydration process, which is the key in enlarging the transport activation energy difference between target and interference ions to improve the separation performance. The K+/Mg2+ selectivity of the UiO-66-(OCH3)2 membrane reaches as high as 1567.8. This work provides a gateway to the understanding of ion transport mechanism and development of high-precision ion separation membranes.
Meta-analysis of identified genomic regions and candidate genes underlying salinity tolerance in rice (Oryza sativa L.)
Authors: Satasiya Pratik , Patel Sanyam , Patel Ritesh , Raigar Om Prakash , Modha Kaushal , Parekh Vipul , Joshi Haimil , Patel Vipul , Chaudhary Ankit , Sharma Deepak , Prajapati Maulik
Published: March 2024

Rice output has grown globally, yet abiotic factors are still a key cause for worry. Salinity stress seems to have the more impact on crop production out of all abiotic stresses. Currently one of the most significant challenges in paddy breeding for salinity tolerance with the help of QTLs, is to determine the QTLs having the best chance of improving salinity tolerance with the least amount of background noise from the tolerant parent. Minimizing the size of the QTL confidence interval (CI) is essential in order to primarily include the genes responsible for salinity stress tolerance. By considering that, a genome-wide meta-QTL analysis on 768 QTLs from 35 rice populations published from 2001 to 2022 was conducted to identify consensus regions and the candidate genes underlying those regions responsible for the salinity tolerance, as it reduces the confidence interval (CI) to many folds from the initial QTL studies. In the present investigation, a total of 65 MQTLs were extracted with an average CI reduced from 17.35 to 1.66 cM including the smallest of 0.01 cM. Identification of the MQTLs for individual traits and then classifying the target traits into correlated morphological, physiological and biochemical aspects, resulted in more efficient interpretation of the salinity tolerance, identifying the candidate genes and to understand the salinity tolerance mechanism as a whole. The results of this study have a huge potential to improve the rice genotypes for salinity tolerance with the help of MAS and MABC.