bluuebunny/crossref_metadata_2025 huggingface dataset:
Thienothiophene‐Benzopyran Derivative and AQ4N‐Assembled Liposomes for Near‐Infrared II Fluorescence Imaging‐Guided Phototherapy, Chemotherapy, and Immune Activation
Authors: Tang Yuanyu , Pan Tangna , Pang E , Zhao Shaojing , Shen Xingxing , Tan Qiuxia , Zhu Pan , He Dan , Wang Benhua , Song Xiangzhi , Lan Minhuan
Published: November 2024

Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has attracted wide attention in tumor treatment. However, the hypoxic tumor microenvironment and the heat shock proteins produced by tumor cells significantly reduce their efficacy. Developing effective phototherapy agents that have high reactive oxygen species generation efficiency and photothermal conversion efficiency (PCE) while simultaneously utilizing the hypoxic tumor microenvironment is of great importance. Here, a thienothiophene‐benzopyran derivative, BTPIC4F‐C10 is designed and synthesized, with near‐infrared (NIR) absorption and fluorescence. Then the lipid nanoparticles (LipBFCA NPs) which encapsulated BTPIC4F‐C10 in a phospholipid bilayer together with hypoxia‐activated prodrug banoxanthrone (AQ4N) are constructed for NIR‐II fluorescence imaging‐guided synergistic PDT/PTT/chemotherapy and immune activation. Under 808 nm laser irradiation, LipBFCA NPs is a high singlet oxygen quantum yield of 20.2% and PCE of 78.8%. With ultra‐high photon energy utilization efficiency of 99%, LipBFCA NPs is an excellent phototherapy effect. The hypoxic environment caused by phototherapy can further activate AQ4N to transform into chemically toxic AQ4 radicals to kill tumor cells. Moreover, phototherapy can induce immunogenic cell death, release tumor‐associated antigens, and activate immune responses. This work provides a new way for the clinical application of fluorescence imaging in guiding tumor diagnosis and treatment.
Uncovering the Salt‐Controlled Porosity Regulation in Coal‐Derived Hard Carbons for Sodium Energy Storage
Authors: Wu Ruiyao , Yin Jian , Liu Yu , Zhang Rui , Zhang Hu , Yang Chen , Wang HuaiYu , Zhu Hui , Ai Lili , Wang Luxiang , Yin Jiao
Published: November 2024

Coal is a promising precursor of hard carbon (HC) anodes for sodium‐ion batteries (SIBs), by virtue of resource abundance, low cost, and high product yield. However, the concomitant inorganic salt is usually recognized as impurities and plays an obscure and even contradictory effect on the regulation of pore structure in HCs. Herein, a two‐step pyrolysis procedure to the representative salty coal is performed, in which the acid washing program is selectively inserted. It is illuminated that salt acts as a template or activating agent for the generation of open pores at low temperatures but inhibits the closure of pores during the following high‐temperature carbonization. The optimized HC delivers a reversible capacity of 322.4 mAh g−1, a high plateau capacity of 192 mAh g−1, and an initial coulombic efficiency of 80%, outperforming to most coal‐based HCs. Assembled with an NVPOF cathode, the full‐cell exhibits a high energy density of 284.7 Wh kg−1. This work not only provides a systematic understanding of salt‐dependent pore structure modulation but also practices a simple, cost‐effective, and potentially scalable technique for the production of coal‐based HCs.
Scalable Slot‐Die Coating of Passivation Layers for Improved Performance of Perovskite Solar Cell Modules
Authors: Zhu Yanqing , Zhang Yuxi , Hu Min , Wan Li , Huang Wenchao , Chu Jingyuan , Hao Yuying , Cheng Yi‐Bing , Simonov Alexandr N. , Lu Jianfeng
Published: November 2024

Upscaling the perovskite solar cell (PSC) while avoiding losses in the power conversion efficiency presents a substantial challenge, especially when transitioning from ≤1 cm2 cells to ≥10 cm2 modules. In addition to the fabrication of key functional layers, scalable technologies for surface passivation, considered indispensable for achieving high‐performance PSCs, are urgently required. However, studies on this topic remain limited. In this study, an industry‐ready slot‐die coating method for the effective passivation of perovskite films as a practical alternative is developed to the spin‐coating procedures commonly used in research. The coating conditions and molecular structure of the passivation agent are systematically optimized to achieve high‐quality film morphology and substantially suppress interface recombination. 2‐chloro‐5‐(trifluoromethyl)‐phenylammonium bromide exhibited the best results, improving the open‐circuit voltage of cells and subcells in a module by 80 ± 4 and 72 ± 10 mV, respectively. Correspondingly, the larger‐area (active area: 10 cm2) modules sustained the highest efficiency of 21.9% under simulated 1‐sun irradiation. The encapsulated devices retained 94% of their initial performances after 750 h of continuous operation. The proposed surface‐passivation slot‐die technology is compatible with high‐throughput processes and is employable for large‐scale PSC fabrication.
Recent Progress in Steroid C(sp3)−H Functionalization
Authors: Wojtkielewicz Agnieszka , Majewski Adam D. , Łotowski Zenon
Published: November 2024

Selective C−H functionalization methods could provide a valuable tool for synthesizing different steroid derivatives, which is essential not only in contexts of developing novel synthetic methodology but also as a direct way for gathering the analogues needed for studying the structure‐activity relationships and obtaining biologically active compounds. The review discusses recent examples of steroid C−H functionalization to various C−X derivatives (C−O, C−C, C−N, C−S, and C−halogen) using available methods emphasizing their scope and limitations.
From Lithium‐Ion to Sodium‐Ion Batteries for Sustainable Energy Storage: A Comprehensive Review on Recent Research Advancements and Perspectives
Authors: Chandra Bhowmik Konok , Rahman Md. Arafat , Billah Md. Muktadir , Paul Aoyon
Published: November 2024

A significant turning point in the search for environmentally friendly energy storage options is the switch from lithium‐ion to sodium‐ion batteries. This review highlights the potential of sodium‐ion battery (NIB) technology to address the environmental and financial issues related to lithium‐ion systems by thoroughly examining recent developments in NIB technology. It is noted that sodium is more abundant and less expensive than lithium, NIBs have several benefits that could drastically lower the total cost of energy storage systems. In addition, this study examines new findings in important fields including electrolyte compositions, electrode materials, and battery performances of lithium‐ion batteries (LIBs) and NIBs. The article highlights advancements in anode and cathode materials, with a focus on improving energy density, cycle stability, and rate capability of both LIBs and NIBs. The review also covers the advances made in comprehending the electrochemical mechanisms and special difficulties associated with NIBs, such as material degradation and sodium ion diffusion. Future research directions are discussed, with an emphasis on enhancing the scalability and commercial viability of sodium‐ion technology over lithium on Electric Grid. Considering sustainability objectives and the integration of renewable energy sources, the review's assessment of sodium‐ion batteries’ possible effects on the future state of energy storage is included in its conclusion.
How teachers' beliefs and pedagogical practices are impacted by the experience of being labeled as an English learner
Authors: Altavilla‐Giordano Jennifer , Monley Nate
Published: November 2024

This study explores how public school teachers who were classified as English learners (ELs) in childhood make sense of the EL category, and how their beliefs shape their work with students who are designated as ELs. One understudied context in the field of effective education for ELs is the experience of teachers who were personally impacted by the label. In this study, seven teachers tell how they discovered that they were labeled as ELs, describe their experiences as EL‐designated students, and explain how those experiences influence their current understanding of the EL label and shape their teaching. By examining these stories through the lenses of labeling, stigma, and sensemaking, the study informs the work of educators who advocate for and instruct students designated as ELs, as well as individuals who train preservice and in‐service teachers.
Transforming teacher attitudes and practices: The efficacy of sustained professional development in culturally responsive education
Authors: Uribe‐Zarain Ximena , Hellman Andrea B. , Bell Angela B.
Published: November 2024

In light of the growing diversity in U.S. schools, this case study explored how sustained professional development (PD) centered around assets‐based approaches can shape the dispositions of teachers of culturally and linguistically diverse (CLD) students. The study followed 84 in‐service teachers who completed a 2‐year intensive TESOL credentialing course series online that employed the cohort model. The study's purpose was to document changes in in‐service teachers' attitudes, knowledge, and practices as they were taught to apply concepts in their practice such as funds of knowledge, cultural wealth, and third space. The results showed significant improvements in teachers' language attitudes, self‐assessed teaching abilities, and implementation of culturally responsive teaching practices, as measured by various assessment tools and exit interviews. More specifically, findings indicated that, while teachers overestimated their abilities at the start of the program, they demonstrated substantial growth on key outcomes based on the large effects of their improvement on language attitudes (Cohen's d = 1.30), self‐assessed skills and efficacy to teach English learners (Cohen's d = 1.88), and observed teaching practice (Cohen's d = 1.35). Overall, the program effectively shifted teachers from deficit‐based to assets‐based perspectives on CLD students, enhancing their ability to create inclusive learning environments and utilize students' diverse backgrounds as educational strengths. Interviews further revealed positive program feedback, with teachers praising strategies for family engagement and language support, affirming the transformative power of sustained, community‐supported professional development. These findings underscore the importance of ongoing, assets‐focused training in teacher education to foster inclusive and effective teaching for CLD learners, supporting a shift in policy and practice towards such models.
Mechanistic study of forskolin oxidation by Fe(III)‐1,10‐phenanthroline complex
Authors: Bibballi Sridhar Swamy
Published: November 2024

The kinetics and mechanism of forskolin oxidation by the Fe(III) ‐ 1,10‐phenanthroline complex ((), (Phen)) have been studied in a perchloric acid medium. This reaction is of the first order in Fe(III) and forskolin. Synchronistic study showed that an increase in [Phenanthroline] increases the rate of the reaction. The conventional spectroscopic study results are the basis for defining the exact reactive species of the reactants that act on the substrate. At the same time, the product formation rate was altered by the solvent, and the temperature conditions proved that the use of the least amount of acid was more favorable for this reaction. Finally, the oxidant is favored in the form of complex [Fe(Phen)3]3+ (), conclusively the possible reaction mechanism discussed with experimental evidenced kinetic results.
Improving impact strength and fracture toughness of epoxy resin through oligoester—A byproduct derived from the unsaturated polyester resin manufacturing process
Authors: Pham Anh‐Tuan , Duc Pham Anh , Ha Ha Thi , Mai Quan‐Doan , Tran Dieu Vinh
Published: November 2024

Epoxy resin, a pivotal polymer with extensive applications, is hampered by inherent inflexibility and brittleness, limiting its potential in scenarios demanding resilience against external forces. This study addresses this limitation by introducing an innovative modification through the integration of epoxy‐oligoester (EOS), derived as a byproduct of unsaturated polyester resin synthesis. EOS, with an epoxy group content of 7.5% and an acid value of 0.25 mg KOH/g, functions as an effective internal toughening agent for epoxy resin. At 15 wt%, EOS significantly augments impact strength (67.7%) and fracture toughness (92.1%), achieved by reducing network density from 0.792 × 10−3 to 0.678 × 10−3 mol cm−3, resulting in lower storage modulus (E′) and glass transition temperature. Additionally, the addition of 15 wt% EOS retards delamination and amplifies delamination energy. Mode I critical strain energy release rate (GIC) increases by 51.2%, from 608.1 to 911.5 J/m2, and Mode II critical strain energy release rate (GIP) rises by 51.7%, from 664.0 to 1007.6 J/m2. These findings underscore the promise of EOS‐modified epoxy in industries necessitating materials with elevated fracture toughness and superior resistance to delamination, such as transportation, maritime, and automotive sectors.
Breastfeeding and secretory factors in idiopathic granulomatous mastitis: Unveiling etiological insights
Authors: Çetin Kenan
Published: November 2024

Background

Idiopathic granulomatous mastitis (IGM) is a rare, chronic inflammatory, and benign breast disease. Its unclear etiology may involve autoimmune reactions, secretion‐related factors, and microorganisms.

Aim

To analyze data from our IGM patient series and compare potential etiological factors.

Methods

We prospectively collected data using follow‐up forms for patients diagnosed with IGM at our breast clinic from September 2014 to December 2020 and analyzed it retrospectively.

Results

The study cohort included 220 patients, with a median age of 34 years (range: 20–58). A majority, 217 patients (98.6%), reported a history of breastfeeding, with a median duration of 36 months (range: 0–156). The median interval between the last breastfeeding session and disease onset was 25 (25th–75th percentiles: 15–44) months. Additionally, 116 patients (53.5%) reported breastfeeding‐related problems. In 41 surgical patients, dense milky‐brown debris in the breast ducts was noted. Although no independent seasonal fluctuations in disease onset were detected, a reduction in IGM cases during the summer months was found to correlate with a general decrease in all breast clinic visits.

Conclusion

Most patients reported recent breastfeeding and half experienced related problems, supporting the secretion theory's relevance in IGM's etiology. The absence of seasonal fluctuations suggests that secretion‐related factors may be more central to IGM development than autoimmunity or infections. These findings offer crucial insights for future research into IGM's complex causes.
The Safe and Appropriate Use of a High-Speed Drill
Authors: Hongo Kazuhiro , Horiuchi Tetsuyoshi , Goto Tetsuya
Published: November 2024

A high-speed drill is an essential tool for any skull base surgery. However, if not appropriately used, it may cause serious inadvertent complications. Here, the authors present one case of surgery for a paraclinoid aneurysm of the internal carotid artery, in which tissue grabbing occurred during the drilling of the anterior clinoid process. This resulted in venous injury to the vessels of the nearby Sylvian fissure. Fortunately, the injury was manageable and caused no significant problems. The authors discuss the basic and other important points for the safe use of a high-speed drill. Discussion includes basic ways of drill handling, the appropriate selection of burrs, and so on. Bone curettage is also mentioned as a safe alternative tool.
Pial Laceration from a Dural Suture Causing Devastating Neurological Deficits
Authors: Goyal-Honavar Abhijit , Gandham Edmond Jonathan , Chacko Ari George
Published: November 2024

A 39-year-old man received empiric treatment for pulmonary tuberculosis (TB). After developing sensory seizures he was restarted on anti-TB drugs when a brain MRI showed a 4.3 cm left parietal enhancing lesion with extensive edema. After TB treatment, imaging showed a reduction in size and edema. Later, he developed headache and seizures, and MRI showed recurrent edema and an enlarging lesion. Neurosurgery decided to biopsy the lesion to obtain a diagnosis. At craniotomy, a frozen section was reported as granulomatous inflammation. However, he returned postOP with a new right hemiparesis and MRI showed a cystic lesion under the motor cortex, with no enhancement. Craniotomy was performed and the lesion was excised and exploration revealed that one of the dural stitches had lacerated the brain as a cause of the cyst formation. The case differential and management is discussed in detail.
Happiness Trends Before and During the COVID-19 Pandemic in Indonesia: Assessing the Influence of Charitable Donations and Pandemic Severity
Authors: Pattinasarany Indera Ratna Irawati
Published: November 2024

Indonesia’s position as the world’s fourth most populous nation, its reputation as one of the most generous countries, and its deep experience with the COVID-19 pandemic provide an intriguing context for exploring happiness, acts of charity, and pandemic severity. This chapter delves into how generosity affects individual well-being during the pandemic, specifically focusing on the moderating influence of regular and occasional donations (sedekah) on the connection between COVID-19 severity and self-reported happiness. Data from the 2017 and 2021 Surveys on Happiness Level Measurement (SPTK) are employed and analyzed using a multilevel mixed-effects ordered logistic model.

The findings reveal that residents in provinces with higher COVID-19 cases reported reduced happiness compared to those in less-affected regions. Furthermore, giving regular and occasional sedekah donations are associated with increased self-reported happiness, particularly among regular donors who feel a stronger sense of purpose and connection to their causes. Conversely, a negative moderation effect indicates that making regular and occasional sedekah diminishes the link between COVID-19 severity and self-reported happiness, resulting in a less significant impact than non-donors. Ultimately, the pandemic’s severity diminishes the positive influence of donations on happiness.

This study thoroughly examines the intricate interplay between external events, acts of generosity, and contextual factors that influence individual well-being amid a global crisis.
Subcriticality Measurements
Authors: Pyeon Cheol Ho , Chiba Go , Endo Tomohiro , Watanabe Kenichi
Published: November 2024

The index of subcriticality is used to quantify the degree of “how deep a target system has a margin below the critical state.” There are three main categories of subcriticality measurement techniques: the static method, the kinetic method, and the reactor noise analysis method. This chapter is dedicated to explaining the following methods that can be carried out at the Kyoto University Critical Assembly: the neutron source multiplication method, the inverse kinetics method, the pulsed neutron source method, and the reactor noise analysis method such as the Feynman-$$\alpha$$
α
method. As described in this chapter, each of the subcriticality measurement techniques has both advantages and disadvantages. Through the explanations of the principles of the measurements and the procedures, this chapter helps readers understand how to properly select the various subcriticality measurement techniques depending on an experimental condition for a target system.
Control Rod Calibration Experiment
Authors: Pyeon Cheol Ho , Chiba Go , Endo Tomohiro , Watanabe Kenichi
Published: November 2024

To assure the safety of a nuclear reactor during operation, it is important to know the control rod worth, which is an absolute value of negative reactivity induced by a control rod insertion. The measurement for the control rod worth is known as the control rod calibration. In addition to the safety viewpoints, the control rod calibration is important also in conducting other reactor physics experiments since various reactivity effects can be quantified from the known control rod worth. To measure the control rod worth during this experimental program at KUCA, the stable period method, the compensation method, and the rod drop method are employed. Details of these methods are described in this chapter.
Application of Ground Penetrating Radar in the Assessment of Aged Roads: Focus On Complex Structures Under Different Weather Conditions
Authors: Abdelsamei Enas , Sheishah Diaa , Runa Boglárka , Balogh Olivér , Tóth Csaba , Primusz Péter , Trenka Sándor , van Leeuwen Boudewijn , Tobak Zalán , Páll Dávid Gergely , Sipos György
Published: November 2024

Ground penetrating radar (GPR) has been widely used to assess asphalt and pavement, especially in quality testing for newly constructed roads. However, its usage has been limited in regard to aged roads. Thus, this study focuses on the applicability of GPR to extract diverse information regarding structure, thickness, and various conditions, including the moisture content of an aged road section that has undergone repeated renewals. First, two methods were employed to calculate the thickness and dielectric values; the reflection amplitude and ground truth methods. The analysis was done by RADAN 7 software. Based on the findings, the average error of thickness on the same day between continuous GPR and the core data were 2.87% and 8.72%, respectively. Second, dielectric analysis of three structural units was performed under different moisture conditions. As a result, the average dielectric values of macadam (3, 3.3, and 4), surface asphalt layer (4, 7.06, and 8.31), and cement-treated base (4.83, 10.88, and 11.88) were determined under dry, medium-wet, and wet conditions, respectively. The volumetric water difference (f) within the pavement was also estimated. As for the asphalt, macadam, and cement-treated base, the difference in the volume fraction of water (f) was 0.06, 0.01, and 0.1, respectively, under dry and wet conditions, and 0.04, 0.004, and 0.09, respectively, under dry and medium-wet conditions. Overall, the findings demonstrate that reasonably accurate assessments of the pavement thickness, structure, dielectric values, and amplitude of aged roads can be achieved by using a GPR survey under various conditions.
Toric Supervarieties with One Odd Dimension
Authors: Jankowski Eric
Published: November 2024

In this paper we describe the notion of a toric supervariety, generalizing that of a toric variety from the classical setting. We give a combinatorial interpretation of the category of quasinormal toric supervarieties with one odd dimension using decorated polyhedral fans. We then use this interpretation to calculate some invariants of these supervarieties and extract geometric information from them.
Effects of Urinary Incontinence Subtypes on Quality of Life and Sexual Function among Women Seeking Weight Loss
Authors: Tian Zhao , Fu Linru , Wang Xiuqi , Lin Tangdi , Chen Wei , Sun Zhijing
Published: November 2024

Introduction and Hypothesis

The objective was to detect subtypes of urinary incontinence (UI) and their effects on quality of life (QoL) and sexual function among women seeking weight loss.

Methods

A cross-sectional study focusing on women seeking weight loss with UI symptoms was carried out. Participants were stratified into three groups: stress UI, urgency UI, and mixed UI groups. The effects of the three groups on QoL and sexual function were compared.

Results

A total of 564 individuals (46.8%) were reported to present with UI symptoms. Among these, 216 (38.3%), 71 (12.6%), and 277 (49.1%) had stress UI, urgency UI, and mixed UI respectively. The severity of UI was greater in the urgency UI and mixed UI groups than in the stress UI group, with varying ratios observed among patients with different severities of UI: stress UI was highest in mild cases, and the mixed UI was highest in moderate or severe cases. Mixed UI had the most detrimental effect on QoL and sexual function. However, after controlling for the severity of UI, mixed UI still had a greater detrimental effect on UI-specific QoL, and no differences were identified among the three groups regarding general QoL or sexual function.

Conclusion

This study revealed variations in the constituent ratios of UI subtypes related to the severity of UI and the effects of various UI subtypes on QoL and sexual function among women seeking weight loss. Notably, the mixed UI demonstrated the most severe symptoms and the most detrimental impact, particularly as assessed by UI-specific QoL questionnaires.
Improved ion detection sensitivity in mass spectrometry imaging using tapping-mode scanning probe electrospray ionization to visualize localized lipids in mouse testes
Authors: Otsuka Yoichi , Okada Maki , Hashidate-Yoshida Tomomi , Nagata Katsuyuki , Yamada Makoto , Goto Motohito , Sun Mengze , Shindou Hideo , Toyoda Michisato
Published: November 2024

Mass spectrometry imaging (MSI) is a promising analytical method to visualize the distribution of lipids in biological tissues. To clarify the relationship between cellular distribution and lipid types in a tissue, it is crucial to achieve both an improvement in ion detection sensitivity and a reduction in the ionization area. We report methods for improving the efficiency of ion transfer to a mass spectrometer and miniaturizing the extraction area of a sample for tapping-mode scanning probe electrospray ionization (t-SPESI), atmospheric pressure sampling, and ionization methods. To verify the efficacy of the new t-SPESI measurement system, MSI was performed on mouse testes with a pixel size of 5 µm. Lipid images of the testes from wild-type (WT) and lysophospholipid acyltransferase 3 (LPLAT3) knockout mice revealed the characteristic distribution of docosahexaenoic acid–containing phospholipids (DHA-PLs). A comparison of the ion images obtained by MSI and optical images of the same tissues stained with hematoxylin and eosin suggested that the distribution of DHA-PLs was significantly altered by spermatogenesis in the WT mouse testes.

Graphical abstract
Investigating the associations between uncarboxylated matrix gla protein as a proxy for vitamin K status and cardiovascular disease risk factors in a general adult population
Authors: Lauridsen Julie Aaberg , Leth-Møller Katja Biering , Møllehave Line Tang , Kårhus Line Lund , Dantoft Thomas Meinertz , Kofoed Klaus Fuglsang , Linneberg Allan
Published: November 2024

Purpose

Vitamin K is an activator of vitamin K dependent proteins, one of which is the potent inhibitor of vascular calcification, matrix Gla protein (MGP). The purpose of this study is to investigate the association between an inverse proxy of functional vitamin K status, plasma dephospho-uncarboxylated MGP (dp-ucMGP), and cardiovascular disease risk factors (CVDRFs).

Methods

In a cross-sectional population-based health examination study of 4,092 individuals aged 24–77 years, the vitamin K status was assessed using plasma dp-ucMGP. All participants were linked to Danish National Prescription Register to obtain information on the use of vitamin K antagonists. The associations between log2 transformed dp-ucMGP values and CVDRFs were determined using regression models adjusted for sex, age, lifestyle factors, kidney function and waist circumference.

Results

Higher dp-ucMGP levels were associated with increased risk of central obesity (Odds Ratio (OR) 4.76, 95% Confidence Intervals (CI) 3.57–6.34), diabetes (OR 1.96, 95% CI 1.11–3.45), hyperlipidaemia (OR 1.43, 95% CI 1.01–2.03), and impaired kidney function (OR 9.83, 95% CI 5.49–17.59) per doubling in dp-ucMGP. Dp-ucMGP was not independently associated with hypertension or arterial stiffness.

Conclusion

Higher dp-ucMGP levels were associated with central obesity, diabetes, hyperlipidaemia, and impaired kidney function. Prospective studies and intervention studies examining the effects of improving vitamin K status are needed to clarify the potential role of vitamin K in relation to these CVDRFs.
Streptococcus pneumoniae and influenza vaccination rates in oncological patients — data from Germany
Authors: Niederstein Emma , Underwood Journey , de Wit Maike , Reinwald Mark , Schwarzlose-Schwarck Sandra , Dammermann Werner , Deckert P. Markus , Kiderlen Til Ramón
Published: November 2024

Objectives

Due to disease- or therapy-associated immunosuppression, oncological patients suffer from significantly higher morbidity and mortality due to infections transmitted by respiratory pathogens such as Streptococcus pneumoniae and influenza virus. Although the German Standing Committee on Vaccination (STIKO) provides specific recommendations for vaccination against these pathogens, there is no data on vaccination rates in this high-risk population.

Methods

Data from the interventional EVO study were analyzed to provide information on vaccination rates against Streptococcus pneumoniae and influenza virus in oncological patients. Numbers presented in this publication summarize baseline and follow-up data of the control group; thus, data were not influenced by the intervention.

Results

Data of 370 patients were analyzed; 20.5% of patients were treated for hematological malignancies and 79.5% for solid cancer. 28.1% of patients had received vaccination against influenza and 32.2% against Streptococcus pneumoniae; for the latter only 7.3% according recommendations. While vaccination rates where even lower for patients with thoracic carcinoma (influenza 26.7% and Streptococcus pneumoniae 6.0% according to STIKO recommendations), rates in patients with multiple myeloma were remarkably higher (39.0% and 14.6%).

Conclusions

Despite strong recommendations to vaccinate and the clear clinical need to prevent infections in the vulnerable group of oncological patients, only the minority was vaccinated against Streptococcus pneumoniae or influenza, underlining the urgent need for better vaccination strategies in this high-risk population.
Energy barriers for boundary nucleation in a two-well model without gauge invariances
Authors: Tribuzio Antonio , Zemas Konstantinos
Published: November 2024

We study energy scaling laws for a simplified, singularly perturbed, double-well nucleation problem confined in a half-space, in the absence of gauge invariance and for an inclusion of fixed volume. Motivated by models for boundary nucleation of a single-phase martensite inside a parental phase of austenite, our main focus in this nonlocal isoperimetric problem is how the relationship between the rank-1 direction and the orientation of the half-space influences the energy scaling with respect to the fixed volume of the inclusion. Up to prefactors depending on this relative orientation, the scaling laws coincide with the corresponding ones for bulk nucleation (Knüpfer in Proc R Soc A Math Phys Eng Sci 467(2127): 695-717, 2011) for all rank-1 directions, but the ones normal to the confining hyperplane, where the scaling is as in a three-gradient problem in full space, resulting in a lower energy barrier (Rüland et al. J Nonlinear Sci 33(2): 25 2023).
Glioblastoma invasion patterns from a clinical perspective—a systematic review
Authors: Percuoco Veronica , Herlin Erica , Prada Francesco , Riva Marco , Pessina Federico , Staartjes Victor E. , Della Pepa Giuseppe Maria , Menna Grazia
Published: November 2024

Glioblastoma (GBM) is the most common and aggressive primary brain tumor. Despite advances in treatment, mechanisms underlying GBM invasion remain incompletely understood. This systematic review synthesizes findings from laboratory and clinical studies to elucidate the molecular mechanisms driving GBM invasion and their implications for prognosis and therapy. This review adhered to PRISMA guidelines, conducting a comprehensive search of PubMed/Medline for studies published up to October 16, 2023. Inclusion criteria focused on studies investigating molecular mechanisms of GBM invasiveness with reported clinical outcomes (overall survival (OS) and progression-free survival (PFS). Exclusion criteria included systematic reviews, case reports, small case series, and studies limited to preclinical data. Risk of bias was assessed using the ROBINS-I tool. From 831 records, 21 studies (2198 patients) met the criteria. Key GBM invasion mechanisms included ECM degradation, vascular invasion, EMT, apoptotic regulation, cytoskeletal organization, and RNA sequencing. Vascular mechanisms were most studied. Bevacizumab resistance linked to poorer outcomes. EMT markers like TWIST and ECM degradation via MMPs such as CD147 correlated with decreased survival. Cytoskeletal and RNA studies highlighted the prognostic significance of tumor subtypes and microenvironmental interactions. This systematic review elucidates the molecular mechanisms underlying GBM invasiveness and their clinical implications. Integrating molecular profiling into routine clinical assessment may enhance prognostic accuracy and therapeutic efficacy, paving the way for personalized treatment strategies.
Development of hepatocellular carcinoma organoid model recapitulating HIF-1A metabolic signature
Authors: Khedr Mennatallah A. , Mohamed Zainab , El-Derby Azza M. , Soliman Malak M. , Edris Amira Abdel Fattah , Badr Eman , El-Badri Nagwa
Published: November 2024

Hypoxia is one of the main hallmarks of hepatocellular carcinoma (HCC) resulting from improper oxygenation and insufficient nourishment of the HCC microenvironment. The effect of hypoxia is mediated by hypoxia-inducible factor-1A (HIF-1A) via targeting various downstream pathways, including glycolysis, angiogenesis, and survival signaling. However, HCC cell lines in a 2-dimensional (2D) setting do not resemble the metabolic signature of HCC. Here we aim to overcome these limitations by developing an HCC organoid that recapitulates the HIF-1A metabolic shift. The enrichment analysis of the RNA-Seq data revealed that HIF-1A-driven glycolytic shift is of the significant pathways. The established organoid model, using xeno-free plasma-derived extracellular matrix (ECM) as a scaffold and nutritive biomatrix, maintained its structural integrity and viability for up to 14 days; the comparative analysis of the cobalt (II) chloride (CoCl2)-treated organoids to the untreated ones unveiled reduced size and proliferative capacity. Interestingly, our organoid model showed an elevated expression of HIF-1A and glycolysis enzymes compared to their counterparts in the CoCl2-treated organoids. HIF-1A molecular expression-translated biochemical signature is further assessed in our spontaneously growing organoids showing an increase in glucose uptake, intracellular pyruvate, extracellular lactate dehydrogenase expression, and extracellular lactate production, while hydrogen peroxide (H2O2), a marker for oxidative metabolism, is reduced. Our data confirmed the potency of the established organoid model to mimic the molecular and biochemical HIF-1A-driven metabolism, which validates its potential use as an in vitro HCC model. Our model naturally simulates hypoxic conditions and simultaneous HIF-1A-dependent glycolysis within HCC rather than using of CoCl2-induced hypoxic conditions.
Evidence and Computer Simulations in Public Health
Authors: Iranzo Valeriano , Pérez-González Saúl
Published: November 2024

In the last decades, the evidence-based approach has become dominant in the biomedical sciences. Its influence has extended from clinical practice to other areas such as drug regulation and public health. Nonetheless, given the limitations of the evidence-based framework, a more pluralist approach towards evidence has been demanded. In this sense, evidential pluralism holds that evidence of mechanisms should complement statistical evidence. This paper aims to explore and discuss the prospects of evidential pluralism in public health. First, we will analyse the evidential standards of the International Agency for Research on Cancer. Those standards are argued to be in line with the pluralist approach. Second, we will consider the main challenges for gathering evidence of mechanisms in public health. For that purpose, diverse types of evidence of mechanisms will be identified. And third, we will assess the role of agent-based models as mechanistic studies. Based on a case study, we will discuss whether agent-based models can provide evidence of mechanisms and mitigate the abovementioned challenges.
Evaluating the performance of intensity prediction equations for the Italian area
Authors: Antonucci Andrea , Lanzano Giovanni , Rovida Andrea , Sgobba Sara , D’Amico Vera , Gomez-Capera Augusto Antonio
Published: November 2024

In this study, we evaluate the performance of five recent Intensity Prediction Equations (IPEs) valid for Italy comparing their predictions with intensities documented at Italian localities. We build four different testing datasets using the data contained in the most recent versions of the Italian Parametric Earthquake Catalogue CPTI15 and Macroseismic Database DBMI15 and we estimate the residuals between observed and predicted intensity values for all the selected IPEs. The results are then analyzed using a measure-oriented approach to score each model according to the goodness of model prediction and a diagnostic-oriented approach to investigate the trend of the residuals as a function of the different variables. The results indicate the capability of all the tested IPEs to reproduce the average decay of macroseismic intensity in Italy although with a general underestimation of high-intensity values. In addition, an in-depth investigation of the spatial and temporal patterns of the event residual term, computed using the best predictive model, is carried out. Lastly, we provide some hints for the selection of calibration datasets for the development of future intensity attenuation models.
Reference gene selection for real-time qPCR in European flounder (Platichthys flesus) using organ-specific RNA-seq data
Authors: Pomianowski Konrad , Burzyński Artur
Published: November 2024

Background

The European flounder is readily chosen as an experimental subject and model in physiological and ecotoxicological studies mostly because of its adaptability to laboratory conditions. Many studies utilise a quantitative PCR (qPCR) approach to ascertain the expression of target genes under experimental conditions. Such an approach relies heavily on the selection of reference genes with stable expression. Yet certain housekeeping genes are commonly used in this role, often without due consideration of their overall expression patterns. Therefore, new approaches should be developed to identify stable reference genes for a given species and to expand the general pool of genes suitable for the reference in qPCR analysis.

Methods and results

Here RNA-seq data of nine flounder organs led to identify four candidate genes of the most stable expression. It was achieved by differential expression analysis and tritoconstrictor script. Specific primers were designed for the complete ORF as well as for qPCR analysis. RT-qPCR efficiencies were tested on ORF amplicon templates. Most of the genes tested showed good amplification in a wide range of template dilutions (107-101), with a correlation coefficient (R2) ranging from 0.991 to 0.998 and a consistent efficiency (E) (Sybr Green I staining and TaqMan molecular probe).

Conclusions

The proposed approach based on differential expression analysis and a new bioinformatic tool is an appropriate selection method of candidates for reference genes in qPCR. The proposed approach, combining differential expression analysis with a new bioinformatics tool, provides an effective method for selecting reference gene candidates for qPCR. As a result, we can propose four genes (polr2f, yif1a, sf3b6, uba52), each with a set of validated primers, as suitable for consideration as reference genes in qPCR analysis in European flounder, an emerging model species.
Concept on plug development in jacked open-ended piles in clay considering total stresses
Authors: Wiesenthal Philipp , Henke Sascha
Published: November 2024

Soil plugging in open-ended piles is likely to occur in dense sandy soils which has been the subject of numerous scientific investigations. In contrast, the plugging behaviour in clayey soils is relatively unknown. In this paper an analytical approach to determine the soil plug resistance and its development during jacking in clayey soils is proposed. The new approach was developed using numerical simulations and was validated by back-calculating a field test from the literature. A total stress approach for the numerical simulations was chosen. The values calculated with the analytical formulas and the numerical solutions as well as the measurements from field tests are in very good agreement, given the high complexity of the interactions between pile and soil. Both the plug resistance and the plug height can be calculated during the jacking process. Further research is required to refine the proposed approach for soil plug resistance evaluation, as the proposed method is believed to enhance the understanding of occurring mechanisms.
A multi-center, multi-organ, multi-omic prediction model for treatment-induced severe oral mucositis in nasopharyngeal carcinoma
Authors: Nicol Alexander James , Lam Sai-Kit , Ching Jerry Chi Fung , Tam Victor Chi Wing , Teng Xinzhi , Zhang Jiang , Lee Francis Kar Ho , Wong Kenneth C. W. , Cai Jing , Lee Shara Wee Yee
Published: November 2024

Purpose

Oral mucositis (OM) is one of the most prevalent and crippling treatment-related toxicities experienced by nasopharyngeal carcinoma (NPC) patients receiving radiotherapy (RT), posing a tremendous adverse impact on quality of life. This multi-center study aimed to develop and externally validate a multi-omic prediction model for severe OM.

Methods

Four hundred and sixty-four histologically confirmed NPC patients were retrospectively recruited from two public hospitals in Hong Kong. Model development was conducted on one institution (n = 363), and the other was reserved for external validation (n = 101). Severe OM was defined as the occurrence of CTCAE grade 3 or higher OM during RT. Two predictive models were constructed: 1) conventional clinical and DVH features and 2) a multi-omic approach including clinical, radiomic and dosiomic features.

Results

The multi-omic model, consisting of chemotherapy status and radiomic and dosiomic features, outperformed the conventional model in internal and external validation, achieving AUC scores of 0.67 [95% CI: (0.61, 0.73)] and 0.65 [95% CI: (0.53, 0.77)], respectively, compared to the conventional model with 0.63 [95% CI: (0.56, 0.69)] and 0.56 [95% CI: (0.44, 0.67)], respectively. In multivariate analysis, only the multi-omic model signature was significantly correlated with severe OM in external validation (p = 0.017), demonstrating the independent predictive value of the multi-omic approach.

Conclusion

A multi-omic model with combined clinical, radiomic and dosiomic features achieved superior pre-treatment prediction of severe OM. Further exploration is warranted to facilitate improved clinical decision-making and enable more effective and personalized care for the prevention and management of OM in NPC patients.
Enhanced design of pCMViR-TSC plasmid vector for sustainably high cargo gene expression in mammalian cells
Authors: Sakaguchi Masakiyo , Kinoshita Rie , Tomonobu Nahoko , Sakaguchi Yoshihiko , Futami Junichiro , Yamauchi Akira , Murata Hitoshi , Yamamoto Ken-ichi , Takahashi Tetta , Gohara Yuma , Ochi Toshiki , Jiang Fan , Komalasari Ni Luh Gede Yoni , Chen Youyi , Ruma I Made Winarsa , Sumardika I Wayan , Zhou Jin , Honjo Tomoko , Kuribayashi Futoshi , Sagayama Kazumi , Toyooka Shinichi , Kondo Eisaku , Inoue Yusuke
Published: November 2024

The first-generation pCMViR-TSC, implemented through the promoter sandwich rule, yields 10- to 100-fold higher gene expression than the standard plasmid used with the CMV (cytomegalovirus) or CAG promoter. However, the vector’s shortcomings limit its utility to transient expression only, as it is not suitable for establishing stable transformants in mammalian cells. To overcome this weakness, we here introduce the improved plasmid vector pSAKA-4B, derived from pCMViR-TSC as a second-generation chromosome-insertable vector. This vector facilitates the linear entry of the expression unit into the TTAA site of DNA universally with transposase assistance. The vector is helpful for the indefinite expression of our target gene. The new vector system is proven here to be efficient in establishing stable transformants with a high likelihood of positive clones that exhibit significantly elevated expression levels of the delivered foreign gene. This system, alongside the first-generation vector, is therefore instrumental for diverse basic research endeavors concerning genes, proteins, cells, and animals, and potentially for clinical applications such as gene therapy.
Know Thyself, Improve Thyself: Personalized LLMs for Self-Knowledge and Moral Enhancement
Authors: Giubilini Alberto , Porsdam Mann Sebastian , Voinea Cristina , Earp Brian , Savulescu Julian
Published: November 2024

In this paper, we suggest that personalized LLMs trained on information written by or otherwise pertaining to an individual could serve as artificial moral advisors (AMAs) that account for the dynamic nature of personal morality. These LLM-based AMAs would harness users’ past and present data to infer and make explicit their sometimes-shifting values and preferences, thereby fostering self-knowledge. Further, these systems may also assist in processes of self-creation, by helping users reflect on the kind of person they want to be and the actions and goals necessary for so becoming. The feasibility of LLMs providing such personalized moral insights remains uncertain pending further technical development. Nevertheless, we argue that this approach addresses limitations in existing AMA proposals reliant on either predetermined values or introspective self-knowledge.
Justifying Our Credences in the Trustworthiness of AI Systems: A Reliabilistic Approach
Authors: Ferrario Andrea
Published: November 2024

We address an open problem in the philosophy of artificial intelligence (AI): how to justify the epistemic attitudes we have towards the trustworthiness of AI systems. The problem is important, as providing reasons to believe that AI systems are worthy of trust is key to appropriately rely on these systems in human-AI interactions. In our approach, we consider the trustworthiness of an AI as a time-relative, composite property of the system with two distinct facets. One is the actual trustworthiness of the AI and the other is the perceived trustworthiness of the system as assessed by its users while interacting with it. We show that credences, namely, beliefs we hold with a degree of confidence, are the appropriate attitude for capturing the facets of the trustworthiness of an AI over time. Then, we introduce a reliabilistic account providing justification to the credences in the trustworthiness of AI, which we derive from Tang’s probabilistic theory of justified credence. Our account stipulates that a credence in the trustworthiness of an AI system is justified if and only if it is caused by an assessment process that tends to result in a high proportion of credences for which the actual and perceived trustworthiness of the AI are calibrated. This approach informs research on the ethics of AI and human-AI interactions by providing actionable recommendations on how to measure the reliability of the process through which users perceive the trustworthiness of the system, investigating its calibration to the actual levels of trustworthiness of the AI as well as users’ appropriate reliance on the system.