bluuebunny/crossref_metadata_2025 huggingface dataset:
Decarboxylative Iodination of Coumarin‐3‐carboxylic Acids: A Facile Access to 3‐Iodocoumarins
Authors: Thotathil Vandana , Sidiq Naheed , Idoudi Souha , Al‐Zoubi Raed M. , Shkoor Mohanad , Dawoud Bani‐Yaseen Abdulilah
Published: July 2024

A straightforward protocol for the direct conversion of readily available coumarin‐3‐carboxylic acids to the corresponding 3‐iodocoumarins is described herein. Heating acetonitrile solution of coumarin‐3‐carboxylic acids, molecular iodine and potassium hydrogen phosphate resulted in the decarboxylative iodination of coumarin‐3‐carboxylic acids via radical mechanism. Various electron rich and electron poor coumarin‐3‐carboxylic acids were compatible with the established reaction conditions and consequently afforded the corresponding 3‐iodocoumarins in (46–93 %) reaction yields with minimum purification efforts. The formed products serve as valuable precursors to streamline more complex organic compounds incorporating coumarin core.
Concentration‐driven morphology change of a self‐aggregated amino acid‐inspired fluorescence‐active copolymer for sustained release of hydrophobic drug
Authors: Manna Kalipada , Roy Arpita , Dey Shaon , Kumar Abhay , Pal Sagar
Published: July 2024

The development of amphiphiles for sustained drug delivery represents a promising approach in biomedical fields. Polymeric self‐assembly with a hydrophobic core offers plenty of opportunities to encapsulate hydrophobic drugs for facilitating targeted delivery to the specific sites of action. Herein, N‐Boc tryptophan has been used to develop a hydrophobic monomer, Boc‐tryptophan‐HEMA (HBT). The HBT monomer has further been grafted on modified alginic acid through the RAFT technique to synthesize a unique amphiphilic copolymer with fluorescence characteristics. The advanced polymer chromatography demonstrates a narrow distribution curve, signifying the living nature of polymerization. The copolymer has exhibited self‐aggregation behavior with two distinct shapes at two different critical aggregation concentrations (CAC). The concentration‐dependent shape variation has been investigated using FESEM and TEM analyses, further supported by a small‐angle x‐ray scattering analysis. The self‐aggregation behavior of the copolymer facilitates the uptake of a model hydrophobic drug (naproxen) and its release in a sustained manner with varied rates at two different concentrations.
Fabrication and characterization of Ecklonia cava phlorotannin‐loaded PVA/PVP blend electrospun nanofibers as a potential diabetic wound dressing biomaterial
Authors: Teh Huey Xhin , Phang Shou Jin , Neo Yun Ping , Looi Mee Lee , Kuppusamy Umah Rani , Arumugam Bavani
Published: July 2024

Diabetic wound healing remains a challenging issue, necessitating advanced dressings with active therapeutic agents to reduce inflammation and promote healing. Ecklonia cava phlorotannin (ECP) possesses therapeutic potential for wound healing including anti‐microbial, antioxidant, and anti‐inflammatory properties. Our previous study demonstrates the therapeutic efficacy of ECP‐loaded nanofibers in an in vitro hyperglycemic wound model. The present paper focuses on the detailed characterization of the polyvinyl alcohol (PVA)/polyvinylpyrrolidone (PVP) blend nanofiber incorporated with ECP. The ideal ratio, PVA80:PVP20, is selected to incorporate with ECP via the blend electrospinning method. To confirm the successful loading of ECP (0.5% and 1%), physicochemical characterization is conducted using scanning electron microscopy, Fourier‐transform infrared spectroscopy, and thermal analysis. Functionality assays are performed to evaluate their applicability as dressing biomaterials. Physicochemical analyses confirm the successful loading of ECP into the nanofibers. Overall, the ECP‐loaded PVA/PVP nanofiber membranes exhibit favorable wound dressing criteria, which attributed to high water absorption capacity (200%–400%), sufficient water vapor transmission rate (1550–1650 g/m2/d), high loading efficiency and slow release. Bioactivity tests indicate that the ECP's effectiveness is unaffected by the electrospinning process. Importantly, these membranes exhibit biocompatibility and nontoxicity to human dermal fibroblasts, indicating their potential as good diabetic wound dressings.
Gut Microbiome and Osteoarthritis: Insights From the Naturally Occurring Canine Model of Osteoarthritis
Authors: Stevens Christina , Norris Samantha , Arbeeva Liubov , Carter Scott , Enomoto Masataka , Nelson Amanda E. , Lascelles B. Duncan X.
Published: July 2024

Objective

The purpose of this study was to enhance the current knowledge of the relationship between the gut microbiome and osteoarthritis (OA) and associated pain using pet dogs as a clinically relevant translational model.

Methods

Fecal samples were collected from 93 owned pet dogs. Dogs were designated as either clinically healthy or OA pain using validated methods. Metagenomic profiling was performed through shotgun sequencing using the Illumina NovaSeq platform. MetaPhlAn2 and HUMAnN2 were used to evaluate bacterial taxonomic and pathway relative abundance. Comparisons between healthy and OA‐pain groups were performed individually for each taxa using nonparametric tests following Benjamini and Hochberg adjustment for multiple comparisons. Permutation analysis of variance was performed using Bray‐Curtis distance matrices. All downstream analyses were completed in R.

Results

No significant differences between healthy and OA‐pain dogs were observed for alpha and beta diversity. We found 13 taxa with nominally significant (P < 0.05) associations with OA case status, but none of the associations remained significant after adjustment for multiple comparisons. No differences in alpha or beta diversities or the Firmicutes to Bacteroidetes ratio were found regarding pain severity, mobility or activity level, age, or body composition score.

Conclusion

Similar to recent studies in humans, the present study did not demonstrate a significant difference in the fecal microbial communities between dogs with OA pain and healthy control dogs. Future research in this naturally occurring model should expand on these data and relate the gut microbiome to gut permeability and circulating proinflammatory and anti‐inflammatory molecules to better understand the influence of the gut microbiome on OA and OA pain.
Optimizing the production of dsRNA biocontrols in microbial systems using multiple transcriptional terminators
Authors: Ross Sebastian J. , Owen Gareth R. , Hough James , Philips Annelies , Maddelein Wendy , Ray John , Kilby Peter M. , Dickman Mark J.
Published: July 2024

Crop pests and pathogens annually cause over $220 billion in global crop damage, with insects consuming 5%–20% of major grain crops. Current crop pest and disease control strategies rely on insecticidal and fungicidal sprays, plant genetic resistance, transgenes, and agricultural practices. Double‐stranded RNA (dsRNA) is emerging as a novel sustainable method of plant protection as an alternative to traditional chemical pesticides. Successful commercialization of dsRNA‐based biocontrols requires the economical production of large quantities of dsRNA combined with suitable delivery methods to ensure RNAi efficacy against the target pest. In this study, we have optimized the design of plasmid DNA constructs to produce dsRNA biocontrols in Escherichia coli, by employing a wide range of alternative synthetic transcriptional terminators before measurement of dsRNA yield. We demonstrate that a 7.8‐fold increase of dsRNA was achieved using triple synthetic transcriptional terminators within a dual T7 dsRNA production system compared to the absence of transcriptional terminators. Moreover, our data demonstrate that batch fermentation production dsRNA using multiple transcriptional terminators is scalable and generates significantly higher yields of dsRNA generated in the absence of transcriptional terminators at both small‐scale batch culture and large‐scale fermentation. In addition, we show that application of these dsRNA biocontrols expressed in E. coli cells results in increased insect mortality. Finally, novel mass spectrometry analysis was performed to determine the precise sites of transcriptional termination at the different transcriptional terminators providing important further mechanistic insight.
Real‐world first‐line treatment with pembrolizumab for non‐small cell lung carcinoma with high PD‐L1 expression: Updated analysis
Authors: Ikezawa Yasuyuki , Morita Ryo , Mizugaki Hidenori , Tateishi Kazunari , Yokoo Keiki , Sumi Toshiyuki , Kikuchi Hajime , Kitamura Yasuo , Nakamura Atsushi , Kobayashi Maki , Aso Mari , Kimura Nozomu , Yoshiike Fumiaki , Megumi Furuta , Tanaka Hisashi , Sekikawa Motoki , Hachiya Tsutomu , Nakamura Keiichi , Hommura Fumihiro , Sukoh Noriaki , Ito Kenichiro , Kikuchi Takashi , Agatsuma Toshihiko , Yokouchi Hiroshi
Published: July 2024

Background

Selecting pembrolizumab monotherapy (MONO) or pembrolizumab plus platinum‐based chemotherapy (COMB) for patients with nonsmall cell lung cancer (NSCLC) and high programmed death‐ligand 1 (PD‐L1) expression is an important issue in clinical practice. We previously conducted a retrospective multicenter observational study of patients with NSCLC and high PD‐L1 expression who received MONO or COMB as a first‐line treatment. Here, we report updated data and evaluate the long‐term outcomes.

Methods

We performed a retrospective multicenter study of 298 patients with NSCLC and high PD‐L1 expression who received MONO or COMB as first‐line treatment between December 2018 and January 2020. We reviewed the medical records and assessed the clinical efficacy and toxicity using a prolonged data cutoff.

Results

In total, 164 (median age: 74 years) and 134 (median age: 68 years) patients received MONO and COMB, respectively; patients who received COMB were younger and had better performance statuses (0–1). At the prolonged data cutoff, the median follow‐up was 20.2 (range: 0.1–41.4) months. The median progression‐free survivals were 7.5 and 13.1 months, and overall survivals (OSs) were 17.2 and 33.7 months for MONO and COMB, respectively. Treatment discontinuation rates were 21.9% and 20.1% for the MONO and COMB, respectively. With prolonged follow‐up, although COMB demonstrated an OS benefit and higher objective response rate than MONO, in the propensity score matching analysis COMB didn't demonstrate a significant benefit compared to the MONO.

Conclusions

COMB may be effective as a first‐line treatment for NSCLC with high PD‐L1 expression in a selected subset of patients.
A review of emerging trends, challenges, and opportunities for utilization of metal nanoclusters in CO2 capturing
Authors: Kapoor Atul , Rajput Jaspreet Kaur
Published: July 2024

CO2, a predominant anthropogenic greenhouse gas, emerges as a primary factor in climate change due to the increasing utilization of fossil fuels, necessitating immediate efforts for the development and implementation of strategies like carbon capture and storage (CCS) to mitigate emissions, considering the ongoing dependence on unsustainable energy and transportation resources. The research endeavours to meet the critical requirement for effective CO2 capture through the exploration of novel sorbent materials, with a specific focus on molecularly precise nanoclusters (NCs), aiming to enhance understanding of the catalytic mechanisms in CO2 reduction and design stable, high‐performance sorbents with controllable properties. Advancing the field, the study delves into the synthesis and examination of molecularly precise nanoclusters (NCs), an emerging domain in nanoscience, with a particular emphasis on well‐defined nanoclusters like thiolate‐protected Au, Ag, and Cu NCs. This strategy provides a distinctive foundation for attaining atomic‐level understanding of electrocatalytic CO2 reduction mechanisms, offering a more precise and customized synthesis to overcome challenges associated with polydispersity in conventional nanoparticles. The study highlights the exceptional catalytic activity of specific Au NCs like Au25 in converting CO2 to CO. It surpasses thermodynamic limits. The study also investigates the influence of surface properties, electrostatic, and steric stability on preventing nanocluster aggregation. It emphasizes the potential of molecularly precise nanoclusters as catalysts for CO2 reduction. Additionally, it suggests avenues for advanced sorbent development with improved performance and stability.
Phosphate‐Containing Glycolipids: A Review on Synthesis and Bioactivity
Authors: Pinheiro Luís , Freitas Marisa , Branco Paula S.
Published: July 2024

Phosphate‐containing glycolipids (PcGL) are scarcer than the better understood glycolipids. They are composed of arrangements of phosphate, carbohydrates and glycerol units and are always found associated with lipids. PcGL are often found associated with cell membranes, suggesting they play roles in cell membrane structure and intercellular interactions. This article aims to provide an up‐to‐date overview of the existing knowledge and research on PcGL, emphasizing their synthesis and wide range of biological activities. When it comes to the synthesis of PcGL compounds, the strategies for glycosylation mainly rely on the thioglycoside donor, the trichloroacetamidate donor and halide donor strategies, while phosphorylation is stapled and falls on either phosphite chemistry or phosphoryl chloride chemistry. Certain bacteria utilize PcGLs in their pathogenicity, triggering an inflammatory response within the host's defense mechanisms. The best‐known examples of these structures are teichoic acids, lipopolysaccharide and the capsular polysaccharide found in bacteria, all of which are frequently implicated in bacterial infections. Given the degree of variability within PcGL structures, they were found to display a wide range of bioactivities. PcGL compounds were found to: (1) have anti‐metastatic properties, (2) behave as agonists or antagonists of platelet aggregation, (3) be mostly pro‐inflammatory, (4) display antifungal and antibiotic activity and (5) have neurogenic activity.
Spatial proteomic profiling of tumor and stromal compartments in non‐small‐cell lung cancer identifies signatures associated with overall survival
Authors: Yaghoubi Naei Vahid , Monkman James , Sadeghirad Habib , Mehdi Ahmed , Blick Tony , Mullally William , O'Byrne Ken , Warkiani Majid Ebrahimi , Kulasinghe Arutha
Published: July 2024

Objectives

Non‐small‐cell lung carcinoma (NSCLC) is the most prevalent and lethal form of lung cancer. The need for biomarker‐informed stratification of targeted therapies has underpinned the need to uncover the underlying properties of the tumor microenvironment (TME) through high‐plex quantitative assays.

Methods

In this study, we profiled resected NSCLC tissues from 102 patients by targeted spatial proteomics of 78 proteins across tumor, immune activation, immune cell typing, immune‐oncology, drug targets, cell death and PI3K/AKT modules to identify the tumor and stromal signatures associated with overall survival (OS).

Results

Survival analysis revealed that stromal CD56 (HR = 0.384, P = 0.06) and tumoral TIM3 (HR = 0.703, P = 0.05) were associated with better survival in univariate Cox models. In contrast, after adjusting for stage, BCLXL (HR = 2.093, P = 0.02) and cleaved caspase 9 (HR = 1.575, P = 0.1) negatively influenced survival. Delta testing indicated the protective effect of TIM‐3 (HR = 0.614, P = 0.04) on OS. In multivariate analysis, CD56 (HR = 0.172, P = 0.001) was associated with better survival in the stroma, while B7.H3 (HR = 1.72, P = 0.008) was linked to poorer survival in the tumor.

Conclusions

Deciphering the TME using high‐plex spatially resolved methods is giving us new insights into compartmentalised tumor and stromal protein signatures associated with clinical endpoints in NSCLC.
Antiplasmodial action of 4‐nitrobenzenesulfonamide chalcones: Design, synthesis, characterisation, in vitro and in silico evaluation against blood stages of Plasmodium falciparum 3D7
Authors: Tom Anju Agnes , Rajendran Vinoth , Thottasseri Ahammed Ameen , Goswami Koustav , Roy Souvik , Gopan Gopika , Mani Maheswaran , Kannan Tharanikkarasu
Published: July 2024

Malaria is an intracellular protozoan parasitic disease caused by Plasmodium species with significant morbidity and mortality in endemic regions. The complex lifecycle of the parasite and the emergence of drug‐resistant Plasmodium falciparum have hampered the efficacy of current anti‐malarial agents. To circumvent this situation, the present study attempts to demonstrate the blood‐stage anti‐plasmodial action of 26 hybrid compounds containing the three privileged bioactive scaffolds (sulfonamide, chalcone, and nitro group) with synergistic and multitarget action. These three parent scaffolds exhibit divergent activities, such as antibacterial, anti‐malarial, anti‐fungal, anti‐inflammatory, and anticancer. All the synthesised compounds were characterised using various spectroscopic techniques. The in vitro blood‐stage inhibitory activity of 26 hybrid compounds was evaluated against mixed‐stage culture (asynchronize) of human malarial parasite P. falciparum, Pf 3D7 at different concentrations ranging from 25.0 µg/mL to 0.78 µg/mL using SYBR 1 green assay, with IC50 values determined after 48 h of treatment based on the drug‐response curves. Two potent compounds (11 and 10), with 2‐Br and 2,6‐diCl substitutions, showed pronounced activity with IC50 values of 5.4 µg/mL and 5.6 µg/mL, whereas others displayed varied activity with IC50 values ranging from 7.0 µg/mL to 22.0 µg/mL. Both 11 and 10 showed greater susceptibility towards mature‐stage trophozoites than ring‐stage parasites. The hemolytic and in vitro cytotoxicity assays revealed that compounds 11 and 10 did not cause any toxic effects on host red blood cells (uninfected), human‐derived Mo7e cells, and murine‐derived BA/F3 cells. The in vitro observations are consistent with the in silico studies using P. falciparum‐dihydrofolate reductase, where 11 and 10 showed a binding affinity of −10.4 Kcal/mol. This is the first report of the hybrid scaffold, 4‐nitrobenzenesulfonamide chalcones, demonstrating its potential as an anti‐plasmodial agent.
Reductions in renin‐angiotensin system inhibitors following hospitalization for heart failure
Authors: Goyal Parag , Chen Ligong , Lau Jennifer D. , Rosenson Robert S. , Levitan Emily B.
Published: July 2024

Aims

Limited data are available that evaluate the efficacy of renin‐angiotensin system inhibitor (RASI) dose‐reduction in older adults with heart failure with reduced ejection fraction following a heart failure hospitalization.

Methods and results

We examined a 5% random sample of Medicare beneficiaries with prescription coverage who were discharged to home following a hospitalization for heart failure with reduced ejection fraction between 1 January 2007 and 30 June 2018 and were treated with RASI prior to hospitalization. We classified patients into three mutually exclusive groups based on RASI dosage before (prescription fills up to 90 days prior to) and after a hospitalization (prescription fills up to 365 days that were most proximate to the discharge date as possible)—same/increased dose, dose‐reduction, and discontinuation. We examined associations between RASI prescribing patterns and outcomes (mortality and all‐cause readmission at 30 days and 1 year) using Cox proportional hazards models. Among 12 794 unique older adults, 36.8% experienced a RASI reduction following their hospitalization for HFrEF—15.7% had a dose‐reduction and 21.1% had a discontinuation. Neither dose‐reduction nor discontinuation was associated with 30‐day mortality. Discontinuation was associated 1‐year mortality, 30‐day all‐cause readmission, and 1‐year all‐cause readmission, whereas dose‐reduction was not.

Conclusion

RASI dose‐reduction occurs in 1 out of 7 HF hospitalizations. In contrast to RASI discontinuation, RASI dose‐reduction was not associated with adverse short or long‐term outcomes. These findings indicate that RASI dose‐reduction is preferred over RASI discontinuation in selected situations where RASI reduction is needed.
Site‐specific serology unveils cross‐reactive monoclonal antibodies targeting influenza A hemagglutinin epitopes
Authors: Paparoditis Philipp C. G. , Fruehwirth Alexander , Bevc Kajetana , Low Jun Siong , Jerak Josipa , Terzaghi Laura , Foglierini Mathilde , Fernandez Blanca , Jarrossay David , Corti Davide , Sallusto Federica , Lanzavecchia Antonio , Cassotta Antonino
Published: July 2024

Efficient identification of human monoclonal antibodies targeting specific antigenic sites is pivotal for advancing vaccines and immunotherapies against infectious diseases and cancer. Existing screening techniques, however, limit our ability to discover monoclonal antibodies with desired specificity. In this study, we introduce a novel method, blocking of binding (BoB) enzyme‐linked immunoassay (ELISA), enabling the detection of high‐avidity human antibodies directed to defined epitopes. Leveraging BoB‐ELISA, we analyzed the antibody response to known epitopes of influenza A hemagglutinin (HA) in the serum of vaccinated donors. Our findings revealed that serum antibodies targeting head epitopes were immunodominant, whereas antibodies against the stem epitope, although subdominant, were highly prevalent. Extending our analysis across multiple HA strains, we examined the cross‐reactive antibody response targeting the stem epitope. Importantly, employing BoB‐ELISA we identified donors harboring potent heterosubtypic antibodies targeting the HA stem. B‐cell clonal analysis of these donors revealed three novel, genealogically independent monoclonal antibodies with broad cross‐reactivity to multiple HAs. In summary, we demonstrated that BoB‐ELISA is a sensitive technique for measuring B‐cell epitope immunogenicity, enabling the identification of novel monoclonal antibodies with implications for enhanced vaccine development and immunotherapies.
Performance of multilayered porous breakwater under irregular waves having different wave spectrum
Authors: Dash Santanu Kumar , Koley Santanu , Paul Subhendu , Dey Rajdip , S Maheswaran
Published: July 2024

In this present work, the performance of a two‐layered thick porous breakwater of trapezoidal structure is investigated under the action of irregular waves. To investigate the physical problem, the classical linear water wave theory has been taken into consideration. To analyze the effect of irregular waves on the multilayered structure, two unidirectional wave spectra, namely the Pierson–Moskowitz and JONSWAP spectra based on the frequency domains are considered. Three different sea states are taken to analyze the impact of irregular waves on the multilayered porous breakwater. The constant boundary element method is used to handle the aforementioned boundary value problem, which is considered one of the most efficient numerical tools for handling complex structured open sea problems. Several wave characteristics associated with the spectral density functions are demonstrated and analyzed for a variety of structural and spectral parameters. The findings suggest that the adoption of suitable porous material for the construction of these breakwaters can significantly enhance the energy dissipation and thereby minimize the wave force on the structure.
The male birth control pill – A new approach to family planning and population control
Authors: Ahmed Huda , Memon Aaima , Hoda Fatimah , Alvares Jenelle
Published: July 2024

With the increase in the world's population, contraception is crucial in population control strategies. Majority of contraceptives produced today are targeted at women; many of whom experience side effects, leading to the discontinuation of these contraceptives after a year of use. As the use of condoms and vasectomies has been subjected to scrutiny, it is necessary for the development of male birth control (BC). Attempts to achieve this include hormonal and non‐hormonal contraception. Hormonal contraception prevents the production of the sperm in the testes; but this mode of BC has been found to be ineffective while also causing behavioural changes in men. In contrast, non‐hormonal male contraception focuses on rendering the sperm immotile to prevent fertilization post‐copulation. Soluble adenylate cyclase is an area of research that has shown promise in this field. Furthermore, two inhibitors, TDI‐10299 and TDI‐11861, have been developed and tested, with the latter, showing greater potency and longer activity, in mice models. Overall, by developing non‐hormonal male contraceptives, men will have more control over their reproductive health. Nonetheless, before such contraceptives can be made widely available, it is important that further research takes place to ensure the safety and effectiveness of these methods.
Protective role of macrophages from maternal–fetal interface in unvaccinated coronavirus disease 2019 pregnant women
Authors: Gay Laetitia , Madariaga Zarza Sandra , Abou Atmeh Perla , Rouvière Marie‐Sarah , Andrieu Jonatane , Richaud Manon , Boumaza Asma , Miquel Laura , Diallo Aïssatou Bailo , Bechah Yassina , Otmani Idrissi Myriem , La Scola Bernard , Olive Daniel , Resseguier Noémie , Bretelle Florence , Mezouar Soraya , Mege Jean‐Louis
Published: July 2024

Pregnant women represent a high‐risk population for Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) infection. The presence of SARS‐CoV‐2 has been reported in placenta from infected pregnant women, but whether the virus influences placenta immune response remains unclear. We investigated the properties of maternal–fetal interface macrophages (MFMs) in a cohort of unvaccinated women who contracted coronavirus disease 2019 (COVID‐19) during their pregnancy. We reported an infiltration of CD163+ macrophages in placenta from COVID‐19 women 19 whereas lymphoid compartment was not affected. Isolated MFMs exhibited nonpolarized activated signature (NOS2, IDO1, IFNG, TNF, TGFB) mainly in women infected during the second trimester of pregnancy. COVID‐19 during pregnancy primed MFM to produce type I and III interferon response to SARS‐CoV‐2 (Wuhan and δ strains), that were unable to elicit this in MFMs from healthy pregnant women. COVID‐19 also primed SARS‐CoV‐2 internalization by MFM in an angiotensin‐converting enzyme 2‐dependent manner. Activation and recall responses of MFMs were influenced by fetal sex. Collectively, these findings support a role for MFMs in the local immune response to SARS‐CoV‐2 infection, provide a basis for protective placental immunity in COVID‐19, and highlight the interest of vaccination in pregnant women.
Marine and terrestrial environmental change during the MIS 5–4 transition (southern North Sea area)
Authors: Waajen Irene M. , Peterse Francien , Wesselingh Frank P. , Busschers Freek S. , Wagner‐Cremer Friederike , van Heteren Sytze , Donders Timme H.
Published: July 2024

The Late Pleistocene Marine Isotope Stage (MIS) 5 – MIS 4 transition (at ca. 75 ka) is globally known to correspond to a period of strong cooling and sea‐level lowering. Terrestrial records indicate the transition had a large impact on terrestrial environments, but the impact on coastal and shallow‐marine areas is poorly documented due to a lack of well‐dated, continuous archives caused by erosion during succeeding glacial lowstands. The extensive offshore deposits of the Brown Bank Formation in the southern North Sea yield a valuable record of this transition in a shallow‐marine environment. We show that the southern North Sea experienced subarctic marine conditions with a high input of terrestrial material during the MIS 5–4 transition. These continued marine conditions, which have not been described earlier for northwestern Europe, show that sea level remained relatively high, and lagged cooling on land inferred from lipid‐biomarker palaeothermometry. The time‐lag between terrestrial cooling and sea‐level fall created a sediment preservation window during the onset of MIS 4 in a shallow‐marine environment. Our record captures changes in both the terrestrial and shallow‐marine environments, and allows for linking terrestrial and marine records of the MIS 5–4 transition in NW Europe.
Second primary malignancies in women with breast cancer
Authors: Chen Courtney , Tseng Joshua , Amersi Farin , Silberman Allan W.
Published: July 2024

Background

Increased screening and treatment advancements have resulted in improved survival rates in women with breast cancer (BC). However, recent data suggests these women have elevated risk of developing a second primary malignancy (SPM) compared to the general population. Limited data exists on factors associated with BC patients developing a SPM.

Method

A retrospective review of a prospective single institution database (1990–2016) identified 782 patients with a history of BC. One hundred and ninety‐four BC patients developed a SPM. Clinicopathologic and treatment characteristics were analyzed.

Results

Of the 194 patients (24.8%) who developed a SPM, 56 (28.9%) BC patients were <50 years old (range: 24–87 years). Two‐thirds (64.9%) had at least one first or second degree relative with a malignancy (no relatives—35.1%; ≥1 relative—62.9%). Most patients had invasive ductal carcinoma (n = 117, 60.3%) or ductal carcinoma in situ (n = 39, 20.1%). Twenty‐two patients (11.3%) had pathogenic genetic mutations. Mean time to developing a SPM was 8.9 years (range: 4 months–50 years). Eighty (47.6%) patients received chemotherapy with 91 (54.5%) completing radiation. The most common SPMs were breast (22%), melanoma (17.8%), gynecologic (14.1%), colorectal (12.6%), hematologic (8.9%), and sarcoma (6.5%). Most breast tumors were estrogen receptor (ER) (n = 99, 78.0%) or progesterone receptor (PR) positive (n = 87, 73.1%) but not HER2‐neu positive (n = 13, 14.0%).

Conclusion

Most BC patients who developed a SPM had ER/PR positive tumors and a family history of malignancy, with most <50 years old. Although chemotherapy and radiation increase cancer risk, there were an equal number of patients with SPMs who did or did not receive either treatment. Most SPMs were breast, soft tissue, gynecologic, hematologic, or colorectal. BC patients should be followed closely given an elevated propensity for developing SPMs.
Different temperature sensitivities of key physiological processes lead to divergent trait response patterns in Arctic phytoplankton
Authors: Rehder Linda , Rokitta Sebastian D. , Hoppe Clara J. M. , Buschmann Isabelle , Jasper Levke , Rost Björn
Published: July 2024

Ocean warming is especially pronounced in the Arctic, and phytoplankton will face thermodynamically driven changes in their physiology, potentially pushing them beyond their thermal optimum. We assessed temperature responses of multiple functional traits over their entire thermal window (growth rates, quotas of particulate organic carbon, nitrogen, and chlorophyll a, as well as photophysiological parameters) in three different Arctic phytoplankton species (Thalassiosira hyalina, Micromonas pusilla, and Nitzschia frigida). Temperature response patterns in growth and biomass production rates indicated that all species exhibit wide thermal windows with highest rates at temperatures that exceed current polar temperatures. Species showed different temperature response patterns in cellular elemental quotas, which originate from the interplay of cell division and biomass production: These processes differ in their temperature sensitivity and optima, resulting in U‐shaped, bell‐shaped, or linear patterns of elemental quotas. Despite unaltered light intensity, higher temperatures increased light acclimation indices in all species while lifetimes of photosystem II reopening decreased in all species, suggesting that warming causes a transition from light saturation to light limitation. Our findings on temperature sensitivities of cell division and biomass production not only indicate that Arctic phytoplankton may benefit from moderate warming, but also highlight that meaningful interpretations of cellular quotas require a consideration of the underlying processes.
Friction and wear behavior of micro‐arc oxidation‐modified graphene/epoxy resin composite coating on TC4 titanium alloy
Authors: Chen X. W. , Tang S. , Xie W. L. , Zhang M. , Song H. , Ran Q. Z. , Zhang D. F. , Zeng D. Z.
Published: July 2024

To enhance the friction and wear performance of TC4 titanium alloy, micro‐arc oxidation(MAO) coating was fabricated on its surface, which was subsequently sealed with a modified graphene/epoxy resin coating to form a composite coating of micro‐arc oxidation ‐modified graphene/epoxy resin. The friction and wear performance of samples sealed by different methods are analyzed and characterized using a scanning electron microscope, an energy spectrometer, and friction and wear tester. The results indicate that the modified graphene/epoxy resin coating successfully combines with the micro‐arc oxidation coating and fills the pores, thereby enhancing the friction and wear performance of the composite coating. In tribological tests, compared with other samples, this composite coating has a lower friction coefficient and specific wear rate, showing excellent friction and wear performance, and its main wear mechanism is adhesive wear. Therefore, the fabrication of a micro‐arc oxidation ‐modified graphene/epoxy resin composite coating can improve the friction and wear performance of TC4 titanium alloy.
An efficient microchip electromembrane extraction online with high‐performance liquid chromatography for the measurement of nicotine in high consumption vegetables
Authors: Barzegar Fatemeh , Kamankesh Marzieh , Mohammadi Abdorreza
Published: July 2024

Introduction

Nicotine, a highly addictive substance, is naturally produced in the Solanaceae family of plants, particularly tobacco. The presence of nicotine in plant foods has adverse effects on the lungs, kidneys, heart, and reproductive system.

Objective

A novel three‐phase microchip flat electromembrane coupled with online high‐performance liquid chromatography (HPLC) was developed to analyze nicotine in tomato, mushroom, eggplant, bell pepper, and red pepper.

Methods

The microchip was connected to the HPLC in online mode. All effective variables were optimized to achieve the best extraction response. The use of electric potential and 2‐nitrophenyl octyl ether −5% di(2‐ethylhexyl) phosphate as a modified supported liquid membrane (SLM) increased the sensitivity and selectivity.

Results

The optimal extraction voltage, extraction time, and ion balance were 40 V, 10 min and 0, respectively. The dynamic linear range was 0.5–1000 ng g−1. The obtained recovery, relative standard deviation, and enrichment factor were 98%, 7%, and 35, respectively. The limits of detection 0.4 ng g−1 and the limits of quantification were obtained 1.3 ng g−1. The highest (105.0 ng g−1) and lowest (3.4 ng g−1) concentrations of nicotine were obtained for eggplant and tomato, respectively.

Conclusion

Selective electromembrane extraction of nicotine from the donor phase to the acceptor phase was performed by optimizing the main variables influencing the method mechanism. The new channel design in this analytical system and online injection increased efficiency, stability, and repeatability. The results revealed that this method is capable for the efficient determination of trace amount of nicotine in edible vegetables.
Real‐world evidence of 18F‐fluciclovine Positron emission tomography/computed tomography performance for recurrent prostate cancer in the Veterans Affairs Health System
Authors: Friedrich Nadine A. , Gu Lin , Waller Justin , De Hoedt Amanda M. , Klaassen Zachary , Freedland Stephen J.
Published: July 2024

Background

There are no population‐level studies assessing 18F‐fluciclovine (fluciclovine) utilization of Positron emission tomography/computed tomography (PET/CT) for biochemically recurrent prostate cancer (PC). We assessed fluciclovine PET/CT in the Veterans Affairs Health Care System.

Methods

Of 1153 men with claims suggesting receipt of fluciclovine PET/CT, we randomly reviewed charts of 300 who indeed underwent fluciclovine PET/CT. The primary outcome was fluciclovine PET/CT result (positive or negative). Comparison among groups stratified by androgen deprivation therapy (ADT) (yes vs. no) and prostate‐specific antigen (PSA) (≤1 vs. >1 ng/mL) at imaging were performed. Logistic regression tested associations between PSA, ADT receipt, and race with fluciclovine PET/CT positive imaging.

Results

Fluciclovine PET/CT positivity rate was 33% for patients with PSA 0–0.5 ng/mL, 21% for >0.5–1.0, 54% for >1.0–2.0, and 66% for >2.0 (p < 0.01). A 59% positivity rate ocurred in patients treated with concurrent ADT versus 37% in those not on ADT (p < 0.01). White were more likely to have a positive scan versus Black patients (55% vs. 38%; p = 0.02). Patients whose primary treatment was radical prostatectomy had a lower positivity rate (33%) versus those treated with radiotherapy (55%) (p < 0.001). On multivariable logistic regression, PSA > 1 ng/mL (all men odds ratio [OR]: 4.06, 95% confidence interval [CI]: 2.07–7.96; men on ADT only OR: 4.42, 95% CI: 1.73–11.26) and use of ADT (OR: 3.94, 95% CI: 1.32–11.75), and White (all men OR: 2.22, 95% CI: 1.20–4.17) predicted positive fluciclovine PET/CT.

Conclusion

This real‐world study assessing 18F‐fluciclovine PET/CT performance in an equal access health care system confirms higher detection rates than traditional imaging methods, but positivity is highly influenced by PSA at time of imaging. Additionally, patients currently receiving ADT have at least four times higher likelihood of a positive scan, showing that scan positivity isn't negatively affected by ADT status in this study. Finally, White men were more likely to have a positive scan, the reasons for which should be explored in future studies.
Qualitätssicherung geschweißter ETFE‐Folien für den Einsatz im Bauwesen
Authors: Runge Dominik , Surholt Felix , Uhlemann Jörg , Stranghöner Natalie
Published: July 2024

ETFE‐Strukturen gelten als etablierte Bauweise, die als Fassaden‐ und Dachkonstruktionen meist weitspannender Gebäude eingesetzt werden. Als Membrane besitzen sie ein komplexes Tragverhalten, das durch die Wechselwirkung aus Beanspruchung, Form und Materialverhalten bestimmt wird. Das Materialverhalten wird durch das viskoelastisch‐plastische Kurz‐ und Langzeit‐Zugtragverhalten der verwendeten Folienprodukte charakterisiert und muss für die Bemessung der dauerhaft beanspruchten ETFE‐Strukturen berücksichtigt werden. Die Herstellung der meist doppeltgekrümmten und individuell gestalteten Flächentragwerke wird durch die Schweißbarkeit des Fluorpolymers ermöglicht. Die Schweißverbindungen gelten als Schwachstelle des Gesamtsystems und sind maßgebend im Tragsicherheitsnachweis. In zwei Forschungsvorhaben wurde zum einen das mono‐ und biaxiale Kurz‐ und Langzeit‐Zugtragverhalten von ETFE‐Folien und zum anderen das Tragverhalten von ETFE‐Flächenschweißnähten untersucht sowie Verfahren zur Standardisierung der Ausführung von ETFE‐Schweißnähten erarbeitet. Auf Basis dieser Erkenntnisse wurden Konzepte, Methoden und Normen entwickelt, die für die Qualitätssicherung von ETFE‐Strukturen herangezogen werden können. Die im Rahmen dieser Forschungsvorhaben erarbeiteten grundlegenden Erkenntnisse werden im vorliegenden Beitrag vorgestellt.
Preparing students for the modern information landscape and navigating science–technology–society issues
Authors: Kruse Jerrid , Voss Sarah , Easter Jaclyn , Kent‐Schneider Isaiah , Menke Lucas , Owens David , Roberts Kean , Woodward Lindsay
Published: July 2024

The goals of science education must be sufficiently broad to support learners navigating changing scientific, social, and media landscapes. This position paper builds upon existing scholarship to articulate a set of constructs useful for navigating the modern information landscape including constructs with a long history in science education (e.g., science content knowledge, science practices, nature of science) as well as those still relatively uncommon in science education (e.g., domain‐general epistemological beliefs, science disciplinary literacy, socioscientific reasoning, science media literacy, nature of technology, and critical consciousness). The paper first defines each construct, discusses how each construct supports navigating the modern information landscape, and explores research concerning the teaching and learning of each construct. Then, in the section “Application of Constructs to the Modern Information Landscape”, the paper succinctly explains how the constructs collectively combat particular struggles people may encounter. In addition to defining and articulating the constructs' utility, we explore strategies educators can use to integrate these constructs into their science teaching. Finally, we discuss implications for teaching, teacher education, and future research.
Asking for help works
Authors: Dobree Lucy
Published: July 2024

Warning: contains discussions around mental health.
Heather Maude Nestel
Authors: Trevan Lucy
Published: July 2024

An extraordinary and remarkable woman for whom a veterinary career was a vocation.
Fossil Fictions
Authors: Höglund Johan
Published: July 2024

This chapter explores twentieth-century fiction that registers how the extractive relationship between land and people described in Chapter 1 developed during the twentieth century. The first part of the chapter focuses on the specific emergencies that were connected to the turn to coal in the nineteenth- and early twentieth-century US, and the final section discusses how the militarization of oil energies in the US gave rise to an increasingly self-assured, but also progressively anxious, climate narrative that worries about both biospheric breakdown and world-system transformation. The chapter introduces the concepts of coal frontier narrative and Petrowar fiction as textual modes that contribute strongly to the formation of the American Climate Emergency Narrative.
Fallout Futures
Authors: Höglund Johan
Published: July 2024

This chapter poses that the writing analysed in the book can be considered as a form of ideological and intellectual residue or pathogen released by the core and invading the American imagination. Just as nuclear fallout travels via the stratosphere to all parts of the planet, this ideological fallout, energised by neoliberal globalization, reaches across the globe where it is shifting human environmental concerns towards an understanding of the future as a personal, regional and/or national security concern. The aim of the final chapter is to refocus the needs of the planet as an entangled, multispecies habitat in the process of being destroyed by militarised capitalism. This chapter thus turns to climate narratives from the peripheries and semiperipheries that exist in close proximity to the US core. These, the chapter shows, register capitalism’s epochal crisis from a radically different position and, in doing so, perform important imaginative work that makes it possible to think outside of the intellectual boundaries established by capitalism and the American Climate Emergency Narrative.
Theory and Previous Research
Authors: Chanda Chiseni Michael
Published: July 2024

This chapter delves into theories explaining Africa’s postcolonial economic development, with a focus on institutions, human capital, and the often-overlooked role of Christian missionaries. It explores how initial colonial setups, particularly missionary activities in education and healthcare, have lasting impacts on contemporary development. Through a concise examination of existing research, the chapter sets the stage for understanding the nuanced dynamics shaping Africa’s post-independence economic trajectory.
Methodology
Authors: Chanda Chiseni Michael
Published: July 2024

In this chapter, I outline the data sources and empirical approaches employed to explore the enduring economic effects of Christian missionaries in Zambia. Utilizing a diverse range of historical, geographical, and contemporary data, I employ distinct empirical strategies. Furthermore, I address the inherent limitations of the data.
Experimental Study on Parameters of Hardening Soil Model with Small Strain Stiffness for Muddy Silty Clay and Silty Sandy Soil in Yangtze Floodplain Area
Authors: Wang Yaning , Wei Desheng , Zhai Lei , Qin Huilai , Chen Zheng , Zhu Yuxuan
Published: July 2024

To obtain test parameters for the hardening soil model with small strain stiffness (HSS) of the muddy silty clay and silty sandy soil in the Nanjing Yangtze River floodplain, the following tests were conducted: consolidation test, consolidated-drained triaxial test, triaxial loading and unloading test, resonant column test and other common geotechnical tests. These test parameters included reference tangent modulus Eoedref, reference secant modulus E50ref, reference unloading and reloading modulus Eurref, failure ratio Rf, etc. A standardized process for determining HSS model parameters of certain types of soils, including relevant laboratory tests procedures, calculations, and analyses, has also been discussed. The test findings conclude with a summary of the model parameters for the typical strata in the Yangtze River floodplain region, providing engineering reference value for the deep foundation excavation and other relevant projects in the Yangtze River floodplain area.
Potential Instability Modes and Support Stability Analysis of Soil Accumulation Slopes Along the Lexi Expressway
Authors: Wu L. S. , Li C. F. , Li T. B. , Ren Y. , Wen Y. , Zhang J. S. , Yang J. F.
Published: July 2024

Geological conditions along the Mabian-Zhaojue section of Leshan -Xichang Expressway are complicated, and during the construction process, landslides and geologic hazards are frequent under the influence of engineering excavation disturbance. In view of the deformation, damage and development and evolution of soil slope under excavation disturbance widely existed along Leshan-Xichang Expressway, taking the soil accumulation body slope on the left side of the section from ZK125 + 654 to ZK125 + 775 along the route as the research object, the potential deformation and damage mechanism and the stability of excavation support were analyzed by using FLAC 3D software. The results show that under the unsupported excavation condition, the slope is mainly dominated by creep-slip deformation of the slope surface; under the unsupported rainstorm condition, the slope undergoes large-scale destabilization damage with excavation. In the excavation and support process, as well as in the rainstorm condition after the completion of support, the stability of the slope as a whole and the support structure are better. The slope is a creep-slip-pulling earth slide in which the rock and soil bodies on the surface of the slope body are sheared off at the potential shear sliding surface in the slope body under the multiple effects of engineering disturbance, rainfall and gravity, and the slope body as a whole is subjected to unloading and traction at the leading edge and squeezing and pushing at the trailing edge, and then it slides along the circular arc shaped shear sliding surface in the accumulation body.