bluuebunny/crossref_metadata_2025 huggingface dataset:
Reactivity of a Morita–Baylis–Hillman Adduct Derivative Bearing a Triphenylamine Moiety with Lysine Models
Authors: Venditti Jacopo , Saletti Mario , Paolino Marco , Contena Stefano , Bonechi Claudia , Giuliani Germano , Giorgi Gianluca , Boccia Antonella Caterina , Botta Chiara , Blancafort Lluís , Cappelli Andrea
Published: July 2024

The reactivity of Morita–Baylis–Hillman Adduct (MBHA) derivative 7 was studied with different primary amine derivatives such as n‐butylamine, Nα‐acetyl‐L‐lysine methyl ester, and a poly‐(L‐lysine) derivative as lysine models to obtain information about the possible reactions in complex protein environments. MBHA derivative 7 reacted with n‐butylamine or Nα‐acetyl‐L‐lysine methyl ester producing monoadducts 9a or 9c, which showed bright emission features in the green region at 526–535 nm with photoluminescence quantum yield values in solutions of 73 % and 51 %, respectively. Based on these results, MBHA derivative 7 can be considered an interesting new fluorogenic probe potentially useful in the labelling of basic amino acid residues. Furthermore, similar to other MBHA derivatives, compound 7 showed the tendency to produce diadducts especially in polar solvents system where specific interactions between the extended aromatic moieties may play a major role.
Batch and Continuous Flow Total Synthesis of Cannabidiol
Authors: Braga Felipe C. , da Silva Felipe L. N. , de O. Ramos Tiago , Rosa João G. H. , de A. Araujo Érica , Junior Nelson F. C. , Wendler Edison P. , Beatriz Adilson , de Souza Rodrigo O. M. A. , Brocksom Timothy J. , de Oliveira Kleber T.
Published: July 2024

Herein, we present a comprehensive total synthesis of cannabidiol integrating both batch and continuous flow conditions. Our approach is planned to streamline the synthesis of olivetolic acid derivatives and utilize an enantiomerically pure monoterpene moiety obtained from naturally occurring (R)‐(+)‐limonene by photocatalysis. Key reactions, including the synthesis of olivetolic ester and a Friedel‐Crafts alkylation, are successfully adapted to continuous flow, resulting in improved yields and selectivities. This study not only offers a scalable and efficient route for cannabidiol synthesis but also contributes to the synthetic approaches to access cannabinoids (diversity synthesis), with potential applications in medicinal and industrial contexts.
Facile Synthesis of β‐trifluoromethyl thioethers via DBN‐catalyzed Hydrothiolation of α‐(Trifluoromethyl)styrenes with Thiols
Authors: Deng Yupian , Huang Jiaqi , Qian Yuhao , Sun Zhudi , Huang Qingchun , Cao Song
Published: July 2024

A very simple and atom‐economical method for the synthesis of vicinal trifluoromethyl thioethers via DBN‐catalyzed hydrothiolation of α‐(trifluoromethyl)styrenes with thiols was reported. The reaction proceeded smoothly under mild reaction conditions and provided the β‐CF3‐thioethers in moderate to good yields in an anti‐Markovnikov manner. Furthermore, this method features several remarkable advantages, such as the use of a catalytic amount of DBN, broad substrate scope, excellent functional group compatibility, and easy scalability.
Volunteering in community‐based sports clubs: A refined insight into the role of commitment
Authors: De Clerck Tom , De Bock Thomas , Van Doren Nele
Published: July 2024

Sports club volunteerism transcends mere organizational support, enriching the lives of volunteers and the wider community. Despite its profound impact, many sports clubs struggle with effectively mobilizing and retaining volunteers. Hence, this study utilized partial correlational and cluster analyses to explore how volunteers' affective commitment (i.e., emotional attachment) and normative commitment (i.e., moral duty) relate to their work effort and the intention to sustain their volunteer work over an extended period of time. A total of 355 volunteers from Flemish sports clubs participated in this study. Partial correlational results revealed a strong link between affective commitment and both volunteer work effort and long‐term involvement. However, cluster analyses revealed a more nuanced picture, identifying four distinct commitment profiles: fully committed, affective commitment (AC) dominant, moderately fully committed, and weakly committed. Comparing these profiles in terms of volunteer outcomes indicated that, while affective commitment was the primary driver of work effort, normative commitment played a crucial role in sustaining volunteer involvement when combined with affective commitment. For sports clubs, these findings emphasize the importance of fostering both affective and normative commitment by creating an inclusive and values‐oriented environment. Additionally, recognizing and understanding volunteers' commitment profiles can inform tailored support strategies, ultimately ensuring a sustainable future for the community.
Biological and Computational Studies of Hydrazone Based Transition Metal(II) Complexes
Authors: Kumar Binesh , Devi Jai , Dubey Amit , Kumar Manish
Published: July 2024

In the chronicles of human history, infectious diseases played a pivotal role, influencing societies, steering advancements in medicine, and significantly impacting the well‐being of people worldwide. Consequently, in the pursuit of identifying effective combating agents for infectious ailments, the Co(II), Ni(II), Cu(II), Zn(II) complexes of N′‐(4‐nitrobenzylidene)benzohydrazide were synthesized in the current investigation. Numerous spectral and physical analysis were conducted to characterize the compounds which revealed octahedral stereochemistry of complexes. The anti‐tuberculosis, anti‐inflammatory, antibacterial and antifungal investigations demonstrated that the compounds (1–5) have significant efficacy for these infectious ailments. The [Zn(L)2(H2O)2] complex (5) has comparable TB inhibition potency to streptomycin as shown by MIC value of 0.0196±0.0003 μmol/mL. Additionally, the anti‐inflammatory, antibacterial and antifungal studies also revealed the comparable inhibiting property of (5) to standard drugs with significant IC50 (07.49±0.08 μM) and MIC (0.0098 μmol/mL) values. Furthermore, pharmacophore modeling with addition of molecular docking, DFT, MESP, ADMET were employed against compounds (1–5) to give a new insight in biological evaluations. The pharmacophore modeling suggested that (5) has a distinctive pharmacophoric features including cationic sites, hydrogen‐bond donors and acceptors which provide valuable insights into rational drug design for specific pharmacological applications. Moreover, another in silico investigations authenticate the bioactivity of (5) through substantial binding affinities, binding energy, stability, hardness, electrophilicity etc. Overall, the combined computational and experimental results highlight the potential of [Zn(L)2(H2O)2] as a promising candidate for tuberculosis treatment, meriting further in vivo investigations.
A case of AML with complex karyotype and chromosomal rearrangement of KMT2A
Authors: Moshref Razavi Habib , Minor Agata
Published: July 2024

Key Clinical Message

This is a case of an elderly patient diagnosed with acute myeloid leukemia (AML). While morphological findings, including numerous long, slender, cigar‐shaped Auer rods, suggested AML with t(8;21), cytogenetic and FISH analysis revealed abnormalities in chromosome 11 and the KMT2A (MLL) gene. The patient also exhibited double minutes, typically seen in AML and linked to a complex karyotype and poor prognosis. Correlating morphological findings with molecular genetics and cytogenetics is crucial for accurate diagnosis and treatment.
Machine Learning‐Inspired Molecular Design, Divergent Syntheses, and X‐Ray Analyses of Dithienobenzothiazole‐Based Semiconductors Controlled by S⋅⋅⋅N and S⋅⋅⋅S Interactions
Authors: Ogaki Takuya , Matsui Yasunori , Okamoto Haruki , Nishida Naoyuki , Sato Hiroyasu , Asada Toshio , Naito Hiroyoshi , Ikeda Hiroshi
Published: July 2024

Inspired by the previous machine‐learning study that the number of hydrogen‐bonding acceptor (NHBA) is important index for the hole mobility of organic semiconductors, seven dithienobenzothiazole (DBT) derivatives 1 a–g (NHBA=5) were designed and synthesized by one‐step functionalization from a common precursor. X‐ray single‐crystal structural analyses confirmed that the molecular arrangements of 1b (the diethyl and ethylthienyl derivative) and 1c (the di(n‐propyl) and n‐propylthienyl derivative) in the crystal are classified into brickwork structures with multidirectional intermolecular charge‐transfer integrals, as a result of incorporation of multiple hydrogen‐bond acceptors. The solution‐processed top‐gate bottom‐contact devices of 1b and 1c had hole mobilities of 0.16 and 0.029 cm2 V−1s−1, respectively.
The Hydronaphthalide Monoanion: Isolation of the “red transient” Birch Intermediate from liquid Ammonia
Authors: von Randow Clara A. , Thiele Günther
Published: July 2024

Birch reactions employing alkali metals in ammonia have been a well‐established method for the reduction and functionalisation of aromatic compounds for nearly 100 years. Speculations regarding intermediates in the reaction pathway have been discussed since the beginning. We hereby report the isolation of NMe4(HNaph) (1), a kinetically trapped intermediate of the Birch reaction of naphthalene and sodium in liquid ammonia. 1 has been fully characterised and has been shown to continue to react to 1,2/1,4‐dihydronaphthalene – the Birch product of the reduction of naphthalene. The reactivity of 1 was investigated towards activity as an electron and hydride transfer agent with both, elements and small organic molecules. 1 demonstrates a tamed reduction potential which allows for controlled reactions such as the selective formation of hexasulphide and hexaselenide anions.
Amorphous Strategy and Doping Copper on Metal–Organic Framework Surface for Enhanced Photocatalytic CO2 Reduction to C2H4
Authors: Zheng Lixiao , Yang Huayong , Zhang Min , Guan Zhongjie , Li Qiuye , Yang Jianjun
Published: July 2024

Amorphous photocatalysts are characterized by numerous grain boundaries and abundant unsaturated sites, which enhance reaction efficiency from both kinetic and thermodynamic perspectives. However, amorphization strategies have rarely been used for photocatalytic CO2 reduction. Doping copper onto a metal–organic framework (MOF) surface can regulate the electronic structure of photocatalysts, promote electron transfer from the MOF to Cu, and improve the separation efficiency of electron‐hole pairs. In this study, an amorphous photocatalyst MOFw‐p/Cu containing highly dispersed Cu (0, I, II) sites was designed and synthesized by introducing a regulator and in situ copper species during the nucleation process of MOF (UiO‐66‐NH2). Various characterizations confirmed that the Cu species were anchored to the organometallic skeleton of the surface amorphization MOF structure. The synergistic effect of Cu doping and surface amorphization in MOFw‐p/Cu can significantly enhance the CO and CH4 yields while promoting the formation of the multicarbon product C2H4. The approach holds promise for developing novel, highly efficient MOFs as photocatalysts for CO2 photoreduction, enabling the production of high‐value‐added C2 products.
Experimental Investigation of Evaporation of Methanol and n‐Pentane on a Submerged Capillary Structure
Authors: Margraf Hendrik , Luke Andrea
Published: July 2024

The heat transfer limit of heat pipes is investigated by pool boiling experiments in a standard apparatus with a capillary layer placed on a copper tube. The capillary layer is a hollow cylinder made of bronze with a wall thickness of 2 mm and the test fluids are methanol and n‐pentane. The setting is comparable to high‐flux tubes already investigated in the literature. In dependence on the heat flux, three to four sections with different characteristics are identified. Compared to plain copper tubes, the heat transfer is partially increased by a factor of 12 until the limit is reached at around 70 kW m−2.
Pan‐Cancer Analysis Links Altered RNA m7G Methyltransferase Expression to Oncogenic Pathways, Immune Cell Infiltrations and Overall Survival
Authors: Su Anni , Song Renhua , Wong Justin J.‐L.
Published: July 2024

Background

N7‐methylguanosine (m7G) modification is one of the most prevalent RNA modifications in humans. Dysregulated m7G modifications caused by aberrant expression of m7G writers contribute to cancer progression and result in worse patient survival in several human cancers. However, studies that systematically assess the frequency and clinical relevance of aberrant m7G writer expression in a pan‐cancer cohort remain to be performed.

Aims

This study aims to systematically investigate the molecular alteration and clinical relevance of m7G methyltransferase in human cancers.

Methods

We analysed genome, transcriptome and clinical data from the Cancer Genome Atlas Research Network spanning 33 types of human cancers for aberrant changes in genes encoding m7G writers.

Result

We demonstrate that m7G writers are dysregulated in human cancers and are associated predominantly with poorer survival. By dividing patients into those with high and low m7G scores, we show that a lower m7G score is generally associated with immune infiltration and better response to immunotherapy.

Conclusion

Our analyses indicate the genetic alterations, expression patterns and clinical relevance of m7G writers across various cancers. This study provides insights into the potential utility of m7G writer expression as a cancer biomarker and proposes the possibility of targeting m7G writers for cancer therapy.
A Fatal Case of Immune Checkpoint Inhibitor‐Mediated Myasthenia Gravis, Myositis, and Cardiomyopathy Overlap Syndrome in Urothelial Carcinoma
Authors: Newman Matthew T. , Bikhchandani Mihir
Published: July 2024

Background

Immune checkpoint inhibitors (ICIs) have led to improved outcomes for many cancer types. However, their use can also precipitate immune‐related adverse events (irAEs) that can affect any organ system. While irAEs are often mild, they rarely affect multiple organ systems concurrently and can be fatal.

Case

We report a fatal case of myasthenia gravis, myositis, and cardiotoxicity overlap syndrome precipitated by the ICI pembrolizumab along with a brief review of available literature.

Conclusion

Early recognition of high grade irAEs and prompt intervention is essential. Despite the poor prognosis of these overlap syndromes, current recommendations offer little guidance for severe cases and warrant a call for increased awareness and expansion of available therapeutics.
Population Pharmacokinetic Modeling and Exposure–Response Analysis for the Antibody–Drug Conjugate Enfortumab Vedotin in Locally Advanced or Metastatic Urothelial Carcinoma
Authors: Zuo Peiying , Bonate Peter , Garg Amit , Matsangou Maria , Tang Mei
Published: July 2024

Enfortumab vedotin is a fully human monoclonal antibody directed to Nectin‐4 and conjugated to monomethyl auristatin E (MMAE), approved for treatment of previously treated locally advanced or metastatic urothelial carcinoma (mUC). This population analysis characterized pharmacokinetics of enfortumab vedotin and free (unconjugated) MMAE, identified covariates affecting pharmacokinetics, and evaluated weight‐based dosing for enfortumab vedotin. Exposure–response analyses characterized relationships between enfortumab vedotin and free MMAE exposures and efficacy/safety endpoints. Data from 748 patients with locally advanced or mUC in 5 clinical studies were analyzed using nonlinear mixed‐effects modeling. Patients received enfortumab vedotin 0.50–1.25 mg/kg every 3 weeks or on days 1, 8, and 15 of a 28‐day cycle. Relevant covariates retained in final models were evaluated for clinical relevance to enfortumab vedotin and free MMAE exposures. Although some covariates produced differences in exposure, the magnitude of changes was not clinically meaningful. Simulations indicated weight‐based dosing yielded more consistent exposures across body weight groups vs. a hypothetical fixed‐dose regimen of enfortumab vedotin 95 mg (calculated for median body weight, 75 kg). Exposure–response analysis showed average enfortumab vedotin concentrations were not a statistically significant predictor of overall survival (hazard ratio 0.91, 95% confidence interval: 0.72–1.14; P = 0.41); all exposure quartiles had a greater median overall survival than chemotherapy (11.0–12.6 vs. 9.0 months). Enfortumab vedotin and free MMAE exposures were statistically significant predictors of grade ≥ 3 treatment‐related adverse events (both P < 0.0001). This analysis supports enfortumab vedotin 1.25 mg/kg on days 1, 8, and 15 of a 28‐day cycle.
Ticagrelor modestly raises plasma riboflavin concentration in humans and inhibits riboflavin transport by BCRP and MRP4
Authors: Deng Feng , Hämäläinen Kreetta , Lehtisalo Minna , Neuvonen Mikko , Niemi Mikko
Published: July 2024

Riboflavin (vitamin B2) has been proposed as a biomarker for breast cancer resistance protein (BCRP) activity. In recent studies in mice, cynomolgus monkeys, and humans, BCRP‐inhibiting drugs increased the plasma concentration of riboflavin. We showed recently that ticagrelor inhibits BCRP and raises the plasma concentrations of the BCRP substrate rosuvastatin in healthy volunteers. In the same drug–drug interaction study, we now investigated whether ticagrelor affects the plasma concentrations of riboflavin. Intake of 90 mg ticagrelor increased the ratio between the peak plasma riboflavin concentration and the fasting riboflavin concentration before ticagrelor administration by 1.20‐fold (90% confidence interval, 1.10–1.32; P = 0.006) compared to placebo. In vitro, riboflavin was transported by BCRP and multidrug‐resistance‐associated protein 4 (MRP4) but no clear transport was observed by MRP2, MRP3, or the P‐glycoprotein. Moreover, ticagrelor inhibited the transport of riboflavin in BCRP‐ and MRP4‐expressing membrane vesicles with unbound 50% inhibitory concentrations of 0.020 and 1.1 μM, respectively. Based on vesicle and tissue protein expression data, the small intestinal MRP4‐mediated efflux clearance of riboflavin (1.2–1.4 nL/min/mg) was estimated to be similar to that mediated by BCRP (0.23–1.3 nL/min/mg). As MRP4 is expressed in the basolateral membrane of enterocytes, it may facilitate the absorption of riboflavin and impair the utility of riboflavin as a biomarker of intestinal BCRP. To conclude, ticagrelor modestly raises the plasma concentration of riboflavin probably by inhibiting intestinal BCRP. Inhibition of intestinal MRP4 may have reduced the absorption of riboflavin and limited the effect of ticagrelor on riboflavin levels.
Measuring Interactions Between Proteins and Small Molecules or Nucleic Acids
Authors: Lackner Angela , Qiu Yanfei , Armanus Emy , Macapagal Alijah Nicholas Kahea , Leonidas Lemuel , Xu Huilin , McNulty Reginald
Published: July 2024

Interactions between proteins and small molecules or nucleic acids play a pivotal role in numerous biological processes critical for human health and are fundamental for advancing our understanding of biological systems. Proteins are the workhorses of the cell, executing various functions ranging from catalyzing biochemical reactions to transmitting signals within the body. Small molecules, including drugs and metabolites, can modulate protein activity, thereby impacting cellular processes and disease pathways. Similarly, nucleic acids, such as DNA and RNA, regulate protein synthesis and function through intricate interactions. Understanding these interactions is crucial for drug discovery and development and can shed light on gene regulation, transcriptional control, and RNA processing, providing insights into genetic diseases and developmental disorders. Moreover, studying protein–small molecule and protein–nucleic acid interactions enhances our comprehension of fundamental biological mechanisms. A wide array of methods to study these interactions range in cost, sensitivity, materials usage, throughput, and complexity. Notably in the last decade, new techniques have been developed that enhance our understanding of these interactions. In this review, we aim to summarize the new state‐of‐the‐art methods for detecting interactions between proteins and small molecules or nucleic acids, as well as discuss older methods that still hold value today. © 2024 Wiley Periodicals LLC.
Impacts of empathy, identity, and ethical branding on sustainable local food consumption
Authors: Tamaki Satoru
Published: July 2024

This study clarifies the pathway to sustainable local food consumption highlighting ethical branding. Literature suggests that ethical brands promote continuous local food consumption, however, the structure of purchasing factors and impact has not been fully elucidated. A model is constructed in which empathy‐based social responsibility and self‐identity drive the purchase of local food, and ethical brand purchasing influences consumers’ perception of retailers’ ethics. The model is tested using a questionnaire survey and three years of actual purchase data on consumer purchases of ethically branded local foods. Results show that purchasing local food products, especially ethically branded ones, is mediated by consumers’ self‐identity toward social responsibility based on empathy, and self‐oriented purchasing enhances consumers’ perception of retailers’ ethics. Theoretical implications of the validated model for the studies on local food and ethical consumption, and the practical implications of ethical branding for organizations striving for sustainable development, are discussed.
The influence of supplier financial violations on clients' environmental, social, and governance performance: Evidence from China's manufacturing industry
Authors: Hu Jianhao , Zheng Changran , Xu Jiahao , Wu Xu
Published: July 2024

The antecedents of environmental, social, and governance (ESG) performance have been extensively studied, yet the impact of supplier behavior has been overlooked. By analyzing data from China's manufacturing industry (2013–2020), we find that suppliers' financial violations enhance the overall ESG performance of client firms, with state ownership further reinforcing this relationship. By further examining the ESG dimensions, our study reveals an asynchronous pattern in firms' performance enhancements. Specifically, supplier financial violations significantly boost client firms' social and governance performance, while state ownership attenuates the positive relationship between supplier financial violations and governance performance. Ultimately, our study establishes a crucial link between the conduct of stakeholders within the supply chain and the firm ESG performance. Our findings also facilitate a more comprehensive assessment of the risks associated with supplier financial violations, aiding decision‐makers in shaping and implementing ESG‐related strategies for firms.
A survey on node localization technologies in UWSNs: Potential solutions, recent advancements, and future directions
Authors: Nain Mamta , Goyal Nitin , Dhurandher Sanjay Kumar , Dave Mayank , Verma Anil Kumar , Malik Amita
Published: July 2024

Location‐based underwater communication applications such as strategic surveillance, disaster prevention, marine research, and mine detection have given the field of underwater wireless sensor networks (UWSN) a head start. Node localization is a prerequisite for accurate data collection, target monitoring, and network management in UWSNs. However, the unique characteristics of the underwater environment, such as signal attenuation, multipath propagation, and variable acoustic properties, pose a major challenge to effective node localization. Accurate sensor node location data is essential for successful underwater data collection, but difficult to achieve as the GPS system cannot be used in an underwater environment. In this paper, existing node localization techniques such as ALS, SLUM, MASL, SLMP, UDB, USP, etc., and recent advances such as the fusion of range‐based and range‐free techniques, the fusion of RSSI and AoA to improve localization accuracy by using directional information in addition to signal strength, and the use of optimization techniques such as PSO, COA, and WOA algorithms to improve the accuracy of the applied node localization algorithm, e.g., TP‐TSFLA, and challenges related to UWSN are discussed. Also, different localization algorithms that affect the accuracy of UWSN localization techniques have been evaluated and compared with NS2 in terms of localization error, localization coverage, energy consumption, and average communication cost metrics. In addition, this paper also provides an up‐to‐date investigation of localization techniques. Finally, the tools available for simulation are presented, followed by open research questions that need to be addressed in the localization of nodes.
Recombinant human epidermal growth factor‐loaded liposomes and transferosomes for dermal delivery: Development, characterization, and cytotoxicity evaluation
Authors: Doustvaghe Yasaman Kiani , Haeri Azadeh , Sisakht Mahsa Mollapour , Amirkhani Mohammad Amir , Vatanpour Hossein
Published: July 2024

Recombinant human epidermal growth factor (rhEGF) is widely utilized as an antiaging compound in wound‐healing therapies and cosmetic purposes. However, topical administration of rhEGF has limited treatment outcomes because of its poor percutaneous penetration and rapid proteinase degradation. To overcome these obstacles, this study aims to develop and characterize rhEGF‐containing conventional liposomes (rhEGF‐CLs) and transferosomes (rhEGF‐TFs) as efficient dermal carriers. Physicochemical characterization such as particle size, zeta potential (ZP), morphology, encapsulation efficiency (EE%), and release properties of nanocarriers as well as in vitro cytotoxicity in human dermal fibroblast (HDF) and human embryonic kidney (HEK293) cell lines were investigated. rhEGF‐TFs at the rhEGF concentration ranging from 0.05 to 1.0 μg/mL were chosen as the optimum formulation due to the desired release profile, acceptable EE%, optimal cell proliferation, and minimal cytotoxicity compared to the control and free rhEGF. However, higher concentrations caused a decrease in cell viability. The ratio 20:80 of Tween 80 to lipid was optimal for rhEGF‐TFs‐2, which had an average diameter of 233.23 ± 2.64 nm, polydispersity index of 0.33 ± 0.05, ZP of −15.46 ± 0.29 mV, and EE% of 60.50 ± 1.91. The formulations remained stable at 5°C for at least 1 month. TEM and SEM microscopy revealed that rhEGF‐TFs‐2 had a regular shape and unilamellar structure. In vitro drug release studies confirmed the superiority of rhEGF‐TFs‐2 in terms of optimal cumulative release of rhEGF approximately 82% within 24 h. Franz diffusion cell study showed higher rhEGF‐TFs‐2 skin permeation compared to free rhEGF solution. Taken together, we concluded that rhEGF‐TFs can be used as a promising formulation for wound healing and skin regeneration products.
Survival costs of reproduction are independent of energy costs in a seabird, the pelagic cormorant
Authors: Barracho Téo , Hatch Scott A. , Kotzerka Jana , Garthe Stefan , Schraft Hannes A. , Whelan Shannon , Elliott Kyle H.
Published: July 2024

Life‐history theory predicts that investment in reproduction should decrease survival (the ‘cost of reproduction’). It is often assumed that energy allocation drives such trade‐offs, with limited energy available for both reproduction and survival. However, the underlying mechanisms remain poorly understood, maybe because survival costs of reproduction are only apparent when resources are limited. Here, we took advantage of a natural experiment created by fluctuating environmental conditions to compare energy expenditure of a seabird, the pelagic cormorant (Phalacrocorax pelagicus), between contrasting population‐scale scenarios of survival costs of reproduction. We used multi‐state capture–recapture modelling across 16 years to identify which breeding seasons induced high survival costs (survival ratebreeders < survival ratenon/failed breeders) and we concomitantly estimated energy expenditure of chick‐rearing males using time‐energy budget models across 4 years. Daily energy expenditure (DEE) of chick‐rearing pelagic cormorants varied significantly among years. However, survival costs of reproduction were observed in only 1 year, and contrary to our expectations, variation in DEE was not associated with population‐level survival costs. Similarly, at the individual level, DEE in 1 year did not predict the probability of being observed again at the colony in following years (apparent survival). Finally, DEE was independent of brood size and brood age, but older individuals tended to expend less energy than younger ones. Given the lack of an apparent energetic ‘cost of reproduction’, lower DEE in older birds could be due to improved efficiency rather than avoidance of costs in old birds. Although future studies should account for potential sex‐specific energetic constraints by including data on female energy expenditure, we conclude that a direct link between the rate of energy expenditure during breeding and subsequent survival is unlikely in this system.
Effect of sex on sodium‐glucose co‐transporter‐2 antagonists and glucagon‐like peptide‐1 agonists in heart failure
Authors: Philip Mevin A. , Webb Carolyn M. , Chakraborty Turja , Collins Peter
Published: July 2024

Background

Recent evidence suggests that medications not primarily targeting the cardiovascular (CV) system may have cardioprotective effects in patients with heart failure (HF), in particular the anti‐diabetic therapies sodium‐glucose co‐transporter‐2 (SGLT‐2) antagonists and glucagon‐like peptide‐1 (GLP‐1) agonists. We conducted a systematic review to assess the pooled evidence for the use of SGLT‐2 antagonists and GLP‐1 agonists in patients with HF and the effect of biological sex on the results.

Methods

MEDLINE, Embase, Cochrane Library and clinical trial databases were searched until February 2023. Randomized controlled trials (RCTs) published in English that included adult participants with HF who were randomized to an SGLT‐2 antagonist or GLP‐1 agonist with a primary or secondary outcome of HF hospitalization (HFH) or CV death were eligible for inclusion. Data pooling was undertaken using a random effects model and odds ratios (ORs) to determine the association between drug and outcome. Sub‐group analyses to investigate sex differences were conducted.

Results

Six RCTs were included (24 781 patients). Four studies investigated SGLT‐2 antagonists, and two studies examined GLP‐1 agonists. SGLT‐2 antagonists improved HFH {OR [95% confidence interval (CI)]: 0.69 [0.63, 0.77], P < 0.001} and CV death [0.87 (0.78, 0.97), P = 0.01] independent of diabetes status, with excellent homogeneity across all four studies. No beneficial effects were found for GLP‐1 agonists. The effects of SGLT‐2 antagonists on HFH and CV death were similar in men and women [OR (95% CI): HFH, 0.70 (0.64, 0.76), P < 0.001 and 0.58 (0.46, 0.74), P < 0.001, respectively; CV death, 0.86 (0.78, 0.95), P = 0.003 and 0.84 (0.73, 0.96), P = 0.01, respectively], and the neutral effect of GLP‐1 agonists on HFH and CV death was similar in men and women (all P > 0.05).

Conclusions

SGLT‐2 antagonists but not GLP‐1 agonists beneficially affect HFH and CV death in patients with HF with or without diabetes. We show for the first time that GLP‐1 agonists have a neutral effect on HFH and CV death in both male and female HF patients and a reduction in HFH and CV death in male and female HF patients taking SGLT‐2 antagonists.
The Possible Mechanism of Improving the Performance of Lead‐Acid Batteries by Using Aluminum Ions to Influence the Gel Structure
Authors: Yang Yali , Cao Jing , Yu Yuwen , Chen Yufang , Ma Zhongyun , Zhou Sha , Ma Xiaoyu , Liu Yi
Published: July 2024

Gel lead‐acid batteries have the advantages of no acid leakage, no maintenance, and a long cycle life. In this article, it was found that Al3+ in the gel electrolyte can shorten the gel time and improve the stability of the gel. The battery test results show that the HRPSoC cycle life of the gel battery can be significantly improved by adding Al3+. In comparison to blank gel batteries without Al3+, HRPSoC cycle life is 8.2 times higher. Additionally, the gel battery with added Al3+ has a 0.5C discharge capacity of 1.8 Ah, which is 2.5 times that of the blank gel battery. The added Al3+ also demonstrates good capacity stability and still retains a capacity of 1.7 Ah after 150 discharge cycles. The kinetic simulation shows that Al3+ may participate in the formation of a silicon gel system and tend to gather around Si atoms to affect the properties of the gel electrolyte.
Porous Thermoelectric Materials for Energy Conversion by Thermoelectrocatalysis
Authors: Wu Jiaqi , Chen Kan , Reece Michael J. , Huang Zhaorong
Published: July 2024

Novel uses of thermoelectric (TE) materials as catalyst and catalyst promoters have been reported recently for a variety of applications such as environmental gas mitigation, battery, and photoreduction of nuclear wastewater. TE Seebeck voltage is found to increase the catalytic activities by tens to hundreds of times, and this effect is termed thermoelectrocatalysis. In these uses, the TE materials are in an open‐circuit configuration, which is different from the usual closed‐circuit configuration in the TE energy generation and cooling devices. A new figure of merit defined as the Seebeck voltage per unit heat loss is proposed for the application of thermoelectrocatalysis. Techniques such as dense bulk porous surface and increased thickness of the TE materials are used for the optimization of the thermoelectrocatalysis of the oxyselenide BiCuSeO for the carbon dioxide hydrogenation reactions.
miR‐124 affects dendritic cells function in CRSwNP by regulating exosomes secretion in nasal mucosal epithelial cells
Authors: Zhang Jie , Chen Luqiu , Dong Yuhan , Bing Xin , Yuan Fanyu , Gao Xiaochen , Cao Xue , Li Chengzhilin , Liu Chengcheng , Qi Wenwen , Xia Ming , Li Xiuguo , Du Hongjie
Published: July 2024

The intricate immunomodulatory mechanism underlying the onset and progression of chronic rhinosinusitis with nasal polyps (CRSwNP) in chronic sinusitis with nasal polyps remains poorly understood, particularly regarding the regulatory role of dendritic cells (DCs). MicroRNA has been identified as a modulator of DC function. Primary cells have a short time in vitro and their biological characteristics have not changed greatly which can better reflect the growth state of cells in the body, so as to obtain data closer to the physiological function in the body. Our research group has been engaged in the culture of human nasal epithelial progenitor cells (hNEPCs) for a long time, and in previous investigations, we observed downregulation of microRNA‐124 (miR‐124) in patients with chronic sinusitis and nasal polyps. Thus, our current study aims to elucidate the regulatory mechanism of DCs in chronic sinusitis with polyps by examining the impact of miR‐124 on DCs in this context. To accomplish this, we took the nasal mucosa of CRSwNP patients and normal nasal mucosa of non‐rhinitis patients for primary culture. We isolated exosomes from these cells for co‐culture experiments with DCs. Flow cytometry analysis was employed to assess the maturation phenotypes (MHC II, CD80 and CD86), cell cycle and apoptosis levels of DCs. Furthermore, enzyme‐linked immunosorbent assay was utilized to measure the levels of pro‐inflammatory cytokines (IL‐10, IL‐12 and IL‐23). The TLR4/NF‐κB signalling pathway in co‐cultured DCs was evaluated using the western blot assay. Through querying the Targetscan website, we predicted Rab27a as a target gene of miR‐124, which was subsequently validated through double luciferase assay, flow cytometry and other experimental approaches. Our findings demonstrate that MiR‐124 modulates the secretion of CRSwNP epithelial exosomes, thereby influencing DC function via its interaction with the target gene Rab27a. These results offer novel insights into potential therapeutic targets for the treatment of CRSwNP.
MicroRNA‐146a‐5p protects retinal ganglion cells through reducing neuroinflammation in experimental glaucoma
Authors: Zhou Han , Yang Rui‐Kang , Li Qian , Li Zhen , Wang Yong‐Chen , Li Shu‐Ying , Miao Yanying , Sun Xing‐Huai , Wang Zhongfeng
Published: July 2024

Neuroinflammation plays important roles in retinal ganglion cell (RGC) degeneration in glaucoma. MicroRNA‐146 (miR‐146) has been shown to regulate inflammatory response in neurodegenerative diseases. In this study, whether and how miR‐146 could affect RGC injury in chronic ocular hypertension (COH) experimental glaucoma were investigated. We showed that in the members of miR‐146 family only miR‐146a‐5p expression was upregulated in COH retinas. The upregulation of miR‐146a‐5p was observed in the activated microglia and Müller cells both in primary cultured conditions and in COH retinas, but mainly occurred in microglia. Overexpression of miR‐146a‐5p in COH retinas reduced the levels pro‐inflammatory cytokines and upregulated the levels of anti‐inflammatory cytokines, which were further confirmed in the activated primary cultured microglia. Transfection of miR‐146a‐5p mimic increased the percentage of anti‐inflammatory phenotype in the activated BV2 microglia, while transfection of miR‐146a‐5p inhibitor resulted in the opposite effects. Transfection of miR‐146a‐5p mimic/agomir inhibited the levels of interleukin‐1 receptor associated kinase (IRAK1) and TNF receptor associated factor 6 (TRAF6) and phosphorylated NF‐κB subunit p65. Dual luciferase reporter gene assay confirmed that miR‐146a‐5p could directly target IRAK1 and TRAF6. Moreover, downregulation of IRAK1 and TRAF6 by siRNA techniques or blocking NF‐κB by SN50 in cultured microglia reversed the miR‐146a‐5p inhibitor‐induced changes of inflammatory cytokines. In COH retinas, overexpression of miR‐146a‐5p reduced RGC apoptosis, increased RGC survival, and partially rescued the amplitudes of photopic negative response. Our results demonstrate that overexpression of miR‐146a‐5p attenuates RGC injury in glaucoma by reducing neuroinflammation through downregulating IRAK1/TRAF6/NF‐κB signaling pathway in microglia.
Health performance assessment modeling and its application to compact medical communities in China
Authors: Yu Miao , Huang Zhongmou , Zhang Dan , Yang Yansui , Chien Ching‐Wen , Tuo Hongwu
Published: July 2024

Some regions in China have already implemented capitation payment or capitation budget management for medical insurance funds. However, there remains a shortage of adequate tools and methodologies to accurately quantify differences in population health risks. Therefore, this paper constructs a health performance assessment model that comprises four steps. The first step is to categorize all participants into health risk groups based on whether they have contracted with a family doctor, their age, sex, and the type of consultation. The second step is to categorize health risk groups based on differences in healthcare resource utilization. The third step is to analyze health performance by examining healthcare resource utilization year over year. The fourth step is to apply the assessment results to assist local finance bureaus and medical insurance bureaus in developing incentive schemes. According to cost weights, the health risk groups are split into six classes: insured residents without health care visits, healthy insured person, slightly ill insured patients, ill insured patients, more seriously disease patients, and severely ill insured patients. We evaluate one compact medical community's health performance by examining changes in the proportion of resource usage group size and expense. From 2019 to 2021, both the proportion of patients with severe and ultra‐severe diseases and the proportion of costs in the sample increased, according to changes in resource utilization levels. This result indicates that the population's overall health has not improved and that the compact medical community is still primarily focused on treating diseases, with poor implementation of health maintenance measures and minimal improvement in health performance.
Effectiveness and feasibility of selective intra‐arterial low dose of cisplatin infusion and concomitant radiotherapy for patients with advanced laryngeal cancer with impaired renal function: A retrospective cohort study
Authors: Imahara Yuji , Ono Takeharu , Tanaka Norimitsu , Chitose Shun‐ichi , Sato Fumihiko , Tanoue Shuichi , Kurita Takashi , Miyata Yusaku , Muraki Koichiro , Ogo Etsuyo , Hattori Chikayuki , Abe Toshi , Umeno Hirohito
Published: July 2024

Background

Chemoradiation therapy with high‐dose cisplatin is the standard regimen against advanced squamous cell carcinoma of the larynx (SCC‐L). However, patients with renal dysfunction are ineligible for this regimen. We investigated the effectiveness and feasibility of selective intra‐arterial low‐dose cisplatin infusion and radiotherapy (modified [m]‐RADPLAT) for patients with impaired renal function.

Methods

We retrospectively reviewed the data of 77 patients with SCC‐L who received m‐RADPLAT.

Results

Fourteen and 63 patients had creatinine clearance (CrCl) values of 30 ≤ CrCl < 60 mL/min and ≥60 mL/min, respectively. The m‐RADPLAT regimen led to no significant changes in serum creatinine or CrCl values post‐treatment. The 5‐year local control, overall survival, and laryngectomy‐free survival rates of the CrCl < 60 and ≥60 groups were 90.0% and 90.5%, 100% and 81.8%, and 100% and 79.0%, respectively. Grade 3 or higher toxicity rates were not significantly different between the groups.

Conclusions

The m‐RADPLAT regimen yielded favorable survival rates and clinical outcomes in patients with impaired renal function.
Primary tracheal adenoid cystic carcinoma: A case report and analysis of the tumor immune microenvironment using single cell RNA sequencing
Authors: Ye Wenda , Clark Evan A. , Sheng Quanhu , Colaianni C. Alessandra , Rohde Sarah L. , Gelbard Alexander
Published: July 2024

Background

Tracheal adenoid cystic carcinoma (ACC) is a slow growing yet aggressive malignancy with high rates of local recurrence as well as distant metastasis. Tracheal ACC exhibit a low mutation burden along with high mutational diversity, and generally do not respond well to chemotherapeutics.

Methods

We present a rare case of primary tracheal ACC initially presenting with nonspecific cervicalgia and globus sensation that was ultimately treated with tracheal resection followed by chemoradiation. Immune profiling of intratumoral T‐cell receptor (TCR) repertoire was subsequently performed using single cell RNA sequencing (scRNAseq).

Results

We describe a rare case of primary tracheal adenoid cystic carcinoma highlighting several management principles as well as providing new insights into intratumor T cell populations.

Conclusions

Primary tracheal ACC is most commonly treated with surgical resection followed by adjuvant therapy. Further characterization of the tumor immune microenvironment is necessary to better understand ACC disease biology and to identify potential therapeutic targets.
Improving cervical screening rates among sexual minorities: Insights from Aotearoa New Zealand
Authors: Ellis Sonja J.
Published: July 2024

Issue Addressed

Sexual minority women (SMW) experience inequities in health outcomes. The extant literature consistently suggests that SMW are much less likely than their heterosexual peers to engage in cervical screening. Using participant's voices, the focus of this study was to explore the ways in which cervical screening rates for SMW might be improved.

Methods

An online survey was completed by SMW (N = 177) aged 25–69 based in Aotearoa New Zealand and representing a range of sexual identities, ethnicities, and geographical regions. The analysis presented here was derived from open‐ended qualitative responses to a single survey item: What do you think could be done to encourage more SMW (lesbians, wahine takatāpui, bisexual women, etc.) to engage in smear testing?

Results

Analysis of the data generated three main themes around how public health services could encourage more SMW to engage in cervical screening: Inclusive health services, clarity of information, and targeted health promotion.

Conclusion

The analysis showed that the inherent heteronormativity among health care professionals and the lack of clear and consistent information specific to SMW may be key factors contributing to lower rates of engagement in screening.

So What?

Given that not engaging in screening is the main risk factor for cervical cancer, it is imperative that active consideration is given to these issues with a view to increasing participation rates among SMW.
Asparagine synthetase and G‐protein coupled estrogen receptor are critical responders to nutrient supply in KRAS mutant colorectal cancer
Authors: Lu Lingeng , Zhang Qian , Aladelokun Oladimeji , Berardi Domenica , Shen Xinyi , Marin Audrey , Garcia‐Milian Rolando , Roper Jatin , Khan Sajid A. , Johnson Caroline H.
Published: July 2024

Survival differences exist in colorectal cancer (CRC) patients by sex and disease stage. However, the potential molecular mechanism(s) are not well understood. Here we show that asparagine synthetase (ASNS) and G protein‐coupled estrogen receptor‐1 (GPER1) are critical sensors of nutrient depletion and linked to poorer outcomes for females with CRC. Using a 3D spheroid model of isogenic SW48 KRAS wild‐type (WT) and G12A mutant (MT) cells grown under a restricted nutrient supply, we found that glutamine depletion inhibited cell growth in both cell lines, whereas ASNS and GPER1 expression were upregulated in KRAS MT versus WT. Estradiol decreased growth in KRAS WT but had no effect on MT cells. Selective GPER1 and ASNS inhibitors suppressed cell proliferation with increased caspase‐3 activity of MT cells under glutamine depletion condition particularly in the presence of estradiol. In a clinical colon cancer cohort from The Cancer Genome Atlas, both high GPER1 and ASNS expression were associated with poorer overall survival for females only in advanced stage tumors. These results suggest KRAS MT cells have mechanisms in place that respond to decreased nutrient supply, typically observed in advanced tumors, by increasing the expression of ASNS and GPER1 to drive cell growth. Furthermore, KRAS MT cells are resistant to the protective effects of estradiol under nutrient deplete conditions. The findings indicate that GPER1 and ASNS expression, along with the interaction between nutrient supply and KRAS mutations shed additional light on the mechanisms underlying sex differences in metabolism and growth in CRC, and have clinical implications in the precision management of KRAS mutant CRC.
Rapid development of neurological infection in a patient with human immunodeficiency virus following schistosomiasis: A case report
Authors: Liu Yan , Zhou Guoqiang , Jiang Wei , Kong Xianglong
Published: July 2024

HIV‐1 and schistosomal infections present significant global health challenges, and neurological manifestations of these pathogens are easily misdiagnosed due to their rarity. Here, we report the case of a 36‐year‐old patient with acquired immunodeficiency syndrome who was initially diagnosed with human immunodeficiency virus‐1 (HIV‐1) infection 4 years earlier, although untreated for approximately 3 years until he began antiretroviral therapy (ART) following a tuberculosis diagnosis and hospitalization. Despite achieving virological suppression of HIV‐1 1 year after ART, he was readmitted with high fever and headache. Initial therapy for suspected tuberculosis based on clinical performance and brain imaging features failed, and further investigation confirmed an intracranial infection caused by schistosomiasis. Following anti‐schistosomal treatment and optimized ART, the patient recovered fully and was discharged. This case of a patient in Asia infected with human immunodeficiency virus (HIV) who rapidly developed a neurological infection subsequent to acquiring schistosomiasis highlights the need for awareness of such coinfections in patients with HIV.