bluuebunny/crossref_metadata_2025 huggingface dataset:
Linker Installation in a Metal–Organic Framework for Enhanced Quantitative Redox Species Recognition
Authors: Han Zongsu , Wang Kun‐Yu , Liang Rong‐Ran , Yang Yihao , Huo Jiatong , Zhou Hong‐Cai
Published: December 2024

Linker installation has proven to be an effective strategy for introducing diverse functional groups into metal–organic frameworks (MOFs). Reductants and oxidants are found in various environments, but their accumulation poses a danger due to their high reactivity, necessitating prompt monitoring instantly, particularly in natural environments and industrial processes. In this study, a series of redox‐active dyes were successfully incorporated into a flexible Zr‐based MOF, PCN‐700, through linker installation strategy. Notably, both the reduction of PCN‐700‐Resazurin towards oxidants and oxidation of PCN‐700‐Amplex Red towards reductants result in the formation of PCN‐700‐Resorufin, which exhibit visible color changes and largely elevated luminescent intensities, giving rise to the quantitative recognition of reductants and oxidants. This work presents a straightforward approach to developing efficient luminescent sensors for the rapid qualitative and quantitative detection of reductants and oxidants, extending the sensing mechanism from common energy transfer to electron transfer and demonstrating the MOF's versability as a highly designable sensing material for target analytes.
Recent Applications of the Sonogashira Reaction in the Synthesis of Drugs and Their Derivatives: A Review
Authors: Yan Fang , Zhang Xiyu , Li Daliang , Zhu Nengbo , Bao Hongli
Published: December 2024

Metal‐catalyzed cross‐coupling reactions are essential tools for constructing C–C bonds in organic synthesis. Among these prominent approaches, the Sonogashira reaction stands out as a key player and is widely utilized in medicinal chemistry. This versatile method enables the creation of complex C (sp2)–C (sp) bonds by linking aryl or vinyl halides with terminal alkynes, facilitating the efficient construction of molecular structures crucial for drug development. A notable application of the Sonogashira reaction is its ability to incorporate aromatic and alkynyl functionalities into pharmaceutical compounds. Depending on the impactful catalytic system evolved gradually, the Sonogashira reaction can involve either double‐metal catalysis or single‐metal catalysis. This review sheds light on the diverse applications of the Sonogashira coupling approach in drug synthesis and the generation of their derivatives.
Effect of Soft Segment Structures on the Properties of Self‐Healing Photopolymerizable Thiocarbamate‐Based Polyurethanes
Authors: Cui Lu , Wang Wenhao , Gao Yanjing , Sun Fang
Published: December 2024

Three self‐healing photopolymerizable thiocarbamate‐based polyurethane oligomers were synthesized using different macromolecular chain extenders: polypropylene glycol (PPG‐1000), polytetrahydrofuran (PTMG‐1000), and polycaprolactone glycol (PCL‐1000). The variations in the soft segment structures had minimal impact on the double bond conversion and gel fraction of the light‐cured self‐healing thiocarbamate‐based polyurethane materials, achieving double bond conversion rates and gel fractions exceeding 87%. Incorporating polycaprolactone diol as the soft segment improved heat resistance and tensile stress but reduced the material's self‐healing ability. Conversely, utilizing polytetrahydrofuran as the soft segment resulted in outstanding overall performance, notably lowering the glass transition temperature to −48.4°C, increasing tensile strain to 1280%, achieving a self‐healing efficiency of up to 90%, and exhibiting good degradation properties.
Pseudosuchian thermometabolism: A review of the past two decades
Authors: Faure‐Brac Mathieu Gabriel
Published: December 2024

Pseudosuchia, one of the two main clades of Archosauria, is today only represented by some 20 extant species, the crocodilians, representing only a fraction of its extinct diversity. Extant crocodilians are ectotherms but present morphological and anatomical features usually associated with endothermy. In 2004, it was proposed that pseudosuchians were ancestrally endothermic and the features observed in extant crocodilians are the remains of this lost legacy. This contribution has two parts: the first part covers 20 years of studies on this subject, first exploring the evidence for a loss of endothermy in extant crocodilians, before covering the variety of proxies used to infer the thermophymetabolic regime of extinct pseudosuchians. In the second part, the quantitative results of these previous studies are integrated into a comprehensive ancestral state reconstruction to discuss a potential scenario for the evolution of thermometabolism. Pseudosuchian endothermy would then have been lost close to the node Crocodylomorpha. The end‐Triassic mass extinction is proposed to have played the role of a filter, leading to the extinction of endothermic pseudosuchians and the survival of ectothermic ones. This difference in survival in Pseudosuchia is compared to those of dinosaurs, and difference in their metabolism is also considered. Pseudosuchian endothermy might have been of a different level than the dinosaurian one and more studies are expected to clarify this question.
C‐Type Lectin S Group TcCTL4 Participates in the Immunity of Tribolium castaneum
Authors: Zhang Yonglei , Ai Huayi , Zhang Ping , Li Bin
Published: December 2024

C‐type lectin S (CTL‐S) plays a crucial role in pathogen recognition and the activation of immune response. In comparison, the proportion of CTL‐S was relatively high in insects, but the study was much smaller than the proportion observed. In this study, we cloned and characterized one CTL‐S, TcCTL4, from Tribolium castaneum. Our analysis revealed that TcCTL4 was highly expressed during the early pupal stage, with expression levels exhibiting a tendency to change with developmental stages. Additionally, tissue expression analysis showed a high expression of TcCTL4 in the central nervous system (CNS). Moreover, we observed a significant increase in TcCTL4 transcripts after bacterial challenge. The RNA interference (RNAi) of TcCTL4 before bacterial treatment resulted in a significant reduction in the transcripts of immune factors (IFs) and antimicrobial peptides (AMPs), indicating that TcCTL4 may regulate AMP expression through the activation of the immune signaling pathway. Furthermore, our investigation revealed that the recombinant protein TcCTL4 (rTcCTL4) not only recognized bacteria but also agglutinated bacteria in a Ca2+‐dependent manner. Enzyme activity analysis suggested that rTcCTL4 could enhance phenoloxidase activity, implying its potential involvement in the prophenoloxidase activation pathway. In conclusion, these results indicate that TcCTL4 is involved in the immunity of T. castaneum, providing valuable insights into insect CTLs.
Exploring aliphatic sulfonamides as multiclass inhibitors of the carbonic anhydrases from the pathogen bacterium Vibrio cholerae
Authors: Paoletti Niccolò , Giovannuzzi Simone , Bonardi Alessandro , De Luca Viviana , Capasso Clemente , Nocentini Alessio , Gratteri Paola , Supuran Claudiu T.
Published: December 2024

This study investigates aliphatic sulfonamide derivatives as inhibitors of the α‐, β‐, and γ‐class carbonic anhydrase (CA) isoforms from Vibrio cholerae (VchCAs). A series of 26 compounds bearing a triazole linker and urea‐ or ether‐based tails were described and evaluated for their inhibitory action using a stopped‐flow CO2 hydrase technique. These inhibitors demonstrated a preferential efficacy against VchCAβ. Specifically, the ureido derivatives showed the highest inhibitory potency with inhibition constants (KIs) in the submicromolar range (0.67–0.93 µM). Selectivity indices were calculated to assess the selective inhibition of VchCAβ over human CA I and II, as well as other VchCA isozymes. Urea‐linked compounds demonstrated a significant 25‐ to 125‐fold selectivity for VchCAβ over hCAs and 14‐ to 26‐fold over other VchCAs. Molecular modeling elucidated the interactions contributing to the efficacy and selectivity of aliphatic sulfonamides as VchCA inhibitors, aligning with and reinforcing the experimental results. The latter suggests that aliphatic sulfonamides could serve as valid targeted therapeutics to treat V. cholerae infections.
A Pillar[5]arene‐Based π‐Conjugated Organic Small Molecule Emitter: Synthesis, Self‐Assembly, and Selective Sensing of Cr2O72− Anion
Authors: Jia Xu‐Xu , Tao Shao‐Ping , Wei Tai‐Bao , Lin Qi , Shi Bingbing , Yao Hong , Qu Wen‐Juan , Chen Jin‐Fa
Published: December 2024

A triphenylamine‐containing π‐conjugated pillar[5]arene luminescent small organic molecule has been synthesized via Suzuki‐coupling reaction. This molecule can self‐assemble to form linear supramolecular polymers in both solution and solid state. The molecule shows enhanced emission compared with parent pillar[5]arene in dilute solution. Based on the bright luminescent behavior, its sensing ability for Cr2O72− anion was studied.
A Principled Approach to Adjust for Unmeasured Time‐Stable Confounding of Supervised Treatment
Authors: Madsen Jeppe Ekstrand Halkjær , Delvin Thomas , Scheike Thomas , Pipper Christian
Published: December 2024

We propose a novel method to adjust for unmeasured time‐stable confounding when the time between consecutive treatment administrations is fixed. We achieve this by focusing on a new‐user cohort. Furthermore, we envisage that all time‐stable confounding goes through the potential time on treatment as dictated by the disease condition at the initiation of treatment. Following this logic, we may eliminate all unmeasured time‐stable confounding by adjusting for the potential time on treatment. A challenge with this approach is that right censoring of the potential time on treatment occurs when treatment is terminated at the time of the event of interest, for example, if the event of interest is death. We show how this challenge may be solved by means of the expectation‐maximization algorithm without imposing any further assumptions on the distribution of the potential time on treatment. The usefulness of the methodology is illustrated in a simulation study. We also apply the methodology to investigate the effect of depression/anxiety drugs on subsequent poisoning by other medications in the Danish population by means of national registries. We find a protective effect of treatment with selective serotonin reuptake inhibitors on the risk of poisoning by various medications (1‐ year risk difference of approximately ) and a standard Cox model analysis shows a harming effect (1‐year risk difference of approximately ), which is consistent with what we would expect due to confounding by indication. Unmeasured time‐stable confounding can be entirely adjusted for when the time between consecutive treatment administrations is fixed.
Kinetic Modeling of the Antibody Disulfide Bond Reduction Reaction With Integrated Prediction of the Drug Load Profile for Cysteine‐Conjugated ADCs
Authors: Weggen Jan Tobias , González Pedro , Hui Kimberly , Bean Ryan , Wendeler Michaela , Hubbuch Jürgen
Published: December 2024

Antibody‐drug conjugates (ADC) constitute a groundbreaking advancement in the field of targeted therapy. In the widely utilized cysteine conjugation, the cytotoxic payload is attached to reduced interchain disulfides which involves a reduction of the native monoclonal antibody (mAb). This reaction needs to be thoroughly understood and controlled as it influences the critical quality attributes (CQAs) of the final ADC product, such as the drug‐to‐antibody ratio (DAR) and the drug load distribution (DLD). However, existing methodologies lack a mechanistic description of the relationship between process parameters and CQAs. In this context, kinetic modeling provides comprehensive reaction understanding, facilitating the model‐based optimization of reduction reaction parameters and potentially reduces the experimental effort needed to develop a robust process. With this study, we introduce an integrated modeling framework consisting of a reduction kinetic model for the species formed during the mAb reduction reaction in combination with a regression model to quantify the number of conjugated drugs by DAR and DLD. The species formed during reduction will be measured by analytical capillary gel electrophoresis (CGE), and the DAR and DLD will be derived from reversed‐phase (RP) chromatography. First, we present the development of a reduction kinetic model to describe the impact of reducing agent excess and reaction temperature on the kinetic, by careful investigation of different reaction networks and sets of kinetic rates. Second, we introduce a cross‐analytical approach based on multiple linear regression (MLR), wherein CGE data is converted into the RP‐derived DAR/DLD. By coupling this with the newly developed reduction kinetic model, an integrated model encompassing the two consecutive reaction steps, reduction and conjugation, is created to predict the final DAR/DLD from initial reduction reaction conditions. The integrated model is finally utilized for an in silico screening to analyze the effect of the reduction conditions, TCEP excess, temperature and reaction time, directly on the final ADC product.
Regulation of Sexual Behavior and Health in German Prisons and Forensic Psychiatric Hospitals
Authors: Hanss Hanna H. , Bründl Susanne , Krasnova Maria , Fuss Johannes
Published: December 2024

Individuals housed in prisons or forensic hospitals experience significant restrictions on their sexual rights. There is a lack of data on how sexual behavior and sexual health of institutionalized persons are managed and to what extent they are based on shared guidelines or decisions of the individual staff. Using a standardized online questionnaire, the heads of 35 prisons and 32 forensic psychiatric hospitals across 14 German federal states were surveyed, reflecting the situation of 16,902 inmates and patients. The findings reveal an absence of shared guidelines as well as an institution‐specific approach to sexual behavior and sexual health. Exploratory multiple linear regression identified four variables that predict differences in the regulation of individual's sexual behavior and sexual health: type of institution (prison or forensic hospital), percentage of institutionalized sex offenders, number of housed individuals, and an item concerning the sexuality‐related attitudes of the respondent. Respondents, particularly in the field of forensic psychiatry, expressed a general desire for guidelines. Our study shows that possibilities for sexual expression and sexual health vary strongly, depending on the institution. Therefore, it appears useful and desirable to develop guidelines on how to regulate sexual behavior and sexual health of institutionalized individuals.
Sample Gifts (In)consistent With the Focal Product: On the Effect of Gift Quantity in Consumer Evaluation
Authors: Yao Feisi , Chen Long
Published: December 2024

Aiming to boost sales, marketers often conduct sales promotions that offer sample gifts of the same brand, conditional on the purchase of a focal product. Based on the monetary value and volume of samples, these promotions can be presented in different formats. For example, when purchasing a focal product, consumers can obtain either a 30 mL sample gift or three 10 mL sample gifts that are either consistent or inconsistent with the focal product. Three experiments were conducted to test this; they revealed that compared with buying a product and getting one gift (vs. multiple), presenting sample gifts consistent (vs. inconsistent) with the focal product is more persuasive regarding consumers' perceived gift benefits. This effect occurs through a repack (vs. unpack) tendency. The observed effect can be accentuated (vs. attenuated) by priming consumers with variety‐seeking (vs. monetary‐saving) motivation.
177Lu Radiolabeled Polydopamine Decorated with Fibroblast Activation Protein Inhibitor for Locoregional Treatment of Glioma
Authors: Wang Yadong , Qiu Long , Ye Tianzhen , Tan Fuyuan , Lyu Jie , Li Feize , Sun Zhizhong , Yang Yuanyou , Zhang Jinsong , Liu Ning , Liao Jiali
Published: December 2024

Radionuclide therapy is expected to be a powerful tool for glioma treatment. Here, we introduced a novel nuclear nanomedicine based on polydopamine (PDA), incorporating fibroblast activation protein inhibitor (FAPI) and macrocyclic chelator (DOTA) for specific cancer targeting and 177Lu labeling. The synthesized nanoradiopharmaceutical, 177Lu‐DOTA‐PEG‐PDA‐FAPI, exhibits good stability in serum, saline and PBS over 5 days. 177Lu‐DOTA‐PEG‐PDA‐FAPI shows efficient specific uptake and internalization when incubated with U87MG cells. In vivo distribution visualized prominent accumulation and long retention ability of 177Lu‐DOTA‐PEG‐PDA‐FAPI at tumor sites after local administration. Moreover, 177Lu‐DOTA‐PEG‐PDA‐FAPI has satisfactory antitumor ability without apparent toxic and side effects observed from therapy assay and H&E staining. This study highlights the feasibility of using PDA as a nanocarrier for glioma endoradiotherapy by targeting fibroblast activation protein.
Drug Discovery Approaches to Target E3 Ligases
Authors: Rodríguez‐Gimeno Alejandra , Galdeano Carles
Published: December 2024

Targeting E3 ligases is a challenging area in drug discovery. Despite the human genome encoding for more than 600 E3 ubiquitin ligases, only a handful of E3 ligases have been pharmacologically modulated or exploited for targeted protein degradation (TPD) strategies. The main obstacle for hijacking these E3 ligases is the lack of small‐molecule ligands. As research into this field advances, the identification of new small molecules capable of binding to E3 ligases has become an essential pursuit. These ligases not only expand the repertoire of druggable targets but also offer the potential for increased specificity and selectivity in protein degradation. The synergy between academia and industry is key, as it combines academic expertise in fundamental research with the industrial capabilities of translating these findings into novel therapeutics. In this review, we provide an overview of the different strategies employed in academia and industry to the discovery of new E3 ligases ligands, showing them with illustrative cases.
How Could the Physical Properties of Poly(vinyl alcohol) Influence Enzymatic Activity? A Detailed Study on Nanofibrous Catalysts Incorporating a Lipase from Burkholderia cepacia
Authors: Tóth Gergő Dániel , Molnár Zsófia , Koplányi Gábor , Gyarmati Benjámin , Szilágyi András , Katona Gábor , Menyhárd Alfréd , Poppe László , Pukánszky Béla , Balogh‐Weiser Diána
Published: December 2024

Utilizing the electrospinning technique to entrap enzymes within nanofibers (providing nanofibrous enzyme catalysts, NEC) offers promising avenues for the scientific and industrial sectors as well. While numerous instances of poly(vinyl alcohol) (PVA)‐based nanofibrous biocatalysts have been documented, a comprehensive investigation to characterize the effect of PVA on catalytic activity is notably lacking. This study systematically investigates the effect of PVA properties, such as molecular weight (24–205 kDa), degree of hydrolysis (DoH, 88% and 98%), and polymer concentration (6–16 wt%), on the structure of PVA nanofibers and on the biocatalytic properties of a lipase from Burkholderia cepacia (BcL) entrapped into PVA nanofibers, ensuring 100% yield of immobilization. The PVA‐enzyme interactions were studied using viscometry, scanning electron microscopy, Raman mapping, differential scanning calorimetry, and computational docking simulations. Stereoselective hydrolysis and transesterification were used to evaluate enzyme activity. Results showed that the molecular weight and DoH of PVA have a significant effect on the biocatalytic activity of nanofibrous enzyme catalysts. Remarkably, activity yields (mostly exceeded 100%, with maximal yields achieved using fully hydrolyzed PVA) with a molecular weight of 61 kDa provided a 10‐fold increase in the specific enzymatic activity of BcL immobilized in nanofibers (90.6 U × g−1) compared to its native form (9.0 U × g−1).
Inter‐ and Intra‐Molecular Charge Redistributions in H‐Bonded Cyanuric Acid*Melamine (CA*M) Networks: Insight From Core Level Spectroscopy and Natural Bond Orbital Analysis
Authors: Toffoli Daniele , Costantini Roberto , Bernes Elisa , Nardi Lorys Di , Balducci Gabriele , Viola Elisa , Fronzoni Giovanna , Cossaro Albano , Lanzilotto Valeria
Published: December 2024

In this work, we elucidate the electronic charge redistributions that occur within the cyanuric acid (CA) and melamine (M) molecules upon formation of the triple H‐bond between the imide group of CA and the diaminopyridine group of M. To achieve this, we investigated 2D H‐bonded assemblies of M, CA and CA*M grown on the Au(111) surface, using X‐ray photoemission (XPS) and near edge X‐ray absorption fine structure (NEXAFS) spectroscopies. Compared to the homomolecular networks, the spectra of the mixed sample reveal core level shifts in opposite directions for CA and M, indicating a nearly complementary charge accumulation on the CA molecule and a charge depletion on the M molecule. These findings were further confirmed by theoretical simulation of the ionization potentials (IPs), which were computed using unsupported models of the H‐bonded networks. A natural bond orbital (NBO) analysis performed on the three systems helped to rationalize the net charge transfer form M to CA. Finally, we observed that intramolecular interactions (electron delocalization effects) contribute progressively to the charge redistributions inside the two molecules when going from the homomolecular to the heteromolecular networks.
Towards White Light Emission Through Metal‐to‐Metal Charge Transfer (MMCT) Effect in Bi3+ Activated Ca2YTi2‐mZrmGa3O12 (0≤m≤2) Garnets
Authors: Sivakumar Gurusamy , Munthasir Akkarakkaran Thayyil Muhammed , Thilagar Pakkirisamy , Natarajan Srinivasan
Published: December 2024

Herein, we report the high‐temperature solid‐state synthesis and intriguing optical features of Bi3+/Ln3+ doped Ca2YTi2Ga3O12 (CYT). The optical properties of CYT were fine‐tuned by judiciously substituting Zr4+ ions at Ti4+ sites and Bi3+, Ln3+ ions at Y3+ sites. All these compounds are crystallized in a cubic crystal system with an Ia‐3d (no. 230) space group. The Bi3+ doped systems showed a broad photoluminescence (PL) band in the yellow‐orange region centered at ~552 nm from the metal‐to‐metal charge transfer state (MMCT). The yellow‐orange emissive CYT:Bix was co‐doped with blue emissive Tm3+ to obtain an excitation wavelength‐dependent color tuneable white light phosphor CYT:Tm0.02Bi0.012. Substituting Zr4+ ions in place of Ti4+ ions in CYT gave rise to CYTZ (Ca2YTi2‐mZrmGa3O12), which upon doping with Bi gave Ca2YZr2Ga3O12:Bix (CYZ:Bix) and they exhibit the 3P0,1→1S0 emission in the violet‐indigo region ( λem=395 nm; λex=315 nm). On co‐doping CYTZ:Bix with Sm3+ ions produced white light emissive Ca2YTi0.1Zr1.9Ga3O12:Bi3+; Sm3+, (CYTZ:Bi3+; Sm3+). CYT:Bix showed slower (microsecond) PL decay than the CYZ:Bix (nanosecond). The crystal structure, steady state, and time‐resolved optical studies, and semiempirical calculations were employed to rationalize the observed optical features of these compounds. The optical features of CYT:Bi0.1, were explored for potential applications in secret writing.
Early Maladaptive Schemas and Dissociative Symptoms: A Systematic Review and Meta‐Analysis
Authors: Blackman Lauren C. , Pizarro‐Campagna Elizabeth , Pilkington Pamela D.
Published: December 2024

Background

Dissociation is an underresearched and important clinical construct associated with impaired functioning and poor quality of life. Improved understanding of the modifiable correlates of dissociation can inform early detection and effective treatments. The aim of this systematic review and meta‐analysis was to synthesise the evidence on the associations between dissociative symptoms and early maladaptive schemas (EMSs).

Method

The reviewed studies reported unadjusted association/s between dissociative symptoms and EMS/s and were published in English in peer‐reviewed journals. PsycINFO, PubMed and CINAHL Complete databases were searched on 17 April 2024, and citation searches were completed on 27 April 2024. Random‐effects meta‐analyses were completed to evaluate the magnitude of the associations between dissociative symptoms and each of the 18 EMSs. Methodological quality was assessed using the AXIS tool.

Results

A total of nine cross‐sectional studies published between 2001 and 2023 were included (pooled N = 2300). Dissociative symptoms were positively correlated with 14 of the 18 EMSs. The largest associations were with the defectiveness/shame (r[7] = 0.45, 95% CI [0.34, 0.56]), vulnerability to harm (r[5] = 0.45, 95% CI [0.30, 0.58]) and social isolation schemas (r[8] = 0.39, 95% CI [0.25, 0.51]). Moderate to considerable heterogeneity was present in 14 of the meta‐analyses.

Conclusions

The emerging findings suggest EMSs are important cognitive correlates of dissociation that warrant increased empirical attention. In particular, longitudinal research is needed to explore temporal causality. Additional research could examine whether targeting EMSs relating to feeling unlovable, isolated and vulnerable to harm can help ameliorate dissociative symptoms.
Characterizing suburban soil and microbial properties along a soil age chronosequence
Authors: Suratt Andie , Behl Kavisha , Hong Wai Lam , Yoon Yae Eun , Allison Steven D.
Published: December 2024

Rapid urbanization is drastically altering ecosystem processes in landscapes around the world. In particular, suburban residential neighborhoods comprise novel ecosystems with water and nutrient inputs that differ greatly from the surrounding land area. These impacts generate concern over the sustainability of urban ecosystems, especially whether they will be characterized by net carbon gain or loss over time. To address this knowledge gap, we established a chronosequence of residential yards in Southern California to test how urban soils change after development. We predicted that urbanized soils would experience shifts in physical characteristics and microbial function over time consistent with ecological succession theory, but residential soils would maintain novel moisture and nutrient regimes compared to undeveloped soils, never “recovering” to a pre‐developed state. We compared different vegetation types to quantify impacts of homeowner landscaping choices and characterized yard soils and their microbial communities. We found that yard soils were nutrient‐ and moisture‐enriched compared to an adjacent undeveloped ecosystem, and turfgrass was associated with higher levels of water and nitrogen. Despite high respiration rates, yard soils accumulated carbon and nitrogen over time. We conclude that suburban residential soils comprise dynamic and heterogeneous ecosystems that are highly influenced by landscaping choices and management practices, and warrant closer study at small management‐relevant scales.
Evaluating Sampling Designs to Survey Fish Diversity in Lakes From Northern Temperate Zones
Authors: García‐Machado Erik , Normandeau Eric , Côté Guillaume , Caza‐Allard Isabeau , Babin Charles , Bernatchez Louis
Published: December 2024

Long‐term biological monitoring and management depend on efficient protocols and methodology to characterize and precisely describe species distributions and diversity. In recent years, environmental DNA has progressively become a tool of choice in survey programs. However, the effect of variables such as sampling effort and sampling design still requires consideration. Simple random, grid, and transect‐based sampling methods are widely used in ecological surveys to obtain an unbiased estimation of species richness and community structure. However, under certain conditions where spatial information is available, sampling design and sequencing depth can be optimized to reduce effort and cost. Here, we evaluate different subsampling approaches to identify sampling strategies that are both easily implemented in the field and provide optimal recovery of species diversity for a given sampling effort. With a homogeneous grid‐based sampling (25–50 samples by lake) of 12 freshwater lakes in southeastern Québec, and using the 12S MiFish metabarcoding primer set, we demonstrate that random and stratified designs perform similarly to detect 90% and 95% of species. However, we found that, under certain circumstances, stratified sampling outperformed random sampling, requiring lower numbers of samples to detect the same species diversity. We also demonstrate that for the minimum sequence threshold and sample replication used in our study, a sequencing depth of 50K reads per sample is adequate to obtain a reliable portrayal of species richness. In this study, we contribute to the effort of eDNA sampling standardization by providing data for selecting the best sampling design, sequence depth, and sample size to detect 90%–95% of fish species found in temperate lakes.
Synthesis and Biological Activity of 2,6‐Disubstituted 7‐Deazapurine Ribonucleosides
Authors: Šinkevičiūtė Ugnė , Dvořáková Marcela , Tichý Michal , Gurská Soňa , Ječmeňová Kateřina , Poštová Slavětínská Lenka , Džubák Petr , Hajdúch Marián , Hocek Michal
Published: December 2024

Several series of 2,6‐disubstituted 7‐deazapurine ribonucleosides were synthesized to investigate their biological activities. The key‐intermediate chloronucleosides were prepared by an anion‐base glycosylation with 2‐amino‐6‐chloro‐7‐deazapurine. The target compounds were obtained by diazotation, either Suzuki and Sonogashira reactions in the case of 2‐arylethynyl‐6‐hetaryl nucleosides or two consecutive Suzuki reactions in the case of 2,6‐diaryl nucleosides. The sequence of diazotation and the first Suzuki reaction is flexible and can be changed depending on the target compounds. Some of the final nucleosides showed moderate cytotoxic activity against several cancer cell lines and low antagonistic activity against a panel of adenosine receptors.
Dynamic Residue Behavior and Risk Assessment of Thiamethoxam With Its Metabolite From Tea Production to Consumption
Authors: Wang Xinru , Yu Huan , Wang Zihan , Zha Chengmin , Luo Fengjian , Chen Zongmao , Zhou Li
Published: December 2024

The entire fate of the widely used insecticide thiamethoxam from field cultivation, manufacturing to brewing were studied. A method to simultaneously detect thiamethoxam and its two metabolites, clothianidin and CGA265307, was developed. The field trial indicated a half‐life of thiamethoxam at 3.2 days on tea leaves, meanwhile, generation of clothianidin was observed with the maximum accumulation of 0.0152 mg/kg after 1 day of thiamethoxam application. The processing factors (PFs) during tea manufacturing ranged from 0.16 to 1.36 and 0.72 to 1.27 for thiamethoxam and clothianidin, respectively. Notably, PFs for thiamethoxam and clothianidin were higher during microwave deenzymed green tea manufacturing than pan deenzymed green tea and traditional black tea. Both thiamethoxam and clothianidin showed high infusion factors during tea brewing, whereas the risk quotient indicated an acceptable dietary risk of thiamethoxam with clothianidin through tea consumption. These findings could facilitate a more accurate assessment of safety risks and better protect the health of tea consumers.
Evaluation of the Uricogenic Effect of Hypoxanthine and the Hypoxanthine‐Lowering Process of Shrimp (Metapenaeus ensis)
Authors: Sha Wanqian , xiao Lu , Tao Chunlin , Hou Chuanli , Wang Yanbo , Liu Huilin , Ren Jiaoyan
Published: December 2024

One of the main reasons for hyperuricemia is high purine intake and restricting the intake of high purine food is the main management for avoiding hyperuricemia. This study assesses the uricogenic effect of hypoxanthine and investigates effective physical field processing for reducing hypoxanthine content in shrimp (Metapenaeus ensis). Using mice models, it is demonstrated that hypoxanthine significantly elevates serum uric acid level, highlighting its role as a primary dietary contributor to hyperuricemia. To mitigate this effect, single, dual, and triple processing approaches involving infrared, steam, and microwave heating were evaluated. While single processing methods showed a moderate reduction in purine content, the combined triple processing (high‐intensity microwave + 140°C infrared + 140°C steam) was most effective, achieving a substantial 62.18% reduction in hypoxanthine. This reduction is attributed to the loss of purines during cooking, interconversion between purines, and possible binding of purine compounds to other substances. Further, in vitro digestion experiments confirm that the purine‐reduced shrimp meat exhibits significantly lower uric acid‐raising capacity. Overall, the study provides valuable insights into the development of purine‐reduced seafood options, contributing to healthier dietary strategies for hyperuricemia management.
Sovereign Credit Ratings: A Friend or Foe to Financial Development of African Countries?
Authors: Arogundade Sodiq , Mduduzi Biyase , Naanwaab Cephas
Published: December 2024

This study examined the impact of sovereign credit rating on financial development. Using a sample of 21 African countries from 1995 to 2019, the empirical result indicates a significant and positive link between sovereign credit rating and financial development that is, higher credit ratings are associated with lower borrowing costs, increased access to capital, and increased investor confidence. The study further finds that (1) sovereign credit ratings improve the financial institutions and markets of the selected countries; (2) the magnitude of the impact of credit rating on financial development is greater for countries with very high financial development; and (3) there is bidirectional causality between credit rating and financial development. The empirical results are remarkably robust to different measures of sovereign credit rating (Fitch and S&P), local currency debt ratings, sub‐categories of financial development (financial market and institution), and various estimators such as the two‐step system GMM, JKS Granger non‐causality, and the Machado and Silva quantile regression. In order to improve the financial depth and access funding from local and international markets to finance the sustainable development goals and Agenda 2063, the study recommends that African countries implement the necessary policies to obtain better ratings.
DBE‐Net: A Dual‐Branch Boundary Enhancement Network for Pathological Image Segmentation
Authors: Liu Zefeng , Liu Zhenyu
Published: December 2024

Pathological image segmentation provides support for the accurate assessment of lesion area by precisely segmenting various tissues and cellular structures in pathological images. Due to the unclear boundaries between targets and backgrounds, as well as the information loss during upsampling and downsampling operations, it remains a challenging task to identify boundary details, especially in differentiating between adjacent tissues, minor lesions, or clustered cell nuclei. In this paper, a Dual‐branch Boundary Enhancement Network (DBE‐Net) is proposed to improve the sensitivity of the model to the boundary. Firstly, the proposed method includes a main task and an auxiliary task. The main task focuses on segmenting the target object and the auxiliary task is dedicated to extracting boundary information. Secondly, a feature processing architecture is established which includes three modules: Feature Preservation (FP), Feature Fusion (FF), and Hybrid Attention Fusion (HAF) module. The FP module and the FF module are used to provide original information for the encoder and fuse information from every layer of the decoder. The HAF is introduced to replace the skip connections between the encoder and decoder. Finally, a boundary‐dependent loss function is designed to simultaneously optimize both tasks for the dual‐branch network. The proposed loss function enhances the dependence of the main task on the boundary information supplied by the auxiliary task. The proposed method has been validated on three datasets, including Glas, CoCaHis, and CoNSep dataset.
Revised minimal important difference values for the visual analogue scale and Foot Health Status Questionnaire when used for plantar heel pain
Authors: Landorf Karl B. , Twyford Georgia N. , Cotchett Matthew P. , Whittaker Glen A.
Published: December 2024

Background

The visual analogue scale (VAS) and the Foot Health Status Questionnaire (FHSQ) are patient‐reported outcome measures that are frequently used to evaluate the management of plantar heel pain. This study aimed to re‐calculate (i.e. revise) the minimal important differences (MIDs) of the VAS and the FHSQ when used for plantar heel pain to enhance the validity and precision of previous estimates.

Methods

This study used an anchor‐based method to calculate MIDs and incorporated best‐practice analyses to ensure credibility of the estimates. Data from 369 participants previously recruited from the community into four randomised controlled trials that evaluated interventions for plantar heel pain were used. VAS and FHSQ data from these participants at baseline and follow‐up were pooled to calculate the MIDs (95% confidence intervals). A 15‐point global rating of change Likert scale was used at follow‐up as the transition scale, which was anchored to baseline. For the VAS, MIDs for two distinct types of pain were calculated: average pain and first‐step pain. For the FHSQ, MIDs for two domains were calculated: foot pain and foot function.

Results

The revised MIDs for the 100 mm VAS were −8.5 mm (95% CI: −12.2 to −4.7) for average pain and −19.2 mm (95% CI: −24.7 to −13.8) for first‐step pain, which represent improvements in pain. The MIDs for the FHSQ were 12.4 points (95% CI: 6.9 to 18.0) for foot pain and 6.4 points (95% CI: 0.9 to 11.9) for foot function, which represent improvements in foot health status.

Conclusions

The revised MIDs from this study for the VAS and the FHSQ when used for plantar heel pain have enhanced validity and precision compared to previous estimates. This is important for clinicians and researchers as it provides a better understanding of how much improvement is required by an individual before an important change is experienced. The revised MIDs will also assist researchers with prospective sample size calculations, so future clinical trials are appropriately powered from a statistical standpoint.
Mitochondrial trifunctional protein deficiency caused by a deep intronic deletion leading to aberrant splicing
Authors: Cassini Thomas , Silverstein Sarah , Behan Molly , Tifft Cynthia J. , Malicdan May Christine , Adams David R. ,   Undiagnosed Diseases Network, Ahn Sun‐Young , Regier Debra S.
Published: December 2024

Trifunctional protein deficiency (TFP) is a disorder of fatty acid beta‐oxidation associated with metabolic, cardiac, and liver dysfunction in severe forms. We present two siblings diagnosed by newborn screening and confirmed by biochemical testing at birth. Their clinical course was complicated by recurrent rhabdomyolysis, retinopathy, and hypoparathyroidism. Both siblings were also diagnosed with focal segmental glomerulosclerosis (FSGS) and bone marrow failure and ultimately died of hypoxemic respiratory failure. Initial sequencing of the TFP‐associated genes HADHA and HADHB showed only a paternally inherited variant in HADHB, NM_000183.3:c.1059del (p.Gly354AspfsTer10). Subsequent evaluation by the Undiagnosed Diseases Network with genome and transcriptome sequencing revealed a rare maternally inherited 17 base pair deletion in HADHB, NM_000183.3:c.1390‐515_1390‐499del, located in the final intron and resulting in a pseudoexon that harbors a premature termination codon. Both sisters were compound heterozygous for this and the paternal premature termination codon. No other variants were detected that were potentially causative for the FSGS and bone marrow failure on genome sequencing. A review of the literature at that time revealed several case reports of the uncommon clinical findings of FSGS, bone marrow failure, and pulmonary involvement in patients with TFP, confirming this clinical diagnosis as the complete explanation for these siblings.
Left‐sided gallbladder and Chilaiditi syndrome in an infant
Authors: Bradstreet Laura J. , Chapman Teresa , Swanson Jonathan O. , Furuya Katryn N.
Published: December 2024

Congenital hepatic anomalies may be associated with important intestinal abnormalities, vascular anomalies, or may be asymptomatic and discovered incidentally. Uncommon and rare anatomic liver and biliary disorders include left‐sided gallbladder, wandering liver, malrotation of the liver, and hepato‐diaphragmatic interposition of the bowel (Chilaiditi syndrome). This report describes an infant with incidentally discovered malpositioning of the gallbladder to the superior surface of the left hepatic lobe, coupled with Chilaiditi syndrome, a configuration that has not been described in the literature. Management considerations are discussed.
Patient and Surgeon Attitudes Toward Opportunistic Salpingectomy During Nongynecological Surgeries for the Prevention of Ovarian Cancer: A Qualitative Study
Authors: Tymm Carly C. , Vattakalam Reena M. , Flum David R. , Wright Jason D. , Fischkoff Katherine N.
Published: December 2024

Background and Objectives

Opportunity salpingectomy (OS), or prophylactic removal of the fallopian tubes during an operation for another indication, is broadly accepted as a risk‐reduction strategy for ovarian cancer during gynecological operations. However, OS during nongynecological abdominal surgery is rare in the United States. A better understanding of surgeon and patient attitudes and perceived barriers to OS during nongynecological surgeries may facilitate implementation in the United States.

Study Design

Qualitative interviews were conducted with general surgeons (n = 10), gynecologic surgeons (n = 10), and patients (n = 20) to assess perspectives and barriers towards OS during nongynecological surgeries. Interviews were transcribed and inductive analysis was carried out to identify themes and categorize responses using NVivo data analysis software.

Results

OS during nongynecological surgery was viewed favorably by most patients and surgeons interviewed. While patients emphasized the importance of raising awareness of OS, both subsets of surgeons highlighted coordination, counseling, and billing barriers that would need to be overcome for efficient implementation.

Conclusion

OS was positively accepted by both patients and surgeons in our cohort. Improved attention to the shared barriers to implementation from our study may facilitate OS implementation during nongynecological surgery in the United States.
Evaluation of Papain–Urea for Enzymatic Debridement of Coagulation Zones Following Ablative Fractional Laser Treatment
Authors: Glahn Joshua Zev , Wang‐Evers Michael , Carlson Abigail R. , Marks Haley , Karasik Daniel , Hilge Felix , Goverman Jeremy , Manstein Dieter
Published: December 2024

Background

Ablative fractional CO2 laser (10,600 nm) treatment creates an array of microscopic treatment zones composed of an ablation zone (AZ) surrounded by a denatured coagulation zone (CZ). The CZ is believed to play a functional role in skin tightening, posttreatment inflammation, and laser‐assisted drug delivery. This study investigates the viability of enzymatic post‐processing to remove the CZ without affecting the surrounding tissue.

Methods

Ex vivo skin samples were treated with either control, papain, urea, or papain–urea solutions before being covered with occlusive dressing and incubated at 37°C for 1 h. Tissue viability as well as AZ and CZ geometries were assessed histologically.

Results

Treatment with all three experimental solutions resulted in a decrease in CZ. The largest average reduction in CZ area was observed in the papain–urea group (44%, p < 0.001), followed by the papain (14%, p < 0.001) and urea (11%, p < 0.001) only groups. Only the papain–urea group showed a significant increase in AZ (14%) and changes in lesion geometry.

Conclusion

This exploratory study of enzymatic post‐processing with papain–urea highlighted the potential of selectively removing the CZ after treatment with ablative fractional laser therapy. If results can be translated to in vivo studies, these findings could expand the use of high‐fluence CO2 laser therapy with functional implications for lowering posttreatment recovery time, providing clinicians more control over skin tightening, and enabling a broader range of laser‐assisted drug delivery.
On Weighted Fractional Calculus With Respect to Functions
Authors: Zahra Tazeen , Fahad Hafiz Muhammad , Rehman Mujeeb ur
Published: December 2024

This paper aims to further explore the existing theory of weighted fractional operators with respect to functions. This theory extends some fundamental results of classical Riemann–Liouville and Caputo fractional derivatives to their weighted counterparts involving fractional differentiation and integration with respect to functions. By investigating the fundamental principles of these operators, we establish mean value theorems, Taylor's theorems, and integration by parts formulae. The Leibniz rule is extended for weighted Riemann–Liouville derivatives with respect to functions. Also, we present necessary conditions for the existence and uniqueness of solutions for a class of initial value problems, involving weighted Caputo fractional derivatives with respect to functions, in a Sobolev space.
Topology Optimization of Elastoplastic Structure Based on Shakedown Strength
Authors: Huang Songhua , Zhang Lele , Chen Geng , Xu Yugong , Chen Min , Liu Zhiyuan , Lim Eng Gee
Published: December 2024

The traditional approach to structural lightweight optimization design, which is based on the elastic limit rule, often results in a structure that exhibits either weight redundancy or strength redundancy to some extent. This study introduces a novel integration of shakedown analysis with structural topology optimization, departing from the conventional elastic limit rule. Shakedown analysis identifies a non‐failure external load region beyond the elastic limit but below the plastic limit, independent of loading history. The proposed method, for the first time, accounts for the influence of self‐equilibrium residual stress at the element level, redefining effective and ineffective elements in topology optimization. Shakedown total stress replaces elastic equivalent stress, offering a comprehensive measure. Utilizing Melan's lower bound theorem, a gradient‐based topology optimization framework for shakedown analysis is developed, ensuring structures stay within the elastic–plastic range, preventing excessive plastic deformation. The approach, employing the moving asymptotes method after adjoint sensitivity analysis of shakedown total stress, is applied to a three‐dimensional L‐shaped bracket. Even with a remarkable 50% reduction in weight, the maximum total shakedown stress of the bracket reveals that it only increases by a modest 17.20% from its initial value. Moreover, compared to traditional topology optimization methods based on either elastic stress or stiffness, the proposed method based on total shakedown stress leads to a higher shakedown limit. Specifically, the configuration designed using the total shakedown stress exhibited increases of 2.01% and 9.82% in the shakedown limit compared to those obtained using stiffness and equivalent elastic stress, respectively. This suggests that the proposed method can effectively balance the trade‐off between shakedown strength and structural stiffness, achieving a 2.01% rise in shakedown strength with only a 2.24% compromise in structural stiffness. These findings highlight the method's effectiveness and potential, emphasizing the benefit of redefining effective and ineffective elements using shakedown stress in topology optimization.