bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and Synthesis of 2‐Nitroimidazole‐1,2,3‐triazole Sulfonamide Hybrids as Potent and Selective Anti‐Trypanosomatid Agents
Authors: Tietz Victória C. , Ortale Maria L. F. , das Neves Amarith R. , Pelizaro Bruno I. , Carvalho Diego B. , Shiguemoto Cristiane Y. K. , Portapilla Gisele B. , Silva Talicia S. , Silva Fernanda , Piranda Eliane M. , Leite Cleison R. , Dantas Fabiana G. S. , Oliveira Kelly M. P. , Guerrero Palimecio G. , Marques Francisco A. , LaGatta Davi C. , Arruda Carla C. P. , de Albuquerque Sergio , Baroni Adriano C. M.
Published: November 2024

A series of 2‐nitroimidazole‐1,2,3‐triazole sulfonamide hybrid analogs were designed using medicinal chemistry approaches, such as bioisosterism, molecular hybridization, Topliss tree decision, and Craig plot. A total of 24 compounds were synthesized via click chemistry in satisfactory yields. Overall, analogs 15 a‐x exhibited relevant in vitro anti‐trypanosomatid activity against amastigote forms of T. cruzi and without cytotoxic effect on LLC–MK2 cells. Analogs 15 b (R1=4‐Cl−Ph; IC50=1.63 μM, SI=>30.65), 15 m (R1=3,4‐di‐Cl−Ph; IC50=0.63 μM, SI=>78.96), and 15 s (R1=Ph‐4‐O−Ph; IC50=0.63 μM, SI=>79.90) demonstrated pronounced antitrypanosomal activity, more active than the reference drug, benznidazole and with good selectivity indexes. Furthermore, analog 15 b (R1=4‐Cl−Ph; IC50=0.5 μM, SI=>100) exhibited an outstanding antileishmanial activity against amastigote forms of Leishmania (L.) amazonensis and impressive selectivity index, comparable to the reference compound amphotericin B. The mutagenicity of compounds 15 b and 15 m were evaluated against Salmonella typhimurium strains (TA98, TA100 and TA102). Compound 15 b exhibited mutageniticy only at a concentration of 500  μg/plate for the TA100 strain, whereas compound 15 m was considered non‐mutagenic. These findings suggest that 2‐nitroimidazoles‐1,2,3‐triazole sulfonamide hybrid analogs are promising anti‐trypanosomatid candidates for future in vivo studies.
How Should we Teach Medicinal Chemistry in Higher Education to Prepare Students for a Future Career as Medicinal Chemists and Drug Designers? – A Teacher's Perspective
Authors: Klahn Philipp
Published: November 2024

In the recent two decades, the multidisciplinary field of medicinal chemistry has undergone several conceptual and technology‐driven paradigm changes with significant impact on the skill set medicinal chemists need to acquire during their education. Considering the need for academic medicinal chemistry teaching, this article aims at identifying important skills, competences, and basic knowledge as general learning outcomes based on an analysis of the relevant stakeholders and concludes effective teaching strategies preparing students for a future career as medicinal chemists and drug designers.
GRIN1‐related epilepsy in a neonate with response to memantine and vigabatrin
Authors: Eiler Isabella , Reecher Hope M. , Carlton Katherine , Cabacungan Erwin , Cohen Susan , Adams Samuel , Jozwik Jenna , Singh Avantika
Published: November 2024

Objective

A newborn with GRIN1‐related early infantile developmental and epileptic encephalopathy (DEE) with striking pharmacoresistance is described with emphasis on potential therapy with memantine and vigabatrin.

Methods

The term neonate manifested electrographic and electroclinical seizures from the first day of life with focal tonic seizures with apnea, bradycardia, and desaturations and later developed epileptic spasms and a hyperkinetic movement disorder. Multiple antiseizure medication trials were unsuccessful. Brain magnetic resonance imaging displayed extensive malformations of cortical development.

Results

Whole‐exome sequencing demonstrated a de novo novel GRIN1 variant (1916T > G,p.Phe639Cys), which can be associated with NMDA receptor dysfunction. Gain‐of‐function mutation was suspected based on phenotype correlation. Seizures markedly improved after initiation of memantine, an NMDA‐receptor antagonist. Memantine was complemented by the concurrent use of vigabatrin, initiated 4 days earlier due to emergence of epileptic spasms. Significant reduction in seizures facilitated discharge from neonatal intensive care unit.

Interpretation

GRIN1‐related disorders occur due to NMDA receptor dysfunction. Patients with gain‐of‐function GRIN1 mutations who present with the phenotype of DEE with extensive bilateral polymicrogyria may benefit from a trial of NMDA‐receptor antagonist therapy and vigabatrin. Further research is warranted to better understand this markedly pharmacoresistant condition and to investigate targeted therapies in GRIN1 DEE.
Unraveling the Stereoisomer Configurations of 1,1’‐bis(tert‐butylphosphino)Ferrocene in the Gas Phase
Authors: Sun Wenhao , Kargin Denis , Kelemen Zsolt , Pietschnig Rudolf , Schnell Melanie
Published: November 2024

The molecular structure of a ferrocene derivative with adjacent centers of chirality, 1,1’‐bis(tert‐butylphosphino)ferrocene, has been examined in the gas phase using broadband microwave spectroscopy under the isolated and cold conditions of a supersonic jet. The diastereomers of 1,1’‐bis(tert‐butylphosphino)ferrocene can adopt homo‐ and hetero‐chiral configurations, owing to the P‐chiral substituents on the cyclopentadienyl rings. Moreover, the internal ring rotation of each diastereomer gives rise to four conformers with eclipsed ring arrangements, where the two tert‐butylphosphino groups were separated by dihedral angles of approximately 72°, 144°, 216°, and 288° with respect to the two ring centers. The interconversion barriers between the conformations are below 2 kJ/mol, whereas the pyramidal inversion of the tert‐butylphosphino groups is hindered by more than 140 kJ/mol, calculated at the B3LYP−D3(BJ)/def2‐QZVP level of theory. In the experimental microwave spectrum, we unambiguously identified the two global‐minimum diastereomers with 72° conformations. The absence of other conformers can be attributed to the relaxation dynamics in the supersonic jet, which transfers the high‐energy conformers to the respective global‐minimum geometries. Additionally, we discovered that London dispersion interactions between the two tert‐butylphosphino groups play a crucial role in stabilizing the structures of this ferrocene complex.
Understanding Occlusion and Temporomandibular Joint Function Using Deep Learning and Predictive Modeling
Authors: Farook Taseef Hasan , Dudley James
Published: November 2024

Objectives

Advancements in artificial intelligence (AI)‐driven predictive modeling in dentistry are outpacing the clinical translation of research findings. Predictive modeling uses statistical methods to anticipate norms related to TMJ dynamics, complementing imaging modalities like cone beam computed tomography (CBCT) and magnetic resonance imaging (MRI). Deep learning, a subset of AI, helps quantify and analyze complex hierarchical relationships in occlusion and TMJ function. This narrative review explores the application of predictive modeling and deep learning to identify clinical trends and associations related to occlusion and TMJ function.

Results

Debates persist regarding best practices for managing occlusal factors in temporomandibular joint (TMJ) function analysis while interpreting and quantifying findings related to the TMJ and occlusion and mitigating biases remain challenging. Data generated from noninvasive chairside tools such as jaw trackers, video tracking, and 3D scanners with virtual articulators offer unique insights by predicting variations in dynamic jaw movement, TMJ, and occlusion. The predictions help us understand the highly individualized norms surrounding TMJ function that are often required to address temporomandibular disorders (TMDs) in general practice.

Conclusions

Normal TMJ function, occlusion, and the appropriate management of TMDs are complex and continue to attract ongoing debate. This review examines how predictive modeling and artificial intelligence aid in understanding occlusion and TMJ function and provides insights into complex dental conditions such as TMDs that may improve diagnosis and treatment outcomes with noninvasive techniques.
Evaluation of Panoramic Radiography Diagnostic Accuracy in the Assessment of Interdental Alveolar Bone Loss Using CBCT
Authors: Anbiaee Najmeh , Pahlavanzadeh Pedram
Published: November 2024

Objectives

Alveolar bone loss (ABL) and periodontal lesions are common diseases that have an undeniable effect on teeth maintenance and health. Current diagnostic methods include probing, intraoral radiography, and panoramic radiography; each has its limitations. In this study, we aimed to assess the diagnostic accuracy of panoramic radiography in the diagnosis of interdental ABL.

Material and Methods

In this cross‐sectional study, panoramic and cone‐beam computed tomography (CBCT) images from 80 patients were collected from the archives of an oral and maxillofacial radiology center. The amount of ABL was obtained by measuring the distance from the Cemento‐Enamel Junction (CEJ) to the alveolar bone crest on both panoramic and CBCT images. Patients were divided into healthy (ABL ≤ 2 mm) and diseased (2 mm < ABL) groups in terms of periodontal disease.

Results

There was no statistically significant difference in the average ABL in the premolar, maxillary molar, and mandibular molar areas between the two techniques. However, in other areas, the ABL size was significantly lower in the panoramic view (p < 0.05). Also, the panoramic technique correctly recognized 89.1% of normal and 88.4% of ABL cases. The overall accuracy of panoramic radiography in the diagnosis of ABL was 85%, indicating the good accuracy of this technique. In maxilla, the highest diagnostic accuracy of the panoramic technique was in the molars, and the lowest was in the incisors. In the mandible, the highest and lowest diagnostic accuracy of the panoramic technique was related to molars and premolars, respectively. According to the kappa statistic, there was a significant good to very good agreement between the two types of techniques in all maxillary areas (p < 0.001).

Conclusions

Panoramic radiography is accurate in showing ABL. Measuring ABL in the posterior mandibular areas in panoramic radiographs is quite reliable; however, in general, digital panoramic radiography shows less ABL than the actual amount.
Cascade Catalytic Systems for Converting CO2 into C2+ Products
Authors: Shi Qiaochu , Zhang Boyu , Wu Zhenhua , Yang Dong , Wu Hong , Shi Jiafu , Jiang Zhongyi
Published: November 2024

The excessive emission and continuous accumulation of CO2 have precipitated serious social and environmental issues. However, CO2 can also serve as an abundant, inexpensive, and non‐toxic renewable C1 carbon source for synthetic reactions. To achieve carbon neutrality and recycling, it is crucial to convert CO2 into value‐added products through chemical pathways. Multi‐carbon (C2+) products, compared to C1 products, offer a broader range of applications and higher economic returns. Despite this, converting CO2 into C2+ products is difficult due to its stability and the high energy required for C−C coupling. Cascade catalytic reactions offer a solution by coordinating active components, promoting intermediate transfers, and facilitating further transformations. This method lowers energy consumption. Recent advancements in cascade catalytic systems have allowed for significant progress in synthesizing C2+ products from CO2. This review highlights the features and advantages of cascade catalysis strategies, explores the synergistic effects among active sites, and examines the mechanisms within these systems. It also outlines future prospects for CO2 cascade catalytic synthesis, offering a framework for efficient CO2 utilization and the development of next‐generation catalytic systems.
Electrochemical Biosensor Based on Gherkin (Cucumis anguria) Peroxidase Immobilized on Chitosan‐Coated Iron Oxide Nanoparticles for Phenolic Compounds Detection
Authors: Ananias Reis Daniel , Caon Natália Bruzamarello , Giuliana Valentini , Alexandre Luis Parize , Rosane Nora Castro , João Victor Nicolini , de Oliveira Inês Rosane Welter Zwirtes
Published: November 2024

This work presents the development of a sustainable and biocompatible electrochemical biosensor for the detection of phenolic compounds, leveraging peroxidase from Cucumis anguria (gherkin) homogenate and chitosan‐coated iron oxide nanoparticles (γ‐Fe2O3@CTS). A simple and cost‐effective method was used to prepare the enzymatic extract, with peroxidase activity confirmed spectrometrically. The γ‐Fe2O3@CTS were synthesized with hydrodynamic radius of 146.8 ± 8.4 nm. Square wave voltammetry was employed to optimize experimental parameters for phenolic detection. Analytical curves were constructed for quercetin, morin, ferulic acid, and 2,5‐dihydroxybenzoic acid (2,5‐DHBA), showing excellent linearity and low detection limits of 0.0556, 24.2, 0.0102 and 1.72 μmol L−1, respectively. These results highlight the potential of this biosensor for future applications in phenolic compound detection for environmental monitoring, food safety, and pharmaceutical industries, where phenolic compounds are significant markers. The biosensor's cost‐effectiveness, simplicity, and biocompatibility make it an attractive tool for on‐site and real‐time analysis of phenolic pollutants, improving sustainability in detection technologies.
Disclosures 18: How to refuse an internal request
Authors: Rainsberger Richard
Published: November 2024

Last month, I sort of left you hanging. I was discussing internal disclosures of education records. And, at the end of the column, I mentioned a situation where a security director asked the dean of students for access to the judicial hearings files under the control of that dean. When asked why he needed those records, he simply said his responsibility to the college required that he be given unlimited access to those records to secure the campus from any threats. That last part was not included in last month's column.
Efficiency and explainability of design‐oriented machine learning models to estimate seismic response, fragility, and loss of a steel building inventory
Authors: Zaker Esteghamati Mohsen , Baddipalli Shivalinga
Published: November 2024

Machine learning (ML) has recently been used as an efficient surrogate to estimate different steps of performance‐based earthquake engineering (PBEE), from dynamic structural analysis to fragility and loss assessments. However, due to the varied data, models, and features in existing literature, the relative efficiency of ML models across different PBEE steps remains unclear. Additionally, the black‐box nature of advanced ML algorithms limits their ability to provide design‐oriented insights, hindering the broader application of ML in PBEE‐based design. This study provides a comprehensive comparison of the accuracy and explainability of design‐oriented ML models across different steps of PBEE using a consistent database of 621 steel moment frames with varying designs and geometry. Eight ML algorithms were used in a careful training workflow comprising feature selection, hyperparameter tuning, cross‐validation, and model inference. The sensitivity of model accuracy to representative PBEE outputs—maximum responses, median fragility, and expected annual loss—was assessed using statistical measures. In addition, the explainability of the best models for each step was examined to explore the relationship between design parameters and the corresponding PBEE output. The results show that while ML models can reasonably map design parameters to all different PBEE outputs, models accuracy was higher for drift responses, median fragilities, and component‐based loss metrics. In addition, the optimal algorithm remained the same across different PBEE steps, where support vector machines and random forests provided the highest accuracy with an average R2 of 0.93 and 0.91 over different outputs on the test set. Although the selected feature sets varied across outputs and algorithms, height, number of stories, fundamental period, and the minimum of the beams’ moment of inertia were influential for both models and notably affected different PBEE outputs.
Imaging‐genomic spatial‐modality attentive fusion for studying neuropsychiatric disorders
Authors: Rahaman Md Abdur , Garg Yash , Iraji Armin , Fu Zening , Kochunov Peter , Hong L. Elliot , Van Erp Theo G. M. , Preda Adrian , Chen Jiayu , Calhoun Vince
Published: November 2024

Multimodal learning has emerged as a powerful technique that leverages diverse data sources to enhance learning and decision‐making processes. Adapting this approach to analyzing data collected from different biological domains is intuitive, especially for studying neuropsychiatric disorders. A complex neuropsychiatric disorder like schizophrenia (SZ) can affect multiple aspects of the brain and biologies. These biological sources each present distinct yet correlated expressions of subjects' underlying physiological processes. Joint learning from these data sources can improve our understanding of the disorder. However, combining these biological sources is challenging for several reasons: (i) observations are domain specific, leading to data being represented in dissimilar subspaces, and (ii) fused data are often noisy and high‐dimensional, making it challenging to identify relevant information. To address these challenges, we propose a multimodal artificial intelligence model with a novel fusion module inspired by a bottleneck attention module. We use deep neural networks to learn latent space representations of the input streams. Next, we introduce a two‐dimensional (spatio‐modality) attention module to regulate the intermediate fusion for SZ classification. We implement spatial attention via a dilated convolutional neural network that creates large receptive fields for extracting significant contextual patterns. The resulting joint learning framework maximizes complementarity allowing us to explore the correspondence among the modalities. We test our model on a multimodal imaging‐genetic dataset and achieve an SZ prediction accuracy of 94.10% (p < .0001), outperforming state‐of‐the‐art unimodal and multimodal models for the task. Moreover, the model provides inherent interpretability that helps identify concepts significant for the neural network's decision and explains the underlying physiopathology of the disorder. Results also show that functional connectivity among subcortical, sensorimotor, and cognitive control domains plays an important role in characterizing SZ. Analysis of the spatio‐modality attention scores suggests that structural components like the supplementary motor area, caudate, and insula play a significant role in SZ. Biclustering the attention scores discover a multimodal cluster that includes genes CSMD1, ATK3, MOB4, and HSPE1, all of which have been identified as relevant to SZ. In summary, feature attribution appears to be especially useful for probing the transient and confined but decisive patterns of complex disorders, and it shows promise for extensive applicability in future studies.
Impact of French lockdowns on bereavement experiences: Insight from ALCESTE analysis revealing psychological resilience and distinct grief dynamics amidst COVID‐19
Authors: Sani Livia , Chemrouk Yasmine , Lassagne Boris , Cape Chad , Ngo Nkana Marie , Cherblanc Jacques , Bacqué Marie‐Frédérique
Published: November 2024

At the beginning of 2020, the entire world was shocked by a global health emergency. According to the literature, fear, high mortality and health restrictions had significant psychological consequences on the population. This study evaluates the French lockdown's impact on the grieving process and how people worked through their grief. Two semi‐structured interviews were conducted with 31 participants who had lost a loved one between March 2020, June, and September 2021 (T0) and 6 months later (T1). Subsequently, they were divided into two groups: those who lost someone during the first lockdown (Group 1) and those who lost someone outside the lockdown periods (Group 2). The interviews were analysed using the ALCESTE software, a statistical analysis tool for textual data based on word co‐occurrences. This research significantly advances the understanding of bereavement during crises, providing new perspectives and practical insights for policymakers, healthcare professionals and support organisations. Its methodological innovation and detailed analysis contribute to the ongoing discussion on grief and resilience in challenging circumstances. Ultimately, this study lays the foundation for improved support and intervention strategies tailored to the needs of bereaved individuals during crises.
Reduction of Chemoresistance by Claudin‐14‐Targeting Peptide in Human Colorectal Cancer Cells
Authors: Mizukami Yuko , Hashimoto Shotaro , Ando Tomoka , Ishikawa Yoshinobu , Eguchi Hiroaki , Yoshino Yuta , Matsunaga Toshiyuki , Matsuhashi Nobuhisa , Ikari Akira
Published: November 2024

The expression of claudins (CLDNs), major components of tight junctions (TJs), is abnormal in various solid tumors. CLDN14 is highly expressed in human colorectal cancer (CRC) tissues and confers chemoresistance. CLDN14 may become a novel therapeutic target for CRC, but CLDN14‐targeting drugs have not been developed. Here, we searched for a CLDN14‐targeting peptide, which can suppress CLDN14 expression and chemoresistance using human CRC‐derived DLD‐1 and LoVo cells. Among some short peptides which mimic the second extracellular loop structure of CLDN14, PSGMK most strongly suppressed the protein expression of CLDN14. The mRNA expression of other endogenous TJ components was unchanged by PSGMK. The PSGMK‐induced reduction of CLDN14 protein was inhibited by chloroquine, a lysosome inhibitor, and monodansylcadaverine, a clathrin‐dependent endocytosis inhibitor, indicating that PSGMK may enhance endocytosis and lysosomal degradation of CLDN14. In a three‐dimensional culture model, the oxidative stress was significantly reduced by PSGMK, whereas hypoxia stress was not. Furthermore, the expression levels of nuclear factor erythroid 2‐related factor 2, an oxidative stress response factor, and its target genes were decreased by PSGMK. These results suggest that PSGMK relieves stress conditions in spheroids. The cell viability of spheroids was decreased by anticancer drugs such as doxorubicin and oxaliplatin, which was exaggerated by the cotreatment with PSGMK. Our data indicate that CLDN14‐targeting peptide, PSGMK has an anti‐chemoresistance effect in CRC cells.
Do Social Trust and a Sense of Community Matter for the Engagement of Australian Migrants?
Authors: Miranti Riyana
Published: November 2024

Previous studies have shown mixed results regarding the potential association between trust and community participation. Only a few studies comprehensively investigated the relationship between different forms of social trust. Most of the previous studies distinguished the different forms of social trust separately. This article investigated trust and a sense of community with a more comprehensive framework in a rarely investigated population, migrants in Australia. The increasing social capital approach has been gaining importance in studying the social/political participation of (ethnic) minorities as this has primarily been seen to suit ‘ethnic’ social capital. The article aims to fill the theoretical gap by including trust and a sense of community and examining their associations with civil engagement in society using the Household, Income and Labour Dynamics in Australia Survey data, a longitudinal survey in Australia with a particular focus on bringing the heterogeneities among groups of migrants. There has been an increasing number of people born overseas—a third of the population, according to the latest Australian Census in 2021. The results show that it is likely that the Australian‐born population requires trust to engage in the community, particularly, in the case of volunteering, but this is not significant in the case of migrants. A high sense of community matters for both types of participation, political and volunteering, among Australian‐born and the first generation of migrants. The results for the second generation of migrants in the context of trust and sense of community are limited, and other factors may influence their community engagement.
Radiographic acceptable zone of endobutton placement in ACL reconstruction: A prospective study
Authors: Sharafatvaziri Arash , Tahami Mohammad , Salimi Maryam , Rabie Hamid , Vosoughi Fardis , Karimpour Morad , Moradkhani Ghazaleh , Soleymani Mosayeb
Published: November 2024

Purpose

During the transportal technique of anterior cruciate ligament (ACL) reconstruction, tunnel outlet location can be varied depending on certain anatomical and technical characteristics. Therefore, we aimed to find out the acceptable zone of endobutton location by introducing several radiographic values.

Methods

Postoperative lateral radiographs of 72 patients were assessed to measure the distances from the centre of the button to the posterior femoral cortex (D1) and to the most distal point of the lateral condyle (D2). Furthermore, based on the anteroposterior (AP) radiographs, the distances from the centre of the button to the lateral femoral cortex (D3) and from the centre of the button to the line connecting the most distal points of the medial and lateral femoral condyles (D4) were assessed. To measure the sensitivity and specificity of each radiographic value (D1, D2, D3 and D4), the area under the receiver operating characteristic curve was calculated. The alpha angle and femoral tunnel length values were considered as gold standards.

Results

Analyses showed that the mean values for D1, D2, D3 and D4 were 13.20 ± 0.54, 39.44 ± 0.31, 1.65 ± 0.15 and 42.66 ± 0.47 mm, respectively. The mean angle was found to be 38.6 ± 0.3°, and the mean femoral tunnel length was 38.6 ± 0.2 mm. Age was significantly related to D2 and the diameter of the femur in AP X‐ray, while body mass index had a significant relation with D3 (p < 0.05).

Conclusion

In this study, a new method was proposed to evaluate the accuracy of anatomical tunnel placement in ACL reconstruction surgery postoperatively. The statistical analysis of the measured variables showed that the mean ratios were 21.79 ± 0.87 for D1, 65.65 ± 0.63 for D2 and 51.90 ± 0.73 for D4. The results indicated that if the tunnel exit location and endobutton placement in the postoperative radiological images fall within the suggested areas, it can be meaningfully concluded that the tunnel is correctly positioned intraarticularly and the ligament reconstruction is anatomical.

Level of Evidence

Level III.
Analgesia in paediatric acute pancreatitis: A scoping systematic review
Authors: Lucocq James , Joseph Nejo , Knoph Cecilie Sigaard , Abu‐EL‐Haija Maisam , Scheers Isabelle , Drewes Asbjorn M. , Pandanaboyana Sanjay
Published: November 2024

Objective

Acute pancreatitis (AP) is a common paediatric condition, yet there is little data to support optimal analgesic practice. The aim of this scoping review was to report analgesic practice, investigate trends in analgesic strategy and evaluate the impact of analgesic modality on outcomes.

Methods

A systematic search of Medline, Embase, CENTRAL, Pubmed Central and Google Scholar was performed by two independent investigators. This review adhered to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses extension for Scoping Reviews checklist.

Results

Three retrospective cohort studies, all conducted in North America, reported on analgesic practice in paediatric AP. The studies included 658 patients (median age, 12 years; female sex, 57%; non‐biliary aetiology, 85.9%). Overall, analgesia was administered in 67% of patients, including opioids in 59.5% (43.8%–71.4%). Rates of acetaminophen (17.9% and 77.7%) and non‐steroidal anti‐inflammatory drugs (7.7% and 40.2%) were reported in two studies. Two studies reported reducing rates of opioid administration or reduced duration of opioid administration since 2017 and 2014, respectively. One study did not find any correlation between opioid administration and sociodemographic factors, length of stay or admission to intensive care units. No studies reported on complications or quality of life. No studies investigated non‐medical modalities. There were no long‐term data on analgesic use post‐discharge.

Conclusions

Opioids are the mainstay of pain treatment in paediatric AP in North America. However, factors that influence the analgesic type, the impact of analgesic modality on the post‐pancreatitis outcome and long‐term analgesic use constitute a knowledge gap. Future studies are needed to inform analgesic use in paediatric AP.
Mechanism analysis of the differences in relieving constipation in a Balb/c constipation model mouse fed human milk probiotics or fermented milk
Authors: Zhao Baoyuan , Wang Yajuan , Wang Shengyuan , Mu Guangqing , Wu Xiaomeng
Published: November 2024

BACKGROUND

Consumers require fermented milk that possesses constipation‐relieving functions. To cater to the ‘natural and additive‐free’ consumption habit, this study is dedicated to developing probiotic fermented milk with constipation‐relief effects. Previously, we isolated two Lactobacillus strains, Lactobacillus MWLp‐12 and Lactobacillus MWLf‐4, from breast milk. This study evaluated the efficacy of these strains and their fermented milk in alleviating constipation in a Balb/c mouse model of constipation. The evaluation criteria included fecal water content, time for first black feces expulsion and propulsion rate of the small intestine. The mechanisms of constipation relief were investigated using gastrointestinal regulatory peptides, colonic tissue pathology, short‐chain fatty acid levels and gut microbiota analyses.

RESULTS

Fecal water content, time for first black feces expulsion and small intestine propulsion rate indicated that both MWLp‐12 and MWLf‐4, as well as their fermented milk, could alleviate constipation in mice. Fermented milk exhibited superior effectiveness for relieving constipation compared to that of the strains alone. The results related to gastrointestinal regulatory peptides and short‐chain fatty acids suggest that the mechanisms of constipation relief by the strains and their fermented milk may involve increased levels of 5‐hydroxytryptamine and substance P in the mouse serum, higher concentrations of short‐chain fatty acids in the intestines and decreased vasoactive intestinal peptide levels in the serum.

CONCLUSION

MWLp‐12, MWLf‐4 and fermented milk relieve constipation in mice. © 2024 Society of Chemical Industry.
Dynamic changes in proanthocyanidin composition, biosynthesis, and histochemistry in spine grape (Vitis davidii Foëx) tissues during berry development
Authors: Yan Yinfang , Li Lin , Zheng Mingyuan , Duan Bingbing , Zhang Jiajing , Li Yashan , Liu Wei , Liu Xu
Published: November 2024

BACKGROUND

Spine grapes are widely cultivated in southern China because of their strong adaptability to hot and humid climates. As a wild species native to China, spine grape (Vitis davidii Foëx) was studied as a resource of proanthocyanidins (PAs). PA composition, biosynthesis, and histochemistry in different tissues (skins, seeds, and stems) during berry development were analyzed in this study.

RESULTS

The findings revealed that PA accumulation occurred in concurrence with flowering and was completed by veraison. High‐performance liquid chromatographic results showed that the epicatechin type was the most dominant. The skins were more likely to accumulate PA polymers. Reverse transcription–quantitative polymerase chain reaction analysis revealed that the expression levels of structural genes (flavonoid‐3′‐hydroxylase, flavonoid‐3′5′‐hydroxylase, dihydroflavonol 4‐reductase, leucoanthocyanidin reductase, and leucoanthocyanidin dioxygenase) were positively associated with PA dynamic changes. Histochemical results revealed that PAs in skins were mainly found in the hypodermis of the exocarp, PAs in seeds were mainly found in the middle layer of the outer integument of the testa, and PAs in stems were mainly found in the phloem.

CONCLUSION

This study provides a clear understanding of the spatial and temporal accumulation of PAs in spine grape, and forms a basis for the analysis of structural profiles and synthesis of PAs and their biological effects. © 2024 Society of Chemical Industry.
Mechanobullous form of epidermolysis bullosa acquisita: Insights into disease mechanisms as inferred by response to rituximab, but not to JAK inhibitors
Authors: Gueissaz L. , Junge A. , Wolf R. , Schlapbach C. , Feldmeyer L. , Borradori L.
Published: November 2024

Epidermolysis bullosa acquisita (EBA) is a rare autoimmune blistering disease associated with IgG autoantibodies directed against type VII collagen. Different clinical forms have been described, including the classical mechanobullous variant resembling epidermolysis bullosa dystrophica, which is typically treatment‐resistant. We here describe a 67‐year‐old patient with a mechanobullous EBA characterized by trauma‐induced blisters on her hands and feet for 9 months. Despite treatments with oral prednisolone, topical steroids or calcineurin inhibitors, doxycycline, ciclosporin, and baracitinib, no improvement was observed. The patient went into complete remission only after administration of rituximab with no lesions off therapy at the 10‐month follow up. Our observation suggests that inflammatory cytokines are not primarily responsible for skin blistering and fragility in mechanobullous EBA. The effectiveness of rituximab provides some insights into the major direct role of autoantibodies in mediating dermo‐epidermal separation in this variant of EBA.
Skin infections caused by Mycobacterium chelonae: Underestimated, especially in immunocompromised patients
Authors: De Krock Celine , Van de gaer Otto , André Emmanuel , Lenaerts Jan Leo , Verschueren Patrick , De Munter Paul , De Haes Petra
Published: November 2024

Mycobacterium chelonae infections are rare but significant in immunocompromised patients, often leading to delayed diagnosis due to a specific clinical signs and the difficulty to culture and identify the causative agent with conventional laboratory techniques. We report a case series of five patients presenting with cutaneous infection due to M. chelonae. An extensive review of the literature was accomplished to provide summary data on the clinical presentation, diagnostic methods and treatment options for these infections. Four out of five patients were receiving immunosuppressive treatments. All patients presented after a prolonged history of painful lesions on the extremities. Sampling and definitive diagnosis implied repeated tissue biopsies and a combination of mycobacterial tests. All patients received a combination of antibiotics comprising a macrolide and achieved complete healing of the skin lesions after 4–12 months. Our case report aims to increase awareness of skin infections caused by M. chelonae and emphasises the importance of early implementation of mycobacterial cultures in the diagnosis of painful ulcerations on the extremities that do not improve to standard systemic antibiotics.
Improved photoprotection in the UVA/visible radiation boundary region is essential to prevent DNA damage, oxidative stress and gene expression changes in human skin
Authors: Lawrence Karl P. , Douki Thierry , Sarkany Robert P. E. , Acker Stephanie , Herzog Bernd , Young Antony R.
Published: November 2024

Background

Studies have demonstrated the potential for damage caused by exposure to radiation at the UVR/visible border region (380–410 nm) and beyond. This includes potentially mutagenic delayed DNA damage, increased gene expression related to photoageing and inflammation, pigmentation and the production of reaction oxygen species. Photoprotection in this region is limited, with a focus on shorter, more energetic UVR regions.

Objectives

To assess the ability of two sunscreens for their ability to prevent photodamage in the UVA/visible region. Both sunscreens were labelled as SPF 15 and would meet requirements for labelling as UVA protective in the EU and USA. Their ingredients were identical apart from the addition of bis‐ (diethylaminohydroxybenzoyl benzoyl) piperazine (BDBP), a recently approved organic filter that absorbs between 350 and 425 nm.

Methods

Sunscreens were assessed in vitro in human cell lines and in vivo in healthy human volunteers (Fitzpatrick skin type I–II volunteers). Endpoints were assessed including oxidative stress, gene expression and DNA damage.

Results

The formulation including the new filter provided significantly more protection than the conventional sunscreen for almost all endpoints tested. The conventional formulation provided some protection compared to unprotected skin or placebo control.

Conclusions

This study demonstrates the requirement for improved photoprotection at the UVR‐visible border region and the importance of assessing sunscreens across a broader range of wavelengths than currently approved protocols require.
Variability and correlations among vital rates and their influence on population growth in mule and black‐tailed deer
Authors: Ruprecht Joel , Forrester Tavis D. , Clark Darren A. , Wisdom Michael J. , Smith Joshua B. , Levi Taal
Published: November 2024

To reverse range‐wide population declines, managers of black‐tailed and mule deer (Odocoileus hemionus) require information on the vital rates and life stages most influential to population growth to target effective management actions. We extracted black‐tailed and mule deer vital rates from a range‐wide literature review and used hierarchical models to summarize vital rates, their variability, and how they correlate with one another. We then used matrix models and life‐stage simulation analysis to determine the individual vital rates that contributed most to annual population growth rate (i.e., lambda). Annual adult female survival explained the greatest amount of variation (62%) in lambda. Annual juvenile survival explained 44% of the variation in lambda, whereas summer or winter juvenile survival by themselves were far less informative. Winter fawn:doe ratios, a metric often collected by management agencies, explained only 10% of the variation in lambda. Given an adult female survival of 0.84, our simulations estimated a lambda of 1.0 (95% credible interval = 0.88–1.14), indicating equal probability that a population would increase or decrease. Simulations further indicated that given adult survival rates <70%, the population would always decline, but as survival increased lambda increased linearly. In contrast, estimates of lambda plateaued when annual juvenile survival reached approximately 0.5, indicating higher survival rates yielded diminishing returns to population stability. Using simulated values within the observed range of vital rate values across the species' geographical distribution, the mean lambda was 0.975 and in 61% of the simulations, lambda was <1. After 20 years, we estimated that this distribution of lambda values would cause populations to decrease in 92% of instances with a mean decrease of 44%. Our results align with observed declines in mule deer populations throughout their range over recent decades and indicate that these trends will continue until management can improve survival of adult females.
Agricultural Land Conversion and Challenges for Tenant Farmers: Empirical Evidence From Pakistan
Authors: Saqib Shahab E. , Yaseen Muhammad , Ali Shoukat , Visetnoi Supawan
Published: November 2024

Agricultural land conversion (ALC) is a common phenomenon, particularly in developing countries that is driven by motives of urban development and growth. This conversion causes a loss of income source, causing unemployment and food insecurity among rural communities. This study aimed to investigate the socioeconomic impacts of ALC on tenant farmers/sharecroppers' households. Data were collected through a questionnaire survey and statistical techniques were used to compare the data before and after the ALC. Moreover, the regression model was employed to estimate the important determinants of land conversion. Results showed that most of the farmers' lands were converted into a non‐agriculture sector and these lands were irrigated. After the land conversion, the farmers' main source of households' income changed from farming to wages, business, or remittances. The proportion of agricultural income to total income significantly declined from 65% to 25%. Animal rearing and agricultural production have significantly declined after the ALC in the study area. The farmers' consumption of most essential commodities has decreased significantly (p < 0.05). Furthermore, the farmers reduced expenditures on non‐food items and overall results showed that these tenant farmers/sharecroppers faced severe consequences of ALC. Crop diversification, farmers' education, experience, and agricultural labor were negatively associated with ALC. Immediate actions from the district and provincial governments are needed to safeguard these households from the adverse impacts of poverty and food insecurity. By improving access to water sources and introducing diversified and integrated farming systems, these lands can become more productive, allowing farmers to cultivate a wider range of crops and raise livestock, making the land more economically viable for continued agricultural use.
Rhodamine B‐Modified Nanocrystalline Cellulose as Fluorescent Sensor for Fe3+ Ion Detection
Authors: Golshan Marzieh , Gheitarani Behnam , Safavi‐Mirmahalleh Seyedeh‐Arefeh , Salami‐Kalajahi Mehdi
Published: November 2024

Iron is crucial for various biological processes in humans, animals, and plants, making precise and efficient monitoring of iron ion concentrations essential. To address this need, a cellulose‐based smart fluorescent material (NCC@NH2@RB) with a conjugated structure is designed and synthesized for the rapid and sensitive detection of Fe3+ ions. This sensor features core‐shell nanoparticles functionalized with rhodamine B (RB), using (3‐aminopropyl)triethoxysilane (APTES) as a linker. The resulting fluorescent probe, composed of nanocrystalline cellulose and RB, exhibits strong fluorescence under ultraviolet light, making it an effective tool for Fe3+ ion detection in water. When Fe3+ ions are introduced into a solution containing NCC@NH2@RB, they bind with weak‐field ligands such as nitrogen and oxygen in the probe's structure, forming complexes. This interaction involves high‐spin coordination and leads to the self‐assembly of Fe3+ ions on the surface of NCC@NH2@RB. The process generates single electrons, increasing paramagnetism and quenching the fluorescence. The NCC@NH2@RB fluorescent probe has a limit of detection (LOD) of 0.01 µM and a limit of quantification (LOQ) of 0.03 µM with linearity at concentrations of 1.0 × 10−4–2.5 × 10−3 m. This fluorescence quenching effect is specific to Fe3+ ions, ensuring that the probe remains unaffected by other metal ions.
Pterostilbene Targets Hallmarks of Aging in the Gene Expression Landscape in Blood of Healthy Rats
Authors: Tello‐Palencia Marco A. , Yang Tony , Sularz Olga , Demers Louis Erik , Ma Yuexi , Boycott Cayla , Zhang Huiying Amelie , Lubecka‐Gajewska Katarzyna , Kumar Sadhri , Ramsey Benjamin S. , Torregrosa‐Allen Sandra , Elzey Bennett D. , Lanman Nadia Atallah , Korthauer Keegan , Stefanska Barbara
Published: November 2024

Scope

Polyphenols from the phytoestrogen group, including pterostilbene (PTS), are known for their antioxidant, anti‐inflammatory, and anti‐cancer effects. In recent reports, phytoestrogens attenuate age‐related diseases; however, their pro‐longevity effects in healthy models in mammals remain unknown. As longevity research demonstrates age‐related transcriptomic signatures in human blood, the current study hypothesizes that phytoestrogen‐supplemented diet may induce changes in gene expression that ultimately confer pro‐longevity benefits.

Methods and results

In the present study, RNA sequencing is conducted to determine transcriptome‐wide changes in gene expression in whole blood of healthy rats consuming diets supplemented with phytoestrogens. Ortholog cell deconvolution is applied to analyze the omics data. The study discovered that PTS leads to changes in the gene expression landscape and PTS‐target genes are associated with functions counteracting hallmarks of aging, including genomic instability, epigenetic alterations, compromised autophagy, mitochondrial dysfunction, deregulated nutrient sensing, altered intercellular interaction, and loss of proteostasis. These functions bridge together under anti‐inflammatory effects through multiple pathways, including immunometabolism, where changes in cellular metabolism (e.g., ribosome biogenesis) impact the immune system.

Conclusion

The findings provide a rationale for pre‐clinical and clinical longevity studies and encourage investigations on PTS in maintaining cellular homeostasis, decelerating the process of aging, and improving conditions with chronic inflammation.
A POD‐TANN Approach for the Multiscale Modeling of Materials and Macro‐Element Derivation in Geomechanics
Authors: Piunno Giovanni , Stefanou Ioannis , Jommi Cristina
Published: November 2024

This paper introduces a novel approach that combines proper orthogonal decomposition (POD) with thermodynamics‐based artificial neural networks (TANNs) to capture the macroscopic behavior of complex inelastic systems and derive macro‐elements in geomechanics. The methodology leverages POD to extract macroscopic internal state variables from microscopic state information, thereby enriching the macroscopic state description used to train an energy potential network within the TANN framework. The thermodynamic consistency provided by TANN, combined with the hierarchical nature of POD, allows to reproduce complex, nonlinear inelastic material behaviors, as well as macroscopic geomechanical systems responses. The approach is validated through applications of increasing complexity, demonstrating its capability to reproduce high‐fidelity simulation data. The applications proposed include the homogenization of continuous inelastic representative unit cells and the derivation of a macro‐element for a geotechnical system involving a monopile in a clay layer subjected to horizontal loading. Eventually, the projection operators directly obtained via POD are exploited to easily reconstruct the microscopic fields. The results indicate that the POD‐TANN approach not only offers accuracy in reproducing the studied constitutive responses, but also reduces computational costs, making it a practical tool for the multiscale modeling of heterogeneous inelastic geomechanical systems.