bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural Basis for Antagonist Binding to Vasopressin V1b Receptor Revealed by the Molecular Dynamics Simulations
Authors: Ślusarz Magdalena J. 
Published: September 2024

ABSTRACTThe human V1b receptor (V1bR) is primarily expressed in the corticotropic cells of the anterior pituitary where it is involved in the regulation of the hypothalamic–pituitary–adrenal (HPA) axis. The activation of V1bR induces the secretion of adrenocorticotropin hormone (ACTH) from the anterior pituitary cells which, in turn, stimulates the production of cortisol via the adrenal cortex. Clinical studies have demonstrated the chronic dysfunction of the HPA axis in patients with several psychiatric disorders. Thus, the inhibition of the V1b receptor and normalizing the HPA axis hyperactivity is a promising approach to the treatment of many stress‐related disorders such as anxiety and depression. Nelivaptan is a selective V1bR antagonist that can be used for this purpose and an excellent molecule to study how antagonists interact with V1bR, especially since in recent years the experimental structures of vasopressin V2 and oxytocin receptors were solved, providing high‐similarity templates for homology modeling of V1bR. Therefore, in this work, six independent molecular dynamics simulations of a V1bR‐nelivaptan complex in a fully hydrated lipid bilayer, yielding a total simulation time of 6.0 μs, have been conducted. In the lowest‐energy complexes obtained in this work and proposed to be the most probable structure of the V1bR‐nelivaptan complex, the location of the ligand inside the receptor pocket is very similar to that of the other ligands observed in the experimental structures of the vasopressin/oxytocin receptor family. The receptor‐ligand interaction has been analyzed and described, revealing the details of the molecular mechanism of this antagonist binding to V1bR and a probable contribution of L2005×40 and T2035×43 to binding selectivity.
Acute treatment residual depression symptoms and functional impairment among depressive patients of different age groups and education levels in China: A prospective, multicenter, randomized study
Authors: Zu Si , Wang Dong , Fang Jiexin , Xiao Le , Zhu Xuequan , Wu Wenyuan , Lin Xiufeng , Wang Gang , Hu Yongdong 
Published: September 2024

AbstractObjectiveA prospective, multicenter, randomized study evaluated the efficacy of major depressive disorder (MDD) patients after 2–3 months of acute treatment based on the dual factors of education and age.MethodsThis study classified the included patients into four groups using two classification parameters: age (≤45 years, vs. >45 years) and education years (≤12 vs. >12). We analyzed age, gender, marital status, personal income, depression onset history, medication use, and follow‐up across various groups. We evaluated residual somatic symptoms and social functioning in depression patients was conducted using the 16‐item Quick Inventory of Depressive Symptomatology Self‐report (QIDS‐SR16), the Patient Health Questionnaire‐15 (PHQ15), and the Sheehan Disability Scale (SDS).ResultsIn China, 16 hospitals, 553 depression patients, and 428 fulfilled the inclusion criteria. Baseline patient data revealed significant differences among the different age groups in gender, marital status, income, first onset age, physical illness, combination of antipsychotics, and benzodiazepines use (all p < .05). Statistically significant differences were observed in overall comparisons among the four groups, encompassing the QIDS‐SR16 score, PHQ15 score, and various SDS parameters (all p < .05). However, no statistically significant differences (all p > .05) were found in residual somatic symptoms and social functioning parameters between different education levels (≤12 years vs. >12 years) at baseline, 3 months, and 6 months, based on total scores on the scale. Repeated measures mixed model indicates that the QIDS‐SR16 assessment indicates statistical differences among various marital statuses, income levels, medical histories, and antipsychotic medication use (p < .05). Furthermore, PHQ‐15 and SDS assessments reveal statistical differences between single and married/cohabiting statuses, physical comorbidities, 3 and 6 months follow‐ups compared to baseline (p < .05).ConclusionThis study indicates that compared to depressive patients >45 years old, those ≤45 years old often exhibit more residual depression, somatic symptoms, and severe social functional impairment; patients' education levels less influence this trend.
An epigenome‐wide study of a needs‐based family intervention for offspring of trauma‐exposed mothers in Kosovo
Authors: Ryan Joanne , Phyo Aung Zaw Zaw , Krasniqi Sebahate Pacolli , Carkaxhiu Selvi Izeti , Fransquet Peter , Kaas‐Petersen Sara Helene , Limani Dafina Arifaj , Xhemaili Vjosa Devaja , Salihu Mimoza , Prapashtica Qendresa , Zekaj Nebahate , Turjaka Vesa , Wang Shr‐Jie , Rushiti Feride , Hjort Line 
Published: September 2024

AbstractIntroductionMaternal stress and trauma during pregnancy have been shown to influence cortisol levels and epigenetic patterns, including DNA methylation, in the offspring. This study aimed to determine whether a tailor‐made family intervention could help reduce cortisol levels in children born to traumatized mothers, and to determine whether it effected offspring DNA methylation. The secondary aim was to determine whether the family intervention influenced DNA methylation aging, a marker of biological aging.MethodsA needs‐based family intervention was designed to help address relational difficulties and family functioning, and included a focus on family strengths and problem‐solving patterns. Women survivors of sexual violence during the Kosovar war in 1998–1999, and their families (children with or without partners) were randomly assigned to 10 sessions of a family therapy over a 3–5‐month period, or to a waitlist control group. Both mothers and children completed assessments prior to and after the intervention phase. Children's blood samples collected at these two time points were used to measure cortisol and epigenome‐wide DNA methylation patterns (Illumina EPIC array). Cortisol levels, and genome‐wide DNA methylation changes pre‐/postintervention were compared between children in the intervention and the waitlist groups. DNA methylation age and accelerated biological aging were calculated.ResultsSixty‐two women–child dyads completed the study, 30 were assigned first to the intervention group, and 32 to the waitlist control group. In adjusted linear regression, the family intervention was associated with a significant decline in cortisol levels compared to the waitlist control (β = −124.72, 95% confidence interval [CI]: −197.4 to −52.1, p = .001). Children in the intervention group, compared to the waitlist control group, showed >1% differential methylation degree at 5819 CpG (5'—C—phosphate—G—3') sites across the genome (p < .01), with the largest methylation difference being 21%. However, none of these differences reached genome‐wide significant levels. There was no significant difference in DNA methylation aging between the two groups.ConclusionWe find evidence that a tailored family‐based intervention reduced stress levels in the children (based on cortisol levels), and modified DNA methylation levels at a number of sites across the genome. This study provides some preliminary evidence to suggest the potential for tailored interventions to help break the intergenerational transmission of trauma, however, large studies powered to detect associations at genome‐wide significant levels are needed.
Macrophages overexpressing interleukin‐10 target and prevent atherosclerosis: Regression of plaque formation and reduction in necrotic core
Authors: Wang Mingyi , Zhou Shanshan , Hu Yingyun , Tong Wei , Zhou Hao , Ma Mingrui , Cai Xingxuan , Zhang Zhengbin , Zhang Luo , Chen Yundai 
Published: September 2024

AbstractAtherosclerosis, a slowly progressing inflammatory disease, is characterized by the presence of monocyte‐derived macrophages. Interventions targeting the inflammatory characteristics of atherosclerosis hold promising potential. Although interleukin (IL)‐10 is widely acknowledged for its anti‐inflammatory effects, systemic administration of IL‐10 has limitations due to its short half‐life and significant systemic side effects. In this study, we aimed to investigate the effectiveness of an approach designed to overexpress IL‐10 in macrophages and subsequently introduce these genetically modified cells into ApoE−/− mice to promote atherosclerosis regression. We engineered RAW264.7 cells to overexpress IL‐10 (referred to as IL‐10M) using lentivirus vectors. The IL‐10M exhibited robust IL‐10 secretion, maintained phagocytic function, improved mitochondrial membrane potentials, reduced superoxide production and showed a tendency toward the M2 phenotype when exposed to inflammatory stimuli. IL‐10M can selectively target plaques in ApoE−/− mice and has the potential to reduce plaque area and necrotic core at both early and late stages of plaque progression. Moreover, there was a significant reduction in MMP9, a biomarker associated with plaque rupture, in IL‐10M‐treated plaques from both the early and late intervention groups. Additionally, the administration of IL‐10M showed no obvious side effects. This study serves as proof that cell therapy based on anti‐inflammatory macrophages might be a promising strategy for the intervention of atherosclerosis.
Phytochemical Characterization and Assessment of Antioxidant and Anti‐Alzheimer Effects of Algerian Seseli Tortuosum
Authors: Slimani Abdelkader , Akkal Wail , Acheraf Benmekhbi Ahmed , Mosbah Asma , Selim Cakmak Yavuz , Lefahal Mostefa , Bousetla Ahlem , Mokrani El Hassen , Bensouici Chawki , Laouer Hocine , Akkal Salah , Nieto Gema 
Published: September 2024

AbstractHPLC analysis, phytochemical screening, thin layer chromatography, polyphenols and flavonoid contents were conducted to determine the bioactive contents of the Algerian Seseli tortuosum plant. Antioxidant activity was tested using DPPH and ABTS scavenging assays, reducing power, phenanthroline and silver nanoparticle (SNP) assays. The anti–Alzheimer's activity of extracts was also performed in vitro and in silico. Phytochemical analysis highlighted the richness ofthe extracts in terms of coumarins, terpenoids and quercetin. The quantitative determination of total polyphenols and flavonoids showed that the highest amounts occurredinthe dichloromethane (DCME) and methanolic (MeOH) extracts. The antioxidant activities indicated a moderate potential. Compared with galantamine, DCME had a significantly greater anti–Alzheimer effect on BChE(CI50=9.14±1.74 μg/ml and 34.75±1.99 μg/ml respectively). An in silicostudy of anti–Alzheimer activity revealed a significant effect of quercetin(−30,13 KJ/mol). Conclusion: This study demonstrated the richness of the phytochemical components of seseli tortuosum,which are responsible for several biological properties, mainly their anti‐Alzheimer potential.
Allosteric Inhibition of the β2‐Adrenergic Receptor: Design and Synthesis of Cmpd‐15 Analogs
Authors: Ye Kexin , Li Qing , Luo Zhijie , Lu Qianchen , Rui Xue , Li Yan , Jin Jie , Jing Chenchen , Hong Meiling , Qian Mingcheng , Zhao Shuai , Hou Yanan , Chen Xin 
Published: September 2024

AbstractWe designed and synthesized 27 new amide and dipeptide derivatives containing a substituted phenylalanine as negative allosteric modulators (NAMs) for the beta‐2 adrenergic receptor (β2AR). These analogs aimed to improve the activity of our lead compound, Cmpd‐15, by introducing variations in three key regions: the meta‐bromobenzyl methylbenzamide (S1), para‐formamidophenylalanine (S2), and 1‐cyclohexyl‐1‐phenylacetyl (S3) groups. The synthesis involved the Pd‐catalyzed β‐C(sp3)‐H arylation of N‐acetylglycine with 1‐iodo‐4‐substituent‐benzenes as the key step. GloSensor cAMP accumulation assay revealed that six analogs (A1, C5, C6, C13, C15 and C17) surpass Cmpd‐15 in β2AR allosteric function. This highlights the crucial role of the S1 region (meta‐bromobenzyl methylbenzamide) in β2AR allostery while suggesting potential replaceability of the S2 region (para‐formamidophenylalanine). These findings serve as a valuable springboard for further optimizing Cmpd‐15, potentially leading to smaller, more active, and more stable β2AR‐targeting NAMs.
Diagnostic challenge of an untypical cutaneous drug reaction from modafinil
Authors: Harvima Rauno J. , Heiskanen‐Kosma Tarja , Arvonen Miika , Harvima Ilkka T. 
Published: September 2024

Key Clinical MessageModafinil used for narcolepsy caused an atypical adverse reaction, as itchy acneiform lesions, subcutaneous nodules and superficial skin wounds after 2 years of use. After extensive examinations for 5 years, modafinil was discontinued, and the healing process began in 3 weeks with completion in 1.5 years.
Multiple, giant lymphangectatic pilomatricomas: A rare clinical entity
Authors: Mohaghegh Fatemeh , Shoushtarizadeh Mohammad , Tabatabaei Elham Tavousi , Derakhshan Maryam , Ghadirian Ali 
Published: September 2024

Key Clinical MessageThis case highlights the rare and atypical presentation of giant, multiple pilomatricomas (PMs) with a pseudo‐bullous appearance and lymphangiomatous pathology. It underscores the importance of considering PM in the differential diagnosis of atypical lesions, especially those mimicking cystic or hemorrhagic malignant conditions, to prevent misdiagnosis and ensure appropriate management.
Possible thoracic metastasis from squamous cell carcinoma of the external auditory canal: A case report
Authors: Takehara Hiroshi , Kodama Ken , Momozane Toru , Takeda Masashi , Shigetsu Kaichi , Kishima Hiroki 
Published: September 2024

Key Clinical MessageAn 80‐year‐old never‐smoking woman, who underwent radiotherapy in combination with simultaneous intra‐arterial chemotherapy for external auditory canal squamous cell carcinoma (SCC) 10 years ago, was referred to our department due to a painful huge chest wall tumor. We conducted surgical resection combined with the right upper lobe and chest wall including the 3rd to 5th ribs and affected serratus anterior muscle. Histologically, atypical keratotic cells with the same morphology as external auditory canal SCC proliferated without the figure of carcinoma in situ or squamous dysplasia of the bronchial epithelium of the lung parenchyma adjacent to the tumor. Take Home Message: If long‐term imaging follow‐up had been performed, it would have been easier to detect it early and differentiate it from metastasis or primary lung cancer.
Fluidized Bed Chemical Vapor Deposition of Copper on Micronic Alumina Powders
Authors: Jellal Ilyass , Vergnes Hugues , Caussat Brigitte 
Published: September 2024

AbstractUniformly coating micronic particles with metals is of main interest for a broad range of applications. This study demonstrates the feasibility of depositing pure copper on the surface of micronic alumina particles by the fluidized bed chemical vapor deposition process from the cheap and nontoxic copper acetylacetonate precursor. Thanks to the development of a preconditioning protocol, a complete fluidization of the particles organized as porous agglomerates was reached. The coating of the individual particles was favored by using conditions involving low deposition rates. The influence of key operating parameters on the process behavior and on the characteristics of the deposit was studied. The deposited copper was of cubic crystal structure without carbon nor oxide contamination.
Melanin and Light
Authors: Menichetti Arianna , Mordini Dario , Montalti Marco 
Published: September 2024

AbstractMelanin is responsible, in Nature, for photoprotection, for this reason it is expected to be poorly photoreactive. However, the photo‐reactivity of melanin and related materials is well documented. Here we discuss some relevant recent examples to demonstrate that, indeed, the actual mechanism of interaction of melanin with light is complex and still not completely understood. Photochemical and photothermal processes are involved, giving a contribution that strongly depends on light wavelength and intensity. Moreover, some interesting experiments demonstrated that photochemical reactivity of melanin related compounds is likely to be indirect, in the sense that the effect of light is to increase the number of radical species rather than creating photoreactive excited state. These suggestions open‐up new perspectives in the interpretation of the role of melanin in photoprotection and in the design of new melanin based photoactive materials for energy conversion, environmental remediation, and nanomedicine. Further complication is given by the role of atmospheric oxygen and humidity in the photoinduced processes. Beside this complexity of behavior makes it difficult a systematic understanding of the interaction of melanin with light, it surely strongly contributes to make the properties of melanin and related materials unique.
Tuning The Intracellular Distribution of [3+2+1] Iridium(III) Complexes In Bacterial And Mammalian Cells By iClick Reaction With Biomolecular Carriers Functionalized With Alkynone Groups
Authors: Müller Victoria V. L. , Moreth Dominik , Kowalski Konrad , Kowalczyk Aleksandra , Gapińska Magdalena , Kutta Roger Jan , Nuernberger Patrick , Schatzschneider Ulrich 
Published: September 2024

AbstractThree iridium(III) triazolato complexes of the general formula [Ir(triazolatoR,R’)(ppy)(terpy)]PF6 with ppy=2‐phenylpyridine and terpy=2,2’:6’,2’’‐terpyridine were efficiently prepared by iClick reaction of [Ir(N3)(ppy)(terpy)]PF6, with alkynes and alkynones, which allowed facile introduction of biological carriers such as biotin and cholic acid. In contrast to the precursor azido complex, which decomposed upon photoexcitation on a very short time scale, the triazolato complexes were stable in solution for up to 48 h. They emit in the spectral region around 540 nm with a quantum yield of 15–35 % in aerated acetonitrile solution and exhibit low cytotoxicity with IC50 values >50 μM for most complexes in L929 and HeLa cells, demonstrating their high suitability as luminescent probes. Cell uptake studies with confocal luminescence microscopy in prokaryotic Gram‐positive S. aureus and Gram‐negative E. coli bacteria as well as eukaryotic mammalian L929 and HeLa cells showed significant uptake in particular of the cholic acid conjugates iridium(III) moiety and distinct intracellular distribution modulated by the nature of the peripheral functional groups that can easily be modified by the iClick reaction.
Global dynamic features and information of adjacent hidden layer enhancement based on autoencoder for industrial process soft sensor application
Authors: Guo Xiaoping , Pan Sulei , Li Yuan 
Published: September 2024

AbstractThere is a lack of consideration of temporal and spatial correlation in the process variables and adjacent hidden layers correlation in the soft sensor model of stacked autoencoders. To address the issue, a novel global dynamic adjacent layer information enhancement auto encoder (GD‐ALIEAE) method is proposed to improve the poor prediction performance. The gated recurrent unit (GRU) and uniform manifold approximation and projection (UMAP) are applied to the GD‐ALIEAE model for obtaining global dynamic features of the temporal and spatial information of process variables by parallel computation. An adjacent layer information correlation algorithm is proposed to avoid the loss of hidden layers information during the stacking process. The algorithm enhances the features of the low layer through nonlinear mapping, combining the low layer and its adjacent layer as input. The input then is fed to the multi‐head attention mechanism to obtain features that contain adjacent layer correlation. Finally, a prediction model is established through a fully connected layer. Through simulation experiments on two industrial cases of sulphur recovery unit and thermal power plant, and compared with models of stacked autoencoder (SAE), stacked isomorphic autoencoder (SIAE), and target‐related stacked autoencoder (TSAE), the effectiveness of the proposed method was verified.
Computational modelling and optimization of physicochemical absorption of CO2 in rotating packed bed
Authors: Zahir Abdul , Kumar Perumal , Saptoro Agus , Shah Milinkumar , Tiong Angnes Ngieng Tze , Kurnia Jundika Candra , Hameed Samreen 
Published: September 2024

AbstractThe current study developed a novel computational fluid dynamics (CFD) model that accounted for both physical and chemical absorption in the multiphase flow and captured the relative dominance of chemical absorption over physical by employing a tunable model parameter ‘enhancement factor’. The CFD model was validated against experimental data in a rotating packed bed, and then the validated model was used to investigate the effect of operational parameters such as rotational speed, monoethanolamine (MEA) concentration, inlet velocity, and MEA‐packing contact angle on the physiochemical absorption. The significance of each operational parameter was then evaluated by the ANOVA analysis, which inferred that the enhancement factor is sensitive to rotational speed, MEA concentration, inlet velocity, and contact angle. The p‐value of MEA concentration and inlet velocity was less than 0.05, which implies that these two variables are the most significant variables for the chemical absorption of CO2. The response surface methodology (RSM) and the artificial neural network (ANN) were also employed to develop the predictive model for the enhancement factor. Among the employed techniques, ANN resulted in R2 closer to 0.99 and could better predict the enhancement factor. The modelling approach and findings of the current study are useful in optimizing the operation of rotating packed‐bed reactor (RPB) for CO2 absorption on the industrial scale.
Medicinal Chemistry in Bosnia and Herzegovina ‐ Past, Present and Perspectives**
Authors: Kondža Martin 
Published: September 2024

AbstractAlthough Bosnia and Herzegovina has had a rich history in medicines and traditional medicines, it historically had poor activity regarding the field of medicinal chemistry in the country. However, this has changed recently as Bosnia and Herzegovina has shown immense potential in this field. A significant milestone occurred in 2019, with the establishment of the Organization Pharmaceutical Research Institute. This non‐governmental organization aims to improve medicinal chemistry in Bosnia and Herzegovina. Through research, partnerships, and educational initiatives, the organization has made substantial strides in promoting pharmaceutical research, education, and innovation. Moreover, the country‘s membership in the European Federation for Medicinal Chemistry and Chemical Biology (EFMC) has further facilitated collaboration with European experts, access to cutting‐edge knowledge and technologies, and harmonization with European standards. Looking to the future, this organization endeavors to improve healthcare, encourage innovation in medicinal chemistry, and promote the development of new therapies. With the efforts to establish an Association of Chemists in Bosnia and Herzegovina, the nation‘s scientific community is poised to flourish, contributing to the advancement of medicinal chemistry and healthcare in the region.