bluuebunny/crossref_metadata_2025_split huggingface dataset:
An image‐based Abplex method for high‐throughput GPCRs antibody discovery
Authors: Jiang Min , Wang Yuanyuan , Yu Xinke , He Yiran , Zheng Xuewen , Qin Jingyi , Gu Yayun , Li Xin , Shi Ying , Ma Xiaochuan , Li Jiong , Pu Kefeng 
Published: November 2023

AbstractAs the field of antibody therapeutics advances rapidly, membrane proteins, particularly G protein‐coupled receptors (GPCRs), have emerged as highly sought‐after drug targets. However, the challenges associated with extracting membrane proteins have created a demand for effective antibody screening systems targeting these proteins. In this study, we propose developing an innovative antibody screening strategy (Abplex) based on high‐content imaging. This approach leverages intact cells that express target membrane proteins, facilitating the presentation of proteins in their native conformation. Furthermore, it acquires both specific and non‐specific binding signals in a single well, thereby bolstering the robustness of the outcomes. The technique involves just one step and can be completed within 50 min, enabling the analysis of a single sample in just one second. The amalgamation of dependable experimental findings, a simplified workflow, reduced hands‐on time, and a swift analytical pace positions our method for superior throughput and precision when juxtaposed with traditional techniques such as CbELISA and FACS. Moreover, we introduce the concept of cell barcoding, wherein cells are labeled with different fluorescence spatial patterns. This feature allows for multiplexed detection to meet the needs of various experiments. The characteristics of Abplex promise to expedite GPCR‐targeting antibody discovery, advance therapeutics and enable new disease treatments.
Mechanistic modeling of empty‐full separation in recombinant adeno‐associated virus production using anion‐exchange membrane chromatography
Authors: Gomis‐Fons Joaquin , Zee Bryan , Hurwit Daniel , Woo James , Moscariello John , Nilsson Bernt 
Published: November 2023

AbstractRecombinant adeno‐associated viral vectors (rAAVs) have become an industry‐standard technology in the field of gene therapy, but there are still challenges to be addressed in their biomanufacturing. One of the biggest challenges is the removal of capsid species other than that which contains the gene of interest. In this work, we develop a mechanistic model for the removal of empty capsids—those that contain no genetic material—and enrichment of full rAAV using anion‐exchange membrane chromatography. The mechanistic model was calibrated using linear gradient experiments, resulting in good agreement with the experimental data. The model was then applied to optimize the purification process through maximization of yield studying the impact of mobile phase salt concentration and pH, isocratic wash and elution length, flow rate, percent full (purity) requirement, loading density (challenge), and the use of single‐step or two‐step elution modes. A solution from the optimization with purity of 90% and recovery yield of 84% was selected and successfully validated, as the model could predict the recovery yield with remarkable fidelity and was able to find process conditions that led to significant enrichment. This is, to the best of our knowledge, the first case study of the application of de novo mechanistic modeling for the enrichment of full capsids in rAAV manufacturing, and it serves as demonstration of the potential of mechanistic modeling in rAAV process development.
Unveiling Stereo‐Electronic Effects in Homogeneous Catalysis Integrating Theory and Experiments: the Potential of Dimeric Iron(III) Salen Complexes in Methyl Levulinate Transesterification
Authors: Perrella Fulvio , Langellotti Vincenzo , Buttarazzi Edoardo , Cucciolito Maria Elena , Melchiorre Massimo , Pinto Gabriella , Prokopenko Valeriia , Rega Nadia , Ruffo Francesco , Petrone Alessio , Esposito Roberto 
Published: November 2023

AbstractBiomass represents an abundant and renewable source of raw materials that can be effectively converted into intermediates and base chemicals. Among these, levulinic acid has garnered significant attention due to its direct derivation from lignocellulosic biomass and the presence of two functional groups, a carboxylic acid, and a ketone, enabling diverse transformations into valuable products. Levulinic acid esters have already found applications in various industrial sectors such as cosmetics, plasticizers, and solvents. In this study, a broad array of alkyl levulinates has been successfully synthesized through homogeneous transesterification catalyzed by Lewis acids. A systematic screening of a library of μ‐oxo‐dinuclear Fe(III) salen complexes has been conducted, aiming to elucidate the impact of steric and electronic properties of their substituents. A complementary theoretical‐computational study based on quantum mechanics calculations and machine learning regression techniques has been employed to unravel the relationship between the structure of the catalysts and their corresponding properties, shedding light on the key factors influencing their catalytic performance.
Hope and career regret: Mediator role of career adaptability and career construction
Authors: Bilgiz‐Öztürk Şeyma , Karabacak‐Çelik Aynur 
Published: November 2023

AbstractAn individual's career path choice is a unique decision that can be relatively difficult to change and lead to significant consequences. A well‐planned career decision‐making process helps individuals to be successful in an occupation. However, an undesirable decision‐making process may hinder career development. This type of undesirable decision‐making possibly leads to regrets in a career; if not addressed, these regrets may be highly destructive. To deepen the understanding of the reasons leading to it, this study focuses on the mediator role of career adaptability and career construction regarding the relationship between hope and regret. We collected the data through convenience sampling, and the participants comprised 550 Turkish university students. Each participant completed Dispositional Hope Scale, Student Career Construction Inventory, Career Adapt‐Abilities Scale—Short Form, and Career Decision Regret Scale. The results revealed that career adaptability and career construction had significant mediator effects regarding the relationship between hope and career regret.
Excited‐State Dynamics of a Photoacid: A Potential Probe for Recognizing Transition from Lamellar to Nonlamellar Inverted Structures of Liposome based Nanocarriers
Authors: Ghosh Gourab , Roy Debanjana Singha , Ghosh Ria , Mukherjee Dipanjan , Biswas Suman , Roy Lopamudra , Chattopadhyay Arpita , Das Ranjan , Pal Samir Kumar 
Published: November 2023

AbstractLiposomes of a cationic lipid dioctadecyldimethylammonium bromide (DODAB) are efficient nanocarriers of nucleic acids. Incorporation of a neutral lipid monoolein (MO) in excess (xMO>0.5) changes the lamellar organization of DODAB liposomes into non‐lamellar inverted structures of DODAB/MO liposomes facilitating nucleic acid delivery to cells. Photoexcitation of 8‐hydroxypyrene‐1,3,6‐trisulfonic acid (HPTS), a photoacid, initiates an excited state proton transfer (ESPT) reaction in its protonated form (ROH*) generating the deprotonated anionic form (RO−*). The fluorescence intensity ratio (IROH*/IRO−*) of these two forms is governed by the ESPT dynamics, and increases with increasing MO content (xMO) in the cationic liposomes of DODAB. Transition from lamellar organization of DODAB liposomes into non‐lamellar inverted structures of DODAB/MO liposomes, due to incorporation of MO (xMO~0.7), is manifested by a significant increase of ESPT time (τPT) and the time constant of wobbling motion (τW) of HPTS. Thus, the lamellar organizations of DODAB or DODAB‐rich (xMO 0.2) liposomes and the non‐lamellar organizations of MO‐rich (xMO~0.7) liposomes are recognized by significantly different excited state dynamics of the photoacid.
Shoaling behaviour in response to turbidity in three‐spined sticklebacks
Authors: MacGregor Hannah E. A. , Ioannou Christos C. 
Published: November 2023

AbstractMany fresh and coastal waters are becoming increasingly turbid because of human activities, which may disrupt the visually mediated behaviours of aquatic organisms. Shoaling fish typically depend on vision to maintain collective behaviour, which has a range of benefits including protection from predators, enhanced foraging efficiency and access to mates. Previous studies of the effects of turbidity on shoaling behaviour have focussed on changes to nearest neighbour distance and average group‐level behaviours. Here, we investigated whether and how experimental shoals of three‐spined sticklebacks (Gasterosteus aculeatus) in clear (<10 Nephelometric Turbidity Units [NTU]) and turbid (~35 NTU) conditions differed in five local‐level behaviours of individuals (nearest and furthest neighbour distance, heading difference with nearest neighbour, bearing angle to nearest neighbour and swimming speed). These variables are important for the emergent group‐level properties of shoaling behaviour. We found an indirect effect of turbidity on nearest neighbour distances driven by a reduction in swimming speed, and a direct effect of turbidity which increased variability in furthest neighbour distances. In contrast, the alignment and relative position of individuals was not significantly altered in turbid compared to clear conditions. Overall, our results suggest that the shoals were usually robust to adverse effects of turbidity on collective behaviour, but group cohesion was occasionally lost during periods of instability.
Immunity in malignant brain tumors: Tumor entities, role of immunotherapy, and specific contribution of myeloid cells to the brain tumor microenvironment
Authors: Kienzler Jenny C. , Becher Burkhard 
Published: November 2023

AbstractMalignant brain tumors lack effective treatment, that can improve their poor overall survival achieved with standard of care. Advancement in different cancer treatments has shifted the focus in brain tumor research and clinical trials toward immunotherapy‐based approaches. The investigation of the immune cell landscape revealed a dominance of myeloid cells in the tumor microenvironment. Their exact roles and functions are the subject of ongoing research. Current evidence suggests a complex interplay of tumor cells and myeloid cells with competing functions toward support vs. control of tumor growth.Here, we provide a brief overview of the three most abundant brain tumor entities: meningioma, glioma, and brain metastases. We also describe the field of ongoing immunotherapy trials and their results, including immune checkpoint inhibitors, vaccination studies, oncolytic viral therapy, and CAR‐T cells. Finally, we summarize the phenotypes of microglia, monocyte‐derived macrophages, border‐associated macrophages, neutrophils, and potential novel therapy targets.
Pharmacokinetics of vitamin dosage forms: A complete overview
Authors: Sugandhi Vrashabh V. , Pangeni Rudra , Vora Lalitkumar K. , Poudel Sagun , Nangare Sopan , Jagwani Satveer , Gadhave Dnyandev , Qin Chaolong , Pandya Anjali , Shah Purav , Jadhav Kiran , Mahajan Hitendra S. , Patravale Vandana 
Published: November 2023

AbstractVitamins are crucial for sustaining life because they play an essential role in numerous physiological processes. Vitamin deficiencies can lead to a wide range of severe health issues. In this context, there is a need to administer vitamin supplements through appropriate routes, such as the oral route, to ensure effective treatment. Therefore, understanding the pharmacokinetics of vitamins provides critical insights into absorption, distribution, and metabolism, all of which are essential for achieving the desired pharmacological response. In this review paper, we present information on vitamin deficiencies and emphasize the significance of understanding vitamin pharmacokinetics for improved clinical research. The pharmacokinetics of several vitamins face various challenges, and thus, this work briefly outlines the current issues and their potential solutions. We also discuss the feasibility of enhanced nanocarrier‐based pharmaceutical formulations for delivering vitamins. Recent studies have shown a preference for nanoformulations, which can address major limitations such as stability, solubility, absorption, and toxicity. Ultimately, the pharmacokinetics of pharmaceutical dosage forms containing vitamins can impede the treatment of diseases and disorders related to vitamin deficiency.
Antiglomerular basement membrane antibody type rapidly progressive glomerulonephritis with seizures: Two cases and literature review
Authors: Han Chongyang , Cui Xiangrong , Tan Zhicheng , Li Yafeng , Qiao Yufeng 
Published: November 2023

AbstractBackgroundRapidly progressive glomerulonephritis (RPGN) is clinically manifestations as a rapidly progressive renal failure and pathologically as crescentic and necrotizing lesions with infiltration of inflammatory cells in the glomeruli. Uremic encephalopathy (UE) usually develops in patients who are suffering from acute or chronic renal failure.ObjectiveThe purpose of this article is to provide reference for clinical diagnosis and treatment of renal disease complicated with seizures. Patients Two cases of anti‐glomerular basement membrane type rapidly progressive glomerulonephritis complicated with seizures were reported.Materials & MethodsIn case 1, a 40‐year‐old woman was hospitalized for the treatment of nausea, anorexia, and fever. On admission, she presented with elevated serum inflammatory indicators, moderate anemia, and advanced acute kidney injury requiring hemodialysis. Her anti‐glomerular basement membrane (GBM) antibody in serum and renal tissues was found to be extremely high. She was finally diagnosed with anti‐GBM disease. She was treated with a combination of corticosteroid pulse therapy, oral cyclophosphamide and prednisolone, and plasma exchange, while continued to require maintenance hemodialysis for end‐stage kidney disease. During treatment, she suddenly suffered blindness, seizure, and consciousness disturbance. She was diagnosed as posterior reversible leukoencephalopathy syndrome by magnetic resonance imaging (MRI). The posterior reversible leukoencephalopathy syndrome subsided quickly after control of her hypertension and reinforcement of immunosuppressive treatment. In case 2, the patient also developed epileptic symptoms on the basis of GBM disease, and was given treatment similar to that of Case 1, so that the epileptic symptoms were controlled.ResultReversible posterior leukoencephalopathy syndrome, especially when accompanied by cerebral hemorrhage, may lead to irreversible and lethal neurological abnormalities, and nephrologists should, therefore, be aware of the potential risk of reversible posterior leukoencephalopathy syndrome in patients with anti‐GBM disease. We can discuss the current two cases in the light of the previous literature.
A case of condyloma acuminatum of the bladder concurrently diagnosed with urothelial carcinoma
Authors: Tsuru Ibuki , Nakamura Masaki , Izumi Taro , Ono Akihiro , Miura Sakiko , Morikawa Teppei , Shigehara Kazuyoshi , Kitamura Tadaichi , Kume Haruki , Shiga Yoshiyuki 
Published: November 2023

IntroductionCondyloma acuminatum usually occurs in the external genitalia and rarely in the bladder mucosa. Here, we report a case of condyloma acuminatum of the bladder that was detected concurrently with urothelial carcinoma.Case presentationA 42‐year‐old man was referred to our urology department with positive urine cytology for urothelial carcinoma. Cystoscopy revealed a broad‐base nonpapillary bladder tumor. The patient underwent a transurethral resection of the bladder tumor. Pathological examination revealed urothelial carcinoma, high‐grade pT1, and concurrent resection of condyloma acuminatum. DNA was extracted from the paraffin‐embedded transurethral resection of the bladder tumor tissue specimens. HPV11 was detected in condylomas by PCR and in situ hybridization, whereas HPV was not detected in urothelial carcinomas.ConclusionWe report a rare case of condyloma acuminatum of the bladder that was concurrently diagnosed with urothelial carcinoma from the same site.
CircFNTA promotes tumorigenesis and progression of gastric cancer via miR‐604/miR‐647/SCN8A axis
Authors: Yu Wei , Shen Jie , Wang Xiaoguang , Qin Hongbo , Xing Chungen 
Published: November 2023

AbstractGastric cancer (GC) is a major contributor to cancer‐related deaths and is characterized by high heterogeneity in epidemiology and histopathology worldwide. Increasing evidence indicates that circular RNAs (circRNAs) play multifaceted roles in cellular processes in human cancers. Here, we demonstrated that circFNTA high expression increases the proliferation, metastasis, and epithelial–mesenchymal transition process and tumorigenicity of GC cells. First, we found that circFNTA was upregulated in GC cells and tissues, and the high circFNTA levels were positively associated with the poor prognosis in GC patients. Using luciferase reporter and RNA‐pull down assays, we elucidated that circFNTA sponged two microRNAs, miR‐604 and miR‐647. In addition, the proliferation and metastatic ability of GC cell reduction caused by silencing circFNTA was hindered by inhibitors of miR‐604 and miR‐647. Moreover, SCN8A was predicted by miRDB as a common target gene of miR‐604 and miR‐647, which was then verified by the luciferase reporter assay. Knockdown of circFNTA causes messenger RNA and protein levels in SCN8A to be downregulated in GC cells. However, this effect was overturned by cotransfection miR‐604 and miR‐647. Also, we identified that SCN8A was downregulated in GC tissues, which was positively correlated with circFNTA expression. In rescue experiments, the attenuated cell proliferation and metastatic ability caused by circFNTA knockdown was reversed by miR‐604 and miR‐647 inhibitors and SCN8A overexpression. Collectively, our findings suggest an oncogenic role of circFNTA in GC progression and elucidate that circFNTA exerts its function by modulating the miR‐604/miR‐647/SCN8A axis.
Illuminating the structural basis of human neurokinin 1 receptor (NK1R) antagonism through classical all‐atoms molecular dynamics simulations
Authors: Mishra Sarbani , Rout Madhusmita , Singh Mahender Kumar , Dehury Budheswar , Pati Sanghamitra 
Published: November 2023

AbstractAdvances in structural biology have bestowed insights into the pleiotropic effects of neurokinin 1 receptors (NK1R) in diverse patho‐physiological processes, thereby highlighting the potential therapeutic value of antagonists directed against NK1R. Herein, we investigate the mode of antagonist recognition to discern the obscure atomic facets germane for the function and molecular determinants of NK1R. To commence discernment of potent antagonists and the conformational changes in NK1R, induced upon antagonist binding, state‐of‐the‐art classical all‐atoms molecular dynamics (MD) simulations in lipid mimetic bilayers have been utilized. MD simulations of structural ensembles reveals the involvement of TM5 and TM6 in tight anchoring of antagonists through a network of interhelical hydrogen‐bonds, while, the extracellular loop 2 (ECL2) governs the overall size and nature of the pocket, thereby modulating NK1R. Consistent comparison between experiments and MD simulation results discerns the predominant role of TM3, TM4, and TM6 in lipid‐NK1R interaction. Correlation between hydrophobic index and helicity of TM domains elucidates their importance in maintaining the structural stability in addition to regulating NK1R antagonism. Taken together, we anticipate that our computational study marks a comprehensive structural basis of NK1R antagonism in lipid bilayers, which may facilitate designing of new therapeutics against associated diseases targeting human neurokinin receptors.
Organocatalyzed cycloaddition reactions of azomethine imines—A lookback
Authors: Jose Bastin K. , Simon Athulya , Subrahmanian Niranjana , Adhwithi P. , Mathai Sindhu 
Published: November 2023

AbstractThe versatile and convergent nature of 1,3‐dipolar cycloaddition reactions has made them an indispensable tool in organic chemistry for synthesizing five‐membered heterocycles. Among the various dipoles, azomethine imines (AMI) constitute a versatile class, increasingly used to synthesize biologically relevant heterocycles. The organocatalytic cycloaddition reactions of azomethine imines are relatively unexplored compared to the corresponding transition metal‐catalyzed reactions. This review highlights the unique organocatalytic cycloaddition reactions of AMI with different dipolarophiles. The cycloaddition of azomethine imines catalyzed by organic bases such as prolinol, proline, alkaloids, 1,4‐diazabicyclo[2.2.2]octane, 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU), primary amines, tertiary amines, N‐heterocyclic carbene, and phosphine are discussed here. The mechanistic and electronic aspects, including broad functional group tolerance, catalyst loading, and reaction conditions, are evaluated. This review also demonstrates the scope and potential reactivity of azomethine imines in organocatalytic cycloadditions. We are positive that the reactions of azomethine imines discussed here will aid in discovering new and efficient reaction pathways in synthesizing biologically active and industrially relevant molecules.