bluuebunny/crossref_metadata_2025 huggingface dataset:
In situ evaluation of the impact of metformin or verapamil coadministration with vildagliptin on its regional absorption from the rabbit’s intestine
Authors: Elmeniar Ahmed M. , Osman Mohamed A. , El‐Gizawy Sanaa A. , Modi Dimple , Charbe Nitin B. , El‐Kattan Ayman F. , El‐Tanani Mohamed , Haggag Yusuf A. , Tambuwala Murtaza M.
Published: February 2024

This research aims to identify regional differences in vildagliptin absorption across the intestinal membrane. Furthermore, it was to investigate the effect of verapamil or metformin on vildagliptin absorptive clearance. The study utilized an in situ rabbit intestinal perfusion technique to determine vildagliptin oral absorption from duodenum, jejunum, ileum, and ascending colon. This was conducted both with and without perfusion of metformin or verapamil. The findings revealed that the vildagliptin absorptive clearance per unit length varied by site and was in the order as follows: ileum < jejunum < duodenum < ascending colon, implying that P‐gp is significant in the reduction of vildagliptin absorption. Also, the arrangement cannot reverse intestinal P‐gp, but the observations suggest that P‐gp is significant in reducing vildagliptin absorption. Verapamil co‐perfusion significantly increased the vildagliptin absorptive clearance by 2.4 and 3.2 fold through the jejunum and ileum, respectively. Metformin co‐administration showed a non‐significant decrease in vildagliptin absorptive clearance through all tested segments. Vildagliptin absorption was site‐dependent and may be related to the intestinal P‐glycoprotein content. This may aid in understanding the important elements that influence vildagliptin absorption, besides drug–drug interactions that can occur in type 2 diabetic patients taking vildagliptin in conjunction with other drugs that can modify the P‐glycoprotein level.
Vitamin D metabolism is altered during aging alone or combined with obesity in male mice
Authors: Bournot Lorrine , Payet Thomas , Marcotorchino Julie , Awada Manar , Rouquet Thaïs , Breniere Thomas , Couturier Charlène , Astier Julien , Halimi Charlotte , Reboul Emmanuelle , Sicard Flavie , Mounien Lourdes , Roux Julien , Bariohay Bruno , Landrier Jean François
Published: February 2024

Aging and obesity are associated with a decrease in plasma 25‐hydroxyvitamin D (25(OH)D) levels. In the context of a growing aging population and the rising incidence of obesity, we hypothesized that aging process, either independently or in combination with obesity, could influence vitamin D (VD) metabolism, consequently resulting in the reduced 25(OH)D plasma concentrations. C57BL/6JRJ young (6 months) and old (23 months) mice fed with control (CD) or high fat diet (HF) were compared. Plasma and adipose concentration of cholecalciferol and 25(OH)D and mRNA expression of genes coding for the main VD actors were analyzed. Aging was associated with a decrease in plasma 25(OH)D levels, whereas combined effect of obesity and aging did not generate a cumulative effect on plasma 25(OH)D levels. The mRNA expression of Cyp27a1, Cyp3a11, and Cyp2j6 were decreased in the liver during aging. Together, these regulations could explain the reduced 25‐hydroxylation. Interestingly, the lack of cumulative reduction of 25(OH)D in aged and obese mice could be related to the strong induction of Cyp2j6. In kidneys, a complex modulation of Cyp27b1 and Cyp24a1 could contribute to the reduced 25‐hydroxylation in the liver. In white adipose tissue, an induction of Cyp2r1 was observed during aging and obesity, together with an increase of 25(OH)D quantity, suggesting an exacerbated storage that may participated to the reduced plasma 25(OH)D levels. These findings support the notion that aging alone or combined with obesity, induces regulation of VD metabolism in the organs, beyond the classical reduction of epidermal VD precursor, which may contribute to the decrease in 25(OH)D levels.
A large‐scale production of mesenchymal stem cells and their exosomes for an efficient treatment against lung inflammation
Authors: Zhang Jinsong , Lin Ruyi , Li Yingyu , Wang Jiawen , Ding Huiqing , Fang Panfeng , Huang Yingzhi , Shi Jing , Gao Jianqing , Zhang Tianyuan
Published: February 2024

Mesenchymal stem cells (MSCs) and their produced exosomes have demonstrated inherent capabilities of inflammation‐guided targeting and inflammatory modulation, inspiring their potential applications as biologic agents for inflammatory treatments. However, the clinical applications of stem cell therapies are currently restricted by several challenges, and one of them is the mass production of stem cells to satisfy the therapeutic demands in the clinical bench. Herein, a production of human amnion‐derived MSCs (hMSCs) at a scale of over 1 × 109 cells per batch was reported using a three‐dimensional (3D) culture technology based on microcarriers coupled with a spinner bioreactor system. The present study revealed that this large‐scale production technology improved the inflammation‐guided migration and the inflammatory suppression of hMSCs, without altering their major properties as stem cells. Moreover, these large‐scale produced hMSCs showed an efficient treatment against the lipopolysaccharide (LPS)‐induced lung inflammation in mice models. Notably, exosomes collected from these large‐scale produced hMSCs were observed to inherit the efficient inflammatory suppression capability of hMSCs. The present study showed that 3D culture technology using microcarriers coupled with a spinner bioreactor system can be a promising strategy for the large‐scale expansion of hMSCs with improved anti‐inflammation capability, as well as their secreted exosomes.
The immune system of prokaryotes: potential applications and implications for gene editing
Authors: Liu Siyang , Liu Hongling , Wang Xue , Shi Lei
Published: February 2024

Gene therapy has revolutionized the treatment of genetic diseases. Spearheading this revolution are sophisticated genome editing methods such as TALENs, ZFNs, and CRISPR‐Cas, which trace their origins back to prokaryotic immune systems. Prokaryotes have developed various antiviral defense systems to combat viral attacks and the invasion of genetic elements. The comprehension of these defense mechanisms has paved the way for the development of indispensable tools in molecular biology. Among them, restriction endonuclease originates from the innate immune system of bacteria. The CRISPR‐Cas system, a widely applied genome editing technology, is derived from the prokaryotic adaptive immune system. Single‐base editing is a precise editing tool based on CRISPR‐Cas system that involves deamination of target base. It is worth noting that prokaryotes possess deamination enzymes as part of their defense arsenal over foreign genetic material. Furthermore, prokaryotic Argonauts (pAgo) proteins, also function in anti‐phage defense, play an important role in complementing the CRISPR‐Cas system by addressing certain limitations it may have. Recent studies have also shed light on the significance of Retron, a reverse transcription transposon previously showed potential in genome editing, has also come to light in the realm of prokaryotic immunity. These noteworthy findings highlight the importance of studying prokaryotic immune system for advancing genome editing techniques. Here, both the origin of prokaryotic immunity underlying aforementioned genome editing tools, and potential applications of deaminase, pAgo protein and reverse transcriptase in genome editing among prokaryotes were introduced, thus emphasizing the fundamental mechanism and significance of prokaryotic immunity.
Effect of extracellular matrices on production and potency of mesenchymal stem cell‐derived exosomes
Authors: Somadder Rittika , Faraj Lina , Datta Saurav , Kanapathipillai Mathumai , Ghosh Gargi
Published: February 2024

Mesenchymal stem cell (MSC) derived exosomes have emerged as potential acellular therapeutics for various tissue regenerative applications. However, successful clinical translation of exosome‐based therapy is limited by lack of a structured production platform. Thus, in this study, the effect of decellularized extracellular matrix (dECM) was assessed on the production and potency of exosomes secreted by bone marrow‐derived human MSCs. The results indicate that there was a ∼2‐fold increase in MSC‐exosome production when MSCs were cultured on dECM compared to TCP. Further, our study revealed that dECM generation induced by ascorbic acid (AA) up to 100 µg mL−1 highly increased exosome yield thereby indicating a potential scale up method for MSC exosome production. The bioactivity of exosomes was investigated by their ability to improve the healing of wounded human skin explants. Wound closure was enhanced in the presence of exosomes isolated from MSCs cultured on ascorbic acid‐induced dECM compared to TCP generated MSC‐exosomes. In summary, this study suggests a promising solution to a major bottleneck in large‐scale production of MSC exosomes for cell‐free therapy.
Tracing endogenous proteins in living cells through electrotransfer of mRNA encoding chromobodies
Authors: Juncker Théo , Richert Ludovic , Masson Murielle , Zuber Guy , Chatton Bruno , Donzeau Mariel
Published: February 2024

Chromobodies made of nanobodies fused to fluorescent proteins are powerful tools for targeting and tracing intracellular proteins in living cells. Typically, this is achieved by transfecting plasmids encoding the chromobodies. However, an excess of unbound chromobody relative to the endogenous antigen can result in high background fluorescence in live cell imaging. Here, we overcome this problem by using mRNA encoding chromobodies. Our approach allows one to precisely control the amount of chromobody expressed inside the cell by adjusting the amount of transfected mRNA. To challenge our method, we evaluate three chromobodies targeting intracellular proteins of different abundance and cellular localization, namely lamin A/C, Dnmt1 and actin. We demonstrate that the expression of chromobodies in living cells by transfection of tuned amounts of the corresponding mRNAs allows the accurate tracking of their cellular targets by time‐lapse fluorescence microscopy.
Improvement of an enzymatic cascade synthesis of nicotinamide mononucleotide via protein engineering and reaction‐process reinforcement
Authors: Peng Feng , Hong Jian , Cui Jie , An Ya‐Ni , Guo Qian , Shen Qi , Cheng Feng , Xue Ya‐Ping , Zheng Yu‐Guo
Published: February 2024

Enzymatic synthesis of β‐nicotinamide mononucleotide (NMN) from D‐ribose has garnered widespread attention due to its cheap material, the use of mild reaction conditions, and the ability to produce highly pure products with the desired optical properties. However, the overall NMN yield of this method is impeded by the low activity of rate‐limiting enzymes. The ribose‐phosphate diphosphokinase (PRS) and nicotinamide phosphoribosyltransferase (NAMPT), that control the rate of the reaction, were engineered to improve the reaction efficacy. The actives of mutants PRS‐H150Q and NAMPT‐Y15S were 334% and 57% higher than that of their corresponding wild‐type enzymes, respectively. Furthermore, by adding pyrophosphatase, the byproduct pyrophosphate which can inhibit the activity of NAMPT was degraded, leading to a 6.72% increase in NMN yield. Following with reaction‐process reinforcement, a high yield of 8.10 g L−1 NMN was obtained after 3 h of reaction, which was 56.86‐fold higher than that of the stepwise reaction synthesis (0.14 g L−1), indicating that the in vitro enzymatic synthesis of NMN from D‐ribose and niacinamide is an economical and feasible route.
Quantitative characterization of tumor cell traction force on extracellular matrix by hydrogel microsphere stress sensor
Authors: Ma Xingquan , Wang Cong , Ji Changchun , Cao Xiaoshan , Dong Yuqing
Published: February 2024

Cell traction force (CTF) is a kind of active force that is a cell senses external environment and actively applies to the contact matrix which is currently a representative stress in cell–extracellular matrix (ECM) interaction. Studying the distribution and variation of CTF during cell–ECM interaction help to explain the impact of physical factors on cell behaviors from the perspective of mechanobiology. However, most of the strategies of characterizing CTF are still limited by the measurement needs in three‐dimensional (3D), quantitative characteristics and in vivo condition. Microsphere stress sensor (MSS) as a new type of technology is capable of realizing the quantitative characterization of CTF in 3D and in vivo. Herein, we employed microfluidic platform to design and fabricate MSS which possesses adjustable fluorescent performances, physical properties, and size ranges for better applicable to different cells (3T3, A549). Focusing on the common tumor cells behaviors (adhesion, spreading, and migration) in the process of metastasis, we chose SH‐SY5Y as the representative research object in this work. We calculated CTF with the profile and distribution to demonstrate that the normal and shear stress can determined different cell behaviors. Additionally, CTF can also regulate cell adhesion, spreading, and migration in different cell states. Based on this method, the quantitative characterization of CFT of health and disease cells can be achieved, which further help to study and explore the potential mechanism of cell–ECM interaction.
Enzyme Kinetics Analysis: An online tool for analyzing enzyme initial rate data and teaching enzyme kinetics
Authors: Mak Daniel A. , Dunn Sebastian , Coombes David , Carere Carlo R. , Allison Jane R. , Nock Volker , Hudson André O. , Dobson Renwick C. J.
Published: February 2024

Enzymes are nature's catalysts, mediating chemical processes in living systems. The study of enzyme function and mechanism includes defining the maximum catalytic rate and affinity for substrate/s (among other factors), referred to as enzyme kinetics. Enzyme kinetics is a staple of biochemistry curricula and other disciplines, from molecular and cellular biology to pharmacology. However, because enzyme kinetics involves concepts rarely employed in other areas of biology, it can be challenging for students and researchers. Traditional graphical analysis was replaced by computational analysis, requiring another skill not core to many life sciences curricula. Computational analysis can be time‐consuming and difficult in free software (e.g., R) or require costly software (e.g., GraphPad Prism). We present Enzyme Kinetics Analysis (EKA), a web‐tool to augment teaching and learning and streamline EKA. EKA is an interactive and free tool for analyzing enzyme kinetic data and improving student learning through simulation, built using R and RStudio's ShinyApps. EKA provides kinetic models (Michaelis–Menten, Hill, simple reversible inhibition models, ternary‐complex, and ping‐pong) for users to fit experimental data, providing graphical results and statistics. Additionally, EKA enables users to input parameters and create data and graphs, to visualize changes to parameters (e.g., or number of measurements). This function is designed for students learning kinetics but also for researchers to design experiments. EKA (enzyme-kinetics.shinyapps.io/enzkinet_webpage/) provides a simple, interactive interface for teachers, students, and researchers to explore enzyme kinetics. It gives researchers the ability to design experiments and analyze data without specific software requirements.
An international multicenter study comparing COVID‐19 omicron outcomes in patients with hematological malignancies treated with obinutuzumab versus rituximab
Authors: Shafat Tali , Grupel Daniel , Porges Tzvika , Abuhasira Ran , Belkin Ana , Deri Ofir , Oster Yonatan , Zahran Shadi , Horwitz Ehud , Horowitz Netanel A. , Khatib Hazim , Batista Marjorie Vieira , Cortez Anita Cassoli , Brosh‐Nissimov Tal , Segman Yafit , Ishay Linor , Cohen Regev , Atamna Alaa , Spallone Amy , Chemaly Roy F. , Ramos‐Ramos Juan Carlos , Chowers Michal , Rogozin Evgeny , Oren Noga Carmi , Keske Şiran , Barchad Orit Wolfovitz , Nesher Lior ,   the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Respiratory Viruses (ESGREV)
Published: February 2024

Objectives

Hematological malignancy (HM) patients treated with anti‐CD20 monoclonal antibodies are at higher risk for severe COVID‐19. A previous single‐center study showed worse outcomes in patients treated with obinutuzumab compared to rituximab. We examined this hypothesis in a large international multicenter cohort.

Methods

We included HM patients from 15 centers, from five countries treated with anti‐CD20, comparing those treated with obinutuzumab (O‐G) to rituximab (R‐G) between December 2021 and June 2022, when Omicron lineage was dominant.

Results

We collected data on 1048 patients. Within the R‐G (n = 762, 73%), 191 (25%) contracted COVID‐19 compared to 103 (36%) in the O‐G. COVID‐19 patients in the O‐G were younger (61 ± 11.7 vs. 64 ± 14.5, p = 0.039), had more indolent HM diagnosis (aggressive lymphoma: 3.9% vs. 67.0%, p < 0.001), and most were on maintenance therapy at COVID‐19 diagnosis (63.0% vs. 16.8%, p < 0.001). Severe‐critical COVID‐19 occurred in 31.1% of patients in the O‐G and 22.5% in the R‐G. In multivariable analysis, O‐G had a 2.08‐fold increased risk for severe‐critical COVID‐19 compared to R‐G (95% CI 1.13–3.84), adjusted for Charlson comorbidity index, sex, and tixagevimab/cilgavimab (T‐C) prophylaxis. Further analysis comparing O‐G to R‐G demonstrated increased hospitalizations (51.5% vs. 35.6% p = 0.008), ICU admissions (12.6% vs. 5.8%, p = 0.042), but the nonsignificant difference in COVID‐19‐related mortality (n = 10, 9.7% vs. n = 12, 6.3%, p = 0.293).

Conclusions

Despite younger age and a more indolent HM diagnosis, patients receiving obinutuzumab had more severe COVID‐19 outcomes than those receiving rituximab. Our findings underscore the need to evaluate the risk–benefit balance when considering obinutuzumab therapy for HM patients during respiratory viral outbreaks.
A meta‐analysis comparing efficacy and safety between proton beam therapy versus carbon ion radiotherapy
Authors: Jang Jeong Yun , Kim Kangpyo , Chen Miao‐Fen , Akimoto Tetsuo , Wang Michael Lian Chek , Kim Min‐Ji , Kim Kyunga , Lee Tae Hoon , Yoo Gyu Sang , Park Hee Chul
Published: February 2024

Background

This study aimed to compare the outcomes of proton beam therapy (PBT) and carbon ion radiotherapy (CIRT) by a systematic review and meta‐analysis of the existing clinical evidence.

Methods

A systematic literature search was performed to identify studies comparing the clinical outcomes of PBT and CIRT. The included studies were required to report oncological outcomes (local control [LC], progression‐free survival [PFS], or overall survival [OS]) or adverse events.

Results

Eighteen articles comprising 1857 patients (947 treated with PBT and 910 treated with CIRT) were included in the analysis. The pooled analysis conducted for the overall population yielded average hazard ratios of 0.690 (95% confidence interval (CI), 0.493–0.967, p = 0.031) for LC, 0.952 (95% CI, 0.604–1.500, p = 0.590) for PFS, and 1.183 (0.872–1.607, p = 0.281) for OS with reference to CIRT. The subgroup analyses included patients treated in the head and neck, areas other than the head and neck, and patients with chordomas and chondrosarcomas. These analyses revealed no significant differences in most outcomes, except for LC in the subgroup of patients treated in areas other than the head and neck. Adverse event rates were comparable in both groups, with an odds ratio (OR) of 1.097 (95% CI, 0.744–1.616, p = 0.641). Meta‐regression analysis for possible heterogeneity did not demonstrate a significant association between treatment outcomes and the ratio of biologically effective doses between modalities.

Conclusion

This study highlighted the comparability of PBT and CIRT in terms of oncological outcomes and adverse events.
Fertility counselling and fertility preservation among early onset female cancer patients—A Finnish register‐based study
Authors: Melin Johanna , Holopainen Elina , Savolainen‐Peltonen Hanna
Published: February 2024

Introduction

Advances in multimodality cancer treatments have increased long‐term survival rates for early onset cancer patients, with 5‐year survival rates reaching 80% in Northern Europe. According to recent recommendations, clinicians should, as early as possible, inform cancer patients about the impact that cancer treatment may have on their fertility. Still, there is limited published data on fertility counselling (FC) and fertility preservation (FP) for cancer patients.

Methods

This register‐based study used hospital records to identify female cancer patients in the hospital district (n = 192) who received FC at the age of 16–42 years between 2011 and 2019.

Results

Altogether, 97 (50.5%) cancer patients were eligible for FP. Of these, 55 (56.7%) underwent FP, whereas 42 (43.3%) declined. Women undergoing FP were recommended cancer treatments with a higher risk of infertility (p = 0.01), and women with breast cancer were more prone to undergo FP than women with lymphoma (p = 0.043). In FP treatment cycles, the mean number of oocytes retrieved (13.9 ± 7.7 vs. 12.0 ± 6.5, p = 0.04) and transferrable embryos (4.7 ± 2.9 vs. 3.7 ± 2.8, p = 0.002) was higher among cancer patients compared to age‐matched comparisons with male or tubal factor infertility. The total mean gonadotropin dose used was higher among cancer patients (2243 ± 963 IU vs. 1679 ± 765 IU, p < 0.001).

Conclusion

We conclude that a good ovarian response during FP can be achieved in female cancer patients.
Innovative Approaches to Sustainable Ammonia Synthesis under Mild Conditions
Authors: Castillejos Eva , García‐Bordejé Enrique
Published: February 2024

Ammonia is one of the most important chemicals in the world because it is a feedstock for fertilizer production and, moreover, it has been proposed as a convenient storage media for renewable H2. Currently, it is produced by Haber‐Bosch process, which entails harsh operation conditions and a high carbon footprint, rendering the process difficult to be run by renewable energy. Therefore, substituting the conventional Haber‐Bosch process by other approach less energy‐intensive and carbon‐free is an urgent need. A milder process for ammonia synthesis will enable the implementation of smaller distributed plants more aligned with renewable energies. For this reason, there is a plethora of current research focusing on the development of suitable catalysts with higher activity and selectivity for nitrogen reduction and processes that will work under less severe operating conditions or even at ambient conditions. Some of the most relevant research approaches are here revised and compared.
Polymeric Carbon Nitride Nanosheets as a Metal‐Free Heterogeneous Catalyst for Highly Efficient Methanolysis of Polycarbonates
Authors: Xu Yanling , Ji Yi , Liu Yue , Deng Weihua , Huang Fei , Zhang Fan
Published: February 2024

Improper end‐of‐life treatments of C−O‐linked plastics have caused serious environmental crises and resource waste. One effective method to solve this issue is the catalytic alcoholysis of these plastics. Traditional homogeneous catalysts or metal‐based heterogeneous catalysts for alcoholysis have some drawbacks, such as difficulty in complete separation, environmental threats, and economic burden. Thus, finding a green, low‐cost, recyclable, and highly efficient catalyst substitute is critical. Here, we reported that polymeric carbon nitride nanosheets can serve as a metal‐free heterogeneous catalyst for the methanolysis of polycarbonate, polyethylene terephthalate, and polylactic acid. The catalyst exhibits remarkable performance and could be reused at least four times. NHx was found to be the predominant active site of the catalyst by characterization and experiments. These results show promise for the design of metal‐free heterogeneous catalysts to depolymerize C−O‐linked plastics.
Internal Vanadium Doping and External Modification Design of P2‐Type Layered Mn‐Based Oxides as Competitive Cathodes toward Sodium‐Ion Batteries
Authors: Li Xin , Lai Xin , Kong Qingquan , An Xuguang , Zhan Jing , Li Xiaolei , Liu Xiaonan , Yao Weitang
Published: February 2024

P2‐type layered manganese‐based oxides have attracted considerable interest as economical, cathode materials with high energy density for sodium‐ion batteries (SIBs). Despite their potential, these materials still face challenges related to sluggish kinetics and structural instability. In this study, a composite cathode material, Na0.67Ni0.23Mn0.67V0.1O2@Na3V2O2(PO4)2F was developed by surface‐coating P2‐type Na0.67Ni0.23Mn0.67V0.1O2 with a thin layer of Na3V2O2(PO4)2F to enhance both the electrochemical sodium storage and material air stability. The optimized Na0.67Ni0.23Mn0.67V0.1O2@5wt %Na3V2O2(PO4)2F exhibited a high discharge capacity of 176 mA h g−1 within the 1.5‐4.1 V range at a low current density of 17 mA g−1. At an increased current density of 850 mA g−1 within the same voltage window, it still delivered a substantial initial discharge capacity of 112 mAh g−1. These findings validate the significant enhancement of ion diffusion capabilities and rate performance in the P2‐type Na0.67Ni0.33Mn0.67O2 material conferred by the composite cathode.
Layer by Layer Spraying Fabrication of Aggregation‐Induced Emission Metal‐Organic Frameworks Thin Film
Authors: Yang Xue‐Xian , Li Chong , Chen Shu‐Mei , Gu Zhi‐Gang , Zhang Jian
Published: February 2024

The development of new metal‐organic frameworks (MOFs) thin films is important for expanding their functions and applications. Herein, we first report a new kind of MOF thin film by using aggregation‐induced emission (AIE) dicarboxyl ligand through a liquid‐phase epitaxial (LPE) layer‐by‐layer (LBL) spraying method (named AIE surface‐coordinated metal‐organic frameworks thin film, AIE‐SURMOF). The obtained AIE‐SURMOF Zn4O(TPE)3 (ZnTPE) has highly growth orientation and homogeneous thin film, showing strong fluorescent property. Furthermore, by loading chiral guest in the MOF pore, the formed chiral encapsulated AIE‐SURMOF can clearly indicate obvious circularly polarized luminescence performance with glum of 0.01. This study provides new MOF thin film and new strategy for expanding function and application of MOF materials.
Bioequivalence Assessment of Two Dapoxetine Hydrochloride Formulations in Healthy Chinese Males Under Fasted and Fed Conditions
Authors: Li Yumin , Zhang Zhen , Xie Jizhen , Lian Xianghua , Zhang Guangtao , Wang Cheng
Published: February 2024

This study evaluated the bioequivalence of the newly developed dapoxetine hydrochloride tablet relative to the marketed reference product by comparing their pharmacokinetic profiles under fasted and fed conditions. A total of 60 healthy Chinese male subjects participated in a single‐center, 2‐period, 2‐sequence, randomized, open‐label, self‐crossover study with a washout period of 14 days, 30 in the fasted group and 30 in the fed group. Following a single 30‐mg oral dose of the test or reference dapoxetine formulation, blood samples were collected before dosing to 72 hours after dosing. Liquid chromatography‐tandem mass spectrometry was performed to measure plasma concentration of dapoxetine and determine pharmacokinetic parameters through noncompartmental analysis. The vital signs and adverse events were also monitored during the study. The 90% confidence intervals of the geometric mean ratios for maximum plasma concentration, area under the plasma concentration‐time curve from time 0 to the last concentration time, and area under the plasma concentration‐time curve from time 0 extrapolated to infinity of the 2 dapoxetine formulations completely fell within the regulatory criteria for bioequivalence of 80%‐125%. In addition, both dapoxetine hydrochloride formulations were generally well tolerated. The generic dapoxetine hydrochloride tablet was bioequivalent to the marketed reference product in healthy Chinese men with no discernible safety differences.
Psychotherapist perceptions of engagement‐building behaviours with youth clients across developmental levels
Authors: Orlowski Edmund W. , Chen Jason I. , Breznik Lindsey H. , Gleason La Donna L. , Karver Marc S.
Published: February 2024

Building a positive therapeutic relationship is a challenging, yet critical, first step in conducting youth psychotherapy. A number of studies in the youth treatment literature have indicated that a positive therapeutic alliance is related to increased treatment attendance, participation, and outcome. Some research has examined therapist behaviours for engaging therapy clients; however, developmental differences in alliance formation have had limited exploration. The current study surveyed clinicians about their use of specific engagement strategies and the developmental stage of their youth clients. It was hypothesised that participants would differentially rate the importance of different aspects of therapeutic engagement based upon a youth client's developmental stage and that these would correspond with differences in specific engagement strategies. A total of 64 clinicians with experience treating youth completed the study. The participants completed a questionnaire administered online that asked them to rate the importance of developmental differences to forming a therapeutic relationship and provide example client behaviours from their clinical experience for each developmental stage. Results showed clinicians felt the relative importance of collaboration, advocacy, and trustworthiness increased with age. These differences were also evidenced in the specific strategies clinicians endorsed in relation to each engagement factor across developmental stages. This program of research will eventually aid in the development of new guidelines for engaging clients in youth psychotherapy. In addition, the results may be used to enhance psychotherapy training for those working with children and adolescents.
A Bayesian approach using spatiotemporal features for suitable next hop selection in opportunistic networks
Authors: Dutta Amit , Borah Satya Jyoti , Singh Jagdeep
Published: February 2024

Opportunistic network (OppNet) belongs to the category of Mobile Ad‐hoc Networks (MANETs), a kind of Delay Tolerant Network (DTN), where the wireless nodes are completely mobile and the data transmission routes are dynamic. The major challenge in developing a routing model for such a network is the unpredictable nature of the movement of the nodes. In this paper, a spatiotemporal prediction model based on human mobility pattern is proposed using Bayesian posterior probability (BPPR) where several clusters are identified within the network and the day and time duration of nodes visiting those clusters are recorded. The Bayesian posterior probability is then used to determine the probability of the neighbor node visiting the destination's cluster. If the calculated probability for that node is higher than a specified threshold, the packet will be forwarded. A comparison of the results obtained on simulation is made with benchmark models—Epidemic, Prophet, HBPR, EDR, NexT, and EBC, to name a few, where it is found that on average the proposed model outperforms the other models in terms of delivery probability, hop count and number of messages dropped by around 23.89%, 24.8%, 24.4%, 37%, 11%, and 42% respectively, with varying number of nodes, TTL, message generation interval, and buffer size. Similar improvements have been observed in terms of the other two metrics. In terms of overhead ratio, the proposed model outperforms Epidemic, Prophet, HBPR, NexT, and EBC. However, as the number of nodes and TTL are varied, BPPR performs better than NexT by around 9% and 12%, respectively, in terms of average latency.
Development of an indoor corridor localization system based on a WCL method with corridor area selection and distance compensation
Authors: Wattananavin Thradon , Booranawong Apidet , Saito Hiroshi
Published: February 2024

In this paper, a received signal strength indicator (RSSI)‐based weighted centroid localization (WCL) method for indoor corridor scenarios is developed and tested. The contribution of the proposed system is that, to scope the area of an unknown target position, the possible corridor area where the target node should be located is automatically selected, and only reference nodes deployed in such an area are applied for position estimation. Additionally, to improve the estimation precision, distance values converted from measured RSSIs and used for the WCL are also compensated to alleviate the RSSI variation problem caused by physical environments. Therefore, our methods can save a number of reference nodes to be used, while localization accuracy can also be achieved. Experiments in the corridor environment using a 2.4 GHz IEEE 802.15.4 wireless sensor network with four reference nodes deployed in the test field dimension of 22 m × 9.3 m have been performed. Experimental results demonstrate that the proposed method, which requires only two reference nodes, outperforms the original WCL method with four reference nodes by 53.053%, as indicated by average localization errors. The results also reveal that the proposed method provides error distances lower than the WCL method for all test target positions, while all estimated positions fall within the corridor areas by 100%.
Water discharge and sediment flux intermittency in the fluvial Escanilla Formation, Spain: Implications for changes in stratigraphic architecture
Authors: Sharma Nikhil , Whittaker Alexander C. , Adatte Thierry , Castelltort Sébastien
Published: February 2024

Water discharge and sediment flux variations are important parameters controlling the morphodynamic behaviour of rivers. Although quantitative estimates for water discharge and sediment flux variability are well‐constrained for modern rivers, far fewer assessments of flow and sediment flux intermittency in ancient fluvial systems from the rock record are available. In this study, a relationship between water discharge, sediment flux variability and patterns of changing fluvial stratigraphic architecture in the Middle Eocene Escanilla Formation, Spain, is explored. Water discharge intermittency factor (IWF), calculated as a ratio of the total water discharge (over the averaging time period) to the instantaneous channel‐forming water discharge if sustained for the same period, ranges from 0.03 to 0.11 in the high amalgamation intervals and from 0.10 to 0.32 in the low amalgamation intervals. Similarly, the sediment flux intermittency factor (ISF) is estimated to be in the range of 0.008 to 0.01 in the high amalgamation intervals and of 0.01 to 0.03 in the low amalgamation intervals. Consequently, high amalgamation intervals were most probably deposited under more intermittent and short‐lived intense precipitation events while low amalgamation intervals were the result of less intermittent flows spread throughout the year. Overall, these estimates are consistent with values from modern ephemeral rivers typically found in arid to semi‐arid climate and is in agreement with available proxy data for the Middle Eocene climatic context of the studied alluvial system. This highlights an important connection between hydroclimate, river morphodynamics and landscape evolution, and has implications to predict river flow and sediment transport across the Earth's surface in the geological past.
An experimental study on fire ignition in collector cable in wind power generation system caused by direct lightning strike
Authors: Seki Ken‐ichi , Tsuchida Takashi , Akiba Atsushi , Tada Hiroyuki , Sekioka Shozo
Published: February 2024

A separable connector is used for the power cables and apparatuses in renewable energy systems. The shield of the collector cable is sometimes an open circuit at one end to reduce power loss due to the shield current. However, this has a disadvantage from the viewpoint of lightning protection. The semiconductive part of the separable connector is grounded for safety. The ground potential rise due to a direct lightning strike to a wind tower sometimes damages the collector cables and power apparatuses in the wind tower. Combustion in a cable is one of the most serious types of lightning‐caused damage. This paper describes an experimental study on fire ignition in a collector cable caused by a ground potential rise due to a direct lightning strike to a receptor. The mechanism leading to fire ignition is discussed based on the experimental results. This paper also proposes a countermeasure against such fire ignition.
The Molecular Structures of Lithium Trichlate, Li[Cl3CSO3]⋅2H2O, and Lithium Tribrate, Li[Br3CSO3]⋅2H2O
Authors: Mertens Alisha , Eppers Katrin , van Gerven David , Wickleder Mathias S.
Published: February 2024

Lithium trichlate, Li[Cl3CSO3] ⋅ 2H2O (triclinic,
, Z=2, a=630.29(3) pm, b=630.65(3) pm, c=1246.10(6) pm, α=100.657(2)°, β=97.813(2)°, γ=107.994(2)°) was obtained from the reaction of (H5O2)[Cl3CSO3] and LiOH in aqueous solution. Similarly, colourless single crystals of the tribrate Li[Br3CSO3] ⋅ 2H2O (triclinic,
, Z=4, a=634.65(4) pm, b=636.83(4) pm, c=2496.8(2) pm, α=83.518°, β=86.081(5)°, γ=72.061(5)°) form in the reaction of aqueous Br3CSO3H and LiOH. The acid (H5O2)[Cl3CSO3] was obtained from the chlorination of CS2, followed by oxidation of the intermediate Cl3CSCl with H2O2. The bromo derivative Br3CSO3H has been prepared by bromination of phenylsulfonate with KOBr and subsequent ion exchange of the obtained potassium salt. Both lithium compounds exhibit molecular dimers according to {Li2(X3CSO3)2/1(H2O)2/1(H2O)2/2} with the Li+ ions in tetrahedral coordination of oxygen atoms. The difference in the crystal structures result from the variation of the orientation of the dimers with respect to each other. The experimental findings for the dimers are in good agreement with DFT calculations.
Allying interfacial engineering of 2D carbon nanosheet‐, graphene‐, and graphdiyne‐based heterostructured electrocatalysts toward hydrogen evolution and overall water splitting
Authors: Mo Wuwei , Foo Joel Jie , Ong Wee‐Jun
Published: February 2024

Electrochemical hydrogen evolution reaction (HER) and overall water splitting (OWS) for renewable energy generation have recently become a highly promising and sustainable strategy to tackle energy crisis and global warming arising from our overreliance on fossil fuels. Previously, tremendous research breakthroughs have been made in 2D carbon‐based heterostructured electrocatalysts in this field. Such heterostructures are distinguished by their remarkable electrical conductivity, exposed active sites, and mechanical stability. Herein, with fundamental mechanisms of electrocatalytic OWS summarized, our review critically emphasized on state‐of‐the‐art 2D carbon nanosheet‐, graphene‐, and graphdiyne‐based heterostructured electrocatalysts in HER and OWS since 2018. Particularly, the three emerging carbonaceous substrates tend to be incorporated with metal carbides, phosphides, dichalcogenides, nitrides, oxides, nanoparticles, single atom catalysts, or layered double hydroxides. Meanwhile, fascinating structural engineering and facile synthesis strategies were also unraveled to establish the structure–activity relationship, which will enlighten future electrocatalyst developments toward ameliorated HER and OWS activities. Additionally, computational results from density functional theory simulations were highlighted as well to better comprehend the synergistic effects within the heterostructures. Finally, current stages and future recommendations of this brand‐new electrocatalyst type were concluded and discussed for advanced catalyst designs and future practical applications.
The effect of surfactant on biosolubilization of weathered coal
Authors: Tong Qian , Wang Yu , Mao Xinping , Wan Chuanyu , Wen Miao , Han Fengpeng
Published: February 2024

Weathered coal is a type of coal with barren utility value, which is exposed on the surface for a prolonged time or shallowly buried in coal seams, and the physicochemical properties of weathered coal have changed compared with high‐quality coal. China is also a country with large reserves of weathered coal, therefore, the value utilization of weathered coal has received tremendous scientific attention. Herein, the main purpose is to explore the combined effect of surfactants and microorganisms on bioconversion of weathered coal to produce humic substances. Tween‐80, Phanaerochaete chrysosporium (J1) and Trametes versicolor (J2) were selected as surfactants and engineering strains to convert weathered coal. 3D fluorescence spectra were used to analyze the species and contents of humic acids during the biosolubilization process of weathered coal. Results revealed that both J1 and J2 exhibited good performance on weathered coal biosolubilization (increasing 10% and 14% compared to the control, respectively). The intensity of weathered coal biosolubilization was significantly increased by 15% and 12% when J1 and J2 were applied in combination with Tween‐80. And the addition of Tween‐80 also distinctly reduced the molecular weight of humic substances. In summary, surfactant plays an important role in bioconversion of weathered coal, while molecular weight of humic substances was different that weathered coal biosolubilization under the co‐action of J1 and Tween‐80 increased and J2 with Tween‐80 was opposite. In short, this project might provide a new strategy for exploring the biodegradation of weathered coal.
Applying k‐nearest neighbors to time series forecasting: Two new approaches
Authors: Tajmouati Samya , Wahbi Bouazza E. L. , Bedoui Adel , Abarda Abdallah , Dakkon Mohamed
Published: February 2024

The k‐nearest neighbors algorithm is one of the prominent techniques used in classification and regression. Despite its simplicity, the k‐nearest neighbors has been successfully applied in time series forecasting. However, the selection of the number of neighbors and feature selection is a daunting task. In this paper, we introduce two methodologies for forecasting time series that we refer to as Classical Parameters Tuning in Weighted Nearest Neighbors and Fast Parameters Tuning in Weighted Nearest Neighbors. The first approach uses classical parameters tuning that compares the most recent subsequence with every possible subsequence from the past of the same length. The second approach reduces the neighbors' search set, which leads to significantly reduced grid size and hence a lower computational time. To tune the models' parameters, both methods implement an approach inspired by cross‐validation for weighted nearest neighbors. We evaluate the forecasting performance and accuracy of our models. Then, we compare them to other approaches, especially, Seasonal Autoregressive Integrated Moving Average, Holt Winters, and Exponential Smoothing State Space Model. Real data examples on retail and food services sales in the United States and milk production in the United Kingdom are analyzed to demonstrate the application and efficiency of the proposed approaches.
Interpretable corn future price forecasting with multivariate time series
Authors: Wu Binrong , Wang Zhongrui , Wang Lin
Published: February 2024

Efforts in corn future price forecasting and early warning play a vital role in guiding the high‐quality development of the agricultural economy. However, recent years have witnessed significant fluctuations in global corn future prices due to the impact of COVID‐19 and the escalating risks associated with geopolitical conflicts. Therefore, there is an urgent need for accurate and efficient methods to forecast corn future prices. To address this challenge, a novel and comprehensive framework for explainable corn future price forecasting is designed. This framework takes into account multiple factors contributing to corn price volatility, including supply and demand dynamics, policy adjustments, international market shocks, global geopolitical risks, and investor concerns within the corn market. During the data processing stage, complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) is utilized to thoroughly explore the volatility characteristics of historical corn future prices. Additionally, a convolutional neural network (CNN) is employed to extract essential forecasting information from corn news data. To enhance interpretability, a novel JADE–TFT interpretable corn future price prediction model is proposed. This model combines adaptive differential evolution with optional external archiving (JADE) to intelligently and efficiently optimize the parameters of the temporal fusion transformers (TFTs). Furthermore, in the empirical study, the introduction of a global geopolitical risk coefficient, Baidu indices such as “corn” and “corn price,” and quantized corn news text features is shown to improve the accuracy of corn future price predictions. The proposed corn future price prediction framework contributes to the healthy development of the global grain futures market, thereby fostering the growth and well‐being of enterprises involved in the grain industry.
Salvage skull base surgery after proton beam therapy for recurrent sinonasal malignancies: A retrospective study
Authors: Okada Shinichi , Mukaigawa Takashi , Goto Seiya , Hiiragi Yohei , Sato Fuyuki , Deguchi Shoichi , Ogawa Hirofumi , Onoe Tsuyoshi , Murayama Shigeyuki , Yasunaga Yoshichika , Hayashi Nakamasa
Published: February 2024

Background

This study aimed to examine treatment outcomes and postoperative complications associated with salvage skull base surgery following radical proton beam therapy (PBT).

Methods

Nine patients who underwent salvage skull base surgery following curative PBT as the initial treatment at our institution between September 2002 and May 2023 were retrospectively reviewed.

Results

The cohort comprised four males and five females with a mean age of 48.1 years. The average proton dose administered during initial therapy was 68.5 Gy (relative biological effectiveness). Among the salvage surgeries, eight were anterior skull base surgeries, and one was an anterior middle skull base surgery. No local recurrences or perioperative deaths were observed. Postoperative complications occurred in three patients (33.3%), all experiencing surgical site infections, with one also having cerebrospinal fluid leakage.

Conclusion

The study demonstrates that salvage skull base surgery after PBT effectively achieves local control and safety in patients with recurrent sinonasal malignancies.
Refining the origin of thermal water using stable isotope, hydrochemistry and GIS approaches in Jiaoxi, Taiwan
Authors: Peng Tsung‐Ren , Lee Jun‐Yi , Zhan Wen‐Jun , Liu Tsang‐Sen , Lin Yu‐Wen , Chu Tyan‐Ming , Tung Chi‐Chu , Chiang Hsieh‐Tang
Published: February 2024

Comprehending the recharge of thermal springs is crucial for preserving the water quality of such springs. However, limited groundwater well data in mountainous areas presents a challenge to determining thermal‐spring recharge areas. This study analyzes the isotopes (δ2H and δ18O) and major ions in rainwater, streamwater, mountain groundwater and thermal spring water in Jiaoxi, located near Taiwan's largest city, Taipei. The results of the isotope‐elevation relationship and GIS recharge analysis indicate that the thermal spring water originated from a remote mountain at elevations of approximately 1170–1480 m, rather than the upstream watershed. The thermal spring water was divided into two groups based on the carbonate saturation index (SI) and isotope composition: the foothill group, which had a positive SI and lower δ value, and the downstream group, which had a negative SI and higher δ value. This study improved the conceptual model of the thermal flow path by demonstrating that the recharge of thermal water is a transboundary regional flow and that the foothill thermal water does not mix with the meteoric water. The revised model also highlights the role of structural lineament trends (faults, fractures and folds) in the movement of regional flow in fractured mountain blocks.