bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA‐Targeted Complexes of Tc and Re for Biomedical Applications
Authors: Palma Elisa , Santos Joana F. , Fernandes Célia , Paulo António
Published: December 2023

Due to their favorable chemical features, Re and Tc complexes have been widely used for the development of new therapeutic agents and imaging probes to solve problems of biomedical relevance. This review provides an update of the most relevant research efforts towards the development of novel cancer theranostic agents using Re and Tc‐based compounds interacting with specific DNA structures. This includes a variety of homometallic complexes, namely those containing M(CO)3 (M=Re, Tc) moieties, that exhibit different modes of interaction with DNA, such as covalent binding, intercalation, groove binding or G‐quadruplex DNA binding. Additionally, heterometallic complexes, designed to potentiate synergistic effects of different metal centers to improve DNA‐targeting, cytotoxicity and fluorescence properties, are also reviewed. Particular attention is also given to 99mTc‐ and 188Re‐labeled oligonucleotides that have been widely explored to develop imaging and therapeutic radiopharmaceuticals through the in vivo hybridization with a specific complementary DNA or RNA target sequence to provide useful molecular tools in precision medicine for cancer diagnosis and treatment. Finally, the need for further improvement of DNA‐targeted Re and Tc‐based compounds as potential therapeutic and diagnostic agents is highlighted, and future directions are discussed.
Ultra‐high voltage gain DC–DC converter based on new interleaved switched capacitor inductor for renewable energy systems
Authors: ALgamluoli Ammar Falah , Wu Xiaohua
Published: December 2023

In this paper, introduces a DC–DC converter design based on a modified hybrid switched inductor‐switched capacitor architecture, aimed at achieving ultra‐high voltage gain in renewable energy systems (RES). The proposed converter involves adding a modified boosting conversion mode (MBM) that interleaves with the main switch to double the voltage transfer gain. Additionally, a modified switched capacitor (MSC) technique, utilizing two diodes as interleaved components, is integrated into the main and auxiliary switches to verify low voltage stress across them. In addition, modified hybrid switched inductors with capacitors (MSIC) and diodes are employed to validate ultra‐high voltage gain. The main advantages of the proposed converter are its high efficiency, low voltage stress across diodes and MOSFETs, and the utilization of low values of inductors and capacitors at high switching frequencies. In addition, the voltage stress across the inductors of the (MSIC) is reduced as the duty cycle increases. Furthermore, the current stress on the main switch is reduced when the charge of capacitor C1 becomes zero. Mathematical models for both continuous conduction mode (CCM) and discontinuous conduction mode (DCM) of the proposed converter are explored. Furthermore, a dual PI controller is designed for the proposed converter to maintain a high fixed output voltage. In addition, the PCB design and experimental testing of the proposed converter to verify the simulation and laboratory results. Specifically, the proposed converter is designed to boost up voltage (30–40 V) to a variable output voltage between 200 and 300 V at 300 W at efficiency 96.7%.
Design of non‐isolated DC‐DC converter using renewable energy source for two‐stage centralized grid connected inverters
Authors: Dhananjaya Mudadla , Anand Vishal , Singh Varsha , Pattnaik Swapnajit , Potnuru Devendra
Published: December 2023

Recent research has focused on high‐power two‐stage photovoltaic (PV) systems, particularly with the introduction of wideband gap silicon carbide (SiC) devices. A massive inductor or interleaved boost converter is utilized in a standard two‐stage system, requiring a significantly larger number of components and subsequently impacting power density. As a result, the purpose of this research is to provide a topology for a high‐power non‐isolated switched capacitor network‐integrated boost converter (SCNIBC). This architecture employs two of every switch/diode/inductor and capacitor. The suggested architecture has a triple voltage boost at 50% duty ratio, excellent efficiency, and very low inrush current. A suitable analysis is performed to determine the voltage gain, component selection, and power loss analysis. Reliability analysis is studied as per the IEC 61709‐2017 standards. A fair comparison with existing state‐of‐the‐art high‐power PV system topologies is offered. Eventually, the steady‐state experimental findings for a 2.5 kW load are confirmed. The results are also validated for a step adjustment in input voltage from 80 V to 96 V. Lastly, the grid connected operation of converter is studied with a H‐bridge inverter under unity, lagging and leading power factors.
Selective cargo sorting in stem cell‐derived small extracellular vesicles: impact on therapeutic efficacy for intervertebral disc degeneration
Authors: Liao Zhiwei , Tong Bide , Zhang Xiaoguang , Zhang Weifeng , Ke Wencan , Liang Huaizhen , Lei Ming , Hua Wenbin , Li Shuai , Song Yu , Wu Xinghuo , Yang Cao
Published: December 2023

Background

Growing evidence has suggested the role of stem cell‐derived small extracellular vesicles (sEVs) in intervertebral disc degeneration (IVDD). The cargo sorting of sEVs, particularly miRNAs, may be influenced when the donor cell is subjected to oxidative stress. Here, we discovered that miRNAs containing specific motifs are selectively sorted into intraluminal vesicles within mesenchymal stem cells (MSCs) in response to oxidative stress.

Methods

Analysis of miRNA cargoes in sEVs derived from normal MSCs (C‐sEVs) or stressed MSCs (T‐sEVs) was conducted using miRNA sequencing. Differential expressed miRNAs in sEVs and the identification of motifs were evaluated through bioinformatics analysis. Protein binding was assessed using immunofluorescent staining and immunoprecipitation analysis. Additionally, RNA pull down and RNA immunoprecipitation (RIP) immunoprecipitation were employed to determine the binding between miRNAs and proteins. The effects of C‐sEVs and T‐sEVs on IVDD were compared by detecting the expression levels of phenotypic genes in vitro or histological evaluation in vivo.

Results

The sorting process of miRNAs is mediated by the nucleocytoplasmic transport of heterogeneous nuclear ribonucleoproteins, which in turn facilitates the phosphorylation of SNAP25 and promotes the transport and secretion of sEVs. Additionally, CHMP1B plays a role in membrane repair and protects against cell ferroptosis upon oxidative stress, concurrently affecting the release of sEVs. Notably, stem cell‐derived sEVs associated with ferroptosis impair the therapeutic efficacy for IVDD. However, the application of engineered sEVs containing a specific miRNA inhibitor exhibits the potential to reinstate the therapeutic efficacy for IVDD both in vitro and in vivo.

Conclusions

Taken together, our findings shed light on the mechanism of miRNAs sorting into sEVs and offer new insights for the optimization of sEV‐based treatments during intervertebral disc regeneration. regeneration.
Hyperglycolysis in endothelial cells drives endothelial injury and microvascular alterations in peritoneal dialysis
Authors: Si Zekun , Su Wenyan , Zhou Zhuoyu , Li Jinjin , Su Cailing , Zhang Ying , Hu Zuoyu , Huang Zhijie , Zhou Hong , Cong Ansheng , Zhou Zhanmei , Cao Wei
Published: December 2023

Background

Endothelial cell (EC) dysfunction leading to microvascular alterations is a hallmark of technique failure in peritoneal dialysis (PD). However, the mechanisms underlying EC dysfunction in PD are poorly defined.

Methods

We combined RNA sequencing with metabolite set analysis to characterize the metabolic profile of peritoneal ECs from a mouse model of PD. This was combined with EC‐selective blockade of glycolysis by genetic or pharmacological inhibition of 6‐phosphofructo‐2‐kinase/fructose‐2,6‐biphosphatase 3 (PFKFB3) in vivo and in vitro. We also investigated the association between peritoneal EC glycolysis and microvascular alterations in human peritoneal samples from patients with end‐stage kidney disease (ESKD).

Results

In a mouse model of PD, peritoneal ECs had a hyperglycolytic metabolism that shunts intermediates into nucleotide synthesis. Hyperglycolytic mouse peritoneal ECs displayed a unique active phenotype with increased proliferation, permeability and inflammation. The active phenotype of mouse peritoneal ECs can be recapitulated in human umbilical venous ECs and primary human peritoneal ECs by vascular endothelial growth factor that was released from high glucose‐treated mesothelial cells. Importantly, reduction of peritoneal EC glycolysis, via endothelial deficiency of the glycolytic activator PFKFB3, inhibited PD fluid‐induced increases in peritoneal capillary density, vascular permeability and monocyte extravasation, thereby protecting the peritoneum from the development of structural and functional damages. Mechanistically, endothelial PFKFB3 deficiency induced the protective effects in part by inhibiting cell proliferation, VE‐cadherin endocytosis and monocyte‐adhesion molecule expression. Pharmacological PFKFB3 blockade induced a similar therapeutic benefit in this PD model. Human peritoneal tissue from patients with ESKD also demonstrated evidence of increased EC PFKFB3 expression associated with microvascular alterations and peritoneal dysfunction.

Conclusions

These findings reveal a critical role of glycolysis in ECs in mediating the deterioration of peritoneal function and suggest that strategies targeting glycolysis in peritoneal ECs may be of therapeutic benefit for patients undergoing PD.
The suppressive efficacy of THZ1 depends on KRAS mutation subtype and is associated with super‐enhancer activity and the PI3K/AKT/mTOR signalling in pancreatic ductal adenocarcinoma: A hypothesis‐generating study
Authors: Huang Lei , Yang Hui , Chen Kaidi , Yuan Jing , Li Jie , Dai Guanghai , Gu Mancang , Shi Yan
Published: December 2023

Background

Inhibition of CDK7, a potent transcription regulator, may bring new hope for treating pancreatic ductal adenocarcinoma (PDAC), which is featured by large genetic heterogeneity and abundant KRAS mutations. This investigation aimed at exploring the discrepant efficacies of THZ1, a small‐molecule covalent CDK7 inhibitor, on PDACs with different KRAS mutations and the underlying mechanisms.

Methods

Associations of CDK7 expression with survival by KRAS mutations were first assessed. Effects of THZ1 on PDAC by different KRAS mutations were then investigated in vitro and in vivo. Moreover, the effects of THZ1 on gene transcription and phosphorylation of RNA polymerase II (RNAPOLII) in different KRAS mutant PDACs were assessed, and the effect of THZ1 on super‐enhancer activity was evaluated using chromatin immunoprecipitation sequencing. Lastly, the effects of THZ1 on the binding of H3K27ac to PIK3CA and on the PI3K/AKT/mTOR signalling were analysed.

Results

High CDK7 expression was significantly linked to worse survival within PDAC patients carrying KRAS‐G12V mutation but not in those with KRAS‐G12D mutation. The apoptosis‐inducing effect of THZ1 was markedly stronger in KRAS‐G12V PDAC than KRAS‐G12D cancer. THZ1 significantly inhibited the growth of xenograft tumour with KRAS‐G12V mutation, and the inhibition was markedly stronger than for KRAS‐G12D tumour. In mini‐cell‐derived xenograft (CDX) models, THZ1 significantly suppressed KRAS‐G12V PDAC but not KRAS‐G12D cancer. THZ1 significantly suppressed the phosphorylation of RNAPOLII, and this effect was stronger in KRAS‐G12V PDAC (especially at ser5). KRAS‐G12V PDAC had more H3K27ac‐binding super‐enhancers, and the inhibition of THZ1 on super‐enhancer activity was also stronger in KRAS‐G12V PDAC. Furthermore, THZ1 significantly weakened the binding of H3K27ac to PIK3CA in KRAS‐G12V PDAC. THZ1 significantly suppressed the PI3K/AKT/mTOR pathway and its downstream markers, and this effect was stronger in KRAS‐G12V cells.

Conclusions

In this hypothesis‐generating study, THZ1 might selectively inhibit certain PDACs with KRAS‐G12V mutation more potently compared with some other PDACs with KRAS‐G12D mutation, which might be associated with its effect on super‐enhancer activity and the PI3K/AKT/mTOR signalling. Our findings might offer novel key clues for the precise management of PDAC and important evidence for future targeted trial design.

Highlights

THZ1 had a stronger effect on PDAC‐bearing KRAS‐G12V mutation than G12D mutation.

Suppressive effect of THZ1 on phosphorylation of RNAPOLII was stronger in KRAS‐G12V than KRAS‐G12D PDAC.

Inhibition of THZ1 on super‐enhancer activity and H3K27ac binding to PIK3CA was stronger in KRAS‐G12V PDAC.

Suppressive effect of THZ1 on PI3K/AKT/mTOR pathway was stronger in KRAS‐G12V PDAC.
The effectiveness of species distribution models in predicting local abundance depends on model grain size
Authors: Brambilla Mattia , Bazzi Gaia , Ilahiane Luca
Published: December 2023

The use of species distribution models (SDMs) to predict local abundance has been often proposed and contested. We tested whether SDMs at different spatiotemporal resolutions may predict the local density of 14 bird species of open/semi‐open habitats. SDMs were built at 1 ha and 1 km, and with long‐term versus a mix of current and long‐term climatic variables. The estimated environmental suitability was used to predict local abundance obtained by means of 275 linear transects. We tested SDM ability to predict abundance for all sampled sites versus occurrence sites, using N‐mixture models to account for imperfect detection. Then, we related the R2 of N‐mixture models to SDM traits. Fine‐grain SDMs appeared generally more robust than large‐grain ones. Considering the all‐transects models, for all species environmental suitability displayed a positive and highly significant effect at all the four combinations of spatial and temporal grains. When focusing only on occurrence transects, at the 1 km grain only one species showed a significant and positive effect. At the 1 ha grain, 62% of species models showed (over both climatic sets) a significant or nearly significant positive effect of environmental suitability on abundance. Grain was the only factor significantly affecting the model's explanatory power: 1 km grain led to lower amounts of variation explained by models. Our work re‐opens the debate about predicting abundance using SDM‐derived suitability, emphasizing the importance of grains and of spatiotemporal resolution more in general. The incorporation of local variables into SDMs at fine grains is key to predict local abundance. SDMs worked out at really fine grains, approaching the average size of territory or home range of target species, are needed to predict local abundance effectively. This may result from the fact that each single cell may represent a potential territory/home range, and hence a higher suitability over a given area means that more potential territories occur there.
1,2,3‐Triazole‐Assisted Heck Cross‐Coupling for the Synthesis of Olefinated Benzosuberene Analogues from Cedrus deodara Oil
Authors: Kumar Ashish , Yamini  , Mehara Pushkar , Sharma Poonam , Das Pralay
Published: December 2023

Herein, we have reported an effective semi‐synthetic strategy for the synthesis of a new class of triazole‐bearing alkenylated benzosuberene analogues from himachalenes, extracted from Cedrus deodara oil. A highly efficient 1,2,3‐triazole triggered Heck cross‐coupling has been developed under palladium catalyzed conditions. The 1,2,3‐triazole moiety helps significantly to activate the carbon‐halogen bond and thereby promotes the coupling product. The developed protocol endures an array of arylated as well as alkylated triazole‐substituted benzocycloheptene to achieve the corresponding products in moderate to good yields.
Analysis of homozygous allele mismatches in paternity tests with massively parallel sequencing
Authors: Ren He , Zhang Jiarong , Yang Tingting , Zhang Xiaomeng , Liu Jinding , Chen Chong , Shi Yan , Chen Ying , Jia Li , Simayijiang Halimureti , Yan Jiangwei
Published: December 2023

In paternity testing, short tandem repeats (STRs) allele mismatches are often detected. Nowadays, polymerase chain reaction‐ and capillary electrophoresis (CE)‐based STR genotyping is the most commonly used method to distinguish alleles based on their length. However, it could not detect alleles of the same size with sequence differences. Massively parallel sequencing (MPS) can determine not only allele sizes but also sequences, which could explain the causes of allele mismatches. Additionally, more types of genetic markers can be detected in a single assay, which increases the discriminatory power and facilitates the analysis of paternity tests. In this study, we analyzed 11 cases with homozygous allele mismatches from routine DNA trio paternity tests using the CE platform. Samples were sequenced using the ForenSeq DNA Signature Prep Kit and the MiSeq FGx Sequencing System. The results show that of the eight father–child mismatch cases and three mother–child mismatch cases, five cases with D5S818 and D8S1179 and one case at D13S317 were classified as non‐amplification. The other three cases and two cases could be defined as mutations. This study suggests that MPS‐based STR genotyping can provide additional information that allows more accurate interpretation of allelic mismatches in paternity testing.
Ni‐Co‐based bimetal organic framework as superior electrode material for hydrogen evolution reaction and supercapacitors
Authors: Bhardwaj Shiva , Srivastava Rishabh , Mageto Teddy , Reddy Sudhakar , Dawsey Tim , Kumar Anuj , Gupta Ram
Published: December 2023

Metal‐organic frameworks (MOFs) possess several desirable properties, including a homogeneous crystal structure, variable porosity, high surface area, and a notable adsorption affinity, making them highly promising contenders for deployment as electrode materials in supercapacitors (SCs) and water electrolyzers, which are acknowledged for the ever‐increasing demand for instantaneous energy. Herein, we report the rationally assembled Ni‐Co‐based bimetallic MOF compounds using a glutaric acid as an organic ligand and low‐temperature hydrothermal treatment that surmounts the electrocatalytic and electrochemical charge storage activity in an alkaline medium. The NiCo‐MOF surpassed the hydrogen evolution reaction (HER) among other as‐synthesized materials, exhibiting the least overpotential of 182 mV at 10 mA/cm2 of current density, showed splendid kinetics with a turnover frequency of 2.86 s−1, and higher stability after 1000 HER cycles in 1 M KOH. Furthermore, NiCo‐MOF impetuses were employed for SC application and displayed the highest specific capacitance of 978 F/g than Ni‐MOF (706 F/g) and Co‐MOF (91 F/g) at 1 A/g of current density. Theoretical studies exhibited that the optimal electronic coupling and synergistic effect due to Ni‐Co sites enhances the overall electronic properties of NiCo‐MOF. Therefore, enhancing its electrochemical performance concerning water‐splitting and charge storage. This study showcases a novel approach for producing ultrathin and flexible bimetallic MOF‐based electrode material to enrich the performance in electrocatalytic HER and SCs.
Association of prognostic nutritional index with mortalities in American adult cancer survivors: A cohort study based on NHANES, 1999–2018
Authors: Zhao Li , Shen Xia , Yang Long , Wang Pengfei , Zhang Jianfeng , Liu Ning , Xie Yan
Published: December 2023

The prognostic nutritional index (PNI) has been associated with disease progression and overall survival among cancer patients. Nonetheless, the association between PNI and mortality risk in adult cancer patients within the United States remains unexplored. This study aims to elucidate the connection between PNI and prognostic outcomes in American adult cancer patients. This cohort study derived data from the National Health and Nutrition Examination database, involving 4366 American adults diagnosed with cancer between 1999 and 2018. The nutritional status was assessed using the PNI, with higher PNI scores indicating a more favorable nutritional status. The study employed Kaplan–Meier curves and Cox proportional hazard regression to investigate the impact of PNI on various outcomes, including all‐cause mortality (ACM), cardiovascular mortality (CAM), and malignancy tumor mortality (MTM) among adult cancer patients. Furthermore, restricted cubic spline models were used to examine the potential nonlinear relationship between the variables by creating hazard ratio (HR) curves at four specific points. The median follow‐up duration was 84 months, during which 1530 (35.04%) cases of ACM occurred, including 331 (13.67%) CAM and 449 (10.45%) MTM. COX regression analysis revealed a significant inverse association between PNI and patient prognosis, with HRs of 0.95 (95% CI: 0.93–0.96, p < .001) for ACM, 0.93 (95% CI: 0.90–0.96, p < .001) for CAM, and 0.94 (95% CI: 0.91–0.97, p < .001) for MTM. Both Kaplan–Meier analyses and restricted cubic spline curves showed significant differences in mortality rates related to PNI (p < .001, nonlinear p < .001). Our study provides compelling evidence of a clear association between PNI and reduced risk of ACM, CAM, and MTM in adult cancer patients in the United States. These findings underscore the significance of incorporating PNI as a possible prognostic indicator for individuals diagnosed with cancer.
Two‐phase flow behavior in CO2 geological storage considering spatial parameter heterogeneity
Authors: Zhong Yiyan , Li Qi , Xu Liang , Wen Yiping , Hou Yunlu , Gao Wenbin
Published: December 2023

Saline aquifer rocks exhibit significant spatial randomness due to geological sedimentation processes. To address the issue of the heterogeneity of rock formations in numerical simulations, it is common practice to homogenize rock layers with similar lithologies. However, the acceptability of the errors generated during homogenized computations is a major concern and should be investigated. Therefore, to study the influence of heterogeneity at the storage site on the CO2 migration behavior, the Monte Carlo simulation–random finite element method (MCS‐RFEM) was combined with a CO2 two‐phase flow model to compare the effects of the coefficient of variation (Cv) and correlation length (λx) of random reservoir permeability fields on the migration distance and extent of CO2 storage under the same mean conditions. The results showed that higher Cv and λx values significantly reduced the CO2 migration distance while increasing the spread extent. Compared to the homogeneous model, at a λx value of 100 m, the CO2 migration distance decreased by 5.05%, while the profile sweep area increased by 6.20%. Concurrently, with increasing Cv, the area with a CO2 volume fraction higher than 0.75 decreased by 20.22%, while an increase in λx resulted in a 42.35% increase in the area with a CO2 volume fraction higher than 0.75. Therefore, reservoirs with high Cv and low λx values are more suitable for safely storing CO2. © 2023 Society of Chemical Industry and John Wiley & Sons, Ltd.
How regulatory frameworks drive differences in home‐care agencies: Results from a national multicenter cross‐sectional study in Switzerland
Authors: Möckli Nathalie , Wächter Matthias , Moffa Giusi , Simon Michael , Martins Tania , Zúñiga Franziska
Published: December 2023

Introduction

The sustainability and rising costs of the health‐care system are of concern. Although health‐care reforms impact various areas of care, there is only limited evidence on how regulations affect home‐care agencies and health‐care delivery.

Objectives

The primary aim was to explore different financial and regulatory mechanisms and how they drive differences in the organizational structures, processes, and work environment of home‐care agencies.

Design and methods

We used data from a national multicenter cross‐sectional study of Swiss home care that included a random sample of 88 home‐care agencies with a total of 3223 employees. Data was collected in 2021 through agency and personnel questionnaires including geographic characteristics, financial and regulatory mechanisms, service provision, financing, work environment, resources and time allocation, and personnel recruitment. We first conducted a cluster analysis to build agency groups with similar financial and regulatory mechanisms. We then performed Fisher's exact, ANOVA, and Kruskal–Wallis tests to determine group differences in organizational structures, processes, and work environments. Finally, we performed a lasso regression to determine which variables were predictive for the groups.

Results

Four agency groups were built, differing in view of financial and regulatory mechanisms and we found differences in the range and amount of services provided, with regard to employment conditions and cost structures.

Discussion

The most prominent differences were found between agency groups with versus agency groups without a service obligation. Financial incentives must be well aligned with the goal of achieving and maintaining financially sustainable, accessible, and high‐quality home care.
Second Fundão Dam Rupture Science Meeting: Updating the science
Authors: Smith Ross E. W. , Furley Tatiana H. , de Souza Abessa Denis M. , Medeiros Laila C. C.
Published: December 2023

The second Fundão Dam Rupture Science Meeting was held in Ouro Preto, Minas Gerais, Brazil, on 21 and 22 September 2022. A total of 100 delegates attended the meeting, which featured high-quality oral presentations and posters over the two days and lively discussions of the science presented. The meeting resulted in nine papers being published in this special series. In the discussion, it was commented that the first meeting had been more a meeting of competitive perspectives but that the second meeting featured a more collaborative sharing of knowledge. Also, there had been substantial improvement in ways to deal with the lack of pre-event data and account for other stressors in the system, and as a result, stronger conclusions regarding the recovery rates of the system were able to be made. Importantly, there was no evidence for a feasible “time bomb” of a future catastrophic release of contaminants, but it was agreed that different scenarios continue to be researched. Integr Environ Assess Manag 2024;20:70–73. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).
Diagnosing and treating acute myelopathies in dogs and cats
Authors: De Frias Joao Miguel , Fenn Joe
Published: December 2023

Background: A variety of acute spinal cord disorders (myelopathies) can occur in dogs and cats. Understanding the typical clinical presentation and examination findings of the most common acute myelopathies is the key to formulating an accurate diagnostic and treatment pathway in clinical veterinary practice.

Aim of the article: This article describes the characteristic clinical features for the most common acute myelopathies in dogs and cats, as well as outlining a diagnostic approach and important treatment considerations to achieve a successful outcome.
Update on diagnosing and managing osteoarthritis in cats
Authors: Langley‐Hobbs Sorrel
Published: December 2023

Background: It is a truth now universally acknowledged that cats suffer from osteoarthritis (OA). Osteoarthritis in cats has received a lot of attention in the past 15 years, but previously it was an infrequently recognised and poorly understood problem. As veterinarians we should be assessing cats (both old and young) for the presence of OA, and should educate owners about the treatment and management of the condition.

Aim of the article: This article aims to provide a broad overview of current diagnosis and management practices for OA in cats, outlining how to confirm an OA diagnosis, the treatment options that are available and when surgery may be required.
Design, synthesis, and histone deacetylase inhibition study of novel 4‐(2‐aminoethyl) phenol derivatives
Authors: Podili Runesh , Mishra K. M. Abha , Akkewar Ashish S. , Kumar Sanjay , Rayala V. V. S. Prasanna Kumari , Kulhari Uttam , Sahu Bidya D. , P. Radhakrishnanand , Sethi Kalyan K.
Published: December 2023

Histone deacetylases (HDACs) have been identified as promising targets for anticancer treatment. The study demonstrates virtual screening, molecular docking, and synthesis of 4‐(2‐aminoethyl) phenol derivatives as HDAC inhibitors. The virtual screening and molecular docking analysis led to the identification of 10 representative compounds, which were evaluated based on their drug‐like properties. The results demonstrated that these compounds effectively interacted with the active site pocket of HDAC 3 through π‐stacking, Zn2+ coordination, hydrogen bonding, and hydrophobic interactions with catalytic residues. Furthermore, a series of 4‐(2‐aminoethyl) phenol derivatives were synthesized, and their HDAC inhibitory activity was evaluated. Compounds 18 and 20 showed significant HDAC inhibitory activity of 64.94 ± 1.17% and 52.45 ± 1.45%, respectively, compared to the solvent control. The promising results of this study encourage further research on 4‐(2‐aminoethyl) phenol derivatives and may provide significant insight into the design of novel small molecule HDAC inhibitors to fight against target‐specific malignancies of chronic obstructive pulmonary disease and nonsmall cell lung cancer in the future.
Medical radiation exposure during gastrointestinal enteral metallic stent placement: Post hoc analysis of the REX‐GI study
Authors: Tokura Junki , Yoshio Toshiyuki , Hayashi Shiro , Yamamoto Masashi , Asai Satoshi , Yakushijin Takayuki , Ikezawa Kenji , Nagaike Koji , Takagi Tadayuki , Fujisawa Toshio , Yamada Takuya , Tsumura Hidetaka , Maetani Iruru , Hori Yasuki , Ihara Hideyuki , Matsunaga Kazuhiro , Kuwai Toshio , Ito Yukiko , Hasatani Kenkei , Komeda Yoriaki , Kurita Akira , Yamaguchi Shinjiro , Maruyama Hirotsugu , Iwashita Takuji , Takenaka Mamoru , Hosono Makoto , Nishida Tsutomu
Published: December 2023

Background and Aim

Recently, the use of various endoscopic procedures performed under X‐ray fluoroscopy guidance has increased. With the popularization of such procedures, diagnostic reference levels (DRLs) have been widely accepted as the global standard for various procedures with ionizing radiation. The Radiation Exposure from Gastrointestinal Fluoroscopic Procedures (REX‐GI) study aimed to prospectively collect actual radiation exposure (RE) data and establish DRLs in gastrointestinal endoscopy units. In this post hoc analysis of the REX‐GI study, we established DRLs for each disease site by analyzing cases of gastrointestinal enteral metallic stent placement.

Methods

The REX‐GI study was a multicenter, prospective observational study conducted to collect actual RE data during gastrointestinal enteral metallic stent placement. To establish DRL values for three disease sites, namely the esophagus, gastroduodenum, and colon, we examined fluoroscopy time (FT; min), number of X‐ray images, air kerma at the patient entrance reference point (Ka,r; mGy), and the air kerma–area product (PKA; Gy cm2) during enteral metallic stent placement.

Results

Five‐hundred and twenty‐three stenting procedures were performed. The DRL values of FT (min) and the number of X‐ray images for the esophagus/gastroduodenum/colon were 9/16/18 min and 9/15/11 min, respectively. Furthermore, the DRL values of Ka,r and PKA for each disease site were 43.3/120/124 mGy and 10.3/36.6/48.4 Gy cm2, respectively. Among the procedures, esophageal stents were significantly associated with the lowest values (P < 0.001).

Conclusion

The characteristics of RE vary according to disease site among gastrointestinal enteral metallic stent placements. Thus, it is desirable to set DRL values based on the disease site.
A REML method for the evidence‐splitting model in network meta‐analysis
Authors: Piepho Hans‐Peter , Forkman Johannes , Malik Waqas Ahmed
Published: December 2023

Checking for possible inconsistency between direct and indirect evidence is an important task in network meta‐analysis. Recently, an evidence‐splitting (ES) model has been proposed, that allows separating direct and indirect evidence in a network and hence assessing inconsistency. A salient feature of this model is that the variance for heterogeneity appears in both the mean and the variance structure. Thus, full maximum likelihood (ML) has been proposed for estimating the parameters of this model. Maximum likelihood is known to yield biased variance component estimates in linear mixed models, and this problem is expected to also affect the ES model. The purpose of the present paper, therefore, is to propose a method based on residual (or restricted) maximum likelihood (REML). Our simulation shows that this new method is quite competitive to methods based on full ML in terms of bias and mean squared error. In addition, some limitations of the ES model are discussed. While this model splits direct and indirect evidence, it is not a plausible model for the cause of inconsistency.
Oxygen Delivery Biomaterials in Wound Healing Applications
Authors: Bayraktar Sema , Üstün Cansu , Kehr Nermin Seda
Published: December 2023

Oxygen (O2) delivery biomaterials have attracted great interest in the treatment of chronic wounds due to their potential applications in local and continuous O2 generation and delivery, improving cell viability until vascularization occurs, promoting structural growth of new blood vessels, simulating collagen synthesis, killing bacteria and reducing hypoxia‐induced tissue damage. Therefore, different types of O2 delivery biomaterials including thin polymer films, fibers, hydrogels, or nanocomposite hydrogels have been developed to provide controlled, sufficient and long‐lasting O2 to prevent hypoxia and maintain cell viability until the engineered tissue is vascularized by the host system. These biomaterials are made by various approaches, such as encapsulating O2 releasing molecules into hydrogels, polymer microspheres and 3D printed hydrogel scaffolds and adsorbing O2 carrying reagents into polymer films of fibers. In this article, different O2 generating sources such as solid inorganic peroxides, liquid peroxides, and photosynthetic microalgae, and O2 carrying perfluorocarbons and hemoglobin are presented and the applications of O2 delivery biomaterials in promoting wound healing are discussed. Furthermore, challenges encountered and future perspectives are highlighted.
A novel missense variant in OTUD5 causes X‐linked multiple congenital anomalies‐neurodevelopmental syndrome
Authors: Tian Weifang , Li Haiyu , Li Ying , Guo Jing , Wang Handuo , Yang Bo , Li Pengyun , Cui Xueyin , Liu Ling
Published: December 2023

Background

The OTUD5 gene encodes a deubiquitinating enzyme (DUB) of the OTU family. Variants of OTUD5 are associated with X‐linked multiple congenital anomalies‐neurodevelopmental syndrome (MCAND). The case described in this study expands the clinical and molecular spectrum of OTUD5.

Methods

Trio‐based clinical exome sequencing (trio‐CES) was performed on a Chinese boy with a clinical phenotype and both of his parents. Sanger sequencing was employed for validation of the variant detected.

Results

The patient presented with characteristic facial features, intellectual disability, motor/language/cognitive, and global developmental delays, limb contractures, and kidney abnormalities, and trio‐CES identified a de novo missense variant, c.1305T>A, of the OTUD5 gene.

Discussion

We describe OTUD5 gene variation in the Chinese population, with the first report of this variant. Additionally, we provide a comprehensive summary of all published cases of MCAND to date, in order to elucidate the primary clinical features of the syndrome and the variability in phenotype severity. This case expands the genetic and clinical phenotypic spectrum of OTUD5‐associated MCAND.
The Ablation of Sensory Neurons Expressing the Nav1.8 Sodium Channel Improves Glucose Homeostasis and Amplifies the GLP‐1 Signaling in Obese Female Mice
Authors: Romaní‐Pérez Marina , Bullich‐Vilarrubias Clara , López‐Almela Inmaculada , Sanz Yolanda
Published: December 2023

Scope

Sensory neurons expressing the sodium channel Nav1.8 contain a repertoire of receptors for nutrient, hormonal, and inflammatory ligands. However, their function in key regulators of energy homeostasis control is not well understood and is completely unexplored in females.

Methods and results

Mice lacking neurons expressing the sodium channel Nav1.8 were generated using an ablation strategy based on cre recombinase‐mediated expression of diphtheria toxin fragment A (DTA) (Nav1.8‐cre/DTA mice) to investigate whether these neurons modulate body weight, food intake, gut hormone secretion, gastrointestinal transit, and glucose tolerance in response to nutrient challenges in a sex‐dependent manner. Male Nav1.8‐cre/DTA mice show resistance to gain weight in response to high‐fat high‐sugar diet (HFHSD), whereas females lacking Nav1.8+ neurons have improved oral glucose tolerance accompanied by higher insulin levels and attenuated glucagon secretion after an oral glucose load. Female Nav1.8‐cre/DTA mice also show higher fasting and postprandial glucagon like peptide‐1 (GLP‐1) levels with an increased number of GLP‐1‐positive cells. Finally, ablation of Nav1.8‐expressing neurons accelerates the gastrointestinal transit in female mice under HFHSD.

Conclusion

This data demonstrates sex‐dependent differences in the Nav1.8‐mediated regulation of energy metabolism, and provides new insights that may help in the design of sex‐specific neuromodulation therapies for metabolic disorders induced by diets rich in fats and simple sugars.
Egg Yolk Lipids Alleviated Dextran Sulfate Sodium‐Induced Colitis by Inhibiting NLRP3 Inflammasome and Regulating Gut Microbiota
Authors: Xiao Nanhai , He Wen , Chen Shuping , Yao Yao , Wu Na , Xu Mingsheng , Du Huaying , Zhao Yan , Tu Yonggang
Published: December 2023

The increasing incidence of inflammatory bowel disease (IBD) has become a global phenomenon. Egg yolk lipids are one of the essential dietary foods, but its effects on intestinal immunity remain unclear. Here, egg yolk lipids are obtained using ethanol extraction and a total of 601 kinds of lipids are detected via lipidomics, including 251 kinds of triglycerides, 133 kinds of phosphatidylcholines, 44 kinds of phosphatidylethanolamines. Then, the study finds that egg yolk lipids significantly alleviate dextran sulfate sodium‐induced colitis and reduce the production of inflammatory factors. Meanwhile, egg yolk lipids also maintain intestinal barrier integrity and decrease lipopolysaccharide translocation by alleviating intestinal structure damage and increasing the numbers of goblet cells and mucin 2. Mechanistically, egg yolk lipids attenuate colitis by inhibiting the assembly and activation of NLRP3 inflammasome. Moreover, the study also finds that egg yolk lipids reverse gut microbiota dysbiosis referring to increased relative abundance of Bacteroides acidifaciens and decrease relative abundance of Akkermansia muciniphila, as well as increased short chain fatty acids concentration in the gut. Together, the study elucidates the anti‐colitis effect of egg yolk lipids and provides positive evidences for egg yolk lipids involving in dietary strategy and IBD therapy.
Rickets and the industrial revolution in France: The example of Provence
Authors: Perrin Marie , Schmitt Aurore , Ardagna Yann
Published: December 2023

This article aims to estimate the prevalence of rickets and its development during the Industrial Revolution in southeastern France through the study of a large skeletal collection from two recently excavated sites in La Ciotat and Marseille. In total, 790 individuals were selected based on their state of preservation: 556 adults and 234 nonadults. All individuals were systematically examined for macroscopic paleopathological evidence of rickets, based on 13 features indicative of vitamin D deficiency. Rickets was rare in our population, with only 3% of the sample showing signs of the disease. Individuals who died during childhood were more likely to present lesions associated with rickets: 7.7% of the nonadult population show signs of rickets against 1.1% of the adult one (Fisher's exact test: p < 0.001). Moreover, these lesions generally indicated early stages with mechanical bowing of long bones being particularly rare, unlike metaphyseal deformities. Far from the expected increase described by medico‐historical literature, incidence was low and showed no change from the 16th to the 20th century. Furthermore, an increase in residual cases in adults results suggest better survival of vitamin D deficiency, which could reflect better handling of the disease. This is the first study dealing with rickets during the Industrial Revolution in France, and based on osteological material, forthcoming analyses should now focus on the incorporation of radiographic and microscopic criteria to further validate our cases and working hypotheses. Additionally, future research could benefit from the inclusion of a broader sample of individuals from early and late modern contexts, but also from the consideration of local medieval contexts providing a detailed overview that could highlight secular changes over a long period.
Vocal Cord Leukoplakia Classification Using Siamese Network Under Small Samples of White Light Endoscopy Images
Authors: You Zhenzhen , Han Botao , Shi Zhenghao , Zhao Minghua , Du Shuangli , Liu Haiqin , Hei Xinhong , Ren Xiaoyong , Yan Yan
Published: December 2023

Objective

Accurate vocal cord leukoplakia classification is instructive for clinical diagnosis and surgical treatment. This article introduces a reliable very deep Siamese network for accurate vocal cord leukoplakia classification.

Study Design

A study of a classification network based on a retrospective database.

Setting

Academic university and hospital.

Methods

The white light image datasets of vocal cord leukoplakia used in this article were classified into 6 classes: normal tissues, inflammatory keratosis, mild dysplasia, moderate dysplasia, severe dysplasia, and squamous cell carcinoma. The classification performance was assessed by comparing it with 6 classical deep learning models, including AlexNet, VGG Net, Google Inception, ResNet, DenseNet, and Vision Transformer.

Results

Experiments show the superior classification performance of our proposed network compared to state‐of‐the‐art methods. The overall accuracy is 0.9756. The values of sensitivity and specificity are very high as well. The confusion matrix provides information for the 6‐class classification task and demonstrates the superiority of our proposed network.

Conclusion

Our very deep Siamese network can provide accurate classification results of vocal cord leukoplakia, which facilitates early detection, clinical diagnosis, and surgical treatment. The excellent performance obtained in white light images can reduce the cost for patients, especially those living in developing countries.
Outcomes for 160 Consecutive Lateral Arm Free Flaps for Head and Neck Reconstruction
Authors: Contrera Kevin J. , Hassan Abbas M. , Shuck John W. , Bobian Michael , Ha Austin Y. , Chang Edward I. , Garvey Patrick B. , Roubaud Margaret S. , Lee Z‐Hye , Hanasono Mathew M. , Gross Neil D. , Myers Jeffrey N. , Yu Peirong , Largo Rene D.
Published: December 2023

Objective

Examine outcomes for lateral arm autologous tissue transfer in head and neck reconstruction.

Study Design

Retrospective cohort study.

Setting

Tertiary cancer center.

Methods

All patients who underwent traditional lateral arm, extended lateral arm, and lateral forearm flaps for head and neck reconstruction from 2012 to 2022 were assessed. Disabilities of the arm, shoulder, and hand (DASH) was measured. Factors associated with complications and enteral or mixed diet were evaluated by multivariable regression.

Results

Among 160 patients followed for a median of 2.3 ± 2.1 years, defects were 54% oral tongue, 18% external, 9% maxilla, 8% buccal mucosa, 9% floor of mouth, and 3% pharynx. Flap types (and median pedicle lengths) were 41% traditional lateral arm (8 cm), 25% extended lateral arm (11.5 cm), and 34% lateral forearm (14 cm). All donor sites were closed primarily; 19.6% and 0% of patients had increased DASH scores 2 and 12 weeks after reconstruction. Major complications occurred in 18.1% of patients, including 6.3% reoperation, 6.9% readmission, 3.7% fistula, and 1.8% flap loss. Complications were independently associated with peripheral vascular disease (odds ratio [OR]: 5.71, 95% confidence interval [CI]: 1.5‐21.6, P = .01), pharyngeal defects (OR: 11.3, 95% CI: 1.4‐94.5, P = .025), and interposition vein grafts (OR: 3.78, 95% CI: 1.1‐13.3, P = .037).

Conclusion

The lateral arm free flap was safe, versatile, and reliable for head and neck reconstruction with low donor‐site morbidity. Complications occurred in a fifth of patients and were associated with peripheral vascular disease, pharyngeal defects, and vein grafts.
Doxorubicin/poly(caprolactone)/polyethylene glycol nanoparticles prepared by electrospray
Authors: Mehrazin Mehdi , Asefnejad Azadeh , Naeimi Farid , Khonakdar Hossein Ali
Published: December 2023

The development of sustainable drug delivery systems is very important in the field of pharmaceutical research and has many advantages over the usual methods of drug administration, including improving effectiveness, reducing side effects, and increasing patient compliance. Among various techniques, electrospraying as a voltage‐driven process has emerged as a promising technology for the fabrication of drug‐loaded nanoparticles. In recent years, the application of electrospray approach for drug release has been widely investigated. However, optimization of electrospray process parameters and development of mathematical models to predict drug release kinetics from microparticles are still challenging. To address these issues, a combination of Central Composite Design (CCD) and Response Surface Methodology (RSM) has been used. This paper focuses on the application of CCD‐RSM for modeling and optimization of doxorubicin (DOX)‐poly(caprolactone) (PCL)‐polyethylene glycol (PEG) microparticles prepared using electrospray method. Doxorubicin, a widely used anticancer drug, exhibits potent cytotoxicity against a wide range of cancers. PCL‐PEG microparticles are promising as drug carriers due to their biocompatibility, controlled release properties, and ability to protect the encapsulated drug from degradation. The CCD‐RSM approach allows systematic investigation and optimization of several formulation and process variables, including polymer concentration, PCL‐PEG weight ratio, and applied voltage on drug release behavior. In addition, the effect of rheology and electrical conductivity of polymer fluid on the size of particles obtained from electrospraying was investigated. The effect of adding folic acid and doxorubicin in the optimized sample of nanoparticles and the effect of different concentrations of doxorubicin were investigated, and SEM, DLS, and FTIR techniques were used to characterize the microparticles, and the MMT test was performed to evaluate their cytotoxicity. The results showed that the optimized formulation is effective for sustained drug release over a long period for drug delivery applications.