bluuebunny/crossref_metadata_2025 huggingface dataset:
ICAM-1 nanoclusters regulate hepatic epithelial cell polarity by leukocyte adhesion-independent control of apical actomyosin
Authors: Cacho-Navas Cristina , López-Pujante Carmen , Reglero-Real Natalia , Colás-Algora Natalia , Cuervo Ana , Conesa José Javier , Barroso Susana , Rivas Gema de , Ciordia Sergio , Paradela Alberto , D’Agostino Gianluca , Manzo Carlo , Feito Jorge , Andrés Germán , Molina-Jiménez Francisca , Majano Pedro , Correas Isabel , Carazo Jose María , Nourshargh Sussan , Huch Meritxell , Millán Jaime
Published: July 2023

Epithelial Intercellular Adhesion Molecule (ICAM)-1 is apically polarized, interacts with and guides leukocytes across epithelial barriers. Polarized hepatic epithelia organize their apical membrane domain into bile canaliculi and ducts, which are not accessible to circulating immune cells but that nevertheless confine most of ICAM-1. Here, by analyzing ICAM-1_KO human hepatic cells, liver organoids from ICAM-1_KO mice and rescue-of-function experiments, we show that ICAM-1 regulates epithelial apicobasal polarity in a leukocyte adhesion-independent manner. ICAM-1 signals to an actomyosin network at the base of canalicular microvilli, thereby controlling the dynamics and size of bile canalicular-like structures (BCs). We identified the scaffolding protein EBP50/NHERF1/SLC9A3R1, which connects membrane proteins with the underlying actin cytoskeleton, in the proximity interactome of ICAM-1. EBP50 and ICAM-1 form nano-scale domains that overlap in microvilli, from which ICAM-1 regulates EBP50 nano-organization. Indeed, EBP50 expression is required for ICAM-1-mediated control of BC morphogenesis and actomyosin. Our findings indicate that ICAM-1 regulates the dynamics of epithelial apical membrane domains beyond its role as a heterotypic cell-cell adhesion molecule and reveal potential therapeutic strategies for preserving epithelial architecture during inflammatory stress.
An application on forecasting for stock market prices: hybrid of some metaheuristic algorithms with multivariate adaptive regression splines
Authors: Sabancı Dilek , Kılıçarslan Serhat , Adem Kemal
Published: July 2023

Purpose

Borsa Istanbul 100 Index, known as BIST100, is the main indicator to measure the performance of the 100 highest stocks publicly traded in Borsa Istanbul concerning market and trading volume. BIST 100 index prediction is a popular research domain for its complex data structure caused by stock price, commodity, interest rate and exchange rate effects. The study proposed hybrid models using both Genetic, Particle Swarm Optimization, Harmony Search and Greedy algorithms from metaheuristic algorithms approach for dimension reduction, and MARS for prediction.

Design/methodology/approach

This paper aims to model in the simplest way through metaheuristic algorithms hybridized with the MARS model the effects of stock, commodity, interest and exchange rate variables on BIST 100 during the Covid-19 pandemic period (in the process of closing) between January 2020 and June 2021.

Findings

The most suitable hybrid model was chosen as PSO & MARS by calculating the RMSE, MSE, GCV, MAE, MAD, MAPE and R2 measurements of training, test and overall dataset to check every model's efficiency. Empirical results demonstrated that the proposed PSO & MARS hybrid modeling procedure gave results both as good as the MARS model and a simpler and non-complex model structure.

Originality/value

Using metaheuristic algorithms as a supporting tool for variable selection can help to identify important independent variables and contribute to the establishment of more non-complex models.ing, test and overall dataset to check every model's efficiency.
Awareness of children's developmental problems and sharing of concerns with parents by preschool teachers and childcare workers: The Japanese context
Authors: Honda Hideo , Sasayama Daimei , Niimi Taemi , Shimizu Ayako , Toibana Yuki , Kuge Rie , Takagi Hidetoshi , Nakajima Aya , Sakatsume Reiko , Takahashi Michiko , Heda Takuma , Nitto Yukari , Tsukada Shota , Nishigaki Akiko
Published: July 2023

Background

This study aims to determine the extent to which preschool teachers and childcare workers are aware of the presence of developmental problems among children and to what extent they share information with parents about their concerns regarding a child's development or diagnosis of neurodevelopmental disorders (NDDs).

Methods

We wrote to all 924 preschools and childcare centres in Japan's Nagano and Yamanashi prefectures to request participants. We then sent survey forms to the preschools and childcare centres that agreed to cooperate for three grades comprising 3‐, 4‐ and 5‐year‐olds in the school year 2020. We asked the staff member in charge of each child to complete the survey. The survey included questions about the teacher's concerns regarding the possibility of an NDD and whether the matter had been shared with the children's parents.

Results

We obtained data for 10 354 children from 206 preschools and childcare centres (response rate = 22.3%). Among these children, 457 (4.4%) had an NDD diagnosis that their parents shared with the teachers. However, the teachers of 1274 children (12.3%) had concerns regarding their development but were not informed by the parents about the diagnosis, if any. These 1274 children included 775 (60.8%) cases where the teachers failed to share their concerns with parents because (1) the teachers could not communicate with parents (n = 119), (2) the teachers were not sure if there was a neurodevelopmental problem (n = 360) and (3) the parents were not aware of the problem (n = 296).

Conclusions

Preschool teachers and childcare workers had concerns about the development of a substantial proportion of children in their charge. However, teachers and childcare workers did not share their concerns regarding many children's developmental problems with their parents. The findings suggest that there are challenges in information‐sharing between teachers/childcare workers and parents.
Influence of abutment shape on peri‐implant tissue conditions: A randomized clinical trial
Authors: Bernabeu‐Mira Juan Carlos , Peñarrocha‐Diago María , Viña‐Almunia José , Romero‐Gavilán Francisco , Pérez‐Sayans Mario , Peñarrocha‐Oltra David
Published: July 2023

Objective

To analyze the influence of 3‐mm high abutments with different shapes (cylindrical abutment vs. wide abutment) on marginal bone‐level changes (bone loss and bone remodeling). The influence of abutment shape on implant success, probing pocket depth (PPD), and bleeding on probing (BoP) was studied as secondary objectives.

Materials and Methods

Patients with a partially edentulous area requiring fixed dental prostheses by two implants in the posterior mandible or maxilla were included. The implants were 1 mm subcrestally placed, and osseointegration healing was submerged. Three‐mm high abutments with two different shapes were randomly placed in second‐stage surgery: cylindrical abutments (cylindrical group) and wide abutments (wide group). Marginal bone‐level changes were measured using parallelized periapical radiographs at abutment placement, at definitive prosthesis placement, and at 1, 3, 6, and 12 months after loading. PPD and BoP were likewise measured at the control visits.

Results

Sixty‐four dental implants in 25 patients were included. Statistically significant differences were found in bone‐level changes. The cylindrical group exhibited less mean marginal bone remodeling (MBR) and marginal bone loss (MBL) than the wide group (p < .05). Moreover, the cylindrical group showed significantly less BoP (p < .05).

Conclusion

Abutment shape had a significant influence upon marginal bone‐level changes during the first 12 months. Cylindrical abutments caused less MBR and MBL than wide abutments. More clinical studies involving longer follow‐ups and analyzing other abutment modifications are needed to improve our understanding of how abutments can affect peri‐implant tissue stability.
Evaluation of finite high cycle fatigue life of hard steels using the elliptical curve method
Authors: Castro Tiago Lima , Araujo Lucas Carneiro , Pereira Marcos Venicius , Darwish Fathi Aref , da Silva Gabriel Araujo , Araújo José Alexander
Published: July 2023

A direct relation where fatigue life
can be determined as a function of macroscopic normal and shear stress amplitudes
and
is established. Using the Carpinteri & Spagnoli (C&S) criterion as a survey tool, elliptical‐level curves in the
domain were revealed and further generalized, providing means to determine
for any given
combination. Predictions obtained through the elliptical curve method (E) were compared with experimental observations, as well as with predictions obtained from adapted versions of popular fatigue criteria, namely, Findley (F), Matake (M), McDiarmid (McD), Susmel & Lazzarin (S&L), C&S, and Papadopoulos (P). The proposed model delivered predictions in fair agreement with experimental observations, and its predictive capability was seen to be the best among all the considered criteria. Finally, a slight bias toward conservativeness was attenuated with the introduction of an adjusting parameter, further improving the predictive capability of the model.
Notes from the taxonomic disaster zone: Evolutionary drivers of intractable species boundaries in an Australian lizard clade (Scincidae: Ctenotus)
Authors: Prates Ivan , Hutchinson Mark N. , Singhal Sonal , Moritz Craig , Rabosky Daniel L.
Published: July 2023

Genomic‐scale datasets, sophisticated analytical techniques, and conceptual advances have disproportionately failed to resolve species boundaries in some groups relative to others. To understand the processes that underlie taxonomic intractability, we dissect the speciation history of an Australian lizard clade that arguably represents a “worst‐case” scenario for species delimitation within vertebrates: the Ctenotus inornatus species group, a clade beset with decoupled genetic and phenotypic breaks, uncertain geographic ranges, and parallelism in purportedly diagnostic morphological characters. We sampled hundreds of localities to generate a genomic perspective on population divergence, structure, and admixture. Our results revealed rampant paraphyly of nominate taxa in the group, with lineages that are either morphologically cryptic or polytypic. Isolation‐by‐distance patterns reflect spatially continuous differentiation among certain pairs of putative species, yet genetic and geographic distances are decoupled in other pairs. Comparisons of mitochondrial and nuclear gene trees, tests of nuclear introgression, and historical demographic modelling identified gene flow between divergent candidate species. Levels of admixture are decoupled from phylogenetic relatedness; gene flow is often higher between sympatric species than between parapatric populations of the same species. Such idiosyncratic patterns of introgression contribute to species boundaries that are fuzzy while also varying in fuzziness. Our results suggest that “taxonomic disaster zones” like the C. inornatus species group result from spatial variation in the porosity of species boundaries and the resulting patterns of genetic and phenotypic variation. This study raises questions about the origin and persistence of hybridizing species and highlights the unique insights provided by taxa that have long eluded straightforward taxonomic categorization.
Deformation Decomposition Versus Energy Decomposition for Chemo- and Poro-Mechanics
Authors: Chua Janel , Karimi Mina , Kozlowski Patrick , Massoudi Mehrdad , Narasimhachary Santosh , Kadau Kai , Gazonas George , Dayal Kaushik
Published: July 2023

We briefly compare the structure of two classes of popular models used to describe poro-mechanics and chemo-mechanics, wherein a fluid phase is transported within a solid phase. The multiplicative deformation decomposition has been successfully used to model permanent inelastic shape change in plasticity, solid–solid phase transformation, and thermal expansion, which has motivated its application to poro-mechanics and chemo-mechanics. However, the energetic decomposition provides a more transparent structure and advantages, such as to couple to phase-field fracture, for models of poro-mechanics and chemo-mechanics.
High Precision Trajectory Learning Method Based Improved Dynamic Movement Primitives for Robot Skill Learning
Authors: Zhai Bin , Zhang Enzheng , Li Bingchen , Fang Xiujun
Published: July 2023

In robot skill learning, the higher accuracy of trajectory reproduction, the smaller difference between the trajectory reproduced by the robot and the expected trajectory, and the higher accuracy and reliability of the robot’s task execution. In robot skill learning methods based on dynamic movement primitives, the problems are found that the tail exponential decay of Gaussian kernel function and the number of shape parameters have a great influence on the accuracy of trajectory reproduction, a high precision trajectory learning method is proposed. A novel truncation processing method is proposed to eliminate the impact of tail exponential decay, and the optimization on the number of shape parameters is used to improve the approximation of the local gradient of the target forcing term, which are combined to improve trajectory reproduction accuracy. The principle of the proposed method is described in detail. The simulation and comparison experiments are performed to verify the effectiveness of the proposed method in improving trajectory reproduction accuracy. This paper makes contributions to the field of robot skill trajectory learning and provides a promising method for improving trajectory reproduction accuracy.
Regularities of Hydrochemical Dynamics in a Two-Dimensional Turbulent Flow of Natural Water
Authors: Danilov-Danilyan V. I. , Rosenthal O. M.
Published: July 2023

Variations in the composition and properties of natural waters, which creates numerous difficulties in water use, cannot always be explained by the influence of external forcing such as weathering or leaching of rocks, changes in the phases of the water regime, and other causes. This is especially true for sub-daily and sub-hourly variations in the water quality, which can be caused by complex, previously unknown dynamic hydrochemical processes. Such a conclusion follows from study of the turbidity and pH of natural water measured with increased frequency, the results of which are presented in this work. These results provide evidence about the existence of quasi-cyclic variations in the controlled parameters with different periods, from minute to daily. Study of the observational data allows us to assume that in this case the hydrochemical dynamics is caused by direct and reverse energy cascades in a two-dimensional turbulent flow of natural water, in which the impurity subsystem may be stratified.
A periodic corrugated metallic nanomesh for broadband light absorption enhancement
Authors: Zhang Hai-Jing , Yan Qi , Li Ying-Yuan , Zhang Tian-Run , Zhang Xu-Lin , Wang Yan-Hui , Liu Yue-Feng
Published: July 2023

Plasmonic nanostructures have been demonstrated for their application in thin film solar cells to enhance absorption. Of particular concern is the novel design, enabling the broadband absorption enhancement. Here, we proposed and implemented a periodic corrugated Au nanomesh for broadband light absorption enhancement. By combining plasmon treatment of pre-stretched substrate and nanosphere lithography, the Au nanomesh on the nanocorrugation with different period has been realized. Compared to the planar nanomesh, the periodic corrugated nanomesh exhibits observable absorption enhancement at broad wavelength range, especially from 700[Formula: see text]nm to 1000[Formula: see text]nm, which is of significance in bring solar energy up to more utilization due to poor absorption of thin film solar cells at the near-infrared band. The enhancement attributes to the spatially geometry deformation of nanomesh supported more plasmonic resonance at the different adjacent frequency. Also, the absorption enhancement is relative to the period of corrugation, which caused by the variation of geometry deformation amplitude of nanomesh. This periodic corrugated metallic nanomesh provides an alternative nanostructured electrode to broadband absorption enhancement for thin film solar cell application.
Metamorphic P–T–t evolution deciphered from episodic monazite growth in granulites of the Chencai Complex and implications for the Early Paleozoic Orogeny, West Cathaysia terrane, South China
Authors: Xia Yanfei , Wang Lijun , Rayner Nicole , Lin Shoufa , Xiao Wenjiao , Yin Changqing , Qian Jiahui , Liu Huan , Zhao Xilin
Published: July 2023

The Early Paleozoic Orogeny in eastern South China has been highly controversial. It has been alternatively interpreted to have formed in an intra-plate setting driven by far-field tectonic forces or at plate boundaries involving subduction–collision. The West Cathaysia terrane in the core of the orogen is characterized by extensive magmatism, intense deformation and especially high-grade metamorphism. Identifying early Paleozoic high-pressure (HP) metamorphism and establishing a complete P–T–t path from the high-grade metamorphic rocks could help us understand the tectono-thermal evolution process and nature of the Early Paleozoic Orogeny. Here, we present results from a felsic granulite from the Chencai Complex in the northeastern West Cathaysia terrane. Petrographic evidence, mineral compositions and phase equilibria modelling indicate that the granulite underwent a pre-peak HP stage with P–T conditions of 13.3–14.7 kbar/696–718°C and low geothermal gradients of 13–14°C km
−1
, and a peak high-temperature stage with P–T conditions of 9.7–11.0 kbar/785–820°C. A clockwise P–T path involving pre-peak decompressional heating, post-peak near-isothermal decompression and near-isobaric cooling processes was constrained for the HP felsic granulite.
In situ
monazite U–Pb geochronology combined with previous results date these metamorphic processes at
c.
440,
c.
425 and
c.
400 Ma, respectively. Our new metamorphic and geochronological data from the HP felsic granulite support the case that the Early Paleozoic Orogeny was a typical collisional one.
An Improved Tuning of PID Controller for PV Battery-Powered Brushless DC Motor Speed Regulation Using Hybrid Horse Herd Particle Swarm Optimization
Authors: RamaKrishnan A. , Shunmugalatha A. , Premkumar K.
Published: July 2023

In this study, speed control of PV battery-powered brushless DC motor (BLDC) is controlled by novel hybrid horse herd particle swarm optimization- (HHHPSO-) tuned proportional integral derivative (PID) controller. The optimal gain parameter of the PID controller is tuned by hybrid horse herd optimization algorithm. The purpose of the newly developed HHHPSO algorithm is to enhance the performance of the classic horse herd algorithm (HHA), specifically in two different ways. In the first place, it bolsters HHA’s aptitude for exploratory learning related to the ageing issue. By doing so, it is possible to circumvent the phenomenon of the local minimum stagnation. Second, it permits HHA to have a superior capability of exploitation with the assistance of hybridization through the utilisation of particle swarm optimization. This hybrid technique helps improve the rate convergences of the HHA method. The time domain-based performance indices were considered as an objective function such as addition of integral of squared speed error, integral of squared current error, and integral of squared electromagnetic torque error for finding the optimal gain values for the PID controller using HHHPSO. The proposed HHHPSO-tuned PID controller for PV battery-powered BLDC motor is tested for various working conditions such as constant speed conditions, varying speed conditions, and varying load conditions and also compared with state-of-the-art method. The proposed method has quick rise time around 20-21 msec, quick settling time around 35-39 msec, zero steady-state error, and zero overshoot than state-of-the-art optimization method. The proposed control techniques were also tested in hardware to confirm the suitability for real-time applications.
GTP Cyclohydrolase Drives Breast Cancer Development and Promotes EMT in an Enzyme-Independent Manner
Authors: Wang Zijing , Zhang Nan , Zhang Miao , Jiang Yao , Ng Aik Seng , Bridges Esther , Zhang Wei , Zeng Xin , Luo Qi , Liang Jiabien , Győrffy Balázs , Hublitz Philip , Liang Zhu , Fischer Roman , Kerr David , Harris Adrian L. , Cai Shijie
Published: July 2023

GTP cyclohydrolase (GCH1) is the rate-limiting enzyme for tetrahydrobiopterin (BH4) biosynthesis. The catalysis of BH4 biosynthesis is tightly regulated for physiological neurotransmission, inflammation, and vascular tone. Paradoxically, BH4 has emerged as an oncometabolite regulating tumor growth, but the effects on tumor development remain controversial. Here, we found that GCH1 potentiated the growth of triple-negative breast cancer (TNBC) and HER2+ breast cancer and transformed nontumor breast epithelial cells. Independent of BH4 production, GCH1 protein induced epithelial-to-mesenchymal transition by binding to vimentin (Vim), which was mediated by HSP90. Conversely, GCH1 ablation impaired tumor growth, suppressed Vim in TNBC, and inhibited EGFR/ERK signaling while activating the p53 pathway in estrogen receptor–positive tumor cells. GCH1 deficiency increases tumor cell sensitivity to HSP90 inhibition and endocrine treatments. In addition, high GCH1 correlated with poor breast cancer survival. Together, this study reveals an enzyme-independent oncogenic role of GCH1, presenting it as a potential target for therapeutic development.

Significance:

GTP cyclohydrolase functions as an oncogene in breast cancer and binds vimentin to induce epithelial-to-mesenchymal transition independently of its enzyme activity, which confers targetable vulnerabilities for developing breast cancer treatment strategies.
Oncogenic Drivers and Therapeutic Vulnerabilities in KRAS Wild-Type Pancreatic Cancer
Authors: Singh Harshabad , Keller Rachel B. , Kapner Kevin S. , Dilly Julien , Raghavan Srivatsan , Yuan Chen , Cohen Elizabeth F. , Tolstorukov Michael , Andrews Elizabeth , Brais Lauren K. , da Silva Annacarolina , Perez Kimberly , Rubinson Douglas A. , Surana Rishi , Giannakis Marios , Ng Kimmie , Clancy Thomas E. , Yurgelun Matthew B. , Schlechter Benjamin L. , Clark Jeffrey W. , Shapiro Geoffrey I. , Rosenthal Michael H. , Hornick Jason L. , Nardi Valentina , Li Yvonne Y. , Gupta Hersh , Cherniack Andrew D. , Meyerson Matthew , Cleary James M. , Nowak Jonathan A. , Wolpin Brian M. , Aguirre Andrew J.
Published: July 2023

Purpose:

Approximately 8% to 10% of pancreatic ductal adenocarcinomas (PDAC) do not harbor mutations in KRAS. Understanding the unique molecular and clinical features of this subset of pancreatic cancer is important to guide patient stratification for clinical trials of molecularly targeted agents.

Experimental Design:

We analyzed a single-institution cohort of 795 exocrine pancreatic cancer cases (including 785 PDAC cases) with a targeted multigene sequencing panel and identified 73 patients (9.2%) with KRAS wild-type (WT) pancreatic cancer.

Results:

Overall, 43.8% (32/73) of KRAS WT cases had evidence of an alternative driver of the MAPK pathway, including BRAF mutations and in-frame deletions and receptor tyrosine kinase fusions. Conversely, 56.2% of cases did not harbor a clear MAPK driver alteration, but 29.3% of these MAPK-negative KRAS WT cases (12/41) demonstrated activating alterations in other oncogenic drivers, such as GNAS, MYC, PIK3CA, and CTNNB1. We demonstrate potent efficacy of pan-RAF and MEK inhibition in patient-derived organoid models carrying BRAF in-frame deletions. Moreover, we demonstrate durable clinical benefit of targeted therapy in a patient harboring a KRAS WT tumor with a ROS1 fusion. Clinically, patients with KRAS WT tumors were significantly younger in age of onset (median age: 62.6 vs. 65.7 years; P = 0.037). SMAD4 mutations were associated with a particularly poor prognosis in KRAS WT cases.

Conclusions:

This study defines the genomic underpinnings of KRAS WT pancreatic cancer and highlights potential therapeutic avenues for future investigation in molecularly directed clinical trials.

See related commentary by Kato et al., p. 4527
Intratumoral IL15 Improves Efficacy of Near-Infrared Photoimmunotherapy
Authors: Fukushima Hiroshi , Furusawa Aki , Kato Takuya , Wakiyama Hiroaki , Takao Seiichiro , Okuyama Shuhei , Choyke Peter L. , Kobayashi Hisataka
Published: July 2023

IL15 is a potent inducer of differentiation and proliferation of CD8+ T and natural killer (NK) cells, making it a promising candidate for cancer immunotherapy. However, limited efficacy of systemic monotherapy utilizing intravenous IL15 suggests the needs for alternative routes of administration or combination treatment with other therapies. Near-infrared photoimmunotherapy (NIR-PIT) is a highly selective anticancer treatment that elicits a massive release of tumor antigens and immunogenic signals. Here, we investigated whether intratumoral IL15 can enhance the effectiveness of cancer cell-targeted NIR-PIT using syngeneic murine tumor models. Intratumoral injection of IL15 was more effective than intraperitoneal IL15 in vivo in suppressing tumor growth and inducing intratumoral immune responses. When the efficacy of CD44-targeted NIR-PIT was compared in vivo between IL15-secreting MC38 (hIL15-MC38) and parental MC38 tumors, the hIL15-MC38/NIR-PIT group showed the best tumor growth inhibition and survival. In addition, the hIL15-MC38/NIR-PIT group showed significant dendritic cell maturation and significant increases in the number and Granzyme B expression of tumor-infiltrating CD8+ T, NK, and natural killer T cells compared with the treated parental line. Furthermore, intratumoral IL15 injection combined with CD44-targeted NIR-PIT showed significant tumor control in MC38 and Pan02-luc tumor models. In bilateral tumor models, CD44-targeted NIR-PIT in hIL15-MC38 tumors significantly suppressed the growth of untreated MC38 tumors, suggesting abscopal effects. Mice that achieved complete response after the combination therapy completely rejected later tumor rechallenge. In conclusion, local IL15 administration synergistically improves the efficacy of cancer cell–targeted NIR-PIT probably by inducing stronger anticancer immunity, indicating its potential as an anticancer treatment strategy.
Being with Donkeys: Insights into the Valuing and Wellbeing of Donkeys in Central Ethiopia
Authors: Geiger Martha , Hockenhull Jo , Buller Henry , Engida Gebre T. , Jemal Kedir M. , Goshu L. , Getachew M. , Banerjee† A. , Burden F. A. , Whay H. R.
Published: July 2023

This paper explores the interwoven lives of donkeys and the people who depend on them for their livelihoods in central Ethiopia. Drawing on data from 12 participatory workshops, insights were elicited into the ways human co-workers value and treat their donkey co-workers. Methodologically, Participatory Rural Appraisal (PRA) and Appreciative Inquiry (AI) techniques were merged to explore the complex and multi-dimensional contributions donkeys make to participants’ lives. Findings reveal working with donkeys can make the difference between destitution and modest survival, but societal perception of donkeys as low-status animals has an impact on their owners’ lives and donkey wellbeing. This research contributes empirical insights on the valuing of donkeys and enables a deepened understanding of human-donkey relations. The combination of PRA and AI in the methodology demonstrates how to formulate a compassionate and empathetic approach for exploring donkey value and wellbeing with marginalized groups.
Effectiveness and safety of high-voltage pulsed radiofrequency to treat patients with primary trigeminal neuralgia: a multicenter, randomized, double-blind, controlled study
Authors: Jia Yitong , Cheng Hao , Shrestha Niti , Ren Hao , Zhao Chunmei , Feng Kunpeng , Luo Fang
Published: July 2023

Background

Trigeminal neuralgia (TN) is a debilitating pain disorder that still lacks an ideal treatment option. Pulsed radiofrequency (PRF), especially with high output voltage, is a novel and minimally invasive technique. PRF is regarded a promising treatment option for TN patients who respond poorly to medical treatment; however, the available evidence still lacks high quality randomized controlled trials (RCTs). Our study aimed to evaluate the long-term (1 year and 2 years) effects and safety of high-voltage PRF in primary TN patients and provide stronger evidence for TN treatment options.

Methods

We performed a multicenter, double-blind, RCT in adults (aged 18–75 years) with primary TN who responded poorly to drug therapy or were unable to tolerate the side effects of drug. Eligible participants were randomly assigned (1:1) to receive either high voltage PRF or nerve block with steroid and local anesthetic drugs. The primary endpoint was the 1-year response rate. This trial has been registered in the clinicaltrials.gov website (registration number: NCT03131466).

Results

One hundred and sixty-two patients were screened for enrollment between April 28th,2017 and September1st, 2019, among whom, 28 were excluded. One hundred and thirty-four participants were randomly assigned to either receive high voltage PRF (n = 67) or nerve block (n = 67). The proportion of patients with a positive response at 1-year after the procedure in the PRF group was significantly higher than that in the nerve block group in the intention-to-treat population (73.1% vs. 32.8%, p < 0.001). There was no difference between groups in the incidence of adverse events.

Conclusions

Our findings support that high voltage PRF could be a preferred interventional choice prior to receiving more invasive surgical treatment or neuro-destructive treatment for TN patients who have poor responses to medical treatment.

Trial registration

Our study has been registered at ClinicalTrials.gov (trial registration number: NCT03131466).
‘Maintaining balance in life’—exploring older adults’ long-term engagement in self-managed digital fall prevention exercise
Authors: Pettersson Beatrice , Lundell Sara , Lundin-Olsson Lillemor , Sandlund Marlene
Published: July 2023

Background

Accidental falls are one of the greatest threats to older adults’ health and well-being. The risk of falling can be significantly reduced with strength and balance interventions. However, there needs to be further knowledge into how older adults can be supported to achieve a maintained exercise behaviour. Therefore, the aim of this study was to explore factors that enabled older adults to maintain their exercise during a 1-year self-managed digital fall prevention exercise intervention.

Methods

This study used a grounded theory methodology. Semi-structured individual interviews were conducted by phone or conference call. Eighteen community-dwelling older adults aged 70 years or more participated. The participants had a self-reported exercise dose of 60 min or more per week during the last three months of participation in a 12-months intervention of self-managed digital fall prevention exercise, the Safe Step randomized controlled trial. Open, axial, and selective coding, along with constant comparative analysis, was used to analyze the data.

Results

The analysis resulted in a theoretical model. We found that the fall prevention exercise habits of adults were developed through three stages: Acting against threats to one’s own identity, Coordinating strategies to establish a routine, and Forming habits through cues and evaluation. The main category of Maintaining balance in life encases the participants transition through the three stages and reflects balance in both physical aspects and in between activities in daily life. The process of maintaining balance in life and desire to do so were mediated both by intrinsic person-dependent factors and the Safe Step application acting as an external mediator.

Conclusion

This study identified three stages of how older adults developed self-managed fall prevention exercise habits, supported by a digital application. The generated theoretical model can inform future interventions aiming to support long-term engagement in digitally supported and self-managed fall prevention interventions.
Histone deacetylase III interactions with BK polyomavirus large tumor antigen may affect protein stability
Authors: Hsu Yueh-Han , Chao Chun-Nun , Huang Hsin-Yi , Zhao Pei-Wen , Hsu Pang-Hung , Shen Cheng-Huang , Chen San-Yuan , Fang Chiung-Yao
Published: July 2023

Background

Human polyomavirus BK (BKPyV) causes associated nephropathy and contributes to urinary tract cancer development in renal transplant recipients. Large tumor antigen (LT) is an early protein essential in the polyomavirus life cycle. Protein acetylation plays a critical role in regulating protein stability, so this study investigated the acetylation of the BKPyV LT protein.

Methods

The BKPyV LT nucleotide was synthesized, and the protein was expressed by transfection into permissive cells. The BKPyV LT protein was immunoprecipitated and subjected to LC-MS/MS analysis to determine the acetylation residues. The relative lysine was then mutated to arginine in the LT nucleotide and BKPyV genome to analyze the role of LT lysine acetylation in the BKPyV life cycle.

Results

BKPyV LT acetylation sites were identified at Lys3 and Lys230 by mass spectrometry. HDAC3 and HDAC8 and their deacetylation activity are required for BKPyV LT expression. In addition, mutations of Lys3 and Lys230 to arginine increased LT expression, and the interaction of HDAC3 and LT was confirmed by coimmunoprecipitation.

Conclusions

HDAC3 is a newly identified protein that interacts with BKPyV LT, and LT acetylation plays a vital role in the BKPyV life cycle.
Individualized lifestyle intervention in PCOS women (IPOS): a study protocol for a multicentric randomized controlled trial for evaluating the effectiveness of an individualized lifestyle intervention in PCOS women who wish to conceive
Authors: Malhotra Neena , Arora Taruna , Suri Vanita , Jena Saubhagya Kumar , Verma Asha , Gowri Mahasampath , Kapoor Nitin , Chalga Manjeet Singh , Kulkarni Bharati , Kamath Mohan S.
Published: July 2023

Background

Polycystic ovary syndrome (PCOS) is a common endocrine condition which affects women in the reproductive age group. South Asian women with PCOS have a higher risk of insulin resistance and metabolic disorder compared to women from other ethnic backgrounds. Lifestyle interventions such as dietary advice and physical exercise are recommended as a first-line management option for infertile women with PCOS. Most of the randomized controlled trials evaluating the role of lifestyle interventions in infertile PCOS women were characterized by methodological issues. The uptake of lifestyle modifications as a treatment strategy in the South Asian population is complicated by a difficult-to-change conventional high-carbohydrate diet and limited availability of space for physical activity in the region.

Methods

The study is designed as an open-label, multicentre, randomized controlled trial in South Asian women with PCOS. Women attending the fertility clinic will be screened for eligibility, and women aged between 19 and 37 years who have been diagnosed with PCOS and wishing to conceive will be invited to participate in the trial. We will include women with body mass index (BMI) between ≥ 23 and ≤ 35 kg/m2 and duration of infertility ≤ 3 years. We plan to randomize women with PCOS into two groups: group A will receive the intervention which will consist of individualized advice on diet and physical exercise along with a telephonic reminder system and follow-up visits, and group B (control) will receive one-time advice on diet and physical exercise. Both groups will receive up to three cycles of ovulation induction with letrozole after 3 months of randomization during the 6-month treatment period. The primary outcome of the trial will be the live birth following conception during the intervention period. The secondary outcomes include clinical pregnancy rate, ongoing pregnancy rate, miscarriage rate, ectopic pregnancy rate, stillbirth, time to pregnancy, mean weight loss, differences in anthropometric parameters, improvement in menstrual regularity and quality of life score.

Discussion

The IPOS trial results could help clarify and provide more robust evidence for advocating an individualized lifestyle intervention in PCOS women who wish to conceive.

Trial registration

Clinical Trial Registry of India CTRI/2023/04/051620. Registered on 13 April 2023.
Public Procurement and Mediation to Facilitate Procedures for the preservation of World's Cultural Heritage
Authors: Sideri Maria
Published: July 2023

All levels of legislation from national rules to international Treaties include provisions for heritage procurement and alternative dispute resolution. Each law has got its own scope and field of application: some of those are obligatory, with direct effect and supreme. Practitioners thus need to apply the right texts for the conclusion of public contracts and for the resolution of their disputes. Mediation is being proposed as a very modern and flexible tool for disputes’ settlements arising in a contest. Some examples of successful public procurement may be found here and a superficial approach to the Hagias-Sofia project.
Sub-wavelength effects in a free electron laser oscillator
Authors: Pongchalee P. , McNeil B. W. J.
Published: July 2023

Previous simulation studies of cavity based free electron lasers (FELs) have utilised models which average the optical field in the FEL interaction over an integer number of radiation wavelengths. In this paper, two unaveraged simulation codes, OPC and Puffin, are combined to enable modelling, for the first time, of a cavity based FEL at the sub-wavelength scale. This enables modelling of effects such as coherent spontaneous emission from the electron beam and sub-wavelength cavity length detuning. A cavity FEL operating in the mid-infrared is modelled and it is shown that, for small sub-wavelength cavity detunings, the FEL can preferentially lase at the third harmonic of the fundamental FEL wavelength. This novel result suggests other modes of operation may be possible and opens up cavity-based FEL operation to investigation of further, potentially useful, modes of operation.
Frequency shift of even-order high harmonic generation in monolayer MoS2
Authors: Zheng Wenyang , Jiang Yang , Wang Shuo , Liu Candong , Bai Ya , Liu Peng , Li Ruxin
Published: July 2023

Sub-optical-cycle electron dynamics in materials driven by intense laser fields can be investigated by high harmonic generation. We observed frequency shift of high harmonic spectrum near the band gap of monolayer MoS2 experimentally. Through semi-classical quantum trajectory analysis, we demonstrated that the phase of transition dipole moment varies according to the recombination timing and momentum of tunneled electrons. It results in either blue- or red-shift of harmonic frequencies, determined by the modulated energy gap by transition dipole phases (TDPs) and Berry connections. Our finding reveals the effect of TDPs on high harmonic frequency in non-central symmetric materials.
Erbium-ytterbium codoped thin-film lithium niobate integrated waveguide amplifier with a 27 dB internal net gain
Authors: Zhang Zhihao , Li Shanming , Gao Renhong , Zhang Haisu , Lin Jintian , Fang Zhiwei , Wu Rongbo , Wang Min , Wang Zhenhua , Hang Yin , Cheng Ya
Published: July 2023

A photonic integrated waveguide amplifier fabricated on erbium-ytterbium (Er-Yb) codoped thin-film lithium niobate (TFLN) has been investigated in this work. A small-signal internal net gain of 27 dB is achieved at a signal wavelength of 1532 nm in the fabricated Er-Yb TFLN waveguide amplifier pumped by a diode laser at ≈980 nm. Experimental characterizations reveal the suitability of waveguide fabrication by the photolithography-assisted chemo-mechanical etching (PLACE) technique and also the gain in an Yb-sensitized-Er material. The demonstrated high-gain chip-scale TFLN amplifier is promising for interfacing with established lithium niobate integrated devices, greatly extending the spectrum of TFLN photonic applications.
UBQLN1 deficiency mediates telomere shortening and IPF through interacting with RPA1
Authors: Zhou Haoxian , Xie Chen , Xie Yujie , He Yunru , Chen Yanlian , Zhang Canfeng , Zhang Yan , Zhao Yong , Liu Haiying
Published: July 2023

Premature telomere shortening is a known factor correlated to idiopathic pulmonary fibrosis (IPF) occurrence, which is a chronic, progressive, age-related disease with high mortality. The etiology of IPF is still unknown. Here, we found that UBQLN1 plays a key role in telomere length maintenance and is potentially relevant to IPF. UBQLN1 involves in DNA replication by interacting with RPA1 and shuttling it off from the replication fork. The deficiency of UBQLN1 retains RPA1 at replication fork, hinders replication and thus causes cell cycle arrest and genome instability. Especially at telomere regions of the genome, where more endogenous replication stress exists because of G rich sequences, UBQLN1 depletion leads to rapid telomere shortening in HeLa cells. It revealed that UBQLN1 depletion also shortens telomere length at mouse lung and accelerates mouse lung fibrosis. In addition, the UBQLN1 expression level in IPF patients is downregulated and correlated to poor prognosis. Altogether, these results uncover a new role of UBQLN1 in ensuring DNA replication and maintaining telomere stability, which may shed light on IPF pathogenesis and prevention.
Association of the risk of obstructive sleep apnoea with the severity of COVID-19
Authors: Arish Nissim , Izbicki Gabriel , Rokach Ariel , Jarjou’i Amir , Kalak George , Goldberg Shmuel
Published: July 2023

Patients with coronavirus 2019 (COVID-19) and obstructive sleep apnoea (OSA) have a worse prognosis than COVID-19 patients without OSA. This study aimed to examine the relationship between OSA risk and the severity of COVID-19 in patients undiagnosed with OSA. Patients diagnosed with COVID-19 and hospitalized or admitted to a community hotel were recruited for the study after recovery during a clinic check-up visit 6–8 weeks after discharge. At this visit, they answered the Epworth Sleeping Scale (ESS) and Berlin questionnaire. Demographic and clinical details were collected from electronic medical records. OSA risk was observed in 37 of 119 included patients (31.1%). Patients with high OSA risk were male, significantly older, had a higher body mass index (BMI), and had higher rates of hypertension and snoring than patients with low OSA risk. Moreover, OSA risk was associated with COVID-19 severity; 48.6% of patients with high risk for OSA suffered from severe COVID-19 compared to 22% of patients with low risk for OSA (p = 0.007). The duration of hospitalization for patients with a high OSA risk was 10.97±9.43 days, while that for those with a low OSA risk was 4.71±6.86 days (p = 0.001). After adjusting for BMI, age, hypertension, and chronic disease, the odds ratio was 4.3 (95%CI, 1.2–16, p = 0.029). A high OSA risk was associated with severe COVID-19 and longer hospitalization. Thus, we recommend that the Berlin and ESS questionnaires be completed for every COVID-19-infected patient at hospitalization, especially in the presence of comorbidities.
Fibrinolytic and antibiotic treatment of prosthetic vascular graft infections in a novel rat model
Authors: Johansen Mikkel Illemann , Rahbek Søren Jensen , Jensen-Fangel Søren , Minero Gabriel Antonio S. , Jensen Louise Kruse , Larsen Ole Halfdan , Erikstrup Lise Tornvig , Seefeldt Anders Marthinsen , Østergaard Lars , Meyer Rikke Louise , Jørgensen Nis Pedersen
Published: July 2023

Objectives

We developed a rat model of prosthetic vascular graft infection to assess, whether the fibrinolytic tissue plasminogen activator (tPA) could increase the efficacy of antibiotic therapy.

Materials and methods

Rats were implanted a polyethylene graft in the common carotid artery, pre-inoculated with approx. 6 log10 colony forming units (CFU) of methicillin resistant Staphylococcus aureus. Ten days after surgery, rats were randomized to either: 0.9% NaCl (n = 8), vancomycin (n = 8), vancomycin + tPA (n = 8), vancomycin + rifampicin (n = 18) or vancomycin + rifampicin + tPA (n = 18). Treatment duration was seven days. Approximately 36 hours after the end of treatment, the rats were euthanized, and grafts and organs were harvested for CFU enumeration.

Results

All animals in the control group had significantly higher CFU at the time of euthanization compared to bacterial load found on the grafts prior to inoculation (6.45 vs. 4.36 mean log10 CFU/mL, p = 0.0011), and both the procedure and infection were well tolerated.

Vancomycin and rifampicin treatment were superior to monotherapy with vancomycin, as it lead to a marked decrease in median bacterial load on the grafts (3.50 vs. 6.56 log10 CFU/mL, p = 0.0016). The addition of tPA to vancomycin and rifampicin combination treatment did not show a further decrease in bacterial load (4.078 vs. 3.50 log10 CFU/mL, p = 0.26). The cure rate was 16% in the vancomycin + rifampicin group vs. 37.5% cure rate in the vancomycin + rifampicin + tPA group. Whilst interesting, this trend was not significant at our sample size (p = 0.24).

Conclusion

We developed the first functional model of an arterial prosthetic vascular graft infection in rats. Antibiotic combination therapy with vancomycin and rifampicin was superior to vancomycin monotherapy, and the addition of tPA did not significantly reduce bacterial load, nor significantly increase cure rate.
Unleashing the horizons of labor quality, digitalization on upgradation of industrial structure in Asian economies
Authors: Zhang Zujie , Madni Ghulam Rasool , Naeem Jaweriya
Published: July 2023

A country’s industrial structure plays a pivotal role in determining its competitiveness, growth, and sustainability. Recently, many Asian countries have experienced significant economic upgradation and transformation and have emerged as major players in global trade. It is crucial to understand the factors contributing in upgradation of industrial structure of Asian economies for their continuous progress and it is little focused in literature. This study explores the effect of labor quality and digitalization on the upgradation of the industrial structure in 32 Asian countries covering the time period from 2010–2021. Multiple econometric techniques are applied for a comprehensive analysis of data, and the findings show that high-quality labor has a positive contribution to upgrading the industrial structure. Moreover, digitalization upgrades the industrial structure by improving connectivity, fostering collaboration, and enhancing productivity. Based on the findings of this study, Asian countries should prioritize investments in education and skill development to enhance human capital quality. Additionally, they should promote policies that facilitate digitalization, including investments in digital infrastructure, the development of digital skills, and the creation of a supportive regulatory environment. Thus, Asian countries can accelerate the upgradation of their industrial structure, leading to sustainable economic growth, increased competitiveness, and improved living standards.