bluuebunny/crossref_metadata_2025 huggingface dataset:
Operative Treatment of Adolescent Hallux Valgus
Authors: Gerchev Alexandar , Tserovska Simona , Georgiev Georgi
Published: March 2022

The hallux valgus deformity in pediatric patients is a common pathology with no definitive criteria for surgical treatment. The purpose of this study is to present mid-term postoperative results after surgical treatment of this foot deformity.
The study included 43 operated feet in 29 patients, with an average age of 14.31 years. Scarf osteotomy was performed in 23 patients, combined with an Akin osteotomy in 14 of the cases; Chevron osteotomy was performed in seven patients, five patients were treated with the mini tightrope technique, two with the Ludloff osteotomy, and six patients with lateral hemiepiphysiodesis of the first metatarsal. We evaluated the change in angular radiographic parameters and the American Orthopaedic Foot & Ankle Society scale for data analysis.
The mean follow-up of the study was 48 ± 33.2 months. The mean preoperative hallux valgus angle showed an average improvement of 30.19° to 12.79° (p < 0.001). Loss of correction of the HVA angle of 20.46° was noted at the time of final follow up (p > 0.05). Favourable correction of the intermetatarsal angle was achieved with improvement of 11.44° preoperatively to 7.35° postoperatively. Significant progression was found for the American Orthopedic Foot & Ankle Society score from 57 points (42–85) before surgery to 80 points (54–100) after surgery. The recurrence rate 6 months after surgery is 30.95% (13 cases). Relapse of the deformity after Scarf osteotomy was observed in nine cases; after mini tight rope technique in three cases, and in one case after Chevron osteotomy.
In conclusion we state that the most important factor influencing the outcomes of treatment and postoperative recurrence rate is skeletal maturity. Surgical treatment should be indicated after growth plate fusion. Conservative treatment via orthotic devices is recommended until that time.
Anti-cyclic Citrullinated Peptide Antibody and Rheumatoid Factor and the Relationship between Periodontitis and Rheumatoid Arthritis
Authors: Bolyarova-Konova Theodora , Stefanov Lyubomir , Kolarov Zlatimir , Grozdanova Radoslava , Nikolova Maria
Published: March 2022

The purpose of this study is to determine the concentration of Rheumatic Factor (RF) and Anti-cyclic Citrullinated Peptide Antibody (ACPA) in serum and in Gingival Crevicular Fluid (GCF) and their dependence on the presence of periodontitis (P) and rheumatoid arthritis (RA). The study involved 81 patients divided into three groups: Group I – patients with P and without RA (with osteoarthritis) – 26 subjects; Group II – patients with P and RA – 30 subjects; Group III – patients with periodontal health (without P) and RA – 25 subjects. For all patients the levels of ACPA and RF (class IgM) have been analyzed by ELISA in serum and GCF. We found a significantly higher incidence of ACPA in the GCF positive individuals and significantly higher mean ACPA values in GCF in Group II patients compared to patients in Group I. We found a significant difference between the frequency of RF in the GCF positive patients in Group II compared to those in Group I as well as the RF in the GCF positive patients in Group II compared to those in Group III. In the study among the patients of Group II we found a significant correlation between the RF and ACPA concentrations in serum and the number of lost teeth. These results are associated with possible enhanced extraarticular synthesis of ACPA and RF in the periodontal tissues in patients with periodontitis and predisposed to RA. Evidence for the effect of RA on periodontitis is the correlation between the concentration of ACPA and RF in serum – biomarkers for RA and the number of lost teeth.
Organic Molecular Markers in Soils Ameliorated with Biochar
Authors: Atanassova Irena , Harizanova Milena , Benkova Maya , Simeonova Tsetska , Nenova Lyuba
Published: March 2022

The study analyzed the organic molecular marker signatures in a maize cultivated Fluvisol ameliorated with 5 and 10 t.ha−1 biochar at the experimental field of the ISSAPP N. Poushkarov institute in Bulgaria. The n-alkane signatures and the carbon preference index (CPI) in the biochar treated soils revealed that sources of SOM were predominantly of microbial/thermal origin, while the source was only thermal in the pure biochar sample, (CPIodd/even0.84). There was evidence from the molecular marker analysis that biochar addition may initially bring improvement of soil microbiological status. There was no significant co-occurrence of polycyclic aromatic hydrocarbons released from biochar several months after incorporation in the soil.
Liquid–liquid interface induced PDMS‐PTFE composite membrane for ethanol perm‐selective pervaporation
Authors: Li Chong , Li Jie , Cai Peng , Cao Tengxuan , Zhang Nai , Wang Naixin , An Quan‐Fu
Published: March 2022

Pervaporation has great potential in the separation of many significant mixtures. However, excessive penetration of separation layer into the substrate pores enhances the transport resistance of solvent molecules, which impedes the development of pervaporation membrane. In this study, a facile floating‐on‐water (FOW) method was used to prepare poly(dimethylsiloxane) (PDMS)/polytetrafluoroethylene (PTFE) composite membranes. The formation of separation layer and preparation of composite membrane were step‐by‐step completed through this liquid–liquid interface induced method. The PDMS layer thickness could be precisely regulated from 0.5 to 8 μm. Moreover, the pore penetration could be controlled by optimizing pre‐crosslinking density, crosslinking time on water and polymer solution volume. The obtained PDMS/PTFE composite membrane exhibited a high flux of 2016 g·m−2·h−1 with the separation factor of 12 when separating ethanol from a 5 wt% ethanol/water mixture. The performance of the membrane could be stable for over 200 h, exhibiting great potential in ethanol perm‐selective pervaporation.
Langerhans cell histiocytosis presenting as a submucosal solitary colonic lesion: A case report and review of the literature
Authors: Huang Shu‐Han , Chen Meng‐Yu , Chou Yuh‐Yu
Published: March 2022

Langerhans cell histiocytosis (LCH) is a rare histiocytic neoplasm. The clinical presentation and the disease extension are variable. LCH may involve a single site, multiple sites within a single system, or multiple systems. Gastrointestinal tract involvement is rare and most often observed in children with multisystem disease. Adult patients with gastrointestinal tract involvement are extremely rare, and only a few cases have been reported. We present a 45‐year‐old man with LCH presenting as a submucosal solitary colonic lesion.
Implementation of chemometrics, design of experiments, and neural network analysis for prior process knowledge assessment, failure modes and effect analysis, scale‐down model development, and process characterization for a chromatographic purification of Teriparatide
Authors: Pathak Mili , Pokhriyal Prashant , Gandhi Irshad , Khambhampaty Sridevi
Published: March 2022

Process understanding and characterization forms the foundation, ensuring consistent and robust biologics manufacturing process. Using appropriate modeling tools and machine learning approaches, the process data can be monitored in real time to avoid manufacturing risks. In this article, we have outlined an approach toward implementation of chemometrics and machine learning tools (neural network analysis) to model and predict the behavior of a mixed‐mode chromatography step for a biosimilar (Teriparatide) as a case study. The process development data and process knowledge was assimilated into a prior process knowledge assessment using chemometrics tools to derive important parameters critical to performance indicators (i.e., potential quality and process attributes) and to establish the severity ranking for the FMEA analysis. The characterization data of the chromatographic operation are presented alongwith the determination of the critical, key and non‐ key process parameters, set points, operating, process acceptance and characterized ranges. The scale‐down model establishment was assessed using traditional approaches and novel approaches like batch evolution model and neural network analysis. The batch evolution model was further used to demonstrate batch monitoring through direct chromatographic data, thus demonstrating its application for continuos process verification. Assimilation of process knowledge through a structured data acquisition approach, built‐in from process development to continuous process verification was demonstrated to result in a data analytics driven model that can be coupled with machine learning tools for real time process monitoring. We recommend application of these approaches with the FDA guidance on stage wise process development and validation to reduce manufacturing risks.
Impact of thoracic endovascular aortic repair on aortic biomechanics: Integration of in silico and ex vivo analysis using porcine model
Authors: Bianchi Daniele , Conti Michele , Bissacco Daniele , Domanin Maurizio , Trimarchi Santi , Auricchio Ferdinando
Published: March 2022

Thoracic endovascular aortic repair (TEVAR) is widespread in clinical practice for treating aortic diseases but it has relevant systemic complications, such as increase of the cardiac workload due to post‐TEVAR aortic stiffening, and local issues such as re‐entry tears due to the tissue damage caused by endograft interaction. The present study aims to elucidate these aortic biomechanical mechanisms by coupling ex vivo and in silico analysis. By ex vivo tests, the pulse wave velocity before and after TEVAR is measured. Uni‐axial tensile tests are performed to measure regional mechanical response of tissue samples, supplied as input data for the in silico analysis. Numerical analysis is finally performed to compute the wall stress induced by the stent‐graft deployment and the arterial pressurization. The ex vivo results highlight an increase of baseline PWV by a mean .78 m/s or 12% after TEVAR with a 100 mm stent‐graft (p <.013). In the in silico analysis, the average von Mises stress in the landing zone increases of about 15% and 20% using, respectively stent‐graft with radial oversizing of 10% and 20%. This work shows the effectiveness of integrated framework to analyze the biomechanical post TEVAR mechanisms. Moreover, the obtained results quantify the effect of prosthesis selection on the stiffening of the aorta after TEVAR and on the local increase of the aortic wall stress that is proportional to the stent‐graft oversizing.
Scalable resource description framework clustering: A distributed approach for analyzing knowledge graphs using minHash locality sensitive hashing
Authors: Agarwal Pratik , Bahadur Sinha Bam
Published: March 2022

Web is becoming rich in data. Some of the sources from where these data are originating includes Blogs, YouTube, Twitter, Emails, E‐commerce, Banking, sensors, and the Internet of Things. But these data are structured in a very poor fashion. The content of the web is becoming heterogeneous in nature both in terms of compendium and structure. It can be said that these data are human‐readable data but the main motive is to draw inferences from these data which is only possible if it can be made machine‐accessible. Clustering is considered an important task to organize these data and draw meaningful inferences from these data. In this paper, a clustering approach is proposed that can be applied to knowledge graphs and the possibility of applying Locality Sensitive Hashing is explored. Given the size of linked data, it is observed that this approach can be effective and scalable in comparison to other clustering approaches such as Hierarchical clustering, K‐Means clustering, and K‐Medoid clustering in discovering different communities that are defined by the link structure of the graph. The experimental results on different types of Linked Data sources justify the efficacy of the proposed model in terms of scalability and efficiency.
SubtStream: Online subtractive stream clustering algorithm
Authors: Milli Musa , Bulut Hasan
Published: March 2022

Real‐time stream data processing has gained high importance with the rapid rise of big data trends in different areas such as social media, finance, business, science, and bioinformatics. Stream data can be characterized as fast, unstable, and big data sets. Due to these properties of stream data, it cannot be processed effectively with traditional algorithms. Just like stream data processing, clustering is also a difficult task. However, researchers have attempted to classify stream data by modifying traditional algorithms or designing new ones. So, in previous studies, incremental methods were used for clustering the stream data. This paper highlights the need to develop an efficient real‐time clustering algorithm for data streams in the presence of concept high drift and an adaptive algorithm for different dimensions. The proposed clustering algorithm, SubtStream, combines decremental (subtractive property) and incremental (additivity property) strategies to overcome the high drift. It also introduces a new dimension‐based approach to adopt the dimension change. We use three radius parameters, Predefined User Parameter, Proactive Adaptive Parameter, and Reactive Adaptive Parameter, to achieve adaptability. The proposed method, SubtStream, showed better performance on synthetic and real data sets.
Fast flow cloud: A stream dataflow framework for cloud FPGA accelerator overlays at runtime
Authors: Bragança Lucas , Canesche Michael , Penha Jeronimo , Campos Josué , Nacif José Augusto M. , Ferreira Ricardo S.
Published: March 2022

Cloud FPGAs provide new energy‐efficient opportunities to design dataflow accelerators. Nevertheless, FPGAs still have challenges to overcome for widespread usages, such as programmability, compilation time (minutes to hours), and hardware knowledge, mainly because it is highly challenging for beginners to learn and use FPGAs. The READY tool recently provides compilation time reduction to the range of microseconds using a CGRA overlay and a friendly, high‐level C++ interface for the Intel/Altera HARPv2 FPGA cloud platform. However, the HARPv2 is not available in any commercial cloud platform. This work extends READY by creating the fast flow cloud framework (FFC). First, FFC offers a simple browser‐based graphical interface for less experienced FPGA users. Second, we improve the CGRA overlay portability to include Xilinx FPGAs and a transparent design flow to deploy in the widespread commercial Amazon AWS F1 cloud. Third, we improve the CGRA reconfiguration engine. Also, we compare the overlay performance of HARPv2 and AWS F1 to an eight‐thread XEON processor. Finally, the framework is open‐source for collaborative development and has clearly defined application programming interfaces for future extensions.
Precipitation change accentuates or reverses temperature effects on aphid dispersal
Authors: Crossley Michael S. , Lagos‐Kutz Doris , Davis Thomas S. , Eigenbrode Sanford D. , Hartman Glen L. , Voegtlin David J. , Snyder William E.
Published: March 2022

Global temperatures are generally increasing, and this is leading to a well documented advancement and extension of seasonal activity of many pest insects. Effects of changing precipitation have received less attention, but might be complex because rain and snow are increasing in some places but decreasing in others. This raises the possibility that altered precipitation could accentuate, or even reverse, the effects of rising temperatures on pest outbreaks. We used >592 K aphid suction‐trap captures over 15 years, in the heavily farmed central USA, to examine how the activity of Aphis glycines (soybean aphid), Rhopalosiphum maidis (corn aphid), and Rhopalosiphum padi (bird cherry‐oat aphid) changed with variation in both temperature and precipitation. Increasing precipitation caused late‐season flight activity of A. glycines and early‐season activity of R. padi to shift earlier, while increasing temperature did the same for early‐season activity of A. glycines and R. maidis. In these cases, precipitation and temperature exhibited directionally similar, but independent, effects. However, precipitation sometimes mediated temperature effects in complex ways. At relatively low temperatures, greater precipitation generally caused late‐season flights of R. maidis to occur earlier. However, this pattern was reversed at higher temperatures with precipitation delaying late‐season activity. In contrast, greater precipitation delayed peak flights of R. padi at lower temperatures, but caused them to occur earlier at higher temperatures. So, in these two cases the interactive effects of precipitation on temperature were mirror images of one another. When projecting future aphid flight phenology, models that excluded precipitation covariates consistently underpredicted the degree of phenological advance for A. glycines and R. padi, and underpredicted the degree of phenological delay for R. maidis under expected future climates. Overall, we found broad evidence that changing patterns of aphid flight phenology could only be understood by considering both temperature and precipitation changes. In our study region, temperature and precipitation are expected to increase in tandem, but these correlations will be reversed elsewhere. This reinforces the need to include both main and interactive effects of precipitation and temperature when seeking to accurately predict how pest pressure will change with a changing climate.
Natural disturbance regimes as a guide for sustainable forest management in Europe
Authors: Aszalós Réka , Thom Dominik , Aakala Tuomas , Angelstam Per , Brūmelis Guntis , Gálhidy László , Gratzer Georg , Hlásny Tomáš , Katzensteiner Klaus , Kovács Bence , Knoke Thomas , Larrieu Laurent , Motta Renzo , Müller Jörg , Ódor Péter , Roženbergar Dušan , Paillet Yoan , Pitar Diana , Standovár Tibor , Svoboda Miroslav , Szwagrzyk Jerzy , Toscani Philipp , Keeton William S.
Published: March 2022

In Europe, forest management has controlled forest dynamics to sustain commodity production over multiple centuries. Yet over‐regulation for growth and yield diminishes resilience to environmental stress as well as threatens biodiversity, leading to increasing forest susceptibility to an array of disturbances. These trends have stimulated interest in alternative management systems, including natural dynamics silviculture (NDS). NDS aims to emulate natural disturbance dynamics at stand and landscape scales through silvicultural manipulations of forest structure and landscape patterns. We adapted a “Comparability Index” (CI) to assess convergence/divergence between natural disturbances and forest management effects. We extended the original CI concept based on disturbance size and frequency by adding the residual structure of canopy trees after a disturbance as a third dimension. We populated the model by compiling data on natural disturbance dynamics and management from 13 countries in Europe, covering four major forest types (i.e., spruce, beech, oak, and pine‐dominated forests). We found that natural disturbances are highly variable in size, frequency, and residual structure, but European forest management fails to encompass this complexity. Silviculture in Europe is skewed toward even‐aged systems, used predominately (72.9% of management) across the countries assessed. The residual structure proved crucial in the comparison of natural disturbances and silvicultural systems. CI indicated the highest congruence between uneven‐aged silvicultural systems and key natural disturbance attributes. Even so, uneven‐aged practices emulated only a portion of the complexity associated with natural disturbance effects. The remaining silvicultural systems perform poorly in terms of retention compared to tree survivorship after natural disturbances. We suggest that NDS can enrich Europe's portfolio of management systems, for example where wood production is not the primary objective. NDS is especially relevant to forests managed for habitat quality, risk reduction, and a variety of ecosystem services. We suggest a holistic approach integrating NDS with more conventional practices.
Toward natural convection solar drying of date palm fruits (Phoenix dactylifera L.): An experimental study
Authors: Sansaniwal Sunil Kumar , Kumar Mahesh , Sahdev Ravinder Kumar , Bhutani Vijay , Manchanda Himanshu
Published: March 2022

Sun‐drying has proven to be the most sustainable technique for preserving food and agricultural products. However, conventional sun‐drying has limited drying capacity and can lead to significant losses in product quality. Greenhouse and indirect solar drying are advanced drying methods with improved product quality. In this article, the natural convection greenhouse dryer and natural convection indirect solar dryer were developed to study date palm fruits' drying characteristics (Phoenix dactylifera L.) in terms of moisture ratio and convective heat transfer coefficients. At the same time, the thermal performance of drying units was examined in terms of energy efficiency. The greenhouse dryer's higher convective heat transfer coefficient reduced drying time, and the indirect solar dryer's energy efficiency was obtained. The experimental data were fitted in various drying models, of which the Lewis model was found to be best fitted. The experimental errors were analyzed in terms of percent uncertainties. The drying costs of dried date palm fruits under greenhouse dryer and indirect solar dryer were found to be INR ₹ 22.37/kg (US$ 0.30/kg) and INR ₹ 30.14/kg (US$ 0.40/kg), respectively. Drying units could be a sustainable way of product drying, particularly in the rural areas where advanced drying mechanisms are still unavailable (1 USD = 74.8 INR as on 03 Feb, 2022).
Magnetic mesoporous KOH/Fe3O4@MCM‐41 nanocatalyst for biodiesel production from waste cooking oil: Optimization of process variables and kinetics study
Authors: Khakestarian Mohaddeseh , Taghizadeh Majid , Fallah Naghmeh
Published: March 2022

In this study, biodiesel production via transesterification of waste cooking oil as feedstocks and methanol was studied over KOH/Fe3O4@MCM‐41 catalyst. The X‐ray diffraction, BET, FT‐IR, and field‐emission scanning electron microscopy techniques were applied to describe the structural characterization of the catalyst. The effects of the catalyst amount, reaction time, and alcohol to oil molar ratio were investigated using central composite design method and ANOVA analysis. Among the evaluated conditions, 3.32 h reaction time, 8.51% loaded catalyst, and 42.36 alcohols to oil molar ratio can provide an optimal biodiesel production of 93.95%. Moreover, the catalyst revealed high‐reusability over three cycles. Based on the reaction kinetics study, several parameters such as rate constants at three temperatures, activation energy and frequency factors were investigated.
A net‐zero Swiss energy system by 2050: Technological and policy options for the transition of the transportation sector
Authors: Kannan Ramachandran , Panos Evangelos , Hirschberg Stefan , Kober Tom
Published: March 2022

The Swiss government sets out a net‐zero emission goal by 2050 while phasing out nuclear energy. This study presents insights on the transport sector's contribution to meet this goal, in terms of which type of vehicle drivetrains and fuel supply options are cost‐effective? What could be critical for the transition of the transportation sector? We use the Swiss TIMES Energy system Model and assess prospective technological scenarios for the whole energy system. The transport module has fast‐charging stations and mechanisms to control e‐mobility charging. Results indicate that extensive direct and indirect electrification of mobility increases the electricity demand up to 22 TWh. While to a certain extent electric cars are competitive even if the climate would not be the priority, carbon neutrality requires a boost for electrified mobility where battery‐ and plug‐in hybrid electric vehicles are largely evolving as a solution for small‐medium size car segments while fuel cell cars are an attractive option for big size car segments. Hybridization of buses and trucks emerges as a competitive option but they are propelled with bio‐ and synthetic fuels. The transport sector emerges as a major driver for the deployment of hydrogen in the energy sector in the long term.
IL‐1 receptor antagonist plus pentoxifylline and zinc for severe alcohol‐associated hepatitis
Authors: Szabo Gyongyi , Mitchell Mack , McClain Craig J. , Dasarathy Srinivasan , Barton Bruce , McCullough Arthur J. , Nagy Laura E. , Kroll‐Desrosiers Aimee , Tornai David , Min Hyesung Alice , Radaeva Svetlana , Holbein M. E. Blair , Casey Lisa , Cuthbert Jennifer
Published: March 2022

Background and Aims

Patients with severe alcohol‐associated hepatitis (AH) have high mortality. Corticosteroids improve survival only for 30 days. We targeted inflammation, cellular injury, and gut leakiness in a randomized clinical trial comparing combination therapy to corticosteroids on 180‐day survival.

Approach and Results

Subjects with a clinical diagnosis of severe AH (Model for End‐Stage Liver Disease [MELD] >20, Maddrey discriminant function [MDF] >32) were randomized to receive methylprednisolone (PRED; 28 days) or a combination of anakinra (14 days) plus pentoxifylline (28 days) plus zinc (COMB; 180 days). The primary endpoint was survival at 180 days. The study was designed in 2013, initiated in October 2014, and completed in March 2018. Five hundred patients were screened to randomize 104 subjects with a clinical diagnosis of AH with a MELD score >20. Fifty‐three patients were randomized into the COMB and 50 to the PRED treatment; 1 dropped out of the study before randomization. Mean age was 45.3 ± 10.4 years; 60.6% were males, 92.3% White, and mean MELD 25.7 ± 3.9. Kaplan‐Meier survival estimate at 180 days was 67.9% in COMB and 56% in PRED (HR = 0.69; p = 0.3001). Survival curves separated by 90 days (COMB, 69.8%; PRED, 58.0%; HR = 0.69; p = 0.28). Survival at 28 days was similar between the COMB (83.4%) and PRED groups (81.2%; HR = 0.91; p = 0.85). There were no unexpected serious adverse events, and incidence of infection was comparable between groups. MELD 20–25 and MELD >26 strata showed nonsignificant treatment effects in favor of COMB.

Conclusions

A combination of anakinra, pentoxifylline plus zinc provides similar survival benefits compared to corticosteroid therapy in severe AH.
Cellular heterogeneity and transcriptomic profiles during intrahepatic cholangiocarcinoma initiation and progression
Authors: Wang Tingjie , Xu Chuanrui , Zhang Zhijing , Wu Hua , Li Xiujuan , Zhang Yu , Deng Nan , Dang Ningxin , Tang Guangbo , Yang Xiaofei , Shi Bingyin , Li Zihang , Li Lei , Ye Kai
Published: March 2022

Background and Aims

Intrahepatic cholangiocarcinoma (ICC) is not fully investigated, and how stromal cells contribute to ICC formation is poorly understood. We aimed to uncover ICC origin, cellular heterogeneity, and critical modulators during ICC initiation/progression, and to decipher how fibroblast and endothelial cells in the stromal compartment favor ICC progression.

Approach and Results

We performed single‐cell RNA sequencing (scRNA‐seq) using AKT/Notch intracellular domain–induced mouse ICC tissues at early, middle, and late stages. We analyzed the transcriptomic landscape, cellular classification and evolution, and intercellular communication during ICC initiation/progression. We confirmed the findings using quantitative real‐time PCR, western blotting, immunohistochemistry or immunofluorescence, and gene knockout/knockdown analysis. We identified stress‐responding and proliferating subpopulations in late‐stage mouse ICC tissues and validated them using human scRNA‐seq data sets. By integrating weighted correlation network analysis and protein–protein interaction through least absolute shrinkage and selection operator regression, we identified zinc finger, MIZ‐type containing 1 (Zmiz1) and Y box protein 1 (Ybx1) as core transcription factors required by stress‐responding and proliferating ICC cells, respectively. Knockout of either one led to the blockade of ICC initiation/progression. Using two other ICC mouse models (YAP/AKT, KRAS/p19) and human ICC scRNA‐seq data sets, we confirmed the orchestrating roles of Zmiz1 and Ybx1 in ICC occurrence and development. In addition, hes family bHLH transcription factor 1, cofilin 1, and inhibitor of DNA binding 1 were identified as driver genes for ICC. Moreover, periportal liver sinusoidal endothelial cells could differentiate into tip endothelial cells to promote ICC development, and this was Dll4‐Notch4‐Efnb2 signaling–dependent.

Conclusions

Stress‐responding and ICC proliferating subtypes were identified, and Zmiz1 and Ybx1 were revealed as core transcription factors in these subtypes. Fibroblast–endothelial cell interaction promotes ICC development.
ATP7B gene therapy of autologous reprogrammed hepatocytes alleviates copper accumulation in a mouse model of Wilson’s disease
Authors: Cai Hongxia , Cheng Xing , Wang Xiao‐Ping
Published: March 2022

Background and Aims

Wilson’s disease (WD) is a rare hereditary disorder due to ATP7B gene mutation, causing pathologic copper storage mainly in the liver and neurological systems. Hepatocyte transplantation showed therapeutic potential; however, this strategy is often hindered by a shortage of quality donor cells and by allogeneic immune rejection. In this study, we aimed to evaluate the function and efficacy of autologous reprogrammed, ATP7B gene‐restored hepatocytes using a mouse model of WD.

Approach and Results

Sufficient liver progenitor cells (LPCs) were harvested by reprogramming hepatocytes from ATP7B−/−
mice with small molecules, which exhibited strong proliferation and hepatic differentiation capacity in vitro. After lentivirus‐mediated mini ATP7B gene transfection and redifferentiation, functional LPC‐ATP7B‐derived hepatocytes (LPC‐ATP7B‐Heps) were developed. RNA sequencing data showed that, compared with LPC–green fluorescent protein–Heps (LPC‐GFP‐Heps) with enrichment of genes that were mainly in pathways of oxidative stress and cell apoptosis, in LPC‐ATP7B‐Heps under high copper stress, copper ion binding and cell proliferation pathways were enriched. LPC‐ATP7B‐Heps transplantation into ATP7B−/−
mice alleviated deposition of excess liver copper with its associated inflammation and fibrosis, comparable with those observed using normal primary hepatocytes at 4 months after transplantation.

Conclusions

We established a system of autologous reprogrammed WD hepatocytes and achieved ATP7B gene therapy in vitro. LPC‐ATP7B‐Heps transplantation demonstrated therapeutic efficacy on copper homeostasis in a mouse model of WD.
The teamwork structure, process, and context of a paediatric cardiac surgery team in Mongolia: A mixed‐methods approach
Authors: Han Seungheon , Choi Sugy , Park Jayoung , Kweon Seoah , Oh Se Jin , Shakya Holly B. , Heo Jongho , Kim Woong‐Han
Published: March 2022

Introduction

Effective teamwork in paediatric cardiac surgery is known to improve team performance and surgical outcomes. However, teamwork in low‐ and middle‐income countries (LMICs), including Mongolia, is understudied. We examined multiple dimensions of teamwork to inform a team‐based training programme to strengthen paediatric cardiac surgical care in Mongolia.

Methods

We used a mixed‐methods approach, combining social network analysis and in‐depth interviews with medical staff, to explore the structure, process, quality, and context of teamwork at a single medical centre. We conceptualised the team's structure based on communication frequency among the members (n = 24) and explored the process, quality, and context of teamwork via in‐depth interviews with select medical staff (n = 9).

Results

The team structure was highly dense and decentralised, but the intensive care unit nurses showed high betweenness‐centrality. In the quality and process domain of teamwork, we did not find a regular joint decision‐making process, leading to the absence of common goals among the team members. Although role assignment among the medical staff was explicit, those strictly defined roles hindered active communication about patient information and responsibility‐sharing. Most interviewees did not agree with the organisational policies that limited discussions among team members; therefore, medical staff continued to share training and work experiences with each other, leading to strong and trustworthy relationships.

Conclusion

The findings of this study underscore the importance of well‐structured and goal‐oriented communication between medical staff, as well as the management of the quality of collaboration within a team to increase teamwork effectiveness in paediatric cardiac surgery teams in LMICs.
Thailand's COVID‐19: How public financial management facilitated effective and accountable health sector responses
Authors: Sachdev Saranya , Viriyathorn Shaheda , Chotchoungchatchai Somtanuek , Patcharanarumol Walaiporn , Tangcharoensathien Viroj
Published: March 2022

Effective Public Financial Management (PFM) systems are crucial during COVID‐19 pandemic to ensure timely mobilisation of sufficient resources and distribution to frontline service providers. All aspects of PFM, from budget acquisition to execution and expenditure reporting and auditing are important aspects in pursuing effective pandemic responses with transparency and accountability. This commentary analyzes how PFM in Thailand adapted to support purchasing of COVID‐19 health services, including laboratories and treatment, vaccines and vaccination servicing, and no‐fault compensation from adverse effects following immunisation. It also discusses the limitations which delay implementation. Financing COVID‐19 services was decided by the Cabinet under a State of Emergency Decree, resulting in expedited budget approval process. Though delays in budget execution were caused by bureaucratic budget spending rules, regulations and approvals, PFM adaptation allowed for services to be provided through the use of hospital revenue with rapid budget execution rules and regulations while maintaining accountability, reporting and auditing. Lastly, while reporting is mandatory with internal audit by related government agencies, and external audit by Office of the Auditor General in place, as of September 2021, report of the COVID‐19 expenditure in 2020 has yet to be made publicly available for transparency and check and balance by the public. It is unclear the degree to which audit systems are fully enforced. Overall, Thailand's PFM systems have provided rapid fund mobilisation sourcing from central budget and loans and clarity in authorisation of spending; the use of hospital revenue provides more flexibility and rapid budget execution.
Association between efficiency and quality of care of public healthcare facilities: Evidence from Pakistan
Authors: Bashir Saima , Nasir Muhammad , Grasic Katja , Moulin Marc , Ali Shehzad
Published: March 2022

Background

Maternal and child health is an important component of the Sustainable Development Goals. Pakistan has one of the worst maternal and neonatal health outcomes in the world. This is despite significant health system investments across the country.

Aims

The objectives of this study are twofold. First, the study estimates the technical efficiency of the public healthcare facilities in Pakistan, defined as the number of obstetric deliveries compared to the number of medical specialists, nurses, and other health and non‐health staff members. Second, the study evaluates the relationship between efficiency and quality of care; the latter is measured in terms of maternal and neonatal mortality.

Materials & Methods

The data were taken from the Pakistan Health Facility Assessment Survey. Efficiency score was calculated for 843 public healthcare facilities, using Stochastic Frontier Analysis. We then used two‐stage residual inclusion approach with bootstrapping to evaluate the relationship between efficiency and quality.

Results and Discussion

The average efficiency score was 0.48 (range: 0–1) and none of the public healthcare facilities were on the frontier, implying that efficiency gains can be made across the board. The relationship between efficiency and quality is found to be positive and statistically significant, that is, more efficient healthcare facilities also had lower rates of maternal and neonatal mortality.

Conclusion

We conclude that more efficient public healthcare facilities also had lower mortality rates, probably due to better infrastructure and health system financing.
Polio amidst COVID‐19 in Pakistan: Ongoing efforts, challenges, and recommendations
Authors: Sahito Abdul Moiz , Saleem Aqsa , Javed Syed Owais , Farooq Minaam , Ullah Irfan , Hasan Mohammad Mehedi
Published: March 2022

Poliomyelitis is a crippling viral disease caused by poliovirus, a positive‐stranded RNA virus that is a serotype of Enterovirus C. Pakistan remains one of the countries in the world where poliomyelitis is still prevalent, posing an obstacle to global poliomyelitis eradication. With the commencement of the COVID‐19 pandemic, polio eradication campaigns have proven less feasible, resulting in an increase in polio cases across the country. Pakistan's healthcare system and socio‐economic framework are incapable of dealing with two deadly viruses at the same time. As a result, effective measures for combating the destruction caused by the spread of the poliovirus are required.
Immersion optical clearing of adipose tissue in rats: ex vivo and in vivo studies
Authors: Yanina Irina Yu. , Tanikawa Yohei , Genina Elina A. , Dyachenko Polina A. , Tuchina Daria K. , Bashkatov Alexey N. , Dolotov Leonid E. , Tarakanchikova Yana V. , Terentuk Georgy S. , Navolokin Nikita A. , Bucharskaya Alla B. , Maslyakova Galina N. , Iga Yasunobu , Takimoto Shinichi , Tuchin Valery V.
Published: March 2022

Optical clearing (OC) of adipose tissue has not been studied enough, although it can be promising in medical applications, including surgery and cosmetology, for example, to visualize blood vessels or increase the permeability of tissues to laser beams. The main objective of this work is to develop technology for OC of abdominal adipose tissue in vivo using hyperosmotic optical clearing agents (OCAs). The maximum OC effect (77%) was observed for ex vivo rat adipose tissue samples exposed to OCA on fructose basis for 90 minutes. For in vivo studies, the maximum effect of OC (65%) was observed when using OCA based on diatrizoic acid and dimethylsulfoxide for 120 minutes. Histological analysis showed that in vivo application of OCAs may induce a limited local necrosis of fat cells. The efficiency of OC correlated with local tissue damage through cell necrosis due to accompanied cell lipolysis
Effect of Denosumab Compared With Risedronate on Bone Strength in Patients Initiating or Continuing Glucocorticoid Treatment
Authors: Geusens Piet , Bevers Melissa SAM , van Rietbergen Bert , Messina Osvaldo D , Lespessailles Eric , Oliveri Beatriz , Chapurlat Roland , Engelke Klaus , Chines Arkadi , Huang Shuang , Saag Kenneth G , van den Bergh Joop P
Published: March 2022

In a randomized clinical trial in patients initiating glucocorticoid therapy (GC-I) or on long-term therapy (GC-C), denosumab every 6 months increased spine and hip bone mineral density at 12 and 24 months significantly more than daily risedronate. The aim of this study was to evaluate the effects of denosumab compared with risedronate on bone strength and microarchitecture measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) in GC-I and GC-C. A subset of 110 patients had high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the distal radius and tibia at baseline and at 12 and 24 months. Cortical and trabecular microarchitecture were assessed with standard analyses and failure load (FL) with micro-finite element analysis. At the radius at 24 months, FL remained unchanged with denosumab and significantly decreased with risedronate in GC-I (−4.1%, 95% confidence interval [CI] −6.4, −1.8) and, in GC-C, it significantly increased with denosumab (4.3%, 95% CI 2.1, 6.4) and remained unchanged with risedronate. Consequently, FL was significantly higher with denosumab than with risedronate in GC-I (5.6%, 95% CI 2.4, 8.7, p < 0.001) and in GC-C (4.1%, 95% CI 1.1, 7.2, p = 0.011). We also found significant differences between denosumab and risedronate in percentage changes in cortical and trabecular microarchitectural parameters in GC-I and GC-C. Similar results were found at the tibia. To conclude, this HR-pQCT study shows that denosumab is superior to risedronate in terms of preventing FL loss at the distal radius and tibia in GC-I and in increasing FL at the radius in GC-C, based on significant differences in changes in the cortical and trabecular bone compartments between treatment groups in GC-I and GC-C. These results suggest that denosumab could be a useful therapeutic option in patients initiating GC therapy or on long-term GC therapy and may contribute to treatment decisions in this patient population. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
7‐chloroquinoline‐chalcone/‐pyrazoline conjugates: Synthesis, antimycobacterial and cytotoxic activities
Authors: Kumar Sumit , Saini Anu , Kumar Ankush , Raj Raghu , Kumar Vipan
Published: March 2022

A series of 1H‐1,2,3‐triazole linked 7‐chloroquinoline‐chalcones and 7‐chloroquinoline‐pyrazolines were synthesized using 1,3‐dipolar cycloaddition and evaluated for their antimycobacterial and cytotoxic activities. The compound having O‐methoxy substituent on ring A and p‐methoxy on ring B along with pyrazoline ring exhibited moderate activity and was noncytotoxic.
Novel High‐Speed Elongation Rheometer
Authors: Bier Alexander M. , Arne Walter , Schubert Dirk W.
Published: March 2022

The elongational viscosity of polymers can be determined by utilizing different devices such as extensional rheometer after Sentmanat (SER), oil bath rheometer after Meissner or tensile rheometer after Münstedt (MTR), with strain rates up to 10 s–1. Although these investigations are already complex, they do not depict real fiber spinning processes where higher elongation strain rates occur. Therefore, a novel method is developed to calculate the elongational viscosity of polymers during the fiber spinning process. To reduce the complexity of the system, two polymethylmethacrylates (PMMAs) with different molar masses are investigated using a capillary rheometer to exclude crystallization effects. The diameter of the polymeric strand is determined via a high‐speed camera from the die exit to the aspirator. In addition, simulations are carried out to describe the temperature profile of the polymeric strand along the spinline. It is possible to determine the elongational viscosity of the polymers in dependence of temperature and strain rates up to 100 s–1, by calibration of the force in an aerodynamic stretching device (aspirator).
Current Strategies in Breast Cancer Therapy: Role of Epigenetics and Nanomedicine
Authors: Sengupta Pallav , Choudhury Hira , Dutta Sulagna , Jacob Shery , Kesharwani Prashant , Gorain Bapi
Published: March 2022

Breast cancer (BC), the most common cancer in women, is incurable due to metastatic spread to distant organs. The existence of epigenetic dysregulation has been shown to contribute to the progression and even metastasize through the transition from epithelial to mesenchymal. Behind failure strategies of conventional treatments, fruitful outcomes of epigenetic drugs have provided the hope of solid tumor management where the reversal of acquired resistance of the cancer cells is possible by epigenome regulation. Several agents have been identified to target epigenetic regulators in the cancer cells exhibiting remarkable potential against solid tumors, including BC. However, unnecessary systemic exposure, solubility issues, and unsuitability for diseased conditions using conventional delivery systems limit their use as cancer therapeutics. The progression of nanotechnology in pharmaceutical delivery has revolutionized cancer therapy, where specific, targeted and efficient delivery of epigenetic agents for alteration of cancerous conditions are ensured. In this review, a focus is made on epigenetic alteration in BC condition with the deliverable potential of the nanocarriers toward the breast tumor microenvironment for proper management. The significance of targeting and controlled release of therapeutics in the improved targeting of cancer cells is highlighted.
Evaluation of a quasi‐dimeric eugenol derivative as repellent against the stored grain insect pest Sitophilusoryzae (Coleoptera Curculionidae)
Authors: Abenaim Linda , Mandoli Alessandro , Venturi Francesca , Bedini Stefano , Conti Barbara
Published: March 2022

BACKGROUND

Essential oils (EOs) and their chemical components are often proposed as an alternative to synthetic pesticides for pest control of foodstuff insect pests. However, their low persistence and strong, spicy odour, make them poorly suitable for use to protect food. Modification of the EOs components molecules increases their molecular weight and reduce their volatility. However, the effectiveness of such modified molecules has, so far, not been tested against stored food insect pests. In this study, the intensity and the duration of the repellence against the insect pest Sitophilus oryzae of a recently synthesized quasi‐dimeric eugenol derivative (ED) (C18H20O4) were compared to those of eugenol and three eugenol related compounds. The hypothesis tested was that by its higher molecular weight and two functional groups the ED would overcome the low persistence and strong and spicy odour drawback of eugenol without compromising the repellence against insects.

RESULTS

The insect behavioural tests showed a greater repellence and persistence of ED than eugenol and the three eugenol related compounds against S. oryzae. The sensory analysis of ED by panel test indicated that ED is significantly less odorous than eugenol without any spicy nor balsamic nuances in its smell profile.

CONCLUSIONS

Because of its high repellence against insects and its low smell intensity for humans, ED could represent a valid repellent for the control of foodstuffs insect pests. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.