bluuebunny/crossref_metadata_2025 huggingface dataset:
Circ_0002131 contributes to LPS-induced apoptosis, inflammation and oxidative injury in HK-2 cells via inhibiting the binding between miR-942-5p and OXSR1
Authors: Zhang Pengjie , Yin Jian , Xun Liru , Ding Tong , Du Shuangkuan
Published: August 2023

Background

Circular RNAs (circRNAs) are implicated in the progression of sepsis-associated acute kidney injury (AKI). Circ_0002131 was shown to aggravate cell inflammation and oxidative stress in sepsis-induced AKI. The aim of this study was to investigate the role and underlying mechanism of circ_0002131 in sepsis-induced AKI.

Methods

Cell Counting Ki-8 assay was used for cell viability detection. Cell apoptosis was measured using flow cytometry. Circ_0002131, microRNA-942-5p (miR-942-5p) and oxidative stress responsive 1 (OXSR1) level analysis was performed through reverse transcription-quantitative polymerase chain reaction assay. The protein levels were examined by western blot. Inflammatory factors were determined using Enzyme-linked immunosorbent assay. Oxidative injury was assessed via commercial kits. Target relation was analyzed by dual-luciferase reporter assay and RNA immunoprecipitation assay.

Results

HK-2 cell viability was suppressed and apoptosis was enhanced by LPS. Circ_0002131 was highly expressed in LPS-treated HK-2 cells and sepsis-induced AKI patients. LPS-induced apoptosis, inflammation and oxidative injury of HK-2 cells were attenuated after silence of circ_0002131. Then, miR-942-5p was identified as a target for circ_0002131, and the regulation of circ_0002131 in LPS-induced cell injury was ascribed to reduce miR-942-5p level. Additionally, circ_0002131 targeted miR-942-5p to elevate OXSR1 expression. MiR-942-5p prevented LPS-evoked HK-2 cell injury via targeting OXSR1.

Conclusion

All results demonstrated that circ_0002131 promoted LPS-mediated HK-2 cell injury via miR-942-5p-mediated upregulation of OXSR1, suggesting that circ_0002131/miR-942-5p/OXSR1 axis was related to sepsis-induced AKI progression.
Yersinia pseudotuberculosis Bacteremia with Splenic Abscesses: A Case Report
Authors: Zewude Rahel Tefera , Stefanovic Aleksandra , Alem Zersenay
Published: August 2023

Introduction:
Yersinia pseudotuberculosis has been known to cause a variety of clinical manifestations ranging from mild enteric illness to bacteremia with septic shock and extraintestinal abscesses. Patients with liver disease and iron overload are at risk of more severe disease manifestations.
Case Report:
A middle aged male with chronic alcohol use disorder presented with confusion and jaundice with ascites and asterixis noted on exam.  His blood work was remarkable for neutrophilic leukocytosis, elevated liver enzymes and lactate. His abdominal CT revealed splenic microabscesses and a cirrhotic liver. Yersinia pseudotuberculosis was recovered from his blood cultures and he was treated with ceftriaxone following susceptibility results.
Conclusion:
Y. pseudotuberculosis should be considered in the differential diagnosis of splenic or other extraintestinal microabscesses particularly in patients with chronic liver disease.
Diagnostic performance of LumiraDx SARS-CoV-2 rapid antigen test compared to PCR for diagnosis of COVID-19 in Liberia
Authors: Badio Moses , Lindan Christina , Johnson Kumblytee , Reilly Cavan , Blie Julie , Shaw-Saliba Katy , Fayiah Tamba , McCullough John , Duworko J. Tanu , Higgs Elizabeth , Martin Jeffrey , Hensley Lisa
Published: August 2023

Background

Diagnosis of SARS-CoV-2 infection in Liberia has primarily relied on polymerase chain reaction (PCR)-based testing at the country’s National Reference Laboratory. This centralized approach caused reporting delays, prompting evaluation of point-of-care antigen-based tests. We assessed the test performance of the LumiraDx™ SARS-CoV-2 Ag test (LumiraDx™, London, UK) in this setting.

Methods

We tested ambulatory individuals screened for enrollment into an observational cohort study of COVID-19 sequelae in Monrovia in 2021. We compared the results of LumiraDx testing of anterior nasal swab specimens to the results of PCR BioFire® R2.1P (bioMérieux, Salt Lake City, Utah) on eluent from nasopharyngeal swabs.

Results

We evaluated 348 individuals. Among the 274 persons with symptoms, 49.3% were PCR-positive and 36.5% were antigen-positive. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of LumiraDx in this group were 72.6% (95% CI: 64.3%-79.9%), 98.6% (95% CI: 94.9%-99.8%), 78.7% (CI: 71.9%-84.6%), and 98.0% (CI: 93.0%-99.8%), respectively. Among the 74 asymptomatic individuals, 12.2% were positive by PCR, and 5.5% by antigen testing, resulting in a sensitivity, specificity, NPV, and PPV of LumiraDx of 44.4% (95% CI: 13.7%-78.8%), 100% (95% CI: 94.5%-100%), 92.9% (CI: 84.1%-97.6%), and 100% (CI: 39.8%-100%), respectively.

Conclusion

Although the specificity and PPV of LumiraDx for diagnosing SARS-CoV-2 were high among persons with and without symptoms, the sensitivity was unacceptably low in both groups, and much less than that reported by the manufacturer. Before new point-of-care diagnostics are adopted, test performance needs to be assessed in the local setting.
DNA tetrahedron as a carrier of doxorubicin for metastatic breast cancer treatment
Authors: Vaswani Payal , Hema Naveena A , Kansara Krupa , Dahle Landon , Kumar Ashutosh , Bhatia Dhiraj
Published: August 2023

Metastatic breast cancer is a significant clinical challenge calling for novel and efficient therapeutic approaches. DNA tetrahedron, a highly programmable nanocage, offers some promising attributes including biocompatibility, stability, and functionalization making it an attractive candidate for drug delivery. In this study, we have explored the potential of DNA tetrahedron as a carrier of doxorubicin, a DNA and RNA synthesis-inhibiting chemotherapy drug. We have encapsulated doxorubicin in DNA tetrahedron (TD: Dox) and subsequently focused on metastatic breast cancer cells for the effect of the same. We showed that TD: Dox has the potential to inhibit the migration of cancerous cells in the 2D model and inhibit the invasion of tumor cells in the 3D model as well. This system also can be uptaken inin vivozebrafish model as well. Overall, this study promises the TD: Dox system as an ideal drug delivery model and a viable approach for metastatic breast cancer treatment.
Evaluation of Loop-Mediated Isothermal Amplification (LAMP) for Rapid Detection ofCampylobacter jejuni
Authors: Caro-Castro Junior , Orellana-Peralta Fiorella , Flores-Leon Diana , Cuch-Meza Evans , Gavilán Ronnie G. , Quino Willi
Published: August 2023

In recent years, the worldwide incidence of diarrheal diseases caused byCampylobacter jejunihas been increasing, causing large-scale outbreaks in developing countries, which added to the capacity of the microorganism to cause Guillain-Barré syndrome (GBS), increasing the need for rapid and timely diagnosis to stop and prevent outbreaks. In this study, a loop-mediated isothermal amplification (LAMP) assay based on thecdtCgene was developed and evaluated for the rapid detection ofC. jejuni, using 91 strains for the standardization and validation. The LAMP assay was compared to whole-genome sequencing as the gold standard. The LAMP assay forC. jejunishowed a sensitivity of 100% (CI: 90.94 - 100%), a specificity of 100% (CI: 89.56 - 100%), a positive predictive value of 100% (CI: 90.94 - 100%) and a negative predictive value of 100% (CI: 89.56 - 100%). The assay demonstrated strong agreement between the LAMP assay and genomic sequencing (kappa value = 1). The LAMP assay based on thecdtCgene is a method that provides reliable and rapid results, with high sensitivity and specificity for the identification ofC. jejuni, and is considered a suitable alternative for the diagnosis of diarrheal infections by this pathogen in low-income countries.
Nutrient levels control root growth responses to high ambient temperature in plants
Authors: Lee Sanghwa , Showalter Julia , Zhang Ling , Cassin-Ross Gaëlle , Rouached Hatem , Busch Wolfgang
Published: August 2023

Global warming will lead to significantly increased temperatures on earth. Plants respond to high ambient temperature with altered developmental and growth programs, termed thermomorphogenesis. Here we show that thermomorphogenesis is conserved in Arabidopsis, soybean, and rice and that it is linked to a decrease in the levels of the two macronutrients nitrogen and phosphorus. We also find that low external levels of these nutrients abolish root growth responses to high ambient temperature. We show that in Arabidopsis, this is due to the function of the transcription factorELONGATED HYPOCOTYL 5(HY5) and its transcriptional regulation of the transceptorNITRATE TRANSPORTER 1.1(NRT1.1). Soybean and Rice homologs of these genes are expressed consistently with a conserved role in regulating temperature responses in a nitrogen and phosphorus level dependent manner. Overall, our data show that root thermomorphogenesis is a conserved feature in species of the two major groups of angiosperms, monocots and dicots, that it leads to a reduction of nutrient levels in the plant, and that it is dependent on sufficient environmental nutrient supply, a regulatory process mediated by the HY5-NRT1.1 module.
Unlocking Predictive Power: A Machine Learning Tool Derived from In-Depth Analysis to Forecast the Impact of Missense Variants in Human Filamin C
Authors: Nagy Michael , Mlynek Georg , Kostan Julius , Smith Luke , Pühringer Dominic , Charron Philippe , Rasmussen Torsten Bloch , Bilinska Zofia , Akhtar Mohammed Majid , Syrris Petros , Lopes Luis R , Elliott Perry M , Gautel Mathias , Carugo Oliviero , Djinović-Carugo Kristina
Published: August 2023

Cardiomyopathies, diseases of the heart muscle, are a leading cause of heart failure. An increasing proportion of cardiomyopathies have been associated with specific genetic changes, such as mutations inFLNC, the gene that codes for filamin C. Altogether, more than 300 variants ofFLNChave been identified in patients, including a number of single point mutations. However, the role of a significant number of these mutations remains unknown. Here, we conducted a comprehensive analysis, starting from clinical data that led to identification of new pathogenic and non-pathogenicFLNCvariants. We selected some of these variants for further characterization that included studies ofin vivoeffects on the morphology of neonatal cardiomyocytes to establish links to phenotype, and thein vitrothermal stability and structure determination to understand biophysical factors impacting function. We used these findings to compile vast datasets of pathogenic and non-pathogenic variant structures and developed a machine-learning-based neural network (AMIVA-F) to predict the impact of single point mutations. AMIVA-F outperformed most commonly used predictors both in disease related as well as neutral variants, approaching ∼80% accuracy. Taken together, our study documents additionalFLNCvariants, their biophysical and structural properties, and their link to the disease phenotype. Furthermore, we developed a state-of-the-art web-based server AMIVA-F that can be used for accurate predictions regarding the effect of single point mutations in human filamin C, with broad implications for basic and clinical research.
Utilizing Heteroatom Types and Numbers from Extensive Ligand Libraries to Develop Novel hERG Blocker QSAR Models Using Machine Learning-based Classifiers
Authors: Haddad Safa , Oktay Lalehan , Erol Ismail , Şahin Kader , Durdagi Serdar
Published: August 2023

The human Ether-à-go-go Related Gene (hERG) channel plays a crucial role in membrane repolarization. Any disruptions in its function can lead to severe cardiovascular disorders like long QT syndrome (LQTS), which increases the risk of serious cardiovascular problems such as tachyarrhythmia and sudden cardiac death. Drug-induced LQTS is a significant concern and has resulted in drug withdrawals in the past. The main objective of this research study is to pinpoint crucial heteroatoms present in ligands that initiate interactions leading to effective blocking of the hERG channel. To achieve this aim, ligand-based quantitative structure-activity relationships (QSAR) models were constructed using extensive ligand libraries, considering the heteroatom types and numbers, and their associated hERG channel blockage pIC50values. Machine learning-assisted QSAR models were developed to analyze the key structural components influencing compound activity. Among various methods, the KPLS method proved to be the most efficient, allowing the construction of models based on eight distinct fingerprints. The study delved into investigating the influence of heteroatoms on the activity of hERG blockers, revealing their significant role. Furthermore, by quantifying the effect of heteroatom types and numbers on ligand activity at the hERG channel, six compound pairs were selected for molecular docking. Subsequent molecular dynamics (MD) simulations and MM/GBSA calculations per residue were performed to comprehensively analyze the interactions of the selected pair compounds.
Large-scale population genomics of Malayan pangolins reveals deep diversification and a new species
Authors: Li Bo , Lan Tianming , Wang Qing , Shi Minhui , Guo Ce , Li Haimeng , Liu Boyang , Liu Shanlin , Finch Kristen , Wang Shiqing , Yang Shangchen , Cui Liangyu , Li Jun , Zhao Xilong , Wang Jiangang , Deng Zhangwen , Wang Xinyu , Ma Yue , Kim Hyeon Jeong , Wasser Samuel K , Wang Kai , Lu Haorong , Yang Dongyi , Chen Jin , Guo Huabing , Yao Yan , Xie Hui , Wang Yiyi , Fan Jiale , Li Wangsheng , Niu Xiaotong , Hou Yinmeng , Yu Jieyao , Lu Jinyao , Li Siyuan , Qiu Zhaowen , Zhang Wei , Bai Suying , Han Lei , Wu Yuxin , Cai Xianchu , Huang Yunting , Wang Zhen , Wang Chen , Li Jiahao , Jiang Yuze , Liu Shasha , Wang Jiayi , Li Li , Hua Yan , Liu Huan , Xu Yanchun
Published: August 2023

Background

Archipelagos and oceanic islands often present high percentage of endemism due to rapid speciation. The Malayan pangolin is a species distributing at both mainland (southern Yunnan, China) and oceanic islands via Malayan peninsula, which may result in deep differentiation among populations. In-depth investigation of population structure and genetic consequences for such species is of vital importance for their protection and conservation, practically for the critically endangered Malayan pangolin that is suffering from poaching, illegal trade, and habitat loss.

Results

Here we carried out a large-scale population genomic analysis for Malayan pangolins, and revealed three highly distinct genetic populations in this species, two of which are now being reported for the first time. Based on multiple lines of genomic and morphological evidence, we postulate the existence of a new pangolin species (Manis_1). Genetic diversity and recent inbreeding were both at a moderate level for both Malayan pangolins andManis_1, but mainland Malayan pangolins presented relatively lower genetic diversity, higher inbreeding and fitness cost than island populations.

Conclusions

We found extremely deep and graded differentiation in Malayan pangolins, with two newly discovered genetic populations and a new pangolin species that is closely related to the Philippine pangolin than the typical Malayan pangolin, but a distant relative of the Indian pangolin. Anthropogenic factors did not significantly weaken the basis of genetic sustainability for Malayan pangolins, but mainland Malayan pangolins should be paid more attention for conservation due to higher genetic risks than island populations.
Assemblies, synapse clustering and network topology interact with plasticity to explain structure-function relationships of the cortical connectome
Authors: Ecker András , Egas Santander Daniela , Abdellah Marwan , Blanco Alonso Jorge , Bolaños-Puchet Sirio , Chindemi Giuseppe , Gowri Mariyappan Dhuruva Priyan , Isbister James B. , King James Gonzalo , Kumbhar Pramod , Magkanaris Ioannis , Muller Eilif B. , Reimann Michael W.
Published: August 2023

Synaptic plasticity underlies the brain’s ability to learn and adapt. While experiments in brain slices have revealed mechanisms and protocols for the induction of plasticity between pairs of neurons, how these synaptic changes are coordinated in biological neuronal networks to ensure the emergence of learning remains poorly understood. Simulation and modeling have emerged as important tools to study learning in plastic networks, but have yet to achieve a scale that incorporates realistic network structure, active dendrites, and multi-synapse interactions, key determinants of synaptic plasticity. To rise to this challenge, we endowed an existing large-scale cortical network model, incorporating data-constrained dendritic processing and multi-synaptic connections, with a calcium-based model of functional plasticity that captures the diversity of excitatory connections extrapolated toin vivo-like conditions. This allowed us to study how dendrites and network structure interact with plasticity to shape stimulus representations at the microcircuit level. In our exploratory simulations, plasticity acted sparsely and specifically, firing rates and weight distributions remained stable without additional homeostatic mechanisms. At the circuit level, we found plasticity was driven by co-firing stimulus-evoked functional assemblies, spatial clustering of synapses on dendrites, and the topology of the network connectivity. As a result of the plastic changes, the network became more reliable with more stimulus-specific responses. We confirmed our testable predictions in the MICrONS datasets, an openly available electron microscopic reconstruction of a large volume of cortical tissue. Our results quantify at a large scale how the dendritic architecture and higher-order structure of cortical microcircuits play a central role in functional plasticity and provide a foundation for elucidating their role in learning.
Value co-creation in a high-performance computing (HPC) service ecosystem: opportunities for European SMEs
Authors: Bhattacharya Suman , Damij Nadja
Published: August 2023

Purpose

This paper aims to develop a conceptual framework as a valuable investigative tool for future empirical studies examining stakeholders’ interactions within a high-performance computing (HPC) service ecosystem and identifying the enablers for better value co-creation under various service provisioning contexts.

Design/methodology/approach

This conceptual paper follows a theory adaptation research design that systematically examines the literature on a substantive topic encompassing HPC technology adoption and usage by European small and medium-sized enterprises (SMEs). Furthermore, it introduces theoretical perspectives from service innovation research as its methodological approach (method theory) to develop a theoretical framework for value co-creation within an HPC service ecosystem.

Findings

The conceptual framework presented in this paper identifies the critical resource elements of SMEs, which can potentially be integrated with other stakeholders’ resources and complement the limited internal resources of SMEs for enhanced value co-creation within an HPC service ecosystem.

Research limitations/implications

The conceptualisation of an HPC service ecosystem and the potential of value co-creation through integrating stakeholders’ resources, presented in this paper, underscore further empirical research in this direction.

Practical implications

Findings from this paper can inform European policymakers for regional development to frame regional strategies and policies that enable SMEs to better uptake HPC services. Service providers can revisit their business models to reconfigure their organisational resources for enhanced value proposition and co-creation.

Social implications

This study advances the agenda of transformative service research that aims uplifting changes and societal well-being through a more inclusive and sustainable value co-creation among a wider set of stakeholders within the service ecosystem.

Originality/value

The paper addresses an under-investigated research gap by examining SMEs’ adoption of HPC services and opportunities for higher value co-creation using a service ecosystem approach based on multi-actor interaction, collaboration and resource integration.
CLIP’s performance indicators: towards a SMART orientation
Authors: Sharma Tanushree , Nidhi Nidhi , Chakravorty Arjun
Published: August 2023

Learning outcomes

This case aims to enhance students’ scholarship and understanding of performance management systems with respect to the formulation of key performance indicators (KPIs). Specifically, working through this case and the assignment questions, students will be able to:▪ critically analyse process-based and outcome-based performance indicators;▪ recommend the right mix of process- and the outcome-based KPIs;▪ apply the specific, measurable, aligned, realistic and time-bound (SMART) framework to the KPIs;▪ create SMART KPIs; and▪ propose when to involve team members in decision-making.

Case overview/synopsis

The Director of the Centre for Learning and Innovative Pedagogies (CLIP), Dr Tanushree Sharma, was in for a surprise when the Dean and the Advisor to the school expressed their dissatisfaction with her approach to framing performance indicators for the management of the Centre.

They categorically advised her to change her process-based orientation to an outcome-based one and create tangible ground-level outcomes. Their feedback made her realize why, in spite of having rolled out several initiatives, the Centre was struggling to demonstrate its impact on student learning and faculty development. It dawned on her that the Centre’s inability to showcase a tangible impact on the school could mar the collective hard toil of the team.

Accepting the feedback and recognizing the merit of designing outcome-based SMART performance indicators, she started working towards them. Although she was able to conceptualize a broad framework, she was uncertain about whether to include only outcome-based KPIs. She was also unsure whether to unilaterally create and assign the key responsibility areas (KRAs) and KPIs or co-create them with her team members. A confluence of factors weighed heavily on her mind – the pressure of limited time, remote working because of the pandemic, moderately experienced team members, voluntary team membership, lack of positional power and her limited organizational influence. With less than a month to the proposal submission, she had no time to waste.

Complexity academic level

The case is suitable for courses on performance management systems, human resources and leadership; however, it is particularly relevant to framing KRAs and KPIs, developing outcome-based KPIs and applying the SMART framework to developing KPIs. It can be used in both postgraduate and undergraduate programmes at business schools.

Supplementary material

Teaching notes are available for educators only.

Subject code

CSS 6: Human Resource Management.
Fractal model of thermal contact conductance of rough surfaces considering substrate deformation
Authors: Sun Xianguang
Published: August 2023

Purpose

The purpose of this study is to propose a fractal model of thermal contact conductance (TCC) of rough surfaces considering substrate deformation. Three deformation modes of the asperity of the rough surface are considered, including elastic deformation, elastic–plastic deformation and full plastic deformation.

Design/methodology/approach

The influences of contact load, fractal dimension and fractal roughness on the TCC of the rough surface were studied.

Findings

The results show that the TCC of the rough surface increases with the increase of contact load. When D > 2.5, the larger the fractal dimension, the higher the increased rate of the TCC of the rough surface with the increase of contact load. The TCC of the rough surface increases with the increase of fractal dimension and decreases with the increase of fractal roughness. The TCC of the rough surface can be achieved by selecting a contact surface with roughness.

Originality/value

A fractal model of TCC of rough surfaces considering substrate deformation was established in this study. The achievements of this study provide some theoretical basis for the investigation of TCC of rough surfaces.
Does a mix of plant‐based dietary fibre affect milk protein true digestibility? An in‐vivo study
Authors: Arora Simran Kaur
Published: August 2023

Milk protein is easily digestible. However, some plant‐based dietary fibres (DF) could impact protein bioavailability. The effect of DF fortification on the true protein digestibility (TPD) of milk was evaluated following the rat balance method. Four groups of rats were fed four different diets. Three diets comprised milk protein as a source of protein along with either DF Blend I (a mix of psyllium husk, oat fibre, microcrystalline cellulose and inulin) or Blend II (psyllium husk, oat bran, wheat fibre and inulin) or cellulose (as control). The fourth group was nitrogen‐free with cellulose (5%). The TPD of milk remained statistically unaffected (ANOVA, P > 0.05), indicating that DF blends are suitable for milk fortification.
Time to Include Blue Carbon from Seaweed in Voluntary Carbon Removal Certification
Authors: van den Burg Sander , Koch Sophie , Raoult Justine , Tsvetkov Bobby , Selnes Trond
Published: August 2023

The EU has proposed a voluntary framework for certification of carbon removals which remains vague on blue carbon and in particular, carbon removal through use of seaweeds. Seaweed is considered an emerging blue carbon option. Various studies have confirmed the potential of seaweed to contribute to long‐term carbon removal, storing it away from the atmosphere for 100 years and more. Certification of seaweed carbon sequestration is promoted, even in other EU communications. This article reviews early experiences with certification of carbon and nutrient removal by aquaculture using the QU.A.L.ITY criteria proposed by the EU. Examples reviewed include the Seaweed Company, Venice Bay, Yokohama Bayside marine, and Chesapeake Bay in the USA. After reviewing these examples, we call on the European Commission to move forward towards certification of blue carbon. If the EU is to lead global climate mitigation efforts, including carbon removal, it should take seaweed blue carbon seriously and include it in its voluntary framework. To enhance the awareness of the relevance and the acceptance of the carbon credits from seaweed, a methodology has to be developed that, building on experiences gained, deals with inherent uncertainties.
Recent advances in extending the shelf life of fresh wet noodles: Influencing factors and preservation technologies
Authors: Obadi Mohammed , Li Yuntong , Xu Bin
Published: August 2023

Fresh wet noodles (FWNs) are popular among people and have attracted increasing attention because of their characteristics of freshness, chewiness, good taste, and better maintenance of noodle flavor. However, due to the high moisture content and abundance of nutrients in FWN, they are prone to spoilage, which shortens their shelf life and reduces their quality, greatly restricting their large‐scale production. Therefore, seeking effective preservation methods to prolong the shelf life is a major breakthrough for the industrialization of FWN. The present review provides a comprehensive overview of the main factors that contribute to the spoilage and degradation of FWN. These factors encompass microorganisms, moisture content, nutritional composition, enzymes, and storage temperature. Moreover, the recent developments in novel shelf‐life extension technology applied to FWN, such as chemical preservatives, natural preservatives, physical treatment technologies, and composite preservation technology, are presented and discussed. From the literature reviewed, the application of technologies, such as adding preservatives, modified atmosphere packaging, microwave, cold plasma, ozone, and other technologies, has a certain effect on improving the shelf life of FWN, but the single preservation technology still has some deficiencies. In order to further improve the preservation efficiency, using two or more preservation methods is an important direction for future research on the preservation technology of FWN.
Audit of surgeon billing in workers compensation‐insured elective spinal surgery in New South Wales, Australia from 2010 to 2018
Authors: Lewin Adriane M. , Naylor Justine M. , Sheridan Mark , Harris Ian A.
Published: August 2023

Background

Medical billing practices have received increasing scrutiny in Australia and worldwide. In 2015, the Australian Government initiated a comprehensive review of the Medicare Benefits Schedule (MBS), including spinal surgery. This study provides a snapshot of five spinal surgeon billing patterns and associated costs in the workers compensation system in New South Wales prior to these changes.

Methods

This retrospective cohort study used workers compensation billing data from the State Insurance Regulatory Authority to capture elective spinal surgeries in New South Wales from 2010 to 2018. The main outcome measures were: proportion of items billed within recommended limits (up to 150% of the listed Australian Medical Association (AMA) fee); surgical billing patterns including repeat billing of items during a single episode of surgery; use of paediatric or scoliosis items; use of surgical items from outside the spinal surgery schedule; co‐billing of items not permitted as per the AMA Fees List item descriptions and associated costs.

Results

There were 12 622 spinal surgeries in 9520 patients. While only 2.2% of items were billed above the recommended limits, 38% of surgeries included at least one of the five billing patterns. The average cost increase was AU$4700 per surgery, 47% greater than surgeries which did not include the specified billing patterns, for a total additional cost of AU$22.9 M over the 9‐year study period.

Conclusion

Five spinal surgery billing patterns accounted for an additional AU$22.9 million in direct surgical costs from 2010 to 2018.
Hypothermia and adverse outcomes during the transfer of extremely low birth weight infants
Authors: Ogunna Uche , Mohinuddin Syed , Ratnavel Nandiran , Greenough Anne , Dassios Theodore
Published: August 2023

Aim

We aimed to explore whether hypothermia during the transfer of extremely low birth weight (ELBW) infants was associated with increased morbidity and mortality.

Methods

Retrospective cohort study of transfers of ELBW infants by the London Neonatal Transfer Service between April 2015 and January 2017. Hypothermia was defined as an axillary temperature below 36.5°C.

Results

Hypothermia was recorded in 36–47% of the 146 transfers depending on the time point of measurement from admission at the referring unit to admission at the receiving unit. Infants with hypothermia had a lower gestational age [25.1 (24.1–26.6) versus 26.0 (25.3–27.0) weeks, p < 0.001], birth weight [750 (600–830) versus 800 (730–885) gr, p = 0.004) and age at referral [1 (0.8–3) versus 1.5 (1–4) hours, p = 0.049] compared to infants without hypothermia. Infants with hypothermia had a longer median (IQR) duration of invasive ventilation [22(6–44) days] compared to infants without hypothermia [10 (4–21) days, p = 0.002]. Infants with hypothermia had a higher incidence of a patent ductus arteriosus and mortality before discharge from neonatal care compared to infants without hypothermia (79% vs. 27%, p = 0.043 and 29% vs. 13%, p = 0.025, respectively).

Conclusion

Among ELBW infants, hypothermia during transfer was common, particularly in infants of lower gestational age. Hypothermia was associated with a longer duration of ventilation and increased mortality before discharge from neonatal care.
Validation of the Finnish version of the food allergy quality of life questionnaire–parent form (F‐FAQLQ‐PF)
Authors: Kivistö J. E. , de Blok B. Flokstra , Protudjer J. L. P. , Ojaniemi I. , Karjalainen J. , Huhtala H. , Dunn Galvin A.
Published: August 2023

Aim

Specific questionnaires about food allergy and health‐related quality of life (HRQoL) have been developed and validated in several languages, but not Finnish. We aimed to validate the Finnish Food Allergy Quality of Life Questionnaire‐Parent Form (FAQLQ‐PF) for children under age 13 years.

Methods

The original FAQLQ‐PF and Food Allergy Independent Measure (FAIM) were translated into Finnish per World Health Organisation guidelines and tested by 72 parents of children under age 13 years with suspected severe peanut or tree nut allergy who were recruited at Allergy Centre in Tampere University Hospital in Tampere, Finland. We calculated the construct validity of the questionnaire by calculating the coefficients between the two measures and used Cronbach's alpha to establish the internal consistency.

Results

The FAQLQ‐PF showed strong correlations with domain structure and internal consistency, based on Spearman's correlations (rho) for the HRQoL questions, FAIM questions and FAIM mean values. The total questionnaire score correlated significantly with the mean FAIM (rho = 0.95, p < 0.001) and individual FAIM questions. The FAQLQ‐PF and domains had good or excellent internal consistency (Cronbach's alpha >0.70).

Conclusion

The Finnish FAQLQ‐PF demonstrated good construct validity and excellent internal consistency for measuring food allergy HRQoL in children under age 13 years.
Changes in physical and mental health in Swedish schoolchildren in the digital age
Authors: Mossberg Karin , Möllborg Per
Published: August 2023

Aim

Poor physical and mental health are common and increasing in Swedish children. The aim was to investigate significant changes in health and digital habits in fourth grade and ninth grade pupils in 2020 compared to 2011.

Methods

A validated questionnaire was conducted in 2011 and 2020 among schoolchildren in fourth (10 years) and ninth grade (15 years) in Sweden. The study population consisted of 196 students in 2020 and 254 students in 2011.

Results

A significant increase was seen in self‐reported sleeping difficulties, tiredness, life dissatisfaction and dissatisfaction with academic abilities among fourth grade children and a sixfold increase in their refusal to go to school. Students in fourth grade also reported that they spent more time on social media and had a reduced interest in sports. Both students in fourth and ninth grade described an increase in attacks of anger and unhappiness, as well as decreased time with family.

Conclusion

We conclude that fourth grade children have more physical and mental health symptoms in 2020 compared to 2011. The ninth grade students showed a high frequency of physical and mental symptoms in 2011, which remained high in 2020. One possible explanation may be that digital habits have increased.
Renal arterial infusion of tempol prevents medullary hypoperfusion, hypoxia, and acute kidney injury in ovine Gram‐negative sepsis
Authors: Betrie Ashenafi H. , Ma Shuai , Ow Connie P. C. , Peiris Rachel M. , Evans Roger G. , Ayton Scott , Lane Darius J. R. , Southon Adam , Bailey Simon R. , Bellomo Rinaldo , May Clive N. , Lankadeva Yugeesh R.
Published: August 2023

Aim

Renal medullary hypoperfusion and hypoxia precede acute kidney injury (AKI) in ovine sepsis. Oxidative/nitrosative stress, inflammation, and impaired nitric oxide generation may contribute to such pathophysiology. We tested whether the antioxidant and anti‐inflammatory drug, tempol, may modify these responses.

Methods

Following unilateral nephrectomy, we inserted renal arterial catheters and laser‐Doppler/oxygen‐sensing probes in the renal cortex and medulla. Noanesthetized sheep were administered intravenous (IV) Escherichia coli and, at sepsis onset, IV tempol (IVT; 30 mg kg−1 h−1), renal arterial tempol (RAT; 3 mg kg−1 h−1), or vehicle.

Results

Septic sheep receiving vehicle developed renal medullary hypoperfusion (76 ± 16% decrease in perfusion), hypoxia (70 ± 13% decrease in oxygenation), and AKI (87 ± 8% decrease in creatinine clearance) with similar changes during IVT. However, RAT preserved medullary perfusion (1072 ± 307 to 1005 ± 271 units), oxygenation (46 ± 8 to 43 ± 6 mmHg), and creatinine clearance (61 ± 10 to 66 ± 20 mL min−1). Plasma, renal medullary, and cortical tissue malonaldehyde and medullary 3‐nitrotyrosine decreased significantly with sepsis but were unaffected by IVT or RAT. Consistent with decreased oxidative/nitrosative stress markers, cortical and medullary nuclear factor‐erythroid‐related factor‐2 increased significantly and were unaffected by IVT or RAT. However, RAT prevented sepsis‐induced overexpression of cortical tissue tumor necrosis factor alpha (TNF‐α; 51 ± 16% decrease; p = 0.003) and medullary Thr‐495 phosphorylation of endothelial nitric oxide synthase (eNOS; 63 ± 18% decrease; p = 0.015).

Conclusions

In ovine Gram‐negative sepsis, renal arterial infusion of tempol prevented renal medullary hypoperfusion and hypoxia and AKI and decreased TNF‐α expression and uncoupling of eNOS. However, it did not affect markers of oxidative/nitrosative stress, which were significantly decreased by Gram‐negative sepsis.
Potential therapeutic target secretogranin II might cooperate with hypoxia‐inducible factor 1α in sunitinib‐resistant renal cell carcinoma
Authors: Fukumoto Wataru , Yoshino Hirofumi , Horike Shin‐Ichi , Kawakami Issei , Tamai Motoki , Arima Junya , Kawahara Ichiro , Mitsuke Akihiko , Sakaguchi Takashi , Inoguchi Satoru , Meguro‐Horike Makiko , Tatarano Shuichi , Enokida Hideki
Published: August 2023

Multitargeted receptor tyrosine kinase inhibitors, including vascular endothelial growth factor (VEGF) inhibitors, such as sunitinib, have been used as the primary targeted agents for patients with recurrent or distant metastasis of advanced renal cell carcinoma (RCC). However, endogenous or acquired sunitinib resistance has become a significant therapeutic problem. Therefore, we focused on mechanisms of sunitinib resistance in RCC. First, we undertook RNA sequencing analysis using previously established sunitinib‐resistant RCC (SUR‐Caki1, SUR‐ACHN, and SUR‐A498) cells. The results showed increased expression of secretogranin II (SCG2, chromogranin C) in SUR‐RCC cells compared to parental cells. The Cancer Genome Atlas database showed that SCG2 expression was increased in RCC compared to normal renal cells. In addition, the survival rate of the SCG2 high‐expression group was significantly lower than that of the RCC low‐expression group. Thus, we investigated the involvement of SCG2 in sunitinib‐resistant RCC. In vitro analysis showed that migratory and invasive abilities were suppressed by SCG2 knockdown SUR cells. As SCG2 was previously reported to be associated with angiogenesis, we undertook a tube formation assay. The results showed that suppression of SCG2 inhibited angiogenesis. Furthermore, coimmunoprecipitation assays revealed a direct interaction between SCG2 and hypoxia‐inducible factor 1α (HIF1α). Expression levels of VEGF‐A and VEGF‐C downstream of HIF1α were found to be decreased in SCG2 knockdown SUR cells. In conclusion, SCG2 could be associated with sunitinib resistance through VEGF regulation in RCC cells. These findings could lead to a better understanding of the VHL/HIF/VEGF pathway and the development of new therapeutic strategies for sunitinib‐resistant RCC.
‘Once you bond … you want to create social change’: Interpersonal relationships in youth activism
Authors: Assan Thalia Thereza
Published: August 2023

This paper calls for greater attention to the interpersonal aspects of youth activism through a sociological and Black feminist exploration of peer relationships within youth political engagement. Drawing on a multi‐method qualitative research, the work foregrounds the perspectives and experiences of Black girls and girls of colour involved in an anti‐racist Scottish youth work charity. I argue that community and friendship ties cultivated participants' activism. Moreover, participants sought to enact social change by undertaking activist educational practices with their peers. This paper demonstrates how studying young people's peer relationships can engender a better understanding of youth activism and support it.
Clinical efficacy of transcrestal sinus floor augmentation, in comparison with lateral approach, in sites with residual bone height ≤6 mm: A systematic review and meta‐analysis
Authors: Shi Shaojie , Han Luyao , Su Jun , Guo Jianmei , Yu Fan , Zhang Wenyun
Published: August 2023

Objective

This paper addressed two focused questions: Focused question 1 (Q1) “what is the clinical efficacy of transcrestal sinus floor augmentation (TSFA), as compared to lateral sinus floor augmentation (LSFA) in sites with residual bone height (RBH) ≤6 mm, in randomized clinical trials (RCTs) and controlled clinical trials (CCTs)?”; Focused question 2 (Q2) “what is the estimated effectiveness of TSFA for outcomes in Q1, in RCTs, CCTs or cohort studies?”

Materials and Methods

An electronic search (PubMed, EMBASE, The Cochrane Central Register of Controlled Trials) and hand search were conducted from January 1986 until December 2022. All eligible clinical studies expressly reporting TSFA in sites with RBH ≤6 mm were included. The data were extracted, and the risk of bias in individual studies was evaluated. Meta‐analysis was performed whenever possible.

Results

Seven RCTs were included for Q1 and 25 studies (9 RCTs, 2 CCTs, 14 single arm cohort studies) for Q2. Q1: Meta‐analysis did not show significant difference in the implant survival, sinus membrane perforation and marginal bone loss between TSFA and LSFA groups. Q2: Meta‐analysis showed TSFA had a high implant survival rate (96.5%, 95% CI: 93.2%–98.9%) at least 1 year after surgery, and limited sinus membrane perforation (5.4%, 95% CI: 2.7%–8.8%). The results also presented higher patient satisfaction for TSFA.

Conclusion

With the limitations of the present study (high risk of bias in individual studies), it can be concluded that there was no significant difference in implant survival, Schneiderian membrane perforation and MBL between two approaches in sites with RBH ≤6 mm.
Long‐term cost‐effectiveness analysis of sacral neuromodulation in the treatment of severe faecal incontinence
Authors: de Miguel Valencia Mario J. , Cabasés Hita Juan M. , Sánchez Iriso Eduardo , Oteiza Martínez Fabiola , Alberdi Ibañez Iñaki , Álvarez López Alfonso , Ortiz Hurtado Héctor , de Miguel Velasco Mario J.
Published: August 2023

Aim

The aim of this study was to evaluate the long‐term cost‐effectiveness of sacral neuromodulation in the treatment of severe faecal incontinence as compared with symptomatic management.

Methods

In the public health field, a micro‐costing evaluation method was conducted from the perspectives of the health system and the society. The incremental cost‐effectiveness ratio was used as a decision index, and we considered various scenarios to evaluate the impact of the cost of symptomatic management and percutaneous nerve evaluation success rate in its calculation. Clinical data were retrieved from a consecutive cohort of 93 patients with severe faecal incontinence undergoing sacral neuromodulation after a failure of conservative (pharmacological and biofeedback) and/or surgical (sphincteroplasty) first‐line treatments were considered.

Results

The long‐term incremental cost‐effectiveness ratio comparing sacral neuromodulation versus symptomatic management was 14347€/QALY and 28523€/QALY from the societal and health service provider's perspectives, respectively. If the definitive pulse generator implant success rate was 100%, incremental cost‐effectiveness would correspond to 6831€/QALY and 16761€/QALY, respectively.

Conclusions

Sacral neuromodulation may be considered a cost‐effective technique in the long‐term treatment of severe faecal incontinence from the societal and health care sector perspectives. Improving patient selection and determining the predictive outcome factors for successful sacral neuromodulation in the treatment of faecal incontinence would improve cost‐effectiveness.
Chimeric antigen receptor T‐cell therapy in hematologic malignancies: Successes, challenges, and opportunities
Authors: Ho Matthew , Zanwar Saurabh , Paludo Jonas
Published: August 2023

The success of chimeric antigen receptor T‐cell (CAR‐T) therapy in hematologic malignancies has realized a longstanding effort toward harnessing the immune system to fight cancer in a truly personalized fashion. Second generation chimeric antigen receptors (CAR) incorporating co‐stimulatory molecules like 4‐1BB or CD28 were able to overcome some of the hindrances with initial CAR constructs resulting in efficacious products. Many second‐generation CAR‐T products have been approved in the treatment of relapsed/refractory hematologic malignancies including multiple myeloma (MM), non‐Hodgkin lymphoma (NHL), and acute lymphoblastic leukemia. However, challenges remain in optimizing the manufacturing, timely access, limiting the toxicity from CAR‐T infusions and improving sustainability of responses derived with CAR‐T therapy. Here, we summarize the clinical trial data leading to approval CAR‐T therapies in MM and NHL, discuss the limitations with current CAR‐T therapy strategies and review emerging strategies for overcoming these limitations.
Neuropathies related to hepatitis E virus infection: A prospective, matched case–control study
Authors: Ripellino Paolo , Lascano Agustina Maria , Scheidegger Olivier , Schilg‐Hafer Lenka , Schreiner Bettina , Tsouni Pinelopi , Vicino Alex , Peyer Anne‐Kathrin , Humm Andrea Monika , Décard Bernhard Friedrich , Pianezzi Enea , Zezza Giulia , Sparasci Davide , Hundsberger Thomas , Dietmann Anelia , Jung Hans , Kuntzer Thierry , Wilder‐Smith Einar , Martinetti‐Lucchini Gladys , Petrini Orlando , Fontana Stefano , Gowland Peter , Niederhauser Christoph , Gobbi Claudio
Published: August 2023

Background

Acute hepatitis E virus (HEV) infection has recently emerged as a potential trigger for acute dysimmune neuropathies, but prospective controlled studies are lacking.

Aims

To compare the frequency of concomitant acute HEV infection in patients with neuralgic amyotrophy (NA), Guillain–Barré syndrome (GBS), and Bell's palsy with a matched control population.

Methods

Swiss multicenter, prospective, observational, matched case–control study over 3 years (September 2019–October 2022). Neurological cases with NA, GBS, or Bell's palsy were recruited within 1 month of disease onset. Healthy controls were matched for age, sex, geographical location, and timing of blood collection. Diagnostic criteria for acute hepatitis E were reactive serum anti‐HEV IgM and IgG assays (ELISA test) and/or HEV RNA detection in serum by real‐time polymerase chain reaction (RT‐PCR). RT‐PCR was performed on sera to confirm IgM positivity.

Results

We included 180 patients (59 GBS, 51 NA, 70 Bell's palsy cases) and corresponding matched controls (blood donors) with median age 51 years for both groups and equal gender distribution. Six IgM+ cases were detected in the NA, two in the GBS, and none in the Bell's palsy group. Two controls were anti‐HEV IgM‐positive. At disease onset, most cases with acute HEV infection had increased liver enzymes. A moderate association (p = 0.027, Fisher's exact test; Cramér's V = −0.25) was observed only between acute HEV infection and NA.

Conclusion

This prospective observational study suggests an association between concomitant acute HEV infection and NA, but not with GBS or Bell's palsy.