bluuebunny/crossref_metadata_2025 huggingface dataset:
The Unmet Diagnostic and Treatment Needs in Large Cell Neuroendocrine Carcinoma of the Lung
Authors: Buium Catalin , Negru Serban , Ionescu Diana , Dediu Mircea
Published: July 2023

Currently, large cell neuroendocrine carcinoma of the lung (LCNEC) is classified as a rare lung cancer subtype, but given the high incidence of lung cancer, the overall number of cases is considerable. The pathologic diagnosis is based on the microscopic appearance of the tumor cells, the amount of intra-tumoral necrosis, the mitotic rate, and the presence of positive neuroendocrine markers identified by immunohistochemistry. Recently, a subdivision into two main categories was proposed based on mutation signatures involving the RB1, TP53, KRAS, and STK11/LKB1 genes, into SCLC-like (small cell lung cancer-like) and NSCLC-like (non-small cell lung cancer-like) LCNEC. In terms of treatment, surgery remains the best option for resectable, stage I–IIIA cases. Chemotherapy and radiotherapy have conflicting evidence. Etoposide/platinum remains the standard chemotherapy regimen. However, based on the newly proposed LCNEC subtypes, some retrospective series report better outcomes using a pathology-driven chemotherapy approach. Encouraging outcomes have also been reported for immunotherapy and targeted therapy, but the real impact of these strategies is still being determined in the absence of adequate prospective clinical trials. The current paper scrutinizes the epidemiology, reviews the reliability of pathologic diagnosis, discusses the need for molecular subtyping, and reviews the heterogeneity of treatment algorithms in LCNEC.
Energy Efficient Solutions: A Multi Criteria Decision Aid Tool to Achieve the Targets of the European EPDB Directive
Authors: Cumo Fabrizio , Pennacchia Elisa , Zylka Claudia
Published: July 2023

The building and construction sector has a significant impact on CO2 emissions and pollutants released into the atmosphere, which contribute to climate change. The EPDB Directive mandates the achievement of a minimum energy class E for all residential buildings by 2030 and an energy class D by 2033. Particularly, in Italy, about 86% of the existing building stock predates the enactment of any energy laws and regulations, making it imperative to apply the energy efficiency interventions. This paper provides a support decision tool for the identification of standardized interventions on the envelope, air conditioning system and domestic hot water production. The study is focused on a specific construction period class (1976 - 1990) in six different climatic zones. The methodological approach is based on a cataloguing phase and definition of Ante Operam energy classes, on the case study identification, the energy requalification interventions identification, solutions simulations, cost estimation. By simulating standardized interventions for each climatic zone, a range of possible combinations will be identified. The most advantageous ones will be determined based on a cost-benefit analysis, considering the potential class jump achieved. The research result is a matrix of energy efficiency interventions that is applicable to each climatic zone and can be extended to the existing housing stock.
Alcohol: Epigenome Alteration and Transgenerational Effect
Authors: Heidari Nazila , Hajikarim-Hamedani Arman , Heidari Amirhossein , Ghane Yekta , Sadat-Shirazi Mitra-Sadat , Ashabi Ghorbangol , Zarrindast Mohammad-Reza
Published: July 2023

While DNA serves as the fundamental genetic blueprint for an organism, it is not a static entity. Gene expression, the process by which genetic information is utilized to create functional products like proteins, can be modulated by a diverse range of environmental factors. Epigenetic mechanisms, encompassing DNA methylation, histone modification, and microRNAs, play a pivotal role in mediating the intricate interplay between the environment and gene expression. Intriguingly, alterations in the epigenome have the potential to be inherited across generations. Ethanol abuse poses significant health issues worldwide. Ethanol has the capability to induce changes in the epigenome, which can be inherited by offspring, thus impacting them even in the absence of direct ethanol exposure. This review article reviewed the alterations caused by ethanol on the epigenome. We thoroughly gathered all relevant papers investigating the behavioral and molecular consequences of parental ethanol exposure on their offspring. In conclusion, the comprehensive analysis of the literature supports the notion that ethanol exposure induces lasting epigenetic alterations, which can influence the behavior and health of future generations. This knowledge emphasizes the significance of addressing the potential transgenerational effects of ethanol and highlights the importance of preventive measures to minimize the adverse impact on offspring.
Effects of Locomotion Regulatory Mode on COVID-19 Anxiety: The Mediating Role of Resilience
Authors: Lo Destro Calogero , Costa Alberto
Published: July 2023

The COVID-19 pandemic has exerted a significant impact on mental health globally. The uncertainty, fear, and stress associated with this crisis have contributed to a heightened prevalence of anxiety, depression, and various other mental health disorders. In this scenario, the present study aimed at investigating the relationship between locomotion regulatory mode, resilience, and COVID-19 anxiety. It is worth noting that previous extensive research has established a significant correlation between high levels of locomotion and diverse positive psychological conditions, such as optimism, reduced hopelessness, and positive affect. A total of 243 participants completed measures of locomotion regulatory mode, resilience, and COVID-19 anxiety. In line with our hypotheses, individuals' locomotion regulatory mode was negatively, although non significatively, associated with COVID-19 anxiety. Furthermore, resilience was found to mediate the relationship between locomotion regulatory mode and COVID-19 anxiety, indicating that individuals displaying high locomotion may be better equipped to cope with the stress and uncertainty of the COVID-19 pandemic due to their greater levels of resilience. Taken together, these findings highlight the importance of considering both locomotion and resilience in managing anxiety related to COVID-19 and suggest that interventions aimed at enhancing resilience may be beneficial particularly for individuals with low locomotion regulatory mode.
Knowing the Mechanisms: How Probiotics Affect the Development and Progression of Cancer
Authors: Patil Abhinandan , Kotekar Devika , Chavan Ghanshyam
Published: July 2023

The stability of the gut barrier is very important for keeping the gut healthy and stopping dangerous substances from getting into the bloodstream. Several diseases, including cancer, have been linked to the gut barrier being broken. Live bacteria called probiotics that are good for the host have been shown to have the ability to improve the gut barrier and lower the risk of cancer in the gastrointestinal system. This review looks at how probiotics affect the health of the gut barrier and what that might mean for preventing cancer. Researchers have found that probiotics strengthen the connections between intestine cells, encourage the production of protective mucins, and change the make-up and balance of the gut bacteria. These processes help keep the gut barrier strong and stop harmful chemicals from getting into the bloodstream. Probiotics may help lower the chance of cancer by reducing inflammation throughout the body and protecting the GI tract from harmful substances. But more study is needed to fully understand the benefits of different probiotic strains, the best amounts to take, and how they affect the health of the gut barrier. Understanding how probiotics, the health of the gut barrier, and the risk of cancer all work together can help us come up with new ways to avoid and treat cancer.
Higher virulence of Diplodia seriata on vines of cv. Cabernet Sauvignon associated with 10-year-old wood compared to young tissue
Authors: Larach Alejandra , Vega-Celedón Paulina , Salgado Eduardo , Salinas Aldo , Riquelme Natalia , Castillo-Novales Diyanira , Sanhueza Paulina , Seeger Michael , Besoain Ximena
Published: July 2023

In vineyards, Botryosphaeria dieback (BD) occurs in young and old plants. In the field, the prevalence and severity of the disease increase proportionally with the age of the vineyards. Among the pathogens that cause (BD), Diplodia seriata is the most prevalent species in Chile and other countries with a Mediterranean climate. To date, no information is available on the sus-ceptibility of adult wood to infection by this pathogen since most of the pathogenicity tests have been carried out on 1- or 2-year-old shoots or detached canes. Therefore, a pathogenicity test was carried out on plants under field conditions, with inoculations in plants, on one-year-old shoots, and 2- and 10-year-old wood in grapevine cv. Cabernet Sauvignon. A pathogenicity test was carried out with two isolates of D. seriata selected in an assay in detached canes that were 2-year-old. The results on plants showed that D. seriata was significantly more aggressive on 10-year-old than on one- or two-year-old tissue. These results were compared with the lesions ob-tained from two-year-old canes. The results of this work are consistent with the damage ob-served in the field, highlight the importance of identifying each pathogenic species that causes (BD) and contribute to the knowledge of the epidemiology of this disease in Mediterranean cli-mates.
Analisis Faktor-Faktor yang Menjelaskan Pengimplementasian Nilai-Nilai Utama (Corevalues) AKHLAK pada Karyawan di PT TASPEN (Persero)
Authors: Yekti Widyaningsih
Published: July 2023

The development of the global economy is currently entering the era of Industry 4.0. Industry 4.0 cannot be faced only with technological development, but must involve social dynamics in it. Every company and agency must create a strategy in dealing with this era, including Badan Usaha Milik Negara (BUMN) by establishing main values that become the reference for the behavior of all human resources in BUMN. These corevalues consist of Trustworthy, Competent, Harmonious, Loyal, Adaptive, and Collaborative (AKHLAK). In practice, AKHLAK has not been implemented properly, even though the corevalues of AKHLAK need to be implemented by all human resources in BUMN. This thesis examines the significant factors explaining the implementation of AKHLAK corevalues on PT TASPEN (Persero) employees and to examine the profile of employees who have implementation corevalues high and low are based on significant factors. The factors used in this study are work motivation, work environment, employee welfare, socialization, employee commitment, religiosity, work stress, age, gender, education level, and years of service. The methods used in solving this research problem are the Partial Least Square (PLS) method and the Classification and Regression Tree (CART) method. The data used is primary data of 209 PT TASPEN (Persero) employees taken using purposive sampling. The results showed that work motivation, socialization, religiosity, and education level can significantly explain the implementation of AKHLAK. The profile of employees who have a high level of implementation of AKHLAK are employees with high level of religiosity, high work motivation, for all categories of educational levels, and work stress levels. The profile of employees who have a low level of implementation of AKHLAK are employees who have low religiosity and work motivation.
Penerapan Metode Support Vector Machines (SVM) dan Metode Naïve Bayes Classifier (NBC) dalam Analisis Sentimen Publik terhadap Konsep Child-free di Media Sosial Twitter
Authors: Dania Siregar  , Faroh Ladayya  , Naufal Zhafran Albaqi  , Bintang Mahesa Wardana
Published: July 2023

Child-free is a concept in which a person chooses not to have children or places and situations that are without the presence of a child. The application of child-free itself is not something new but is commonplace in many developed countries. Along with the rapid flow of information, this child-free concept began to be discussed virally, especially on Indonesian social media, such as Twitter. People’s views on this concept are certainly diverse, some agree and some disagree. Sentiment analysis is the mining of all people’s expressions and views on a phenomenon or product online in the form of text. Through a large sample collection of opinions and expressions, we can capture the voices or views of society, understand the dynamics that are taking place, and even know the extent to which the issue begins to touch aspects of people’s social life. This study aims to conduct sentiment analysis by comparing the performance of two different methods used to classify people’s views in the form of text data crawled tweets from Twitter. The two methods compared are Support Vector Machines (SVM) and Naive Bayes Classifier (NBC). Another purpose of this study is to provide an overview of public sentiment on social media Twitter about the concept of child-free. The results of this study showed that the data experienced an imbalance so to overcome it used SMOTE, SMOTE managed to increase the sensitivity of the prediction of minor data.  The classification method that produces better predictions using the F1-weighted average criteria is SMOTE-SVM by reaching 95.639% for training data and 60.45% for testing data.  The opinions that support child-free mostly have to do with parents' unpreparedness to take care of children, while opinions that reject child-free think that it is contrary to Islam and child-free decisions will make it difficult for old age because no one takes care of them.
Graduate Student Library Needs at Memorial University of Newfoundland: A Case Study
Authors: Kavanagh Victoria , Barykina Natalia
Published: July 2023

Libraries are important structures for graduate students in research intensive universities, such as Memorial University of Newfoundland (MUN). Given the complex needs of those students, it is crucial to have an updated glimpse into what works and does not work for students. The objectives of this survey were to investigate graduate students’ awareness and use of library services and resources at MUN and to explore how important and adequate existing services and resources seemed to MUN graduate students. Fortunately, the survey findings showed favourably in terms of user satisfaction, with many of the library services and resources that were rated as very important also being rated as very satisfactory. Other findings indicated that respondents placed increased importance on access to comprehensive collections of E-resources, which is not surprising given the conditions of the COVID-19 pandemic. Also found was an increased need for writing resources and literature search strategies. Overall, a recurring theme for improvement was an increased promotion of our services and resources so that we can better reach our students. The insights gained from the survey will help us target this area of improvement and direct future development of graduate student-focused services and resources.
The Developments And Challenges Of Citizen Journalism In Indonesia
Authors: Nuswantari Sekar Arum , Alyasuci Puteri
Published: July 2023

Citizen journalism arises because technology provides opportunities for consumers to become content producers, which can be referred to as user-generated content (UGC). With the emergence of the ability of citizens to produce content, citizen journalism has become an alternative to content produced by the mainstream media, especially after the presence of social media. In practice, citizen journalism will always go hand in hand with the mainstream media, which of course has bigger resources. Academic attention to citizen journalism has also developed from the beginning when this activity was formed until it developed into an alternative media for the public. The author focuses on previous studies, to be able to explain whether there are challenges behind the development of citizen journalism. This article is a literature review as a method, prioritizing articles collected from the accredited journal index system and the Google Scholar search engine. The results found that citizen journalism is still developing, both as an alternative media and as part of the mainstream media. However, in its development journalism has challenges in issues of ethics, law, accuracy, and reliability. The results of this study are expected to provide recommendations for future researchers related to ethics, law, accuracy, and reliability of citizen journalism.
The Predictive Roles Of Leadership And Communicating Religious Commitment In Energy Sustainability Change Readiness
Authors: Panggabean Hana , Murniati Juliana , Atmoko Benedictus Ratri , Marta Rustono Farady , Azahari Helmi
Published: July 2023

Industrial fields of Indonesia are facing challenging issues of energy sustainability. As the country’s second-largest energy consumer behind the transportation sector, industrial’s consumption is massively dominated by non-renewable energy and the lack of adequate energy waste management. Organizations need to build employee readiness to change toward energy sustainability. Leadership is reasonably a significant predictor of organizational change readiness (RtC). Religious commitment (RC) emerges as a personal motivator for pro-environmental behaviour because individuals perceive looking after nature and the environment as adhering to religious values and teachings. The society of Indonesia views religiosity as a virtue and values social hierarchy as one of the most substantial social structures. Accordingly, this study aims to examine the predictive roles of leadership and RC on organizational RtC and the features in communicating both predictors in change leadership. A mix-method approach was carried out by delivering questionnaires (N=257), conducting interviews, and focus group discussions with 35 managers and employees in the textile industry. A significant influence of leadership on RtC is found, strengthened by the impact of RC. Qualitative findings depicted religious meanings of energy sustainability and how leaders communicate their religiosity in employee behavioral changes.
Effectiveness of a screening tool to assess prevention and rehabilitation needs of 45 to 59 years old in primary care – study protocol of a pragmatic randomized controlled trial (PReHa45)
Authors: Burchardi Jennifer Marie , Spyra Karla , Brünger Martin
Published: July 2023

Background: For years it has been stated that the need for prevention and rehabilitation is not always identified early enough. Although many individuals have regular contact with a general practitioner (GP), this access path for applying for a prevention or rehabilitation service has not been fully exploited. The important role of GPs in supporting the intention to apply is highlighted in the research. This study aims to evaluate the effectiveness of the “check-up 45+” to support GPs both in identifying the need for prevention and rehabilitation services and in submitting applications.
Methods: The study is designed as a two-arm, pragmatic 1:1 randomised controlled study (RCT), which will be conducted in about 20 general practices in the German states of Berlin and Brandenburg. Patients (n=1,654) aged from 45 to 59 years will be recruited by medical assistants. In addition to usual care, both study groups will receive a questionnaire covering socio-economic and occupational variables to be filled out immediately in the waiting room. The intervention group passes through the “check-up 45+”. This includes the completion of the “screening 45+” that aims to assess the need for prevention and rehabilitation services. Medical assistants will immediately evaluate this 2-page screening tool. If a need is identified and confirmed by the GP, information and application documents will be handed over. Moreover, the application process for rehabilitation services is simplified. Primary outcome is the proportion of applications for prevention or rehabilitation services financed by the German Pension Insurance. Administrative data will be provided for this purpose. Secondary outcomes include the proportion of approved applications and completed services. In addition, the proportion of persons with a need for prevention or rehabilitation according to the “check-up 45+” will be examined. Semi-structured interviews will be conducted and content-analysed to determine the practicability and acceptance of the “check-up 45+” by the relevant stakeholders.
Discussion: Prevention and rehabilitation need is insufficiently identified and addressed so far. This study will determine the effectiveness and of the “check-up 45+” in primary care.
Trial registration: German Clinical Trials Register (DRKS00028303, 03.03.2022).
Coinfection of dengue and hepatitis A viruses: a rare case report
Authors: Saldaña Christian Alberto Rodriguez , Fiestas-Cordova Jessenia , Saldaña-Flores José Gerardo , Abramonte-Tene Walter David
Published: July 2023

Introduction:Dengue fever and hepatitis A are viral infections that are prevalent in developing countries. Coinfection with both viruses is a rare occurrence and presents a diagnostic challenge due to their overlapping symptoms. Laboratory tests are required to confirm the diagnosis of each infection. We present a case of a young female with dengue and hepatitis A coinfection.Case presentation:A 25-year-old female presented with abdominal pain, vomiting, and jaundice. Laboratory tests revealed leukopenia, elevated liver enzymes, and positive hepatitis A virus antibodies. During hospitalization, the patient was diagnosed with dengue fever through serological testing.Conclusions:Coinfection with dengue fever and hepatitis A is possible and may result in more severe symptoms and complications. Diagnosis requires laboratory testing, and treatment is primarily supportive care. Healthcare providers should consider testing for both viruses in patients with overlapping symptoms.
Earliest human funerary rites in insular Wallacea 15,500 to 14,700 years ago
Authors: Hawkins Stuart , Zetika Gabriella , Kinaston Rebecca , Firmando Yulio , Sari Devi , Suniarti Yuni , Lucas Mary , Roberts Patrick , Reepmeyer Christian , Maloney Tim , Kealy Shimona , Stirling Claudine , Reid Malcolm , Barr David , Kleffmann Torsten , Kumar Abhishek , Yuwono Pratiwi , Litster Mirani , Husni Muhammad , Ririmasse Marlon , Ita Mahirta , Mujabuddawat Muhammad , Harriyadi Harriyadi , O'Connor Sue
Published: July 2023

The insular region of Wallacea has become a focal point for studying early human evolution in island environments. Here we focus on how socioeconomic adaptations, under changing climatic conditions, influenced the belief systems and burial practices of past foragers at Ratu Mali 2, an elevated coastal cave site on the small, impoverished island of Kisar dated to 15.5–3.7 ka. This multidisciplinary study reveals the impressive flexibility of our species in the most marginal of environments by demonstrating extreme marine dietary adaptations as well as engagement with an extensive trade and exchange network across open seas. A male and a female, interred in a single grave at Ratu Mali 2 by 14.7 ka are the oldest known human burials in Wallacea with established funerary rites. These findings enable exploration of how human societies and belief systems adapted to rising sea levels in Wallacea after the Last Glacial Maximum.
TTR-INR guided warfarin adjustment protocol: A strategy to improve time in therapeutic range in patients with atrial fibrillation receiving warfarin
Authors: Kosum Paisit , Siranart Noppachai , Nissaipan Kunathip , Laohapiboolrattana Wattakorn , Sowalertrat Walit , Triamamornwooth Kanittha , Arunphan Rawiwan , Sri Apiradee , Rungpradubvong Voravut
Published: July 2023

Background:Atrial fibrillation (AF) is a causing ischemic stroke. Warfarin remains a viable oral anticoagulant for many patients. Time in therapeutic range (TTR) is still not widely applied in clinical practice.Purpose:To study the association of change of TTR after implementation of TTR-INR guided warfarin adjustment protocol in patients with AF receiving warfarin.Methods:This is a prospective study of patients with AF at warfarin clinic of King Chulalongkorn Memorial Hospital. TTR was calculated by using Rosendaal linear interpolation method at baseline, 6 and 12 months after protocol implementation. Patient characteristics and outcomes (TTR improvement, embolic and bleeding events, and mortality) were collected. McNemar’s Chi-square test and paired t-test were used to evaluate the relationship between protocol implementation and outcomes.Results:A total of 57 patients were primary analyzed (mean age of 72 years, 50% females). The TTR at baseline was 65% (53% of patients had TTR less than 65%). After 12 months of protocol implementation, TTR were significantly improved (80%) (p<0.001). Significant improvement of proportion of patients with TTR ³65% was shown after protocol implementation (from 47% to 88%) (p<0.001). Three patients died during the follow-up. No ischemic or major bleeding events were occurred during the follow-up in the first 12 months.Conclusion:The TTR was significantly improved after 12 months of protocol implementation. This strategy may offer additional value in TTR improvement and good outcomes in patients with AF receiving warfarin.
Landslide Hazard Zonation (LHZ) Mapping of the Doon Valley using Remote Sensing and GIS Techniques
Authors: Mani Ashish , Kumari Maya
Published: July 2023

The occurrence of landslides is a cataclysmic natural hazard that mainly occurs in hilly areas due to factors like earthquakes, cloud burst, extreme rainfall, human pressure, etc. which causes loss of biodiversity, property, and life. Effective and comprehensive landslide risk management is crucial for landslide susceptibility. Utilizing remote sensing and GIS techniques, this work focuses on Landslide Hazard Zonation mapping in the Doon Valley. The SRTM DEM data at 30m resolution and Sentinel-2B data at 10m resolution have been used to perform the remote sensing and GIS operations in Arc GIS Software. Thematic layers such as LULC, Slope, Geology, Soil Type, Elevation, Drainage Density, Vegetation, and Aspect were produced utilizing remote sensing and GIS data. The Weighted Overlay, a multi-criteria analysis method, was applied to assign attribute values to each thematic layer based on their importance, which was then combined to calculate the Landslide Hazard Zone. The findings of this study demonstrate that landslides are more likely to occur near and above the Main Boundary Fault / Thrust. The High to Very High Hazard Zone covers 16.64% of the total area, making landslides occurring more frequently. Additionally, the study found that the Doon Valley rivers' upper segments are more susceptible to landslides than their lower segments. By integrating Remote Sensing and GIS techniques, it is possible to obtain extensive knowledge of regions prone to landslides. This information will be helpful for decision-makers and planners to reduce the impact of landslides in the near future.
Lambertella (Rutstroemiaceae, Helotiales) from Northern Thailand
Authors: Lest Anis Sri , Wedaralalage Thilini Chethana Kandawatte
Published: July 2023

During our excursions for discomycetes from 2019–2021 in forests and plantations in northern Thailand, several Lambertella-like specimens were found. Morphological observation and BLAST sequence data search confirmed that six newly collected specimens belong to Lambertella. Further phylogenetic analysis using maximum likelihood and Bayesian inference analyses based on combined ITS and LSU sequence data and morphological examination coupled with chemical reactions, confirmed six Lambertella species. Lambertella aurantiaca was established as a new geographical record, and the other five specimens, L. fusoidea, L. phanensis, L. sessilis, L. takensis, and L. tectonae were introduced as novel species. The highlight of the current study is to contribute a complete morphological description of Lambertella aurantiaca since its introduction in 1964, emend the morphological criteria for Lambertella sensu stricto, and provide sequence data for all the Lambertella species described in the current study, including the extant species, L. aurantiaca for the first time, which are essential for future studies.
From Voxels to Prognosis: AI-Driven Quantitative Chest CT Analysis Forecasts ICU Requirements in 78 COVID-19 Cases
Authors: Bumm Rudolf , Zaffino Paolo , Lasso Andras , Estépar Raúl San José , Pieper Steven , Wasserthal Jakob , Spadea Maria Francesca , Latshang Tsogyal , Kawel-Böhm Nadine , Wäckerlin Adrian , Werner Raphael , Hässig Gabriela , Furrer Markus , Kikinis Ron
Published: July 2023

Background: The aim of the current study was to investigate the distribution and extent of lung involvement in patients with COVID-19 with AI-supported, automated computer analysis and to assess the relationship between lung involvement and the need for intensive care unit (ICU) admission. A secondary aim was to compare the performance of computer analysis with the judgment of radiological experts.
Methods: A total of 81 patients from an open-source COVID database with confirmed COVID-19 infection were included in the study. Three patients were excluded. Lung involvement was assessed in 78 patients using computed tomography (CT) scans, and the extent of infiltration and collapse was quantified across various lung lobes and regions. The associations between lung involvement and ICU admission were analyzed. Additionally, the computer analysis of COVID-19 involvement was compared against a human rating provided by radiological experts.
Results: The results showed a higher degree of infiltration and collapse in the lower lobes compared to the upper lobes (p < 0.05) No significant difference was detected in the COVID-19-related involvement of the left and right lower lobes. The right middle lobe demonstrated lower involvement compared to the right lower lobes (p < 0.05). When examining the regions, significantly more COVID-19 involvement was found when comparing the posterior vs. the anterior halves of the lungs and the lower vs. the upper half of the lungs. Patients, who required ICU admission during their treatment exhibited significantly higher COVID-19 involvement in their lung parenchyma according to computer analysis, compared to patients who remained in general wards. Patients with more than 40% COVID-19 involvement were almost exclusively treated in intensive care. A high correlation was observed between computer detection of COVID-19 affections and expert rating by radiological experts.
Conclusion: The findings suggest that the extent of lung involvement, particularly in the lower lobes, dorsal lungs, and lower half of the lungs, may be associated with the need for ICU admission in patients with COVID-19. Computer analysis showed a high correlation with expert rating, highlighting its potential utility in clinical settings for assessing lung involvement. This information may help guide clinical decision-making and resource allocation during ongoing or future pandemics. Further studies with larger sample sizes are warranted to validate these findings.
Carbon Footprints of Bank Loans and Economic Activities' Carbon Dioxide Emissions: Insights from Advanced Economics
Authors: Othman Anwar Hasan Abdullah
Published: July 2023

This paper examines the relationship between the intensity of Carbon Footprints of Bank Loans (CFBLs) and CO2 emissions emitted by advanced economies to assess if financial institutions' lending strategies contribute to addressing climate change risk. Using GMM estimator, the study analysed yearly panel data from 12 advanced economies encompassing 44 industries from 2005 to 2018. The findings of the study reveal that the intensity of CFBLs in advanced economies has inverse association with CO2 emissions from most economic activities (nearly 86.36%). This is an indication that banks' lending portfolios strategies in advanced economies are more sustainable, supporting low-carbon transitions and helping in climate change risk mitigation. Nonetheless, banks still need to be more disciplined about environmental protection measures, such as carbon disclosure requirements, carbon risk assessments, and incorporating environmental, social, and governance factors into their lending decisions and practices. These policies can increase transparency, accountability, and promote environmentally friendly lending practices, contributing to the global effort to address climate change.
Solid tumors exploit proton-sensing GPR65 for orchestration of an immunosuppressive tumor microenvironment
Authors: Bopp Tobias , Truong-Andrevici Natalia , Fontaine Jean-Fred , Klein Matthias , Rapp Steffen , Wilson Alicia , Kunz Sebastian , Sprang Maximillian , Mueller Luise , Schmitz Marc , WIld Philipp , Wolf Sebastian , Kindler Thomas , Gaida Matthias , Cipriani Barbara , Grabbe Stephan , Andrade-Navarro Miguel , Schild Hansjoerg , Hughes Stuart , Bohn Toszka
Published: July 2023

Extracellular acidification profoundly influences anti-tumor immunity but the molecular details of this immune evasion mechanism are not well understood. Here we demonstrate that tumor-associated macrophages (TAM) are capable of sensing H+ ions in a G protein-coupled receptor (GPR)65-dependent manner. This sensing induces a functional polarization of TAM towards an anti-inflammatory phenotype and shapes the composition of the tumor microenvironment (TME). Detailed analyses demonstrated that these anti-inflammatory TAM produce chemokines that attract neutrophil-like cells resulting in an immunosuppressive TME. In contrast, incapability of sensing H+ ions via the GPR65 leads to an improved anti-tumor immune response resulting in the rejection of strongly acidic tumors. Correspondingly, we show that a genetic coding variant in the human GPR65 locus results in strong anti-tumor immunity and improved overall survival.
Demographic, pain, and quality of life factors in unilateral and bilateral total knee arthroplasty: a population-based retrospective cohort study of 23,033 patients
Authors: Leech Samantha A , Khaira Akashroop , Epp Spencer , Schneider Geoff , Werle Jason , Ng Richard , Harris Ashley D , Manske Sarah L
Published: July 2023

Background
The Alberta Bone and Joint Health Institute (ABJHI) has a comprehensive registry capturing clinical, demographic, and patient-reported outcome measures on all knee arthroplasties performed in the province of Alberta, Canada. This large database provides an opportunity to study the outcomes of total knee arthroplasties (TKA) in patients who underwent unilateral or bilateral procedures.
Methods
Pain and quality of life outcomes of 29,157 TKAs performed in 23,033 patients for knee osteoarthritis performed in Alberta, Canada from January 2013 to February 2020 were examined. This study: (1) investigates whether having both knees replaced results in better pain and quality of life outcomes than replacing only one knee (using multivariate analysis of variance) and (2) identifies if pain and quality of life outcomes impact the likelihood of needing surgery in the contralateral knee after a first TKA (using univariate and multivariate Cox proportional hazards models). Patient-reported outcomes were measured using questionnaires: the Western Ontario and McMaster Universities Arthritis Index (WOMAC) to assess knee pain, and the EuroQol-5D-5L (EQ-5D) to assess quality of life.
Results
Patients who had surgery on both knees had approximately 5% better WOMAC (pain) and EQ-5D (quality of life) questionnaire scores 12 months post-surgery than those who had surgery on only one knee. Additionally, for every 1-point higher pre-operative WOMAC pain score (i.e., less pain) there was a 1% decreased likelihood of undergoing a contralateral TKA compared to a 46% decreased likelihood per 1-point improvement in quality of life. Dementia, back pain, and hospital readmission were associated with a 68%, 17%, and 44% decreased likelihood of contralateral TKA respectively. By contrast, patients with obesity were 36% more likely to undergo bilateral TKA (p < 0.05).
Conclusions
Preoperative knee pain and quality of life play a statistically significant role in determining which patients undergo bilateral TKA. Additionally, bilateral TKA resulted in better patient-reported outcomes compared to unilateral TKA. Though clinical significance cannot be drawn from the low response rates for the patient-reported outcomes, these findings provide a basis for future research on patient-reported outcomes within the Canadian healthcare system.
Positioning, power and agency in postgraduate primary care supervision: a study of trainee narratives
Authors: Jackson Dawn , Josephine Brady , Donna Dawkins
Published: July 2023

Background

Postgraduate supervision takes place within complex training environments, where experiences are shaped by the socio-cultural context and wider profession, and where tensions permeate. Bordin’s working alliance-based model of supervision suggests that quality relationships encompass agreement on the goals and tasks of supervision, in the context of an emotional bond. However, as trainees and their supervisors navigate the demands of providing safe clinical care, alongside educational support, disagreement on expectations for supervision may emerge. By applying a critical lens, this research draws on positioning theory to explore General Practice trainees’ experiences of supervision.

Methods

In 2017-2019 a series of narrative interviews were undertaken with 13 General Practice trainees in the United Kingdom (UK). Participants were purposively sampled based on end-of-year performance, gender, training location and training status. Interviews were analysed using Brown and Gilligan’s Listening Guide, which was adapted to incorporate an exploration of positioning, power and agency.

Results

Trainees appeared to hold variable positions, such as ‘insiders’, ‘outsiders’, ‘peers’ and ‘problem trainees’. Supervisors, through talk and the degree of access afforded, contributed to this positioning. Some trainees viewed their supervisors as brokers and guides as they navigated their training, whilst others were suspicious of the supervisor role. For trainees who raised concerns about their supervisor through formal channels, results were not often satisfactory. Others chose to navigate difficulty in supervision through informal means. This typically involved mastery of artefacts of training, such as the electronic appointment book or training portfolio.

Conclusions

This paper builds on Bordin’s model of supervision to encourage greater clarity in supervisory discussions, exploring assumptions, and recognising the influences of environment, power, positioning, and agency. We have developed a Model of the Supervisory Alliance in Postgraduate GP Training (MSA-GP) to serve as a springboard for discussion for trainees and their supervisors.
Deciphering intratumoral heterogeneity of hepatocellular carcinoma with microvascular invasion with radiogenomic analysis
Authors: Wang Yi , Zhu Gui-Qi , Yang Rui , Wang Cheng , Qu Wei-Feng , Chu Tian-Hao , Yang Li , Zhou Chang-Wu , Miao Geng-Yun , Tang Zheng , Yang Chun , Liu Wei-Ren , Shi Ying-Hong , Zeng Meng-Su
Published: July 2023

Background and aims:
The recurrence and metastasis of hepatocellular carcinoma (HCC) are mainly caused by microvascular invasion (MVI). Our study aimed to uncover the cellular atlas of MVI+ HCC and investigate the underlying immune infiltration patterns with radiomics features.
Methods
Three MVI positive HCC and three MVI negative HCC samples were collected for single-cell RNA-seq analysis. 26 MVI positive HCC and 30 MVI negative HCC tissues were underwent bulk RNA-seq analysis. For radiomics analysis, radiomics features score (Radscore) were built using preoperative contrast MRI for MVI prediction and overall survival prediction. We deciphered the metabolism profiles of MVI+ HCC using scMetabolism and scFEA. The correlation of Radscore with the level of APOE+ macrophages and iCAFs was identified. Whole Exome Sequencing (WES) was applied to distinguish intrahepatic metastasis (IM) and multicentric occurrence (MO). Transcriptome profiles were compared between IM and MO.
Results
Elevated levels of APOE + macrophages and iCAFs were detected in MVI+ HCC. There was a strong correlation between the infiltration of APOE+ macrophages and iCAFs, as confirmed by immunofluorescent staining. MVI positive tumors exhibited increased lipid metabolism, which was attributed to the increased presence of APOE + macrophages. APOE+ macrophages and iCAFs were also found in high levels in IM, as opposed to MO. The difference of infiltration level and Radscore between two nodules in IM was relatively small. Furthermore, we developed Radscore for predicting MVI and HCC prognostication that were also able to predict the level of infiltration of APOE+ macrophages and iCAFs.
Conclusion
This study demonstrated the interactions of cell subpopulations and distinct metabolism profiles in MVI+ HCC. Besides, MVI prediction Radscore and MVI prognostic Radscore were highly correlated with the infiltration of APOE+ macrophages and iCAFs, which helped to understand the biological significance of radiomics and optimize treatment strategy for MVI+ HCC.
An In-silico Analysis of OGT gene association with diabetes mellitus
Authors: Ayodele Abigail O. , Udosen Brenda , Oluwagbemi Olugbenga O. , Oladipo Elijah K. , Omotuyi Idowu , Isewon Itunuoluwa , Nash Oyekanmi , Soremekun Opeyemi , Fatumo Segun
Published: July 2023

O-GlcNAcylation is a nutrient-sensing post-translational modification process. This cycling process involves two main proteins; the O-linked N-acetylglucosamine transferase (OGT) catalyzing the addition, and the glycoside hydrolase OGA (O-GlcNAcase) catalyzing the removal of the O-GlCNAc moiety on nucleocytoplasmic proteins. This process is necessary for various important cellular functions. The O-linked N-acetylglucosamine transferase (OGT) gene is responsible for the production of the OGT protein. Several studies have shown the overexpression of this protein to have biological implications in metabolic diseases like cancer and diabetes mellitus (DM). In this study, we retrieved a total of 159 SNPs with clinical significance from the SNPs database and we probed the functional effects, stability profile, and evolutionary conservation of these to determine their fit for this research. We then identified 7 SNPs (G103R, N196K, Y228H, R250C, G341V, L367F, and C845S) with predicted deleterious effects across the four tools used (PhD-SNPs, SNPs&Go, PROVEAN, and PolyPhen2). Proceeding with this, we used ROBETTA, a homology modeling tool, to model the proteins with these point mutations and carried out a structural bioinformatics method – molecular docking – using the Glide model of the Schrodinger Maestro suite. We used a previously reported inhibitor of OGT, OSMI-1, as the ligand for these mutated protein models, and as a result, very good binding affinities and interactions were observed between this ligand and the active site residues within 4Å of OGT. We conclude that these mutation points may be used for further downstream analysis as drug targets for the treatment of diabetes mellitus.
GRP94 is an IGF-1R Chaperone and Regulates Beta Cell Death in Diabetes
Authors: Wang Hongjun
Published: July 2023

High workload-induced cellular stress can cause pancreatic islet β cell death and dysfunction, or β cell failure, a hallmark of type 2 diabetes mellitus. Thus, activation of molecular chaperones and other stress-response genes prevents β cell failure. To this end, we have shown that deletion of the glucose-regulated protein 94 (GRP94) in Pdx1+ pancreatic progenitor cells led to pancreas hypoplasia and reduced β cell mass during pancreas development in mice. Here we show that GRP94 was involved in β cell adaption and compensation (or failure) in islets from leptin receptor-deficient (db/db) mice in an age-dependent manner. GRP94-deficient cells were more susceptible to cell death induced by various diabetogenic stress conditions. We also identified a new client of GRP94, insulin-like growth factor-1 receptor (IGF-1R), a critical factor for β cell survival and function that may mediate the effect of GRP94 in the pathogenesis of diabetes. This study has identified essential functions of GRP94 in β cell failure related to diabetes.
The complete chloroplast genome and phylogenetic analysis of Dahlia pinnata Cavanilles 1791(Asteraceae: Dahlia)
Authors: Duan Shan-De , Zheng Kua-Yue , Liu Yang , Li Xing-Ru , Xiang Di-Ying , Hao Li-Hong , Chen Duan-Fen , Niu Shan-Ce
Published: July 2023

Dahlia pinnata Cavanilles 1791 is an important ornamental plant worldwide. The chloroplast genome has obvious advantages in studies of systematic evolution at the plant classification and species level, making it an important resource for phylogenetic research.Here, we sequenced the full chloroplast genome from D. pinnata 'Chocolate' and found that it exhibited a typical tetrad structure. The full-length D. pinnata chloroplast genome was 152,107 bp, with a GC content of 38.45%. The genome included an 83,704 bp large single-copy (LSC) region, an 18,347 bp small single-copy (SSC) region, and a pair of 25,028 bp inverted repeats (IRa and IRb). A total of 134 genes were annotated, including 86 protein-coding genes, 38 transfer RNA genes, 8 ribosomal RNA genes, and 2 pseudogenes. Analysis of password preferences shows that passwords chosen by D. pinnata tend to end with A/U. A total of 161 SSR markers were detected in the simple sequence repeat (SSR) analysis. Phylogenetic analysis that the Dahlia species formed a monophyly. Dahlia was clustered with Cosmos-Bidens, which differed from studies using nuclear genomic DNA. We suggest that nuclear-cytoplasmic incongruences may be widespread in Asteraceae, and should be thoroughly evaluated in order to understand the true evolutionary history of this economically-important group of plants.