bluuebunny/crossref_metadata_2025 huggingface dataset:
Streamlining Neuroradiology Workflow with AI for Improved Cerebrovascular Structure Monitoring
Authors: Banerjee Subhashis , Nysjö Fredrik , Dhara Ashis Kumar , Wikström Johan , Strand Robin
Published: July 2023

The use of radiological imaging to examine intracranial blood vessels is critical for both preoperative planning and postoperative follow-up. Automated segmentation of cerebrovascular anatomy from Time-Of-Flight Magnetic Resonance Angiography (TOFMRA) can provide radiologists with a more detailed and precise view of these vessels. In this paper, we introduce a domain generalized artificial intelligence (AI) solution for volumetric monitoring of cerebrovascular structures from multi-center MRAs. Our approach utilizes a multi-task deep convolutional neural network (CNN) with a topology-aware loss function to learn voxelwise segmentation of the cerebrovascular tree. We use Decorrelation Loss to achieve domain regularization for the encoder network, and auxiliary tasks to provide additional regularization and enable the encoder to learn higher-level intermediate representations for improved performance. We compare our method to six state-of-the-art 3D vessel segmentation methods, using retrospective TOF-MRA datasets from multiple private and public data sources scanned at six different hospitals, with and without vascular pathologies. The proposed model achieved the best scores in all the qualitative performance measures. Furthermore, we have developed an AI-assisted Graphical User Interface (GUI) based on our research to assist radiologists in their daily work and establish a more efficient work process that saves time.
Dynamic performance analysis and parameter collaborative optimization of floating seal dam compliant foil face gas seal
Authors: Chen Yuan , Xiong Cong , Li Yuntang , Li Xiang , Xue Xiaofeng , Wang Bingqing , Gan Yuan
Published: July 2023

Under the consideration of axial displacement excitation, the floating seal dam compliant foil face gas seal (FSD-CFFGS) is taken as the research object. based on the theory of gas lubrication and elastic mechanics, the seal dynamics equation, transient Reynolds equation and foil deformation equation are solved by coupling method. The dynamic performance difference between FSD-CFFGS and rigid surface face gas seal (RSFGS) is compared and analyzed, Besides, parameter optimization is carried out to improve dynamic stability and leakage control performance. The results show that the dynamic performance of the FSD-CFFGS is significantly improved compared with the RSFGS. The dynamic performance of FSD-CFFGS can be effectively improved by reasonably configuring the structural or mechanical parameters such as the supporting foil compliance coefficient, spring stiffness, auxiliary seal ring damping, and the flexibly mounted stator’s mass.
Renewable energy, agriculture, and carbon dioxide emissions nexus: implications for sustainable development in sub-Saharan African countries
Authors: Wang Jingyi , Jiang Chenglin , Li Mingquan , Zhang Shuai , Zhang Xuebiao
Published: July 2023

Sub-Saharan Africa (SSA) has experienced a high economic growth rate over the last two decades, which has been accompanied by concerns about increasing carbon dioxide (CO2) emissions. This study aims to find out whether renewable energy and agriculture can help reduce CO2 emissions for selected SSA countries. A balanced dataset for 38 SSA countries covering the period 2000-2019 is utilized. The differentiated-generalized method of moments (GMM) is employed as a benchmark estimation method. The regional heterogeneity analysis of countries at different income levels is then carried out. The moderating role of government governance in the energy-agriculture-environment nexus is also investigated. The following conclusions are highlighted: (1) the consumption of renewable energy can reduce CO2 emissions, while agriculture increases them; (2) the mitigating effect of renewable energy on CO2 emissions is relatively larger in countries at a low income level. countries than in high-income countries, while agriculture aggravates CO2 emissions in lower middle-income and low-income regions, but mitigates emissions in upper middle-income regions; (3) governance quality turns the mitigating role of renewable energy use on CO2 emissions into an increasing one, and exaggerates the polluting effect of agriculture. Finally, the study proposes policy implications for improving renewable energy use and green agricultural growth to achieve sustainable development in SSA.
Phylogeny, distribution, and pathogenicity of fusarioid fungi associated with chickpea wilt in Sinaloa and Sonora, Mexico
Authors: Cota-Barreras Carlos Ivan , García-Estrada Raymundo Saul , León-Félix Josefina , Valenzuela-Herrera Victor , Mora-Romero Guadalupe Arlene , Leyva-Madrigal Karla Yeriana , Tovar-Pedraza Juan Manuel
Published: July 2023

Wilt disease complex, is the most important disease of chickpeas (Cicer arietinum L.) in the production areas from Mexico. Disease symptoms include root rot, yellowing, wilting, poor growth, discoloration of vascular tissues, and death of plants. This study aimed to identify the fusarioid species associated with chickpea wilt in northwest Mexico by the combination of phylogenetic analyses and morphological characterization, as well as to determine their pathogenicity and virulence on chickpea seedlings. A total of 80 isolates of fusarioid fungi were obtained from symptomatic plants of 16 chickpea fields distributed in Sinaloa and Sonora, Mexico. Subsequently, a subset of 41 isolates representing the range of geographic origin was selected for further morphological characterization, phylogeny, and pathogenicity tests. Phylogenetic analyses of partial fragments of the translation elongation factor 1-alpha (tef1-α) and RNA polymerase second largest subunit (rpb2) genes were used to determine the identity of 26 Fusarium isolates and 15 Neocosmospora isolates to species level. Pathogenicity tests were performed on chickpea seedlings (cv. Blanco Sinaloa) under greenhouse conditions. Phylogenetic analyses of 41 fungal isolates of this study allowed the identification of Fusarium languescens (51.2%), Neocosmospora falciformis (36.6%), F. nirenbergiae (7.3%), and F. verticillioides (4.9%). All fungal isolates were found to be pathogenic on chickpea seedlings and a significant difference in virulence was observed. To our knowledge, F. languescens and F. nirenbergiae, belonging to the Fusarium oxysporum species complex, as well as F. verticillioides belonging to the Fusarium fujikuroi species complex are recorded for the first time as causal agents of chickpea wilt in Mexico and worldwide.
Effect of symptomatic rate on spreading of COVID-19 evaluated by a flexible compartment model
Authors: Ohmori Hiroo
Published: July 2023

For COVID-19, many of the infected individuals become symptomatic after the latent period is ended and should be isolated from the community. After the isolation period is ended, they become recovered individuals who have immunity and return to the community. Thus, they are capable of infecting susceptible individuals only during the latent period. Some infected individuals, however, are asymptomatic through the recovery period, which includes the latent period. They are infectious but not isolated. They stay in the community and continue infecting susceptible individuals through the recovery period, inducing an increase in the number of infected individuals, though they become recovered individuals who also have immunity in the community after the recovery period is ended. The number of ‘symptomatic and isolated’ infected individuals and/or of ‘asymptomatic and staying’ infected individuals is controlled by the symptomatic rate. Thus, the symptomatic rate affects the number of infectious individuals continuing to infect susceptible individuals in the community. At the same time, the symptomatic rate affects the number of isolated individuals and, as a result, the number of recovered individuals and the population excluding the individuals kept in isolation. Since the contact rate between infected individuals and susceptible individuals is affected by both the number of recovered individuals having returned to the community and the population excluding the individuals kept in isolation, the symptomatic rate also affects the contact rate. Namely, the symptomatic rate affects not only the number of infectious individuals but also the contact rate. This symptomatic rate could change commonly depending on the characteristics of virus and/or on the health conditions of infected individuals. However, the symptomatic rate could be changed/decided in the middle of infection duration by political and/or medical interventions because the symptomatic rate practically means the isolation rate, and the isolation rate and/or the number of isolated individuals could be decided by some political and/or medical interventions induced by, for example, the capacity of hospital care. Therefore, the evaluation of the effect of the symptomatic rate could provide reference materials for political and/or medical measures. The effects of vaccination and isolation by PCR were also examined for cases with different symptomatic rates. The results of evaluation by a flexible compartment model, which is a model including the symptomatic rate as a term in the calculation equation and being able to evaluate the effect of isolated/recovered individuals on the spread of COVID-19, show that a small difference in the symptomatic rate causes a large difference in the number of infected individuals and in the infection duration. Vaccination and PCR tests were effective in reducing the number of infected individuals for cases with any symptomatic rates.
Labor Market and Earnings Impacts of Intimate Partner Violence against Women in Nigeria
Authors: Brown Derek S , McNelly Samantha , Meinhart Melissa , Sesay Ibrahim , Poulton Catherine , Stark Lindsay
Published: July 2023

Background
Little is known regarding economic impacts of IPV in humanitarian settings, and the limited number of costing studies tend to focus on the health burden of IPV without considering consider the labor burden. Examining the myriad costs associated with IPV expands understanding of the urgency to address IPV.
Methods
Our top-down costing study examines the labor costs of lifetime experience IPV among conflict and non-conflict affected populations of women ages 15–49 in Nigeria. The study integrates the 2018 Nigeria Demographic and Health Survey and 2013-17 Uppsala Conflict Data Program data with earnings data from the Gender Development Index in the United Nations Human Development Report 2021/2022. Estimated IPV prevalence was multiplied by the probability of not working, using logistic regression models to estimate the number of women who were no longer active in the labor force in the past year due to lifetime IPV exposure. The economic value of lost income was quantified by multiplying our estimates by median gender-specific earnings data, based on 2017 purchasing power parity exchange rates.
Results
Combined with an average loss of 4.14% in reduced likelihood of working, the average annual lost female earnings were an estimated $592,000,000 USD for conflict-affected areas and $2,325,000,000 for non-conflict affected areas. Despite using conservative assumptions, estimated annual costs approach $3.0 billion USD, about 1% of Nigeria’s total economic output.
Conclusions
This is a societal cost, not strictly limited to women, but borne by families, government, and all of Nigeria. If stronger funding and prevention measures could reduce the incidence of IPV against women in Nigeria, a substantial portion of these costs could be reclaimed. These high labor market costs demonstrate that there is an economic case to be made, alongside a moral imperative, for stronger protections for girls and women in Nigeria.
Columnar joints in intermediate and felsic volcanic rocks
Authors: Li Yongquan
Published: July 2023

Columnar joints are among the most spectacular structures in various types of igneous rocks. In contrast to basaltic rocks, very few studies systematically examine this structure in other types of igneous rocks. Here, I focus on columnar joints in intermediate and felsic volcanic rocks (IFVRs) which outcrop in eastern and southern China through detailed field observations and measurements. The interpretations and analyzed results show that: (1) Columnar joint is not rare in IFVRs which have similar internal structures to columnar jointed basaltic lavas, but the high viscosity usually inhibits their formation potential of columnar joints in intermediate and felsic lavas (ratio of formation probabilities between IFVRs and basalts is ~ 1/29 in eastern and southern China). (2) Columnar joints in IFVRs usually display curved structure that are likely formed by the slightly downslope of solidified top part and the local rotation of the isotherms, which can be classified as entablature. (3) The largely variable size (side length = ~ 10–161 cm) and ordering (Hexagonality Index = ~ 0.68–1.5) of columns in IFVRs are not directly associated with their major element compositions, but most possibly are controlled by their emplaced styles, surrounding environments and rock textures. (4) High effusion rates of lavas and/or pyroclastic flows emplaced in flat areas (i.e., Basin floor, canyon, lava lake, caldera interior) through stagnant cooling processes (~ 1.4–35°C/h) would be the key mechanisms to form columnar joints in IFVRs.
Real-world experience and clinical impact of drug-drug interactions in HR+/HER2- advanced breast cancer patients treated with abemaciclib plus endocrine therapy: the AB-ITALY study
Authors: Pisegna Simona , Scagnoli Simone , Toss Angela , Caputo Roberta , De Laurentiis Michelino , Palleschi Michela , De Giorgi Ugo , Cortesi Enrico , fabbri maria agnese , Fabi Alessandra , Paris Ida , Orlandi Armando , Curigliano Giuseppe , Criscitiello Carmen , garrone ornella , Tomasello Gianluca , D'Auria Giuliana , Vici Patrizia , Ricevuto Enrico , Domati Federica , Piombino Claudia , Parola Sara , Scafetta Roberta , Cirillo Alessio , Salimbeni Beatrice Taurelli , Lisa Francesca Sofia Di , Strigari Lidia , Preissner Robert , Simmaco Maurizio , Santini Daniele , Marchetti Paolo , Botticelli Andrea
Published: July 2023

BACKGROUND
Abemaciclib demonstrated clinical benefit in women affected by HR+/HER2- advanced breast cancer (aBC). Drug-drug interactions (DDIs) can lead to a reduced treatment efficacy or increased toxicity. This retro-prospective study aimed to evaluate outcomes, DDIs’ impact and toxicities of abemaciclib combined with endocrine therapy in a real-world setting.
METHODS
Patients from 12 referral Italian hospitals with HR+/HER2- aBC who received abemaciclib were included. Clinical data about comorbidities, concurrent medications, outcomes and adverse events (AE) were collected. Drug-PIN® (Personalized Interactions Network) is a tool recognizing the role of multiple interactions between active and/or pro-drug forms combined with biochemical and demographic patient data. The software was used to define the Drug-PIN score and Drug-PIN tier (green, yellow, dark yellow and red) for each patient. Univariate and multivariate analysis were performed to identify predictors of patients PFS or toxicity.
RESULTS
One hundred seventy-three patients were included. 13% of patients had > 75years. Overall response rate (ORR) was 63%. The median PFS (mPFS) of the overall population was 22 months (mo), while mOS was not reached. Patients treated with abemaciclib in combination with AI and fulvestrant had a mPFS of 36 and 19 mo, respectively. The most common toxicities were diarrhoea, asthenia and neutropenia detected in 63%,49%,49% of patients, respectively. The number of concomitant medications and comorbidities were not associated with survival outcomes (22 vs 17 mo, p = 0.068, p = 0.99). Drug-PIN tier from dark yellow to red and Drug-PIN score > 12 were associated with shorter PFS compared to no/low risk DDIs and score < 12 (15 vs 23, p = 0.005, p = 0.0017). Drug interaction was confirmed as an independent biomarker in a multivariate model (p = 0.02). No difference in any-grade AE, severe toxicities and diarrhoea was detected among different age subgroups. No association was found between Drug-PIN score or Drug-PIN tier and overall toxicity (p = 0.44), severe AEs (p = 0.11) or drug reduction (p = 0.27)
CONCLUSIONS
Efficacy and safety of abemaciclib plus ET were confirmed in a real-world setting, even in elderly population and patients with comorbidities. Evaluation of DDIs with Drug-PIN appear to be an independent predictor of PFS.
Increasing sensitivity of the terrestrial ecosystem to climate change in China
Authors: Wei Fangli , Fu Bojie , Zhang Wenmin , Sun Chuanlian , Hu Ying
Published: July 2023

Changes in heat and moisture significantly co-alter ecosystem functioning. However, knowledge on the dynamics of ecosystem responses to climate change is limited. Here, we quantify long-term ecosystem sensitivity (ES) based on weighted ratios of vegetation productivity variability and multiple climate variables from satellite observations, greater values of which indicate more yields per hydrothermal condition change. Our results show that ES exhibits large spatial variability and increases with the aridity index. A positive temporal trend of ES is found in 61.28% of the study area from 2001 to 2021, which is largely attributed to a declining vapor pressure deficit and constrained by solar radiation. Moreover, carbon dioxide plays a dual role; in moderation it promotes the fertilization effect, whereas in excess, it suppresses vegetation growth by triggering droughts. Our findings highlight that moisture stress between land and atmosphere is one of the key prerequisites for ecosystem stability, offsetting part of the negative effects of heat.
Detection of bla kpc gene among carbapenemase producing Klebsiella pneumoniae isolated from different clinical specimens at tertiary care hospital of Nepal
Authors: Baral Rakshya , Tuladhar Reshma , Manandhar Sarita , Singh Anjana , Sherchan Samendra
Published: July 2023

Background
Klebsiella pneumoniae infections have become a major cause of hospital acquired infection worldwide with the increased rate of acquisition of resistance to antibiotics. Carbapenem resistance mainly among Gram negative is an ongoing problem which causes serious outbreaks dramatically limiting treatment options. This prospective cross-sectional study was designed to detect blaKPC gene from carbapenem resistant K. pneumoniae.
Materials and Methods
This prospective cross-sectional study was designed to detect blaKPC gene from carbapenem resistant K. pneumoniae. A totally of 1118 different clinical specimen were processed and screened for KPC producing K. pneumoniae phenotypically using Meropenem (10µg) disc. The blaKPC gene was amplified from the isolates of K. pneumoniae to detect the presence of this gene. Of the total samples processed, 18.6% (n = 36) were K. pneumoniae with 61.1% (n = 22) meropenem resistant. All isolates were susceptible to polymyxin B. This study demonstrated the higher level of MDR 91.7% (n = 33) and KPC production 47.2% (n = 17) among K. pneumoniae isolates. The blaKPC gene was detected in 8.3% (n = 3) of Meropenem resistant isolates.
Result
A totally of 1118 different clinical specimens were processed and screened for KPC producing K. pneumoniae phenotypically using Meropenem (10µg) disc. The blaKPC gene was amplified from the isolates of K. pneumoniae to detect the presence of this gene. Of the total samples processed, 18.6% (n = 36) were K. pneumoniae with 61.1% (n = 22) meropenem resistant. All isolates were susceptible to polymyxin B. This study demonstrated the higher level of MDR 91.7% (n = 33) and KPC production 47.2% (n = 17) among K. pneumoniae isolates. The blaKPC gene was detected in 8.3% (n = 3) of meropenem resistant isolates.
Conclusion
Since the study demonstrates the higher level of MDR and KPC producing K. pneumonia isolates that has challenged the use of antimicrobial agents, continuous microbiology, and molecular surveillance to assist early detection and minimize the further dissemination of blaKPC should be initiated. We anticipate that the findings of this study will be useful in understanding the prevalence of KPC-producing K. pneumoniae in Nepal.
Accessing Gold π-Acid Reactivity under Electrochemical Anode Oxidation (EAO) through Oxidation Relay
Authors: Shi Xiaodong , Zhang Shuyao , Wei Jingwen , Ye Xiaohan , Perez Angel
Published: July 2023

The gold π-acid activation under electrochemical condition is achieved for the first time. While EAO allowing easy access to gold(III) intermediates over alternative chemical oxidation under mild conditions, the reported examples so far limited to coupling reactions due to the rapid AuIII reductive elimination. Using aryl hydrazine-HOTf salt as precursors, the π-activation reaction mode was realized through oxidation relay. Both alkene and alkyne di-functionalization were achieved with excellent functional group compatibility and regioselectivity, which extended the versatility and utility of electrochemical gold redox chemistry for future applications to come.
Comparison of osteoclast differentiation protocols from human induced pluripotent stem cells of different tissue origins
Authors: Blümke Alexander , Ijeoma Erica , Simon Jessica , Wellington Rachel , Purwaningrum Medania , Doulatov Sergei , Leber Elizabeth , Scatena Marta , Giachelli Cecilia M
Published: July 2023

Background:
Ever since their discovery, induced pluripotent stem cells (iPSCs) have been extensively differentiated into a large variety of cell types. However, a limited amount of work has been dedicated to differentiating iPSCs into osteoclasts. While several differentiation protocols have been published, it remains unclear which protocols or differentiation methods are preferrable regarding the differentiation of osteoclasts.
Methods:
In this study we compare the osteoclastogenesis capacity of a peripheral blood mononuclear cell (PBMC)-derived iPSC line to a fibroblast-derived iPSC line in conjunction with either embryoid body-based or monolayer-based differentiation strategies. Both cell lines and differentiation protocols were investigated regarding their ability to generate osteoclasts and their inherent robustness and ease of use. The ability of both cell lines to remain undifferentiated while propagating using a feeder-free system was assessed using alkaline phosphatase staining. This was followed by evaluating mesodermal differentiation and the characterization of hematopoietic progenitor cells using flow cytometry. Finally, osteoclast yield and functionality based on resorptive activity, Cathepsin K and tartrate-resistant acid phosphatase (TRAP) expression were assessed. Results were validated using qRT-PCR throughout the differentiation stages.
Results:
Embryoid-body based differentiation yielded CD45+, CD14+, CD11b+ subpopulations which in turn differentiated into osteoclasts which demonstrated TRAP positivity, Cathepsin K expression and mineral resorptive capabilities. This was regardless of which iPSC line was used. Monolayer-based differentiation yielded lower quantities of hematopoietic cells that were mostly CD34+ and did not subsequently differentiate into osteoclasts.
Conclusions:
The outcome of this study demonstrates the successful differentiation of osteoclasts from iPSCs in conjunction with the embryoid-based differentiation method, while the monolayer-based method did not yield osteoclasts. No differences were observed regarding osteoclast differentiation between the PBMC and fibroblast-derived iPSC lines.
A design methodology for nonlinear oscillator chains enabling energy localization tuning and soliton stability enhancement with optimal damping
Authors: Barbosa Arthur , Kacem Najib , Bouhaddi Noureddine
Published: July 2023

In this paper, Intrinsic Localized Modes (ILMs) are investigated in coupled nonlinear oscillators, with a specific focus on creating stationary solitons. The main objective is to establish a design methodology for reproducing the Nonlinear Schr¨odinger Equation (NLSE) in mechanical systems, even in the presence of damping. A three-dimensional diagram is developed in order to illustrate stable parameter regions for damped stationary solitons. Moreover an analysis of the influence of the number of oscillators in the system, and a numerical investigation regarding the stability of solitonic behavior is done. Through numerical analyses, it is observed that the developed algorithm not only has the capability to locate the highest amplitudes in the chain of oscillators but also to control the intensity at which these amplitudes are located according to design requirements. The proposed methodology expands the understanding of energy localization in nonlinear systems and holds potential for practical applications.
Role for environmental factors on the relationship between seasons of conception and preterm birth: An observational study in China
Authors: Zou Shujing , Liang Yuxiu , Wang Zhaojun , Bai Shuoxin , Du Shuang , Zhao Xiaodong , Lin Shaoqian , Wang Zhiping
Published: July 2023

Background：The relationship between season and the risk of preterm birth is not consistent. Importantly, the role of environmental factors in it is not clear.
Methods：Based on the baseline of the Jinan birth cohort, our study focused on seasons of conception to examine the relationship. The mothers from the birth cohort were the subjects, and they were interviewed face-to-face by the questionnaire. The average exposure levels of temperature and humidity during the first 30 days of pregnancy were calculated, and those of air pollutants were assessed by an inverse distance weighting method.
Results: A total of 4.4 % (263/5984) of mothers had premature babies. The rates of preterm birth were higher in winter (6.0 %) and summer (4.5 %) than that in spring (3.1 %) at the 0.05 significant level. In the multivariate logistic regression model, the adjusted odds ratio (OR) and 95 % confidence interval (CI) for the risk of preterm birth at conception in winter and summer were 2.228 (1.512-3.316) and1.541 (1.055-2.277). However, after further adjustment for humidity, only the association between winter conception and preterm birth remained statistically significant (OR: 2.353, 95% CI: 1.594-3.511). Moreover, the humidity partially mediated the relationship (41.2 %) between conception in winter and preterm birth, and humidity in winter was negatively associated with the risk of preterm birth (indirect effect = -0.007, P < 0.001).
Conclusions: For women living in the temperate regions, conception in summer and winter may increase the risk of preterm birth, and this association persisted in winter after adjusting for environmental factors. During the first 30 days of pregnancy, lower levels of humidity exposure in winter contributed to and mediated the relationship. The results may provide epidemiological evidence for pregnancy planning and care of women from the perspective of environmental factors.
Mycoplanecins, potent anti-tuberculosis antibiotics: Elucidation of unusual biosynthesis and DnaN-targeting mode of action
Authors: Müller Rolf , Fu Chengzhang , Liu Yunkun , Walt Christine , Rasheed Sari , Bader Chantal , Lukat Peer , Neuber Markus , Haeckl Jake , Blankenfeldt Wulf , Kalinina Olga
Published: July 2023

DNA polymerase III sliding clamp (DnaN) was recently validated as a new anti-tuberculosis target employing griselimycins. Three (2S,4R)-4-methylproline moieties of methylgriselimycin play significant roles in target binding and metabolic stability. Here, we identify the mycoplanecin biosynthetic gene cluster by genome mining using bait genes from the 4-methylproline pathway. We isolate and structurally elucidate four mycoplanecins comprising scarce homo-amino acids and 4-alkylprolines. Evaluating mycoplanecin E against Mycobacterium tuberculosis surprisingly reveals an excitingly low minimum inhibition concentration at 83 ng/mL, thus outcompeting griselimycin by approximately 24-fold. We show that mycoplanecins bind DnaN with nanomolar affinity and provide a co-crystal structure of mycoplanecin A-bound DnaN. Additionally, we reconstitute the biosyntheses of the unusual L-homoleucine, L-homonorleucine, and (2S,4R)-4-ethylproline building blocks by characterizing in vitro the full set of eight enzymes involved. The biosynthetic study, bioactivity evaluation, and drug target validation of mycoplanecins pave the way for their further development to tackle multidrug-resistant mycobacterial infections.
Bovine Herpes Virus Type 1 (BoHV-1) seroprevalence, risk factor and Bovine Viral Diarrhoea (BVD) co-infection analysis from Ireland
Authors: Barrett Damien , Lane Elizabeth , Lozano Jose Maria , O’Keeffe Kate , Byrne Andrew William
Published: July 2023

Surveillance of endemic pathogens is essential for disease control, providing an evidence base for policy and advice. Bovine Herpes Virus Type 1 (BoHV-1), the causative agent of Infectious Bovine Rhinotracheitis (IBR), has been found to have high seroprevalence within the Irish cattle population. The aim of the present study was to establish seroprevalence levels for culled cattle in Ireland aged <30months and to establish whether BVD exposure and other factors was associated with BoHV-1 exposure. We employed random effects logit models coupled with repeated bootstrap sampling to provide robust estimates. The final dataset contained results for 5,273 animals tested over two study years, 2018 and 2020. The animal-level seroprevalence of BoHV-1 was 21.43% (1,130/5,273; 95%CI:20.32%-22.53%). Univariable analysis suggested that BoHV-1seropositivity risk was associated with BVDV serodiagnosis status, age, sex, year sampled, herd type, herd-size, and metrics of movement into the herd. Final random-effects multivariable models suggested increased risk associated with increasing herd size of the last herd, movements made by animals during the previous year, and the year the animal was sampled. Despite BVDV status and sex being retained in the final model, repeated bootstrap sampling of the regression model to estimate biased-corrected 95%CI suggested that these associations were not robust. The overall apparent prevalence of BoHV-1 exposure for culled cattle in Ireland was declined in 2020 relative to 2018 (from 23.32% to 17.61%). Herd-size and the movement of animals were found to be important factors associated with animal-level risk, but there was less statistical support for sex-based or BVDV status associations.
Predictors of Hospital Nursing Staff’s Adherence to Safe Injection Guidelines, Applying the Protection Motivation Theory, in Fars Province, Iran
Authors: Karimi Masoud , Khorramaki Zakieh , faradonbeh Maryam Rabiei , Ghaedi Maryam , Ashoori Fatemeh , Asadollahi Abdolrahim
Published: July 2023

Background: Needle stick injuries (NSI) can lead to dangerous infectious diseases for health care workers. This study aimed to determine the Predictors of observance of safe injection guidelines in hospital nursing staff, based on protection motivation theory.
Methods: This cross-sectional study, was conducted on nursing staff of randomly selected five teaching and general hospitals of Shiraz University of Medical Sciences, Fars province, Iran, 2021. Data were collected by a researcher-made questionnaire which was developed based on protection motivation theory. Data were processed and analyzed using SPSS 22 and Amos 24 at a significance level of <0.05. Pearson’s correlation coefficient, Multiple linear regression and Structural Equation Modeling were used.
Results: The average age of 280 participants was 32.5±8.09 years. Most of participants [80%] have encountered NSI, patients’ blood, or body fluids at least once. Protection motivation was the only predictor of protective behaviors (β=0.573), while perceived efficacy (β=0.142) and perceived rewards (β=-0.229) were the strongest predictors of motivation. The structural equation modeling analysis showed that standardized total effects of protection motivation, perceived response costs, rewards and efficacy on the protective behaviors were 0.573, -0.159, -.104, and 0.81 respectively. While standardized total effects of perceived rewards, efficacy and response cost on protection motivation were -0.229, 0.142, and -0.033 accordingly. The model fit indices indicated the acceptable final model fit,
Conclusion: The results suggest that the educational interventions for hospital nurses to comply with safe injection guidelines should be focused more on perceived efficacy, perceived effectiveness, and perceived rewards
Assessing the Inter-rater Reliability of the Usability Model for Software Development Processes and Practices
Authors: Fontdevila Diego , Genero Marcela , Paez Nicolás , Oliveros Alejandro
Published: July 2023

Software processes and practices have a leading role in software development and in the last few decades a wide variety of processes and practices have emerged to face the challenges arising in the software industry. The success of process and practice adoption initiatives depends at least partially on the experience and satisfaction of the people who use them, thus making usability an interesting process quality attribute. This paper describes the inter-rater reliability evaluations performed on the UMP to assess consistency among metric values produced by different evaluators. It presents two inter-rater reliability assessment studies, the Scrum study and the TDD-BDD study. The paper presents four inter-rater reliability statistics for the process and practices under study, a comparative analysis of their strengths and weaknesses, and an analysis of the study results and their interpretation. The results show varying reliability results among the different UMP metrics, which seem to depend mostly on object of evaluation (Scrum, TDD, BDD), metric subjectivity and context sensitivity. The UMP was refined from the data gathered in the studies and a metric categorization is proposed to facilitate metric usage.
Limited Intercarpal Fusion vs. Proximal Row Carpectomy in the treatment of SLAC or SNAC Wrist, results after 3.5 years.
Authors: Gvozdenovic Robert , Schioedt Martina Agerskov , Solgaard Lars , Vadstrup Lars Soelberg , Soee Niels Henrik
Published: July 2023

The present study compares the postoperative clinical, radiological, and patient-reported functional results between the surgical procedures Proximal Row Carpectomy and Limited Carpal Fusion, in the treatment of SLAC and SNAC conditions of the wrist. 15 Proximal Row Carpectomy patients and 45 Limited Carpal Fusion patients were included in the study. Postoperative outcomes were assessed and compared for pain at load, range of motion, grip strength, Quick-DASH, and satisfaction. A radiological assessment was performed at the follow-up.
The Proximal Row Carpectomy patients had a mean age of 60 years (range 31-77) and a mean follow-up of 42 months. The Limited Carpal Fusion patients had a mean age of 58 years (range 35-76) and a mean follow-up of 41 months. The patients treated with Limited Carpal Fusion performed significantly better regarding pain, radial-ulnar motion, and the Quick-DASH (p = 0.002, p = 0.003, and p= 0.002), respectively. The grip strength difference between the treatment groups was stratified for gender and was found significantly better for men in the LCF-treated patients, but not different for women (p = 0.03, p = 0.26), respectively. Differences in volar-dorsal motion between the groups were insignificant (p = 0.525). A higher conversion rate to total wrist fusion was observed in the patients treated with the Proximal Row Carpectomy. All the Proximal Row Carpectomy patients had osteoarthritis at follow-up, whereas it was seen in 19% of the Limited Carpal Fusion patients. The patient-reported satisfaction was substantially better for the Limited Carpal Fusion patients. In conclusion, besides the findings of the grip strength which was most likely affected by different gender dispersion between treatment groups, the findings are in favour of Limited Carpal Fusion compared to Proximal Row Carpectomy, among patients treated for SNAC and SLAC wrist conditions. Further, preferably prospective studies are needed to confirm or reject our findings.
Development of UME CRM 1008: Certified Reference Material for C - reactive protein
Authors: Oztug Merve , Saban Evren , Kucuk Meltem , Isleyen Alper , Akgoz Muslum
Published: July 2023

A certified reference material (CRM) specifically designed for C-reactive protein (CRP) measurement in clinical laboratories was produced in this study. CRP, a protein synthesized by the liver, serves as an indicator of inflammation when present in elevated concentrations in the bloodstream. The primary goal is to ensure accurate measurement and quality control in accredited clinical laboratories. To achieve this, a recombinant CRP solution was selected as the most suitable candidate material for the CRM due to its exceptional purity. The homogeneity and stability of the developed CRM were thoroughly examined using size exclusion chromatography high performance liquid chromatography (SEC-HPLC). Additionally, amino acid analysis coupled with isotope dilution mass spectrometry (ID-LC/MS-AAA) was employed to determine the precise protein concentration of CRP in the CRM solution. The evaluation of uncertainties originating from factors such as characterization, homogeneity, long-term stability, and short-term stability data was incorporated to assess the uncertainty associated with the certified CRP value. Consequently, the certified value of the CRM, denoted as UME CRM 1008, was determined to be 43.2 ± 2.2 µmol kg-1, with an expanded uncertainty at a coverage factor of k = 2. The resulting CRP-certified reference material from this study will serve as an essential standard for validating CRP measurement methods and fulfilling quality control requirements within clinical laboratories. The ultimate aim is to make this reference material widely accessible to both national and international laboratories, thereby promoting accurate and standardized CRP measurements across the world.
Incorporation of nano-hydroxyapatite into experimental resin infiltrant and its performance on color stability and reinforcement in demineralized enamel: in vitro study
Authors: Zago Jade Laísa Gordilio , de Cerqueira Gabriela Alves , de Souza Robson Ferreira , Aguiar Flávio Henrique Baggio , Tabchoury Cínthia Pereira Machado , Marchi Giselle Maria
Published: July 2023

Objective The aim of the study was to evaluate the influence of the incorporation of 10% nano-hydroxyapatite into an experimental resin infiltranton color stability and cross-sectional microhardness.Material and methods 135 blocks were divided into five groups: H: healthy; MB: white spot; I: Icon®; E: experimental; EH: experimental containing 10% nano-hydroxyapatite. For color evaluation (n = 15), CIEL*a*b* values were obtained at the following time points: T0 (before immersion), T1 (14 days after immersion), and T2 (28 days after). Data were applied to CIEDE2000 formula. Cross-sectional microhardness (n = 12) data from the MB, I, E, and EH groups were applied to the mineral loss formula (∆S). Polarized Light Optical Microscopy images were obtained (n = 5) at 40x magnification. Shapiro-Wilk test was used to assess data normality for color stability and mineral loss. One-way ANOVA analysis was performed, followed by Bonferroni's post hoc test (color stability) and Tukey's test (mineral loss).Results In color stability results, regardless of time, there was no significant difference between H and MB groups; at 14 days and at 28 days, MB differed from all infiltrated groups, and H differed from E and EH. For ∆S, MB group showed a significant difference compared to I and EH groups but did not differ from E.Conclusion E and EH showcased similar performance to I regarding color variation. In terms of ∆S, I and EH had less mineral loss, suggesting a reinforcement of the dental structure.Clinical Relevance: Predict color stability and structural reinforcement of resinous infiltrants applied to white spot lesions.
Concurrent inhibition of oncogenic and wild-type RAS-GTP for cancer therapy
Authors: Singh Mallika , Holderfield Matthew , Lee Bianca , Jiang Jingjing , Tomlinson Aidan , Seamon Kyle , Mira Alessia , Patrucco Enricho , Goodhart Grace , Dilly Julien , Gindin Yevgeniy , Dinglasan Nuntana , Wang Ying , Lai Lick Pui , Cai Shurui , Jiang Lingyan , Yang Yu , Nasholm Nicole , Evans James , Montazer Nilufar , Lai Oliver , Shi Jade , Ahler Ethan , Chang Stephanie , Salvador Anthony , Marquez Abby , Cregg Jim , Liu Yang , Milin Anthony , Chen Anqi , Ziv Tamar Bar , Parsons Dylan , Knox John , Roth Jennifer , Rees Matthew , Ronan Melissa , Cuevas-Navarro Antonio , Hu Feng , Lito Piro , Santamaria David , Aguirre Andrew , Waters Andrew , Der Channing , Ambrogio Chiara , Wang Zhengping , Gill Adrian , Koltun Elena , Smith Jacqueline , Wildes David
Published: July 2023

RAS oncogenes (collectively NRAS, HRAS, and especially KRAS) are among the most frequently mutated genes in cancer, with common driver mutations occurring at codons 12, 13 and 611. Small molecule inhibitors of the KRASG12C oncoprotein have demonstrated clinical efficacy in patients with multiple cancer types and have led to regulatory approvals for the treatment of non-small-cell lung cancer (NSCLC)2,3. Nevertheless, KRASG12C mutations account for only ~14% of KRAS mutated cancers4 and there are no approved KRAS inhibitors for the majority of patients with tumors harboring other common RAS mutations. Here, we describe RMC-7977, a reversible, tri-complex RAS inhibitor with broad spectrum activity for both mutant and wild-type (WT) KRAS, NRAS, and HRAS variants (a RASMULTI(ON) inhibitor). Preclinically, RMC-7977 demonstrated potent activity against RAS-addicted tumors carrying various RAS genotypes, particularly cancer models with KRAS codon 12 mutations (KRASG12X). RMC-7977 led to tumor regressions and was well tolerated in diverse RAS-addicted preclinical cancer models. Additionally, RMC-7977 inhibited the growth of KRASG12C cancer models that are resistant to KRASG12C inhibitors due to restoration of RAS pathway signaling. Thus, RASMULTI(ON) inhibitors can target multiple oncogenic and WT RAS isoforms and hold the potential to treat a wide range of RAS-addicted cancers with high unmet clinical need. A related RASMULTI(ON) inhibitor, RMC-6236, is currently under clinical evaluation in patients with KRASG12X mutant solid tumors (NCT05379985).
Gut microbiota-derived 5-hydroxyindoleacetic acid from Pumpkin Polysaccharides supplementation alleviates colitis through Epac/Rap1 signaling activation
Authors: Zhang Qiao , Wang Qi , Li Xiaodong , Wu Minglan , Wu Xia , Zhao Qingwei , Li Weifen , Hu Xingjiang
Published: July 2023

Aims
Polysaccharides from Pumpkin (Cucurbita moschata Duchesne) (PP) have many pharmacological activities, including anti-oxidant, immune, and intestinal microbiota regulation. These activities have provided some reminders of its potential therapeutic effect on ulcerative colitis (UC), but this has not yet been confirmed. This study explores the potential modulatory roles of gut microbial metabolites (5-hydroxyindole acetic acid, 5-HIAA) after PP treatment in protecting against UC and to elucidate the underlying molecular mechanisms.
Results
The average molecular weight of PP was 3.10 × 105 Da, and PP mainly comprised Mannose, Rhamnose, Galacturonic acid, Galactosamine, Glucose, and Xylose with molar ratios of 1.58:3.51:34.54:1.00:3.25:3.02. PPs (50, 100 mg/kg) could significantly resist dextran sodium sulfate (DSS) induced UC on C57BL/6 mice by improving gut microbiota dysbiosis and intestinal mucosal barrier function. Metabolomic profiling analysis showed that PP supplementation resulted in the enrichment of 5-HIAA, which exhibited individual and synergistic anti-UC activities. The results of the transcriptome and confirmatory experiments suggested that Rap1 pathway activation may participate in the anti-UC effect of PPs. 8-pCPT-2’-O-Me-cAMP (Epac/Rap1 signaling antagonist) showed similar anti-UC activity to PP and 5-HIAA, while the effect of ESI-05 (Epac/Rap1 signaling inhibitor) was opposite. Furthermore, exogenous treatment with 5-HIAA activated the Epac/Rap1 signaling pathway both in vitro and in vivo, which may be related to elevated cAMP levels in the colon.
Conclusions
This study revealed that PP could be developed to treat UC and other diseases associated with an imbalance in the intestinal microbiota. The gut microbiota-5-HIAA-Epac/Rap1 axis plays an important role in intestinal homeostasis and may provide a novel approach for the prevention of UC by manipulating gut microbial serotonin metabolites.
Prognostic value of moderate or massive ascites in patients with advanced gastric cancer
Authors: Iwai Naoto , Ohara Tomoya , Okuda Takashi , Oka Kohei , Sakai Hiroaki , Kajiwara-Kubtota Mariko , Tsuji Toshifumi , Sakagami Junichi , Kagawa Keizo , Doi Toshifumi , Inoue Ken , Dohi Osamu , Yoshida Naohisa , Uchiyama Kazuhiko , Ishikawa Takeshi , Takagi Tomohisa , Konishi Hideyuki , Itoh Yoshito
Published: July 2023

Background
Advanced gastric cancer is one of highly aggressive malignancies. The available literature does not provide the prognostic value of ascites based on its degree because most clinical trials exclude patients who present with massive ascites. Therefore, this study aimed to examine whether the presence or degree of ascites has a prognostic value in patients with advanced gastric cancer in clinical settings.
Methods
Totally, 124 patients with advanced gastric cancer were recruited. The degree of ascites was assessed using computed tomography (CT) and classified as none, small, moderate, or massive. The overall survival (OS) was compared based on the presence or degree of ascites. Furthermore, the Cox proportional hazards analysis was performed to ascertain the predictors of OS.
Results
The cumulative one year, and two year OS rates in patients without ascites were 43.5%, and 20.2%, respectively, whereas those in patients with ascites were 29.1%, and 13.6%, respectively (P = 0.116). The cumulative one year, and two year OS rates in patients without moderate or massive ascites were 39.5%, and 20.9%, respectively, whereas those in patients with moderate or massive ascites were 28.0%, and 4.0%, respectively (P = 0.027). In the multivariate analysis, diffuse-type (hazard ratio [HR], 1.532; 95% confidence interval [CI], 1.002–2.343; P = 0.049), moderate or massive ascites (HR, 2.153; 95% CI, 1.301–3.564; P = 0.003), and chemotherapy (HR, 0.189; 95% CI, 0.101–0.352; P < 0.001) were significant predictive factors of OS.
Conclusion
We determined that moderate or massive ascites influenced OS of patients with advanced gastric cancer.