bluuebunny/crossref_metadata_2025 huggingface dataset:
Exclusion of a Giant Right Coronary Artery Aneurysm with Concomitant Bypass Grafting
Authors: Mullis Danielle , Alnasir Daniel , Garrison Alyssa , Vargas Nataly , Tsai Lilian , MacArthur John
Published: December 2024

Coronary artery aneurysms (CAAs) are defined as a dilation of 1.5 times the diameter of a normal adjacent coronary artery, and CAAs larger than 20 cm are classified as giant. CAAs are typically asymptomatic, but complications can be fatal. There is currently no consensus on treatment, although medical, percutaneous, and surgical options have all been previously described in the literature. Additionally, there is little published video footage of the surgical exclusion of giant coronary artery aneurysms. This report describes the case of a 53-year-old man with a persistent globus sensation who was found to have a 4.5 cm right coronary artery aneurysm with diffuse calcification of the right coronary artery. He underwent exclusion of the aneurysm and coronary artery bypass grafting (radial artery to the right coronary artery and left internal mammary artery to the left anterior descending artery). Due to heavy calcification in the vessel wall, the right coronary artery both proximal and distal to the aneurysm was ligated with a pericardial buttress. The patient had no major adverse events and was discharged six days after surgery. This report includes detailed video footage of the giant coronary artery aneurysm exclusion technique. This case and accompanying video footage will help prepare surgeons to manage adult patients with CAAs and diffuse coronary atherosclerosis.
Maxillary Sinus Lift Surgery: “Description and Comparison of the Different Techniques” Clinical Case of Sinus Lift and Placement of Phibo TSH and TSA Implants
Authors: Lloret Antonio , Rogel Carlos
Published: December 2024

A bibliographic review was carried out on the different procedures and most common materials for augmentation or elevation of the maxillary sinus for the posterior or joint placement of endosseous implants. The objective of this work is to present a clinical case and review the existing literature. The topic has been widely discussed by different specialists, describing the different techniques, and also that it is a procedure with a high success rate. On the other hand, it can usually be performed in an outpatient clinic, respecting the concepts of asepsis that must be considered in oral surgery procedures: correct preparation of the equipment, sterilization of instruments and disinfection of the surgical field. That is, all instruments in previously sterilized airtight bags, surgical fields and sterile gloves, table and equipment, all properly disinfected. In addition, both the care team and the surgeon must have disposable sterile surgical caps and gowns. It is important to highlight that when handling bone fillers, they must also be packaged with the maximum sterilization protocols for their use.
Modelling Seasonal Variation and Lassa Fever Outbreak in Nigeria: A Predictive Approach
Authors: Musa Adesola , Osuolale Kazeem , Lawal Dayo , Salako Abideen , Aponinuola Fewajesuyan , Tijani Wakilat , Adigun Abass , Salako Babatunde
Published: December 2024

Background: Lassa fever, a severe viral hemorrhagic fever caused by the Lassa virus, is a significant public health concern in West Africa, particularly in Nigeria. First identified in the 1950s, Lassa fever has been a persistent threat, causing outbreaks annually. This study investigates the temporal patterns and trends of Lassa fever outbreaks in Nigeria between 2017 and 2023, leveraging a comprehensive dataset from the Nigerian Centre for Disease Control (NCDC). Objective: The goal of this study is to analyze the seasonal variations and predict future occurrences of Lassa fever outbreaks in Nigeria. By employing the Box-Jenkins time series analysis and geo-spatial analysis, we aim to: Identify temporal patterns by Examining monthly and annual trends in Lassa fever case numbers, Forecast future outbreaks by utilizing an ARIMA model to predict future incidence rates and inform public health strategies by providing evidence-based recommendations to improve Lassa fever prevention and control efforts. Methods: This study utilized a secondary dataset comprising over 60 data points collected from the NCDC portal between 2017 and 2023. The Box-Jenkins time series analysis, specifically the ARIMA model, was employed to analyze the temporal patterns and forecast future trends. The model's adequacy was assessed using the Ljung-Box test. Additionally, geo-spatial analysis was conducted to visualize the spatial distribution of Lassa fever cases. Results: The analysis revealed distinct seasonal patterns in Lassa fever incidence, influenced by Nigeria's climatic and environmental conditions. Monthly fluctuations in confirmed cases were observed, with peak periods aligning with specific seasons. The ARIMA (0, 1, 1)(0, 1, 1)12 model demonstrated a strong fit to the data, providing reliable forecasts for future outbreaks. Conclusion: This study underscores the importance of strengthening surveillance systems for early detection and rapid response to Lassa fever outbreaks, particularly during peak seasons. Implementing effective rodent control measures, promoting good hygiene practices, and improving environmental sanitation are crucial for reducing the risk of Lassa fever transmission. Furthermore, enhancing collaboration between government agencies, healthcare providers, and research institutions is essential for optimizing Lassa fever prevention and control efforts.
Application of VES and Physicochemical Analysis for the Evaluation of Dissolved Minerals in the Alluvial Aquifers of Part of Yenagoa, Bayelsa State
Authors: Amakiri Arobo , Okorobia Ebi , Amonieah Jiriwari , Otugo Vivian
Published: December 2024

The sufficient provision and sustenance of quality water have been of a fundamental consequence in the social and economic developmental activities of humans over the years, especially in Bayelsa state and Nigeria at large, where developmental activities are on the increase. Potable water is essential to humans and animals alike, for personal, communal, industrial and societal uses. This study seeks to investigate the concentration of dissolved minerals, using an integrated approach of VES data and physicochemical analysis of ground water samples in parts of Bayelsa state, south-south Nigeria. Vertical Electrical Sounding was implemented in ten stations and interpreted using IPI2WIN software. The results from the VES interpretation revealed that the area is constituted of four to five geoelectric layers. Four distinct sounding curve types (H, HK, K and KH) were identified; with the H and K type curves being dominant. The dominant curve types show that the area has two main hydrologic regimes (of low and high Iron (Fe) concentration). The results show that in VES stations with K-type curve, the stratigraphy consists of the three to four layers, with varying thickness and corresponding resistivities; with the third or fourth layers identified as the aquifer layer. At H-type curve locations, the stratigraphy consists of the top soil, the clay layer, and the sand layer, which was identified as the aquifer. The physicochemical characteristics of water samples, collected from drilled boreholes in the vicinity of the VES locations of the study area, were analyzed for prominent physical and chemical constituents, including EC, pH, TDS, Na, K, Ca, Mg, Fe, Cl, SO, NO, and HCO. Physicochemical analysis was achieved using the standard APHA methods and compared with WHO standard. The results showed that the concentration of the chemical constituents varied spatially in the study area. The analysis revealed that 90% of the mean concentration of measured parameters were within the WHO’s standard in all the samples, except for Mn (with a value of 0.532 mg/L) and Fe2+ (with a value of 0.88 mg/L) which was seen to be high in five of the boreholes in locations with H-type curves, hence correlating areas of high groundwater contamination to VES stations of the H-Curve type. The high Mn and Fe concentrations in the groundwater of some of the locations, makes the water unsuitable for drinking and may require treatment. Further analysis of the ground water samples, indicated that, Chloride and Sulphate are the predominant anions while, Calcium and Magnesium are the predominant cations in groundwater within the study area.
SARS-CoV-2 Infection, Vaccination, and Irritable Bowel Syndrome in Veterans: A Cross-Sectional Study
Authors: Parsi Arash , Verne George , Jiang Yu , Theus Sue , Sullivan Josh , Zhou Qiqi
Published: December 2024

Background: The association and interaction between SARS-CoV-2 (COVID-19) infection and irritable bowel syndrome (IBS) has not been adequately explored. We sought to determine whether a mechanistic relationship exists and whether vaccination against COVID-19 plays a role in this relationship. Methods: Using the Veterans Affairs (VA) electronic healthcare database, we obtained a random sample of veterans in October 2022 for this cross-sectional study. Demographic characteristics of the participants (e.g., age, sex, race), prior COVID infection, COVID vaccination status, and IBS diagnosis were extracted from the VA medical records. Univariate and multivariate logistic regression analyses were performed to determine potential associations between the listed factors and IBS diagnosis. Results: A total of 9,112 veterans were analyzed. In univariate analysis, race, COVID infection, and vaccination were significantly associated with IBS. In multivariate regression analysis, only the effects of COVID infection and vaccination were statistically significant. The odds ratios for development of IBS among veterans with COVID infection versus those without was 1.94 (95% CI: 1.53-2.45), and for vaccinated versus unvaccinated, was 1.49 (95% CI: 1.18-1.89). Further analysis showed that vaccinated veterans who did not contract COVID infection had a lower risk of developing IBS compared to unvaccinated veterans who contracted COVID. Conclusions: The results of this study suggest that veterans with COVID infection are almost twice as likely to develop IBS compared to those who have never had COVID infection. Vaccinated veterans have a lower risk of contracting COVID and subsequently, a diminished chance of developing IBS. Overall, vaccination of veterans with protection against COVID diminishes the risk of IBS development.
Physico-Chemical and Biochemical Characteristics of the Assabonou Mango Variety with a View to Valorization
Authors: Gueu-Kehi Minkapieu , Bouatenin Koffi , Kouamé Kohi , Djè Koffi , Koussemon Marina
Published: December 2024

In Côte d'Ivoire, mango (Mangifera indica) is one of the most widely consumed fruits after banana. However, the assabonou variety, an existing wild variety, is less consumed because of its fibrous character. With a view to promoting its consumption, the aim of this work is to characterize this mango from a nutritional point of view, with a view to its possible valorization. The physico-chemical and biochemical characteristics of this mango were analysed. For the analyses, 10 kg of assabonou mango were collected from each of the five villages in the Yamoussoukro district (Apkessekro, Assabonou, Logbakro, N'gokro and Sahabo). The physico-chemical analyses carried out showed that the pH of assabonou variety mangoes juices from these various towns ranged from 4.20 ± 0.17 to 4.53 ± 0.05. The titratable acidity varied from 0.56±0.01 to 0.063±0.01%. Titratable acidity ranged from 0.56±0.01 to 0.063±0.01%. Soluble sugar content ranged from 12.16±0.28° Brix to 14.83±0.57° Brix. Dry matter content ranged from 13.75±2.20% to 20.38±1.81%. Biochemical analysis showed that assabonou mango variety samples were essentially rich in Potassium, Magnesium and Calcium, with averages of 55.56 mg/100g MS, 12.61 mg/100g MS and 19.30 mg/100g MS respectivelyMacronutrients included digestible carbohydrates (15.192 g/100 g DM), fiber (2.44 g/100 g DM), protein (0.73 g/100 g DM), total sugars (13.69 g/100 g DM) and reducing sugars (1.72 g/100 g DM). In view of its nutritional potential, steps should be taken to limit losses due to rotting during harvesting periods, by planning its transformation into fermented products for the production of beverages or novel foods.
Spectra Analysis of Endocrine Related Compounds and Heavy Metals in Petroleum Hydrocarbon Impacted Soil
Authors: Obinna Ezenwelu , Chijioke Ilechukwu , Eberechukwu Iloanya , Joy Onwah , Chidiebere Chigbo , Henry Oparaji
Published: December 2024

There has been increasing influx of noxious pollutants into the ecosystem, these recalcitrant affect all biosphere of life including human progression. Petroleum compounds are the chief source of hydrocarbons and their processing contributes to various fractions of potent poisons into the ecosystem. Petroleum hydrocarbon impacted soil was sampled from spilled sites located within the hinters of Rivers state Nigeria and using a spectroscopic assay method, they were examined for the presence of heavy metals and chemicals associated to bisphenol-A bioaccumulation. The collection point for the control experiment was roughly 1.04 kilometers away from the suburban city. The test and control studies revealed the presence of heavy metals Fe, Pb, and Cu, respectively. However, the concentrations of Fe and Pb were rather high, measuring 14.01±0.05b and 3.52±0.2a mg/ml, respectively. Cu was found at 3.22±025c and 1.08±045c mg/ml for the test and control experiment respectively while 4.56±0.15c mg/g of Pb was identified in the test experiment only Heavy metals of Cd, Ni, As, Pb and Mn were below detectable limit in both experiments, respectively. FTIR spectroscopy revealed that sample II's amide I was severely deformed, but all of the damaged soil samples had significant hydroxylation at about 3300 cm-1. The impacted soil sample also exhibited evidence of amide I bending. Because of the population's increasing demand for elite supplies, there is a growing number of oil drilling and exploration businesses in our nation, making the current study of clinical and environmental health vital. The results of this assessment will serve as a suitable manual for monitoring organizations, enabling them to strictly enforce policies for exploration and tighten all departure ports in order to safeguard the ecosystem right away.
Influence of Physico-Chemical Parameters on the Seasonal Dynamic of Salmonella spp Isolated from Urban Streams in Yaounde (Cameroon)
Authors: Bessa Henriette , Nougang Mireille , Adjia Ghislaine , Takem Gloria , Nnomo Bernadette , Kweyang Blandine , Djimeli Chrétien , Ewoti Olive , Eheth Jean , Nola Moïse , Njine Thomas
Published: December 2024

As water resources in urban areas are becoming increasingly degraded, due in large part to poor sanitation, a study has been was conducted to examine the influence of physicochemical parameters and seasonal variation on the distribution of the enterobacteria Escherichia coli and Salmonella spp that have been isolated from the urban streams in the city of Yaounde. Bi-monthly water samples were collected from nine rivers during 12 months (April 2010 to March 2011). The isolation of bacterial germs was done according to the classical method. Physicochemical parameters were analyzed according to Standard methods. Salmonella spp was detected all over the studied year with a high prevalence of 49.4%. This prevalence varies from one season to another. Escherichia coli ranged between 2.5 x 103 to 67.1 x 103UFC/100ml with highest prevalence observed during the long dry season. Physicochemical parameters revealed neutral to slightly alkaline waters (pH6.7 – 8.8), with low mineralization (EC= 126 – 743 µS/cm). Dissolved oxygen was generally less than 4 mg/l. Physicochemical parameters also showed temporal homogeneity in most of the variables (pH, EC, TDS, total hardness, alkalinity, Na, K, Mg, Ca). None of the physicochemical environmental variables analyzed had any specific influence on the presence of Escherichia coli or Salmonella. Furthermore, there was no significant correlation between the presence of Escherichia coli and Salmonella spp, as the sources of Salmonella spp contamination are probably different from those of E. coli. The observed pollution of rivers is related to the large anthropogenic activities in particular, the multiplicity of small farming closed to markets and houses, and husbandry activities along the streams which are important sources of organic matter. These rivers constitute a pool of Salmonella that can be easily disseminated in to different ecological systems and therefore represent a serious health risk for people who may come into direct or indirect contact with this pathogen.
Spatial Based Analysis of Internally Displaced People in The Case of East Harerge Zone, Oromia Region, Ethiopia
Authors: Obse Birhanu , Kebede Tsion , Belayhun Matiwos
Published: December 2024

Internally displaced persons (IDPs) are individuals or groups forced to flee their homes due to human-induced or natural causes. This study aims to analyze IDPs in East Harerge Zone using Geographic Information System, focusing on spatial aspects of internal displacement. The research examines the causes, hotspot areas, spatial patterns, trends, and statistics of displacements in the Zone. A mixed research approach was employed to understand the contextual situation of IDPs, incorporating their own meanings, experiences, and challenges. Primary data sources included observations and key informant interviews with Zonal, Woreda Disaster Risk Management Office (DRMO) officials, and humanitarian workers in East Harerge. Secondary data sources comprised published and unpublished documents such as Displacement Tracking Matrix (DTM) datasets from 2017-2022, humanitarian reports, journals, books, administrative boundary data, and IDP population figures. The study reveals a high number of displacements in East Harerge Zone from 2017 to 2022, with IDPs originating from 15 out of 24 Woredas (63%) and displaced to various locations within the country, including Dire Dawa, Somali Region, and other regions. Conversely, IDPs were also displaced to East Harerge Zone from the Somali region, residing in 22 out of 24 Woredas (92%). The spatial distribution of displacement, causes, hotspot areas, and existing IDP sites were discussed in a spatial context using ArcGIS software. The causes of displacement were analyzed in conflict, drought, and flood-induced bases. Therefore, this study will be an input for All disaster risk management offices starting from National to Woreda level to make better decision and policy to strengthen spatial bases disaster management mechanism using GIS and remote sensing technologies.
An Empirical Investigation and Analysis of Foreign Aid- Economic Growth Nexus in Sierra Leone (1980-2023)
Authors: Hadji Sylvester , Bockarie Momoh
Published: December 2024

Sierra Leone, being a small and poor developing country, colossally relies on foreign aid, cardinally as a result of infinitesimal Gross Domestic Product (GDP) and improper resource management. The study elects to investigate and analyse foreign aid-economic growth nexus in Sierra Leone for the period 1980-2023. The study uses time series secondary data obtained from various sources such as the International Financial Statistics (IFS), Central Bank of Sierra Leone (CBSL), Ministry of Finance (MoF), World Development Indicators (WDI) and Sierra Leone Central Statistics Office (SLCSO). Various macroeconomic variables including investment to GDP ratio, exchange rate, terms of trade, inflation and public debt were specified in the model used in this study. A time series growth model was estimated using ordinary least squares (OLS) and Newey-West estimation techniques. The Hendry’s general-to-specific method was used to arrive at the estimated model. Stationarity test, using Augmented Dickey-Fullah Generalised Least Squares (ADF-GLS) and the Perron Vogelsang tests for unit root, was carried out for all variables in the model to avoid spurious regression results which are common with time series analysis of macroeconomic data using OLS technique. The study empirically reveals a positive and significant impact on economic growth in Sierra Leone for the period being investigated. The study, therefore, provides key recommendations consistent with the findings, among which, is the need for policymakers to exercise tremendous efforts to further attract foreign aid to Sierra Leone in order to boost output and economic growth, ensuring that such resources are well managed.
Review of Opportunities and Challenges in China-Afghanistan Relations Post-U.S. Withdrawal
Authors: Acxir Abdul , RahmanZai Shams
Published: December 2024

The relationship between China and Afghanistan has witnessed significant changes over the years, encompassing various political, economic, and security dimensions. Afghanistan's strategic location as a bridge between Central and South Asia holds particular significance for China, serving as a key transit route for infrastructure projects like the Belt and Road Initiative (BRI), the China-Pakistan Economic Corridor (CPEC), and others. Additionally, Afghanistan's rich mineral reserves, including copper, oil, and lithium, are particularly attractive to China, especially for its technology and electronics manufacturing industries. Therefore, despite these attractions, China seeks to establish peace and stability in Afghanistan to enable the country to serve as a reliable economic and trade partner. However, despite the opportunities present in bilateral relations, the unstable security situation in Afghanistan, especially after the withdrawal of international forces, the presence of regional powers like India, Pakistan, and Iran, and their competition for influence in Afghanistan, along with security concerns, represent significant challenges that could impact bilateral relations. This article uses a descriptive library-based method to address the question: What opportunities and challenges exist in China-Afghanistan relations, and how can both countries manage these challenges to capitalize on opportunities to strengthen bilateral cooperation? It is assumed that China and Afghanistan, by leveraging economic opportunities stemming from Afghanistan's natural resources and joint infrastructure projects, can strengthen their relations, provided both countries manage security challenges and regional competition wisely to ensure the necessary stability for such cooperation.
Partially Embedded Metal Rings on the Right Middle Finger and Entrapment of Rings on the Right Index and Ring Fingers in a Psychiatric Patient: A Case Study
Authors: Ranjan Kumar
Published: December 2024

Rings are not only commonly worn as symbols of love and commitment, such as wedding rings, but they also serve as decorative pieces in various cultures. The finger rings are made up of materials of different grades (Soft or hard metals), influenced by availability and social customs. However, these accessories can sometimes become problematic when they get stuck on the fingers. This problem tends to occur more frequently in women and younger people. Most of patients present with distal digit swelling and pain, and sometimes present late with gangrene of the involved digits. In most cases, trapped rings do not cause any vascular or neurological damage, but timely removal is critical to prevent complications such as the tourniquet effect, where blood flow to the digit is compromised. The removal of rings is necessary under certain clinical conditions, especially in emergencies where swelling or trauma complicates the situation. Patients with psychological disorders or substance abuse problems may sometimes resist the removal of rings, making treatment more complicated. In this case report, we discuss the management of a psychiatric patient who presented with significant swelling in three digits due to embedded rings, highlighting the delayed treatment and the methods used for successful ring removal. In our case, we managed to remove entrapped and embedded finger rings by non-destructive and destructive methods with good outcomes.
A Method for Determination of Hydrocarbon and Nitrogenous Biochemical Oxygen Demands in Natural Waters by Manometric Method
Authors: Sargsyan Suren
Published: December 2024

The aim of the work was the simultaneous determination of hydrocarbon biochemical oxygen demand - cBOD and nBOD (nitrogen) in the same water sample without using a nitrification inhibitor by the manometric method. Daily measurements of cBOD are determined by recording the pressure drop resulting from the absorption of carbon dioxide released by the oxidation of hydrocarbon organic matter by microorganisms with KOH (potassium hydroxide). Here, the processes of oxidation of mineral substances in water and especially the developing nitrification processes, which absorb oxygen dissolved in water and cause an additional pressure drop in the vessel, are a disturbing factor, for the measurement of which, in the daily 24-hour cycle of registrations, it is recommended to close the absorption hole of the vial with KOH for 8 hours. The 24-hour nBOD and cBOD results are calculated from the result of the pressure drop in these 8 hours. In the paper, in the form of a table, the detailed form of calculation of the recorded results of BODs at two pH-s of a natural water sample within 1-20 days is given. The possibility of anthropogenic impact assessment using this method is shown on the example of natural water. It is concluded that with the proposed method of measuring BODs records the complete and separate results of cBOD are recorded under conditions of developing nitrification in water. All information from both nitrification and BOD-full is recorded simultaneously, which gives a complete picture of the overall oxygen balance in the water. The proposed method is practically applicable and fully comparable with the results obtained by the standard manometric method.
Assessments of Challenges and Opportunities for Practicing Irrigated Rice Production in Ethiopia
Authors: Mekonen Belachew
Published: December 2024

Rice production in Ethiopia, though not traditionally a staple, has become a key focus in the country’s efforts to enhance food security and reduce dependency on imports. Despite favorable agroecological conditions for rice farming, productivity remains low due to several challenges, including inadequate access to improved seeds, irrigation systems, and modern mechanization. This study evaluates the challenges and opportunities for practicing irrigated rice production in Ethiopia, analyzing both challenges and opportunities through a mixed-methods approach. Primary data was collected via field surveys, key informant interviews, and focus group discussions with farmers, agricultural experts, and policymakers across diverse regions. Key challenges include poor water management, limited adoption of modern technologies, high input costs, weak market access, climate variability, and infrastructure limitations. However, Ethiopia's diverse agroecological zones and government support provide opportunities for sustainable rice cultivation, particularly through improved irrigation, adoption of modern technologies, and enhanced market linkages. The study concludes that a comprehensive, multi-faceted approach involving government, NGOs, and farmers is essential to unlocking the potential of irrigated rice production in Ethiopia. Recommendations include improving water management, promoting public-private partnerships, expanding access to credit, and implementing climate-smart agricultural strategies to boost rice production and enhance food security.
Comparative Study of Two Thoracic External Beam Radiotherapy Regimen 30Gy in 10 Fractions Versus 20Gy in 5 Fractions for Palliation of Symptoms in Non-Small Cell Lung Cancer
Authors: Karim Md. , Ghosh Ashim , Khatun Rawshan , Khatun Julekha , Chakrabarty Nishan
Published: December 2024

Metastatic non-small cell lung cancer (NSCLC) frequently manifests with symptoms from the primary tumor within the chest, such as shortness of breath, chest pain, coughing, and hemoptysis. Thoracic palliative radiotherapy is a viable option for alleviating symptoms in these patients, who typically have a poor prognosis and are not candidates for curative treatment. Given their limited survival, a shorter treatment period that achieves adequate palliation is often preferred. Hypofractionated thoracic radiotherapy may meet this criterion. This quasi-experimental study, conducted at the Department of Radiotherapy, Rajshahi Medical College Hospital from January to December 2020, aimed to compare the response and acute toxicity of two thoracic external beam radiotherapy (EBRT) regimens—30 Gy in 10 fractions versus 20 Gy in 5 fractions—in the palliation of symptoms in NSCLC patients. Seventy-two diagnosed NSCLC patients with chest tumor-related symptoms (cough, dyspnea, hemoptysis, chest pain) unsuitable for radical treatment were enrolled and allocated into two groups by a non-randomized technique. Arm-A received 30 Gy in 10 fractions, while Arm-B received 20 Gy in 5 fractions. Patients were assessed before radiotherapy, at the end of treatment, and at 4 and 8 weeks post-treatment. The study found that both Arm-A and Arm-B showed highly significant improvement in all symptoms compared to pre-treatment status (p < 0.001), with no significant difference between the two arms (p > 0.05). In Arm-A, 22.22% of patients achieved complete symptomatic response and 44.44% showed improvement, while in Arm-B, 19.44% of patients achieved complete symptomatic response and 50% showed improvement. No statistically significant difference was observed between the two arms regarding clinical symptomatic response (p > 0.05) or treatment-related toxicities (p > 0.05), all of which were manageable. In conclusion, both treatment regimens were equally effective in symptom palliation and had comparable toxicity profiles, supporting the use of either regimen depending on patient needs and resource availability.
Managerial Myopia and Corporate Sustainable Development Capabilities
Authors: Feng Na
Published: December 2024

Currently, the economy of China is demonstrating positive momentum. However, it also faces pressures stemming from structural adjustments and changes in the external environment. Ensuring sustainable development at the corporate level is crucial for maintaining overall economic stability and sustained growth within the nation. This paper utilizes A-share listed companies from 2007 to 2022 as a research sample and employs methods such as text analysis to measure managerial myopia, thereby investigating the relationship between managerial myopia and corporate sustainable development capabilities. The study finds a significant negative correlation between managerial myopia and corporate sustainable development capabilities, with the level of financialization of the corporate playing a mediating role: managerial myopia can lead to an increase in the level of financialization of the corporate, thereby weakening corporate sustainable development capabilities. Furthermore, internal controls and managerial incentive pay weaken the negative relationship between managerial myopia and corporate sustainable development capabilities. This paper also analyzes the degree to which managerial myopia weakens the sustainable development capabilities of enterprises with different property rights and different institutional investor shareholding ratios. It is found the detrimental impact of managerial myopia on the sustainable development capabilities of state-owned enterprises and corporate with lower institutional investor shareholding is more pronounced.
Job Satisfaction Among Teachers at Schools in Nepalese Context
Authors: Lamsal Hiranya , Bhandari Narayan , Neupane Shyam
Published: December 2024

Teachers have a pivotal role in building the future of any nation. Considering this fact, this study aims to examine and analyze the job satisfaction among teachers at community and institutional schools of Devdaha Municipality. The study had attempted to analyze the factors determining the job satisfaction of teachers. The data were collected through performing structured questionnaire survey as a data collection instrument. Job satisfaction among school teachers in Devdaha Municipality were measured with a 5-point Likert scale. Except the demographic variables of the respondents, choices of all items were based on five points. The collected data were analyzed using Microsoft excel, and SPSS statistical package. The reliability statistics, analysis of demographic profile, descriptive statistics, analysis of relationship between components of demographic profile and dependent variable were used to accomplish the objectives of the research. The study concludes that different factors like pay, supervision promotion, fringe benefits have effects on teacher's job satisfaction.
Achieving Healthcare Value through Care Plan Accountability
Authors: Rezen John
Published: December 2024

U.S. medical costs continue to outpace the GDP despite the introduction of multiple accountable care efforts established to reduce unnecessary expenditures. These increasing costs have a negative impact on patients who are experiencing increased out-of-pocket expenses as well as employers who must shoulder a large part of the healthcare cost burden. While there are multiple societal factors contributing to the rising medical costs, our healthcare system can play a more effective role in addressing this problem. This role begins with fundamental changes to our reimbursement systems placing an emphasis on individual plans of care and adding greater accountability through free market controls. A comprehensive plan of care lays out the roles of care plan participants across medical, social, and behavioral services with a corresponding budget covering all the services provided as well as the expected outcomes from each service. An initial free market control is patient authority to accept or reject the plan of care with a corresponding financial responsibility for compliance in care plan execution. The elements of provider accountability include a public provider performance reporting system across quality, costs and patient satisfaction factors as well as a reimbursement system that incentivizes effective care planning and execution. This shift in focus from incremental care to care planning and execution combined with the institution of pro-competitive and financial accountability measures is expected to bring greater value to healthcare by improving patient outcomes while reducing medical costs.
Fibrin Clot Shields Formation in the Tumor Microenvironment, Induced By Cancer Cells' Hypercoagubility, Serves As Scaffolds for Invasion and Protection Against Anticancer Treatments
Authors: Huong Tran Chi Mai , Van Dreden Patrick , Mbemba Elisabeth , Rousseau Aurelie , Lefkou Eleftheria , Sabbah Michele , Gerotziafas Grigoris
Published: December 2024

Introduction: Neoangogenesis, vascular mimicry and highly permeable blood vessels expose cancer cells to coagulation factors from plasma. The expression of Tissue Factor (TF) by cancer cells leads to local hypercoagubility in the tumor microenvironment. We aimed to study the ability of cancer cells to induce fibrin formation in the tumor microenvironment, and the role of fibrin in cancer cells' physiology.

Materials and methods: Highly procoagulant pancreatic cancer cells (BXPC3), highly procoagulant and invasive breast cancer cells (MDA-MB231), weakly procoagulant and non-invasive breast cancer cells (MCF7) were cultured in the presence of of normal human platelet-poor plasma (PPP) diluted 10% in RPMI-1640 media (PPP-media). Structural characteristics of fibrin clot were analyzed using Scanning Electron Microscopy. Fibrinolytic activities were studied by quantifying tissue-type plasminogen activator (t-PA) and D-Dimer concentrations. Cancer cells' invasion was observed using Laser Scanning Confocal Microscopy. The efficacity of paclitaxel (PTX) and 4-hydroxytamoxifen (4OHTam), at their IC50 concentrations, on cancer cells viability in the absence and presence of fibrin clot shields was assessed.

Results: Culture of cancer cells in the presence of PPP-media led to the formation of Fibrin Clot Shields (FCS) in a “bird's nest-like” architecture. MDA-MB231 cells led to the formation of the most dense FCS with finest fibers, smallest pores and highest number of intersections, as contrast to MCF7 cells. The structure of FCS formed by BXPC3 are intermediated. Adding 1 pM of TF to the culture media of MCF7 led to FCS with similar structures to those of BXPC3 cells. MCF7 cells do not possess fibrinolytic activity as contrast to the other two cell lines. All of the three cancer cell lines showed invasion ability in the presence of FCS. The presence of FCS also abrogated the efficacity of PTX and 4OHTam in inducing cell death.

Conclusions: The procoagulant fingerprint of cancer cells leads to the formation of FCS in the microenvironment. We showed for the first time a clear image of the architecture of FCS formed by cancer cells. FCS serve as scaffolds for cell invasion and protection against anticancer treatments such as PTX and 4OHTam. These results suggested FCS as a new mechanism for resistance to treatments and a potential new target to improve treatments' efficacity.
Mechanistic Modeling to Support Hemostatic Equivalency of Antithrombin Lowering in People with Hemophilia A or B
Authors: Leiser Randolph , Kaddi Chanchala , Tao Mengdi , Salvador Ane , Seth Chhabra Ekta , Zaph Susana
Published: December 2024

Fitusiran is an investigational siRNA therapeutic that lowers antithrombin (AT) to increase thrombin generation and rebalance hemostasis in people with hemophilia A (PwHA) or B (PwHB), irrespective of inhibitor status. Three completed phase 3 clinical studies [ATLAS A/B (NCT03417245), ATLAS INH (NCT03417102), and ATLAS PPX (NCT03549871)] have demonstrated that fitusiran prophylaxis significantly reduced bleeding events compared to on-demand or prior prophylaxis treatment with clotting factor concentrate (CFC) or bypassing agents (BPA) (Srivastava et al. Lancet Haematol 2023; Young et al. Lancet 2023; Kenet et al. Blood 2022).

A quantitative systems pharmacology (QSP) model of the coagulation pathway was previously applied to support the hemostatic equivalency of fitusiran prophylaxis (i.e., AT lowering) in PwHA (Kaddi et al., 2022). Unlike prior models of the coagulation cascade, this QSP model considers the impact of α-2-macroglobulin, a key regulator of thrombin with increased influence at reduced AT levels, that is critical to understand the impact of fitusiran on thrombin generation (Kattula et al. Blood 2020). The prior analysis was informed by thrombin generation assay (TGA) data from donor-derived spiked plasma and clinical TGA metrics from the Ph1/2 clinical studies of fitusiran and predicted that the targeted therapeutic range of 15-35% AT resulted in a thrombin peak profile which was comparable to 20-40% supplemental FVIII activity in PwHA.

The current analysis extends previous work by applying the validated QSP model to support hemostatic equivalency in both PwHA and PwHB, considering TGA metrics from completed phase 3 clinical studies of fitusiran in patients with inhibitors (ATLAS-INH) and without inhibitors (ATLAS-A/B).

Virtual populations of untreated severe PwHA (<1% FVIII activity) and PwHB (<2% FIX activity) were used to simulate TGA metrics which were validated against clinical and literature data. Simulated TGA metrics from these virtual populations after AT lowering (15-35%) were compared to those treated with supplemental factor. Based on this analysis, the peak thrombin generated at 15-35% AT was predicted to be similar to peak thrombin from treatment with 20-40% supplemental FVIII activity for PwHA, and 20-40% supplemental FIX activity for PwHB.

By considering the impact of α-2-macroglobulin, the QSP model provides a mechanistic representation of thrombin generation under conditions of AT lowering in PwHA and PwHB. This analysis predicted similar factor equivalency of 20-40% in both PwHA and PwHB for the target therapeutic range of fitusiran (15-35% AT). Clinical data on the efficacy and safety of treatment of breakthrough bleeds with reduced dosing of CFC/BPA further support these results.
Genomic Analysis Defines Increased Circulating, Monocyte-Derived Macrophages That Promote Immune Suppression in Mouse Models of FGFR1-Driven Leukemogenesis and Defines a Multigene Signature That Predicts AML Outcomes
Authors: Fang Hui , Zhang Ting , Lu Xiaocui , Matsunaga Atsuko , Eisfeld Ann-Kathrin , Hedrick Catherine , Hu Tianxiang
Published: December 2024

Background: The development of FGFR1-driven stem cell leukemia and lymphoma syndrome (SCLL) is accompanied by an increase in highly heterogenous myeloid derived suppressor cells (MDSCs), which leads to suppression of all immune effector cells in mouse models of the disease. This murine model provides the opportunity to define the genetic events that underly leukemia induced immune evasion.

Methods: A combination of CyTOF and scRNA-Seq was used to define the phenotypes and genotypes in leukemia induced macrophages. Pharmaceutical inhibition and correlative analysis was performed to examine the function and clinical significance of these macrophages.

Results: CyTOF analysis demonstrated an increase in levels of circulating macrophages in the peripheral blood during leukemia progression, which was further confirmed by flow cytometry. The connection between MDSC and macrophages was defined. These macrophages were derived not only from Ly6CHi M-MDSC, but also from the Ly6CInt and Ly6CLo monocytic populations. Consistently, single cell sequencing analysis demonstrated accumulation of non-classical monocytes (ncMono) during leukemia progression, which also show increased expression of macrophage markers. Trajectory analysis revealed a transition from cMono to ncMono, and potential genes orchestrating this transition process have been identified. Furthermore, T cell suppression assays demonstrated the immune suppressive abilities of leukemia-induced circulatory macrophages. Importantly, treatment of leukemic mice with the CSF1R inhibitor GW2580, which suppresses macrophage function and reduces their viability, leads to improved survival accompanied by reduced levels of leukemia cells and increased T-cell levels. This suggests that the leukemia induced macrophages are responsible, at least in part, for the suppression of immune effector cells. In newly diagnosed AML patients, those showing a high ncMono score, which was generated based on a specific ncMono gene signature, correlated with poorer survival, compared with those with a low ncMono score.

Conclusion. Overall, we demonstrate that a major part of the immune suppression in SCLL leukemia models involves suppression of T-cell function by circulating macrophages, and targeting macrophages in this system improves survival of mice engrafted with leukemia cells. In addition, we have also defined specific genetic reprogramming that is associated with the transition of monocytes into macrophages during leukemogenesis, potentially providing opportunities to target and reverse the immune suppressive microenvironment to improve AML outcome.
Efficacy and Safety of Beceltinib Capsules in the Treatment of Persistent or Chronic Primary Immune Thrombocytopenia: A Multicenter, Randomized, Open-Label, Phase 1/2 Study
Authors: Zhou Hu , Song Xuewen , Sheng Zengmei , Zhang Feng , Wu Guocai , Zhao Lidong , Zhou ZePing , Shou Lihong , Chen Lili , Wang Xiaotao , Huang Jian , Fu Rong , Chen Dan , Huang Ruibin , Jiao Zongjiu , Lu Jian , Ruan Yajun , Jiao Yu
Published: December 2024

Abstract:

Introduction:

Immune thrombocytopenia (ITP) is a complex autoimmune disease characterized by abnormally low blood platelet count, resulting in an increased risk of bleeding. Beceltinib, an oral irreversible covalent inhibitor of Bruton's tyrosine kinase, has shown potential as a therapeutic approach for ITP. This study aimed to evaluate the efficacy and safety of Beceltinib in adult patients with persistent or chronic ITP.

Methods:

In this multicenter, randomized, open-label, phase 1/2 study, adult patients with primary ITP who had previously failed standard therapy or could not tolerate it were enrolled. Patients were randomly assigned to receive either 50mg, 75mg, or 100mg of Beceltinib twice daily for 24 weeks. The primary endpoint was the proportion of patients achieving platelet counts of ≥50×109/L for at least two consecutive weeks during the treatment period. The secondary efficacy end points were sustained platelet response which defined as the proportion of patients with at least 4 platelet counts≥50×109/L during the last 6 visits within 24 weeks without rescue medication use. Safety monitoring, including adverse events, physical examinations, and bleeding risk assessments, was conducted throughout the trial. Pharmacokinetics and pharmacodynamics of Beceltinib were also explored.

Results:

A total of 32 patients were enrolled in the study, and 13 patients (40.6%) achieved the primary endpoint which is two consecutive platelet counts of at least 50 x 109/L during 24-week treatment period. Out of the responders, 11 patients (84.6%) demonstrated a sustained response, indicating that majority of the patients who positively responded to Beceltinib exhibited continued efficacy. The median cumulative response duration was 22 weeks (interquartile range, 12 to 31). The median time to the first platelet counts of at least≥50×109/L was 3 week (range, 1 to 9). Patients who had responded to glucocorticoids in the past showed better primary platelet response (61.5%, 8 of 13) and sustained platelet response (53.8%, 7 of 13). Dose adjustments were made in some patients, and the effective rate varied across different dose levels. The incidence of adverse reactions was 43.8%, with most being mild (grades 1 or 2). The study demonstrated that Beceltinib was generally well-tolerated by ITP patients.

Conclusion:

This study suggests that Beceltinib may have potential efficacy and safety for the second-line treatment of ITP. The findings provide new treatment options for clinical practice. Further studies are needed to validate these results and assess the long-term effects of Beceltinib in ITP patients.