bluuebunny/crossref_metadata_2025 huggingface dataset:
The Climacteric Gothic: Impotence and Menopause in the Eighteenth Century
Authors: Chow Jeremy , Zigarovich Jolene
Published: December 2024

By charting climacteric bodies – aged, gendered, and (de)sexualised ones – in the Gothic fictions of the Romantic period, this article explores socio-political concerns prompted by impotence and menopause. Enlightenment-era biomedical treatises fixated on the ageing body as a problem for gender and the state. This article weaves these medical and often pseudo-medical archives with Gothic fictions to argue that ageing distinctly interrogates growing anxieties concerning the health of the state and its investment in reproductive futurity. By reading canonical Romantic Gothic narratives, such as Horace Walpole's The Castle of Otranto (1764) and Matthew Lewis's The Monk (1796), as well as less studied ones, such as Charlotte Smith's Emmeline (1788), we uncover emergent understandings of eighteenth-century health, gender, and sexuality. Ultimately, the article exposes how menopause and impotence are configured by this medico-literary archive in hopes of advancing Gothic studies’ attention to ageing, not as spectacle, but as fundamental to the genre's evolution and socio-cultural significance.
Possibility of local radiation therapy of the prostate during radium223 therapy
Authors: Kulakova A. S. , Vetrov V. A. , Benzion D. L. , Ilyushkina V. А. , Makarova Yu. V. , Novichkov N. D.
Published: December 2024

Introduction. Patients with metastatic castration-resistant prostate cancer (mCRPC) are a complex and heterogeneous group whose primary treatment goals are to both prolong life and preserve quality of life. Among patients with mCRPC, there is a group with a progressive tumor process in the prostate gland, in which local irradiation along with systemic Ra 223 (Ra223) therapy would lead to improved oncological outcomes.

Purpose of the study. To evaluate the efficacy and safety of Ra223 in patients with mCRPC in routine clinical practice and to assess the feasibility of local radiation therapy of the prostate in patients with mCRPC receiving Ra223 therapy.

Materials and methods. This study included 189 patients with mCRPC who received 1 to 6 injections of Ra223 as part of routine clinical practice. The patients were divided into two groups. Group 1 included patients who received systemic therapy only – 153 (81%), while group 2 consisted of patients who received local irradiation of the prostate gland along with Ra223 therapy – 36 (19%) patients.

Conclusions. The use of radium223 in combination with localized radiotherapy for the treatment of the prostate has shown promising results in increasing disease control rate (DCR) in patients with mCRPC. Concurrent localized irradiation of the prostate against the radium223 therapy background did not show the result in increased hematological toxicity, which favorably affecting the tolerability of the radionuclide treatment. At the same time, localized radiation reactions occurring during localized prostate irradiation did not prevent patients from completing the full course (six injections) of the radionuclide radium223 treatment.
Local treatment of disintegrating breast tumors
Authors: Gergenreter Yu. S. , Kurchatkin V. N.
Published: December 2024

The group of patients with stage 4 disease has the worst prognosis and treatment results, with a decaying tumor ulcer forming in 2–5% of cases. Treatment of skin tumor ulceration includes antitumor therapy combined with local treatment of the tumor ulcer. Local treatment of decaying tumors consists of sanitation, washing with antiseptic solutions, and clearing the ulcer of necrotic masses by mechanical, chemical, and enzymatic methods. Bleeding is the most important problem of symptomatic treatment. “Hemostatic collagen sponge with silver” due to the combination of components not only stops capillary bleeding, but also promotes epithelialization of the wound defect against the background of antiseptic action.
Disseminated spontaneous postsplenectomy splenosis mimicking disseminated malignant tumor process. Clinical observation
Authors: Medvedeva B. M. , Darenskaya A. D. , Topalov E. S.
Published: December 2024

This article is devoted to such a benign acquired condition as postsplenectomy splenosis, which is often incorrectly interpreted as a primary malignant tumor or secondary (metastatic) tumor process. The article provides a modern definition of the concept of «splenosis», examines the main mechanisms of autotransplantation of splenic tissue, indicates the most typical localizations of splenosis foci, provides the timing of the onset of splenosis, considers possible clinical manifestations and potential complications of this condition, discusses modern approaches to diagnostics, differential diagnostics of splenosis, tactics of management and treatment of such patients in detail, and also provides own author’s clinical observation of disseminated spontaneous postsplenectomy splenosis mimicking disseminated malignant tumor process. The feature of this clinical case is the presence of hereditary microspherocytosis (congenital microspherocytic hemolytic anemia, Minkowski-Chauffard disease) in the patient, which served as the reason for splenectomy. The article is illustrated with original computed tomography and magnetic resonance imaging.
Current status on coffee leaf rust (hemileia vastatrix) in sidama and gedeo zone, southern Ethiopia
Authors: Wariyo Ano , Gebreselassie Habtamu , Gerbatsedik Wondmagegnehu , Belachew Kifle
Published: December 2024

Coffee is the most important and second traded commodity next to oil in the world. In Ethiopia, coffee leaf rust caused by Hemileia vastatrix is one of the third most economically important diseases of Coffee Arabica. The current status of coffee leaf rust was intensively assessed and examined in 189 sample coffee farms from six districts across major coffee growing areas of the Southern Ethiopia. At each farm, ten randomly selected trees on a diagonal transect across the farm were assessed for disease incidence and severity. The survey data showed that coffee leaf rust was present in all assessed district varying in magnitude and extent of damage. The highest overall mean of rust incidence (38.6%) and severity (13.80%) was recorded at Dilla zuria while the lowest incidence (10.52%) and severity (1.38%) was at Yergachaffee district. The highest altitude range was obtained at Yergachaffee (1838-2056) while the lowest was at Dilla zuria (1434-1825) district. Overall mean severity and incidence result indicate that, there was statistical (p = 0.058 for severity, p = 0.044 for incidence) and negative correlation between intensity and altitude (severity, r= -0.80 and incidence, r= -0.82). The linear regression equation of severity and incidence obtained from the data was Y= -0.036X+73.16 and Y = -0.074X +158.9 (where Y= percentage CLR severity and incidence, respectively and X= altitude). This regression equation implies that, in higher elevation areas the rust intensity was low as compare to the lower elevation. Finally, the disease was remarkably increasing from time to time in all assessed coffee farms. Therefore, appropriate measurement like farmers’ awareness creation and training on how to control disease as well as appropriate agronomic managements has to be seriously undertaken. In addition, development of coffee leaf rust resistant varieties to southern Ethiopia through resistant breeding has to be set high priority.
Smallholder farmers’ perceptions of agricultural extension in adoption of new technologies in Kakamega County, Kenya
Authors: Nyairo Newton M. , Pfeiffer Linda J. , Russell Mark
Published: December 2024

This exploratory study assesses factors that harness agricultural technology adoption among smallholder farmers in Kakamega County, Kenya by evaluating the key variables that influence sustainable adoption of agricultural innovations in the area. A survey was randomly administered in June and July 2018 among smallholder farming households in seven sub-counties (N=78) of Kakamega County. A logistic regression model, capturing factors presumed to influence the adoption of agricultural innovations, was estimated. Results suggest that even in smallholder farms, the farm size is important in adoption of innovations. Results also indicate limited or no farmer interaction (55%) with extension services. Farmers reported application of fertilizer and use of push-pull technology as less important in maintaining soil health. The regression model findings suggest that variables typically presumed to influence adoption in the literature are insignificant in this case study. The statistical significance of the farm size variable implies that agricultural extension messages can be tailored to a variety of farmer audiences for suitable adoption based on farm size. The diffusion of innovation theory remains a valid and relevant framework in studying adoption. This study reiterates the critical role that farmers or their environment play in the adoption process.
Agricultural extension agents’ education and turnover intentions in public extension services in Ethiopia
Authors: Jilito Mideksa F. , Wedajo Desalegn Y.
Published: December 2024

Agricultural extension agents provide informal education to equip farmers with new knowledge and skills. They play critical roles for the transfer of agricultural knowledge, technologies, and innovations. However, most of them dissatisfied and intend to find other employment in Ethiopia. Thus, this study was conducted to examine agricultural extension agents’ education, perceptions towards job satisfaction, and turnover intention in public agricultural extension services in Ethiopia. The sample frame was the list of all first, second, and third-year mid-career students joined Haramaya University to upgrade their educational qualification. Total 123 extension agents were involved in the study. Primary data were collected using a structured questionnaire and analyzed using descriptive statistics. Results revealed that about 89.40% of extension agents acquired new knowledge, skills, practices, and attitudinal change during attending their education at Haramaya University. Results also showed that extension agents were dissatisfied with their current job and organization in terms of payment, promotion, benefits, and recognition. Furthermore, survey results indicate that about 68.3% of extension agents intended to leave their current position and extension organization after completing a Bachelor of Science degree. Therefore, government, private sectors and other stakeholders who work in extension organizations should work on the education and training programs, work motivation, and job satisfaction of agricultural extension agents by designing various incentive packages to increase their work motivation and reduce turnover intentions.
Agricultural information sharing for climatic risk adaptation by smallholder livestock farmers in Eastern Amhara Region, Ethiopia
Authors: Assefa Habtemariam , Kibwika Paul , Kyazze Florence B. , Getinet Million
Published: December 2024

This study aims at appraising the needed agricultural information, sources and the pathways that livestock farmers used for climatic risk adaptation in Eastern Amhara Region and also, determining factors that influenced farmer’s decision in selecting information pathways. Cross-section survey research design was used for the study. Sample was selected using multistage sampling design. From three agroecological zones, three districts and nine PAs were covered by the study. In the household survey, 317 livestock farmers were interviewed for quantitate data collection. Furthermore, FGD and Key Informant interviews were conducted to supplement survey’s result. Data were analysed using STATA (version 14) software. Descriptive and inferential statistical analysis were deployed. The study revealed that livestock farmers needed different agricultural information to adapt climatic risks. The prominent information was relating to feed quality improvement, feed preservation, animal health management and soil and water conservations. Most farmers obtained the information from relatives, extension workers and fellow farmers. Informal discussion, farm-visit, training and village-meetings were the pathways that livestock farmers used to acquire agricultural information. The decision of a farmer in selecting information pathways was determined by different factors, but they differ from pathway to pathways. For example, radio selection was influenced by livestock size the farmer owned and extension access, while train was influenced by membership of farmer groups and credit access. In conclusion, livestock farmers need a diverse agricultural information to adapt climatic risks. They acquire the information from their intimate sources through affordable information pathways. To be effective in climatic risk adaptation, information provision should be need based, delivered through multisource and pathways. Besides, the existing conventional information pathways should also be supported by ICT resources and demonstration. Considering the determinate factors of information pathway selection is very crucial in designing information diffusion strategy.
Cereal crops production in Pakistan: Trends instability and growth
Authors: Kakar Jhangir S. , Lodhi Abdul S. , Nazir Adnan , Akhtar Shoaib , Iqbal Muhammad A.
Published: December 2024

Cereal grains have been considered as the primary source of the human diet for centuries. The present study tends to investigate trends, instability and growth in cereal crops in Pakistan. Using times series data from 1951 to 2020 (70 years). Linear, quadratic, and exponential growth models were used to forecast and find the best-fitted model. Also, Coppock’s Instability Index was measured for the area and production of selected cereal crops in Pakistan. Results indicate that wheat, rice and maize showed a positive growth trend. While bajra (millet) and jowar (sorghum) depicted a negative decreasing trend for area and production. The Coppock Index was determined to be more in production for wheat, rice and maize (76, 74 and 85 %). Likewise, the area for the selected cereal crops did not have much variable instability in the past 70 years. In accordance with these outcomes, the public line departments should intervene and promote these non-traditional cereal food crops as they are important sources of nutrition. Also, it would share benefits in the country’s economy.
PENINGKATAN KAPASITAS REMAJA DALAM PENCEGAHAN HIV MELALUI PROGRAM SKILLS FOR ADOLESCENTS WITH HEALTHY SEXUALITY DI SEKOLAH MENENGAH ATAS, GEGERKALONG, KOTA BANDUNG
Authors: Lindayani Linlin , Darmawati Irma , Mutiar Astri
Published: December 2024

Remaja merupakan kelompok rentan penularan HIV di Indonesia, dengan 41.987 remaja usia 10-19 tahun terdiagnosis HIV pada 2023. Penularan terjadi melalui hubungan seksual berisiko (30%) dan penggunaan jarum suntik (4,1%). Jawa Barat, khususnya Bandung, memiliki prevalensi tinggi, termasuk di Kelurahan Gegerkalong, pusat pendidikan dan wisata. Lingkungan ini menghadapi perilaku remaja berisiko, seperti seks bebas, penggunaan narkoba, dan penyimpangan seksual. Data Puskesmas Karangsetra menunjukkan 192 remaja di Gegerkalong terinfeksi HIV. SMA Kartika XIX-2, dengan siswa yang mengalami masalah seperti seks pranikah dan kehamilan dini, menjadi fokus intervensi pencegahan HIV berbasis pendidikan dan teknologi. Program ini mengintegrasikan aplikasi HIV Info Corner dengan metode pelatihan keterampilan hidup untuk remaja. Tujuan utamanya adalah meningkatkan pemahaman, keterampilan pencegahan, dan pemanfaatan konseling daring. Program juga mendukung Merdeka Belajar Kampus Merdeka (MBKM) serta pencapaian SDGs, khususnya kesehatan dan pendidikan berkualitas. Hasilnya adalah terbentuknya kelompok remaja peduli HIV, peningkatan keterampilan remaja, dan kerja sama berkelanjutan dengan sekolah dan puskesmas melalui pusat konseling (PILING). Dengan pendekatan inovatif ini, diharapkan tercipta generasi bebas AIDS di masa depan.
Social preferences in chickens–effects of domestication and tameness
Authors: Gjøen Johanna , Jensen Per
Published: December 2024

It has been suggested that evolution of domesticated phenotypes may have evolved as a result of correlated selection responses to reduced fear, a prominent feature in early domestication. To investigate whether domestication changes in social preferences can be attributed to increased tameness, we studied two lines of Red Junglefowl, ancestors of domesticated chickens, bidirectionally selected during 12 generations for high (HF) or low (LF) fear of humans and compared the differences between these lines to those between unselected Red Junglefowl (RJF) and domesticated White Leghorn egg layers (WL). One bird at a time was observed on its own for 12 min in an arena with one adjacent pen behind netting on each side. One of the adjacent pens contained familiar birds, and the other contained unfamiliar birds. Towards the end of the observation period, a sudden stressful stimulus was displayed, and we compared the reactions of the breeds to this as well. Male RJF spent more time close to the unfamiliar birds than WL, and performed more agonistic behaviour, but this was not mirrored in the selected birds. For females, it was WL that performed the most agonistic behaviour. Both LF and WL males showed more non-agonistic social exploration than HF and RJF respectively. Male LF and WL emitted more food calls than HF and RJF respectively. We conclude that several differences between RJF and WL were mirrored in the selection lines, with LF behaving more like domesticated WL. This is in line with the hypothesis that selection for tameness may have driven domestication related changes in social behaviour against conspecifics.
Upgradeable diamond smart contracts in decentralized autonomous organizations
Authors: van Vulpen Paul , Heijnen Hidde , Mens Samuel , Kroon Thijn , Jansen Slinger
Published: December 2024

Upgradeable smart contracts allow decentralized autonomous organizations (DAOs) to address bugs, enhance security, and expand functionality post-deployment. The proxy pattern enables smart contract upgradeability but introduces admin-centric governance, where power is concentrated in a single or small number of addresses. This paper explores the potential of decentralized smart contract governance to overcome admin centric governance while achieving flexibility in governing smart contracts. We investigate the Diamond Pattern as a flexible upgradeable contract framework that allows for modular smart contracts. Using the SecureSECO DAO as a case study, we examine how the diamond pattern can be configured for decentralized governance. The used architecture allows DAOs to upgrade smart contracts collectively through community consensus, and the implementation provides proposals, votes, and execution without requiring technical knowledge. The study highlights the benefits of this approach, namely, flexibility in smart contract governance, enhanced modularity, and a single point of interaction for governance. We also discuss limitations and challenges for upgradeable smart contracts such as the decision-making delays and potential vulnerabilities. To encourage adoption of consensus governance, we call for the creation of user-friendly tooling and smart contract facets.
Adaptive compensation for multi-axial real-time hybrid simulation via nonlinear parameter estimation
Authors: Ruiz Santiago , Song Wei
Published: December 2024

For Real-time hybrid simulation (RTHS) to be stable and accurate, it is essential to address the time desynchronization issue between the numerical and physical substructures. Desynchronization is primarily caused by time delays, inherent dynamics of the control plant, system uncertainties, and noises. While existing adaptive compensators have shown effective tracking performance in single-input single-output (SISO) RTHS, their effectiveness in multi-input multi-output (MIMO) RTHS has not been fully demonstrated. MIMO-RTHS presents additional challenges due to its larger solution space, and significant dynamic coupling between actuators. To address these challenges, this study introduces an adaptive compensation framework for MIMO-RTHS. The proposed framework utilizes a control law based on the inverse dynamics of the control plant, incorporating real-time adaptive parameter updates through Extended Kalman Filter (EKF) and Unscented Kalman Filter (UKF) methods. Both the transfer function (TF) and discrete-time state-space (SS) models of the plant are employed in distinct parameter estimation cases. The performance of the proposed compensation is validated through a multi-axial RTHS (maRTHS) benchmark problem. Extensive simulations on the maRTHS incorporating various earthquake inputs, sensor noise, and model uncertainties, demonstrated an excellent tracking performance and strong robustness across four parameter estimation cases (EKF-TF, UKF-TF, EKF-SS, and UKF-SS). The use of UKF with SS model (UKF-SS) achieved superior performance, effectively managing nonlinearities and noise without requiring low-pass filtering.
Helicobacter pylori resistance in Hainan Province, China: investigating phenotypes and genotypes through whole-genome sequencing
Authors: Lv Yan-Ting , Li Da , Zhang Da-Ya , Chen Shi-Ju , Chen Run-Xiang , Wang Yang , Yang Wei-Zhong , Gao Lei , Zeng Jun-Tao , Xiong Jian-Xin , Huang Qiu-Ya , Huang Jing , Zhang Qiao-Guan , Chen Jia-Jia , Bai Fei-Hu
Published: December 2024

Helicobacter pylori is increasingly resistant to antibiotics, significantly lowering eradication rates and posing a major public health challenge. This study investigated the distribution of antibiotic-resistant phenotypes and genotypes of H. pylori in Hainan Province. It determined the minimum inhibitory concentrations (MICs) of six antibiotics using the E-test method and detected resistance genes via Sanger sequencing. Furthermore, we compared resistance detection based on phenotypic analysis and whole genome sequencing (WGS) across 19 clinical isolates of H. pylori. A total of 140 H. pylori strains were isolated. The resistance rates to levofloxacin (LEV), clarithromycin (CLA), and metronidazole (MTZ) were 37.9%, 40.0%, and 93.6%, respectively. Notably, only 3.3% of the strains were susceptible to all six antibiotics. Multidrug-resistant strains accounted for 25.0% of the total, with no resistance detected to amoxicillin (AMX), tetracycline (TET), or furazolidone (FR) during the study period. Genotypic resistance to CLA and LEV showed near-perfect concordance with phenotypic resistance, with Kappa values of 0.910 and 0.938, respectively. Although all isolates were phenotypically sensitive to TET, 16 exhibited a mutation in the 16S rRNA gene (A926G). All strains harboring the R16H/C mutation and truncated rdxA were resistant to metronidazole, demonstrating a specificity of 100%. Therefore, FR, AMX, and TET are recommended as suitable empirical treatment options for H. pylori infections in this region. Genotypic analysis provides a reliable method for predicting resistance to CLA and LEV. WGS proves to be a valuable tool for identifying novel resistance loci in H. pylori and contributes to the phylogenetic classification of strains.
Deep learning based bio-metric authentication system using a high temporal/frequency resolution transform
Authors: Maleki Lonbar Sajjad , Beigi Akram , Bagheri Nasour , Peris-Lopez Pedro , Camara Carmen
Published: December 2024

Introduction

Identity verification plays a crucial role in modern society, with applications spanning from online services to security systems. As the need for robust automatic authentication systems increases, various methodologies—software, hardware, and biometric—have been developed. Among these, biometric modalities have gained significant attention due to their high accuracy and resistance to falsification. This paper focuses on utilizing electrocardiogram (ECG) signals for identity verification, capitalizing on their unique, individualized characteristics.

Methods

In this study, we propose a novel identity verification framework based on ECG signals. Notable datasets, such as the NSRDB and MITDB, are employed to evaluate the performance of the system. These datasets, however, contain inherent noise, which necessitates preprocessing. The proposed framework involves two main steps: (1) signal cleansing to remove noise and (2) transforming the signals into the frequency domain for feature extraction. This is achieved by applying the Wigner-Ville distribution, which converts ECG signals into image data. Each image captures unique cardiac signal information of the individual, ensuring distinction in a noise-free environment. For recognition, deep learning techniques, particularly convolutional neural networks (CNNs), are applied. The GoogleNet architecture is selected for its effectiveness in processing complex image data, and is used for both training and testing the system.

Results

The identity verification model achieved impressive results across two benchmark datasets. For the NSRDB dataset, the model achieved an accuracy of 99.3% and an Equal Error Rate (EER) of 0.8%. Similarly, for the MITDB dataset, the model demonstrated an accuracy of 99.004% and an EER of 0.8%. These results indicate that the proposed framework offers superior performance in comparison to alternative biometric authentication methods.

Discussion

The outcomes of this study highlight the effectiveness of using ECG signals for identity verification, particularly in terms of accuracy and robustness against noise. The proposed framework, leveraging the Wigner-Ville distribution and GoogleNet architecture, demonstrates the potential of deep learning techniques in biometric authentication. The results from the NSRDB and MITDB datasets reflect the high reliability of the model, with exceptionally low error rates. This approach could be extended to other biometric modalities or combined with additional layers of security to enhance its practical applications. Furthermore, future research could explore additional preprocessing techniques or alternative deep learning architectures to further improve the performance of ECG-based identity verification systems.
How does co-regulation with Adaptive Learning Technologies affect primary school students' goal-setting, regulation of practice behavior and learning outcomes?
Authors: Horvers Anne , Kooi Rianne , Knoop-van Campen Carolien A. N. , Dijkstra Rick , Baars Martine , Molenaar Inge
Published: December 2024

Introduction

Monitoring and controlling learning is often difficult for primary school students. This issue is partially resolved when Adaptive Learning Technologies (ALTs) take over part of these self-regulated learning (SRL) processes. Trace data in ALTs provides elaborate information on students' learning process, which can be translated into monitoring support. However, this data does not provide insight into students' goal-setting behavior, which is a crucial part of the monitoring loop. Therefore, we developed a form of co-regulation between the student and the ALT with goal-setting prompts and monitoring support.

Method

This experimental study compared an experimental condition in which primary school students worked with the co-regulation intervention while practicing mathematics problems in the ALT to a control condition where they only practiced with the ALT. Firstly, we examined the effects of co-regulation with ALTs on regulation of practice behavior and learning outcomes by comparing the experimental and control conditions. Secondly, to gain further insight into students' goal-setting behavior in co-regulation, we examined how the experimental condition set their goals and attained them.

Results

Results showed that students in the experimental condition were more effective in regulating their practice behavior, shown by more problems solved and higher accuracy than the control condition. Similar learning gain was found in both conditions on the easy and intermediate learning topics. For the hard learning topic, the control condition showed a higher learning gain. Higher week goals than day goals on all three learning topics and similar goals were set between the learning topics. Students' goal attainment was less for the easy compared to the hard learning topic.

Discussion

Combined, these results indicate that co-regulation with an ALT positively affects students' regulation of practice behavior and goal- setting behavior but does not yet increase learning gain. A practical implication is that teachers could support students by explicitly providing students with goal-setting opportunities.
Immune dysregulation as a driver of bronchiolitis obliterans
Authors: Deng Kuimiao , Lu Gen
Published: December 2024

Bronchiolitis obliterans (BO) is a disease characterized by airway obstruction and fibrosis that can occur in all age groups. Bronchiolitis obliterans syndrome (BOS) is a clinical manifestation of BO in patients who have undergone lung transplantation or hematopoietic stem cell transplantation. Persistent inflammation and fibrosis of small airways make the disease irreversible, eventually leading to lung failure. The pathogenesis of BO is not entirely clear, but immune disorders are commonly involved, with various immune cells playing complex roles in different BO subtypes. Accordingly, the US Food and Drug Administration (FDA) has recently approved several new drugs that can alleviate chronic graft-versus-host disease (cGVHD) by regulating the function of immune cells, some of which have efficacy specifically with cGVHD-BOS. In this review, we will discuss the roles of different immune cells in BO/BOS, and introduce the latest drugs targeting various immune cells as the main target. This study emphasizes that immune dysfunction is an important driving factor in its pathophysiology. A better understanding of the role of the immune system in BO will enable the development of targeted immunotherapies to effectively delay or even reverse this condition.
Adjuvant immunotherapy after neoadjuvant immunochemotherapy and esophagectomy for esophageal squamous cell carcinoma: a real-world study
Authors: Feng Jifeng , Wang Liang , Yang Xun , Chen Qixun
Published: December 2024

Background

The role of immunotherapy in the adjuvant setting seems promising in recent years. As per the findings of the CheckMate 577 trial, patients with esophageal cancer (EC) who had neoadjuvant chemoradiation with residual pathologic disease should be considered adjuvant immunotherapy (AIT). However, it is unknown if individuals with esophageal squamous cell carcinoma (ESCC) who have received neoadjuvant immunochemotherapy (NICT) followed by radical surgery also require AIT.

Methods

A retrospective analysis was performed on the data from patients who underwent NICT and radical surgery for ESCC between 2019 and 2020. To compare disease-free survival (DFS) and overall survival (OS), Kaplan-Meier survival curves were produced. To determine the parameters linked to DFS and OS, a Cox model using hazard ratios (HRs) was completed.

Results

Among the 292 eligible patients, 215 cases with a mean age of 63.3 ± 6.8 years, including 190 (88.4%) men and 25 (11.6%) women, were finally recruited. The percentage of R0 resection was 98.3%. After NICT, 65 (30.2%) patients achieved pathological complete response. AIT was given to 78 (36.3%) patients following radical resection. For all patients, the 3-year DFS and OS were 62.3% and 74.0%, respectively. In terms of 3-year DFS (61.5% vs. 62.8%, P=0.984) or OS (76.9% vs. 72.3%, P=0.384), no statistically significant difference was found between patients with and without AIT. AIT significantly improved survival in patients with ypT+N+ (DFS: 23.9% vs. 38.5%, P=0.036; OS: 37.0% vs. 61.5%, P=0.010), but not in those with ypT0N0 or ypT+N0. It was found that AIT was related to both DFS (HR: 0.297; P<0.001) and OS (HR: 0.321; P=0.001) in patients with ypT+N+.

Conclusion

In ypT+N+ ESCC patients, AIT after NICT followed by radical surgery reduces the recurrence and death, thereby improving the DFS and OS. Randomized controlled trials ought to be conducted to further assess the results of this retrospective investigation.
The clinical value of local consolidative therapy for oligo-residual disease in PD-1/PD-L1 inhibitors-treated non-small cell lung cancer
Authors: Su Yuqi , Luo Pan , Ni Ling , Hu Jianbin , Weng Jie , Shen Erdong , Zhou Qiang , Chen Tao , Xiao Jiwen , Xiao Jia , Xie Wangti , Shan Rong , Yao Xiang , Wen Fang
Published: December 2024

Background

Few real-world studies exist regarding the clinical value of local consolidative therapy (LCT) for oligo-residual disease (ORD) in NSCLC patients treated with immune checkpoint inhibitors. Therefore, we retrospectively evaluated whether LCT could improve the prognosis of NSCL patients with ORD after effective first-line PD-1/PD-L1 inhibitors treatment.

Methods

A total of 132 patients with metastatic NSCLC who had received first-line PD-1/PD-L1inhibitors-based systemic treatment and developed ORD (defined as residual tumors limited to three organs and five lesions) were included. The LCT group consisted of 41 patients received LCTs for oligo-residual lesions before treatment failure, and the remaining 91 patients, who did not receive local therapies, constituted the non-LCT group. The progression-free survival (PFS) and overall survival (OS) of the two groups were analyzed.

Results

With a median follow-up of 12.0 months, 86 patients developed progressive disease and 42 patients died. Compared with the non-LCT group, LCT group exhibited significant longer progression-free survival (PFS) (median 11.0 vs. 7.0 months, P=0.017) and overall survival (OS) (median 26.0 vs. 17.0 months, P=0.003). Multivariable analysis demonstrated that LCT was an independent predictor of prolonged PFS (HR=0.606, 95% CI=0.370–0.964, P=0.035) and OS (HR=0.467, 95% CI=0.229–0.949, P=0.035). Subgroup analysis revealed that the dominant population considerably benefited from LCT in terms of PFS and OS included patients with 1-2 residual tumor sites (mPFS: 11.0 vs. 7.0 months, P=0.013; mOS: 23.0 vs. 17.0 months, P=0.018) and those with high PD-L1 expression (mPFS: 13.0 vs. 7.0 months, P=0.018; mOS: 34.0 vs. 16.0 months, P=0.030). In addition, the All-LCT group had significantly longer PFS (mPFS 16.0 vs. 7.0, P=0.002) and OS (mOS 28.0 vs. 17.0, P= 0.002) than did the non-LCT group. However, patients who received LCT to only some of their lesions had not experienced improvements in PFS (P=0.546) or OS (P=0.198).

Conclusion

LCT may provide extra survival benefits among patients with oligo-residual NSCLC after effective first-line PD-1/PD-L1 inhibitors treatment, particularly in those patients with one or two residual lesions, high PD-L1 expression, or who had received LCT for all lesions. LCT may be a novel treatment option for this specific population.
South Atlantic meridional overturning circulation and its respective heat and freshwater transports from sustained observations near 34.5°S
Authors: Pita Ivenis , Goes Marlos , Volkov Denis L. , Dong Shenfu , Schmid Claudia
Published: December 2024

The Atlantic Meridional Overturning Circulation (AMOC) drives northward Meridional Heat Transport (MHT) and affects climate and weather patterns, regional sea levels, and ecosystems. This study uses a methodology recently applied in 22.5°S to estimate the strength and structure of the AMOC, MHT and freshwater (FWT) transports at 34.5°S since 2005. For this, temperature and salinity profiles from sustained observations were used in conjunction with satellite and reanalysis data under two mapping methodologies: (i) an optimized mapping and (ii) a two-layer feed-forward neural network approach. There is strong agreement between both methods for AMOC, MHT and FWT estimates, thus showing the mapping methodologies are robust. In addition, the AMOC variability estimate is significantly correlated with the monthly SAMBA array data (correlation of 0.41). The mean AMOC transport of 17.0 ± 1.6 Sv, a MHT of 0.6 ± 0.1 PW, and a FWT of -0.02 ± 0.01 Sv are estimated between January 2005 and May 2023 at 34.5°S. The MHT and FWT are analyzed in terms of their horizontal (Hhor and Fhor) and overturning contributions (Hov and Fov), and vertical structures. The MHT is dominated by the overturning contribution (correlation of 0.92), while the FWT is controlled by the overturning contribution driven by the wind via Ekman transport at seasonal timescale, and by horizontal contribution at longer timescales. Both horizontal heat (Hhor) and freshwater (Fhor) components are mostly confined to the upper 500 m, with the geostrophic Fov and Fhor offsetting each other between 50 m and 500 m, and the Ekman Fov in the upper 50 m determining the negative FWT. Finally, the estimated mean Fov of -0.15 Sv agrees with previous estimates that the AMOC exports freshwater in the South Atlantic, and suggests that the AMOC is unstable. Although a long-term trend in the Fov was not detected in the past 20 years, there is a salinification trend (0.05 ± 0.01 PSU/decade) in the upper 300 m near 34.5°S since 2005.
Two-decade variability and trend of chlorophyll-a in the Arabian Sea and Persian Gulf based on reconstructed satellite data
Authors: Yang Mengmeng , Khan Faisal Ahmed , Fang Hua , Maúre Elígio de Raús , Ishizaka Joji , Liu Dong , Wang Shengqiang
Published: December 2024

The spatiotemporal variability of chlorophyll-a (Chl-a) in the Arabian Sea (AS) and Persian Gulf (PG) has been widely studied, but long-term trends and influencing factors remain less understood due to data gaps. This study investigates Chl-a variability and trends from 2001 to 2019 using reconstructed MODIS-Terra monthly Chl-a and sea surface temperature (SST) data, employing the Data Interpolating Empirical Orthogonal Functions (DINEOF) method for high-accuracy reconstruction. Results reveal pronounced seasonal variability, with Chl-a peaks exceeding 3 mg m-3 during southwestern monsoons and ranging between 1–3 mg m-3 during northeastern monsoons, with the lowest levels in transitional months. Spatially, the highest Chl-a concentrations were observed in the western and northeastern AS, influenced by summer southwestern (SW) and winter northeastern (NE) monsoons. Trend analysis using Sen’s slope and the Mann-Kendall test indicates significant Chl-a declines (-0.002 to 0) along ASPG coasts, with slight increases (~0.005) in the southeastern AS and southern PG. Rising SST anomalies (SST_A) correlated with reduced Chl-a anomalies (Chl-a_A) in the western AS, while increased wind anomalies (Wind_A) enhanced Chl-a_A in the western AS but decreased it in the southern PG. These findings enhance our understanding of the complex environmental dynamics shaping the ASPG ecosystems.
Analyzing lipid profiles and dyslipidemia prevalence in hypertensive patients: a cross-sectional study from primary community health institutions
Authors: Wang Wenxin , Li Xinmin , Lv Deliang , Wu Xiaobing , Xie Fengzhu , Xie Wei , Wang Jinxiao , Zhao Zhiguang
Published: December 2024

Background

A significant proportion of hypertensive patients also suffer from comorbid dyslipidemia, which critically influences their treatment outcomes and overall prognosis. Given its implications, the lipid profiles of hypertensive individuals warrant increased attention for more effective clinical management.

Methods

We analyzed data from 92,443 hypertensive patients registered at primary community health institutions in 2021. Employing a cross-sectional study design, we assessed the distribution of lipid levels and the prevalence of various dyslipidemia subtypes. Stepwise forward logistic regression was used to identify factors associated with dyslipidemia, adjusting for gender, age, body size, and other relevant characteristics.

Results

According to the 2023 Chinese Guidelines for the Management of Lipids, the overall prevalence of dyslipidemia was 37.5%. Subtype analysis revealed prevalence of high total cholesterol (TC) at 11.2%, high triglycerides (TG) at 16.0%, low high-density lipoprotein cholesterol (HDL-C) at 16.0%, and high low-density lipoprotein cholesterol (LDL-C) at 10.2%. TG abnormalities were more common among males (16.8%), whereas TC abnormalities predominated in females (14.4%). Notably, hypertensive patients with diabetes had higher levels of TG compared to non-diabetics (p = 0.009). Those with stroke and liver disease comorbidities exhibited lower TG levels than their counterparts (p = 0.018 and p < 0.001, respectively). Additionally, HDL-C levels were significantly lower in hypertensives with diabetes, coronary artery disease, and central obesity (p < 0.001, p = 0.026, p < 0.001, respectively). Regression analysis indicated that dyslipidemia prevalence correlates significantly with gender, age, diabetes, coronary heart disease, stroke, family history of hypertension, body mass index (BMI), central obesity, frequency of physical activity, smoking status, regular alcohol consumption, and abdominal ultrasound findings.

Conclusion

Our study underscores the necessity of rigorous lipid monitoring and analysis of dyslipidemia-influencing factors for the development of effective health management strategies within the community. There is a critical need to examine lipid profiles comprehensively and implement targeted therapeutic interventions aimed at managing hyperlipidemia, a modifiable risk factor for cardiovascular disease.
The role of blended learning in improving medical students’ academic performance: evidence from Pakistan
Authors: Ashraf Muhammad Azeem , Tsegay Samson Maekele , Gull Nida , Saeed Muneeba , Dawood Hussain
Published: December 2024

Objective

The study examines the role of blended learning in improving medical students’ academic performance through self-regulatory learning and technological competence and identifies the moderating role of perceived institutional support in the relationships between self-regulatory learning, perceived teacher credibility, technological competencies, and academic performance.

Methods

The study was based on behavioral learning theory as a theoretical framework, and an adapted questionnaire was used to collect the data. In total, 275 medical students participated in the study, and the data was analyzed using structural equation modeling techniques with SmartPLS.

Results

The results indicate that self-regulatory learning significantly affects student academic performance and mediates the role of teachers’ credibility and technological competencies. Furthermore, perceived institutional support is a significant moderator in the relationship between self-regulated learning, technological competencies, and teacher credibility.

Conclusion

The study highlights the importance of self-regulated learning in students’ academic achievement. Moreover, it suggests that educational institutions should advance teachers’ competence and encourage collaborative learning to enhance students’ learning, motivation, and academic performance.
Protective effects of docosahexaenoic acid combined with bilberry extract on myopic Guinea pigs
Authors: Lin Tainan , Hu Jianzhang , Wen Qian , Liu Xiaoting , Lin Jinghua , Shi Qiaomei , Lin Miao , Huang Weifu
Published: December 2024

This study aims to investigate the protective effects of docosahexaenoic acid (DHA) combined with bilberry extract (BE) on myopic guinea pigs. In total, 105 healthy pigmented guinea pigs aged 2 weeks were selected and randomly divided into five groups. The normal control (NC) group received no treatment, while the experimental groups wore −6.0D lenses on the right eye to establish an animal model of lens-induced myopia (LIM). These groups were further divided based on different treatments: normal feeding, DHA treatment, BE treatment, and combined DHA + BE treatment. Refractive error and axial length for both eyes were measured before modeling, after 4 weeks of modeling, and after 8 weeks of treatment. Fundus examination was performed, and choroidal thickness, choroidal vascularity index (CVI), maximal mixed response in dark adaptation (Max-ERG), and cone cell response in light adaptation (Cone-ERG) were measured. After 8 weeks of treatment, we observed a significant reduction in refractive error and shortening of axial length, improvement in fundus condition, and increased choroidal thickness and CVI in the LIM + DHA + BE group. Electroretinogram (ERG) showed that the amplitudes of a-wave and b-wave were enhanced in both Max-ERG and Cone-ERG tests. The LIM + DHA + BE group exhibited superior effects compared to the LIM + DHA group and the LIM + BE group. The combination of DHA and BE delayed the progression of LIM in guinea pigs and was more effective than DHA or BE alone. The synergistic effect of DHA and BE offers a new approach to the prevention and treatment of myopia.
Abnormal c-Fos expression in TetTag mice containing fos-EGFP
Authors: Wilmot Jacob H. , Warren Tracy L. , Diniz Cassiano R. A. F. , Carda Deger , Lafreniere Marrisa M. , Nord Alex S. , Wiltgen Brian J.
Published: December 2024

Molecular and genetic techniques now allow selective tagging and manipulation of the population of neurons, often referred to as “engram cells,” that were active during a specific experience. One common approach to labeling these cells is to use the fos-tTA transgenic mouse (TetTag). In addition to tagging cells active during learning, it is common to examine the reactivation of these cells using immediate early gene (IEG) expression as an index of neural activity. There are currently multiple TetTag lines available. The original line, cryopreserved at MMRRC, contains only the fos-tTA transgene, while Jackson Labs provides a version of the mouse that expresses both the fos-tTA and fos-shEGFP genes. In the current experiments, we examined IEG expression in these two mouse lines. Unexpectedly, we found that Jackson fos-tTA/fos-shEGFP mice express increased levels of c-Fos in the hippocampus compared to wild type animals when examined with immunohistochemistry (IHC). The expression of other IEGs, such as Arc and Egr-1, was not elevated in these mice, suggesting that the overexpression of c-Fos is not the result of increased excitability or broad changes in gene expression. qPCR revealed that Jackson fos-tTA/fos-shEGFP mice express mRNA corresponding to a c-Fos-Exon1-GFP fusion molecule, which may bind to C-Fos antibodies during IHC and inflate apparent c-Fos expression. Jackson fos-tTA/fos-shEGFP mice did not differ from their wild-type counterparts in fear expression or memory, indicating no behavioral effect of the presence of a c-Fos-GFP fusion protein. These results identify a major limitation inherent in the use of Jackson fos-tTA/fos-shEGFP mice.