bluuebunny/crossref_metadata_2025 huggingface dataset:
A single point mutation on FLT3L-Fc protein increases the risk of immunogenicity
Authors: Qin Dan , Phung Qui , Wu Patrick , Yin Zhaojun , Tam Sien , Tran Peter , ElSohly Adel M. , Gober Joshua , Hu Zicheng , Zhou Zhenru , Cohen Sivan , He Dongping , Bainbridge Travis W. , Kemball Christopher C. , Zarzar Jonathan , Sreedhara Alavattam , Stephens Nicole , Decalf Jérémie , Moussion Christine , Ye Zhengmao , Balazs Mercedesz , Li Yinyin
Published: February 2025

Introduction

As a crucial asset for human health and modern medicine, an increasing number of biotherapeutics are entering the clinic. However, due to their complexity, these drugs have a higher potential to be immunogenic, leading to the generation of anti-drug antibodies (ADAs). Clinically significant ADAs have an impact on pharmacokinetics (PK), pharmacodynamics (PD), effectiveness, and/or safety. Thus, it is crucial to understand, manage and minimize the immunogenicity potential during drug development, ideally starting from the molecule design stage.

Methods

In this study, we utilized various immunogenicity risk assessment methods, including in silico prediction, dendritic cell internalization, MHC-associated peptide proteomics, in vitro HLA peptide binding, and in vitro T cell proliferation, to assess the immunogenicity risk of FLT3L-Fc variants.

Results

We identified a single point mutation in the human FLT3L-Fc protein that introduced highly immunogenic T cell epitopes, leading to the induction of T cell responses and thereby increasing the immunogenicity risk in clinical settings. Consequently, the variant with this point mutation was removed from further consideration as a clinical candidate.

Discussion

This finding underscores the necessity for careful evaluation of mutations during the engineering of protein therapeutics. The integration of multiple immunogenicity risk assessment tools offers critical insights for informed decision-making in candidate sequence design and therapeutic lead selection.
Cichlid fishes are promising underutilized models to investigate helminth-host-microbiome interactions
Authors: Vanhove Maarten P. M. , Koblmüller Stephan , Fernandes Jorge M. O. , Hahn Christoph , Plusquin Michelle , Kmentová Nikol
Published: February 2025

The “Old Friends Hypothesis” suggests insufficient exposure to symbionts hinders immune development, contributing to increased immune-related diseases in the Global North. The microbiome is often the focus; helminths, potentially also offering health benefits, lack attention. Infection and effect of helminths are influenced and perhaps determined by micro-organisms. Mechanisms behind parasite-microbiome interactions are poorly understood, despite implications on host health. These interactions are typically studied for single helminth species in laboratory animal models, overlooking helminth diversity. Reviewing research on relationships between helminth and microbial diversity yielded 27 publications; most focused on human or other mammalian hosts, relying on natural exposure rather than experimental helminth inoculation. Only about half investigated host health outcomes. Remaining knowledge gaps warrant considering additional candidate model systems. Given the high helminthiasis burden and species diversity of helminths, we propose seeking models in the Global South, where a considerable proportion of research on diversity aspects of helminth-microbiome interactions took place. Low availability of genomic resources for helminths in the Global South, however, necessitates more integrative helminthological research efforts. Given substantial similarities in immune systems, several fishes are models for human health/disease. More effort could be done to establish this for cichlids, whose representatives in the African Great Lakes provide a well-delineated, closed natural system relevant to human health in view of fish-borne zoonoses and other water-borne parasites. A good baseline exists for these cichlids’ genomics, parasitology, and microbiology. We suggest exploring African Great Lake cichlids as model hosts for interactions between microbial diversity, helminth diversity, and host health.
Autophagy-related protein LC3β and its association with clinical-pathological characteristics, mismatch repair proteins and survival in colorectal carcinoma
Authors: Gakinya Samuel , Nzioka Ancent K. , Mugo Alex G. , Onyuma Timothy , Ogutu James
Published: February 2025

Introduction

Autophagy is a metabolic process that serves to maintain cellular homeostasis as well as enable the cell to adapt to metabolic stress. In malignant cells, autophagy has been associated with drug resistance, metastasis and poor outcome. Colorectal carcinoma is a leading cause of cancer morbidity and mortality worldwide. The management and outcome are dependent on the tumor clinical and pathological characteristics. Autophagy is a potential therapeutic target as well as prognostic biomarker given its role in cancer pathogenesis. This study aimed at evaluating the autophagy status of colorectal carcinomas for tumors diagnosed at the Aga Khan University Hospital, Nairobi and establish its association with clinical-pathological characteristics including age, tumor location, tumor grade, tumor pathological stage, tumor nodal stage, tumor budding, tumor-infiltrating lymphocytes (TILs), Mismatch repair protein status (MMR), HER2 status and patient survival.

Methods

The study assessed the autophagy status of 114 colorectal carcinoma cases using immunohistochemistry for autophagy related protein LC3β. The clinical-pathological characteristics were determined by examining the medical records and evaluation of hematoxylin and eosin-stained slides. HER2 and MMR status were evaluated using immunohistochemistry. The treatment outcome was determined from the patient's records by checking for date of last visit or death.

Results and discussion

The mean age of patients in our study was 58years. There were more males 61.8% (n = 70) than females 38.6% (n = 44). Most of the patients had high pathological tumor stage of pT3 and pT4. Majority of the tumors showed intermediate tumor budding and weak tumor-infiltrating lymphocytes. The mismatch repair deficiency and HER2 overexpression were found in 14.9% (n = 17) and 2.6% (n = 3) of the cases respectively. LC3β was overexpressed in 36% (n = 41) of the cases and was significantly more common in females (p = 0.013). The LC3β status showed no significant association with age, tumor location, tumor grade, tumor stage, nodal stage, tumor budding, tumor-infiltrating lymphocytes, MMR status, HER2 status or patient survival. Future prospective studies are recommended to further explore the utility of autophagy as a prognostic and predictive biomarker.
Analysis of fungal microbiota diversity and potential pathogenic fungi in oral secretions and gut feces of captive giant pandas
Authors: Ma Xiaoping , Zeng Xiangwen , Huang Zhi , Li Gen , Liu Ruiguo , Luo Rongyan , Li Xinni , Ling Shanshan , Wang Chengdong , Gu Yu
Published: February 2025

Background

Maintaining good oral and gut health is essential for the wellbeing of animals, and fungi are key components of the oral and gut microbiota. This study aims to explore the diversity and seasonal dynamics of oral and gut fungal communities in captive giant pandas, with a focus on their potential functional roles in health and digestion.

Methods

In the study, we collected saliva and fecal samples from 60 captive giant pandas were collected in different seasons, oral and gut fungi were analyzed using internal transcribed spacer (ITS) amplicon sequencing. We used α and β diversity analyses to examine the differences in species diversity and composition among the different seasons. Furthermore, we validated the ITS amplicon sequencing results through fungal isolation and identification.

Results

Analyses of α and β diversity revealed both the differences and similarities between the fungal communities in the oral and gut microbiomes of giant pandas. Ascomycota and Basidiomycota were predominant in both oral and gut groups, while the dominant genera in the four seasons were Cutaneotrichosporon, and unidentified_Chaetothyriales_sp. Additionally, Cladosporium and Candida were predominant in the oral and gut fungus, respectively, across all four seasons. Notably, fungal abundance and diversity in the oral microbiome were significantly higher than in the gut microbiome, a pattern observed throughout most seasons. Several potentially pathogenic fungi, such as Fusarium, Candida and Aspergillus, were detected in healthy giant pandas, with most showing increased abundance during winter. It is worth mentioning that we found a distinct bias in the functional communities of oral and gut fungi. The abundance of saprophytic fungi in the gut is relatively high, which may be related to their role in cellulose digestion.

Conclusion

The abundance and diversity of fungal communities in the oral cavity and gut of giant pandas exhibit significant seasonal variations. While the oral cavity hosts a higher abundance and diversity of fungi, the species composition of fungal community composition is similar to that of the intestines. The majority of gut fungi are likely derived from the oral cavity or diet, the significant seasonal variation in gut fungal community structure further suggests that long-term resident fungi may not be present in the gut.
Dietary supplementation with L-citrulline improves amino acid composition and broiler performance, and modulates gut microbiota
Authors: Ma Yan , Liu Tingting , Chen Shuaihu , Shen Hong , Wang Jungang
Published: February 2025

Poultry lacks carbamoyl phosphate synthetase, which is a key enzyme in the endogenous synthesis of arginine, thus poultry must obtain arginine from their diet. Citrulline (L-Cit), as a precursor of arginine, produces the same biological effects as arginine, and may even be more effective. In these experiments, we discovered that the addition of L-Cit significantly increased production performance, antioxidant and immune properties, and modulated the intestinal microbiota. The study involved 240 1-day-old male yellow-feathered broilers randomly assigned to one of four treatment groups: control (CON), 0.5% L-Cit, 1% L-Cit, and 1.5% L-Cit, with 10 replicates per group and six birds per replicate. The feeding trial lasted for 63 days. The body weight at 42 days and 63 days, as well as the average daily weight gain from day 1 to 63, increased linearly and quadratically with the addition of L-citrulline. The plasma concentrations of citrulline, ornithine, and arginine increased linearly with the dose of L-Cit. L-citrulline increased total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) levels and decreased interleukin-1β (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α). Dietary addition of 1% L-Cit also significantly altered the overall composition of the broiler intestinal microbiota, increasing the relative abundance of Prevotellaceae_UCG-001 while reducing the relative abundance of Synergistota and Campylobacterota. This indicates that L-Cit can enhance the production performance of broilers, and improve antioxidant activity and immune functions, thereby protecting intestinal health. The optimum dietary amount of L-Cit is 1 to 1.5%.
Blood pressure improvement after resection of non-functioning adrenal adenomas: influencing factors and serum metabolic features
Authors: Zhang Jianlei , Wu Peiqiang , Chen Yule , Wang Min , Song Wenbin
Published: February 2025

Introduction

Non-functioning adrenal adenomas (NFAs) are typically regarded as benign tumors that lack hormonal secretion. However, emerging evidence has shown that some patients with NFAs and hypertension experience improvements in blood pressure after adrenalectomy, indicating a potential correlation between NFAs and hypertension. Nevertheless, the precise mechanisms that underpin this phenomenon remain elusive.

Methods

We collected data from all patients with adrenal adenomas who underwent unilateral laparoscopic partial or total adrenalectomy at the First Affiliated Hospital of Xi’an Jiaotong University in 2023. A statistical analysis was conducted on factors such as tumor diameter, duration of hypertension, BMI, and age. Additionally, we gathered serum samples from six patients who experienced postoperative blood pressure improvement and six patients who did not. These samples were subjected to targeted and untargeted metabolomic analyses to identify significant serum metabolites.

Results

Our findings revealed that 50.9% of patients with NFAs and hypertension experienced blood pressure improvement after surgery. Additionally, patients in the improvement group (IG) exhibited larger tumor diameters alongside shorter durations of hypertension compared to their counterparts in the nonimprovement group (NIG). Untargeted metabolomic analysis identified 89 differentially abundant metabolites in the serum between the IG and NIG. In particular, we found that guanidinoacetic acid (GAA), a precursor of creatine synthesis that possibly participates in the occurrence of hypertension, was enriched in patients in the IG and reduced after surgery.

Discussion

The findings of our study indicated that duration of hypertension and tumor diameter may exert an influence on the extent of postoperative blood pressure improvement, and NFAs might promote hypertension through GAA-related creatine metabolism.
Path planning of mobile robot based on improved double deep Q-network algorithm
Authors: Wang Zhenggang , Song Shuhong , Cheng Shenghui
Published: February 2025

Aiming at the problems of slow network convergence, poor reward convergence stability, and low path planning efficiency of traditional deep reinforcement learning algorithms, this paper proposes a BiLSTM-D3QN (Bidirectional Long and Short-Term Memory Dueling Double Deep Q-Network) path planning algorithm based on the DDQN (Double Deep Q-Network) decision model. Firstly, a Bidirectional Long Short-Term Memory network (BiLSTM) is introduced to make the network have memory, increase the stability of decision making and make the reward converge more stably; secondly, Dueling Network is introduced to further solve the problem of overestimating the Q-value of the neural network, which makes the network able to be updated quickly; Adaptive reprioritization based on the frequency penalty function is proposed. Experience Playback, which extracts important and fresh data from the experience pool to accelerate the convergence of the neural network; finally, an adaptive action selection mechanism is introduced to further optimize the action exploration. Simulation experiments show that the BiLSTM-D3QN path planning algorithm outperforms the traditional Deep Reinforcement Learning algorithm in terms of network convergence speed, planning efficiency, stability of reward convergence, and success rate in simple environments; in complex environments, the path length of BiLSTM-D3QN is 20 m shorter than that of the improved ERDDQN (Experience Replay Double Deep Q-Network) algorithm, the number of turning points is 7 fewer, the planning time is 0.54 s shorter, and the success rate is 10.4% higher. The superiority of the BiLSTM-D3QN algorithm in terms of network convergence speed and path planning performance is demonstrated.
Individually guided neuromodulation in special operator veterans with symptoms of PTSD and traumatic brain injury: preliminary data from a chart review
Authors: Frueh B. Christopher , Crowder Celeste , Taghva Alexander
Published: February 2025

Introduction

Special operations forces (SOF) are at particular risk of suffering from Posttraumatic Stress Disorder (PTSD) and Traumatic Brain Injury (TBI), and often these two conditions are comorbid, with the inciting event causing both conditions. These conditions present with broad-band electroencephalogram (EEG) abnormalities that may be amenable to neuromodulation.

Methods

This retrospective chart review reports on preliminary safety and clinical response data of individualized neuromodulation in a cohort of SOF veterans suffering from symptoms of PTSD and TBI. 33 male SOF veterans with TBI and PTSD symptoms received α-guided repetitive transcranial magnetic stimulation (α-rTMS) 5 days per week, with the magnetic pulse frequency set to their individual alpha frequency (IAF). Data on clinical scale scores at baseline and conclusion of treatment were extracted, including Rivermead Post-Concussion Questionnaire (RPQ), PTSD Checklist for DSM-5 (PCL-5) and side-effects.

Results

Thirty-three (33) charts containing pre-post scales for at least one of the clinical measures collected were reviewed. TBI symptom severity decreased an average of 54% on the RPQ (p < 0.01) and PTSD symptom severity decreased an average of 37.6% on the PCL-5 (p < 0.01). For participants with PCL-5 scores above the screening threshold of 33, 69% no longer met clinical criteria for PTSD at the end of the human performance program. Side effects were consistent with those reported for standard TMS, most frequently headache and fatigue.

Conclusion

Significant reductions in TBI clinical symptoms as well as significant decreases in PTSD clinical severity were reported in SOF veterans who underwent α-rTMS. Side effects were equivalent to those observed in normal TMS. Data supports the need for α-rTMS clinical trials in the SOF veteran population to further demonstrate the clinical impact of this approach.
Diagnosis and treatment of a rare bilateral primary thyroid cancer: a case report
Authors: Lin Hai , Zhang Xinyu , Yan Na , Guo Tao , Chen Qiu , Huang Xianen , Wang Dandan , Wu Weili
Published: February 2025

Preoperative ultrasound examination of thyroid nodules is the most economical and effective screening method for diagnosing thyroid nodules. Fine-needle aspiration biopsy (FNAB) cytology guided by ultrasound has high sensitivity and specificity in distinguishing benign and malignant thyroid nodules. However, approximately 25% of thyroid nodules cannot be determined by FNAB, and accurate differentiation of benign and malignant thyroid nodules is critical for patient prognosis. Here, we report the diagnosis and surgical treatment process of a rare patient with bilateral thyroid malignant tumor of independent origin. This patient had significantly elevated levels of calcitonin (Ctn: 130.00 pg/mL) and carcinoembryonic antigen (CEA: 16.13 ng/mL). Ultrasound shows a solid nodule on the left side of the thyroid gland, measuring 1.2*0.8*0.9cm, TI-RADS 4A; right solid nodule, 1.3*0.7*0.9 cm, TI-RADS 3. A fine needle biopsy of the left nodule showed little glandular epithelium and no evidence of malignancy. Multi-gene joint analysis of RET C634R in the left nodule and BRAF V600E in the right nodule indicated a potential diagnosis of left medullary thyroid carcinoma (MTC) and right papillary thyroid carcinoma (PTC). Postoperative pathology revealed the left thyroid nodule was MTC and the right nodule was PTC. The patient’s bilateral thyroid nodules are independent primary malignant lesions. This case emphasizes the important significance of combined analysis of ultrasound, serum biomarkers, cellular pathology, molecular detection, and paraffin pathology in the differential diagnosis of benign and malignant multiple thyroid nodules. It provides a reference for future diagnosis and treatment decisions of multiple thyroid nodules.
CT radiomics based model for differentiating malignant and benign small (≤20mm) solid pulmonary nodules
Authors: Sun Jing-Xi , Zhou Xuan-Xuan , Yu Yan-Jin , Wei Ya-Ming , Shi Yi-Bing , Xu Qing-Song , Chen Shuang-Shuang
Published: February 2025

Background

Currently, the computed tomography (CT) radiomics-based models, which can evaluate small (≤ 20 mm) solid pulmonary nodules (SPNs) are lacking. This study aimed to develop a CT radiomics-based model that can differentiate between benign and malignant small SPNs.

Methods

This study included patients with small SPNs between January 2019 and November 2021. The participants were then randomly categorized into training and testing cohorts with an 8:2 ratio. CT images of all the patients were analyzed to extract radiomics features. Furthermore, a radiomics scoring model was developed based on the features selected in the training group via univariate and multivariate logistic regression analyses. The testing cohort was then used to validate the developed predictive model.

Results

This study included 210 patients, 168 in the training and 42 in the testing cohorts. Radiomics scores were ultimately calculated based on 9 selected CT radiomics features. Furthermore, traditional CT and clinical risk factors associated with SPNs included lobulation (P < 0.001), spiculation (P < 0.001), and a larger diameter (P < 0.001). The developed CT radiomics scoring model comprised of the following formula: X = -6.773 + 12.0705×radiomics score+2.5313×lobulation (present: 1; no present: 0)+3.1761×spiculation (present: 1; no present: 0)+0.3253×diameter. The area under the curve (AUC) values of the CT radiomics-based model, CT radiomics score, and clinicoradiological score were 0.957, 0.945, and 0.853, respectively, in the training cohort, while that of the testing cohort were 0.943, 0.916, and 0.816, respectively.

Conclusions

The CT radiomics-based model designed in the present study offers valuable diagnostic accuracy in distinguishing benign and malignant SPNs.
Reliability of the Fenton growth curve method in predicting birth weight in newborns born at or before 36 weeks gestational age
Authors: Gungor Sara , Hou Wei , Decristofaro Joseph , Maduekwe Echezona T.
Published: February 2025

Objectives

The study aimed to assess the reliability of the Fenton curve superimposed with fetal weight percentile in predicting the birth weight of infants born ≤36 weeks gestational age.

Study design

This prospective observational study, conducted from December 2018 to May 2019, examined infants born ≤36 weeks gestational age. The Fenton curve was used to extrapolate the fetal growth percentile (Fenton curve method) and predict the birth weight of the infants on the day of delivery. The study excluded infants who were large or small for gestational age and those diagnosed with congenital anomalies or Hydrops fetalis. The Fenton curve method was used to predict the actual birth weight of 65 infants born at Stony Brook University Hospital and was compared with their actual birth weight using a two-sample t-test and Bland–Altman test.

Results

The study enrolled 65 infants, including 37 females, 2 Asians, 6 Blacks, 17 Hispanics, and 40 whites, with a mean gestational age of 32.1 ± 3.6 weeks and a mean actual birth weight of 1,860 ± 677 grams. The results showed no significant difference between the predicted and actual birth weight (p = 0.17), with a median difference of 32.2 grams between the predicted and actual weight.

Conclusion

The study found that the Fenton curve method reliably predicted the birth weight of infants born ≤36 weeks of gestational age. The results indicate that in normally grown fetuses, healthcare providers in the delivery room could potentially use Fenton curve predicted birth weight for drug dosage and equipment sizing in scenarios where obtaining actual birth weight is not possible. Nonetheless, additional analysis in larger cohorts is needed before this method can be universally adopted.
Development of a phenotypic screening assay to measure activation of cancer-associated fibroblasts
Authors: Ilg Marcus M. , Lapthorn Alice R. , Harding Sophie L. , Minhas Tariq , Koduri Gouri , Bustin Stephen A. , Cellek Selim
Published: February 2025

Background

In cancer metastasis, tumor cells condition distant tissues to create a supportive environment, or metastatic niche, by driving the activation of cancer-associated fibroblasts (CAFs). These CAFs remodel the extracellular matrix, creating a microenvironment that supports tumor growth and compromises immune cell function, enabling cancer cells to evade immune detection. Consequently, targeting the activation of CAFs has been proposed as a therapeutic strategy to hinder metastatic spread. Our objective was to develop the first in vitro phenotypic screening assay capable of assessing this activation process.

Methods

Human primary lung fibroblasts were co-cultured with highly invasive breast cancer cells (MDA-MB-231) to identify changes in the expression of selected genes using RT-qPCR. An In-Cell ELISA (ICE)-based assay using human lung fibroblasts, MDA-MB-231 cells and human monocytes (THP-1 cells) was developed to measure the activation of CAFs. Another ELISA assay was used to measure released osteopontin.

Results

When lung fibroblast were co-cultured with MDA-MB-231 cells, among the 10 selected genes, the genes for osteopontin (SPP1), insulin like growth factor 1 (IGF1), periostin (POSTN) and α-smooth muscle actin (α-SMA, ACTA2) elicited the greatest fold change (55-, 37-, 8- and 5-fold respectively). Since osteopontin, IGF-1 and periostin are secreted proteins and α-SMA is an intracellular cytoskeleton protein, α-SMA was chosen to be the readout biomarker for the ICE assay. When fibroblasts were co-cultured with MDA-MB-231 cells and monocytes in the 96 well ICE assay, α-SMA expression was increased 2.3-fold yielding a robust Z′ of 0.56. A secondary, low throughput assay was developed by measuring the release of osteopontin which showed a 6-fold increase when fibroblasts were co-cultured with MDA-MB-231 cells and monocytes.

Discussion

This phenotypic assay is the first to measure the activation of CAFs in a 96-well format, making it suitable for medium-to high-throughput screening of potential therapeutic compounds. By focusing on observable cellular phenotypic changes rather than targeting specific molecular pathways, this assay allows for a broader and unbiased identification of compounds capable of modulating CAF activation.
Time in the therapeutic range, bleeding event, and their determinants in older patients with atrial fibrillation on warfarin in Ethiopia: multicenter cross-sectional study
Authors: Addisu Zenaw Debasu , Demsie Desalegn Getnet , Tafere Chernet , Yazie Taklo Simeneh , Endeshaw Destaw , Tefera Bereket Bahiru , Berihun Malede , Beyene Dessale Abate
Published: February 2025

Background

Atrial fibrillation (AF) poses significant thromboembolism and bleeding risks, especially in older adults. Warfarin continues to be a primary treatment option, and maintaining the Time in Therapeutic Range (TTR) is critical for ensuring its effectiveness. However, suboptimal TTR is associated with increased risks of stroke, bleeding, and mortality. Despite its importance, there is limited data on warfarin management in Ethiopian older adults with AF. Therefore, this study aimed to determine the TTR, bleeding events, and their determinants, in older patients with AF in Ethiopia receiving warfarin therapy.

Method

In this study, older patients with AF who were treated with warfarin and had follow-up visits between May 2021 and May 2024, and met the inclusion criteria, were included. Patients were categorized based on TTR into two groups: poor anticoagulation (TTR < 65%) and good anticoagulation quality (TTR ≥ 65%). Bivariate and Multivariate Logistic regression was performed to predict determinants of a TTR < 65% and bleeding events. Odds ratios with 95% confidence intervals (CIs) were calculated, and statistical significance was set at P < 0.05.

Results

In this study, 384 patients with AF were included. Of this 53.4% were female. Of these 71% of patients had a TTR below 65%, 29% achieved ≥65%, with a median TTR of 45%. Bleeding events were reported by 13.5% of patients. Poor TTR was significantly associated with age (AOR = 1.199, 95% CI: 1.109–1.297), chronic kidney disease (AOR = 27.809, 95% CI: 7.57–101.76), and infrequent INR monitoring at 31–90-day intervals (AOR = 0.15, 95% CI: 0.004–0.051). Regarding determinants of bleeding events, Patients with diabetes mellitus had a 2.6-fold higher bleeding risk (AOR = 2.585, 95% CI: 1.069–6.250), and a CHA2DS2-VASc score ≥3 significantly increased bleeding risk compared to scores ≤2 (AOR = 7.562, 95% CI: 2.770–20.640).

Conclusion

This study highlights suboptimal warfarin therapy among older Ethiopian patients with AF. Poor anticoagulation was associated with advanced age, chronic kidney disease, and infrequent INR monitoring, while diabetes mellitus and high CHA₂DS₂-VASc scores increased bleeding risks. Close monitoring and frequent INR checks are essential to improving outcomes.
A systematic review of structural neuroimaging markers of psychotherapeutic and pharmacological treatment for obsessive-compulsive disorder
Authors: Moreau Allison L. , Hansen Isabella , Bogdan Ryan
Published: February 2025

Identifying individual difference factors associated with treatment response and putative mechanisms of therapeutic change may improve treatment for Obsessive Compulsive Disorder (OCD). Our systematic review of structural neuroimaging markers (i.e., morphometry, structural connectivity) of psychotherapy and medication treatment response for OCD identified 26 eligible publications from 20 studies (average study total n=54 ± 41.6 [range: 11-175]; OCD group n=29 ± 19) in child, adolescent, and adult samples evaluating baseline brain structure correlates of treatment response as well as treatment-related changes in brain structure. Findings were inconsistent across studies; significant associations within the anterior cingulate cortex (3/5 regional, 2/8 whole brain studies) and orbitofrontal cortex (5/10 regional, 2/7 whole brain studies) were most common, but laterality and directionality were not always consistent. Structural neuroimaging markers of treatment response do not currently hold clinical utility. Given increasing evidence that associations between complex behavior and brain structure are characterized by small, but potentially meaningful, effects, much larger samples are likely needed. Multivariate approaches (e.g., machine learning) may also improve the clinical predictive utility of neuroimaging data.
On the emergent capabilities of ChatGPT 4 to estimate personality traits
Authors: Piastra Marco , Catellani Patrizia
Published: February 2025

This study investigates the potential of ChatGPT 4 in the assessment of personality traits based on written texts. Using two publicly available datasets containing both written texts and self-assessments of the authors’ psychological traits based on the Big Five model, we aimed to evaluate the predictive performance of ChatGPT 4. For each sample text, we asked for numerical predictions on an eleven-point scale and compared them with the self-assessments. We also asked for ChatGPT 4 confidence scores on an eleven-point scale for each prediction. To keep the study within a manageable scope, a zero-prompt modality was chosen, although more sophisticated prompting strategies could potentially improve performance. The results show that ChatGPT 4 has moderate but significant abilities to automatically infer personality traits from written text. However, it also shows limitations in recognizing whether the input text is appropriate or representative enough to make accurate inferences, which could hinder practical applications. Furthermore, the results suggest that improved benchmarking methods could increase the efficiency and reliability of the evaluation process. These results pave the way for a more comprehensive evaluation of the capabilities of Large Language Models in assessing personality traits from written texts.
Ascent Trajectory Optimization Using Second-Order Birkhoff Pseudospectral Methods
Authors: Xue Xiaopeng , Xie Yujia , Zhou Hui , Gong Qinghai , Zhao Dangjun
Published: February 2025

This paper proposes a novel convex optimization framework for two-stage launch vehicle (TSLV) ascent trajectory planning from liftoff to orbit insertion, featuring two groundbreaking advancements over existing convex optimization methodologies: (1) an innovative second-order Birkhoff pseudospectral (BPS) method is developed that reduces the number of dynamic equality constraints by 50% compared to traditional PS methods, meanwhile, an augmented variable transcription technique is used to formulate inequality constraints; therefore, the sparsity ratio of the inequality matrix is reduced to less than 1%; (2) a new iterative solution strategy initialized by a few guesses is proposed to efficiently obtain the optimal solution. The framework is rigorously supported by theoretical convergence guarantees and validated through comprehensive numerical experiments. The numerical results demonstrate around a 50% reduction in computational time compared to the differential PS baseline method. With the significantly reduced computational cost, the proposed method exhibits strong potential for real-time onboard implementation in the future.
Assessment of RC Columns Under Axial Compression for Un-Corroded and Corroded Stirrups Scenarios: A Practice-Oriented Numerical Approach
Authors: Ahamed Aabith , Nifla Fathima , Thamboo Julian , Asad Mohammad , Zahra Tatheer
Published: February 2025

This paper presents a practice-oriented numerical modelling procedure to assess the loadbearing capacity of reinforced concrete (RC) columns under axial compression loading. A simplified procedure was incorporated to analyse the performance of RC columns with corroded stirrups, a prevalent deterioration phenomenon in corroded RC columns. The modelling framework incorporates material and geometric nonlinearities caused by material and buckling failure under axial compression, utilising the Arc-length algorithm with integrated geometric imperfections. Stirrup corrosion scenarios were incorporated by removing stirrups and modifying core concrete confinement properties, providing a practice-oriented approach to assess the loadbearing capacity of corroded columns. The study focused on square RC columns that are commonly used in low-rise buildings with nominal reinforcement detailing. The modelling method was validated against experimental data, and it showed a good agreement. A comprehensive parametric analysis was then conducted to examine the effects of critical design parameters, including (1) slenderness, (2) eccentricity, (3) stirrup corrosion, and (4) material properties, on axial compression performance. Parametric analyses demonstrated that the developed modelling technique appropriately predicted the axial compression behaviour of un-corroded RC columns in alignment with analytical design rules. For stirrup-corroded RC columns, the absence of confinement for up to 300 mm length near the base, due to stirrup corrosion, led to premature buckling. Based on the analysed cases, the reduction in bearing capacity of the stirrup-corroded RC columns could range between 4.9 and 18.6% (higher for slender columns) as compared to corresponding un-corroded RC columns.
Revisiting Endoreversible Carnot Engine: Extending the Yvon Engine
Authors: Zhao Xiu-Hua , Ma Yu-Han
Published: February 2025

Curzon and Ahlborn’s 1975 paper, a pioneering work that inspired the birth of the field of finite-time thermodynamics, unveiled the efficiency at maximum power (EMP) of the endoreversible Carnot heat engine, now commonly referred to as the Curzon–Ahlborn (CA) engine. Historically, despite the significance of the CA engine, similar findings had emerged at an earlier time, such as the Yvon engine proposed by J. Yvon in 1955 that shares the exact same EMP, that is, the CA efficiency ηCA. However, the special setup of the Yvon engine has circumscribed its broader influence. This paper extends the Yvon engine model to achieve a level of generality comparable to that of the CA engine. With the power expression of the extended Yvon engine, we directly explain the universality that ηCA is independent of the heat transfer coefficients between the working substance and the heat reservoirs. A rigorous comparison reveals that the extended Yvon engine and CA engine represent the steady-state and cyclic forms of the endoreversible Carnot heat engine, respectively, and are equivalent.
Speed–Load Insensitive Fault Diagnosis Method of Wind Turbine Gearbox Based on Adversarial Training
Authors: Zhou Wenjie , Zhou Quan , Zhang Jie
Published: February 2025

The rotational speed and load torque of wind turbine gearboxes can vary widely during operation, which has an obvious impact on the gearbox fault diagnosis carried out based on vibration signals. To address this problem, this paper proposes a fault diagnosis method that introduces an adversarial training mechanism and designs a game learning strategy among the feature extractor, fault recognizer, rotational speed estimator, and load estimator. In this way, the network tends to acquire fault features with weaker correlation with rotational speed and load and thus improves the performance of the fault diagnosis network in the face of the samples from the rotational speed and load ranges that are not covered by the training set. At the same time, in order to verify the effectiveness of the proposed method, in this paper, we have designed an experimental platform for wind turbine gearbox scaling, carried out simulation experiments of variable speed and torque faults, collected experimental data, and constructed a variable speed and load fault dataset. Comparing the proposed method with the baseline model, when confronted with data from RPMs or load ranges not covered by the training set, the accuracy of the baseline model drops by anywhere from 10.54% to 16.46%, while the accuracy of the method drops by only 1.39%. The results show that the method can effectively improve the performance of the fault diagnosis network when facing a variation of speed and load.
Anti-Inflammatory Potential of Wampee (Clausena lansium (Lour.) Skeels) Polyphenol Extract in Ulcerative Colitis: Gut Microbiota and TLR4-p38 MAPK/NF-κB Signaling Axis Regulation
Authors: Shang Kaijie , Zhao Zhiheng , Chen Hua , Bian Xiaonan , Zhong Xianquan , Hu Xiaoping , Lin Xue , Wang Lu
Published: February 2025

The consumption of wampee has traditionally been utilized to alleviate gastrointestinal inflammation and associated disorders; however, its exact mechanism has remained unknown. The aim of this study was to elucidate the therapeutic efficacy and underlying mechanism of wampee polyphenol extract (WPE) in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC). The findings revealed that WPE alleviated diverse symptoms of UC, regulated various inflammatory cytokines, and effectively protected the colon tissue structure and barrier integrity, thereby inhibiting LPS translocation. Moreover, WPE restored the richness and diversity of gut microbiota and optimized its structure at the phylum and genus levels, causing a notable improvement in short- chain fatty acid (SCFA) metabolism, particularly acetic acid, propionic acid, and butyric acid. Consequently, WPE was demonstrated to effectively suppress the LPS-induced TLR4-p38 MAPK/NF-κB signaling pathway by modulating gut microbiota and SCFA metabolism. These findings provided a theoretical basis for the use of wampee as a potential functional natural food for UC.
Investigation of the Gel Properties and Gelation Mechanism of a Surimi Blend Composed of Skipjack Tuna (Katsuwonus pelamis) and Purpleback Flying Squid (Symplectoteuthis oualaniensis)
Authors: Liao Jianwei , Shi Haohao , Wang Jiamei , Xia Guanghua , Zhao Yongqiang , Yu Gang , Shen Xuanri
Published: February 2025

The objective of the present study was to investigate the gel properties and gelation mechanism of a surimi blend consisting of Katsuwonus pelamis and Symplectoteuthis oualaniensis. Superior gel properties, including gel strength, cooking loss and water holding capacity, were observed in mixed surimi. With increasing proportions of K. pelamis in the blend, an increase in hardness, gumminess and chewiness emerged, which compromised the resilience and whiteness of the gels. The detection of apparent viscosity revealed the shear-thinning properties of mixed surimi. The results of the molecular force measurements and differential scanning calorimetry demonstrated that heterogeneous myofibrillar proteins interacted into rigid protein aggregates with the help of enhanced hydrophobic interactions, subsequently increasing the values of G’ and G”. According to the FTIR spectrum, as the proportion of K. pelamis gradually increased, the protein secondary structure of surimi transitioned from a random coil to a β-sheet, facilitating the formation of a more ordered network structure. A marked improvement in the microstructure was observed via SEM. Therefore, the incorporation of surimi can be employed to optimize gel properties.
Improving Recruitment and Retention: A Management Framework to Utilize DMAIC and Kaizen for Student Support in Engineering Education
Authors: Yelamarthi Kumar , Powell Elizabeth , Hussein Mazen
Published: February 2025

The Clay N. Hixson Student Success Center within the College of Engineering at Tennessee Tech University has undergone a transformative upgrade by integrating the Define, Measure, Analyze, Improve, and Control (DMAIC) framework with select Kaizen principles for continuous improvement to enhance student support services. Key performance indicators (KPIs) have been employed to assess the achievement of core goals, significantly advancing recruitment, retention, and overall student success. Implementing the DMAIC framework has streamlined processes such as a unified degree map and a math bridge program, resulting in a 53% increase in incoming first-year students and broadening the College of Engineering’s outreach. These efforts have also contributed to a 10% increase in first-to-second-year retention rates. Through the utilization of DMAIC, the regular redistribution of advisor caseloads and cross-training has been facilitated, ensuring timely student support without overburdening advisors. Additionally, targeted academic support initiatives have reduced the at-risk student population from 19% to 11%. These management techniques extend to multiple initiatives, including enhancements to high school summer camps, advisor listening sessions, and student surveys designed to meet evolving student needs. Creating specialized areas for academic advisors has also supported their professional growth, contributing to better student outcomes. This paper comprehensively analyzes these strategies and provides valuable insights for institutions seeking to apply DMAIC and continuous improvement models to strengthen student support systems.
Research Progress of Halide Perovskite Nanocrystals in Biomedical Applications: A Review
Authors: Wang Guiyun , Qi Yanxia , Zhou Zhiyan , Liu Zhuang , Wang Ruowei
Published: February 2025

Halide perovskite nanocrystals have rapidly emerged as a prominent research topic in materials science over the past decade owing to their exceptional optoelectronic properties and tunability. Their distinctive characteristics, including high light absorption coefficients, high quantum yields, narrow-band emissions, low defect densities, and adjustable chemical compositions and sizes, position them as highly promising candidates for applications in optoelectronic devices, energy conversion units, and other related systems. However, due to the toxicity and instability of halide perovskite nanocrystals, their widespread application in the biomedical field has been limited in the past. In recent years, numerous innovative coating strategies have been reported to effectively enhance the stability of halide perovskite nanocrystals while confining their toxic metal ions within the coating layers, thereby significantly improving their biocompatibility. This review provides a comprehensive summary of the recent progress of halide perovskite nanocrystals in the field of biomedicine. It covers coating strategies to enhance stability and biocompatibility, as well as the applications of coated halide perovskite nanocrystals in biomedicine, with a particular focus on their unique advantages in bioimaging and chemical sensing. Finally, we address unresolved issues and challenges, such as the metabolic pathways and final products of halide perovskite nanocrystals in vivo. We hope to inspire researchers in the field and provide direction for future studies.
A Time-Delay Overlapping Modulation-Based Maritime High-Speed and High-Spectral-Efficiency Communication Technology
Authors: Dou Xinyu , Ma Teng , Liang Dequn
Published: February 2025

To simultaneously address dual demands on the spectral efficiency and the data transmission rate of maritime communications, in this paper, a novel maritime communication technology based on time-delay overlapping modulation (TDOM) is proposed. In TDOM, multiple carriers are delayed in turn and directly overlapped in the time domain to form the communication symbol. In this way, the strict orthogonality between carriers can be broken through, indicating that the frequency interval between carriers can be much narrower than ever. In other words, TDOM can achieve non-orthogonal communication and realize both higher spectral efficiency and a higher maritime communication rate. The system architecture is designed, and its performance is analyzed and compared with that of other typical maritime communication technologies such as the very-high-frequency data exchange system (VDES). It is shown that TDOM can reach up to 20 times the peak communication rate and the spectral efficiency of VDES. As a digital modulation technology implemented in the physical layer, the proposed TDOM can be extended to other communication systems such as satellite communications or 4G/5G based off-shore communications.
Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance
Authors: Su Yanyu , Li Yi , Yi Qiaolian , Xu Yingchun , Sun Tianshu , Li Yingxing
Published: February 2025

Antifungal resistance poses a critical global health threat, particularly in immuno-compromised patients. Beyond the traditional resistance mechanisms rooted in heritable and stable mutations, a distinct phenomenon known as heteroresistance has been identified, wherein a minority of resistant fungal cells coexist within a predominantly susceptible population. Heteroresistance may be induced by pharmacological factors or non-pharmacological agents. The reversible nature of it presents significant clinical challenges, as it can lead to undetected resistance during standard susceptibility testing. As heteroresistance allows fungal pathogens to survive antifungal treatment, this adaptive strategy often leads to treatment failure and recurring infection. Though extensively studied in bacteria, limited research has explored its occurrence in fungi. This review summarizes the current findings on antifungal heteroresistance mechanisms, highlighting the clinical implications of fungal heteroresistance and the pressing need for deeper mechanism insights. We aim to bring together the latest research advances in the field of antifungal heteroresistance, summarizing in detail its known characteristics, inducing factors, molecular mechanisms, and clinical significance, and describing the similarities and differences between heteroresistance, tolerance and persistence. Further research is needed to understand this phenomenon and develop more effective antifungal therapies to combat fungal infections.