bluuebunny/crossref_metadata_2025 huggingface dataset:
Innovative Approaches in Computer Forensics, Innovative Applications and Comparative Analysis of GUI and Shortcut Methods
Authors: Siyez Özgecan
Published: October 2024

This article examines two different methods used in digital forensics—GUI (Graphical User Interface) and shortcut-based methods—and compares their innovative applications in detail. The GUI provides automation and transparency in digital forensic processes with its user-friendly interface, while the shortcut-based methods offer more flexibility and customization. In the analysis of audio and video recordings, the GUI is more effective in detecting visual details like body language, while the shortcut method allows faster and more customizable analysis. Both methods are evaluated in terms of their advantages and disadvantages, use cases, legal compliance, and data security. Additionally, the article discusses how suitable these methods are within the framework of the EU Artificial Intelligence Act and in which situations each method should be preferred. This study presents innovative approaches not found in the literature, providing a guide for future research in the field of digital forensics. By combining the visual strengths of the GUI with the speed and flexibility of the shortcut methods, more efficient results can be achieved in digital forensic investigations.
Chemical reaction engineering of nutritional phenomena in the human body
Authors: Chen Xiao Dong
Published: October 2024

Unlike many accomplished fields, human nutrition lacks the support of engineering science. Here, the aspects of food processing in the gastro-intestinal (GI) tract are reviewed, highlighting the experimental chemical reaction engineering (CRE) approach to digestion studies in particular. As a first look at human nutrition in terms of conservation laws, the differential forms of mass and energy balances are presented, emphasizing the chemical and biochemical reaction rates of generation and consumption and the heats associated with these reactions, respectively. These rates and the heats should be very meaningful for understanding the dynamics of nutrition within the body, though they remain unknown. Without solving the differential equations, global integrations of the mass balances within each organ, up to the organ boundary, can create control volumes for gaining new insights, such as the transient multicomponent nature of the stomach “reactor” emptying. Global integration within the human body to the boundaries of the entire GI tract, from the mouth to anus, finds the GI tract to be a “pipe outside the body.” This has revealed interesting aspects, highlighting the human body as a “molecular machine.” It is envisaged that the terms outlined here ought to be established in the future to improve human nutrition.
Intensified greenhouse gas prediction: Configuring Gate with Fine-Tuning Shifts with Bi-LSTM and GRU System
Authors: Sha Mohemmed , Emmanuel Sam , Bindhu A. , Mustaq Mohamed
Published: October 2024

Introduction

On a global scale, climate change refers to persistent alterations in weather conditions and temperature patterns. These modifications have far-reaching implications across the world. GHGs (Greenhouse Gases) play a crucial role in driving climate change. Most of these emissions originate from human activities, particularly those contributing to releasing CO2 and CH4. In the conventional approach, identifying emissions involves recognizing and quantifying the sources and amounts of GHG released into the atmosphere. However, this manual identification method has limitations, including being time-consuming, relying on incomplete resources, prone to human error, and lacking scalability and coverage.

Methodology

To address these challenges, a technology-based system is necessary for effectively identifying GHG emissions. The proposed method utilized the configuration of a gating mechanism incorporating fine-tuning shifts in the Bi-LSTM-GRU algorithm to predict GHG emissions in top-emitting countries. The PRIMAP-host dataset is used in the respective method comprising subsector data such as CO2, CH4, and N2O to attain this. In the presented model, Bi-LSTM is used to capture significant features, handle vanishing gradient problems, etc., because of its process in both directions. Conversely, it is limited by overfitting and long-term dependencies.

Results and discussion

GRU is used with Bi-LSTM to address the issue for the advantages of memory efficiency, handling long-term dependencies, rapid training process and minimizes the overfitting by infusion of GRU in the input layer of BiLSTM with tuning process in the BiLSTM. Here, the configuration of gates with fine-tuning shifts to improve the prediction performance. Moreover, the efficiency of the proposed method is calculated with performance metrics. Where RMSE value is 0.0288, MAPE is 0.0007, and the R-Square value is 0.99. In addition, internal and external comparisons are carried out to reveal the greater performance of the respective research.
Effective tricuspid regurgitation reduction is associated with renal improvement and reduced heart failure hospitalization
Authors: Felbel Dominik , von Winkler Juliana , Paukovitsch Michael , Gröger Matthias , Walther Elene , Andreß Stefanie , Schneider Leonhard , Markovic Sinisa , Rottbauer Wolfgang , Keßler Mirjam
Published: October 2024

Background

Several studies have demonstrated an association between tricuspid regurgitation (TR) and organ dysfunction including hepatic and renal insufficiency. Improvement of liver function following transcatheter edge-to-edge repair (T-TEER) has already been linked to reduction of venous congestion due to TR reduction. This study analyzes whether TR-reduction using T-TEER is also associated with improved renal function.

Methods and results

The TRIC-ULM registry includes 92 selected patients undergoing T-TEER between March 2017 and May 2023. Estimated glomerular filtration rate (eGFR) improvement was evident in 53 patients (57%) at 3-months follow-up (FU) and defined by FU eGFR > baseline eGFR. Median age was 80 [interquartile range 75–83] years, pre- and postinterventional TR grades were 4 [3–5] and 1 [1–2], baseline eGFR was 36 [30–53] ml/min and New Yeark Heart Association (NYHA) IV was evident in 15% of patients. Multiple logistic regression analysis revealed TR vena contracta reduction (Odds ratio (OR) 1.35 [95% CI: 1.12–1.64] per mm, p = 0.002) and reduced preinterventional tricuspid annular plane systolic excursion (TAPSE) [OR 0.89 (95% CI: 0.79–0.99) per mm, p = 0.033] to independently predict renal improvement at FU. An eGFR improvement threshold of >9 ml/min was associated with reduced 1-year heart failure hospitalization rates [adjusted hazard ratio 0.22 (95% CI: 0.07–0.62) p = 0.005].

Conclusion

Effective tricuspid edge-to-edge repair is associated with improved renal function and reduced heart failure hospitalization. In patients without renal improvement at 3-months follow-up, residual tricuspid regurgitation should be reevaluated for reintervention.
AI-enabled detection of QRS fragmentation from 12-lead electrocardiogram and its clinical relevance for predicting malignant arrhythmia onset
Authors: Ingelaere Sebastian , Villa Amalia , Varon Carolina , Van Huffel Sabine , Vandenberk Bert , Willems Rik
Published: October 2024

Background

Electrocardiographic markers differentiating between death caused by ventricular arrhythmias and non-arrhythmic death could improve the selection of patients for implantable cardioverter-defibrillator (ICD) implantation. QRS fragmentation (fQRS) is a parameter of interest, but subject to debate. We investigated the association of an automatically quantified probability of fragmentation with the outcome in ICD patients.

Methods

From a single-center retrospective registry, all patients implanted with an ICD between January 1996 and December 2018 were eligible for inclusion. Patients with active pacing were excluded. From the electronical medical record, clinical characteristics at implantation were collected and a 12-lead ECG was exported and analyzed by a previously validated machine-learning algorithm to quantify the probability of fQRS. To compare fQRS(+) and fQRS(−) patients, dichotomization was performed using the Youden index. Patients with a high probability of fragmentation in any region (anterior, inferior or lateral), were labeled fQRS(+). The impact of this fQRS probability on outcomes was investigated using Cox regression.

Results

A total of 1,242 patients with a mean age of 62.6 ± 11.5 years and a reduced left ventricular ejection fraction of 31 ± 12% were included of which 227 (18.3%) were female. The vast majority suffered from ischemic heart disease (64.3%) and were implanted in primary prevention (63.8%). 538 (43.3%) had a high probability of fragmentation in any region. Patients with a high probability of fragmentation had more frequently dilated cardiomyopathy (39.4% vs. 33.0%, p = 0.019), left bundle branch block (40.8% vs. 32.5%, p = 0.006) and a higher use of cardiac resynchronization therapy with defibrillator (CRT-D) devices (33.9% vs. 26.3%, p = 0.004). After adjustment in a multivariable Cox model, there was no significant association between the probability of global or regional fQRS and appropriate ICD therapy, inappropriate shock and short- or long-term mortality.

Conclusion

There was no association between the automatically quantified probability of the presence of fQRS and outcome. This lack of predictive value might be due to the algorithm used, which identifies only the presence but not the severity of fragmentation.
Biofuser: a multi-source data fusion platform for fusing the data of fermentation process devices
Authors: Zhang Dequan , Jiang Wei , Lou Jincheng , Han Xuanzhou , Xia Jianye
Published: October 2024

In the past decade, the progress of traditional bioprocess optimization technique has lagged far behind the rapid development of synthetic biology, which has hindered the industrialization process of synthetic biology achievements. Recently, more and more advanced equipment and sensors have been applied for bioprocess online inspection to improve the understanding and optimization efficiency of the process. This has resulted in large amounts of process data from various sources with different communication protocols and data formats, requiring the development of techniques for integration and fusion of these heterogeneous data. Here we describe a multi-source fusion platform (Biofuser) that is designed to collect and process multi-source heterogeneous data. Biofuser integrates various data to a unique format that facilitates data visualization, further analysis, model construction, and automatic process control. Moreover, Biofuser also provides additional APIs that support machine learning or deep learning using the integrated data. We illustrate the application of Biofuser with a case study on riboflavin fermentation process development, demonstrating its ability in device faulty identification, critical process factor identification, and bioprocess prediction. Biofuser has the potential to significantly enhance the development of fermentation optimization techniques and is expected to become an important infrastructure for artificial intelligent integration into bioprocess optimization, thereby promoting the development of intelligent biomanufacturing.
Accessing medical care in the era of the digital revolution: arguing the case for the “digitally marginalised”
Authors: Choolayil Anoop C. , Paranthaman Sadhishkumar , Kuttiatt Vijesh Sreedhar
Published: October 2024

This article explores the intersection of healthcare accessibility and digitalisation from a rights perspective. Drawing from two illustrative cases presented to a filariasis management clinic in Puducherry, where the authors are affiliated, the article argues that despite the multiple benefits that digital health poses, there are individuals and sections of society that experience marginalisation in healthcare owing to digitalisation. Collating the data generated through the observations of the authors and the narratives of the patients, the article illustrates that such marginalisation can originate even from a relatively simple ICT adaptation like text message-based appointments, inducing health inequities. The impact of such digital marginalisation disproportionately affects vulnerable sections like older adults and the rural population in an intersectional pattern where disadvantages compound to produce larger health inequities for the affected. The study advocates for bridging the digital divide through efforts including digital literacy–when possible–and alternative solutions like dedicated helpdesks, training healthcare staff and involving NGOs and voluntary organisations to ensure health equity for the digitally marginalised.
Modeling the effect of dispersion and attenuation for frequency-dependent amplitude variation with offset
Authors: Du Haoqi , Zhang Jian , Zhao Dongchang , Wang Shuaiyang , Xu Jiaqian
Published: October 2024

As research in oil and gas exploration progresses, unconventional resources, such as shale gas, are increasingly becoming the focal point in the global pursuit of oil and gas resource. Shale gas reservoirs significantly differ from conventional sandstone reservoirs in aspects such as rock composition, pore type, occurrence mode, fluid, etc., thereby amplifying the challenges associated with geophysical modeling and the prediction of sweet spots. Since the formation and storage of shale gas are positively correlated with shale fracturing, a modeling approach based on Chapman theory is introduced to complete frequency-dependent petrophysical modeling. Additionally, the Frequency-dependent Amplitude Variation with Offset (FAVO) technique can estimate velocity dispersion by using the reflection coefficient information related to incidence angle and frequency. This method can more effectively identify fluids within shale reservoir. However, current FAVO forward modeling only considers the velocity dispersion and attenuation at the interface, neglecting the attenuation dispersion effects during interlayer propagation. To this end, we utilize Chapman-based petrophysical modeling as a foundation and conduct seismic forward modeling studies employing the compound matrix method. Through experimental analysis, we meticulously examine the attenuation dispersion effects at interfaces and within layers. Finally, we conduct FAVO simulations that vividly delineate the interplay between reservoir parameters and seismic responses.
Single center experience in localization of insulinoma by selective intraarterial calcium stimulation angiography - a case series of 15 years
Authors: Halmi Sándor , Berta Eszter , Diószegi Ágnes , Sira Lívia , Fülöp Péter , Nagy Endre V. , Győry Ferenc , Kanyári Zsolt , Tóth Judit , Bhattoa Harjit Pal , Bodor Miklós
Published: October 2024

Background

Insulinomas are rare insulin-secreting neuroendocrine neoplasms of the pancreas. First-line treatment is the surgical removal of the tumor, however, the localization with standard imaging techniques is often challenging. With the help of selective intraarterial calcium stimulation the insulinoma’s localization can be narrowed down to one third of the pancreas which the selected artery supplies.

Objective

We aimed to prove the usefulness of the calcium stimulation test in case of 9 patients treated between 2006 and 2021 diagnosed with endogenous hyperinsulinemic hypoglycemia confirmed by fasting test, where conventional imaging methods, like transabdominal ultrasound, CT or MRI failed to detect the source of hyperinsulinemia.

Methods

We performed selective intraarterial calcium stimulation with angiography with calcium gluconate injected to the main supporting arteries of the pancreas (splenic, superior mesenteric and gastroduodenal arteries); blood samples were obtained from the right hepatic vein before, and 30, 60 and 120 seconds after calcium administration.

Results

With selective angiography we found a significant elevation of insulin levels taken from the right hepatic vein in five of the nine cases. On histopathology, the lesions were between 1-2 cm, in one case malignancy was also confirmed. In four patients we found a significant rise of insulin levels obtained from all catheterized sites, which confirmed the diagnosis of nesidioblastosis. In three cases no surgery was performed, and the symptoms relieved with medical treatment.

Conclusions

Selective intraarterial calcium stimulation remains an important tool in localization of the source of insulin excess, especially in cases where other diagnostic modalities fail.
Association between small intestine bacterial overgrowth and psychiatric disorders
Authors: Bogielski Bartosz , Michalczyk Katarzyna , Głodek Piotr , Tempka Bartosz , Gębski Wojciech , Stygar Dominika
Published: October 2024

Small intestinal bacterial overgrowth (SIBO) is a gastrointestinal condition characterized by abnormal colonization of bacteria in the small intestine, leading to overgrowth and alteration, which is linked to gastrointestinal issues, potentially affecting neurological and mental health. Despite existing research, we still do not understand how SIBO affects tryptophan metabolism and psychiatric diseases. We investigated the literature for connections between SIBO, tryptophan metabolism disruptions, and psychiatric disorders like autism, schizophrenia, Alzheimer’s, and Parkinson’s diseases. We also explored the interaction between thyroid disorders and their influence on SIBO and psychiatric illnesses. PubMed and Google Scholar databases were searched using keywords and phrases, individual and in combinations, like “SIBO,” “gut microbiota,” “neurologic disorders,” “mental disorders,” “tryptophan,” “dopamine,” and “thyroid disease.” We focused on original research and review papers that presented empirical studies conducted on animal models and human subjects published in English between February 1992 to February 2023. The initial 2 634 534 records were preliminary screened based on title and abstract and then subjected to full-text review to exclude publications with insufficient data on SIBO, lack of a psychiatric disorder component, or methodological limitations compromising the integrity of the findings. The analysis highlights the significance of the association between psychiatric disorders and SIBO, emphasizing the role of gut-microbial diversity in mental health. We advocate for more detailed studies, including longitudinal research, to clarify the causal relationships between SIBO, gut dysbiosis, and psychiatric disorders and for an integrated approach while treating complex psychiatric conditions.
U-shaped association between dietary niacin intake and chronic kidney disease among US elderly: a nationwide cross-sectional study
Authors: Xie Zhouzhou , Peng Shansen , Ou Gejun , Zhou Xiaoqi , Zhang Guihao , Jiang Huiming , Zhang Tianhui , Chen Nanhui
Published: October 2024

Background

In addition to hypertension or diabetes, elderly people are also considered one of the high-risk groups for chronic kidney disease (CKD). Although niacin is recognized for its renal protective properties, the link between dietary niacin intake and CKD remains uncertain. This study investigated this relationship in the elderly.

Methods

We included participants aged 60 and older from the National Health and Nutrition Examination Survey (NHANES) for the years 2003-2018. Dietary niacin intake was assessed through two non-consecutive 24-hour dietary recalls. CKD was diagnosed in individuals with a urine albumin-to-creatinine ratio exceeding 30 mg/g or an estimated glomerular filtration rate below 60 mL/min per 1.73 m^2. The study cohort comprised 4,649 participants, 1,632 of whom had CKD. Propensity score matching (PSM) was utilized to adjust for baseline differences between the groups.

Results

Our analysis, using smooth curve fitting and generalized additive models both before and after PSM, found a U-shaped curve depicting the relationship between dietary niacin intake and CKD risk, confirmed by a log-likelihood ratio test (P < 0.05). Threshold effect analysis (after PSM) indicated a reduced risk of CKD in older adults with a niacin intake below 38.83 mg per day [odds ratio (OR) = 0.99, 95% confidence interval (CI) 0.97-1.00]. In contrast, higher intake levels significantly increased the risk (OR = 1.03, 95% CI 1.00-1.06). Subgroup analysis indicated that these associations were consistent across different stratification variables (P for interaction > 0.05).

Conclusion

Our findings suggested a U-shaped association between dietary niacin intake and CKD risk among older Americans. However, further prospective cohort studies are needed to confirm this finding.
Complex factors combinations driving tea growers to adopt ecological agricultural practices in tea gardens
Authors: Yan Zhaoshuo , Zhang Wenzhe , Liu Xiao , Li Zhengyuan , Zhao Yutao , Zeng Mingjiang , Gao Shuilian
Published: October 2024

Introduction

The implementation of ecological agriculture practices in Chinese tea gardens plays a vital role in mitigating N2O emissions and addressing environmental degradation. Nevertheless, a dearth of discourse exists regarding the intricacies surrounding farmers' adoption of tea garden ecological agriculture practices (TGEAP), particularly the complex interplay between adoption factors and outcomes.

Methods

Using data of 310 farmers, this study employed complexity theories and Stimulus-Organism-Response theories, and integrated Partial Least Squares Structural Equation Modeling and fuzzy-set Qualitative Comparative Analysis to explore the complex relationships between farmer characteristics, internal and external factors, and adoption of farmer.

Results

The results show three influential paths in the Stimulus-Organism-Response model, and environmental protection attitude (EPA) and production expectation (PE) act as intermediaries. Notably, EPA exhibits a masking effect in one pathway. These paths linked closely to three farmer characteristics. Beyond the Stimulus-Organism-Response model, nine combinations lead to farmers' adoption, and four to non-adoption.

Discussion

We discover scenarios where opposing environmental states or age lead to adoption, explaining the masking effect. These combinations highlight how a favorable environment influences both adoption and non-adoption. We also discuss other combinations that lead to adoption or non-adoption. The study suggests that governments employ targeted incentives to facilitate tea farmers' transition in agriculture.
Peripheral immune profiling of soft tissue sarcoma: perspectives for disease monitoring
Authors: Almeida Jani Sofia , Sousa Luana Madalena , Couceiro Patrícia , Andrade Tânia Fortes , Alves Vera , Martinho António , Rodrigues Joana , Fonseca Ruben , Freitas-Tavares Paulo , Santos-Rosa Manuel , Casanova José Manuel , Rodrigues-Santos Paulo
Published: October 2024

Studying the tumor microenvironment and surrounding lymph nodes is the main focus of current immunological research on soft tissue sarcomas (STS). However, due to the restricted opportunity to examine tumor samples, alternative approaches are required to evaluate immune responses in non-surgical patients. Therefore, the purpose of this study was to evaluate the peripheral immune profile of STS patients, characterize patients accordingly and explore the impact of peripheral immunotypes on patient survival. Blood samples were collected from 55 STS patients and age-matched healthy donors (HD) controls. Deep immunophenotyping and gene expression analysis of whole blood was analyzed using multiparametric flow cytometry and real-time RT-qPCR, respectively. Using xMAP technology, proteomic analysis was also carried out on plasma samples. Unsupervised clustering analysis was used to classify patients based on their immune profiles to further analyze the impact of peripheral immunotypes on patient survival. Significant differences were found between STS patients and HD controls. It was found a contraction of B cells and CD4 T cells compartment, along with decreased expression levels of ICOSLG and CD40LG; a major contribution of suppressor factors, as increased frequency of M-MDSC and memory Tregs, increased expression levels of ARG1, and increased plasma levels of IL-10, soluble VISTA and soluble TIMD-4; and a compromised cytotoxic potential associated with NK and CD8 T cells, namely decreased frequency of CD56dim NK cells, and decreased levels of PRF1, GZMB, and KLRK1. In addition, the patients were classified into three peripheral immunotype groups: "immune-high," "immune-intermediate," and "immune-low." Furthermore, it was found a correlation between these immunotypes and patient survival. Patients classified as "immune-high" exhibited higher levels of immune-related factors linked to cytotoxic/effector activity and longer survival times, whereas patients classified as "immune-low" displayed higher levels of immune factors associated with immunosuppression and shorter survival times. In conclusion, it can be suggested that STS patients have a compromised systemic immunity, and the correlation between immunotypes and survival emphasizes the importance of studying peripheral blood samples in STS. Assessing the peripheral immune response holds promise as a useful method for monitoring and forecasting outcomes in STS.
Histamine and Th2 cytokines independently and synergistically upregulate MMP12 expression in human M2 macrophages
Authors: Pereira da Fonseca Alice , Traidl Stephan , Gutzmer Ralf , Schaper-Gerhardt Katrin , Werfel Thomas , Mommert Susanne
Published: October 2024

Beyond Th2 cells and various immune cells, M2 macrophages have been identified in lesional skin of atopic dermatitis (AD) indicating their involvement in the disease’s underlying mechanisms. MMP12, a matrix-degrading enzyme, which is predominantly produced by macrophages, is increased in skin lesions of AD patients. In this study we investigated the expression of MMP12 mRNA in lesional AD skin at single cell level through RNA sequencing (scRNA-seq) and the expression of MMP12 in M2 macrophages from healthy individuals and AD patients in response to Th2 cytokines and histamine using quantitative PCR and ELISA. Additionally, we analyzed macrophages from dupilumab-treated AD patients using the same methods to assess the influence of Th2 cytokines on MMP12 expression ex-vivo. ScRNA-seq identified macrophages as the primary producers of MMP12 in lesional AD skin. In-vitro, both MMP12 mRNA and protein expression were significantly increased in monocytes during differentiation to M2 macrophages in the presence of histamine, of Th2 cytokines or of Th2 cytokines in combination with histamine. In M2 macrophages obtained from dupilumab-treated AD patients, the upregulation of MMP12 expression by IL-4 and IL-13 was attenuated. Our findings unveil a novel mechanism whereby Th2 cytokines and histamine regulate MMP12 expression, potentially impacting skin barrier homeostasis in AD.
Clones reactive to apoptotic cells and specific chemical adducts are prevalent among human thymic B cells
Authors: Hertel Andrea , Aguiar Talita , Mashiko Shunya , Núñez Sarah , Moore Carolina , Gao Baoshan , Ausmeier Mattea , Roy Poloumi , Zorn Emmanuel
Published: October 2024

Introduction

Thymus resident B cells were described more than 40 years ago. In early human life, these cells are found predominantly in the medulla and overwhelmingly display an unswitched IgM+ phenotype. The reactivity of thymic IgM B cells, however, is still unclear.

Methods

Here, we generated 120 IgM-producing B cell clones from 3 separate thymus specimens obtained from infant, adolescent, and adult donors. Using flow cytometry and a unique high-dimensional ELISA platform, we investigated the clones’ reactivity to apoptotic cells as well as to common chemical adducts exposed on modified amino acids and other macromolecules.

Results

Regardless of the age, approximately 30-40% of thymic IgM B cells reacted to apoptotic cells. Further, 30-40% displayed reactivity to at least one adduct, including malondialdehyde, Homocysteine, and NEDD 8. Four distinct reactivity patterns were identified through this profiling. Notably, a significant association was observed between reactivity to apoptotic cells, and to one or more adducts, suggesting that the same determinants were recognized in both assays. Additionally, thymic IgM B cells reactive to adducts were more likely to recognize intra-nuclear or intra-cytoplasmic structures in Hep-2 cells as revealed by immunofluorescence staining.

Conclusion/Discussion

Collectively, our findings suggest that thymic IgM B cells actively uptake apoptotic bodies and cellular debris in the medulla by binding specific chemical adducts. This mechanism could underpin their antigen-presenting function and further support their role in T-cell negative selection.
Coagulation-related genes for thyroid cancer prognosis, immune infltration, staging, and drug sensitivity
Authors: Sun Yuxiao , Zhang Yifei , Yang Yuchuan , Liu Weihao , Yin Detao
Published: October 2024

Introduction

Thyroid cancer (THCA) is the most common endocrine tumor. Coagulation may be associated with the development of cancer, but its role in THCA patients is not yet clear.

Methods

In this study, we determined the predictive value of coagulation biomarker D-dimer for THCA patient lateral lymph node metastasis (LLNM) through receiver operating characteristics (ROC) analysis and logistic regression analysis. Subsequently, this study used the TCGA database to identify coagulation-related molecular subtypes through consensus clustering analysis and compared their prognosis. We identified coagulation-related genes (CRGs) associated with prognosis in thyroid cancer through gene expression data and clinical information, and constructed a prognostic model by selecting the prognostic CRGs using LASSO regression. Patients were divided into high-risk and low-risk groups based on the median score. Subsequently, prognosis, clinical characteristics, gene mutation occurrence, immune infiltration, function, and drug sensitivity of the two groups were analyzed. We also constructed a nomogram combining the model and clinical features. Finally, the expression of the prognostic CRGs was validated by RT-qPCR.

Results

D-dimers had better performance in predicting LLNM(the area under the curve was 0.656 (95% CI 0.580-0.733), with a cut-off value of 0.065 mg/l), and D-dimer>0.065mg/l was an independent predictor of LLNM. Then, we selected 8 prognostic CRGs to construct a predictive model. The prognosis of low-risk group patients was significantly better than that of high-risk group (P<0.001). The results showed significant differences in clinical characteristics, gene mutation occurrence, immune infiltration, function, and drug sensitivity between the high-risk and low-risk groups. We validated by qPCR that these 8 prognostic CRGs were overexpressed in THCA cell lines.

Discussion

Overall, this study provided an in-depth exploration of the potential role of the coagulation in thyroid cancer and its clinical significance, offering a new theoretical basis and research direction for personalized therapy and prognostic evaluation.
Myeloid-derived growth factor promotes M2 macrophage polarization and attenuates Sjögren’s syndrome via suppression of the CX3CL1/CX3CR1 axis
Authors: Yang Zi , Liu Mangnan , Chang Zhichao , Du Conglin , Yang Yang , Zhang Chen , Hu Liang
Published: October 2024

Introduction

Primary Sjögren syndrome (pSS) is a systemic autoimmune disease that is characterized by the infiltration of immune cells into the salivary glands. The re-establishment of salivary glands (SGs) function in pSS remains a clinical challenge. Myeloid-derived growth factor (MYDGF) has anti-inflammatory, immunomodulatory, and tissue-functional restorative abilities. However, its potential to restore SGs function during pSS has not yet been investigated.

Methods

Nonobese diabetic (NOD)/LtJ mice (pSS model) were intravenously administered with adeno-associated viruses carrying MYDGF at 11 weeks of age. Salivary flow rates were determined before and after treatment. Mice were killed 5 weeks after MYDGF treatment, and submandibular glands were collected for analyses of histological disease scores, inflammatory cell infiltration, PCR determination of genes, and Western blotting of functional proteins. Furthermore, mRNA sequencing and bioinformatics were used to predict the mechanism underlying the therapeutic effect of MYDGF.

Results

Treatment of NOD/LtJ mice with MYDGF alleviated pSS, as indicated by increased salivary flow rate, reduced lymphocyte infiltration, attenuated glandular inflammation, and enhanced AQP5 and NKCC1 expression. The gene expression levels of cytokines and chemokines, including Ccl12, Ccl3, Il1r1, Ccr2, Cx3cr1, Il7, Mmp2, Mmp14, Il1b, and Il7, significantly decreased after treatment with MYDGF, as determined by RNA sequencing. Meanwhile, MYDGF inhibits infiltration of macrophages (Mϕ) in SGs, induces polarization of M2ϕ, and suppresses C-X3C motif ligand 1 (CX3CL1)/C-X3C motif receptor 1 (CX3CR1) axis.

Conclusions

Our findings showed that MYDGF could revitalize the SGs function of pSS, inhibit infiltration of Mϕ, and promote M2ϕ polarization via suppression of the CX3CL1/CX3CR1 axis, which has implications for potential therapy for pSS.
The role of exosomes in liver cancer: comprehensive insights from biological function to therapeutic applications
Authors: Zhang Yinghui , Zhang Congcong , Wu Nan , Feng Yuan , Wang Jiayi , Ma Liangliang , Chen Yulong
Published: October 2024

In recent years, cancer, especially primary liver cancer (including hepatocellular carcinoma and intrahepatic cholangiocarcinoma), has posed a serious threat to human health. In the field of liver cancer, exosomes play an important role in liver cancer initiation, metastasis and interaction with the tumor microenvironment. Exosomes are a class of nanoscale extracellular vesicles (EVs)secreted by most cells and rich in bioactive molecules, including RNA, proteins and lipids, that mediate intercellular communication during physiological and pathological processes. This review reviews the multiple roles of exosomes in liver cancer, including the initiation, progression, and metastasis of liver cancer, as well as their effects on angiogenesis, epithelial-mesenchymal transformation (EMT), immune evasion, and drug resistance. Exosomes have great potential as biomarkers for liver cancer diagnosis and prognosis because they carry specific molecular markers that facilitate early detection and evaluation of treatment outcomes. In addition, exosomes, as a new type of drug delivery vector, have unique advantages in the targeted therapy of liver cancer and provide a new strategy for the treatment of liver cancer. The challenges and prospects of exosome-based immunotherapy in the treatment of liver cancer were also discussed. However, challenges such as the standardization of isolation techniques and the scalability of therapeutic applications remain significant hurdles.
Study on the effects of laser shock peening on the microstructure and properties of 17-7PH stainless steel
Authors: Li Kangwen , Yu Weichen , Li Yaping , Bao Haidong , Cao Yupeng , Wang Yujiang
Published: October 2024

To investigate the surface integrity of 17-7PH stainless steel welded structural components used in aviation, laser shock peening (LSP) with different power densities was applied to stainless steel welded joints. The microstructural morphology, structural features, full-width at half-maximum, microhardness, and surface roughness of the stainless steel welded joint specimens before and after LSP were characterized and measured using SEM, TEM, XRD, a microhardness tester, and a high-resolution confocal microscope. The effects of different laser power densities on the microstructure and properties of the stainless steel welded joints were explored. Results indicate that the stainless steel welded joints exhibit a typical BCC phase. Laser shock peening promotes grain refinement in the welded joints, leading to the phase transformation of residual austenite into martensite. The surface roughness of the specimen is positively correlated with laser power density. At a power density of 5.17 GW/cm2, the surface roughness increased to 1.919 μm, which is 117.08% higher than that of the non-peened specimen. The microhardness of the specimens shows a decreasing trend with increasing power density. When the power density is 2.79 GW/cm2, the microhardness of the specimen significantly increases to 462.94 HV0.5, which is 22.26% higher than that of the non-peened specimen.
Experience and challenges delivering hepatitis C virus treatment for people who inject drugs in Kenya
Authors: Boke Joyce , Monroe-Wise Aliza , Umutesi Grace , Mbogo Loice , Sambai Betsy , Bukusi David , Chohan Bhavna , Scott John , Gitau Esther , Sinkele William , Musyoki Helgar , Herbeck Joshua , Farquhar Carey , Guthrie Brandon L.
Published: October 2024

Despite having a higher risk of hepatitis C virus (HCV) infections, people who inject drugs (PWID) in sub-Saharan Africa (SSA) have limited access to HCV treatment. There is scarce literature on treatment delivery modalities that overcome logistical and financial barriers. We utilized different service delivery modalities to provide direct-acting antivirals (DAAs) to PWIDs infected with HCV through methadone clinics and needle and syringe program (NSP) sites in Kenya. In collaboration with Kenya’s National AIDS and STI Control Programme (NASCOP), we enrolled individuals with active HCV infection confirmed by HCV RNA detection from methadone and NSP sites in Nairobi, Mombasa, and Kilifi counties. Liver function and hepatitis B virus (HBV) status were assessed at baseline. Those eligible for treatment were offered ledipasvir-sofosbuvir treatment provided by NASCOP through directly observed therapy (DOT). Participants completed a follow-up visit 12 weeks after completing treatment to measure sustained viral response (SVR-12). Challenges faced while delivering HCV treatment at participating sites included the limited availability and reliability of laboratory assays, and financial constraints faced by PWIDs to attend daily DOT. Based on our experience, strategies to deliver HCV treatment for PWID in Kenya should consider improving the availability of laboratory tests and prioritizing treatment through methadone centers to achieve good outcomes.
Ubiquitin-proteasome system in Plasmodium: a potential antimalarial target to overcome resistance – a systematic review
Authors: Gonçalves Adriana F. , Lima-Pinheiro Ana , Ferreira Pedro E.
Published: October 2024

Background

Malaria is a devasting parasitic disease that causes over half a million deaths every year. The necessity for prompt and thorough antimalarial drug discovery and development is accelerated by the rise in multidrug resistance and the lack of an effective vaccine. The Plasmodium spp. proteasome represents a prospective target for antimalarial treatment since several chemotherapy types have been shown to potently and selectively limit the growth of parasites. Combined with first-line artemisinin medicines, it creates synergy, even in the artemisinin-resistant parasites.

Methods

PRISMA guidelines were used in the development of this systematic review. A literature search was performed in March 2024 in PubMed, Science Direct, and Scopus databases, with the following keywords: ((antimalarial resistance) AND (plasmodium OR malaria) AND (proteasome)) NOT (cancer [Title/Abstract]). Only articles with the susceptibility assessment were included.

Results

Herein, 35 articles were included in the systematic review, which was divided into two subcategories: those that studied the UPS inhibitors, which accounted for 25 articles, and those that studied genetic modifications, including knockouts, knockdowns, and mutations, in the UPS toward antimalarial resistance, accounting for 16 articles. 6 articles included both subcategories. In total, 16 categories of inhibitors were analyzed, together with two knockdowns, one knockout, and 35 mutations.

Conclusion

In this study, we reviewed the literature for available inhibitors and their respective susceptibility and ability to develop resistance toward Plasmodium spp. 26 s proteasome. The proteasome was highlighted as a potential antimalarial target and as an artemisinin partner drug. However, host toxicity and susceptibility to resistance appear as the main obstacle in the development of highly potent drugs, indicating a need for additional scrutiny during any further drug development efforts.
A simple and cost-effective transformation system for Porphyromonas gingivalis via natural competence
Authors: Abe Kimihiro , Yahara Hiroko , Nakao Ryoma , Yamaguchi Takehiro , Akeda Yukihiro
Published: October 2024

Porphyromonas gingivalis is a major oral bacterial pathogen responsible for severe periodontal diseases. Numerous studies have used genetic approaches to elucidate the molecular mechanisms underlying its pathogenicity. Typically, electroporation and conjugation are utilized for mutagenesis of P. gingivalis; however, these techniques require specialized equipment such as high-voltage electroporators, conjugative plasmids and donor strains. In this study, we present a simple, cost-effective transformation method for P. gingivalis without any special equipment by exploiting its natural DNA competence. P. gingivalis ATCC 33277 was grown to the early-exponential phase and mixed with a donor DNA cassette. This mixture was then spotted onto a BHI-HM blood-agar plate and incubated for one day to promote colony biofilm formation. The resulting colony biofilm was suspended in a liquid medium and spread onto antibiotic-containing agar plates. Transformants appeared within 4 to 5 days, achieving a maximum efficiency of 7.7 × 106 CFU/μg. Although we optimized the transformation conditions using a representative strain ATCC 33277, but the method was also effective for other P. gingivalis strains, W83 and TDC60. Additionally, we discovered that deletion of PGN_0421 or PGN_0519, encoding putative ComEA and ComEC, abolished competency, indicating that these gene products are essential for the natural competence.
Somatostatin interneuron fate-mapping and structure in a Pten knockout model of epilepsy
Authors: Drake Austin W. , Jerow Lilian G. , Ruksenas Justin V. , McCoy Carlie , Danzer Steve C.
Published: October 2024

Disruption of inhibitory interneurons is common in the epileptic brain and is hypothesized to play a pivotal role in epileptogenesis. Abrupt disruption and loss of interneurons is well-characterized in status epilepticus models of epilepsy, however, status epilepticus is a relatively rare cause of epilepsy in humans. How interneuron disruption evolves in other forms of epilepsy is less clear. Here, we explored how somatostatin (SST) interneuron disruption evolves in quadruple transgenic Gli1-CreERT2, Ptenfl/fl, SST-FlpO, and frt-eGFP mice. In these animals, epilepsy develops following deletion of the mammalian target of rapamycin (mTOR) negative regulator phosphatase and tensin homolog (Pten) from a subset of dentate granule cells, while downstream Pten-expressing SST neurons are fate-mapped with green fluorescent protein (GFP). The model captures the genetic complexity of human mTORopathies, in which mutations can be restricted to excitatory neuron lineages, implying that interneuron involvement is later developing and secondary. In dentate granule cell (DGC)-Pten knockouts (KOs), the density of fate-mapped SST neurons was reduced in the hippocampus, but their molecular phenotype was unchanged, with similar percentages of GFP+ cells immunoreactive for SST and parvalbumin (PV). Surviving SST neurons in the dentate gyrus had larger somas, and the density of GFP+ processes in the dentate molecular layer was unchanged despite SST cell loss and expansion of the molecular layer, implying compensatory sprouting of surviving cells. The density of Znt3-immunolabeled puncta, a marker of granule cell presynaptic terminals, apposed to GFP+ processes in the hilus was increased, suggesting enhanced granule cell input to SST neurons. Finally, the percentage of GFP+ cells that were FosB positive was significantly increased, implying that surviving SST neurons are more active. Together, findings suggest that somatostatin-expressing interneurons exhibit a combination of pathological (cell loss) and adaptive (growth) responses to hyperexcitability and seizures driven by upstream Pten KO excitatory granule cells.
Association of hearing loss and risk of depression: a systematic review and meta-analysis
Authors: Wei Jingxuan , Li Yang , Gui Xiongbin
Published: October 2024

Background

Previous studies have suggested a possible link between hearing loss and the risk of depression. However, the strength of this association remains uncertain across varying follow-up periods, age groups, cohort studies, and longitudinal study designs.

Methods

We conducted an extensive literature search across PubMed, Embase, and the Cochrane Library databases to retrieve pertinent studies. The quality of observational studies was assessed using the Newcastle–Ottawa Scale. Synthesis and meta-analysis of odds ratios (ORs) along with corresponding 95% confidence intervals (CIs) were performed using Stata 14.0. Funnel plot analysis and Egger’s regression test were utilized to assess potential publication bias.

Results

This meta-analysis comprised 24 cohort studies conducted between 2007 and 2024, with sample sizes ranging from 548 to 254,466 participants. Among these participants, 24,304 had experienced depression events. The pooling analysis shows that hearing loss is associated with an increased risk of depression (OR = 1.35; 95%CI: 1.27–1.44). In the subgroup analysis, the retrospective cohort exhibited a slightly higher risk of depression compared to the prospective cohort (OR = 1.43; 95% CI: 1.30–1.58). There are differences in the risk of depression among young, middle-aged, and older individuals, with older adults facing a higher risk (OR = 1.33, 95% CI: 1.21–1.45). Additionally, the risk of depression was slightly higher in the sudden sensorineural hearing loss (SSNHL) group compared to the non-SSNHL group (OR = 1.62; 95% CI: 1.27–2.07). Furthermore, in cohorts with a follow-up time ≥ 5 years, the risk of depression was higher compared to those with <5 years of follow-up (OR = 1.39; 95% CI: 1.26–1.54).

Conclusion

Our meta-analysis shows that hearing loss increases the risk of depression. These findings provide evidence that hearing loss should be recognized as an independent risk factor for depression.

Clinical trial registration

https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42024502043.
Borehole disposal of spent fuel and other high-level wastes: the case for deep, vertical, fully cased holes in saturated “hard” rock
Authors: Gibb Fergus , Beswick John , Travis Karl
Published: October 2024

Driven by major advances in deep drilling technology and the geological understanding of the deep continental crust over the past 70 years, disposal in deep boreholes has moved from being technically unachievable to the point that it now offers a viable solution for the most hazardous nuclear wastes that could effectively be implemented “tomorrow”—i.e., within a few years. Moreover, disposal in deep boreholes is arguably superior in almost every respect to the mined and engineered repositories being pursued for high level waste by most countries. During the first 50 years of their evolution, almost all deep borehole disposal concepts shared five key aspects: (i) the hole was as deep as possible, (ii) it was vertical, (iii) it was fully cased, and (iv) it was in “hard” basement rock (v) saturated with aqueous fluid (groundwater). Technical advances in drilling over the last 20 years have encouraged proposed versions of the concept which depart from one or more of these aspects, but it is our contention that all five fundamental aspects should be retained. This paper summarises the more important arguments supporting this view. In order to meet the necessary post-closure (radiological) safety requirements, engineer out possible operational problems during construction and waste-package deployment, and capitalise on the main benefits of borehole disposal, the hole itself must be over 3 km deep, vertical, fully cased, and in suitably hard (ideally granitic) host rock saturated with aqueous fluid.