bluuebunny/crossref_metadata_2025 huggingface dataset:
Histone post-translational modification and heterochromatin alterations in neurodegeneration: revealing novel disease pathways and potential therapeutics
Authors: Fisher Raven M. A. , Torrente Mariana P.
Published: September 2024

Alzheimer’s disease (AD), Parkinson’s disease (PD), Frontotemporal Dementia (FTD), and Amyotrophic lateral sclerosis (ALS) are complex and fatal neurodegenerative diseases. While current treatments for these diseases do alleviate some symptoms, there is an imperative need for novel treatments able to stop their progression. For all of these ailments, most cases occur sporadically and have no known genetic cause. Only a small percentage of patients bear known mutations which occur in a multitude of genes. Hence, it is clear that genetic factors alone do not explain disease occurrence. Chromatin, a DNA-histone complex whose basic unit is the nucleosome, is divided into euchromatin, an open form accessible to the transcriptional machinery, and heterochromatin, which is closed and transcriptionally inactive. Protruding out of the nucleosome, histone tails undergo post-translational modifications (PTMs) including methylation, acetylation, and phosphorylation which occur at specific residues and are connected to different chromatin structural states and regulate access to transcriptional machinery. Epigenetic mechanisms, including histone PTMs and changes in chromatin structure, could help explain neurodegenerative disease processes and illuminate novel treatment targets. Recent research has revealed that changes in histone PTMs and heterochromatin loss or gain are connected to neurodegeneration. Here, we review evidence for epigenetic changes occurring in AD, PD, and FTD/ALS. We focus specifically on alterations in the histone PTMs landscape, changes in the expression of histone modifying enzymes and chromatin remodelers as well as the consequences of these changes in heterochromatin structure. We also highlight the potential for epigenetic therapies in neurodegenerative disease treatment. Given their reversibility and pharmacological accessibility, epigenetic mechanisms provide a promising avenue for novel treatments. Altogether, these findings underscore the need for thorough characterization of epigenetic mechanisms and chromatin structure in neurodegeneration.
The complex relationship between vitamin D and kidney stones: balance, risks, and prevention strategies
Authors: Zhang Fan , Li Wenjian
Published: September 2024

The association between vitamin D and kidney stones is characterized by a remarkable multi-dimensional complexity involving numerous physiological and metabolic pathways. Vitamin D is pivotal in maintaining calcium-phosphorus metabolic homeostasis and bone health. However, fluctuations in its intake, whether excessive or insufficient, May potentially increase the risk of kidney stones. Vitamin D exerts its influence on kidney stone formation indirectly by increasing the efficiency of intestinal calcium absorption and regulating renal calcium excretion. Moreover, there is a robust correlation between various states of vitamin D, particularly its active form, 1,25-dihydroxyvitamin D, and the development of numerous kidney stones. This finding underscores the necessity of individualized medical treatment in vitamin D supplementation and kidney stone prevention. When developing treatment strategies, it is essential to consider the patient’s genetic background, lifestyle, environmental factors, and overall health. To prevent the formation of kidney stones, it is recommended that patients adopt a comprehensive approach, which May include measures such as moderate sun exposure, dietary modification, moderate exercise, and weight management. These preventive measures are designed to maintain healthy calcium and phosphorus metabolism and reduce kidney stone formation risk. Future studies should aim to elucidate the detailed mechanisms of vitamin D metabolism, individual differences, and the role of genes in this process. Furthermore, the role of lifestyle interventions in preventing kidney stones requires greater attention. Moreover, the implementation of large-scale, long-term prospective studies and randomized controlled trials will facilitate the assessment of the actual effects of diverse vitamin D supplementation strategies, thereby providing a robust scientific foundation for advancing more precise prevention strategies and clinical guidelines.
Mendelian randomization analyses explore the effects of micronutrients on different kidney diseases
Authors: Shi Chengdong , Cao Hongliang , Zeng Guoqiang , Wu Hao , Wang Yuantao
Published: September 2024

Background

The impact of micronutrients, including vitamins and minerals, on different kidney diseases has been reported in some observational studies; however, their causal relationship remains uncertain. We aimed to ascertain the causal genetic relationships between micronutrients and different kidney diseases using the Mendelian randomization (MR) method.

Methods

Instrumental variables (IVs) for genetically predicting calcium (Ca), iron (Ir), Zinc (Zn), selenium (Se), copper (Cu), vitamin D (Vit D), and vitamin C (Vit C) levels in humans were obtained, and a bidirectional two-sample MR was used to examine potential associations between the levels of these seven micronutrients and the risk of seven different kidney diseases including hypertensive renal disease, diabetic nephropathy, IgA nephropathy, membranous nephropathy, cystic nephropathy, chronic kidney disease (CKD), and chronic tubulo-interstitial nephritis. Five different MR analyses were conducted, with the main method being the inverse variance-weighted (IVW) method. Moreover, sensitivity analyses were performed to assess heterogeneity and potential pleiotropy.

Results

The IVW method revealed that Ca levels were associated with a decreased risk of hypertensive renal disease (OR = 0.61, 95% CI: 0.40–0.93, p-value = 0.022), and Se levels were associated with a decreased risk of hypertensive renal disease (OR = 0.72, 95% CI: 0.53–0.99, p-value = 0.040), diabetic nephropathy (OR = 0.83, 95% CI: 0.73–0.93, p-value = 0.002), and CKD (OR = 0.87, 95% CI: 0.77–0.99, p-value = 0.028). Conversely, Vit D levels were associated with an increased risk of polycystic kidney disease (OR = 1.76, 95% CI: 1.15–2.69, p-value = 0.0095). In addition, no potential causal relationship was found between vitamin C levels, iron levels, zinc levels, and copper levels and different kidney diseases. Meanwhile, inverse Mendelian randomization showed no potential causal relationship between different chronic kidney diseases and micronutrients. The Cochrane’s Q test, MR-Egger regression, and MR-PRESSO did not suggest heterogeneity and pleiotropy, providing evidence of the validity of the MR estimates.

Conclusion

Our results indicate a cause-and-effect connection between micronutrients and certain kidney diseases, but additional study is required to provide more conclusive evidence. This research has the potential to assist clinicians in managing the consumption of specific micronutrients among individuals with chronic kidney diseases, as well as in promoting disease prevention among both healthy populations and those who are susceptible to chronic underlying conditions.
Association of COX-inhibitors with cancer patients’ survival under chemotherapy and radiotherapy regimens: a real-world data retrospective cohort analysis
Authors: Flausino Lucas E. , Ferreira Isabella N. , Tuan Wen-Jan , Estevez-Diz Maria Del Pilar , Chammas Roger
Published: September 2024

Introduction

We conducted an extensive, sex-oriented real-world data analysis to explore the impact and safety of non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors (coxibs) on cancer treatment outcomes. This is particularly relevant given the role of the COX-2/PGE2 pathway in tumor cell resistance to chemotherapy and radiotherapy.

Methods

The study applied a retrospective cohort design utilizing the TriNetX research database consisting of patients receiving cancer treatment in 2008-2022. The treated cohorts included patients who were prescribed with coxibs, aspirin or ibuprofen, while individuals in the control cohort did not receive these medicines during their cancer treatment. A 1:1 propensity score matching technique was used to balance the baseline characteristics in the treated and control cohorts. Then, Cox proportional hazards regression and logistic regression were applied to assess the mortality and morbidity risks among patient cohorts in a 5-year follow-up period.

Results

Use of coxibs (HR, 0.825; 95% CI 0.792-0.859 in females and HR, 0.884; 95% CI 0.848-0.921 in males) and ibuprofen (HR, 0.924; 95% CI 0.903-0.945 in females and HR, 0.940; 95% CI 0.917-0.963 in males) were associated with improved survival. Female cancer patients receiving aspirin presented increased mortality (HR, 1.078; 95% CI 1.060-1.097), while male cancer patients also had improved survival when receiving aspirin (HR, 0.966; 95% CI 0.951-0.980). Cancer subtype specific analysis suggests coxibs and ibuprofen correlated with survival, though ibuprofen and aspirin increased emergency department visits’ risk. Secondary analyses, despite limited by small cohort sizes, suggest that COX inhibition post-cancer diagnosis may benefit patients with specific cancer subtypes.

Discussion

Selective COX-2 inhibition significantly reduced mortality and emergency department visit rates. Further clinical trials are needed to determine the optimal conditions for indication of coxibs as anti-inflammatory adjuvants in cancer treatment.
Aspirin reduces the mortality risk of patients with community-acquired pneumonia: a retrospective propensity-matched analysis of the MIMIC-IV database
Authors: Wang Guangdong , Sun Jiaolin , Zhang Yaxin , Wang Na , Liu Tingting , Ji Wenwen , Lv Lin , Yu Xiaohui , Cheng Xue , Li Mengchong , Hu Tinghua , Shi Zhihong
Published: September 2024

Background

Community-acquired pneumonia (CAP) is a common infectious disease characterized by inflammation of the lung parenchyma in individuals who have not recently been hospitalized. It remains a significant cause of morbidity and mortality worldwide. Aspirin is a widely used drug, often administered to CAP patients. However, the benefits of aspirin remain controversial.

Objective

We sought to determine whether aspirin treatment has a protective effect on the outcomes of CAP patients.

Methods

We selected patients with CAP from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Propensity score matching (PSM) balanced baseline differences. A multivariate Cox regression model assessed the relationship between aspirin treatment and 28-day mortality.

Results

A total of 3,595 patients were included, with 2,261 receiving aspirin and 1,334 not. After PSM, 1,219 pairs were matched. The 28-day mortality rate for aspirin users was 20.46%, lower than non-users. Multivariate Cox regression indicated aspirin use was associated with decreased 28-day mortality (HR 0.75, 95% CI 0.63–0.88, p < 0.001). No significant differences were found between 325 mg/day and 81 mg/day aspirin treatments in terms of 28-day mortality, hospital mortality, 90-day mortality, gastrointestinal hemorrhage, and thrombocytopenia. However, intensive care unit (ICU) stay was longer for the 325 mg/day group compared to the 81 mg/day group (4.22 vs. 3.57 days, p = 0.031).

Conclusion

Aspirin is associated with reduced 28-day mortality in CAP patients. However, 325 mg/day aspirin does not provide extra benefits over 81 mg/day and may lead to longer ICU stays.
Additional effects of herbal medicine combined with bisphosphonates for primary osteoporosis: a systematic review and meta-analysis
Authors: Yoo Young-Seo , Kim Min-Gyeong , Park Hee-Joo , Chae Min-Young , Choi Yu-Jin , Oh Chae-Kun , Son Chang-Gue , Lee Eun-Jung
Published: September 2024

Background

Osteoporosis (OP) is a significant medical issue associated with population aging. Recent research on herbal medicines (HMs) for OP has been increasing, with these therapies sometimes used in conjunction with bisphosphonates (BPs), the standard treatment for OP. We conducted a systematic review and meta-analysis to evaluate the effects of combining HMs with BPs on improving bone mineral density (BMD) in patients with primary OP.

Methods

We searched nine databases—PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure Wanfang, KISS, Kmbase, Science On, and Oasis—up to 31 August 2023. We selected randomized controlled trials (RCTs) comparing BMD between HMs plus BPs and BPs alone in primary OP. A meta-analysis with BMD as the primary outcome was performed using RevMan version 5.4. Study quality and evidence certainty were assessed through Cochrane’s risk of bias2 and GRADE.

Results

Out of 43 RCTs involving 4,470 participants (mean age 65.8 ± 6.6 years), 35 RCTs with 3,693 participants were included in the meta-analysis. The combination of HMs and BPs was found to be more effective in improving BMD compared to BPs alone, with improvements of 0.10 g/cm2 at the lumbar spine (33 RCTs, 95% CI: 0.07–0.12, p < 0.001, I2 = 93%) and 0.08 g/cm2 at the femoral neck (20 RCTs, 95% CI: 0.05–0.12, p < 0.001, I2 = 94%), though this result was associated with high heterogeneity, high risk of bias, and very low certainty of evidence.

Conclusion

Our data suggest the possibility that combining HMs with BPs may improve BMD in primary OP more effectively than using BPs alone. However, the results should be interpreted with caution due to the high heterogeneity and low quality of the studies included in the review. Therefore, further well-designed RCTs are needed to confirm these findings.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023392139.
Quantitative pulmonary pharmacokinetics of tetrandrine for SARS-CoV-2 repurposing: a physiologically based pharmacokinetic modeling approach
Authors: Wang Furun , Dong Liuhan , Hu Juanwen , Yang Shijie , Wang Lingchao , Zhang Zhiwei , Zhang Wenpeng , Zhuang Xiaomei
Published: September 2024

Tetrandrine (TET) has been traditionally used in China as a medication to treat silicosis and has recently demonstrated anti-SARS-CoV-2 potential in vitro. By recognizing the disparity between in vitro findings and in vivo performance, we aimed to estimate the free lung concentration of TET using a physiologically based pharmacokinetic (PBPK) model to link in vitro activity with in vivo efficacy. Comparative pharmacokinetic studies of TET were performed in rats and dogs to elucidate the pharmacokinetic mechanisms as well as discern interspecies variations. These insights facilitated the creation of an animal-specific PBPK model, which was subsequently translated to a human model following thorough validation. Following validation of the pharmacokinetic profile from a literature report on single oral dosing of TET in humans, the plasma and lung concentrations were predicted after TET administration at approved dosage levels. Finally, the antiviral efficacy of TET in humans was assessed from the free drug concentration in the lungs. Both in vivo and in vitro experiments thus confirmed that the systemic clearance of TET was primarily through hepatic metabolism. Additionally, the lysosomal capture of basic TET was identified as a pivotal factor in its vast distribution volume and heterogeneous tissue distribution, which could modulate the absorption dynamics of TET in the gastrointestinal tract. Notably, the PBPK-model-based unbound lung concentration of TET (1.67–1.74 μg/mL) at the recommended clinical dosage surpassed the in vitro threshold for anti-SARS-CoV-2 activity (EC90 = 1.52 μg/mL). Thus, a PBPK model was successfully developed to bridge the in vitro activity and in vivo target exposure of TET to facilitate its repurposing.
Virtually isolated: social identity threat predicts social approach motivation via sense of belonging in computer-supported collaborative learning
Authors: Bick Nathalie , Froehlich Laura , Voltmer Jan-Bennet , Raimann Jennifer , Reich-Stiebert Natalia , Seidel Niels , Burchart Marc , Martiny Sarah E. , Nikitin Jana , Stürmer Stefan , Martin Andreas
Published: September 2024

Collaboration improves multiple academic and social outcomes. Accordingly, computer-supported collaborative learning (CSCL) can be beneficial in distance education contexts to overcome the issues specific to online learning (e.g., underperformance, low identification with university). Distance universities often attract a substantial number of non-traditional students (e.g., students with disability, students with migration background). Despite their representation, non-traditional students face negative stereotypes and associated social consequences, including social identity threat, diminished sense of belonging, and less motivation for social interactions. In the context of online learning, where there is little individuating information, social categories like socio-demographic group memberships become salient, activating stereotypes. Consequently, socio-demographic group memberships can have detrimental consequences for the integration of non-traditional students. The purpose of the present study was to (a) determine the extent of social identity threat for students in higher distance education, (b) explore the social consequences of this threat in the same context, (c) validate these findings through longitudinal analyses embedded in a CSCL task, and (d) use learning analytics to test behavioral outcomes. In a longitudinal study with three measurement occasions over 8 weeks (N = 1,210), we conducted path analyses for cross-sectional associations and Random Intercept Cross-Lagged Panel Models for longitudinal predictions. The results showed that non-traditional students mostly reported higher social identity threat than traditional students. While the expected longitudinal within-person effects could not be demonstrated, we found stable between-person effects: students who reported higher levels of social identity threat also reported lower sense of belonging and lower social approach motivation. Exploratory analyses of actual online collaboration during CSCL offer potential avenues for future research. We conclude that social identity threat and its social consequences play an important role in higher distance education and should therefore be considered for successful CSCL.
Individualized multi-modal MRI biomarkers predict 1-year clinical outcome in first-episode drug-naïve schizophrenia patients
Authors: Zhang Aoxiang , Yao Chenyang , Zhang Qian , Zhao Ziyuan , Qu Jiao , Lui Su , Zhao Youjin , Gong Qiyong
Published: September 2024

Background

Antipsychotic medications offer limited long-term benefit to about 30% of patients with schizophrenia. We aimed to explore the individual-specific imaging markers to predict 1-year treatment response of schizophrenia.

Methods

Structural morphology and functional topological features related to treatment response were identified using an individualized parcellation analysis in conjunction with machine learning (ML). We performed dimensionality reductions using the Pearson correlation coefficient and three feature selection analyses and classifications using 10 ML classifiers. The results were assessed through a 5-fold cross-validation (training and validation cohorts, n = 51) and validated using the external test cohort (n = 17).

Results

ML algorithms based on individual-specific brain network proved more effective than those based on group-level brain network in predicting outcomes. The most predictive features based on individual-specific parcellation involved the GMV of the default network and the degree of the control, limbic, and default networks. The AUCs for the training, validation, and test cohorts were 0.947, 0.939, and 0.883, respectively. Additionally, the prediction performance of the models constructed by the different feature selection methods and classifiers showed no significant differences.

Conclusion

Our study highlighted the potential of individual-specific network parcellation in treatment resistant schizophrenia prediction and underscored the crucial role of feature attributes in predictive model accuracy.
Abdominal impacts of handlebar injuries in the PIPER child model: a prevention study
Authors: Arneitz Christoph , Erlinger Nico , Klug Corina , Senica Simone Oliver , Kuenzer Thomas , Spitzer Peter , Schalamon Georg , Schalamon Johannes
Published: September 2024

Aim

Analysis of data from bicycle accidents reveals that handlebar impacts are a significant cause of injury, particularly among children. Despite existing safety regulations, such as helmet requirements, little attention is given to abdominal injuries. The aim of this study is to investigate the influence of handlebar ends on abdominal loading during bicycle crashes.

Methods

This study delves into the impact of five different handlebar designs on abdominal injuries during bicycle crashes, using finite element simulations with detailed Human Body Models (HBMs) of a six-year-old child (PIPER child model, Version 0.99.0). Four impact locations were identified in the injury scenario, selected according to the anatomical location of the most commonly injured organs, liver, pancreas, spleen and abdomen.

Results

Grip design features, such as shape and rigidity, significantly influence injury outcomes. Grips designed specifically for children demonstrate superior performance in reducing abdominal loading and injury metrics compared to standard grips. The highest injury potential was seen in a damaged handlebar end.

Conclusion

These findings underscore the importance of improved handlebar designs and standardized safety measures, especially for children. Implementation of such measures could mitigate the significant health and economic burden associated with handlebar-related injuries and enhance overall bicycle safety for children.
Association between weight-adjusted waist circumference index and depression in older patients with hypertension: a study based on NHANES 2007–2016
Authors: Niu Yi , Sun Yuqin , Xie Yijie , Yu Shun
Published: September 2024

Objective

Our aim was to assess the relationship between weight-adjusted waist circumference index (WWI) and the prevalence of depression in older adult hypertensive patients in the United States.

Methods

We selected individuals from the National Health and Nutrition Examination Survey (NHANES) database from 2007 to 2016 and used logistic regression analyses, subgroup analyses, and dose–response curves to assess the associations between the WWI index and the prevalence of depression in older hypertensive patients with age, sex, and BMI.

Results

A total of 4,228 participants aged ≥60 years with hypertension were included in our study; 364 patients were assessed for depression. After correction for confounders, each unit increase in WWI increased the risk of depression in older hypertensive patients by 19% (OR = 1.19, 95% CI: 0.99, 1.43). Dose–response curves showed that the WWI index was positively associated with the prevalence of depression in older hypertensive patients when the WWI index was ≥11.6. Based on subgroup analyses, this association was particularly pronounced in individuals ≥70 years of age, women, and individuals with a BMI of 25 or greater.

Conclusion

Higher WWI scores were positively associated with the prevalence of depression in older hypertensive patients and correlated with gender, age and BMI. This is notable, although a causal relationship cannot be established at this time.
Social determinants of health impact on cancer affecting children, adolescents, and young adults: systematic review and meta-analysis
Authors: Sharara Muhannad , Tjioe Kellen Cristine , Miranda-Galvis Marisol , Santellano Juarez Brenda , Agrawal Gagan , Balas E. Andrew , Johnson Theodore S. , Cortes Jorge E.
Published: September 2024

Objective

To analyze the impact of social determinants of health (SDH) on cancer outcomes of children and adolescents and young adults (AYA) treated for cancer.

Study design

The protocol for this study was registered at PROSPERO (CRD402022346854). A search strategy was implemented across six databases over the last two decades. The focus narrowed to 31 studies conducted in the United States, involving patients between the ages of 15 and 39, assessing survival outcomes based on SDH factors. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Analytical Cross-Sectional Studies was employed for risk of bias assessment.

Results

The most extensively examined SDH factors were neighborhood socioeconomic status (nSES) and health insurance status. Other variables investigated were location of care (6/31), poverty level (5/31), education level (3/31), marital status (4/31), median income (3/31), travel distance to medical facility (3/31), language isolation (2/31), and unemployment (1/31). The primary outcome evaluated was overall survival (OS) and cancer-specific survival (CSS). Meta-analyses focusing on hematological malignancies revealed statistically significant associations, such as lowest nSES correlating with worse OS [hazard ratio (HR):1.46, 95%-CI:1.29–1.66] and CSS (HR:1.43, 95%-CI:1.20–1.72), Medicaid/public insurance linked to worse OS (HR: 1.21, 95%-CI:1.16–1.26), and no insurance associated with worse OS (HR:1.35, 95%-CI:1.17–1.55).

Conclusion

The study highlights the fragmented and incomplete nature of research on SDH in cancer treatment in this age group. Health insurance coverage and nSES were the most studied, revealing significant impacts on patient survival. Identifying vulnerable patients through such analyses could inform policy decisions and address existing gaps in SDH research more effectively.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, PROSPERO (CRD402022346854).
Electrotactile displays: taxonomy, cross-modality, psychophysics and challenges
Authors: Ray Rahul Kumar , Kumar Vasudevan Madhan , Manivannan M.
Published: September 2024

Touch is one of the primary senses, and the receptors for touch sense are spread across the whole human body. Electrotactile displays provide tactile feedback to generate different sensations (such as tickling, tingling, itching, and pressure) in human-computer interfaces or man-machine interactions. These displays encode tactile properties, such as shape and texture, facilitating immersive experiences in virtual or remote environments. Their compact form factor and low maintenance requirements render them versatile for myriad applications. This paper is a comprehensive survey of the design and implementation of electrotactile displays, elucidating their taxonomy, cross-modal integration strategies, and psychophysical underpinnings. Emphasizing the crucial role of psychophysics, it delineates how human perception informs the design and utilization of electrotactile displays. Furthermore, this paper identifies prevalent challenges in electrotactile displays and outlines future directions to advance their development and deployment.
Case Report: Staged treatment of ankle deformity and first metatarsal deficiency after motorcycle spoke injury with Taylor external frame combined with fibular head grafting
Authors: Zhang Le , Yan Yuxin , Ren Pengyu , Hou Yong , Liu Dan , Fan Caiwen , Cheng Kehuan , Zhang Jun , Shi Liangliang
Published: September 2024

The treatment of the sequelae of severe foot injuries caused by motorcycle spoke injury, especially in pediatric patients, allows for new options and surgical protocols. The tarsometatarsal joint and the first metatarsal were reconstructed by precise preoperative design using the TSF space external fixation technique in one stage to correct the foot deformity and restore the volume and length, and free grafting of the fibular head with epiphysis in the second stage. This method is the first of its kind reported. The patient’s foot deformity was corrected, walking, walking up and down stairs, and running functions were achieved, and the bone quality could grow with age. The combination of TSF six-axis spatial external fixation technique and microscopic technique can maximize the patient’s appearance and function and is worth promoting.
Proof-of-concept evaluation of next-generation sequencing-based liquid biopsy for non-invasive cancer detection in cats
Authors: Ruiz-Perez Carlos A. , Nakashe Prachi , Marshall Maggie A. , Marass Francesco , Tang Tuong , McLennan Lisa M. , Kroll Marissa , Flesner Brian K. , Gray Suzanne , Rafalko Jill M. , Grosu Daniel S. , Hicks Susan C. , Tynan John A. , Tsui Dana W.Y. , Flory Andi , Kruglyak Kristina M.
Published: September 2024

This proof-of-concept evaluation demonstrates that next-generation sequencing-based liquid biopsy can detect genomic alterations in the blood of cats with cancer and the absence of such alterations in the blood of presumably cancer-free cats. Two cats with cytologically confirmed lymphoma and nine presumably cancer-free cats were included in this analysis. Whole blood was collected from each subject and samples were subjected to DNA extraction, library preparation, and next-generation sequencing. Both cancer-diagnosed subjects had somatic copy number variants (a “cancer signal”) identified in cell-free DNA, suggesting the current presence of cancer in these subjects. All nine presumably cancer-free subjects had unremarkable genomic profiles, suggesting the absence of cancer in these subjects. Liquid biopsy using next-generation sequencing of cell-free DNA allows for blood-based detection of cancer-associated genomic alterations in cats. Such technology has the potential to offer considerable utility in veterinary medicine, particularly for the non-invasive prioritization of small cell intestinal lymphoma versus inflammatory bowel disease in cats with gastrointestinal signs. This study lays the foundation for future studies to fully validate this type of testing for use in clinical practice.
Comparative analysis of superovulated versus uterine-embryo synchronized recipients for embryo transfer in cynomolgus monkeys (Macaca fascicularis)
Authors: Lee Dong-Ho , Yoon Seung-Bin , Jo Yu-Jin , Mo Jun Won , Kwon Jeongwoo , Lee Sang Il , Kwon Jungkee , Kim Ji-Su
Published: September 2024

Introduction

Assisted reproductive technologies (ARTs), such as intracytoplasmic sperm injection and embryo transfer, are essential for generating genetically edited monkeys. Despite their importance, ARTs face challenges in recipient selection in terms of time and the number of animals required. The potential of superovulated monkeys, commonly used as oocyte donors, to serve as surrogate mothers, remains underexplored. The study aimed to compare the efficacy of superovulated and uterine-embryo synchronized recipients of embryo transfer in cynomolgus monkeys (Macaca fascicularis).

Methods

This study involved 23 cynomolgus monkeys divided into two groups–12 superovulated recipients and 11 synchronized recipients. The evaluation criteria included measuring endometrial thickness on the day of embryo transfer and calculating pregnancy and implantation rates to compare outcomes between groups.

Results

The study found no statistically significant differences in endometrial thickness (superovulated: 4.48 ± 1.36 mm, synchronized: 5.15 ± 1.58 mm), pregnancy rates (superovulated: 30.8%, synchronized: 41.7%), and implantation rates (superovulated: 14.3%, synchronized: 21.9%) between the groups (p > 0.05).

Conclusion

The observations indicate that superovulated recipients are as effective as synchronized recipients for embryo transfer in cynomolgus monkeys. This suggests that superovulated recipients can serve as viable options, offering an efficient and practical approach to facilitate the generation of gene-edited models in this species.
Production of Neutron-Absorbing Zirconium-Boron Alloy by Self-Propagating High-Temperature Synthesis and Its Refining via Electron Beam Melting
Authors: Mukhachev Anatoly , Yelatontsev Dmytro , Kharytonova Olena , Grechanyuk Nickolay
Published: September 2024

The paper presents the results of the study of the processes of self-propagating high-temperature synthesis of Zr-1%B alloy and its refining by electron beam melting. Experiments on the influence of boron’s amorphous and crystalline modifications on the safety parameters of the synthesis process of Zr-1%B alloy necessitated the conversion of amorphous boron into crystalline form by electron beam melting, with an increase in its purity from 94% to 99.9%. High efficiency of vacuum induction and electron beam equipment was demonstrated, which provided a high purity of the Zr-1%B alloy of at least 99.9%. The alloy ingots had a uniform distribution of the alloying element (boron) all over the volume. The obtained alloy is suitable for the production of materials with thermal neutron capture cross-sections of up to 40 barns for neutron protection.
MSLKSTNet: Multi-Scale Large Kernel Spatiotemporal Prediction Neural Network for Air Temperature Prediction
Authors: Gao Feng , Fei Jiaen , Ye Yuankang , Liu Chang
Published: September 2024

The spatiotemporal forecasting of temperature is a critical issue in meteorological prediction, with significant implications for fields such as agriculture and energy. With the rapid advancement of data-driven deep learning methods, deep learning-based spatiotemporal sequence forecasting models have seen widespread application in temperature spatiotemporal forecasting. However, statistical analysis reveals that temperature evolution varies across temporal and spatial scales due to factors like terrain, leading to a lack of existing temperature prediction models that can simultaneously learn both large-scale global features and small to medium-scale local features over time. To uniformly model temperature variations across different temporal and spatial scales, we propose the Multi-Scale Large Kernel Spatiotemporal Attention Neural Network (MSLKSTNet). This model consists of three main modules: a feature encoder, a multi-scale spatiotemporal translator, and a feature decoder. The core module of this network, Multi-scale Spatiotemporal Attention (MSSTA), decomposes large kernel convolutions from multi-scale perspectives, capturing spatial feature information at different scales, and focuses on the evolution of multi-scale spatial features over time, encompassing both global smooth changes and local abrupt changes. The results demonstrate that MSLKSTNet achieves superior performance, with a 35% improvement in the MSE metric compared to SimVP. Ablation studies confirmed the significance of the MSSTA unit for spatiotemporal forecasting tasks. We apply the model to the regional ERA5-Land reanalysis temperature dataset, and the experimental results indicate that the proposed method delivers the best forecasting performance, achieving a 42% improvement in the MSE metric over the widely used ConvLSTM model for temperature prediction. This validates the effectiveness and superiority of MSLKSTNet in temperature forecasting tasks.
A Variational Theory for Biunivalent Holomorphic Functions
Authors: Krushkal Samuel L.
Published: September 2024

Biunivalent holomorphic functions form an interesting class in geometric function theory and are connected with special functions and solutions of complex differential equations. This class has been investigated by many authors, mainly to find the coefficient estimates. The assumption of biunivalence is rigid; this rigidity means that, for example, only the initial Taylor coefficients have been estimated. The aim of this paper is to develop a variational technique for biunivalent functions, which provides a power tool for solving the general extremal problems on the classes of such functions. It involves quasiconformal analysis.
Alternatives to Traditional Aging of Bobal Red Wines from Semi-Arid Climate: Influence on Phenolic Composition and Related Properties
Authors: Osorio Alises María , Sánchez Palomo Eva , González-Viñas M. Ángel
Published: September 2024

The effect of oak chips on the phenolic composition, color characteristics, and antioxidant capacity of Bobal red wines caused by contact with oak chips at different stages of the winemaking process has been studied. Performance liquid chromatography–diode array detection (HPLC-DAD) was used to determine the detailed phenolic composition of wines and antioxidant activity, and chromatic characteristics were determined by spectrophotometric methods. Standard red winemaking process was applied to make the Bobal control wine. The rest of the wines were elaborated with oak chip contact at two dose levels (3 and 6 g/L) in different phases of the winemaking process: during alcoholic fermentation (AF), during malolactic fermentation (MLF), and in young wines. The phenolic composition, antioxidant activity, and chromatic characteristics of Bobal control wines were slightly but significantly modified by contact with the oak chips. Wines in contact with oak chips during malolactic fermentation showed a decrease in the concentration of resveratrol-monomer stilbenes, monomeric anthocyanins, and pyranoanthocyanins. In general, the concentration of total resveratrol is influenced by the dose level used, resulting in a 10% decrease when the dose level is 6 g/L compared to the 3 g/L dose.
Pulmonary Nodule Detection, Segmentation and Classification Using Deep Learning: A Comprehensive Literature Review
Authors: Marinakis Ioannis , Karampidis Konstantinos , Papadourakis Giorgos
Published: September 2024

Lung cancer is a leading cause of cancer-related deaths worldwide, emphasizing the significance of early detection. Computer-aided diagnostic systems have emerged as valuable tools for aiding radiologists in the analysis of medical images, particularly in the context of lung cancer screening. A typical pipeline for lung cancer diagnosis involves pulmonary nodule detection, segmentation, and classification. Although traditional machine learning methods have been deployed in the previous years with great success, this literature review focuses on state-of-the-art deep learning methods. The objective is to extract key insights and methodologies from deep learning studies that exhibit high experimental results in this domain. This paper delves into the databases utilized, preprocessing steps applied, data augmentation techniques employed, and proposed methods deployed in studies with exceptional outcomes. The reviewed studies predominantly harness cutting-edge deep learning methodologies, encompassing traditional convolutional neural networks (CNNs) and advanced variants such as 3D CNNs, alongside other innovative approaches such as Capsule networks and transformers. The methods examined in these studies reflect the continuous evolution of deep learning techniques for pulmonary nodule detection, segmentation, and classification. The methodologies, datasets, and techniques discussed here collectively contribute to the development of more efficient computer-aided diagnostic systems, empowering radiologists and dfhealthcare professionals in the fight against this deadly disease.
All-Dielectric Metasurface-Based Terahertz Molecular Fingerprint Sensor for Trace Cinnamoylglycine Detection
Authors: Xu Qiyuan , Sun Mingjun , Wang Weijin , Shi Yanpeng
Published: September 2024

Terahertz (THZ) spectroscopy has emerged as a superior label-free sensing technology in the detection, identification, and quantification of biomolecules in various biological samples. However, the limitations in identification and discrimination sensitivity of current methods impede the wider adoption of this technology. In this article, a meticulously designed metasurface is proposed for molecular fingerprint enhancement, consisting of a periodic array of lithium tantalate triangular prism tetramers arranged in a square quartz lattice. The physical mechanism is explained by the finite-difference time-domain (FDTD) method. The metasurface achieves a high quality factor (Q-factor) of 231 and demonstrates excellent THz sensing capabilities with a figure of merit (FoM) of 609. By varying the incident angle of the THz wave, the molecular fingerprint signal is strengthened, enabling the highly sensitive detection of trace amounts of analyte. Consequently, cinnamoylglycine can be detected with a sensitivity limit as low as 1.23 μg·cm−2. This study offers critical insights into the advanced application of THz waves in biomedicine, particularly for the detection of urinary biomarkers in various diseases, including gestational diabetes mellitus (GDM).
Does Cognitive Load Affect Measures of Consciousness?
Authors: Nilsen André Sevenius , Storm Johan Frederik , Juel Bjørn Erik
Published: September 2024

Background: Developing and testing methods for reliably measuring the state of consciousness of individuals is important for both basic research and clinical purposes. In recent years, several promising measures of consciousness, grounded in theoretical developments, have been proposed. However, the degrees to which these measures are affected by changes in brain activity that are not related to changes in the degree of consciousness has not been well tested. In this study, we examined whether several of these measures are modulated by the loading of cognitive resources. Methods: We recorded electroencephalography (EEG) from 12 participants in two conditions: (1) while passively attending to sensory stimuli related to the measures and (2) during increased cognitive load consisting of a demanding working memory task. We investigated whether a set of proposed objective EEG-based measures of consciousness differed between the passive and the cognitively demanding conditions. Results: The P300b event-related potential (sensitive to conscious awareness of deviance from an expected pattern in auditory stimuli) was significantly affected by concurrent performance on a working memory task, whereas various measures based on signal diversity of spontaneous and perturbed EEG were not. Conclusion: Because signal diversity-based measures of spontaneous or perturbed EEG are not sensitive to the degree of cognitive load, we suggest that these measures may be used in clinical situations where attention, sensory processing, or command following might be impaired.
A Review of Comprehensive Post-Occupancy Evaluation Feedback on Occupant-Centric Thermal Comfort and Building Energy Efficiency
Authors: Zhao Jing , Abdul Aziz Faziawati , Deng Yiyu , Ujang Norsidah , Xiao Yi
Published: September 2024

The post-occupancy evaluation process is pivotal for assessing the performance of indoor and outdoor living environments after occupation. This evaluation involves a multifaceted analysis, encompassing energy efficiency, indoor environmental quality, outdoor spaces, and occupant satisfaction. Despite the inherent advantages and potential applicability of post-occupancy evaluation in residential buildings, the lack of uniformity in research methodologies, data collection techniques, investigative approaches, and result interpretation has impeded cross-comparisons and method replication. In a concerted effort to enhance the understanding of prevailing post-occupancy evaluation methodologies, this study undertook a comprehensive systematic literature review of post-occupancy evaluation practices within the residential domain from 2000 to 2023. The results unequivocally underscored the pervasive lack of consistency in methodological applications, tool deployment, and data reporting across diverse post-occupancy evaluation investigations. The objectives of this review aimed to examine the existing post-occupancy evaluation (POE) methods, assess occupant-centric thermal comfort, evaluate the impact of POE feedback on building design, and develop recommendations for architects, engineers, facility managers, and policymakers on leveraging POE feedback to enhance thermal comfort and energy efficiency in buildings. This study offers critical insights into advocating for a more standardized and cohesive post-occupancy evaluation approach. The findings of this review can direct the establishment of a coherent and consistently implemented post-occupancy evaluation framework within the realm of residential architecture.
Diffusion-Weighted Magnetic Resonance Imaging for the Diagnosis of Lymph Node Metastasis in Patients with Biliary Tract Cancer
Authors: Murakami Takashi , Shimizu Hiroaki , Nojima Hiroyuki , Shuto Kiyohiko , Usui Akihiro , Kosugi Chihiro , Koda Keiji
Published: September 2024

Objective: The diagnostic efficacy of the apparent diffusion coefficient (ADC) in diffusion-weighted magnetic resonance imaging (DW-MRI) for lymph node metastasis in biliary tract cancer was investigated in the present study. Methods: In total, 112 surgically resected lymph nodes from 35 biliary tract cancer patients were examined in this study. The mean and minimum ADC values of the lymph nodes as well as the long-axis and short-axis diameters of the lymph nodes were assessed by computed tomography (CT). The relationship between these parameters and the presence of histological lymph node metastasis was evaluated. Results: Histological lymph node metastasis was detected in 31 (27.7%) out of 112 lymph nodes. Metastatic lymph nodes had a significantly larger short-axis diameter compared with non-metastatic lymph nodes (p = 0.002), but the long-axis diameter was not significantly different between metastatic and non-metastatic lymph nodes. The mean and minimum ADC values for metastatic lymph nodes were significantly reduced compared with those for non-metastatic lymph nodes (p < 0.001 for both). However, the minimum ADC value showed the highest accuracy for the diagnosis of histological lymph node metastasis, with an area under the curve of 0.877, sensitivity of 87.1%, specificity of 82.7%, and accuracy of 83.9%. Conclusions: The minimum ADC value in DW-MRI is highly effective for the diagnosis of lymph node metastasis in biliary tract cancer. Accurate preoperative diagnosis of lymph node metastasis in biliary tract cancer should enable the establishment of more appropriate treatment strategies.
Rheological Properties and Performance Evaluation of Different Types of Composite-Modified Asphalt in Cold Regions
Authors: Hu Guihua , Chen Xiaowei , Zhao Song , Ouyang Jian
Published: September 2024

In low-temperature environments, asphalt materials harden easily and become brittle, and the repeated action of traffic load further aggravates the cracking of and damage to the asphalt mixture. In order to explore high-performance asphalt pavement materials that are more suitable for cold climates, this paper selected four modifiers, namely SBS, rubber powder, SBR and TPS. With SBS as the main agent, combined with other modifiers, three types of base asphalts with grades of 70#, 90# and 110# were compositely modified to prepare 12 different combinations of composite-modified asphalt samples. The optimal dosage of the modifier was determined by the basic performance test of asphalt, and the compatibility, interaction energy and mechanical properties of the modifier and base asphalt at different temperatures were analyzed by molecular dynamics simulation. Subsequently, the high- and low-temperature rheological properties of various modified asphalts were systematically evaluated using a dynamic shear rheology test (DSR) and a bending beam rheology test (BBR), and the rheological properties and road performance indicators of each composite-modified asphalt were comprehensively compared so as to select the road materials most suitable for cold areas. The research results show that different grades of base asphalt and modifiers show good compatibility in the range of 160–175 °C. Among them, rubber powder and TPS modifier significantly improve the high-temperature mechanical properties of SBS-modified asphalt, while rubber powder and SBR modifier significantly improve its low-temperature mechanical properties. The DSR and BBR test results further show that SBS/rubber powder composite-modified asphalt exhibits excellent rheological properties under both high- and low-temperature conditions, and is the preferred solution for road materials in cold regions.