bluuebunny/crossref_metadata_2025 huggingface dataset:
Advancing immunotherapy for melanoma: the critical role of single-cell analysis in identifying predictive biomarkers
Authors: He Ru , Lu Jiaan , Feng Jianglong , Lu Ziqing , Shen Kaixin , Xu Ke , Luo Huiyan , Yang Guanhu , Chi Hao , Huang Shangke
Published: July 2024

Melanoma, a malignant skin cancer arising from melanocytes, exhibits rapid metastasis and a high mortality rate, especially in advanced stages. Current treatment modalities, including surgery, radiation, and immunotherapy, offer limited success, with immunotherapy using immune checkpoint inhibitors (ICIs) being the most promising. However, the high mortality rate underscores the urgent need for robust, non-invasive biomarkers to predict patient response to adjuvant therapies. The immune microenvironment of melanoma comprises various immune cells, which influence tumor growth and immune response. Melanoma cells employ multiple mechanisms for immune escape, including defects in immune recognition and epithelial-mesenchymal transition (EMT), which collectively impact treatment efficacy. Single-cell analysis technologies, such as single-cell RNA sequencing (scRNA-seq), have revolutionized the understanding of tumor heterogeneity and immune microenvironment dynamics. These technologies facilitate the identification of rare cell populations, co-expression patterns, and regulatory networks, offering deep insights into tumor progression, immune response, and therapy resistance. In the realm of biomarker discovery for melanoma, single-cell analysis has demonstrated significant potential. It aids in uncovering cellular composition, gene profiles, and novel markers, thus advancing diagnosis, treatment, and prognosis. Additionally, tumor-associated antibodies and specific genetic and cellular markers identified through single-cell analysis hold promise as predictive biomarkers. Despite these advancements, challenges such as RNA-protein expression discrepancies and tumor heterogeneity persist, necessitating further research. Nonetheless, single-cell analysis remains a powerful tool in elucidating the mechanisms underlying therapy response and resistance, ultimately contributing to the development of personalized melanoma therapies and improved patient outcomes.
Drivers of seasonal to decadal mixed layer carbon cycle variability in subantarctic water in the Munida Time Series
Authors: Vance Jesse M. , Currie Kim , Suanda Sutara H. , Law Cliff S.
Published: July 2024

Using ancillary datasets and interpolation schemes, 20+ years of the Munida Time Series (MTS) observations were used to evaluate the seasonal to decadal variability in the regional carbon cycle off the southeast coast of New Zealand. The contributions of gas exchange, surface freshwater flux, physical transport processes and biological productivity to mixed layer carbon were diagnostically assessed using a mass-balanced surface ocean model. The seasonal and interannual variability in this region is dominated by horizontal advection of water with higher dissolved inorganic carbon (DIC) concentration primarily transported by the Southland Current, a unique feature in this western boundary current system. The large advection term is primarily balanced by net community production and calcium carbonate production, maintaining a net sink for atmospheric CO2 with a mean flux of 0.84±0.62 mol C m-2 y-1. However, surface layer pCO2 shows significant decadal variability, with the growth rate of 0.53±0.26 μatm yr-1 during 1998–2010 increasing to 2.24±0.47 μatm yr-1 during 2010–2019, driven by changes in advection and heat content. Changes in circulation have resulted in the regional sink for anthropogenic CO2 being 50% higher and pH 0.011±.003 higher than if there had been no long-term changes in circulation. Detrended cross-correlation analysis was used to evaluate correlations between the Southern Annular Mode, the Southern Oscillation Index and various regional DIC properties and physical oceanographic processes over frequencies corresponding the duration of the MTS. The drivers of variability in the regional carbon cycle and acidification rate indicate sensitivity of the region to climate change and associated impacts on the Southern Ocean and South Pacific.
Correction and harmonization of dissolved oxygen data from autonomous platforms in the South Adriatic Pit (Mediterranean Sea)
Authors: Gerin Riccardo , Martellucci Riccardo , Savonitto Gilda , Notarstefano Giulio , Comici Cinzia , Medeot Nevio , Garić Rade , Batistić Mirna , Dentico Carlotta , Cardin Vanessa , Zuppelli Piero , Bussani Antonio , Pacciaroni Massimo , Mauri Elena
Published: July 2024

Dissolved oxygen (DO) is one of the most important drivers of ocean biogeochemical cycles and marine life, and in many areas its concentration has declined due to climate change. In recent decades, a growing number of autonomous oceanographic platforms has been equipped with sensors for direct in situ measurements of oxygen levels. However, to ensure high quality and comparable data, these observations need to be validated or, if necessary, corrected. In this paper, we compiled all the available DO data collected by Argo floats and gliders in the South Adriatic Pit (Mediterranean Sea) between 2014 and 2020. This dataset includes data for which it was not possible to apply conventional quality-control methods. Therefore, we had to apply tailored procedures based on well-established best practices for correction. The aim is to showcase how these tailored procedures allowed us to achieve the best possible quality of data and generate consistent datasets. The drift of the glider DO sensors related to storage was also estimated. The described procedure could be useful in similar cases where the conventional methods are not viable, thus making available potentially useful data.
Image stitching and target perception for Autonomous Underwater Vehicle-collected side-scan sonar images
Authors: Zhang Zhuoyu , Wu Rundong , Li Dejun , Lin Mingwei , Xiao Sa , Lin Ri
Published: July 2024

Introduction

Autonomous Underwater Vehicles (AUVs) are capable of independently performing underwater navigation tasks, with side-scan sonar being a primary tool for underwater detection. The integration of these two technologies enables autonomous monitoring of the marine environment.

Methods

To address the limitations of existing seabed detection methods, such as insufficient robustness and high complexity, this study proposes a comprehensive seabed detection method based on a sliding window technique. Additionally, this study introduces a sonar image stitching method that accounts for variations in image intensity and addresses challenges arising from multi-frame overlaps and gaps. Furthermore, an autonomous target perception framework based on shadow region segmentation is proposed, which not only identifies targets in side-scan sonar images but also provides target height measurements.

Results

Comprehensive seabed detection method improves accuracy by 31.2% compared to the peak detection method. In experiments, the height measurement error for this method was found to be 9%.

Discussion

To validate the effectiveness of the proposed seabed detection method, sonar image stitching method, and target perception framework, comprehensive experiments were conducted in the Qingjiang area of Hubei Province. The results obtained from the lake environment demonstrated the effectiveness of the proposed methods.
Structural and mechanical properties of Cu-SiCp nanocomposites fabricated by accumulative roll bonding (ARB)
Authors: Ghaderi Omid , Zare Mehran , Sadabadi Hamed , Toroghinejad Mohammad Reza , Najafizadeh Abbas , Church Benjamin C. , Rohatgi Pradeep K.
Published: July 2024

In this study, the accumulative roll bonding (ARB) method, a severe plastic deformation (SPD) process, was used to fabricate copper-2 wt% silicon carbide composite strips. The ARB process was successfully conducted for up to nine cycles on pure copper strips with silicon carbide particles distributed between them, as well as on monolithic copper. Equiaxed tensile and Vickers hardness tests were conducted to evaluate the mechanical properties of the samples. SEM was utilized to study the fracture surfaces and to determine the fracture mechanism of ARB processed monolithic copper and composite samples after the tensile test. Texture parameters were calculated through X-ray analysis. The Rietveld method using MAUD software were employed to assess the crystallite size of the samples. Results indicated that average amount of porosity decreased and interface bonding between copper strip layers improved with increasing the number of ARB cycles. Moreover, an increased number of cycles led to homogeneous distribution of SiC particles within the copper matrix. The tensile strength of the fabricated composites improved with an increase in the number of cycles, ultimately reaching 483 MPa after nine cycles, compared to 388 MPa for the composite processed with a single cycle of ARB and 194 MPa for annealed copper strips. Initially, the elongation of the composite samples decreased dramatically to about 6% after applying five cycle of ARB process from the 46% observed for annealed pure copper strip. However, it improved as the process continued, reaching 8.9% after the ninth cycle. Investigation of fracture surfaces after the tensile test using SEM revealed that the dominant failure mode was shear ductile fracture. Analysis of sample textures demonstrated that the dominant texture was (100). Crystallite sizes for pure copper and nine cycles-rolled composites, as determined by Reitveld method, reached 111 nm and 89 nm, respectively.
Local thermal warpage deformation of polypropylene injection molded flat part and neural network prediction model
Authors: Wang Jian , Liu Tao , Zheng Kaihuang , Liu Hao , Cui Hongdao , Li Hang
Published: July 2024

Warpage deformation is a typical phenomenon for polymer injection-molded parts, mainly caused by unbalanced cooling, and it is inevitable. Complex process parameters usually lead to uncontrollable thermal behavior of the polymer materials during injection molding and significant experimental errors. This work presents an experimental mold with a flat mold cavity and nine local heating sections to determine the exact effect of temperature difference on the thermal deformation of injection molded parts. Through local heating at different positions, different warpage deformation was caused. Experimental results demonstrated the relationship between the local temperature and the local thermal warpage. The predicted results of local temperature distribution by numerical simulation presented a strong negative correlation with the experimental results (R2 = 67%); however, the warpage prediction results by numerical simulation were moderate (R2 = 35%). Machine learning with neural networks was further conducted based on the experimental results. When more data was given with a suitable neural network structure, the model prediction accuracy of warpage could be up to 97%, while for the extrapolation test, the prediction accuracy could also be up to 89%. This local thermal heating technique and neural network modeling method can be applied in further theoretical investigation of warpage of injection molded parts and support the development of new models with high accuracy in predicting warpage deformation.
Household income unequally affects genetic susceptibility to pulmonary diseases: evidence from bidirectional Mendelian randomization study
Authors: Xu Hongfa , Deng Hailian , Wu Yueying , Yang Yu , Zheng Xifeng
Published: July 2024

Objectives

Previous observational studies have reported a close association between socioeconomic status and pulmonary disease-related morbidity. However, the inherent causal effects remain unclear. Therefore, this bidirectional Mendelian randomization (MR) study aimed to identify the causal relationship between household income and genetic susceptibility to pulmonary diseases.

Methods

An MR study was conducted on a large cohort of European individuals, using publicly available genome-wide association study datasets using a random-effects inverse-variance weighting model as the main standard. Simultaneously, MR-Egger regression, weighted median, and maximum likelihood estimation were applied as supplements. Sensitivity analysis, comprising a heterogeneity test and horizontal pleiotropy test, was performed using the Cochran’s Q, MR-Egger intercept, and MR-PRESSO tests to ensure the reliability of the conclusion.

Results

A higher household income tended to lower the risk of genetic susceptibility to chronic obstructive pulmonary disease (COPD, OR: 0.497, 95% CI = 0.337–0.733, p < 0.001), asthma (OR: 0.687, 95% CI = 0.540–0.876, p = 0.002), and lung cancer (OR: 0.569, 95% CI = 0.433–0.748, p < 0.001), and further indicated potential causality with pneumonia (OR: 0.817; 95% CI = 0.686–0.972, p = 0.022). No association was evident with COVID-19 (OR: 0.934, 95% CI = 0.764–1.142, p = 0.507), tuberculosis (OR: 0.597, 95% CI = 0.512–1.189, p = 0.120), or bronchiectasis (OR: 0.680, 95% CI = 0.311–1.489, p = 0.400). Reverse MR analysis suggested no reverse causal relationship between pulmonary disease and household income status, while sensitivity analysis verified the reliability of the results.

Conclusion

The results revealed that the population with a higher household income tended to have a lower risk of genetic susceptibility to COPD, asthma, and lung cancer.
Association between SARC-F scores and risk of adverse outcomes in older patients with cardiovascular disease: a prospective study at a tertiary hospital in the south of Vietnam
Authors: Nguyen Tan Van , Nguyen Tuan Dinh , Cao Dinh Hung , Nguyen Tuan Dinh , Ngo Trinh Thi Kim , Do Dung Viet , Le Thanh Dinh
Published: July 2024

Introduction

Older patients typically face elevated mortality rates and greater medical resource utilization during hospitalizations compared to their younger counterparts. Sarcopenia, serving as a prognostic indicator, is related to disability, diminished quality of life, and increased mortality. The SARC-F questionnaire, known for its cost-effectiveness, offers a valuable means of assessing sarcopenia. This study aims to explore the association between SARC-F scores and risk of adverse outcomes in elderly patients with cardiovascular disease at a Ho Chi Minh City hospital.

Method

Participants aged 60 and above, admitted to the Department of Cardiology - Interventional and Cardiovascular Emergency of Thong Nhat Hospital in Ho Chi Minh City from November 2021 to June 2022, were recruited for the prospective, single-center study. The prognostic outcomes included all-cause death and the initial occurrence of emergency re-hospitalization within 6 months’ post-discharge. The Kaplan–Meier analysis compared the overall survival rates between different SARC-F score groups.

Results

The study enrolled 285 patients with a median age of 74 (67, 81). During a 6-month follow-up period, there were 14 cases of mortality. A SARC-F score of 4 or higher was significantly associated with an increased risk of all-cause mortality, with HR of 2.02 (95% CI: 1.39–2.92, p < 0.001), and higher incidence of re-hospitalization events with RR of 1.66 (95% CI: 1.06 to 2.59, p = 0.026). Kaplan–Meier survival analysis indicated a notably higher mortality rate in the patients with high SARC-F scores (p < 0.001).

Conclusion

In elderly patients with cardiovascular disease, the SARC-F questionnaire could serve as a simple and cost-effective method for detecting mortality and the risk of re-hospitalization.
Unraveling the relationship between gut microbiota and site-specific endometriosis: a Mendelian randomization analysis
Authors: Tang Yuanyuan , Yang Jiangbing , Hang Fu , Huang Hui , Jiang Li
Published: July 2024

Background

Although numerous studies have illustrated the connection between gut microbiota and endometriosis, a conspicuous gap exists in research focusing on the pathogenesis of endometriosis at various sites and its linkage with infertility.

Methods

In this study, we used a two-sample Mendelian randomization analysis to investigate the effect of gut microbiota on the development of endometriosis in different regions, including the uterus, ovary, fallopian tube, pelvic peritoneum, vagina, and rectovaginal septum, as well as the intestine. Additionally, we explored the correlation between gut microbiota and endometriosis-induced infertility. Genetic associations with gut microbes were obtained from genome-wide association study (GWAS) datasets provided by the MiBioGen consortium, whereas endometriosis-related GWAS data were sourced from the FinnGen dataset. In our analysis, single-nucleotide polymorphisms were used as instrumental variables, with the primary estimation of the causal effect performed via the inverse variance weighting method. Our sensitivity analyses incorporated heterogeneity tests, pleiotropy tests, and the leave-one-out method.

Results

We identified associations at the genus level between four bacterial communities and endometriosis. Subsequently, several associations between the gut microbiota and various subtypes of endometriosis at different anatomical sites were recognized. Specifically, three genera were linked with ovarian endometriosis, six genera were associated with tubal endometriosis, four genera showed links with pelvic peritoneum endometriosis, five genera were connected with vaginal and rectovaginal septum endometriosis, and seven genera demonstrated linkages with intestinal endometriosis. Additionally, one genus was associated with adenomyosis, and three genera exhibited associations with endometriosis-induced infertility.

Conclusion

Our study elucidates associations between gut microbiota and site-specific endometriosis, thereby augmenting our understanding of the pathophysiology of endometriosis. Moreover, our findings pave the way for potential therapeutic strategies targeting gut microbiota for individuals grappling with endometriosis-related infertility.
A bibliometric study of global trends in T1DM and intestinal flora research
Authors: Cui Xinxin , Wu Zhen , Zhou Yangbo , Deng Longji , Chen Yu , Huang Hanqiao , Sun Xiangbin , Li Yu , Wang Haixia , Zhang Li , He Jia
Published: July 2024

Background

Type 1 diabetes mellitus (T1DM) is a chronic metabolic disease that seriously jeopardizes human physical and mental health and reduces quality of life. Intestinal flora is one of the critical areas of exploration in T1DM research.

Objective

This study aims to explore the research hotspot and development trend of T1DM and intestinal flora to provide research direction and ideas for researchers.

Methods

We used the Web of Science (WOS) Core Collection and searched up to 18 November 2023, for articles on studies of the correlation between T1DM and intestinal flora. CiteSpace, VOSviewers and R package “bibliometrix” were used to conduct this bibliometric analysis.

Results

Eventually, 534 documents met the requirements to be included, and as of 18 November 2023, there was an upward trend in the number of publications in the field, with a significant increase in the number of articles published after 2020. In summary, F Susan Wong (UK) was the author with the most publications (21), the USA was the country with the most publications (198), and the State University System of Florida (the United States) was the institution with the most publications (32). The keywords that appeared more frequently were T cells, fecal transplants, and short-chain fatty acids. The results of keywords with the most robust citation bursts suggest that Faecalibacterium prausnitzii and butyrate may become a focus of future research.

Conclusion

In the future, intestinal flora will remain a research focus in T1DM. Future research can start from Faecalibacterium prausnitzii and combine T cells, fecal bacteria transplantation, and short-chain fatty acids to explore the mechanism by which intestinal flora affects blood glucose in patients with T1DM, which may provide new ideas for the prevention and treatment of T1DM.
Analysis of the improved mechanism of Rhodobacter sphaeroides VK-2-3 coenzyme Q10 by reverse metabolic engineering
Authors: Zhang Long , Wang Le-yi , Han Yi-jun , Liu Yan-xin , Li Yong-li , Hu Jian-hua , Tian Zhi-jie , Liu Zhan-ying
Published: July 2024

Coenzyme Q10 (CoQ10) is an essential medicinal ingredient. In this study, we obtained a high-yielding mutant strain of CoQ10, VK-2-3, by subjecting R. sphaeroides V-0 (V-0) to a 12C6+ heavy ion beam and high-voltage prick electric field treatment. To investigate the mutation mechanism, the complete genomes of VK-2-3 and V-0 were sequenced. Collinearity analysis revealed that the nicotinamide adenine dinucleotide-dependent dehydrogenase (NAD) gene underwent rearrangement in the VK-2-3 genome. The NAD gene was overexpressed and silenced in V-0, and this construct was named RS.NAD and RS.ΔNAD. The results showed that the titers of CoQ10 in the RS.NAD and RS.ΔNAD increased and decreased by 16.00 and 33.92%, respectively, compared to those in V-0, and these differences were significant. Our results revealed the mechanism by which the VK-2-3 CoQ10 yield increases through reverse metabolic engineering, providing insights for genetic breeding and mechanistic analysis.
Bidirectional two-sample Mendelian randomization analysis identifies causal associations between oxidative stress and Parkinson’s disease
Authors: Lv Lingling , Long Zhe , Tan Xuling , Qin Lixia , Yan Weiqian , Zhang Hainan , Ren Feng , Wang Chunyu
Published: July 2024

Background

Observational studies have shown that oxidative stress (OS) is associated with Parkinson’s disease (PD). However, whether such observations reflect cause–effect remains largely unknown. To test this, we performed a two-sample bidirectional Mendelian randomization (MR) analysis to investigate the causal-effects between OS biomarkers and PD.

Methods

We selected summary statistics data for single-nucleotide polymorphisms (SNPs) associated with catalase (n = 13), glutathione peroxidases (n = 12), superoxide dismutase (n = 13), vitamin A (n = 7), vitamin C (n = 10), vitamin E (n = 12), vitamin B12 (n = 8), folate (n = 14), copper (n = 6), Zinc (n = 7), and iron (n = 23) levels, and the corresponding data for PD from the International Parkinson Disease Genomics Consortium (IPDGC, 33,674 cases and 449,056 controls). Inverse-variance weighted (IVW) MR analyses were conducted to estimate associations of OS with PD. Reverse MR analysis was further performed to predict the causal effects of PD on the above OS biomarkers.

Results

As for PD, the IVW method suggested that the Zinc (Zn) levels was significantly associated with PD (OR = 1.107, 95% CI 1.013–1.211; p = 0.025), which is consistent with results from the weighted median analyses. Moreover, the results remained consistent and robust in the sensitivity analysis. However, there were no significant associations of catalase, glutathione peroxidases, superoxide dismutase, vitamin A, vitamin C, vitamin E, vitamin B12, folate, copper, or iron with PD. As for OS, our reverse MR analysis also did not support a causal effect of liability to PD on OS.

Conclusion

The MR study supported the causal effect of Zn on PD. These findings may inform prevention strategies and interventions directed toward OS and PD.
Interdisciplinary fetal-neonatal neurology training improves brain health across the lifespan
Authors: Scher Mark S.
Published: July 2024

Integrated fetal, neonatal, and pediatric training constitute an interdisciplinary fetal-neonatal neurology (FNN) program. A dynamic neural exposome concept strengthens curriculum content. Trainees participate in mentoring committee selection for guidance during a proposed two-year program. Prenatal to postnatal clinical learning re-enforces early toxic stressor interplay that influences gene–environment interactions. Maternal-placental-fetal triad, neonatal, or childhood diseases require diagnostic and therapeutic decisions during the first 1,000 days when 80 % of neural connections contribute to life-course phenotypic expression. Pediatric follow-up through 3 years adjusts to gestational ages of preterm survivors. Cumulative reproductive, pregnancy, pediatric and adult exposome effects require educational experiences that emphasize a principle-to-practice approach to a brain capital strategy across the lifespan. More rigorous training during fetal, neonatal, and pediatric rotations will be offered to full time trainees. Adult neurology residents, medical students, and trainees from diverse disciplines will learn essential topics during time-limited rotations. Curriculum content will require periodic re-assessments using educational science standards that maintain competence while promoting creative and collaborative problem-solving. Continued career-long learning by FNN graduates will strengthen shared healthcare decisions by all stakeholders. Recognition of adaptive or maladaptive neuroplasticity mechanisms requires analytic skills that identify phenotypes associated with disease pathways. Developmental origins and life-course concepts emphasize brain health across the developmental-aging continuum, applicable to interdisciplinary research collaborations. Social determinants of health recognize diversity, equity, and inclusion priorities with each neurological intervention, particularly for those challenged with disparities. Diagnostic and therapeutic strategies must address resource challenges particularly throughout the Global South to effectively lower the worldwide burden of neurologic disease. Sustainable development goals proposed by the World Health Organization offer universally applicable guidelines in response to ongoing global and regional polycrises. Gender, race, ethnicity, and socio-economic equality promote effective preventive, rescue and reparative neuroprotective interventions. Global synergistic efforts can be enhanced by establishing leadership within academic teaching hubs in FNN training to assist with structure and guidance for smaller healthcare facilities in each community that will improve practice, education and research objectives. Reduced mortality with an improved quality of life must prioritize maternal-pediatric health and well-being to sustain brain health across each lifespan with transgenerational benefits.
A protein-rich meal provides beneficial glycemic and hormonal responses as compared to meals enriched in carbohydrate, fat or fiber, in individuals with or without type-2 diabetes
Authors: Ekberg Neda Rajamand , Catrina Sergiu-Bogdan , Spégel Peter
Published: July 2024

Introduction

Diet stands as a pivotal modifiable risk factor influencing weight gain and the onset of type-2 diabetes (T2D). This study delves into the variation in glucose and regulatory pancreatic hormone levels subsequent to the consumption of meals with differing macronutrient compositions.

Methods

The cohort comprised 20 individuals diagnosed with T2D and 21 without diabetes. Participants underwent a cross-over design, consuming four isocaloric meals (600 kcal) enriched in carbohydrate, fiber, fat and protein. Plasma glucose, insulin and glucagon levels were measured at -30, and -5 min, followed by subsequent measurements every 30 min for 240 min post meal intake. Quantification of alterations in the postprandial state was accomplished through the incremental area under the curve (iAUC) and the incremental peak height for the insulin:glucagon ratio (IGR) and plasma glucose levels. The meal demonstrating the lowest responses across these variables was deemed the optimal meal.

Results

Meals rich in protein and fat, and consequently low in carbohydrate, exhibited reduced incremental peak and iAUC for both glucose and the IGR in comparison to the other meals. While the protein-enriched meal neared optimal standards, it proved less efficient for individuals without T2D and possessing a low BMI, as well as in those with T2D and poor glycemic control.

Conclusion

Our findings endorse the adoption of protein-enriched, low-carbohydrate meals to curtail the meal-induced anabolic hormonal response while averting excessive fluctuations in glucose levels.
John Yudkin’s hypothesis: sugar is a major dietary culprit in the development of cardiovascular disease
Authors: Ting Kenneth K.Y.
Published: July 2024

To date, the risk of developing atherosclerosis has extended beyond Western countries and now affecting individuals from various ethnic backgrounds and age groups. Traditional risk factors of atherosclerosis, such as hypercholesterolemia, has been better controlled than before due to highly effective and inexpensive therapies at lowering plasma cholesterol levels. However, the role of reducing dietary cholesterol intake, as a public healthy strategy, in preventing the occurrence of cardiovascular mortalities has been recently challenged. Indeed, despite our continuous decline of dietary cholesterol intake within the last 50 years, the incidence of cardiovascular mortalities has continued to rise, thus raising the possibility that other dietary factors, such as fructose-containing sugars, are the major culprit. In the 1970s, John Yudkin first proposed that sugar was the predominant dietary factor that underlies the majority of cardiovascular mortalities, yet his hypothesis was dismissed. However, over the last 25 years substantial scientific evidence has been accumulated to support Yudkin’s hypothesis. The objectives of this review are to highlight Yudkin’s significant contribution to nutritional science by reviewing his hypothesis and summarizing the recent advances in our understanding of fructose metabolism. The metabolic consequences of fructose metabolism, such as fructose-induced uricemia, insulin resistance, lipoprotein hyperproduction and chronic inflammation, and how they are linked to atherosclerosis as risk factors will be discussed. Finally, the review will explore areas that warrant future research and raise important considerations that we need to evaluate when designing future studies.
Updates on protein-prenylation and associated inherited retinopathies
Authors: Ashok Sudhat , Ramachandra Rao Sriganesh
Published: July 2024

Membrane-anchored proteins play critical roles in cell signaling, cellular architecture, and membrane biology. Hydrophilic proteins are post-translationally modified by a diverse range of lipid molecules such as phospholipids, glycosylphosphatidylinositol, and isoprenes, which allows their partition and anchorage to the cell membrane. In this review article, we discuss the biochemical basis of isoprenoid synthesis, the mechanisms of isoprene conjugation to proteins, and the functions of prenylated proteins in the neural retina. Recent discovery of novel prenyltransferases, prenylated protein chaperones, non-canonical prenylation-target motifs, and reversible prenylation is expected to increase the number of inherited systemic and blinding diseases with aberrant protein prenylation. Recent important investigations have also demonstrated the role of several unexpected regulators (such as protein charge, sequence/protein-chaperone interaction, light exposure history) in the photoreceptor trafficking of prenylated proteins. Technical advances in the investigation of the prenylated proteome and its application in vision research are discussed. Clinical updates and technical insights into known and putative prenylation-associated retinopathies are provided herein. Characterization of non-canonical prenylation mechanisms in the retina and retina-specific prenylated proteome is fundamental to the understanding of the pathogenesis of protein prenylation-associated inherited blinding disorders.
Rapid genome sequencing for critically ill infants: an inaugural pilot study from Turkey
Authors: Guner Yilmaz Bengisu , Akgun-Dogan Ozlem , Ozdemir Ozkan , Yuksel Bayram , Hatirnaz Ng Ozden , Bilguvar Kaya , Ay Beril , Ozkose Gulsah Sebnem , Aydin Eylul , Yigit Ayca , Bulut Aybike , Esen Fatma Nisa , Beken Serdar , Aktas Selma , Demirel Atalay , Arcagok Baran Cengiz , Kazanci Ebru , Bingol İbrahim , Umur Ozge , Sik Guntulu , Isik Ugur , Ersoy Melike , Korkmaz Ayse , Citak Agop , Mardinoglu Adil , Ozbek Ugur , Alanay Yasemin
Published: July 2024

Introduction

Rare and ultra-rare genetic conditions significantly contribute to infant morbidity and mortality, often presenting with atypical features and genetic heterogeneity that complicate management. Rapid genome sequencing (RGS) offers a timely and cost-effective approach to diagnosis, aiding in early clinical management and reducing unnecessary interventions. This pilot study represents the inaugural use of next-generation sequencing (NGS) as a diagnostic instrument for critically ill neonatal and pediatric ICU patients in a Turkish hospital setting.

Methods

Ten infants were enrolled based on predefined inclusion criteria, and trio RGS was performed. The mean age of the participants was 124 days, with congenital abnormalities being the most common indication for testing. Three patients had consanguineous parents. The mean turnaround time from enrollment to delivery of results was 169 h, with a diagnostic yield of 50%.

Results

Three patients received a definitive molecular diagnosis, impacting their clinical management. Two patients benefited from the exclusion of Mendelian conditions, leading to alternative diagnoses.

Discussion

This study demonstrates the feasibility and results of RGS in Turkish hospital settings, emphasizing the importance of timely genetic diagnosis in reducing the diagnostic odyssey for families and improving patient care. Further research is needed to evaluate the cost-effectiveness and applicability of RGS in the Turkish healthcare system for children with diseases of uncertain etiology.
Piperacillin/tazobactam treatment in children: evidence of subtherapeutic concentrations
Authors: Ye Panpan , Shi Jinyi , Guo Zixuan , Yang Xinmei , Li Qian , Chen Keguang , Zhao Furong , Zhou Haiyan , Zhang Yehui , van den Anker John , Song Linlin , Zhao Wei
Published: July 2024

Objective

Piperacillin/tazobactam (PIP/TAZ) is used for the treatment of lower respiratory tract bacterial infections in children. This study was performed to evaluate if the current dosing regimen results in therapeutic drug concentrations.

Patients and methods

Patients suspected or proven to have lower respiratory tract bacterial infection and administrated PIP/TAZ intravenously for a duration of no less than 0.5 h, q6h–q12h daily, were enrolled. Blood samples were collected, and PIP concentrations were determined by high-performance liquid chromatography. The individual predicted concentration of PIP was evaluated using the individual empirical Bayesian estimate method. The evaluated PK/PD targets included (1) 70% time when the predicted free drug concentration exceeds the minimum inhibitory concentration (fT > MIC) and (2) 50% fT > 4× MIC. Probability of target attainment (PTA) was assessed by the proportion of patients who reached the PK/PD targets. The PIP concentrations between different groups of patients were compared.

Results

A total of 57 samples were collected from 57 patients with a median age of 2.26 years (0.17–12.58). For the PK/PD targets of 70% fT > MIC and 50% fT > 4× MIC for Pseudomonas aeruginosa and Klebsiella pneumoniae, the PTA was all 0. The median Cmin of PIP was significantly higher in infants than in children, and the median Cmin after administration in q8h was significantly higher than that after administration in q12h.

Conclusion

The current dose regimen of PIP/TAZ leads to extremely low plasma concentrations in most children with lower respiratory tract bacterial infections. More optimized dosing regimens or better alternative therapies need to be further explored.
Numerical analysis and experimental verification of time-dependent heat conduction under the action of ultra-short pulse laser
Authors: Wang Yan , Liu Jingting , Wang Chunyan , Fan Xinmin , Liu Zhaohong , Huang Xiaodong , Zhang Lujun , Li Sensen , Zhang Yu
Published: July 2024

Thermal action is a crucial process in laser processing. The classical Fourier heat conduction theory, which assumes an infinite speed of heat propagation, is commonly applied to describe steady-state and mild transient thermal processes. However, under the influence of ultra-short pulse lasers, such as those with picosecond and femtosecond durations, the heat propagation speed within the material is finite and deviates from Fourier’s law. This article addresses the unique characteristics of heat conduction in materials subjected to ultra-short pulse laser exposure by integrating Fourier’s law with the Gaussian distribution of the actual pulse laser output power density and the material’s optical absorption properties. It introduces a time variable to establish a time-dependent heat conduction equation. This equation is numerically analyzed using a difference algorithm. Based on this, simulation and experimental studies on the processing of dental hard tissues with a 1064 nm ps laser were conducted. The results show that the experimental processing depths were slightly larger than the simulation results, which may be due to damage to the dental hard tissues and the thermomechanical effects during processing. The results offer a technical reference for adjusting laser parameters in the ultra-short pulse laser processing technique.
Perception of misinformation on social media among Chinese college students
Authors: Jiang Bowen , Wang Desheng
Published: July 2024

Background

Chinese college students predominantly use social media applications to collect information, communicate with each other, advance their education, and go shopping. Research has highlighted the spread of misinformation or fake news on social media, and this has affected college students negatively as they are the most frequent users of social media.

Objective

This research aims to investigate Chinese college students’ perceptions of misinformation on social media, including their views on the consequences of misinformation, insights into the reasons for its dissemination, how misinformation impacts their mental health, and their perspectives on how to control misinformation.

Methods

This study followed a qualitative approach, selecting 36 participants from 12 universities in China, collecting data through semi-structured interviews, and analyzing the data to enable thematic analysis.

Results

Chinese college students are aware of the adverse impact of spreading misinformation on social media. They believe that false information is disseminated primarily due to inadequate punishment for those who intentionally spread it. Most college students lack proficiency in identifying misinformation, and they expect the government to do more to control the misinformation phenomenon. Moreover, misinformation on social media may cause Chinese college students to feel dysphoric, angry, and even depressed, thereby affecting their mental health. This research indicates that the public and government should make efforts to address the misinformation phenomenon in order to protect college students from being harmed.
The potential of psychiatric outpatient centers to reduce the length of stay in inpatient facilities and the negative impact of COVID-19 on the availability of psychiatric services: the case of Latvia
Authors: Taube Maris
Published: July 2024

The move from psychiatric hospitals to community-based care is the goal of policies in many countries. Latvia has attempted to reach this goal by establishing two outpatient centers in Riga. Since 2005, when the first outpatient centers opened, the ability of day clinics to reduce the total length of stay for hospital inpatients has been observed, although using the outpatient centers did not affect the number of patients treated. The open-door inpatient wards of the centers also attracted a new patient group. However, due to the COVID-19 pandemic, the number and length of stay of both outpatients and inpatients at psychiatric hospitals decreased. Therefore, other factors that can affect the move from psychiatric hospital inpatient care to outpatient centers should be further investigated.
Characterization of double humanized BLT-mice with stable engraftment of a human gut bacterial microbiome
Authors: Daharsh Lance , Lohani Saroj Chandra , Ramer-Tait Amanda E. , Li Qingsheng
Published: July 2024

Humanized mice with human-like immune systems are commonly used to study immune responses to human-specific pathogens. However, one limitation of using humanized mice is their native murine gut microbiota, which significantly differs from that in humans. Given the importance of the gut microbiome to human health, these differences may profoundly impact the ability to translate results from humanized mouse studies to humans. Further, there is a critical need for improved pre-clinical models to study the complex in vivo relationships of the gut microbiome, immune system, and human disease. We previously created double humanized mice with a functional human immune system and a stable, human-like gut microbiome. Here, we characterized the engrafted human gut bacterial microbiome in our double humanized mouse model generated by transplanting fecal material from healthy human donors into the gut of humanized mice. Analysis of bacterial microbiomes in fecal samples from double humanized mice revealed they had unique 16S rRNA gene profiles consistent with those of the individual human donor samples. Importantly, transplanted human-like gut microbiomes were stable in mice for the duration of the study, extending up to 14.5 weeks post-transplant. Microbiomes of double humanized mice also harbored predicted functional capacities that more closely resembled those of the human donors than humanized mice. In conclusion, our study highlights the successful engraftment of human fecal microbiota in BLT humanized mice and underscores the stability of this model, offering a valuable platform for investigating the intricate interplay among the human gut microbiome, immune system, and various diseases in vivo.
An evaluation of the effectiveness of immersive virtual reality training in non-specialized medical procedures for caregivers and students: a brief literature review
Authors: Clay Casey J. , Budde John R. , Hoang Andrea Q. , Gushchyan Armen
Published: July 2024

As technological advancements continue to redefine the landscape of adult education and training, virtual reality (VR) has emerged as a potent tool for enhancing skill acquisition. This literature review synthesizes existing research on the utilization of immersive and discrete VR in training adults in the medical domain. The primary focus was on understanding the effectiveness, challenges, and potential applications of VR-based training programs. Specifically, we reviewed studies related to practical skills critical to safety that target a non-surgical, discrete medical procedure (e.g., diabetes care procedures, how to correctly set a G-tube, CPR, correct personal protective equipment [PPE] usage) using an immersive VR technology as a training modality. Further, the studies reviewed had to include a comparison of immersive VR training to that of a business-as-usual (BAU) method. We conducted a review of the six studies that met the criteria and coded variables related to what technology was used, targeted skills being trained, social validity, effectiveness of the intervention, and whether generalization occurred. Key themes explored in the literature include the role of immersive experiences in enhancing learning outcomes when comparing VR training to BAU and the adaptability of VR platforms to different skill sets. Special attention was given to identifying factors that contribute to the success or limitation of VR-based training initiatives, including individual differences, technology acceptance, and effectiveness.
Radiation belt phase space density: calculation analysis and model dependence
Authors: da Silva D. E. , Elkington S. R. , Li X. , Hudson M. K. , Boyd A. J. , Jaynes A. N. , Wiltberger M.
Published: July 2024

The reprocessing of radiation belt electron flux measurements into phase space density (PSD) as a function of the adiabatic invariants is a widely-used method to address major questions regarding electron energization and loss in the outer radiation belt. In this reprocessing, flux measurements j (α, E) at local pitch angles α, energies E, and optionally magnetometer measurements B, are combined with a global magnetic field model to express the phase space density f (L*) in terms of the third invariant Φ ∝ 1/L* at fixed first and second invariants M and K. While the general framework of the calculation is agreed upon, implementation details vary amongst the literature, and the issue of magnetic field model dependence is rarely addressed. This work reviews the steps of the calculation with lists of commonly used implementation options. For the first time, analysis is presented to display the effect of doing the calculation with different implementation options and with different backing models (including both empirical and MHD-driven models). The results are summarized to inform evaluation of existing results and future efforts calculating and analyzing radiation belt electron phase space density. Three events are analyzed, and while differences are found, the primary structural interpretations of the phase space density analysis exhibit model independence.
Reservoirs of P and fertilizer with technology on the path to sustainability in coffee production
Authors: Siman Felipe Cunha , Andrade Felipe Vaz , Stauffer Eduardo , Mendonça Eduardo de Sá
Published: July 2024

Phosphorus (P) is found in the soil in organic (Po) and inorganic (Pi) forms and in compartments with different lability, normally being separated into labile, moderately labile, restricted lability and non-labile forms. The different sources of fertilizers used in the long term may change the form and availability of P over time, increasing or not its availability to plants, which can positively influence coffee productivity. This work aimed to evaluate in the field the effects of phosphate fertilizers with associated technology on the availability of P in soil with high P adsorption capacity after successive fertilizations in Coffea canephora Pierre ex A.Froehner crop. In the experiment, three phosphate sources (conventional MAP – MAP, polymer-coated MAP – MAPPOL and MAP + filter cake – MAPTF); two doses (100 and 150 % of the recommendation); and two nitrogen sources (conventional urea – UC and urea coated with polymer and sulfur – UPS) were used. After 3 years of field experimentation, the soil was collected at a depth of 0–10 cm and then, the labile, moderately labile, and restricted lability fractions were determined. Phosphate fertilizers with associated technology obtained better results in relation to MAP in terms of Pi and Po contents for the labile compartment over time, with an average increase of 66.02 mg dm−3 P in the soil. For the moderately labile fraction, fertilizers with associated technology increased the Pi content (HCl 1M) in the soil in relation to MAP, by 2.56 mg dm−3, representing an increase of 37.92%. These compartments are considered an important reserve of available P for crops grown in soils with high adsorption capacity. Phosphate fertilizers with integrated protection (MAPPOL + MAPTF) compared to MAP increased productivity by 6.79 and 11.62 % in the 2017/2018 and 2018/2019 harvests, respectively. Phosphate fertilizers with associated technology promote P dynamics in different soil compartments, increasing Coffea canephora Pierre ex A. Froehner productivity and sustainability.