bluuebunny/crossref_metadata_2025 huggingface dataset:
Curbing Breast Cancer by Altering V-ATPase Action on F-Actin, Heterochromatin, ETV7 and mTORC2 Signaling
Authors: Khan Zeina S.
Published: June 2024

Background/Aims: Motivated by the vacuolar proton pump’s importance in cancer, we investigate the effects of proton pump inhibition on breast cancer cell migration and proliferation, F-actin polymerization, lamin A/C, heterochromatin, and ETV7 expressions, nuclear size and shape, and AKT/mTOR signaling. Methods: Lowly metastatic MCF7 and highly metastatic MDA-MB-231 breast cancer cells were treated with 120 nM of proton pump inhibitor Bafilomycin A1 for 24 hours. Cell migration was studied with wound- scratch assays, ATP levels with a chemiluminescent assay; cell proliferation was quantified by a cell area expansion assay. Nuclear size and shape were determined using DAPI nuclear stain and fluorescence microscopy. The levels of F-actin, lamin A/C, heterochromatin, and ETV7 were quantified using both immunocytochemistry and western blots; p-mTORC1, p-mTORC2, mTOR, p-AKT, and AKT were measured by western blots. Results: We reveal that proton pump inhibition reduces F-actin polymerization, cell migration, proliferation, and increases heterochromatin in both lowly and highly metastatic cells. Surprisingly, Bafilomycin decreases lamin A/C in both cell lines. Inhibition has different effects on ETV7 expression in lowly and highly metastatic cells, as well as nuclear area, perimeter, and circularity. Bafilomycin also significantly decreases p-mTORC1, p-MTORC2, and MTOR expression in both cell lines, whereas it significantly decreases p-AKT in lowly metastatic cells and surprisingly significantly increases p-AKT in highly metastatic cells. Our proton pump inhibition protocol reduces V-ATPase levels (~25%) within three hours. V-ATPase levels vary in time for both control and inhibited cells, and inhibition reduces cellular ATP. Conclusion: Proton pumps promote F-actin polymerization and decrease heterochromatin, facilitating invasion. These pumps also upregulate both mTORC1 and mTORC2, thus highlighting the relevance of vacuolar proton pumps as metastatic cancer targets.
Revisiting Sex, Class and Realism: British Cinema 1956–1963
Authors: Hill John
Published: June 2024

This article looks back at the context in which Sex, Class and Realism: British Cinema 1956–1963 was written, the issues it addressed and some of the influences on it. It then considers some of the criticisms it has received and assesses its contribution to the study of British cinema of this period.
The Portrait of Villain in Horror Movie Await Further Instructions
Authors: Samarudin Sarman , Muarifuddin Muarifuddin
Published: June 2024

This research aims to describe the portrait of the villain in the horror movie Await Further Instructions with a formulaic approach by J. G. Cawelti to provide an overview of movie development, especially the villain elements in horror movies. The descriptive-qualitative method was used in this research. The data for this research were collected by watching, pausing, identifying, classifying, and then analyzed by presenting, describing, and interpreting the data as well as concluding the analysis result. This research found four villain elements that are the same as horror villains in general (convention) and two different elements of villain (invention) that depict new sources of fear, such as motive antagonist (constructed by the media) and iconic symbol (mass media). The researcher concluded that in the horror movie Await Further Instructions, there is development in the elements of the villain that depict or represent people today being more afraid of mass media power than supernatural or unexplainable powers, such as ghosts, aliens, monsters, serial killers, and others.
Examining the psychometric properties of the Columbia Speech Quality Instrument in cochlear implant users
Authors: Lalwani Anil K. , Chun Michael B. , Hwa Tiffany P. , Chern Alexander , Tian Likun , Chen Stephanie Y. , Stewart Michael G. , Mancuso Dean , Cellum Ilana P.
Published: June 2024

Objective

Although speech recognition among cochlear implant (CI) users improved over the past few decades, many still report poor speech quality. Currently, there is no validated tool to measure speech quality. The objective was to examine whether a previously validated speech quality tool is applicable in the CI population using psychometric analysis.

Design

Cross-sectional psychometric analysis of the Columbia Speech Quality Instrument (CSQI; previously validated in normal-hearing individuals; consists of 2 original and 7 manipulated speech clips designed to accentuate selected speech characteristics) was performed in adult English-speaking CI recipients (N = 36). Subjects rated each clip using a visual analog scale (VAS) on 14 characteristics: cartoonish/not-cartoonish, clear/unclear, like/dislike, breathy/not-breathy, smooth/rough, echo-y/not-echo-y, tinny/bassy, soothing/not-soothing, natural/unnatural, mechanical/not-mechanical, hoarse/smooth, pleasant/unpleasant, male/female, and speech-like/not-speech-like. Main outcome measures included validity, reliability, and factor structure.

Results

Content validity was previously confirmed during instrument design. Construct validity by item-item correlation analysis demonstrated correlation of 12/14 items with ≥1 other retained item (r ≥ 0.35, Spearman). Reliability was confirmed by internal consistency; factor analysis using two subsets selected by Scree plot and factor loading ≥0.4 demonstrated Cronbach alpha coefficients of 0.89 and 0.74 for factors 1 and 2, respectively. Tinny/bassy and male/female were the only characteristics that did not pass construct validity or internal consistency.

Conclusions

The CSQI has strong psychometric properties in the CI population; however, our findings support removal of tinny/bass and male/female characteristics from the final instrument prior to implementation in the CI population. The CSQI can be utilized in cochlear implantees to investigate effects of changes in speech processing strategies and postoperative outcomes with different devices.
Transdermal microneedle patches as a promising drug delivery system for anti-obesogenic molecules
Authors: Sánchez-Trasviña Calef , Coronel-Meneses David , Escobar-Fernández Aleyda Margarita , Mayolo-Deloisa Karla
Published: June 2024

Obesity, characterized by excessive storage of lipids, has become a global pandemic with high incidence levels, and its forecast is not encouraging. Currently, there are different strategies to treat obesity; however, these conventional methods have various limitations. Lifestyle changes may result in poor outcomes due to the complexity of obesity causes, pharmaceutic treatments produce severe side effects, and bariatric surgery is highly invasive. In the search for alternative treatments to fight obesity, transdermal drug delivery systems of anti-obesogenic molecules have gained particular attention. However, the diffusion of molecules through the skin is the main drawback due to the characteristics of different layers of the skin, principally the stratum corneum and its barrier-like behavior. In this sense, microneedles patches (MP) have emerged to overcome this limitation by piercing the skin and allowing drug delivery inside the body. Although MP have been studied for some years, it was not until about 2017 that their potential as anti-obesogenic treatment was reported. This article aims to summarize and analyze the strategies employed to produce MP and to embed the active molecules against obesity. Special attention is focused on the microneedle’s material, geometry, array, and additional delivery strategies, like nanoencapsulation. MP are a promising tool to develop an easy-access treatment, avoiding the digestive tract and with the capacity to enhance the anti-obesogenic activity by delivering one or more active molecules.
The DNA repair kinase ATM regulates CD13 expression and cell migration
Authors: Stevenson Louise K. , Page Amy J. , Dowson Matthew , ElBadry Sameh K. , Barnieh Francis M. , Falconer Robert A. , El-Khamisy Sherif F.
Published: June 2024

Classically, ATM is known for its role in sensing double-strand DNA breaks, and subsequently signaling for their repair. Non-canonical roles of ATM include transcriptional silencing, ferroptosis, autophagy and angiogenesis. Angiogenesis mediated by ATM signaling has been shown to be VEGF-independent via p38 signaling. Independently, p38 signaling has been shown to upregulate metalloproteinase expression, including MMP-2 and MMP-9, though it is unclear if this is linked to ATM. Here, we demonstrate ATM regulates aminopeptidase-N (CD13/APN/ANPEP) at the protein level. Positive correlation was seen between ATM activity and CD13 protein expression using both “wildtype” (WT) and knockout (KO) ataxia telangiectasia (AT) cells through western blotting; with the same effect shown when treating neuroblastoma cancer cell line SH-SY5Y, as well as AT-WT cells, with ATM inhibitor (ATMi; KU55933). However, qPCR along with publically available RNAseq data from Hu et al. (J. Clin. Invest., 2021, 131, e139333), demonstrated no change in mRNA levels of CD13, suggesting that ATM regulates CD13 levels via controlling protein degradation. This is further supported by the observation that incubation with proteasome inhibitors led to restoration of CD13 protein levels in cells treated with ATMi. Migration assays showed ATM and CD13 inhibition impairs migration, with no additional effect observed when combined. This suggests an epistatic effect, and that both proteins may be acting in the same signaling pathway that influences cell migration. This work indicates a novel functional interaction between ATM and CD13, suggesting ATM may negatively regulate the degradation of CD13, and subsequently cell migration.
A closer look at how the dispersive liquid–liquid microextraction method works. Investigation of the effect of solvent mixture composition on the quality and stability of the cloudy state
Authors: Zaruba Serhii , Ovšonková Michaela , Makoś-Chełstowska Patrycja , Andruch Vasil
Published: June 2024

The dispersive liquid–liquid microextraction (DLLME) is one of the most popular miniaturized extraction procedures. In this paper, the degree of dispersion and dispersion stability were studied with the aim to assess the correlations of these parameters with efficiency for the selected analytical application. The dependence between the degree of dispersion (cloudy state quality) and its stability obtained by various emulsification procedures, such as solvent-assisted emulsification (using various dispersive solvents) and mechanical emulsification (using auxiliary energies), is investigated and discussed. It was found out that the degree of dispersion depends on the type of emulsification procedure and decreases in the series: solvent-assisted (SA-) = ultrasound-assisted (UA-) > air-assisted (AA-) > vortex-assisted (VA-) emulsification. The emulsion stability depends on the degree of dispersion and there were 1810 and 2070 s for the most effective emulsification procedures, such us solvent-assisted and ultrasound-assisted emulsification, respectively. A comparison between the sensitivity of the analytical methods (using spectrophotometric determination of the anionic surfactants) and the degree of dispersion have been made. The sensitivity of the methods was ranked as follows: DLLME > UA-LLME > VA-LLME > AA-LLME.
Wall motion assessment by feature tracking in pediatric patients with coronary anomalies undergoing dobutamine stress CMR
Authors: Sachdeva Shagun , Molossi Silvana , Reaves-O’Neal Dana , Masand Prakash , Doan Tam T.
Published: June 2024

Background

Left ventricular (LV) wall motion assessment is an important adjunct in addition to perfusion defects in assessing ischemic changes. This study aims to investigate the feasibility and utility of performing feature tracking (FT) in pediatric patients with coronary anomalies undergoing dobutamine stress CMR to assess wall motion abnormalities (WMA) and perfusion defects.

Method

This is a retrospective study where 10 patients with an inducible first-pass perfusion (FPP) defect and 10 without were selected. Global LV circumferential strain/strain rate (GCS/GCSR) was measured at rest and at peak stress (systole and diastole) using a commercially available feature tracking software. Peak GCS and GCSR were compared to indexed wall motion score (WMSI) between groups with and without FPP defect and in subjects with and without WMA.

Results

The median age of patients was 13.5 years (Q1, 11 years; Q3, 15 years). Five subjects had qualitatively WMA at peak stress. A moderate correlation of GCS with WMSI at peak stress (0.48, p = 0.026) and a significant difference between GCS at rest and stress in patients with no inducible WMA (p = 0.007) were seen. No significant difference was noted in GCS between rest and stress in patients with WMA (p = 0.13). There was a larger absolute GCS/GCSR at peak stress in subjects with no inducible FPP defect or WMA.

Conclusion

Smaller absolute GCS and a lack of significant change in GCS at peak stress in those with inducible WMA or perfusion defect are suggestive of compromised LV deformation in subjects with inducible WMA. Given these findings, GCS derived from CMR-FT may be used to objectively assess WMA in pediatric patients undergoing stress CMR.
Type 2 diabetes mellitus in acute myocardial infarction: a persistent significant burden on long-term mortality
Authors: Bouisset Frédéric , Bataille Vincent , Schiele François , Puymirat Etienne , Fayol Antoine , Simon Tabassome , Danchin Nicolas , Ferrières Jean
Published: June 2024

Objective

The long-term impact of type 2 diabetes mellitus (T2DM) after an acute myocardial infarction (AMI) has not been thoroughly investigated yet. This study aimed to assess the long-term impact of T2DM after AMI.

Research design and methods

We analyzed the data of three nationwide observational studies from the French Registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) program, conducted over a 1-month period in 2005, 2010, and 2015. Patients presenting T2DM were classified as diabetic, and patients presenting type 1 diabetes mellitus were excluded. We identified factors related to all-cause death at 1-year follow-up and divided 1,897 subjects into two groups, paired based on their estimated 1-year probability of death as determined by a logistic regression model.

Results

A total of 9,181 AMI patients were included in the analysis, among them 2,038 (22.2%) had T2DM. Patients with diabetes were significantly older (68.2 ± 12.0 vs. 63.8 ± 14.4, p < 0.001) and had a higher prevalence of a prior history of percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), or heart failure (22.5% vs. 13.0%, 7.1% vs. 3.1% and 6.7 vs. 3.8% respectively, p < 0.001 for all). Even after matching two groups of 1,897 patients based on propensity score for their 1-year probability of death, diabetes remained associated with long-term mortality, with an HR of 1.30, 95%CI (1.17–1.45), p < 0.001.

Conclusions

T2DM per se has an adverse impact on long-term survival after myocardial infarction. Independently of the risk of short-term mortality, patients with diabetes who survived an AMI have a 30% higher risk of long-term mortality.
Inflammation in Fabry disease: stages, molecular pathways, and therapeutic implications
Authors: Kurdi Hibba , Lavalle Lucia , Moon James C. C. , Hughes Derralynn
Published: June 2024

Fabry disease, a multisystem X-linked disorder caused by mutations in the alpha-galactosidase gene. This leads to the accumulation of globotriaosylceramide (Gb3) and globotriaosylsphingosine (Lyso-Gb3), culminating in various clinical signs and symptoms that significantly impact quality of life. Although treatments such as enzyme replacement, oral chaperone, and emerging therapies like gene therapy exist; delayed diagnosis often curtails their effectiveness. Our review highlights the importance of delineating the stages of inflammation in Fabry disease to enhance the timing and efficacy of diagnosis and interventions, particularly before the progression to fibrosis, where treatment options are less effective. Inflammation is emerging as an important aspect of the pathogenesis of Fabry disease. This is thought to be predominantly mediated by the innate immune response, with growing evidence pointing towards the potential involvement of adaptive immune mechanisms that remain poorly understood. Highlighted by the fact that Fabry disease shares immune profiles with systemic autoinflammatory diseases, blurring the distinctions between these disorders and highlighting the need for a nuanced understanding of immune dynamics. This insight is crucial for developing targeted therapies and improving the administration of current treatments like enzyme replacement. Moreover, our review discusses the complex interplay between these inflammatory processes and current treatments, such as the challenges posed by anti-drug antibodies. These antibodies can attenuate the effectiveness of therapies, necessitating more refined approaches to mitigate their impact. By advancing our understanding of the molecular changes, inflammatory mediators and causative factors that drive inflammation in Fabry disease, we aim to clarify their role in the disease's progression. This improved understanding will help us see how these processes fit into the current landscape of Fabry disease. Additionally, it will guide the development of more effective diagnostic and therapeutic approaches, ultimately improving patient care.
Variable gearing at the ankle during walking in adults and young children: implications for foot development and evolution
Authors: Zeininger Angel , Schmitt Daniel , Jensen Jody L. , Shapiro Liza J.
Published: June 2024

Introduction: The human foot has evolved over the past seven million years from a relatively mobile, grasping appendage to a highly derived structure with a heel pad and longitudinal arch that can absorb shock at heel strike and weight-bearing yet also function as a powerful lever at toe-off. It has been proposed that the modern human foot evolved to allow our species to use “variable gearing” during walking and running. In this model, the gears of the human foot are defined relative to the ankle center of rotation as R, the distance from the ground reaction resultant vector, and r, the distance from the calf muscle vector. The gear ratio defines the torque generated to propel the body or stretch the triceps surae muscles. We test the hypothesis that variable gearing is associated with modern human pedal anatomy and a heel-to-toe rollover that allows a shift from “low gear” to “high gear” during stance.

Methods: Using force plate and video analysis, we examined variable gearing in adults and children engaging in adult heel strike (AHS = 35), flat foot contact (FFC = 39), or initial heel contact (IHC = 26).

Results and Discussion: Our hypothesis was partly supported. Although variable gearing was observed in IHC steps and was greater than in FFC steps, it was not as developed as in AHS steps. This may be related to anatomical and motor control differences between juvenile and adult feet, suggesting that adult anatomy, including a high arch, and neural control are critical for full use of variable gearing and that this feature would have evolved in later hominins around two million years ago with the appearance of a fully modern foot.
Adding immersive virtual reality laboratory simulations to traditional teaching methods enhances biotechnology learning outcomes
Authors: Beatrice Peter , Grimaldi Annalisa , Bonometti Stefano , Caruso Enrico , Bracale Marcella , Montagnoli Antonio
Published: June 2024

Immersive virtual reality (VR) simulations are increasingly being used in diverse educational and training contexts to supplement traditional learning methods. The high versatility of virtual laboratories allows students to take advantage of many benefits, like experiencing dangerous reactions, time-consuming protocols, or expensive equipment without the necessity of a real science laboratory. However, little research is currently available to support the efficacy and efficiency of this new learning tool. In this context, the main objective of this study was to assess the influence of biotechnology training by using immersive VR technologies on the student’s motivational and learning outcomes as compared with learning with conventional methods only. To this aim we tested two diverse strategies, respectively VR simulations were used in place of or in addition to the teacher’s introductory lesson of a hands-on laboratory experience. Aligned questionaries were administered before and after the proposed activities to assess theoretical knowledge, self-efficacy, interest in biotechnology, and engagement of the participants. We found that when the introductory lesson to a biotechnology hands-on laboratory is replaced with an equivalent immersive VR simulation, the student’s learning outcomes are lower with respect to the traditional approach. On the contrary, when VR simulations are integrated as an additional tool to the existing learning methods, higher learning outcomes were observed demonstrating a deeper understanding of the learning contents. Furthermore, our study showed that learning with immersive VR simulations motivates students more than the traditional methods, thus, using this new technology in addition to the existing educational methods in biotechnology could be considered as a win-win strategy to raise the attention of the students while increasing the learning outcomes.
Interpretable machine learning identifies metabolites associated with glomerular filtration rate in type 2 diabetes patients
Authors: An Tian-Feng , Zhang Zhi-Peng , Xue Jun-Tang , Luo Wei-Ming , Li Yang , Fang Zhong-Ze , Zong Guo-Wei
Published: June 2024

Objective

The co-occurrence of kidney disease in patients with type 2 diabetes (T2D) is a major public health challenge. Although early detection and intervention can prevent or slow down the progression, the commonly used estimated glomerular filtration rate (eGFR) based on serum creatinine may be influenced by factors unrelated to kidney function. Therefore, there is a need to identify novel biomarkers that can more accurately assess renal function in T2D patients. In this study, we employed an interpretable machine-learning framework to identify plasma metabolomic features associated with GFR in T2D patients.

Methods

We retrieved 1626 patients with type 2 diabetes (T2D) in Liaoning Medical University First Affiliated Hospital (LMUFAH) as a development cohort and 716 T2D patients in Second Affiliated Hospital of Dalian Medical University (SAHDMU) as an external validation cohort. The metabolite features were screened by the orthogonal partial least squares discriminant analysis (OPLS-DA). We compared machine learning prediction methods, including logistic regression (LR), support vector machine (SVM), random forest (RF), and eXtreme Gradient Boosting (XGBoost). The Shapley Additive exPlanations (SHAP) were used to explain the optimal model.

Results

For T2D patients, compared with the normal or elevated eGFR group, glutarylcarnitine (C5DC) and decanoylcarnitine (C10) were significantly elevated in GFR mild reduction group, and citrulline and 9 acylcarnitines were also elevated significantly (FDR<0.05, FC > 1.2 and VIP > 1) in moderate or severe reduction group. The XGBoost model with metabolites had the best performance: in the internal validate dataset (AUROC=0.90, AUPRC=0.65, BS=0.064) and external validate cohort (AUROC=0.970, AUPRC=0.857, BS=0.046). Through the SHAP method, we found that C5DC higher than 0.1μmol/L, Cit higher than 26 μmol/L, triglyceride higher than 2 mmol/L, age greater than 65 years old, and duration of T2D more than 10 years were associated with reduced GFR.

Conclusion

Elevated plasma levels of citrulline and a panel of acylcarnitines were associated with reduced GFR in T2D patients, independent of other conventional risk factors.
The positive association between hyperuricemia and polycystic ovary syndrome and analysis of related factors
Authors: Gong Zhentao , Sun Yanwen , Zhang Lingshan , Zhu Xiaoyong , Shi Yingli
Published: June 2024

Purpose

To examine the potential association between polycystic ovary syndrome (PCOS) and hyperuricemia and to elucidate the underlying contributory factors.

Methods

Retrospective study on 603 women with PCOS and 604 women without PCOS. Anthropometric features, reproductive hormone profiles, and metabolic parameters were measured and compared between two groups of patients. Examinations of correlations between SUA levels and other parameters were conducted to discern potential correlations.

Results

Both serum uric acid levels and the incidence of hyperuricemia exhibited statistically significant elevations in women with PCOS when compared to their counterparts without PCOS. Nonetheless, this statistical difference was not found between the obese subgroup after stratifying study subjects by body mass index (BMI). Pearson’s correlation analysis underscored the prominence of BMI as a robust factor influencing SUA levels in women, regardless of their PCOS status. Furthermore, multivariable linear regression model demonstrated significant positive associations between SUA levels and several variables, namely dehydroepiandrosterone sulfate (DHEA-S), free androgen index (FAI), total cholesterol (TC), triglycerides (TG), free fatty acids (FFA), fasting insulin (FINS), homeostatic model assessment of insulin resistance (HOMA-IR), area under the curve for insulin (AUC-I), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Additionally, it is noteworthy that the prevalence of hyperuricemia exhibited a positive association with fasting plasma glucose (FPG) levels, while conversely, it displayed a negative association with estradiol (E2) levels.

Conclusions

PCOS is associated with a significant elevation of SUA level and hyperuricemia prevalence. HA, IR, and dyslipidemia may be the mediators in the pathogenesis of hyperuricemia in women with PCOS.
Impact of breastfeeding on risk of glucose intolerance in early postpartum after gestational diabetes
Authors: Vanlaer Yana , Minschart Caro , Vrolijk Hannah , Van Crombrugge Paul , Moyson Carolien , Verhaeghe Johan , Devlieger Roland , Vandeginste Sofie , Verlaenen Hilde , Vercammen Chris , Maes Toon , Dufraimont Els , Roggen Nele , De Block Christophe , Jacquemyn Yves , Mekahli Farah , De Clippel Katrien , Van Den Bruel Annick , Loccufier Anne , Van Pottelbergh Inge , Myngheer Nele , Abrams Pascale , Vinck Wouter , Leuridan Liesbeth , Driessens Sabien , Billen Jaak , Matthys Christophe , Bogaerts Annick , Laenen Annouschka , Mathieu Chantal , Benhalima Katrien
Published: June 2024

Aims

To determine the impact of breastfeeding on the risk of postpartum glucose intolerance in women with gestational diabetes.

Methods

Sub-analysis of two multi-centric prospective cohort studies (BEDIP-N and MELINDA) in 1008 women with gestational diabetes. Data were collected during pregnancy and at a mean of 12 weeks postpartum. Multivariate logistic regression was used to estimate the effect of breastfeeding on glucose intolerance, with adjustment for ethnicity, education, income, professional activity and BMI.

Results

Of all participants, 56.3% (567) breastfed exclusively, 10.1% (102) gave mixed milk feeding and 33.6% (339) did not breastfeed. Mean breastfeeding duration was 3.8 ± 2.4 and 3.7 ± 2.1 months in the breastfeeding and mixed milk feeding groups (p=0.496). The rate of glucose intolerance was lower in both the breastfeeding [22.3% (126)] and mixed milk feeding [25.5% (26)] groups compared to the no breastfeeding group [29.5% (100)], with an adjusted OR of 0.7 (95% CI 0.5–1.0) for glucose intolerance in the breastfeeding group compared to no breastfeeding group and an adjusted OR of 0.7 (95% CI 0.4–1.2) for the mixed milk feeding group compared to the no breastfeeding group. Postpartum, breastfeeding women had a lower BMI, less often postpartum weight retention, lower fasting triglycerides, less insulin resistance and a higher insulin secretion-sensitivity index-2 than the mixed milk feeding and no breastfeeding group. The mixed milk feeding group was more often from an non-White background, had a lower blood pressure and lower fasting triglycerides compared to the no breastfeeding group.

Conclusions

Breastfeeding (exclusive and mixed milk feeding) is associated with less glucose intolerance and a better metabolic profile in early postpartum in women with gestational diabetes.
Analysis of single nucleotide polymorphisms of the metabotropic glutamate receptors in a transgender population
Authors: Fernández Rosa , Ramírez Karla , Lorente-Bermúdez Roberto , Gómez-Gil Esther , Mora Mireia , Guillamon Antonio , Pásaro Eduardo
Published: June 2024

Introduction

Gender incongruence (GI) is characterized by a marked incongruence between an individual’s experienced/expressed gender and the assigned sex at birth. It includes strong displeasure about his or her sexual anatomy and secondary sex characteristics. In some people, this condition produces a strong distress with anxiety and depression named gender dysphoria (GD). This condition appears to be associated with genetic, epigenetics, hormonal as well as social factors. Given that L-glutamate is the major excitatory neurotransmitter in the central nervous system, also associated with male sexual behavior as well as depression, we aimed to determine whether metabotropic glutamate receptors are involved in GD.

Methods

We analyzed 74 single nucleotide polymorphisms located at the metabotropic glutamate receptors (mGluR1, mGluR3, mGluR4, mGluR5, mGluR7 and mGluR8) in 94 transgender versus 94 cisgender people. The allele and genotype frequencies were analyzed by c2 test contrasting male and female cisgender and transgender populations. The strength of the associations was measured by binary logistic regression, estimating the odds ratio (OR) for each genotype. Measurement of linkage disequilibrium, and subsequent measurement of haplotype frequencies were also performed considering three levels of significance: P ≤ 0.05, P ≤ 0.005 and P ≤ 0.0005. Furthermore, false positives were controlled with the Bonferroni correction (P ≤ 0.05/74 = 0.00067).

Results

After analysis of allele and genotypic frequencies, we found twenty-five polymorphisms with significant differences at level P ≤ 0.05, five at P ≤ 0.005 and two at P ≤ 0.0005. Furthermore, the only two polymorphisms (rs9838094 and rs1818033) that passed the Bonferroni correction were both related to the metabotropic glutamate receptor 7 (mGluR7) and showed significant differences for multiple patterns of inheritance. Moreover, the haplotype T/G [OR=0.34 (0.19–0.62); P<0.0004] had a lower representation in the transgender population than in the cisgender population, with no evidence of sex cross-interaction.

Conclusion

We provide genetic evidence that the mGluR7, and therefore glutamatergic neurotransmission, may be involved in GI and GD.
Artificial neural networks for predicting the performance of heat pumps with horizontal ground heat exchangers
Authors: Zhou Yu , Narsilio Guillermo , Makasis Nikolas , Soga Kenichi , Chen Peng , Aye Lu
Published: June 2024

A Ground Coupled Heat Pump (GCHP) is a highly energy efficient heating, ventilation, and air conditioning (HVAC) system that utilises the ground as the heat source when heating and as the heat sink when cooling. This paper investigates GCHP systems with horizontal Ground Heat Exchangers (GHEs) in the rural industry, exemplifying the technology for poultry (chicken) sheds in Australia. This investigation aims to provide an Artificial Neural Network (ANN) model that can be used for GCHP design at various locations with different climates. To this extent, a Transient System Simulation Tool (TRNSYS) model for a typical horizontal GHE applied in a rural farm was first verified. Using this model, over 700,000 hourly performance data items were obtained, covering over 80 different yearly loading patterns under three different climate conditions. The simulated performance data was then used to train the ANN. As a result, the trained ANN can predict the performance of GCHP systems with identical (multiple) GHEs even under climatic conditions (and locations) that have not been specifically trained for. Unlike other works, the newly introduced ANN model is accurate even with limited types of input data, with high accuracy (less than 5% error in most cases tested). This ANN model is 100 times computationally faster than TRNSYS simulations and 10,000 times faster than finite element models.
Phosphorus in farm roadway substrates: contrasting spatial and temporal patterns in dairy and beef farms
Authors: Sifundza Lungile Senteni , Murnane John G. , Daly Karen , Lopez-Sangil Luis , Leach Simon , Tuohy Patrick , Cardiff John , Fenton Owen
Published: June 2024

The mobilisation and impact of roadway runoff on dairy farms has been established as a sub-component of the nutrient transfer continuum. It is acknowledged that fresh nutrient sources deposited on roadways dominate runoff and recent work has shown that available phosphorus (P) in roadway substrates is also an important source component. The objectives of this study were to understand spatial and temporal available P concentrations in roadway substrate (aggregate and soil mix) across dairy and beef farms during the open (February–October, when cows use the roadway network and fields) and closed (November–January, when cows were housed) periods and identify locations which could be considered critical source areas (CSA). For the study, roadway substrate samples were taken at 18 locations on each farm, across eight sampling periods, and were analysed for available P. Results showed that mean available P concentrations (Morgan’s P) in the sampling locations ranged from 15.9 to 101.4 mg L-1 for the Dairy Farm, from 4.1 to 59.4 mg L-1 for Beef Farm 1 and from 6.3 to 23.2 mg L-1 for Beef Farm 2. In open period, the results showed that mean available P concentrations were 75.4 ± 30.9, 14.9 ± 3.2 and 13.4 ± 2.5 mg L-1 for the Dairy Farm, Beef Farm 1 and Beef Farm 2, respectively. In closed period, the mean available P were 40.3 ± 17.2, 10.4 ± 1.0 and 9.8 ± 0.2 mg L-1 for Dairy Farm, Beef Farm 1 and Beef Farm 2, respectively. Overall, P concentrations on the Dairy Farm roadways was up to 4 times greater than that in the Beef Farms’ roadways. Compared to soils in adjacent fields, P concentrations in the Dairy and Beef Farms roadways was up-to 7 and 2 times higher, respectively. Critical roadway sections that required mitigation were two in the Dairy Farm, one in Beef Farm 1 and two in Beef Farm 2. In addition to fresh faeces and urine (i.e., dominant source of nutrients in farm roadways), this study showed that nutrient enriched roadway materials are a labile P source. Thus, future mitigation of roadway runoff must consider all roadway nutrient sources, including livestock fresh excreta as well as used roadway surface materials.
Polymorphism Pro64His within galectin-3 has functional consequences at proteome level in thyroid cells
Authors: Silvestri Roberto , Zallocco Lorenzo , Corrado Alda , Ronci Maurizio , Aceto Romina , Ricci Benedetta , Cipollini Monica , Dell’Anno Irene , De Simone Chiara , De Marco Giuseppina , Ferrarini Eleonora , Beghelli Daniela , Mazzoni Maria Rosa , Lucacchini Antonio , Gemignani Federica , Giusti Laura , Landi Stefano
Published: June 2024

Introduction

The single nucleotide polymorphism (SNP) rs4644 at codon 64 of galectin-3 (gal-3, gene name: LGALS3), specifying the variant proline (P64) to histidine (H64), is known to affect the protein’s functions and has been associated with the risk of several types of cancer, including differentiated thyroid carcinoma (DTC).

Materials and methods

To deepen our understanding of the biological effects of this SNP, we analyzed the proteome of two isogenic cell lines (NC-P64 vs. NA-H64) derived from the immortalized non-malignant thyrocyte cell line Nthy-Ori, generated through the CRISPR-Cas9 technique to differ by rs4644 genotype. We compared the proteome of these cells to detect differentially expressed proteins and studied their proteome in relation to their transcriptome.

Results

Firstly, we found, consistently with previous studies, that gal-3-H64 could be detected as a monomer, homodimer, and heterodimer composed of one cleaved and one uncleaved monomer, whereas gal-3-P64 could be found only as a monomer or uncleaved homodimer. Moreover, results indicate that rs4644 influences the expression of several proteins, predominantly upregulated in NA-H64 cells. Overall, the differential protein expression could be attributed to the altered mRNA expression, suggesting that rs4644 shapes the function of gal-3 as a transcriptional co-regulator. However, this SNP also appeared to affect post-transcriptional regulatory mechanisms for proteins whose expression was oppositely regulated compared to mRNA expression. It is conceivable that the rs4644-dependent activities of gal-3 could be ascribed to the different modalities of self-dimerization.

Conclusion

Our study provided further evidence that rs4644 could affect the gal-3 functions through several routes, which could be at the base of differential susceptibility to diseases, as reported in case-control association studies.
Integrative transcriptomic profiling of ncRNAs and mRNAs in developing mouse lens
Authors: Zhang Liyun , Liu Xin , Li Wei , Liu Kaiqing , Zhang Jing , Liu Xinhua , Wang Jiantao
Published: June 2024

In recent years, burgeoning research has underscored the pivotal role of non-coding RNA in orchestrating the growth, development, and pathogenesis of various diseases across organisms. However, despite these advances, our understanding of the specific contributions of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) to lens development remains notably limited. Clarifying the intricate gene regulatory networks is imperative for unraveling the molecular underpinnings of lens-related disorders. In this study, we aimed to address this gap by conducting a comprehensive analysis of the expression profiles of messenger RNAs (mRNAs), lncRNAs, and circRNAs at critical developmental time points of the mouse lens, encompassing both embryonic (E10.5, E12.5, and E16.5) and postnatal stages (P0.5, P10.5, and P60). Leveraging RNA-sequencing technology, we identified key transcripts pivotal to lens development. Our analysis revealed differentially expressed (DE) mRNAs, lncRNAs, and circRNAs across various developmental stages. Particularly noteworthy, there were 1831 co-differentially expressed (CO-DE) mRNAs, 150 CO-DE lncRNAs, and 13 CO-DE circRNAs identified during embryonic stages. Gene Ontology (GO) enrichment analysis unveiled associations primarily related to lens development, DNA conformational changes, and angiogenesis among DE mRNAs and lncRNAs. Furthermore, employing protein–protein interaction networks, mRNA–lncRNA co-expression networks, and circRNA–microRNA–mRNA networks, we predicted candidate key molecules implicated in lens development. Our findings underscore the pivotal roles of lncRNAs and circRNAs in this process, offering fresh insights into the pathogenesis of lens-related disorders and paving the way for future exploration in this field.
Insights into neurosteroids and their role in women with epilepsy
Authors: Vadlamudi Lata , Ashley Daniel Paul , Voinescu P. Emanuela
Published: June 2024

Epilepsy, is a serious neurological condition, characterized by recurring, unprovoked seizures and affects over 50 million people worldwide. Epilepsy has an equal prevalence in males and females, and occurs throughout the life span. Women with epilepsy (WWE) present with unique challenges due to the cyclical fluctuation of sex steroid hormone concentrations during their life course. These shifts in sex steroid hormones and their metabolites are intricately intertwined with seizure susceptibility and affect epilepsy during the life course of women in a complex manner. Here we present a review encompassing neurosteroids—steroids that act on the brain regardless of their site of synthesis in the body; the role of neurosteroids in women with epilepsy through their life-course; exogenous neurosteroid trials; and future research directions. The focus of this review is on progesterone and its derived neurosteroids, given the extensive basic research that supports their role in modulating neuronal excitability.
A novel host restriction factor MRPS6 mediates the inhibition of PDCoV infection in HIEC-6 cells
Authors: Jiang Yuhang , Zhang Guoqing , Li Letian , Chen Jing , Hao Pengfei , Gao Zihan , Hao Jiayi , Xu Zhiqiang , Wang Maopeng , Li Chang , Jin Ningyi
Published: June 2024

Introduction

Porcine deltacoronavirus (PDCoV) is a zoonotic pathogen with a global distribution, capable of infecting both pigs and humans. To mitigate the risk of cross-species transmission and potential outbreaks, it is crucial to characterize novel antiviral genes, particularly those from human hosts.

Methods

This research used HIEC-6 to investigate PDCoV infection. HIEC-6 cells were infected with PDCoV. Samples were collected 48 h postinfection for proteomic analysis.

Results

We discovered differential expression of MRPS6 gene at 48 h postinfection with PDCoV in HIEC-6 cells. The gene expression initially increased but then decreased. To further explore the role of MRPS6 in PDCoV infection, we conducted experiments involving the overexpression and knockdown of this gene in HIEC-6 and Caco2 cells, respectively. Our findings revealed that overexpression of MRPS6 significantly inhibited PDCoV infection in HIEC-6 cells, while knockdown of MRPS6 in Caco2 cells led to a significant increase of virus titer. Furthermore, we investigated the correlation between PDCoV infection and the expression of MRPS6. Subsequent investigations demonstrated that MRPS6 exerted an augmentative effect on the production of IFN-β through interferon pathway activation, consequently impeding the progression of PDCoV infection in cellular systems. In conclusion, this study utilized proteomic analysis to investigate the differential protein expression in PDCoV-infected HIEC-6 cells, providing evidence for the first time that the MRPS6 gene plays a restrictive role in PDCoV virus infection.

Discussion

Our findings initially provide the validation of MRPS6 as an upstream component of IFN-β pathway, in the promotion of IRF3, IRF7, STAT1, STAT2 and IFN-β production of HIEC-6 via dual-activation from interferon pathway.
Optimization of a home hospitalization program for hematopoietic stem cell transplantation with ehealth integration and clinical pharmacist involvement
Authors: Moreno-Martinez Maria-Estela , Riba Mireia , García-Cadenas Irene , Esquirol Albert , Yusta Marta , Redondo Sara , De Dios Anna , Portos Jose Manuel , Aso Olga , Marcos-Fendian Angel , Font Núria , Briones Javier , Martino Rodrigo , Feliu Anna
Published: June 2024

Home hospitalization represents an alternative to traditional hospitalization, providing comparable clinical safety for hematological patients. At-home therapies can range from the delivery of intravenous antibiotics to more complex scenarios, such as the care during the early period after hematopoietic stem cell transplantation and chimeric antigen receptor T-cell therapy. Early discharge from conventional hospitalization is feasible and helps reduce hospital resources and waiting lists. The coordinated efforts of multidisciplinary teams, including hematologists, nurses, and pharmacists, ensure patient safety and continuity of care. The traditional model of home hospitalization relies on home visits and telephone consultations with physicians and nurses. However, the use of eHealth technologies, such as MY-Medula, can enhance communication and monitoring, and thereby improve patient outcomes with no additional costs. The active involvement of a clinical pharmacist in home hospitalization programs is essential, not only for the proper logistical management of the medication but also to ensure its appropriateness, optimize treatment, address queries from the team and patients, and promote adherence. In conclusion, the implementation of hematopoietic stem cell transplantation and chimeric antigen receptor T-cell therapy home hospitalization programs that use both an eHealth tool and a multidisciplinary care model can optimize patient care and improve quality of life without increasing healthcare costs.
Plasma metabolites as mediators in immune cell-pancreatic cancer risk: insights from Mendelian randomization
Authors: Zhang Ke , Zhu Jie , Wang Peng , Chen Yuan , Wang Zhengwang , Ge Xinyu , Wu Junqing , Chen Long , Lu Yipin , Xu Peng , Yao Jie
Published: June 2024

Background

Immune cells play a crucial role in the development and progression of pancreatic cancer, yet the causal relationship remains uncertain due to complex immune microenvironments and conflicting research findings. Mendelian randomization (MR), this study aims to delineate the causal relationships between immune cells and pancreatic cancer while identifying intermediary factors.

Methods

The genome-wide association study (GWAS) data on immune cells, pancreatic cancer, and plasma metabolites are derived from public databases. In this investigation, inverse variance weighting (IVW) as the primary analytical approach to investigate the causal relationship between exposure and outcome. Furthermore, this study incorporates MR-Egger, simple mode, weighted median, and weighted mode as supplementary analytical approaches. To ensure the reliability of our findings, we further assessed horizontal pleiotropy and heterogeneity and evaluated the stability of MR results using the Leave-one-out method. In conclusion, this study employed mediation analysis to elucidate the potential mediating effects of plasma metabolites.

Results

Our investigation revealed a causal relationship between immune cells and pancreatic cancer, highlighting the pivotal roles of CD11c+ monocytes (odds ratio, ORIVW=1.105; 95% confidence interval, 95%CI: 1.002–1.218; P=0.045), HLA DR+ CD4+ antigen-presenting cells (ORIVW=0.920; 95%CI: 0.873–0.968; P=0.001), and HLA DR+ CD8br T cells (ORIVW=1.058; 95%CI: 1.002–1.117; P=0.041) in pancreatic cancer progression. Further mediation analysis indicated that oxalate (proportion of mediation effect in total effect: -11.6%, 95% CI: -89.7%, 66.6%) and the mannose to trans-4-hydroxyproline ratio (-19.4, 95% CI: -136%, 96.8%) partially mediate the relationship between HLA DR+ CD8br T cells and pancreatic cancer in nature. In addition, our analysis indicates that adrenate (-8.39%, 95% CI: -18.3%, 1.54%) plays a partial mediating role in the association between CD11c+ monocyte and pancreatic cancer, while cortisone (-26.6%, 95% CI: 138%, -84.8%) acts as a partial mediator between HLA DR+ CD4+ AC and pancreatic cancer.

Conclusion

This MR investigation provides evidence supporting the causal relationship between immune cell and pancreatic cancer, with plasma metabolites serving as mediators. Identifying immune cell phenotypes with potential causal effects on pancreatic cancer sheds light on its underlying mechanisms and suggests novel therapeutic targets.