bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteinuria and proximal tubular epithelial cells: correlation between immunofluorescence, histology, and degree of proteinuria
Authors: Chow Maria Bernadette CY , Yildiz Vedat , Biederman Laura , Dasgupta Alana , Satoskar Anjali A. , Chow Aaron , Nadasdy Tibor , Brodsky Sergey V.
Published: October 2024

Proteins are filtered from the blood through the glomerular filtration barrier. Filtered proteins are reabsorbed by proximal tubular epithelial cells (PTECs), which have been shown to possess the ability to regulate protein reabsorption. Histologically, these reabsorbed proteins are seen as tubular protein reabsorption droplets (TPRDs). Experimental studies indicate that PTECs play an important role in regulating proteinuria but the correlations between TPRD and the degree of proteinuria in human kidney biopsies have not been investigated in detail. Consecutive native kidney biopsies with non-proliferative glomerular disease performed at the OSUWMC for a 1-year period were analyzed. Cases with acute glomerular diseases and inadequate biopsies were excluded. The staining intensity and the percentage of TPRDs, as well as other morphologic parameters, were assessed. A total of 109 kidney biopsies were included in the study. A reverse correlation was identified between the percentage of albumin TPRDs and proteinuria (p = 0.047). There were positive correlations between proteinuria and the staining intensity for IgG TPRDs (p = 0.05) and the degree of acute tubular necrosis (ATN) (p = 0.015). In patients with no ATN, positive correlations between proteinuria and albumin and IgG TPRDs were seen, whereas in patients with ATN, these correlations were lost. A positive correlation was seen between proteinuria and chronic kidney injury. A strong correlation was noted between the degree of proteinuria and podocyte foot process effacement. Our data indicate that PTECs regulate proteinuria by absorbing proteins from the urine filtrate. Therefore, based on the human renal biopsy material, our study confirms that well-functioning renal PTECs play an important role in the regulation of proteinuria.
Associations between T-cell traits and narcolepsy type 1: new insights from a Mendelian randomization study
Authors: Chen Shiqin , Lv Tian , Li Zongshan , Pan Gonghua , Chen Yiqiao , Zhao Xingwang , Zhang Lisan
Published: October 2024

Background

Narcolepsy type 1 (NT1) is primarily caused by a malfunctioning immune system in which T-cells damage the hypothalamus. To elucidate the causal relationships between biomarkers in T-cells and NT1, we employed Mendelian randomization (MR) analysis.

Methods

We conducted a two-sample MR analysis utilizing genetically predicted T-cell traits to examine their effects on NT1. Genome-wide association study summary data were extracted from studies by Valeria (3,757 participants) for 211 T-cell traits, Ollila (6,073 cases and 84,856 controls) for NT1. The MR analysis was executed at two threshold levels. Inverse variance weighted, Wald ratio, weighted median, and MR-Egger regression methods were used for the MR analysis. Odds ratios (ORs) were calculated, and heterogeneity tests, as well as pleiotropy tests, were conducted.

Results

After Bonferroni correction at the significant level (p < 1.18 × 10−4), a higher ratio of naive CD4− CD8− T-cells was identified as a risk factor for NT1 (OR = 10.50; 95% CI: 6.98, 15.90, p = 3.89 ×10−29). Conversely, CD4 on HLA DR+ CD4+ T cells (mean fluorescence intensity, MFI) exhibited a negative correlation with NT1. At nominally significant levels (p < 0.05) for both threshold levels, HVEM (herpesvirus entry mediator) on naive CD8+ T cells (MFI) was suggested as a protective factor for NT1. Additionally, a higher ratio of CD25++ CD45RA− CD4 not regulatory T cells, CD127 on CD45RA− CD4 not regulatory T cells (MFI), CD127 on CD28+ CD4+ T cells (MFI), CD3 on HLA DR+ T cells (MFI), and CD3 on HLA DR+ CD4+ T cells (MFI) were suggested as risk factors for NT1.

Conclusion

This study confirmed the causal effects of CD4+ and CD8+ T-cells on NT1 and found several novel T-cell-related characteristics.
The neurocognitive correlates of DTI indicators of white matter disorganization in pediatric moderate-to-severe traumatic brain injury
Authors: Ignacio Daniel A. , Babikian Talin , Dennis Emily L. , Bickart Kevin C. , Choe Meeryo , Snyder Aliyah R. , Brown Anne , Giza Christopher C. , Asarnow Robert F.
Published: October 2024

Introduction

Neuroimaging has expanded our understanding of pediatric brain disorders in which white matter organization and connectivity are crucial to functioning. Paralleling the known pathobiology of many neurodevelopmental disorders, traumatic brain injury (TBI) in childhood can alter trajectories of brain development. Specifically, diffusion tensor imaging (DTI) studies in TBI have demonstrated white matter (WM) abnormalities that suggest microstructural disruptions that may underlie atypical neurodevelopment. The neurocognitive correlates of these previous findings will be explored in this study.

Methods

Indicators of WM organization were collected in 44 pediatric patients with moderate/severe TBI and 76 controls over two post-injury time points: T1 (8–20 weeks) and T2 (54–96 weeks). Our previous work identified two TBI subgroups based on information processing differences: one with slower interhemispheric transfer times (IHTT) of visual information than controls and another with comparable IHTT. We extend this prior work by evaluating neurocognitive trajectories associated with divergent WM structure post-injury in slow and normal IHTT TBI subgroups.

Results

At T1, both TBI subgroups performed significantly worse than controls on a norm-referenced working memory index (WMI), but only the Normal IHTT TBI subgroup significantly improved over the 12-month follow-up period (p = 0.014) to match controls (p = 0.119). In contrast, the Slow IHTT TBI subgroup did not show any recovery in working memory performance over time and performed more poorly than the control group (p < 0.001) at T2. Improvement in one of the two WMI subtests was associated with DTI indicators of WM disorganization in CC tracts to the precentral, postcentral, frontal, and parietal cortices. IHTT and WM mean diffusivity predicted 79% of the variance in cognitive recovery from T1 to T2 when also accounting for other known predictors of TBI recovery.

Discussion

In the year following TBI, some pediatric patients experienced persisting working memory disturbance while others exhibited recovery; stratification was based on an event-related potential marker. More or less improvement in neurocognition was also associated with the degree of WM disorganization. IHTT, measured post-acutely after TBI, and progression of WM disorganization over time predicted neurocognitive trajectories at the chronic timeframe - potentially representing a prognostic biomarker.
A review on targeted temperature management for cardiac arrest and traumatic brain injury
Authors: Ito Hiroshi , Hosomi Sanae , Nishida Takeshi , Nakamura Youhei , Iba Jiro , Ogura Hiroshi , Oda Jun
Published: October 2024

Therapeutic hypothermia inhibits organ damage by suppressing metabolism, which makes it a therapy of choice for treating various diseases. Specifically, it is often used to treat conditions involving central nervous system disorders where it is expected to positively impact functional prognosis. Although keeping the body temperature at a hypothermic level has been conventionally used, how to manage the body temperature correctly remains a topic of debate. Recently, the concept of temperature management has been proposed to improve the quality of body temperature control and avoid hyperthermia. This review focuses on the effect of temperature on the central nervous system in conditions involving central nervous system disorders and the practice of temperature management in clinical situations.
Reproductive hormones and sex chromosomes drive sex differences in the sleep–wake cycle
Authors: Ralston Micah , Ehlen J. Christopher , Paul Ketema
Published: October 2024

There are well-documented gender differences in the risk and severity of sleep disorders and associated comorbidities. While fundamental sex differences in sleep regulatory mechanisms may contribute to gender disparities, biological responses to sleep loss and stress may underlie many of the risks for sleep disorders in women and men. Some of these sex differences appear to be dependent on sex chromosome complement (XX or XY) and the organizational effects of reproductive hormones. Reproductive development plays a critical role in the ability of sex chromosomes and reproductive hormones to produce sex differences in sleep and wakefulness. Rodent models reveal that reproductive hormones drive many but not all sex differences in sleep–wake architecture. The ability of reproductive hormones to alter sleep are often dependent on responses to sleep loss and stress. However, in the absence of reproductive hormones (in gonadectomized rodents) sex differences in sleep amount and the ability to recover from sleep loss persist. The suprachiasmatic nucleus (SCN) and the ventrolateral preoptic nucleus (VLPO) of the hypothalamus play crucial regulatory roles in mediating the effects of reproductive hormones on the sleep–wake cycle. Taken together, the work reviewed here reveals that the reproductive hormone environment and sex chromosome complement may underlie gender disparities in sleep patterns and the risk for sleep disorders.
More than microglia: myeloid cells and biomarkers in neurodegeneration
Authors: Kodosaki Eleftheria , Bell Rosie , Sogorb-Esteve Aitana , Wiltshire Katharine , Zetterberg Henrik , Heslegrave Amanda
Published: October 2024

The role of myeloid cells (granulocytes and monocytes) in neurodegeneration and neurodegenerative disorders (NDD) is indisputable. Here we discuss the roles of myeloid cells in neurodegenerative diseases, and the recent advances in biofluid and imaging myeloid biomarker research with a focus on methods that can be used in the clinic. For this review, evidence from three neurodegenerative diseases will be included, Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS). We discuss the potential for these biomarkers to be used in humans with suspected NDD as prognostic, diagnostic, or monitoring tools, identify knowledge gaps in literature, and propose potential approaches to further elucidate the role of myeloid cells in neurodegeneration and better utilize myeloid biomarkers in the understanding and treatment of NDD.
Association between body roundness index and osteoarthritis: a cross-sectional analysis of NHANES 2011–2018
Authors: Liang Huazheng , Si Wenyue , Li Lin , Yang Kaiying
Published: October 2024

Objective

The objective of this study was to investigate the potential association between body roundness index (BRI) and the risk of osteoarthritis (OA) in US adults.

Methods

A cross-sectional analysis consisting of 20,232 participants was conducted using data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. Participants (≥20 years of age) were included and divided into OA and non-OA groups. Then, the demographics and characteristics of the participants were compared between the two groups. The relationship between BRI and OA was assessed using a multivariate logistic regression model with fitted smoothed curve techniques. Additionally, subgroup analyses on the correlation between BRI and OA were performed.

Results

The BRI scores in OA group were significantly higher than in the non-OA group (6.60 ± 2.62 vs. 5.46 ± 2.34, p < 0.001). Multivariate logistic analysis revealed that a significantly positive association between BRI and OA (OR = 1.12, 95% CI: 1.09–1.14, p < 0.001). In the subgroup analysis, only the race subgroup showed a significant difference between BRI and OA (p < 0.001).

Conclusion

Our findings highlight a significantly positive association between BRI and OA prevalence in the general US population.
Performance of DNA methylation and blood-borne tumor indicators in detecting colorectal neoplasia and adenomas: a comparative study with the fecal occult blood test
Authors: Chen Ming , Zhang Ji , Xu Bin , Yao Bilian , Wang Zhenzhen , Chen Ying , Cai Kaiyu , Zhang Chenli
Published: October 2024

Objectives

To evaluate the performance of stool methylated syndecan2 (mSDC2), methylated septin9 (mSEPT9), fecal occult blood test (FOBT), carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125) and carbohydrate antigen 199 (CA199) in detecting colorectal neoplasia and adenomas.

Methods

Blood-borne CEA, CA125, and CA199 levels were measured by electrochemiluminescence. The SDC2 methylation was detected by Methylation Detection Kit for Human SDC2 Gene (Real time PCR), and the SEPT9 methylation was detected by the Septin9 Gene Methylation Detection Kit based on PCR fluorescent probe assay. The colonoscopy combined with tissue biopsy pathology was used as a validation criterion for colorectal neoplasia.

Results

In detecting colorectal neoplasia, the AUCs of mSDC2, FOBT and mSEPT9 were 0.935 (95% CI: 0.915-0.956, P<0.001), 0.824 (95% CI: 0.617-1.000, P<0.001) and 0.671 (95% CI: 0.511-0.831, P<0.001), respectively. The sensitivity of mSDC2, FOBT and mSEPT9 were 100.0%, 66.7% and 40.0%, respectively. But the AUC of CEA, CA125 and CA199 were not statistically significant for colorectal neoplasia (all P>0.05). The combined application of mSEPT9 and mSDC2 showed the best predictive performance (AUC: 0.956, 95% CI: 0.887~1.000). For adenomas, the AUC of FOBT was extremely low (AUC: 0.524, 95% CI: 0.502-0.545, P=0.004). The CEA, CA125, CA199, mSEPT9 and mSDC2 were not statistically significant in detecting adenomas (all P>0.05).

Conclusions

For individual tests, FOBT and mSDC2 are relatively better indicators for detecting colorectal neoplasia compared to mSEPT9, CEA, CA125 and CA199. The combined form of mSEPT9 and mSDC2 to detect colorectal neoplasia has good predictive performance. However, none of these indicators demonstrated significant predictive power for detecting adenomas in our study.
Case report: Single gene testing and comprehensive genomic profiling in non-small cell lung cancer—a case series of divergent results from a large reference laboratory
Authors: Strickland Kyle C. , Nesline Mary K. , Previs Rebecca A. , Ko Heidi , Cooper Maureen , Rushton Jennifer R. , Wallen Zachary D. , Pabla Sarabjot , Conroy Jeffrey M. , Sausen Mark , Saini Kamal S. , Cantini Luca , Jensen Taylor J. , Caveney Brian J. , Eisenberg Marcia , Severson Eric A. , Ramkissoon Shakti
Published: October 2024

Clinical management of non-small cell lung cancer (NSCLC) requires accurate identification of tumor-specific genetic alterations to inform treatment options. Historically, providers have relied on single-gene testing (SGT) for actionable variants due to a perception of cost-effectiveness and/or efficient turnaround time compared to next-generation sequencing (NGS). However, not all actionable variants may be evaluated through SGT modalities, and an SGT approach can exhaust valuable tissue needed for more comprehensive analyses. In contrast, comprehensive genomic profiling (CGP) tests employ NGS to sequence megabases of DNA and RNA to evaluate all relevant molecular alterations, providing a broader genetic profile to identify actionable alterations that SGT may not accurately or efficiently assess. Here, we briefly describe four cases from a large reference laboratory in which actionable alterations were identified by CGP but not SGT. The discussion highlights the utility and advantages of using CGP to provide complete and timely treatment options and clinical trial opportunities for patients with NSCLC.
Comparative prediction of lymph node metastasis in pT1 colorectal cancer among Western and Japanese guidelines
Authors: Tanino Fumiaki , Yamashita Ken , Morimoto Shin , Takehara Yudai , Yamamoto Noriko , Kamigaichi Yuki , Nishimura Tomoyuki , Tanaka Hidenori , Takigawa Hidehiko , Urabe Yuji , Kuwai Toshio , Shimamoto Fumio , Oka Shiro
Published: October 2024

Background

Additional surgery with lymph node (LN) dissection is recommended for pT1 colorectal carcinoma (CRC) resected by endoscopy, based on pathological risk factors for LN metastasis (LNM), according to guidelines by the Japanese Society for Cancer of the Colon and Rectum (JSCCR), National Comprehensive Cancer Network (NCCN), and European Society for Medical Oncology (ESMO).

Methods

We retrospectively analyzed 560 consecutive patients with T1 CRC who underwent endoscopic resection alone (n=190) or initial or additional surgery with LN dissection (n=370) between 1992 and 2017 at Hiroshima University Hospital. Patients were classified into LNM low- and high-risk groups according to guidelines by the JSCCR, NCCN, and ESMO as follows. Patients without any specified pathological LNM risk factor were included in the LNM low-risk group, while the high-risk group comprised all other patients. We analyzed the LNM predictive ability of each guideline.

Results

The LNM high-risk rate, sensitivity, specificity, positive and negative predictive values, accuracy of LNM risk, and AUC for LNM predictive ability were 82%, 100%, 19%, 9%, 100%, 26% and 0.596 in the JSCCR guidelines; 52%, 98%, 52%, 15%, 99%, 56%, and 0.749 in the NCCN; and 54%, 98%, 50%, 15%, 99%, 54%, and 0.743 in the ESMO, respectively.

Conclusions

The JSCCR guidelines could diagnose LNM in all cases but had the highest false-positive rate. It is important to reduce unnecessary additional surgeries for pT1 CRCs after ER.
Case Report: New phenotype of late-onset Stüve–Wiedemann syndrome due to a C-terminal variant in the LIFR gene
Authors: Melnik Evgenia , Sharova Margarita , Kenis Vladimir , Morgul Anna , Zabnenkova Viktoria , Markova Tatiana
Published: October 2024

An early diagnosis of Stüve–Wiedemann syndrome is crucial due to its high neonatal lethality and the potential for autonomic dysfunction in children. Herein, we describe a patient with a late-onset, arthrogryposis-like phenotype form of Stüve–Wiedemann syndrome. While most cases result in neonatal complications, our patient only presented with camptodactyly, ulnar deviation of the wrist, and minor facial features at birth, resembling an arthrogryposis-like phenotype. The condition went undiagnosed until adolescence when noticeable gait and posture abnormalities emerged. Clinical and radiological findings confirmed the diagnosis of benign Stüve–Wiedemann syndrome with light autonomic dysregulation. Notably, our patient lacked the typical bent bone features but showed widened metaphyses and thickened femoral necks. Genetic analysis revealed a novel variant in the last exon of the LIFR gene, possibly explaining the mild phenotype. This case expands our understanding of Stüve–Wiedemann syndrome variability, aiding in earlier detection and better medical-genetic counseling.
Detoxification and benefits on acute heart failure in mice- of fuziline using glycyrrhetinic acid: an integrated biochemical analysis
Authors: Chang Nianwei , Hou Chunyu , Zhai Yue , Zhang Wenying , Hu Zengmei , Wang Xiaoying
Published: October 2024

Introduction

Aconiti Lateralis Radix Praeparata (lateral roots of Aconitum carmichaelii Debeaux, Fuzi), is commonly used to treat various cardiovascular diseases, particularly heart failure. However, its strong cardiotoxicity limits its clinical applicability. Glycyrrhizae radix et rhizoma, (the root of Glycyrrhiza uralensis Fisch., Gancao), is known to synergistically increase the cardiotonic effects of Fuzi and alleviate the myocardial injury caused by Fuzi to some extent. However, the detailed mechanism via which the combination of Fuzi and Gancao reduces toxicity and increases or preserves the efficacy of Fuzi requires further investigation.

Methods

Oxidative stress injury models in H9C2 cells and mice with acute heart failure were established to evaluate the optimal synergistic protective concentration of Fuziline and Glycyrrhetinic acid (GA). A GA probe was then synthesized and used for target fishing using chemical and biological methods. Finally, the target and its function were verified using fluorescence co-localization, Western blotting, protein interaction analysis, molecular docking, and calcium ion imaging.

Results

The best pharmacodynamic potential was achieved with a 1:1 or 2:1 ratio of Fuziline and GA concentrations. At these ratios, they regulated the protein levels of the downstream players of the Ca2+ signaling pathway via MDH2 and CALR, thereby balancing Ca2+ homeostasis in the myocardial tissue and mitigating the effects of heart failure.

Conclusion

This study aimed to investigate the compatibility of Fuziline and GA, the active metabolites of a traditional Chinese medicine (TCM) pair, in exerting their cardiac effects, identify the direct biological targets and verify the mechanism of compatibility.
The efficacy and safety of addition of pegylated interferon to long-term nucleos(t)ide analogue therapy on functional cure of chronic hepatitis B patient: a systematic review and meta-analysis
Authors: Zhang Xu , Yang Xianzhao , Tan Lingjie , Tian Yujia , Zhao Zhiren , Ru Shuying
Published: October 2024

Objective

This meta-analysis aims to assess the efficacy and safety of adding pegylated interferon (Peg-IFN) to long-term nucleos(t)ide analogs (NAs) treatment for achieving functional cure in patients with chronic hepatitis B (CHB).

Methods

This meta-analysis was registered in PROSPERO (CRD42024519116). We searched PubMed, Embase, Cochrane Library and Web of Science for randomized controlled trials that compared adding Peg-IFN to long-term NAs with NAs alone for the treatment of CHB. Relative risks (RR) and 95% confidence interval (CI) were pooled using a random-effects model.

Results

Seven trials with 692 participants were included. Compared to NAs monotherapy, sequential combination therapy significantly increased the HBsAg seroclearance rate (RR 4.37, 95%CI: 1.92–9.55; I2 = 0%) and HBsAg seroconversion rate (RR 3.98, 95%CI: 1.50–10.54; I2 = 0%), and the results reached statistical significance. Compared to NAs monotherapy, sequential combination therapy showed a significant increase in HBeAg seroclearance rate (RR 2.04; 95%CI: 0.47–8.82; I2 = 73%) and HBeAg seroconversion rate (RR 2.10; 95%CI: 0.41–10.71; I2 = 67%), but did not reach statistical significance. Sequential combination therapy was more likely to experience adverse events. Although most reactions are mild and reversible, vigilant monitoring for treatment-related adverse events is essential, with prompt intervention when needed.

Conclusion

For CHB patients on long-term NAs treatment, sequential combination therapy boosts HBsAg seroclearance and HBsAg seroconversion rates compared to monotherapy. However, it may increase adverse events. Additional studies are needed to thoroughly evaluate its clinical effectiveness, given the current limited research available.

Systematic Review Registration:

PROSPERO, identifier CRD42024519116.
Epileptic seizures induced by pentylenetetrazole kindling accelerate Alzheimer-like neuropathology in 5×FAD mice
Authors: Zou Yulian , Wang Chengyan , Li Huang , Zhong Meihua , Lin Jin , Hu Yan , Chen Zhou , Gan Chen-Ling
Published: October 2024

Clinical studies have shown that epileptic seizures worsen Alzheimer’s disease (AD) pathology and related cognitive deficits; however, the underlying mechanism is unclear. To assess the effects of seizures on the progression of AD, chronic temporal lobe epilepsy was induced in five familial AD mutation (5×FAD) mice by kindling with the chemoconvulsant pentylenetetrazole (PTZ) at 3–3.5 months of age. The amyloidogenic pathway, tauopathy, synaptic damage, neuronal death, neurological inflammatory response and associated kinase signaling pathway dysregulation were examined at 9 months of age. We found that APP, p-APP, BACE1, Aβ and kinase-associated p-tau levels were elevated after PTZ kindling in 5×FAD mice. In addition, PTZ kindling exacerbated hippocampal synaptic damage and neuronal cell death, as determined by scanning electron microscopy and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining, respectively. Finally, the levels of the neuroinflammation markers GFAP and Iba1, as well as the inflammatory cytokine IL-1β, were increased after PTZ insult. PTZ kindling profoundly exacerbated extracellular regulated kinase (ERK)-death-associated protein kinase (DAPK) signaling pathway overactivation, and acute ERK inhibitor treatment downregulated Aβ production and p-APP and p-tau levels in epileptic 5×FAD mice. In addition, long-term use of the antiseizure drug carbamazepine (CBZ) alleviated seizure-induced accelerated amyloid and tau pathology and ERK-DAPK overactivation in 5×FAD mice. Collectively, these results demonstrate that seizure-induced increases in AD-like neuropathology in 5×FAD mice are partially regulated by the ERK-DAPK pathway, suggesting that the ERK-DAPK axis could be a new therapeutic target for the treatment of AD patients with comorbid seizures.
Multi-branch fusion graph neural network based on multi-head attention for childhood seizure detection
Authors: Li Yang , Yang Yang , Song Shangling , Wang Hongjun , Sun Mengzhou , Liang Xiaoyun , Zhao Penghui , Wang Baiyang , Wang Na , Sun Qiyue , Han Zijuan
Published: October 2024

The most common manifestation of neurological disorders in children is the occurrence of epileptic seizures. In this study, we propose a multi-branch graph convolutional network (MGCNA) framework with a multi-head attention mechanism for detecting seizures in children. The MGCNA framework extracts effective and reliable features from high-dimensional data, particularly by exploring the relationships between EEG features and electrodes and considering the spatial and temporal dependencies in epileptic brains. This method incorporates three graph learning approaches to systematically assess the connectivity and synchronization of multi-channel EEG signals. The multi-branch graph convolutional network is employed to dynamically learn temporal correlations and spatial topological structures. Utilizing the multi-head attention mechanism to process multi-branch graph features further enhances the capability to handle local features. Experimental results demonstrate that the MGCNA exhibits superior performance on patient-specific and patient-independent experiments. Our end-to-end model for automatic detection of epileptic seizures could be employed to assist in clinical decision-making.
Utilizing VSWIR spectroscopy for macronutrient and micronutrient profiling in winter wheat
Authors: Gill Anmol Kaur , Gaur Srishti , Sneller Clay , Drewry Darren T.
Published: October 2024

This study explores the use of leaf-level visible-to-shortwave infrared (VSWIR) reflectance observations and partial least squares regression (PLSR) to predict foliar concentrations of macronutrients (nitrogen, phosphorus, potassium, calcium, magnesium, and sulfur), micronutrients (boron, copper, iron, manganese, zinc, molybdenum, aluminum, and sodium), and moisture content in winter wheat. A total of 360 fresh wheat leaf samples were collected from a wheat breeding population over two growing seasons. These leaf samples were used to collect VSWIR reflectance observations across a spectral range spanning 350 to 2,500 nm. These samples were then processed for nutrient composition to allow for the examination of the ability of reflectance to accurately model diverse chemical components in wheat foliage. Models for each nutrient were developed using a rigorous cross-validation methodology in conjunction with three distinct component selection methods to explore the trade-offs between model complexity and performance in the final models. We examined absolute minimum predicted residual error sum of squares (PRESS), backward iteration over PRESS, and Van der Voet’s randomized t-test as component selection methods. In addition to contrasting component selection methods for each leaf trait, the importance of spectral regions through variable importance in projection scores was also examined. In general, the backward iteration method provided strong model performance while reducing model complexity relative to the other selection methods, yielding R2 [relative percent difference (RPD), root mean squared error (RMSE)] values in the validation dataset of 0.84 (2.45, 6.91), 0.75 (1.97, 18.67), 0.78 (2.13, 16.49), 0.66 (1.71, 17.13), 0.68 (1.75, 14.51), 0.66 (1.72, 12.29), and 0.84 (2.46, 2.20) for nitrogen, calcium, magnesium, sulfur, iron, zinc, and moisture content on a wet basis, respectively. These model results demonstrate that VSWIR reflectance in combination with modern statistical modeling techniques provides a powerful high throughput method for the quantification of a wide range of foliar nutrient contents in wheat crops. This work has the potential to advance rapid, precise, and nondestructive field assessments of nutrient contents and deficiencies for precision agricultural management and to advance breeding program assessments.
Creating demand for unmet needs: Agile Storytelling
Authors: Mehta Jade , Long Emily , Bynagari Vidhur , Shojaei Fereshtehossadat , Shojaei Fatemehalsadat , O’Brien Andrew R. W. , Boustani Malaz
Published: October 2024

Introduction

The translational gap from the discovery of evidence-based solutions to their implementation in healthcare delivery organizations derives from an incorrect assumption that the need for change among executive, administrative, or clinical personnel is the same as the demand for change. For sickle cell disease (SCD), implementation of evidence-based guidelines is often delayed or obstructed due to lack of demand. This challenge allows for the persistence of resource limitations and care delivery models that do not meet the community's unique needs. Agile Storytelling is a process built on the scientific foundations of behavioral economics, complexity science, and network science to create local demand for the implementation of evidence-based solutions.

Methods

Agile Storytelling includes a design phase and a testing phase. The design phase converts the evidence-based solution into a minimally viable story of a hero, a villain, struggle, drama, and a resolution. The testing phase evaluates the effectiveness of the story via a series of storytelling sprints in the target local healthcare delivery organization. The efficacy of Agile Storytelling was tested in an iterative n-of-1 case study design.

Results

Agile Storytelling was used in a large, urban, healthcare system within the United States to facilitate implementation of national SCD best-practice guidelines. After repeated failures attempting to use national and local data regarding the high societal need to hire a SCD-specific social worker, an Agile change conductor using Agile Storytelling was able to create demand for the new position within a week. This decision has ultimately improved patient outcomes and led to the adoption of a specialized collaborative care team for SCD within the health network.

Discussion

Agile Storytelling can lead to structured, effective, and informed storytelling to create local demand within healthcare delivery organizations.
Analyzing urban water metabolism of Adama city using water mass balance method for advancing water sensitive interventions
Authors: Tesfay Abraha , Assefa Tibebu , Gebremariam Ephrem
Published: October 2024

Urban water metabolism focuses on measuring water inflows and outflows within a defined urban system. As an emerging concept, it provides valuable understandings into water flow dynamics, supporting evidence-based decision-making. One approach to quantify these flows is the urban water mass balance method, which accounts for both human-induced and natural water resources. By equating these flows, it identifies whether water movement within the system is linear or circular. The primary goal of water mass balance analysis is to assess how closely a city aligns with water-sensitive management approaches. However, urban metabolism studies are rare in developing countries, where cities often lack the experience to estimate water inflows and outflows for informed water-sensitive interventions. This study addresses this gap by analyzing Adama city in Ethiopia using the water mass balance method to measure its water metabolism. The result revealed that the city faces a negative water balance with outflows exceeding inflows by 46.89 million cubic meters annually. The results indicated that Adama’s water flow follows a linear “take-make-use-dispose” model. The imbalance in Adama’s water cycle is driven by urbanization, impervious surfaces, and climate change, which increase runoff and evaporation. The study found that 61.3% of the city’s water comes from a centralized system, with 90% sourced from distant rivers through a telecoupling system. In the city, inadequate water harvesting, high population density and intensive water use are worsening water scarcity. Urban water metabolism indicators reveal significant losses and indicating the need for water conservation efforts. Despite the reliance on centralized systems, the study identifies strong potential for decentralized solutions and alternative water harvesting. To tackle these challenges, the research recommends adopting water-sensitive strategies such as low-impact development, sustainable urban drainage systems, and water-sensitive urban design and planning. These approaches can reduce the negative effects of urbanization, mitigate urban water scarcity risks and improve water management through water sensitive management approach. The study also emphasizes the need for collaborative learning, community involvement, and innovative technologies, supported by legal frameworks to ensure effective water wise interventions. Shifting toward circular water management and decentralized water systems will boost Adama’s resilience and promote sustainable water resource management, making the city more internally self-sufficient.
A hapten design strategy to enhance the selectivity of monoclonal antibodies against malachite green
Authors: Wu Min-Fu , Xu Nuo , Li Sha , Huang Yi-Lan , Wu Min-Hua , Li Jia-Dong , Chen Ri-Sheng , Xiong Wen-Ming , Li Yong-Jun , Lei Hong-Tao , Huang Xin-An , Xu Zhen-Lin
Published: October 2024

Malachite green (MG), a triphenylmethane dye, is used in the aquaculture industry as a disinfectant and insect repellent due to its potent bactericidal and pesticidal properties. However, its use poses potential environmental and health risks. This study analyzed and designed two haptens using computer simulation. Serum data confirmed the feasibility of introducing an arm at the dimethylamine group. Subsequently, a highly selective monoclonal antibody strain was successfully prepared based on the hapten. After optimizing the working conditions of indirect competitive enzyme-linked immunosorbent assay (IC-ELISA), the IC50 value was 0.83 ng/mL, with a detection limit (IC10) of 0.08 ng/mL and a linear range of 0.19–3.52 ng/mL. The developed monoclonal antibody exhibited a crossover rate of less than 0.1% with other similar structures and can be used to establish an immunoassay.
Analyzing postoperative complications in colorectal cancer surgery: a systematic review enhanced by artificial intelligence
Authors: Andras Dan , Lazar Angela Madalina , Crețoiu Dragoş , Berghea Florian , Georgescu Dragos Eugen , Grigorean Valentin , Iacoban Simona Raluca , Mastalier Bogdan
Published: October 2024

Introduction

Colorectal cancer stands as a predominant cause of cancer-related mortality worldwide. Despite progressive strides in surgical methodologies, the specter of postoperative complications is very large, significantly impacting both morbidity and mortality rates. This review aims to meticulously examine existing scholarly works to gauge the prevalence, severity, and therapeutic approaches to postoperative complications arising from colorectal cancer surgeries.

Methods

Employing a systematic approach, this study reviewed 135 peer-reviewed publications from the period of 2000–2023. The corpus was organized into categories reflective of the postoperative complications discussed: anastomotic leakage, port-site metastases, small bowel adhesions and obstructions, thrombosis, ileus, postoperative infections, urinary dysfunctions, and cardiovascular dysfunctions. Advanced artificial intelligence tools were leveraged for in-depth literature searches and semantic analyses to pinpoint research lacunae.

Results

The analysis revealed that anastomotic leakage and postoperative infections garnered the majority of academic focus, representing 35% and 25% of the studies, respectively. Conversely, port-site metastases and cardiovascular dysfunctions were less frequently examined, accounting for merely 5% and 3% of the literature. The reviewed studies indicate a disparity in the reported prevalence rates of each complication, oscillating between 3% and 20%. Furthermore, the review identified a dearth of evidence-based management protocols, underscored by a pronounced heterogeneity in treatment guidelines.

Conclusions

The literature is replete with analyses on anastomotic leakage and postoperative infections; however, there exists a glaring scarcity of exhaustive research on other postoperative complications. This review emphasizes the pressing need for uniform treatment guidelines and spotlights areas in dire need of further research, aiming at the comprehensive enhancement of patient outcomes following colorectal cancer surgery.
Association of SPP1 and NCAPG genes with milk production traits in Chinese Holstein cows: polymorphism and functional validation analysis
Authors: Wang Chuanchuan , Chen Yafei , Zhao Jinyan , Feng Xiaofang , Ma Ruoshuang , Wang Hua , Xue Lin , Tian Jinli , Yang Lijuan , Gu Yaling , Zhang Juan
Published: October 2024

Milk production traits play an important role in dairy cattle breeding, and single nucleotide polymorphisms can be used as effective molecular markers for milk production trait marker-assisted breeding in dairy cattle. Based on the results of the preliminary GWAS, candidate genes SPP1 and NCAPG associated with milk production traits were screened. In this study, the aim was to screen and characterize the SNPs of SPP1 and NCAPG genes about milk production traits. Two SNPs and one haplotype block of the SPP1 gene and four SNPs and one haplotype block of the NCAPG gene were obtained by amplification, sequencing and association analysis, and all six SNPs were located in the exon region. Association analysis showed that all six SNPs were significantly associated with milk protein percentage. Linkage disequilibrium analysis showed that 2 SNPs of SPP1 (g. 36,700,265 C > T and g. 36,693,596 C > A) constituted a haplotype that correlated with milk protein percentage, and the dominant haplotype was H2H2, which was CCTT. 4 SNPs of NCAPG (g. 37,342,705 C > A, g. 37,343,379 G > T, g. 37,374,314 C > A and g. 37,377,857 G > A) constituted a haplotype associated with milk protein percentage, 305-days milk protein yield and 305 days milk yield. Tissue expression profiling results revealed that SPP1 and NCAPG had the highest expression in mammary tissue. Interference with SPP1 and NCAPG inhibited the proliferation of Bovine mammary epithelial cells. (BMECs), down-regulated the expression of PCNA, CDK2 and CCND1, up-regulated the expression of BAX and BAD, and promoted apoptosis. Reduced triglyceride synthesis in BMECs, down-regulated the expression of DGAT1, DGAT2, LPIN1, and AGPAT6.SPP1 and NCAPG are involved in the synthesis of milk proteins, and interfering with SPP1 and NCAPG decreased the secretion of β-casein, κ-casein, and αs1-casein, as well as up-regulated the CSN2 and CSN3 expression. The above results indicate that the SNP loci of SPP1 and NCAPG can be used as potential molecular markers to improve milk production traits in dairy cows, laying the foundation for marker-assisted selection. It also proves that SPP1 and NCAPG can be used as candidate key genes for milk production traits in dairy cows, providing new insights into the physiological mechanisms of lactation regulation in dairy cows.
Changes of vitamin D, Th17/Treg related cytokines and their correlations with disease activity in chronic spontaneous urticaria
Authors: Qiu Yangyang , Qiu Xiaoyan , Chen Yuting , Chen Meiqing , Huang Ling , Lin Xinyu , Wei Yi , Yang Ji , Gao Lujuan
Published: October 2024

Aims

To investigate levels of 25-hydroxyvitamin-D (25HVD), interleukin-17 (IL-17), IL-27, IL-35, and transforming growth factor β1 (TGF-β1) in chronic spontaneous urticaria (CSU) patients and their correlations with disease activity.

Methods

An observational, case-control study was conducted. Eighty-one CSU patients and fifty-eight healthy individuals were recruited into two groups. Serum levels of 25HVD, IL-17, IL-27, IL-35, TGF-β1 were determined via enzyme-linked immunosorbent assay (ELISA). Disease activity of CSU was assessed using urticaria activity score (UAS).

Results

Serum level of 25HVD was significantly lower in CSU group compared to control group (P < 0.001). Serum levels of IL-17 (P < 0.001), IL-27 (P < 0.001), TGF-β1 (P = 0.01) were significantly higher in CSU group than those in control group. In CSU group, the level of 25HVD was negatively associated with IgE (P < 0.01) and positively correlated with IL-35 (P < 0.01). In addition, serum level of IL-17 was negatively correlated with disease activity among female patients (P < 0.05).

Conclusion

Deficiency of 25HVD is associated with development of CSU, the underlying mechanism might be related with IL-35. Likewise, IL-17, IL-27, IL-35, and TGF-β1 might also contribute to development of CSU.
Mitochondrial Reactive Oxygen Species Dysregulation in Heart Failure with Preserved Ejection Fraction: A Fraction of the Whole
Authors: Martinez Caroline Silveira , Zheng Ancheng , Xiao Qingzhong
Published: October 2024

Heart failure with preserved ejection fraction (HFpEF) is a multifarious syndrome, accounting for over half of heart failure (HF) patients receiving clinical treatment. The prevalence of HFpEF is rapidly increasing in the coming decades as the global population ages. It is becoming clearer that HFpEF has a lot of different causes, which makes it challenging to find effective treatments. Currently, there are no proven treatments for people with deteriorating HF or HFpEF. Although the pathophysiologic foundations of HFpEF are complex, excessive reactive oxygen species (ROS) generation and increased oxidative stress caused by mitochondrial dysfunction seem to play a critical role in the pathogenesis of HFpEF. Emerging evidence from animal models and human myocardial tissues from failed hearts shows that mitochondrial aberrations cause a marked increase in mitochondrial ROS (mtROS) production and oxidative stress. Furthermore, studies have reported that common HF medications like beta blockers, angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and mineralocorticoid receptor antagonists indirectly reduce the production of mtROS. Despite the harmful effects of ROS on cardiac remodeling, maintaining mitochondrial homeostasis and cardiac functions requires small amounts of ROS. In this review, we will provide an overview and discussion of the recent findings on mtROS production, its threshold for imbalance, and the subsequent dysfunction that leads to related cardiac and systemic phenotypes in the context of HFpEF. We will also focus on newly discovered cellular and molecular mechanisms underlying ROS dysregulation, current therapeutic options, and future perspectives for treating HFpEF by targeting mtROS and the associated signal molecules.
Fruits, Spices and Honey Phenolic Compounds: A Comprehensive Review on Their Origin, Methods of Extraction and Beneficial Health Properties
Authors: Lazaridis Dimitrios G. , Kitsios Apostolos-Panagiotis , Koutoulis Antonios S. , Malisova Olga , Karabagias Ioannis K.
Published: October 2024

Numerous health benefits have been attributed in the last decades to the regular consumption of fruits, vegetables, herbs and spices, along with honey, in a balanced diet. In this context, the aim of the present review was to provide the literature with the most relevant studies focusing on the determination protocols of these polyphenols and other reducing agents in selected fruits (orange, lemon, grapefruit, prunus, apricot, peach, plum, sweet cherry), spices (oregano, cinnamon, clove, saffron, turmeric) and honey of different botanical origin (nectar or honeydew). In addition, the content and the extraction methods of these compounds, along with their metabolic pathway, have been critically evaluated and discussed. Results showed that all fruits, spices and honey exhibit a considerably high antioxidant activity, which is mainly owed to their phytochemical content. Therefore, a balanced diet consisting of the combination of the foods studied herein may comprise a shield against chronic and other pathophysiological disorders and may be achieved through consecutive educational programs for consumers at an international level.
Optimization and Implication of Adipose-Derived Stem Cells in Craniofacial Bone Regeneration and Repair
Authors: Gu Cong , Tang Qinghuang , Li Liwen , Chen YiPing
Published: October 2024

Adipose-derived stem cells (ADSCs) have emerged as a promising resource for craniofacial bone regeneration due to their high abundance and easy accessibility, significant osteogenic potential, versatile applications, and potential for personalized medicine, which underscore their importance in this field. This article reviews the current progress of preclinical studies that describe the careful selection of specific ADSC subpopulations, key signaling pathways involved, and usage of various strategies to enhance the osteogenic potential of ADSCs. Additionally, clinical case reports regarding the application of ADSCs in the repair of calvarial defects, cranio-maxillofacial defects, and alveolar bone defects are also discussed.
External Validation of the Predictive Accuracy of Clinical and Immunological Scores in COVID-19 Outcomes in a Retrospective Cohort Study
Authors: Tanase Alina Doina , Petrescu Emanuela-Lidia , Hoinoiu Teodora , Bojoga Daliana-Emanuela , Timar Bogdan
Published: October 2024

Background and Objectives: The COVID-19 pandemic has necessitated the development of reliable prognostic tools to predict patient outcomes and guide clinical decisions. This study evaluates the predictive utility of several clinical scores—PAINT, ISARIC4C, CHIS, COVID-GRAM, SOFA, and CURB-65—for in-hospital mortality among COVID-19 patients, comparing their effectiveness at admission and seven days post-symptom onset. Methods: In this retrospective cohort study conducted at the Clinical Emergency Hospital Pius Brînzeu in Timișoara, adult patients hospitalized with confirmed SARS-CoV-2 infection were included. The study was approved by the Local Ethics Committee, adhering to GDPR and other regulatory standards. Prognostic scores were calculated using patient data at admission and Day 7. Statistical analyses included ROC curves, Kaplan–Meier survival analysis, and multivariate Cox regression. Results: The study comprised 269 patients, with a notable distinction in outcomes between survivors and non-survivors. Non-survivors were older (mean age 62.12 years) and exhibited higher comorbidity rates, such as diabetes (55.56% vs. 31.06%) and cardiovascular diseases (48.15% vs. 29.81%). Prognostic scores were significantly higher among non-survivors at both time points, with PAINT and ISARIC4C showing particularly strong predictive performances. The AUROC for PAINT increased from 0.759 at admission to 0.811 by Day 7, while ISARIC4C demonstrated an AUROC of 0.776 at admission and 0.798 by Day 7. Multivariate Cox regression indicated that a PAINT score above 8.10 by Day 7 was associated with a hazard ratio (HR) of 4.9 (95% CI: 3.12–7.72) for mortality. Conclusions: The study confirms the strong predictive value of the PAINT, ISARIC4C, CHIS, COVID-GRAM, SOFA, and CURB-65 scores in determining mortality risk among hospitalized COVID-19 patients. These scores can significantly aid clinicians in early-risk stratification and resource prioritization, potentially enhancing patient management and outcomes in acute care settings.