bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental evolution of extremotolerant and extremophilic fungi under osmotic stress
Authors: Hariri Akbari Farhad , Song Zewei , Turk Martina , Gunde‐Cimerman Nina , Gostinčar Cene
Published: April 2024

Experimental evolution was carried out to investigate the adaptive responses of extremotolerant fungi to a stressful environment. For 12 cultivation cycles, the halotolerant black yeasts Aureobasidium pullulans and Aureobasidium subglaciale were grown at high NaCl or glycerol concentrations, and the halophilic basidiomycete Wallemia ichthyophaga was grown close to its lower NaCl growth limit. All evolved Aureobasidium spp. accelerated their growth at low water activity. Whole genomes of the evolved strains were sequenced. No aneuploidies were detected in any of the genomes, contrary to previous studies on experimental evolution at high salinity with other species. However, several hundred single‐nucleotide polymorphisms were identified compared with the genomes of the progenitor strains. Two functional groups of genes were overrepresented among the genes presumably affected by single‐nucleotide polymorphisms: voltage‐gated potassium channels in A. pullulans at high NaCl concentration, and hydrophobins in W. ichthyophaga at low NaCl concentration. Both groups of genes were previously associated with adaptation to high salinity. Finally, most evolved Aureobasidium spp. strains were found to have increased intracellular and decreased extracellular glycerol concentrations at high salinity, suggesting that the strains have optimised their management of glycerol, their most important compatible solute. Experimental evolution therefore not only confirmed the role of potassium transport, glycerol management, and cell wall in survival at low water activity, but also demonstrated that fungi from extreme environments can further improve their growth rates under constant extreme conditions in a relatively short time and without large scale genomic rearrangements.
Accurate prediction of dynamic protein–ligand binding using P‐score ranking
Authors: Ibrahim Peter E. G. F. , Zuccotto Fabio , Zachariae Ulrich , Gilbert Ian , Bodkin Mike
Published: April 2024

Protein–ligand binding prediction typically relies on docking methodologies and associated scoring functions to propose the binding mode of a ligand in a biological target. Significant challenges are associated with this approach, including the flexibility of the protein–ligand system, solvent‐mediated interactions, and associated entropy changes. In addition, scoring functions are only weakly accurate due to the short time required for calculating enthalpic and entropic binding interactions. The workflow described here attempts to address these limitations by combining supervised molecular dynamics with dynamical averaging quantum mechanics fragment molecular orbital. This combination significantly increased the ability to predict the experimental binding structure of protein–ligand complexes independent from the starting position of the ligands or the binding site conformation. We found that the predictive power could be enhanced by combining the residence time and interaction energies as descriptors in a novel scoring function named the P‐score. This is illustrated using six different protein–ligand targets as case studies.
Sarcopenia, adiposity and large discordance between cystatin C and creatinine‐based estimated glomerular filtration rate in patients with cancer
Authors: Hanna Paul E. , Ouyang Tianqi , Tahir Ismail , Katz‐Agranov Nurit , Wang Qiyu , Mantz Lea , Strohbehn Ian , Moreno Daiana , Harden Destiny , Dinulos James E. , Cosar Duru , Seethapathy Harish , Gainor Justin F. , Shah Sachin J. , Gupta Shruti , Leaf David E. , Fintelmann Florian J. , Sise Meghan E.
Published: April 2024

Background

Creatinine‐based estimated glomerular filtration rate (eGFRCRE) may overestimate kidney function in patients with sarcopenia. While cystatin C‐based eGFR (eGFRCYS) is less affected by muscle mass, it may underestimate kidney function in patients with obesity. We sought to evaluate the relationship between body composition defined by computed tomography (CT) scans and discordance between creatinine, eGFRCRE and eGFRCYS in adult patients with cancer.

Methods

This study is a cross‐sectional study of consecutive adults with cancer with an abdominal CT scan performed within 90 days of simultaneous eGFRCRE and eGFRCYS measurements between May 2010 and January 2022. Muscle and adipose tissue cross‐sectional areas were measured at the level of the third lumbar vertebral body using a validated deep‐learning pipeline. CT‐defined sarcopenia was defined using independent sex‐specific cut‐offs for skeletal muscle index (<39 cm2/m2 for women and <55 cm2/m2 for men). High adiposity was defined as the highest sex‐specific quartile of the total (visceral plus subcutaneous) adiposity index in the cohort. The primary outcome was eGFR discordance, defined by eGFRCYS > 30% lower than eGFRCRE; the secondary outcome was eGFRCYS > 50% lower than eGFRCRE. The odds of eGFR discordance were estimated using multivariable logistic regression modelling. Unadjusted spline regression was used to evaluate the relationship between skeletal muscle index and the difference between eGFRCYS and eGFRCRE.

Results

Of the 545 included patients (mean age 63 ± 14 years, 300 [55%] females, 440 [80.7%] non‐Hispanic white), 320 (58.7%) met the criteria for CT‐defined sarcopenia, and 136 (25%) had high adiposity. A total of 259 patients (48%) had >30% eGFR discordance, and 122 (22.4%) had >50% eGFR discordance. After adjustment for potential confounders, CT‐defined sarcopenia and high adiposity were both associated with >30% eGFR discordance (adjusted odds ratio [aOR] 1.90, 95% confidence interval [CI] 1.12–3.24; aOR 2.01, 95% CI 1.15–3.52, respectively) and >50% eGFR discordance (aOR 2.34, 95% CI 1.21–4.51; aOR 2.23, 95% CI 1.19–4.17, respectively). A spline model demonstrated that as skeletal muscle index decreases, the predicted difference between eGFRCRE and eGFRCYS widens considerably.

Conclusions

CT‐defined sarcopenia and high adiposity are both independently associated with large eGFR discordance. Incorporating valuable information from body composition analysis derived from CT scans performed as a part of routine cancer care can impact the interpretation of GFR estimates.
Attentional development is altered in toddlers with congenital heart disease
Authors: Bonthrone Alexandra F. , Kyriakopoulou Vanessa , Mason Luke , Chew Andrew , Falconer Shona , Kelly Christopher J. , Simpson John , Pushparajah Kuberan , Johnson Mark H. , Edwards A. David , Nosarti Chiara , Jones Emily J. H. , Counsell Serena J.
Published: April 2024

Background

Congenital Heart Disease (CHD) is the most common congenital abnormality. Survival rates are over 90%, however infants with CHD remain at high risk of attention and executive function impairments. These abilities are difficult to assess in toddlers because clinical assessments rely on language abilities which are commonly delayed in CHD. Our aim was to characterise visual attention in toddlers with CHD compared to controls and identify associations with parent‐rated effortful control.

Methods

Thirty toddlers with CHD (19 male, median (IQR) age at assessment 22.2 (22–23.1) months) and 66 controls from the developing human connectome project (36 male, age at assessment 22 (21.5–23.8) months) using eye‐tracking tasks designed to assess multiple components of visual attention. Analyses of co‐variance and regressions were used to identify differences between groups and relationships between gaze behaviours and parent‐rated effortful control.

Results

Toddlers with CHD were less accurate when switching behaviours (set‐shifting) [median (IQR) 79%, (28–100)] compared to controls [100% (86–100), pFDR = 0.032], with worse accuracy associated with lower parent‐rated effortful control in CHD but not controls (interaction pFDR = 0.028). Reaction times were slower during selective [CHD 1243 ms (986–1786), controls 1065 ms (0851–1397), pFDR<0.001] and exogenous attention tasks [CHD 312 ms (279–358), control 289 (249–331), (pFDR = 0.032) and endogenous attention was less mature (prolonged looks at facial stimuli CHD 670 ms (518–885), control 500 ms (250–625), (pFDR = 0.006). These results were unrelated to differences in cognition or socioeconomic status. In contrast, the allocation of attentional resources was preserved in CHD.

Conclusions

We identified a profile of altered attention and early executive functioning development in CHD. Eye‐tracking may provide clinically feasible, early objective measures of attention and executive function development in CHD.
Canal disinfection using Nd: YAG Laser, synchronized microbubble‐photodynamic activation, and carbon quantum dots on microhardness, smear layer removal, and extrusion bond strength of zirconia post to canal dentin. An invitro scanning electron microscopic analysis
Authors: Alkhudhairy Fahad
Published: April 2024

Evaluation of the impact of the latest root canal disinfectant, that is carbon quantum dots (CQDs), synchronized microbubble‐photodynamic activation (SYMPA), and Nd: YAG laser along with ethylenediaminetetraacetic acid (EDTA) as a final irrigant on the Marten hardness (MH), smear layer (SL) removal, and extrusion bond strength (EBS) of zirconia post to the canal dentin. Eighty intact single‐rooted premolars were obtained and disinfected using 0.5% chloramine‐T solution. Root canal preparation was performed using ProTaper files followed by obturation. The post space was prepared for prefabricated zirconia post and all the teeth were randomly divided into four groups based on the disinfection used (n = 20 each) Group 1: 5.25% NaOCl + 17% EDTA (Control), Group 2: Nd: YAG laser + 17% EDTA, Group 3: SYMPA + 17% EDTA, and Group 4: CQDs + 17% EDTA. MH, SL removal, and EBS of zirconia post‐bonded to root dentin were performed using a microhardness tester, scanning electron microscope (SEM), and universal testing machine, respectively. Both intragroup and intergroup comparisons were performed using one‐way analysis of variance (ANOVA) and posthoc‐Tukey test for significant difference (p < .05). Group 2 samples (Nd: YAG laser + 17% EDTA) (0.24 ± 0.06 GPa) exhibited highest values of MH. Samples in group 3 (SYMPA + 17% EDTA) treated teeth unveiled the lowest MH scores (0.13 ± 0.02 GPa). Moreover, the coronal third of Group 3 specimens (SYMPA and 17% EDTA) (1.54 ± 0.31) eliminated SL from the canal with the greatest efficacy as well as presented the highest EBS (10.13 ± 0.69 MPa). However, the apical third of Group 1 samples (5.25% NaOCl + 17% EDTA) (2.95 ± 0.33) exhibited the least efficient elimination of SL from the radicular dentin as well as the lowest bond strength (5.11 ± 0.19 MPa) of zirconia post to the dentin. The SYMPA technique with 17% EDTA proved highly effective in removing the SL from canal dentin and enhancing the EBS of zirconia posts. The least preferable method for SL removal and MH improvement was found to be 5.25% NaOCl + 17% EDTA. CQDs and Nd: YAG laser demonstrated satisfactory smear layer removal properties from the canal, along with achieving appropriate bond strength of zirconia posts.

Research Highlights

Nd: YAG laser and 17% EDTA as canal disinfectant exhibited the highest values of MH.

Specimens irrigated with SYMPA and 17% EDTA eliminated SL from the canal with the greatest efficacy.

The coronal third of Group 3 (SYMPA + 17% EDTA) samples unveiled the highest zirconia post‐bond integrity score to the canal dentin.

Cohesive failure was a dominant failure type among different experimental groups.
Neuropathogenic role of astrocyte‐derived extracellular vesicles in HIV‐associated neurocognitive disorders
Authors: Chemparathy Divya T. , Ray Sudipta , Ochs Chase , Ferguson Natasha , Gawande Dinesh Y. , Dravid Shashank M. , Callen Shannon , Sil Susmita , Buch Shilpa
Published: April 2024

Our previous findings demonstrated that astrocytic HIF‐1α plays a major role in HIV‐1 Tat‐mediated amyloidosis which can lead to Alzheimer's‐like pathology‐a comorbidity of HIV‐Associated Neurocognitive Disorders (HAND). These amyloids can be shuttled in extracellular vesicles, and we sought to assess whether HIV‐1 Tat stimulated astrocyte‐derived EVs (ADEVs) containing the toxic amyloids could result in neuronal injury in vitro and in vivo. We thus hypothesized that blocking HIF‐1α could likely mitigate HIV‐1 Tat‐ADEV‐mediated neuronal injury. Rat hippocampal neurons when exposed to HIV‐1 Tat‐ADEVs carrying the toxic amyloids exhibited amyloid accumulation and synaptodendritic injury, leading to functional loss as evidenced by alterations in miniature excitatory post synaptic currents. The silencing of astrocytic HIF‐1α not only reduced the biogenesis of ADEVs, as well as amyloid cargos, but also ameliorated neuronal synaptodegeneration. Next, we determined the effect of HIV‐1 Tat‐ADEVs carrying amyloids in the hippocampus of naive mice brains. Naive mice receiving the HIV‐1 Tat‐ADEVs, exhibited behavioural changes, and Alzheimer's ’s‐like pathology accompanied by synaptodegeneration. This impairment(s) was not observed in mice injected with HIF‐1α silenced ADEVs. This is the first report demonstrating the role of amyloid‐carrying ADEVs in mediating synaptodegeneration leading to behavioural changes associated with HAND and highlights the protective role of HIF‐1α.
Diagnostic Model for Proliferative HCC Using LI‐RADS: Assessing Therapeutic Outcomes in Hepatectomy and TKI‐ICI Combination
Authors: Lu Mengtian , Yan Zuyi , Qu Qi , Zhu Guodong , Xu Lei , Liu Maotong , Jiang Jifeng , Gu Chunyan , Chen Ying , Zhang Tao , Zhang Xueqin
Published: April 2024

Background

Proliferative hepatocellular carcinoma (HCC), aggressive with poor prognosis, and lacks reliable MRI diagnosis.

Purpose

To develop a diagnostic model for proliferative HCC using liver imaging reporting and data system (LI‐RADS) and assess its prognostic value.

Study Type

Retrospective.

Population

241 HCC patients underwent hepatectomy (90 proliferative HCCs: 151 nonproliferative HCCs), divided into the training (N = 167) and validation (N = 74) sets. 57 HCC patients received combination therapy with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs).

Field Strength/Sequence

3.0 T, T1‐ and T2‐weighted, diffusion‐weighted, in‐ and out‐phase, T1 high resolution isotropic volume excitation and dynamic gadoxetic acid‐enhanced imaging.

Assessment

LI‐RADS v2018 and other MRI features (intratumoral artery, substantial hypoenhancing component, hepatobiliary phase peritumoral hypointensity, and irregular tumor margin) were assessed. A diagnostic model for proliferative HCC was established, stratifying patients into high‐ and low‐risk groups. Follow‐up occurred every 3–6 months, and recurrence‐free survival (RFS), progression‐free survival (PFS) and overall survival (OS) in different groups were compared.

Statistical Tests

Fisher's test or chi‐square test, t‐test or Mann–Whitney test, logistic regression, Harrell's concordance index (C‐index), Kaplan–Meier curves, and Cox proportional hazards. Significance level: P < 0.05.

Results

The diagnostic model, incorporating corona enhancement, rim arterial phase hyperenhancement, infiltrative appearance, intratumoral artery, and substantial hypoenhancing component, achieved a C‐index of 0.823 (training set) and 0.804 (validation set). Median follow‐up was 32.5 months (interquartile range [IQR], 25.1 months) for postsurgery patients, and 16.8 months (IQR: 13.2 months) for combination‐treated patients. 99 patients experienced recurrence, and 30 demonstrated tumor nonresponse. Differences were significant in RFS and OS rates between high‐risk and low‐risk groups post‐surgery (40.3% vs. 65.8%, 62.3% vs. 90.1%, at 5 years). In combination‐treated patients, PFS rates differed significantly (80.6% vs. 7.7% at 2 years).

Data Conclusion

The MR‐based model could pre‐treatment identify proliferative HCC and assist in prognosis evaluation.

Level of Evidence

4.

Technical Efficacy

Stage 2.
Sofosbuvir–velpatasvir in children 3–17 years old with hepatitis C virus infection
Authors: Jonas Maureen M. , Romero Rene , Rosenthal Philip , Lin Chuan‐Hao , Verucchi Gabriella , Wen Jessica , Balistreri William F. , Whitworth Suzanne , Bansal Sanjay , Leung Daniel H. , Narkewicz Michael R. , Gonzalez‐Peralta Regino P. , Mangia Alessandra , Karnsakul Wikrom , Rao Girish S. , Shao Jiang , de Jong Jan , Parhy Bandita , Osinusi Anu , Kersey Kathryn , Murray Karen F. , Sokal Etienne M. , Schwarz Kathleen B.
Published: April 2024

Background

The safety and efficacy of sofosbuvir–velpatasvir in children aged 3–17 years with chronic hepatitis C virus (HCV) infection of any genotype were evaluated.

Methods

In this Phase 2, multicenter, open‐label study, patients received once daily for 12 weeks either sofosbuvir–velpatasvir 400/100 mg tablet (12–17 years), 200/50 mg low dose tablet or oral granules (3–11 years and ≥17 kg), or 150/37.5 mg oral granules (3–5 years and <17 kg). The efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Dose appropriateness was confirmed by intensive pharmacokinetics in each age group.

Findings

Among 216 patients treated, 76% had HCV genotype 1% and 12% had genotype 3. Rates of SVR12 were 83% (34/41) among 3–5‐year‐olds, 93% (68/73) among 6–11‐year‐olds, and 95% (97/102) among 12–17‐year‐olds. Only two patients experienced virologic failure. The most common adverse events were headache, fatigue, and nausea in 12–17‐year‐olds; vomiting, cough, and headache in 6–11‐year‐olds; and vomiting in 3–5‐year‐olds. Three patients discontinued treatment because of adverse events. Four patients had serious adverse events; all except auditory hallucination (n = 1) were considered unrelated to study drug. Exposures of sofosbuvir, its metabolite GS‐331007, and velpatasvir were comparable to those in adults in prior Phase 2/3 studies. Population pharmacokinetic simulations supported weight‐based dosing for children in this age range.

Interpretation

The pangenotypic regimen of sofosbuvir–velpatasvir is highly effective and safe in treating children 3–17 years with chronic HCV infection.
Does Meal or Water Intake Affect Ultrasound Attenuation Coefficient Estimate?
Authors: Ferraioli Giovanna , De Silvestri Annalisa , Barr Richard G.
Published: April 2024

Objectives

To assess whether meal or water intake may affect the measurement of the ultrasound (US) attenuation coefficient (AC) imaging, a parameter that is directly related to liver fat content.

Methods

The study was performed in two centers (Italy and USA). AC was obtained using the ATI algorithm implemented in the Aplio i‐series US systems (Canon Medical Systems, Japan) by one operator at each center. Measurements were performed at baseline and 5, 15, 30, 45 minutes after drinking 500 mL of water (group 1), or 30, 45, 60, 90, 120 minutes after eating a meal of about 600 kcal (group 2). Multilevel generalized estimating equations for repeated measures were used for the statistical analysis to consider the clustered nature of the data.

Results

Twenty‐six individuals were enrolled: 11 (10 females; age, 43.7 ± 12.5 years) in Italy and 15 (10 females; age, 60.7 ± 6.3 years) in USA. At B‐mode US, 10 (38.5%) had liver steatosis. The baseline AC values, in decibel/centimeter/megahertz, were 0.64 (0.12) in group 1 and 0.66 (0.13) in group 2. There was not any significant difference in AC values at every time‐point after water or meal intake either in group 1 or group 2. This result did not change including sex, age, and skin‐to‐liver capsule into the models.

Conclusions

The measurement of the AC, which is a biomarker of liver steatosis, does not require a fasting state and drinking water does not affect the result.
Surgical complications and subsequent revision surgeries among noma cases treated in Ethiopia
Authors: Gebretsadik Heron Gezahegn
Published: April 2024

Introduction

Noma, an overlooked infectious disease, inflicts severe facial tissue damage, posing substantial challenges in patient care. This study delves into surgical complications and subsequent revision surgeries among noma cases treated in Ethiopia.

Materials and Methods

The research employed a cross‐sectional retrospective review of medical records treated between 2007 and 2019 retrieved from the Facing Africa database.

Results

The review encompasses 235 noma cases. Twenty‐four cases (19 females and 5 males) experienced various complications, predominately major complications leading to subsequent revision surgeries. The identified complications included flap necrosis, abscess formation, tenderness, graft site infection, flap bulking, dental misalignment, corner of the mouth dehiscence, infected bone and plate, flap malpositioning, restricted mouth opening with ankylosis, neuropathic pain, recurrent flap infection, and offensive odor. Revision surgeries included wound cleansing, abscess drainage, skin graft removal, exploratory surgery, wound care, debulking, scar removal, debridement, trismus release, commisuroplasty, and flap repositioning.

Conclusion

These findings illuminate the intricacies of noma surgery in Ethiopia, emphasizing the importance of understanding the nature and frequency of complications for optimizing treatment outcomes. Insights from this study can guide healthcare providers, especially novice surgeons, and policymakers, in refining surgical interventions and enhancing outcomes for noma patients. Improved knowledge in this realm is crucial for advancing patient care and developing targeted interventions.

Level of Evidence

5.
Temporal evolution of plankton and particles distribution across a mesoscale front during the spring bloom
Authors: Panaïotis Thelma , Poteau Antoine , Riquier Émilie Diamond , Catalano Camille , Courchet Lucas , Motreuil Solène , Coppola Laurent , Picheral Marc , Irisson Jean‐Olivier
Published: April 2024

The effect of mesoscale features on the distribution of planktonic organisms are well documented. Yet, the interaction between these spatial features and the temporal scale, which can result in sudden increases of the planktonic biomass, is less known and not described at high resolution. A permanent mesoscale front in the Ligurian Sea (north‐western Mediterranean) was repeatedly sampled between January and June 2021 using a SeaExplorer glider equipped with an Underwater Vision Profiler 6 (UVP6), a versatile in situ imager. Both plankton and particle distributions were resolved throughout the spring bloom to assess whether the front was a location of increased zooplankton concentration and whether it constrained particle distribution. Over the 5 months, the glider performed more than 5000 dives and the UVP6 collected 1.1 million images. We focused our analysis on shallow (300 m) transects, which gave a horizontal resolution of 900 m. About 13,000 images of planktonic organisms were retained. Ordination methods applied to particles and plankton concentrations revealed strong temporal variations during the bloom, with a succession of various zooplankton communities. Changes in particle abundance and size could be explained by changes in the plankton community. The front had a strong influence on particle distribution, while the signal was not as clear for plankton, probably because of the relatively small number of imaged organisms. This work confirms the need to sample both plankton and particles at fine scale to understand their interactions, a task for which automated in situ imaging is particularly adapted.
Long‐Term Globus Pallidus Internus Deep Brain Stimulation in Pediatric Non‐Degenerative Dystonia: A Cohort Study and a Meta‐Analysis
Authors: Duga Valentina , Giossi Riccardo , Romito Luigi Michele , Stanziano Mario , Levi Vincenzo , Panteghini Celeste , Zorzi Giovanna , Nardocci Nardo
Published: April 2024

Background

The evidence in the effectiveness of deep brain stimulation in children with medication‐refractory non‐degenerative monogenic dystonia is heterogeneous and long‐term results are sparse.

Objectives

The objective is to describe long‐term outcomes in a single‐center cohort and compare our results with a meta‐analysis cohort form literature.

Methods

We performed a retrospective single‐center cohort study including consecutive pediatric patients with non‐degenerative genetic or idiopathic dystonia treated with globus pallidus internus deep brain stimulation at our center and a systematic review and individual‐patient data meta‐analysis with the same inclusion criteria. The primary outcome was the change from baseline in the Burke‐Fahn‐Marsden Dystonia Rating Scale‐movement (BFMDRS‐M) score.

Results

The clinical cohort included 25 patients with a mean study follow‐up of 11.4 years. The meta‐analysis cohort included 224 patients with a mean follow‐up of 3 years. Overall, the BFMDRS‐M mean improvements at 1 year and at last follow‐up were 41% and 33% in the clinical cohort and 58.9% and 57.2% in the meta‐analysis cohort, respectively. TOR1A‐dystonia showed the greatest and most stable BFMDRS‐M improvement in both cohorts at 1 year and at last follow‐up (76.3% and 74.3% in the clinical cohort; 69.6% and 67.3% in the meta‐analysis cohort), followed by SGCE‐dystonia (63% and 63.9% in the meta‐analysis cohort). THAP1‐dystonia (70.1% and 29.8% in the clinical cohort; 52.3% and 42.0% in the meta‐analysis cohort) and KMT2B‐dystonia (33.3% and 41.3% in the clinical cohort; 38.0% and 26.7% in the meta‐analysis cohort) showed a less pronounced or sustained response.

Conclusion

Globus pallidus deep brain stimulation long‐term treatment seems effective with a possible gene‐specific differential effect. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Human Breast Milk Exosomal miRNAs are Influenced by Premature Delivery and Affect Neurodevelopment
Authors: Ma Ling , Huo Yanyan , Tang Qingyuan , Wang Xiulian , Wang Weiqin , Wu Dan , Li Yicheng , Chen Lingyan , Wang Shasha , Zhu Yiwen , Wang Wenli , Liu Yuan , Xu Nanjie , Chen Li , Yu Guangjun , Chen Jinjin
Published: April 2024

Scope

This study investigates the exosomal microRNA (miRNA) profiles of term and preterm breast milk, including the most abundant and differentially expressed (DE) miRNAs, and their impact on neurodevelopment in infants.

Methods and Results

Mature milk is collected from the mothers of term and preterm infants. Using high‐throughput sequencing and subsequent data analysis, exosomal miRNA profiles of term and preterm human breast milk (HBM) are acquired and it is found that the let‐7 and miR‐148 families are the most abundant miRNAs. Additionally, 23 upregulated and 15 downregulated miRNAs are identified. MiR‐3168 is the most upregulated miRNA in preterm HBM exosome, exhibiting targeting activity toward multiple genes involved in the SMAD and MAPK signaling pathways and playing a crucial role in early neurodevelopment. Additionally, the effects of miR‐3168 on neurodevelopment is confirmed and it is determined that it is an essential factor in the differentiation of neural stem cells (NSCs).

Conclusion

This study demonstrates that miRNA expression in breast milk exosomes can be influenced by preterm delivery, thereby potentially impacting neurodevelopment in preterm infants.
Phenylbutyric acid inhibits hypoxia‐induced trophoblast apoptosis and autophagy in preeclampsia via the PERK/ATF‐4/CHOP pathway
Authors: Li Yinfeng , Guo Yongjie , Wu Dan , Ai Ling , Wu Rongrong , Ping Zepeng , Zhu Kangyuan
Published: April 2024

Preeclampsia (PE) is a common pregnancy complication with a high mortality rate. Abnormally activated endoplasmic reticulum stress (ERS) is believed to be responsible for the destruction of key placental cells‐trophoblasts. Phenylbutyric acid (4‐PBA), an ERS inhibitor, is involved in regulating the development of ERS‐related diseases. At present, how 4‐PBA affects trophoblasts and its mechanisms is still unclear. In this study, PE cell models were established by stimulating HTR‐8/SVneo cells with hypoxia. To verify the underlying mechanisms of 4‐PBA on PE, CCT020312, an activator of PERK, was also used. The results showed that 4‐PBA restored hypoxia‐induced trophoblast viability, inhibited HIF‐1α protein expression, inflammation, and PERK/ATF‐4/CHOP pathway. Hoechst 33342 staining and flow cytometry results confirmed that 4‐PBA decreased hypoxia‐induced apoptosis in trophoblasts. The results of the JC‐1 analysis and apoptosis initiation enzyme activity assay also demonstrated that 4‐PBA inhibited apoptosis related to the mitochondrial pathway. Furthermore, by detecting autophagy in trophoblasts, an increased number of autophagic vesicles, damaged mitochondria, enhanced dansylcadaverine fluorescence, enhanced levels of autophagy proteins Beclin‐1, LC3II, and decreased p62 were seen in hypoxia‐stimulated cells. These changes were reversed by 4‐PBA. Furthermore, it was observed that CCT020312 reversed the effects of 4‐PBA on the viability, apoptosis, and autophagosome number of hypoxia‐induced trophoblasts. In summary, 4‐PBA reduces autophagy and apoptosis via the PERK/ATF‐4/CHOP pathway and mitochondrial pathway, thereby restoring the viability of hypoxic trophoblasts. These findings provide a solid evidence base for the use of 4‐PBA in PE treatment and guide a new direction for improving the outcomes of patients with PE.
Nanocarrier‐embedded gels: Precision drug delivery via liposomal and niosomal platforms
Authors: Trucillo Paolo , Nebbioso Viviana , Brancaccio Raffaele , Gigante Laura
Published: April 2024

Recent research in drug delivery has significantly advanced our knowledge of liposome and niosome‐based gels, contributing to the dynamic landscape of pharmaceutical advancements. The incorporation of these vesicular carriers into gel formulations enhanced stability, while prolonging shelf‐life and improving the bioavailability of encapsulated molecules. The synergy between liposomes/niosomes and gel matrices, facilitated by a robust gel structure, provided a protective environment, ensuring sustained drug release and prolonged stability. Liposome‐based gels proved to be versatile carriers for various therapeutic applications, demonstrating efficiency in solubilizing poorly soluble drugs and acting as potent penetration enhancers for optimal skin delivery. Today, the incorporation of liposomes in gels serves as local depots, thus being a fundamental condition for sustained and controlled drug release to optimize patient's outcomes. Insights into niosome‐based gels reveal their potential in overcoming conventional drug delivery challenges, positioning them as promising platforms for controlled and targeted drug release due to enhanced stability. Recent investigations highlight the adaptability of niosomal gels in encapsulating both hydrophobic and hydrophilic drugs, ensuring superior stability and sustained release. The tunable properties of niosomal gels also contributed to optimize bioadhesion and permeation across biological membranes. The primary objective of this work is to present the cutting‐edge findings in liposome and niosome‐based gel research, highlighting their path in modern drug delivery. These innovative solutions offer more efficient and targeted therapeutic interventions, addressing the ever‐evolving landscape of medicine.
Dragline silk fibers from golden orb‐web spider Trichonephila clavata ensure structural and mechanical robustness against ultraviolet radiation
Authors: Ueda Yuushiro , Yazawa Kenjiro
Published: April 2024

A diurnal spider, Trichonephila clavata (T. clavata), is often called a golden orb‐weaver because its dragline or lifeline silk fibers exhibit a golden color. However, little is known about the biological roles of the golden pigment. Meanwhile, Araneus ventricosus, which is a nocturnal spider, spins colorless silk fibers. Here, we investigated the effect of ultraviolet (UV) irradiation on physical properties of silk fibers obtained from these diurnal and nocturnal spiders. After UV exposure, the dragline silk of the nocturnal spiders appeared abraded and became insoluble due to gelation, whereas the diurnal spider silk remained intact. A dynamic mechanical thermal analysis under different humidity conditions revealed that the storage modulus of the silk from the nocturnal spider dropped markedly at low humidity levels after UV irradiation. This indicated that the molecular weight of this silk degraded under UV exposure and that the number of terminal amino and carboxyl groups increased due to the breakage of the main protein chains. In contrast, the structural and mechanical properties of the diurnal spider silk were maintained regardless of the UV irradiation. Therefore, the golden pigments in the dragline silk of T. clavata most likely played a role in protecting the silk from UV damage.
Association of elevated tricuspid regurgitation velocity with cerebrovascular and kidney disease in children with sickle cell disease
Authors: Ilonze Chibuzo , Rai Parul , Galadanci Najibah , Zahr Rima , Okhomina Victoria I. , Kang Guolian , Padmanabhan Dakshin , Lebensburger Jeffrey , Alishlash Ammar Saadoon
Published: April 2024

Background

Tricuspid regurgitation velocity (TRV), measured by echocardiography, is a surrogate marker for pulmonary hypertension. Limited pediatric studies have considered the association between TRV and surrogate markers of end‐organ disease.

Methods

We conducted a cross‐sectional study that evaluated the prevalence of elevated TRV ≥2.5 m/s and its associations with renal and cerebrovascular outcomes in children with sickle cell disease (SCD) 1–21 years of age in two large sickle cell cohorts, the University of Alabama at Birmingham (UAB) sickle cell cohort, and the Sickle Cell Clinical Research and Intervention Program (SCCRIP) cohort at St. Jude Children's Research Hospital. We hypothesized that patients with SCD and elevated TRV would have higher odds of having either persistent albuminuria or cerebrovascular disease.

Results

We identified 166 children from the UAB cohort (mean age: 13.49 ± 4.47 years) and 325 children from the SCCRIP cohort (mean age: 13.41 ± 3.99 years) with echocardiograms. The prevalence of an elevated TRV was 21% in both UAB and SCCRIP cohorts. Elevated TRV was significantly associated with cerebrovascular disease (odds ratio [OR] 1.88, 95% confidence interval [CI]: 1.12–3.15; p = .017) and persistent albuminuria (OR 1.81, 95% CI: 1.07–3.06; p = .028) after adjusting for age, sex, treatment, and site.

Conclusion

This cross‐sectional, multicenter study identifies associations between surrogate markers of pulmonary hypertension with kidney disease and cerebrovascular disease. A prospective study should be performed to evaluate the longitudinal outcomes for patients with multiple surrogate markers of end‐organ disease.
A novel strategical approach to mitigate low velocity impact damage in composite laminates
Authors: Amorim L. , Santos A. , Nunes J. P. , Dias G. , Viana J. C.
Published: April 2024

This paper describes a new interleaving methodology to improve composite laminates' low velocity impact (LVI) damage resistance. The approach relies on analyzing interlaminar stress in a conventional aircraft laminate to determine the appropriate interleaving strategy. A model was built to identify the larges interlaminar stress, and two interleaving strategies were defined, normal and shear stress. Four thin interleaving veils were used to validate strategies. Non‐ and interleaved laminates were submitted to LVI tests at 13.5, 25 and 40 (J) of energy. Despite interleaved laminates revealed an increase in thickness and resin volume fraction compared to the reference, they were limited to 10% and 7.6% on shear stress interleaved layups. Interleaved laminates also demonstrated an improved external and internal LVI damage resistance, especially when shear stress interleaving strategy was adopted, preventing external damage and mitigating internal damage up to 59%. No correlation between the veil's type and impact damage demonstrates the importance of interleaving strategies over the veil's characteristics.

Highlights

Simplified quasi‐static elastic Abaqus model identified the largest in‐plane normal (axial and transversal) and shear interlaminar stresses;

Four thin veils were used to validate interleaving strategies adopted;

All laminates were produced using the same conditions to minimize process influence on experimental tests;

Under low velocity impact (LVI) tests, interleaving laminates in the largest shear stress interlaminar can prevent external damage and mitigate internal damage up to 59%, comparing to the reference;

No correlation between the veils and damage demonstrates the relevance of the interleaving strategy over the veil type.
Registration of ‘S16‐16814R’: A glyphosate‐tolerant, high‐oleic soybean cultivar
Authors: Chen Pengyin , Shannon Grover , Vieira Caio Canella , Lee Dongho , do Nascimento Emanuel Ferrari , Hunt Destiny , Lee Yi‐Chen , Ali Md Liakat , Crisel Melissa , Smothers Scotty , Clubb Michael , Mitchum Melissa Goellner , Meinhardt Clinton G. , Usovsky Mariola
Published: April 2024

There is a demand for soybean [Glycine max (L.) Merr.] cultivars with more functional soybean oil for food and industrial applications. Soybean breeding programs have devoted more efforts to developing high‐yielding soybean cultivars with elevated oil content and improved fatty acid profiles. The University of Missouri – Fisher Delta Research, Extension, and Education Center soybean breeding program has developed and released the high‐oleic soybean cultivar ‘S16‐16814R’ (Reg. no. CV‐561, PI 704911). It is a maturity group 4‐late (relative maturity 4.9), glyphosate‐tolerant (Roundup Ready 1) soybean cultivar with high oleic (84.0%) acid content and a reduced linolenic (3.5%) acid content. S16‐16814R is resistant to multiple nematode species, including soybean cyst nematode races 2 (HG Type 1.2.5.7), 3 (HG Type 5.7), and 5 (HG Type 2.5.7); southern root‐knot nematode; and reniform nematode. S16‐16814R was evaluated from 2017 to 2020 in 61 environments across eight southern US states. It averaged 92% of the check mean for yield, indicating competitive yield performance across multiple environments.
Structure optimization of linear shaped charge based on different explosives
Authors: Mao Xin , Ma Tianbao , Liu Jing
Published: April 2024

In order to improve the damage ability of traditional shaped charge, a special linear shaped charge is designed. The driving characteristics of B explosive, HMX based explosive (JO‐8) and CL‐20 based explosive on linear explosively formed projectile (LEFP) are compared. The forming effect of LEFP is analyzed, the structural parameters of LEFP are designed, and the structure of shaped charge is optimized by combining genetic algorithm (NSGA‐II) and sequence quadratic programming (NLPQL). The Pulsed X‐ray experiment of scale LEFP is carried out. The results show that: (1) under the same structure, the LEFP formed by the shaped charge using CL‐20 explosive has better performance; (2) the LEFP formed by optimized B explosive is superior to that formed by unoptimized JO‐8 explosive, while LEFP formed by optimized JO‐8 explosive is superior to that formed by CL‐20 explosive, which indicates that explosives with lower energy density can also produce better LEFP after optimization; (3) The experimental results are consistent with the numerical results, which verifies the reliability of the numerical simulation and the effectiveness of the optimization method.
The Phenix‐AlphaFold webservice: Enabling AlphaFold predictions for use in Phenix
Authors: Poon Billy K. , Terwilliger Thomas C. , Adams Paul D.
Published: April 2024

Advances in machine learning have enabled sufficiently accurate predictions of protein structure to be used in macromolecular structure determination with crystallography and cryo‐electron microscopy data. The Phenix software suite has AlphaFold predictions integrated into an automated pipeline that can start with an amino acid sequence and data, and automatically perform model‐building and refinement to return a protein model fitted into the data. Due to the steep technical requirements of running AlphaFold efficiently, we have implemented a Phenix‐AlphaFold webservice that enables all Phenix users to run AlphaFold predictions remotely from the Phenix GUI starting with the official 1.21 release. This webservice will be improved based on how it is used by the research community and the future research directions for Phenix.
iLight2: A near‐infrared optogenetic tool for gene transcription with low background activation
Authors: Baloban Mikhail , Kasatkina Ludmila A. , Verkhusha Vladislav V.
Published: April 2024

Optogenetic tools (OTs) operating in the far‐red and near‐infrared (NIR) region offer advantages for light‐controlling biological processes in deep tissues and spectral multiplexing with fluorescent probes and OTs acting in the visible range. However, many NIR OTs suffer from background activation in darkness. Through shortening linkers, we engineered a novel NIR OT, iLight2, which exhibits a significantly reduced background activity in darkness, thereby increasing the light‐to‐dark activation contrast. The resultant optimal configuration of iLight2 components suggests a molecular mechanism of iLight2 action. Using a biliverdin reductase knock‐out mouse model, we show that iLight2 exhibits advanced performance in mouse primary cells and deep tissues in vivo. Efficient light‐controlled cell migration in wound healing cellular model demonstrates the possibility of using iLight2 in therapy and, overall, positions it as a valuable addition to the NIR OT toolkit for gene transcription applications.
Biophysical insights into the dimer formation of human Sirtuin 2
Authors: Suzuki Noa , Konuma Tsuyoshi , Ikegami Takahisa , Akashi Satoko
Published: April 2024

Sirtuin 2 (SIRT2) is a class III histone deacetylase that is highly conserved from bacteria to mammals. We prepared and characterized the wild‐type (WT) and mutant forms of the histone deacetylase (HDAC) domain of human SIRT2 (hSIRT2) using various biophysical methods and evaluated their deacetylation activity. We found that WT hSIRT2 HDAC (residues 52–357) forms a homodimer in a concentration‐dependent manner with a dimer–monomer dissociation constant of 8.3 ± 0.5 μM, which was determined by mass spectrometry. The dimer was disrupted into two monomers by binding to the HDAC inhibitors SirReal1 and SirReal2. We also confirmed dimer formation of hSIRT2 HDAC in living cells using a NanoLuc complementation reporter system. Examination of the relationship between dimer formation and deacetylation activity using several mutants of hSIRT2 HDAC revealed that some non‐dimerizing mutants exhibited deacetylation activity for the N‐terminal peptide of histone H3, similar to the wild type. The hSIRT2 HDAC mutant Δ292–306, which lacks a SIRT2‐specific disordered loop region, was identified to exist as a monomer with slightly reduced deacetylation activity; the X‐ray structure of the mutant Δ292–306 was almost identical to that of the WT hSIRT2 HDAC bound to an inhibitor. These results indicate that hSIRT2 HDAC forms a dimer, but this is independent of deacetylation activity. Herein, we discuss insights into the dimer formation of hSIRT2 based on our biophysical experimental results.
Impact of pharmaceutical care for asthma patients on health‐related outcomes: An umbrella review
Authors: Montero Pérez Olalla , Salazar González Fernando , Sánchez Gómez Ernesto , Pérez Guerrero Concepción
Published: April 2024

Recent systematic reviews suggest that pharmacists' interventions in asthma patients have a positive impact on health‐related outcomes. Nevertheless, the association is not well established, and the role of clinical pharmacists is poorly represented. The aim of this overview of systematic reviews is to identify published systematic reviews assessing the impact of pharmacists' interventions on health‐related outcomes measured in asthma patients. PubMed, Embase, Scopus, and Cochrane Library were searched from inception to December 2022. Systematic reviews of all study designs and settings were included. Methodological quality was assessed using AMSTAR 2. Two investigators performed study selection, quality assessment and data collection independently. Nine systematic reviews met the inclusion criteria. Methodological quality was rated as high in one, low in two, and critically low in six. Reviews included 51 primary studies reporting mainly quality of life, asthma control, lung capacity, and therapeutic adherence. Only four studies were carried out in a hospital setting and only two reviews stated the inclusion of severe asthma patients. The quality of the systematic reviews was generally low, and this was the major limitation of this overview of systematic reviews. However, solid evidence supports that pharmaceutical care improves health‐related outcomes in asthma patients.
Procedure excellence: Changing paradigms to enable human reliability
Authors: Wolf‐Stokes Elliot , Fisher Rob
Published: April 2024

A multi‐year review of process safety event learning data revealed that procedure usability and human factors were leading the trends of performance deviations by front‐line personnel. These insights prompted an enterprise‐wide Agile project to build capability focused on effective written guidance using science‐based tools and advanced error reduction techniques. Application of the Agile methodology was critical to gaining stakeholder commitment and establishing a comprehensive procedure integrity lifecycle to drive continuous improvement. Chemours partnered with an external consultant to create a holistic framework applicable to vital process safety roles with an orientation toward operational excellence. We share preliminary learnings and best practices leveraged from the nuclear industry, including systemic drivers to procedural deviations, the “top five error drivers” in written guidance, human performance modes (mental models), and key principles to enable human reliability.
Plant‐derived artificial miRNA effectively reduced the proliferation of aphid (Aphidoidea) through spray‐induced gene silencing
Authors: Wang Yuan , Li Xuanlin , Zhu Chenghong , Yi Shijie , Zhang Yan , Hong Zhi
Published: April 2024

BACKGROUND

Aphids (Hemiptera: Aphididae) are notorious sap‐sucking insects that rampantly threaten agricultural production worldwide. Current management against aphids in the field heavily relies on chemical pesticides, which makes economical and eco‐friendly methods urgently needed. Spray‐induced gene silencing (SIGS) offers a powerful and precise approach to pest management. However, the high costs and instability of double‐stranded RNA (dsRNA) regulators applied for downstream RNA interference (RNAi) still limit this strategy. It remains uncertain if RNAi regulators applied in SIGS could extend to small RNA (sRNA), especially miRNA.

RESULTS

We chose two sRNA sequences, miR‐9b and miR‐VgR, whose corresponding targets ABCG4 and VgR are both essential for aphid growth and development. The efficacy of these sequences was initially verified by chemically synthetic single‐stranded RNA (syn‐ssRNA). Through spray treatment, we observed a significantly decreased survival number and increased abnormality rate of green peach aphids fed on the host under laboratory conditions. Based on our previous study, we generated transgenic plants expressing artificial miR‐9b (amiR‐9b) and miR‐VgR (amiR‐VgR). Remarkably, plant‐derived amiRNA exerted potent and long‐lasting inhibitory efficacy with merely one percent concentration of chemical synthetics. Notably, the simultaneous application of amiR‐9b and amiR‐VgR exhibited superior inhibitory efficacy.

CONCLUSION

We explored the potential use of sRNA‐based biopesticide through SIGS while investigating the dosage requirements. To optimize this strategy, the utilization of plant‐derived amiRNA was proposed. The results suggested that attributed to stability and durability, deploying amiRNA in pest management is a potential and promising solution for the field application. © 2024 Society of Chemical Industry.