bluuebunny/crossref_metadata_2025 huggingface dataset:
Finite element and theoretical investigations on PVC–CFRP confined concrete columns under axial compression
Authors: Isleem Haytham F. , Jagadesh P. , Qaidi Shaker , Althoey Fadi , Rahmawati Cut , Najm Hadee Mohammed , Sabri Mohanad Muayad Sabri
Published: December 2022

This article examines the performance of Carbon Fibre Reinforced Polymer (CFRP) on Concrete Filled with Polymer Vinyl Chloride Tube (CFPT) columns under axial compression. Firstly, 44 CFPT specimens from the literature were analyzed using ABAQUS software to understand the compressive behavior of specimens under applied displacement. Secondly, 268 CFPT specimens are simulated to understand the influence of CFRP on these control specimens with a varying number of FRP layers and wrapping depth. Other variables such as the unconfined concrete strength, the thickness of the PVC tube, and the size and slenderness ratio of the columns were also studied. Studies are extended to confinement damage plasticity model analysis of CFRP-CFPT (CCFPT) columns. Relationships between the load-carrying capacity of CCFPT columns and the CFRP properties were developed. The effect of these parameters on the CFPT leads to the development of analytical models. It is an advantage to applying a such new type of composite columns in various applications.
Pulmonary EV miRNA profiles identify disease and distinct inflammatory endotypes in COPD
Authors: Burke Hannah , Cellura Doriana , Freeman Anna , Hicks Alex , Ostridge Kris , Watson Alastair , Williams Nicholas P. , Spalluto C. Mirella , Staples Karl J. , Wilkinson Tom M. A.
Published: December 2022

Introduction

Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition without effective disease modifying therapies. Identification of novel inflammatory endotype markers such as extracellular vesicles (EVs), which are important intercellular messengers carrying microRNA (miRNA), may enable earlier diagnosis and disease stratification for a targeted treatment approach. Our aim was to identify differentially expressed EV miRNA in the lungs of COPD patients compared with healthy ex-smokers and determine whether they can help define inflammatory COPD endotypes.

Methods

EV miRNA were isolated and sequenced from ex-smoking COPD patients and healthy ex-smoker bronchoalveolar lavage fluid. Results were validated with RT-qPCR and compared to differential inflammatory cell counts.

Results

Expression analysis identified five upregulated miRNA in COPD (miR-223-3p, miR-2110, miR-182-5p, miR-200b-5p and miR-625-3p) and three downregulated miRNA (miR-138-5p, miR-338-3p and miR-204-5p), all with a log2 fold change of >1/−1, FDR < 0.05. These miRNAs correlated with disease defining characteristics such as FEF 25–75% (a small airways disease measure) and DLCO% (a surrogate measure of emphysema). Receiver operator curve analysis demonstrated miR-2110, miR-223-3p, and miR-182-5p showed excellent combinatory predictive ability (AUC 0.91, p < 0.0001) in differentiating between health and mild COPD. Furthermore, miR-223-3p and miR-338-3p correlated with airway eosinophilia and were able to distinguish “pure eosinophilic” COPD from other airway inflammatory subtypes (AUC 0.94 and 0.85, respectively).

Discussion

This is the first study to identify differentially expressed miRNA in COPD bronchoalveolar lavage fluid EVs. These findings suggest specific lung derived EV miRNA are a strong predictor of disease presence even in mild COPD. Furthermore, specific miRNA correlated with inflammatory cell numbers in COPD, and may have a role in defining inflammatory endotypes for future treatment stratification.
Case report: An intraretinal macrocyst with crystalline content and retinal detachment
Authors: Cai Chang , Zhou Jialin , Wang Qiuyu , Li Weihou , Liu Danning
Published: December 2022

Introduction

An intraretinal macrocyst is a cavity located in the outer plexiform layer of the retina. It is commonly filled with liquid or blood. To date, few case reports of intraretinal macrocysts with crystalline content and retinal detachment have been published.

Case presentation

A 44-year-old woman with no history of other diseases complained of decreased vision in her right eye that had persisted for 20 days. The best corrected visual acuity of the right eye was hand motion. Comprehensive ophthalmic examinations were performed, including a vision test, slit lamp fundus examination, ocular B-scan ultrasound, and orbital magnetic resonance imaging. We performed vitrectomy and retinotomy to sufficiently remove the macrocyst and relieve retinal traction. We then reattached the retina and filled it with silicone oil. During the surgery, we found that the cyst had crystalline content, which has not been previously reported, to the best of our knowledge. Finally, the pathological results confirmed a final diagnosis of intraretinal macrocyst. Six months later, we performed a second operation to remove the silicone oil and implant an intraocular lens. After both surgeries, the best corrected visual acuity of the patient's right eye was restored to 20/200, and the retina had repositioned.

Conclusion

Intraretinal macrocysts are very rare. Both orbital magnetic resonance imaging and ocular B-scan ultrasound are essential for their diagnosis. Our results indicated that vitrectomy was the best way to remove the cyst and reattach the retina.
International oncology drug approvals for multiregional or single-country clinical trials: A systematic review
Authors: Zhang Min , Onakpoya Igho , Rupalla Katrin
Published: December 2022

Background

Cancer remains one of the most common causes of morbidity and mortality worldwide. Multiregional (MRCTs) and single-country clinical trials are two common approaches to support new oncology drug approvals internationally. However, systematic reviews comparing MRCTs with single-country trials for international oncology drug approval are lacking.

Methods

We searched health agency websites to retrieve all approved oncology drugs from 2010 to 2022. ClinicalTrials.gov was used to retrieve all pivotal study information. We used an adapted version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2) and Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) checklist to assess the risk-of-bias in randomized and non-randomized trials, respectively.

Results

A total of 48 new drugs and biologics (comprising 215 pivotal clinical trials) with initial marketing approval in the United States, European Union, Japan, and China were included. The reporting quality of MRCTs vs. single-country studies was similar. The median time interval for approval was significantly longer for MRCTs than for single-country bridging studies (1,399 vs. 975 days, P < 0.0001), whereas the median time interval for approval was shorter for MRCTs than for single-country standalone studies. The time gap for oncology drugs approved before 2015 was significantly longer than for those approved after 2015. The median timeline for approval in MRCTs involving 3 regions showed the shortest time-to-approval compared with MRCTs involving 4–5 and 1–2 regions. There was no significant difference in the time-to-approval among different tumor types and product types.

Conclusion

The median time-to-approval of MRCTs was significantly longer than that of single-country bridging studies but shorter than that of single-country standalone studies, primarily involving 3 regions as the most frequent pattern and the shortest time-to-approval to operate MRCTs as a pivotal trial. Single-country bridging studies still provide essential supplements for international oncology drug approvals if MRCTs do not apply. Future studies should explore how to shorten the time-to-approval for MRCTs.

Systematic review registration

[https://www.researchregistry.com/browsethe-registry#registryofsystematicreviewsmeta-analyses/], identifier [1390].
Computed tomography-based assessment of radiographic progression in spine and sacroiliac joints after pregnancy in women with radiographic axial spondyloarthritis
Authors: Lee Kyung-Ann , Lee So Yun , Kim Se Hee , Kim Hyun-Sook , Kim Hae-Rim , Lee Sang-Hoon
Published: December 2022

Background

Mechanical stress are one of the pathogenesis of axial spondyloarthritis (axSpA). During pregnancy, the mechanical overload on the spine and pelvis increases due to gravid uterus. We aimed to investigate whether pregnancy affects radiographic progression in patients with radiographic axSpA (r-axSpA) based on computed tomography (CT) evaluations.

Materials and methods

This retrospective study included women with r-axSpA aged 19–49 years who underwent at least two CT evaluations of the whole spine and/or sacroiliac joints (SIJs) at intervals of 2–4 years. To compare radiographic progression after delivery, we classified the patients into two groups: delivery group and controls. The delivery group was restricted to women who had the first CT ∼2 years before delivery and the second CT ∼2 years after delivery. The CT Syndesmophyte Score (CTSS) (0–522) and SIJ scores (0–40) were used to evaluate spinal syndesmophytes and erosion, joint space narrowing, and sclerosis of the SIJs.

Results

A total of 21 women in the delivery group and 38 women in the control group were included. The median (Q1–Q3) CTSS at baseline in the delivery group and controls was 19 (16–23) and 20 (13.25–27.75), and the median progression was 1 (0–3) and 0 (0–1) during the median 2.9-year follow-up, respectively. The median (Q1–Q3) SIJ score at baseline in the delivery group and controls was 13 (8–22) and 11 (6–22), and the median progression was 1.5 (0–3) and 1 (0–2), respectively. Using cut-off 0.5, 52.9, and 61.9% of r-axSpA patients and 39.3 and 44.4% of controls showed progression of whole spine and SIJs, respectively. However, no difference in proportion of spinal and SIJ progression and absolute score changes per time point was observed between two groups. Moreover, the SIJ score changes were comparable according to the delivery method.

Conclusion

Pregnancy and delivery do not affect the radiographic progression of the spine and SIJs in women with r-axSpA assessed by CT.
Can the implementation of clinical practice guidelines improve clinical competence of physicians and kidney function of patients with type 2 diabetes mellitus?
Authors: Martínez-Martínez Petra , Cueto-Manzano Alfonso M. , Cortés-Sanabria Laura , Martínez-Ramírez Héctor R. , Rojas-Campos Enrique , Hernández-Herrera Aurora
Published: December 2022

Background

There are many clinical practice guidelines (CPGs) in Nephrology; however, there is no evidence that their availability has improved the clinical competence of physicians or the outcome of patients with chronic kidney disease (CKD). This study was aimed to evaluate the effect of implementation of CPGs for early CKD on family physicians (FP) clinical competence and subsequently on kidney function preservation of type 2 diabetes mellitus (DM2) patients at a primary healthcare setting.

Methods

A prospective educative intervention (40-h) based on CPGs for Prevention, Diagnosis and Treatment of Early CKD was applied to FP; a questionnaire to evaluate clinical competence was applied at the beginning and end of the educative intervention (0 and 2 months), and 12 months afterwards. DM2 patients with CKD were evaluated during 1-year of follow-up with estimated glomerular filtration rate (eGFR) and albuminuria.

Results

After educative intervention, there was a significant increase in FP clinical competence compared to baseline; although it was reduced after 1 year, it remained higher compared to baseline. One-hundred thirteen patients with early nephropathy (58 stage 1, 55 stage 2) and 28 with overt nephropathy (23 stage 3, 5 stage 4) were studied. At final evaluation, both groups maintained eGFR [(mean change) early 0.20 ± 19 pNS; overt 0.51 ± 13 mL/min pNS], whereas albuminuria/creatinuria (early −67 ± 155 p < 0.0001; overt −301 ± 596 mg/g p < 0.0001), systolic blood pressure (early −10 ± 18 p < 0.05; overt −8 ± 20 mmHg p < 0.05), and total cholesterol (early −11 ± 31 p < 0.05; overt −17 ± 38 mg/dL p < 0.05) decreased. Diastolic blood pressure, waist circumference and LDL-cholesterol were also controlled in early nephropathy patients.

Conclusions

CPGs for Prevention, Diagnosis and Treatment of CKD, by means of an educative intervention increases FP clinical competence and improves renal function in DM2 patients with CKD.
Photoinhibition of comammox reaction in Nitrospira inopinata in a dose- and wavelength-dependent manner
Authors: Gottshall Ekaterina Y. , Godfrey Bruce , Li Bo , Abrahamson Britt , Qin Wei , Winkler Mari
Published: December 2022

Apparent contribution of complete ammonia-oxidizing organisms (comammox) to the global nitrogen cycle highlights the necessity for understanding niche differentiation of comammox bacteria among other ammonia oxidizers. While the high affinity for ammonia of the comammox species Nitrospira inopinata suggests their niche partitioning is expected to be centered in oligotrophic environments, their absence in nutrient-depleted environments (such as the oceans) suggests that other (abiotic) factors might control their distribution and spatial localization within microbial communities. Many ammonia- and nitrite-oxidizing organisms are sensitive to light; however, the photosensitivity of comammox has not been explored. Since comammox bacteria encode enzymatic machinery homologous to canonical ammonia-and nitrite-oxidizers, we hypothesized that comammox N. inopinata, the only available pure culture of this group of microorganisms, may be inhibited by illumination in a similar manner. We evaluated the impact of light intensity, wavelength, and duration on the degree of photoinhibition for cultures of the comammox species N. inopinata and the soil ammonia-oxidizing archaea Nitrososphaera viennensis. Both species were highly sensitive to light. Interestingly, mimicking diurnal light exposure caused an uncoupling of ammonia and nitrite oxidation in N. inopinata, indicating nitrite oxidation might be more sensitive to light exposure than ammonia oxidation. It is likely that light influences comammox spatial distribution in natural environments such as surface fresh waters according to diurnal cycles, light attenuation coefficients, and the light penetration depths. Our findings therefore provide ecophysiological insights for further studies on comammox both in field and laboratory settings.
Glaesserella parasuis autotransporters EspP1 and EspP2 are novel IgA-specific proteases
Authors: Wang Zhichao , Gu Jiayun , Xiao Kunxue , Zhu Wenlong , Lin Yan , Wen Siting , He Qigai , Xu Xiaojuan , Cai Xuwang
Published: December 2022

Background

Glaesserella parasuis causes Glässer’s disease, which is associated with severe polyarthritis, fibrinous polyserositis and meningitis, and leads to significant economic losses to the swine industry worldwide. IgA is one of the most important humoral immune factors present on mucosal surfaces, and it plays a crucial role in neutralizing and removing pathogens. G. parasuis is able to colonize the mucosal membrane of respiratory tract without being eliminated. Nevertheless, the immune evasion mechanism of G. parasuis in thwarting IgA remains unclear.

Aims

The object of this study is to characterize the IgA degradation activity of Mac-1-containing autotransporter EspP1 and EspP2 from G. parasuis.

Methods

The swine IgA was purified and incubated with EspP1 and EspP2 respectively. Western blotting was used to detect the cleavage of swine IgA. Generation of EspP1 and EspP2 mutant protein were used to explore the putative active sites of EspPs. LC-MS/MS based N/C-terminal sequencing was performed to measure the cleavage sites in swine IgA.

Result

Our results show that G. parasuis EspP1 and EspP2 cleave swine IgA in a dose- and time- dependent manner. G. parasuis lose the IgA protease activity after simultaneously delete espP1 and espP2 indicating that EspP1 and EspP2 are the only two IgA proteases in G. parasuis. The IgA protease activity of EspP1 and EspP2 is affected by the putative active sites which contain Cys47, His172 and Asp194/195. Swine IgA is cleaved within Cα1 and Cα3 domains upon incubation with EspPs. Moreover, EspPs can degrade neither IgG nor IgM while G. parasuis possess the ability to degrade IgM unexpectedly. It suggests that G. parasuis can secrete other proteases to cleave IgM which have never been reported.

Conclusion

We report for the first time that both EspP1 and EspP2 are novel IgA-specific proteases and cleave swine IgA within the Cα1 and Cα3 domains. These findings provide a theoretical basis for the EspPs-induced immune evasion.
Modulating gut microbiota and metabolites with dietary fiber oat β-glucan interventions to improve growth performance and intestinal function in weaned rabbits
Authors: Ma Li , Luo Zhengzhong , Huang Yixin , Li Yan , Guan Jing , Zhou Tao , Du Zhenlong , Yong Kang , Yao Xueping , Shen Liuhong , Yu Shumin , Zhong Zhijun , Hu Yanchun , Peng Guangneng , Shi Xiaodong , Cao Suizhong
Published: December 2022

The effect of oat β-glucan on intestinal function and growth performance of weaned rabbits were explored by multi-omics integrative analyses in the present study. New Zealand White rabbits fed oat β-glucan [200 mg/kg body weight (BW)] for 4 weeks, and serum markers, colon histological alterations, colonic microbiome, colonic metabolome, and serum metabolome were measured. The results revealed that oat β-glucan increased BW, average daily gain (ADG), average daily food intake (ADFI), and decreased serum tumor necrosis factor-α (TNF-α) interleukin-1β (IL-1β), and lipopolysaccharide (LPS) contents, but did not affect colonic microstructure. Microbiota community analysis showed oat β-glucan modulated gut microbial composition and structure, increased the abundances of beneficial bacteria Lactobacillus, Prevotellaceae_UCG-001, Pediococcus, Bacillus, etc. Oat β-glucan also increased intestinal propionic acid, valeric acid, and butyric acid concentrations, decreased lysine and aromatic amino acid (AAA) derivative contents. Serum metabolite analysis revealed that oat β-glucan altered host carbohydrate, lipid, and amino acid metabolism. These results suggested that oat β-glucan could inhibit systemic inflammation and protect intestinal function by regulating gut microbiota and related metabolites, which further helps to improve growth performance in weaned rabbits.
Volleying plasma membrane proteins from birth to death: Role of J-domain proteins
Authors: Sagarika Preeti , Yadav Kirpa , Sahi Chandan
Published: December 2022

The function, stability, and turnover of plasma membrane (PM) proteins are crucial for cellular homeostasis. Compared to soluble proteins, quality control of plasma membrane proteins is extremely challenging. Failure to meet the high quality control standards is detrimental to cellular and organismal health. J-domain proteins (JDPs) are among the most diverse group of chaperones that collaborate with other chaperones and protein degradation machinery to oversee cellular protein quality control (PQC). Although fragmented, the available literature from different models, including yeast, mammals, and plants, suggests that JDPs assist PM proteins with their synthesis, folding, and trafficking to their destination as well as their degradation, either through endocytic or proteasomal degradation pathways. Moreover, some JDPs interact directly with the membrane to regulate the stability and/or functionality of proteins at the PM. The deconvoluted picture emerging is that PM proteins are relayed from one JDP to another throughout their life cycle, further underscoring the versatility of the Hsp70:JDP machinery in the cell.
Quantitative gastrointestinal function and corresponding symptom profiles in autonomic neuropathy
Authors: Langford Jordan S. , Tokita Eric , Martindale Cecilia , Millsap Leah , Hemp James , Pace Laura A. , Cortez Melissa M.
Published: December 2022

Purpose

Peripheral neuropathies with autonomic nervous system involvement are a recognized cause of gastrointestinal dysmotility for a wide spectrum of diseases. Recent advances in wireless motility capsule testing allow improved sampling of regional and whole gut motility to aid in the diagnosis of gastrointestinal motility disorders and may provide additional insight into segment-specific enteric involvement of peripheral neuropathies affecting autonomic nervous system function.

Methods

We utilized standardized autonomic nervous system (ANS) reflex assessment and wireless motility capsule testing to evaluate 20 individuals with idiopathic autonomic neuropathy and unexplained gastrointestinal symptoms. Additionally, we examined the relationship between quantifiable autonomic neuropathy and gastrointestinal dysmotility at specific neuroanatomical levels. Symptom profiles were evaluated using the 31-item Composite Autonomic Symptom Score questionnaire (COMPASS-31) and compared to wireless motility capsule data.

Results

We found that transit times were predominately abnormal (delayed) in the foregut (10 of 20; 50%), while contractility abnormalities were far more prominent in the hindgut (17 of 20; 85%), and that motility and symptom patterns, as assessed by the COMPASS-31 GI domain items, generally corresponded. Finally, we also found that there was neuroanatomical overlap in the presence of autonomic reflex abnormalities and WMC-based transit and/or contractility abnormalities.

Conclusions

We found that transit times were predominately abnormal in the foregut and midgut, while contractility abnormalities were far more prominent in the hindgut in individuals with idiopathic autonomic neuropathy. There was a high rate of agreement in segmental wireless motility capsule data with neuroanatomically corresponding standardized ANS function measures (e.g., cardiovagal, sudomotor, adrenergic). Expanded sudomotor testing, including additional neuroanatomical segments, could provide additional indirect assessment of visceral involvement in ANS dysfunction.
Outcomes associated with antithrombotic strategies in heart failure with reduced ejection fraction and sinus rhythm following acute ischemic stroke
Authors: Patel Parth , Tiongson Justin , Chen Austin , Siegal Taylor , Oak Solomon , Golla Akhil , Kamen Scott , Thon Jesse M. , Vigilante Nicholas , Rana Ameena , Hester Taryn , Siegler James E.
Published: December 2022

Purpose

Insufficient data exist regarding the benefit of long-term antiplatelet vs. anticoagulant therapy in the prevention of recurrent ischemic stroke in patients with ischemic stroke and heart failure with reduced ejection fraction (HFrEF). Therefore, this study aimed to compare longitudinal outcomes associated with antiplatelet vs. anticoagulant use in a cohort of patients with stroke and with an ejection fraction of ≤40%.

Methods

We retrospectively analyzed single-center registry data (2015–2021) of patients with ischemic stroke, HFrEF, and sinus rhythm. Time to the primary outcome of recurrent ischemic stroke, major bleeding, or death was assessed using the adjusted Cox proportional hazards model and was compared between patients treated using anticoagulation (±antiplatelet) vs. antiplatelet therapy alone after propensity score matching using an intention-to-treat (ITT) approach, with adjustment for residual measurable confounders. Sensitivity analyses included the multivariable Cox proportional hazards model using ITT and as-treated approaches without propensity score matching.

Results

Of 2,974 screened patients, 217 were included in the secondary analyses, with 130 patients matched according to the propensity score for receiving anticoagulation treatment for the primary analysis, spanning 143 patient-years of follow-up. After propensity score matching, there was no significant association between anticoagulation and the primary outcome [hazard ratio (HR) 1.10, 95% confidence interval (CI): 0.56–2.17]. Non-White race (HR 2.26, 95% CI: 1.16–4.41) and the presence of intracranial occlusion (HR 2.86, 95% CI: 1.40–5.83) were independently associated with the primary outcome, while hypertension was inversely associated (HR 0.42, 95% CI: 0.21–0.84). There remained no significant association between anticoagulation and the primary outcome in sensitivity analyses.

Conclusion

In HFrEF patients with an acute stroke, there was no difference in outcomes of antithrombotic strategies. While this study was limited by non-randomized treatment allocation, the results support future trials of stroke patients with HFrEF which may randomize patients to anticoagulation or antiplatelet.
Lysophosphatidylcholines and phosphatidylcholines as biomarkers for stroke recovery
Authors: Huang Meiling , Xu Shaohang , Zhou Mingchao , Luo Jiao , Zha Fubing , Shan Linlin , Yang Qingqing , Zhou Baojin , Wang Yulong
Published: December 2022

Stroke is a serious global public health issue, associated with severe disability and high mortality rates. Its early detection is challenging, and no effective biomarkers are available. To obtain a better understanding of stroke prevention, management, and recovery, we conducted lipidomic analyses to characterize plasma metabolic features. Lipid species were measured using an untargeted lipidomic analysis with liquid chromatography-tandem mass spectrometry. Sixty participants were recruited in this cohort study, including 20 healthy individuals and 40 patients with stroke. To investigate the association between lipids related to long-term functional recovery in stroke patients. The primary independent variable was activities of daily living (ADL) dependency upon admission to the stroke unit and at the 3-month follow-up appointment. ADL dependency was assessed using the Barthel Index. Eleven significantly altered lipid species between the stroke and healthy groups were detected and displayed in a hierarchically clustered heatmap. Acyl carnitine, triacylglycerol, and ceramides were detected as potential lipid markers. Regarding the association between lipid profiles and functional status of patients with stroke the results indicated, lysophosphatidylcholines (LPC) and phosphatidylcholines were closely associated with stroke recovery. LPC may contribute positively role in patient's rehabilitation process via an anti-inflammatory mechanism. Appropriate management or intervention for lipid levels is expected to lead to better clinical outcomes.
The influential factors and non-pharmacological interventions of cognitive impairment in children with ischemic stroke
Authors: Xu Gang , Hao Fuchun , Zhao Weiwei , Qiu Jiwen , Zhao Peng , Zhang Qian
Published: December 2022

Background

The prevalence of pediatric ischemic stroke rose by 35% between 1990 and 2013. Affected patients can experience the gradual onset of cognitive impairment in the form of impaired language, memory, intelligence, attention, and processing speed, which affect 20–50% of these patients. Only few evidence-based treatments are available due to significant heterogeneity in age, pathological characteristics, and the combined epilepsy status of the affected children.

Methods

We searched the literature published by Web of Science, Scopus, and PubMed, which researched non-pharmacological rehabilitation interventions for cognitive impairment following pediatric ischemic stroke. The search period is from the establishment of the database to January 2022.

Results

The incidence of such impairment is influenced by patient age, pathological characteristics, combined epilepsy status, and environmental factors. Non-pharmacological treatments for cognitive impairment that have been explored to date mainly include exercise training, psychological intervention, neuromodulation strategies, computer-assisted cognitive training, brain-computer interfaces (BCI), virtual reality, music therapy, and acupuncture. In childhood stroke, the only interventions that can be retrieved are psychological intervention and neuromodulation strategies.

Conclusion

However, evidence regarding the efficacy of these interventions is relatively weak. In future studies, the active application of a variety of interventions to improve pediatric cognitive function will be necessary, and neuroimaging and electrophysiological measurement techniques will be of great value in this context. Larger multi-center prospective longitudinal studies are also required to offer more accurate evidence-based guidance for the treatment of patients with pediatric stroke.
Common targetable inflammatory pathways in brain transcriptome of autism spectrum disorders and Tourette syndrome
Authors: Alshammery Sarah , Patel Shrujna , Jones Hannah F. , Han Velda X. , Gloss Brian S. , Gold Wendy A. , Dale Russell C.
Published: December 2022

Neurodevelopmental disorders (NDDs), including autism-spectrum disorders (ASD) and Tourette syndrome (TS) are common brain conditions which often co-exist, and have no approved treatments targeting disease mechanisms. Accumulating literature implicates the immune system in NDDs, and transcriptomics of post-mortem brain tissue has revealed an inflammatory signal. We interrogated two RNA-sequencing datasets of ASD and TS and identified differentially expressed genes, to explore commonly enriched pathways through GO, KEGG, and Reactome. The DEGs [False Discovery Rate (FDR) <0.05] in the ASD dataset (n = 248) and the TS dataset (n = 156) enriched pathways involving inflammation, cytokines, signal transduction and cell signalling. Of the DEGs from the ASD and TS analyses, 23 were shared, all of which were up-regulated: interaction networks of the common protein-coding genes using STRING revealed 5 central up-regulated hub genes: CCL2, ICAM1, HMOX1, MYC, and SOCS3. Applying KEGG and Reactome analysis to the 23 common genes identified pathways involving the innate immune response such as interleukin and interferon signalling pathways. These findings bring new evidence of shared immune signalling in ASD and TS brain transcriptome, to support the overlapping symptoms that individuals with these complex disorders experience.
Discovery of imidazole-based GSK-3β inhibitors for transdifferentiation of human mesenchymal stem cells to neurons: A potential single-molecule neurotherapeutic foresight
Authors: Gupta Varsha , Mahata Tanushree , Roy Rajsekhar , Gharai Prabir Kumar , Jana Aniket , Garg Shubham , Ghosh Surajit
Published: December 2022

The transdifferentiation of human mesenchymal stem cells (hMSC) to functional neurons is crucial for the development of future neuro-regenerative therapeutics. Currently, transdifferentiation of hMSCs to neurons requires a “chemical cocktail” along with neural growth factors. The role of the individual molecules present in a “chemical cocktail” is poorly understood and may cause unwanted toxicity or adverse effects. Toward, this goal, we have showcased the discovery of an imidazole-based “single-molecule” transdifferentiation initiator SG-145C. This discovery was achieved via screening of a small molecule library through extensive in silico studies to shortlist the best-fitting molecules. This discovery evolved through a careful selection to target Glycogen synthase kinase-3β (GSK-3β), which is one of the important proteins responsible for neurogenesis. Rigorous computational experiments, as well as extensive biological assays, confirmed that SG-145C has significant potential to transdifferentiate hMSCs to neurons. Interestingly, our results suggest that SG-145C can inhibit the proteasomal degradation of phosphorylated β-catenin, in turn promoting transdifferentiation of hMSCs into neurons via the Wnt pathway.
Association between oxidative balance score and new-onset hypertension in adults: A community-based prospective cohort study
Authors: Lee Jun-Hyuk , Son Da-Hye , Kwon Yu-Jin
Published: December 2022

Introduction

Oxidative stress plays a key role in the pathophysiology of hypertension development. The oxidative balance score (OBS) comprises dietary and lifestyle pro- and anti-oxidant components and reflects the overall oxidative stress burden. We aimed to evaluate the association between the OBS and new-onset hypertension (HTN) using large, community-based, prospective Korean cohort data.

Methods

Among 10,030 participants aged 40–69 years included in the Korean Genome and Epidemiology Study, the data of 5,181 participants were analyzed. The hazard ratio (HR) and 95% confidence interval (CI) for new-onset HTN according to sex-specific OBS quartile groups were calculated using univariable and multivariable Cox proportional hazard regression analyses.

Results

During the mean 13.6-year follow-up period, 1,157 men and 1,196 women developed new-onset HTN. Compared to the Q1 group, the adjusted HRs (95%CI) for new-onset HTN in the Q2, Q3, and Q4 groups were 0.96 (0.82–1.16), 0.85 (0.72–0.99), and 0.71 (0.59–0.86) in men and 0.81 (0.69–0.95), 0.81(0.68–0.95), and 0.70 (0.57–0.84) in women, respectively.

Discussion

Individuals with high OBS are at lower risk of developing HTN. This study suggests that a healthy lifestyle and antioxidant rich diet could be a preventive strategy for HTN.
Preoperative embolization in the treatment of patients with metastatic epidural spinal cord compression: A retrospective analysis
Authors: Zhang Bin , Yu Haikuan , Zhao Xiongwei , Cao Xuyong , Cao Yuncen , Shi Xiaolin , Wang Zheng , Liu Yaosheng
Published: December 2022

Purpose

The purpose of the study was to assess the effectiveness and safety of preoperative embolization in the treatment of patients with metastatic epidural spinal cord compression (MESCC).

Methods

A retrospective analysis of 138 MESCC patients who underwent decompressive surgery and spine stabilization was performed in a large teaching hospital. Among all enrolled patients, 46 patients were treated with preoperative embolization (the embolization group), whereas 92 patients did not (the control group). Patient’s baseline clinical characteristics, surgery-related characteristics, and postoperative neurological status, complications, and survival prognoses were collected and analyzed. Subgroup analysis was performed according to the degree of tumor vascularity between patients with and without preoperative embolization.

Results

Patients with severe hypervascularity experienced more mean blood loss in the control group than in the embolization group, and this difference was statistically significant (P=0.02). The number of transfused packed red cells (PRC) showed a similar trend (P=0.01). However, for patients with mild and moderate hypervascularity, both blood loss and the number of PRC transfusion were comparable across the two groups. Regarding decompressive techniques, the embolization group (64.29%, 9/14) had a higher proportion of circumferential decompression in comparison to the control group (30.00%, 9/30) among patients with severe hypervascularity (P=0.03), whereas the rates were similar among patients with mild (P=0.45) and moderate (P=0.54) hypervascularity. In addition, no subgroup analysis revealed any statistically significant differences in operation time, postoperative functional recovery, postoperative complications, or survival outcome. Multivariate analysis showed that higher tumor vascularity (OR[odds ratio]=3.69, 95% CI [confident interval]: 1.30-10.43, P=0.01) and smaller extent of embolization (OR=4.16, 95% CI: 1.10-15.74, P=0.04) were significantly associated with more blood loss.

Conclusions

Preoperative embolization is an effective and safe method in treating MESCC patients with severe hypervascular tumors in terms of intra-operative blood loss and surgical removal of metastatic tumors. Preoperative tumor vascularity and extent of embolization are independent risk factors for blood loss during surgery. This study implies that MESCC patients with severe hypervascular tumors should be advised to undergo preoperative embolization.
Solar data uncertainty impacts on MCMC methods for r-process nucleosynthesis
Authors: Vassh Nicole , McLaughlin Gail C. , Mumpower Matthew R. , Surman Rebecca
Published: December 2022

In recent work, we developed a Markov Chain Monte Carlo (MCMC) procedure to predict the ground state masses capable of forming the observed Solar r-process rare-earth abundance peak. By applying this method to nucleosynthesis calculations which make use of distinct astrophysical conditions and comparing our results to the latest precision mass measurements, we are able to shed light on the conditions/masses capable of producing a rare-earth peak which matches Solar data. Here we examine how our mass predictions change when using a few different sets of r-process Solar abundance residuals that have been reported in the literature. We explore how the differing error estimates of these Solar evaluations propagate through the Markov Chain Monte Carlo to our mass predictions. We find that Solar data which reports the rare-earth peak to have its highest abundance at mass number A = 162 can require distinctly different mass predictions from data with the peak centered at A = 164. Nevertheless, we find that two important general conclusions from past work, regarding the inconsistency of ‘cold’ astrophysical outflows with current mass measurements and the need for local stability at N = 104 in ‘hot’ scenarios, remain robust in the face of differing Solar data evaluations. Additionally, we show that the masses our procedure finds capable of producing a peak at A < 164 are not in line with the latest precision mass measurements.
Experimental study on the rise of aqueous foams in vertical pipes
Authors: Álvarez Salazar Valeriano S. , Sigalotti Leonardo Di G. , Medina Ovando Abraham , Carvajal-Mariscal Ignacio , Klapp Jaime
Published: December 2022

In this paper we report experiments on the growth of dry foams and their rise in vertical pipes of different circular cross-sectional radii with length over diameter ratios in the interval 25 ≤ h/D ≤ 80 for applications in the study of fracture stimulation in enhanced oil recovery processes. Air injection at the bottom of the pipes is performed at a constant flow rate by means of a single capillary tube. The formation and rising of the foam was investigated for two different cases: 1) when the top cap of the vertical pipes is open and 2) when it is closed. We find that the position and velocity of the foam front as well as the foam dispersivity are both dependent on the pipe diameter and on whether its top end is open or capped. When the top is open, the foam column grows faster compared to the case when it is sealed. In pipes with h/D ≥ 30, the growth rate is non-linear and faster than in pipes with h/D < 30 in which cases the foam rises at an almost constant rate. As the diameter of the pipe increases, the size of the produced bubbles also increases. In closed-top pipes the foams tend to be more homogeneous than in open top pipes. The experimental observations indicate that under foam drainage driven by gravity, the liquid flow velocity across the Plateau borders is indicative of a drainage model based on a plug-like flow in channels with fully mobile interfaces, where viscous dissipation occurs only in the nodes.
Magnetic resonance imaging for characterization of hepatocellular carcinoma metabolism
Authors: Wang Lixia , Yang Ju Dong , Yoo Charles C. , Lai Keane K. Y. , Braun Jonathan , McGovern Dermot P. B. , Xie Yibin , Pandol Stephen J. , Lu Shelly C. , Li Debiao
Published: December 2022

With a better understanding of the pathophysiological and metabolic changes in hepatocellular carcinoma (HCC), multiparametric and novel functional magnetic resonance (MR) and positron emission tomography (PET) techniques have received wide interest and are increasingly being applied in preclinical and clinical research. These techniques not only allow for non-invasive detection of structural, functional, and metabolic changes in malignant tumor cells but also characterize the tumor microenvironment (TME) and the interactions of malignant tumor cells with the TME, which has hypoxia and low pH, resulting from the Warburg effect and accumulation of metabolites produced by tumor cells and other cellular components. The heterogeneity and complexity of the TME require a combination of images with various parameters and modalities to characterize tumors and guide therapy. This review focuses on the value of multiparametric magnetic resonance imaging and PET/MR in evaluating the structural and functional changes of HCC and in detecting metabolites formed owing to HCC and the TME.
Temporal dynamics of the chicken mycobiome
Authors: Davies Cary Pirone , Summers Katie Lynn , Arfken Ann M. , Darwish Nadia , Chaudhari Atul , Frey Juli Foster , Schreier Lori , Proszkowiec-Weglarz Monika
Published: December 2022

The microbiome is an integral part of chicken health and can affect immunity, nutrient utilization, and performance. The role of bacterial microbiota members in host health is relatively well established, but less attention has been paid to fungal members of the gastrointestinal tract (GIT) community. However, human studies indicate that fungi play a critical role in health. Here, we described fungal communities, or mycobiomes, in both the lumen and mucosa of the chicken ileum and cecum from hatch through 14 days of age. We also assessed the effects of delayed access to feed immediately post-hatch (PH) on mycobiome composition, as PH feed delay is commonly associated with poor health performance. Chicken mycobiomes in each of the populations were distinct and changed over time. All mycobiomes were dominated by Gibberella, but Aspergillus, Cladosporium, Sarocladium, Meyerozyma, and Penicillium were also abundant. Relative abundances of some taxa differed significantly over time. In the cecal and ileal lumens, Penicillium was present in extremely low quantities or absent during days one and two and then increased over time. Meyerozyma and Wickerhamomyces also increased over time in luminal sites. In contrast, several highly abundant unclassified fungi decreased after days one and two, highlighting the need for improved understanding of fungal gut biology. Mycobiomes from chicks fed during the first 2 days PH versus those not fed during the first 2 days did not significantly differ, except during days one and two. Similarities observed among mycobiomes of fed and unfed chicks at later timepoints suggest that delays in PH feeding do not have long lasting effects on mycobiome composition. Together, these results provide a foundation for future mycobiome studies, and suggest that negative health and production impacts of delayed feeding are not likely related to the development of fungal populations in the GIT.
Roles of plastid-located phosphate transporters in carotenoid accumulation
Authors: Hao Dong-Li , Zhou Jin-Yan , Huang Ya-Nan , Wang Hao-Ran , Li Xiao-Hui , Guo Hai-Lin , Liu Jian-Xiu
Published: December 2022

Enhanced carotenoid accumulation in plants is crucial for the nutritional and health demands of the human body since these beneficial substances are acquired through dietary intake. Plastids are the major organelles to accumulate carotenoids in plants and it is reported that manipulation of a single plastid phosphate transporter gene enhances carotenoid accumulation. Amongst all phosphate transport proteins including phosphate transporters (PHTs), plastidial phosphate translocators (pPTs), PHOSPHATE1 (PHO1), vacuolar phosphate efflux transporter (VPE), and Sulfate transporter [SULTR]-like phosphorus distribution transporter (SPDT) in plants, plastidic PHTs (PHT2 & PHT4) are found as the only clade that is plastid located, and manipulation of which affects carotenoid accumulation. Manipulation of a single chromoplast PHT (PHT4;2) enhances carotenoid accumulation, whereas manipulation of a single chloroplast PHT has no impact on carotenoid accumulation. The underlying mechanism is mainly attributed to their different effects on plastid orthophosphate (Pi) concentration. PHT4;2 is the only chromoplast Pi efflux transporter, and manipulating this single chromoplast PHT significantly regulates chromoplast Pi concentration. This variation subsequently modulates the carotenoid accumulation by affecting the supply of glyceraldehyde 3-phosphate, a substrate for carotenoid biosynthesis, by modulating the transcript abundances of carotenoid biosynthesis limited enzyme genes, and by regulating chromoplast biogenesis (facilitating carotenoid storage). However, at least five orthophosphate influx PHTs are identified in the chloroplast, and manipulating one of the five does not substantially modulate the chloroplast Pi concentration in a long term due to their functional redundancy. This stable chloroplast Pi concentration upon one chloroplast PHT absence, therefore, is unable to modulate Pi-involved carotenoid accumulation processes and finally does affect carotenoid accumulation in photosynthetic tissues. Despite these advances, several cases including the precise location of plastid PHTs, the phosphate transport direction mediated by these plastid PHTs, the plastid PHTs participating in carotenoid accumulation signal pathway, the potential roles of these plastid PHTs in leaf carotenoid accumulation, and the roles of these plastid PHTs in other secondary metabolites are waiting for further research. The clarification of the above-mentioned cases is beneficial for breeding high-carotenoid accumulation plants (either in photosynthetic or non-photosynthetic edible parts of plants) through the gene engineering of these transporters.
Bursaphelenchus xylophilus detection and analysis system based on CRISPR – Cas12
Authors: Wang Xiang , Wang Lai-Fa , Cao Ye-Fan , Yuan Yan-Zhi , Hu Jian , Chen Zu-Hai , Zhu Fei , Wang Xi-Zhuo
Published: December 2022

Pine wilt disease is caused by the pine wood nematode (Bursaphelenchus xylophilus) and leads to wilting and death of pines. It is one of the most damaging diseases of pines worldwide. Therefore, accurate and rapid detection methods are of great importance for the control of B. xylophilus. Traditional detection methods have some problems, such as being time-consuming and requiring expensive instruments. In this study, the loop-mediated isothermal amplification (LAMP) and clustered regularly interspaced short palindromic repeats (CRISPR) were used to establish a set of intelligent detection and analysis system for B. xylophilus, called LAMP-CRISPR/Cas12a analysis, which integrated field sampling, rapid detection and intelligent control analysis. The process can be completed within 1 hour, from sample pretreatment and detection to data analysis. Compared with the single LAMP method, the LAMP-CRISPR/Cas12a assay uses species-specific fluorescence cleavage to detect target amplicons. This process confirms the amplicon identity, thereby avoiding false-positive results from non-specific amplicons, and the large amounts of irrelevant background DNA do not interfere with the reaction. The LAMP-CRISPR/Cas12a assay was applied to 46 pine wood samples and the samples carrying B. xylophilus nematodes were successfully identified. To meet the needs of different environments, we designed three methods to interpret the data: 1) naked eye interpretation; 2) lateral flow biosensor assay; and 3) integrated molecular analysis system to standardize and intellectualize the detection process. Application of the B. xylophilus detection and analysis system will reduce the professional and technical requirements for the operating environment and operators and help to ensure the accuracy of the detection results, which is important in grass-root B. xylophilus detection institutions.
The coordinated regulation mechanism of rice plant architecture and its tolerance to stress
Authors: Zhao Huibo , Liu Xiong , Wang Jiajia , Qian Qian , Zhang Guangheng
Published: December 2022

Rice plant architecture and stress tolerance have historically been primary concerns for rice breeders. The “Green Revolution” and super-rice breeding practices have demonstrated that ideal plant architecture can effectively improve both stress tolerance and yield. The synergistic selection and breeding of rice varieties with ideal architecture and stress tolerance can increase and stabilize yield. While rice plant plant architecture and stress tolerance are separately regulated by complicated genetic networks, the molecular mechanisms underlying their relationships and synergism have not yet been explored. In this paper, we review the regulatory mechanism between plant architecture, stress tolerance, and biological defense at the different level to provide a theoretical basis for the genetic network of the synergistic regulation and improvement of multiple traits.