bluuebunny/crossref_metadata_2025 huggingface dataset:
TGF-β1 promotes SCD1 expression via the PI3K-Akt-mTOR-SREBP1 signaling pathway in lung fibroblasts
Authors: Zhou Zili , Liang Shixiu , Zhou Zicong , Liu Jieyi , Zhang Jinming , Meng Xiaojing , Zou Fei , Zhao Haijin , Yu Changhui , Cai Shaoxi
Published: January 2023

Background

Lung fibroblast activation is associated with airway remodeling during asthma progression. Stearoyl-CoA desaturase 1 (SCD1) plays an important role in the response of fibroblasts to growth factors. This study aimed to explore the effects of SCD1 on fibroblast activation induced by transforming growth factor-β1 (TGF-β1) and the role of the phosphatidylinositol-3-kinase-AKT serine-threonine protein kinase-mechanistic target of rapamycin (PI3K-Akt-mTOR) pathway on the regulation of SCD1 expression in airway remodeling.

Methods

Female C57BL/6 mice were sensitized and challenged with house dust mites to generate a chronic asthma model. The inhibitor of SCD1 was injected i.g. before each challenge. The airway hyper-responsiveness to methacholine was evaluated, and airway remodeling and airway inflammation were assessed by histology. The effects of SCD1 on fibroblast activation were evaluated in vitro using an SCD1 inhibitor and oleic acid and via the knockdown of SCD1. The involvement of the PI3K-Akt-mTOR-sterol regulatory element-binding protein 1 (SREBP1) pathway in lung fibroblasts was investigated using relevant inhibitors.

Results

The expression of SCD1 was increased in fibroblasts exposed to TGF-β1. The inhibition of SCD1 markedly ameliorated airway remodeling and lung fibroblast activation in peripheral airways. The knockdown or inhibition of SCD1 resulted in significantly reduced extracellular matrix production in TGF-β1-treated fibroblasts, but this effect was reversed by the addition of exogenous oleic acid. The PI3K-Akt-mTOR-SREBP1 pathway was found to be involved in the regulation of SCD1 expression and lung fibroblast activation.

Conclusions

The data obtained in this study indicate that SCD1 expression contributes to fibroblast activation and airway remodeling and that the inhibition of SCD1 may be a therapeutic strategy for airway remodeling in asthma.
Early longitudinal changes in left ventricular function and morphology in diabetic pigs: evaluation by 3.0T magnetic resonance imaging
Authors: Yan Wei-Feng , Xu Hua-Yan , Jiang Li , Zhang Lu , Guo Ying-Kun , Li Yuan , Shen Li-Ting , Min Chen-Yan , Yang Zhi-Gang
Published: January 2023

Background

Previous researches on large animal models of diabetic cardiomyopathy were insufficient. The aim of this study was to evaluate early changes in left ventricular (LV) function and morphology in diabetic pigs using a cardiac magnetic resonance (CMR) time-volume curve and feature tracking technique.

Methods

Streptozotocin (STZ) was used to induce diabetic in sixteen pigs. 3.0T MRI scanned the pig’s heart before and 2, 6, 10 and 16 months after modelling. CMR biomarkers, including time-volume curve and myocardial strain, were compared to analyse the longitudinal changes in LV function and morphology. Pearson correlation was used to evaluate the relationship between LV strain and remodelling. Cardiac specimens were obtained at 6, 10, and 16 months after modelling to observe the myocardial ultrastructural and microstructure at different courses of diabetes.

Results

Twelve pigs developed diabetes. The 80% diastolic volume recovery rate (DVR) at 6 months after modelling was significantly higher than that before modelling (0.78 ± 0.08vs. 0.67 ± 0.15). The LV global longitudinal peak strain (GLPS) (− 10.21 ± 3.15 vs. − 9.74 ± 2.78 vs. − 9.38 ± 3.71 vs. − 8.71 ± 2.68 vs. − 6.59 ± 2.90%) altered gradually from the baseline data to 2, 6, 10 and 16 months after modelling. After 16 months of modelling, the LV remodelling index (LVRI) of pigs increased compared with that before modelling (2.19 ± 0.97 vs. 1.36 ± 0.45 g/ml). The LVRI and myocardial peak strain were correlated in diabetic pigs (r= − 0.40 to − 0.54), with GLPS being the most significant. Electron microscopy and Masson staining showed that myocardial damage and fibrosis gradually increased with the progression of the disease.

Conclusion

Intravenous injection of STZ can induce a porcine diabetic cardiomyopathy model, mainly characterized by decreased LV diastolic function and strain changes accompanied by myocardial remodelling. The changes in CMR biomarkers could reflect the early myocardial injury of diabetic cardiomyopathy.
In-silico design and evaluation of an epitope-based serotype-independent promising vaccine candidate for highly cross-reactive regions of pneumococcal surface protein A
Authors: Afshari Elnaz , Cohan Reza Ahangari , Sotoodehnejadnematalahi Fattah , Mousavi Seyed Fazlollah
Published: January 2023

Background

The pathogenicity of pneumococcus with high morbidity, mortality, and multi-drug resistance patterns has been increasing. The limited coverage of the licensed polysaccharide-based vaccines and the replacement of the non-vaccine serotypes are the main reasons for producing a successful serotype-independent vaccine. Pneumococcal surface protein A (PspA) is an extremely important virulence factor and an interesting candidate for conserved protein-based pneumococcal vaccine classified into two prominent families containing five clades. PspA family-elicited immunity is clade-dependent, and the level of the PspA cross-reactivity is restricted to the same family.

Methods

To cover and overcome the clade-dependent immunity of the PspAs in this study, we designed and tested a PspA1-5c+p vaccine candidate composed of the highest immunodominant coverage of B- and T-cell epitope truncated domain of each clade focusing on two cross-reactive B and C regions of the PspAs. The antigenicity, toxicity, physicochemical properties, 3D structure prediction, stability and flexibility of the designed protein using molecular dynamic (MD) simulation, molecular docking of the construct withHLADRB1*(01:01) and human lactoferrin N-lop, and immune simulation were assessed using immunoinformatics tools. In the experimental section, after intraperitoneal immunization of the mice with Alum adjuvanted recombinant PspA1-5c+p, we evaluated the immune response, cross-reactivity, and functionality of the Anti-PspA1-5c+p antibody using ELISA, Opsonophagocytic killing activity, and serum bactericidal assay.

Results

For the first time, this work suggested a novel PspA-based vaccine candidate using immunoinformatics tools. The designed PspA1-5c+p protein is predicted to be highly antigenic, non-toxic, soluble, stable with low flexibility in MD simulation, and able to stimulate both humoral and cellular immune responses. The designed protein also could interact strongly with HLADRB1*(01:01) and human lactoferrin N-lop in the docking study. Our immunoinformatics predictions were validated using experimental data. Results showed that the anti-PspA1-5c+p IgG not only had a high titer with strong and same cross-reactivity coverage against all pneumococcal serotypes used but also had high and effective bioactivity for pneumococcal clearance using complement system and phagocytic cells.

Conclusion

Our findings elucidated the potential application of the PspA1-5c+p vaccine candidate as a serotype-independent pneumococcal vaccine with a strong cross-reactivity feature. Further in-vitro and in-vivo investigations against other PspA clades should be performed to confirm the full protection of the PspA1-5c+p vaccine candidate.
β-glucan protects against necrotizing enterocolitis in mice by inhibiting intestinal inflammation, improving the gut barrier, and modulating gut microbiota
Authors: Zhang Xingdao , Zhang Yuni , He Yu , Zhu Xingwang , Ai Qing , Shi Yuan
Published: January 2023

Background

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease with high morbidity and mortality, affecting preterm infants especially those with very low and extremely low birth weight. β-glucan has manifested multiple biological effects including anti-inflammatory, regulation of gut microbiota, and immunomodulatory activities. This study aimed to investigate the effects of β-glucan on NEC.

Methods

Neonatal C57BL/6 mice were randomly divided into three groups: Control group, NEC group and β-glucan group. Newborn 3-day-old mice were gavaged with either 1 mg/ml β-glucan or phosphate buffer saline at 0.03 ml/g for 7 consecutive days before NEC induction and a NEC model was established with hypoxia combined with cold exposure and formula feeding. All the pups were killed after 72-h modeling. Hematoxylin–eosin staining was performed to assess the pathological injury to the intestines. The mRNA expression levels of inflammatory factors in intestinal tissues were determined using quantitative real-time PCR. The protein levels of TLR4, NF-κB and tight junction proteins in intestinal tissues were evaluated using western blotting and immunohistochemistry. 16S rRNA sequencing was performed to determine the structure of the gut microbiota.

Results

β-glucan administration ameliorated intestinal injury of NEC mice; reduced the intestinal expression of TLR4, NF-κB, IL-1β, IL-6, and TNF-α; increased the intestinal expression of IL-10; and improved the expression of ZO-1, Occludin and Claudin-1 within the intestinal barrier. Pre-treatment with β-glucan also increased the proportion of Actinobacteria, Clostridium butyricum, Lactobacillus johnsonii, Lactobacillus murinus, and Lachnospiraceae bacterium mt14 and reduced the proportion of Klebsiella oxytoca g Klebsiella in the NEC model.

Conclusion

β-glucan intervention prevents against NEC in neonatal mice, possibly by suppressing the TLR4-NF-κB signaling pathway, improving intestinal barrier function, and partially regulating intestinal microbiota.
Morbid obesity impacts mortality among inpatients with type a aortic dissection: an analysis of the national inpatient sample
Authors: Xu Xiao , Yin Renqi , Zhi Kangkang , Qin Yingyi , Tu Boxiang , Wu Shengyong , Dong Ziwei , Liu Dongxu , He Jia
Published: January 2023

Background

Stanford type A aortic dissection (T(A)AD) is one of the most dangerous cardiovascular diseases and morbid obesity is associated with the prognosis of many cardiovascular diseases. The aim of this study is to investigate the impact of morbid obesity on in-hospital mortality, total hospital costs and discover the prevalence of morbid obesity among inpatients with T(A)AD.

Methods

Patients with a primary diagnosis of T(A)AD were identified from the National Inpatient Sample database (NIS) from 2008 to 2017. These patients were categorized into non-obesity, obesity and morbid obesity. Multivariable regression models were utilized to assess the association between obesity/morbid obesity and in-hospital mortality, total cost and other clinical factors. The temporal trend in prevalence of obesity/morbid obesity in T(A)ADs and the trend of in-hospital mortality among different weight categories were also explored.

Results

From the NIS database 8489 T(A)AD inpatients were identified, of which 7230 (85.2%) patients were non-obese, 822 (9.7%) were obese and 437 (5.1%) were morbid obese. Morbid obesity was associated with increased risk of in-hospital mortality (odds ratio [OR] 1.39; 95% confidence interval [CI] 1.03–1.86), 8% higher total cost compared with the non-obese patients. From 2008 to 2017, the rate of obesity and morbid obesity in patients with T(A)AD have significantly increased from 7.36 to 11.33% (P < 0.001) and from 1.95 to 7.37% (P < 0.001). Factors associated with morbid obesity in T(A)ADs included age, female, elective admission, hospital region, dyslipidemia, smoking, rheumatoid arthritis/collagen vascular diseases, chronic pulmonary disease, diabetes and hypertension.

Conclusions

Morbid obesity are connected with worse clinical outcomes and more health resource utilization in T(A)AD patients. Appropriate medical resource orientation and weight management education for T(A)AD patients may be necessary.
Psoralea corylifolia L.: a comprehensive review of its botany, traditional uses, phytochemistry, pharmacology, toxicology, quality control and pharmacokinetics
Authors: Chen Lele , Chen Shuguang , Sun Peng , Liu Xinyue , Zhan Zhaoshuang , Wang Jiafeng
Published: January 2023

Psoralea corylifolia L. (PCL), referred to as “Bu-gu-zhi” in Chinese, has great medicinal values since ancient times. PCL is the dried ripe fruit of Psoralea corylifolia L., which has been widely used in traditional Chinese medicine (TCM) for the treatment of kidney-yang deficiency, enuresis and urinary frequency, chills and pain of the waist and knees, dawn diarrhea and vitiligo. In this paper, a systematic of the botany, traditional uses, phytochemistry, pharmacology, toxicology, quality control and pharmacokinetics of PCL was presented, along with future research directions. According to the results, PCL contains approximately 163 chemical components, including coumarins, flavonoids, monoterpene phenols, benzofurans, glycosides, lipids, fatty acids, and volatile oils. PCL and its active ingredients have a variety of pharmacological activities, such as anti-inflammatory, antibacterial, antiviral, antioxidant, antitumor, antiosteoporosis, cardioprotective, neuroprotective, and immunomodulatory. Further study of quality control standards and potential mechanisms of PCL is also needed. In addition, more toxicological studies will also contribute to the progress of clinical trials.
FOXD3 confers chemo-sensitivity in ovarian cancer through a miR-335/DAAM1/myosin II axis-dependent mechanism
Authors: Wang Shufen , Ma Yan , Hu Yi , Zhao Xia , Li Yilin , Ouyang Shuming , Luo Guifang
Published: January 2023

Background

Chemotherapy is among the most common treatment methods for ovarian cancer (OC). However, chemoresistance limits the effectiveness of chemotherapy and leads to treatment failure. We herein investigate the biological effect of forkhead box D3 (FOXD3) in the chemoresistance of OC cells.

Methods

Expression of FOXD3, miR-335 and disheveled-associated activator of morphogenesis 1 (DAAM1) was detected in OC cells and tissues. The regulatory network of FOXD3/miR-335/DAAM1 was validated by dual-luciferase reporter and ChIP assays in vitro. After ectopic expression and depletion experiments in carboplatin/paclitaxel (CP)-resistant (A2780CP) or sensitive (A2780S) OC cells, cell viability, colony formation and apoptosis were tested by CCK-8 assay, colony formation assay and flow cytometry respectively. Effects of FOXD3 on the chemoresistance of OC cells in vivo were evaluated in OC xenografts in nude mice.

Results

Overexpression of FOXD3 impaired the proliferation and chemoresistance of OC cells, which was related to the promotion of the miR-335 expression. Functionally, DAAM1 was a putative target of miR-335. Silencing of DAAM1 was responsible for the inhibition of myosin II activation, consequently leading to suppressed OC cell proliferation and chemoresistance. In vivo results further showed that FOXD3 weakened the chemoresistance of OC cells to CP.

Conclusion

Taken together, we unveil a novel FOXD3/miR-335/DAAM1/myosin II axis that regulates the chemoresistance of OC both in vitro and in vivo.
The effect of guselkumab on inhibiting radiographic progression in patients with active psoriatic arthritis: study protocol for APEX, a Phase 3b, multicenter, randomized, double-blind, placebo-controlled trial
Authors: Ritchlin Christopher T. , Coates Laura C. , Mease Philip J. , van der Heijde Désirée , Song Jiao , Jiang Yusang , Shawi May , Kollmeier Alexa P. , Rahman Proton
Published: January 2023

Background

Guselkumab, a fully human monoclonal antibody targeting the interleukin (IL)-23p19 subunit, is approved to treat adults with active psoriatic arthritis (PsA). In the Phase 3 DISCOVER-2 trial of 739 bilogico-naïve patients with active PsA, guselkumab 100 mg resulted in less radiographic progression, assessed via change from baseline in PsA-modified van der Heijde-Sharp (vdH-S) score, compared with placebo at week (W) 24 when given at W0, W4, and then every 4 weeks (Q4W) or Q8W. The least squares mean differences from placebo were -0.66 for guselkumab Q4W (p=0.011) and -0.43 for guselkumab Q8W (p=0.072). Reports suggest baseline C-reactive protein (CRP) and joint erosions are strongly prognostic of poor outcomes, especially radiographic progression, in PsA patients. We designed a trial (APEX) to further assess the effect of guselkumab on radiographic progression in patients with active PsA and risk factors for radiographic progression.

Methods

Patients are eligible for APEX if they have had PsA for ≥6 months and active disease (≥3 swollen and ≥3 tender joints, CRP ≥0.3 mg/dL) despite prior therapy with conventional synthetic disease-modifying antirheumatic drugs, apremilast, and/or nonsteroidal anti-inflammatory drugs, with ≥2 joints with erosions on baseline radiographs (hands and feet). The primary and major secondary endpoints are the proportion of patients achieving ≥20% improvement in American College of Rheumatology response criteria (ACR20) response at W24 and change from baseline at W24 in PsA-modified vdH-S score, respectively. Sample sizes of 350/250/350 for guselkumab Q8W/guselkumab Q4W/placebo are expected to provide >99% power to detect significant differences in W24 ACR20 response rates for each guselkumab group vs placebo, as well as ≥90% (Q4W vs placebo) and ≥80% (Q8W vs placebo) power to detect a significant difference in PsA-modified vdH-S score change at W24. A Cochran-Mantel-Haenszel test and analysis of covariance will compare treatment efficacy for the primary and major secondary endpoints, respectively.

Discussion

DISCOVER-2 findings informed the design of APEX, a Phase 3b study intended to further evaluate the impact of guselkumab in patients with active PsA and known risk factors for radiographic progression.

Trial registration

This trial was registered at ClinicalTrials.gov, NCT04882098. Registered on 11 May 2021.
More extensive hypometabolism and higher mortality risk in patients with right- than left-predominant neurodegeneration of the anterior temporal lobe
Authors: Frings Lars , Blazhenets Ganna , Binder Raphael , Bormann Tobias , Hellwig Sabine , Meyer Philipp T.
Published: January 2023

Background

Left-predominant neurodegeneration of the anterior temporal lobe (ATL) and the associated syndrome termed semantic variant primary progressive aphasia (svPPA) are well characterized. Less is known about right-predominant neurodegeneration of the ATL, which has been associated with the clinical syndrome named right temporal variant of frontotemporal dementia (rtvFTD). Here, we assessed glucose metabolism across the brain, cognitive performance, and mortality in patients with right-predominant neurodegeneration of the ATL.

Methods

Patients with predominant hypometabolism of the ATL on FDG PET (as a measure of neurodegeneration) were retrospectively identified and categorized into those with asymmetrical right, left, or symmetric bilateral involvement (N = 10, 17, and 8). We compared whole-brain, normalized regional glucose metabolism using SPM12, cognitive performance on the CERAD Neuropsychological Assessment Battery, and mortality risk (age- and sex-adjusted Cox proportional hazard model) between groups.

Results

Hypometabolism was most pronounced and extensive in patients with right-predominant neurodegeneration of the ATL. Beyond the right temporal lobe, right frontal and left temporal lobes were affected in these patients. Cognitive performance was similarly impaired in all three groups, with predominant naming and hippocampal-dependent memory deficits. Mortality risk was 6.1 times higher in patients with right- than left-predominant ATL neurodegeneration (p < 0.05). Median survival duration after PET was shortest in patients with right- and longest in patients with left-predominant ATL neurodegeneration (5.7 vs 8.3 years after examination).

Discussion

More extensive neurodegeneration and shorter survival duration in patients with right- than left-predominant neurodegeneration of the ATL might indicate that the former consult memory clinics at a later disease stage, when symptoms like naming and episodic memory deficits have already emerged. At the time of diagnosis, the shorter survival duration of patients with right- than left-predominant ATL neurodegeneration should be kept in mind when counseling patients and caregivers.
On-site Gram staining that increases a post-test probability of an ominous infection: a case of necrotizing fasciitis caused by Vibrio vulnificus: a case report
Authors: Kannae Mikinori , Oka Yusuke , Hamada Yohei , Urakami Toshiharu , Aoki Yosuke
Published: January 2023

Background

Gram staining is a classic but standard and essential procedure for the prompt selection of appropriate antibiotics in an emergency setting. Even in the era of sophisticated medicine with technically developed machinery, it is not uncommon that a classic procedure such as Gram staining is the most efficient for assisting physicians in making therapeutic decisions in a timely fashion.

Case presentation

A 65-year-old Asian man with alcoholic cirrhosis complicated by esophageal varices was brought to the emergency division of Saga Medical School Hospital in early August, complaining of severe pain, redness, swelling, and purpura of the lower extremities. On physical examination he appeared in a critically ill condition suggestive of deep-seated soft tissue infection, raising a pre-test probability of streptococci, staphylococci, Vibrio sp., or Aeromonas sp. as a causative pathogen. A characteristic of his residency in an estuarine area is that raw seafood ingestion, as documented in this patient prior to the current admission, predisposes those who have a chronic liver disease to a life-threatening Vibrio vulnificus infection.

Given the pathognomonic clinical features suggestive of necrotizing fasciitis, our immediate attempt was to narrow down the differential list of candidate pathogens by obtaining clinical specimens for microbiological investigation, thus inquiring about the post-test probability of the causative pathogen. The Gram stain of the small amount of discharge from the test incision of the affected lesion detected Gram-negative rods morphologically compatible with V. vulnificus. After two sets of blood culture, intravenous meropenem and minocycline were immediately administered before the patient underwent emergency surgical debridement. The next day, both blood culture and wound culture retrieved Gram-negative rods, which were subsequently identified as V. vulnificus by mass spectrometry, matrix-assisted laser desorption/ionization. The antibiotics were switched to intravenous ceftriaxone and minocycline.

Conclusion

The pre-test probability of V. vulnificus infection was further validated by on-site Gram staining in the emergency division. This case report highlights the significance of a classic procedure.
Joint computation offloading and resource allocation strategy for D2D-assisted and NOMA-empowered MEC systems
Authors: Khan Umar Ajaib , Chai Rong , Ahmad Shabeer , Almughalles Waleeed
Published: January 2023

Multi-access edge computing (MEC) emerged as a promising network paradigm that provides computation, storage and networking features within the edge of the pervasive mobile radio access network. This paper jointly considers computation offloading and resource allocation problem in device-to-device (D2D)-assisted and non-orthogonal multiple access (NOMA)-empowered MEC systems, where each mobile device (MD) is allowed to execute its task in one of the three ways, i.e., local computing, MEC offloading or D2D offloading. We invoke orthogonal multiple access (OMA) and NOMA schemes for MDs that select D2D offloading mode, allowing them to assign tasks to their peers using OMA or NOMA. The original problem is formulated as an overall energy consumption minimization problem, which proves to be NP-hard, making it intractable to solve optimally. We start from a simple case, OMA case and transform the original problem into two sub-problems, i.e., resource allocation sub-problem and computation offloading sub-problem and propose two heuristic algorithms to obtain the sub-optimal solutions of both sub-problems. Then, for the MDs selecting D2D offloading mode, we conduct user pairing and apply the NOMA scheme. Finally, simulation results demonstrate the efficiency of the proposed scheme when compared with the related schemes.
Assisted Da Vinci robotic surgery combined with 3D printing technology applied in septal myectomy
Authors: Zhang Shuaipeng , Liu Zhuang , Liu Haiyuan , Zhang Chengxin
Published: January 2023

Generally, the standard surgical route of Morrow begins with the incision of median sternal, which leads to more trauma, pains and discomforts to patients with hypertrophic obstructive cardiomyopathy (HOCM). It is more difficult and rough to perform the competed resection of hypertrophic myocardium due to complicated anatomical morphology of left ventricular outflow tract and limited visual field of left ventricle during surgery. As the novel surgical strategy, firstly, under the guiding of 3D printing technology, the platform of effective preoperative evaluation focusing on how to resect the hypertrophic myocardium is established. Then, combined with assisted Da Vinci robotic surgery system, the outcome of patient with HOCM is positive and promised.
The bovine foot skin microbiota is associated with host genotype and the development of infectious digital dermatitis lesions
Authors: Bay V. , Gillespie A. , Ganda E. , Evans N. J. , Carter S. D. , Lenzi L. , Lucaci A. , Haldenby S. , Barden M. , Griffiths B. E. , Sánchez-Molano E. , Bicalho R. , Banos G. , Darby A. , Oikonomou G.
Published: January 2023

Background

Bovine Digital Dermatitis (BDD) is a prevalent infectious disease, causing painful foot skin lesions and lameness in cattle. We describe herein the bovine foot skin microbiota and its associations with BDD using 16S rRNA gene amplicon and shotgun metagenomic sequencing on samples from 259 dairy cows from three UK dairy farms.

Results

We show evidence of dysbiosis, and differences in taxonomy and functional profiles in the bovine foot skin microbiome of clinically healthy animals that subsequently develop BDD lesions, compared to those that do not. Our results suggest that taxonomical and functional differences together with alterations in ecological interactions between bacteria in the normal foot skin microbiome may predispose an animal to develop BDD lesions. Using genome-wide association and regional heritability mapping approaches, we provide first evidence for interactions between host genotype and certain members of the foot skin microbiota. We show the existence of significant genetic variation in the relative abundance of Treponema spp. and Peptoclostridium spp. and identify regions in the bovine genome that explain a significant proportion of this variation.

Conclusions

Collectively this work shows early changes in taxonomic and functional profiles of the bovine foot-skin microbiota in clinically healthy animals which are associated with subsequent development of BDD and could be relevant to prevention of disease. The description of host genetic control of members of the foot skin microbiota, combined with the association of the latter with BDD development offer new insights into a complex relationship that can be exploited in selective breeding programmes.
The effects of using an auto-subtitle system in educational videos to facilitate learning for secondary school students: learning comprehension, cognitive load, and satisfaction
Authors: Malakul Sivakorn , Park Innwoo
Published: January 2023

While subtitles are considered a primary learning support tool for people who cannot understand video narration in foreign languages, recent advancements in artificial intelligence (AI) technologies have played a pivotal role in automatic subtitling on online video platforms such as YouTube. This study examines the effects of three different types of subtitles in the Thai language (i.e., auto-subtitles, edited subtitles, and no subtitles) on learning comprehension, cognitive load, and satisfaction to determine whether it is feasible to use AI technology as an auto-subtitles system to facilitate online learning with educational videos. To that aim, 79 Thai secondary school students from three Mathayom 5 (Grade 11) computer science classrooms participated in this study. This study used the static group comparison, which is the Posttest-Only Control Group Design. The results of this study found that the auto-subtitles system that generates Thai language subtitles for English educational videos has greater feasibility of implementation to facilitate online learning when compared to editorial subtitles by Thai natives. Therefore, Thai subtitles generated by the auto-subtitles system in English educational videos can facilitate students’ learning comprehension, cognitive load, and satisfaction.
Investigation of the mechanism of the anomalous Hall effects in Cr2Te3/(BiSb)2(TeSe)3 heterostructure
Authors: Cho Seong Won , Lee In Hak , Lee Youngwoong , Kim Sangheon , Khim Yeong Gwang , Park Seung-Young , Jo Younghun , Choi Junwoo , Han Seungwu , Chang Young Jun , Lee Suyoun
Published: January 2023

The interplay between ferromagnetism and the non-trivial topology has unveiled intriguing phases in the transport of charges and spins. For example, it is consistently observed the so-called topological Hall effect (THE) featuring a hump structure in the curve of the Hall resistance (Rxy) vs. a magnetic field (H) of a heterostructure consisting of a ferromagnet (FM) and a topological insulator (TI). The origin of the hump structure is still controversial between the topological Hall effect model and the multi-component anomalous Hall effect (AHE) model. In this work, we have investigated a heterostructure consisting of BixSb2−xTeySe3−y (BSTS) and Cr2Te3 (CT), which are well-known TI and two-dimensional FM, respectively. By using the so-called “minor-loop measurement”, we have found that the hump structure observed in the CT/BSTS is more likely to originate from two AHE channels. Moreover, by analyzing the scaling behavior of each amplitude of two AHE with the longitudinal resistivities of CT and BSTS, we have found that one AHE is attributed to the extrinsic contribution of CT while the other is due to the intrinsic contribution of BSTS. It implies that the proximity-induced ferromagnetic layer inside BSTS serves as a source of the intrinsic AHE, resulting in the hump structure explained by the two AHE model.

Graphical abstract
Same-day comparative protocol PET/CT-PET/MRI [68 Ga]Ga-DOTA-TOC in paragangliomas and pheochromocytomas: an approach to personalized medicine
Authors: Prado-Wohlwend Stefan , Ballesta-Moratalla Mónica , Torres-Espallardo Irene , del Olmo-García María Isabel , Bello-Arques Pilar , Olivas-Arroyo Consuelo , Merino-Torres Juan Francisco
Published: January 2023

Background

PET/MRI is an emerging imaging modality which enables the evaluation and quantification of biochemical processes in tissues, complemented with accurate anatomical information and low radiation exposure. In the framework of theragnosis, PET/MRI is of special interest due to its ability to delineate small lesions, adequately quantify them, and therefore to plan targeted therapies. The aim of this study was to validate the diagnostic performance of [68 Ga]Ga-DOTA-TOC PET/MRI compared to PET/CT in advanced disease paragangliomas and pheochromocytomas (PGGLs) to assess in which clinical settings, PET/MRI may have a greater diagnostic yield.

Methods

We performed a same-day protocol with consecutive acquisition of a PET/CT and a PET/MRI after a single [68 Ga]Ga-DOTA-TOC injection in 25 patients. Intermodality agreement, Krenning Score (KS), SUVmax (Standard Uptake Value), target-to-liver-ratio (TLR), clinical setting, location, and size were assessed.

Results

The diagnostic accuracy with PET/MRI increased by 14.6% compared to PET/CT especially in bone and liver locations (mean size of new lesions was 3.73 mm). PET/MRI revealed a higher overall lesion uptake than PET/CT (TLR 4.12 vs 2.44) and implied an upward elevation of the KS in up to 60% of patients. The KS changed in 30.4% of the evaluated lesions (mean size 11.89 mm), in 18.4% of the lesions it increased from KS 2 on PET/CT to a KS ≥ 3 on PET/MRI and 24.96% of the lesions per patient with multifocal disease displayed a KS ≥ 3 on PET/MR, that were not detected or showed lower KS on PET/CT. In 12% of patients, PET/MRI modified clinical management.

Conclusions

PET/MRI showed minor advantages over conventional PET/CT in the detection of new lesions but increased the intensity of SSRs expression in a significant number of them, opening the door to select which patients and clinical settings can benefit from performing PET/MRI.
Fathers’ involvement in complementary feeding of children in Damot Woyde District, South Ethiopia: a community-based cross-sectional study
Authors: Wolkanto Amare Abebe , Gemebo Tsegaye Demissie , Dake Samson Kastro , Hailemariam Tewodros Getachew
Published: January 2023

Background

In infant and young child feeding practice parents are the primary agents for childcare activities, such as feeding. Mothers’ role in infant and young child feeding practice has been the focus of previous research. The involvement of fathers in child-feeding practice has rarely been studied. Thus, this study aimed to assess fathers’ involvement in the complementary feeding of children and identify factors associated with it in Southern Ethiopia.

Methods

A community-based cross-sectional study was conducted which included a survey, in-depth interviews, and focus group discussions (FGDs). The survey was conducted with 593 fathers who have at least one child of age 6-23 months. Four FGDs were conducted with fathers, and 21 in-depth interviews were conducted with fathers, mothers, and community health workers. The survey data were entered into Epi data software version 1.4.4.0 and statistical analysis was performed using SPSS software version 20. Bivariate and multivariate logistic regression analyses were performed and statistical significance was considered at p < 0.05. All interviews and FGDs were transcribed, coded, categorized, and analyzed using open code software version 4.0.2.

Results

Of the total sample of 593, 50.9% of the fathers in the study were involved in their children’s complementary feeding practices. Fathers with better household income (AOR = 1.56; 95% CI: 1.09, 2.22) and good perception of child complementary feeding practice (AOR = 1.79; 95% CI: 1.28, 2.52) were more likely to be involved in their children’s complementary feeding practice. The majority of the fathers had better knowledge about the recommended complementary feeding practices.

Conclusions

Income-generating activities and behavioral change communication for fathers should be encouraged to improve their involvement in child feeding. Community-based nutrition programs should also give due attention to increasing the involvement of fathers.
Research on Pickering emulsification technology based on the concept of “combination of medicine and adjuvant” to improve the pH stability of volatile oil in solid preparations—taking Lingzhu Pulvis as an Example
Authors: Peng Lei , Wang Mei , Zhang Xiao-Fei , Guo Dong-Yan , Zhai Bing-Tao , Zou Jun-Bo , Shi Ya-Jun
Published: January 2023

Lingzhu Pulvis are widely used in clinical practice because of their therapeutic effects, but their stability and efficacy are affected by the easy oxidation and volatility of Acorus calamus. In this study, we combined the idea of “combination of medicine and adjuvant” and introduced Pickering emulsion technology to use the ingredients of Lingzhu Pulvis as the stabilizer of Pickering emulsion. Pearl powder was selected as the stabilizer by the type of emulsion formation and the state of emulsion layer, and the optimal preparation method was 0.065 g·ml− 1 of pearl powder and 45% oil, prepared using high-pressure homogenization method (500 bar, three times). The malondialdehyde and peroxide contents in the crude oil and Pickering emulsion groups were analyzed under different pH environments, and it was clear that the Pickering emulsion group possessed higher antioxidant properties. The volatile oil of Acorus calamus in different groups was analyzed using GC-MS, and seven differential components were screened by processing the analytical data with R language, which were further determined that the differential components changed more slowly and had significantly improved stability in the Pickering emulsion group. This study provides a reference for the improvement of stability of other solid formulations containing oil in Chinese medicine.
Genetic generalized epilepsy: factors associated with drug resistance polytherapy
Authors: Hosny Hassan , Elfayoumy Nervana , Adly Mahmoud , Abdelghany Hend
Published: January 2023

Background

Different studies investigating generalized genetic epilepsy (GGE) have shown that achieving 5 years of remission, early seizure remission, and needing antiseizure medication (ASM) monotherapy may predict favorable long-term outcomes.

Results

This is a retrospective analytical cohort study. Records of patients with GGE diagnoses at a large epilepsy center in Cairo served as the data source. 630 patients (297 male patients (47.1%) and 333 female (52.9%)) were included, their median onset age was 13 years. The follow-up period of this study was at least 4 years. 418 patients (66.1%) were early remitters, 160 patients (25.4%) were late remitters, and 52 patients (8.3%) were intractable. In addition, 367 patients (58.3%) needed a single ASM to achieve a maximum remission period (monotherapy group), while 263 patients (41.7%) needed ASM polytherapy. Stepwise regression analysis revealed that absence seizures, clusters of seizures, seizure frequency before treatment, and dose of sodium valproate (VPA) until the first remission were independent predictors for polytherapy. Moreover, absence seizures, seizure frequency before treatment, VPA dose, and catamenial seizures in females were independent predictors of intractability.

Conclusion

The majority of GGE have a favorable outcome, some clinical features could predict the need for polytherapy and failure of remission on treatment.
Changes of lysosome by L-serine in rotenone-treated hippocampal neurons
Authors: Shin Sumin , Hwang Su-Kyeong , Mun Ji Young
Published: January 2023

Oxidative stress destroys cellular organelles and damages DNA, eventually leading to degenerative brain disorders. Persistent mitochondrial damage by oxidative stress eventually causes cells to inhibit the function of lysosomes. Rotenone used in this study inhibits complex 1 of the mitochondrial electron transport chain. Due to this inhibition, the production of free radicals is promoted, and oxidative stress can occur. To test as a role of antioxidant, L-serine was treated before treatment of rotenone to HT22 hippocampal cells. Then, changes in the activity and structure of lysosomes were analyzed. As a result, the oxidative stress caused by rotenone in HT22 cells was protected by L-serine. L-serine reduced free radicals in cells, and the damaged lysosomal structure and lysosome activity were also protected.
Association of MTHFR C677T polymorphism with risk of preterm birth in Indian mothers: a case–control study
Authors: Rathod Pratibha , Desai Ajesh , Chandel Divya
Published: January 2023

Background

Since MTHFR is the key enzyme in folate metabolism, its reduction can lead to hyperhomocysteinemia, which can have a negative impact on pregnancy outcome. Moreover, MTHFR polymorphism has also been linked with oxidative stress and genotoxicity. Identifying its ethnicity-specific association can help to reduce the incidence of preterm birth (PTB). Material and methods: Age-matched preterm birth mothers (< 37 weeks) and full-term mothers (> 37 weeks) were carefully selected for the study. The polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method was adopted to analyse MTHFR C677T polymorphism. Oxidative stress (OS) analysis was performed by measuring the levels of antioxidants (superoxide dismutase (SOD) and catalase (CAT)) and OS damage markers (lipid peroxidation (LPO), total protein). Genotoxicity was confirmed by the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. The statistical analysis was performed by Student’s t test, chi-square test, and one-way ANOVA. The relevant risk of premature delivery was represented by odds ratios (ORs) with 95% confidence intervals (95% CIs).

Results

The MTHFR polymorphism showed statistical significance for PTB outcome with CT and TT genotype frequencies at p < 0.01 and p < 0.05, respectively, between cases and controls. Within the PTB categories (extreme-, very-, moderate-PTB), TT genotype showed statistical significance at (p < 0.05), while CT genotype remained insignificant. Also, statistically high oxidative stress and DNA damage were observed in cases compared to controls for all genotypes. Furthermore, the T allele of the MTHFR gene was found to be linked with significantly increased OS and DNA damage on comparison within the groups.

Conclusions

This study confirms the MTHFR C677T polymorphism, oxidative stress, and genotoxicity biomarkers are associated with the PTB outcome. Analysis of these biomarkers during pregnancy can be of clinical significance.
Novel oral anticoagulant use in adults with congenital heart disease: a single-center experience report
Authors: Samarai Daniel , Isma Nazim , Lindstedt Sandra , Hlebowicz Joanna
Published: January 2023

Background

Adults with congenital heart disease (ACHD) are a group with an increased risk of thromboembolic complications and arrhythmias. Vitamin K antagonists are the most commonly used thromboprophylaxis therapy in this population. Studies on the efficacy and safety of novel oral anticoagulants (NOAC) are scare in ACHD. A retrospective study on ACHD patients on NOAC treatment registered in the National Quality Registry for Congenital Heart Disease, SWEDCON, and National Quality Registry for Atrial fibrillation and Anticoagulation, AuriculA, from Southern Sweden.

Results

Thirty patients who had been taking NOAC treatment for a minimum of 3 months were included. Their median age was 55 years (SD 17 years) and 57% were male. Median follow-up was 17 months (IQR: 10–41). Eliquis was the most used NOAC (47%). Median CHA2DS2-VASc score was 2 (IQR: 0–3) and HAS-BLED was 1 (IQR: 0–2). Complex ACHD was prevalent in 27% of the patients. No thromboembolic events were recorded; however, one major bleeding, unspecified, was reported during the total cumulative patient follow-up time of 64 years.

Conclusions

The results of our study, although limited in size, suggest that NOAC appear safe and effective in ACHD patients. Further and larger studies on NOAC in ACHD patients are warranted.
Clinical and manometric evaluation of postoperative anorectal function in patients after trans-anal pull-through for Hirschsprung disease
Authors: Foroutan Hamidreza , Homapour Farhad , Dehghani Mohsen , Niazkar Hamid Reza , Sufi Hoda , Zibaee Behdad
Published: January 2023

Background

Transanal endorectal pull-through (TEPT) surgery is a new trend in the treatment of Hirschsprung disease, and evaluating its functional outcome is difficult. The purpose of this study is to evaluate the defecation pattern after TEPT surgery in pediatrics.

Material and methods

In this cross-sectional survey, 40 patients with Hirschsprung disease were studied. They underwent a one-stage transanal pull-through procedure from May 2007 till April 2015 in Namazi hospital by the same surgeon. All the patients had the aganglionic segment in the rectosigmoid, confirmed by pre-operation barium enema and post-operation histopathology. The patients were 40 children with mean operation age of 36.6 months old. The success rate of surgery was evaluated by following the questionnaire form. Clinical evaluation with bowel function score and anorectomanometry were carried out.

Result

One hundred percent of them had a daily stool. Eighty-five percent of patients never experienced pain during defecation, 10% experienced occasional pain, and the rest felt pain with every defecation. Just one case (5%) reported using a laxative. Regarding improvements after the operation, 75% were completely okay, 20% felt much better, and 5% reported some improvements. The average National Health Service score was 8.375, which seems satisfactory. The mean average anal sphincter in the group with soiling was 39.67 and in the group without soiling was 34.83, which is in the normal range in both groups, and there was no significant difference between these groups (P > 0.05).

Conclusion

The defecation pattern after TEPT surgery were satisfactory in almost all cases, even in infancy. Most patients had satisfactory manometry and clinical result.
Fault?fracture reservoir identification method based on SRGAN and reconstructed super?resolution seismic signals
Authors: Xu Tianji , Qin Zhengye , Bo Feng , Ling Liyang , Xu Hongtao , Wei Shuijian , Cheng Bingjie
Published: January 2023

To address the problem of fault?fracture reservoir identification, a new method based on super?resolution (SR) seismic signal reconstruction is established to identify faults, sliding fracture zones and induced fracture zones. First, based on a super?resolution generation countermeasure (SRGAN) deep learning method, an SR seismic signal reconstruction network framework is designed with a discriminant network (D), a generation network (G) and a visual geometry group network (V). Through the perceptual loss, objective control functions and iterative parameter updates, the nonlinear feature learning advantages of the deep network are introduced, the noise is eliminated, weak signals are recovered, and low resolution (LR) signals are restored, allowing the seismic signal to be reconstructed into an SR signal. Second, the SR seismic signal is used to extract the geometric attributes, such as the coherence based on the gradient structure tensor (GST) and the curvature based on the fractional derivative approximation (FDA). Third, principal component analysis (PCA) is used to reduce the feature dimension of the seismic attributes such as the GST coherence and FDA curvature and extract the principal components with the strongest correlations, thus eliminating redundant and residual noise interference, highlighting the spatial distribution and internal details of the fault?fracture reservoir, and allowing a fine description of the fault?fracture reservoir to be developed. Finally, this method achieves a good application effect for reconstructing SR seismic signals and identifying fault?fracture reservoirs in the Sichuan Basin of China.
Kernel method for gravity forward simulation in implicit probabilistic geologic modeling
Authors: Liang Zhouji , de la Varga Miguel , Wellmann Florian
Published: January 2023

Gravity is one of the most widely used geophysical data types in subsurface exploration. In the recent developments of stochastic geologic modeling, gravity data serve as an additional constraint to the model construction. The gravity data can be included in the modeling process as the likelihood function in a probabilistic joint inversion framework and allow the quantification of uncertainty in geologic modeling directly. A fast but also precise forward gravity simulation is essential to the success of the probabilistic inversion. Hence, we have developed a gravity kernel method, which is based on the widely adopted analytical solution on a discretized grid. As opposed to a globally refined regular mesh, we construct local tensor grids for individual gravity receivers, respecting the gravimeter locations and the local sensitivities. The kernel method is efficient in terms of computing and memory use for mesh-free implicit geologic modeling approaches. This design makes the method well suited for many-query applications, such as Bayesian machine learning using gradient information calculated from automatic differentiation. Optimal grid design without knowing the underlying geometry is not straightforward before evaluating the model. Therefore, we further provide a novel perspective on a refinement strategy for the kernel method based on the sensitivity of the cell to the corresponding receiver. Numerical results are presented and found superior performance compared to the conventional spatial convolution method.