bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

AbstractPsoralea 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractMulti-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

AbstractGenerally, 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

Abstract

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.