bluuebunny/crossref_metadata_2025 huggingface dataset:
High-Fidelity Multiphysics FCEV bus study with detailed HVAC, cabin, and Hydrogen Fuel Cell models
Authors: Ensbury Theodor , Picarelli Alessandro , Dempsey Mike
Published: November 2022

Hydrogen Fuel Cells are potentially a viable zero emission propulsion technology for heavy commercial vehicles, like buses. This paper presents a detailed proof of concept Dymola model of an FCEV bus, built using the VeSyMA suite of libraries. Particular attention is paid to the use the high-fidelity Hydrogen Library from Dassault Systèmes for the fuel cell. Representative physical ancillary systems, coupled with detailed thermochemical modelling, enables detailed transient effects on fuel cell performance to be captured. A multizonal cabin model with independent zonal thermal properties, combined with a multi-physics HVAC model provide a realistic current drain on the drive battery. Such detail is important in understanding accurately the conditions the Fuel Cell will experience during operation. A model such as this has many real-world applications, such as component design and selection; concept evaluation; Fuel Cell degradation, maintenance, and durability analysis; accurate range estimation and controller development.
Spanish Abstract Meaning Representation: Annotation of a General Corpus
Authors: Shira Wein  , Lucia Donatelli  , Ethan Ricker  , Calvin Engstrom  , Alex Nelson  , Leonie Harter  , Nathan Schneider
Published: November 2022

Abstract Abstract Meaning Representation (AMR), originally designed for English, has been adapted to a number of languages to facilitate cross-lingual semantic representation and analysis. We build on previous work and present the first sizable, general annotation project for Spanish AMR. We release a detailed set of annotation guidelines and a corpus of 486 gold-annotated sentences spanning multiple genres from an existing, cross-lingual AMR corpus. Our work constitutes the second largest non-English gold AMR corpus to date. Fine-tuning an AMR to-Spanish generation model with our annotations results in a BERTScore improvement of 8.8%, demonstrating initial utility of our work.
A novel diG motif in ORF3a protein of SARS-Cov-2 for intracellular transport
Authors: Cruz-Cosme Ruth , Zhang Jiantao , Liu Dongxiao , Mahase Vidhyanand , Sallapalli Bhargava Teja , Chang Peixi , Zhang Yanjin , Teng Shaolei , Zhao Richard Y. , Tang Qiyi
Published: November 2022

The ongoing SARS-CoV-2/COVID-19 pandemic caused a global public health crisis. Yet, everyone’s response to SARS-CoV-2 infection varies, and different viral variants confer diverse pathogenicity. Thus, it is imperative to understand how viral determinants contribute to COVID-19. Viral ORF3a protein is one of those viral determinants, as its functions are linked to induction of cell and tissues damages, disease severity and cytokine storm that is a major cause of COVID-19-related death. ORF3a is a membrane-associated protein. Upon synthesis, it is transported from endoplasmic reticulum, Golgi apparatus to plasma membrane and subcellular endomembranes including endosomes and lysosomes. However, how ORF3a is transported intracellularly remains elusive. The goal of this study was to carry out a systematic mutagenesis study to determine the structural relationship of ORF3a protein with its subcellular locations. Single amino acid (aa) and deletion mutations were generated in the putative function-relevant motifs and other regions of interest. Immunofluorescence and ImageJ analyses were used to determine and quantitate subcellular locations of ORF3a mutants in comparison with wildtype ORF3a. The wildtype ORF3a localizes predominantly (Pearson’s coefficients about 0.8) on the membranes of endosomes and lysosomes. Consistent with earlier findings, deletion of the YXXΦ motif, which is required for protein export, retained ORF3a in the Golgi apparatus. Interestingly, mutations in a double glycine (diG) region (aa 187–188) displayed a similar phenotype to the YXXΦ deletion, implicating a similar role of the diG motif in intracellular transport. Indeed, interrupting any one of the two glycine residues such as deletion of a single (dG188), both (dG187/dG188) or substitution (G188Y) of these residues led to ORF3a retention in the Golgi apparatus (Pearson’s coefficients ≥0.8). Structural analyses further suggest that the diG motif supports a type-II β-turn between the anti-parallel β4 and β5 sheets and connects to the YXXΦ motif via hydrogen bonds between two monomers. The diG- YXXΦ interaction forms a hand-in-hand configuration that could facilitate dimerization. Together, these observations suggest a functional role of the diG motif in intracellular transport of ORF3a.
Doughty-electronegative heteroatom-induced defective MoS2 for the hydrogen evolution reaction
Authors: Xiao Zhaohui , Luo Shengdao , Duan Wei , Zhang Xu , Han Shixing , Liu Yipu , Yang Liang , Lin Shiwei
Published: November 2022

Producing hydrogen through water electrolysis is one of the most promising green energy storage and conversion technologies for the long-term development of energy-related hydrogen technologies. MoS2 is a very promising electrocatalyst which may replace precious metal catalysts for the hydrogen evolution reaction (HER). In this work, doughty-electronegative heteroatom defects (halogen atoms such as chlorine, fluorine, and nitrogen) were successfully introduced in MoS2 by using a large-scale, green, and simple ball milling strategy to alter its electronic structure. The physicochemical properties (morphology, crystallization, chemical composition, and electronic structure) of the doughty-electronegative heteroatom-induced defective MoS2 (N/Cl-MoS2) were identified using SEM, TEM, Raman, XRD, and XPS. Furthermore, compared with bulk pristine MoS2, the HER activity of N/Cl-MoS2 significantly increased from 442 mV to 280 mV at a current of 10 mA cm−2. Ball milling not only effectively reduced the size of the catalyst material, but also exposed more active sites. More importantly, the introduced doughty-electronegative heteroatom optimized the electronic structure of the catalyst. Therefore, the doughty-electronegative heteroatom induced by mechanical ball milling provides a useful reference for the large-scale production of green, efficient, and low-cost catalyst materials.
Polysaccharides from Vaccaria segetalis seeds reduce urinary tract infections by inhibiting the adhesion and invasion abilities of uropathogenic Escherichia coli
Authors: Yao Rongmei , Mao Xin , Xu Yingli , Qiu Xue , Zhou Lirun , Wang Yaxin , Pang Bo , Chen Mengping , Cao Shan , Bao Lei , Bao Yanyan , Guo Shanshan , Hu Limin , Zhang Haijiang , Cui Xiaolan
Published: November 2022

The seeds of Vaccaria segetalis (Neck.) are from a traditional medicinal plant Garcke, also called Wang-Bu-Liu-Xing in China. According to the Chinese Pharmacopoeia, the seeds of V. segetalis can be used for treating urinary system diseases. This study was designed to investigate the underlying mechanism of VSP (polysaccharides from Vaccaria segetalis) against urinary tract infections caused by uropathogenic Escherichia coli (UPEC). Here, both in vitro and in vivo infection models were established with the UPEC strain CFT073. Bacterial adhesion and invasion into bladder epithelial cells were analyzed. We found that VSP reduced the adhesion of UPEC to the host by inhibiting the expression of bacterial hair follicle adhesion genes. VSP also reduced the invasion of UPEC by regulating the uroplakins and Toll-like receptors of host epithelial cells. In addition, the swarming motility and flagella-mediated motility genes flhC, flhD and Flic of UPEC were diminished after VSP intervention. Taken together, our findings reveal a possible mechanism by which VSP interferes with the adhesion and invasion of UPEC.
Metagenomic next-generation sequencing assists the diagnosis treatment of fungal osteoarticular infections
Authors: Zhang Chaofan , Lin Yunzhi , Huang Changyu , Huang Zida , Fang Xinyu , Bai Guochang , Zhang Zeyu , Li Wenbo , Zhang Wenming
Published: November 2022

Background

Fungal osteoarticular infection (FOI) is not commonly seen in clinical practice but proposes a great challenge to orthopedic surgeons. In this study, we aimed to investigate the risk factors, the clinical features, and surgical outcomes of FOI in our institution. Specifically, we aimed to explore the role of metagenomic next-generation sequencing (mNGS) in the diagnosis and treatment of FOI.

Methods

All the patients who were diagnosed and managed with FOI in our institution from January 2007 to December 2020 were retrospectively reviewed, including primary fungal implant-related infection, primary fungal osteomyelitis or arthritis, and fungal infections secondary to bacterial osteomyelitis or implant-related bacterial infections. The potential risk factors and the clinical and surgical features were analyzed. The pathogen data were compared between culture and the mNGS test.

Results

A total of 25 patients were included, namely, 12 primary implant-related infections, 7 primary fungal osteomyelitis or arthritis, and 6 fungal infections secondary to bacterial osteomyelitis or implant-related bacterial infections. Most cases had undergone multiple surgeries or long-term antibiotic treatment. Diagnosis was mainly based on microbial culture and the mNGS test. Optimization of culture methods and the use of mNGS assisted the diagnosis. Specifically, mNGS was performed in 12 patients, 5 of whom were culture-negative. In the remaining seven cases, mNGS demonstrated the same results as culture. Management of FOI was complicated as most patients required multiple surgeries followed by long-term antifungal treatment. In selected cases, antifungal-impregnated cement spacer retention can be an optional choice. The overall success rate was 100% (25/25) for our cohort.

Conclusion

We concluded that patients with comorbidities and a history of multiple surgeries or long-term antibiotics are under higher risk for FOI. Use of mNGS assists the diagnosis and treatment of FOI. Surgery combined with long-term antifungal treatment achieved satisfactory outcomes. In selected cases, antifungal-impregnated cement spacer retention can be an optional treatment choice.
Myocardial strain imaging in Duchenne muscular dystrophy
Authors: Earl Conner C. , Soslow Jonathan H. , Markham Larry W. , Goergen Craig J.
Published: November 2022

Cardiomyopathy (CM) is the leading cause of death for individuals with Duchenne muscular dystrophy (DMD). While DMD CM progresses rapidly and fatally for some in teenage years, others can live relatively symptom-free into their thirties or forties. Because CM progression is variable, there is a critical need for biomarkers to detect early onset and rapid progression. Despite recent advances in imaging and analysis, there are still no reliable methods to detect the onset or progression rate of DMD CM. Cardiac strain imaging is a promising technique that has proven valuable in DMD CM assessment, though much more work has been done in adult CM patients. In this review, we address the role of strain imaging in DMD, the mechanical and functional parameters used for clinical assessment, and discuss the gaps where emerging imaging techniques could help better characterize CM progression in DMD. Prominent among these emerging techniques are strain assessment from 3D imaging and development of deep learning algorithms for automated strain assessment. Improved techniques in tracking the progression of CM may help to bridge a crucial gap in optimizing clinical treatment for this devastating disease and pave the way for future research and innovation through the definition of robust imaging biomarkers and clinical trial endpoints.
Efficacy and safety of dorzagliatin for type 2 diabetes mellitus: A meta-analysis and trial sequential analysis
Authors: Yu Yunfeng , Yang Xingyu , Tong Keke , Yin Shuang , Hu Gang , Zhang Fei , Jiang Pengfei , Zhou Manli , Jian Weixiong
Published: November 2022

Objective

To evaluate the efficacy and safety of dorzagliatin in the treatment of type 2 diabetes mellitus (T2DM) by using meta-analysis and trial sequential analysis (TSA).

Method

Search for clinical trials of dorzagliatin for T2DM in eight databases, with a time limit of build to July 2022. The included studies that met the requirements were carried out for meta-analysis and TSA.

Results

In terms of efficacy endpoints, meta-analysis showed that dorzagliatin decreased glycated hemoglobin A1c(HbA1c) [mean difference (MD) −0.65%, 95% confidence interval (CI) −0.76 ~ −0.54, P < 0.00001], fasting plasma glucose (FPG) (MD −9.22 mg/dL, 95% CI −9.99 ~ −8.44, P < 0.00001), 2 h postprandial glucose (2h-PPG) (MD −48.70 mg/dL, 95% CI −55.45 ~ −41.96, P < 0.00001), homeostasis model assessment 2 of insulin resistance (HOMA2-IR) (MD −0.07, 95% CI −0.14 ~ −0.01, P = 0.03) and increased homeostasis model assessment 2 of ß-cells function (HOMA2-β) (MD 2.69, 95% CI 1.06 ~ 4.31, P = 0.001) compared with placebo. And TSA revealed that the benefits observed for the current information set were conclusive, except for HOMA2-IR. In comparison with placebo, dorzagliatin increased triglyceride(TG) (MD 0.43 mmol/L, 95% CI 0.30 ~ 0.56, P < 0.00001), total cholesterol (TC) (MD 0.13 mmol/L, 95% CI 0.05 ~ 0.21, P = 0.001), body weight (MD 0.38 kg, 95% CI 0.12–0.63, P = 0.004) and body mass index (BMI) (MD 0.14 kg/m2, 95% CI 0.05–0.24, P = 0.003), while low density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were comparable. And TSA demonstrated that TG, TC, body weight, and BMI were conclusive. In terms of safety endpoints, dorzagliatin increased total adverse events (AEs) [risk ratio (RR) 1.56, 95% CI 1.06 ~ 2.30, P = 0.03], while serious AEs, hyperlipidemia, and hypoglycaemia were all comparable. And TSA indicated that the results need to be confirmed by additional studies. Harbord regression showed no publication bias.

Conclusion

Dorzagliatin was effective in lowering glycemia, reducing insulin resistance and improving islet ß-cells function without affecting blood pressure, LDL-C, and HDL-C. Although dorzagliatin caused a mild increase in TG and TC, it did not increase the incidence of hyperlipidemia, and the small increases in body weight and BMI were not clinically significant enough. In terms of safety, the total AEs caused by dorzagliatin may be a cumulative effect of single AEs, with no drug-related adverse event being reported at a higher incidence than placebo alone. Dorzagliatin's serious AEs, hyperlipidemia, and hypoglycemia are comparable to that of placebo, and dorzagliatin has a good safety profile.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=371802 identifier: CRD42022371802.
Electrocardiographic phenotype of exercise-induced arrhythmogenic cardiomyopathy: A retrospective observational study
Authors: Miljoen Hielko , Spera Francesco , Van Kolen Katrien , Saenen Johan , Claessen Guido , Huybrechts Wim , Sarkozy Andrea , Heidbuchel Hein
Published: November 2022

Introduction

The right ventricle can be susceptible to pathologic alterations with exercise. This can cause changes to the ECG. Our aim was to identify the electrocardiographic phenotype of exercise induced (ExI) arrhythmogenic cardiomyopathy (ACM).

Methods

A retrospective analysis of ECGs at rest, peak exercise and 1 min of recovery in four groups of individuals was performed: Arrhythmogenic Cardiomyopathy with genetic confirmation (Gen-ACM; n = 16), (genetically negative) ExI-ACM (n = 15), control endurance athletes (End; n = 16) and sedentary individuals (Sed; n = 16). The occurrence of ventricular arrhythmias (VA) and, at each stage, QRS duration, Terminal Activation Delay (TAD), the ratio of the sum of the QRS durations in the right precordials (V1-V3) over that in the left precordials (V4-V6; R/L duration ratio), the presence of complete RBBB and T-wave inversion (TWI) beyond lead V2 were evaluated.

Results

At rest, complete RBBB was exclusively found in Gen-ACM (6%) and ExI-ACM (13%). No epsilon waves were identified. TWI beyond V2 was uniquely present in Gen-ACM (73%) and ExI-ACM (38%; p < 0.001). VA was present in Gen-ACM (88%); ExI-ACM (80%), End (25%) and Sed (19%; p < 0.001). The presence of R/L duration ratio of >1.2 and TAD ≥ 55 ms were not significantly different over the four groups (p = 0.584 and p = 0.218, respectively). At peak exercise the most striking finding was a significant decrease of the R/L duration ratio in individuals with ACM, which was the result of lateral precordial QRS prolongation.

Conclusion

ExI-ACM shares important ECG-features with Gen-ACM, suggesting a similar underlying pathogenesis regardless of the presence or absence of desmosomal mutations.
Adaptive granularity in tensors: A quest for interpretable structure
Authors: Pasricha Ravdeep S. , Gujral Ekta , Papalexakis Evangelos E.
Published: November 2022

Data collected at very frequent intervals is usually extremely sparse and has no structure that is exploitable by modern tensor decomposition algorithms. Thus, the utility of such tensors is low, in terms of the amount of interpretable and exploitable structure that one can extract from them. In this paper, we introduce the problem of finding a tensor of adaptive aggregated granularity that can be decomposed to reveal meaningful latent concepts (structures) from datasets that, in their original form, are not amenable to tensor analysis. Such datasets fall under the broad category of sparse point processes that evolve over space and/or time. To the best of our knowledge, this is the first work that explores adaptive granularity aggregation in tensors. Furthermore, we formally define the problem and discuss different definitions of “good structure” that are in practice and show that the optimal solution is of prohibitive combinatorial complexity. Subsequently, we propose an efficient and effective greedy algorithm called ICEBREAKER, which follows a number of intuitive decision criteria that locally maximize the “goodness of structure,” resulting in high-quality tensors. We evaluate our method on synthetic, semi-synthetic, and real datasets. In all the cases, our proposed method constructs tensors that have a very high structure quality.
A study of intercultural adaptation in the Sino-American joint training dual degree programs
Authors: Yueyue Cai , Nordin Nor Akmar , Panatik Siti Aisyah
Published: November 2022

Introduction

This study focuses on the factors influencing the intercultural adaptation stress and strategies of students in the Sino-American Joint Training Dual Degree Program.

Methods

A total number of 400 questionnaires were distributed to Chinese students who participating in the Program and the 355 responded. Motivation and Expectation Scale, Acculturative Stress Scale for International Students and The Intercultural Adaptation Strategies Scale were adopted to measure variables. Regression test, one-way Analysis of Variance (ANOVA) and Structural Equation Model (SEM) were applied to analyze the survey data.

Results

The results revealed that the number of local friends, the length of stay in the US, the motivation to study abroad, and the expectation to study abroad have a negative influence on the intercultural adaptation stress of the students. The greater the number of local friends, the longer the length of stay of study abroad, the stronger the motivation and expectation to study abroad, their intercultural adaptation strategies favor integration and assimilation.

Discussion

Based on the findings, this study examines which teaching and learning management methods Chinese institutions should apply to help students reduce the negative effects of intercultural adaptation stress and to choose intercultural adaptation strategies for integration and assimilation when undertaking teaching and learning activities for the Sino-American Joint Training Dual Degree Program.
Implementing an online peer tutoring intervention to promote reading skills of elementary students: Effects on fluency and accuracy
Authors: Sanches-Ferreira Manuela , Martins Helena , Valquaresma Andreia , Alves Sílvia
Published: November 2022

The global COVID-19 pandemic disrupted face-to-face teaching, having a significant impact on the teaching-learning process. As a result, many students spent less time reading (and learning to read) than they did during face-to-face instruction, requiring the use of alternative approaches of instruction. A combined online and peer tutoring intervention was designed to improve reading skills such as fluency and accuracy. Following a quasi-experimental design, this study sought to evaluated the impact of implementing an online peer tutoring intervention on the development of reading fluency and accuracy in a sample of 91 2nd and 4th graders (49.6% female). Children were aged 6–10 years old (M = 7.81, SD = 1.10) and were enrolled in five classrooms (A, B, C, D, and E) from three schools in the Portuguese district of Porto, between January and May 2021. A set of 10 texts were chosen from official textbooks to assess reading fluency and accuracy. Classes were evaluated in three moments: initial (pre-intervention), intermediate (after 10 sessions) and final (post-test, after other 10 sessions). In order to examine the effects of the intervention, there was a 8-week lag between the start of the intervention in classes A, B, and C (experimental group) and classes D and E (control group). Moreover, classes D and E started intervention with a gap of 5 weeks between them. Students in the experimental group registered significant higher improvements in reading accuracy and fluency than in the control group. Interaction effects revealed that students with an initial lower performance (i.e., at the frustration level) showed higher increases in reading accuracy. Furthermore, 2nd graders showed higher increases throughout the intervention while the 4th graders stablished their progress after the first 10 sessions of intervention. Despite the study’s limitations, the findings support the positive impact that online peer tutoring can have on promoting students’ reading skills, adding to the ongoing discussion—which has gained a special emphasis with the COVID-19 pandemic—about the development of effective strategies to promote reading abilities in the first years of school.
Complex impacts of gallstone disease on metabolic syndrome and nonalcoholic fatty liver disease
Authors: Lyu Jingting , Lin Qinghong , Fang Zhongbiao , Xu Zeling , Liu Zhengtao
Published: November 2022

Background

Patients with gallstone disease (GSD) often have highly co-occurrence with metabolic syndrome (MetS) and Nonalcoholic fatty liver disease (NAFLD) both associated with insulin resistance (IR). Meanwhile, highly prevalence of NAFLD was found in patients who received cholecystectomy. However, the associations of GSD with MetS, NAFLD is inconsistent in the published literature. And risk of cholecystectomy on NAFLD is unclear.

Methods

We searched the Medline EMBASE and WOS databases for literature that met our study topic. To be specific, studies with focus on associations between GSD and MetS/NAFLD, and risk evaluation on cholecystectomy and NAFLD incidence were enrolled for further analysis. The random effect model was used to calculate the combined relative ratio (RR) and odds ratio (OR)and 95% confidence interval (CI).

Results

Seven and six papers with focus on connections between GSD and NAFLD/MetS prevalence. Correspondingly, seven papers with focus on risk of cholecystectomy on NAFLD occurrence were also enrolled into meta-analysis. After pooling the results from individual study, patients with GSD had higher risk of MetS (OR:1.45, 95%CI: 1.23-1.67, I2 = 41.1%, P=0.165). Risk of GSD was increased by 52% in NAFLD patients (pooled OR:1.52, 95%CI:1.24-1.80). And about 32% of increment on NAFLD prevalence was observed in patients with GSD (pooled OR: 1.32, 95%CI:1.14-1.50). With regard to individual MetS components, patients with higher systolic blood pressure were more prone to develop GSD, with combined SMD of 0.29 (96%CI: 0.24-0.34, P<0.05). Dose-response analysis found the GSD incidence was significantly associated with increased body mass index (BMI) (pooled OR: 1.02, 95%CI:1.01-1.03) in linear trends. Patients who received cholecystectomy had a higher risk of post-operative NAFLD (OR:2.14, 95%CI: 1.43-2.85), P<0.05). And this impact was amplified in obese patients (OR: 2.51, 95%CI: 1.95-3.06, P<0.05).

Conclusion

Our results confirmed that controls on weight and blood pressure might be candidate therapeutic strategy for GSD prevention. And concerns should be raised on de-novo NAFLD after cholecystectomy.
Toxic effects of combined exposure of tritiated water and genistein on the growth and development of zebrafish and its mechanism
Authors: Cui Fengmei , Zhang Qixuan , Wan Jun , Sun Liang , Chen Na , Xue Huiyuan , Wang Tianzi , Luo Fajian , Chen Qiu , Tu Yu
Published: November 2022

Water pollution and control are important issues of our lasting concern. Environmental media often contains a variety of compounds. Tritium is widely present in nature due to human activities. As an endocrine disruptor, genistein is widely found in water body. Will it cause damage when combined with tritiated water and genistein? In this study, Zebrafish embryos were randomly divided into 4 groups: blank control group (simple E3 medium), tritiated water exposure group (tritiated water with a final concentration of 3.7*102Bq/mL in the medium), and genistein exposure group (the final concentration of 1.4 mg/L genistein in the medium) and the combined exposure group of tritiated water and genistein (3.7*102 Bq/mL tritium water +1.4 mg/L genistein). The results show that tritiated water with 3.7*102 Bq/ml exposure alone did not affect the development of zebrafish embryos. However, the survival rate, hatching rate and heart rate of zebrafish larvae decreased combined exposure with genistein, and the abnormality rate and apoptotic cells in the embryos and the level of oxidative stress increased. The results of RNA sequencing showed that the combined exposure of tritiated water and genistein affected the gene expression of zebrafish embryos. Differential genes were mainly enriched in many pathways, such as p53 signaling pathway, steroid hormone biosynthesis, PPAR signaling pathway, metabolism of xenobiotics by cytochrome P450. The results of qRT-PCR and gene knockout experiment showed that cyp19a1b gene may plays an important role in the toxic effects of combined exposure.
Delimiting species in the taxonomically challenging orchid section Pseudophrys: Bayesian analyses of genetic and phenotypic data
Authors: Joffard Nina , Buatois Bruno , Arnal Véronique , Véla Errol , Montgelard Claudine , Schatz Bertrand
Published: November 2022

Accurate species delimitation is critical for biodiversity conservation. Integrative taxonomy has been advocated for a long time, yet tools allowing true integration of genetic and phenotypic data have been developed quite recently and applied to few models, especially in plants. In this study, we investigated species boundaries within a group of twelve Pseudophrys taxa from France by analyzing genetic, morphometric and chemical (i.e., floral scents) data in a Bayesian framework using the program integrated Bayesian Phylogenetics and Phylogeography (iBPP). We found that these twelve taxa were merged into four species when only genetic data were used, while most formally described species were recognized as such when only phenotypic (either morphometric or chemical) data were used. The result of the iBPP analysis performed on both genetic and phenotypic data supports the proposal to merge Ophrys bilunulata and O. marmorata on the one hand, and O. funerea and O. zonata on the other hand. Our results show that phenotypic data are particularly informative in the section Pseudophrys and that their integration in a model-based method significantly improves the accuracy of species delimitation. We are convinced that the integrative taxonomic approach proposed in this study holds great promise to conduct taxonomic revisions in other orchid groups.
Obstetric management of the most common autoimmune diseases: A narrative review
Authors: Fernández-Buhigas Irene
Published: November 2022

Historically, women with an autoimmune disease (AD) could not get pregnant due to infertility frequently linked to the medical condition or because the pregnancy was contraindicated, as it could harm the mother and the future child. Sometimes, pregnancy was contraindicated because the medication needed to control the AD could not be given during pregnancy. All these items are no longer true nowadays. Fertility treatments have advanced, obstetric care is better, and the medical treatments of autoimmune diseases have progressed, so women with any kind of AD are encouraged to get pregnant, and their presence in obstetric clinics is arising. This is challenging for the obstetricians, as to be sure that these pregnancies are safe for the mother and the future child, the obstetricians need to know the natural evolution of these conditions, the impact of pregnancy and postpartum on the illness, and the impact of the AD in the pregnancy. In this narrative review, we aim to make a brief resume of the obstetric management of the most common diseases (Systemic lupus erythematosus, antiphospholipid syndrome, the Anti-Ro/SSA and Anti-La/SSB antigen-antibody systems, rheumatoid arthritis, Sjögren's syndrome and Undifferentiated systemic rheumatic disease and overlap syndromes).
Cellular immune states in SARS-CoV-2-induced disease
Authors: Mortezaee Keywan , Majidpoor Jamal
Published: November 2022

The general immune state plays important roles against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Cells of the immune system are encountering rapid changes during the acute phase of SARS-CoV-2-induced disease. Reduced fraction of functional CD8+ T cells, disrupted cross-talking between CD8+ T cells with dendritic cells (DCs), and impaired immunological T-cell memory, along with the higher presence of hyperactive neutrophils, high expansion of myeloid-derived suppressor cells (MDSCs) and non-classical monocytes, and attenuated cytotoxic capacity of natural killer (NK) cells, are all indicative of low efficient immunity against viral surge within the body. Immune state and responses from pro- or anti-inflammatory cells of the immune system to SARS-CoV-2 are discussed in this review. We also suggest some strategies to enhance the power of immune system against SARS-CoV-2-induced disease.
The negative effect of antibiotics on RCC patients with immunotherapy: A systematic review and meta-analysis
Authors: Luo Zhiqiang , Hao Siyuan , Li Yuxuan , Cheng Lei , Zhou Xuedong , Gunes Emine Gulsen , Liu Shiyu , Chen Jing
Published: November 2022

Background

Microbiome dysbiosis is considered a predictive biomarker of clinical response in renal cell carcinoma (RCC), which can be regulated by antibiotics (ATB). Multiple studies have shown that concomitant ATB administration has inhibitory effects on immunotherapy in RCC. This review aimed to assess the impact of ATB on patient survival and tumor response in RCC with immunotherapy.

Methods

Literature evaluating the effect of ATB on immunotherapy in RCC from Cochrane Library®, PubMed®, Embase®, Scopus®, and Web of Science® were systematically searched. Hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS), odds ratio (OR) for objective response rate (ORR) and primary progressive disease (PD) were pooled as effect sizes for clinical outcomes. Subgroup analysis was conducted to reveal the determinants of the effect of ATB on immunotherapy, including time windows of ATB exposure to immunotherapy initiation, ICIs treatment and study location. The leave-one-out approach was adopted to analyze the heterogeneity formulated. Cumulative meta-analysis adding by time was used to observe dynamic changes of the results.

Results

Ten studies were included in the systematic review and six studies (with n=1,104 patients) were included in the meta-analysis, four studies were excluded for overlapping patients with subsequent larger studies and lack of unique patient-level data. ATB administration was significantly correlated with shorter PFS (HR=2.10, 95%CI [1.54; 2.85], I2 = 2% after omitting study Derosa et al, 2021 detected by leave-one-out approach), shorter OS (HR=1.69, 95%CI [1.34; 2.12], I2 = 25%) and worse ORR (OR=0.58, 95%CI [0.41; 0.84]), but no difference was observed in risk of PD (OR=1.18, 95%CI [0.97; 1.44]). No significant differences existed among the subgroups for determining the determinants of ATB inhibition.

Conclusions

Concomitant ATB with immunotherapy was associated with worse PFS, OS and ORR in RCC. No publication bias was observed in this study.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=349577, identifier CRD42022349577.
Deep learning classification of early normal-tension glaucoma and glaucoma suspect eyes using Bruch’s membrane opening-based disc photography
Authors: Seo Sat Byul , Cho Hyun-kyung
Published: November 2022

Purpose

We aimed to investigate the performance of a deep learning model to discriminate early normal-tension glaucoma (NTG) from glaucoma suspect (GS) eyes using Bruch’s membrane opening (BMO)-based optic disc photography.

Methods

501 subjects in total were included in this cross-sectional study, including 255 GS eyes and 246 eyes of early NTG patients. BMO-based optic disc photography (BMO overview) was obtained from spectral-domain optical coherence tomography (OCT). The convolutional neural networks (CNN) model built from scratch was used to classify between early NTG and GS. For diagnostic performances of the model, the accuracy and the area under the curve (AUC) of the receiver operating characteristic curve (ROC) were evaluated in the test set.

Results

The baseline demographics were age, 48.01 ± 13.03 years in GS, 54.48 ± 11.28 years in NTG (p = 0.000); mean deviation, −0.73 ± 2.10 dB in GS, −2.80 ± 2.40 dB in NTG (p = 0.000); and intraocular pressure, 14.92 ± 2.62 mmHg in GS, 14.79 ± 2.61 mmHg in NTG (p = 0.624). Our CNN model showed the mean AUC of 0.94 (0.83–1.00) and the mean accuracy of 0.91 (0.82–0.98) with 10-fold cross validation for discriminating between early NTG and GS.

Conclusion

The performance of the CNN model using BMO-based optic disc photography was considerably good in classifying early NTG from GS. This new disc photography of BMO overview can aid in the diagnosis of early glaucoma.
Electronic logbooks (e-logbooks) for the continuous assessment of medical licentiates and their medical skill development in the low-resource context of Zambia: A mixed-methods study
Authors: Barteit Sandra , Schmidt Jelena , Kakusa Mwanja , Syakantu Gardner , Shanzi Aubrey , Ahmed Yusuf , Malunga Gregory , Blass Klaus , Nieder Jessica , Andreadis Petros , Neuhann Florian
Published: November 2022

Background

Countries in sub-Saharan Africa continue to face insufficient health education resources and facilities, as well as a severe shortage of health care professionals. In 2019, the Levy Mwanawasa Medical University (LMMU) in Lusaka was launched to address the shortage of healthcare professionals implementing a decentralized training model utilizing selected regional and district hospitals in Zambia as training sites for various cadres. Decentralization makes it more challenging to monitor the learning process as part of continuous assessment; consequently, adequate approaches are necessary to ensure the quality and quantity of medical skills training. Electronic logbooks (e-logbooks) provide a promising tool for monitoring and evaluation of the medical training process.

Objective

We designed and implemented an e-logbook for Medical Licentiate students based on an existing software system. We evaluated the feasibility of this e-logbook, its acceptability among a cohort of Medical Licentiate students and their mentors, as well as its facilitators and barriers.

Materials and methods

During the course of a five-week-long clinical rotation in a training site in Kabwe, Zambia, two mentors and ten students participated in the pilot study and its evaluation. A mixed-methods approach utilized log-based usage data from the e-logbook web platform and conducted semi-structured in-depth interviews.

Results

Overall, both students and mentors accepted e-logbooks as a means to monitor skills development in this context, indicating that e-logbooks are a feasible tool in this decentralized setting. Feedback pointed out that the design and software-induced terminology of the e-logbook posed usability issues. The complexity and greater time commitment (mentors used a web-based platform instead of an app) limited the e-logbook’s potential.

Conclusion

We conclude that there is acceptability of monitoring medical skill development through a tablet-based e-logbook. However, the e-logbook in its current form (based on an existing software system, with limited adaptation possibilities to the local context) was insufficient for the LMMU environment. Given that this was attributable to design flaws rather than technology issues or rejection of the e-logbook as a quality assessment tool in and of itself, we propose that the e-logbook be implemented in a co-design approach to better reflect the needs of students and mentors.
Functional production of clostridial circularin A in Lactococcus lactis NZ9000 and mutational analysis of its aromatic and cationic residues
Authors: Liu Fangfang , van Heel Auke J. , Chen Jingqi , Kuipers Oscar P.
Published: November 2022

Circular bacteriocins, also known as bacterial head-to-tail cyclized peptides, are a subgroup of ribosomally synthesized and post-translationally modified peptides (RiPPs). Compared with their conventional linear counterparts, circular bacteriocins are highly stable over a broad temperature and pH range, and circularization decreases proteolytic degradation by exopeptidases. These features render them great potential as scaffold candidates to withstand strident conditions in food- and pharmaceutical applications. However, the biosynthesis and bioactivity of circular bacteriocins still remain largely unknown. To investigate and gain more insights into the biosynthesis of circular bacteriocins and to achieve efficient production and characterization of bacteriocin variants, we developed an efficient cloning and heterologous expression system for clostridial circularin A and successfully produced this circular peptide in Lactococcus lactis NZ9000. We report three system formats with single plasmid or plasmid combinations to achieve successful cloning and functional production of circularin A in L. lactis. These systematic varieties enabled us to choose the appropriate method to efficiently obtain various constructs with desired properties. With the established heterologous systems in L. lactis, we performed several mutagenesis studies in the precursor peptide to study its structure/function relationships. The overlay activity assay revealed that these mutant variants had variable effects on different indicator strains: lysine substitution for certain glutamine residue(s) greatly decreased its bioactivity against Clostridium perfringens and L. lactis NZ9000, and alanine replacement for the cationic residues significantly reduced the activity against Lactobacillus sake ATCC 15521, whereas alanine substitution for the aromatic residues decreased its bioactivity against all three testing strains dramatically. Moreover, the conditions for bacteriocin production were optimized. Results show that supplementing the minimal medium with extra glucose (or sucrose) and immediate nisin-induction improved the peptide yield significantly. Briefly, we developed an excellent system for the production of circularin A and a wide range of variant peptides in a convenient host, as well as a method for fast detection of peptide production and activity. This system facilitated our mutagenesis studies which provided valuable insights into the effects of mutating specific residues on its biosynthesis and bioactivity, and will eventually enable more complex research into the biosynthesis of circularin A.
Cardiorespiratory fitness is associated with fMRI signal in right cerebellum lobule VIIa Crus I and II during spatial navigation in older adult women
Authors: Kern Kathryn L. , McMains Stephanie A. , Storer Thomas W. , Moffat Scott D. , Schon Karin
Published: November 2022

Spatial navigation is a cognitive skill critical for accomplishing daily goal-directed behavior in a complex environment; however, older adults exhibit marked decline in navigation performance with age. Neuroprotective interventions that enhance the functional integrity of navigation-linked brain regions, such as those in the medial temporal lobe memory system, may preserve spatial navigation performance in older adults. Importantly, a well-established body of literature suggests that cardiorespiratory fitness has measurable effects on neurobiological integrity in the medial temporal lobes, as well as in other brain areas implicated in spatial navigation, such as the precuneus and cerebellum. However, whether cardiorespiratory fitness modulates brain activity in these regions during navigation in older adults remains unknown. Thus, the primary objective of the current study was to examine cardiorespiratory fitness as a modulator of fMRI activity in navigation-linked brain regions in cognitively healthy older adults. To accomplish this objective, cognitively intact participants (N = 22, aged 60–80 years) underwent cardiorespiratory fitness testing to estimate maximal oxygen uptake (V·O2max) and underwent whole-brain high-resolution fMRI while performing a virtual reality navigation task. Our older adult sample demonstrated significant fMRI signal in the right and left retrosplenial cortex, right precuneus, right and left inferior parietal cortex, right and left cerebellum lobule VIIa Crus I and II, right fusiform gyrus, right parahippocampal cortex, right lingual gyrus, and right hippocampus during encoding of a virtual environment. Most importantly, in women but not men (N = 16), cardiorespiratory fitness was positively associated with fMRI activity in the right cerebellum lobule VIIa Crus I and II, but not other navigation-linked brain areas. These findings suggest that the influence of cardiorespiratory fitness on brain function extends beyond the hippocampus, as observed in other work, to the cerebellum lobule VIIa Crus I and II, a component of the cerebellum that has recently been linked to cognition and more specifically, spatial processing.
Morphological investigations of endomorphin-2 and spinoparabrachial projection neurons in the spinal dorsal horn of the rat
Authors: Yin Jun-Bin , Lu Ya-Cheng , Li Fei , Zhang Ting , Ding Tan , Hu Huai-Qiang , Chen Ying-Biao , Guo Hong-Wei , Kou Zhen-Zhen , Zhang Ming-Ming , Yuan Jun , Chen Tao , Li Hui , Cao Bing-Zhen , Dong Yu-Lin , Li Yun-Qing
Published: November 2022

It has been proved that endomorphin-2 (EM2) produced obvious analgesic effects in the spinal dorsal horn (SDH), which existed in our human bodies with remarkable affinity and selectivity for the μ-opioid receptor (MOR). Our previous study has demonstrated that EM2 made synapses with the spinoparabrachial projection neurons (PNs) in the SDH and inhibited their activities by reducing presynaptic glutamate release. However, the morphological features of EM2 and the spinoparabrachial PNs in the SDH have not been completely investigated. Here, we examined the morphological features of EM2 and the spinoparabrachial PNs by using triple fluorescence and electron microscopic immunohistochemistry. EM2-immunoreactive (-ir) afferents directly contacted with the spinoparabrachial PNs in lamina I of the SDH. Immunoelectron microscopy (IEM) were used to confirm that these contacts were synaptic connections. It was also observed that EM2-ir axon terminals contacting with spinoparabrachial PNs in lamina I contained MOR, substance P (SP) and vesicular glutamate transporter 2 (VGLUT2). In lamina II, MOR-ir neurons were observed to receive direct contacts from EM2-ir varicosities. The synaptic connections among EM2, MOR, SP, VGLUT2, and the spinoparabrachial PNs were also confirmed by IEM. In sum, our results supply morphological evidences for the analgesic effects of EM2 on the spinoparabrachial PNs in the SDH.
Learning from magnetotactic bacteria: mms6 protects stem cells from oxidative damage
Authors: Wei Nai-Li , Xu Wenjing , Tang Hai-Liang , Xie Qiang , Zhai Yuting , Chen Jian , Zhang Xiao-Yong , Zhu Jian-Hong
Published: November 2022

Oxidative damage generally exists in stroke and impairs stem cells’ survival; however, the problem is difficult to treat. In order to help stem cells to resist this damage, we inserted a magnetotactic bacteria (MB) gene, mms6, into the neural stem cell genome by lentiviral transfection. It was found that the transfection of mms6 significantly improved the survival rate of stem cells in the condition of iron overload but not hypoxia. The bioenergetic profile also revealed that iron overloading weakened the mitochondrial respiration and spare respiration capacity of stem cells, but that these were enhanced after the expression of mms6. Additionally, Western blotting (WB) data revealed that mms6 upregulated the expression of glutathione peroxidase (GPX4), which protected stem cells from oxidative damage and ferroptosis. In order to determine the possible mechanisms, we analyzed the interactions between the MMS6 protein, Fe2+, and GPX4 via analog computation. The predicted models found that the MMS6 protein had a direct chelating site in the region of M6A with divalent iron; it also had weak binding with GPX4. Taken together, the magnetotactic bacterial gene mms6 protected stem cells from oxidative damage via binding with Fe2+, which could help them adapt to the microenvironment of stroke.
Dynamically attentive viewport sequence for no-reference quality assessment of omnidirectional images
Authors: Wang Yuhong , Li Hong , Jiang Qiuping
Published: November 2022

Omnidirectional images (ODIs) have drawn great attention in virtual reality (VR) due to the capability of providing an immersive experience to users. However, ODIs are usually subject to various quality degradations during different processing stages. Thus, the quality assessment of ODIs is of critical importance to the community of VR. The quality assessment of ODIs is quite different from that of traditional 2D images. Existing IQA methods focus on extracting features from spherical scenes while ignoring the characteristics of actual viewing behavior of humans in continuously browsing an ODI through HMD and failing to characterize the temporal dynamics of the browsing process in terms of the temporal order of viewports. In this article, we resort to the law of gravity to detect the dynamically attentive regions of humans when viewing ODIs. In this article, we propose a novel no-reference (NR) ODI quality evaluation method by making efforts on two aspects including the construction of Dynamically Attentive Viewport Sequence (DAVS) from ODIs and the extraction of Quality-Aware Features (QAFs) from DAVS. The construction of DAVS aims to build a sequence of viewports that are likely to be explored by viewers based on the prediction of visual scanpath when viewers are freely exploring the ODI within the exploration time via HMD. A DAVS that contains only global motion can then be obtained by sampling a series of viewports from the ODI along the predicted visual scanpath. The subsequent quality evaluation of ODIs is performed merely based on the DAVS. The extraction of QAFs aims to obtain effective feature representations that are highly discriminative in terms of perceived distortion and visual quality. Finally, we can adopt a regression model to map the extracted QAFs to a single predicted quality score. Experimental results on two datasets demonstrate that the proposed method is able to deliver state-of-the-art performance.