bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of a mcr-1 and CRISPR-Cas System Co-harboring Plasmid in a Carbapenemase-Producing High-Risk ST11 Klebsiella pneumoniae Strain
Authors: Cheng Yi-Hsiang , Chou Sheng-Hua , Huang Po-Han , Yang Tsuey-Ching , Juan Yu-Fan , Kreiswirth Barry N. , Lin Yi-Tsung , Chen Liang
Published: October 2021

We set out to study the prevalence of the mcr-1 gene in carbapenemase-producing Klebsiella pneumoniae (CPKP) strains, and to determine whether its presence is associated with a fitness cost. A total of 234 clinical CPKP isolates were collected from a tertiary medical center in Taiwan from January 2018 to January 2019. The mcr-1 and carbapenemase genes were detected by polymerase chain reaction (PCR) followed by Sanger sequencing. The mcr-1-positive carbapenemase-producing strain was characterized by whole genome sequencing, a plasmid stability test and a conjugation assay. In vitro growth rate and an in vivo virulence test were compared between the parental mcr-1-positive strain and its mcr-1 plasmid-cured strain. We identified only one mcr-1 positive strain (KP2509), co-harboring blaKPC–2 and blaOXA–48, among 234 (1/234, 0.43%) CPKP strains. KP2509 and its Escherichia coli mcr-1 transconjugant showed moderate colistin resistance (MIC = 8 mg/L). The mcr-1 is located on a large conjugative plasmid (317 kb), pKP2509-MCR, with three replicons, IncHI, IncFIB, and IncN. Interestingly, a complete Type IV-A3 CRISPR-Cas system was identified in pKP2509-MCR. Plasmid pKP2509-MCR was highly stable in KP2509 after 270 generation of passage, and the pKP2509-MCR cured strain PC-KP2509 showed similar growth rate and in vivo virulence in comparison to KP2509. The prevalence of mcr-1 in CPKP strains remains low in our center. Notably, we identified a large plasmid with multiple replicons containing both the mcr-1 and the Type IV-3A CRISPR-Cas genes. The further spread of this highly stable plasmid raises concern that it may promote the increase of mcr-1 prevalence in CPKP.
Prediction of Clinical Deep Brain Stimulation Target for Essential Tremor From 1.5 Tesla MRI Anatomical Landmarks
Authors: Engelhardt Julien , Cuny Emmanuel , Guehl Dominique , Burbaud Pierre , Damon-Perrière Nathalie , Dallies-Labourdette Camille , Thomas Juliette , Branchard Olivier , Schmitt Louise-Amélie , Gassa Narimane , Zemzemi Nejib
Published: October 2021

Background: Deep brain stimulation is an efficacious treatment for refractory essential tremor, though targeting the intra-thalamic nuclei remains challenging.

Objectives: We sought to develop an inverse approach to retrieve the position of the leads in a cohort of patients operated on with optimal clinical outcomes from anatomical landmarks identifiable by 1.5 Tesla magnetic resonance imaging.

Methods: The learning database included clinical outcomes and post-operative imaging from which the coordinates of the active contacts and those of anatomical landmarks were extracted. We used machine learning regression methods to build three different prediction models. External validation was performed according to a leave-one-out cross-validation.

Results: Fifteen patients (29 leads) were included, with a median tremor improvement of 72% on the Fahn–Tolosa–Marin scale. Kernel ridge regression, deep neural networks, and support vector regression (SVR) were used. SVR gave the best results with a mean error of 1.33 ± 1.64 mm between the predicted target and the active contact position.

Conclusion: We report an original method for the targeting in deep brain stimulation for essential tremor based on patients' radio-anatomical features. This approach will be tested in a prospective clinical trial.
Association Analysis of HIMP and SHIMP Quantitative Parameters in Patients With Vestibular Neuritis and Healthy Participants
Authors: Chen Feiyun , Chen Zichen , Zhang Yuzhong , Wei Xinyu , Zhao Huandi , Hu Juan , Cheng Ying , Ren Xiaoyong , Zhang Qing
Published: October 2021

Background: The Head Impulse Paradigm (HIMP) and Suppression Head Impulse Paradigm (SHIMP) are objective, quantitative methods that directly test the vestibulo-ocular reflex (VOR) and are increasingly becoming a standard in evaluating patients with vestibular disorders.

Objective: The main objective was to assess the correlations between HIMP and SHIMP parameters in patients with superior vestibular neuritis (VN) and healthy participants. Additionally, the correlations between the parameters of each method were analyzed.

Methods: A retrospective cohort, non-randomized study was designed. HIMP and SHIMP were performed on 40 patients with VN and 20 healthy participants (40 ears). HIMP and SHIMP parameters were measured and calculated. Pearson's or Spearson's correlations were used to establish the associations among them.

Results: A strong positive correlation was found between HIMP and SHIMP gain (Pearson's r = 0.957, p = 0.000), while strong negative correlations were detected between HIMP and SHIMP saccade amplitudes (r = −0.637, p = 0.000) and percentages of overt saccades (r = −0.631, p = 0.000). In HIMP, strong and moderate positive correlations were identified between gain and saccade amplitude (R2 = 0.726, p = 0.000) and gain and saccade percentage (R2 = 0.558, p = 0.000), respectively. By contrast, an extremely weak positive correlation was observed between gain and latency (R2 = 0.053, p = 0.040). In SHIMP, strong and moderate positive correlations were found between gain and saccade percentage (R2 = 0.723, p = 0.000) and gain and saccade amplitude (R2 = 0.525, p = 0.000), respectively, but no correlation was detected between gain and latency (R2 = 0.006, p = 0.490).

Conclusions: HIMP and SHIMP-related parameters were highly correlated (inter-method). Within each method (intra-method), moderate to strong correlations in VOR assessment were observed. These results further contribute to our understanding of the relationship between HIMP and SHIMP as well as to the diagnosis.
Weekly Paclitaxel, Carboplatin, and Cetuximab as First-Line Treatment of Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma for Patients Ineligible to Cisplatin-Based Chemotherapy: A Retrospective Monocentric Study in 60 Patients
Authors: Carinato Hélène , Burgy Mickaël , Ferry Régine , Fischbach Cathie , Kalish Michal , Guihard Sébastien , Brahimi Youssef , Flesch Henri , Bronner Guy , Schultz Philippe , Frasie Véronique , Thiéry Alicia , Demarchi Martin , Petit Thierry , Jung Alain C. , Wagner Pierre , Coliat Pierre , Borel Christian
Published: October 2021

Objective

For most patients suffering from recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC), chemotherapy is the main option after considering surgery and reirradiation. Cetuximab combined with a platinum-fluorouracil regimen (EXTREME) has been the standard of care for over a decade. Nevertheless, a significant number of patients remain unfit for this regimen because of age, severe comorbidities, or poor performance status. The aim of this study is to investigate an alternative regimen with sufficient efficacy and safety.

Methods

We reviewed retrospectively the medical charts of all patients treated with paclitaxel, carboplatin, and cetuximab (PCC) at our institution. Eligibility criteria were as follows: first-line R/M-HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx not suitable for local therapy, cisplatin, and/or 5-FU ineligibility, ECOG-PS: 0–2. PCC consisted of paclitaxel 80 mg/m2, carboplatin AUC 2, and cetuximab at an initial dose of 400 mg/m2 then 250 mg/m2, for 16 weekly administrations followed by cetuximab maintenance for patients for whom a disease control was obtained. The primary endpoint was overall survival (OS), and secondary endpoints were overall response rate (ORR), progression free survival (PFS), and safety.

Results

We identified 60 consecutive patients treated with PCC between 2010 and 2016 at our institution. Thirty-one patients (52%) were ECOG-PS 2. Fifty-five patients (92%) were cisplatin ineligible. ORR was 43.3% (95% CI, 30.8–55.8), and disease control rate was 65% (95% CI, 52.9–77.1). With a median follow-up of 35.7 months (IQR 28.6–48.8), median PFS was 5.8 months (95% CI, 4.5–7.2), and median OS was 11.7 months (95% CI, 7.5-14.8). For ECOG-PS 0–1 patients, median OS was 14.8 months (95% CI, 12.2–21.7) while it was only 7.5 months (95%CI: 5.5-12.7) for ECOG-PS 2 patients (p < 0.04). Grades III–IV toxicities occurred in 30 patients (50%). Most toxicities were hematologic. Six patients (10%) had febrile neutropenia. Nonhematologic toxicities were reported such as cutaneous toxicities, neuropathy, infusion-related reactions, or electrolyte disorders.

Conclusion

The weekly PCC regimen seems to be an interesting option in cisplatin-unfit patients. This study shows favorable PFS and OS when compared with what is achieved with the EXTREME regimen and a high controlled disease rate with predictable and manageable toxicities even in the more fragile population.
Novel Insights Into MALAT1 Function as a MicroRNA Sponge in NSCLC
Authors: Zhou Qinfeng , Liu Lianfang , Zhou Jing , Chen Yuanyuan , Xie Dacheng , Yao Yinan , Cui Dawei
Published: October 2021

The long non-coding RNA metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) was initially found to be overexpressed in early non-small cell lung cancer (NSCLC). Accumulating studies have shown that MALAT1 is overexpressed in the tissue or serum of NSCLC and plays a key role in its occurrence and development. In addition, the expression level of MALAT1 is significantly related to the tumor size, stage, metastasis, and distant invasion of NSCLC. Therefore, MALAT1 could be used as a biomarker for the early diagnosis, severity assessment, or prognosis evaluation of NSCLC patients. This review describes the basic properties and biological functions of MALAT1, focuses on the specific molecular mechanism of MALAT1 as a microRNA sponge in the occurrence and development of NSCLC in recent years, and emphasizes the application and potential prospect of MALAT1 in molecular biological markers and targeted therapy of NSCLC.
Radioresistance of Human Cancers: Clinical Implications of Genetic Expression Signatures
Authors: de Mey Sven , Dufait Inès , De Ridder Mark
Published: October 2021

Although radiotherapy is given to more than 50% of cancer patients, little progress has been made in identifying optimal radiotherapy - drug combinations to improve treatment efficacy. Using molecular data from The Cancer Genome Atlas (TCGA), we extracted a total of 1016 cancer patients that received radiotherapy. The patients were diagnosed with head-and-neck (HNSC - 294 patients), cervical (CESC - 166 patients) and breast (BRCA - 549 patients) cancer. We analyzed mRNA expression patterns of 50 hallmark gene sets of the MSigDB collection, which we divided in eight categories based on a shared biological or functional process. Tumor samples were split into upregulated, neutral or downregulated mRNA expression for all gene sets using a gene set analysis (GSEA) pre-ranked analysis and assessed for their clinical relevance. We found a prognostic association between three of the eight gene set categories (Radiobiological, Metabolism and Proliferation) and overall survival in all three cancer types. Furthermore, multiple single associations were revealed in the other categories considered. To the best of our knowledge, our study is the first report suggesting clinical relevance of molecular characterization based on hallmark gene sets to refine radiation strategies.
Single-Center Evaluation of Treatment Success Using Two Different Protocols for MRI–Guided Transurethral Ultrasound Ablation of Localized Prostate Cancer
Authors: Hatiboglu Gencay , Popeneciu Valentin , Bonekamp David , Burtnyk Mathieu , Staruch Robert , Distler Florian , Radtke Jan Philipp , Motsch Johann , Schlemmer Heinz Peter , Pahernik Sascha , Nyarangi-Dix Joanne
Published: October 2021

Objectives

To assess differences in 24-month oncologic and functional outcomes in men with low to intermediate-risk prostate cancer treated with MRI-guided transurethral ultrasound ablation (TULSA) using intentionally conservative versus intensified treatment parameters.

Patients and Methods

Patients from a single center involved in two multicenter trials were included in this analysis. This included 14 of 30 patients with Gleason 3 + 3 from a Phase I study using intentionally conservative treatment parameters, and 15 of 115 patients with Gleason ≤ 3 + 4 from a pivotal study using intensified parameters. Follow-up data compared across these cohorts included 12-month biopsy and MRI for all patients, and 24-month PSA, micturition and quality of life (IIEF, IPSS, IPSS-QOL). The prognostic value of baseline parameters and PSA kinetics on 12-month histological recurrence was evaluated by logistic regression.

Results

12-month biopsy revealed clinically significant residual disease in 4 (29%) and 2 (14%) patients from the Phase I and pivotal studies, respectively. PSA nadir was 0.7 ng/ml for Phase I and 0.5 ng/ml for pivotal study patients. Patient age at diagnosis, use of MRI fusion/systematic prostate biopsy, number of obtained cores at initial biopsy, PSA course, and PSA nadir were identified as prognostic factors for treatment success. All but one patient from each cohort maintained erection firmness sufficient for penetration. No cases of pad use were reported at 24 months. There were no Grade 4 or higher adverse events, and no late toxicity related to the procedure.

Conclusion

Two-year follow-up demonstrated the efficacy of TULSA for the treatment of localized prostate cancer, and the durability of PSA and functional outcomes. Intensifying treatment parameters in the pivotal trial had no impact on safety or functional outcomes through 24 months, while reducing the recurrence rate for clinically significant disease. Careful patient selection by MRI fusion/systematic prostate biopsy and adequate follow-up through routine 12-month biopsy are recommended.
Concurrence of Congenital Muscular Torticollis and Congenital Torticollis Due to Other Anomalies: Two Case Reports
Authors: Kim Min-Wook , Kim Da-Ye , Lee Dong-Woo , Ryoo Da-Hye , Kim Jaewon , Jang Dae-Hyun
Published: October 2021

Introduction: Congenital muscular torticollis (CMT) is the most common cause of torticollis in infants; other causes, including osseous, ocular, and central nervous system torticollis can easily be overlooked. We report two rare cases of CMT with concurrent osseous or ocular torticollis.

Case 1: A 1-month-old female infant with a right neck mass and right-tilting head posture was referred. Neck ultrasonography showed diffuse hypertrophy and hyperechoic findings on the right sternocleidomastoid (SCM) muscle, which was consistent with right CMT. A clavicle X-ray imaging was conducted to identify an associated fracture due to birth trauma on the same day and a suspected congenital vertebral anomaly was coincidentally found. Subsequent three-dimensional computed tomography of the cervical spine showed a T1 hemivertebra causing the right-tilting head. The patient was diagnosed with the concurrent manifestation of CMT and congenital osseous torticollis.

Case 2: A 3-month-old male infant with a 20° head tilt to the right with a limited cervical range of motion was referred. Neck ultrasonography showed a fibromatosis colli in the right SCM, suggesting CMT. He proceeded to physical therapy for seven months; however, there was little clinical improvement in his head and neck posture. The patient underwent an additional ophthalmologic examination and orbital magnetic resonance imaging (MRI) at 10 months of age. The result showed congenital agenesis of the left fourth cranial nerve with hypoplasia of the superior oblique muscle causing the right-tilting of the head. Ultimately, the boy was diagnosed with a concurrent manifestation of CMT and congenital ocular torticollis.

Conclusion: Unless careful examinations are conducted, congenital vertebral anomalies and congenital agenesis of the fourth cranial nerve can go unnoticed in the present two cases. If a patient with CMT displays unusual features or does not respond to physical therapy, clinicians should consider not only a differential diagnosis but also concurrence with other causes of congenital torticollis.
The Therapeutic Principle of Combined Strengthening Qi and Eliminating Pathogens in Treating Middle-Advanced Primary Liver Cancer: A Systematic Review and Meta-Analysis
Authors: She Yingqi , Huang Qinfeng , Ye Zhen , Hu Yu , Wu Mingquan , Qin Kaihua , Wei Ailing , Yang Xin , Liu Yuyao , Zhang Cuihan , Ye Qiaobo
Published: October 2021

Background: The combination of strengthening Qi and eliminating pathogens is an available therapeutic principle in traditional Chinese medicine (TCM) for primary liver cancer (PLC) at middle-advanced stage. However, there is a lack of reasonable evidence to support the proper application of this therapeutic principle. This meta-analysis aims to evaluate the efficacy and safety of Chinese medicinal formulas (CMFs), including two subgroup analyses of the principle of strengthening Qi and eliminating pathogens.

Method: Clinical trials were obtained through searching of EMBASE, Web of Science, PubMed, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journal Database, Chinese Biomedical Literature Database, and two clinical trial registries. The randomized controlled trials with the combination of CMFs and transcatheter arterial chemoembolization (TACE) in the experiment group were acceptable, in contrast to the TACE alone in the control group. The statistics analysis was performed on Review Manager 5.4.

Results: A total of eligible 24 trials were accessed in this work. Overall, CMFs could improve the survival duration of 6 months, 1 year, and 2 years, Karnofsky Performance Status, tumor objective response rate (ORR), AFP, and symptom. In the subgroup analysis, trials complying with the principle of single strengthening Qi did not show any significant difference in increasing tumor ORR. Meanwhile, the principle of combined strengthening Qi and eliminating pathogens was uncertain in improving symptoms and 1-year and 2-year survival time. In addition, the outcome indexes of ALT and AST were heterogeneous. In last, the total occurrence of adverse events could not be reduced via using CMFs. Patients treated with CMFs exhibited liver injury, fever, and white blood cell decline, with mild events occurring more frequently and severe events occurring less.

Conclusion: CMFs are an effective treatment method to cure PLC at the middle-advanced stage. Adopting the principle of single strengthening Qi presents better efficacy in the long term by prolonging the survival duration. Following the principle of combined strengthening Qi and eliminating pathogens could be more beneficial to patients in short term by lessening the tumor size. CMFs have the advantage of reducing certain serious adverse events.
ROS/JNK/C-Jun Pathway is Involved in Chaetocin Induced Colorectal Cancer Cells Apoptosis and Macrophage Phagocytosis Enhancement
Authors: Wang Huihui , Wen Chuangyu , Chen Siyu , Li Weiqian , Qin Qiyuan , He Lu , Wang Fang , Chen Junxiong , Ye Weibiao , Li Wende , Peng Junsheng , Yang Xiangling , Liu Huanliang
Published: October 2021

There is an urgent need for novel agents for colorectal cancer (CRC) due to the increasing number of cases and drug-resistance related to current treatments. In this study, we aim to uncover the potential of chaetocin, a natural product, as a chemotherapeutic for CRC treatment. We showed that, regardless of 5-FU-resistance, chaetocin induced proliferation inhibition by causing G2/M phase arrest and caspase-dependent apoptosis in CRC cells. Mechanically, our results indicated that chaetocin could induce reactive oxygen species (ROS) accumulation and activate c-Jun N-terminal kinase (JNK)/c-Jun pathway in CRC cells. This was confirmed by which the JNK inhibitor SP600125 partially rescued CRC cells from chaetocin induced apoptosis and the ROS scavenger N-acetyl-L-cysteine (NAC) reversed both the chaetocin induced apoptosis and the JNK/c-Jun pathway activation. Additionally, this study indicated that chaetocin could down-regulate the expression of CD47 at both mRNA and protein levels, and enhance macrophages phagocytosis of CRC cells. Chaetocin also inhibited tumor growth in CRC xenograft models. In all, our study reveals that chaetocin induces CRC cell apoptosis, irrelevant to 5-FU sensitivity, by causing ROS accumulation and activating JNK/c-Jun, and enhances macrophages phagocytosis, which suggests chaetocin as a candidate for CRC chemotherapy.
Role of Bioactive Constituents of Panax notoginseng in the Modulation of Tumorigenesis: A Potential Review for the Treatment of Cancer
Authors: Tan Ming-Ming , Chen Min-Hua , Han Fang , Wang Jun-Wei , Tu Yue-Xing
Published: October 2021

Cancer is a leading cause of death, affecting people in both developed and developing countries. It is a challenging disease due to its complicated pathophysiological mechanism. Many anti-cancer drugs are used to treat cancer and reduce mortality rates, but their toxicity limits their administration. Drugs made from natural products, which act as multi-targeted therapy, have the ability to target critical signaling proteins in different pathways. Natural compounds possess pharmacological activities such as anti-cancer activity, low toxicity, and minimum side effects. Panax notoginseng is a medicinal plant whose extracts and phytochemicals are used to treat cancer, cardiovascular disorders, blood stasis, easing inflammation, edema, and pain. P. notoginseng’s secondary metabolites target cancer’s dysregulated pathways, causing cancer cell death. In this review, we focused on several ginsenosides extracted from P. notoginseng that have been evaluated against various cancer cell lines, with the aim of cancer treatment. Furthermore, an in vivo investigation of these ginsenosides should be conducted to gain insight into the dysregulation of several pathways, followed by clinical trials for the potential and effective treatment of cancer.
On the Role of LGN/V1 Spontaneous Activity as an Innate Learning Pattern for Visual Development
Authors: Behpour Sahar , Field David J. , Albert Mark V.
Published: October 2021

Correlated, spontaneous neural activity is known to play a necessary role in visual development, but the higher-order statistical structure of these coherent, amorphous patterns has only begun to emerge in the past decade. Several computational studies have demonstrated how this endogenous activity can be used to train a developing visual system. Models that generate spontaneous activity analogous to retinal waves have shown that these waves can serve as stimuli for efficient coding models of V1. This general strategy in development has one clear advantage: The same learning algorithm can be used both before and after eye-opening. This same insight can be applied to understanding LGN/V1 spontaneous activity. Although lateral geniculate nucleus (LGN) activity has been less discussed in the literature than retinal waves, here we argue that the waves found in the LGN have a number of properties that fill the role of a training pattern. We make the case that the role of “innate learning” with spontaneous activity is not only possible, but likely in later stages of visual development, and worth pursuing further using an efficient coding paradigm.
Potential Biotechnological Applications of Autophagy for Agriculture
Authors: Thanthrige Nipuni , Bhowmik Sudipta Das , Ferguson Brett J. , Kabbage Mehdi , Mundree Sagadevan G. , Williams Brett
Published: October 2021

Autophagy is a genetically regulated, eukaryotic cellular degradation system that sequestrates cytoplasmic materials in specialised vesicles, termed autophagosomes, for delivery and breakdown in the lysosome or vacuole. In plants, autophagy plays essential roles in development (e.g., senescence) and responses to abiotic (e.g., nutrient starvation, drought and oxidative stress) and biotic stresses (e.g., hypersensitive response). Initially, autophagy was considered a non-selective bulk degradation mechanism that provides energy and building blocks for homeostatic balance during stress. Recent studies, however, reveal that autophagy may be more subtle and selectively target ubiquitylated protein aggregates, protein complexes and even organelles for degradation to regulate vital cellular processes even during favourable conditions. The selective nature of autophagy lends itself to potential manipulation and exploitation as part of designer protein turnover machinery for the development of stress-tolerant and disease-resistant crops, crops with increased yield potential and agricultural efficiency and reduced post-harvest losses. Here, we discuss our current understanding of autophagy and speculate its potential manipulation for improved agricultural performance.
A Two-Sided Lockdown? Social Class Variations in the Implementation of Homeschooling During the COVID-19 Lockdown
Authors: Sanrey Camille , Goudeau Sébastien , Stanczak Arnaud , Darnon Céline
Published: October 2021

The COVID-19 pandemic deeply affected how schools and families functioned through most of 2020. In particular, school closures meant parents took on a more central role in their children’s learning. This study analyzed social class variations in the quantity and quality of homeschooling during the lockdown. Through an online questionnaire, 360 parents reported (1) their digital equipment and use, (2) the perceptions of their ability to homeschool their children, (3) how they handled homeschooling and (4) the extent to which they supported other activities considered more or less “profitable” from an educational point of view (e.g., reading, watching television). A social position index was used as a proxy of social class. The results indicated that all parents were highly involved in setting up homeschooling and that the lower the parents’ social position, the more they spent time homeschooling their children. However, in line with the digital divide literature, the lower the parents’ social position, the lower the digital equipment and the less the parents felt capable of homeschooling. Finally, the higher the social position of the families, the more children spent time doing activities considered to be “educationally profitable,” and the less they spent time doing “unprofitable activities.” Thus, even if all parents were highly involved in homeschooling, higher social position parents were better equipped both materially and psychologically to face the challenge of homeschooling. The long-term impact of these processes on the perpetuation of social class inequalities are discussed.
Eye Movement Measures of Within-Language and Cross-Language Activation During Reading in Monolingual and Bilingual Children and Adults: A Focus on Neighborhood Density Effects
Authors: Whitford Veronica , Joanisse Marc F.
Published: October 2021

We used eye movement measures of first-language (L1) and second-language (L2) paragraph reading to investigate how the activation of multiple lexical candidates, both within and across languages, influences visual word recognition in four different age and language groups: (1) monolingual children; (2) monolingual young adults; (3) bilingual children; and (4) bilingual young adults. More specifically, we focused on within-language and cross-language orthographic neighborhood density effects, while controlling for the potentially confounding effects of orthographic neighborhood frequency. We found facilitatory within-language orthographic neighborhood density effects (i.e., words were easier to process when they had many vs. few orthographic neighbors, evidenced by shorter fixation durations) across the L1 and L2, with larger effects in children vs. adults (especially the bilingual ones) during L1 reading. Similarly, we found facilitatory cross-language neighborhood density effects across the L1 and L2, with no modulatory influence of age or language group. Taken together, our findings suggest that word recognition benefits from the simultaneous activation of visually similar word forms during naturalistic reading, with some evidence of larger effects in children and particularly those whose words may have differentially lower baseline activation levels and/or weaker links between word-related information due to divided language exposure: bilinguals.
From Hand to Eye With the Devil In-Between: Which Cognitive Mechanisms Underpin the Benefit From Handwriting Training When Learning Visual Graphs?
Authors: Fernandes Tânia , Araújo Susana
Published: October 2021

Cognitive science has recently shown a renewed interest on the benefit from training in handwriting (HW) when learning visual graphs, given that this learning experience improves more subsequent visual graph recognition than other forms of training. However, the underlying cognitive mechanism of this HW benefit has been elusive. Building on the 50 years of research on this topic, the present work outlines a theoretical approach to study this mechanism, specifying testable hypotheses that will allow distinguishing between confronting perspectives, i.e., symbolic accounts that hold that perceptual learning and visual analysis underpin the benefit from HW training vs. embodied sensorimotor accounts that argue for motoric representations as inner part of orthographic representations acquired via HW training. From the evidence critically revisited, we concluded that symbolic accounts are parsimonious and could better explain the benefit from HW training when learning visual graphs. The future challenge will be to put at test the detailed predictions presented here, so that the devil has no longer room in this equation.
Exploring the Intra Entrepreneurship-Employee Engagement-Creativity Linkage and the Diverse Effects of Gender and Marital Status
Authors: Kang Tae-Won , Sinha Paresha N. , Park Chang-Il , Lee Yong-Ki
Published: October 2021

This research examines which of the sub-dimensions of intra entrepreneurship (innovativeness, pro-activeness, risk-taking), and corporate social responsibility (CSR) support affects employee engagement (organizational and job engagement), which leads to employee creativity. The study uses survey data from SME employees in South Korea and applies the Structural Equation Modeling (SEM)-Artificial Neural Network (ANN) approach, to find that innovativeness and CSR support affect creativity through mediating roles of organizational engagement and job engagement, where job engagement plays a mediating role in the relationship between organizational engagement and creativity. The study also examines how employee gender and marital status effects the relative importance of intra entrepreneurship, organizational engagement, and job engagement on creativity. Findings of ANN analysis evaluates the effects per group (male-unmarried, male-married, female-unmarried, female-married) and shows how the importance of organizational engagement, job engagement, CSR support and innovativeness differ for each group. Contribution to theory and practice are discussed.
Engaging Leadership: How to Promote Work Engagement?
Authors: Schaufeli Wilmar
Published: October 2021

This paper introduces the notion of engaging leadership and reviews the empirical work done so far. Engaging leadership is defined as leadership behavior that facilitates, strengthens, connects and inspires employees in order to increase their work engagement. It can be measured with a reliable and valid self-report scale. As predicted by Self-Determination Theory, on which the concept of engaging leadership is based, basic need satisfaction mediates the relationship between engaging leadership and work engagement. This is true both for individual employees as well as the team level. In addition, job characteristics (job demands and job resources) seem to play a similar mediating role, just as personal resources. Furthermore, research shows that engaging leadership has a beneficial effect on individual and team performance which illustrates its relevance for organizations. Future research should focus, amongst others, on the opposite of engaging leadership (i.e., disengaging leadership) and interventions to foster engaging leadership. Moreover, alternative affective, cognitive and behavioral pathways should be explored that might play a role in addition to the motivational (through need fulfillment) and material (through job characteristics) pathways that have been investigated so far.
Higher Acceptance of Videotelephonic Counseling Formats in Psychosomatic Medicine in Times of the COVID-19 Pandemic
Authors: Lohmiller Jacqueline , Schäffeler Norbert , Zipfel Stephan , Stengel Andreas
Published: October 2021

Background: Due to the COVID-19 pandemic, the healthcare system in general and psychosomatics in particular were forced to change counseling-specific services and break up established structures. At the beginning of 2020, phone as well as videotelephonic counseling options had to be quickly established.

Methods: Patients (n = 278) of the department of psychosomatic medicine and psychotherapy at the University Hospital Tübingen were asked to complete an ad hoc questionnaire to assess the acceptance of the counseling format following each counseling session (office, phone, video) in the period between July 2020 and February 2021.

Results: Satisfaction and acceptance of the three counseling formats (office, phone, video) were rated (1–6) on average as “good” to “very good” in the three subgroups (1.5 ± 0.9). Likewise, the “therapeutic relationship” scored high in all three subgroups in terms of establishing a strong therapeutic relationship (4.4 ± 1.5). “Hurdles” were rated as low and tolerable (1.8 ± 1.3). The global assessment of therapeutic contact was significantly better in the video group compared to phone and office consultation (p < 0.05). Predictor analyses showed that there was an influence of age, but not gender, on the acceptance of digital counseling formats in the present sample [F(1, 277) = 4.50, p = 0.04].

Discussion & Conclusion: Digital consultation formats were perceived by patients as promising addition to the classic face-to-face setting. Digital formats (phone, video) were not generally preferred to face-to-face counseling, but especially video counseling was accepted and perceived with great satisfaction and acceptance. Accordingly, the additional use of digital counseling formats, especially video-telephony, could be an opportunity to enrich the existing structures also after the pandemic.
Examining the Causal Inference of Leptin and Soluble Plasma Leptin Receptor Levels on Schizophrenia: A Mendelian Randomization Study
Authors: Chen Guoqing , Wang Qiuling , Xue Ranran , Liu Xia , Yu Hao
Published: October 2021

Background: Observational studies that have supported the role of the leptin level in schizophrenia (SCZ) risk are conflicting. Therefore, we performed a two-sample Mendelian randomization (MR) analysis to investigate whether the circulating leptin and soluble plasma leptin receptor (sOB-R) levels play a causal role in SCZ risk.

Methods: We first selected five independent single-nucleotide polymorphisms (SNPs) associated with the circulating leptin level and three independent SNPs associated with the sOB-R level from two genome-wide association studies (GWASs) of European individuals. Then, we extracted their associations with SCZ using a large-scale GWAS that consisted of 40,675 patients with SCZ and 64,643 controls of European ancestry. We performed an MR analysis using the inverse variance-weighted (IVW) method to examine the causal effect of leptin on SCZ risk. Moreover, we performed sensitivity analyses to verify our MR results using the weighted median and MR-Egger methods.

Results: According to the IVW method, genetically predicted circulating leptin levels were not associated with SCZ risk (OR = 1.98, for per 1-SD unit increase in leptin level; 95% CI, 0.87–4.53; p = 0.10). In addition, the sOB-R level showed no causal effect on the SCZ risk using IVW (OR = 0.98 for per 1-SD unit increase in sOB-R level; 95% CI, 0.97–1.00; p = 0.06). Our sensitivity analysis results confirmed our MR findings.

Conclusions: By estimating the causal effect of leptin on SCZ risk using the MR methods, we identified no effect of genetically predicted circulating leptin or the sOB-R level on SCZ. As such, our study suggests that leptin might not be a risk factor for SCZ.
A Rare Subtype of Non-small Cell Lung Cancer: Report of 159 Resected Pathological Stage I–IIIA Pulmonary Lymphoepithelioma-Like Carcinoma Cases
Authors: Jiang Rong-Rong , Feng Xiao-Li , Zhu Wen-Ting , Guo Man-Xia , Tan Xue-Li , Jiang Xiao-Juan , Dou Xiao-Meng , Liu Li
Published: October 2021

Background: The current study analyzed resected stage I–IIIA pulmonary lymphoepithelioma-like carcinoma (LELC) cases to define the clinical characteristics, prognosis and long-term outcomes of resected LELC, with the purpose of guiding clinical management for this rare tumor.

Methods: Resected stage I–IIIA LELC, adenocarcinoma (ADC) and squamous cell carcinoma (SCC) cases from our center were enrolled. Propensity score matching (PSM) was applied to minimize the selection bias. Overall survival (OS) and disease-free survival (DFS) were compared between groups. Multivariate analyses were performed to identify the prognostic factors, and a nomogram was developed.

Results: A total of 159 LELCs, 2,757 ADCs, and 1,331 SCCs were included. LELC, dominated among younger patients and non-smokers. LELC was a poorly differentiated disease that lacked driver gene mutations and was positive for immunohistochemistry indicators of squamous cell lineage. Survival analyses revealed that OS was significantly better for LELC than for other common non-small cell lung cancers (NSCLCs) both before PSM (all P < 0.001) and after PSM (all P < 0.05). Further analyses revealed that early pathological node stage and preoperative albumin level ≥35 were identified as independent prognostic factors favoring OS and DFS.

Conclusions: LELC, dominated among younger and non-smoking populations, lacked driver gene mutations and was positive for immunohistochemistry indicators of squamous cell lineage. The survival outcome of LELC was better than other common NSCLCs.
Effects of Total Dissolved Gas Supersaturation on the Survival of Juvenile Procypris rabaudi and Juvenile Myxocyprinus asiaticus at Varying Water Depth in a Natural River
Authors: Liu Xiaoqing , Su Wen , Cao Chenyang , Li Zhiqin , Wang Yuanming , Shi Haoran , Yang Yao , Xu Liangfang
Published: October 2021

Total dissolved gas (TDG) supersaturation, which can be caused by flood discharge, results in gas bubble disease (GBD) in fish and threatens their survival downstream of dams. TDG supersaturation has become a serious environmental problem in the Yangtze River. Few studies have evaluated the effect of TDG supersaturation on fish in natural rivers during periods of flood discharge. To estimate fish tolerance to TDG supersaturation under natural conditions, juvenile Myxocyprinus asiaticus and juvenile Procypris rabaudi were exposed to TDG-supersaturated water for 96 h at various depths (0–0.3 m, 0.3–1.3 m, 1.3–2.3 m and 0–2.3 m) during periods of flood discharge of Dagangshan hydropower station. The results showed that juvenile Procypris rabaudi and juvenile Myxocyprinus asiaticus exhibited obvious GBD signs. An increase in exposure time decreased survival probability of the two species. Deeper water depths can increase the tolerance of juvenile Procypris rabaudi to TDG supersaturation in natural rivers during periods of flood discharge while it cannot improve the survival of juvenile Myxocyprinus asiaticus. Compared with juvenile Myxocyprinus asiaticus, juvenile Procypris rabaudi showed weaker tolerance of TDG supersaturation in shallow water, and juvenile Procypris rabaudi were more vulnerable to TDG supersaturation than juvenile Myxocyprinus asiaticus even if the TDG level (116%) was low.
Staphylococcus pseudintermedius’s PBP4 Is Directly Associated with the Dissociated Oxacillin and Cefoxitin Phenotype
Authors: Gagetti Paula , Rosato Roberto R. , Rosato Adriana E.
Published: October 2021

Staphylococcus pseudintermedius is an important pathogen responsible for infections in dogs and in humans. The emergence and dissemination of methicillin-resistant S. pseudintermedius (MRSP) and the multidrug resistance frequently seen in this species make difficult the treatment of these pathogens. The cefoxitin disk is widely used as a marker of methicillin resistance mediated by the mecA gene in Staphylococcus aureus and other staphylococcal species; however, it is not useful to detect β-lactam resistance of MRSP in clinical microbiology laboratories. The purpose of this study was to elucidate the molecular bases of the dissociated phenotype between oxacillin and cefoxitin antibiotics. By using a combinatorial approach that included the Penicillin-Binding Proteins’ (PBP) profile, their affinity for different β-lactam antibiotics and the analyses of PBPs’ sequence, we provide evidence that PBP4 showed still affinity for its target cefoxitin, impairing its phenotypic resistant detection in MRSP. Together, these findings provide evidence that S. pseudintermedius PBP4 is directly associated with the dissociated oxacillin and cefoxitin phenotype.
Antimicrobial Susceptibility and Detection of Virulence-Associated Genes in Escherichia coli Strains Isolated from Commercial Broilers
Authors: Kocúreková Tímea , Karahutová Lívia , Bujňáková Dobroslava
Published: October 2021

The aim of this study was to investigate the presence of iron-uptake and virulence genes, antibiotic resistance profiles, and phylogenetic relatedness in 115 Escherichia coli (E. coli) strains isolated from broilers in Slovakia and to determine their potential threat to human health. The most frequent phylogroups were B1 (37%) and A (21%), and 33.9% strains were included in pathogenic groups. The commonly observed iron-uptake genes were feoB (94%), sitA (83%), and iutA (58%). Protectins (iss, kpsMTII) were identified in 30% of samples. Four percent of B2-associated broilers carried the papC (P fimbria) gene connected with upper urinary tract infection. The dominant resistance was to tetracycline (49%), ampicillin (66%), ampicillin + sulbactam (27%), ciprofloxacin (61%), and trimethoprim + sulfonamide (34%); moreover, sporadically occurring resistance to cephalosporins, aminoglycosides, fluoroquinolones, and polypeptide colistin was observed. Genotypic analysis of resistance revealed the presence of blaCTX-M-1 and blaCTX-M-2 in two isolates from broilers. Commercial broilers can be reservoirs of virulent and resistant genes as well as E. coli causing (extra-)intestinal infections, which can be a potential threat to humans via direct contact and food.
Extracts of Waste from Poplar Wood Processing Alleviate Experimental Dextran Sulfate-Induced Colitis by Ameliorating Oxidative Stress, Inhibiting the Th1/Th17 Response and Inducing Apoptosis in Inflammatory Lymphocytes
Authors: Wang Wenjie , Zhang Yiwei , Cao Jiamin , Xu Jiahui , Zhao Linguo , Fang Xianying
Published: October 2021

As a fast-growing tree, poplar is widely planted and typically used for wood processing in China. During poplar wood processing, a large amount of poplar sawdust (PS) and poplar leaves (PL) are produced and abandoned. To make full use of poplar resources and clarify the use of poplar as a feed additive, the active ingredients in PS and PL were extracted and isolated, and the anti-inflammatory effects of the extracts on mice with dextran sulfate sodium (DSS)-induced colitis were investigated. In vitro anti-inflammatory experiments showed that the ethyl acetate extract of PS and PL (PSE and PLE, respectively) could significantly inhibit the proliferation of concanavalin A (Con A)-activated lymphocytes. Salicortin, tremulacin and salireposide were identified in both PSE and PLE. Oral administration of PSE and PLE rescued DSS-induced colonic shortening, repaired tissue damage, and decreased the disease activity index (DAI). The antioxidant capacity, including the increased activities of glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD and catalase (CAT) and decreased activity of myeloperoxidase (MPO), in the colons of mice with colitis was enhanced through the activation of ERK after treatment with PSE and PLE. The ratio of Th1 to Th17 cells, which can lead to inflammation in the spleen, was significantly decreased by the administration of PSE and PLE, while the phosphorylation of related transcription factors (p65, STAT1, and STAT3) was inhibited. Furthermore, PSE and PLE could induce apoptosis in Con A-activated lymphocytes, which may be associated with the increase in p-TBK1, as the molecular docking results also indicated that salireposide in PSE and PLE could interact with the TBK1 protein. Overall, our study provides a promising feed additive for improving intestinal inflammation in animals and a method for the full utilization of poplar resources.
Next-Generation Ultrasol Curcumin Boosts Muscle Endurance and Reduces Muscle Damage in Treadmill-Exhausted Rats
Authors: Sahin Emre , Orhan Cemal , Erten Fusun , Er Besir , Acharya Manutosh , Morde Abhijeet A. , Padigaru Muralidhara , Sahin Kazim
Published: October 2021

Curcumin positively affects performance during exercise and subsequent recovery. However, curcumin has limited bioavailability unless consumed in larger doses. In the current study, we examined the impact of a new formulation of curcumin, Next-Generation Ultrasol Curcumin (NGUC), which is relatively more bioavailable than natural curcumin on exhaustion time, grip strength, muscle damage parameters, and serum and muscle proteins. A total of 28 rats were randomly grouped as control (C, non-supplemented), exercise (E, non-supplemented), E+NGUC100 (supplemented with 100 mg/kg BW NGUC), and E+NGUC200 (supplemented with 200 mg/kg NGUC). Grip strength and exhaustion time were increased with NGUC supplementation (p < 0.0001). Creatine kinase (CK), lactate dehydrogenase (LDH), lactic acid (LA), myoglobin, malondialdehyde (MDA) concentrations were reduced in serum, and muscle tissue in NGUC supplemented groups (p < 0.05). In contrast, NGUC supplementation elevated the antioxidant enzyme levels compared to the non-supplemented exercise group (p < 0.01). Additionally, inflammatory cytokines were inhibited with NGUC administration (p < 0.05). NGUC decreased PGC-1α, p-4E-BP1, p-mTOR, MAFbx, and MuRF1 proteins in muscle tissue (p < 0.05). These results indicate that NGUC boosts exercise performance while reducing muscle damage by targeting antioxidant, anti-inflammatory, and muscle mass regulatory pathways.