bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining the Importance of Developing Entrepreneurial Communication Skills in Accelerator Programs: A Focus Group Based Approach
Authors: McGloin Rory , Saxton Arianna , Rao Aditi , Hintz Elizabeth , Coletti Amanda , Hamlin Emily , Turner Meredith , Mathieu Jennifer
Published: June 2023

Entrepreneurial accelerator programs have emerged within university settings as a solution to reduce the notably high failure rate of new ventures. Accelerators seek to support entrepreneurs by providing services and experiences that prepare participants to confront challenges that occur throughout the entrepreneurial journey and connect them to a broader business ecosystem. However, despite existing research that points to a correlation between an entrepreneur’s communication skills and the firm’s ability to achieve key business milestones, the existing literature does not identify which specific communication skills entrepreneurs need nor the situations/audiences in which these skills are most applicable. Therefore, this study conducted five focus group interviews with 14 established entrepreneurs from the United States who have participated in a university accelerator program in an effort to uncover the most valuable communication skills for entrepreneurs and the situations in which these skills apply. The findings illuminate how the development of specific communication factors such as confidence when presenting, flexibility, and empathetic listening are essential for entrepreneurs to engage with a wide range of audiences. This study also provides recommendations for university accelerators seeking to facilitate the development of these communication skills in their programming.
Elevated Serum IL-2 Levels are Associated With Major Depressive Disorder: A Case-Control Study
Authors: Suhee Farhana Islam , Shahriar Mohammad , Islam Sardar Mohammad Ashraful , Bhuiyan Mohiuddin Ahmed , Islam Md. Rabiul
Published: June 2023

Objectives:

Numerous earlier studies have stated an association between major depressive disorder (MDD) and altered expression of inflammatory process. However, it still needs to determine whether the alteration of cytokines is the causative factor or a consequence of this disorder. Therefore, we attempted to evaluate the role of the pro-inflammatory cytokine IL-2 in the pathophysiology of depression.

Methods:

We collected blood samples from 111 MDD patients and 112 healthy controls (HCs) matched by age and sex. Diagnostic and statistical manual of mental disorders (DSM-5) score was used to assess study participants. We determined the severity of depression using the Hamilton Depression (Ham-D) rating scale. We assayed serum levels of IL-2 using the Enzyme-Linked Immunosorbent Assay (ELISA) kit.

Results:

Elevated levels of IL-2 were detected in MDD patients than HCs (29.79 ± 6.18 and 12.77 ± 4.84 pg/ml, P < 0.05). We observed a higher level of IL-2 in female MDD patients compared to female HCs (31.98 ± 8.34 and 7.76 ± 0.36 pg/ml, P < 0.05). We witnessed a sex-specific correlation between the serum IL-2 levels and the Ham-D score and found that the females with higher Ham-D scores had higher serum IL-2 levels. Moreover, the ROC curve represented the good diagnostic performance of serum IL-2 levels as a biomarker with sensitivity and specificity values of 83.7% and 80.4%, respectively.

Conclusions:

The current study findings indicate that elevated serum IL-2 levels are associated with MDD. This alteration may be the cause of triggering depression or a result of the activated inflammatory process during the depression. Therefore, we recommend further interventional research to clarify the actual reasons for these altered IL-2 levels in MDD patients.
Scientometric analysis of highly cited papers on avascular necrosis of the femoral head from 1991 to 2022
Authors: Vaishya Raju , Gupta Brij Mohan , Mamdapur Ghouse Modin N. , Vaish Abhishek , Migliorini Filippo
Published: June 2023

Introduction

A highly cited paper (HCP) is considered a landmark that can influence both research and clinical practice. The characteristics of HCPs in avascular necrosis of the femoral head (AVNFH) were identified and the research status was explored in a scientometric analysis.

Methods

The present bibliometric analysis were based on the Scopus database from 1991 to 2021. Microsoft Excel and VOSviewer were used for co-authorship, co-citation, and co-occurrence analysis. From 8496 papers, only 2.9% (244) were HCPs, with 200.8 citations registered per article.

Results

Of the HCPs, 11.9% and 12.3% were externally funded and had international collaboration, respectively. These were published in 84 journals by 1625 authors from 425 organizations of 33 countries. The USA, Japan, Switzerland, and Israel were the leading countries.The lead research organizations were Sinai Hospital and John Hopkins University (USA). The most impactful organizations were University of Arkansas for Medical Science, and Good Samaritan Hospital (USA). R.A. Mont (USA) and K.H. Koo (South Korea) were the most prolific contributing authors, while R. Ganz (Switzerland) and R.S. Weinstein (USA) registered the most impactful contributions. The most prolific publishing journal was the Journal of Bone and Joint Surgery.

Conclusion

The HCPs contributed to the knowledge of AVNFH by examining research perspectives and identifying important subareas through keyword analysis.

Level of evidence: Not applicable.

Trial registration: Not applicable.
Agent-based models in urban transportation: review, challenges, and opportunities
Authors: Bastarianto Faza Fawzan , Hancock Thomas O. , Choudhury Charisma Farheen , Manley Ed
Published: June 2023

Objective

This paper aims to provide a comprehensive overview of the current state of agent-based models, focusing specifically on their application in urban transportation research. It identifies research gaps and challenges while outlining the key potential directions for future research.

Methodology

To conduct this study, a bibliometric analysis has been performed on 309 documents obtained from the Scopus database. The resulting clustering analysis has been further supplemented with content analysis.

Findings

The analysis reveals the existence of nine distinct clusters representing a wide range of research methods and problem interpretations in the field. In-depth examination of selected publications within each cluster has helped to identify key challenges faced by agent-based modelling approaches. These challenges include enhancing computing efficiency, developing unified calibration and validation methods, ensuring reproducibility of work, and incorporating various modules or frameworks into models to accurately replicate the complexities of the transport system and travel behaviour within specific application contexts.
Transgenerational exposure to ocean acidification impacts the hepatic transcriptome of European sea bass (Dicentrarchus labrax)
Authors: Auffret Pauline , Servili Arianna , Gonzalez Anne-Alicia , Fleury Marie-Lou , Mark Felix Christopher , Mazurais David
Published: June 2023

Physiological effects of ocean acidification associated with elevated CO2 concentrations in seawater is the subject of numerous studies in teleost fish. While the short time within-generation impact of ocean acidification (OA) on acid-base exchange and energy metabolism is relatively well described, the effects associated with transgenerational exposure to OA are much less known. Yet, the impacts of OA can vary in time with the potential for acclimation or adaptation of a species. Previous studies in our lab demonstrated that transgenerational exposure to OA had extensive effects on the transcriptome of the olfactory epithelium of European sea bass (Dicentrarchus labrax), especially on genes related to ion balance, energy metabolism, immune system, synaptic plasticity, neuron excitability and wiring. In the present study, we complete the previous work by investigating the effect of transgenerational exposure to OA on the hepatic transcriptome of European sea bass. Differential gene expression analysis was performed by RNAseq technology on RNA extracted from the liver of two groups of 18 months F2 juveniles that had been exposed since spawning to the same AO conditions as their parents (F1) to either actual pH or end-of-century predicted pH levels (IPCC RCP8.5), respectively. Here we show that transgenerational exposure to OA significantly impacts the expression of 236 hepatic transcripts including genes mainly involved in inflammatory/immune responses but also in carbohydrate metabolism and cellular homeostasis. Even if this transcriptomic impact is relatively limited compared to what was shown in the olfactory system, this work confirmed that fish transgenerationally exposed to OA exhibit molecular regulation of processes related to metabolism and inflammation. Also, our data expand the up-regulation of a key gene involved in different physiological pathways including calcium homeostasis (i.e.pthr1), which we already observed in the olfactory epithelium, to the liver. Even if our experimental design does not allow to discriminate direct within F2 generation effects from transgenerational plasticity, these results offer the perspective of more functional analyses to determine the potential physiological impact of OA exposure on fish physiology with ecological relevance.
Genome-wide analysis of MdPLATZ genes and their expression during axillary bud outgrowth in apple (Malus domestica Borkh.)
Authors: Li Jiuyang , Zhao Yongliang , Zhang Yaohui , Ye Feng , Hou Zhengcun , Zhang Yuhang , Hao Longjie , Li Guofang , Shao Jianzhu , Tan Ming
Published: June 2023

Background

Branching is a plastic character that affects plant architecture and spatial structure. The trait is controlled by a variety of plant hormones through coordination with environmental signals. Plant AT-rich sequence and zinc-binding protein (PLATZ) is a transcription factor that plays an important role in plant growth and development. However, systematic research on the role of the PLATZ family in apple branching has not been conducted previously.

Results

In this study, a total of 17 PLATZ genes were identified and characterized from the apple genome. The 83 PLATZ proteins from apple, tomato, Arabidopsis, rice, and maize were classified into three groups based on the topological structure of the phylogenetic tree. The phylogenetic relationships, conserved motifs, gene structure, regulatory cis-acting elements, and microRNAs of the MdPLATZ family members were predicted. Expression analysis revealed that MdPLATZ genes exhibited distinct expression patterns in different tissues. The expression patterns of the MdPLATZ genes were systematically investigated in response to treatments that impact apple branching [thidazuron (TDZ) and decapitation]. The expression of MdPLATZ1, 6, 7, 8, 9, 15, and 16 was regulated during axillary bud outgrowth based on RNA-sequencing data obtained from apple axillary buds treated by decapitation or exogenous TDZ application. Quantitative real-time PCR analysis showed that MdPLATZ6 was strongly downregulated in response to the TDZ and decapitation treatments, however, MdPLATZ15 was significantly upregulated in response to TDZ, but exhibited little response to decapitation. Furthermore, the co-expression network showed that PLATZ might be involved in shoot branching by regulating branching-related genes or mediating cytokinin or auxin pathway.

Conclusion

The results provide valuable information for further functional investigation of MdPLATZ genes in the control of axillary bud outgrowth in apple.
Prevalence of Salmonella Typhimurium and Salmonella Enteritidis isolated from poultry meat: virulence and antimicrobial-resistant genes
Authors: Nazari Moghadam Marziye , Rahimi Ebrahim , Shakerian Amir , Momtaz Hassan
Published: June 2023

Salmonellosis, a zoonotic disease, is one of the leading causes of foodborne illness worldwide. It is responsible for most infections caused by consumption of contaminated food. In recent years, a significant increase in the resistance of these bacteria to common antibiotics has been observed, posing a serious threat to global public health. The aim of this study was to investigate the prevalence of virulent antibiotic-resistant Salmonella spp. strains in Iranian poultry markets. A total of 440 chicken meat samples were randomly selected from meat supply and distribution facilities in Shahrekord and tested for bacteriological contamination. After culturing and isolating the strains, identification was performed using the classical bacteriological method and PCR. To determine antibiotic resistance, a disc diffusion test was performed according to the recommendations of the French Society of Microbiology. PCR was used to detect resistance and virulence genes. Only 9% of the samples were positive for Salmonella. These were Salmonella typhimurium isolates. All Salmonella typhimurium serotypes tested positive for the rfbJ, fljB, invA and fliC genes. Resistance to TET, cotrimoxazole, NA, NIT, piperacillin/tazobactam and other antibiotics was found in 26 (72.2%), 24 (66.7%), 22 (61.1%) and 21 (58.3%) isolates, respectively. The sul1, sul2 and sul3 genes were present in 20, 12 and 4 of 24 cotrimoxazole-resistant bacteria, respectively. Chloramphenicol resistance was found in six isolates, but more isolates tested positive for the floR and cat two genes. In contrast, 2 (33%) of the cat three genes, 3 (50%) of the cmlA genes and 2 (34%) of the cmlB genes were all positive. The results of this investigation showed that Salmonella typhimurium is the most common serotype of the bacterium. This means that most of the antibiotics commonly used in the livestock and poultry industries are ineffective against most Salmonella isolates, which is important for public health.
Case–control association study of congenital heart disease from a tertiary paediatric cardiac centre from North India
Authors: Kukshal Prachi , Joshi Radha O , Kumar Ajay , Ahamad Shadab , Murthy Prabhatha Rashmi , Sathe Yogesh , Manohar Krishna , Guhathakurta Soma , Chellappan Subramanian
Published: June 2023

Background

Congenital Heart diseases (CHDs) account for 1/3rd of all congenital birth defects. Etiopathogenesis of CHDs remain elusive despite extensive investigations globally. Phenotypic heterogeneity witnessed in this developmental disorder reiterate gene-environment interactions with periconceptional factors as risk conferring; and genetic analysis of both sporadic and familial forms of CHD suggest its multigenic basis. Significant association of de novo and inherited variants have been observed. Approximately 1/5th of CHDs are documented in the ethnically distinct Indian population but genetic insights have been very limited. This pilot case–control based association study was undertaken to investigate the status of Caucasian SNPs in a north Indian cohort.

Method

A total of 306 CHD cases sub-classified into n = 198 acyanotic and n = 108 cyanotic types were recruited from a dedicated tertiary paediatric cardiac centre in Palwal, Haryana. 23 SNPs primarily prioritized from Genome-wide association studies (GWAS) on Caucasians were genotyped using Agena MassARRAY Technology and test of association was performed with adequately numbered controls.

Results

Fifty percent of the studied SNPs were substantially associated in either allelic, genotypic or sub-phenotype categories validating their strong correlation with disease manifestation. Of note, strongest allelic association was observed for rs73118372 in CRELD1 (p < 0.0001) on Chr3, rs28711516 in MYH6 (p = 0.00083) and rs735712 in MYH7 (p = 0.0009) both on Chr 14 and were also significantly associated with acyanotic, and cyanotic categories separately. rs28711516 (p = 0.003) and rs735712 (p = 0.002) also showed genotypic association. Strongest association was observed with rs735712(p = 0.003) in VSD and maximum association was observed for ASD sub-phenotypes.

Conclusions

Caucasian findings were partly replicated in the north Indian population. The findings suggest the contribution of genetic, environmental and sociodemographic factors, warranting continued investigations in this study population.
Effects of major urban redesign on sedentary behavior, physical activity, active transport and health-related quality of life in adults
Authors: Stappers N. E.H. , Bekker M. P.M. , Jansen M. W.J. , Kremers S. P.J. , de Vries N. K. , Schipperijn J. , Van Kann D. H.H.
Published: June 2023

Background

The built environment is increasingly recognized as a determinant for health and health behaviors. Existing evidence regarding the relationship between environment and health (behaviors) is varying in significance and magnitude, and more high-quality longitudinal studies are needed. The aim of this study was to evaluate the effects of a major urban redesign project on physical activity (PA), sedentary behavior (SB), active transport (AT), health-related quality of life (HRQOL), social activities (SA) and meaningfulness, at 29–39 months after opening of the reconstructed area.

Methods

PA and AT were measured using accelerometers and GPS loggers. HRQOL and sociodemographic characteristics were assessed using questionnaires. In total, 241 participants provided valid data at baseline and follow-up. We distinguished three groups, based on proximity to the intervention area: maximal exposure group, minimal exposure group and no exposure group.

Results

Both the maximal and minimal exposure groups showed significantly different trends regarding transport-based PA levels compared to the no exposure group. In the exposure groups SB decreased, while it increased in the no exposure group. Also, transport-based light intensity PA remained stable in the exposure groups, while it significantly decreased in the no exposure group. No intervention effects were found for total daily PA levels. Scores on SA and meaningfulness increased in the maximal exposure group and decreased in the minimal and no exposure group, but changes were not statistically significant.

Conclusion

The results of this study emphasize the potential of the built environment in changing SB and highlights the relevance of longer-term follow-up measurements to explore the full potential of urban redesign projects.

Trial registration

This research was retrospectively registered at the Netherlands Trial Register (NL8108).
The role of rhIGF-1/BP3 in the prevention of pulmonary hypertension in bronchopulmonary dysplasia and its underlying mechanism
Authors: Qu Sehua , Shan Lianqiang , Chen Xin , Zhang Zhen , Wu Yumeng , Chen Yun , Zhuo Feixiang , Wang Yitong , Dong Huaifu
Published: June 2023

Background

This study aimed to determine whether postnatal treatment with recombinant human IGF-1 (rhIGF-1)/binding peptide 3 (BP3) ameliorates lung injury and prevents pulmonary hypertension (PH) in bronchopulmonary dysplasia (BPD) models.

Methods

We used two models of BPD in this study: one model that was associated with chorioamnionitis (CA), stimulated by intra-amniotic fluid and exposure to lipopolysaccharide (LPS), whereas the other was exposed to postnatal hyperoxia. Newborn rats were treated with rhIGF-1/BP3 (0.2 mg/Kg/d) or saline via intraperitoneal injection. The study endpoints included the wet/dry weight (W/D) ratio of lung tissues, radial alveolar counts (RACs), vessel density, right ventricular hypertrophy (RVH), lung resistance, and lung compliance. Hematoxylin and eosin (H&E) and Masson staining were used to evaluate the degree of lung injury and pulmonary fibrosis. IGF-1 and eNOS expression were detected using western blotting or quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The levels of SP-C, E-cadherin, N-cadherin, FSP1, and Vimentin in the lung tissues were detected by immunofluorescence.

Results

LPS and hyperoxia treatment increased lung injury and pulmonary fibrosis, enhanced RVH and total respiratory resistance, and decreased RAC, pulmonary vascular density and pulmonary compliance in young mice (all p < 0.01). Simultaneously, LPS and hyperoxia induced an increase in epithelial-mesenchymal transition (EMT) in airway epithelial cells. However, rhIGF-1/BP3 treatment reduced lung injury and pulmonary fibrosis, decreased RVH and total respiratory resistance, and enhanced RAC, pulmonary vascular density and pulmonary compliance, as well as inhibited EMT in airway epithelial cells in LPS and hyperoxia treated mice.

Conclusion

Postnatal rhIGF-1/BP3 treatment relieved the effects of LPS or hyperoxia on lung injury and prevented RVH, providing a promising strategy for the treatment of BPD.
MAKO robot-assisted total knee arthroplasty cannot reduce the aggravation of ankle varus incongruence after genu varus correction ≥ 10°: a radiographic assessment
Authors: Jin Gang , Fan Yongyong , Jiang Lingjun , Chen Zhongyi , Wang Chenglong
Published: June 2023

Introduction

The objective of this study was to investigate the ankle alignment alterations after the correction of knee varus deformity in MAKO robot-assisted total knee arthroplasty (MA-TKA).

Methods

A retrospective analysis was conducted for 108 patients with TKA from February 2021 to February 2022. Patients were divided into two groups based on MAKO robot involvement during the procedure: the MA-TKA group (n = 36) and the conventional manual total knee arthroplasty (CM-TKA) group (n = 72). The patients were divided into four subgroups according to the degree of surgical correction of the knee varus deformity. Seven radiological measurements were evaluated pre and post-surgery: mechanical tibiofemoral angle (mTFA), mechanical lateral distal femoral angle (mLDFA), medial proximal tibial angle (MPTA), lateral distal tibial angle (LDTA), tibial plafond inclination angle (TPIA), talar inclination angle (TIA), and tibiotalar tilt angle (TTTA). TTTA is a quantitative representation of the extent of ankle incongruence.

Results

The number of mTFA, mLDFA, and MPTA outliers in the MA-TKA group was significantly lower compared to the CM-TKA group (P<0.05). Knee varus deformity was properly corrected and the mechanical axis was restored in all patients, regardless of the treatment group. Only for varus corrections ≥ 10° did TTTA change significantly (p < 0.01) and ankle varus incongruence aggravate post-operation. The ΔTTTA correlated negatively with ΔTFA (r=-0.310,P = 0.001) and correlated positively with ΔTPIA (r = 0.490,P = 0.000). When the varus correction was ≥ 7.55°, the probability of ankle varus incongruence exacerbation increased 4.86-fold.

Conclusion

Compared with CM-TKA, MA-TKA osteotomy showed more precision but was unable to reduce post-operation ankle varus incongruence. When the varus correction ≥ 10°, ankle varus incongruence aggravated, while when the varus correction ≥ 7.55°, the probability of ankle varus incongruence increased 4.86-fold. This may occasion the pathogenesis of ankle pain following TKA.
Preemptive middle glenohumeral ligament release in arthroscopic rotator cuff repair does not reduce the postoperative stiffness: a retrospective comparative study
Authors: Takahashi Ryosuke , Kajita Yukihiro , Harada Yohei , Iwahori Yusuke
Published: June 2023

Background

This study aimed to evaluate the efficacy of preemptive middle glenohumeral ligament (MGHL) release in arthroscopic rotator cuff repair (ARCR) to reduce postoperative stiffness.

Methods

Patients who underwent ARCR were enrolled and allocated into two groups retrospectively: the preemptive MGHL release group (n = 44) and the preemptive MGHL non-release group (n = 42). Clinical outcomes were assessed and compared between the two groups, including the range of motion, Japanese Orthopedic Association Shoulder Score, Constant Shoulder Score, and the University of California, Los Angeles Score preoperatively and 3 months, 6 months, and 12 months postoperatively and complications. The integrity of the repaired tendon was assessed at the 12-month follow-up using magnetic resonance imaging.

Results

There were no significant differences between the groups in all range of motion and all functional scores at any of the assessed time points. There was also no significant difference in the healing failure rate 2.3% in the preemptive MGHL group and 2.4% in the preemptive MGHL non-release group (p = .97), and postoperative stiffness was 2.3% in the preemptive MGHL group and 7.1% in the preemptive MGHL non-release group (p = .28). There was no postoperative instability in both group.

Conclusion

ARCR effectively facilitates the recovery of range of motion and function in patients with a rotator cuff tear. However, preemptive MGHL release could not be an effective method to reduce postoperative stiffness.
Minimally invasive percutaneous new designed transpedicular lag-screw fixation for the management of Hangman fracture using O-arm-based navigation: a clinical study
Authors: Liu Yijie , Li Xuefeng , Chen Tangyiheng , Chen Jie , Zhu Yi , Chu Genglei , Yang Huilin , Jiang Weimin
Published: June 2023

Background

To investigate the outcomes and safety of using minimally invasive percutaneous new transpedicular lag-screw fixation with intraoperative, full rotation, three-dimensional image (O-arm)-based navigation for the management of Hangman fracture.

Methods

Twenty-two patients with Hangman fracture were treated with minimally invasive percutaneous new transpedicular lag-screws using intraoperative, full rotation, and three-dimensional image (O-arm)-based navigation. The preoperative and postoperative conditions of the patients were evaluated according to the ASIA (American Spinal Injury Association) scale. The patient's VAS (visual analog scale) scores before and after surgery, operation time, cervical vertebral activity, intervertebral angle and bone healing were recorded and collected, and repeated measures analysis of variance was used for statistical analysis.

Results

All patients were satisfactorily repositioned after surgery, and the VAS scores for neck pain were significantly lower than those before surgery on the first day and at 1 month, 3 months and the last follow-up (P < 0.001). According to the ASIA scale, four patients recovered from preoperative grade D to postoperative grade E. Bony fusion was achieved for all cases, and the range of neck rotation was restored to normal at the last follow-up. The post-surgery angular displacement (AD) demonstrated the stability of C2-3 after our new screw fixation for the treatment of Hangman fracture.

Conclusions

Minimally invasive percutaneous new transpedicular lag-screw fixation using intraoperative, full rotation, three-dimensional image (O-arm)-based navigation achieved satisfactory clinical results with the advantages of immediate stability, safety and effectivity. We suggest that it is a reliable and advanced technique for the management of Hangman fracture.
Virtual screening–molecular docking–activity evaluation of Ailanthus altissima (Mill.) swingle bark in the treatment of ulcerative colitis
Authors: Ma Shan-bo , Liu Lun , Li Xiang , Xie Yan-hua , Shi Xiao-peng , Wang Si-wang
Published: June 2023

Background

The dried bark of Ailanthus altissima (Mill.) Swingle is widely used in traditional Chinese medicine for the treatment of ulcerative colitis. The objective of this study was to explore the therapeutic basis of the dried bark of Ailanthus altissima (Mill.) Swingle for the treatment of ulcerative colitis based on Virtual Screening–Molecular Docking–Activity Evaluation technology.

Methods

By searching the Traditional Chinese Medicine Systems Pharmacology TCMSP Database and Analysis Platform, 89 compounds were obtained from the chemical components of the dried bark of Ailanthus altissima (Mill.) Swingle. Then, after preliminarily screening the compounds based on Lipinski’s rule of five and other relevant conditions, the AutoDock Vina molecular docking software was used to evaluate the affinity of the compounds to ulcerative colitis-related target proteins and their binding modes through use of the scoring function to identify the best candidate compounds. Further verification of the compound’s properties was achieved through in vitro experiments.

Results

Twenty-two compounds obtained from the secondary screening were molecularly docked with ulcerative colitis-related target proteins (IL-1R, TLR, EGFR, TGFR, and Wnt) using AutoDock Vina. The free energies of the highest scoring compounds binding to the active cavity of human IL-1R, TLR, EGFR, TGFR, and Wnt proteins were − 8.7, − 8.0, − 9.2, − 7.7, and − 8.5 kcal/mol, respectively. The potential compounds, dehydrocrebanine, ailanthone, and kaempferol, were obtained through scoring function and docking mode analysis. Furthermore, the potential compound ailanthone (1, 3, and 10 µM) was found to have no significant effect on cell proliferation, though at 10 µM it reduced the level of pro-inflammatory factors caused by lipopolysaccharide.

Conclusion

Among the active components of the dried bark of Ailanthus altissima (Mill.) Swingle, ailanthone plays a major role in its anti-inflammatory properties. The present study shows that ailanthone has advantages in cell proliferation and in inhibiting of inflammation, but further animal research is needed to confirm its pharmaceutical potential.
A whole transcriptome profiling analysis for antidepressant mechanism of Xiaoyaosan mediated synapse loss via BDNF/trkB/PI3K signal axis in CUMS rats
Authors: Meng Pan , Zhang Xi , Liu Tong-tong , Liu Jian , Luo Yan , Xie Ming-xia , Yang Hui , Fang Rui , Guo Dong-wei , Zhong Zi-yan , Wang Yu-hong , Ge Jin-Wen
Published: June 2023

Background

Depression is a neuropsychiatric disease resulting from deteriorations of molecular networks and synaptic injury induced by stress. Traditional Chinese formula Xiaoyaosan (XYS) exert antidepressant effect, which was demonstrated by a great many of clinical and basic investigation. However, the exact mechanism of XYS has not yet been fully elucidated.

Methods

In this study, chronic unpredictable mild stress (CUMS) rats were used as a model of depression. Behavioral test and HE staining were used to detect the anti-depressant effects of XYS. Furthermore, whole transcriptome sequencing was employed to establish the microRNA (miRNA), long non-coding RNA (lncRNA), circular RNA (circRNA), and mRNA profiles. The biological functions and potential mechanisms of XYS for depression were gathered from the GO and KEGG pathway. Then, constructed the competing endogenous RNA (ceRNA) networks to illustrate the regulatory relationship between non-coding RNA (ncRNA) and mRNA. Additionally, longest dendrite length, total length of dendrites, number of intersections, and density of dendritic spines were detected by Golgi staining. MAP2, PSD-95, SYN were detected by immunofluorescence respectively. BDNF, TrkB, p-TrkB, PI3K, Akt, p-Akt were measured by Western Blotting.

Results

The results showed that XYS could increase the locomotor activity and sugar preference, decreased swimming immobility time as well as attenuate hippocampal pathological damage. A total of 753 differentially expressed lncRNAs (DElncRNAs), 28 circRNAs (DEcircRNAs), 101 miRNAs (DEmiRNAs), and 477 mRNAs (DEmRNAs) were identified after the treatment of XYS in whole transcriptome sequencing analysis. Enrichment results revealed that XYS could regulate multiple aspects of depression through different synapse or synaptic associated signal, such as neurotrophin signaling and PI3K/Akt signaling pathways. Then, vivo experiments indicated that XYS could promote length, density, intersections of synapses and also increase the expression of MAP2 in hippocampal CA1, CA3 regions. Meanwhile, XYS could increase the expression of PSD-95, SYN in the CA1, CA3 regions of hippocampal by regulating the BDNF/trkB/PI3K signal axis.

Conclusion

The possible mechanism on synapse of XYS in depression was successfully predicted. BDNF/trkB/PI3K signal axis were the potential mechanism of XYS on synapse loss for its antidepressant. Collectively, our results provided novel information about the molecular basis of XYS in treating depression.
Longitudinal reallocations of time between 24-h movement behaviours and their associations with inflammation in children and adolescents: the UP&DOWN study
Authors: Segura-Jiménez Víctor , Pedišić Željko , Gába Aleš , Dumuid Dorothea , Olds Timothy , Štefelová Nikola , Hron Karel , Gómez-Martínez Sonia , Marcos Ascensión , Castro-Piñero José
Published: June 2023

Background

While there is evidence that physical activity, sedentary behaviour (SB) and sleep may all be associated with modified levels of inflammatory markers in adolescents and children, associations with one movement behaviour have not always been adjusted for other movement behaviours, and few studies have considered all movement behaviours in the 24-hour day as an exposure.

Purpose

The aim of the study was to explore how longitudinal reallocations of time between moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), SB and sleep are associated with changes in inflammatory markers in children and adolescents.

Methods

A total of 296 children/adolescents participated in a prospective cohort study with a 3-year follow-up. MVPA, LPA and SB were assessed by accelerometers. Sleep duration was assessed using the Health Behavior in School-aged Children questionnaire. Longitudinal compositional regression models were used to explore how reallocations of time between movement behaviours are associated with changes in inflammatory markers.

Results

Reallocations of time from SB to sleep were associated with increases in C3 levels (difference for 60 min/d reallocation [d60] = 5.29 mg/dl; 95% confidence interval [CI] = 0.28, 10.29) and TNF-α (d60 = 1.81 mg/dl; 95% CI = 0.79, 15.41) levels. Reallocations from LPA to sleep were also associated with increases in C3 levels (d60 = 8.10 mg/dl; 95% CI = 0.79, 15.41). Reallocations from LPA to any of the remaining time-use components were associated with increases in C4 levels (d60 ranging from 2.54 to 3.63 mg/dl; p < 0.05), while any reallocation of time away from MVPA was associated with unfavourable changes in leptin (d60 ranging from 3088.44 to 3448.07 pg/ml; p < 0.05).

Conclusions

Reallocations of time between 24-h movement behaviours are prospectively associated with some inflammatory markers. Reallocating time away from LPA appears to be most consistently unfavourably associated with inflammatory markers. Given that higher levels of inflammation during childhood and adolescence are associated with an increased risk of chronic diseases in adulthood, children and adolescents should be encouraged to maintain or increase the level of LPA to preserve a healthy immune system.
Optogenetic stimulation of basal forebrain cholinergic neurons prevents neuroinflammation and neuropsychiatric manifestations in pristane induced lupus mice
Authors: Yun Yang , Wang Xuejiao , Xu Jingyi , Chen Jingyu , Wang Xueru , Yang Pingting , Qin Ling
Published: June 2023

Background

Neuroinflammation has been identified as one of the primary pathogenic factors of neuropsychiatric systemic lupus erythematosus (NPSLE). However, there are no dedicated treatments available in clinics to alleviate neuroinflammation in NPSLE. It has been proposed that stimulating basal forebrain (BF) cholinergic neurons may provide potent anti-inflammatory effects in several inflammatory diseases, but its potential role in NPSLE remains unexplored. This study aims to investigate whether and how stimulating BF cholinergic neurons has a protective effect on NPSLE.

Results

Optogenetic stimulation of BF cholinergic neurons significantly ameliorated olfactory dysfunction and anxiety- and depression-like phenotype in pristane induced lupus (PIL) mice. The increased expression of adhesion molecules (P-selectin and vascular cell adhesion molecule-1 (VCAM-1)), leukocyte recruitment, blood-brain barrier (BBB) leakage were significantly decreased. Notably, the brain histopathological changes, including the elevated levels of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), IgG deposition in the choroid plexus and lateral ventricle wall and lipofuscin accumulation in the cortical and hippocampal neurons, were also significantly attenuated. Furthermore, we confirmed the colocalization between the BF cholinergic projections and the cerebral vessels, and the expression of α7-nicotinic acetylcholine receptor (α7nAChR) on the cerebral vessels.

Conclusion

Our data indicate that stimulation of BF cholinergic neurons could play a neuroprotective role in the brain through its cholinergic anti-inflammatory effects on cerebral vessels. Therefore, this may be a promising preventive target for NPSLE.
Incidence and root causes of medication errors by anesthetists: a multicenter web-based survey from 8 teaching hospitals in Ethiopia
Authors: Firde Meseret
Published: June 2023

Bakground

The operating room is a demanding and time-constrained setting, in comparison to primary care settings, where perioperative medication administration is more complicated and there is a high risk that the patient will experience a medication error. Without consulting the pharmacist or seeking assistance from other staff members, anesthesia clinicians prepare, deliver, and monitor strong anesthetic drugs. The purpose of this study was to determine the Incidence and root causes of medication errors by anesthetists in Amhara region, Ethiopia.

Methods

A multi-center cross sectional web-based survey study was conducted from October 1 to November 30, 2022, across eight referral and teaching hospitals of Amhara region. A self-administered semi structured questionnaire was distributed using survey planet. Data analysis was conducted using SPSS version 20. Descriptive statistics were computed and binary logistic regression was used for data analysis. A p-value < 0.05 was considered statistically significant.

Results

The study included 108 anesthetists in total, yielding a response rate of 42.35%. Out of 104 anesthetists, Majority of participants (82.7%) were male. During their clinical practice, more than half (64.4%) of participants experienced atleast one drug administration error. 39 (37.50%) of the respondents revealed that they experienced more medication errors while on night shifts. Anesthetists who did not always double-check their anesthetic drugs before administration had a 3.51 higher risk of developing MAEs compared to those who always double-check anesthetic drugs before administration (AOR = 3.51; 95% CI: 1.34, 9.19). Additionally, participants who administer medications that have been prepared by someone else are about five times more likely to experience MAEs than participants who prepare their own anesthetic medications prior to administration (AOR = 4.95; 95% CI: 1.54, 15.95).

Conclusion

The study found a considerable rate of errors in the administration of anaesthetic drugs. The failure to always double-check medications before administration and the use of drugs prepared by another anaesthetist were identified to be underlying root causes for drug administration errors.
Time to treatment and mortality for clinical sepsis subtypes
Authors: Yang Anne , Kennedy Jason N. , Reitz Katherine M. , Phillips Gary , Terry Kathleen M. , Levy Mitchell M. , Angus Derek C. , Seymour Christopher W.
Published: June 2023

Background

Sepsis is common, deadly, and heterogenous. Prior analyses of patients with sepsis and septic shock in New York State showed a risk-adjusted association between more rapid antibiotic administration and bundled care completion, but not an intravenous fluid bolus, with reduced in-hospital mortality. However, it is unknown if clinically identifiable sepsis subtypes modify these associations.

Methods

Secondary analysis of patients with sepsis and septic shock enrolled in the New York State Department of Health cohort from January 1, 2015 to December 31, 2016. Patients were classified as clinical sepsis subtypes (α, β, γ, δ-types) using the Sepsis ENdotyping in Emergency CAre (SENECA) approach. Exposure variables included time to 3-h sepsis bundle completion, antibiotic administration, and intravenous fluid bolus completion. Then logistic regression models evaluated the interaction between exposures, clinical sepsis subtypes, and in-hospital mortality.

Results

55,169 hospitalizations from 155 hospitals were included (34% α, 30% β, 19% γ, 17% δ). The α-subtype had the lowest (N = 1,905, 10%) and δ-subtype had the highest (N = 3,776, 41%) in-hospital mortality. Each hour to completion of the 3-h bundle (aOR, 1.04 [95%CI, 1.02–1.05]) and antibiotic initiation (aOR, 1.03 [95%CI, 1.02–1.04]) was associated with increased risk-adjusted in-hospital mortality. The association differed across subtypes (p-interactions < 0.05). For example, the outcome association for the time to completion of the 3-h bundle was greater in the δ-subtype (aOR, 1.07 [95%CI, 1.05–1.10]) compared to α-subtype (aOR, 1.02 [95%CI, 0.99–1.04]). Time to intravenous fluid bolus completion was not associated with risk-adjusted in-hospital mortality (aOR, 0.99 [95%CI, 0.97–1.01]) and did not differ among subtypes (p-interaction = 0.41).

Conclusion

Timely completion of a 3-h sepsis bundle and antibiotic initiation was associated with reduced risk-adjusted in-hospital mortality, an association modified by clinically identifiable sepsis subtype.
Bipolar haemostatic forceps versus standard therapy by haemoclip + / − epinephrine injection as initial endoscopic treatment in active non-variceal upper GI bleeding: study protocol for a prospective, randomized multicentre trial (BeBop-Trial)
Authors: Schmitz Daniel , Thielemann Lucas , Grassmann Felix
Published: June 2023

Background

Patients with active nonvariceal upper gastrointestinal bleeding (NVUGIB) usually require urgent endoscopic treatment. Standard therapy (ST) using haemoclip + / − epinephrine injection is not always successful. Bipolar haemostatic forceps (HemoStat/Pentax®) are an approved medical device for the treatment of gastrointestinal bleeding. However, their use as a primary endoscopic treatment for active NVUGIB has not yet been proven in a randomized prospective study.

Methods

This is a prospective, randomized, multicentre superiority trial (n ≥ 5). Patients with active NVUGIB will be randomized (1:1) to ST and to experimental therapy (ET) by application of bipolar haemostatic forceps.

In the case of failed initial treatment within 15 min, crossover treatment will be attempted first. Rescue treatment (e.g. via over-the-scope-clip) will then be allowed after 30 min. All patients will also receive standard therapy with proton pump inhibitors. Forty-five patients per treatment arm are required to demonstrate an absolute difference of 25.4% with a power of 80% and a significance level of 0.05.

Discussion

The hypothesis of the study is that bipolar haemostatic forceps are superior to ST in terms of successful primary haemostasis and the absence of recurrent bleeding within 30 days (combined endpoint). The 1:1 randomization is also ethically justifiable for this study, as both procedures are approved for the intervention in question. To further increase the safety of the patients in the study, crossover treatment and rescue treatment are planned. The prospective design seems feasible in a reasonable time frame (recruitment period of 12 months), as nonvariceal upper gastrointestinal bleeding is common. Anticoagulants and/or antiplatelet drugs could be an important confounding factor in the statistical analysis that needs to be taken into account and calculated if necessary. In conclusion, this randomized, prospective, multicentre study could make an important contribution to answering the question of whether bipolar haemostatic forceps could be the first-line therapy in the endoscopic treatment of stage Forrest I a + b NVUGIB.

Trial registration

ClinicalTrials.gov NCT05353062. Registered on April 30 2022.
ReporTree: a surveillance-oriented tool to strengthen the linkage between pathogen genetic clusters and epidemiological data
Authors: Mixão Verónica , Pinto Miguel , Sobral Daniel , Di Pasquale Adriano , Gomes João Paulo , Borges Vítor
Published: June 2023

Background

Genomics-informed pathogen surveillance strengthens public health decision-making, playing an important role in infectious diseases’ prevention and control. A pivotal outcome of genomics surveillance is the identification of pathogen genetic clusters and their characterization in terms of geotemporal spread or linkage to clinical and demographic data. This task often consists of the visual exploration of (large) phylogenetic trees and associated metadata, being time-consuming and difficult to reproduce.

Results

We developed ReporTree, a flexible bioinformatics pipeline that allows diving into the complexity of pathogen diversity to rapidly identify genetic clusters at any (or all) distance threshold(s) or cluster stability regions and to generate surveillance-oriented reports based on the available metadata, such as timespan, geography, or vaccination/clinical status. ReporTree is able to maintain cluster nomenclature in subsequent analyses and to generate a nomenclature code combining cluster information at different hierarchical levels, thus facilitating the active surveillance of clusters of interest. By handling several input formats and clustering methods, ReporTree is applicable to multiple pathogens, constituting a flexible resource that can be smoothly deployed in routine surveillance bioinformatics workflows with negligible computational and time costs. This is demonstrated through a comprehensive benchmarking of (i) the cg/wgMLST workflow with large datasets of four foodborne bacterial pathogens and (ii) the alignment-based SNP workflow with a large dataset of Mycobacterium tuberculosis. To further validate this tool, we reproduced a previous large-scale study on Neisseria gonorrhoeae, demonstrating how ReporTree is able to rapidly identify the main species genogroups and characterize them with key surveillance metadata, such as antibiotic resistance data. By providing examples for SARS-CoV-2 and the foodborne bacterial pathogen Listeria monocytogenes, we show how this tool is currently a useful asset in genomics-informed routine surveillance and outbreak detection of a wide variety of species.

Conclusions

In summary, ReporTree is a pan-pathogen tool for automated and reproducible identification and characterization of genetic clusters that contributes to a sustainable and efficient public health genomics-informed pathogen surveillance. ReporTree is implemented in python 3.8 and is freely available at https://github.com/insapathogenomics/ReporTree.