bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcome of Ultrasound Guided Anterior Quadratus Lumborum Block After Video Laparoscopic Cholecystectomies: A Prospective Randomized Clinical Trial
Authors: Alves Brandão Virna Guedes , Silva Gustavo Nascimento , Alvim Fiorelli Rossano Kepler , Perez Marcelo Vaz
Published: March 2023

Background

Laparoscopy revolutionizing digital and robotic technology for surgical practice. The ability of anesthetic agents and neuronal blockade to modify the response to surgical trauma has been widely studied in the last few years.

Objectives

evaluate if Anterior Quadratus Lumborum Block contributes to attenuate surgical repercussions, having as primary parameters analgesia and secondary the pulmonary function and neuroendocrine response to trauma.

Methods

prospective, controlled, Double-blind study, in which 51 patients scheduled for eletive laparoscopic cholecystectomy were randomly selected and distributed into 2 groups. Control group received general anesthesia, and the intervention group was submitted to general anesthesia plus Anterior Quadratus Lumborum Block. The parameters evaluated were: postoperative pain, respiratory muscle pressure, and inflammatory response to surgical stress with the plasma dosage of Interleukin 6, C-Reactive protein and cortisol. The following situations were excluded: refusal to participate in the study; body mass index greater than or equal to 40, peripheral neuropathies, coagulopathies or hypersensitivity to drugs used; infection at the puncture site; fever, purities; dementia or other states that would prevent the adequate understanding of the use of the numeric-verbal scale of pain; immunological diseases, diabetes, malignant neoplasia, use of opioids or anti-inflammatory drugs in the preoperative period; antidepressants and anticonvulsants, conversion open surgery, re-exploration and hospital stay.

Results

Slowed Interleukin 6 cytokine production and decrease in cortisol release, accompanied by significant attenuation of surgical repercussion on lung function and significant reduction in postoperative pain scores and consumption of pain medication.

Conclusion

An important strategy for analgesia in abdominal laparoscopic surgery.
Recognition and CBT for Paternal Perinatal Depression in Primary Care: A Case Report
Authors: Skilbeck Lilian , Spanton Christopher , Roylance Ian
Published: March 2023

Perinatal depression is prevalent in primary care in the United Kingdom. The recent NHS agenda implemented specialist perinatal mental health services to improve women’s access to evidence-based care. Although there is ample research on maternal perinatal depression, paternal perinatal depression remains overlooked. Fatherhood can have a positive long-term protective impact on men’s health. However, a proportion of fathers also experience perinatal depression which often correlates with maternal depression. Research reports that paternal perinatal depression is a highly prevalent public health concern. As there are no current specific guidelines for screening for paternal perinatal depression, it is often unrecognized, misdiagnosed, or untreated in primary care. This is concerning as research reports a positive correlation between paternal perinatal depression with maternal perinatal depression and overall family well-being. This study illustrates the successful recognition and treatment of a paternal perinatal depression case in a primary care service. The client was a 22-year-old White male living with a partner who was 6 months pregnant. He attended primary care with symptoms consistent with paternal perinatal depression as indicated by his interview and specified clinical measures. The client attended 12 sessions of cognitive behavioral therapy, conducted weekly over a period of 4 months. At the end of treatment, he no longer portrayed symptoms of depression. This was maintained at 3-month follow-up. This study highlights the importance of screening for paternal perinatal depression in primary care. It could benefit clinicians and researchers who may wish to better recognize and treat this clinical presentation.
Kinematic analysis and development of cable-driven rehabilitation robot for cerebral palsy patients
Authors: Aria H Partovi , Ahrabi M , Allahverdi F , Korayem M Habibnejad
Published: March 2023

This study aimed to analyze the kinematic development of a rehabilitation cable robot for patients with cerebral palsy problems. For this purpose, the walking pattern of a healthy person was analyzed in the robot by extracting his kinematic model. Therefore, a seven-link model was considered, and changes in the mass center of the links and then movements during the gait cycle were obtained with the angles related to joint changes. Next, the person’s integration with the rehabilitation cable robot was investigated with the resolution of the direct kinematic problem. In addition, the change-related outputs of the cables were obtained by the person’s movement and the attached belt. The robot was further proposed because the specific change diagram of the cables facilitates understanding how much motor torque is needed to change the length of the cable. It is noteworthy that the static person balance is provided in the existing rehabilitation robots. However, in this structure, the balance is done by the six degrees of freedom robot so that the robot can return the person to the original path when he loses his balance. Cable systems for the lower limbs (thighs and shanks) are also simulated to rehabilitate the patient. The obtained results from the simulation and the obtained output from kinematic equations for lower limb movements were also compared, and the highest deference was 2.2, 1.8, 1.8, and 1.5% for shank-back, shank-front, thigh-back, and thigh-front of the leg in the corresponding points in the outputs of both software, respectively.
Research on the evolution of tripartite data protection strategy based on game theory
Authors: Yang Mingxin , Feng Lei , Zhang Xiaoming
Published: March 2023

In recent years, data leakage incidents have been frequently exposed, and personal privacy protection has become a major issue. To explore the laws of data leakage and solve practical problems, the reasons for data leakage and the evolution of players’ strategy in the game are discussed. After sorting out the interest relationship of data leakage incidents, a three-party evolution model of invaders, operators, and regulators is established to analyze the evolution path from the perspective of a single party. The Lyapunov theory is used to analyze the stability of equilibrium points of the system and then verified by MATLAB simulation. The influence relationship of various parameters on the system is analyzed. Finally, the ideal state is defined and the system is attempted to be modified. The results demonstrate that under the current system, the evolution direction cannot be changed by the initial intention of players. The game result will eventually form a situation with a strong attack from invaders, advanced defense from operators, and extensive management from regulators. The attack level can be reduced by adjusting the controllable parameters, modifying the evolution path, and calculating the parameter range.
Efficacy analysis of neoadjuvant chemotherapy with or without anthracyclines in female patients with HER2-positive breast cancer in China: a nationwide, multicenter, 10-year retrospective study (CSBrS-012)
Authors: Chen Heyan , Maimaitiaili Amina , Liu Zhenzhen , Ling Rui , Zhao Yi , Yang Hongjian , Liu Yunjiang , Liu Ke , Zhang Jianguo , Mao Dahua , Yu Zhigang , Liu Yinhua , Fu Peifen , Wang Jiandong , Jiang Hongchuan , Zhao Zuowei , Tian Xingsong , Cao Zhongwei , Wu Kejin , Song Ailin , Jin Feng , He Jianjun , Fan Zhimin , Zhang Huimin
Published: March 2023

Background:

In the era of targeted therapy, whether patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer are exempted from anthracycline usage in the neoadjuvant setting is controversial.

Objectives:

Our objective was to retrospectively analyze the differences in pathological complete remission (pCR) rates between the anthracycline group and the nonanthracycline group.

Design:

The CSBrS-012 study (2010–2020) included female primary breast cancer patients with neoadjuvant chemotherapy (NAC) who underwent standard breast and axillary surgery post-NAC.

Methods:

A logistic proportional hazard model was applied to estimate the association of covariates with pCR. Propensity score matching (PSM) was performed to balance the differences in baseline characteristics, and subgroup analyses were performed using the Cochran–Mantel–Haenszel test.

Results:

A total of 2507 patients were enrolled: the anthracycline group ( n = 1581, 63%) and the nonanthracycline group ( n = 926, 37%). A pCR was recorded in 17.1% (271/1581) of patients in the anthracycline group and in 29.3% (271/926) in the nonanthracycline group, and the difference in the pCR rate between the two groups was statistically significant [odds ratio (OR) = 2.00, 95% confidence interval (CI) (1.65–2.43); p < 0.001). In the subsequent subgroup analysis, substantial differences in pCR rates between the anthracycline and nonanthracycline groups were detected in the nontargeted [OR = 1.91, 95% CI (1.13–3.23); p = 0.015] and dual-HER2-targeted populations [OR = 0.55, 95% CI (0.33–0.92); p = 0.021) before PSM, whereas differences vanished after PSM. The pCR rates between the anthracycline and nonanthracycline groups did not differ for the single target population, either before or after PSM.

Conclusion:

In the presence of trastuzumab and/or pertuzumab, the pCR rate of patients with HER2-positive breast cancer receiving anthracycline was not superior to that of patients receiving nonanthracycline. Thus, our study further provides clinical evidence for exempting anthracycline treatment in HER2-positive breast cancer in the era of targeted therapy.
Contact tracing apps, nationalism, and users with disability in the Global South: The faith in state and collective objective
Authors: Rohman Abdul , Pitaloka Dyah
Published: March 2023

Contact tracing apps have magnified the potential usefulness of mobile media and communication technologies for responding to disruptive events such as the COVID-19 pandemic. Their efficacy and ethical debates have become the focus of recent studies in the Global North. Reasons for using contact tracing apps among users with disability living in the Global South, however, seem to be understudied. Through cases from Indonesia and Vietnam, this study found that nationalistic values were among the reasons for using contact tracing apps as reflected in the users’ faith in the state and inclination to support its collective objective to control the pandemic. The users believed the state would be accountable in managing the personal and mobility data the contact tracing apps collected. Using contact tracing apps represented the users’ sense of capabilities to individually partake in the existing efforts to control the pandemic.
A case of epidermal growth factor receptor tyrosine kinase inhibitor effectiveness in epidermal growth factor receptor mutation-positive squamous cell carcinoma
Authors: Matsumura Sosuke , Ano Satoshi , Kikuchi Norihiro , Masuda Michiko , Osawa Hajime , Kondo Yuzuru , Ishii Yukio , Hizawa Nobuyuki
Published: March 2023

A 71-year-old non-smoker woman was admitted to our hospital because of left front chest pain. A computed tomography scan showed a large mass of >7.0 cm in the lower left part of the lung and multiple organ metastases in the liver, brain, bone, and left adrenal gland. Pathological analysis of a resected specimen obtained by bronchoscopy revealed keratinization. In addition, p40 was positive and thyroid transcription factor-1, synaptophysin, CD56, and chromogranin A were negative by immunohistochemistry. Programmed cell death ligand 1 expression was 1%–10%, and exon 19 deletion was detected. We diagnosed the patient with stage IVB lung squamous cell carcinoma and administered osimertinib. Osimertinib was later replaced with afatinib because of grade 3 skin rash. Overall, the size of the cancer was decreased. Furthermore, her symptoms, laboratory data, and computer tomographic findings markedly improved. In summary, we experienced a case of epidermal growth factor receptor–positive lung squamous cell carcinoma that was responsive to epidermal growth factor receptor tyrosine kinase inhibitors.
Preoperative Computed Tomographic Angiography Can Predict Need for Branch Pulmonary Artery Intervention in Patients With Ductal-Dependent Pulmonary Blood Flow
Authors: Graff Kirsten , Hlavacek Anthony M. , Aizcorbe Nicholas , Bradley Scott M. , Chowdhury Shahryar M.
Published: March 2023

Background

Neonates with ductal-dependent pulmonary blood flow (DD-PBF) are at risk for pulmonary artery (PA) stenosis. The objective of this study was to identify preoperative cardiovascular computed tomography angiography (CTA) measures that are associated with the need for branch PA intervention.

Methods

We identified neonates with DD-PBF who underwent preoperative CTA at our center and were followed for 24 months. The primary outcome was requiring intervention for branch PA stenosis at the initial or subsequent procedure. Patients were divided into three groups: 1) No PA intervention, 2) Initial PA intervention, and 3) Remote PA intervention. Measurements of the branch PAs and patent ductus arteriosus (PDA) were made prospectively.

Results

Forty patients were included, 7 (18%) did not receive a PA intervention, 23 (58%) were in the initial PA intervention group, and 10 (25%) were in the remote PA intervention group. The distance from PA bifurcation to the largest diameter of the PA that receives the PDA showed a difference between the no-intervention group versus the initial and remote intervention groups (0.8 mm [IQR 0.7, 2.0], 8.2 mm [IQR 1.9, 13.7], 8.5 mm [IQR 6.5, 11.1], respectively, P  =  .02). The receiver operating characteristic curve showed a distance >2.2 mm had a sensitivity  =  91% and specificity  =  86% in predicting the need for PA intervention.

Conclusion

The distance from the PA bifurcation to the largest diameter of the branch PA that accepts the PDA on preoperative CTA is highly predictive of the need for initial or remote PA intervention in this group. Preoperative CTA should be considered for risk stratification in neonates undergoing intervention for DD-PBF.
Analysis of Taiwan Emergency Physicians’ Core Competencies Based on ACGME Criteria
Authors: Hsu Kuo-Fang , Huang Ping-Lung , Lee Tian-Shyug , Lee Bruce C. Y.
Published: March 2023

The development of physicians’ core competency is related to the quality of medical practice. Accordingly, knowing how to cultivate and evaluate core competency is an important issue for medical education and management. This study used the comprehensive core competency framework proposed by the Accreditation Council for Graduate Medical Education (ACGME) and employed fuzzy AHP (FAHP) and DEMANTEL methods to analyze the weight and priority, as well as the cause-and-effect cluster. The FAHP analysis yielded the following rankings of factors’ importance: (1) patient care (C1; 27.83%), (2) medical knowledge (C2; 20.77%), (3) professionalism (C5; 17.93%), (4) interpersonal and communication skills (C4; 17.41%), (5) practice-based learning and improvement (C3; 15.52%), and (6) systems-based practice (C6; 8.233%). In terms of the DEMANTEL, the effect cluster included patient care (C1), professionalism (C5) and systems-based practice (C6), and the cause cluster included medical knowledge (C2), practice-based learning and improvement (C3), and interpersonal and communication skills (C4). The findings showed that patient care (C1) results from attitudes, patience, and the other five ACGME Core Competencies. Furthermore, emergency physicians’ development also requires humanities and ethics training and practice to ensure practice-based learning (C3). This study demonstrates the importance of various factors in developing emergency physicians’ core competencies, and the ﬁndings may provide a reference for future attempts at such competency development.
Neuromarketing Tools Used in the Marketing Mix: A Systematic Literature and Future Research Agenda
Authors: Alsharif Ahmed H. , Salleh Nor Zafir Md , Abdullah Mazilah , Khraiwish Ahmad , Ashaari Azmirul
Published: March 2023

Although neuromarketing research has developed, the current studies lack to provide comprehensive insights into neuromarketing and marketing mix. Therefore, this study has designed to provide a comprehensive overview of neuromarketing, classification of neuroimaging and physiological tools are currently used in the marketing mix, and highlights the neural responses of consumer’s behavior (e.g., emotions, attention, motivation, reward processing, and perception) to be considered in the marketing mix. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework to select relevant documents for this article. In this study, 106 articles and review papers were extracted and analyzed from the Web of Science database to fill the gap in the literature. We found that 10 tools have been used in studying the marketing mix, such as advertising, brand, price, and product). For example, electroencephalography was the most applied tool, while advertising was the most marketing mix employed. We also found that the frontal and temporal gyri were correlated with pleasure/displeasure and high/low arousal. The occipital lobe is linked to attention processes, while the hippocampus relates to long and short-term memory. Such findings provide valuable insights into the neural responses in marketing mix research.
The Moderating Role of Generation on Residents’ Support for P2P Vacation Accommodations: Millennials versus Older Generations
Authors: Garau-Vadell Joan B. , Gutiérrez-Taño Desiderio , Díaz-Armas Ricardo J.
Published: March 2023

Massive-scale peer-to-peer vacation accommodation has become one of the most relevant recent trends in the tourism industry. The phenomenon coincides in time with the emergence of the millennial generation alleged to influence a distinctive behavior. Grounded in the Social Exchange Theory, the study presents a comparative analysis of millennial residents’ and previous generations’ support for P2P vacation accommodations. The article explores differences in support for the new activity, in the perception of its impacts, and on how the residents back their support. A quantitative survey was conducted with a sample of 1,285 residents from Tenerife (Spain), a major international tourist destination with a large number of P2P vacation accommodations. Results reveal that millennial residents display more support for P2P vacation accommodations. However, it is not based on structural differences in how they build their support, rather on a greater perception of positive economic, socio-cultural, and environmental impacts than previous generations. Relevant tourism destination and DMO implications are derived.
Open Distance Learning in Medical Education: Does It Improve Students’ Motivation?
Authors: Lee Jun Xin , Ahmad Azman Ahmad Hathim , Ng Jing Yi , Ismail Noor Akmal Shareela
Published: March 2023

The COVID-19 pandemic has affected the way of teaching and learning in medicine. Conventional medical education has been fully transformed to open distance learning that includes the full utilization of various digital platforms. Thus, this study explored the impact of digital learning usage on learning motivation among medical students of Universiti Kebangsaan Malaysia (UKM) before and during the COVID-19 pandemic period. A validated Students Motivation towards Science Learning (SMTSL) tool was used to assess the learning motivation of UKM undergraduate medical students throughout years 1 to 5. Digital learning during the COVID-19 pandemic was significantly higher compared to before the pandemic ( p < .05) but there was no significant difference ( p = .872) in learning motivation. The use of digital learning among clinical students was significantly higher during the COVID-19 pandemic as compared to preclinical students ( p < .05). There was a moderately strong correlation ( r = .512) between digital learning and learning motivation. Hence, digital learning should be utilized as an additional driving factor to increase learning motivation, especially during this current pandemic.
Revisiting the Drivers of Firm Value; An Empirical Investigation on Manufacturing Firms
Authors: Panda Ajaya Kumar , Nanda Swagatika , Hegde Apoorva , Paital Rashmi Ranjan
Published: March 2023

The study aims to ascertain the key determinants of firm value and to analyze the contribution of each determinant at different percentiles of the probability distribution of firm value for 1,592 firms across eight major Indian manufacturing firms. The sample consists of data from 2009 to 2020 and studies the variables such as enterprise value, effective tax rate, firm size, profitability, firms’ growth rate, financial leverage, asset tangibility, and non-debt tax shield. The study employed, linear, non-linear, and non-parametric panel regression models. Quantile regression models are further used to decompose the determinants at various quantiles of firm value. Several diagnostic tests such as Breusch–Pagan, White’s Test, and Sargan Test are used to ensure robust estimates. The results obtained from this study show the presence of a concave relationship between firm value with firm size, financial leverage, and non-debt tax shield. Effective tax rates and inflation rates substantially and positively affect the value of firms in higher percentiles. The capital structure is found to significantly and positively affect the value of firms in the lower percentile. The profitability is also found to contribute to the value of firms across all the quantiles, whereas sales growth fails to strongly drive the value.
The Lack of Circulation of Elites in Lebanon: Towards Communitocracy and Autocratization
Authors: Cortés Francisco Salvador Barroso , Kairouz Christophe
Published: March 2023

The article examines how the lack of circulation of political elites has contributed to setting up an economic–political system designed to avoid the construction of a political entity and common Lebanese identity for fear of losing their traditional role and privileges on the political scene. Toward this, the article provides a general assessment of the Lebanese consociational democracy to understand the elements and factors hampering this form of political governance. Then it delves into the main socio-political factors that allow the triumph of communitocracy. It shows how the lack of circulation on elites, on the one hand, the consociational system on the other, affect democratization and nation-building processes. It throws light on the misbehavior of the Lebanese elites concerning the challenge that democracy and national building represent.
Walking alone or walking together: A spatial evaluation of children’s travel behavior to school
Authors: Rybarczyk Greg , Ozbil Ayse , Yesiltepe Demet , Argin Gorsev
Published: March 2023

The purpose of this research is to extend our understanding of children’s walking behavior to school in an understudied region of the world, Istanbul, Turkey. Children (aged 11–17) and their parents were surveyed to comprehend subjective and objective factors on walking behavior to school when alone or with someone. Using participatory mapping and GIS, a route detour index was first created to highlight differences in walking behaviors. A robust spatial analysis, consisting of spatial statistics and a hierarchical spatial error model, then signified important survey responses, urban design factors from space syntax, and neighborhood composition and contextual variables on between-group route choices. Empirical and geovisual analysis confirmed that accompanied children deviated more from GIS shortest routes to school than their unaccompanied peers, and “hot-spot” analysis showed it was dependent on where children reside. The spatial error models exhibited notable relations among route choice, children’s age, health, and gender. Parent attitudes concerning greenspace positively affected children’s longer route choices, while street connectivity had the opposite influence. Surprisingly, neighborhood walkability did not impact children’s route choice decisions for either group. The results provide new insights on how to encourage additional walking trips to school.
Operative vs Nonoperative Management of Achilles Tendon Rupture: A Cost Analysis
Authors: Murdock Christopher J. , Ochuba Arinze J. , Xu Amy L. , Snow Morgan , Bronheim Rachel , Vulcano Ettore , Aiyer Amiethab A.
Published: March 2023

Background:

Achilles tendon rupture (ATR) is a common injury with a growing incidence rate. Treatment is either operative or nonoperative. However, evidence is lacking on the cost comparison between these modalities. The objective of this study is to investigate the cost differences between operative and nonoperative treatment of ATR using a large national database.

Methods:

Patients who received treatment for an ATR were abstracted from the large national commercial insurance claims database, Marketscan Commercial Claims and Encounters Database (n = 100 825) and divided into nonoperative (n = 75 731) and operative (n = 25 094) cohorts. Demographics, location, and health care charges were compared using multivariable regression analysis. Subanalysis of costs for medical services including clinic visits, imaging studies, opioid usage, and physical therapy were conducted. Patients who underwent secondary repair were excluded.

Results:

Operative treatment was associated with increased net and total payments, coinsurance, copayment, deductible, coordination of benefits (COB) / savings, greater number of clinic visits, radiographs, magnetic resonance imaging (MRI) scans, and physical therapy (PT) sessions, and with higher net costs due to clinic visits, radiographs, MRIs, and PT ( P < .001). Operative repair at an ambulatory surgical center was associated with a lower net and total payment, and a significantly higher deductible compared to in-hospital settings ( P < .001). Both cohorts received similar numbers of opioid prescriptions during the study period. Yet, operative patients had a significantly shorter duration of opioid use. After controlling for confounders, operative repair was also independently associated with lower net costs due to opioid prescriptions.

Conclusion:

Compared with nonoperatively managed ATR, surgical repair is associated with greater costs partially because of greater utilization of clinic visits, imaging, and physical therapy sessions. However, surgical costs may be reduced when procedures are performed in ambulatory surgery centers vs hospital facilities. Nonoperative treatment is associated with higher prescription costs secondary to longer duration of opioid use.

Level of Evidence:

Level III, retrospective cohort study.
The value of the urban field in technology-driven knowledge economies: The role of the state
Authors: Moisio Sami , Rossi Ugo
Published: March 2023

This article shows how the market valuation of start-up companies and the corporate-designed creation of human capital reveal some of the material and more intangible ways in which the economisation of the urban field plays out in the contemporary knowledge economy. The proposed analysis seeks to make visible how both direct and indirect state action enables the different dimensions of the urban field to come together, become valuable and jointly constitute what Michael Hardt and Antonio Negri have called the ‘metropolis’. In so doing, the article underlines that the different dimensions of the urban field figure prominently albeit differently partake in processes of extraction of knowledge value in monetised or sociocultural form. At the conceptual level, we critically engage with the existing literature on emergent forms of state capitalism by putting forward a governmental analytic on state power in contemporary urbanised knowledge capitalism. Empirically, we develop our arguments through two case studies. First, we examine the start-up unicorn Wolt, often considered as one of the national champion start-ups in Finland (together with a handful of mobile game developers). Second, we scrutinise the arrival of the Apple software developer Academy in Naples, a widely celebrated state-capital interaction in an economically struggling urban context in southern Italy. These cases are among the many that motivate one to re-think the entanglement of urban space, state governmentality and value extraction as it unfolds today in urbanised knowledge economies.
Concert Prep the Standards Way
Authors: Hatch Emily
Published: March 2023

When music teachers think about the three artistic processes of the National Core Arts Standards (create, perform, and respond), we know that without a doubt that we teach students how to perform. Every year we prepare classes for school and community performances where students sing and play songs that they have learned. We know how to rehearse and refine performances in preparation for these regular performances. However, the standards outline more components to performing than just rehearsing and presenting. This column will explore concert preparation from the lens of the National Core Arts Standards and suggest activities and assessment strategies for each part of the standard.
Clinically relevant combined effect of polygenic background, rare pathogenic germline variants, and family history on colorectal cancer incidence
Authors: Hassanin Emadeldin , Spier Isabel , Bobbili Dheeraj R. , Aldisi Rana , Klinkhammer Hannah , David Friederike , Dueñas Nuria , Hüneburg Robert , Perne Claudia , Brunet Joan , Capella Gabriel , Nöthen Markus M. , Forstner Andreas J. , Mayr Andreas , Krawitz Peter , May Patrick , Aretz Stefan , Maj Carlo
Published: March 2023

Background and aims

Summarised in polygenic risk scores (PRS), the effect of common, low penetrant genetic variants associated with colorectal cancer (CRC), can be used for risk stratification.

Methods

To assess the combined impact of the PRS and other main factors on CRC risk, 163,516 individuals from the UK Biobank were stratified as follows: 1. carriers status for germline pathogenic variants (PV) in CRC susceptibility genes (APC, MLH1, MSH2, MSH6, PMS2), 2. low (< 20%), intermediate (20–80%), or high PRS (> 80%), and 3. family history (FH) of CRC. Multivariable logistic regression and Cox proportional hazards models were applied to compare odds ratios and to compute the lifetime incidence, respectively.

Results

Depending on the PRS, the CRC lifetime incidence for non-carriers ranges between 6 and 22%, compared to 40% and 74% for carriers. A suspicious FH is associated with a further increase of the cumulative incidence reaching 26% for non-carriers and 98% for carriers. In non-carriers without FH, but high PRS, the CRC risk is doubled, whereas a low PRS even in the context of a FH results in a decreased risk. The full model including PRS, carrier status, and FH improved the area under the curve in risk prediction (0.704).

Conclusion

The findings demonstrate that CRC risks are strongly influenced by the PRS for both a sporadic and monogenic background. FH, PV, and common variants complementary contribute to CRC risk. The implementation of PRS in routine care will likely improve personalized risk stratification, which will in turn guide tailored preventive surveillance strategies in high, intermediate, and low risk groups.
Classical monocyte-derived macrophages as therapeutic targets of umbilical cord mesenchymal stem cells: comparison of intratracheal and intravenous administration in a mouse model of pulmonary fibrosis
Authors: Choi Sun Mi , Mo Yosep , Bang Ji-Young , Ko Young Gyun , Ahn Yoon Hae , Kim Hye Young , Koh Jaemoon , Yim Jae-Joon , Kang Hye-Ryun
Published: March 2023

Background

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease that has no cure. Although mesenchymal stem cells (MSCs) have been reported to ameliorate lung inflammation and fibrosis in mouse models, their mechanisms of action remain unknown. Therefore, we aimed to determine the changes in various immune cells, especially macrophages and monocytes, involved in the effects of MSC treatment on pulmonary fibrosis.

Methods

We collected and analyzed explanted lung tissues and blood from patients with IPF who underwent lung transplantation. After establishing a pulmonary fibrosis model via the intratracheal administration of bleomycin (BLM) to 8-week-old mice, MSCs derived from human umbilical cords were administered intravenously or intratracheally on day 10 and the lungs were immunologically analyzed on days 14 and 21. Flow cytometry was performed to analyze the immune cell characteristics, and gene expression levels were examined using quantitative reverse transcription-polymerase chain reaction.

Results

In the histological analysis of explanted human lung tissues, the terminally fibrotic areas contained a larger number of macrophages and monocytes than the early fibrotic areas of the lungs. When human monocyte-derived macrophages (MoMs) were stimulated with interleukin-13 in vitro, the expression of type 2 macrophage (M2) markers was more prominent in MoMs from the classical monocyte subset than in those from intermediate or non-classical monocyte subsets, and MSCs suppressed M2 marker expression independent of MoM subsets. In the mouse model, the increased number of inflammatory cells in the bronchoalveolar lavage fluid and the degree of lung fibrosis observed in BLM-treated mice were significantly reduced by MSC treatment, which tended to be more prominent with intravenous administration than intratracheal administration. Both M1 and M2 MoMs were upregulated in BLM-treated mice. The M2c subset of M2 MoMs was significantly reduced by MSC treatment. Among M2 MoMs, M2 MoMs derived from Ly6C+ monocytes were most effectively regulated by the intravenous administration, not intratracheal administration, of MSCs.

Conclusions

Inflammatory classical monocytes may play a role in lung fibrosis in human IPF and BLM-induced pulmonary fibrosis. Intravenous rather than intratracheal administration of MSCs may ameliorate pulmonary fibrosis by inhibiting monocyte differentiation into M2 macrophages.
Nomogram prediction for the risk of venous thromboembolism in patients with lung cancer
Authors: Lei Haike , Tao Dan , Zhang Ningning , Sun Mao , Sun Lisi , Yang Dingyi , Jiang Yong , Zhou Wei , Xie Yue , Wang Ying
Published: March 2023

Objective

The aim of this study was to establish a nomogram graph model to accurately predict the venous thromboembolism (VTE) risk probability in the general population with lung cancer.

Methods

Based on data from patients with lung cancer in Chongqing University Cancer Hospital of China, the independent risk factors of VTE were identified by the logistic univariable and multivariable analysis and were integrated to construct a nomogram, which was validated internally. The predictive effectiveness of the nomogram was evaluated by the receiver operating characteristic curve (ROC) and calibration curve.

Results

A total of 3398 lung cancer patients were included for analysis. The nomogram incorporated eleven independent VTE risk factors including karnofsky performance scale (KPS), stage of cancer, varicosity, chronic obstructive pulmonary disease (COPD), central venous catheter (CVC), albumin, prothrombin time (PT), leukocyte counts, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), dexamethasone, and bevacizumab. The C-index of the nomogram model was 0.843 and 0.791 in the training and validation cohort, respectively, demonstrating good discriminative power. The calibration plots of the nomogram revealed excellent agreement between the predicted and actual probabilities.

Conclusions

We established and validated a novel nomogram for predicting the risk of VTE in patients with lung cancer. The nomogram model could precisely estimate the VTE risk of individual lung cancer patients and identify high-risk patients who are in need of a specific anticoagulation treatment strategy.
CircDNAJC11 interacts with TAF15 to promote breast cancer progression via enhancing MAPK6 expression and activating the MAPK signaling pathway
Authors: Wang Bin , Chen Hang , Deng Yumei , Chen Hong , Xing Lei , Guo Yuping , Wang Min , Chen Junxia
Published: March 2023

Background

Breast cancer (BC) is a common malignant tumor in women worldwide. Circular RNA (circRNA) has been proven to play a critical role in BC progression. However, the exact biological functions and underlying mechanisms of circRNAs in BC remain largely unknown.

Methods

Here, we first screened for differentially expressed circRNAs in 4 pairs of BC tissues and adjacent non-tumor tissues using a circRNA microarray. Functionally, gain- and loss-of-function experiments in vitro and in vivo showed that circDNAJC11 promoted BC cell proliferation, migration, invasion, and tumor growth. Mechanistically, RNA pull-down, mass spectrum, RNA immunoprecipitation, fluorescence in situ hybridization assays, and rescue experiments were executed.

Results

We found that circDNAJC11 was significantly upregulated in triple-negative breast cancer tissues and cells. Clinical data revealed that the high expression of circDNAJC11 was closely correlated with a poor prognosis of BC patients and could be an independent risk factor for BC prognosis. Functionally, gain- and loss-of-function experiments in vitro and in vivo showed that circDNAJC11 promoted BC cell proliferation, migration, invasion, and tumor growth. Mechanistically, RNA pull-down, mass spectrum, RNA immunoprecipitation, fluorescence in situ hybridization assays, and rescue experiments were executed. We demonstrated that circDNAJC11 combined with TAF15 to promote BC progression via stabilizing MAPK6 mRNA and activating the MAPK signaling pathway.

Conclusions

The circDNAJC11/TAF15/MAPK6 axis played a crucial role in the progression and development of BC, suggesting that circDNAJC11 might be a novel biomarker and therapeutical target for BC.
IFNAR signaling of neuroectodermal cells is essential for the survival of C57BL/6 mice infected with Theiler’s murine encephalomyelitis virus
Authors: Bühler Melanie , Li Dandan , Li Lin , Runft Sandra , Waltl Inken , Pavlou Andreas , Kalinke Ulrich , Ciurkiewicz Malgorzata , Huehn Jochen , Floess Stefan , Beineke Andreas , Baumgärtner Wolfgang , Gerhauser Ingo
Published: March 2023

Background

Theiler’s murine encephalomyelitis virus (TMEV) is a single-stranded RNA virus that causes encephalitis followed by chronic demyelination in SJL mice and spontaneous seizures in C57BL/6 mice. Since earlier studies indicated a critical role of type I interferon (IFN-I) signaling in the control of viral replication in the central nervous system (CNS), mouse strain-specific differences in pathways induced by the IFN-I receptor (IFNAR) might determine the outcome of TMEV infection.

Methods

Data of RNA-seq analysis and immunohistochemistry were used to compare the gene and protein expression of IFN-I signaling pathway members between mock- and TMEV-infected SJL and C57BL/6 mice at 4, 7 and 14 days post-infection (dpi). To address the impact of IFNAR signaling in selected brain-resident cell types, conditional knockout mice with an IFNAR deficiency in cells of the neuroectodermal lineage (NesCre±IFNARfl/fl), neurons (Syn1Cre±IFNARfl/fl), astrocytes (GFAPCre±IFNARfl/fl), and microglia (Sall1CreER±IFNARfl/fl) on a C57BL/6 background were tested. PCR and an immunoassay were used to quantify TMEV RNA and cytokine and chemokine expression in their brain at 4 dpi.

Results

RNA-seq analysis revealed upregulation of most ISGs in SJL and C57BL/6 mice, but Ifi202b mRNA transcripts were only increased in SJL and Trim12a only in C57BL/6 mice. Immunohistochemistry showed minor differences in ISG expression (ISG15, OAS, PKR) between both mouse strains. While all immunocompetent Cre-negative control mice and the majority of mice with IFNAR deficiency in neurons or microglia survived until 14 dpi, lack of IFNAR expression in all cells (IFNAR−/−), neuroectodermal cells, or astrocytes induced lethal disease in most of the analyzed mice, which was associated with unrestricted viral replication. NesCre±IFNARfl/fl mice showed more Ifnb1, Tnfa, Il6, Il10, Il12b and Ifng mRNA transcripts than Cre−/−IFNARfl/fl mice. IFNAR−/− mice also demonstrated increased IFN-α, IFN-β, IL1-β, IL-6, and CXCL-1 protein levels, which highly correlated with viral load.

Conclusions

Ifi202b and Trim12a expression levels likely contribute to mouse strain-specific susceptibility to TMEV-induced CNS lesions. Restriction of viral replication is strongly dependent on IFNAR signaling of neuroectodermal cells, which also controls the expression of key pro- and anti-inflammatory cytokines during viral brain infection.
A full genome tiling array enhanced the inspection and quarantine of SARS-CoV-2
Authors: Qi Runzi , Wang Gang , Wang Xu , Li Cheng , Huang Lei , Xiao Weixi , Shao Bing , Zhou Chunya , Ding Xun , Li Feng , Zhou Wei
Published: March 2023

As the worldwide spreading epidemic of SARS-CoV-2, quick inspection and quarantine of passengers for SARS-CoV-2 infection are essential for controlling the spread of SARS-CoV-2, especially the cross-border transmission. This study reports a SARS-CoV-2 genome sequencing method based on a re-sequencing tiling array successfully used in border inspection and quarantine. The tiling array chip has four cores, with one core of 240,000 probes dedicated to the whole genome sequencing of the SAR-CoV-2 genome. The assay protocol has been improved to reduce the detection time to within one day and can detect 96 samples in parallel. The detection accuracy has been validated. This fast and simple procedure is also of low cost and high accuracy, and it is particularly suitable for the rapid tracking of viral genetic variants in custom inspection applications. Combining these properties means this method has significant application potential in the clinical investigation and quarantine of SARS-CoV-2. We used this SARS-CoV-2 genome re-sequencing tiling array to inspect and quarantine China's entry and exit ports in the Zhejiang Province. From November 2020 to January 2022, we observed the gradual shift of SARS-CoV-2 variants from the D614G type to the Delta Variant, and then to the dominance of the Omicron variant recently, consistently with the global emergency pattern of the new SARS-CoV-2 variant.
Lung versus gut exposure to air pollution particles differentially affect metabolic health in mice
Authors: Bosch Angela J. T. , Rohm Theresa V. , AlAsfoor Shefaa , Low Andy J. Y. , Keller Lena , Baumann Zora , Parayil Neena , Stawiski Marc , Rachid Leila , Dervos Thomas , Mitrovic Sandra , Meier Daniel T. , Cavelti-Weder Claudia
Published: March 2023

Background

Air pollution has emerged as an unexpected risk factor for diabetes. However, the mechanism behind remains ill-defined. So far, the lung has been considered as the main target organ of air pollution. In contrast, the gut has received little scientific attention. Since air pollution particles can reach the gut after mucociliary clearance from the lungs and through contaminated food, our aim was to assess whether exposure deposition of air pollution particles in the lung or the gut drive metabolic dysfunction in mice.

Methods

To study the effects of gut versus lung exposure, we exposed mice on standard diet to diesel exhaust particles (DEP; NIST 1650b), particulate matter (PM; NIST 1649b) or phosphate-buffered saline by either intratracheal instillation (30 µg 2 days/week) or gavage (12 µg 5 days/week) over at least 3 months (total dose of 60 µg/week for both administration routes, equivalent to a daily inhalation exposure in humans of 160 µg/m3 PM2.5) and monitored metabolic parameters and tissue changes. Additionally, we tested the impact of the exposure route in a “prestressed” condition (high-fat diet (HFD) and streptozotocin (STZ)).

Results

Mice on standard diet exposed to particulate air pollutants by intratracheal instillation developed lung inflammation. While both lung and gut exposure resulted in increased liver lipids, glucose intolerance and impaired insulin secretion was only observed in mice exposed to particles by gavage. Gavage with DEP created an inflammatory milieu in the gut as shown by up-regulated gene expression of pro-inflammatory cytokines and monocyte/macrophage markers. In contrast, liver and adipose inflammation markers were not increased. Beta-cell secretory capacity was impaired on a functional level, most likely induced by the inflammatory milieu in the gut, and not due to beta-cell loss. The differential metabolic effects of lung and gut exposures were confirmed in a “prestressed” HFD/STZ model.

Conclusions

We conclude that separate lung and gut exposures to air pollution particles lead to distinct metabolic outcomes in mice. Both exposure routes elevate liver lipids, while gut exposure to particulate air pollutants specifically impairs beta-cell secretory capacity, potentially instigated by an inflammatory milieu in the gut.
TGM2 accelerates migration and differentiation of BMSCs by activating Wnt/β-catenin signaling
Authors: Liu Feng , Wu Mingzheng , Wu Xixia , Chen Dan , Xie Ming , Pan Hao
Published: March 2023

Background

Transglutaminase 2 (TGM2) is a gene previously reported to be associated with the differentiation of bone marrow mesenchymal stem cells (BMSCs). The study was developed to reveal the impact of TGM2 on the migration and differentiation of BMSCs.

Methods

Cells were isolated from bone marrow of mice and then the surface antigens were identified by flow cytometry. Wound healing assays were conducted to assess the migratory ability of BMSCs. The mRNA levels of TGM2 and osteoblast-associated genes (ALP, OCN, and RUNX2) were subjected to RT-qPCR analysis, and protein levels of these genes as well as β-catenin were quantitated by western blotting. Alizarin red staining was conducted for detection of osteogenic ability. The activation of Wnt signaling was assessed by TOP/FOP flash assays.

Results

Surface antigens were positively identified in MSCs, indicating good multidirectional differentiation ability of cells. TGM2 silencing suppressed BMSC migration while weakening mRNA and protein levels of osteoblast-associated genes. While TGM2 overexpression exerts the opposite impact on cell migration and expression levels of osteoblast-associated genes. Additionally, overexpressed TGM2 promotes the mineralization of BMSCs according to results of Alizarin red staining. Moreover, TGM2 activated the Wnt/β-catenin signaling, and DKK1 (an inhibitor of Wnt signaling) reversed the promoting influence of TGM2 on cell migration and differentiation.

Conclusion

TGM2 promotes the migration and differentiation of BMSCs via activation of the Wnt/β-catenin signaling.