bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Outcomes of Additional Below-The-Ankle Intervention Compared to Below-The-Knee Intervention Alone: A Post-Hoc Analysis of a Prospective Multicenter Study
Authors: Metser Gil , Puma Joseph , Mustapha Jihad , Adams George L. , Ratcliffe Justin , Khullar Pankaj , Rosero Joshua H. C. , Armstrong Ehrin J. , Zayed Mohamed , Green Philip
Published: May 2022

Purpose

To investigate the clinical implication of additional below-the-ankle (BTA) intervention in patients with chronic limb-threatening ischemia (CLTI) undergoing below-the-knee (BTK) intervention.

Materials and Methods

A sub-analysis was performed using data from the LIBERTY trial ( ClinicalTrials.gov identifier NCT01855412), a prospective, observational, core-laboratory adjudicated, multicenter study of endovascular intervention in 1204 patients. Patients with CLTI (Rutherford Classification 4-6) who underwent BTK intervention were included in this sub-analysis. Participants were then stratified into 2 treatment groups according to whether at least one lesion intervened on was BTA (n=66) or not (n=273). The decision on whether and where to intervene was made during the procedure. The main outcome measures included major amputation, target vessel revascularization (TVR), major adverse events (MAE), survival, amputation-free survival, major adverse limb events or peri-operative death (MALE-POD), and all-cause death. Other outcome measures included procedural success, procedural complications, and wound healing rate.

Results

There were no differences in procedural success or severe angiographic complications between the 2 groups. At 1-year post-procedure, patients in the BTK group had a higher rate of freedom from major amputation (95.0% vs. 86.9%, respectively; HR: 2.87, 95% CI: 1.17-7.03), a higher rate of freedom from TVR (80.1% vs. 66.9%, respectively; HR: 1.94, 95% CI: 1.14-3.32), a higher rate of freedom from MALE-POD (94.6% vs. 86.9%, respectively; HR: 2.65, 95% CI: 1.10-6.41), and a higher rate of freedom from MAE at both 1 (76.0% vs. 60.1%, respectively; HR: 2.00, 95% CI: 1.24-3.22) and 3 years post procedure (67.5% vs. 55.8%, respectively; HR: 1.69, 95% CI: 1.08-2.65). There was a significantly lower rate of survival in the BTK group at 3 years (74.3% vs. 91.1%, respectively; HR: 0.35, 95% CI: 0.14-0.87). After risk adjustment, there was a higher rate of all-cause death in the BTK group at 3 years (19.4% vs. 9.1%, respectively; p=0.023) post-intervention.

Conclusion

Patients with disease requiring intervention to BTA lesions have a potential increased amputation rate in the short term, but BTA intervention carries a potential survival benefit in the long term when compared to BTK intervention alone.
The politics of international broadcasters: A comparison between Indonesia and Australia
Authors: Masduki
Published: May 2022

Seeking to assess the current state of international broadcasters (IBs) within the framework of public diplomacy, this paper assesses the relevance of state-sponsored IBs within the contemporary public diplomacy. This paper focuses on the IBs of two neighboring countries, Indonesia and Australia, and political authorities’ dynamic support for their services. Data were obtained through desk reviews of IB policies, in-depth interviews, and online observation of the websites of Siaran Luar Negeri (SLN, Indonesia's IB) and ABC Radio Australia (RA, Australia's IB). This paper finds that both countries have continued to use IBs for their public diplomacy, yet ‘political parallelism’ determines the position and sustainability of each. SLN has had limited political support and faced a series of managerial crises, while RA has enjoyed the fruitful support of the Australian authorities and has been heavily involved in public diplomacy in the Asia–Pacific region.
The meeting after the meeting: A conceptualization and process model
Authors: Meinecke Annika L. , Handke Lisa
Published: May 2022

This article offers initial theorizing on an understudied phenomenon in the workplace: the meeting after the meeting (MATM). As an informal and unscheduled event, the MATM takes place outside managerial control and has potentially far-reaching consequences. However, our current knowledge of the MATM relies primarily on practitioner observations, and conceptual work that integrates the MATM into the larger meeting science literature is missing. This article fills this gap by outlining key defining features of the MATM that can be used to structure future research. Moreover, and based on theorizing concerning the affect-generating nature of meetings, we develop an affect-based process model that focuses on the antecedents and boundary conditions of the MATM at the episodic level and shines light on meetings as a sequential phenomenon.
Surgical Management of a Giant Left Ventricular Fibroma in a Newborn
Authors: Egunov Oleg A. , Krivoshchekov Evgeny V. , Cetta Frank , Putrova Olesya D. , Sokolov Alexander A. , Yanulevich Olga S.
Published: May 2022

This clinical case report describes surgical management of a giant left ventricular fibroma and postoperative venoarterial extracorporeal membrane oxygenation support in a newborn male. Transthoracic echocardiography performed at 9-month follow-up showed an ejection fraction of 33% and a cardiac index of 4.5 liters per minute per square meter.
Perception of Head Teachers and Education Secretaries on Home Grown School Feeding Program in Nigeria
Authors: Igboji Jonathan Ogbonna , Umoke MaryJoy , Obande-Ogbuinya Nkiru Edith , Agu Martins Nonso , Mbamalu Oby Justina
Published: May 2022

The study investigated head teachers, and, education administrators’ view of the Home Grown School Feeding Program and the associated sociodemographic variables. The study adopted a descriptive cross sectional design. Fifty-four government owned primary schools in Ebonyi State, Nigeria, participated in the study. Head teachers and education secretaries completed a paper-and-pen questionnaire and described their perception about Home Grown School Feeding Program impact on pupil registration, presence, retention, dropout, and the problems that may be associated with the program implementation. SPSS version 23 was used to interpret the data. Results showed that head teachers perception on HGSFP was good on its effect on pupils’ enrolment, attendance, retention, and dropout. Nonexistence of lawful framework and strategy for sustenance of HGSFP, insufficient funding, inability to monitor food preparation, inadequate teaching space and equipment to deal with extra admission were challenges perceived. Sociodemographic factors such as age, sex, education level, and location were not significant ( p > .05). Head teachers perception was good though they have their concerns on aspects of implementation. Program implementation agencies should improve funding, monitoring, and educational infrastructure for the smooth running of the program.
Active agents of change: A conceptual framework for social justice-orientated citizenship education
Authors: Egan-Simon Daryn
Published: May 2022

Social justice–orientated citizenship education (SJCE) can help young people to develop the knowledge, skills and dispositions to work collectively towards solutions to problems such as human rights violations, global poverty and environmental sustainability (DeJaeghere and Tudball, 2007; Banks, 2017; Hartung, 2017). Furthermore, SJCE can enable young people to think critically, consciously and compassionately and allow them to grow intellectually with a concern for equality and justice. This paper presents a conceptual framework for SJCE for educators and educational researchers wishing to explore citizenship education within social justice contexts. The framework is based on four constitutive elements: agency, dialogue, criticality and emancipatory knowledge, and has its philosophical foundations deeply rooted in the values and principles of critical pedagogy (Kincheloe, 2004; McLaren, 2014; Giroux, 2016). This conceptual framework for SJCE is ultimately concerned with developing justice-orientated active agents of change who are concerned with making the world more democratic, equitable and just.
Calcitonin gene-related peptide-targeting drugs and Raynaud’s phenomenon: a real-world potential safety signal from the WHO pharmacovigilance database
Authors: Gérard Alexandre O. , Merino Diane , Van Obberghen Elise K. , Rocher Fanny , Destere Alexandre , Lantéri-Minet Michel , Drici Milou-Daniel
Published: May 2022

Background

Migraine is responsible for significant disability and societal burden. Recently, drugs targeting the calcitonin gene-related peptide (CGRP) pathway raised new hopes. CGRP, a potent vasodilator, plays a key role in the pathogenesis of migraine attacks. The deficiency of CGRP is involved in Raynaud’s phenomenon, which consists of abnormal vasoconstriction of the digits. We aimed to assess the potential association of Raynaud’s phenomenon with CGRP-targeting drugs, analyzing real-world data from the World Health Organization (VigiBase®).

Methods

We queried all reports of Raynaud’s phenomenon involving a CGRP-targeting drug. We sought disproportionate reporting of Raynaud’s phenomenon with these drugs. For this purpose, we relied on the calculation of the Information Component (IC). A positive lower end of the 95% confidence interval (CI) of the IC defines a statistically significant association. As migraine patients are prone to Raynaud’s phenomenon, we also calculated the IC of Raynaud’s phenomenon with CGRP-targeting drugs compared to 5HT1B/D agonists (triptans), and beta-blockers used in the treatment of migraine.

Results

Overall, 99 reports of Raynaud’s phenomenon involving CGRP-targeting drugs have been yielded in VigiBase®. The most reported CGRP-targeting drug was erenumab, with 56 reports (56.6%). The median time to onset was 84 days. No fatality was notified, but one patient suffered from gangrene and extremity necrosis. As a whole, CGRP-targeting drugs were significantly associated with Raynaud’s phenomenon, with an IC of 3.3 (95%CI: 3.0–3.5). There was a disproportionate reporting of Raynaud’s phenomenon with CGRP-targeting drugs compared to triptans (IC 0.4; 95%CI: 0.1–0.6) and to beta-blockers (IC 0.5; 95%CI: 0.2–0.7) as well.

Conclusions

There is a significant disproportionality signal of Raynaud’s phenomenon with CGRP-targeting. This signal stands out when CGRP-targeting drugs are compared to other drugs used in patients with migraine. This study is limited by missing data in pharmacovigilance reports. CGRP-targeting drugs may be subject to Weber effect and reporting bias. Nonetheless, CGRP blockade might be the last straw that disrupts the physiological balance of vascular response in patients at-risk of Raynaud’s phenomenon. Pending further data regarding vascular safety of CGRP-targeting drugs, caution is warranted in these patients.
Prevalence and genotypes distribution of group A rotavirus among outpatient children under 5 years with acute diarrhea in Shanghai, China, 2012–2018
Authors: Lu Lijuan , Zhong Huaqing , Jia Ran , Su Liyun , Xu Menghua , Cao Lingfeng , Liu Pengcheng , Ao Yuanyun , Dong Niuniu , Xu Jin
Published: May 2022

Background

Group A rotavirus (RVA) remains the main causative agent of acute diarrhea among children under five years in countries that have not yet introduced the RVA vaccine worldwide. Long-term and continuous monitoring data on RVA infection in outpatient children were lacking in Shanghai. We investigated the prevalence and distribution of RVA genotypes in outpatient children with acute diarrhea in Shanghai from 2012 to 2018.

Methods

Stool specimens of outpatient children under five years were collected from the Children’s Hospital of Fudan University in Shanghai, China. All the samples enrolled in this study were detected and characterized for the P and G genotypes of RVA were determined using the semi-multiplex RT-PCR technique.

Results

Of 1814 children enrolled with acute diarrhea and having specimens collected, 246 (13.6%) were infected with RVA. The highest frequency of RVA was observed in children younger than two years old (87.0%, 214/246). Year-round RVA transmission was observed and the RVA detection rate peaked every winter and troughed in summer. In this study, 12 different RVA strains were identified in children. G9P[8] (49.2%, 121/246) was detected as the most prevalent genotype, followed by G–P[8] (22.8%, 56/246), G3P[8] (11.4%, 28/246), and G9P- (4.9%, 12/246). Although RVA strains detected in this study varied with the time, G9P[8] has been the most predominant circulating genotype since 2012. Furthermore, 12.2% (30/246) RVA positive samples were co-infected with other diarrhea viruses.

Conclusion

The present analysis showed that RVA was still a major cause of children with acute diarrhea in Shanghai from 2012 to 2018. A great diversity of RVA strains circulated in children with acute diarrhea with G9P[8] being the predominant genotype since 2012. Long-term and continuous monitoring of RVA genotypes is therefore indispensable to refine future vaccine strategy in Shanghai.
Establishment of patient-derived organoids and a characterization-based drug discovery platform for treatment of pancreatic cancer
Authors: Watanabe Sadanori , Yogo Akitada , Otsubo Tsuguteru , Umehara Hiroki , Oishi Jun , Kodo Toru , Masui Toshihiko , Takaishi Shigeo , Seno Hiroshi , Uemoto Shinji , Hatano Etsuro
Published: May 2022

Background

Pancreatic cancer is one of the most lethal tumors. The aim of this study is to provide an effective therapeutic discovery platform for pancreatic cancer by establishing and characterizing patient-derived organoids (PDOs).

Methods

PDOs were established from pancreatic tumor surgical specimens, and the mutations were examined using a panel sequence. Expression of markers was assessed by PCR, immunoblotting, and immunohistochemistry; tumorigenicity was examined using immunodeficient mice, and drug responses were examined in vitro and in vivo.

Results

PDOs were established from eight primary and metastatic tumors, and the characteristic mutations and expression of cancer stem cell markers and CA19–9 were confirmed. Tumorigenicity of the PDOs was confirmed in subcutaneous transplantation and in the peritoneal cavity in the case of PDOs derived from disseminated nodules. Gemcitabine-sensitive/resistant PDOs showed consistent responses in vivo. High throughput screening in PDOs identified a compound effective for inhibiting tumor growth of a gemcitabine-resistant PDO xenograft model.

Conclusions

This PDO-based platform captures important aspects of treatment-resistant pancreatic cancer and its metastatic features, suggesting that this study may serve as a tool for the discovery of personalized therapies.
High neutrophil-to-lymphocyte ratio is a significant predictor of depressive symptoms in maintenance hemodialysis patients: a cross-sectional study
Authors: Feng Jianan , Lu Xiangxue , Li Han , Wang Shixiang
Published: May 2022

Background

Depression is one of the most important psychiatric disorders in chronic kidney disease patients who undergo maintenance hemodialysis (MHD). Previous studies have shown that low-grade inflammation is involved in the progression of depressive symptoms. The neutrophil-to-lymphocyte ratio (NLR) is an inflammatory marker that is inexpensive and easy to measure. However, the association between NLR and depression symptoms in MHD patients has not been examined.

Methods

In this single-center, cross-sectional study, we included 160 patients undergoing MHD. The Patient Health Questionnaire-9 (PHQ-9) was used to assess depressive symptoms. NLR was calculated as the ratio of neutrophils to lymphocytes. Multinomial logistic regression and multivariate linear regression analyses were used to examine the association between NLR and depressive symptoms in MHD patients.

Results

Depressive symptoms were detected in 36.7% of the 160 MHD patients. Multinomial logistic regression showed that NLR was a significant predictor of mild (odds ratio [OR]: 1.383, 95% confidence interval [CI]: 1.015–1.884, p = 0.04) and moderate/moderately severe depressive symptoms (OR: 1.441, 95% CI: 1.017–2.042, p = 0.04) in MHD patients, adjusted for age, sex, Kt/V, dialysis duration, history of kidney transplantation, history of hypertension, and Charlson comorbidity index score. In addition, multivariate linear regression analysis showed that NLR was an independent influencing factor for PHQ-9 score in MHD patients, after adjusting for confounding factors.

Conclusions

These findings suggest that NLR can be used as a biomarker for predicting depressive symptoms in MHD patients.
Access to health services among culturally and linguistically diverse populations in the Australian universal health care system: issues and challenges
Authors: Khatri Resham B. , Assefa Yibeltal
Published: May 2022

Background

About half of first- or second-generation Australians are born overseas, and one-in-five speak English as their second language at home which often are referred to as Culturally and Linguistically Diverse (CALD) populations. These people have varied health needs and face several barriers in accessing health services. Nevertheless, there are limited studies that synthesised these challenges. This study aimed to explore issues and challenges in accessing health services among CALD populations in Australia.

Methods

We conducted a scoping review of the literature published from 1st January 1970 to 30th October 2021 in four databases: PubMed, Scopus, Embase, and the Web of Science. The search strategy was developed around CALD populations and the health services within the Australian context. We used Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines for selection and Arksey and O’Malley framework for analysis of relevant articles. A narrative synthesis of data was conducted using inductive thematic analysis approach. Identified issues and challenges were described using an adapted socioecological model.

Results

A total of 64 studies were included in the final review. Several challenges at various levels were identified to influence access to health services utilisation. Individual and family level challenges were related to interacting social and health conditions, poor health literacy, multimorbidity, diminishing healthy migrants’ effect. Community and organisational level challenges were acculturation leading to unhealthy food behaviours and lifestyles, language and communication problems, inadequate interpretation services, and poor cultural competency of providers. Finally, challenges at systems and policy levels included multiple structural disadvantages and vulnerabilities, inadequate health systems and services to address the needs of CALD populations.

Conclusions

People from CALD backgrounds have multiple interacting social factors and diseases, low access to health services, and face challenges in the multilevel health and social systems. Health systems and services need to focus on treating multimorbidity through culturally appropriate health interventions that can effectively prevent and control diseases. Existing health services can be strengthened by ensuring multilingual health resources and onsite interpreters. Addressing structural challenges needs a holistic policy intervention such as improving social determinants of health (e.g., improving living and working conditions and reducing socioeconomic disparities) of CALD populations, which requires a high level political commitment.
Scutellaria barbata D.Don (SBD) extracts suppressed tumor growth, metastasis and angiogenesis in Prostate cancer via PI3K/Akt pathway
Authors: Sheng Dongya , Zhao Bei , Zhu Wenjing , Wang Tiantian , Peng Yu
Published: May 2022

Background

Scutellaria barbata D.Don (SBD) is derived from the dried whole plant of Labiate which has been widely used to treat patients with multiple cancer. It was previously reported that the ethanol extract of SBD is able to promote apoptosis, and inhibit cell proliferation and angiogenesis in cancer.

Materials and methods

CCK8, Edu assays and colony formation assay were performed to assess the effect of SBD on PCa cell growth. Effect of SBD on apoptosis and cell cycle was detected by flow cytometry. Transwell and wounding healing assay were conducted to detect the invasion and migration activities of PCa cells. Western blot was employed to detect the protein expression. 2RRV1 mouse xenograft model was established to detect the effect of SBD on prostate cancer. Angiogenesis was analysed by coculturing PCa cell lines and HUVECs.

Results

The results showed that SBD induced a significant decrease in cell viability and clonogenic growth in a dose-dependent manner. SBD induced cell apoptosis and cell cycle G2/M phase arrest by inactivating PI3K/AKT signalling pathway. Treatment with SBD also significantly decreased the cell migration and invasion via phenotypic inversion of EMT that was characterized by the increased expression of E-cadherin and Vimentin, and decreased expression of N-cadherin, which could be partially attributed to inhibiting PI3K/AKT signalling pathway. Subsequently, using AKT inhibitor MK2206, we concluded that PI3K/AKT are also involved in cell apoptosis and metastasis of PCa cells stimulated by SBD. Apart from its direct effects on PCa cells, SBD also exhibited anti-angiogenic properties. SBD alone or conditioned media from SBD-treated PCa cells reduced HUVEC tube formation on Matrigel without affecting HUVEC viability. Furthermore, 22RV1 xenograft C57BL/6 mice treated with SBD in vivo showed a significant inhibitory in tumour size and tumour weight without toxicity. In addition, administration with medium- or high-dose of SBD significantly inhibited the cell proliferation and enhanced the damage to tumour tissues.

Conclusions

Collectively, our in vitro and in vivo findings suggest that SBD has the potential to develop into a safe and potent alternative therapy for PCa patients.
Outcomes from a hybrid implementation-effectiveness study of the living well during pregnancy Tele-coaching program for women at high risk of excessive gestational weight gain
Authors: de Jersey Susan , Meloncelli Nina , Guthrie Taylor , Powlesland Hilary , Callaway Leonie , Chang Angela T. , Wilkinson Shelley , Comans Tracy , Eakin Elizabeth
Published: May 2022

Background

Excess gestational weight gain (GWG) is associated with short-term perinatal complications and longer term cardiometabolic risks for mothers and their babies. Dietitian counselling and weight gain monitoring for women at risk of high pregnancy weight gain is recommended by clinical practice guidelines. However, face-to-face appointments, during a time with high appointment burden, can introduce barriers to engaging with care. Telephone counselling may offer a solution. The Living Well during Pregnancy (LWdP) program is a dietitian-delivered telephone coaching program implemented within routine antenatal care for women at risk of excess GWG. This program evaluation used a hybrid implementation-effectiveness design guided by the RE-AIM framework to report on the primary outcomes (reach, adoption, implementation, maintenance) and secondary outcomes (effectiveness) of the LWdP intervention.

Methods

The LWdP program evaluation compared data from women participating in the LWdP program with a historical comparison group (pregnant women receiving dietetic counselling for GWG in the 12 months prior to the study). The primary outcomes were described for the LWdP program. Between group comparisons were used to determine effectiveness of achieving appropriate GWG and pre and post intervention comparisons of LWdP participants was used to determine changes to dietary intake and physical activity.

Results

The LWdP intervention group (n = 142) were compared with women in the historical comparison group (n = 49). Women in the LWdP intervention group attended 3.4 (95% CI 2.9–3.8) appointments compared with 1.9 (95% CI, 1.6–2.2) in the historical comparison group. GWG was similar between the two groups, including the proportion of women gaining weight above the Institute of Medicine recommendations (70% vs 73%, p = 0.69). Within group comparison showed that total diet quality, intake of fruit and vegetables and weekly physical activity were all significantly improved from baseline to follow-up for the women in LWdP, while consumption of discretionary food and time spent being sedentary decreased (all p < 0.05).

Conclusion

The LWdP program resulted in more women accessing care and positive improvements in diet quality, intuitive eating behaviours and physical activity. It was as effective as face-to-face appointments for GWG, though more research is required to identify how to engage women earlier in pregnancy and reduce appointment burden.
Malignant solitary fibrous tumor of the pleura
Authors: Khouzam Matthew S. , Khouzam Nayer
Published: May 2022

Background

Solitary fibrous tumors of the pleura are rare diseases of the thoracic cavity. They frequently grow unnoticed until they exert compressive effects on adjacent organs. Treatment of solitary fibrous tumors of the pleura is surgical resection. Post-operative surveillance is recommended to identify early recurrent disease.

Case presentation

We present a rare case of a 76-year-old female patient with no previous pulmonary history who presented with progressive dyspnea, fatigue, and involuntary weight loss. On chest X-ray and computed chest tomography scan, she was found to have a 16.7 cm × 12.8 cm × 10.1 cm bulky mass occupying the left hemithorax with associated compressive atelectasis of the lung. She underwent a computed tomography guided biopsy that revealed the mass to be a solitary fibrous tumor. The patient underwent left muscle sparing lateral thoracotomy with complete resection of the tumor. Post procedure, the left lung fully expanded. 18 months post-resection, she developed a 3.3 cm × 1.7 cm tumor along the left internal thoracic artery lymph node chain which was histologically identical to the resected tumor. The patient is currently being treated with bevacizumab and temozolomide.

Conclusion

Solitary fibrous tumors are very rare pleural tumors. Surgical resection is the treatment of choice followed by close post-operative surveillance.
Abnormal glucose regulation in Chinese patients with coronary artery disease: a gender analysis
Authors: Liu Juan , He Li-Qun , Zhu Wei , Duan Gang-Feng , Fang Yong , Feng Ying , Tian Li-Qun , Zheng Qiong-Li
Published: May 2022

Background

Diabetes and impaired glucose regulation are very common in patients with coronary artery disease (CAD). In this study, we aim to investigate the prevalence of abnormal glucose regulation in men and women in Chinese CAD patients.

Methods

In this retrospective study, 4100 patients (male, n = 2873; female, n = 1227)with CAD were enrolled. The mean age of these patients was 63 years. The demographic data, medical history, echocardiography findings and blood investigations were collected and analyzed.

Results

In this population, 953 (24%) patients had definite diagnosis of type 2 diabetes mellitus, including 636 males (23%) and 317 females (27%). There was a higher prevalence of diabetes in females than men (p < 0.05). For the remaining patients, 48% (n = 959) undergone an oral glucose tolerance test (OGTT), which revealed that 83 male patients (12%) and 41 female patients (16%) suffered from the type 2 diabetes (p > 0.05). 283 men (40%) and 105 women (41%) had impaired glucose regulation (IGR) (p > 0.05). Only 338 men (25%) and 109 women (19%) showed the normal glucose regulation, implying a higher prevalence of abnormal glucose regulation in females (p < 0.01). The odd ratio (OR) showed that women were more prone to have diabetes mellitus or IGT than men and the OR was 1.44 and 1.43 respectively.

Conclusion

Abnormal glucose regulation is highly prevalent in CAD patients. The women are more prone to have diabetes mellitus or IGT than men.
Spatiotemporal variations in urban CO2 flux with land-use types in Seoul
Authors: Park Chaerin , Jeong Sujong , Park Moon-Soo , Park Hoonyoung , Yun Jeongmin , Lee Sang-Sam , Park Sung-Hwa
Published: May 2022

Background

Cities are a major source of atmospheric CO2; however, understanding the surface CO2exchange processes that determine the net CO2flux emitted from each city is challenging owing to the high heterogeneity of urban land use. Therefore, this study investigates the spatiotemporal variations of urban CO2flux over the Seoul Capital Area, South Korea from 2017 to 2018, using CO2flux measurements at nine sites with different urban land-use types (baseline, residential, old town residential, commercial, and vegetation areas).

Results

Annual CO2flux significantly varied from 1.09 kg C m− 2year− 1at the baseline site to 16.28 kg C m− 2year− 1at the old town residential site in the Seoul Capital Area. Monthly CO2flux variations were closely correlated with the vegetation activity (r = − 0.61) at all sites; however, its correlation with building energy usage differed for each land-use type (r = 0.72 at residential sites and r = 0.34 at commercial sites). Diurnal CO2flux variations were mostly correlated with traffic volume at all sites (r = 0.8); however, its correlation with the floating population was the opposite at residential (r = − 0.44) and commercial (r = 0.80) sites. Additionally, the hourly CO2flux was highly related to temperature. At the vegetation site, as the temperature exceeded 24 ℃, the sensitivity of CO2absorption to temperature increased 7.44-fold than that at the previous temperature. Conversely, the CO2flux of non-vegetation sites increased when the temperature was less than or exceeded the 18 ℃ baseline, being three-times more sensitive to cold temperatures than hot ones. On average, non-vegetation urban sites emitted 0.45 g C m− 2 h− 1of CO2throughout the year, regardless of the temperature.

Conclusions

Our results demonstrated that most urban areas acted as CO2emission sources in all time zones; however, the CO2flux characteristics varied extensively based on urban land-use types, even within cities. Therefore, multiple observations from various land-use types are essential for identifying the comprehensive CO2cycle of each city to develop effective urban CO2reduction policies.
Prostate cancer multiparametric magnetic resonance imaging visibility is a tumor-intrinsic phenomena
Authors: Khoo Amanda , Liu Lydia Y. , Sadun Taylor Y. , Salmasi Amirali , Pooli Aydin , Felker Ely , Houlahan Kathleen E. , Ignatchenko Vladimir , Raman Steven S. , Sisk Anthony E. , Reiter Robert E. , Boutros Paul C. , Kislinger Thomas
Published: May 2022

Multiparametric magnetic resonance imaging (mpMRI) is an emerging standard for diagnosing and prognosing prostate cancer, but ~ 20% of clinically significant tumors are invisible to mpMRI, as defined by the Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) score of one or two. To understand the biological underpinnings of tumor visibility on mpMRI, we examined the proteomes of forty clinically significant tumors (i.e., International Society of Urological Pathology (ISUP) Grade Group 2)—twenty mpMRI-visible and twenty mpMRI-invisible, with matched histologically normal prostate. Normal prostate tissue was indistinguishable between patients with visible and invisible tumors, and invisible tumors closely resembled the normal prostate. These data indicate that mpMRI-visibility arises when tumor evolution leads to large-magnitude proteomic divergences from histologically normal prostate.
Sequence-dependent synergistic effect of aumolertinib-pemetrexed combined therapy on EGFR-mutant non-small-cell lung carcinoma with pre-clinical and clinical evidence
Authors: Ao Luyao , Fang Shencun , Zhang Kexin , Gao Yang , Cui Jiawen , Jia Wenjing , Shan Yunlong , Zhang Jingwei , Wang Guangji , Liu Jiali , Zhou Fang
Published: May 2022

Background

Inevitably developed resistance of the third-generation ﻿epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) limited its clinical benefit on non-small cell lung cancer (NSCLC). Upfront combination therapy is promising to prevent this resistance. Compelling clinical evidence indicated the failure of third-generation EGFR TKIs combined with either immunotherapy or antiangiogenic agents. In comparison, combined treatment of third-generation EGFR TKIs and chemotherapy might be a favorable choice. Herein, we systematically analyzed and compared the effects of pemetrexed and a novel third-generation EGFR TKI aumolertinib combined in different sequences, ﻿subsequently revealed the potential mechanisms and proved the optimal combination ﻿schedule with clinical retrospective study.

Methods

Three combination schedules involving pemetrexed and aumolertinib in different sequences were developed. Their inhibition effects on cell proliferation and metastasis were firstly compared upon three human NSCLC cell lines in vitro, by cell counting kit-8, colony formation, wound healing and transwell assays respectively. Further evaluation in vivo was proceeded upon H1975 and HCC827 xenograft model. Gene and protein expression were detected by Q-PCR and western blot. Drug concentration was determined by LC–MS/MS. VEGF secretion was determined by ELISA. Tumor vessel was visualized by immunofluorescence. Lastly, a clinical retrospective study was raised with 65 patients’ data.

Results

The combination of pemetrexed and aumolertinib exhibited a sequence-dependent and EGFR mutant-dependent synergistic effect in vitro and in vivo. Only treatment with aumolertinib following pemetrexed (P-A) exhibited synergistic effect with stronger anti-tumor growth and anti-metastasis ability than monotherapy and also other combination sequences. This synergism could exclusively be observed in H1975 and HCC827 but not A549. Pathway analysis showed that P-A significantly enhanced the suppression of EGFR pathway. In addition, our results intriguingly found an obvious reduction of VEGF secretion and the accompanying normalization of the intratumor vessel, consequently increasing intratumoral accumulation of pemetrexed in P-A group. Finally, the clinical retrospective study verified the synergistic effect of P-A combination by significantly superior tumor response than aumolertinib monotherapy.

Conclusion

Aumolertinib-pemetrexed combined therapy is promising for EGFR mutant NSCLC but only in right administration sequence. P-A could become an advantageous combination strategy in clinical with synergistic inhibition of tumor growth and metastasis.
Investigation of the relationship between community-acquired respiratory distress syndrome toxin and the high-mobility group box protein 1-toll-like receptors-myeloid differentiation factor 88 signaling pathway in Mycoplasma pneumoniae pneumonia
Authors: Fan Yujie , Ding Ying , Li Yuqin , Zhang Dandan , Yu Min , Zhou Wei-fang , Kong Xiaoxing
Published: May 2022

Background

In recent years, reports of refractory Mycoplasma pneumoniae pneumonia (RMPP) have gradually increased, including reports on how these conditions threaten the lives of children. However, the specific mechanism of Mycoplasma pneumoniae pneumonia (MPP) remains unclear. This study aimed to investigate the relationship between community-acquired respiratory distress syndrome toxin (CARDS TX) and High-mobility group box protein 1-Toll-like receptors-Myeloid differentiation factor 88 (HMGB1-TLRs-MyD88) in MPP and to examine the immune pathogenesis of Mycoplasma pneumoniae infection.

Methods

Children who were diagnosed with MPP and examined by bronchoscopy were included in the MPP group. Additionally, children who underwent bronchoscopy because of bronchial foreign bodies in the same period were included in the control group. Gene expression of CARDS TX, HMGB1, Toll-like receptor 2 (TLR2), Toll-like receptor 4 (TLR4), MyD88, and cluster of differentiation 14 (CD14) in bronchoalveolar lavage fluid (BALF) were detected using real-time reverse transcription-polymerase chain reaction. Correlations between CARDS TX and HMGB1-TLRs-MyD88 were analyzed.

Results

CARDS TX, HMGB1, TLR2, MyD88, and CD14 mRNA expression in BALF in the MPP group was significantly higher than that in the control group (all P < 0.05). CARDS TX mRNA expression was positively correlated with HMGB1, TLR2, MyD88, and CD14 mRNA expression (all P < 0.05). Furthermore, HMGB1 mRNA expression was positively correlated with TLR2, MyD88, and CD14 mRNA expression (all P < 0.05).

Conclusions

CARDS TX may participate in the immune pathogenesis of MPP through the HMGB1-TLRs/CD14-MyD88 pathway.
Specific antibody titer decay in neonates prenatally exposed to Toxoplasma gondii and their mothers
Authors: Salomè Serena , Grieco Claudia , Barra Pasquale Fabio , Capone Eleonora , Grasso Fiorentino , Carraturo Francesca , Dolce Pasquale , Salvatore Paola , Capasso Letizia , Raimondi Francesco
Published: May 2022

Background

For infants exposed in utero to Toxoplasma gondii, current guidelines recommend monitoring the specific antibody titer until 12 months of age. In this study, we investigated the antibody titer decay in the mother-infant dyad.

Methods

This is a single center, population-based cohort study of neonates referred for prenatal exposure to Toxoplasma gondii from January 2014 to December 2020. All infants underwent clinical, laboratory, and instrumental investigation for at least 12 months.

Results

A total of 670 eligible neonates were referred to the Perinatal Infection Unit of the University Federico II of Naples. 636 (95%) completed the serological follow up until 12 months. Specific IgG antibodies negativization occurred in 628 (98.7%) within 5 months. At 9 and 12 months, all patients had negative IgG. An initial neonatal IgG antibody titer ≥ 200 IU/ml was associated with a longer time to negativization (184 [177.5;256] days when above threshold vs. 139.5 [101;179] days when below it; p < 0.001). Maternal IgG antibody titer ≥ 200 IU/ml at childbirth was also associated to delayed time to negativization in the infant (179 [163;184] days above the threshold vs 125 [96.8;178] days below it; p < 0.001). Specific antibody negativization was irreversible in all patients.

Conclusions

Lower anti-Toxoplasma antibody titers detected at birth in the mother-infant-dyad lead to an earlier and irreversible negativization. This information allows for customisation of the infant follow up program and avoids invasive and expensive tests.
The effect of (-)-epigallocatechin gallate as an adjunct to non-surgical periodontal treatment: a randomized clinical trial
Authors: Zeng Jiajun , Wang Yanfeng , Yuan Qiao , Luan Qingxian
Published: May 2022

Background

EGCG is proven to be of good effect to relieve periodontal inflammation, but it has not been applied as a local delivery medicine in patients with periodontitis widely. The aim of this clinical trial was to evaluate the adjunctive effect of (-)-epigallocatechin gallate (EGCG) aqueous solution as a coolant during scaling and root planing in the management of chronic periodontitis.

Methods

A double-blind, randomized controlled study was performed on 15 patients with moderate to severe chronic periodontitis. The bilateral maxillary teeth were randomly divided into the test side and the control side on every individual. On the control side, the periodontal therapy was routinely performed. And on the test side, in the process of periodontal therapy, the distilled water in the ultrasonic scaler was replaced with a 5-mg/mL EGCG solution. The probing depth (PPD), clinical attachment level (CAL), bleeding index (BI), gingival index (GI), and plaque index (PI) were recorded at baseline and 6 and 12 weeks after the treatment.

Results

PPD, CAL, BI, GI, and PI generally improved after treatment in both groups. At the sixth week and the twelfth week of review, PPD, CAL, GI, and PI had no statistical difference (p >0.05) between the two groups. At the review of the twelfth week, BI on the test side decreased significantly (p <0.05).

Conclusions

Using EGCG solution as the irrigant instead of water has an additional benefit on the bleeding index at the 12-week review. However, the rest clinical parameters had no additional benefit.

Trial registration

ClinicalTrials.gov ChiCTR2000029831, date of registration: Feb 15, 2020.
Spatial heterogeneity of knockdown resistance mutations in the dengue vector Aedes albopictus in Guangzhou, China
Authors: Zheng Xueli , Zheng Zihao , Wu Shanshan , Wei Yong , Luo Lei , Zhong Daibin , Zhou Guofa
Published: May 2022

Background

The city of Guangzhou has been the epicenter of dengue fever in China since the 1990s, with Aedesalbopictus being the primary vector. The main method used to control vectors and prevent dengue fever has been the application of chemical insecticides; however, this control strategy has resulted in the development of resistance to these insecticides in mosquitoes. Here we report our investigation of the patterns of knockdown resistance (kdr) mutations in 15 field populations of Ae.albopictus collected from 11 districts in Guangzhou.

Results

Four mutant alleles (V1016G, F1534S, F1534C, F1534L) were detected in domain II and III of the voltage-gated sodium channel (VGSC) gene. Various allele frequencies of kdr mutations were observed (3.1–25.9% for V1016G, 22.6–85.5% for F1534S, 0–29.0% for F1534L, 0.6–54.2% for F1534C). Seven kdr haplotypes (VF, VS, VL, VC, GF, GC, GS) were identified; the highest frequency of haplotypes was found for the single mutant haplotype VS (50.8%), followed by the wild-type VF haplotype (21.7%) and the single mutant haplotype VC (11.9%). Of the three double mutant haplotypes, GF was the most frequent (8.8%), followed by GC (1.2%) and GS (0.8%). Aedesalbopictus showed spatial heterogeneity in deltamethrin resistance in populations collected in Guangzhou. We also observed significant differences in haplotype frequency. The frequency of the VC haplotype was significantly higher in high-risk dengue areas than in low-risk ones.

Conclusions

The kdr allele V1016G was discovered for the first time in Guangzhou. Genetic isolation in mosquito populations and long-term insecticide selection seem to be responsible for the persistent, patchy distribution of kdr mutant alleles. The small-scale spatial heterogeneity in the distribution and frequency of kdr mutations may have important implications for vector control operations and insecticide resistance management strategies.

Graphical Abstract
New insights into the distribution of cardio-pulmonary nematodes in road-killed wild felids from Romania
Authors: Deak Georgiana , Ionică Angela Monica , Pop Raul Alexandru , Mihalca Andrei Daniel , Gherman Călin Mircea
Published: May 2022

Background

The population of wild felids is large and stable in Romania with many carnivore habitats being protected. Felids can be infected with a wide variety of cardio-pulmonary nematodes and can act as reservoirs of infection for domestic cats. The aim of this study was to evaluate the distribution and species diversity of cardio-pulmonary nematodes in wild felids from Romania.

Methods

A total of 54 wild felids (7 Lynx lynx and 47 Felis silvestris) were legally collected from different locations in Romania and analysed by complete parasitological necropsy. The entire respiratory tract was longitudinally opened and checked for the presence of nematodes. Detected nematodes were collected and morphologically identified to species level.

Results

Two Eurasian lynxes and 29 European wildcats were positive for cardio-pulmonary nematodes. Eurasian lynxes were infected with two species of cardio-pulmonary nematodes, Eucoleus aerophilus and Troglostrongylus brevior, while in wildcats the dominant parasite was E. aerophilus (34.0%) followed by Angiostrongylus chabaudi (23.4%) and T. brevior (14.9%). Dirofilaria immitis and Aelurostrongylus abstrusus were each detected in two wildcats (4.3%).

Conclusions

The present study expanded the epidemiological knowledge on felid cardiopulmonary nematodes in Romania. We confirmed the presence of A. abstrusus in wildcats and a patent infection with T. brevior in Eurasian lynx.

Graphical Abstract
Deficiency of PKCλ/ι alleviates the liver pathologic impairment of Schistosoma japonicum infection by thwarting Th2 response
Authors: Mei Congjin , Yang Yingying , Dong Panpan , Song Lijun , Zhou Yonghua , Xu Yongliang , Yu Chuanxin
Published: May 2022

Background

The activation of immune response driven by the eggs of Schistosoma japonicum and the subsequent secretions is the culprit behind granulomatous inflammation and liver fibrosis. Evidence suggests that PKCλ/ι participates in a variety of physiological and pathological processes, including the regulation of metabolism, growth, proliferation and differentiation of cells. However, the role of PKCλ/ι in liver disease caused by Schistosoma japonicum remains unclear.

Methods

In the present study, we observe the pathological changes of egg-induced granulomatous inflammation and fibrosis in the liver of mice infected by Schistosoma japonicum by using conditional PKCλ/ι-knockout mice and wild-type control. Immune cytokines and fibrogenic factors were analyzed by performing flow cytometry and real-time fluorescence quantitative PCR.

Results

The results of H&E and Masson staining show that the degree of granulomatous lesions and fibrosis in the liver of the infected PKCλ/ι-knockout mice was significantly reduced compared with those of the infected wild-type mice. The mean area of single granuloma and hepatic fibrosis in the PKCλ/ι-knockout mice was significantly lower than that of the wild-type mice (85,295.10 ± 5399.30 μm2 vs. 1,433,702.04 ± 16,294.01 μm2, P < 0.001; 93,778.20 ± 8949.05 μm2 vs. 163,103.01 ± 11,103.20 μm2, P < 0.001), respectively. Serological analysis showed that the ALT content was significantly reduced in the infected knockout mice compared with infected wild-type mice. RT-PCR analysis showed that IL-4 content in knockout mice was significantly increased after Schistosoma japonicum infection, yet the increase was less than that in infected wild-type mice (P < 0.05). PKCλ/ι deficiency led to reduced expression of fibrosis-related factors, including TGF-β1, Col-1, Col-3, α-SMA and liver DAMP factor HMGB1. Flow cytometry analysis showed that the increasing percentage of Th2 cells, which mainly secrete IL-4 cytokines in spleen cells, was significantly lower in PKCλ/ι-deficient mice compared with wild-type mice after infection (P < 0.05).

Conclusions

Our data demonstrate that PKCλ/ι deficiency alleviating granulomatous inflammation and fibrosis in the liver of mice with S. japonicum infection by downregulating Th2 immune response is the potential molecular mechanism behind the role of PKCλ/ι in schistosomiasis.

Graphical Abstract