bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of the Effectiveness of Topical Product of Commiphora Mukul Oleo Gum Resin on Dermal Wound Healing: An Experimental Study
Authors: Malayeri Alireza , Abdevand Zeinab Zaheri , Rashedi Masoud , Hamedi Shokouh Sadat , Basir Zahra , Golfakhrabadi Fereshteh
Published: September 2022

In Persian Medicine, many plants have been used in wound healing for thousands of years, and recent evidence indicates the beneficial effects of plant extracts on healing skin wounds. Commiphora mukul oleo gum resin has been considered for a long time due to its various properties such as milk-enhancing, diuretic, and healing the mouth and larynx wounds. The present study aimed to evaluate the effect of Commiphora mukul oleo gum resin on wound healing in rats. Forty-two albino Wistar rats have randomly divided into six groups: The first group was without treatment, the second group was treated with Eucerin, the third group was treated with phenytoin cream %1, the fourth to sixth groups were treated with Commiphora mukul ointment 2%, 4%, and 8% respectively. Treatment was performed once a day for 14 days, and the wound area was measured daily. At the end of the experiment, blood samples were taken to measure vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). The histological evaluation and the strength test of the repaired tissue were performed. The results showed that seven days after treatment, the wound area decreased significantly in the groups treated with mukul gum extract compared to the control groups (p0.05). At the end of the experiment, there was no significant difference in wound area reduction between the groups. Commiphora mukul gum extract increased VEGF and significantly improved skin elasticity. The results of this study indicate the Wound healing potential of Commiphora mukul.
The Relationship Between Workplace Burnout and Male Depression Symptom Assessed by the Korean Version of the Gotland Male Depression Scale
Authors: Moon Jung Yeon , Choi Tae Young , Won Eun Soo , Won Geun Hui , Kim So Yeun , Lee Hye Jeong , Yoon Seoyoung
Published: September 2022

Screening for depression in males is important because their symptoms differ from those of females, ranging from indications of aggression to attempts at suicide. Men and women differ in their responses to job stress. There are no tools that have been verified, developed, or translated for screening male depression in Korea. Our team translated the Gotland Male Depression Scale (GMDS) into Korean. The Korean version of GMDS (K-GMDS) and Maslach Burnout Inventory-General Survey (MBI-GS) were administered to 277 office workers in one public institution. Gender differences in each scale score were measured along with the correlation between the K-GMDS and the MBI-GS. There was no significant difference in the K-GMDS score between males and females, whereas females scored significantly higher on the MBI-GS ( p < .001). The correlation between the K-GMDS total score and the MBI total score (male: r = .702, p < .001, female: r = .375, p < .001) and MBI subscale scores were higher in males than females. Gender moderated the relationship between total K-GMDS and total MBI scores ( p < .001). The Korean version of the GMDS is suitable for screening male depression symptoms in the workplace. The results of the K-GMDS demonstrated a strong correlation between depressive symptoms and work-related burnout among men. This study can be used as a basis for studying male depression symptoms in Korea, which has not been studied extensively. This will prove beneficial for work environments.
A Systematic Comparison of In-Person and Video-Based Online Interviewing
Authors: Lobe Bojana , Morgan David L. , Hoffman Kim
Published: September 2022

Due to the increasing popularity of online qualitative interviewing methods, we provide a systematically organized evaluation of their advantages and disadvantages in comparison to traditional in-person interviews. In particular, we describe how individual interviews, dyadic interviews, and focus groups operate in both face-to-face and videoconferencing modes. This produces five different areas for comparison: logistics and budget, ethics, recruitment, research design, and interviewing and moderating. We conclude each section with set of recommendations, and conclude with directions for future research in online interviewing.
Signals hierarchical feature enhancement method for CNN-based fault diagnosis
Authors: Zhang Huang , Zhang Shuyou , Wang Zili , Qiu Lemiao , Zhang Yiming
Published: September 2022

The high noise and low energy characteristics of the raw signals collected by sensors make the signal features weak and difficult to train. The purpose of this paper is to enhance the fault features of abnormal signals using the hierarchical feature enhancement method (HFE) which contains three layers. In the first layer, the signals are decomposed into multiple modals estimated by a variational optimization problem. The modals we choose are used to reconstruct the signals to form a complex matrix used to extract features in the second layer. In the third layer, the feature signals are converted into two-dimensional space and then are input into the convolutional neural network (CNN) for fault diagnosis after HFE since CNN helps to mine deeper features and compute in parallel on a large scale. The experimental results effectively verify the performance of the HFE for enhancing the weak fault features and preventing noise interference. The signals analyzed by HFE used as input greatly improve the diagnosis ability of CNN. In addition, the ablation and comparison experiments are conducted which still show superiority.
Learning based multi-scale feature fusion for retinal blood vessels segmentation
Authors: Zhang Ting , Wei Lifang , Chen Nan , Li Jun
Published: September 2022

Many eye-related diseases will lead to blindness or worse when it is lack of treatment in the early stages of the disease. Retinal vessel is important for doctors to detect eye diseases, even though the increase of some thin vessels may also mean the occurrence of certain diseases. Therefore, automatic retinal vessel segmentation is of great help to doctors in diagnosing diseases. In this paper, an automatic vessel segmentation method is proposed for retinal image, which is based on support vector machine combining multi-scale feature fusion model and B-COSFIRE filter response. Firstly, the inverted green channel image is enhanced by B-COSFIRE filter to strengthen bar-like vessel structures. Then the features are extracted by means of line operator in a multiresolution way, namely that each filtered image is down-sampled to cover a wider area, hence each sampled pixels can obtain not only the global but also local information. Then the final obtained features from three scales together along the depth direction are combined to train the SVM model. Finally, we use the classifier model to predict blood vessels. The proposed algorithm is evaluated on the public available fundus images datasets (DRIVE: Precision = 0.8657, Se = 0.7088, Sp = 0.9660 and ACC = 0.9900; STARE: Precision = 0.8782, Se = 0.6189, Sp = 0.9908 and ACC = 0.9494). The experiment results show that our proposed algorithm has effects on retinal vessels segmentation.
Courage, resistance and vulnerability in memory culture: Swedish Museum education and the representation of the Holocaust survivor at the turn of the twenty-first century
Authors: Tinning Katrine
Published: September 2022

This article provides a Swedish perspective on critical memory culture and the use of difficult history in museum education. It is based on a detailed study of the educational resource the Teacher’s Guide, published by the Swedish Museum of Cultural History in Lund named Kulturen in 2006 in connection with their permanent exhibition, To Survive. Voices from Ravensbrück. The Guide shows how women, imprisoned in the Ravensbrück concentration camp, found ways to resist their situation and overcome their victim position. It also relates to the role Sweden played in the rescue of the women from the camp. First, the article explicates the narrative structure of the guidebook and examines how it characterises the survivors as resistance heroines and presents their story as a story of courage. Then, the article relates the Teacher’s Guide to two contemporary phenomena in Sweden: a governmental educational campaign to raise young people’s awareness of the Holocaust and foster engagement in resistance to present neo-fascism and a historiographical debate taking issue with negative and difficult aspects of Sweden’s involvement in the Second World War. The Teacher’s Guide is discussed based on Aleida Assmann’s concept of self-critical memory culture, Judith Butler’s notion of vulnerability and the concept of difficult history in museum pedagogy. It is argued that by emphasising courage and neglecting vulnerability in its story of resistance, the Guide deprives the audience of the opportunity of responding adequately to the difficult history of surviving the Holocaust as a history of ambiguity. Ultimately, it is argued that the Guide constitutes a hindrance to the emergence of a self-critical memory culture on the Holocaust in Sweden.
A failed attempt to explain relative motion illusions via motion blur, and a new sparse version
Authors: Bach Michael
Published: September 2022

Visual patterns can evoke marked, even beautiful motion illusions even if they are static; eye movements in all likelihood serve as temporal modulators. This paper concentrates on Ouchi-type “relative” or “sliding” motion illusions. It outlines an eye-motion-evoked motion-blur hypothesis, which does not correctly predict the shift direction of maximal illusion. This failure led to a nearly new particularly simple stimulus: an arrangement of dashed lines that strongly evokes a relative motion illusion, the “orthogonal dotted lines sway.” The latter is well explained by motion integration.
Child Adoption among Igbo Christians in Nigeria: A “Paradox”?
Authors: Nnadi Fabian U , Uwaegbute Kingsley I
Published: September 2022

This article argues that the practice of child adoption among Igbo Christians of Nigeria is some kind of “paradox.” This is because, Igbo Christians reject and practice child adoption at the same time. This applies to Igbo Christians irrespective of denominations. Igbo cultural practices like the quest for children to partake in inheritance, the denial of participation in some traditional roles, the individualized nature of Igbo contemporary society, and Christian teaching on love contribute to this. The findings in this article challenge previous scholarship which claims that Igbo Christians do not practice Child adoption although they are sympathetic to it.
A mixed-methods examination of public attitudes toward vascularized composite allograft donation and transplantation
Authors: Gardiner Heather M , Davis Ellen E , Alolod Gerard P , Sarwer David B , Siminoff Laura A
Published: September 2022

Background:

This mixed-methods study examined the general public’s knowledge and attitudes about vascularized composite allografts. The availability of these anatomical gifts to treat individuals with severe disfiguring injuries relies largely on decisions made by family members. If vascularized composite allograft transplantation is to become more readily available, the knowledge and beliefs of the general public must be explored to ensure vascularized composite allograft donation approaches adequately support the donation decision-making process.

Methods:

We conducted six focus groups with 53 members of the general public, which were audio-recorded for accuracy and transcribed. Before each session, participants completed a brief survey assessing donation-related knowledge, attitudes, and beliefs. Analysis of qualitative data entailed the constant comparison method in the development and application of a schema for thematic coding. Descriptive statistics and Spearman’s rank coefficient were used in the analysis of the quantitative data.

Results:

Respondents were most knowledgeable about solid organ donation and least knowledgeable about vascularized composite allograft donation. Six major themes emerged: (1) strong initial reactions toward vascularized composite allografts, (2) limited knowledge of and reservations about vascularized composite allografts, (3) risk versus reward in receiving a vascularized composite allograft, (4) information needed to authorize vascularized composite allograft donation, (5) attitudes toward donation, and (6) mistrust of the organ donation system.

Conclusion:

The general public has low levels of knowledge and high levels of hesitation about vascularized composite allograft donation and transplantation. Education campaigns to familiarize the general public with vascularized composite allografts and specialized training for donation professionals to support informed family decision-making about vascularized composite allograft donation may address these issues.
Use of doxorubicin chemotherapy following debulking surgery in the treatment of a cat with mesenteric hemangiosarcoma
Authors: Simon Kerry L , Cook Matthew R , Husbands Brian D , Long Mackenzie E , Hokamp Jessica A , Helms Timothy H , Shive Heather R , Lumbrezer Johnson Sarah , Hostnik Eric , Selmic Laura E
Published: September 2022

Case summary

A 7-year-old male castrated domestic shorthair cat presented with a 5-day history of inappetence. A mid-abdominal mass was palpated and, on exploratory laparotomy, a cystic mass arising from the root of the mesentery was observed. The mass was drained, debulked and omentalized. Histopathologic examination and immunohistochemistry supported a diagnosis of hemangiosarcoma. Adjuvant doxorubicin was started and, prior to the third of five doses of doxorubicin, repeat abdominal ultrasound showed complete response of the primary tumor. Continued monitoring 240 days following histopathologic diagnosis revealed suspected metastasis to local lymph nodes, though the primary tumor remained absent on abdominal ultrasound. A second course of five doses of doxorubicin chemotherapy was completed. Serial abdominal ultrasounds demonstrated stable disease in the locoregional lymph nodes with no visible recurrence of the primary tumor. The cat presented 430 days following diagnosis with lethargy and inappetence. Abdominal ultrasound revealed suspected metastatic mesenteric and ileocolic lymphadenopathy, hepatic metastasis and peritoneal effusion, and the owner elected for humane euthanasia. Necropsy findings and negative immunohistochemical staining for lymphatic vessel endothelial receptor-1 were consistent with a metastatic mesenteric hemangiosarcoma.

Relevance and novel information

Hemangiosarcoma is an uncommon malignancy in cats, and few cases describing treatment have been reported. To our knowledge, this is the first report to describe the use of debulking surgery and adjuvant doxorubicin chemotherapy in the treatment of mesenteric hemangiosarcoma resulting in extended survival in a cat. Multimodal therapy can be considered for the management of cats with mesenteric hemangiosarcoma.
Who Are They and Where? Insights Into the Social and Spatial Dimensions of Imagined Audiences From a Mobile Diary Study of Twitter Users
Authors: Stoltenberg Daniela , Pfetsch Barbara , Keinert Alexa , Waldherr Annie
Published: September 2022

Social media users hardly know who is reading their posts, but they form ideas about their readership. Researchers have coined the term imagined audience for the social groups that actors imagine seeing their public communication. However, social groups are not the only aspect that requires imagination: In the potentially borderless online environment, the geographical scope and locations of one’s audience are also unknown. Furthermore, research has demonstrated that imagined audiences vary between people and situations, but what explains these variations is unclear. In this article, we address these two gaps—the geographical scope and predictors of imagined audiences—using data from a mobile experience sampling method study of 105 active Twitter users from Berlin, Germany. Our results show that respondents mostly think of a geographically broad audience, which is spread out across the country or even globally. The imagined geographical scope and social groups depend on both the communicator and the usage situation. While the audience’s social composition especially depends on tweet content and respondents’ sociodemographic characteristics, the geographical scope is best explained by respondents’ biography and personal mobility, including their experience of living in other countries and local residential duration.
Novice School Counselors’ Burnout Profiles and Professional Experiences: A Mixed-Methods Study
Authors: Bardhoshi Gerta , Um Byeolbee , Niles Jennifer , Li Huijuan , Han Eunae , Brown Margaux
Published: September 2022

This convergent mixed-methods study examined the distinct burnout profiles of novice school counselors and their respective professional experiences. A cluster analysis yielded a three-factor solution revealing unique burnout profiles. Qualitative analyses identified job-related challenges and resources impacting the work performance of novice school counselors. We provide recommendations for school counselor training.
Estimating Ideal Sleep Duration by Physical Fitness in South Korean Adults: A Correlational Epidemiological Study
Authors: Lee Jong Hyeon , Lee Jae Min , Jeong Hee Seong , So Wi-Young
Published: September 2022

This study aimed to verify the relationship between ideal sleep duration and physical fitness in South Korean adults and older adults. The secondary analysis data of 2,832 adults (19–64 years) and 629 older adults (65 years and above), obtained from the 2015 National Fitness Survey, were analyzed. Participants completed various physical fitness tests (grip strength, sit-ups, standing long jump, 50 m dash, sit-and-reach, and 20 m shuttle run in adults; grip strength, sit-up, sit-to-stand, sit-and-reach, back-scratch, one-leg standing test, and 6-minute walk in older adults) and were divided into four groups based on self-reported sleep duration. Group differences in physical fitness variables were analyzed with one-way analysis of variance, and Pearson’s correlation was used to verify the relationship between sleep duration and physical fitness; statistical significance was set at p < .05. In adult males, there was a positive correlation between explosive muscular strength (standing long jump) and sleep duration ( p = .046), whereas in adult females, there was a negative correlation between cardiopulmonary endurance (20 m shuttle run) and sleep duration ( p =.026). However, in older adults, there was no significant correlation between sleep duration and physical fitness ( p > .05). Further, across the sample, there were no significant group differences in physical fitness variables. A positive correlation exists between sleep duration and muscular strength in adult males and a negative correlation between sleep duration and cardiorespiratory endurance in adult females. Designing sleep and exercise programs based on these results may improve physical fitness among adults and older adults. Future studies that include controlled variables that affect physical fitness and sleep patterns are warranted.
Can Corruption Facilitate Industrial Structure Upgrade in China? The Moderating Role of Government-Business Relationships
Authors: Yao Fang , Zhao Kai , Xu Xiaoyu , Liu Wenfei
Published: September 2022

The literature on corruption is extensive. However, specific effects of corruption on industrial structure upgrade have received little attention in the context of China. Therefore, following the concept of organizational performance and social capital theory, a number of panel models are developed to explore how different institution domains (i.e., government’s willingness to reform, business ownership structure, and government-business collusion) moderate the effect size of corruption on upgrading the industrial structure in China. The results are generally robust after endogeneity corrections, and suggest that the effect size of corruption on the industrial structure upgrade is evidently moderated by willingness to reform and ownership structure, but government-business collusion does not appear to have a similar effect. These findings explain the variation in the corruption-performance link, and provide a novel perspective for policy makers and regulators to understand the evolutionary path of corruption within the process of economic transition in China. A local government must thoroughly understand the dynamics of an industrial structure upgrade and acquire competencies and knowledge about when the effect of corruption reaches its inflection point and how its downside can be alleviated by placing specific formal and informal institutional reforms.
Internal Control Systems and Performance of Emerging Market Firms: The Moderating Roles of Leadership Consistency and Quality
Authors: Hoai Tu Thanh , Nguyen Nguyen Phong
Published: September 2022

This study aims to investigate the potential interaction between leadership and the internal control structure and determine whether this interaction can benefit emerging market businesses by increasing the effectiveness of their internal controls. Drawing upon the cognitive consistency and expectancy theories, this study develops and tests a mediated moderation model to examine how leadership consistency and quality can be integrated to regulate the effectiveness of internal control systems toward enhancing firm performance. The partial least squares structural equation modeling (PLS-SEM) results from survey data from 206 Vietnamese firms indicated the following: (a) internal control effectiveness mediates the effect of the internal control structure on firm performance; (b) leadership consistency positively moderates the impact of the internal control structure on internal control effectiveness; and (c) the moderating effect of leadership consistency is strengthened with a higher level of leadership quality. These findings lead to several theoretical and practical implications.
Engaging With Objects and Feelings: The Making of Live Music Space in Shanghai’s Livehouses
Authors: Luo Mengyu , Xiao Jian , Zhong Wenyu
Published: September 2022

Livehouse is a small venue for live music performance, a term commonly used in the Asian context. This article adopts an insider’s perspective to look at the connections between livehouse and its audiences. Instead of treating spaces and objects as silent textures of live music experiences, we regard livehouse as an active site filled with ideas and feelings. The meaning of livehouse is made by audiences through both human and non-human agents and extends to the broader social and cultural context of Shanghai. By highlighting the power of things and networking in between, this article combines the affordance theory to illustrate the experiential dimensions and interpretive processes of livehouse audiences in Shanghai. Drawing on ethnographic data from 26 in-depth interviews and participant observation, we conclude the social, cultural, and emotional affordances of livehouses perceived through tangible and intangible objects and settings.
“A Beautiful Experience”: The Cultural Transitions of Latin American Minor League Baseball (MiLB) Players
Authors: Gentile Patrick C. , Arth Zachary W.
Published: September 2022

This article aims to understand how Latino Minor League Baseball (MiLB) players describe their cultural transitions to life in the United States (US) while pursuing baseball professionally. Moreover, through the lens of social identity theory (SIT), this article investigates how these players primarily identify themselves. To better understand the experiences these players have gone through to pursue their lifelong goals of being professional players, 24 current Latino MiLB players and one coach, who recently retired as a player, were interviewed. Interview questions asked about their early transitions, the main cultural differences between their home countries and the US, and how they identify themselves while in the US. It was concluded from the interviews that, while there were difficulties, the majority of their transitions were positive. It was also found that players primarily identify themselves in terms of personality traits and nationality.
Higher education and regional development of Shenzhen municipality in China’s greater bay area
Authors: Xie Xiujuan , Huang Qian , Jung Jisun
Published: September 2022

Shenzhen City in Southeast China has developed from a small fishing village into a modern metropolis since China adopted an open-door policy in 1978. In accordance with its national plan and strategy, China has been striving to develop its international Guangdong–Hong Kong–Macau Greater Bay Area (GBA). Owing to its rapidly developing economy, industries and innovative technologies, Shenzhen is an important city in the GBA. Shenzhen’s higher education (HE) is supposedly crucial for its advancement as an innovation hub. However, the HE in Shenzhen is reportedly not adept with the city’s economic development. Although some Chinese studies have focused on Shenzhen’s HE-related issues, such as integration of and co-operation with the GBA’s policies, not many international studies have assessed how universities can help to ensure overall regional development. Thus, in this study, using Shenzhen’s case in the GBA, we explore the roles of universities in regional development. We review several policy documents and literature based on the glonacal framework to collect relevant data in text and generated themes. The study findings address the critical roles of Shenzhen universities in regional development such as promoting research capacity, fostering international collaboration and upgrading the GBA’s HE sector.
Palliative care and its own identity, through an autoethnography: do you recognize these patterns?
Authors: Neto Isabel Galriça
Published: September 2022

Introduction:

After more than 25 years working in palliative care (PC) observing thousands of patients and family behaviors, I use my long experience and notes as a source of data for a qualitative research study. The aim is to identify frequent families’ behavior patterns in PC and better describe the culture in PC.

Methods:

This article is part of a larger project, using autoethnography as methodology, with the aim of helping doctors and interested health professionals better understand the culture and reality of PC. The focus is not the author but patients and families’ patterns of social behavior – the social context – within the end-of-life period and how to deal with these professionally. Confidentiality and privacy of patients’ data were guaranteed.

Results:

The vast number of treated cases, the regular observation and recording, and the continuous reflection and analysis over many years have led to these results. Due to editorial restrictions, in this article I only describe four of at least eight typical scenarios I have identified. Each is given a short title and I explore some of their inside-issues, integrating previous knowledge, research, and explanations, with practical suggestions on how to deal with them.

Significance:

As far as we know, these scenarios/patterns have never been described in this way. This work expands knowledge, innovates, and contributes to better describing PC culture. The final goal is to create a set of scripts that can be used to help clinicians quickly identify the clinical situation and how to deal with it in clinical practice. Reflecting on how patients and families frequently behave in PC can be very useful and then teach other professionals to better deal with these challenges.
Long-term conditions, multimorbidity and colorectal cancer risk in the UK Biobank cohort
Authors: Corcoran Neave ME , Mair Frances S , Nicholl Barbara , Macdonald Sara , Jani Bhautesh Dinesh
Published: September 2022

Purpose

Early identification of colorectal cancer (CRC) is an international priority. Multimorbidity (presence of ≥2 long-term conditions (LTCs)) is increasing and the relationship between CRC and LTCs is little-understood. This study explores the relationship between individual LTCs, multimorbidity and CRC incidence and mortality.

Methods

Longitudinal analysis of the UK Biobank cohort, participants recruited 2006–2010; N = 500,195; excluding previous CRC at baseline. Baseline data was linked with cancer/mortality registers. Demographic characteristics, lifestyle factors, 43 LTCs, CRC family history, non-CRC cancers, and multimorbidity count were recorded. Variable selection models identified candidate LTCs potentially predictive of CRC outcomes and Cox regression models tested for significance of associations between selected LTCs and outcomes.

Results

Participants’ age range: 37–73 (mean age 56.5; 54.5% female). CRC was diagnosed in 3669 (0.73%) participants, and 916 (0.18%) died from CRC during follow-up (median follow-up 7 years). CRC incidence was higher in the presence of heart failure (Hazard Ratio (HR) 1.96, 95% Confidence Interval (CI) 1.13–3.40), diabetes (HR 1.15, CI 1.01–1.32), glaucoma (HR 1.36, CI 1.06–1.74), male cancers (HR 1.44, CI 1.01–2.08). CRC mortality was higher in presence of epilepsy (HR 1.83, CI 1.03–3.26), diabetes (HR 1.32, CI 1.02–1.72), osteoporosis (HR 1.67, CI 1.12–2.58). No significant association was found between multimorbidity (≥2 LTCs) and CRC outcomes.

Conclusions

The associations of certain LTCs with CRC incidence and mortality has implications for clinical practice: presence of certain LTCs in patients presenting with CRC symptoms could trigger early investigation and diagnosis. Future research should explore causative mechanisms and patient perspectives.
Dabrafenib plus trametinib in patients with relapsed/refractoryBRAFV600E mutation–positive hairy cell leukemia
Authors: Kreitman Robert J. , Moreau Philippe , Ravandi Farhad , Hutchings Martin , Gazzah Anas , Michallet Anne-Sophie , Wainberg Zev A. , Stein Alexander , Dietrich Sascha , de Jonge Maja J. A. , Willenbacher Wolfgang , De Grève Jacques , Arons Evgeny , Ilankumaran Palanichamy , Burgess Paul , Gasal Eduard , Subbiah Vivek
Published: September 2022

BRAF V600E is the key oncogenic driver mutation in hairy cell leukemia (HCL). We report the efficacy and safety of dabrafenib plus trametinib in patients with relapsed/refractory BRAF V600E mutation–positive HCL. This open-label, phase 2 study enrolled patients with BRAF V600E mutation–positive HCL refractory to first-line treatment with a purine analog or relapsed after ≥2 prior lines of treatment. Patients received dabrafenib 150 mg twice daily plus trametinib 2 mg once daily until disease progression, unacceptable toxicity, or death. The primary endpoint was investigator-assessed objective response rate (ORR) per criteria adapted from National Comprehensive Cancer Network-Consensus Resolution guidelines. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Fifty-five patients with BRAF V600E mutation–positive HCL were enrolled. The investigator-assessed ORR was 89.0% (95% confidence interval, 77.8%-95.9%); 65.5% of patients had a complete response (without minimal residual disease [MRD]: 9.1% [negative immunohistochemistry of bone marrow {BM} biopsy], 12.7% [negative BM aspirate flow cytometry {FC}], 16.4% [negative immunohistochemistry and/or FC results]; with MRD, 49.1%), and 23.6% had a partial response. The 24-month DOR was 97.7% with 24-month PFS and OS rates of 94.4% and 94.5%, respectively. The most common treatment-related adverse events were pyrexia (58.2%), chills (47.3%), and hyperglycemia (40.0%). Dabrafenib plus trametinib demonstrated durable responses with a manageable safety profile consistent with previous observations in other indications and should be considered as a rituximab-free therapeutic option for patients with relapsed/refractory BRAF V600E mutation–positive HCL. This trial is registered at www.clinicaltrials.gov as #NCT02034110.
A biomarker assay to risk-stratify patients with symptoms of respiratory tract infection
Authors: Husain Shahid , Sage Andrew T. , del Sorbo Lorenzo , Cypel Marcelo , Martinu Tereza , Juvet Stephen C. , Mariscal Andrea , Wright Julie , Chao Bonnie T. , Shamandy Alaa A. , Mousavi S. Hossein , Ma Jin , Wang Bo , Valero Jerome , Liu Mingyao , Landes Megan , Balachandran Sharaniyaa , Hudson Kimberley , Ngai Michelle , Capuano Marialessia , Gelardi Maria , Lupia Enrico , Marinowic Daniel R. , Friedrich Frederico O. , Schmitz Carine R.R. , dos Santos Leticya S.M. , Barbe-Tuana Florencia M. , Jones Marcus H. , Kain Kevin C. , Mazzulli Tony , Sabbah Sam , Keshavjee Shaf
Published: September 2022

Background

Patients who present to an emergency department (ED) with respiratory symptoms are often conservatively triaged in favour of hospitalisation. We sought to determine if an inflammatory biomarker panel that identifies the host response better predicts hospitalisation in order to improve the precision of clinical decision making in the ED.

Methods

From April 2020 to March 2021, plasma samples of 641 patients with symptoms of respiratory illness were collected from EDs in an international multicentre study: Canada (n=310), Italy (n=131) and Brazil (n=200). Patients were followed prospectively for 28 days. Subgroup analysis was conducted on confirmed coronavirus disease 2019 (COVID-19) patients (n=245). An inflammatory profile was determined using a rapid, 50-min, biomarker panel (RALI-Dx (Rapid Acute Lung Injury Diagnostic)), which measures interleukin (IL)-6, IL-8, IL-10, soluble tumour necrosis factor receptor 1 (sTNFR1) and soluble triggering receptor expressed on myeloid cells 1 (sTREM1).

Results

RALI-Dx biomarkers were significantly elevated in patients who required hospitalisation across all three sites. A machine learning algorithm that was applied to predict hospitalisation using RALI-Dx biomarkers had a mean±sdarea under the receiver operating characteristic curve of 76±6% (Canada), 84±4% (Italy) and 86±3% (Brazil). Model performance was 82±3% for COVID-19 patients and 87±7% for patients with a confirmed pneumonia diagnosis.

Conclusions

The rapid diagnostic biomarker panel accurately identified the need for inpatient care in patients presenting with respiratory symptoms, including COVID-19. The RALI-Dx test is broadly and easily applicable across many jurisdictions, and represents an important diagnostic adjunct to advance ED decision-making protocols.
Transcriptomic clustering of critically ill COVID-19 patients
Authors: López-Martínez Cecilia , Martín-Vicente Paula , Gómez de Oña Juan , López-Alonso Inés , Gil-Peña Helena , Cuesta-Llavona Elías , Fernández-Rodríguez Margarita , Crespo Irene , Salgado del Riego Estefanía , Rodríguez-García Raquel , Parra Diego , Fernández Javier , Rodríguez-Carrio Javier , Jimeno-Demuth Francisco José , Dávalos Alberto , Chapado Luis A. , Coto Eliecer , Albaiceta Guillermo M. , Amado-Rodríguez Laura
Published: September 2022

Background

Infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may cause a severe disease, termed coronavirus disease 2019 (COVID-19), with significant mortality. Host responses to this infection, mainly in terms of systemic inflammation, have emerged as key pathogenetic mechanisms and their modulation has shown a mortality benefit.

Methods

In a cohort of 56 critically ill COVID-19 patients, peripheral blood transcriptomes were obtained at admission to an intensive care unit (ICU) and clustered using an unsupervised algorithm. Differences in gene expression, circulating microRNAs (c-miRNAs) and clinical data between clusters were assessed, and circulating cell populations estimated from sequencing data. A transcriptomic signature was defined and applied to an external cohort to validate the findings.

Results

We identified two transcriptomic clusters characterised by expression of either interferon-related or immune checkpoint genes, respectively. Steroids have cluster-specific effects, decreasing lymphocyte activation in the former but promoting B-cell activation in the latter. These profiles have different ICU outcomes, despite no major clinical differences at ICU admission. A transcriptomic signature was used to identify these clusters in two external validation cohorts (with 50 and 60 patients), yielding similar results.

Conclusions

These results reveal different underlying pathogenetic mechanisms and illustrate the potential of transcriptomics to identify patient endotypes in severe COVID-19 with the aim to ultimately personalise their therapies.
Narrative review to capture patients’ perceptions and opinions about non-response and response to biological therapy for severe asthma
Authors: Coleman Courtney , Khaleva Ekaterina , Rattu Anna , Frankemölle Betty , Nielsen Hanna , Roberts Graham , Williams Clare
Published: September 2022

Background

There are now many biological therapies to treat severe asthma. To assess which work best for which patient, we need to develop definitions of response. This narrative review aims to capture severe asthma patients’ perceptions about non-response and response to biological therapy.

Methods

Four bibliographic databases were searched from inception to September 2021. Grey literature was searched with the involvement of patient representatives. A thematic approach was used for synthesis. No qualitative studies specifically explore patients’ perspectives on response to biological therapy for severe asthma. Three papers and one published asthma patient interview were included. Relevant grey literature was included from online discussion forums, blogs and social media websites.

Results

Adult patients framed positive response to biological therapy in terms of reduced burden of disease and treatment. Both were multifaceted. Some patients experienced reduced benefit from biological therapy over time. There was a group of patients who described a limited response or non-response to biological therapy. This was framed within the context of continuing hospitalisation and oral corticosteroid treatment. The speed of onset of benefit was felt to be important by some.

Conclusions

Definitions of non-response and response need to be patient-centred, yet there is a complete lack of qualitative research focused on this topic. By combining relevant published and grey literature we have provided a description of adult patients’ perceptions of response to biological therapy in severe asthma. We now need to understand the views of children and adolescents with severe asthma and their carers, and diverse patient experiences in real-world settings.
Default mode and fronto-parietal network associations with IQ development across childhood in autism
Authors: Lee Joshua K. , Cho An Chuen Billy , Andrews Derek S. , Ozonoff Sally , Rogers Sally J. , Amaral David G. , Solomon Marjorie , Nordahl Christine Wu
Published: September 2022

Background

Intellectual disability affects approximately one third of individuals with autism spectrum disorder (autism). Yet, a major unresolved neurobiological question is what differentiates autistic individuals with and without intellectual disability. Intelligence quotients (IQs) are highly variable during childhood. We previously identified three subgroups of autistic children with different trajectories of intellectual development from early (2–3½ years) to middle childhood (9–12 years): (a) persistently high: individuals whose IQs remained in the normal range; (b) persistently low: individuals whose IQs remained in the range of intellectual disability (IQ < 70); and (c) changers: individuals whose IQs began in the range of intellectual disability but increased to the normal IQ range. The frontoparietal (FPN) and default mode (DMN) networks have established links to intellectual functioning. Here, we tested whether brain regions within the FPN and DMN differed volumetrically between these IQ trajectory groups in early childhood.

Methods

We conducted multivariate distance matrix regression to examine the brain regions within the FPN (11 regions x 2 hemispheres) and the DMN (12 regions x 2 hemispheres) in 48 persistently high (18 female), 108 persistently low (32 female), and 109 changers (39 female) using structural MRI acquired at baseline. FPN and DMN regions were defined using networks identified in Smith et al. (Proc Natl Acad Sci U S A 106:13040–5, 2009). IQ trajectory groups were defined by IQ measurements from up to three time points spanning early to middle childhood (mean age time 1: 3.2 years; time 2: 5.4 years; time 3: 11.3 years).

Results

The changers group exhibited volumetric differences in the DMN compared to both the persistently low and persistently high groups at time 1. However, the persistently high group did not differ from the persistently low group, suggesting that DMN structure may be an early predictor for change in IQ trajectory. In contrast, the persistently high group exhibited differences in the FPN compared to both the persistently low and changers groups, suggesting differences related more to concurrent IQ and the absence of intellectual disability.

Conclusions

Within autism, volumetric differences of brain regions within the DMN in early childhood may differentiate individuals with persistently low IQ from those with low IQ that improves through childhood. Structural differences in brain networks between these three IQ-based subgroups highlight distinct neural underpinnings of these autism sub-phenotypes.
European road transport policy assessment: a case study for Germany
Authors: Schulthoff Michael , Kaltschmitt Martin , Balzer Christoph , Wilbrand Karsten , Pomrehn Michael
Published: September 2022

In the EU, the transport sector is the only sector with increasing GHG emissions compared to 1990. While harmful emissions have decreased due to successful regulation, transport performance, fossil fuel consumption and thus CO2 emissions have continued to increase, despite powertrain efficiency improvements. Meaningful regulation, which can be market-based (MBI) and non-market-based (NMBI) by nature, is needed to meet climate targets. To understand the mechanisms, effects and limitations of MBI and NMBI, this study investigates and evaluates selected regulations in the German road transportation sector until 2020. Therefore, this study identifies, describes, and categorizes environmental policy instrument types. Based on this step, selected instruments in the road transportation sector are identified by their type and implemented policies are described and assessed. Furthermore, an assessment methodology is developed to evaluate and score target achievement, cost-efficiency and practical feasibility by linking the outcomes of instruments to its goals. Based on the findings of this assessment, conclusions and recommendations are developed and discussed. Finally, results and general properties of policies and their type of instruments are extrapolated, and general statements about market and non-market-based instruments in a broader context for future regulation and market designs are projected. The study discovers that fuel producers and distributors, vehicle manufacturers and sellers are directly regulated by non-marked-based instruments, despite the EU Emissions Trading Scheme (ETS). On the customer side, primarily market-based implemented except for low-emission zones, which are direct regulations. The study finds that holistic representation and realistic internalization of external effects in a market is complex and will never be complete. Still, sufficient representation can be enough to drive transformation in the transport sector. The CO2 price itself is not sufficiently representing the consequential costs of climate change induced by road transport, but it helps to make low-carbon alternatives economically viable. Overall, the study finds that most implemented regulations in the German road transport sector were successful in relation to their goals.
Comprehensive genomic characterization of cotton cationic amino acid transporter genes reveals that GhCAT10D regulates salt tolerance
Authors: Chen Xiugui , Wu Zhe , Yin Zujun , Zhang Yuexin , Rui Cun , Wang Jing , Malik Waqar Afzal , Lu Xuke , Wang Delong , Wang Junjuan , Guo Lixue , Wang Shuai , Zhao Lanjie , Zebinisso Qaraevna Bobokhonova , Chen Chao , Wang Xiuping , Ye Wuwei
Published: September 2022

Background

The cationic amino acid transporters (CAT) play indispensable roles in maintaining metabolic functions, such as synthesis of proteins and nitric oxide (NO), biosynthesis of polyamine, and flow of amino acids, by mediating the bidirectional transport of cationic amino acids in plant cells.

Results

In this study, we performed a genome-wide and comprehensive study of 79 CAT genes in four species of cotton. Localization of genes revealed that CAT genes reside on the plasma membrane. Seventy-nine CAT genes were grouped into 7 subfamilies by phylogenetic analysis. Structure analysis of genes showed that CAT genes from the same subgroup have similar genetic structure and exon number. RNA-seq and real-time PCR indicated that the expression of most GhCAT genes were induced by salt, drought, cold and heat stresses. Cis-elements analysis of GhCAT promoters showed that the GhCAT genes promoters mainly contained plant hormones responsive elements and abiotic stress elements, which indicated that GhCAT genes may play key roles in response to abiotic stress. Moreover, we also conducted gene interaction network of the GhCAT proteins. Silencing GhCAT10D expression decreased the resistance of cotton to salt stress because of a decrease in the accumulation of NO and proline.

Conclusion

Our results indicated that CAT genes might be related with salt tolerance in cotton and lay a foundation for further study on the regulation mechanism of CAT genes in cationic amino acids transporting and distribution responsing to abiotic stress.
Factors associated with EMS on-scene time and its regional difference in road traffic injuries: a population-based observational study
Authors: Ito Shingo , Asai Hideki , Kawai Yasuyuki , Suto Shunji , Ohta Sachiko , Fukushima Hidetada
Published: September 2022

Background

The outcome of road traffic injury (RTI) is determined by duration of prehospital time, patient’s demographics, and the type of injury and its mechanism. During the emergency medical service (EMS) prehospital time interval, on-scene time should be minimized for early treatment. This study aimed to examine the factors influencing on-scene EMS time among RTI patients.

Methods

We evaluated 19,141 cases of traffic trauma recorded between April 2014 and March 2020 in the EMS database of the Nara Wide Area Fire Department and the prehospital database of the emergency Medical Alliance for Total Coordination of Healthcare (e-MATCH). To examine the association of the number of EMS phone calls until hospital acceptance, age ≥65 years, high-risk injury, vital signs, holiday, and nighttime (0:00–8:00) with on-scene time, a generalized linear mixed model with random effects for four study regions was conducted.

Results

EMS phone calls were the biggest factor, accounting for 5.69 minutes per call, and high-risk injury accounted for an additional 2.78 minutes. Holiday, nighttime, and age ≥65 years were also associated with increased on-scene time, but there were no significant vital sign variables for on-scene time, except for the level of consciousness. Regional differences were also noted based on random effects, with a maximum difference of 2 minutes among regions.

Conclusions

The number of EMS phone calls until hospital acceptance was the most significant influencing factor in reducing on-scene time, and high-risk injury accounted for up to an additional 2.78 minutes. Considering these factors, including regional differences, can help improve the regional EMS policies and outcomes of RTI patients.