bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in survival of patients with non–small cell lung cancer in Japan: An interrupted time series study
Authors: Taniyama Yukari , Oze Isao , Koyanagi Yuriko N. , Kawakatsu Yukino , Ito Yuri , Matsuda Tomohiro , Matsuo Keitaro , Mitsudomi Tetsuya , Ito Hidemi
Published: November 2022

The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) gefitinib and erlotinib were approved for metastatic or relapsed non–small cell lung cancer (NSCLC) in Japan in 2002 and 2007, respectively. EGFR mutation testing was also approved in 2007. Although clinical trials showed efficacy in NSCLC patients harboring activating EGFR mutations, these effects have rarely been reported in real‐world practice. We evaluated changes in survival in NSCLC patients following introduction of these agents and EGFR mutation testing by extracting patients diagnosed with NSCLC from 1993 through 2011 from six prefectural population‐based cancer registries in Japan. Relative survival (RS) was calculated by sex, histological subtype, and cancer stage. We conducted interrupted time series analysis to assess survival changes following introduction of EGFR‐TKIs and EGFR mutation testing. 120,068 patients with NSCLC were analyzed. One‐ and three‐year RS gradually increased in overall NSCLC for men and women. For adenocarcinoma, among men, slopes of 1‐ and 3‐year RS increased steeply in patients diagnosed from 2007 through 2011; among women, significant level increases were seen in 1‐year RS in patients diagnosed in 2002 (4.55% [95% confidence interval: 1.76‐7.33]) and 2007 (3.40% [1.27‐5.52]). These significant level increases were particularly obvious in women with adenocarcinoma at an advanced stage. Our results suggest that recent improvements in survival in men and women with adenocarcinoma are due at least partly to introduction of EGFR‐TKIs into real‐world practice, and to prescription based on appropriate patient selection following introduction of EGFR mutation testing into real‐world practice in Japan.
Rac1 promotes the reprogramming of glucose metabolism and the growth of colon cancer cells through upregulating SOX9
Authors: Liang Jiaxin , Liu Qiang , Xia Longzheng , Lin Jinguan , Oyang Linda , Tan Shiming , Peng Qiu , Jiang Xianjie , Xu Xuemeng , Wu Nayiyuan , Tang Yanyan , Su Min , Luo Xia , Yang Yiqing , Liao Qianjin , Zhou Yujuan
Published: November 2022

Metabolic reprogramming is the survival rule of tumor cells, and tumor cells can meet their high metabolic requirements by changing the energy metabolism mode. Metabolic reprogramming of tumor cells is an important biochemical basis of tumor malignant phenotypes. Ras‐related C3 botulinum toxin substrate 1 (Rac1) is abnormally expressed in a variety of tumors and plays an important role in the proliferation, invasion, and migration of tumor cells. However, the role of Rac1 in tumor metabolic reprogramming is still unclear. Herein, we revealed that Rac1 was highly expressed in colon cancer tissues and cell lines. Rac1 promotes the proliferation, migration, and invasion of colon cancer cells by upregulating SOX9, which as a transcription factor can directly bind to the promoters of HK2 and G6PD genes and regulate their transcriptional activity. Rac1 upregulates the expression of SOX9 through the PI3K/AKT signaling pathway. Moreover, Rac1 can promote glycolysis and the activation of the pentose phosphate pathway in colon cancer cells by mediating the axis of SOX9/HK2/G6PD. These findings reveal novel regulatory axes involving Rac1/SOX9/HK2/G6PD in the development and progression of colon cancer, providing novel promising therapeutic targets.
The authoritarian trade‐off: A synthetic control analysis of development and social coercion in the Xinjiang Uyghur Autonomous Region
Authors: Peng Linan , Callais Justin T.
Published: November 2022

The Xinjiang Uyghur Autonomous Region (XUAR) has recently experienced a series of policies seeking economic development and intensive methods of social coercion. A unique leader, Chen Quanguo, brought these changes to the XUAR in 2016. This paper seeks to examine the effects of Chen's regime. We specifically examine three outcomes: GDP per capita, arrest rates, and spending on public security. Using the synthetic control method, we find that Chen's regime had no significant effect on the development. However, his policies led to much higher rates of arrest and larger spending on public security.
Antineoplastic chemotherapy and immunosuppression in liver transplant recipients: Squaring the circle?
Authors: Coupier Antoine , Gallien Yves , Boillot Olivier , Walter Thomas , Guillaud Olivier , Vallin Mélanie , Thimonier Elsa , Erard Domitille , Dumortier Jérôme
Published: November 2022

Background

Malignancies are a major cause of late death after liver transplantation (LT). In LT recipients presenting a malignancy, antineoplastic chemotherapy is central part of the therapeutic arsenal, but management of both immunosuppressive and antineoplastic chemotherapy can be very challenging. The aim of the present retrospective study was to describe a recent single center cohort of LT recipients treated with antineoplastic cytotoxic chemotherapy.

Methods

All LT recipients who received antineoplastic chemotherapy in our center between 2005 and 2021 were included.

Results

The study population included 72 antineoplastic chemotherapy courses in 69 patients. There was a majority of men (81.9%); median age at LT was 54.9 (range 1–68) and was 63.0 (18–79) at the diagnosis of malignancy. Lung carcinomas (23.6%), head and neck carcinomas (20.8%), lymphomas (16.7%), and recurrent hepatocellular carcinoma (HCC) (8.3%) were the most frequent malignancies. Neoadjuvant (30.6%), adjuvant (12.5%) or palliative (54.2%) chemotherapy was performed. Immunosuppressive regimen was modified from a calcineurin inhibitor (CNI)‐based to an everolimus‐based regimen (63.5% of CNI discontinuation). Median survival after diagnosis of malignancy was 22.5 months and 5‐year survival was 30.1%. Chemotherapy regimen was considered optimal in 81.9% of the cases. Multivariate analysis disclosed that non‐PTLD N+ stage malignancy (HR = 5.52 95%CI [1.40;21.69], p = .014), non‐PTLD M+ stage malignancy (HR = 10.55 95%CI [3.20;34.73], p = .0001), and suboptimal chemotherapy (HR = 2.73 95%CI [1.34;5.56], p = .005) were significantly associated with poorer prognosis. No rejection episode occurred during chemotherapy.

Conclusions

The present study is the first one focused on antineoplastic chemotherapy in LT recipients. Our results suggest that immunosuppressive drugs and antineoplastic chemotherapy can be managed satisfactorily in most cases but this needs confirmation from larger cohorts.
Risk of cognitive impairment in men with advanced prostate cancer treated with NHAs: A systematic review and network meta‐analysis
Authors: Huang Shi‐Wei , Chen Li‐Chin , Tseng Chi‐Shin , Chen Chung‐Hsin , Yuan Lun‐Hsiang , Shau Wen‐Yi , Pu Yeong‐Shiau
Published: November 2022

Novel hormonal agents (NHAs) have significantly improved outcomes in men with advanced prostate cancer. However, it remains unclear whether NHAs are associated with subsequent cognitive impairment. Thus, we sought to perform a network meta‐analysis to compare the risk of cognitive impairment across NHA types. Databases (PubMed, Embase, Scopus, and Web of Science), trial registries (Clinicaltrial.gov), the European Medicines Agency, and the US Food and Drug Administration drug safety reports were searched from inception through July 30, 2021. Eligible studies were clinical trials evaluating the risk of cognitive impairment between NHAs and placebo/standard care. Two independent investigators extracted the data and performed quality assessments using the Cochrane Risk of Bias Tool and ROBINS‐I. We estimated the risk ratios by the frequentist approach and calculated the ranking probabilities of all treatments with the surface under the cumulative ranking probabilities. The primary outcome and secondary outcome were odds ratio (OR) and incidence rate ratio of cognitive impairment, respectively. We identified 15 trials with 14,723 participants comparing HNAs with placebo/standard care. Treatments associated with cognitive impairment, from the most to the least, were enzalutamide (OR, 3.66; 95% confidence interval [CI], 2.84–4.73), apalutamide (OR, 1.76; 95% CI, 1.08–2.87), abiraterone acetate (OR, 1.64; 95% CI, 1.01–2.45), and darolutamide (OR, 1.11 95% CI, 0.51–2.39). After adjustment of treatment time duration, enzalutamide still had the highest risk of cognitive impairment with an incidence rate ratio of 2.17 (95% CI, 1.65–2.78). These findings suggest that NHAs, especially enzalutamide, may increase the risk of cognitive impairment compared with placebo/standard care.
Systematic review with meta‐analysis: Branched‐chain amino acid supplementation in liver disease
Authors: van Dijk Anne M. , Bruins Slot Alexandra S. , Portincasa Piero , Siegerink Sebastiaan N. , Chargi Najiba , Verstraete Carina J. R. , de Bruijne Joep , Vleggaar Frank P. , van Erpecum Karel J.
Published: November 2022

Background

Dietary supplementation with branched‐chain amino acids (BCAA) is often used in cirrhotic patients to improve nutritional status. We wanted to explore the evidence for BCAA supplementation in chronic liver disease.

Methods

We searched MEDLINE and EMBASE for studies with BCAA supplementation with the presence of a disease‐control group (placebo or no intervention) using search terms ‘liver cirrhosis’, ‘hepatocellular carcinoma’, ‘branched chain amino acids’ and relevant synonyms. Risk of bias was assessed using ROBINS‐I and RoB 2.0 tools. Meta‐analyses were performed with a random‐effects model. Results were reported following EQUATOR guidelines.

Results

Of 3378 studies screened by title and abstract, 54 were included (34 randomized controlled trials, 5 prospective case–control studies, 13 retrospective case–control studies: in total 2308 patients BCAA supplementation, 2876 disease‐controls). Risk of bias was high/serious for almost all studies. According to meta‐analyses, long‐term (at least 6 months) BCAA supplementation in cirrhotic patients significantly improved event‐free survival (p = .008; RR .61 95% CI .42–.88) and tended to improve overall survival (p = .05; RR .58 95% CI .34–1.00). Two retrospective studies suggested the beneficial effects during sorafenib for hepatocellular carcinoma. Available studies reported no beneficial effects or contradictory results of BCAA after other specific therapeutic interventions (resection or radiological interventions for hepatocellular carcinoma, liver transplantation, paracentesis or variceal ligation). No convincing beneficial effects of BCAA supplementation on liver function, nutritional status or quality of life were found. No study reported serious side effects of BCAA.

Conclusions

Prophylactic BCAA supplementation appears safe and might improve survival in cirrhotic patients.
Host condition and pathogen identity influence bacterial infection survival in the common eastern firefly,Photinus pyralis
Authors: Lower Sarah E. , Gilani Owais , Tuffy Madden J. , Patel Deeshani N. , Zhu Zhengkai , Chambers Moria C.
Published: November 2022

The degree to which host, pathogen, and environmental characteristics determine fitness outcomes in response to infection across the tree of life is a key question in ecoimmunology. Because infection experiments require large sample sizes and careful controls, studies have generally been limited to lab‐adapted organisms.

Photinus pyralisis a charismatic firefly that is abundant during its annual summer emergence in the Eastern United States. Here, we assess the importance of host condition, pathogen identity and dose, and pre‐infection environment on survival outcomes in response to bacterial infection in wild‐caught adult maleP. pyralis.

Although survival after sterile saline injection was not statistically different from survival of uninjected controls, survival kinetics support sterile saline injection as the most appropriate control.

Serratia marcescensandProvidencia rettgeriinfections increased mortality, especially at high doses. In contrast to fruit fly studies,Providencia sneebia, Pseudomonas aeruginosa,andEnterococcus faecalisinfections did not. Infection with higher doses ofP. rettgerihad an increased risk of death for fireflies caught later in the season than those captured earlier, but seasonality did not significantly interact with dose to impact mortality with any of the other bacterial species.

These results highlight the importance of considering host, pathogen, and environmental factors when investigating infection outcomes in wild‐caught, non‐model systems. The differences in survival between fireflies and fruit flies emphasise that further studies in a broad array of organisms are needed to explore the diversity of infection responses across the tree of life.
Monkeypox: A challenge for and to geographers
Authors: Brown Gavin
Published: November 2022

The World Health Organisation declared the 2022 Monkeypox outbreak a ‘Public Health Emergency of International Concern’, following the rapid spread of infections in non‐endemic countries. Unlike its usual epidemiology in Africa, most cases reported since May 2022 have been among gay, bisexual, and other men who have sex with men (GBMSM). This commentary provides an overview of the current Monkeypox outbreak and public health responses to it, drawing out their uneven geographies and the contribution geographers could make to understanding this. The empirical focus is on Monkeypox in England, but the challenges posed are relevant to the dynamics of the outbreak in the USA and Europe. The commentary concludes by challenging geographers to collaborate across sub‐disciplinary boundaries to undertake research that can understand and explain not only the specific dynamics of Monkeypox but also broader geographical aspects of GBMSM's lives that could underpin effective public health work with these populations.
Nitrogen fertilization value of compost and dried dung in soils with contrasting synthetic nitrogen fertilization histories
Authors: Langworthy Adam D. , Corkrey Ross , Rawnsley Richard P. , Raedts Pieter J. M. , Hills James L.
Published: November 2022

If the production of forage for dairy cattle is to become less reliant on synthetic nitrogen (N) fertilizers, there is need to better understand and account for the N contributed by on‐farm and imported organic amendments. A 254‐day aerobic soil incubation study (typical length of a growing season in many temperate dairying regions) quantified the inorganic (mineral) N supply from a commercial compost and dried bovine dung (i.e., on‐farm effluent solids). Amendments were incubated in soils with contrasting synthetic N fertilization histories (i.e., 70–100 vs. 350–400 kg N/ha per year) to evaluate if higher synthetic N fertilization histories would reduce the lag time that often exists between organic amendment application and significant release of inorganic N for plant uptake. This proposition was based on previous research, which showed greater soil inorganic N availability accelerating organic amendment decomposition. Our experiment did find that the release of inorganic N from evaluated organic amendments was greater in soils with higher synthetic N fertilization histories, but that this effect was not apparent until after the first 6‐months of this 9‐month experiment. Despite this finding, soils with contrasting synthetic N fertilization histories were not found to differ in their initial inorganic N content, nor microbial activity or other physiochemical properties known to affect N mineralization. Our study highlighted the long‐term vision needed when transitioning from synthetic N fertilizers to organic amendments, with most of the N present in the compost and dried dung remaining unavailable for forage production (i.e., remained bound in organic carbon‐based molecules).
Conceptual and practical challenges associated with understanding patient safety within community‐based mental health services
Authors: Averill Phoebe , Vincent Charles , Reen Gurpreet , Henderson Claire , Sevdalis Nick
Published: November 2022

Introduction

Patient safety problems stemming from healthcare delivery constitute a global public health concern and represent a pervasive barrier to improving care quality and clinical outcomes. However, evidence generation into safety in mental health care, particularly regarding community‐based mental health services, has long fallen behind that of physical health care, forming the focus of fewer research publications and developed largely in isolation from the wider improvement science discipline. We aimed to investigate the state of the field, along with key conceptual and empirical challenges to understanding patient safety in community‐based mental health care.

Methods

A narrative review surveyed the literature to appraise the conceptual obstacles to advancing the science of patient safety in community‐based mental health services. Sources were identified through a combination of a systematic search strategy and targeted searches of theoretical and empirical evidence from the fields of mental health care, patient safety and improvement science.

Results

Amongst available evidence, challenges in defining safety in the context of community mental health care, evaluating safety in long‐term care journeys and establishing what constitutes a ‘preventable’ safety problem, were identified. A dominant risk management approach to safety in mental health care, positioning service users as the origin of risk, has seemingly prevented a focus on proactive safety promotion, considering iatrogenic harm and latent system hazards.

Conclusion

We propose a wider conceptualization of safety and discuss the next steps for the integration and mobilization of disparate sources of ‘safety intelligence’, to advance how safety is conceived and addressed within community mental health care.

Patient and Public Contribution

This paper was part of a larger research project aimed at understanding and improving patient safety in community‐based mental health care. Although service users, carers and healthcare professionals were not involved as part of this narrative review, the views of these stakeholder groups were central to shaping the wider research project. For a qualitative interview and focus group study conducted alongside this review, interview topic guides were informed by this narrative analysis, designed jointly and piloted with a consultation group of service users and carers with experience of community‐based mental health services for working‐age adults, who advised on key questioning priorities.
Barriers and enabling factors in weight management of patients with nonalcoholic fatty liver disease: A qualitative study using the COM‐B model of behaviour
Authors: Gu Yunpeng , Zhou Run , Kong Tingting , Zhang Wei , Chen Yutong , Wang Chunmei , Shi Junping , Hu Yanli
Published: November 2022

Background

Nonalcoholic fatty liver disease (NAFLD) is a global public health problem. Lifestyle modifications aimed at promoting weight loss and weight maintenance remain the current first‐line treatments for NAFLD.

Objective

We aim to identify barriers and enabling factors in weight management among patients with NAFLD using the capability, opportunity, motivation, behaviour (COM‐B) model of behaviour.

Design

This study adopted a qualitative design using semistructured interviews analysed with content analysis and the COM‐B framework.

Setting and Participants

Interviews were conducted with 27 patients with NAFLD who experienced successful or unsuccessful weight reduction.

Results

Our study included 27 participants: 15 participants with successful weight loss (successful weight loss refers to a decrease in body weight ≥7% of the initial body weight for patients with NAFLD) and 12 participants with unsuccessful weight loss. Thirty‐five themes (19 barriers and 16 facilitators) were mapped onto the COM‐B model as barriers and facilitators to weight management among patients with NAFLD. The key barriers were lack of time and energy, lack of awareness of weight, lack of attention to NAFLD, treating food as a reward or compensation and social entertainment. The key facilitators were having basic weight loss knowledge and skills, strong motivation, attention to NAFLD, unsuccessful weight loss experiences and positive feedback from phased success.

Conclusion

In addition to identifying factors consistent with existing studies, this study identified factors that influence weight management in NAFLD patients, such as basic weight loss skills and rational thinking before weight loss, which were not previously reported. This has clinical implications for clinical healthcare providers and health management services for the improvement of education and support regarding lifestyle improvement and weight management in patients with NAFLD.

Patient or Public Contribution

We recruited potential participants from the Bariatric Clinic, Hepatology Clinic and Physical Examination Center of hospitals between March 2021 and October 2021. Twenty‐seven patients with NAFLD who had successful or unsuccessful weight loss experiences participated in the study and responded to questions on weight management.
Thermal transitions and microstructure of starch‐apple pomace‐based systems
Authors: Rocha Parra Andrés F. , Barrera Gabriela N. , Ribotta Pablo D. , Ferrero Cristina
Published: November 2022

Apple pomace (AP) is the by‐product obtained after juice extraction. It is a potential ingredient for the fibre enrichment of foods. In the present work, AP was combined in gluten free‐mixtures with cassava starch (CS), rice flour (RF), egg white (EW) and sucrose (SR) to analyse its effect on thermal transitions of starch and the batter and bread crumb microstructures. Model systems with all or part of the main ingredients (CS:RF:AP:EW:SR in 4:4:1:1:1 proportions) and a batter formulation with AP were prepared by dry mixing and then dispersing the solids in water. CLSM allowed observing the distribution of egg proteins, AP and RF particles and CS granules. The batter enriched with AP exhibited higher apparent viscosities and dilatant behaviour. Thermal transitions were analysed by DSC. Endotherms ranged between 57 and 97°C. Gluten‐free bread microstructure was analysed by SEM. A more irregular and compact crumb structure was observed when AP was used, with the air cell walls constituted by gelatinized starch granules and AP particles interpenetrating them. By measuring the firmness of crumb along storage, it could be concluded that amylopectin retrogradation was partially inhibited by the presence of AP in model systems but in bread, this inhibiting effect was not evident.
Ladder of competencies for education middle managers in England
Authors: Corbett Stephen
Published: November 2022

Utilising new empirical research this study adapts an existing literature‐based competency framework into a hierarchy of competencies needed for education middle managers in England to be effective in their role. The study involved a national survey (n = 164) of further education middle managers and is the first quantitative study investigating the role since 2002. The original contribution of the study is the development of a new ladder of competencies for education middle managers which outlines a suggested ordering of competency development with due consideration to prior training and qualifications. This can enable an improved approach to recruitment, selection and development of education middle managers. The paper presents parameters for consideration when developing competency frameworks for roles more widely which include: prior training, experience, expectations, and challenges of the post‐holder as well as the external working environment. It highlights the value of such considerations and demonstrates the importance in paying due regard to them.
Segmentación legal del trabajo en China, la India, Malasia y Viet Nam
Authors: COONEY Sean
Published: November 2022

Siguiendo el marco de Dingeldey et al. (2021), pero con un enfoque cualitativo, se analiza la segmentación legal del trabajo en China, la India, Malasia y Viet Nam, prestando atención a los niveles de exclusión y a las jerarquías de protección otorgada. El autor observa varios factores que diferencian a estos países de los del Norte y que determinan sus mercados de trabajo: el tamaño relativo de la población activa que opera fuera de la cobertura efectiva de la reglamentación laboral; la terminología jurídica, de difícil traducción a los idiomas occidentales; y la historia jurídica, especialmente en lo que respecta al desajuste entre los marcos jurídicos y el mercado laboral resultante del colonialismo.
Contemporary updates on ventricular arrhythmias: from mechanisms to management
Authors: Bhaskaran Ashwin , De Silva Kasun , Kumar Saurabh
Published: November 2022

Ventricular arrhythmias (VAs) are a group of heart rhythm disorders that can be life‐threatening and cause significant morbidity. VA in the presence of structural heart disease (SHD) has distinct prognostic implications and requires a comprehensive and multifaceted approach for investigation and management. Early specialist referral should be considered for all patients with VA. Particular urgency is recommended in patients with syncope, nonsustained/sustained VA on Holter monitor and SHD on cardiac imaging because of the heightened risk of sudden cardiac death. Comprehensive phenotyping is recommended for most patients with VA, encompassing noninvasive cardiac functional testing, multimodality imaging and genetic testing in select circumstances. Management of idiopathic VA is guided heavily by symptom burden and the presence of ventricular systolic impairment. In SHD, guideline‐directed heart failure therapy and device implantation are critical considerations. Whilst commonly used and well‐established, antiarrhythmic drugs can be hampered by toxicity and failure of adequate arrhythmia control. Catheter ablation is increasingly being considered a feasible first‐line alternative to medical therapy, where outcomes are influenced by disease aetiology and scar burden in SHD. Catheter ablation is associated with reduced arrhythmia recurrence and burden and improved quality of life at follow‐up.
Gene targeting as a therapeutic avenue in diseases mediated by the complement alternative pathway
Authors: Dreismann Anna K , Hallam Thomas M , Tam Lawrence CS , Nguyen Calvin V , Hughes Jane P , Ellis Scott , Harris Claire L
Published: November 2022

The complement alternative pathway (AP) is implicated in numerous diseases affecting many organs, ranging from the rare hematological disease paroxysmal nocturnal hemoglobinuria (PNH), to the common blinding disease age‐related macular degeneration (AMD). Critically, the AP amplifies any activating trigger driving a downstream inflammatory response; thus, components of the pathway have become targets for drugs of varying modality. Recent validation from clinical trials using drug modalities such as inhibitory antibodies has paved the path for gene targeting of the AP or downstream effectors. Gene targeting in the complement field currently focuses on supplementation or suppression of complement regulators in AMD and PNH, largely because the eye and liver are highly amenable to drug delivery through local (eye) or systemic (liver) routes. Targeting the liver could facilitate treatment of numerous diseases as this organ generates most of the systemic complement pool. This review explains key concepts of RNA and DNA targeting and discusses assets in clinical development for the treatment of diseases driven by the alternative pathway, including the RNA‐targeting therapeutics ALN‐CC5, ARO‐C3, and IONIS‐FB‐LRX, and the gene therapies GT005 and HMR59. These therapies are but the spearhead of potential drug candidates that might revolutionize the field in coming years.
Unraveling the electric field effect on the grain‐boundary migration in alumina through phase field modeling
Authors: Liang Shuibao , Zhang Xin‐Ping
Published: November 2022

It is experimentally demonstrated that the electric field drives the grain‐boundary (GB) migration in ceramics, but this has not been interpreted mechanistically. This work develops a phase field model to study the GB migration in alumina (Al2O3) and validate through the comparison with previous experiments. Results show that the GBs move to the small grain domain. Under an electric field in the positive bias direction, GB migration is enhanced, whereas the migration to the small grain domain is inhibited under the electric field in the negative bias direction. The enhancement or inhibition effect becomes more pronounced with increasing the electric field. The high negative bias induces decrease in the GB migration velocity even with the migration direction altering. It is revealed that GB migrations are dominated by the competitive effect between the curvature and electric field driving forces, and an analytical expression of the critical electric field is derived.
Optical characterization of boron carbide powders synthesized with varying B‐to‐C ratios
Authors: Brown‐Shaklee Harlan J. , Neuman Eric W. , Fahrenholtz William G. , Hilmas Gregory E.
Published: November 2022

Boron carbide powders were synthesized from elemental powders and studied using X‐ray diffraction (XRD) and UV–visible diffuse reflectance, Raman, and diffuse reflectance IR spectroscopies. Following reaction at 1400°C for 6 h, synthesized powders exhibited possible faulting as suggested by XRD patterns. B3C, B4.3C, and B5C powders contained graphitic carbon whereas the boron carbides with higher B/C ratios contained no residual carbon, suggesting that the carbon rich phase boundary is likely temperature dependent. Analysis by Raman and IR spectroscopy suggested that Raman spectra are influenced by excitation frequency due to resonance. We suggest that measurement of boron carbides with resonant Raman lifts the selection rules to allow measurement of Raman silent modes that are present in the IR spectra. Optical reflectance of the boron carbide powders revealed that the B/C ratio governed the indirect and direct optical band gaps of the faulted powders. B3C and B4.3C powders were light gray in spite of the presence of the carbon, whereas B5C, B6.5C, B10C, and B12C were gray, green, brown, and dark brown, respectively. Increasing carbon content increased the optical indirect band gap from 1.3 eV for B12C to 3.2 eV for B3C, causing the observed color changes.
Experiences of early‐career nurses working in specialist adolescent/young adult cancer units: A narrative inquiry
Authors: Cable Maria , Watts Tessa , Reagon Carly , Kelly Daniel
Published: November 2022

Aim

To explore the experiences of early‐career registered nurses working in specialist adolescent/young adult cancer units.

Design

Narrative Inquiry.

Methods

A purposive sample of nine early‐career registered nurses from six specialist adolescent/young adult cancer units in the United Kingdom participated in online in‐depth narrative conversations between October 2020 and January 2021. Data were analysed thematically using Clandinin and Connelly's (2000) metaphorical three‐dimensional narrative inquiry approach focussed on commonplaces of temporality, sociality and place.

Results

The intensity and complexity of the nursing work associated with young patients and their families, over protracted periods, impacted the nurses personally and professionally. The similarity of age between patients and nurses was shown as having benefits as well as posing risks. The complexity of four types of nursing labour was highlighted: emotional, cognitive, physical and organizational providing justification for the provision of specialist training and support.

Conclusion

This study presents unique insights into the complex work of early‐career nurses in specialist units that reveal challenges in caring for the distinct needs of this cancer patient population.

Impact Statement

Better understanding of the experience of adolescent/young adult nursing work is revealed. Nurse managers could use these findings to consider the level of expertise on cancer units and ensure a spread of ages and experience. Managers and funders should also consider the clinical supervision and well‐being needs of nurses so that they can thrive in these unique environments. Educators could use findings to develop curricula and reinforce messages of self‐care, reflection and boundary management. The findings of this study may be transferable to other areas where early‐career nurses care for younger age groups.

Public and Patient Engagement and Involvement in Research Statement

No patient or public contribution was requested or required as this research wanted to examine nurses' experiences and not those of patients or the public.
Screening by high‐throughput sequencing for pathogenic variants in cystic fibrosis: Benefit of introducing personalized therapies
Authors: de Melo Ana Cristina Vieira , de Souza Karla Simone Costa , da Silva Heglayne Pereira Vital , Maia Jussara Melo de Cerqueira , Dantas Vera Maria , Bezerra João Felipe , de Rezende Adriana Augusto
Published: November 2022

This short report documented cystic fibrosis transmembrane conductance regulator (CFTR) variants in 37 patients with cystic fibrosis (CF) in the Rio Grande do Norte region of Northeast Brazil. The high‐throughput sequencing technology (HTS) genetic testing provided a definitive molecular diagnosis in 31 patients (83.8%). Among them, 25 patients' carriers of the c.1521_1523delCTT variant, categorized as a class 2 mutation, can be currently treated with CFTR modulator drugs. Five children aged 2–5 years could benefit from double lumacaftor/ivacaftor therapy, and 20 patients aged >6 years could be treated with the triple‐combination elexacaftor/tezacaftor/ivacaftor therapy. Thus, the identification of pathogenic variants associated with the development of this disease allows for the introduction of therapy with CFTR modulators that favour better patient management.
Modeling the impact of spray drying conditions on some Maillard reaction indicators in nano‐filtered whey
Authors: Gómez‐Narváez Fáver , Díaz‐Osorio Alejandra , Gómez‐Narváez Santiago , Simpson Ricardo , Contreras‐Calderón José
Published: November 2022

The objective of this study was to develop a mathematical model to predict the loss of available lysine and the formation of Maillard reaction (MR) compounds in sweet whey during spray drying process. The heat damage and other spray drying process‐related variables were estimated with the compartment model coupled to the drying kinetics of droplets. The model was adequate to determine the outlet temperature of air and the final moisture content of the product. The model predicted available lysine losses like those found experimentally. However, the model predicted a higher furosine concentration than that found experimentally. The browning index exhibited no significant increase for experimental and calculated results during the spray drying, possibly because the MR did not reach the final stages. The model showed to be comparable to those reported in the literature, with the advantages of being computationally less time‐consuming and providing confidence intervals for the response variables.

Practical applications

This work presents the integration of several mathematical models to predict the loss of available lysine and the formation of some heat damage indicators during the spray drying of whey. The model contributes to the understanding of relevant variables—such as residence time distribution, global heat transfer coefficient of the dryer, thermal properties of the drying media, glass transition temperature, drying kinetics, drying air inlet, and outlet temperature among others—on the loss of food quality regarding the thermal process. This information could help the decision‐making process that can lead to the optimization of spray drying to obtain food with minimal thermal damage and therefore the maximum amount of available nutrient content.
Synchondrosis fusion contributes to the progression of postnatal craniofacial dysmorphology in syndromic craniosynostosis
Authors: Hoshino Yukiko , Takechi Masaki , Moazen Mehran , Steacy Miranda , Koyabu Daisuke , Furutera Toshiko , Ninomiya Youichirou , Nuri Takashi , Pauws Erwin , Iseki Sachiko
Published: November 2022

Syndromic craniosynostosis (CS) patients exhibit early, bony fusion of calvarial sutures and cranial synchondroses, resulting in craniofacial dysmorphology. In this study, we chronologically evaluated skull morphology change after abnormal fusion of the sutures and synchondroses in mouse models of syndromic CS for further understanding of the disease. We found fusion of the inter‐sphenoid synchondrosis (ISS) in Apert syndrome model mice (Fgfr2S252W/+) around 3 weeks old as seen in Crouzon syndrome model mice (Fgfr2cC342Y/+). We then examined ontogenic trajectories of CS mouse models after 3 weeks of age using geometric morphometrics analyses. Antero‐ventral growth of the face was affected in Fgfr2S252W/+ and Fgfr2cC342Y/+ mice, while Saethre–Chotzen syndrome model mice (Twist1+/−) did not show the ISS fusion and exhibited a similar growth pattern to that of control littermates. Further analysis revealed that the coronal suture synostosis in the CS mouse models induces only the brachycephalic phenotype as a shared morphological feature. Although previous studies suggest that the fusion of the facial sutures during neonatal period is associated with midface hypoplasia, the present study suggests that the progressive postnatal fusion of the cranial synchondrosis also contributes to craniofacial dysmorphology in mouse models of syndromic CS. These morphological trajectories increase our understanding of the progression of syndromic CS skull growth.
Evaluation of plasma zonulin level and its relationship with inflammatory cytokines in patients with vitiligo
Authors: Arslan Selami , Altunisik Nihal , Turkmen Dursun , Uremis Muhammed M. , Sener Serpil , Turkoz Yusuf
Published: November 2022

Background

It has been proven that there is an increase in intestinal permeability in some autoimmune diseases. In our study, we purposed to assess intestinal permeability in vitiligo disease by looking at zonulin levels. At the same time, we aimed to examine the correlation of inflammatory cytokines and lipopolysaccharide (LPS) levels with zonulin.

Methods

Forty‐one patients and 41 healthy participants were involved in our study. Blood samples were taken from all patients and controls, and the levels of zonulin, tumor necrosis factor (TNF)‐α, interleukin (IL)‐6 and LPS were examined.

Results

The mean of zonulin in the patient group was found to be statistically higher than the control group (p < 0.05). A positive correlation was found between zonulin level and IL‐6, TNF‐α, and LPS levels (p < 0.05). TNF‐α and LPS levels in the vitiligo group were significantly higher than in the control group, but there was no such significance in terms of IL‐6 levels.

Conclusion

We think that serum zonulin level increases and intestinal permeability increases in vitiligo disease.
Associations between social network characteristics and sexual minority disclosure concern among Black men who have sex with men living with and without HIV
Authors: Eschliman Evan L. , Poku Ohemaa B. , Winiker Abigail K. , Latkin Carl A. , Tobin Karin E.
Published: November 2022

In addition to the pervasive anti‐Black racism faced by Black people in the United States, Black men who have sex with men (BMSM) face sexual minority stigma and, among BMSM living with HIV, HIV‐related stigma. These multilevel social forces shape social networks, which are important sources of resources, support, and behavior regulation. This study quantitatively examined the relationship between social network characteristics and sexual minority stigma (e.g., homophobia, biphobia), assessed by reported concerns around disclosing one's sexual minority status, among BMSM in Baltimore, Maryland in 2014 (N = 336). A majority of participants (63.7%) reported experiencing medium or high levels of sexual minority disclosure concern. In a multiple linear regression model, participants with higher sexual minority disclosure concerns reported lower network density and fewer good friends who are gay or bisexual men. Stratifying the same multiple linear regression model by HIV status supports the importance of an intersectional understanding of sexual minority and HIV‐related stigma. These findings can help health‐related programs address the complex relationships between sexual minority stigma, social networks, and HIV status within this multiply‐marginalized and high‐priority population.
LINC01608 activated by YY1 facilitate hepatocellular carcinoma progression by modulating the EGFR/ERK axis
Authors: Han Mengzhen , Liu Furong , Li Xinxin , Zhang Hongwei , Pan Yonglong , Liu Yachong , Zhu He , Liang Huifang , Chen Xiaoping , Liao Zhibin , Zhang Zhanguo , Zhang Bixiang
Published: November 2022

Background

Long non‐coding RNAs (LncRNAs) have been demonstrated to associate with a variety of cancers. However, the mechanisms of LncRNAs in hepatocellular carcinoma (HCC) progression are still not fully clarified.

Methods

LINC01608 expression level in HCC and adjacent normal tissues was detected by real‐time‐quantitively PCR (RT‐qPCR) in clinical samples and in situ hybridization (ISH) in tissue microarray. Several functional assays were performed to determine the biological effects of LINC01608 in HCC cells in vitro, while subcutaneous xenograft models and lung metastasis models in nude mice and immunohistochemistry (IHC) results showed the role of LINC01608 in HCC progression in vivo. The combination of LINC01608 with miR‐875‐5p and target genes was elucidated by dual‐luciferase report assays, RNA immunoprecipitation (RIP) assays and fluorescence in situ hybridization (FISH) assays. Finally, bioinformatics analysis and chromatin immunoprecipitation (CHIP) were performed to investigate the mechanism of Yin Yang‐1 (YY1) regulating LINC01608 transcription.

Results

LINC01608 was overexpressed in HCC tissues, and high LINC01608 expression predicted poor overall survival (OS) and disease‐free survival (DFS) in HCC patients. LINC01608 could promote HCC cell proliferation, migration, invasion and epithelial‐mesenchymal transition (EMT) in vitro and in vivo. Furthermore, we demonstrated that LINC01608 could sponge to miR‐875‐5p and activate the EGFR/ERK pathway. Moreover, we identified transcriptional factor YY1 could bind to the promoter of LINC01608 and induce its transcription.

Conclusion

LINC01608 could serve as a promising prognostic biomarker of HCC. YY1‐activated LINC01608 could promote HCC progression by associating with miR‐875‐5p to induce the EGFR/ERK signalling pathway. This discovery might provide therapeutic strategies for HCC.
Lentiviral overexpression of VEGFC in transplanted MSCs leads to resolution of swelling in a mouse tail lymphedema model
Authors: Michalaki Eleftheria , Rudd Josephine M. , Liebman Lauren , Wadhwani Rahul , Wood Levi B. , Willett Nick J. , Dixon J. Brandon
Published: November 2022

Background

Dysfunction of the lymphatic system following injury, disease, or cancer treatment can lead to lymphedema, a debilitating condition with no cure. Despite the various physical therapy and surgical options available, most treatments are palliative and fail to address the underlying lymphatic vascular insufficiency driving lymphedema progression. Stem cell therapy provides a promising alternative in the treatment of various chronic diseases with a wide range of therapeutic effects that reduce inflammation, fibrosis, and oxidative stress, while promoting lymphatic vessel (LV) regeneration. Specifically, stem cell transplantation is suggested to promote LV restoration, rebuild lymphatic circulation, and thus potentially be utilized towards an effective lymphedema treatment. In addition to stem cells, studies have proposed the administration of vascular endothelial growth factor C (VEGFC) to promote lymphangiogenesis and decrease swelling in lymphedema.

Aims

Here, we seek to combine the benefits of stem cell therapy, which provides a cellular therapeutic approach that can respond to the tissue environment, and VEGFC administration to restore lymphatic drainage.

Materials & Methods

Specifically, we engineered mesenchymal stem cells (MSCs) to overexpress VEGFC using a lentiviral vector (hVEGFC MSC) and investigated their therapeutic efficacy in improving LV function and tissue swelling using near infrared (NIR) imaging, and lymphatic regeneration in a single LV ligation mouse tail lymphedema model.

Results

First, we showed that overexpression of VEGFC using lentiviral transduction led to an increase in VEGFC protein synthesis in vitro. Then, we demonstrated hVEGFC MSC administration post‐injury significantly increased the lymphatic contraction frequency 14‐, 21‐, and 28‐days post‐surgery compared to the control animals (MSC administration) in vivo, while also reducing tail swelling 28‐days post‐surgery compared to controls.

Conclusion

Our results suggest a therapeutic potential of hVEGFC MSC in alleviating the lymphatic dysfunction observed during lymphedema progression after secondary injury and could provide a promising approach to enhancing autologous cell therapy for treating lymphedema.
Undergraduate paramedicine students' experiences of feedback during clinical placement on‐road: A scoping review
Authors: Carroll Amy G. , Peddle Monica R. , Malik Gulzar
Published: November 2022

Feedback on performance enhances student confidence and clinical skills and promotes safe clinical practice. Experiences of feedback are well documented across many health disciplines; however, less is known about paramedicine students' experiences of feedback on‐road in an emergency ambulance. The aim of this scoping review was to identify what is known about paramedicine students' experiences of feedback during clinical placement on‐road in an emergency ambulance. A review of studies between 2000 and 2021 was undertaken, guided by the Joanna Briggs Institute Methodology for JBI Scoping Reviews and reported using the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) Extension for Scoping Reviews. Databases included CINAHL, EMBASE, EBSCO, MEDLINE, Web of Science, Cochrane, ERIC (ProQuest), ProQuest (Nursing and Allied Health), Trove, and Open Accessd Theses and Dissertations. Three studies were identified. Feedback is valued by paramedicine students; however, it can be personal and destructive in nature. Paramedics are enthusiastic and supportive and provide clear feedback. Paramedics face challenges supervising students and may lack preparation to provide feedback. There is limited evidence on paramedicine students’ experiences of feedback during clinical placement. Further exploration is needed to gain further understanding.