bluuebunny/crossref_metadata_2025 huggingface dataset:
Multivariate versus univariate spectrum analysis of dentine sialophosphoprotein (DSPP) for root resorption prediction: a clinical trial
Authors: Mohd Zain Mohd Norzaliman , Md Yusof Zalhan , Basri Katrul Nadia , Yazid Farinawati , Teh Yong Xian , Ashari Asma , Zainal Ariffin Shahrul Hisham , Megat Abdul Wahab Rohaya
Published: April 2022

Background

A force applied during orthodontic treatment induces inflammation to root area and lead to root resorption known as orthodontically induced inflammatory root resorption (OIIRR). Dentine sialophosphoprotein (DSPP) is one of the most abundant non-collagenous proteins in dentine that was released into gingival crevicular fluid (GCF) during OIIRR. The aim of this research is to compare DSPP detection using the univariate and multivariate analysis in predicting classification level of root resorption.

Methods

The subjects for this study consisted of 30 patients in 3 group classified as normal, mild, and severe groups of OIIRR. The GCF samples were taken from upper permanent central incisors in the normal and mild group while the upper primary second molars in the severe group. The DSPP qualitative detection limit was determined by analyzing the whole absorption spectrum utilizing multivariate analysis embedded with different preprocessing method. The multivariate analysis represents the multi-wavelength spectrum while univariate analyzes the absorption of a single wavelength.

Results

The results showed that the multivariate analysis technique using partial least square-discriminate analysis (PLS-DA) with the preprocess method has successfully improved in classification prediction for the normal and mild group at 0.88 percent accuracy. The multivariate using PLS-DA algorithm with Mean Center preprocess method was able to predict normal and mild tooth resorption classes better than the univariate analysis. The classification parameters have improved in term of the specificity, precision and accuracy.

Conclusion

Therefore, the multivariate analysis helps to predict an early detection of tooth resorption complimenting the sensitivity of the univariate analysis.

Trial registration NCT 05077878 (14/10/2021).
Assessing demand for doctoral-prepared PA faculty: a five-year longitudinal study
Authors: Kayingo Gerald , Kibe Lucy , Venzon Aldreen , Gordes Karen L. , Cawley James F.
Published: April 2022

Purpose

Many health profession programs have transitioned to doctoral credentials. While a master’s degree is the terminal degree for the physician assistant (PA) profession, there is increasing discussion regarding the doctoral degree as the PA terminal credential in US higher education.This study examines trends, demand and economic opportunities for doctoral prepared PA faculty; specifically, assessing to what extent PA faculty employers prefer doctoral credentials.

Methodology

This longitudinal retrospective observational study assessed commonly required/preferred academic credentials in PA faculty job postings. Data from 2014 to 2020 was obtained from the labor analytics firm Burning Glass Technologies (BGT) and other academic job search engines. Data on current PA faculty and program directors were obtained from Physician Assistant Education Association (PAEA) survey reports. Wage gap analysis was performed to gain additional insight for the supply and demand of PA educators with a doctoral degree.

Results

Of the 612 unique job ads posted from 232 PA programs between 2014 and 2020, approximately 38.9% (238) stated a preference or requirement for a doctoral degree. Nearly half of the postings for program directors and leadership positions preferred candidates with doctorates. There was a correlation between tenure eligibility positions (20.1%) and preference/requirement for doctoral credentials. PAEA survey data (2014–2019) revealed approximately 24% PA faculty and 45–48% of program directors held a doctoral degree with Doctor of Philosophy (PhD) as the most frequently held doctorate. No significant difference existed in wages for faculty with or without doctoral degree.

Conclusions

Based on a national sample of PA program job ads, there is a preference for doctoral-prepared PA educators and the demand for these candidates is greater than market supply. Our analysis has implications for individual faculty career planning, employers and the PA profession as it debates transition to a terminal doctoral credential. Further studies should assess the impact of doctoral credentials on PA education by examining measurable outcomes.
Engaging with EPIO, a digital pain self-management program: a qualitative study
Authors: Bostrøm Katrine , Varsi Cecilie , Eide Hilde , Børøsund Elin , Kristjansdottir Ólöf B. , Schreurs Karlein M. G. , Waxenberg Lori B. , Weiss Karen E. , Morrison Eleshia J. , Nordang Elise Flakk , Stubhaug Audun , Nes Lise Solberg
Published: April 2022

Background

Chronic pain conditions entail significant personal and societal burdens and improved outreach of evidence-based pain self-management programs are needed. Digital cognitive-behavioral self-management interventions have shown promise. However, evidence is still scarce and several challenges with such interventions for chronic pain exist. Exploring patients' experiences and engagement with digital interventions may be an essential step towards developing meaningful digital self-management interventions for those living with chronic pain.

Objectives

This study aimed to gain insight into the experiences of people with chronic pain when engaging with EPIO, an application (app)-based cognitive-behavioral pain self-management intervention program.

Methods

Participants (N = 50) living with chronic pain received access to the EPIO intervention in a feasibility pilot-study for 3 months. During this time, all participants received a follow-up phone call at 2–3 weeks, and a subsample (n = 15) also participated in individual semi-structured interviews after 3 months. A qualitative design was used and thematic analysis was employed aiming to capture participants’ experiences when engaging with the EPIO intervention program.

Results

Findings identifying program-related experiences and engagement were organized into three main topics, each with three sub-themes: (1) Engaging with EPIO; motivation to learn, fostering joy and enthusiasm, and helpful reminders and personalization, (2) Coping with pain in everyday life; awareness, practice and using EPIO in everyday life, and (3) The value of engaging with the EPIO program; EPIO – a friend, making peace with the presence of pain, and fostering communication and social support.

Conclusions

This qualitative study explored participants’ experiences and engagement with EPIO, a digital self-management intervention program for people living with chronic pain. Findings identified valued aspects related to motivation for engagement, and showed how such a program may be incorporated into daily life, and encourage a sense of acceptance, social support and relatedness. The findings highlight vital components for facilitating digital program engagement and use in support of self-management for people living with chronic pain.

Trial registration

ClinicalTrials.gov NCT03705104.
Surgical wait times and socioeconomic status in a public healthcare system: a retrospective analysis
Authors: Law Tyler J. , Stephens Derek , Wright James G.
Published: April 2022

Background

One aim of publicly-funded health care systems is to provide equitable access to care irrespective of ability to pay. At the same time, differences in socioeconomic status (SES) are associated with health outcomes and access to care, including waiting times for surgery. In public systems where both high- and low-SES patients use the same resources, low-SES patients may be adversely impacted in surgical waiting times. The purpose of this study was to determine whether a publicly-funded health system can provide equitable access to surgical care across socioeconomic status.

Methods

Patient-level records were obtained from a comprehensive provincially-administered surgical wait time database, encompassing years 2006–2015 and 98% of Ontario hospitals. Patient SES was determined by linking postal code with the Material and Social Deprivation Index. Surgical waiting times (time in days between decision to treat and surgery) accounted for patient-initiated delays in treatment, and regression analysis considered age, SES, rurality, sex, priority level for surgical urgency (assigned by surgeons), surgical subspecialty, number of visits, and procedure year.

Results

For the 4,253,305 surgical episodes, the mean wait time was 62.3 (SD 75.4) days. Repeated measures least squares regression analysis showed the least deprived SES quintile waited 3 days longer than the most deprived quintile. Wait times dropped in the initial study period but then increased. The proportion of procedures exceeding wait time access targets remained low at 11–13%.

Conclusions

The least deprived SES quintile waited the longest, although the absolute difference was small. This study demonstrates that publicly-funded healthcare systems can provide equitable access to surgical care across SES.
What older people and their relatives say is important during acute hospitalisation: a qualitative study
Authors: Mickelson Weldingh Nina , Kirkevold Marit
Published: April 2022

Background

Due to the growing population of older people across the world, providing safe and effective care is an increasing concern. Older persons in need for hospitalisation often have, or are susceptible to develop, cognitive impairment. Hospitals need to adapt to ensure high-quality care for this vulnerable patient group. Several age-friendly frameworks and models aiming at reducing risks and complications have been promoted. However, care for older people must be based on the persons’ reported needs, and relatives are often an important part of older persons’ social support. The primary aim of this study was to explore older peoples’ and their relatives’ experiences of acute hospitalisation and determine what is important for them to experience a good hospital stay. The study was not limited to patients with cognitive impairment; but included a wider group of older individuals vulnerable to developing delirium, with or without an underlying chronic cognitive impairment.

Methods

This study had a qualitative research design in which people aged 75 years or older and their relatives were interviewed during an acute hospitalisation. The study was conducted at two medical wards at a large university hospital in Norway, and included a total of 60 participants. All interviews were informed by a semi-structured interview guide and were thematically analysed.

Results

Four major themes were identified in the older people’s and the relatives’ descriptions of how they experienced the hospital stay and what was important for them during the hospital stay: being seen and valued as a person, individualised care, patient-adapted communication and information, and collaboration with relatives. The themes span both positive and negative experiences, reflecting great variability in the experiences described. The presence of these four characteristics promoted positive experiences among patients and relatives, whereas the absence or negative valuation of them promoted negative experiences.

Conclusions

The findings underscore the interrelatedness of older people and their relatives and that patients and relatives are quite consistent in their experiences and opinions. This suggests that listening to the concerns of relatives is important, as they can voice the older patient’s needs and concerns in situations where older people might find it difficult to do so. Furthermore, the results underscore how ‘small things’ matter in relation to how health professionals capture the patient’s individual values, need for care, information and involvement of relatives and that these are essential to ensure predictability and security and a good stay for older people and their relatives.
Autism spectrum disorders as a risk factor for adolescent self-harm: a retrospective cohort study of 113,286 young people in the UK
Authors: Widnall Emily , Epstein Sophie , Polling Catherine , Velupillai Sumithra , Jewell Amelia , Dutta Rina , Simonoff Emily , Stewart Robert , Gilbert Ruth , Ford Tamsin , Hotopf Matthew , Hayes Richard D. , Downs Johnny
Published: April 2022

Background

Individuals with autism spectrum disorder (ASD) are at particularly high risk of suicide and suicide attempts. Presentation to a hospital with self-harm is one of the strongest risk factors for later suicide. We describe the use of a novel data linkage between routinely collected education data and child and adolescent mental health data to examine whether adolescents with ASD are at higher risk than the general population of presenting to emergency care with self-harm.

Methods

A retrospective cohort study was conducted on the population aged 11–17 resident in four South London boroughs between January 2009 and March 2013, attending state secondary schools, identified in the National Pupil Database (NPD). Exposure data on ASD status were derived from the NPD. We used Cox regression to model time to first self-harm presentation to the Emergency Department (ED).

Results

One thousand twenty adolescents presented to the ED with self-harm, and 763 matched to the NPD. The sample for analysis included 113,286 adolescents (2.2% with ASD). For boys only, there was an increased risk of self-harm associated with ASD (adjusted hazard ratio 2·79, 95% CI 1·40–5·57, P<0·01). Several other factors including school absence, exclusion from school and having been in foster care were also associated with a higher risk of self-harm.

Conclusions

This study provides evidence that ASD in boys, and other educational, social and clinical factors, are risk factors for emergency presentation with self-harm in adolescents. These findings are an important step in developing early recognition and prevention programmes.
Distinct clinical and somatic mutational features of breast tumors with high-, low-, or non-expressing human epidermal growth factor receptor 2 status
Authors: Zhang Guochun , Ren Chongyang , Li Cheukfai , Wang Yulei , Chen Bo , Wen Lingzhu , Jia Minghan , Li Kai , Mok Hsiaopei , Cao Li , Chen Xiaoqing , Lin Jiali , Wei Guangnan , Li Yingzhi , Zhang Yuchen , Balch Charles M. , Liao Ning
Published: April 2022

Background

HER2-low breast cancers were reported to have distinct clinicopathological characteristics from HER2-zero; however, the difference in their genetic features remains unclear. This study investigated the clinical and molecular features of breast tumors according to HER2 status.

Methods

We analyzed the clinicopathological and genomic data of 523 Chinese women with breast cancer. Genomic data was generated by targeted next-generation sequencing (NGS) of breast tumor samples using a commercial 520 gene panel. The cohort was stratified according to HER2 status as HER2-zero (n = 90), HER2-low (n = 231), and HER2-positive (n = 202) according to their immunohistochemistry and fluorescence in situ hybridization results.

Results

HER2-low breast tumors were enriched with hormone receptor-positive tumors, and who had lower Ki67 expression levels. Genes were differentially mutated across HER2 subgroups. HER2-low tumors had significantly more mutations involved in PI3K-Akt signaling than HER2-positive (p < 0.001) and HER2-zero breast tumors (p < 0.01). HER2-zero tumors had more mutations in checkpoint factors (p < 0.01), Fanconi anemia (p < 0.05), and p53 signaling and cell cycle pathway (p < 0.05) compared to HER2-low breast tumors. Compared with HER2-zero tumors, HER2-low tumors had significantly lower pathological complete response rates after neoadjuvant therapy (15.9% vs. 37.5%, p = 0.042) and proportion of relapsed/progressed patients across follow-up time points (p = 0.031), but had comparable disease-free survival (p = 0.271).

Conclusion

Our results demonstrate the distinct clinical and molecular features and clinical outcomes of HER2-low breast tumors.
Pathogenic variants carrier screening in New Brunswick: Acadians reveal high carrier frequency for multiple genetic disorders
Authors: Robichaud Philippe Pierre , Allain Eric P. , Belbraouet Sarah , Bhérer Claude , Mamelona Jean , Harquail Jason , Crapoulet Stéphanie , Crapoulet Nicolas , Bélanger Mathieu , Ben Amor Mouna
Published: April 2022

Background

Founder populations that have recently undergone important genetic bottlenecks such as French-Canadians and Ashkenazi Jews can harbor some pathogenic variants at a higher carrier rate than the general population, putting them at a higher risk for certain genetic diseases. In these populations, there can be considerable benefit to performing ethnic-based or expanded preconception carrier screening, which can help in the prevention or early diagnosis and management of some genetic diseases. Acadians are descendants of French immigrants who settled in the Atlantic Coast of Canada in the seventeenth century. Yet, the Acadian population has never been investigated for the prevalence/frequency of disease-causing genetic variants.

Methods

An exome sequencing panel for 312 autosomal recessive and 30 X-linked diseases was designed and specimens from 60 healthy participants were sequenced to assess carrier frequency for the targeted diseases.

Results

In this study, we show that a sample population of Acadians in South-East New Brunswick harbor variants for 28 autosomal recessive and 1 X-linked diseases, some of which are significantly more frequent in comparison to reference populations.

Conclusion

Results from this pilot study suggests a need for further investigation of genomic variation in this population and possibly implementation of targeted carrier and neonatal screening programs.
HOXC6 impacts epithelial-mesenchymal transition and the immune microenvironment through gene transcription in gliomas
Authors: Huang Hui , Huo Zhengyuan , Jiao Jiantong , Ji Wei , Huang Jin , Bian Zheng , Xu Bin , Shao Junfei , Sun Jun
Published: April 2022

Background

Gliomas are the most common primary malignant tumours of the central nervous system (CNS). To improve the prognosis of glioma, it is necessary to identify molecular markers that may be useful for glioma therapy. HOXC6, an important transcription factor, is involved in multiple cancers. However, the role of HOXC6 in gliomas is not clear.

Methods

Bioinformatic and IHC analyses of collected samples (n = 299) were performed to detect HOXC6 expression and the correlation between HOXC6 expression and clinicopathological features of gliomas. We collected clinical information from 177 to 299 patient samples and estimated the prognostic value of HOXC6. Moreover, cell proliferation assays were performed. We performed Gene Ontology (GO) analysis and gene set enrichment analysis (GSEA) based on ChIP-seq and public datasets to explore the biological characteristics of HOXC6 in gliomas. RNA-seq was conducted to verify the relationship between HOXC6 expression levels and epithelial-mesenchymal transition (EMT) biomarkers. Furthermore, the tumour purity, stromal and immune scores were evaluated. The relationship between HOXC6 expression and infiltrating immune cell populations and immune checkpoint proteins was also researched.

Results

HOXC6 was overexpressed and related to the clinicopathological features of gliomas. In addition, knockdown of HOXC6 inhibited the proliferation of glioma cells. Furthermore, increased HOXC6 expression was associated with clinical progression. The biological role of HOXC6 in gliomas was primarily associated with EMT and the immune microenvironment in gliomas. High HOXC6 expression was related to high infiltration by immune cells, a low tumour purity score, a high stromal score, a high immune score and the expression of a variety of immune checkpoint genes, including PD-L1, B7-H3 and CLTA-4.

Conclusions

These results indicated that HOXC6 might be a key factor in promoting tumorigenesis and glioma progression by regulating the EMT signalling pathway and might represent a novel immune therapeutic target in gliomas.
Emerging role of circular RNAs in the pathogenesis of ovarian cancer
Authors: Ghafouri-Fard Soudeh , Khoshbakht Tayyebeh , Hussen Bashdar Mahmud , Taheri Mohammad , Samsami Majid
Published: April 2022

Ovarian cancer is a female malignancy with high fatality-to-case ratio, which is due to late detection of cancer. Understanding the molecular mechanisms participating in these processes would facilitate design of therapeutic modalities and identification of novel tumor markers. Recent investigations have shown contribution of circular RNAs (circRNAs) in the evolution of ovarian cancer. These transcripts are produced through a back-splicing mechanism. The enclosed configuration of circRNAs protects them from degradation and potentiates them as biomarkers. Several circRNAs such as circMUC16, circRNA_MYLK, circRNA-UBAP2, circWHSC1, hsa_circ_0013958, circFGFR3, hsa_circRNA_102958 and circ_0072995 have been found to be up-regulated in this cancer, acting as oncogenes. On the other hand, circ-ITCH, circPLEKHM3, circ_100395, circ_0078607, circATRNL1, circHIPK3, circRHOBTB3, circEXOC6B, circ9119 and CDR1as are among down-regulated circRNAs in ovarian cancer. Expression levels of circCELSR1, circ_CELSR1, circATL2, circNRIP1, circTNPO3 and hsa_circ_0000714 have been shown to affect resistance of ovarian cancer cells to chemotherapy. Moreover, circ_100395, circFGFR3, circ_0000554, circCELSR1, circ-PTK2, circLNPEP, circ-CSPP1, circ_0000745, circ_100395 and circPLEKHM3 have been shown to regulate epithelial-mesenchymal transition and metastatic ability of ovarian cancer cells. In the current review, we explain the roles of circRNAs in the evolution and progression of ovarian cancer.
Strategies comparison in response to the two waves of COVID-19 in the United States and India
Authors: Yang Junyan , Shi Leiyu , Chen Haiqian , Wang Xiaohan , Jiao Jun , Yang Manfei , Liu Meiheng , Sun Gang
Published: April 2022

Background

This study aimed to compare the prevention and control strategies adopted by the United States and India in the COVID-19 outbreak and analyze the effectiveness of their strategies, in order to provide empirical experience for the prevention and control of the epidemic.

Methods

This study extracted official data on COVID-19 from various official websites, summarized the policies in place in the United States and India, and evaluated the effectiveness of their policies.

Results

The United States has adopted a series of mitigation strategies to control the two waves of epidemic, including strengthening virus detection, calling on the people to wear masks and so on. As of May 30, 2021, although the daily new cases there decreased to some extent, the effect was not ideal. The US’s daily new cases ranked fourth and the cumulative number of confirmed cases ranked first in the world. India has adopted containment strategies in the initial stage of the outbreak, making the epidemic relatively stable. In the later stage, India has turned to adopt mitigation strategies. In addition, many factors including the lack of medical resources and premature relaxation measures led to the rapid deterioration of the epidemic situation. As of May 30, 2021, although the daily new cases in India has a downward trend, it ranked first in the world, and the cumulative number of confirmed cases ranked second.

Conclusion

There are differences between the epidemic prevention strategies adopted by the United States and India, especially India’s containment strategies which helped it better control the epidemic in the early stage. However, the epidemic in the two countries is still severe. With the advent of virus mutants and the absence of immune barriers, it is meaningful that the two countries continue to take non-pharmacotherapy intervention measures and accelerate vaccination, according to specific national conditions adopt containment strategies that can control the epidemic more quickly when necessary, and pay attention to the risk of epidemic rebound caused by premature relaxation of epidemic prevention policies.
Anaphylactic reactions in the build-up phase of rush immunotherapy for bee venom allergy in pediatric patients: a single-center experience
Authors: Glaeser Antonia , Müller Christoph , Bode Sebastian
Published: April 2022

Background

Anaphylaxis occurs in up to 3.5% of hymenoptera stings and can be a life-threatening emergency. Venom immunotherapy (VIT) provides excellent protection from further episodes of anaphylaxis and is well tolerated. In this study the frequency of anaphylactic reactions in pediatric patients undergoing rush bee venom immunotherapy was assessed as well as possible risk factors and modified up-dosing schemes are reported.

Methods

19 consecutive pediatric patients, who had previously experienced an anaphylactic reaction following a bee sting and showed IgE-mediated sensitization to bee venom, underwent inpatient rush immunotherapy with bee venom extract. We retrospectively compared serological findings (total IgE, serum tryptase level, sensitization to Api m1, Api m3 and Api m10 bee venom allergens) and possible risk factors between patients who experienced an anaphylactic reaction during immunotherapy and patients who did not.

Results

Three of the included 19 patients (15.8%) developed anaphylactic reactions to rush bee venom immunotherapy, all of them between administration of 40 and 80 µg of bee venom extract. However, all three patients reached the standard maintenance dose of 100 µg of bee venom following a modified VIT schedule without any further complications. Total serum IgE levels as well as Api m3 sensitization levels were significantly higher in patients showing an adverse reaction to bee VIT compared to those who did not experience any complications. There were no statistically significant differences concerning age, pre-existing conditions, type and severity of the initial reaction and Api m1, Api m10 and serum tryptase levels between the two subgroups.

Conclusion

Even if anaphylactic reactions occur during the build-up phase of VIT for bee venom in children and adolescents, venom immunotherapy can and should be continued in most cases.
TLR4 mutation protects neurovascular function and cognitive decline in high-fat diet-fed mice
Authors: Obadia Nathalie , Andrade Giulia , Leardini-Tristão Marina , Albuquerque Letícia , Garcia Celina , Lima Flavia , Daleprane Júlio , Castro-Faria-Neto Hugo C. , Tibiriçá Eduardo , Estato Vanessa
Published: April 2022

Background

Metabolic syndrome (MS) is defined as a low-grade proinflammatory state in which abnormal metabolic and cardiovascular factors increase the risk of developing cardiovascular disease and neuroinflammation. Events, such as the accumulation of visceral adipose tissue, increased plasma concentrations of free fatty acids, tissue hypoxia, and sympathetic hyperactivity in MS may contribute to the direct or indirect activation of Toll-like receptors (TLRs), specifically TLR4, which is thought to be a major component of this syndrome. Activation of the innate immune response via TLR4 may contribute to this state of chronic inflammation and may be related to the neuroinflammation and neurodegeneration observed in MS. In this study, we investigated the role of TLR4 in the brain microcirculation and in the cognitive performance of high-fat diet (HFD)-induced MS mice.

Methods

Wild-type (C3H/He) and TLR4 mutant (C3H/HeJ) mice were maintained under a normal diet (ND) or a HFD for 24 weeks. Intravital video-microscopy was used to investigate the functional capillary density, endothelial function, and endothelial–leukocyte interactions in the brain microcirculation. Plasma concentrations of monocyte chemoattractant protein-1 (MCP-1), adipokines and metabolic hormones were measured with a multiplex immunoassay. Brain postsynaptic density protein-95 and synaptophysin were evaluated by western blotting; astrocytic coverage of the vessels, microglial activation and structural capillary density were evaluated by immunohistochemistry.

Results

The HFD-induced MS model leads to metabolic, hemodynamic, and microcirculatory alterations, as evidenced by capillary rarefaction, increased rolling and leukocyte adhesion in postcapillary venules, endothelial dysfunction, and less coverage of astrocytes in the vessels, which are directly related to cognitive decline and neuroinflammation. The same model of MS reproduced in mice deficient for TLR4 because of a genetic mutation does not generate such changes. Furthermore, the comparison of wild-type mice fed a HFD and a normolipid diet revealed differences in inflammation in the cerebral microcirculation, possibly related to lower TLR4 activation.

Conclusions

Our results demonstrate that TLR4 is involved in the microvascular dysfunction and neuroinflammation associated with HFD-induced MS and possibly has a causal role in the development of cognitive decline.
Mutation of KIT in cellular extraskeletal myxoid chondrosarcoma: a case report and literature review
Authors: Wang Chen , You Zhi-Jie , Chen Xiao-Yan , Lin Jie , Wu Yi-Juan
Published: April 2022

Background

Extraskeletal myxoid chondrosarcomas (EMCs) are solid tumors that have been genetically and biologically characterized. Only a few studies have discussed the role of the KIT gene or CD117 expression in EMCs, identified by immunohistochemical (IHC) staining. Herein, we present a novel case of cellular EMC exhibiting an EWSR1-NR4A3 fusion, KIT exon 13 mutations and strong diffuse expression of CD117.

Case presentation

A 69-year-old man presented with a fist-sized tumor on his left shoulder. CT revealed a tumor in the left thoracic and dorsal muscle space. The tumor was completely resected. Histologically, the tumor cells had a nodular structure and infiltrated the peripheral fat and muscle tissues. The tumor cells were uniform in size with round nuclei, well-defined nucleoli and eosinophilic cytoplasm. Immunohistochemically, the tumor cells were positive for CD117, vimentin, CD56 and NSE and focally expressed desmin; the cells were negative for myogenin, S-100, SYN, INSM1, CD34, STAT6, INI-1, Brachyury, ERG, TLE1, AE1/AE3, WT-1, CD99 and SMA. NGS revealed an EWSR1-NR4A3 fusion and KIT exon 13 mutations. The patient had no further treatment after surgery, and no recurrence or metastasis occurred during the ~ 10 month follow-up period.

Conclusions

Molecular detection is an indispensable technique for diagnosing cellular EMCs. The KIT mutations noted in this case report may offer fresh insights into EMCs treatment options.
Reduction of motorcycle-related deaths over 15 years in a developing country
Authors: Yasin Yasin J. , Eid Hani O. , Alao David O. , Grivna Michal , Abu-Zidan Fikri M.
Published: April 2022

Background

There have been major improvements in the trauma system and injury prevention in Al-Ain City. We aimed to study the impact of these changes on the incidence, pattern, injury severity, and outcome of hospitalized motorcycle-related injured patients in Al-Ain City, United Arab Emirates.

Methods

This is a retrospective analysis of two separate periods of prospectively collected data which were retrieved from Al-Ain Hospital Trauma Registry (March 2003 to March 2006 compared with January 2014 to December 2017). All motorcycle-injured patients who were admitted to Al-Ain Hospital for more than 24 h or died in the Emergency Department or after hospitalization were studied.

Results

The incidence of motorcycle injuries dropped by 37.1% over the studied period. The location of injury was significantly different between the two periods (p = 0.02, Fisher's exact test), with fewer injuries occurring at streets/highways in the second period (69.1% compared with 85.3%). The anatomical injury severity of the head significantly increased over time (p = 0.03), while GCS on arrival significantly improved (p < 0.0001), indicating improvements in both prehospital and in-hospital trauma care. The mortality of the patients significantly decreased (0% compared with 6%,p = 0.002, Fisher's exact test).

Conclusions

The incidence of motorcycle injuries in our city dropped by almost 40% over the last 15 years. There was a significant reduction in the mortality of hospitalized motorcycle-injured patients despite increased anatomical severity of the head injuries. This is attributed to improvements in the trauma care system, including injury prevention, and both prehospital and in-hospital trauma care.
Integrated analysis of single-cell and bulk RNA sequencing data reveals a pan-cancer stemness signature predicting immunotherapy response
Authors: Zhang Zhen , Wang Zi-Xian , Chen Yan-Xing , Wu Hao-Xiang , Yin Ling , Zhao Qi , Luo Hui-Yan , Zeng Zhao-Lei , Qiu Miao-Zhen , Xu Rui-Hua
Published: April 2022

Background

Although immune checkpoint inhibitor (ICI) is regarded as a breakthrough in cancer therapy, only a limited fraction of patients benefit from it. Cancer stemness can be the potential culprit in ICI resistance, but direct clinical evidence is lacking.

Methods

Publicly available scRNA-Seq datasets derived from ICI-treated patients were collected and analyzed to elucidate the association between cancer stemness and ICI response. A novel stemness signature (Stem.Sig) was developed and validated using large-scale pan-cancer data, including 34 scRNA-Seq datasets, The Cancer Genome Atlas (TCGA) pan-cancer cohort, and 10 ICI transcriptomic cohorts. The therapeutic value of Stem.Sig genes was further explored using 17 CRISPR datasets that screened potential immunotherapy targets.

Results

Cancer stemness, as evaluated by CytoTRACE, was found to be significantly associated with ICI resistance in melanoma and basal cell carcinoma (both P < 0.001). Significantly negative association was found between Stem.Sig and anti-tumor immunity, while positive correlations were detected between Stem.Sig and intra-tumoral heterogenicity (ITH) / total mutational burden (TMB). Based on this signature, machine learning model predicted ICI response with an AUC of 0.71 in both validation and testing set. Remarkably, compared with previous well-established signatures, Stem.Sig achieved better predictive performance across multiple cancers. Moreover, we generated a gene list ranked by the average effect of each gene to enhance tumor immune response after genetic knockout across different CRISPR datasets. Then we matched Stem.Sig to this gene list and found Stem.Sig significantly enriched 3% top-ranked genes from the list (P = 0.03), including EMC3, BECN1, VPS35, PCBP2, VPS29, PSMF1, GCLC, KXD1, SPRR1B, PTMA, YBX1, CYP27B1, NACA, PPP1CA, TCEB2, PIGC, NR0B2, PEX13, SERF2, and ZBTB43, which were potential therapeutic targets.

Conclusions

We revealed a robust link between cancer stemness and immunotherapy resistance and developed a promising signature, Stem.Sig, which showed increased performance in comparison to other signatures regarding ICI response prediction. This signature could serve as a competitive tool for patient selection of immunotherapy. Meanwhile, our study potentially paves the way for overcoming immune resistance by targeting stemness-associated genes.
PTH (1-34) enhances the therapeutic effect of bone marrow mesenchymal stem cell-derived exosomes by inhibiting proinflammatory cytokines expression on OA chondrocyte repair in vitro
Authors: Shao Li-tao , Luo Liang , Qiu Jie-hong , Deng David Y. B.
Published: April 2022

Background

The effects of bone marrow mesenchymal stem cells (BMSCs) during the treatment of cartilage damage have been proven to be attributed to paracrine mechanisms, particularly the effect of exosomes. Exosomes from different batches are inhomogeneous, and different treatment effects are observed between samples. The purpose of this research was to find more effective and homogeneous exosomes for the repair of chondrocytes in osteoarthritis (OA). We observed the potential effects and possible mechanisms of exosomes derived from parathyroid hormone (PTH) (1-34)-preconditioned BMSCs (ExoPTH) in the alleviation of OA.

Materials and methods

Exosomes derived from BMSCs (ExoBMSC) and ExoPTH were isolated by differential centrifugation. Primary rat chondrocytes were used to establish the OA model by interleukin 1 beta (IL-1β) in vitro. The effects of these two types of exosomes on OA chondrocyte proliferation, migration, apoptosis, and extracellular matrix formation were measured and compared. We observed changes in IL-2, TNF-α, and IL-6 levels via Western blotting (WB), and quantitative real-time PCR (qRT–PCR).

Results

We successfully extracted ExoBMSC and ExoPTH and established an IL-1β-induced OA model in primary chondrocytes from rats. Our study showed that IL-2, TNF-α, and IL-6 levels increased significantly in OA chondrocytes; however, both ExoBMSC and ExoPTH reduced the levels of IL-2, TNF-α, and IL-6. In addition, ExoPTH exhibited stronger anti-inflammatory effects. ExoPTH had a more marked effect on proliferation, migration, and production of the extracellular matrix (Col-II) in OA chondrocytes than ExoBMSC at 24 h.

Conclusion

ExoPTH increased the migration, proliferation, and chondral matrix formation of OA chondrocytes in vitro. In OA chondrocyte therapy, the potential mechanism of ExoPTH might involve the inhibition of production of proinflammatory cytokines. Although the two types of exosomes had some similar effects, most effects of ExoPTH were better than those of ExoBMSC, so ExoPTH may have a better ability to alleviate OA.
The angiopoietin-like protein 4, apolipoprotein C3, and lipoprotein lipase axis is disrupted in patients with rheumatoid arthritis
Authors: de Armas-Rillo Laura , Quevedo-Abeledo Juan Carlos , Hernández-Hernández Vanesa , de Vera-González Antonia , González-Delgado Alejandra , García-Dopico José A. , González-Gay Miguel Á. , Ferraz-Amaro Iván
Published: April 2022

Background

Modulators of triglyceride metabolism include lipoprotein lipase (LPL), angiopoietin-like protein 4 (ANGPTL4), and apolipoprotein C-3 (ApoC3). There is evidence on the influence of this triangle of molecules on an increased risk of atherosclerotic cardiovascular disease (CV) in the general population. Patients with rheumatoid arthritis (RA) present changes in lipid profiles and accelerated CV disease. In the present study, we set out to study whether the ANGPTL4, ApoC3, and LPL axis differs in subjects with RA compared to controls. In a further step, we investigated the relationship of this axis with subclinical atherosclerosis in patients with RA.

Methods

Cross-sectional study that included 569 individuals, 323 patients with RA and 246 age-matched controls. ANGPTL4, ApoC3 and LPL, and standard lipid profiles were analyzed in patients and controls. Carotid intima-media thickness (cIMT) and carotid plaques were assessed in RA patients. A multivariable analysis was performed to assess whether the ANGPTL4, ApoC3, and LPL axis was altered in RA and to study its relationship with RA dyslipidemia and subclinical carotid atherosclerosis.

Results

Most lipid profile molecules did not differ between patients and controls. Despite this, and after fully multivariable analysis including CV risk factors, use of statins, and changes in the lipid profile caused by the disease itself, patients with RA showed higher serum levels of ANGPTL4 (beta coef. 295 [95% CI 213–376] ng/ml, p<0.001) and ApoC3 (beta coef. 2.9 [95% CI 1.7–4.0] mg/dl, p<0.001), but lower circulating LPL (beta coef. −174 [95% CI −213 to −135] ng/ml, p<0.001). ANGPTL4 serum levels were positively and independently associated with a higher cIMT in patients with RA after fully multivariable adjustment.

Conclusion

The axis consisting in ANGPTL4, ApoC3, and LPL is disrupted in patients with RA. ANGPTL4 serum levels are positively and independently associated with a higher cIMT in RA patients.
GATA25, a novel regulator, accelerates the flowering time of Arabidopsis thaliana
Authors: Kim Kihwan , Lee Jooeun , Kim Byeonggyu , Shin Juhyung , Kang Tae-An , Kim Won-Chan
Published: April 2022

Intrinsic and exogenous signals in conjunction precisely regulate the initiation of flowering. Both signals influence flowering time, which is an integral part of plant reproduction. The signals converge through different pathways, and their coordinated action leads to the onset of flowering. Genetic pathways related to the regulation of flowering time are well-known from research into the molecular genetics of Arabidopsis thaliana. Specifically, crucial components of the photoperiodic pathway and floral integrators play a critically significant role in flowering. In this study, we found that GATA25 is a novel transcription factor that accelerates flowering time under long days. GATA25 encodes C-X2-C-X20-C-X2-C conserved cysteine residues of the zinc-finger domain and CCT domain which process photoperiodic flowering and regulate circadian rhythms. Flowering was accelerated by overexpression of GATA25 throughout the Arabidopsis thaliana. In contrast, GATA25 fused to SRDX (SUPERMAN repressive domain X)-motif plants showed delayed flowering. We also demonstrated that GATA25 induced the expression of floral integrator genes and photoperiodic pathway-related genes. Together, these results suggest that GATA25 might act to accelerate flowering time.
MRI study of medial meniscus degeneration of osteoarthritic knees with or without posterior root tear
Authors: Hisashi Kosuke , Muneta Takeshi , Kohno Yuji , Sasaki Mana , Yamazaki Junya , Hayashi Haruhisa , Koga Hideyuki , Morito Toshiyuki
Published: April 2022

Purpose

The purpose of this study was to compare the medial meniscus (MM) degeneration, meniscus extrusion, and tibial joint inclination by using MRI to consider the pathogenesis of posterior root tear (PRT) in medial-type knee osteoarthritis (KOA) both with and without medial meniscus posterior root tear (MMPRT).

Methods

This study used open MRI with flexion sagittal view and included 324 medial-type osteoarthritic knees with a Kellegren–Lawrence grade of 2 or less. Following the exclusion process, 151 knees were selected for MRI analysis. MM degeneration grading was performed according to Jerosch by 5 degrees of 0–4 in four different portions from anterior to posterior. MM medial extrusion (MMME), MM posterior extrusion (MMPE), medial tibial medial slope (MTMS), and medial tibial posterior slope (MTPS) were measured according to previous studies.

Results

MM degeneration in the anterior portion to MCL averaged 1.72 ± 0.67 in the PRT group (n = 48) and 1.40 ± 0.78 in the non-PRT group (n = 103). The degeneration grade was statistically higher in the PRT group than in the non-PRT group (p = 0.050). There was no difference in MM degeneration in the other three portions. MMME averaged 4.02 ± 1.12 mm in the PRT group and 3.11 ± 1.11 mm in the non-PRT group. MMPE averaged 4.22 ± 0.87 mm in the PRT group and 2.83 ± 1.12 mm in the non-PRT group. Both MMME and MMPE in the PRT group were statistically larger than those in the non-PRT group (p < 0.001). There was no difference in MTMS between the two groups. MTPS averaged 6.34 ± 2.25° in the PRT group and 5.28 ± 2.23° in the non-PRT group. The MTPS of the PRT group was statistically larger than that of the non-PRT group (p = 0.007).

Conclusion

The severity of MM degeneration, extrusion of MM, and degree of tibial slope were compared between medial-type KOA with and without PRT using an open MRI. MM degeneration was more severe anteriorly in the PRT group. The PRT group showed larger MMME and MMPE with greater MTPS.

Level of evidence

III. Retrospective cohort study.
Bronchial artery hypertrophy-associated perioperative pulmonary hemorrhage in cardiovascular surgery: a case report
Authors: Abe Shinji , Kamikubo Yasuhiro , Kato Nobuyasu , Kato Hiroki , Ooka Tomonori , Shingu Yasushige , Wakasa Satoru
Published: April 2022

Background

Pulmonary hemorrhage is a life-threatening complication of cardiovascular surgery. Bronchial artery hypertrophy, a rare pathology associated with inflammatory and ischemic respiratory diseases, increases the risk of pulmonary hemorrhage; however, its involvement in cardiovascular surgery is not well known. We present two cardiovascular surgical cases in which embolization of the hypertrophied bronchial artery was effective in controlling perioperative pulmonary hemorrhage.

Case presentation

The first case was a 51-year-old man with chronic obstructive pulmonary disease who developed acute type A aortic dissection. After emergent surgery, his blood pressure suddenly dropped in the intensive care unit; computed tomography revealed a right hemothorax. Because a 4-mm dilated bronchial artery was identified on preoperative computed tomography, the hemothorax was suspected to be associated with bronchial artery hypertrophy. Selective bronchial arteriography was emergently performed and revealed a right pulmonary parenchymal blush. After subsequent coil embolization of the bronchial artery, the parenchymal blush disappeared, and his hemodynamic condition stabilized. The second case was a 66-year-old man with bronchiectasis who was referred for redo aortic valve replacement due to structural valve deterioration. A bioprosthesis was previously implanted to avoid permanent anticoagulation because the patient had repeated episodes of hemoptysis; however, he still had persistent hemosputum during admission for the redo aortic valve replacement. A dilated bronchial artery 3.7 mm in size was incidentally identified on preoperative computed tomography, and hence, the repeated hemosputum was suspected to be associated with bronchial artery hypertrophy. Bronchial arteriography revealed a right pulmonary parenchymal blush, and prophylactic embolization of the bronchial artery was performed. The hemosputum disappeared after the procedure, and redo aortic valve replacement was performed uneventfully 8 days later.

Conclusion

In cardiovascular surgery, the risk of pulmonary hemorrhage associated with bronchial artery hypertrophy should be considered, especially in patients with inflammatory and ischemic respiratory diseases.
Confirmed presence of aedes (rusticoidus) refiki Medschid, 1928 in a continental dry Mediterranean peri-urban environment in south-central Spain
Authors: Casades-Martí Laia , Frías Mario , Delacour Sarah , Ruiz-Fons Francisco
Published: April 2022

Background

The ‘snow-melt mosquito’ aedes (rusticoidus) refiki is a rare species with a wide distribution in Europe that is usually defined as an aggressive mosquito for mammals, including humans. During a mosquito survey in a peri-urban area in south-central mainland Spain, adult Ae. refiki females were captured and identified by morphological traits. The presence of this species of mosquito has never been molecularly confirmed under continental dry Mediterranean climatic influence with scarce number of days with snow on soil. The aim of this study was to confirm by amplification and sequencing of mitochondrial cytochrome c oxidase subunit I (COI) and internal transcribed spacer 2 (ITS2) region.

Results

We also successfully amplified and typed the species molecularly by COI and ITS2 regions. The peri-urban area where Ae. refiki was found contrasts with the reported cold, humid and snowy environments required by the species to breed.

Conclusions

This finding suggests that the species is already adapted to continental dry Mediterranean environments, questioning whether it is a truly stenotopic species of cold snowy environments.