bluuebunny/crossref_metadata_2025 huggingface dataset:
Thyrotoxicosis and dilated cardiomyopathy in developing countries
Authors: Abera Bisrat Tesfay , Abera Merhawit Atsbha , Berhe Gebretsadik , Abreha Girmatsion Fisseha , Gebru Hirut Teame , Abraha Hiluf Ebuy , Ebrahim Mohamedawel Mohamedniguss
Published: June 2021

Background

Thyrotoxicosis is the state of thyroid hormone excess. But, in sub-Saharan Africa (SSA), specifically Northern Ethiopia, scientific evidence about thyrotoxicosis and its cardiac complications like dilated cardiomyopathy is limited. Therefore, this study aimed to explore the thyrotoxicosis presentation and management and identify factors associated with dilated cardiomyopathy in a tertiary hospital in Northern Ethiopia.

Methods

An institution-based cross-sectional study was conducted in Ayder Comprehensive Specialized Hospital from 2017 to 2018. Data from 200 thyrotoxicosis cases were collected using a structured questionnaire. After describing variables, logistic regression was conducted to identify independent predictors of dilated cardiomyopathy. Statistical significance was declared atp < 0.05.

Results

Mean age at presentation of thyrotoxicosis was 45 years and females accounted for 89 % of the cases. The most frequent etiology was multinodular toxic goiter (51.5 %). As well, the most common symptoms and signs were palpitation and goiter respectively. Thyroid storm occurred in 6 % of the cases. Out of 89 patients subjected to echocardiography, 35 (39.3 %) of them had dilated cardiomyopathy. And, the odds of dilated cardiomyopathy were higher in patients who had atrial fibrillation (AOR = 15.95, 95 % CI:5.89–38.16,p = 0.001) and tachycardia (AOR = 2.73, 95 % CI:1.04–7.15,p = 0.040). All patients took propylthiouracil and 13.0 % of them experienced its side effects. Concerning β-blockers, propranolol was the most commonly (78.5 % of the cases) used drug followed by atenolol (15.0 %). Six patients underwent surgery.

Conclusions

In developing countries like Ethiopia, patients with thyrotoxicosis have no access to methimazole which is the first-line anti-thyroid drug. Besides, they greatly suffer from dilated cardiomyopathy (due to late presentation) and side effects of propylthiouracil. Therefore, we recommend that patients should get adequate health information about thyrotoxicosis and anti-thyroid drugs including their side effects. Additionally, hospitals and other concerned bodies should also avail of TSH tests and methimazole at an affordable cost. Furthermore, community awareness about iodized salt and iodine-rich foods should be enhanced.
Developing an integrated model of community-based palliative care into the primary health care (PHC) for terminally ill cancer patients in Iran
Authors: Hojjat-Assari Suzanne , Rassouli Maryam , Madani Maxwell , Heydari Heshmatolah
Published: June 2021

Background

Patients with cancer commonly experience pain and suffering at the end of life days. Community-based palliative care can improve the quality of life of terminally-ill cancer patients and provide them with a merciful death. The purpose of this study was to develop an integrated model of community-based palliative care into PHC for terminally ill cancer patients.

Method

This study is a health system research (HSR) that was conducted in three phases from October 2016 to July 2020. In the first phase, dimensions of community-based palliative care were explored in patients with cancer using qualitative methods and conventional content analysis. In the second phase, a scoping review was carried out to complete the collected data from the qualitative phase of the study. Based on the collected data in the first and second phases of the study, a preliminary draft of community-based palliative care was developed for patients with cancer based on the framework of the World Health Organization. Finally, the developed model was validated using the Delphi technique in the third phase of the study.

Results

Data analysis indicated that providing community-based care to patients with cancer is influenced by the context of care. According to the developed model, patients are identified as terminally ill, and then are referred to the local comprehensive health center in a reverse manner. After patients’ referral, they can receive appropriate healthcare until death by the home care team in relation to the comprehensive health center based on the framework of primary healthcare.

Conclusions

This model was developed based on the current Iranian healthcare structure and the needs of terminally ill cancer patients. According to the model, healthcare is provided in a reverse manner from the subspecialty centers to patients’ homes in order to provide easy access to palliative care. It is suggested to use this model as a pilot at the regional level.
Willingness and associated factors of working with older people among undergraduate nursing students in China: a cross-sectional study
Authors: Guo Yujie , Yang Lei , Zhu Lingli , Wan Yu , Zhang Shujun , Zhang Jie
Published: June 2021

Background

The aging population has become a serious challenge for health care service and will lead to an increasing demand for nurses to work with older people. However, working with older people has always been an unpopular career choice among nursing students. This study aimed to further explore the willingness and associated factors of undergraduate nursing students to work with older people in China.

Methods

A convenience sampling method was employed from May to July 2017 among undergraduate nursing students from a nursing school in Nantong China. Demographic data, the Chinese version of the Kogan’s Old Person’s Scale, the Chinese version of the Facts of Aging Quiz and the motivation questionnaire were used to collect data. A series of Mann-Whitney U test, Kruskal-Wallis H test, Spearman correlation test and Ordinal logistic regression analysis were applied to analyze the data.

Results

Of the 853 students surveyed, 38.1 % were willing to work with older people after graduation. Expectancy, interest, attainment value, cost, prejudice, whether they like nursing profession and whether they participated in elderly-related activities were the most significant predictors of the students’ willingness to work with older people.

Conclusions

Nursing students expressed a low level of willingness to work with older people upon graduation. Nursing educators have an important part in challenging students’ stereotype of older people and inspire their career choice in caring for older people through both well-designed curriculum and elderly-related activities, and relevant education departments should actively optimize aged-related courses, strengthen professional ethics and gratitude education, and improve nursing students’ sense of identity and mission in caring for older people, so as to improve their willingness to work with older people.
Emotion management and stereotypes about emotions among male nurses: a qualitative study
Authors: Martínez-Morato Sergio , Feijoo-Cid Maria , Galbany-Estragués Paola , Fernández-Cano Maria Isabel , Arreciado Marañón Antonia
Published: June 2021

Background

Nursing requires a high load of emotional labour. The link between nursing, emotional labour and the female sex, complicates the figure of the male nurse, because masculinity is associated with physical or technical (rather than emotional) and moreover is defined in contrast to femininity. Our objective was to understand how emotion management is described by male nurses who work in the paediatrics department of a Spanish tertiary hospital.

Methods

Qualitative descriptive study. The participants were selected through intentional sampling in the paediatrics department of a Spanish tertiary hospital. We conducted semi-structured interviews until reaching data saturation. We carried out a content analysis, using Lincoln and Guba’s definition of scientific rigour.

Results

We identified two key themes in the data: 1) Stereotypes related to the emotional aspects of care: Participants took for granted some gender stereotypes while questioning others and defended alternative ways of managing emotions related to care. 2) Emotion management strategies: Participants described keeping an emotional distance, setting boundaries, relativising problems and using distraction and humour.

Discussion

Nursing care is conditioned by gender roles and stereotypes that present men as less capable than women of feeling and managing emotions. However, emotion management is necessary in nursing care—especially in paediatrics—and our participants reported using strategies for it. Although participants continued to interpret care in terms of traditional roles, they contradicted them in adapting to the emotional labour that their job requires.

Conclusions

New behaviours are emerging among male nurses, in which care and emotion management are not exclusively the purview of women. Our participants reproduced some gender stereotypes while disrupting others, and they tended to cling to the stereotypes that were favourable to them as male nurses. As we work towards a gender-neutral profession, these results represent a first step: male participants reported that they provide care and manage their emotions as well as (or better than) women. However, because they substantiated their claims by drawing on negative stereotypes of women, further progress must be made.
Understanding acceptability in the context of text messages to encourage medication adherence in people with type 2 diabetes
Authors: Bartlett Y. Kiera , Kenning Cassandra , Crosland Jack , Newhouse Nikki , Miles Lisa M. , Williams Veronika , McSharry Jenny , Locock Louise , Farmer Andrew J. , French David P.
Published: June 2021

Background

Acceptability is recognised as a key concept in the development of health interventions, but there has been a lack of consensus about how acceptability should be conceptualised. The theoretical framework of acceptability (TFA) provides a potential tool for understanding acceptability. It has been proposed that acceptability measured before use of an intervention (anticipated acceptability) may differ from measures taken during and after use (experienced acceptability), but thus far this distinction has not been tested for a specific intervention. This paper 1) directly compares ratings of anticipated and experienced acceptability of a text message-based intervention, 2) explores the applicability of the TFA in a technology-based intervention, and 3) uses these findings to inform suggestions for measuring acceptability over the lifespan of technology-based health interventions.

Methods

Data were obtained from a quantitative online survey assessing anticipated acceptability of the proposed text messages (n = 59) and a 12-week proof-of-concept mixed methods study assessing experienced acceptability while receiving the text messages (n = 48). Both quantitative ratings by return text message, and qualitative data from participant interviews were collected during the proof-of-concept study.

Results

The quantitative analysis showed anticipated and experienced acceptability were significantly positively correlated (rs > .4). The qualitative analysis identified four of the seven constructs of the TFA as themes (burden, intervention coherence, affective attitude and perceived effectiveness). An additional two themes were identified as having an important impact on the TFA constructs (perceptions of appropriateness and participants’ role). Three suggestions are given related to the importance of appropriateness, what may affect ratings of acceptability and what to consider when measuring acceptability.

Conclusions

The high correlation between anticipated and experienced acceptability was a surprising finding and could indicate that, in some cases, acceptability of an intervention can be gauged adequately from an anticipated acceptability study, prior to an expensive pilot or feasibility study. Directly exploring perceptions of appropriateness and understanding whether the acceptability described by participants is related to the intervention or the research - and is for themselves or others - is important in interpreting the results and using them to further develop interventions and predict future use.
Persistence and baseline determinants of seropositivity and reinfection rates in health care workers up to 12.5 months after COVID-19
Authors: Dobaño Carlota , Ramírez-Morros Anna , Alonso Selena , Vidal-Alaball Josep , Ruiz-Olalla Gemma , Vidal Marta , Rubio Rocío , Cascant Emma , Parras Daniel , Rodrigo Melero Natalia , Serra Pau , Carolis Carlo , Santamaria Pere , Forcada Anna , Mendioroz Jacobo , Aguilar Ruth , Moncunill Gemma , Ruiz-Comellas Anna
Published: June 2021

We assessed the duration and baseline determinants of antibody responses to SARS-CoV-2 spike antigens and the occurrence of reinfections in a prospective cohort of 173 Spanish primary health care worker patients followed initially for 9 months and subsequently up to 12.5 months after COVID-19 symptoms onset. Seropositivity to SARS-CoV-2 spike and receptor-binding domain antigens up to 149–270 days was 92.49% (90.17% IgG, 76.3% IgA, 60.69% IgM). In a subset of 64 health care workers who had not yet been vaccinated by April 2021, seropositivity was 96.88% (95.31% IgG, 82.81% IgA) up to 322–379 days post symptoms onset. Four suspected reinfections were detected by passive case detection, two among seronegative individuals (5 and 7 months after the first episode), and one low antibody responder. Antibody levels significantly correlated with fever, hospitalization, anosmia/hypogeusia, allergies, smoking, and occupation. Stable sustainment of IgG responses raises hope for long-lasting COVID-19 vaccine immunity.
Discovery of sensorineural hearing loss and ossicle deformity in a Chinese Li nationality family with spondyloepiphyseal dysplasia congenita caused by p.G504S mutation of COL2A1
Authors: Wu Kan , Li Zhumei , Zhu Yuhua , Wang Xiaocheng , Chen Guohui , Hou Zhaohui , Zhang Qiujing
Published: June 2021

Background

Spondyloepiphyseal dysplasia congenita (SEDC) is an autosomal dominant chondrodysplasia characterized by disproportionate short stature, abnormal epiphyses, and flattened vertebral bodies. COL2A1 has been confirmed as the pathogenic gene. Hearing loss represents an infrequent manifestation for 25–30% of patients with SEDC. The characteristics of the hearing impairment were rarely documented.

Methods

Audiological, ophthalmic, imaging examinations were conducted on the family members. The whole exome sequencing (WES) was performed to detect the candidate gene, and the Sanger sequencing was used to confirm the causative variation.

Results

COL2A1 c.1510G>A (p.G504S), a hot spot variation, was identified as the disease-causing mutation of the Chinese Li nationality family with SEDC. This variation was co-segregated with the SEDC phenotype in the family and was absent in the 1000 Genomes Project, ESP and ExAC. Clinically, several manifestations were first demonstrated in SEDC patients caused by p.G504S, including sensorineural hearing loss, auditory ossicles deformity, retinal detachment, sacrum cracked and elbow and wrist joints deformity. Other classical SEDC manifestations such as bones and joints pain, midfacial dysplasia, disproportionate short stature, spinal deformity, thoracocyllosis, coxa arthropathy, myopia and waddling gait were also showed in the family patients.

Conclusion

We first identified the mutation p.G504S in COL2A1 gene as the pathogenesis in a Chinese Li nationality family and reported the correlation between p.G504S and atypical clinical phenotypes including sensorineural hearing loss, auditory ossicles deformity, retinal detachment, sacrum cracked and elbow and wrist joints deformity. Our findings would extend the phenotypic spectrum of SEDC and deepen clinicians' understanding of genotype–phenotype correlation of the disease.
Mechanism of protective effect of xuan-bai-cheng-qi decoction on LPS-induced acute lung injury based on an integrated network pharmacology and RNA-sequencing approach
Authors: Zhu Huahe , Wang Shun , Shan Cong , Li Xiaoqian , Tan Bo , Chen Qilong , Yang Yunxiang , Yu Hongji , Yang Aidong
Published: June 2021

Xuan-bai-cheng-qi decoction (XCD), a traditional Chinese medicine (TCM) prescription, has been widely used to treat a variety of respiratory diseases in China, especially to seriously infectious diseases such as acute lung injury (ALI). Due to the complexity of the chemical constituent, however, the underlying pharmacological mechanism of action of XCD is still unclear. To explore its protective mechanism on ALI, firstly, a network pharmacology experiment was conducted to construct a component-target network of XCD, which identified 46 active components and 280 predicted target genes. Then, RNA sequencing (RNA-seq) was used to screen differentially expressed genes (DEGs) between ALI model rats treated with and without XCD and 753 DEGs were found. By overlapping the target genes identified using network pharmacology and DEGs using RNA-seq, and subsequent protein–protein interaction (PPI) network analysis, 6 kernel targets such as vascular epidermal growth factor (VEGF), mammalian target of rapamycin (mTOR), AKT1, hypoxia-inducible factor-1α (HIF-1α), and phosphoinositide 3-kinase (PI3K) and gene of phosphate and tension homology deleted on chromsome ten (PTEN) were screened out to be closely relevant to ALI treatment. Verification experiments in the LPS-induced ALI model rats showed that XCD could alleviate lung tissue pathological injury through attenuating proinflammatory cytokines release such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β. Meanwhile, both the mRNA and protein expression levels of PI3K, mTOR, HIF-1α, and VEGF in the lung tissues were down-regulated with XCD treatment. Therefore, the regulations of XCD on PI3K/mTOR/HIF-1α/VEGF signaling pathway was probably a crucial mechanism involved in the protective mechanism of XCD on ALI treatment.
Reduction of estimated fluid volumes following initiation of empagliflozin in patients with type 2 diabetes and cardiovascular disease: a secondary analysis of the placebo-controlled, randomized EMBLEM trial
Authors: Tanaka Atsushi , Shimabukuro Michio , Teragawa Hiroki , Okada Yosuke , Takamura Toshinari , Taguchi Isao , Toyoda Shigeru , Tomiyama Hirofumi , Ueda Shinichiro , Higashi Yukihito , Node Koichi ,   the EMBLEM Investigators
Published: June 2021

Backgrounds/Aim

Sodium glucose co-transporter 2 inhibitors promote osmotic/natriuretic diuresis and reduce excess fluid volume, and this improves cardiovascular outcomes, including hospitalization for heart failure. We sought to assess the effect of empagliflozin on estimated fluid volumes in patients with type 2 diabetes and cardiovascular disease (CVD).

Methods

The study was a post-hoc analysis of the EMBLEM trial (UMIN000024502), an investigator-initiated, multi-center, placebo-controlled, double-blinded, randomized-controlled trial designed primarily to evaluate the effect of 24 weeks of empagliflozin treatment on vascular endothelial function in patients with type 2 diabetes and established CVD. The analysis compared serial changes between empagliflozin (10 mg once daily, n = 52) and placebo (n = 53) in estimated plasma volume (ePV), calculated by the Straus formula and estimated the extracellular volume (eEV), determined by the body surface area, measured at baseline and 4, 12, and 24 weeks after initiation of treatment. Correlations were examined between the changes from baseline to week 24 in each estimated fluid volume parameter and several clinical variables of interest, including N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration.

Results

In an analysis using mixed-effects models for repeated measures, relative to placebo empagliflozin reduced ePV by − 2.23% (95% CI − 5.72 to 1.25) at week 4, − 8.07% (− 12.76 to − 3.37) at week 12, and − 5.60% (− 9.87 to − 1.32) at week 24; eEV by − 70.3 mL (95% CI − 136.8 to − 3.8) at week 4, − 135.9 mL (− 209.6 to − 62.3) at week 12, and − 144.4 mL (− 226.3 to − 62.4) at week 24. The effect of empagliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in log-transformed NT-proBNP was positively correlated with change in ePV (r = 0.351, p = 0.015), but not with change in eEV.

Conclusions

Our data demonstrated that initiation of empagliflozin treatment substantially reduced estimated fluid volume parameters in patients with type 2 diabetes and CVD, and that this effect was maintained for 24 weeks. Given the early beneficial effect of empagliflozin on cardiovascular outcomes seen in similar patient populations, our findings provide an important insight into the key mechanisms underlying the clinical benefit of the drug.

Trial registration University Medical Information Network Clinical Trial Registry, number 000024502
Triglyceride glucose index combined with plaque characteristics as a novel biomarker for cardiovascular outcomes after percutaneous coronary intervention in ST-elevated myocardial infarction patients: an intravascular optical coherence tomography study
Authors: Zhao Xiaoxiao , Wang Ying , Chen Runzhen , Li Jiannan , Zhou Jinying , Liu Chen , Zhou Peng , Sheng Zhaoxue , Chen Yi , Song Li , Zhao Hanjun , Yan Hongbing
Published: June 2021

Background and aim

This prospective study explored plaque morphology according to the underlying culprit lesion pathology (rupture versus erosion) in relation to the triglyceride glucose (TyG) index in patients with acute ST-elevated myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention and optical coherence tomography (OCT) for culprit lesions to elucidate the effects of the TyG index and type of plaque on the incidence of major adverse cardiovascular events (MACEs).

Methods and outcomes

A total of 274 patients with STEMI aged ≥ 18 years who underwent pre-intervention OCT imaging of culprit lesions between March 2017 and March 2019 were enrolled. The TyG index was calculated using the formula ln[fasting TG (mg/dL) × fasting glucose (mg/dL)/2]. Patients with plaque rupture (PR) and plaque erosion (PE) were divided into three groups across the TyG tertiles. MACEs were defined as a composite of all-cause death, myocardial infarction (MI) recurrence, and ischaemic stroke.

In fully adjusted analyses, the middle tertile of TyG was significantly associated with greater rates of MACEs in patients with PR but not in those with PE (relative to the low tertile, HR [hazard ratio], 6.01; 95% confidence interval [CI], 1.25–28.88; P = 0.025). Cox regression models indicated a significantly higher HR for MACEs in patients in the middle tertile of TyG than in those in the low tertile of TyG after full additional adjustment (HR, 5.45; 95% CI, 1.10–27.09; P = 0.038). However, being in the high tertile of TyG independently and significantly increased the risk of major bleeding events among patients with PE (HR, 2.50; 95% CI, 1.11–5.65; P = 0.028). The area under the receiver operating characteristic curve for predicting MACEs to evaluate the diagnostic value of the TyG index combined with the morphological characteristics of plaque after full adjustment was 0.881 (sensitivity = 94.74%, specificity = 78.04%, cut-off level = 0.73). Kaplan–Meier curves were generated for the cumulative incidence of MACEs for up to a median of 1.98 years stratified by tertiles of TyG among the PR and PE subgroups. Among patients with PR, there were significant differences among the tertiles of TyG (p = 0.030).

Conclusion and relevance

Microstructural OCT features of culprit lesions in combination with the TyG index, a surrogate estimate of insulin resistance, can be used in clinical practice to support risk stratification and predict adverse events in patients with STEMI.
Myc-associated zinc-finger protein promotes clear cell renal cell carcinoma progression through transcriptional activation of the MAP2K2-dependent ERK pathway
Authors: Ren Li-Xin , Qi Jin-Chun , Zhao An-Ning , Shi Bei , Zhang Hong , Wang Dan-Dan , Yang Zhan
Published: June 2021

Background

The dysfunction of myc-related zinc finger protein (MAZ) has been proven to contribute to tumorigenesis and development of multiple cancer types. However, the biological roles and clinical significance of MAZ in clear cell renal carcinoma (ccRCC) remain unclear.

Methods

MAZ expression was examined in ccRCC and normal kidney tissue by quantitative real-time PCR and Western blot. Statistical analysis was used to evaluate the clinical correlation between MAZ expression and clinicopathological characteristics to determine the relationship between MAZ expression and the survival of ccRCC patients. The biological roles of MAZ in cells were investigated in vitro using MTT and colony assays. Luciferase reporter assays and chromatin immunoprecipitation (ChIP) were used to investigate the relationship between MAZ and its potential downstream signaling molecules.

Results

MAZ expression is elevated in ccRCC tissues, and higher levels of MAZ were correlated with poor survival of patients with ccRCC. MAZ upregulation elevates the proliferation ability of ccRCC cells in vitro, whereas silencing MAZ represses this ability. Our results further reveal that MAZ promotes cell growth, which is dependent on ERK signaling. Importantly, we found that MAZ positively regulates MAP2K2 expression in ccRCC cells. Mechanistically, MAZ binds to the MAP2K2 promoter and increases MAP2K2 transcription. Furthermore, MAP2K2 levels were shown to be increased in ccRCC tissues and to be associated with a poor prognosis of ccRCC patients. MAP2K2 upregulation activates the ERK signaling pathway and promotes ccRCC progression.

Conclusion

These results reveal that the MAZ/MAP2K2/ERK signaling axis plays a crucial role in promoting ccRCC progression, which suggests the potential therapeutic utility of MAZ in ccRCC.
Chemodynamic nanomaterials for cancer theranostics
Authors: Xin Jingqi , Deng Caiting , Aras Omer , Zhou Mengjiao , Wu Chunsheng , An Feifei
Published: June 2021

It is of utmost urgency to achieve effective and safe anticancer treatment with the increasing mortality rate of cancer. Novel anticancer drugs and strategies need to be designed for enhanced therapeutic efficacy. Fenton- and Fenton-like reaction-based chemodynamic therapy (CDT) are new strategies to enhance anticancer efficacy due to their capacity to generate reactive oxygen species (ROS) and oxygen (O2). On the one hand, the generated ROS can damage the cancer cells directly. On the other hand, the generated O2 can relieve the hypoxic condition in the tumor microenvironment (TME) which hinders efficient photodynamic therapy, radiotherapy, etc. Therefore, CDT can be used together with many other therapeutic strategies for synergistically enhanced combination therapy. The antitumor applications of Fenton- and Fenton-like reaction-based nanomaterials will be discussed in this review, including: (iþ) producing abundant ROS in-situ to kill cancer cells directly, (ii) enhancing therapeutic efficiency indirectly by Fenton reaction-mediated combination therapy, (iii) diagnosis and monitoring of cancer therapy. These strategies exhibit the potential of CDT-based nanomaterials for efficient cancer therapy.
Nephrectomy improves the survival of metastatic renal cell cancer patients with moderate to good performance status—results from a Finnish nation-wide population-based study from 2005 to 2010
Authors: Laru Lauri , Ronkainen Hanna , Ohtonen Pasi , Vaarala Markku H.
Published: June 2021

Background

The purpose of this study was to evaluate the effects of cytoreductive nephrectomy (CN) and metastasectomies on the survival of patients with synchronous metastatic renal cell cancer (mRCC) using real-life, population-based national dataset.

Methods

Nationwide data, including all cases of synchronous mRCC in Finland diagnosed on a 6-year timeframe, based on the Finnish Cancer Registry and complemented with patient records from the treating hospitals, were analyzed. Patients with Eastern Cooperative Oncology Group (ECOG) performance status 3–4 were excluded. Univariate and adjusted multivariable survival analysis were performed, including subgroup analysis for patients with different medical therapies. Nephrectomy complications were also analyzed.

Results

A total of 732 patients were included in the analysis. CN was performed for 389 (53.1%) patients, whereas 68 (9.3%) patients underwent nephrectomy and metastasectomies of all lesions (surgery with curative intent). Median overall survival (OS) for patients who did not undergo nephrectomy was 5.9 (95% confidence interval [CI] = 4.6–7.2) months. Patients who had a CN had a median OS of 16.6 (95% CI = 14.2–19.1, p < 0.001) months, whereas patients who had surgery with curative intent had a median OS of 51.3 (95% CI = 36.0–66.6, p < 0.001) months. The survival benefit of CN and metastasectomies remained significant in all medical therapy subgroups and in both of the applied multivariable statistical models.

Conclusions

Surgical treatment of metastatic renal cell cancer is associated with a significant survival benefit in patients with good and moderate performance status, regardless of the chosen medical therapy.
Using the longest run subsequence problem within homology-based scaffolding
Authors: Schrinner Sven , Goel Manish , Wulfert Michael , Spohr Philipp , Schneeberger Korbinian , Klau Gunnar W.
Published: June 2021

Genome assembly is one of the most important problems in computational genomics. Here, we suggest addressing an issue that arises in homology-based scaffolding, that is, when linking and ordering contigs to obtain larger pseudo-chromosomes by means of a second incomplete assembly of a related species. The idea is to use alignments of binned regions in one contig to find the most homologous contig in the other assembly. We show that ordering the contigs of the other assembly can be expressed by a new string problem, the longest run subsequence problem (LRS). We show that LRS is NP-hard and present reduction rules and two algorithmic approaches that, together, are able to solve large instances of LRS to provable optimality. All data used in the experiments as well as our source code are freely available. We demonstrate its usefulness within an existing larger scaffolding approach by solving realistic instances resulting from partial Arabidopsis thaliana assemblies in short computation time.
Gene expression analysis in EBV-infected ataxia-telangiectasia cell lines by RNA-sequencing reveals protein synthesis defect and immune abnormalities
Authors: Tatfi Moussab , Perthame Emeline , Hillion Kenzo-Hugo , Dillies Marie-Agnès , Menager Hervé , Hermine Olivier , Suarez Felipe
Published: June 2021

Background

Epstein–Barr virus (EBV) targets B-cells where it establishes a latent infection. EBV can transform B-cells in vitro and is recognized as an oncogenic virus, especially in the setting of immune compromise. Indeed, immunodeficient patients may fail to control chronic EBV infection, leading to the development EBV-driven lymphoid malignancies. Ataxia telangiectasia (AT) is a primary immune deficiency caused by mutations in theATMgene, involved in the repair of double-strand breaks. Patients with AT are at high risk of developing cancers, mostly B-cell lymphoid malignancies, most of which being EBV-related. Aside from immune deficiency secondary to AT, loss of ATM function could also hinder the control of the virus within B-cells, favoring lymphomagenesis in AT patients.

Results

We used RNA sequencing on lymphoblastoid cell lines derived from patients with AT and healthy donors to analyze and compare both cellular and viral gene expression. We found numerous deregulated signaling pathways involving transcription, translation, oncogenesis and immune regulation. Specifically, the translational defect was confirmed in vitro, suggesting that the pathogenesis of AT may also involve a ribosomal defect. Concomitant analysis of viral gene expression did not reveal significant differential gene expression, however, analysis of EBV interactome suggests that the viral latency genes EBNA-3A, EBNA-3C and LMP1 may be disrupted in LCL from AT patients.

Conclusion

Our data support the notion that ATM deficiency deregulates cellular gene expression possibly disrupting interactions with EBV latent genes, promoting the oncogenic potential of the virus. These preliminary findings provide a new step towards the understanding of EBV regulation and of AT pathogenesis.
Cancer: a mirrored room between tumor bulk and tumor microenvironment
Authors: Hernández-Camarero Pablo , López-Ruiz Elena , Marchal Juan Antonio , Perán Macarena
Published: June 2021

It has been well documented that the tumor microenvironment (TME) plays a key role in the promotion of drug resistance, the support of tumor progression, invasiveness, metastasis, and even the maintenance of a cancer stem-like phenotype. Here, we reviewed TME formation presenting it as a reflection of a tumor’s own organization during the different stages of tumor development. Interestingly, functionally different groups of stromal cells seem to have specific spatial distributions within the TME that change as the tumor evolves into advanced stage progression which correlates with the fact that cancer stem-like cells (CSCs) are located in the edges of solid tumor masses in advanced tumors.

We also focus on the continuos feedback that is established between a tumor and its surroundings. The “talk” between tumor mass cells and TME stromal cells, marks the evolution of both interlocuting cell types. For instance, the metabolic and functional transformations that stromal cells undergo due to tumor corrupting activity.

Moreover, the molecular basis of metastatic spread is also approached, making special emphasis on the site-specific pre-metastatic niche formation as another reflection of the primary tumor molecular signature.

Finally, several therapeutic approaches targeting primary TME and pre-metastatic niche are suggested. For instance, a systematic analysis of the TME just adjacent to the tumor mass to establish the proportion of myofibroblasts-like cancer-associated fibroblasts (CAFs) which may in turn correspond to stemness and metastases-promotion. Or the implementation of “re-education” therapies consisting of switching tumor-supportive stromal cells into tumor-suppressive ones. In summary, to improve our clinical management of cancer, it is crucial to understand and learn how to manage the close interaction between TME and metastasis.
A trans locus causes a ribosomopathy in hypertrophic hearts that affects mRNA translation in a protein length-dependent fashion
Authors: Witte Franziska , Ruiz-Orera Jorge , Mattioli Camilla Ciolli , Blachut Susanne , Adami Eleonora , Schulz Jana Felicitas , Schneider-Lunitz Valentin , Hummel Oliver , Patone Giannino , Mücke Michael Benedikt , Šilhavý Jan , Heinig Matthias , Bottolo Leonardo , Sanchis Daniel , Vingron Martin , Chekulaeva Marina , Pravenec Michal , Hubner Norbert , van Heesch Sebastiaan
Published: June 2021

Background

Little is known about the impact of trans-acting genetic variation on the rates with which proteins are synthesized by ribosomes. Here, we investigate the influence of such distant genetic loci on the efficiency of mRNA translation and define their contribution to the development of complex disease phenotypes within a panel of rat recombinant inbred lines.

Results

We identify several tissue-specific master regulatory hotspots that each control the translation rates of multiple proteins. One of these loci is restricted to hypertrophic hearts, where it drives a translatome-wide and protein length-dependent change in translational efficiency, altering the stoichiometric translation rates of sarcomere proteins. Mechanistic dissection of this locus across multiple congenic lines points to a translation machinery defect, characterized by marked differences in polysome profiles and misregulation of the small nucleolar RNA SNORA48. Strikingly, from yeast to humans, we observe reproducible protein length-dependent shifts in translational efficiency as a conserved hallmark of translation machinery mutants, including those that cause ribosomopathies. Depending on the factor mutated, a pre-existing negative correlation between protein length and translation rates could either be enhanced or reduced, which we propose to result from mRNA-specific imbalances in canonical translation initiation and reinitiation rates.

Conclusions

We show that distant genetic control of mRNA translation is abundant in mammalian tissues, exemplified by a single genomic locus that triggers a translation-driven molecular mechanism. Our work illustrates the complexity through which genetic variation can drive phenotypic variability between individuals and thereby contribute to complex disease.
Controlling bacteriological contamination of environmental surfaces at the biological isolation and containment unit of a veterinary teaching hospital
Authors: Verdial C. , Carneiro C. , Machado I. , Tavares L. , Almeida V. , Oliveira M. , Gil S.
Published: June 2021

Background

The Biological Isolation and Containment Unit (BICU) is a subunit of the Teaching Hospital of the Faculty of Veterinary Medicine of the University of Lisbon, Portugal, for the admission of animals with confirmed infectious diseases or under clinical suspicion and waiting for a diagnosis. As a high-risk environment for the transmission of infectious agents, it is extremely important to implement programs for the surveillance of nosocomial microorganisms in these facilities. The purpose of this study was to evaluate the level of bacterial contamination of the BICU environmental surfaces and to implement corrective actions on disinfection protocols. Swab samples were collected from selected environmental surfaces in 3 different areas of the BICU (isolation, work, and preparatory rooms) to evaluate the total aerobic bacterial load and investigate the presence of 4 nosocomial microorganisms: vancomycin-resistant Enterococcus spp., methicillin-resistant Staphylococcus aureus, 3rd-generation cephalosporin-resistant Escherichia coli, and carbapenem-resistant Pseudomonas aeruginosa. Bacterial quantification was performed by using non-selective media, while specific selective media were used for the isolation of the target microorganisms. Isolates were identified based on their macro and microscopic characteristics and their biochemical profile. Subsequently, new disinfection protocols were implemented, and their effectiveness evaluated.

Results

The surfaces with the highest bacterial load in the isolation, preparatory, and worker’s rooms were the cages, hand-held sponge, and telephone, respectively. Regarding the 4 pathogens investigated, Enterococcus spp. were the most frequently isolated (11.3%), followed by E. coli (1.5%) and P. aeruginosa (1.5%). One of the P. aeruginosa isolates obtained was resistant to imipenem. In the end, new disinfection protocols were implemented, which proved to be effective in reducing bacterial counts by 99.99% in cages and the sponge, and by 90 to 99% on the telephone.

Conclusions

This study allows to conclude that the cages and the human contact surfaces were the most contaminated in the isolation rooms. Nevertheless, the new disinfection strategies seemed to be effective in reducing environmental contamination, including by some potentially nosocomial agents, although more samples must be analyzed for definitive conclusions. These results may contribute to highlight the importance of infection prevention and control measures, as fundamental tools to reduce the spread of infectious agents in the hospital environment.
Estimating Previous Quantization Factors on Multiple JPEG Compressed Images
Authors: Battiato Sebastiano , Giudice Oliver , Guarnera Francesco , Puglisi Giovanni
Published: June 2021

The JPEG compression algorithm has proven to be efficient in saving storage and preserving image quality thus becoming extremely popular. On the other hand, the overall process leaves traces into encoded signals which are typically exploited for forensic purposes: for instance, the compression parameters of the acquisition device (or editing software) could be inferred. To this aim, in this paper a novel technique to estimate “previous” JPEG quantization factors on images compressed multiple times, in the aligned case by analyzing statistical traces hidden on Discrete Cosine Transform (DCT) histograms is exploited. Experimental results on double, triple and quadruple compressed images, demonstrate the effectiveness of the proposed technique while unveiling further interesting insights.
Novel insights into the genetically obese (ob/ob) and diabetic (db/db) mice: two sides of the same coin
Authors: Suriano Francesco , Vieira-Silva Sara , Falony Gwen , Roumain Martin , Paquot Adrien , Pelicaen Rudy , Régnier Marion , Delzenne Nathalie M. , Raes Jeroen , Muccioli Giulio G. , Van Hul Matthias , Cani Patrice D.
Published: June 2021

Background

Leptin-deficient ob/ob mice and leptin receptor-deficient db/db mice are commonly used mice models mimicking the conditions of obesity and type 2 diabetes development. However, although ob/ob and db/db mice are similarly gaining weight and developing massive obesity, db/db mice are more diabetic than ob/ob mice. It remains still unclear why targeting the same pathway—leptin signaling—leads to the development of two different phenotypes. Given that gut microbes dialogue with the host via different metabolites (e.g., short-chain fatty acids) but also contribute to the regulation of bile acids metabolism, we investigated whether inflammatory markers, bacterial components, bile acids, short-chain fatty acids, and gut microbes could contribute to explain the specific phenotype discriminating the onset of an obese and/or a diabetic state in ob/ob and db/db mice.

Results

Six-week-old ob/ob and db/db mice were followed for 7 weeks; they had comparable body weight, fat mass, and lean mass gain, confirming their severely obese status. However, as expected, the glucose metabolism and the glucose-induced insulin secretion were significantly different between ob/ob and db/db mice. Strikingly, the fat distribution was different, with db/db mice having more subcutaneous and ob/ob mice having more epididymal fat. In addition, liver steatosis was more pronounced in the ob/ob mice than in db/db mice. We also found very distinct inflammatory profiles between ob/ob and db/db mice, with a more pronounced inflammatory tone in the liver for ob/ob mice as compared to a higher inflammatory tone in the (subcutaneous) adipose tissue for db/db mice. When analyzing the gut microbiota composition, we found that the quantity of 19 microbial taxa was in some way affected by the genotype. Furthermore, we also show that serum LPS concentration, hepatic bile acid content, and cecal short-chain fatty acid profiles were differently affected by the two genotypes.

Conclusion

Taken together, our results elucidate potential mechanisms implicated in the development of an obese or a diabetic state in two genetic models characterized by an altered leptin signaling. We propose that these differences could be linked to specific inflammatory tones, serum LPS concentration, bile acid metabolism, short-chain fatty acid profile, and gut microbiota composition.
Microbiota long-term dynamics and prediction of acute graft-versus-host disease in pediatric allogeneic stem cell transplantation
Authors: Ingham Anna Cäcilia , Kielsen Katrine , Mordhorst Hanne , Ifversen Marianne , Aarestrup Frank M. , Müller Klaus Gottlob , Pamp Sünje Johanna
Published: June 2021

Background

Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) exhibit changes in their gut microbiota and are experiencing a range of complications, including acute graft-versus-host disease (aGvHD). It is unknown if, when, and under which conditions a re-establishment of microbial and immunological homeostasis occurs. It is also unclear whether microbiota long-term dynamics occur at other body sites than the gut such as the mouth or nose. Moreover, it is not known whether the patients’ microbiota prior to HSCT holds clues to whether the patient would suffer from severe complications subsequent to HSCT. Here, we take a holobiont perspective and performed an integrated host-microbiota analysis of the gut, oral, and nasal microbiota in 29 children undergoing allo-HSCT.

Results

The bacterial diversity decreased in the gut, nose, and mouth during the first month and reconstituted again 1–3 months after allo-HSCT. The microbial community composition traversed three phases over 1 year. Distinct taxa discriminated the microbiota temporally at all three body sides, includingEnterococcusspp.,Lactobacillusspp., andBlautiaspp. in the gut. Of note, certain microbial taxa appeared already changed in the patients prior to allo-HSCT as compared with healthy children. Acute GvHD occurring after allo-HSCT could be predicted from the microbiota composition at all three body sites prior to HSCT. The reconstitution of CD4+T cells, TH17, and B cells was associated with distinct taxa of the gut, oral, and nasal microbiota.

Conclusions

This study reveals for the first time bacteria in the mouth and nose that may predict aGvHD. Monitoring of the microbiota at different body sites in HSCT patients and particularly through involvement of samples prior to transplantation may be of prognostic value and could assist in guiding personalized treatment strategies. The identification of distinct bacteria that have a potential to predict post-transplant aGvHD might provide opportunities for an improved preventive clinical management, including a modulation of microbiomes. The host-microbiota associations shared between several body sites might also support an implementation of more feasible oral and nasal swab sampling-based analyses. Altogether, the findings suggest that the microbiota and host factors together could provide actionable information to guiding precision medicine.
Correction to: A novel splicing variant of ANXA11 in a patient with amyotrophic lateral sclerosis: histologic and biochemical features
Authors: Sainouchi Makoto , Hatano Yuya , Tada Mari , Ishihara Tomohiko , Ando Shoichiro , Kato Taisuke , Tokunaga Jun , Ito Gaku , Miyahara Hiroaki , Toyoshima Yasuko , Yokoseki Akio , Ozawa Tetsutaro , Akazawa Kohei , Onodera Osamu , Kakita Akiyoshi
Published: June 2021

An amendment to this paper has been published and can be accessed via the original article.
Hydrophilization of corn seeds by non-equilibrium gaseous plasma
Authors: Recek Nina , Vesel Alenka , Zaplotnik Rok , Paul Domen , Primc Gregor , Gselman Peter , Mozetič Miran
Published: June 2021

Plasma agriculture is a promising niche of interdisciplinary research where the physics, of non-equilibrium gases meets surface chemistry and biological responses. Despite numerous scientific papers, the interaction of gaseous plasma with seeds is not understood enough to make the technique useful in practical agriculture. An obstacle is an improper methodology adopted by different authors. In this paper, we show that the surface wettability does not depend on discharge parameters such as power and pressure, but rather on the fluence of oxygen atoms onto the seed surface. The proper methodology is demonstrated for the case of corn seeds. The surface activation, which enables improved water uptake or good adhesion of a coating, progresses relatively linearly up to the O-atom fluence of 3 × 1024 m−3 and remains constant thereafter. The minimal water contact angle achievable using oxygen plasma treatment is a few degrees.