bluuebunny/crossref_metadata_2025 huggingface dataset:
Exercise during CHemotherapy for Ovarian cancer (ECHO) trial: design and implementation of a randomised controlled trial
Authors: Hayes Sandra , Obermair Andreas , Mileshkin Linda , Davis Alison , Gordon Louisa G , Eakin Elizabeth , Janda Monika , Beesley Vanessa L , Barnes Elizabeth H , Spence Rosalind Renee , Sandler Carolina , Jones Tamara , Vagenas Dimitrios , Webb Penny , Andrews John , Brand Alison , Lee Yeh Chen , Friedlander Michael , Pumpa Kate , O’Neille Helene , Williams Merran ,   The ECHO Collaborative, Stockler Martin
Published: April 2023

Introduction

Epidemiological evidence supports an association between higher levels of physical activity and improved cancer survival. Trial evidence is now needed to demonstrate the effect of exercise in a clinical setting. TheExercise duringCHemotherapy forOvarian cancer (ECHO) trial is a phase III, randomised controlled trial, designed to determine the effect of exercise on progression-free survival and physical well-being for patients receiving first-line chemotherapy for ovarian cancer.

Methods and analysis

Participants (target sample size: n=500) include women with newly diagnosed primary ovarian cancer, scheduled to receive first-line chemotherapy. Consenting participants are randomly allocated (1:1) to either theexercise intervention(plus usual care) orusual carealone, with stratification for recruitment site, age, stage of disease and chemotherapy delivery (neoadjuvant vs adjuvant). The exercise intervention involves individualised exercise prescription with a weekly target of 150 minutes of moderate-intensity, mixed-mode exercise (equivalent to 450 metabolic equivalent minutes per week), delivered for the duration of first-line chemotherapy through weekly telephone sessions with a trial-trained exercise professional. The primary outcomes are progression-free survival and physical well-being. Secondary outcomes include overall survival, physical function, body composition, quality of life, fatigue, sleep, lymphoedema, anxiety, depression, chemotherapy completion rate, chemotherapy-related adverse events, physical activity levels and healthcare usage.

Ethics and dissemination

Ethics approval for the ECHO trial (2019/ETH08923) was granted by the Sydney Local Health District Ethics Review Committee (Royal Prince Alfred Zone) on 21 November 2014. Subsequent approvals were granted for an additional 11 sites across Queensland, New South Wales, Victoria and the Australian Capital Territory. Findings from the ECHO trial are planned to be disseminated via peer-reviewed publications and international exercise and oncology conferences.

Trial registration number

Australian New Zealand Clinical Trial Registry (ANZCTRN12614001311640;https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367123&isReview=true).
Improving employment outcomes for people with disability in small and medium enterprises: protocol for a scoping review
Authors: Keating Byron W , Worsteling Asha
Published: April 2023

Introduction

Improving the employment of people with disability (PWD) has emerged as a key priority for governments worldwide as a strategy for improving health outcomes through greater economic participation. However, a significant barrier remains the lack of understanding among businesses regarding the requirements for a disability-inclusive workplace. This challenge is particularly salient for small and medium enterprises (SMEs) that lack dedicated human resources to develop supportive organisational cultures. This scoping review will assist smaller businesses in enhancing their capacity to employ PWD by undertaking a synthesis of the factors that will enhance SME capacity to hire and retain PWDs.

Methods and analysis

This protocol uses the six-staged process for scoping reviews proposed by Arksey and O’Malley. This process begins with identifying the scoping review research question (Stage 1) and discussing how studies will be selected (Stage 2). The search will include all English-language articles within Web of Science, Scopus, PsycINFO, PubMed, Cochrane Library, Embase, Medline, EBSCO Global Health and CINAHL since inception. We will also include relevant secondary sources from the grey literature. Following the search process, we will present information on selecting studies for inclusion in the scoping review (Stage 3) and chart the data relating to the included studies (Stage 4). In conclusion, the scoping review protocol will synthesise and report the results (Stage 5) and provide information on consultation with relevant stakeholders during the initial protocol specifications (Stage 6).

Ethics and dissemination

Since the scoping review methodology aims at synthesising information from available publications, this study does not require ethical approval. We will submit an article reporting the results of the scoping review for publication in a scientific journal, present the findings at relevant conferences and disseminate them as part of future workshops with professionals in disability employment.
A little bit pregnant:towards a pluralist account of non-sexual reproduction
Authors: Hall Georgina Antonia
Published: April 2023

Fertility clinicians participate in non-sexual reproductive projects by providing assisted reproductive technology (ART) to those hoping to reproduce, in support of their reproductive goals. In most countries where ART is available, the state regulates ART as a form of medical treatment. The predominant position in the reproductive rights literature frames the clinician’s role as medical technician, and the state as a third party with limited rights to interfere. These roles broadly align with established functions of clinician and state in Western liberal democracies, where doctors have duties to provide safe, beneficial and legal healthcare to all who seek it. Recognised state responsibilities include safeguarding equitable access to medical services and protecting and promoting reproductive liberty.

I argue against this normative moral framing of clinician and state involvement in non-sexual reproduction, suggesting that clinician and state join the non-sexual reproductive project at the point of triggering conception. Begetting a child is more than just the provision and regulation of healthcare; it generates rights and confers responsibilities on all who join this morally significant project. All who collaborate have the right to join or refuse to join the project. I suggest this is intuitively understood in the sexual realm, but not in the non-sexual realm. My key substantive claim is that non-sexual reproduction is a pluralist pursuit that morally implicates more than the genetic and gestational contributors. I find that while the moral basis of a clinician or the state’s right to refuse to join the ART project is the same as for those providing gestational or genetic input, the reasons that morally underpin their refusal differs.
Strategic validation of variants of uncertain significance inECHS1genetic testing
Authors: Kishita Yoshihito , Sugiura Ayumu , Onuki Takanori , Ebihara Tomohiro , Matsuhashi Tetsuro , Shimura Masaru , Fushimi Takuya , Ichino Noriko , Nagatakidani Yoshie , Nishihata Hitomi , Nitta Kazuhiro R , Yatsuka Yukiko , Imai-Okazaki Atsuko , Wu Yibo , Osaka Hitoshi , Ohtake Akira , Murayama Kei , Okazaki Yasushi
Published: April 2023

Background

Enoyl-CoA hydratase short-chain 1 (ECHS1) is an enzyme involved in the metabolism of branched chain amino acids and fatty acids. Mutations in theECHS1gene lead to mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, resulting in the accumulation of intermediates of valine. This is one of the most common causative genes in mitochondrial diseases. While genetic analysis studies have diagnosed numerous cases withECHS1variants, the increasing number of variants of uncertain significance (VUS) in genetic diagnosis is a major problem.

Methods

Here, we constructed an assay system to verify VUS function forECHS1gene. A high-throughput assay usingECHS1knockout cells was performed to index these phenotypes by expressing cDNAs containing VUS. In parallel with the VUS validation system, a genetic analysis of samples from patients with mitochondrial disease was performed. The effect on gene expression in cases was verified by RNA-seq and proteome analysis.

Results

The functional validation of VUS identified novel variants causing loss ofECHS1function. The VUS validation system also revealed the effect of the VUS in the compound heterozygous state and provided a new methodology for variant interpretation. Moreover, we performed multiomics analysis and identified a synonymous substitution p.P163= that results in splicing abnormality. The multiomics analysis complemented the diagnosis of some cases that could not be diagnosed by the VUS validation system.

Conclusions

In summary, this study uncovered newECHS1cases based on VUS validation and omics analysis; these analyses are applicable to the functional evaluation of other genes associated with mitochondrial disease.
Contact patterns of UK home delivery drivers and their use of protective measures during the COVID-19 pandemic: a cross-sectional study
Authors: Bridgen Jessica R E , Wei Hua , Whitfield Carl , Han Yang , Hall Ian , Jewell Chris P , van Tongeren Martie J A , Read Jonathan M
Published: April 2023

Objectives

To quantify contact patterns of UK home delivery drivers and identify protective measures adopted during the pandemic.

Methods

We conducted a cross-sectional online survey to measure the interactions of 170 UK delivery drivers during a working shift between 7 December 2020 and 31 March 2021.

Results

Delivery drivers had a mean number of 71.6 (95% CI 61.0 to 84.1) customer contacts per shift and 15.0 (95% CI 11.2 to 19.2) depot contacts per shift. Maintaining physical distancing with customers was more common than at delivery depots. Prolonged contact (more than 5 min) with customers was reported by 5.4% of drivers on their last shift. We found 3.0% of drivers had tested positive for SARS-CoV-2 since the start of the pandemic and 16.8% of drivers had self-isolated due to a suspected or confirmed case of COVID-19. In addition, 5.3% (95% CI 2.3% to 10.2%) of participants reported having worked while ill with COVID-19 symptoms, or with a member of their household having a suspected or confirmed case of COVID-19.

Conclusion

Delivery drivers had a large number of face-to-face customer and depot contacts per shift compared with other working adults during this time. However, transmission risk may be curtailed as contact with customers was of short duration. Most drivers were unable to maintain physical distance with customers and at depots at all times. Usage of protective items such as face masks and hand sanitiser was widespread.
Mechanisms of vocational interventions for return to work from musculoskeletal conditions: a mediation analysis of the MI-NAV trial
Authors: Cashin Aidan G , Øiestad Britt Elin , Aanesen Fiona , Storheim Kjersti , Tingulstad Alexander , Rysstad Tarjei Langseth , Lee Hopin , McAuley James H , Sowden Gail , Wynne-Jones Gwenllian , Tveter Anne Therese , Grotle Margreth
Published: April 2023

Objectives

To investigate whether and to what extent, return to work (RTW) expectancy and workability mediate the effect of two vocational interventions on reducing sickness absence in workers on sick leave from a musculoskeletal condition.

Methods

This is a preplanned mediation analysis of a three-arm parallel randomised controlled trial which included 514 employed working adults with musculoskeletal conditions on sick leave for at least 50% of their contracted work hours for ≥7 weeks. Participants were randomly allocated (1:1:1) to one of three treatment arms; usual case management (UC) (n=174), UC plus motivational interviewing (MI) (n=170) and UC plus a stratified vocational advice intervention (SVAI) (n=170). The primary outcome was the number of sickness absence days over 6 months from randomisation. Hypothesised mediators included RTW expectancy and workability assessed 12 weeks after randomisation.

Results

The mediated effect of the MI arm compared with UC on sickness absence days through RTW expectancy was −4.98 days (−8.89 to −1.04), and workability was −3.17 days (−8.55 to 2.32). The mediated effect of the SVAI arm compared with UC on sickness absence days through RTW expectancy was −4.39 days (−7.60 to −1.47), and workability was −3.21 days (−7.90 to 1.50). The mediated effects for workability were not statistically significant.

Conclusions

Our study provides new evidence for the mechanisms of vocational interventions to reduce sickness absence related to sick leave due to musculoskeletal conditions. Changing an individual’s expectation that RTW is likely may result in meaningful reductions in sickness absence days.

Trial registration number

NCT03871712.
The most important theoretical developments leading to the current understanding of heavy-element stability
Authors: Möller Peter
Published: April 2023

We discuss the sequence of developments that over the past 90 years led to current insights on heavy-element stability. The semi-empirical mass model, and its extension to deformed shapes, developed in the period 1936–1950 allowed the interpretation of nuclear fission. Around 1950 the spherical single-particle model was developed, soon after with extension to deformed nuclei. Speculations about a shell-stabilized region of spherical heavy elements near $$Z=126$$

Z
=
126

were made. In the 1960ies Strutinsky combined the single-particle and macroscopic liquid-drop models into a unified picture, the shell-correction, or macroscopic-microscopic method. Now it was also realized that although $$Z=126$$

Z
=
126

was present, an often stronger spherical gap in calculated proton single-particle level diagrams, $$Z=114$$

Z
=
114

, was also present, but its significance had previously been overlooked. A large number of studies of the stability of nuclei in the “shell-stabilized” region surrounding $$Z=114$$

Z
=
114

and $$N=184$$

N
=
184

followed. Initially the assumption was that elements just beyond the actinides, would be too unstable to be observed. The 1970ies saw considerable work in refining the initial single-particle and macroscopic models. This set the stage for global studies, which took off in the 1980ies and have continued until today. The more accurate nuclear-structure models allowed calculations of masses, decay-chain properties and branching between different decay modes to useful accuracy and predictive quality. A completely unexpected result was that the calculations showed the existence of an area of relatively stable deformed nuclei in the presumed “sea of instability” between the actinides and the next postulated spherical magic numbers.
Measurement of the cosmic charged particle rate at sea level in the latitude range 35$$^{\circ }$$ $$\div $$ 82$$^{\circ }$$ N with the PolarquEEEst experiment
Authors: Abbrescia M. , Avanzini C. , Baldini L. , Ferroli R. Baldini , Batignani G. , Battaglieri M. , Boi S. , Bossini E. , Carnesecchi F. , Cavazza D. , Cicalò C. , Cifarelli L. , Coccetti F. , Coccia E. , Corvaglia A. , De Gruttola D. , De Pasquale S. , Galante L. , Garbini M. , Gemme G. , Gnesi I. , Gramstad E. , Grazzi S. , Håland E. S. , Hatzifotiadou D. , La Rocca P. , Liu Z. , Lombardo L. , Mandaglio G. , Margotti A. , Maron G. , Mazziotta M. N. , Mulliri A. , Nania R. , Noferini F. , Nozzoli F. , Ould-Saada F. , Palmonari F. , Panareo M. , Panetta M. P. , Paoletti R. , Parvis M. , Pellegrino C. , Perasso L. , Pinazza O. , Pinto C. , Pisano S. , Riggi F. , Righini G. , Ripoli C. , Rizzi M. , Sartorelli G. , Scapparone E. , Schioppa M. , Scioli G. , Scribano A. , Selvi M. , Taiuti M. , Terreni G. , Trifirò A. , Trimarchi M. , Vistoli C. , Votano L. , Williams M. C. S. , Zichichi A. , Zuyeuski R.
Published: April 2023

After its successful campaign of measurements beyond the Polar Arctic Circle, the PolarquEEEst experiment measured the cosmic charged particle rate at sea level in a latitude interval between 35$$^{\circ }$$

∘

N and 82$$^{\circ }$$

∘

N. In this paper, these measurements are described and the corresponding results are discussed.
A Single Image Dehazing Method Based on End-to-End CPAD-Net Network in Deep Learning Environment
Authors: Song Chaoda , Liu Jun
Published: April 2023

To address the issues of blurred details and distortion of color in the images recovered by the original AOD-Net dehazing method, this paper proposes a CPAD-Net dehazing network model based on attention mechanism and dense residual blocks. The network is improved on the basis of AOD-Net, which can reduce the errors arising from the separately determined transmittance and atmospheric light values. A new dense residual block structure is designed to replace the traditional convolution method, which effectively improves the detail processing capability and the representation ability of the network model for image feature information. On this basis, the attention module determines how to learn the weights according to the feature importance of distinct channels and distinct pixels, and then obtain the recovery of images in terms of color and texture. The experiments showed that the dehazing efficiency of our method are richer in texture detail information and more natural in color recovery. Compared with other algorithms, the PSNR and SSIM indexes of our method are considerably superior to those listed algorithms, which definitively demonstrates that the dehazing effect of our method is more effective, and the recovered images are more realistic and natural.
Corrigendum to Reducing ω-model reflection to iterated syntactic reflection
Authors: Pakhomov Fedor , Walsh James
Published: April 2023

We fix a gap in a proof in our paper Reducing [Formula: see text]-model reflection to iterated syntactic reflection.
Liquidity Creation, Bank Competition and Revenue Diversification
Authors: Tran Vuong Thao , Nguyen Hoa
Published: April 2023

We examine the individual and joint effects of bank competition and revenue diversification on liquidity creation. We find that bank competition and revenue diversification have a positive impact on banks’ propensity to create liquidity. Competition appears to primarily impact on-balance-sheet liquidity creation while revenue diversification is a key driver of off-balance-sheet liquidity creation. When considered together, each has a moderating effect on the other in relation to liquidity creation suggesting a substitution effect between competition and revenue diversification. Such substitution effect, however, is found predominantly for small and medium banks and during crisis periods. Our findings suggest that policymakers and regulators should be cautious of a one-size-fits-all approach to bank competition and revenue diversification in promoting bank stability.
Stock Price Trends Prediction Based on the Classical Models with Key Information Fusion of Ontologies
Authors: Jin Dawei , Hu Yiyi , Chen Jingyu , Xia Mengran
Published: April 2023

An ontology of the financial field can support effective association and integration of financial knowledge. Based on behavioral finance, social media is increasingly applied as one of the data sources for information fusion in stock forecasting to approximate the patterns of market changes. By predicting Tesla (TSLA) stock price trends, this study finds that satisfactory forecasting results can be achieved using classical models and incorporating key information features from the technical indicator ontology class and the investor behavior ontology class, even in the face of the impact of the COVID-19 epidemic. In the post-epidemic period, the
back propagation neural network (BPNN)
model is used to predict the price trend of TSLA for the next five trading days with an accuracy of up to 91.34%, an F1 score of 0.91, and a return of up to 268.42% obtained from simulated trading. This study extends the research on stock forecasting using fused information in the ontology of the financial field, providing a new basis for general investors in the selection of fusion information and the application of trading strategies and providing effective support for organizations to make intelligent financial decisions under uncertainty.
Commensal microbiota regulate renal gene expression in a sex-specific manner
Authors: Moore Brittni N. , Pluznick Jennifer L.
Published: April 2023

It is unknown whether the microbiome influences host gene expression in the kidney. Here, we utilized an unbiased, bulk RNA-sequencing approach to compare gene expression in the kidneys of male and female mice with or without gut microbiota. This report demonstrates that renal gene expression is modulated by the microbiome in a sex- and tissue-specific manner.
Risk Assessment of Water and Sand Inrush in Mining under Thick Loose Layer Based on Comprehensive Weight-Cloud Model
Authors: Zhang Wenquan , Wu Xintao , Wu Xunan , Lei Yu , Shao Jianli , Wang Zaiyong
Published: April 2023

Many deep mining mines in southwestern Shandong Province of China are covered with thick loose layers. When mining near the loose layers, there is a risk of water and sand inrush, which threatens the personal safety of miners. The prediction of sudden water and sand inrush is difficult due to the comprehensive influence of many factors, and the influencing factors are fuzzy and random. To solve this problem, in this paper, a new risk assessment method of water and sand inrush based on comprehensive weight and cloud model was proposed. Seven factors are selected as indexes: the aquifer thickness, the thickness ratio of sand layer to clay layer, the thickness of bottom clay layer, the coal seam thickness, the percentage of core recovery, the geological structure, and the bedrock thickness. The assessment index system is established, and the index is divided into three grades. A comprehensive weighting method, which combines analytic hierarchy process (AHP), entropy weight method (EWM), and minimum entropy principle, is used to reasonably assign the weight of index. Based on the cloud generator equation, the membership function is obtained. The assessment result of the assessment object is obtained by combining the membership degree and the weight of index. The comprehensive weight-cloud model assessment method is applied to the risk assessment of water and sand inrush in the 6311-2 working face in the sixth mining area of Baodian Coal Mine. According to the assessment results, the following conclusions can be drawn: (1) the bedrock thickness and the coal seam thickness are the main factors of water and sand inrush under loose layer mining; (2) the assessment results obtained by the comprehensive weight-cloud model method are consistent with the actual situation. The assessment method can provide scientific reference for the safe mining under the thick loose layer in the deep mines of southwest Shandong.
Multiple Myeloma in People of Working Age: A Systematic Review and Evidence Synthesis of Experiences of Paid and Unpaid Work
Authors: Forbat Liz , Sedgley Tim , Bellussi Laura
Published: April 2023

Introduction. This review sought to synthesise the qualitative evidence pertaining to the experiences of myeloma patients and relatives of work, given the distinct symptom burden and illness trajectory. Methods and Designs. CINAHL, Medline, Web of Science, PsychINFO, SocIndex were searched on 22-Apr-2022. No limiters were used for language or date of publication. CASP was used for critical appraisal. An integrative synthesis was conducted to inductively construct analytic themes PROSPERO CRD42022323137. Results. 34 articles were included, published from 2004 to 2022. Nineteen were assessed as having low risk of bias, and four with moderate risk of bias. The following four themes were derived from analysis of the papers: (i) side effects, medicines, and stigma; (ii) relationships; (iii) creation and maintenance of identity; (iv) privilege and income. Conclusion. Myeloma impacts the engagement of patients and relatives in paid and unpaid work, yet very little is currently known on how the cancer impacts these important interdependent systems. Addressing workplace stigma, understanding the role of workplace relationships, the construction of self through work, interpreting data through a lens of life-course and, privilege offer helpful starting points.
Robust Frequency Control of Microgrids: A Mixed

H

2

/

H

∞

Virtual Inertia Emulation
Authors: Maleki Shahryar , Nikoukar Javad , Tousifian Mohammad Hassan
Published: April 2023

This article proposes a robust inertial controller for converter-based distributed generators employed in low-inertia power systems like microgrids. The increasing penetration level of renewable energy sources based on power electronics converters in modern power systems reduces the inertial features of the system. It also increases concerns associated with the system uncertainty and sensitivity against disturbances. To cope with these challenges, by employing the proposed linear matrix inequality (LMI)-based mixed

H

2

/

H

∞

robust method, an optimal robust controller aided for inertial support as well as fast frequency restoration is provided. Using the proposed solution not only presents a better inertial response but also proposes a faster frequency restoration, by which the system’s frequency can be restored immediately following any disturbance, even in the presence of system uncertainties. Through in-detailed frequency response analysis and time-domain simulations for different scenarios, it is illustrated that the proposed mechanism can be successfully employed to address the inertial requirements in power electronic-based power systems. In addition, the proposed LMI-based mixed

H

2

/

H

∞

control solution is compared with a number of other solutions to illustrate its better performance against disturbances. Simulation results validate the merits and effectiveness of the proposed controller.
Table S7 from Genome-wide CRISPR screen reveals RAB10 as a synthetic lethal gene in colorectal and pancreatic cancers carrying SMAD4 loss.
Authors: Erasimus Helene , Kolnik Vanessa , Lacroix Frederic , Sidhu Sukhvinder S , D'Agostino Stephane , Lemaitre Olivier , Rohaut Alexandre , Sanchez Isabelle , Thill Gilbert , Didier Michel , Debussche Laurent , Marcireau Christophe
Published: April 2023

sgRNAs against RAB10
Supplementary Figure 7 from Genome-wide CRISPR screen reveals RAB10 as a synthetic lethal gene in colorectal and pancreatic cancers carrying SMAD4 loss.
Authors: Erasimus Helene , Kolnik Vanessa , Lacroix Frederic , Sidhu Sukhvinder S , D'Agostino Stephane , Lemaitre Olivier , Rohaut Alexandre , Sanchez Isabelle , Thill Gilbert , Didier Michel , Debussche Laurent , Marcireau Christophe
Published: April 2023

Proteins level assessment by western blotting
Data from Genome-wide CRISPR Screen Reveals RAB10 as a Synthetic Lethal Gene in Colorectal and Pancreatic Cancers Carrying SMAD4 Loss
Authors: Erasimus Hélène , Kolnik Vanessa , Lacroix Frédéric , Sidhu Sukhvinder , D'Agostino Stéphane , Lemaitre Olivier , Rohaut Alexandre , Sanchez Isabelle , Thill Gilbert , Didier Michel , Debussche Laurent , Marcireau Christophe
Published: April 2023

The TGFβ signaling mediator SMAD4 is frequently mutated or deleted in colorectal and pancreatic cancers. SMAD4 acts as a tumor suppressor and its loss is associated with poorer patient outcomes. The purpose of this study was to find synthetic lethal interactions with SMAD4 deficiency to find novel therapeutic strategies for the treatment of patients with SMAD4-deficient colorectal or pancreatic cancers. Using pooled lentiviral single-guide RNA libraries, we conducted genome-wide loss-of-function screens in Cas9-expressing colorectal and pancreatic cancer cells harboring altered or wild-type SMAD4. The small GTPase protein RAB10 was identified and validated as a susceptibility gene in SMAD4-altered colorectal and pancreatic cancer cells. Rescue assays showed that RAB10 reintroduction reversed the antiproliferative effects of RAB10 knockout in SMAD4-negative cell lines. Further investigation is necessary to shed light on the mechanism by which RAB10 inhibition decreases cell proliferation of SMAD4-negative cells.
Significance:
This study identified and validated RAB10 as new synthetic lethal gene with SMAD4. This was achieved by conducting a whole-genome CRISPR screens in different colorectal and pancreatic cell lines. A future RAB10 inhibitors could correspond to a new therapeutic solution for patients with cancer with SMAD4 deletion.
Data from Genome-wide CRISPR screen reveals RAB10 as a synthetic lethal gene in colorectal and pancreatic cancers carrying SMAD4 loss.
Authors: Erasimus Helene , Kolnik Vanessa , Lacroix Frederic , Sidhu Sukhvinder S , D'Agostino Stephane , Lemaitre Olivier , Rohaut Alexandre , Sanchez Isabelle , Thill Gilbert , Didier Michel , Debussche Laurent , Marcireau Christophe
Published: April 2023

Abstract
The TGF-β signaling mediator SMAD4 is frequently mutated or deleted in colorectal and pancreatic cancers. SMAD4 acts as a tumor suppressor and its loss is associated with poorer patient outcomes. The purpose of this study was to find synthetic lethal interactions with SMAD4 deficiency in order to find novel therapeutic strategies for the treatment of patients with SMAD4-deficient colorectal or pancreatic cancers. Using pooled lentiviral sgRNA libraries, we conducted genome-wide loss-of-function screens in Cas9-expressing colorectal and pancreatic cancer cells harboring altered or wild-type SMAD4. The small GTPase protein RAB10 was identified and validated as a susceptibility gene in SMAD4-altered colorectal and pancreatic cancer cells. Rescue assays showed that RAB10 re-introduction reversed the anti-proliferative effects of RAB10 KO in SMAD4 negative cell lines. Further investigation is necessary to shed light on the mechanism by which RAB10 inhibition decreases cell proliferation of SMAD4-negative cells.
Breastfeeding Success and Newborn Health before and during the COVID-19 Pandemic:A Single-Centre Comparative Study
Authors: Lapillonne Alexandre , Pichon Christine , Renaudin Benoit , Nicloux Muriel , Rigourd virginie , Ville Yves
Published: April 2023

Introduction: Due to the SARS-CoV-2 pandemic, adjustments in patient and visitor traffic were made in hospitals to limit viral exposure. The primary objective of our study was to compare the breastfeeding success of healthy newborns in a maternity ward during the 2020 lockdown period compared with the same period in the previous year. Material and Methods: Single-center comparative study based on prospectively collected data. All neonates born alive, from a single pregnancy, and with a gestational age greater than 36 weeks were considered for this study. Results: 309 infants born in 2020 and 330 born in 2019 were included. Among women who desired to exclusively breastfeed, the rate of exclusive breastfeeding at discharge from the maternity ward was higher in 2020 than in 2019 (85 vs. 79%; p = 0.078). After logistic regression analysis adjusted for potential confounders (i.e., maternal BMI, parity, mode of delivery, gestational age, and size at birth), study period remained significantly and independently associated with exclusive breastfeeding at discharge (OR [95% CI] = 1.645 [1.005; 2.694]; p = 0.046). Newborns born in 2020 were less likely to have weight loss ≥10% than those born in 2019 (OR [95% CI] = 2.596 [1.148; 5.872]; p = 0.017) but had similar need for phototherapy (p = 0.41). Conclusion: The success of exclusive breastfeeding during the 2020 lockdown period was increased compared with the same period in 2019.
The Two-Way Route between Delirium Disorder and Dementia: Insights from COVID-19
Authors: Bommarito Giulia , Garibotto Valentina , Frisoni Giovanni B , Assal Frédéric , Lalive Patrice H , Allali Gilles
Published: April 2023

Background: Delirium disorder is a frequent neurological complication of SARS-CoV-2 infection and associated with increased disease severity and mortality. Cognitive impairment is a major risk factor for developing delirium disorder during COVID-19, which, in turn, increases the risk of subsequent neurological complications and cognitive decline. Summary: The bidirectional connection between delirium disorder and dementia likely resides at multiple levels, and its pathophysiological mechanisms during COVID-19 include endothelial damage, blood-brain barrier dysfunction, and local inflammation, with activation of microglia and astrocytes. Here, we describe the putative pathogenic pathways underlying delirium disorder during COVID-19 and highlight how they cross with the ones leading to neurodegenerative dementia. Key Messages: The analysis of the two-sided link can offer useful insights for confronting with long-term neurological consequences of COVID-19 and framing future prevention and early treatment strategies.
Early versus Delayed Tumor-Specific Therapy and Survival in Patients with Lung Cancer: A Retrospective Study
Authors: Geiken-Weinstock Rike , Reyners Anna K.L. , Griesinger Frank , Otremba Burkhard Joerg , Hoheisel Michael , Bäsecke Jörg
Published: April 2023

Introduction: The timing of tumor-specific palliative therapy and its influence on the survival of patients with stage IV lung cancer remain unclear. Methods: 375 patients with stage IV lung cancer who experienced an early or delayed therapy (early or delayed therapy group [TG]) were investigated using histology and ECOG performance score (ECOG-PS)-related subgroups. Kaplan-Meier and Cox regression analyses were used for survival analyses. Results: Patients in the early TG had a significantly shorter median overall survival (OS) than those in the delayed TG (6 vs. 11 months). Patients with an ECOG-PS of ≥1 were significantly more present in the early TG than in the delayed TG (66.8 vs. 51.9%). But an early therapy was also significantly associated to a shorter median OS in ECOG-matched subgroups (ECOG-PS of 0, 7 vs. 23 months; ECOG ≥1, 6 vs. 8 months). An early therapy was associated to a significantly worse median OS in histological subgroups (NSCLC, 5 vs. 11 months; SCLC, 7 vs. 11 months) and was an independent risk factor in uni- and multivariate analyses. Conclusions: An early initiation of cancer-specific therapy was associated with a shorter survival time in palliative lung cancer patients, independent of the ECOG-PS and histological subtype.
Health Profiles among Community-Dwelling Older Adults with Cognitive Impairment and Their Implications for Caregiving Experience
Authors: Sung Pildoo , Lim-Soh Jeremy , Chan Angelique
Published: April 2023

Introduction: Identifying health conditions of persons with cognitive impairment (PCI) in the community and exploring their implications for caregiving experience are vital for effective allocation of healthcare resources. This study examined distinct PCI health profiles among community-dwelling PCI and their association with caregiving burden and benefits. Methods: Latent profile analysis and multivariable regression were applied to dyadic data from 266 PCI and their caregivers in Singapore. Results: Three PCI health profiles were identified: less impaired (40% of PCI), moderately impaired (30%), and severely impaired (30%). Caregivers for severely impaired PCI were more likely to report a higher level of caregiving burden, and caregivers for moderately impaired PCI were more likely to report a higher level of caregiving benefits, compared to caregivers for less impaired PCI. Conclusion: The findings captured heterogeneity in health status among PCI in the community. Tailored interventions, based on PCI health profiles, should be designed to reduce caregiving burden and increase caregiving benefits.
Robertsonian Fusion Site in Rineloricaria pentamaculata (Siluriformes: Loricariidae): Involvement of 5S Ribosomal DNA and Satellite Sequences
Authors: Glugoski Larissa , Deon Geize A. , Nogaroto Viviane , Moreira-Filho Orlando , Vicari Marcelo Ricardo
Published: April 2023

Cytogenetic studies demonstrated that unstable chromosomal sites in armored catfishes (Loricariidae) triggered intense karyotypic diversification, mainly derived from Robertsonian rearrangements. In Loricariinae, the presence of ribosomal DNA (rDNA) clusters and their flanking repeated regions (such as microsatellites or partial transposable element sequences) was proposed to facilitate chromosomal rearrangements. Hence, this study aimed to characterize the numerical chromosomal polymorphism observed in Rineloricaria pentamaculata and evaluate the chromosomal rearrangements which originated diploid chromosome number (2n) variation, from 56 to 54. Our data indicate a centric fusion event between acrocentric chromosomes of pairs 15 and 18, bearing 5S rDNA sites on their short (p) arms. This chromosome fusion established the numerical polymorphism, decreasing the 2n from original 56 (karyomorph A) to 55 in karyomorph B and 54 in karyomorph C. Although vestiges of telomeric sequences were evidenced at the fusion point, no 5S rDNA was detected in this region. The acrocentric chromosomes involved in the origin of the fusion were enriched with (CA)n and (GA)n microsatellites. Repetitive sequences in the acrocentric chromosomes subtelomeres have facilitated the rearrangement. Our study thus reinforces the view on the important role of particular repetitive DNA classes in promoting chromosome fusions which frequently drive Rineloricaria karyotype evolution.
O lugar da ética na crítica da economia política do jovem Marx
Authors: Rosa Otto Sanchez-Crespo da
Published: April 2023

O presente artigo visa analisar os Manuscritos econômico-filosóficos de 1844 em vista da dimensão ética presente na crítica da economia política. Em linhas gerais, trata-se de compreender em que medida certa concepção da essência humana baliza a crítica. Para tanto, a investigação é dividida em quatro momentos, nas críticas ao “cinismo da economia política”, ao “trabalho alienado”, ao dinheiro e à “moral da economia política”.
Palinofácies de uma seção aflorante de folhelhos da Formação Barreirinha (Devoniano), borda sul da Bacia do Amazonas, Brasil: implicações paleoambientais
Authors: Souza Iasmine Maciel Silva , Dino Rodolfo , Antonioli Luzia , Ribeiro Hélio Jorge Portugal Severiano , Cerqueira José Roberto , Andrade Consuelo Lima Navarro de , Garcia Karina Santos , Queiroz Antônio Fernando de Souza , Teixeira Leonardo Sena Gomes
Published: April 2023

O presente trabalho tem como objetivo estudar as palinofácies e o paleoambiente deposicional da Formação Barreirinha e sua relação com a geoquímica orgânica de estudos prévios, na porção sul da Bacia do Amazonas, Brasil. Para isso, aplicaram-se técnicas de análises de palinofácies e os resultados da geoquímica orgânica (carbono orgânico total e pirólise Rock-Eval) em 23 amostras de folhelhos de uma seção aflorante da Formação Barreirinha (Devoniano), borda sul da Bacia do Amazonas. Com a análise da palinofácies, verificou-se que há uma predominância de matéria orgânica de origem marinha: matéria orgânica amorfa (MOA) e acritarcas. As associações palinológicas indicaram que a sedimentação da Formação Barreirinha ocorreu, inicialmente, em ambiente marinho distal óxico-anóxico, gradando para ambiente deposicional marinho distal anóxico. A integração dos resultados daanálise de palinofácies, associada com os dados de estudos prévios, possibilitou a identificação de dois níveis de predominância do querogênio: tipo II, na porção média a superior da seção; e tipos III e II/III, na porção inferior da seção. Com os resultados das análises de geoquímica orgânica, verificou-se que o material apresenta bom potencial para geração de hidrocarbonetos, com base nos valores de COT que alcançaram percentuais de até 6,29%, S2 atingindo 23,1 (mg HC/g rocha), e o índice de hidrogênio (IH) com valores entre 69 e 377 (mg HC/g rocha). Os valores de Tmáx variaram de 425 a 435°C, e os valores de índice de coloração de esporos (ICE) entre 3,5 e 4,5, indicando imaturidade térmica para a geração de hidrocarbonetos.
Accelerated Vascular Aging in Chronic Kidney Disease: The Potential for Novel Therapies
Authors: Hobson S. , Arefin S. , Witasp A. , Hernandez L. , Kublickiene K. , Shiels P.G. , Stenvinkel P.
Published: April 2023

The pathophysiology of vascular disease is linked to accelerated biological aging and a combination of genetic, lifestyle, biological, and environmental risk factors. Within the scenario of uncontrolled artery wall aging processes, CKD (chronic kidney disease) stands out as a valid model for detailed structural, functional, and molecular studies of this process. The cardiorenal syndrome relates to the detrimental bidirectional interplay between the kidney and the cardiovascular system. In addition to established risk factors, this group of patients is subjected to a plethora of other emerging vascular risk factors, such as inflammation, oxidative stress, mitochondrial dysfunction, vitamin K deficiency, cellular senescence, somatic mutations, epigenetic modifications, and increased apoptosis. A better understanding of the molecular mechanisms through which the uremic milieu triggers and maintains early vascular aging processes, has provided important new clues on inflammatory pathways and emerging risk factors alike, and to the altered behavior of cells in the arterial wall. Advances in the understanding of the biology of uremic early vascular aging opens avenues to novel pharmacological and nutritional therapeutic interventions. Such strategies hold promise to improve future prevention and treatment of early vascular aging not only in CKD but also in the elderly general population.
Hypertension as Cardiovascular Risk Factor in Chronic Kidney Disease
Authors: Burnier Michel , Damianaki Aikaterini
Published: April 2023

Hypertension is the leading modifiable cause of premature death and hence one of the global targets of World Health Organization for prevention. Hypertension also affects the great majority of patients with chronic kidney disease (CKD). Both hypertension and CKD are intrinsically related, as hypertension is a strong determinant of worse renal and cardiovascular outcomes and renal function decline aggravates hypertension. This bidirectional relationship is well documented by the high prevalence of hypertension across CKD stages and the dual benefits of effective antihypertensive treatments on renal and cardiovascular risk reduction. Achieving an optimal blood pressure (BP) target is mandatory and requires several pharmacological and lifestyle measures. However, it also requires a correct diagnosis based on reliable BP measurements (eg, 24-hour ambulatory BP monitoring, home BP), especially for populations like patients with CKD where reduced or reverse dipping patterns or masked and resistant hypertension are frequent and associated with a poor cardiovascular and renal prognosis. Even after achieving BP targets, which remain debated in CKD, the residual cardiovascular risk remains high. Current antihypertensive options have been enriched with novel agents that enable to lower the existing renal and cardiovascular risks, such as SGLT2 (sodium-glucose cotransporter-2) inhibitors and novel nonsteroidal mineralocorticoid receptor antagonists. Although their beneficial effects may be driven mostly from actions beyond BP control, recent evidence underline potential improvements on abnormal 24-hour BP phenotypes such as nondipping. Other promising novelties are still to come for the management of hypertension in CKD. In the present review, we shall discuss the existing evidence of hypertension as a cardiovascular risk factor in CKD, the importance of identifying hypertension phenotypes among patients with CKD, and the traditional and novel aspects of the management of hypertensives with CKD.
Cardiovascular Calcification Heterogeneity in Chronic Kidney Disease
Authors: Hutcheson Joshua D. , Goettsch Claudia
Published: April 2023

Patients with chronic kidney disease (CKD) exhibit tremendously elevated risk for cardiovascular disease, particularly ischemic heart disease, due to premature vascular and cardiac aging and accelerated ectopic calcification. The presence of cardiovascular calcification associates with increased risk in patients with CKD. Disturbed mineral homeostasis and diverse comorbidities in these patients drive increased systemic cardiovascular calcification in different manifestations with diverse clinical consequences, like plaque instability, vessel stiffening, and aortic stenosis. This review outlines the heterogeneity in calcification patterning, including mineral type and location and potential implications on clinical outcomes. The advent of therapeutics currently in clinical trials may reduce CKD-associated morbidity. Development of therapeutics for cardiovascular calcification begins with the premise that less mineral is better. While restoring diseased tissues to a noncalcified homeostasis remains the ultimate goal, in some cases, calcific mineral may play a protective role, such as in atherosclerotic plaques. Therefore, developing treatments for ectopic calcification may require a nuanced approach that considers individual patient risk factors. Here, we discuss the most common cardiac and vascular calcification pathologies observed in CKD, how mineral in these tissues affects function, and the potential outcomes and considerations for therapeutic strategies that seek to disrupt the nucleation and growth of mineral. Finally, we discuss future patient-specific considerations for treating cardiac and vascular calcification in patients with CKD—a population in need of anticalcification therapies.
Role of the Microbiome in Gut-Heart-Kidney Cross Talk
Authors: Glorieux Griet , Nigam Sanjay K. , Vanholder Raymond , Verbeke Francis
Published: April 2023

Homeostasis is a prerequisite for health. When homeostasis becomes disrupted, dysfunction occurs. This is especially the case for the gut microbiota, which under normal conditions lives in symbiosis with the host. As there are as many microbial cells in and on our body as human cells, it is unlikely they would not contribute to health or disease. The gut bacterial metabolism generates numerous beneficial metabolites but also uremic toxins and their precursors, which are transported into the circulation. Barrier function in the intestine, the heart, and the kidneys regulates metabolite transport and concentration and plays a role in inter-organ and inter-organism communication via small molecules. This communication is analyzed from the perspective of the remote sensing and signaling theory, which emphasizes the role of a large network of multispecific, oligospecific, and monospecific transporters and enzymes in regulating small-molecule homeostasis. The theory provides a systems biology framework for understanding organ cross talk and microbe-host communication involving metabolites, signaling molecules, nutrients, antioxidants, and uremic toxins. This remote small-molecule communication is critical for maintenance of homeostasis along the gut-heart-kidney axis and for responding to homeostatic perturbations. Chronic kidney disease is characterized by gut dysbiosis and accumulation of toxic metabolites. This slowly impacts the body, affecting the cardiovascular system and contributing to the progression of kidney dysfunction, which in its turn influences the gut microbiota. Preserving gut homeostasis and barrier functions or restoring gut dysbiosis and dysfunction could be a minimally invasive way to improve patient outcomes and quality of life in many diseases, including cardiovascular and kidney disease.
Heroism and Loot in the Iliad
Authors: Quint David
Published: April 2023

The Iliad takes for granted the material motives of war and its heroes’ pursuit of booty, exchangeable wealth as well as tokens of honor. The poem nonetheless prefers that the hero fight for epic praise, and it shows that a warrior’s acquisitiveness may get in the way of his glory. It explores the issue in a subplot built around the actions of Diomedes in books 5–6 and 10–11: the hero obtains horses and armor in alternation, and his desire for spoils is mirrored by Hector’s in book 17. The subplot contrasts with the main plot of Achilles, who refuses to be bought off by Agamemnon’s gifts and who for a while stands outside of material exchange. But such exchange—the prizes Achilles gives out at the funeral games in book 23, the ransom he accepts from Priam in book 24—enables the hero’s return to human community and dignifies the taking of loot itself.