bluuebunny/crossref_metadata_2025 huggingface dataset:
A biomechanical analysis of different meshes for reconstructions of the pelvic floor in the porcine model
Authors: Trageser Nadja , Sauerwald Axel , Ludwig Sebastian , Malter Wolfram , Wegmann Kilian , Karapanos Leonidas , Radosa Julia , Jansen Alina Katharina , Eichler Christian
Published: November 2021

Purpose

Many different surgical approaches have been established for the repair of a pelvic organ prolapse. Especially in laparoscopic surgery, it is important to generate easy surgical techniques with similar stability. This study shall simplify the choice of mesh by evaluating three polypropylene meshes regarding their biomechanical properties.

Methods

Biomechanical testing was performed in the porcine model. The meshes are fixated on porcine fresh cadaver cervices after subtotal hysterectomy. The apical part of the mesh is fixated with parallel screw clamps at the testing frame. Forty-one trials were performed overall, subdivided into four subgroups. The groups differ in mesh type and fixation method. Maximum load, displacement at failure and stiffness parameters were evaluated with an Instron 5565® test frame.

Results

SERATEX® E11 PA (E11) showed the highest values for maximum load (199 ± 29N), failure displacement (71 ± 12 mm) and stiffness (3.93 ± 0.59 N/mm). There was no significant difference in all three evaluated parameters between SERATEX® B3 PA (B3) and SERATEX® SlimSling® with bilateral fixation (SSB). SERATEX® SlimSling® with unilateral fixation (SSU) had the lowest stiffness (0.91 ± 0.19 N/mm) and maximum load (30 ± 2 N) but no significant difference in displacement at failure.

Conclusion

All meshes achieved a good tensile strength, but the results of maximum load show that the E11 is superior to the other meshes. Through a bilateral fixation of SERATEX® SlimSling®, a simple operating method is generated without a loss of stability.
Galectin network in osteoarthritis: galectin-4 programs a pathogenic signature of gene and effector expression in human chondrocytes in vitro
Authors: Pichler Katharina M. , Fischer Anita , Alphonsus Jürgen , Chiari Catharina , Schmidt Sebastian , Kenn Michael , Schreiner Wolfgang , Weinmann Daniela , Rothbauer Mario , Windhager Reinhard , Gabius Hans‑Joachim , Toegel Stefan
Published: November 2021

Galectin-4 (Gal-4) is a member of the galectin family, which have been identified as galactose-binding proteins. Gal-4 possesses two tandem repeat carbohydrate recognition domains and acts as a cross-linking bridge in sulfatide-dependent glycoprotein routing. We herein document its upregulation in osteoarthritis (OA) in correlation with the extent of cartilage degradation in vivo. Primary human OA chondrocytes in vitro respond to carbohydrate-inhibitable Gal-4 binding with the upregulation of pro-degradative/-inflammatory proteins such as interleukin-1β (IL-1β) and matrix metalloproteinase-13 (MMP-13), as documented by RT-qPCR-based mRNA profiling and transcriptome data processing. Activation of p65 by phosphorylation of Ser536 within the NF-κB pathway and the effect of three p65 inhibitors on Gal-4 activity support downstream involvement of such signaling. In 3D (pellet) cultures, Gal-4 presence causes morphological and biochemical signs of degradation. Taken together, our findings strongly support the concept of galectins acting as a network in OA pathogenesis and suggest that blocking their activity in disease progression may become clinically relevant in the future.
Holzkohle als CO2-neutrales Reduktionsmittel in Recyclingprozessen der Nichteisenmetallurgie
Authors: Antrekowitsch Jürgen , Dornig Christian , Hanke Gustav
Published: November 2021

Die Metallurgie ist wie viele andere Industriezweige seit einigen Jahren geprägt von Bemühungen, den CO2-Footprint entscheidend zu senken. Im Vordergrund stehen Technologien auf Basis von Wasserstoff, welche allerdings aus unterschiedlichsten Gründen wie beispielsweise hohen Kosten, notwendiger Umstellung von Verfahren oder erhöhter Sicherheitstechnik, schwierig umzusetzen sind. Eine Alternative kann in der Verwendung von pyrolysierter Biomasse gesehen werden, welche in mehreren Bereichen in der Lage ist, fossilen Kohlenstoff direkt zu substituieren. Die vorliegende Arbeit beschreibt die grundsätzliche Charakteristik von Holzkohlen aus Biomasse sowie Anwendungsmöglichkeiten und damit verbundene Vorteile und Nachteile. Dabei sind aus technischer Sicht vor allem die Reaktivität und die Festigkeit wesentliche Kriterien. Vom wirtschaftlichen Standpunkt aus müssen Verfügbarkeit und Preisbildung im Detail betrachtet werden. Zusammengefasst lässt sich ein positives Resümee ziehen, was den Einsatz entsprechender Holzkohlen vor allem in kleineren metallurgischen Einheiten betrifft, speziell in Hinblick auf eine zeitnahe wirtschaftliche Umsetzung.
Landscape controls of surface-water/groundwater interactions on shallow outwash lakes: how the long-term groundwater signal overrides interannual variability due to evaporative effects
Authors: Hokanson K. J. , Rostron B. J. , Devito K. J. , Hopkinson C. , Mendoza C. A.
Published: November 2021

The spatial and temporal controls on variability of the relative contributions of groundwater within and between flow systems to shallow lakes in the low-relief glaciated Boreal Plains of Canada were evaluated. Eleven lakes located in a coarse glacial outwash, of varying topographic positions and potential groundwater contributing areas, were sampled annually for stable O and H isotope ratios over the course of 8 years. It was demonstrated that landscape position is the dominant control over relative groundwater contributions to these lakes and the spatial pattern of the long-term isotopic compositions attributed to groundwater overrides interannual variability due to evaporative effects. Lakes at low landscape positions with large potential groundwater capture areas have relatively higher and more consistent groundwater contributions and low interannual variability of isotopic composition. Isolated lakes high in the landscape experience high interannual variability as they have little to no groundwater input to buffer the volumetric or isotopic changes caused by evaporation and precipitation. An alternative explanation that lake morphometry (area and volume) control long-term isotopic compositions is tested and subsequently refuted. Landscape position within coarse outwash is a strong predictor for relative groundwater input; however, surface-water connections can short circuit groundwater pathways and confound the signal. A hydrogeological case study for three of the study lakes is used to contextualize and further demonstrate these results.
Use of biologic agents and methotrexate improves renal manifestation and outcome in patients with rheumatoid arthritis: a retrospective analysis
Authors: Sawamura Masato , Sawa Naoki , Yamanouchi Masayuki , Ikuma Daisuke , Sekine Akinari , Mizuno Hiroki , Kawada Masahiro , Hiramatsu Rikako , Hayami Noriko , Hasegawa Eiko , Suwabe Tatsuya , Hoshino Junichi , Kono Kei , Kinowaki Keiichi , Ohashi Kenichi , Yamaguchi Yutaka , Ubara Yoshifumi
Published: November 2021

Background and purpose

We examined whether advances in treatment strategies from older disease-modifying antirheumatic drugs (DMARDs) to new biologic agents and methotrexate improved renal complications and outcome in patients with rheumatoid arthritis (RA).

Methods

We reviewed records of 156 patients with RA who underwent kidney biopsy at our institute between January 1990 and December 2019. All patients were assigned to one of three periods: period 1, 1990–1999 (n = 48); period 2, 2000–2009(n = 57); period 3, 2010–2019 (n = 51).

Results

Membranous nephropathy, nephrosclerosis, AA-amyloidosis, and IgA nephropathy were the four major renal manifestations of RA. AA-amyloidosis was diagnosed by kidney biopsy in 21 patients: period 1, 7 patients (15%); period 2, 10 patients (18%); and period 3, 4 patients (8%). The 4 patients in period 3 were in the years 2010–2014, and no new case of AA-amyloidosis was recorded from 2015 to 2019. In all 21 of the patients with AA-amyloidosis, neither a biologic agent nor methotrexate was administered. Fifteen of the 21 patients required dialysis, and 13 died in periods 1–3 because of amyloid-related cardiac dysfunction less than 2 years after the initiation of dialysis. Two of them are doing well using biologic agent despite dialysis. The remaining three patients who received a biologic agent or methotrexate does not progress to end-stage renal failure. In addition, the other renal complications showing progression to dialysis also decreased over time.

Conclusion

Advances in treatment strategies have improved renal outcome and reduced mortality in patients with RA.
Stress events and Changes in Dysfunctional Attitudes and Automatic Thoughts Following Recovery from Depression in Inpatient Psychotherapy: Mediation Analyses with Longitudinal Data
Authors: Rojas Roberto , Behnke Alexander , Hautzinger Martin
Published: November 2021

Background

Stressful event exposure, dysfunctional attitudes (DA), negative automatic thoughts (NAT), and declining positive automatic thoughts (PAT) have been associated with depressive relapse/recurrence. Few studies have investigated the course of these variables and their relevance for relapse/recurrence in remitted depression.

Methods

Following successful inpatient treatment, in 39 remitted depressive patients, stressful events, DA, NAT, PAT, and depressive relapse/recurrence were assessed five times during a 16-month follow-up. Data were analyzed with mixed effect models, and mediation effects were tested.

Results

Stressful events after discharge correlated with depressive relapse/recurrence. This association was mainly mediated by a stress-related decline of PAT within four months post discharge. Patients’ DA were relatively stable during the observation period and did not depend on stressful events, indicating DA as a risk trait for depressive relapse/recurrence. Mediation analyses revealed that independent of stress, DA were linked to depressive relapse/recurrence through more NAT.

Conclusion

Our findings suggest stressful events evoke relapse/recurrence in remitted depression through rapid deterioration of PAT after discharge from inpatient therapy. DA are expressed through NAT which additionally contribute to higher risk of depressive relapse/recurrence. Consequently, maintenance therapy requires techniques to promote the maintenance of PAT, and to effectively restructure DA and NAT.
Removing mains interference from the mfERG by applying a post-processing digital notch filter: for the good or the bad?
Authors: Heinrich Sven P.
Published: November 2021

Purpose

Ideally, the multifocal electroretinogram (mfERG) is recorded without noticeable intrusion of mains interference. However, sometimes contamination is difficult to avoid. A post-processing digital notch filter can help to recover the retinal response even in severe cases of mains interference. While a digital filter can be designed to have little to no impact on peak times, filtering out mains interference also removes the retinal signal content of the same frequency, which may result in a change of amplitude. The present study addressed this issue in the standard first order kernel mfERG.

Methods

In 24 recordings from routine exams with no perceivable mains interference, the effects of 50-Hz and 60-Hz non-causal digital notch filters on amplitude and peak time were assessed. Furthermore, the effect of filtering on contaminated traces was demonstrated and simulated mains interference was used to provide an example of nonlinear superposition of retinal signal and mains interference.

Results

mfERG amplitudes were reduced by 0%–15% (median 6%) with the 50-Hz filter and remained virtually unaffected with the 60-Hz filter. Simulations illustrate that spurious high-frequency components can occur in the filtered signal if a strongly contaminated signal is clipped due to a limited input range of the analog-to-digital converter.

Conclusion

The application of a 50-Hz digital notch filter to mfERG traces causes a mild amplitude reduction which will not normally affect the clinical interpretation of the data. The situation is even more favorable with a 60-Hz digital notch filter. Caution is necessary if the assumption of linear additivity of retinal signal and mains interference is violated.
Computable Constants for Korn’s Inequalities on Riemannian Manifolds
Authors: Knops R. J.
Published: November 2021

A method is presented for the explicit construction of the non-dimensional constant occurring in Korn’s inequalities for a bounded two-dimensional Riemannian differentiable simply connected manifold subject to Dirichlet boundary conditions. The method is illustrated by application to the spherical cap and minimal surface.
Efficient Proximal Mapping Computation for Low-Rank Inducing Norms
Authors: Grussler Christian , Giselsson Pontus
Published: November 2021

Low-rank inducing unitarily invariant norms have been introduced to convexify problems with a low-rank/sparsity constraint. The most well-known member of this family is the so-called nuclear norm. To solve optimization problems involving such norms with proximal splitting methods, efficient ways of evaluating the proximal mapping of the low-rank inducing norms are needed. This is known for the nuclear norm, but not for most other members of the low-rank inducing family. This work supplies a framework that reduces the proximal mapping evaluation into a nested binary search, in which each iteration requires the solution of a much simpler problem. The simpler problem can often be solved analytically as demonstrated for the so-called low-rank inducing Frobenius and spectral norms. The framework also allows to compute the proximal mapping of increasing convex functions composed with these norms as well as projections onto their epigraphs.
Why bother the public? A critique of Leslie Cannold’s empirical research on ectogenesis
Authors: Smajdor Anna
Published: November 2021

Can discussion with members of the public show philosophers where they have gone wrong? Leslie Cannold argues that it can in her 1995 paper ‘Women, Ectogenesis and Ethical Theory’, which investigates the ways in which women reason about abortion and ectogenesis (the gestation of foetuses in artificial wombs). In her study, Cannold interviewed female non-philosophers. She divided her participants into separate ‘pro-life’ and ‘pro-choice’ groups and asked them to consider whether the availability of ectogenesis would change their views about the morality of dealing with an unwanted pregnancy. The women in Cannold’s study gave responses that did not map onto the dominant tropes in the philosophical literature. Yet Cannold did not attempt to reason with her participants, and her engagement with the philosophical literature is oddly limited, focussing only on the pro-choice perspective. In this paper, I explore the question of whether Cannold is correct that philosophers’ reasoning about abortion is lacking in some way. I suggest that there are alternative conclusions to be drawn from the data she gathered and that a critical approach is necessary when attempting to undertake philosophy informed by empirical data.
Activity Trends in the Propane Dehydrogenation Reaction Catalyzed by MIII Sites on an Amorphous SiO2 Model: A Theoretical Perspective
Authors: Praveen C. S. , Comas-Vives A.
Published: November 2021

One class of particularly active catalysts for the Propane Dehydrogenation (PDH) reaction are well-defined M(III) sites on amorphous SiO2. In the present work, we focus on evaluating the catalytic trends of the PDH for four M(III) single-sites (Cr, Mo, Ga and In) on a realistic amorphous model of SiO2 using density functional theory-based calculations and the energetic span model. We considered a catalytic pathway spanned by three reaction steps taking place on selected MIII–O pair of the SiO2 model: σ-bond metathesis of propane on a MIII–O bond to form M-propyl and O–H group, a β-H transfer step forming M–H and propene, and the H–H coupling step producing H2 and regenerating the initial M–O bond. With the application of the energetic span model, we found that the calculated catalytic activity for Ga and Cr is comparable to the ones reported at the experimental level, enabling us to benchmark the model and the methodology used. Furthermore, results suggest that both In(III) and Mo(III) on SiO2 are potential active catalysts for PDH, provided they can be synthesized and are stable under PDH reaction conditions.
Die Auswirkungen der Frühphase der COVID-19 Pandemie auf die Erwerbssituation und die finanzielle Lage von Familien in Österreich
Authors: Steiber Nadia , Siegert Christina
Published: November 2021

In dieser Forschungsnotiz werden erste Ergebnisse der AKCOVID-Studie vorgestellt. Diese untersucht auf Basis von repräsentativen Befragungsdaten die Auswirkungen der Pandemie auf die finanzielle Lage von Familien in Österreich. Dabei wird die Situation von Haushalten mit Kindern vor Beginn der Corona-Krise (Februar 2020) mit der Situation im Frühsommer 2020 verglichen. Die deskriptiven Ergebnisse zeigen, dass ein großer Teil der Familien bereits drei Monate nach Beginn der Krise die ökonomischen Folgen der Pandemie spürte und aufgrund krisenbedingter Veränderungen der elterlichen Erwerbssituation auf Teile des Haushaltseinkommens verzichten musste. Die Zahl der Familien mit finanziellen Problemen (subjektive Armutsgefährdung) stieg deutlich an, v. a. unter Alleinerziehenden und Paaren mit mehr als zwei Kindern. Damit wird deutlich, dass vor allem jene Familien, die sich bereits vor der Krise in einer vulnerablen finanziellen Situation befanden, schon sehr früh direkt von den ökonomischen Folgen der Pandemie betroffen waren. Viele Familien sorgten sich, dass sie aufgrund der Krise Einkommenseinbußen erleiden und finanzielle Probleme bekommen werden.
Consensus on the secondary prevention of primary liver cancer
Authors: Nan Yuemin , Xu Xiaoyuan , Gao Yanhang , Wang Rongqi , Li Wengang , Yang Ming , Liu Lingdi , Duan Zhongping , Jia Jidong , Wei Lai , Zhuang Hui ,   Chinese Society of Hepatology, Chinese Medical Association, Ding Huiguo , Duan Zhongping , Fan Jiangao , Fang Qinmao , Gao Yanhang , Hu Peng , Jia Jidong , Li Wengang , Liu Jingfeng , Niu Junqi , Nan Yuemin , Shang Jia , Wang Rongqi , Wei Lai , Yu Yanyan , Zhang Yuguo , Zhao Suxian , Zhou Jian , Zhao Weifeng , Xu Xiaoyuan , Xie Chuanmiao , Xie Wen , Yang Ming , Zhuang Hui
Published: November 2021

To standardize the effective prevention, surveillance, and diagnosis of primary liver cancer, the Chinese Society of Hepatology, Chinese Medical Association, invited clinical experts and methodologists to develop the Consensus on the Secondary Prevention of Primary Liver Cancer, which was based on the clinical and scientific advances on hepatocellular carcinoma. The purpose is to provide a current basis for the prevention, surveillance, and early diagnosis of primary liver cancer in patients with chronic liver diseases.
Impact of urbanization trends on production of key staple crops
Authors: Andrade José F. , Cassman Kenneth G. , Rattalino Edreira Juan I. , Agus Fahmuddin , Bala Abdullahi , Deng Nanyan , Grassini Patricio
Published: November 2021

Urbanization has appropriated millions of hectares of cropland, and this trend will persist as cities continue to expand. We estimate the impact of this conversion as the amount of land needed elsewhere to give the same yield potential as determined by differences in climate and soil properties. Robust spatial upscaling techniques, well-validated crop simulation models, and soil, climate, and cropping system databases are employed with a focus on populous countries with high rates of land conversion. We find that converted cropland is 30–40% more productive than new cropland, which means that projection of food production potential must account for expected cropland loss to urbanization. Policies that protect existing farmland from urbanization would help relieve pressure on expansion of agriculture into natural ecosystems.
How Do People Generalize Causal Relations over Objects? A Non-parametric Bayesian Account
Authors: Zhao Bonan , Lucas Christopher G. , Bramley Neil R.
Published: November 2021

How do people decide how general a causal relationship is, in terms of the entities or situations it applies to? What features do people use to decide whether a new situation is governed by a new causal law or an old one? How can people make these difficult judgments in a fast, efficient way? We address these questions in two experiments that ask participants to generalize from one (Experiment 1) or several (Experiment 2) causal interactions between pairs of objects. In each case, participants see an agent object act on a recipient object, causing some changes to the recipient. In line with the human capacity for few-shot concept learning, we find systematic patterns of causal generalizations favoring simpler causal laws that extend over categories of similar objects. In Experiment 1, we find that participants’ inferences are shaped by the order of the generalization questions they are asked. In both experiments, we find an asymmetry in the formation of causal categories: participants preferentially identify causal laws with features of the agent objects rather than recipients. To explain this, we develop a computational model that combines program induction (about the hidden causal laws) with non-parametric category inference (about their domains of influence). We demonstrate that our modeling approach can both explain the order effect in Experiment 1 and the causal asymmetry, and outperforms a naïve Bayesian account while providing a computationally plausible mechanism for real-world causal generalization.
Pathologie der hepato-pankreato-biliären Tumoren
Authors: Cathomas Gieri , Terracciano Luigi M.
Published: November 2021

Zusammenfassung. Die malignen Tumoren der hepato-pankreato-biliären Organe sind mehrheitlich typische Adenokarzinome mit Ausnahme der Leber, wo sie wegen ihrer charakteristischen Morphologie als hepatozelluläre Neoplasien bezeichnet werden. Neben diesen klassischen morphologischen Ansätzen haben in den letzten Jahren molekulare und vor allem morphomolekulare Untersuchungen viele neue Erkenntnisse ergeben, immer mit dem Ziel, den Patienten eine bestmögliche Therapie zukommen zu lassen. So wird heute zum Beispiel die fokale noduläre Hyperplasie (FNH) der Leber als reaktive Veränderung angesehen, welche keine weiteren Therapien braucht. Auf der einen Seite erlaubt die molekulare Stratifizierung der Leberzelladenome, Risikotumoren zu erkennen und entsprechend operativ zu behandeln. Als weiteres Beispiel seien Tumoren der extra- und intrahepatischen Gallengänge aufgeführt, welche heute in «Small-Duct-Type» und «Large-Duct-Type» unterschieden werden, welche unterschiedliche, therapeutisch relevante molekulare Profile aufweisen. Die vorliegende Arbeit gibt eine Übersicht über die wichtigsten und häufigsten Tumoren der hepato-pankreato-biliären Organe.
Lebereigene Tumoren – Hepatozelluläres und das Cholangiozelluläre Karzinom
Authors: Soysal Savas Deniz , Kollmar Otto
Published: November 2021

Zusammenfassung. Lebertumoren werden häufig als Zufallsbefund in der Sonographie entdeckt. Weiterführende Diagnostik sind das MRT mit Gadolinium-Kontrastmittel oder das 3-Phasen-Abdomen-CT. Auf eine Biopsie bei einem Leberrundherd kann bei genauer Kenntnis der radiologischen und klinischen Präsentation verzichtet werden. Patienten mit Lebereigenen Tumoren und / oder unklaren Befunden sollten in einem Leberzentrum vorgestellt werden. Nur die chirurgisch-onkologische R0-Resektion ist kurativ.
Genetic background in late-onset sensorineural hearing loss patients
Authors: Uehara Natsumi , Fujita Takeshi , Yamashita Daisuke , Yokoi Jun , Katsunuma Sayaka , Kakigi Akinobu , Nishio Shin-ya , Nibu Ken-ichi , Usami Shin-ichi
Published: November 2021

Genetic testing for congenital or early-onset hearing loss patients has become a common diagnostic option in many countries. On the other hand, there are few late-onset hearing loss patients receiving genetic testing, as late-onset hearing loss is believed to be a complex disorder and the diagnostic rate for genetic testing in late-onset patients is lower than that for the congenital cases. To date, the etiology of late-onset hearing loss is largely unknown. In the present study, we recruited 48 unrelated Japanese patients with late-onset bilateral sensorineural hearing loss, and performed genetic analysis of 63 known deafness gene using massively parallel DNA sequencing. As a result, we identified 25 possibly causative variants in 29 patients (60.4%). The present results clearly indicated that various genes are involved in late-onset hearing loss and a significant portion of cases of late-onset hearing loss is due to genetic causes. In addition, we identified two interesting cases for whom we could expand the phenotypic description. One case with a novel MYO7A variant showed a milder phenotype with progressive hearing loss and late-onset retinitis pigmentosa. The other case presented with Stickler syndrome with a mild phenotype caused by a homozygous frameshift COL9A3 variant. In conclusion, comprehensive genetic testing for late-onset hearing loss patients is necessary to obtain accurate diagnosis and to provide more appropriate treatment for these patients.
Oxidative damage-induced hyperactive ribosome biogenesis participates in tumorigenesis of offspring by cross-interacting with the Wnt and TGF-β1 pathways in IVF embryos
Authors: Huang Yue , Li Zhiling , Lin En , He Pei , Ru Gaizhen
Published: November 2021

In vitro fertilization (IVF) increases the risk of tumorigenesis in offspring. The increased oxidative damage during IVF may be involved in tumor formation. However, the molecular mechanisms underlying this phenomenon remain largely unclear. Using a well-established model of oxidatively damaged IVF mouse embryos, we applied the iTRAQ method to identify proteins differentially expressed between control and oxidatively damaged zygotes and explored the possible tumorigenic mechanisms, especially with regard to the effects of oxidative damage on ribosome biogenesis closely related to tumorigenesis. The iTRAQ results revealed that ribosomal proteins were upregulated by oxidative stress through the Nucleolin/β-Catenin/n-Myc pathway, which stimulated ribosomes to synthesize an abundance of repair proteins to correct the damaged DNA/chromosomes in IVF-derived embryos. However, the increased percentages of γH2AX-positive cells and apoptotic cells in the blastocyst suggested that DNA repair was insufficient, resulting in aberrant ribosome biogenesis. Overexpression of ribosomal proteins, particularly Rpl15, which gradually increased from the 1-cell to 8-cell stages, indicated persistent hyperactivation of ribosome biogenesis, which promoted tumorigenesis in offspring derived from oxidatively damaged IVF embryos by selectively enhancing the translation of β-Catenin and TGF-β1. The antioxidant epigallocatechin-3-gallate (EGCG) was added to the in vitro culture medium to protect embryos from oxidative damage, and the expression of ribosome-/tumor-related proteins returned to normal after EGCG treatment. This study suggests that regulation of ribosome biogenesis by EGCG may be a means of preventing tumor formation in human IVF-derived offspring, providing a scientific basis for optimizing in vitro culture conditions and improving human-assisted reproductive technology.
Coordination between cell proliferation and apoptosis after DNA damage in Drosophila
Authors: Ruiz-Losada Mireya , González Raul , Peropadre Ana , Gil-Gálvez Alejandro , Tena Juan J. , Baonza Antonio , Estella Carlos
Published: November 2021

Exposure to genotoxic stress promotes cell cycle arrest and DNA repair or apoptosis. These “life” or “death” cell fate decisions often rely on the activity of the tumor suppressor gene p53. Therefore, the precise regulation of p53 is essential to maintain tissue homeostasis and to prevent cancer development. However, how cell cycle progression has an impact on p53 cell fate decision-making is mostly unknown. In this work, we demonstrate that Drosophila p53 proapoptotic activity can be impacted by the G2/M kinase Cdk1. We find that cell cycle arrested or endocycle-induced cells are refractory to ionizing radiation-induced apoptosis. We show that p53 binding to the regulatory elements of the proapoptotic genes and its ability to activate their expression is compromised in experimentally arrested cells. Our results indicate that p53 genetically and physically interacts with Cdk1 and that p53 proapoptotic role is regulated by the cell cycle status of the cell. We propose a model in which cell cycle progression and p53 proapoptotic activity are molecularly connected to coordinate the appropriate response after DNA damage.
Towards unraveling the moisture-induced shape memory effect of wood: the role of interface mechanics revealed by upscaling atomistic to composite modeling
Authors: Zhang Chi , Chen Mingyang , Keten Sinan , Derome Dominique , Carmeliet Jan
Published: November 2021

The moisture-induced shape memory effect (SME) is one of the most intriguing phenomena of wood, where wood can stably retain a certain deformed shape and, upon moisture sorption, can recover the original shape. Despite the long history of wood utilization, the SME is still not fully understood. Combining molecular dynamics (MD) and finite-element (FE) modeling, a possible mechanism of the SME of wood cell walls is explored, emphasizing the role of interface mechanics, a factor previously overlooked. Interface mechanics extracted from molecular simulations are implemented in different mechanical models solved by FEs, representing three configurations encountered in wood cell walls. These models incorporate moisture-dependent elastic moduli of the matrix and moisture-dependent behavior of the interface. One configuration, denoted as a mechanical hotspot with a fiber–fiber interface, is found to particularly strengthen the SME. Systematic parametric studies reveal that interface mechanics could be the source of shape memory. Notably, upon wetting, the interface is weak and soft, and the material can be easily deformed. Upon drying, the interface becomes strong and stiff, and composite deformation can be locked. When the interface is wetted again and weakened, the previously locked deformation cannot be sustained, and recovery occurs. The elastic energy and topological information stored in the cellulose fiber network is the driving force of the recovery process. This work proposes an interface behaving as a moisture-induced molecular switch.
A polygenic risk score for multiple myeloma risk prediction
Authors: Canzian Federico , Piredda Chiara , Macauda Angelica , Zawirska Daria , Andersen Niels Frost , Nagler Arnon , Zaucha Jan Maciej , Mazur Grzegorz , Dumontet Charles , Wątek Marzena , Jamroziak Krzysztof , Sainz Juan , Várkonyi Judit , Butrym Aleksandra , Beider Katia , Abildgaard Niels , Lesueur Fabienne , Dudziński Marek , Vangsted Annette Juul , Pelosini Matteo , Subocz Edyta , Petrini Mario , Buda Gabriele , Raźny Małgorzata , Gemignani Federica , Marques Herlander , Orciuolo Enrico , Kadar Katalin , Jurczyszyn Artur , Druzd-Sitek Agnieszka , Vogel Ulla , Andersen Vibeke , Reis Rui Manuel , Suska Anna , Avet-Loiseau Hervé , Kruszewski Marcin , Tomczak Waldemar , Rymko Marcin , Minvielle Stephane , Campa Daniele
Published: November 2021

There is overwhelming epidemiologic evidence that the risk of multiple myeloma (MM) has a solid genetic background. Genome-wide association studies (GWAS) have identified 23 risk loci that contribute to the genetic susceptibility of MM, but have low individual penetrance. Combining the SNPs in a polygenic risk score (PRS) is a possible approach to improve their usefulness. Using 2361 MM cases and 1415 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium, we computed a weighted and an unweighted PRS. We observed associations with MM risk with OR = 3.44, 95% CI 2.53–4.69, p = 3.55 × 10−15 for the highest vs. lowest quintile of the weighted score, and OR = 3.18, 95% CI 2.1 = 34–4.33, p = 1.62 × 10−13 for the highest vs. lowest quintile of the unweighted score. We found a convincing association of a PRS generated with 23 SNPs and risk of MM. Our work provides additional validation of previously discovered MM risk variants and of their combination into a PRS, which is a first step towards the use of genetics for risk stratification in the general population.
Starvation-induced proteasome assemblies in the nucleus link amino acid supply to apoptosis
Authors: Uriarte Maxime , Sen Nkwe Nadine , Tremblay Roch , Ahmed Oumaima , Messmer Clémence , Mashtalir Nazar , Barbour Haithem , Masclef Louis , Voide Marion , Viallard Claire , Daou Salima , Abdelhadi Djaileb , Ronato Daryl , Paydar Mohammadjavad , Darracq Anaïs , Boulay Karine , Desjardins-Lecavalier Nicolas , Sapieha Przemyslaw , Masson Jean-Yves , Sergeev Mikhail , Kwok Benjamin H. , Hulea Laura , Mallette Frédérick A. , Milot Eric , Larrivée Bruno , Wurtele Hugo , Affar El Bachir
Published: November 2021

Eukaryotic cells have evolved highly orchestrated protein catabolic machineries responsible for the timely and selective disposal of proteins and organelles, thereby ensuring amino acid recycling. However, how protein degradation is coordinated with amino acid supply and protein synthesis has remained largely elusive. Here we show that the mammalian proteasome undergoes liquid-liquid phase separation in the nucleus upon amino acid deprivation. We termed these proteasome condensates SIPAN (Starvation-Induced Proteasome Assemblies in the Nucleus) and show that these are a common response of mammalian cells to amino acid deprivation. SIPAN undergo fusion events, rapidly exchange proteasome particles with the surrounding milieu and quickly dissolve following amino acid replenishment. We further show that: (i) SIPAN contain K48-conjugated ubiquitin, (ii) proteasome inhibition accelerates SIPAN formation, (iii) deubiquitinase inhibition prevents SIPAN resolution and (iv) RAD23B proteasome shuttling factor is required for SIPAN formation. Finally, SIPAN formation is associated with decreased cell survival and p53-mediated apoptosis, which might contribute to tissue fitness in diverse pathophysiological conditions.
Structural basis of Ty3 retrotransposon integration at RNA Polymerase III-transcribed genes
Authors: Abascal-Palacios Guillermo , Jochem Laura , Pla-Prats Carlos , Beuron Fabienne , Vannini Alessandro
Published: November 2021

Retrotransposons are endogenous elements that have the ability to mobilise their DNA between different locations in the host genome. The Ty3 retrotransposon integrates with an exquisite specificity in a narrow window upstream of RNA Polymerase (Pol) III-transcribed genes, representing a paradigm for harmless targeted integration. Here we present the cryo-EM reconstruction at 4.0 Å of an active Ty3 strand transfer complex bound to TFIIIB transcription factor and a tRNA gene. The structure unravels the molecular mechanisms underlying Ty3 targeting specificity at Pol III-transcribed genes and sheds light into the architecture of retrotransposon machinery during integration. Ty3 intasome contacts a region of TBP, a subunit of TFIIIB, which is blocked by NC2 transcription regulator in RNA Pol II-transcribed genes. A newly-identified chromodomain on Ty3 integrase interacts with TFIIIB and the tRNA gene, defining with extreme precision the integration site position.
3D in vitro M2 macrophage model to mimic modulation of tissue repair
Authors: Sapudom Jiranuwat , Karaman Shaza , Mohamed Walaa K. E. , Garcia-Sabaté Anna , Quartey Brian C. , Teo Jeremy C. M.
Published: November 2021

Distinct anti-inflammatory macrophage (M2) subtypes, namely M2a and M2c, are reported to modulate the tissue repair process tightly and chronologically by modulating fibroblast differentiation state and functions. To establish a well-defined three-dimensional (3D) cell culture model to mimic the tissue repair process, we utilized THP-1 human monocytic cells and a 3D collagen matrix as a biomimetic tissue model. THP-1 cells were differentiated into macrophages, and activated using IL-4/IL-13 (MIL-4/IL-13) and IL-10 (MIL-10). Both activated macrophages were characterized by both their cell surface marker expression and cytokine secretion profile. Our cell characterization suggested that MIL-4/IL-13 and MIL-10 demonstrate M2a- and M2c-like subtypes, respectively. To mimic the initial and resolution phases during the tissue repair, both activated macrophages were co-cultured with fibroblasts and myofibroblasts. We showed that MIL-4/IL-13 were able to promote matrix synthesis and remodeling by induction of myofibroblast differentiation via transforming growth factor beta-1 (TGF-β1). On the contrary, MIL-10 demonstrated the ability to resolve the tissue repair process by dedifferentiation of myofibroblast via IL-10 secretion. Overall, our study demonstrated the importance and the exact roles of M2a and M2c-like macrophage subtypes in coordinating tissue repair in a biomimetic model. The established model can be applied for high-throughput platforms for improving tissue healing and anti-fibrotic drugs testing, as well as other biomedical studies.
RETRACTED ARTICLE: Performance of sustainable self-compacting fiber reinforced concrete with substitution of marble waste (MW) and coconut fibers (CFs)
Authors: Ahmad Jawad , Aslam Fahid , Martinez-Garcia Rebeca , Ouni Mohamed Hechmi El , Khedher Khalid Mohamed
Published: November 2021

Self compacting concrete (SCC) is special type of concrete which is highly flowable and non-segregated and by its own mass, spreads into the formwork without any external vibrators, even in the presence of thick reinforcement. But SSC is also brittle nature like conventional concrete, which results in abrupt failure without giving any deformation (warning), which is undesirable for any structural member. Thus, self-compacting concrete (SCC) needs some of tensile reinforcement to enhance tensile strength and prevent the unsuitable abrupt failure. But fiber increased tensile strength of concrete more effectively than compressive strength. Hence, it is essential to add pozzolanic materials into fiber reinforced concrete to achieve high strength, durable and ductile concrete. This study is conducted to assess the performance of SCC with substitutions of marble waste (MW) and coconut fiber (CFs) into SCC. MW utilized as cementitious (pozzolanic) materials in percentage of 5.0 to 30% in increment of 5.0% by weight of binder and concrete is reinforced with CFs in proportion of 0.5 to 3.0% in increment of 0.5% by weight of binder. Rheological characteristics were measured through its filling and passing ability by using Slump flow, Slump T50, L-Box, and V-funnel tests while mechanical characteristics were measured through compressive strength, split tensile strength, flexure strength and bond strength (pull out) tests. Experimental investigation show that MW and CFs decrease the passing ability and filling ability of SCC. Additionally, Experimental investigation show that MW up to 20% and CFs addition 2.0% by weight of binder tend to increase the mechanical performance of SCC. Furthermore, statistical analysis (RSM) was used to optimize the combined dose of MW and CFs into SCC to obtain high strength self-compacting concrete.
A repeated-measures study on emotional responses after a year in the pandemic
Authors: Mozes Maximilian , van der Vegt Isabelle , Kleinberg Bennett
Published: November 2021

The introduction of COVID-19 lockdown measures and an outlook on return to normality are demanding societal changes. Among the most pressing questions is how individuals adjust to the pandemic. This paper examines the emotional responses to the pandemic in a repeated-measures design. Data (n = 1698) were collected in April 2020 (during strict lockdown measures) and in April 2021 (when vaccination programmes gained traction). We asked participants to report their emotions and express these in text data. Statistical tests revealed an average trend towards better adjustment to the pandemic. However, clustering analyses suggested a more complex heterogeneous pattern with a well-coping and a resigning subgroup of participants. Linguistic computational analyses uncovered that topics and n-gram frequencies shifted towards attention to the vaccination programme and away from general worrying. Implications for public mental health efforts in identifying people at heightened risk are discussed. The dataset is made publicly available.
Quantifying the effect of genetic, environmental and individual demographic stochastic variability for population dynamics in Plantago lanceolata
Authors: Steiner Ulrich K. , Tuljapurkar Shripad , Roach Deborah A.
Published: November 2021

Simple demographic events, the survival and reproduction of individuals, drive population dynamics. These demographic events are influenced by genetic and environmental parameters, and are the focus of many evolutionary and ecological investigations that aim to predict and understand population change. However, such a focus often neglects the stochastic events that individuals experience throughout their lives. These stochastic events also influence survival and reproduction and thereby evolutionary and ecological dynamics. Here, we illustrate the influence of such non-selective demographic variability on population dynamics using population projection models of an experimental population of Plantago lanceolata. Our analysis shows that the variability in survival and reproduction among individuals is largely due to demographic stochastic variation with only modest effects of differences in environment, genes, and their interaction. Common expectations of population growth, based on expected lifetime reproduction and generation time, can be misleading when demographic stochastic variation is large. Large demographic stochastic variation exhibited within genotypes can lower population growth and slow evolutionary adaptive dynamics. Our results accompany recent investigations that call for more focus on stochastic variation in fitness components, such as survival, reproduction, and functional traits, rather than dismissal of this variation as uninformative noise.
Disparate effects of MMP and TIMP modulation on coronary atherosclerosis and associated myocardial fibrosis
Authors: Kremastiotis Georgios , Handa Ishita , Jackson Christopher , George Sarah , Johnson Jason
Published: November 2021

Matrix metalloproteinase (MMP) activity is tightly regulated by the endogenous tissue inhibitors (TIMPs), and dysregulated activity contributes to extracellular matrix remodelling. Accordingly, MMP/TIMP balance is associated with atherosclerotic plaque progression and instability, alongside adverse post-infarction cardiac fibrosis and subsequent heart failure. Here, we demonstrate that prolonged high-fat feeding of apolipoprotein (Apo)e-deficient mice triggered the development of unstable coronary artery atherosclerosis alongside evidence of myocardial infarction and progressive sudden death. Accordingly, the contribution of select MMPs and TIMPs to the progression of both interrelated pathologies was examined in Apoe-deficient mice with concomitant deletion of Mmp7, Mmp9, Mmp12, or Timp1 and relevant wild-type controls after 36-weeks high-fat feeding. Mmp7 deficiency increased incidence of sudden death, while Mmp12 deficiency promoted survival, whereas Mmp9 or Timp1 deficiency had no effect. While all mice harboured coronary disease, atherosclerotic burden was reduced in Mmp7-deficient and Mmp12-deficient mice and increased in Timp1-deficient animals, compared to relevant controls. Significant differences in cardiac fibrosis were only observed in Mmp-7-deficient mice and Timp1-deficient animals, which was associated with reduced capillary number. Adopting therapeutic strategies in Apoe-deficient mice, TIMP-2 adenoviral-overexpression or administration (delayed or throughout) of a non-selective MMP inhibitor (RS-130830) had no effect on coronary atherosclerotic burden or cardiac fibrosis. Taken together, our findings emphasise the divergent roles of MMPs on coronary plaque progression and associated post-MI cardiac fibrosis, highlighting the need for selective therapeutic approaches to target unstable atherosclerosis alongside adverse cardiac remodelling while negating detrimental adverse effects on either pathology, with targeting of MMP-12 seeming a suitable target.
Long-term results of ulnar and radial reconstruction with interpositional grafting using the deep inferior epigastric artery for chronic hand ischemia
Authors: Ahn Hee Chang , Oh Se Won , Yoon Jung Soo , Park Seong Oh
Published: November 2021

Chronic hand ischemia causes cold intolerance, intractable pain, and digital ulceration. If ischemic symptoms persist despite pharmacologic treatments, surgical interventions should be considered. This retrospective study evaluated the long-term results after ulnar and radial reconstruction using an interpositional deep inferior epigastric artery (DIEA) graft combined with periarterial sympathectomy. Patients who underwent this surgery from March 2003 to February 2019 were included. To evaluate variables influencing recurrence after the procedure, patients were divided into the recurred and non-recurred groups and their data were compared. Overall, 62 cases involving 47 patients were analyzed (16 and 46 cases in the recurred and non-recurred groups, respectively). The median DIEA graft length was 8.5 cm. The rates of rheumatic disease and female patients were significantly higher in the recurred than in the non-recurred group, without significant between-group differences in postoperative complication rates. In the multivariate analysis, underlying rheumatic disease and graft length had significant effects on recurrence. In Kaplan–Meier analysis, the 5- and 10-year symptom-free rates were 81.3% and 68.0%, respectively, with lower rates for cases with rheumatic disease. Thus, arterial reconstruction using an interpositional DIEA graft provides long-term sustainable vascular supply in patients with chronic hand ischemia, especially in those without rheumatic disease.