bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Test Method Variables on Sensitivity of Neocloeon Triangulifer to a Reference Toxicant in Short-Term, Effluent Style Evaluations
Authors: Soucek David J. , Dickinson Amy , Norberg-King Teresa J.
Published: August 2022

Recent literature has demonstrated the sensitivity of mayflies to environmental contaminants. However, to date, there are no methods approved by the US Environmental Protection Agency for using sensitive insects like mayflies in whole-effluent toxicity or receiving water toxicity tests. The parthenogenetic mayfly Neocloeon triangulifer has been shown to be amenable to continuous culture in the laboratory, and methods have been described for its use in both acute and chronic toxicity studies. The goal of the present study was to investigate aspects of N. triangulifer testing and culturing methods that might require adjustment so that they are applicable for testing effluents and receiving waters in a short-term exposure. To this end, the influence of organism age, test duration, and test temperature on sensitivity to NaCl as a reference toxicant were tested (concentrations ranging from 182 to 2489 mg/L). Further studies were conducted to assess the utility of commercially available diets and the influence of nutrient amendment of water on organism growth and sensitivity. Seven-day NaCl tests started with less than 24-h-old larvae were similar in sensitivity to 14-day and full life chronic tests, and were much more sensitive than those started with 7-day-old organisms. Reducing test temperature from 25 °C to 22 °C had a minor influence on culture timing, and little impact on sensitivity to NaCl. In other experiments, reconstituted test water supplemented with nutrients to potentially improve in-test food quality had minimal effect on growth at 7 days and did not significantly alter acute sensitivity to NaCl relative to unamended reconstituted water. A suitable commercially available, ready-to-feed diet substitute for cultured diatoms was not found. Testing N. triangulifer in effluents or receiving waters with the methods recommended will complement similar methods for Ceriodaphnia dubia. Environ Toxicol Chem 2022;41:2758–2768. © 2022 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
Assessment of health system performance in Germany: Survey‐based insights into the perspective of people with private health insurance
Authors: Achstetter Katharina , Blümel Miriam , Köppen Julia , Hengel Philipp , Busse Reinhard
Published: August 2022

Introduction

The World Health Organization (WHO) defined intermediate and overall goals to assess the performance of health systems. As the population perspective becomes more important for improving health systems, the aim of this study was to gain insights into the perspective of people with private health insurance (PHI) in Germany along the predefined WHO goals.

Methods

A cross‐sectional survey was conducted in 2018 among people with PHI in Germany. The questionnaire included items on all intermediate (access, coverage, quality, and safety) and overall WHO goals (improved health, responsiveness, social and financial risk protection, and improved efficiency). Descriptive analyses were conducted for the total sample and subgroups (gender, age, income, and health status).

Results

In total, 3601 respondents (age 58.5 ± 14.6; 64.7% male) assessed the German health system. For example, 3.3%–7.5% of the respondents with subjective needs reported forgone care in the past 12 months due to waiting time, distance, or financial reasons and 14.4% suspected medical errors in their care. During the last physician visit 94.2% experienced respectful treatment but only 60.6% perceived coordination of care as good. Unnecessary health services were perceived by 24.2%. For many items significant subgroup differences were found, particularly for age groups (18–64 vs. 65+).

Conclusion

Conducting a health system performance assessment from the population perspective gained new and unique insights into the perception of people with PHI in Germany. Areas to improve the health system were seen in, for example, coordination of care, financial risk protection, and quality of care, and inequalities between subgroups were identified.
Anticipated impacts of climate change on women's health: A background primer
Authors: Pandipati Santosh , Abel David E.
Published: August 2022

Due to human activities, atmospheric greenhouse gas levels have increased dramatically, leading to an increase in the global mean surface temperature by 1.1° Celsius. Unless we can achieve a significant reduction in emissions, the global mean surface temperature will continue to rise to a dangerous level. Adverse outcomes of this warming will include extreme weather events, a deterioration of food, water and air quality, decreased food security, and an increase in vector‐borne infectious disease. Political and economic instability as well as mass population migration will result in reduced access to healthcare resources. Mitigation of and adaptation to climate change will be key determinants of humanity's survival in the face of this existential crisis. Women will be more adversely affected by climate change than men, and pregnant persons will be particularly vulnerable. Particular differential impacts on women include higher heat and particulate‐related morbidity and mortality; pregnancy risks including preterm birth, fetal growth lag, hypertensive disorders; and mental health impacts. To prepare for the climate crisis, it  is imperative for women's healthcare providers to assist their patients through political advocacy, provide family planning services, and focus on nutrition and lifestyle counseling.
Epidemiology and Financial Burden of Adult Chronic Hypoparathyroidism
Authors: Bjornsdottir Sigridur , Ing Steven , Mitchell Deborah M , Sikjaer Tanja , Underbjerg Line , Hassan-Smith Zaki , Sfeir Jad , Gittoes Neil J , Clarke L Bart L
Published: August 2022

Chronic hypoparathyroidism is characterized by low serum calcium, increased serum phosphorus, and inappropriately low or decreased serum parathyroid hormone. This rare disorder is associated with a variety of complications. The prevalence, incidence, mortality, financial burden, and epidemiology of complications of this disorder are not well understood. This narrative review summarizes current information on the epidemiology and complications of chronic hypoparathyroidism. The reported prevalence of chronic hypoparathyroidism ranges from 6.4–37/100,000, and the incidence is reported to be 0.8–2.3/100,000/year. Mortality is not increased in studies from Denmark or South Korea but was increased in studies from Scotland and Sweden. The financial burden of this disorder is substantial because of increased health care resource utilization in two studies but not well quantitated. Recognized complications include hypercalciuria, nephrocalcinosis, kidney stones, and chronic kidney disease; low bone turnover and possibly upper extremity fractures; cardiac and vascular calcifications; basal ganglia calcifications, cataracts, infections, neuropsychiatric complications, and difficulties with pregnancy. This review concludes that chronic hypoparathyroidism is a rare disorder associated with significant morbidity that may not increase overall mortality but is associated with a substantial financial burden. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Parathyroid Hormone Therapy for Managing Chronic Hypoparathyroidism: A Systematic Review and Meta-Analysis
Authors: Yao Liang , Li Jing , Li Meixuan , Lin Clement , Hui Xu , Tamilselvan Divyalakshmi , Kandi Maryam , Sreekanta Ashwini , Makhdami Nima , Ali Dalal S. , Dandurand Karel , Yang Kehu , Bilezikian John P. , Brandi Maria Luisa , Clarke Bart L. , Mannstadt Michael , Rejnmark Lars , Khan Aliya A. , Guyatt Gordon
Published: August 2022

The efficacy and safety of parathyroid hormone (PTH) therapy for managing long-term hypoparathyroidism is being evaluated in ongoing clinical trials. We undertook a systematic review and meta-analysis of currently available randomized controlled trials to investigate the benefits and harms of PTH therapy and conventional therapy in the management of patients with chronic hypoparathyroidism. To identify eligible studies, published in English, we searched Embase, PubMed, and Cochrane CENTRAL from inception to May 2022. Two reviewers independently extracted data and assessed the risk of bias. We defined patients' important outcomes and used grading of recommendations, assessment, development, and evaluation (GRADE) to provide the structure for quantifying absolute effects and rating the quality of evidence. Seven randomized trials of 12 publications that enrolled a total of 386 patients proved eligible. The follow-up duration ranged from 1 to 36 months. Compared with conventional therapy, PTH therapy probably achieves a small improvement in physical health-related quality of life (mean difference [MD] 3.4, 95% confidence interval [CI] 1.5–5.3, minimally important difference 3.0, moderate certainty). PTH therapy results in more patients reaching 50% or greater reduction in the dose of active vitamin D and calcium (relative risk [RR] = 6.5, 95% CI 2.5–16.4, 385 more per 1000 patients, high certainty). PTH therapy may increase hypercalcemia (RR =2.4, 95% CI 1.2–5.04, low certainty). The findings may support the use of PTH therapy in patients with chronic hypoparathyroidism. Because of limitations of short duration and small sample size, evidence from randomized trials is limited regarding important benefits of PTH therapy compared with conventional therapy. Establishing such benefits will require further studies. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Myonuclear permanence in skeletal muscle memory: a systematic review and meta‐analysis of human and animal studies
Authors: Rahmati Masoud , McCarthy John J. , Malakoutinia Fatemeh
Published: August 2022

One aspect of skeletal muscle memory is the ability of a previously trained muscle to hypertrophy more rapidly following a period of detraining. Although the molecular basis of muscle memory remains to be fully elucidated, one potential mechanism thought to mediate muscle memory is the permanent retention of myonuclei acquired during the initial phase of hypertrophic growth. However, myonuclear permanence is debated and would benefit from a meta‐analysis to clarify the current state of the field for this important aspect of skeletal muscle plasticity. The objective of this study was to perform a meta‐analysis to assess the permanence of myonuclei associated with changes in physical activity and ageing. When available, the abundance of satellite cells (SCs) was also considered given their potential influence on changes in myonuclear abundance. One hundred forty‐seven peer‐reviewed articles were identified for inclusion across five separate meta‐analyses; (1–2) human and rodent studies assessed muscle response to hypertrophy; (3–4) human and rodent studies assessed muscle response to atrophy; and (5) human studies assessed muscle response with ageing. Skeletal muscle hypertrophy was associated with higher myonuclear content that was retained in rodents, but not humans, with atrophy (SMD = −0.60, 95% CI −1.71 to 0.51, P = 0.29, and MD = 83.46, 95% CI −649.41 to 816.32, P = 0.82; respectively). Myonuclear and SC content were both lower following atrophy in humans (MD = −11, 95% CI −0.19 to −0.03, P = 0.005, and SMD = −0.49, 95% CI −0.77 to −0.22, P = 0.0005; respectively), although the response in rodents was affected by the type of muscle under consideration and the mode of atrophy. Whereas rodent myonuclei were found to be more permanent regardless of the mode of atrophy, atrophy of ≥30% was associated with a reduction in myonuclear content (SMD = −1.02, 95% CI −1.53 to −0.51, P = 0.0001). In humans, sarcopenia was accompanied by a lower myonuclear and SC content (MD = 0.47, 95% CI 0.09 to 0.85, P = 0.02, and SMD = 0.78, 95% CI 0.37–1.19, P = 0.0002; respectively). The major finding from the present meta‐analysis is that myonuclei are not permanent but are lost during periods of atrophy and with ageing. These findings do not support the concept of skeletal muscle memory based on the permanence of myonuclei and suggest other mechanisms, such as epigenetics, may have a more important role in mediating this aspect of skeletal muscle plasticity.
Total flavonoids of Rhizoma drynariae promote angiogenesis and osteogenesis in bone defects
Authors: Lin Haixiong , Wang Xiaotong , Li Zige , Huang Minling , Feng Junjie , Chen Huamei , Gao Junyan , Feng Yuanlan , Wu Jingjing , Tang Shengyao , Zhou Ruoyu , Ren Yueyi , Huang Feng , Jiang Ziwei
Published: August 2022

Bone defects are difficult to heal, which conveys a heavy burden to patients' lives and their economy. The total flavonoids of Rhizoma drynariae (TFRD) can promote the osteogenesis of distraction osteogenesis. However, the dose effect is not clear, the treatment period is short, and the quality of bone formation is poor. In our study, we observed the long‐term effects and dose effects of TFRD on bone defects, verified the main ingredients of TFRD in combination with network pharmacology for the first time, explored its potential mechanism, and verified these findings. We found that TFRD management for 12 weeks regulated osteogenesis and angiogenesis in rats with 4‐mm tibial bone defects through the PI3K/AKT/HIF‐1α/VEGF signaling pathway, especially at high doses (135 mg kg−1 d−1). The vascularization effect of TFRD in promoting human umbilical vein endothelial cells was inhibited by PI3K inhibitors. These results provide a reference for the clinical application of TFRD.
Identifying plant species in kettle holes using UAV images and deep learning techniques
Authors: Correa Martins José Augusto , Marcato Junior José , Pätzig Marlene , Sant'Ana Diego André , Pistori Hemerson , Liesenberg Veraldo , Eltner Anette
Published: August 2022

The use of uncrewed aerial vehicle to map the environment increased significantly in the last decade enabling a finer assessment of the land cover. However, creating accurate maps of the environment is still a complex and costly task. Deep learning (DL) is a new generation of artificial neural network research that, combined with remote sensing techniques, allows a refined understanding of our environment and can help to solve challenging land cover mapping issues. This research focuses on the vegetation segmentation of kettle holes. Kettle holes are small, pond‐like, depressional wetlands. Quantifying the vegetation present in this environment is essential to assess the biodiversity and the health of the ecosystem. A machine learning workflow has been developed, integrating a superpixel segmentation algorithm to build a robust dataset, which is followed by a set of DL architectures to classify 10 plant classes present in kettle holes. The best architecture for this task was Xception, which achieved an average F1‐score of 85% in the segmentation of the species. The application of solely 318 samples per class enabled a successful mapping in the complex wetland environment, indicating an important direction for future health assessments in such landscapes.
Theoretical Progress of 2D Six‐Membered‐Ring Inorganic Materials as Anodes for Non‐Lithium‐Ion Batteries
Authors: Yu Tong , Yang Huicong , Cheng Hui‐Ming , Li Feng
Published: August 2022

The use and storage of renewable and clean energy has become an important trend due to resource depletion, environmental pollution, and the rising price of refined fossil fuels. Confined by the limited resource and uneven distribution of lithium, non‐lithium‐ion batteries have become a new focus for energy storage. The six‐membered‐ring (SMR) is a common structural unit for numerous material systems. 2D SMR inorganic materials have unique advantages in the field of non‐lithium energy storage, such as fast electrochemical reactions, abundant active sites and adjustable band gap. First‐principles calculations based on density functional theory (DFT) can provide a basic understanding of materials at the atomic‐level and establish the relationship between SMR structural units and electrochemical energy storage. In this review, the theoretical progress of 2D SMR inorganic materials in the field of non‐lithium‐ion batteries in recent years is discussed to summarize the common relationship among 2D SMR non‐lithium energy storage anodes. Finally, the existing challenges are analyzed and potential solutions are proposed.
Coordination Engineering of Ultra‐Uniform Ruthenium Nanoclusters as Efficient Multifunctional Catalysts for Zinc–Air Batteries
Authors: Guo Yingying , Wu Donghai , Li Minhan , Wang Kaixi , Zhang Shouren , He Guangli , Yin Hengbo , Huang Chenyu , Yang Baocheng , Zhang Jianan
Published: August 2022

The lack of highly efficient, inexpensive catalysts severely hinders the large‐scale application of electrochemical energy conversion technologies (e.g., electrochemical hydrogen evolution reaction (HER) for hydrogen production, metal–air batteries (Cathode: oxygen reduction reaction (ORR))). As a new class of nanomaterials with a high ratio of surface atoms and tunable composition and electronic structure, metal nanocluster (NCs) are promising candidates as catalysts. Herein, a novel catalyst using S,N‐doped carbon matrix (NSCSs) is synthesized to efficiently stabilize high density and ultra‐uniform ruthenium (Ru) nanoclusters (Ru@NSCSs) by small‐molecule self‐assembly pyrolysis approach. The obtained Ru@NSCSs catalyst exhibits outstanding HER activity in all pH conditions (especially with a low overpotential of 5 mV at a current density of 10 mA cm−2 in 1 m KOH) and excellent ORR performance (half‐wave potential (E
1/2) of 0.854 V in 0.1 m KOH). Based on the experimental investigations and theoretical calculations, it is discovered that the S‐atom can modulate the electronic structure and optimization of redox states on the surficial sites of Ru NCs during the ORR process. This work provides a feasible strategy for understanding and regulating the metal–support interface of ultra‐uniform nanoclusters catalysts.
3D printed concrete as stay‐in‐place formwork: Mechanics during casting and curing
Authors: Bekaert Michiel , Van Tittelboom Kim , De Schutter Geert
Published: August 2022

Research in 3D concrete printing has gained an exponential increase in attention over the last decades. The automated production process can be beneficial to reduce material use and increase form freedom of produced elements. Disadvantages are the difficulty to apply reinforcement, the speed of execution if massive elements have to be made and the uncertain durability performance of the printed material. These aspects still lead to reticence in the concrete construction industry to use 3D printing at a large scale. To lower the threshold to move from the conventional toward the new construction technique, a combination of 3D printed and conventional concrete is proposed namely concrete elements with stay‐in‐place 3D printed formwork. In this paper, experimental research has been performed to investigate the behavior of 3D printed formwork during casting and curing of fresh material. Cylindrical formwork was printed on small scale and filled with self‐compacting concrete. During the experiments, strain development and temperature evolution were measured in and around the elements. The obtained data was analyzed taking in attention the material characteristics of both materials in order to separate the different mechanisms. Results showed that the formwork is subjected to the lateral pressure of the cast concrete, moisture warping and thermal curling. The strains in the formwork increase significantly after casting as a result of moisture warping and thermal curling. The peak strain of the concrete element is reached during the hydration phase of the cast concrete. As the cast concrete stiffened in a slightly deformed formwork, residual strains will be present after the element cooled down.
Introduction
Authors: Checchi Daniele , Jappelli Tullio , Uricchio Antonio
Published: August 2022

Universities are showing increasing interest in measuring research quality, teaching quality and the relationship between them. Research quality affects individual academic careers and has become important for the efficient allocation of public funding which in many countries and especially countries in Europe is the main component of university financial resources. Teaching quality affects students’ careers, and higher quality teaching can reduce dropout rates, improve student performance, and facilitate graduates’ transition to the labor market. The quality of the research and teaching in universities has mutual effects, since good quality and effective teaching is often related to good research performance. Mobility can emphasize these dynamics; the best students and the best teachers may be concentrated in a few universities creating potential quality gaps among public universities.
Multi-population phase oscillator networks with higher-order interactions
Authors: Bick Christian , Böhle Tobias , Kuehn Christian
Published: August 2022

The classical Kuramoto model consists of finitely many pairwisely coupled oscillators on the circle. In many applications a simple pairwise coupling is not sufficient to describe real-world phenomena as higher-order (or group) interactions take place. Hence, we replace the classical coupling law with a very general coupling function involving higher-order terms. Furthermore, we allow for multiple populations of oscillators interacting with each other through a very general law. In our analysis, we focus on the characteristic system and the mean-field limit of this generalized class of Kuramoto models. While there are several works studying particular aspects of our program, we propose a general framework to work with all three aspects (higher-order, multi-population, and mean-field) simultaneously. In this article, we investigate dynamical properties within the framework of the characteristic system. We identify invariant subspaces of synchrony patterns and study their stability. It turns out that the so called all-synchronized state, which is one special synchrony pattern, is never asymptotically stable. However, under some conditions and with a suitable definition of stability, the all-synchronized state can be proven to be at least locally stable. In summary, our work provides a rigorous mathematical framework upon which the further study of multi-population higher-order coupled particle systems can be based.
How do you play that makerspace game? An ethnographic exploration of the habitus of engineering makerspaces
Authors: Alemán Melissa W. , Tomko Megan E. , Linsey Julie S. , Nagel Robert L.
Published: August 2022

Drawing upon Bourdieu’s conceptualization of habitus, this ethnographic study explores the cultural bases guiding engineering makerspaces at a public university in the United States. Students carry forms of capital that impact their entry into these learning spaces, over time becoming disciplined in the “game” of makerspaces as they accumulate capital through everyday talk and storytelling. Communication constructs the makerspace habitus as students (1) move from outsider to insider as they acquire forms of capital; (2) negotiate a habitus characterized by tensions of access vs. exclusivity; (3) learn to use the vocabularies of innovation and creativity; and (4) cultivate supportive making communities. Findings point to the critical role of intentional communication and space design in cultivating inclusive makerspace cultures.
Assessing nonlinearities and heterogeneity in debt sustainability analysis: a panel spline approach
Authors: Owusu Benjamin , Bökemeier Bettina , Greiner Alfred
Published: August 2022

This paper empirically studies public debt sustainability with the penalized panel splines approach for 25 EU economies from 2000 to 2019 by estimating the response of the primary surplus to lagged debt relative to GDP, respectively. A positive coefficient on average indicates sustainable policies, which is supported by all our results. Moreover, we show that this relationship is not homogeneous across the distribution of the debt ratios but varies with the magnitude of public debt to GDP. The estimations reveal a strongly increasing reaction for small and high debt ratios while it is rather flat for intermediate levels. This holds for normal times, too, whereas during years of economic crisis a monotonously increasing response can be observed. Additionally, for a cluster consisting of smaller EU economies, there is an indication of ‘fiscal fatigue’, meaning that the effort of active fiscal counter-steering peters out for high ratios of public debt to GDP. The same effect can be observed for the whole sample and a sample including the large EU economies, once Greece is removed.
Critical evaluation of the role of external calibration strategies for IM-MS
Authors: Feuerstein Max L. , Hernández-Mesa Maykel , Valadbeigi Younes , Le Bizec Bruno , Hann Stephan , Dervilly Gaud , Causon Tim
Published: August 2022

The major benefits of integrating ion mobility (IM) into LC–MS methods for small molecules are the additional separation dimension and especially the use of IM-derived collision cross sections (CCS) as an additional ion-specific identification parameter. Several large CCS databases are now available, but outliers in experimental interplatform IM-MS comparisons are identified as a critical issue for routine use of CCS databases for identity confirmation. We postulate that different routine external calibration strategies applied for traveling wave (TWIM-MS) in comparison to drift tube (DTIM-MS) and trapped ion mobility (TIM-MS) instruments is a critical factor affecting interplatform comparability. In this study, different external calibration approaches for IM-MS were experimentally evaluated for 87 steroids, for which TWCCSN2, DTCCSN2 and TIMCCSN2 are available. New reference CCSN2 values for commercially available and class-specific calibrant sets were established using DTIM-MS and the benefit of using consolidated reference values on comparability of CCSN2 values assessed. Furthermore, use of a new internal correction strategy based on stable isotope labelled (SIL) internal standards was shown to have potential for reducing systematic error in routine methods. After reducing bias for CCSN2 between different platforms using new reference values (95% of TWCCSN2 values fell within 1.29% of DTCCSN2 and 1.12% of TIMCCSN2 values, respectively), remaining outliers could be confidently classified and further studied using DFT calculations and CCSN2 predictions. Despite large uncertainties for in silico CCSN2 predictions, discrepancies in observed CCSN2 values across different IM-MS platforms as well as non-uniform arrival time distributions could be partly rationalized.
Properties of graphs specified by a regular language
Authors: Diekert Volker , Fernau Henning , Wolf Petra
Published: August 2022

Traditionally, graph algorithms get a single graph as input, and then they should decide if this graph satisfies a certain property $$\varPhi $$
Φ
. What happens if this question is modified in a way that we get a possibly infinite family of graphs as an input, and the question is if there is a graph satisfying $$\varPhi $$
Φ
in the family? We approach this question by using formal languages for specifying families of graphs, in particular by regular sets of words. We show that certain graph properties can be decided by studying the syntactic monoid of the specification language L if a certain torsion condition is satisfied. This condition holds trivially if L is regular. More specifically, we use a natural binary encoding of finite graphs over a binary alphabet $$\varSigma $$
Σ
, and we define a regular set $$\mathbb {G}\subseteq \varSigma ^*$$

G
⊆

Σ
∗

such that every nonempty word $$w\in \mathbb {G}$$

w
∈
G

defines a finite and nonempty graph. Also, graph properties can then be syntactically defined as languages over $$\varSigma $$
Σ
. Then, we ask whether the automaton $$\mathcal {A}$$
A
specifies some graph satisfying a certain property $$\varPhi $$
Φ
. Our structural results show that we can answer this question for all “typical” graph properties. In order to show our results, we split L into a finite union of subsets and every subset of this union defines in a natural way a single finite graph F where some edges and vertices are marked. The marked graph in turn defines an infinite graph $$F^\infty $$

F
∞

and therefore the family of finite subgraphs of $$F^\infty $$

F
∞

where F appears as an induced subgraph. This yields a geometric description of all graphs specified by L based on splitting L into finitely many pieces; then using the notion of graph retraction, we obtain an easily understandable description of the graphs in each piece.
Pembrolizumab, radiotherapy, and an immunomodulatory five-drug cocktail in pretreated patients with persistent, recurrent, or metastatic cervical or endometrial carcinoma: Results of the phase II PRIMMO study
Authors: De Jaeghere Emiel A. , Tuyaerts Sandra , Van Nuffel An M. T. , Belmans Ann , Bogaerts Kris , Baiden-Amissah Regina , Lippens Lien , Vuylsteke Peter , Henry Stéphanie , Trinh Xuan Bich , van Dam Peter A. , Aspeslagh Sandrine , De Caluwé Alex , Naert Eline , Lambrechts Diether , Hendrix An , De Wever Olivier , Van de Vijver Koen K. , Amant Frédéric , Vandecasteele Katrien , Denys Hannelore G.
Published: August 2022

A phase II study (PRIMMO) of patients with pretreated persistent/recurrent/metastatic cervical or endometrial cancer is presented. Patients received an immunomodulatory five-drug cocktail (IDC) consisting of low-dose cyclophosphamide, aspirin, lansoprazole, vitamin D, and curcumin starting 2 weeks before radioimmunotherapy. Pembrolizumab was administered three-weekly from day 15 onwards; one of the tumor lesions was irradiated (8Gyx3) on days 15, 17, and 19. The primary endpoint was the objective response rate per immune-related response criteria (irORR) at week 26 (a lower bound of the 90% confidence interval [CI] of > 10% was considered efficacious). The prespecified 43 patients (cervical, n = 18; endometrial, n = 25) were enrolled. The irORR was 11.1% (90% CI 2.0–31.0) in cervical cancer and 12.0% (90% CI 3.4–28.2) in endometrial cancer. Median duration of response was not reached in both cohorts. Median interval-censored progression-free survival was 4.1 weeks (95% CI 4.1–25.7) in cervical cancer and 3.6 weeks (95% CI 3.6–15.4) in endometrial cancer; median overall survival was 39.6 weeks (95% CI 15.0–67.0) and 37.4 weeks (95% CI 19.0–50.3), respectively. Grade ≥ 3 treatment-related adverse events were reported in 10 (55.6%) cervical cancer patients and 9 (36.0%) endometrial cancer patients. Health-related quality of life was generally stable over time. Responders had a significantly higher proportion of peripheral T cells when compared to nonresponders (p = 0.013). In conclusion, PRIMMO did not meet its primary objective in both cohorts; pembrolizumab, radiotherapy, and an IDC had modest but durable antitumor activity with acceptable but not negligible toxicity.

Trial registration ClinicalTrials.gov (identifier NCT03192059) and EudraCT Registry (number 2016-001569-97).
Stability-instability transition in tripartite merged ecological networks
Authors: Emary Clive , Malchow Anne-Kathleen
Published: August 2022

Although ecological networks are typically constructed based on a single type of interaction, e.g. trophic interactions in a food web, a more complete picture of ecosystem composition and functioning arises from merging networks of multiple interaction types. In this work, we consider tripartite networks constructed by merging two bipartite networks, one mutualistic and one antagonistic. Taking the interactions within each sub-network to be distributed randomly, we consider the stability of the dynamics of the network based on the spectrum of its community matrix. In the asymptotic limit of a large number of species, we show that the spectrum undergoes an eigenvalue phase transition, which leads to an abrupt destabilisation of the network as the ratio of mutualists to antagonists is increased. We also derive results that show how this transition is manifest in networks of finite size, as well as when disorder is introduced in the segregation of the two interaction types. Our random-matrix results will serve as a baseline for understanding the behaviour of merged networks with more realistic structures and/or more detailed dynamics.
Involvement of glutamine synthetase 2 (GS2) amplification and overexpression in Amaranthus palmeri resistance to glufosinate
Authors: Noguera Matheus M. , Porri Aimone , Werle Isabel S. , Heiser James , Brändle Frank , Lerchl Jens , Murphy Brent , Betz Michael , Gatzmann Fanny , Penkert Martin , Tuerk Clara , Meyer Lucie , Roma-Burgos Nilda
Published: August 2022

Main conclusion

Amplification and overexpression of the target site glutamine synthetase, specifically the plastid-located isoform, confers resistance to glufosinate in Amaranthus palmeri. This mechanism is novel among glufosinate-resistant weeds.

Amaranthus palmeri has recently evolved resistance to glufosinate herbicide. Several A. palmeri populations from Missouri and Mississippi, U.S.A. had survivors when sprayed with glufosinate-ammonium (GFA, 657 g ha−1). One population, MO#2 (fourfold resistant) and its progeny (sixfold resistant), were used to study the resistance mechanism, focusing on the herbicide target glutamine synthetase (GS). We identified four GS genes in A. palmeri; three were transcribed: one coding for the plastidic protein (GS2) and two coding for cytoplasmic isoforms (GS1.1 and GS1.2). These isoforms did not contain mutations associated with resistance. The 17 glufosinate survivors studied showed up to 21-fold increase in GS2 copies. GS2 was expressed up to 190-fold among glufosinate survivors. GS1.1 was overexpressed > twofold in only 3 of 17, and GS1.2 in 2 of 17 survivors. GS inhibition by GFA causes ammonia accumulation in susceptible plants. Ammonia level was analyzed in 12 F1 plants. GS2 expression was negatively correlated with ammonia level (r =  – 0.712); therefore, plants with higher GS2 expression are less sensitive to GFA. The operating efficiency of photosystem II (ϕPSII) of Nicotiana benthamiana overexpressing GS2 was four times less inhibited by GFA compared to control plants. Therefore, increased copy and overexpression of GS2 confer resistance to GFA in A. palmeri (or other plants). We present novel understanding of the role of GS2 in resistance evolution to glufosinate.
The SNARC effect: a preregistered study on the interaction of horizontal, vertical, and sagittal spatial–numerical associations
Authors: Aleotti Sara , Massaccesi Stefano , Priftis Konstantinos
Published: August 2022

Small numbers are processed faster through left-sided than right-sided responses, whereas large numbers are processed faster through right-sided than left-sided responses [i.e., the Spatial–Numerical Association of Response Codes (SNARC) effect]. This effect suggests that small numbers are mentally represented on the left side of space, whereas large numbers are mentally represented on the right side of space, along a mental number line. The SNARC effect has been widely investigated along the horizontal Cartesian axis (i.e., left–right). Aleotti et al. (Cognition 195:104111, 2020), however, have shown that the SNARC effect could also be observed along the vertical (i.e., small numbers-down side vs. large numbers-up side) and the sagittal axis (i.e., small numbers-near side vs. large numbers-far side). Here, we investigated whether the three Cartesian axes could interact to elicit the SNARC effect. Participants were asked to decide whether a centrally presented Arabic digit was odd or even. Responses were collected through an ad hoc-made response box on which the SNARC effect could be compatible for one, two, or three Cartesian axes. The results showed that the higher the number of SNARC-compatible Cartesian axes, the stronger the SNARC effect. We suggest that numbers are represented in a three-dimensional number space defined by interacting Cartesian axes.
Splenic artery embolization changes the management of blunt splenic injury: an observational analysis of 680 patients graded by the revised 2018 AAST-OIS
Authors: Lin Being-Chuan , Wu Cheng-Hsien , Wong Yon-Cheong , Chen Huan-Wu , Fu Chen-Ju , Huang Chen-Chih , Wu Chen-Te , Hsieh Chi-Hsun
Published: August 2022

Background

This study aimed to evaluate the management of blunt splenic injury (BSI) and highlight the role of splenic artery embolization (SAE).

Methods

We conducted a retrospective review of all patients with BSI over 15 years. Splenic injuries were graded by the 2018 revision of the American Association for the Surgery of Trauma-Organ Injury Scale (AAST-OIS). Our hospital provide 24/7 in-house surgeries and 24/7 in-house interventional radiology facility. Patients with BSI who arrived hypotensive and were refractory to resuscitation required surgery and patients with vascular injury on abdominal computed tomography were considered for SAE.

Results

In total, 680 patients with BSI, the number of patients who underwent nonoperative management with observation (NOM-obs), SAE, and surgery was 294, 234, and 152, respectively. The number of SAEs increased from 4 (8.3%) in 2001 to 23 (60.5%) in 2015 (p < 0.0001); conversely, the number of surgeries decreased from 21 (43.8%) in 2001 to 4 (10.5%) in 2015 (p = 0.001). The spleen-related mortality rate of NOM-obs, SAEs, and surgery was 0%, 0.4%, and 7.2%, respectively. In the SAE subgroup, according to the 2018 AAST-OIS, 234 patients were classified as grade II, n = 3; III, n = 21; IV, n = 111; and V, n = 99, respectively.; and compared with 1994 AST-OIS, 150 patients received a higher grade and the total number of grade IV and V injuries ranged from 96 (41.0%) to 210 (89.7%) (p < 0.0001). On angiography, 202 patients who demonstrated vascular injury and 187 achieved hemostasis after SAE with a 92.6% success rate. Six of the 15 patients failed to SAE preserved the spleen after second embolization with a 95.5% salvage rate.

Conclusions

Our data confirm the superiority of the 2018 AAST-OIS and support the role of SAE in changing the trend of management of BSI.

Graphical abstract
Long-term results of minimally invasive transanal surgery for rectal tumors in 249 consecutive patients
Authors: Maeda Kotaro , Koide Yoshikazu , Katsuno Hidetoshi , Tajima Yosuke , Hanai Tsunekazu , Masumori Koji , Matsuoka Hiroshi , Shiota Miho
Published: August 2022

Purpose

To delineate the long-term results of minimally invasive transanal surgery (MITAS) for selected rectal tumors.

Methods

We analyzed data, retrospectively, on consecutive patients who underwent MITAS between 1995 and 2015, to establish the feasibility, excision quality, and perioperative and oncological outcomes of this procedure.

Results

MITAS was performed on 243 patients. The final histology included 142 cancers, 47 adenomas, and 52 neuroendocrine tumors (NET G1). A positive margin of 1.6% and 100% en bloc resection were achieved. The mean operative time was 27.4 min. Postoperative morbidity occurred in 7% of patients, with 0% mortality. The median follow-up was 100 months (up to ≥ 5 years or until death in 91.8% of patients). Recurrence developed in 2.9% of the patients. The 10-year overall survival rate was 100% for patients with NET G1 and 80.3% for those with cancer. The 5-year DFS was 100% for patients with Tis cancer, 90.6% for those with T1 cancer, and 87.5% for those with T2 or deeper cancers. MITAS for rectal tumors ≥ 3 cm resulted in perioperative and oncologic outcomes equivalent to those for tumors < 3 cm.

Conclusion

MITAS is feasible for the local excision (LE) of selected rectal tumors, including tumors ≥ 3 cm. It reduces operative time and secures excision quality and long-term oncological outcomes.
The riskiness of stock versus money market investment with stochastic rates
Authors: Szabó Dávid Zoltán , Bihary Zsolt
Published: August 2022

To efficiently assess the performance of investing in stocks rather than in a bank account for the long run, stochastic interest rate modelling is advocated. We introduce a correlated stochastic interest rate model that addresses this problem. We derive analytic formulas for general spectral risk measures in our setting, and apply our results to Value at Risk, Expected Shortfall and GlueVaR. We characterize the short- and long-term behaviour of these risk measures. We fit our model to financial markets, perform an empirical study and evaluate risk numbers for realistic scenarios in the future. Our results reveal sizeable sensitivities on parameter estimation, but we may conclude that holding stocks for less than a few decades bears significant risk.
Health and labor force participation among older workers in Switzerland: a growth curve analysis
Authors: Feer Sonja , Lipps Oliver , Dratva Julia , Baumann Isabel
Published: August 2022

This study investigated how individual trajectories of self-rated health (SRH) and working hours among older workers in Switzerland are interrelated and how this relationship varies based on occupation. We used data from the Swiss Household Panel to analyze the long-term trajectories of older workers measured in terms of working hours and SRH. The sample included more than 4000 workers aged 50 to 65(men)/64(women). We ran a bivariate response multilevel model for growth that allowed the examination of between- and within-individual changes over time. On a between-individual level, we found that the upper non-manual workers were the most heterogeneous occupational group in terms of working hours and the lower non-manual workers were the most heterogeneous occupational group in terms of health. Within all occupational groups, we found a significant relationship between the level of working hours and level of SRH. The individual-level statistics showed consistently strongest effects for manual workers. This result confirms our hypothesis that labor force participation in individuals of the manual occupational group is more sensitive to their health status. Our findings contribute to the debate regarding the importance of older workers’ health in the context of the extension of working life.
Inventing Engineered Organoids for end-stage liver failure patients
Authors: Antarianto Radiana D , Mahmood Amer , Giselvania Angela , Asri Dewi Ayu AA Prima , Gustinanda Jatmiko , Pawitan Jeanne Adiwinata
Published: August 2022

End-stage liver disease (ESLD) is a term used clinically in reference to a group of liver diseases with liver transplantation as the choice of treatment. Due to the limitations of liver transplantation, alternative treatments are needed. The use of primary human hepatocytes represents a valid alternative treatment, but the limitations related to hepatocyte quality, viability, function, conservation, and storage need to be overcome. Transplanted hepatocytes have only been followed for 6–9 months. Therefore, long-term causes of failures are not yet established, including rejection, apoptosis, or other causes. Other alternative therapies to replace liver transplantation include plasmapheresis, hemodiafiltration, and artificial livers. Unfortunately, these methods are highly limited due to availability, high cost, anaphylaxis reaction, development-deposition of immune-complexes, and restricted functionality. Liver organoids, which utilize stem cells instead of ‘impractical’ adult hepatocytes, may be a solution for the development of a complex bioartificial liver. Recent studies have explored the benefits of differentiating mature hepatocytes from stem cells inside a bioreactor. When the use of human-induced Hepatocytes (hiHeps) was investigated in mouse and pig models of liver failure, liver failure markers were decreased, hepatocyte function indicated by albumin synthesis improved, and survival time increased. Bioartificial liver treatment may decrease the infiltration of inflammatory cells into liver tissue by down-regulating pro-inflammatory cytokines.
Identification of novel proteins involved in P2X7-mediated signaling cascades
Authors: Sassenbach Lukas
Published: August 2022

High concentration of extracellular ATP acts as a danger signal that is sensed by the P2X7 receptor (P2X7R). This ATP-gated ion channel has been shown to induce multiple metabotropic events such as changes in plasma membrane composition and morphology, ectodomain shedding, activation of lipases, kinases, and transcription factors as well as cytokine release. The specific signaling pathways and molecular mechanisms remain largely obscure. Using an unbiased genome-scale CRISPR/Cas9 screening approach in a murine T cell line, Ryoden et al. (2022, 2020) identified three proteins involved in P2X7 regulation and signaling: Essential for Reactive Oxygen Species (EROS) is essential for P2X7 folding and maturation, and Xk and Vsp13a are required for P2X7-mediated phosphatidyl serine exposure and cell lysis. They further provide evidence for an interaction of Xk and Vsp13a at the plasma membrane and confirm the role of Xk in ATP-induced cytolysis in primary CD25+CD4+ T cells from Xk−/− mice.
Blended-eLearning Improves Alcohol Use Care in Kenya: Pragmatic Randomized Control Trial Results and Parallel Qualitative Study Implications
Authors: Clair Veronic , Musau Abednego , Mutiso Victoria , Tele Albert , Atkinson Katlin , Rossa-Roccor Verena , Bosire Edna , Ndetei David , Frank Erica
Published: August 2022

Alcohol use is the 5th most important risk factor contributing to the global burden of diseases, with stigma and a lack of trained health workers as the main barriers to adequate care. This study assesses the impact of providing blended-eLearning courses teaching the alcohol, smoking, and substance involvement screening test (ASSIST) screening and its linked brief intervention (BI). In public and private facilities, two randomized control trials (RCTs) showed large and similar decreases in alcohol use in those receiving the BI compared to those receiving only the ASSIST feedback. Qualitative findings confirm a meaningful reduction in alcohol consumption; decrease in stigma and significant practice change, suggesting lay health workers and clinicians can learn effective interventions through blended-eLearning; and significantly improve alcohol use care in a low- and middle-income country (LMIC) context. In addition, our study provides insight into why lay health workers feedback led to a similar decrease in alcohol consumption compared to those who also received a BI by clinicians.
Extreme heavy metal and blasphemy in Iran: the case of Confess
Authors: Eckerström Pasqualina
Published: August 2022

Since the revolution in 1979, the Islamic Republic of Iran has imprisoned musicians, especially punk, hip-hop, and hard rock bands, as well as those playing heavy metal subgenres. Extreme heavy metal artists and fans emerged in the 1990s. The government soon targeted them as Satanists and began a systematic crackdown on metalheads. The metalcore band Confess is the most well-known case. The band was arrested in 2015 on counts of blasphemy, disturbing public opinion through the production of music, participating in interviews with the opposition media and propaganda against the Islamic Republic of Iran, among other charges. The majority of secular countries today do not consider extreme heavy metal to be transgressive. This is not the case in contexts where religious traditions have a significant influence on society. By analysing the narrative of the band Confess, the purpose of this paper is to provide an understanding of how Iranian extreme metal musicians resist religious oppression, challenge their government, religious precepts, and social values through their music.