bluuebunny/crossref_metadata_2025 huggingface dataset:
2020 ESC Guidelines on Sports Cardiology and Exercise in Patients
with Cardiovascular Disease
Authors: Malik Anaya
Published: December 2021

ADVISING individuals with diseases of the heart on what types and intensities of sport to participate in is not a practice cardiologists typically have official guidelines on. A taskforce from ESC has now come together and created guidelines, the first of their kind, on exercise and sports participation in patients with cardiovascular disease. The guidelines were presented at the ESC Congress 2020 in a session chaired by Prof Antonio Pelliccia, Scientific Director of the Institute of Sports Medicine & Science from Rome, Italy.

Pelliccia was joined by Prof Martin Halle, President of the European Association of Preventive Cardiology (EAPC), Munich, Germany, and Prof Matthias Wilhem, Head of the Centre for Preventive Cardiology, Sports Medicine, Department of Cardiology at the Inselspital, University Hospital of Bern, Switzerland. The guidelines derived from the need to assist patients who had experienced cardiovascular events and were questioning their limits of sports participation. Prof Halle commented on his experience in the taskforce: “The level of evidence is rather low, so it is very much the personal perspective and the experience of the experts which made us come to that one conclusion in the guidelines. It is something that should be developed in years to come.”

A series of videos were shown, presented by specialists who were invited to discuss some of the most relevant topics of the guidelines.
An Overview of Novel and Emerging Therapies for Inflammatory Bowel Disease
Authors: Sumona Bhattacharya Sumona Bhattacharya , Raymond K. Cross Raymond K. Cross
Published: December 2021

Inflammatory bowel disease, consisting of Crohn’s disease and ulcerative colitis, causes chronic gastrointestinal symptoms and can lead to morbidity and mortality if uncontrolled or untreated. However, for patients with moderate-to-severe disease, currently available therapies do not induce or maintain remission in >50% of patients. This underscores the need for additional therapies. In this review, the authors detail the novel therapies vedolizumab, tofacitinib, and ustekinumab and delve into therapies which may come onto the market within the next 10 years, including JAK-1 inhibitors (filgotinib and upadacitinib), IL-23 inhibitors (guselkumab, mirikizumab, and risankizumab), the anti-β4β7 and anti-βEβ7 integrin monoclonal antibody etrolizumab, the sphingosine-1-phosphate subtypes 1 and 5 modulator ozanimod, and mesenchymal stem cells. Further studies are required before these emerging therapies gain approval.
Lessons Learned from a Global History of Pandemics
Authors: Archer-Diaby Lenos
Published: December 2021

PANDEMIC: the term making headlines across the world, instilling fear in many, and urging scientists across the world to unite and find a cure. For as long as the global population has exploited freedom of travel, so too have infectious diseases spread. Outbreaks have been nearly constant since the dawn of mankind; however, not all escalate to global levels. There have been many pandemics in history, the most recent being COVID-19 declared as such by the World Health Organization (WHO) on March 12th, 2020.1 As the COVID-19 pandemic continues to disrupt our everyday lives, it is important to look back in history and reflect on what previous pandemics have taught us.
Ecology and metabolic activity of cyanobacteria in large different types of lowland reservoirs in the European part of Russia
Authors: Korneva Lyudmila G. , Solovyova Vera V. , Sidelev Sergey I. , Chernova Ekaterina N. , Russkich Yana V.
Published: December 2021

A comparative of the species composition and ecological-geographical characteristics of cyanobacteria plankton of 13 reservoirs of the Volga-Kama cascade and the Don (Sheksna, Ivankovo, Uglich, Rybinsk, Gorky, Cheboksary, Kuibyshev, Saratov, Volgograd, Kama, Votkinsk, Nizhnekamsk and Tsimlyansk reservoirs) is analysed. An assessment of the change in the distribution of cyanobacteria biomass in a latitudinal gradient along the Volga cascade is presented. The seasonal and long-term (1954–2016) dynamics of the abundance, biomass and the ratio of functional groups of cyanobacteria in the Rybinsk Reservoir, the second largest in the cascade of Volga reservoirs, are analyzed. A positive long-term trend of abundance and diversity of cyanobacteria and the leveling of their biomass between reservoirs along a cascade in recent years has been established. An increase in the abundance and diversity of nonheterocystous species was established in the direction from the Upper to the Lower Volga and during the long-term succession of phytoplankton of the Rybinsk Reservoir. This is associated with an increase of water mineralization. Based on current research in the 2010s of the Volga, Kama and Don cascade reservoirs, 14 variants of microcystin structures were identified, the diversity of which depended on the composition of the producing species. Using PCR analysis, the main producers of microcystins (Microcystis and Dolichospermum) were identified. Cyanobacteria Cuspidothrix issatschenkoi and/or Raphidiopsis mediterranea have been identified as possible producers of neurotoxic anatoxin-a in the Tsimlyansk Reservoir. It was shown that water temperature and nitrogen were the greatest importance for development of microcystin-producing species of cyanobacteria.
Phototrophic communities of Kulunda Steppe soda lakes (Altai Region): history of algological studies and modern data.
Authors: Samylina Olga S.
Published: December 2021

The Kulunda Steppe soda lakes are the only occurrence of hypersaline soda lakes in Russia. They are characterized by a variable hydrological regime with cyclic high-amplitude fluctuations of temperature and brine concentration. The algae of the Kulunda Steppe soda lakes were first studied by Soviet phycologists headed by N.N. Voronikhin in 1927–1932 and new taxa were described: algal genus Lochmiopsis Woronich. et Popova (later revised to Ctenocladus circinnatus Borzì) and cyanobacterial species Aphanocapsa salina Woronich., Synechocystis crassa Woronich., Trichormus (Anabaena) pseudovariabilis (Woronich.) Komárek et Anagnostidis, Anabaenopsis issatschenkoi Woronich., Anabaenopsis milleri Woronich., Anabaenopsis nadsonii Woronich., Oscillatoria deflexa var. crassa Woronich., Limnospira (Arthrospira, Spirulina) fusiformis (Woronich.) Komárek et Lund. Later (since 2007) studies were continued by the microbiologists from the Winogradsky Institute of Microbiology RAS. In this work, a comparison of the algological diversity found in the soda lakes of the Kulunda Steppe during periods 1929–1932 and 2007–2020 is made, and a brief overview of taxonomic problems of selected eukaryotic algae and cyanobacteria is given. In total, 33 morphotypes of cyanobacteria were identified. Most species of algae and cyanobacteria were described based on the exclusively morphological criteria. Thus, their phylogenetic position remains unclear and requires careful analysis using a modern polyphasic approach.
The Shared Economy
Authors: LOH KC
Published: December 2021

Abstract: The theory of marginal utility describes how consumers choose between goods. However, marginal utility has also found application in a wide range of weightier subjects. For example, marginal utility can be used in the allocation of resources in healthcare programmes. This paper posits that marginal utility is also applicable in the allocation of the national income among corporations, government, and households. Using data from the UK Office for National Statistics, this paper finds that for the most part of the decade, from 2009 to 2018, household disposable income fell short of what might be considered an optimal share of the national income.
Can a Glove-Coach Technology Significantly Increase the Efficacy of Cardiopulmonary Resuscitation on Non-healthcare Professionals? A Controlled Trial
Authors: Musiari Michele , Saporito Andrea , Ceruti Samuele , Biggiogero Maira , Iattoni Martina , Glotta Andrea , Cantini Laura , Capdevila Xavier , Cassina Tiziano
Published: December 2021

Introduction: Cardiovascular accidents are the world's leading cause of death. A good quality cardiopulmonary resuscitation (CPR) can reduce cardiac arrest-associated mortality. This study aims to test the coaching system of a wearable glove, providing instructions during out-of-hospital CPR.

Materials and Methods: We performed a single-blind, controlled trial to test non-healthcare professionals during a simulated CPR performed on an electronic mannequin. The no-glove group was the control. The primary outcome was to compare the accuracy of depth and frequency of two simulated CPR sessions. Secondary outcomes were to compare the decay of CPR performance and the percentage of the duration of accurate CPR.

Results: About 130 volunteers were allocated to 1:1 ratio in both groups; mean age was 36 ± 15 years (min–max 21–64) and 62 (48%) were men; 600 chest compressions were performed, and 571 chest compressions were analyzed. The mean frequency in the glove group was 117.67 vs. 103.02 rpm in the control group (p < 0.001). The appropriate rate cycle was 92.4% in the glove group vs. 71% in the control group, with a difference of 21.4% (p < 0.001). Mean compression depth in the glove group was 52.11 vs. 55.17 mm in the control group (p < 0.001). A mean reduction of compression depth over time of 5.3 mm/min was observed in the control group vs. 0.83 mm/min of reduction in the glove group.

Conclusion: Visual and acoustic feedbacks provided through the utilization of the glove's coaching system were useful for non-healthcare professionals' CPR performance.
Therapeutic Applications of Extracellular Vesicles for Myocardial Repair
Authors: Liu Chunping , Bayado Nathan , He Dongyue , Li Jie , Chen Huiqi , Li Longmei , Li Jinhua , Long Xinyao , Du Tingting , Tang Jing , Dang Yue , Fan Zhijin , Wang Lei , Yang Phillip C.
Published: December 2021

Cardiovascular disease is the leading cause of human death worldwide. Drug thrombolysis, percutaneous coronary intervention, coronary artery bypass grafting and other methods are used to restore blood perfusion for coronary artery stenosis and blockage. The treatments listed prolong lifespan, however, rate of mortality ultimately remains the same. This is due to the irreversible damage sustained by myocardium, in which millions of heart cells are lost during myocardial infarction. The lack of pragmatic methods of myocardial restoration remains the greatest challenge for effective treatment. Exosomes are small extracellular vesicles (EVs) actively secreted by all cell types that act as effective transmitters of biological signals which contribute to both reparative and pathological processes within the heart. Exosomes have become the focus of many researchers as a novel drug delivery system due to the advantages of low toxicity, little immunogenicity and good permeability. In this review, we discuss the progress and challenges of EVs in myocardial repair, and review the recent development of extracellular vesicle-loading systems based on their unique nanostructures and physiological functions, as well as the application of engineering modifications in the diagnosis and treatment of myocardial repair.
Recombinant Human Follicle-Stimulating Hormone Alfa Dose Adjustment in US Clinical Practice: An Observational, Retrospective Analysis of a Real-World Electronic Medical Records Database
Authors: Mahony Mary C. , Hayward Brooke , Mottla Gilbert L. , Richter Kevin S. , Beall Stephanie , Ball G. David , D’Hooghe Thomas
Published: December 2021

Purpose

To determine the pattern of dose adjustment of recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa) during ovarian stimulation (OS) for assisted reproductive technology (ART) in a real-world setting.

Methods

This was an observational, retrospective analysis of data from an electronic de-identified medical records database including 39 clinics in the USA. Women undergoing OS for ART (initiated 2009–2016) with r-hFSH-alfa (Gonal-f® or Gonal-f RFF Redi-ject®) were included. Assessed outcomes were patients’ baseline characteristics and dosing characteristics/cycle.

Results

Of 33,962 ART cycles, 13,823 (40.7%) underwent dose adjustments: 23.4% with ≥1 dose increase, 25.4% with ≥1 dose decrease, and 8.1% with ≥1 increase and ≥1 decrease. Patients who received dose adjustments were younger (mean [SD] age 34.8 [4.58] years versus 35.9 [4.60] years, p<0.0001) and had lower BMI (25.1 [5.45] kg/m2 versus 25.5 [5.45] kg/m2, p<0.0001) than those who received a constant dose. The proportion of patients with non-normal ovarian reserve was 38.4% for those receiving dose adjustment versus 51.9% for those with a constant dose. The mean (SD) number of dose changes/cycle was 1.61 (0.92) for cycles with any dose adjustment, 1.72 (1.03) for cycles with ≥1 dose increase, 2.77 (1.00) for cycles with ≥1 dose increase and ≥1 decrease (n=2,755), and 1.88 (1.03) for cycles with ≥1 dose decrease.

Conclusions

Dose adjustment during OS is common in clinical practice in the USA and occurred more often in younger versus older patients, those with a high versus non-normal ovarian reserve or those with ovulation disorders/polycystic ovary syndrome versus other primary diagnoses of infertility.
Combined Oral Contraceptives and Venous Thromboembolism: Review and Perspective to Mitigate the Risk
Authors: Morimont Laure , Haguet Hélène , Dogné Jean-Michel , Gaspard Ulysse , Douxfils Jonathan
Published: December 2021

Many factors must be considered and discussed with women when initiating a contraceptive method and the risk of venous thromboembolism (VTE) is one of them. In this review, we discuss the numerous strategies that have been implemented to reduce the thrombotic risk associated with combined oral contraceptives (COCs) from their arrival on the market until today. Evidences suggesting that COCs were associated with an increased risk of VTE appeared rapidly after their marketing. Identified as the main contributor of this risk, the dosage of the estrogen, i.e., ethinylestradiol (EE), was significantly reduced. New progestins were also synthetized (e.g., desogestrel or gestodene) but their weak androgenic activity did not permit to counterbalance the effect of EE as did the initial progestins such as levonorgestrel. Numerous studies assessed the impact of estroprogestative combinations on hemostasis and demonstrated that women under COC suffered from resistance towards activated protein C (APC). Subsequently, the European Medicines Agency updated its guidelines on clinical investigation of steroid contraceptives in which they recommended to assess this biological marker. In 2009, estradiol-containing COCs were marketed and the use of this natural form of estrogen was found to exert a weaker effect on the synthesis of hepatic proteins compared to EE. In this year 2021, a novel COC based on a native estrogen, i.e., estetrol, will be introduced on the market. Associated with drospirenone, this preparation demonstrated minor effects on coagulation proteins as compared with other drospirenone-containing COCs. At the present time, the standard of care when starting a contraception, consists of identifying the presence of hereditary thrombophilia solely on the basis of familial history of VTE. This strategy has however been reported as poorly predictive of hereditary thrombophilia. One rationale and affordable perspective which has already been considered in the past could be the implementation of a baseline screening of the prothrombotic state to provide health care professionals with objective data to support the prescription of the more appropriate contraceptive method. While this strategy was judged too expensive due to limited laboratory solutions, the endogenous thrombin potential-based APC resistance assay could now represent an interesting alternative.
Mild Anemia May Affect Thyroid Function in Pregnant Chinese Women During the First Trimester
Authors: Nie Guan-ying , Wang Rui , Liu Peng , Li Ming , Sun Dian-jun
Published: December 2021

Background

Pregnant women are often susceptible to anemia, which can damage the thyroid gland. However, compared with moderate and severe anemia, less attention has been paid to mild anemia. The purpose of this study was to evaluate the effect of mild anemia on the thyroid function in pregnant women during the first trimester.

Methods

A total of 1,761 women in the first trimester of their pregnancy were enrolled from Shenyang, China, and divided into mild anemia and normal control groups based on their hemoglobin levels. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) levels were compared between the two groups.

Results

The TSH levels of pregnant women with mild anemia were higher than those of pregnant women without mild anemia (p < 0.05). Normal control women were selected to set new reference intervals for TSH, FT3, and FT4 levels during the first trimester, which were 0.11–4.13 mIU/l, 3.45–5.47 pmol/l, and 7.96–16.54 pmol/l, respectively. The upper limit of TSH 4.13 mU/l is close to the upper limit 4.0 mU/l recommended in the 2017 American Thyroid Association (ATA) guidelines, indicating that exclusion of mild anemia may reduce the difference in reference values from different regions. Mild anemia was related to 4.40 times odds of abnormally TSH levels (95% CI: 2.84, 6.76) and 5.87 increased odds of abnormal FT3 (95% CI: 3.89, 8.85). The proportion of hypothyroidism and subclinical hypothyroidism in patients with mild anemia was higher than that in those without anemia (0.6% vs. 0, p = 0.009; 12.1% vs. 1.9%, p < 0.001). Mild anemia was related to 7.61 times increased odds of subclinical hypothyroidism (95% CI: 4.53, 12.90).

Conclusions

Mild anemia may affect thyroid function during the first trimester, which highlights the importance of excluding mild anemia confounding when establishing a locally derived specific reference interval for early pregnancy.
NDRG1 Activity in Fat Depots Is Associated With Type 2 Diabetes and Impaired Incretin Profile in Patients With Morbid Obesity
Authors: Stafeev Iurii , Sklyanik Igor , Mamontova Elizaveta , Michurina Svetlana , Shestakova Ekaterina , Yah’yaev Kamil , Yurasov Anatoliy , Masnikov Denis , Sineokaya Maria , Ratner Elizaveta , Vorotnikov Alexander , Menshikov Mikhail , Parfyonova Yelena , Shestakova Marina
Published: December 2021

Objective

We aimed to investigate insulin-, mTOR- and SGK1-dependent signaling basal states in morbidly obese patients’ fat. We analyzed the correlation between the signaling activity, carbohydrate metabolism, and incretin profiles of patients.

Methods

The omental and subcutaneous fat was obtained in patients with obesity. The omental study included 16 patients with normal glucose tolerance (NGT) and 17 patients with type 2 diabetes mellitus (T2DM); the subcutaneous study included 9 NGT patients and 12 T2DM patients. Insulin resistance was evaluated using the hyperinsulinemic euglycemic clamp test and HOMA-IR index. The oral glucose tolerance test (OGTT) for NGT patients and mixed meal tolerance test (MMTT) for T2DM patients were performed. The levels of incretins (GLP-1, GIP, oxyntomodulin) and glucagon were measured during the tests. Signaling was analyzed by Western blotting in adipose tissue biopsies.

Results

We have shown equal levels of basal phosphorylation of insulin- and mTOR-dependent signaling in omental fat depot in NGT and T2DM obese patients. Nevertheless, pNDRG1-T346 was decreased in omental fat of T2DM patients. Correlation analysis has shown an inverse correlation of pNDRG1-T346 in omental fat and diabetic phenotype (HbA1c, impaired incretin profile (AUC GLP-1, glucagon)). Moreover, pNDRG1-T346 in subcutaneous fat correlated with impaired incretin levels among obese patients (inverse correlation with AUC glucagon and AUC GIP).

Conclusions

According to results of the present study, we hypothesize that phosphorylation of pNDRG1-T346 can be related to impairment in incretin hormone processing. pNDRG1-T346 in adipose tissue may serve as a marker of diabetes-associated impairments of the systemic incretin profile and insulin sensitivity.
Association Between the Triglyceride–Glucose Index and the Incidence of Diabetes in People With Different Phenotypes of Obesity: A Retrospective Study
Authors: Zou Su , Yang Chenxi , Shen Rui , Wei Xiang , Gong Junwen , Pan Yali , Lv Yang , Xu Yingjia
Published: December 2021

Aim

We aimed to examine the relationship between the Triglyceride–glucose (TyG) index and the incidence of type 2 diabetes in people with different phenotypes of obesity.

Methods

From May 1, 1994 to December 31, 2016, 15,464 participants were enrolled in the medical examination program at the Murakami Memorial Hospital to determine the relationship between the TyG index and the incidence of type 2 diabetes in people with different phenotypes of obesity after 5.38 years of follow-up.

Results

Besides triglycerides, HbA1c%, and FPG, the incidence of type 2 diabetes was found to be significantly associated with the TyG index (p <0.001), age (p <0.001), BMI (p = 0.033), current smoker (p <0.001), and fatty liver (p <0.001). In participants with visceral fat obesity and/or ectopic fat obesity and normal BMI, the TyG index was significantly associated with the incidence of type 2 diabetes after adjusting for confounding factors. In patients with BMI ≥25 mg/m2, although there was a trend of the relationship between the TyG index and the incidence of type 2 diabetes, the relationship was no longer positive.

Conclusion

In participants with obesity involving visceral fat obesity and/or fatty liver and normal BMI which is not a measure of body fat distribution, there was a significant association between the TyG index and incidence of T2DM.
Modelling Particulate Matter Using Multivariate and Multistep Recurrent Neural Networks
Authors: Saini Tushar , Chaturvedi Pratik , Dutt Varun
Published: December 2021

Air quality is a major problem in the world, having severe health implications. Long-term exposure to poor air quality causes pulmonary and cardiovascular diseases. Several studies have also found that deteriorating air quality also causes substantial economic losses. Thus, techniques that can forecast air quality with higher accuracy may help reduce health and economic consequences. Prior research has utilized state-of-the-art artificial neural network and recurrent neural network models for forecasting air quality. However, a comprehensive investigation of different architectures of recurrent neural network, especially LSTMs and ensemble techniques, has been less explored. Also, there have been less explorations of long-term air quality forecasts via these methods exists. This research proposes the development and calibration of recurrent neural network models and their ensemble, which can forecast air quality in terms of PM2.5 concentration 6 hours ahead in time. For forecasting air quality, a vanilla-LSTM, a stack-LSTM, a bidirectional-LSTM, a CNN-LSTM, and an ensemble of individual LSTM models were trained on the UCI Machine Learning Beijing dataset. Data were split into two parts, where 80% of data were used for training the models, while the remaining 20% were used for validating the models. For comparative analysis, four regression losses were calculated, namely root mean squared error, mean absolute percentage error, mean absolute error and Pearson’s correlation coefficient. Results revealed that among all models, the ensemble model performed the best in predicting the PM2.5 concentrations. Furthermore, the ensemble model outperformed other models reported in literature by a long margin. Among the individual models, the bidirectional-LSTM performed the best. We highlight the implications of this research on long-term forecasting of air quality via recurrent and ensemble techniques.
Biomass-Based Adsorbents for Removal of Dyes From Wastewater: A Review
Authors: Aragaw Tadele Assefa , Bogale Fekadu Mazengiaw
Published: December 2021

Dyes, especially azo dyes contained in wastewaters released from textile, pigment, and leather industries, are entering into natural waterbodies. This results in environmental deterioration and serious health damages (for example carcinogenicity and mutagenesis) through food chains. Physiochemical, membrane processes, electrochemical technology, advanced oxidation processes, reverse osmosis, ion exchange, electrodialysis, electrolysis, and adsorption techniques are commonly used conventional treatment technologies. However, the limitations of most of these methods include the generation of toxic sludge, high operational and maintenance costs. Thus, technological advancements are in use to remediate dyes from effluents. Adsorption using the nonconventional biomass-based sorbents is the greatest attractive alternatives because of their low cost, sustainability, availability, and eco-friendly. We present and reviewed up-to-date publications on biomass-based sorbents used for dye removal. Conceptualization and synthesizing their state-of-the-art knowledge on their characteristics, experimental conditions used were also discussed. The merits and limitations of various biosorbents were also reflected. The maximum dye adsorption capacities of various biosorbents were reviewed and synthesized in the order of the biomass type (algae, agricultural, fungal, bacterial, activated carbon, yeast, and others). Surface chemistry, pH, initial dye concentration, temperature, contact time, and adsorbent dose as well as the ways of the preparations of materials affect the biosorption process. Based on the average dye adsorption capacity, those sorbents were arranged and prioritized. The best fit of the adsorption isotherms (for example Freundlich and Langmuir models) and basic operating parameters on the removal dyes were retrieved. Which biomass-based adsorbents have greater potential for dye removal based on their uptake nature, cost-effectiveness, bulk availability, and mono to multilayer adsorption behavior was discussed. The basic limitations including the desorption cycles of biomass-based adsorbent preparation and operation for the implementation of this technology were forwarded.
Life History and the Transitions to Eusociality in the Hymenoptera
Authors: da Silva Jack
Published: December 2021

Although indirect selection through relatives (kin selection) can explain the evolution of effectively sterile offspring that act as helpers at the nest (eusociality) in the ants, bees, and stinging wasps (aculeate Hymenoptera), the genetic, ecological, and life history conditions that favor transitions to eusociality are poorly understood. In this study, ancestral state reconstruction on recently published phylogenies was used to identify the independent transitions to eusociality in each of the taxonomic families that exhibit eusociality. Semisociality, in which a single nest co-foundress monopolizes reproduction, often precedes eusociality outside the vespid wasps. Such a route to eusociality, which is consistent with groups consisting of a mother and her daughters (subsocial) at some stage and ancestral monogamy, is favored by the haplodiploid genetic sex determination of the Hymenoptera (diploid females and haploid males) and thus may explain why eusociality is common in the Hymenoptera. Ancestral states were also reconstructed for life history characters that have been implicated in the origins of eusociality. A loss of larval diapause during unfavorable seasons or conditions precedes, or coincides with, all but one transition to eusociality. This pattern is confirmed using phylogenetic tests of associations between state transition rates for sweat bees and apid bees. A loss of larval diapause may simply reflect the subsocial route to eusociality since subsociality is defined as females interacting with their adult daughters. A loss of larval diapause and a gain of subsociality may be associated with an extended breeding season that permits the production of at least two broods, which is necessary for helpers to evolve. Adult diapause may also lower the selective barrier to a first-brood daughter becoming a helper. Obligate eusociality meets the definition of a major evolutionary transition, and such transitions have occurred five times in the Hymenoptera.
Reconnecting the Elwha River: Spatial Patterns of Fish Response to Dam Removal
Authors: Duda Jeffrey J. , Torgersen Christian E. , Brenkman Samuel J. , Peters Roger J. , Sutton Kathryn T. , Connor Heidi A. , Kennedy Phil , Corbett Stephen C. , Welty Ethan Z. , Geffre Anna , Geffre Josh , Crain Patrick , Shreffler Dave , McMillan John R. , McHenry Mike , Pess George R.
Published: December 2021

The removal of two large dams on the Elwha River was completed in 2014 with a goal of restoring anadromous salmonid populations. Using observations from ongoing field studies, we compiled a timeline of migratory fish passage upstream of each dam. We also used spatially continuous snorkeling surveys in consecutive years before (2007, 2008) and after (2018, 2019) dam removal during summer baseflow to assess changes in fish distribution and density over 65 km of the mainstem Elwha River. Before dam removal, anadromous fishes were limited to the 7.9 km section of river downstream of Elwha Dam, potamodromous species could not migrate throughout the river system, and resident trout were the most abundant species. After dam removal, there was rapid passage into areas upstream of Elwha Dam, with 8 anadromous species (Chinook, Coho, Sockeye, Pink, Chum, Winter Steelhead, Summer Steelhead, Pacific Lamprey, and Bull Trout) observed within 2.5 years. All of these runs except Chum Salmon were also observed in upper Elwha upstream of Glines Canyon Dam within 5 years. The spatial extent of fish passage by adult Chinook Salmon and Summer Steelhead increased by 50 km and 60 km, respectively, after dam removal. Adult Chinook Salmon densities in some previously inaccessible reaches in the middle section of the river exceeded the highest densities observed in the lower section of the river prior to dam removal. The large number (>100) of adult Summer Steelhead in the upper river after dam removal was notable because it was among the rarest anadromous species in the Elwha River prior to dam removal. The spatial extent of trout and Bull Trout remained unchanged after dam removal, but their total abundance increased and their highest densities shifted from the lower 25 km of the river to the upper 40 km. Our results show that reconnecting the Elwha River through dam removal provided fish access to portions of the watershed that had been blocked for nearly a century.
Native Forests Show Resilience to Selective Timber Harvesting in Southeast Queensland, Australia
Authors: Neumann Mathias , Adams Mark A. , Lewis Tom
Published: December 2021

There is little published information on effects of management on the structure of mixed species forests in Queensland, Australia. We used long-term growth, abundance and dimension data from permanent plots to test the hypothesis that harvesting would reduce numbers of large trees and growth increments, while increasing recruitment. This hypothesis is key to policy and management decisions for forests covering about 9.5 million hectares. Inclusion of data on changes in forest structure (e.g., tree diameter, stem density) helps in assessment of forest suitability as habitat for a range of species. Growth rate (basal area) varied widely among forest types. Growth of each of four key species (i.e., Eucalyptus pilularis, Corymbia citriodora ssp. variegata, Callitris glaucophylla, and Eucalyptus crebra) reflected variation in rainfall across the study region. Callitris glaucophylla, a native conifer, is dominant when rainfall is < 600 mm per year. Corymbia citriodora ssp. variegata grows across much wider ranges in rainfall (600–1,200 mm year–1) at rates similar to Callitris glaucophylla. Historic harvesting increased recruitment and also increased the symmetry of diameter distributions. Harvesting has not reduced the current density of larger trees (diameter at breast height, DBH ≥ 60 cm) at a regional scale. Stand growth was unaffected by management principally owing to an increase in the density of trees of smaller diameter (10–20 cm DBH). Self-thinning limits potential stocking and we tested 3 methods for predicting self-thinning across forest types. We found that the slope of self-thinning lines under drier conditions is mostly < –2, suggesting highly dynamic self-thinning. Using a species-boundary line approach, growth is predicted to slow when basal areas reach around 66.1 m2 ha–1 in E. pilularis, 19.0 m2 ha–1 in C. citriodora ssp. variegata, 16.5 m2 ha–1 in Callitris glaucophylla, and 14.2 m2 ha–1 in E. crebra. The slope of the self-thinning line for E. pilularis was –1.662, similar to Reineke’s Stand Density Index (slope –1.605). To date, there is little evidence that selective harvesting and thinning have had negative impacts on rates of growth, on timber production, carbon sequestration or on aspects of forest structure regarded as important for biodiversity.
Use of Molecular Genetic Methods to Reduce the Risk of Incorrect Identification of Fish Strains in Brazilian Aquaculture
Authors: Deoclécio da Silva Luana Maria , do Prado Fernanda Dotti , Hashimoto Diogo Teruo , Senhorini José Augusto , Foresti Fausto , Porto-Foresti Fabio
Published: December 2021

The identification of fish species using traditional methods is generally based only on morphological characteristics and these methods are currently under review. This kind of identification of hybrid fishes solely based on their morphologies may be unreliable, especially when the samples include juveniles and post-F1 lineage fishes. Therefore, in the present study, we used molecular markers to accurately identify the fish species of economic interest that are used as materials in the projects developed in research institutions. We evaluated six lots of fishes sampled from different research centers, containing a total of 84 specimens acquired from private fish farms that were considered to be the representatives of pure species. Genetic analyses of all the specimens revealed that, globally, 22 samples (26.2%) were interspecific hybrids, while 20 (90.9%) samples were surprisingly characterized as post-F1 hybrids. This result confirms that hybrids are sold in markets without adequate labeling and also indicates the lack of proper control of the commercialization and management of stocks and products in fish farms. In addition, we determined that molecular diagnosis was an extremely effective and necessary method to test the reliability of biological materials currently used in scientific research.
Two-Way Development of the Genetic Model for Endometrial Tumorigenesis in Mice: Current and Future Perspectives
Authors: Maru Yoshiaki , Hippo Yoshitaka
Published: December 2021

Endometrial cancer (EC) is the most common malignancy of the female reproductive tract worldwide. Although comprehensive genomic analyses of EC have already uncovered many recurrent genetic alterations and deregulated signaling pathways, its disease model has been limited in quantity and quality. Here, we review the current status of genetic models for EC in mice, which have been developed in two distinct ways at the level of organisms and cells. Accordingly, we first describe the in vivo model using genetic engineering. This approach has been applied to only a subset of genes, with a primary focus on Pten inactivation, given that PTEN is the most frequently altered gene in human EC. In these models, the tissue specificity in genetic engineering determined by the Cre transgenic line has been insufficient. Consequently, the molecular mechanisms underlying EC development remain poorly understood, and preclinical models are still limited in number. Recently, refined Cre transgenic mice have been created to address this issue. With highly specific gene recombination in the endometrial cell lineage, acceptable in vivo modeling of EC development is warranted using these Cre lines. Second, we illustrate an emerging cell-based model. This hybrid approach comprises ex vivo genetic engineering of organoids and in vivo tumor development in immunocompromised mice. Although only a few successful cases have been reported as proof of concept, this approach allows quick and comprehensive analysis, ensuring a high potential for reconstituting carcinogenesis. Hence, ex vivo/in vivo hybrid modeling of EC development and its comparison with corresponding in vivo models may dramatically accelerate EC research. Finally, we provide perspectives on future directions of EC modeling.
Inclusive Resettlement? Integration Pathways of Resettled Refugees With Disabilities in Germany and Canada
Authors: Korntheuer Annette , Hynie Michaela , Kleist Martha , Farooqui Safwathullah , Lutter Eva , Westphal Manuela
Published: December 2021

The purpose of this article is to explore the existing intersectional knowledge on integration and resettlement of refugees with disabilities in two of the top five resettlement countries in the world, Germany and Canada. There is limited research on the intersection of migration and disability, especially in the context of refugee resettlement. Reflecting the dominant pathways of migration in each country, what little research there is focuses on asylum seekers in Germany, and immigrants in Canada. The review describes settlement programs in each country. We draw from the global literature around forced migration and disability, as well as disability and migration more broadly in each country, to enhance the limited existing research and conduct an intersectional analysis at the level of systems, discourses and subjective narratives. Findings highlight three dominant themes that weave across all three levels: being a “burden” on society, being invisible, and agency and resistance. Finally, drawing from the theoretical stance of Disability Studies, critical, and holistic integration theories we discuss how this intersectional analysis highlights the importance of reshaping the policies, discourse and definition of integration, and the consequences this can have on research, service delivery, and evaluation of integration and resettlement.
Identification of an Autophagy-Related Pair Signature for Predicting Prognoses and Immune Activity in Pancreatic Adenocarcinoma
Authors: Zhang Qian , Lv Liping , Ma Ping , Zhang Yangyang , Deng Jiang , Zhang Yanyu
Published: December 2021

Background

Pancreatic adenocarcinoma (PAAD) spreads quickly and has a poor prognosis. Autophagy research on PAAD could reveal new biomarkers and targets for diagnosis and treatment.

Methods

Autophagy-related genes were translated into autophagy-related gene pairs, and univariate Cox regression was performed to obtain overall survival (OS)-related IRGPs (P<0.001). LASSO Cox regression analyses were performed to construct an autophagy-related gene pair (ARGP) model for predicting OS. The Cancer Genome Atlas (TCGA)-PAAD cohort was set as the training group for model construction. The model predictive value was validated in multiple external datasets. Receiver operating characteristic (ROC) curves were used to evaluate model performance. Tumor microenvironments and immune infiltration were compared between low- and high-risk groups with ESTIMATE and CIBERSORT. Differentially expressed genes (DEGs) between the groups were further analyzed by Gene Ontology biological process (GO-BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and used to identify potential small-molecule compounds in L1000FWD.

Results

Risk scores were calculated as follows: ATG4B|CHMP4C×(-0.31) + CHMP2B|MAP1LC3B×(0.30) + CHMP6|RIPK2 ×(-0.33) + LRSAM1|TRIM5×(-0.26) + MAP1LC3A|PAFAH1B2×(-0.15) + MAP1LC3A|TRIM21×(-0.08) + MET|MFN2×(0.38) + MET|MTDH×(0.47) + RASIP1|TRIM5×(-0.23) + RB1CC1|TPCN1×(0.22). OS was significantly shorter in the high-risk group than the low-risk group in each PAAD cohort. The ESTIMATE analysis showed no difference in stromal scores but a significant difference in immune scores (p=0.0045) and ESTIMATE scores (p=0.014) between the groups. CIBERSORT analysis showed higher naive B cell, Treg cell, CD8 T cell, and plasma cell levels in the low-risk group and higher M1 and M2 macrophage levels in the high-risk group. In addition, the results showed that naive B cells (r=-0.32, p<0.001), Treg cells (r=-0.31, p<0.001), CD8 T cells (r=-0.24, p=0.0092), and plasma cells (r=-0.2, p<0.026) were statistically correlated with the ARGP risk score. The top 3 enriched GO-BPs were signal release, regulation of transsynaptic signaling, and modulation of chemical synaptic transmission, and the top 3 enriched KEGG pathways were the insulin secretion, dopaminergic synapse, and NF-kappa B signaling pathways. Several potential small-molecule compounds targeting ARGs were also identified.

Conclusion

Our results demonstrate that the ARGP-based model may be a promising prognostic indicator for identifying drug targets in patients with PAAD.
Long-Term Effects of Allogeneic Hematopoietic Stem Cell Transplantation on Systemic Inflammation in Sickle Cell Disease Patients
Authors: de Azevedo Júlia Teixeira Cottas , Costa Thalita Cristina de Mello , Lima Keli Cristina , Maciel Thiago Trovati , Palma Patrícia Vianna Bonini , Darrigo-Júnior Luiz Guilherme , Setanni Grecco Carlos Eduardo , Stracieri Ana Beatriz P. L. , Elias Juliana Bernardes , Pieroni Fabiano , Guerino-Cunha Renato Luiz , Pinto Ana Cristina Silva , De Santis Gil Cunha , Covas Dimas Tadeu , Hermine Olivier , Simões Belinda Pinto , Oliveira Maria Carolina , Malmegrim Kelen Cristina Ribeiro
Published: December 2021

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only currently available curative treatment for sickle cell disease (SCD). However, the effects of HSCT on SCD pathophysiology are poorly elucidated. Here, we assessed red blood cell (RBC) adhesiveness, intensity of hemolysis, vascular tone markers and systemic inflammation, in SCD patients treated with allogeneic HSCT. Thirty-two SCD patients were evaluated before and on long-term follow-up after HSCT. Overall survival was 94% with no severe (grade III-IV) graft-vs-host disease and a 22% rejection rate (graft failure). Hematological parameters, reticulocyte counts, and levels of lactate dehydrogenase (LDH), endothelin-1 and VCAM-1 normalized in SCD patients post-HSCT. Expression of adhesion molecules on reticulocytes and RBC was lower in patients with sustained engraftment. Levels of IL-18, IL-15 and LDH were higher in patients that developed graft failure. Increased levels of plasma pro-inflammatory cytokines, mainly TNF-α, were found in SCD patients long-term after transplantation. SCD patients with sustained engraftment after allo-HSCT showed decreased reticulocyte counts and adhesiveness, diminished hemolysis, and lower levels of vascular tonus markers. Nevertheless, systemic inflammation persists for at least five years after transplantation, indicating that allo-HSCT does not equally affect all aspects of SCD pathophysiology.
Effect of Different Disease-Modifying Therapies on Humoral Response to BNT162b2 Vaccine in Sardinian Multiple Sclerosis Patients
Authors: Pitzalis Maristella , Idda Maria Laura , Lodde Valeria , Loizedda Annalisa , Lobina Monia , Zoledziewska Magdalena , Virdis Francesca , Delogu Giuseppe , Pirinu Federica , Marini Maria Giuseppina , Mingoia Maura , Frau Jessica , Lorefice Lorena , Fronza Marzia , Carmagnini Daniele , Carta Elisa , Orrù Valeria , Uzzau Sergio , Solla Paolo , Loi Federica , Devoto Marcella , Steri Maristella , Fiorillo Edoardo , Floris Matteo , Zarbo Ignazio Roberto , Cocco Eleonora , Cucca Francesco
Published: December 2021

Objectives

Vaccination against COVID-19 is highly recommended to patients affected by multiple sclerosis (MS); however, the impact of MS disease-modifying therapies (DMTs) on the immune response following vaccination has been only partially investigated. Here, we aimed to elucidate the effect of DMTs on the humoral immune response to mRNA-based anti-SARS-CoV-2 vaccines in MS patients.

Methods

We obtained sera from 912 Sardinian MS patients and 63 healthy controls 30 days after the second dose of BNT162b2 vaccine and tested them for SARS-CoV-2 response using anti-Spike (S) protein-based serology. Previous SARS-CoV-2 infection was assessed by anti-Nucleocapsid (N) serology. Patients were either untreated or undergoing treatment with a total of 13 different DMTs. Differences between treatment groups comprised of at least 10 patients were assessed by generalized linear mixed-effects model. Demographic and clinical data and smoking status were analyzed as additional factors potentially influencing humoral immunity from COVID-19 vaccine.

Results

MS patients treated with natalizumab, teriflunomide, azathioprine, fingolimod, ocrelizumab, and rituximab showed significantly lower humoral responses compared to untreated patients. We did not observe a statistically significant difference in response between patients treated with the other drugs (dimethyl fumarate, interferon, alemtuzumab and glatiramer acetate) and untreated patients. In addition, older age, male sex and active smoking were significantly associated with lower antibody titers against SARS-CoV-2. MS patients previously infected with SARS-CoV-2 had significantly higher humoral responses to vaccine than uninfected patients.

Conclusion

Humoral response to BNT162b2 is significantly influenced by the specific DMTs followed by patients, as well as by other factors such as previous SARS-CoV-2 infection, age, sex, and smoking status. These results are important to inform targeted strategies to prevent clinically relevant COVID-19 in MS patients.