bluuebunny/crossref_metadata_2025 huggingface dataset:
CLOSING THE SCIENCE PROCESS SKILLS GAP BETWEEN STUDENTS WITH HIGH AND LOW LEVEL ACADEMIC ACHIEVEMENT
Authors: Prayitno Baskoro Adi , Corebima Duran , Susilo Herawati , Zubaidah Siti , Ramli Murni
Published: August 2021

Science Process Skills (SPSs) are fundamental skills to mastering science. To nurture students' SPS, inquiry based learning and student-center activities may work effectively. This study aims at analyzing: How Inquiry-based Learning and Student Team Achievement Division (INSTAD) affects science process skills compared with inquiry-based learning, Student Teams Achievement Divisions (STAD), and conventional learning method. The participants were 136 grade 7 students from 27 public middle schools in Surakarta, Indonesia. They were divided into 68 students with higher academic (HA) achievement and 68 students with lower academic (LA) achievement. A nonequivalent control group design with pretest and posttest were applied to get data on SPSs using a sort of essay test. The result indicates that: (1) While the outcomes of INSTAD and inquiry-based learning are comparable, they are significantly different compared with the outcomes of STAD and conventional learning. (2) Students in HA group have higher SPS than students in LA groups. (3) INSTAD, on an equal level with inquiry-based learning, significantly increases the students’ SPSs. Compared with other three methods, INSTAD was confirmed the most effective in closing the science process skills gaps between students in HA group and LA group. Keywords: inquiry-based learning, INSTAD, STAD, science process skills.
PENGARUH BYSTANDER EFFECT, WHISTLEBLOWING, DAN PERILAKU ETIS TERHADAP FINANCIAL STATEMENT FRAUD
Authors: - Maharani , Mahmudah Hadi
Published: August 2021

In an organization or company, fraud is usually discovered by people within the organization. The existence of evidence of fraud, whether strong or weak, sometimes does not make people who know the fraud report to the authorities. The purpose of this study was to determine the effect of the bystander effect, whistleblowing, and ethical behavior on financial statement fraud. The method used is a quantitative method. The population in this study were all Bekasi District Civil Servants who served in the financial division of each agency. This study uses primary data from a questionnaire. The data were analyzed using multiple regression analysis. The results of this study indicate that the bystander effect has a positive effect on Financial Statement Fraud, while the whistleblowing variable and eris behavior have a negative effect on Financial Statement Fraud.
Fitness Costs Associated to an Ile2041Asn Mutation in the Geophyte Sorghum halepense Resistant to ACCase-Inhibiting Herbicides
Authors: Panozzo Silvia , Sattin Maurizio
Published: August 2021

Sorghum halepense (L.) Pers. is a troublesome weed of maize which reproduces through seeds and rhizomes. Resistance to ACCase-inhibiting herbicides due to a target-site mutation Ile-Asn in position 2041 of the ACCase gene was confirmed in several populations in Italy. The presence of fitness costs related to the allelic variant Ile2041Asn has never been investigated in ACCase-resistant S. halepense. Three growth analyses pot experiments were performed starting from rhizome buds (Exp1 and Exp3) or seed (Exp2). Plant development was monitored throughout the life cycle through destructive samplings. The mutation responsible for resistance to ACCase inhibitors was detected in all plants included in the experiments using a Cleaved Amplified Polymorphic Sequence method. Classical growth analysis was performed for the multiple sampling experiments (Exp1 and Exp2) and allometric relationships were calculated for the different dry weight plant parts in all experiments. Allometric relationships showed that susceptible (S) and ACCase resistant (R) biotypes allocated biomass differently in the reproductive structures: S populations allocated on average 30% more biomass in the panicles, whereas R populations allocated 12% more biomass to rhizomes than S populations. This was more evident when the experiments started from rhizomes buds. Reproductive allocation and reproductive effort were higher in S biotypes and R biotypes, respectively. The higher production of rhizomes and the lower production of seeds of the R biotype can significantly impact the evolution of herbicide resistance under continuous application of herbicides with the same mode of action. A medium-long term resistance management strategy which implements appropriate soil tillage and crop rotation taking into account the different reproductive attitude of biotypes S and R should be devised.
Compound Flooding: Dependence at Sub-daily Scales Between Extreme Storm Surge and Fluvial Flow
Authors: Robins Peter E. , Lewis Matt J. , Elnahrawi Mariam , Lyddon Charlotte , Dickson Neil , Coulthard Tom J.
Published: August 2021

Estuaries are potentially exposed to compound flooding where weather-driven extreme sea levels can occur synchronously with extreme fluvial discharge to amplify the hazard. The likelihood of compound flooding is difficult to determine due to multiple interacting physical processes operating at sub-daily scales, and poor observation records within estuaries with which to determine potential future probabilistic scenarios. We hypothesize that fluvial extremes can occur within the peak of the surge in small/steep catchments because of rapid runoff times, whilst the length-scale in larger/flatter catchments will result in fluvial and marine extremes being out-of-phase. Data (15 min river flow and hourly sea level) spanning 40 years were analyzed to assesses the behaviour and timings of fluvial and sea level extremes in two contrasting estuaries: Humber and Dyfi (United Kingdom). Compound events were common in the Dyfi, a small/steep catchment on Britain’s west coast with fast fluvial response times. Almost half of the 937 skew-surge events (95th-percentile) occurred within a few hours of an extreme fluvial peak, suggesting that flood risk is sensitive to the storm timing relative to high tide—especially since flows persisted above the 95th-percentile typically for less than 12 h. Compound events were more frequent during autumn/winter than spring/summer. For the Humber, a larger/flatter catchment on the east coast with slower fluvial response times, extreme fluvial and skew-surge peaks were less frequent (half as many as the Dyfi) and compound events were less common (15% of events co-occurred). Although flows in the Humber persisted above the 95th-percentile for typically between one and 4 days, hence overlapping several high tides and possibly other surges. Analysis of 56 flooding events across both estuaries revealed: 1) flooding is more common in the Dyfi than Humber; 2) Dyfi flooding is driven by 99th-percentile flows lasting hours and co-occurring with a 95th percentile skew-surge; 3) Humber flooding was driven by 95th-percentile flows lasting days, or surge-driven—but rarely co-occurring. Our results suggest that compound flooding studies require at least hourly data (previous analyses have often used daily-means), especially for smaller systems and considering the potential intensification of rainfall patterns into the future.
Cold Sensitivity in Ulnar Neuropathy at the Elbow - Relation to Symptoms and Disability, Influence of Diabetes and Impact on Surgical Outcome
Authors: Zimmerman Malin , Peyron Hanna , Svensson Ann-Marie , Eeg-Olofsson Katarina , Nyman Erika , Dahlin Lars B.
Published: August 2021

Cold sensitivity, an abnormal response to exposure to cold, is debilitating. It often affects people with nerve injuries and diabetes. Knowledge about the occurrence and prognostic impact of cold sensitivity in people with ulnar neuropathy at the elbow (UNE) is limited. We aimed to investigate the occurrence of cold sensitivity in UNE in relation to disability, the influence of diabetes and impact on surgical outcome. Data concerning 1270 persons operated on for UNE from 2010-2016 from the Swedish National Register for Hand Surgery (HAKIR) were matched with data from the Swedish National Diabetes Register (NDR). Disability and symptoms were assessed preoperatively, and at three and 12 months postoperatively using QuickDASH and a symptom-specific survey (HQ-8) containing one item regarding cold sensitivity. Differences regarding grade of cold sensitivity, occurrence of diabetes, QuickDASH scores and HQ-8 scores were studied. A linear regression analysis was performed to predict surgical outcome based on preoperative cold sensitivity. The mean age of the cases was 52 ± SD 14 years and 48% were women. Preoperatively, 427 answered the questionnaire. Severe cold sensitivity was present in 140/427 (33%) cases, moderate in 164/427 (38%) and mild in 123/427 (29%) cases. Cases with severe preoperative cold sensitivity reported higher QuickDASH scores at all times compared to cases with mild cold sensitivity. Relative change in QuickDASH scores over time did not differ between the groups. Cases with diabetes reported worse cold sensitivity preoperatively, but not postoperatively. All HQ-8 items improved with surgery, but cases with severe cold sensitivity reported worse persisting symptoms. Cold sensitivity is a major problem among those with UNE and an even greater preoperative problem among people with diabetes. It is associated with more symptoms and disability pre- and post-operatively. All cases, regardless of preoperative degree of cold sensitivity improve with surgery.
The Emerging Mechanisms of Wnt Secretion and Signaling in Development
Authors: Mehta Shefali , Hingole Swapnil , Chaudhary Varun
Published: August 2021

Wnts are highly-conserved lipid-modified secreted proteins that activate multiple signaling pathways. These pathways regulate crucial processes during various stages of development and maintain tissue homeostasis in adults. One of the most fascinating aspects of Wnt protein is that despite being hydrophobic, they are known to travel several cell distances in the extracellular space. Research on Wnts in the past four decades has identified several factors and uncovered mechanisms regulating their expression, secretion, and mode of extracellular travel. More recently, analyses on the importance of Wnt protein gradients in the growth and patterning of developing tissues have recognized the complex interplay of signaling mechanisms that help in maintaining tissue homeostasis. This review aims to present an overview of the evidence for the various modes of Wnt protein secretion and signaling and discuss mechanisms providing precision and robustness to the developing tissues.
Differential Roles of Actin Crosslinking Proteins Filamin and α-Actinin in Shear Flow-Induced Migration of Dictyostelium discoideum
Authors: Cole Aaron , Buckler Sarah , Marcucci Jack , Artemenko Yulia
Published: August 2021

Shear flow-induced migration is an important physiological phenomenon experienced by multiple cell types, including leukocytes and cancer cells. However, molecular mechanisms by which cells sense and directionally migrate in response to mechanical perturbation are not well understood. Dictyostelium discoideum social amoeba, a well-established model for studying amoeboid-type migration, also exhibits directional motility when exposed to shear flow, and this behavior is preceded by rapid and transient activation of the same signal transduction network that is activated by chemoattractants. The initial response, which can also be observed following brief 2 s stimulation with shear flow, requires an intact actin cytoskeleton; however, what aspect of the cytoskeletal network is responsible for sensing and/or transmitting the signal is unclear. We investigated the role of actin crosslinkers filamin and α-actinin by analyzing initial shear flow-stimulated responses in cells with or without these proteins. Both filamin and α-actinin showed rapid and transient relocalization from the cytosol to the cortex following shear flow stimulation. Using spatiotemporal analysis of Ras GTPase activation as a readout of signal transduction network activity, we demonstrated that lack of α-actinin did not reduce, and, in fact, slightly improved the response to acute mechanical stimulation compared to cells expressing α-actinin. In contrast, shear flow-induced Ras activation was significantly more robust in filamin-null cells rescued with filamin compared to cells expressing empty vector. Reduced responsiveness appeared to be specific to mechanical stimuli and was not due to a change in the basal activity since response to global stimulation with a chemoattractant and random migration was comparable between cells with or without filamin. Finally, while filamin-null cells rescued with filamin efficiently migrated upstream when presented with continuous flow, cells lacking filamin were defective in directional migration. Overall, our study suggests that filamin, but not α-actinin, is involved in sensing and/or transmitting mechanical stimuli that drive directed migration; however, other components of the actin cytoskeleton likely also contribute to the initial response since filamin-null cells were still able to activate the signal transduction network. These findings could have implications for our fundamental understanding of shear flow-induced migration of leukocytes, cancer cells and other amoeboid-type cells.
Folate-Functionalized DNA Origami for Targeted Delivery of Doxorubicin to Triple-Negative Breast Cancer
Authors: Pal Suchetan , Rakshit Tatini
Published: August 2021

DNA origami has emerged as a versatile platform for diverse applications, namely, photonics, electronics, (bio) sensing, smart actuator, and drug delivery. In the last decade, DNA origami has been extensively pursued for efficient anticancer therapy. However, challenges remain to develop strategies that improve the targeting efficiency and drug delivery capability of the DNA origami nanostructures. In this direction, we developed folate-functionalized DNA origami that effectively targets and delivers doxorubicin (DOX), a well-known anticancer drug to the folate receptor alpha (FOLR1) expressing triple-negative breast cancer (TNBC) cells in vitro. We show that folate-functionalized DNA origami structure targets and kills FOLR1 overexpressing cells with better efficacy than nontargeted origami. We envision that this study will open up the possibility of target specific delivery of anticancer drug combinations using the versatile DNA origami nanostructures to the drug resistant cancer cells.
Etiological Value of Sterile Inflammation in Preeclampsia: Is It a Non-Infectious Pregnancy Complication?
Authors: Banerjee Sayani , Huang Zheping , Wang Zhengke , Nakashima Akitoshi , Saito Shigeru , Sharma Surendra , Cheng Shibin
Published: August 2021

Understanding of sterile inflammation and its associated biological triggers and diseases is still at the elementary stage. This becomes more warranted in cases where infections are not associated with the pathology. Detrimental effects of bacterial and viral infections on the immune responses at the maternal-fetal interface as well as pregnancy outcomes have been well documented. However, an infection-induced etiology is not thought to be a major contributing component to severe pregnancy complications such as preeclampsia (PE) and gestational diabetes. How is then an inflammatory signal thought to be associated with these pregnancy complications? It is not clear what type of inflammation is involved in the onset of PE-like features. We opine that sterile inflammation regulated by the inflammasome-gasdermins-caspase-1 axis is a contributory factor to the onset of PE. We hypothesize that increased production and release of damage-associated molecular patterns (DAMPs) or Alarmins such as high-mobility group box1 (HMGB1), cell-free fetal DNA, uric acid, the NOD-like receptor pyrin-containing receptor 3 (NLRP3) inflammasome, IL-1β and IL-18 occur in the PE placenta. Some of these molecules have already been observed in the placenta from women with PE. Mechanistically, emerging evidence has demonstrated that excessive placental endoplasmic reticulum (ER) stress, impaired autophagy and gasdermine D (GSDMD)-mediated intrinsic pyroptosis are key events that contribute to systemic sterile inflammation in patients with PE, especially early-onset PE (e-PE). In this review, we highlight the advances on the roles of sterile inflammation and inflammatory signaling cascades involving ER stress, autophagy deficiency and pyroptosis in PE pathophysiology. Deciphering the mechanisms underlying these inflammatory pathways may provide potential diagnostic biomarkers and facilitate the development of therapeutic strategies to treat this devastating disease.
Development of an Antibiotic Resistance Breaker to Resensitize Drug-Resistant Staphylococcus aureus: In Silico and In Vitro Approach
Authors: Thamilselvan Gopalakrishnan , Sarveswari Hema Bhagavathi , Vasudevan Sahana , Stanley Alex , Shanmugam Karthi , Vairaprakash Pothiappan , Solomon Adline Princy
Published: August 2021

Efflux pumps are one of the predominant microbial resistant mechanisms leading to the development of multidrug resistance. In Staphylococcus aureus, overexpression of NorA protein enables the efflux of antibiotics belonging to the class of fluoroquinolones and, thus, makes S. aureus resistant. Hence, NorA efflux pumps are being extensively exploited as the potential drug target to evade bacterial resistance and resensitize bacteria to the existing antibiotics. Although several molecules are reported to inhibit NorA efflux pump effectively, boronic acid derivatives were shown to have promising NorA efflux pump inhibition. In this regard, the current study exploits 6-(3-phenylpropoxy)pyridine-3-boronic acid to further improve the activity and reduce cytotoxicity using the bioisostere approach, a classical medicinal chemistry concept. Using the SWISS-Bioisostere online tool, from the parent compound, 42 compounds were obtained upon the replacement of the boronic acid. The 42 compounds were docked with modeled NorA protein, and key molecular interactions of the prominent compounds were assessed. The top hit compounds were further analyzed for their drug-like properties using ADMET studies. The identified potent lead, 5-nitro-2-(3-phenylpropoxy)pyridine (5-NPPP), was synthesized, and in vitro efficacy studies have been proven to show enhanced efflux inhibition, thus acting as a potent antibiotic breaker to resensitize S. aureus without elucidating any cytotoxic effect to the host Hep-G2 cell lines.
Cardiac Fibrosis: Cellular Effectors, Molecular Pathways, and Exosomal Roles
Authors: Jiang Wenyang , Xiong Yuyan , Li Xiaosong , Yang Yuejin
Published: August 2021

Cardiac fibrosis, a common pathophysiologic process in most heart diseases, refers to an excess of extracellular matrix (ECM) deposition by cardiac fibroblasts (CFs), which can lead to cardiac dysfunction and heart failure subsequently. Not only CFs but also several other cell types including macrophages and endothelial cells participate in the process of cardiac fibrosisviadifferent molecular pathways. Exosomes, ranging in 30–150 nm of size, have been confirmed to play an essential role in cellular communications by their bioactive contents, which are currently a hot area to explore pathobiology and therapeutic strategy in multiple pathophysiologic processes including cardiac fibrosis. Cardioprotective factors such as RNAs and proteins packaged in exosomes make them an excellent cell-free system to improve cardiac function without significant immune response. Emerging evidence indicates that targeting selective molecules in cell-derived exosomes could be appealing therapeutic treatments in cardiac fibrosis. In this review, we summarize the current understandings of cellular effectors, molecular pathways, and exosomal roles in cardiac fibrosis.
Revealing 60 years of Earthquake Swarms in the Southern Red Sea, Afar and the Gulf of Aden
Authors: Ruch Joël , Keir Derek , Passarelli Luigi , Di Giacomo Domenico , Ogubazghi Ghebrebrhan , Jónsson Sigurjón
Published: August 2021

Earthquake swarms occur sporadically at divergent plate boundaries but their recurrence over multiple decades and relation to magmatic spreading activity remain poorly understood. Here we study more than 100 earthquake swarms over a 60-year period in the southern Red Sea, Afar, and Gulf of Aden region. We first compiled an earthquake-swarm catalogue by integrating reexamined global and local earthquake catalogues from 1960 to 2017. This yielded 134 earthquake swarms that mainly cluster in 19 different areas in the study region, showing that in most cases swarms recur every few decades in the same area. The swarms exhibit a range of earthquake magnitudes and often include multiple M3 to M5 events with some swarms having occasional larger earthquakes over M6, primarily in southern Afar. Many of the earthquake swarms were clearly associated with rifting events, consisting of magmatic intrusions, surface faulting, and in some cases volcanic eruptions. Together, the swarms suggest that extension at these divergent plate boundaries occurs episodically along <100 km long segments, some of which were previously unrecognized. Within the study region, the Gulf of Aden shows the most frequent swarm activity, followed by Afar and then the southern Red Sea. The results show that the three areas were subject to an increase of earthquake-swarm activity from 2003 to 2013 in the form of three rifting episodes and at least seven volcanic eruptions. We interpret that the most likely controls on temporal variations in earthquake swarm activity are either temporal variations in magma supply, or rifting-induced stress change that trigger clusters of swarms.
Between Necessity and Legal Responsibility: The Development of EEWS in Italy and its International Framework
Authors: Valbonesi Cecilia
Published: August 2021

Earthquake Early Warning Systems (EEWSs) represent a technical-scientific challenge aimed at improving the chance of the population exposed to the earthquake shaking of surviving or being less affected. The ability of an EEWS to affect the risk and, in particular, vulnerability and exposure, may determine serious legal responsibilities for people involved in the system, as scientists and experts. The main question concerns, in fact, the relationship between EEWSs and the predictability and avoidability of earthquake effects-i.e., the ground shaking affecting citizens and infrastructures - and the possibility for people to adopt self-protective behavior and/or for industrial infrastructures to be secured. In Italy, natural disasters, such as the 2009 L’Aquila earthquake, teach us that the relationship between science and law is really difficult. So, before EEW’s become operational in Italy, it is necessary to: 1) examine the legislative and technical solutions adopted by some of the international legal systems in countries where this service is offered to citizens; 2) reconstruct the international and European regulatory framework that promotes the introduction of EW systems as life-saving tools for the protection of the right to life and understand whether and how these regulatory texts can impose an obligation on the Italian legal system to develop EEWS; 3) understand what responsibilities could be ascribed to the scientists and technicians responsible for managing EEWS in Italy, analyzing the different impact of vulnerability and exposure on the predictability and avoidability of the harmful event; 4) reflect on the lessons that our legal system will have to learn from other Countries when implementing EEW systems. In order to find appropriate solutions, it is essential to reflect on the opportunity to provide shared and well-structured protocols and creating detailed disclaimers clearly defining the limits of the service. A central role must be recognized to education, because people should not only expect to receive a correct alarm but must be able to understand the uncertainties involved in rapid estimates, be prepared to face the risk, and react in the right way.
Oocyte Degeneration After ICSI Is Not an Indicator of Live Birth in Young Women
Authors: Hu Xiaokun , Liu Yuliang , Zhang Xiubing , Lee Pingyin , Wen Yangxing , Ding Chenhui , Zhou Canquan , Xu Yanwen
Published: August 2021

Introduction

Intracytoplasmic sperm injection (ICSI) was introduced in 1990s as one of the most dramatic breakthroughs in assisted reproductive technology. Even with advances in ICSI technology, this mechanical micromanipulation carries a 5 to 19% risk of oocyte degeneration. Whether the presence of oocyte degeneration reflects the sibling oocyte quality and predicts the sibling embryo development potential and clinical pregnancy outcomes remains controversial. There is no study showing the competence of the sibling embryos from the prospective of cumulative live birth rate. Whether oocyte degeneration is associated with poor quality of the remainder of the cohort remains further to be elucidated.

Method

This retrospective observational study included a total of 488 OPU cycles underwent ICSI with fresh cleavage stage embryo transfer and successive frozen/thawed embryo transfer (FET) cycles from January 2018 to December 2019. All female patients were under the age of 35 years, and underwent ICSI with or without oocyte degeneration (OD). Cycles with at least one oocyte degenerated were defined as oocyte degeneration group (OD group), and cycles with no oocyte degenerated were defined as non-OD group. The OD group was further divided to three subgroups according to different oocyte degeneration rate (<10%, 10-20%, and >20%).

Results

There were no significant differences with regards to implantation rate (38.5% vs 35.1%, P=0.302), clinical pregnancy rate (54.9% vs 50.3%, P=0.340), and LBR per OPU cycle (47.0% vs 42.9%, P=0.395) between OD and non-OD groups. Initial gonadotropin dosage, E2 level on hCG day and the number of matured oocytes appeared to be independent risk factors for OD. The adjusted odds ratio of live birth rate per OPU cycle were similar in different oocyte degeneration rate subgroups. The ongoing pregnancy/LBR per transfer in FET cycles was not significantly different between OD group and non-OD groups (38.8% vs 43.9%, P=0.439). The cumulative LBR per OPU cycle was also comparable between OD and non-OD group (63.4% vs 64.8%, P=0.760).

Conclusion

The results provide cycle-based evidence that the presence of oocyte degeneration after ICSI is not an indicator for predicting the cumulative live birth rate per OPU cycle in young women.
Sodium-Glucose Co-Transporter-2 Inhibitors in Non-Diabetic Adults With Overweight or Obesity: A Systematic Review and Meta-Analysis
Authors: Zheng Hanrui , Liu Min , Li Sheyu , Shi Qingyang , Zhang Shengzhao , Zhou Yiling , Su Na
Published: August 2021

Background

Sodium-glucose-cotransporter-2 (SGLT2) inhibitors have proven to be effective in improving glycemic control and lowering body weight in patients with type 2 diabetes mellitus. However, the efficacy and safety on weight loss in adults with overweight or obesity but not diabetes remain unclear. In this article, we aimed to identify the efficacy and safety of SGLT2 inhibitors in adults with overweight or obesity but not diabetes in randomized controlled studies (RCTs).

Methods

We searched for RCTs concerning SGLT2 inhibitors in adults with overweight or obesity but not diabetes in Medline (Ovid SP), Embase (Ovid SP), Cochrane Central Register of Controlled Trials (Ovid SP), and ClinicalTrials.gov up to February 2021. The primary outcomes were changes in body weight and body mass index (BMI). Trial sequential analysis (TSA) was used to test the reliability of the primary outcomes. We analyzed the data using Review Manager 5.3 and pooled data to calculate the mean differences (MDs) or the relative risk (RR). We assessed the evidence quality of evidence of outcomes according to GRADE.

Results

Six randomized controlled trials involving 872 individuals were included in the meta-analysis. Compared to the placebo group, the SGLT2 inhibitors group had statistically significant reductions in absolute changes in body weight (MD: -1.42 kg, 95% CI: -1.70 to -1.14; P<0.00001) and BMI (MD: -0.47 kg/m2, 95% CI: -0.63 to -0.31; P<0.00001) in SGLT2 inhibitors group, as indicated by TSA. However, no significant benefits were observed in the SGLT2 inhibitors group in terms of waist circumference (MD: -1.34 cm, 95%CI: -2.75 to 0.07; Z=1.86, P=0.06) compared with the placebo group. The GRADE profiles indicated very low-quality evidence for body weight change and low-quality evidence for BMI change. SGLT2 inhibitors were generally safe and well tolerated.

Conclusion

SGLT2 inhibitors could be used in selected adults with overweight and obesity but not diabetes if they are at low risk of genital infection and urinary infection. Further studies are warranted to confirm the efficacy and safety of SGLT2 inhibitors in adults with overweight or obesity but not diabetes for long-term weight management.

Systematic Review Registration

[https://www.crd.york.ac.uk/prospero/#loginpage], identifier [PROSPERO, CRD42021252931]
The “GEnomics of Musculo Skeletal Traits TranslatiOnal NEtwork”: Origins, Rationale, Organization, and Prospects
Authors: Koromani Fjorda , Alonso Nerea , Alves Ines , Brandi Maria Luisa , Foessl Ines , Formosa Melissa M. , Morgenstern Milana Frenkel , Karasik David , Kolev Mikhail , Makitie Outi , Ntzani Evangelia , Pietsch Barbara Obermayer , Ohlsson Claes , Rauner Martina , Soe Kent , Soldatovic Ivan , Teti Anna , Valjevac Amina , Rivadeneira Fernando
Published: August 2021

Musculoskeletal research has been enriched in the past ten years with a great wealth of new discoveries arising from genome wide association studies (GWAS). In addition to the novel factors identified by GWAS, the advent of whole-genome and whole-exome sequencing efforts in family based studies has also identified new genes and pathways. However, the function and the mechanisms by which such genes influence clinical traits remain largely unknown. There is imperative need to bring multidisciplinary expertise together that will allow translating these genomic discoveries into useful clinical applications with the potential of improving patient care. Therefore “GEnomics of MusculoSkeletal traits TranslatiOnal NEtwork” (GEMSTONE) aims to set the ground for the: 1) functional characterization of discovered genes and pathways; 2) understanding of the correspondence between molecular and clinical assessments; and 3) implementation of novel methodological approaches. This research network is funded byThe European Cooperation in Science and Technology(COST). GEMSTONE includes six working groups (WG), each with specific objectives: WG1-Study populations and expertise groups:creating, maintaining and updating an inventory of experts and resources (studies and datasets) participating in the network, helping to assemble focus groups defined by phenotype, functional and methodological expertise. WG2-Phenotyping:describe ways to decompose the phenotypes of the different functional studies into meaningful components that will aid the interpretation of identified biological pathways. WG3Monogenic conditions - human KO models:makes an inventory of genes underlying musculoskeletal monogenic conditions that aids the assignment of genes to GWAS signals and prioritizing GWAS genes as candidates responsible for monogenic presentations, through biological plausibility. WG4Functional investigations: creating a roadmap of genes and pathways to be prioritized for functional assessment in cell and organism models of the musculoskeletal system. WG5Bioinformaticsseeks the integration of the knowledge derived from the distinct efforts, with particular emphasis on systems biology and artificial intelligence applications. Finally, WG6Translational outreach: makes a synopsis of the knowledge derived from the distinct efforts, allowing to prioritize factors within biological pathways, use refined disease trait definitions and/or improve study design of future investigations in a potential therapeutic context (e.g. clinical trials) for musculoskeletal diseases.
The Stimulation and Coordination Mechanisms of the Carbon Emission Trading Market of Public Buildings in China
Authors: Li Lingyan , Duan Mimi , Guo Xiaotong , Wang Yao
Published: August 2021

The most important issue related to the establishment of carbon emission trading in China is how to motivate the owners of public buildings to participate. However, Existing research few considered the characteristics of public building owners and the influence of various uncertain factors in carbon emission trading investments. To fill this gap, this study constructs a carbon emission trading investment decision model of public building owners to study the mechanism that encourages them to participate, incorporating these characteristics and uncertain factors. The findings are as follows. First, carbon price is important in adjusting the emission reductions of different owners to minimize the total social cost of emission-reduction measures. Second, the price of carbon-emission permits has a significant impact on the investment threshold and decision-making behavior of public building owners. Finally, reducing the cost of energy-conservation and emission-reduction technologies in public buildings and appropriately subsidizing owners for their emission-reduction investment were effective methods to motivate them to participate in carbon emission trading. The results were used to quantitatively analyze the impact of a carbon emission trading mechanism on the decision-making behavior of public building owners and to construct the carbon emission trading mechanism used in China’s public building industry.
Recent Advances in Model Predictive and Sliding Mode Current Control Techniques of Multiphase Induction Machines
Authors: Rodas Jorge , Gonzalez-Prieto Ignacio , Kali Yassine , Saad Maarouf , Doval-Gandoy Jesus
Published: August 2021

Multiphase machines have attracted the attention of the research and industrial communities due to their advantages, namely better power distribution and fault-tolerant capabilities without extra hardware. However, the multiphase machine requires high-performance control strategies to take advantage of these features. From this perspective, the field-oriented control with the inner current control loop that uses using an explicit modulation stage has been considered the benchmark solution thanks to the reduced harmonic distortion obtained with this regulation strategy. Nevertheless, nonlinear controllers, thanks to their inherent nature, allow exploiting the extra multiphase capabilities in a simplified manner. Consequently, this paper aims to concentrate and discuss the latest developments on nonlinear current control of two of the most popular multiphase electric drive configurations, five-phase and six-phase. Then, this paper covers mainly finite-control-set model predictive control and their variations. Moreover, sliding-mode control is also explained. Finally, this paper includes experimental assessments of the most recent nonlinear current control techniques considering steady-state and transient conditions, stability and performance analysis.
Tree Mortality: Testing the Link Between Drought, Embolism Vulnerability, and Xylem Conduit Diameter Remains a Priority
Authors: Anfodillo Tommaso , Olson Mark E.
Published: August 2021

Global climate change-induced droughts are provoking events of forest mortality worldwide, with loss of tree biomass and consequent ecosystem services. Ameliorating the effects of drought requires understanding the causes of forest mortality, with failure of the hydraulic system being an important contributor. Comparative anatomical data strongly suggest that, all else being equal, wider conduits are more vulnerable to drought-induced embolism than narrow ones. However, physiology experiments do not provide consistent support for such a link. If a vulnerability-diameter link exists, though, it would contribute not only to explaining and predicting forest mortality but also to interventions to render individual trees more drought resistant. Given that xylem conduits scale with plant height, taller plants have wider conduits. If there is a vulnerability-diameter link, then this would help explain why taller plants are often more vulnerable to climate change-induced drought. Links between conduit diameter, plant height, and vulnerability would also provide guidance for standardizing sampling of hydraulic variables across individuals and suggest that selecting for relatively narrow conduits at given height from the tree top could produce more drought resistant varieties. As a result, given current ambiguities, together with the potential importance of a link, it is important to maintain the vulnerability-diameter link as a research priority.
Quantitative Analysis of Protein Evolution: The Phylogeny of Osteopontin
Authors: Wang Xia , Weber Georg F.
Published: August 2021

The phylogenetic analysis of proteins conventionally relies on the evaluation of amino acid sequences or coding sequences. Individual amino acids have measurable features that allow the translation from strings of letters (amino acids or bases) into strings of numbers (physico-chemical properties). When the letters are converted to measurable properties, such numerical strings can be evaluated quantitatively with various tools of complex systems research. We build on our prior phylogenetic analysis of the cytokine Osteopontin to validate the quantitative approach toward the study of protein evolution. Phylogenetic trees constructed from the number strings differentiate among all sequences. In pairwise comparisons, autocorrelation, average mutual information and box counting dimension yield one number each for the overall relatedness between sequences. We also find that bivariate wavelet analysis distinguishes hypermutable regions from conserved regions of the protein. The investigation of protein evolution via quantitative study of the physico-chemical characteristics pertaining to the amino acid building blocks broadens the spectrum of applicable research tools, accounts for mutation as well as selection, gives assess to multiple vistas depending on the property evaluated, discriminates more accurately among sequences, and renders the analysis more quantitative than utilizing strings of letters as starting points.
Clinical Benefits and Safety of Gemtuzumab Ozogamicin in Treating Acute Myeloid Leukemia in Various Subgroups: An Updated Systematic Review, Meta-Analysis, and Network Meta-Analysis
Authors: Xu Qingyu , He Shujiao , Yu Li
Published: August 2021

Background

Previous trials demonstrated evidence involving the total effects of gemtuzumab ozogamicin (GO), an anti-CD33 humanized antibody, on treating acute myeloid leukemia (AML). In this updated systematic review, meta-analysis, and network meta-analysis (NMA), we aimed to comprehensively explore the clinical benefits and safety of GO in various subtypes of AML.

Methods

PubMed, Embase, Cochrane, and Chinese databases were filtered to search randomized controlled trials (RCTs) and retrospective cohort studies that compared clinical efficiency and toxicity of GO with non-GO groups in AML. Random-effects models were used to calculate pooled effect sizes and 95% confidence intervals (CIs). Relative risk (RR) was used for estimating complete remission (CR), early death, and toxicity. Hazard risk (HR) was accomplished to evaluate survival.

Results

Fifteen RCTs and 15 retrospective cohort studies were identified (GO: 4,768; Control: 6,466). GO tended to improve CR (RR 0.95, p = 0.084), followed by significantly improved survival (overall survival: HR 0.86, p = 0.003; event-free survival: HR 0.86, p = 0.015; relapse-free survival: HR 0.83, p = 0.001; cumulative incidence of relapse: HR 0.82, p < 0.001). GO benefits of CR and survival were evident in favorable- and intermediate-risk karyotypes (p ≤ 0.023). GO advantages were also associated with nucleophosmin 1 mutations (p ≤ 0.04), wild-type FMS-like tyrosine kinase 3 internal tandem duplication gene (p ≤ 0.03), age of <70 years (p < 0.05), de novo AML (p ≤ 0.017), and CD33(+) (p ≤ 0.021). Both adding GO into induction therapy (p ≤ 0.011) and a lower (<6 mg/m2) dose of GO (p ≤ 0.03) enhanced survival. Prognosis of combined regimens with GO was heterogeneous in both meta-analysis and NMA, with several binding strategies showing improved prognosis. Additionally, GO was related to increased risk of early death at a higher dose (≥6 mg/m2) (RR 2.01, p = 0.005), hepatic-related adverse effects (RR 1.29, p = 0.02), and a tendency of higher risk for hepatic veno-occlusive disease or sinusoidal obstruction syndrome (RR 1.56, p = 0.072).

Conclusions

These data indicated therapeutic benefits and safety of GO in AML, especially in some subtypes, for which further head-to-head RCTs are warranted.

Systematic Review Registration

[PROSPERO: https://www.crd.york.ac.uk/prospero/], identifier [CRD42020158540].
A Novel Single Cell RNA-seq Analysis of Non-Myeloid Circulating Cells in Late Sepsis
Authors: Darden Dijoia B. , Dong Xiaoru , Brusko Maigan A. , Kelly Lauren , Fenner Brittany , Rincon Jaimar C. , Dirain Marvin L. , Ungaro Ricardo , Nacionales Dina C. , Gauthier Marie , Kladde Michael , Brusko Todd M. , Bihorac Azra , Moore Frederick A. , Loftus Tyler , Bacher Rhonda , Moldawer Lyle L. , Mohr Alicia M. , Efron Philip A.
Published: August 2021

Background

With the successful implementation of the Surviving Sepsis Campaign guidelines, post-sepsis in-hospital mortality to sepsis continues to decrease. Those who acutely survive surgical sepsis will either rapidly recover or develop a chronic critical illness (CCI). CCI is associated with adverse long-term outcomes and 1-year mortality. Although the pathobiology of CCI remains undefined, emerging evidence suggests a post-sepsis state of pathologic myeloid activation, inducing suboptimal lymphopoiesis and erythropoiesis, as well as downstream leukocyte dysfunction. Our goal was to use single-cell RNA sequencing (scRNA-seq) to perform a detailed transcriptomic analysis of lymphoid-derived leukocytes to better understand the pathology of late sepsis.

Methods

A mixture of whole blood myeloid-enriched and Ficoll-enriched peripheral blood mononuclear cells from four late septic patients (post-sepsis day 14-21) and five healthy subjects underwent Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq).

Results

We identified unique transcriptomic patterns for multiple circulating immune cell subtypes, including B- and CD4+, CD8+, activated CD4+ and activated CD8+ T-lymphocytes, as well as natural killer (NK), NKT, and plasmacytoid dendritic cells in late sepsis patients. Analysis demonstrated that the circulating lymphoid cells maintained a transcriptome reflecting immunosuppression and low-grade inflammation. We also identified transcriptomic differences between patients with bacterial versus fungal sepsis, such as greater expression of cytotoxic genes among CD8+ T-lymphocytes in late bacterial sepsis.

Conclusion

Circulating non-myeloid cells display a unique transcriptomic pattern late after sepsis. Non-myeloid leukocytes in particular reveal a host endotype of inflammation, immunosuppression, and dysfunction, suggesting a role for precision medicine-guided immunomodulatory therapy.
Delayed Disease in Cynomolgus Macaques Exposed to Ebola Virus by an Intranasal Route
Authors: Johnston Sara C. , Wilhelmsen Catherine L. , Shamblin Joshua , Kimmel Adrienne , Zelko Justine , Wollen Suzanne , Goff Arthur J.
Published: August 2021

Ebola virus remains a significant public health concern due to high morbidity and mortality rates during recurrent outbreaks in endemic areas. Therefore, the development of countermeasures against Ebola virus remains a high priority, and requires the availability of appropriate animal models for efficacy evaluations. The most commonly used nonhuman primate models for efficacy evaluations against Ebola virus utilize the intramuscular or aerosol route of exposure. Although clinical disease signs are similar to human cases, disease progression in these models is much more rapid, and this can pose significant hurdles for countermeasure evaluations. The objective of the present study was to evaluate the Ebola virus disease course that arises after cynomolgus macaques are exposed to Ebola virus by a mucosal route (the intranasal route). Two different doses (10 pfu and 100 pfu) and delivery methodologies (drop-wise and mucosal atomization device) were evaluated on this study. Differences in clinical disease between dose and delivery groups were not noted. However, a delayed disease course was identified for approximately half of the animals on study, and this delayed disease was dose and administration method independent. Therefore, it appears that mucosal exposure with Ebola virus results in a disease course in cynomolgus macaques that more accurately replicates that which is documented for human cases. In summary, the data presented support the need for further development of this model as a possible alternative to parenteral and small-particle aerosol models for the study of human Ebola virus disease and for countermeasure evaluations.
Transcriptome Profiling of Atlantic Salmon Adherent Head Kidney Leukocytes Reveals That Macrophages Are Selectively Enriched During Culture
Authors: Smith Nicole C. , Umasuthan Navaneethaiyer , Kumar Surendra , Woldemariam Nardos T. , Andreassen Rune , Christian Sherri L. , Rise Matthew L.
Published: August 2021

The Atlantic salmon (Salmo salar) is an economically important fish, both in aquaculture and in the wild. In vertebrates, macrophages are some of the first cell types to respond to pathogen infection and disease. While macrophage biology has been characterized in mammals, less is known in fish. Our previous work identified changes in the morphology, phagocytic ability, and miRNA profile of Atlantic salmon adherent head kidney leukocytes (HKLs) from predominantly “monocyte-like” at Day 1 of in vitro culture to predominantly “macrophage-like” at Day 5 of culture. Therefore, to further characterize these two cell populations, we examined the mRNA transcriptome profile in Day 1 and Day 5 HKLs using a 44K oligonucleotide microarray. Large changes in the transcriptome were revealed, including changes in the expression of macrophage and immune-related transcripts (e.g. csf1r, arg1, tnfa, mx2), lipid-related transcripts (e.g. fasn, dhcr7, fabp6), and transcription factors involved in macrophage differentiation and function (e.g. klf2, klf9, irf7, irf8, stat1). The in silico target prediction analysis of differentially expressed genes (DEGs) using miRNAs known to change expression in Day 5 HKLs, followed by gene pathway enrichment analysis, supported that these miRNAs may be involved in macrophage maturation by targeting specific DEGs. Elucidating how immune cells, such as macrophages, develop and function is a key step in understanding the Atlantic salmon immune system. Overall, the results indicate that, without the addition of exogenous factors, the adherent HKL cell population differentiates in vitro to become macrophage-like.