bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can Indirect Evaluation Methods and Their Fusion Products Reduce Uncertainty in Actual Evapotranspiration Estimates?
Authors: Shao Xingmin , Zhang Yongqiang , Liu Changming , Chiew Francis H. S. , Tian Jing , Ma Ning , Zhang Xuanze 
Published: May 2022

AbstractAccurately estimating actual evapotranspiration (ET) across global land surface is one of the key challenges in terrestrial hydrological cycles and energy flux balance studies. Gridded ET products have the potential for application in ungauged basins, but their uncertainties are possibly large and it remains unclear which one is best for a given basin. The water balance (WB) method provides a direct estimate of basin scale ET, but it cannot be used in ungauged basins where streamflow data are unavailable. Here, we first assess the performance of ET from 10 global ET products against WB ET estimates in 43 large river basins. The paper then uses three indirect evaluation methods [Three Cornered Hat (TCH), Arithmetic Average (AA), and Bayesian Three Cornered Hat] to identify the optimal ET products without the need of prior information, and to generate fusion products combining the ET from multiple products. Using the evaluation results derived from the WB method as the reference, the results show that the three methods have great success in identifying poorer products, suggesting that they are useful in filtering poor ET products in applications. However, the ability of such methods in identifying better ET products degrades slightly. The AA fusion product, which combines ET outputs from multiple products, is marginally better than the best single ET product in many of the 43 basins. Because of its simplicity, it could be used to reduce the uncertainty in ET estimates from multiple products for ungauged basins and regions.
Four-Octyl itaconate ameliorates periodontal destruction via Nrf2-dependent antioxidant system
Authors: Xin Liangjing , Zhou Fuyuan , Zhang Chuangwei , Zhong Wenjie , Xu Shihan , Jing Xuan , Wang Dong , Wang Si , Chen Tao , Song Jinlin 
Published: May 2022

AbstractPeriodontitis is a widespread oral disease characterized by continuous inflammation of the periodontal tissue and an irreversible alveolar bone loss, which eventually leads to tooth loss. Four-octyl itaconate (4-OI) is a cell-permeable itaconate derivative and has been recognized as a promising therapeutic target for the treatment of inflammatory diseases. Here, we explored, for the first time, the protective effect of 4-OI on inhibiting periodontal destruction, ameliorating local inflammation, and the underlying mechanism in periodontitis. Here we showed that 4-OI treatment ameliorates inflammation induced by lipopolysaccharide in the periodontal microenvironment. 4-OI can also significantly alleviate inflammation and alveolar bone loss via Nrf2 activation as observed on samples from experimental periodontitis in the C57BL/6 mice. This was further confirmed as silencing Nrf2 blocked the antioxidant effect of 4-OI by downregulating the expression of downstream antioxidant enzymes. Additionally, molecular docking simulation indicated the possible mechanism under Nrf2 activation. Also, in Nrf2−/− mice, 4-OI treatment did not protect against alveolar bone dysfunction due to induced periodontitis, which underlined the importance of the Nrf2 in 4-OI mediated periodontitis treatment. Our results indicated that 4-OI attenuates inflammation and oxidative stress via disassociation of KEAP1-Nrf2 and activation of Nrf2 signaling cascade. Taken together, local administration of 4-OI offers clinical potential to inhibit periodontal destruction, ameliorate local inflammation for more predictable periodontitis.
Cannabinoid Receptor-1 suppresses M2 macrophage polarization in colorectal cancer by downregulating EGFR
Authors: Deng You-Ming , Zhao Cheng , Wu Lei , Qu Zhan , Wang Xin-Yu 
Published: May 2022

AbstractCannabinoid receptors, CB1 and CB2, have been implicated as emerging targets for cancer therapy. Herein, we investigated the potential regulation mechanism of CB1 and its implications in colorectal cancer. CB1 and EGFR expression were examined in colorectal cancer cell lines. The effects of CB1 agonist ACEA and its antagonist AM251 on the proliferation, migration and invasion of colorectal cancer cells and the expression of M1 and M2 macrophage markers were examined. EGFR overexpression was performed with plasmids containing EGFR gene. Tumor xenografts were constructed to explore the effects of CB1 activation on tumorigenesis. We showed that CB1 was downregulated while EGFR was upregulated in colorectal cancer cells. The activation of CB1 suppressed the proliferation, migration and invasion of colorectal cancer cells and the differentiation of M2 macrophages, while CB1 inhibition had opposite effects. Moreover, the alterations in tumorigenesis and M2 macrophage activation induced by CB1 activation were counteracted by EGFR overexpression. Besides, CB1 silencing promoted tumor cell proliferation and M2 polarization which was counteracted by EGFR knockdown. In vivo, CB1 activation also repressed tumorigenesis and M2 macrophage activation. The present study demonstrated that CB1 activation suppressed M2 macrophage through EGFR downregulation in colorectal cancers. These findings first unveiled the potential avenue of CB1 as a targeted therapy for colorectal cancer.
Blocking phospholamban with VHH intrabodies enhances contractility and relaxation in heart failure
Authors: De Genst Erwin , Foo Kylie S. , Xiao Yao , Rohner Eduarde , de Vries Emma , Sohlmér Jesper , Witman Nevin , Hidalgo Alejandro , Kolstad Terje R. S. , Louch William E. , Pehrsson Susanne , Park Andrew , Ikeda Yasuhiro , Li Xidan , Mayr Lorenz M. , Wickson Kate , Jennbacken Karin , Hansson Kenny , Fritsche-Danielson Regina , Hunt James , Chien Kenneth R. 
Published: May 2022

AbstractThe dysregulated physical interaction between two intracellular membrane proteins, the sarco/endoplasmic reticulum Ca2+ ATPase and its reversible inhibitor phospholamban, induces heart failure by inhibiting calcium cycling. While phospholamban is a bona-fide therapeutic target, approaches to selectively inhibit this protein remain elusive. Here, we report the in vivo application of intracellular acting antibodies (intrabodies), derived from the variable domain of camelid heavy-chain antibodies, to modulate the function of phospholamban. Using a synthetic VHH phage-display library, we identify intrabodies with high affinity and specificity for different conformational states of phospholamban. Rapid phenotypic screening, via modified mRNA transfection of primary cells and tissue, efficiently identifies the intrabody with most desirable features. Adeno-associated virus mediated delivery of this intrabody results in improvement of cardiac performance in a murine heart failure model. Our strategy for generating intrabodies to investigate cardiac disease combined with modified mRNA and adeno-associated virus screening could reveal unique future therapeutic opportunities.
STING agonism reprograms tumor-associated macrophages and overcomes resistance to PARP inhibition in BRCA1-deficient models of breast cancer
Authors: Wang Qiwei , Bergholz Johann S. , Ding Liya , Lin Ziying , Kabraji Sheheryar K. , Hughes Melissa E. , He Xiadi , Xie Shaozhen , Jiang Tao , Wang Weihua , Zoeller Jason J. , Kim Hye-Jung , Roberts Thomas M. , Konstantinopoulos Panagiotis A. , Matulonis Ursula A. , Dillon Deborah A. , Winer Eric P. , Lin Nancy U. , Zhao Jean J. 
Published: May 2022

AbstractPARP inhibitors (PARPi) have drastically changed the treatment landscape of advanced ovarian tumors withBRCAmutations. However, the impact of this class of inhibitors in patients with advancedBRCA-mutant breast cancer is relatively modest. Using a syngeneic genetically-engineered mouse model of breast tumor driven byBrca1deficiency, we show that tumor-associated macrophages (TAMs) blunt PARPi efficacy both in vivo and in vitro. Mechanistically, BRCA1-deficient breast tumor cells induce pro-tumor polarization of TAMs, which in turn suppress PARPi-elicited DNA damage in tumor cells, leading to reduced production of dsDNA fragments and synthetic lethality, hence impairing STING-dependent anti-tumor immunity. STING agonists reprogram M2-like pro-tumor macrophages into an M1-like anti-tumor state in a macrophage STING-dependent manner. Systemic administration of a STING agonist breaches multiple layers of tumor cell-mediated suppression of immune cells, and synergizes with PARPi to suppress tumor growth. The therapeutic benefits of this combination require host STING and are mediated by a type I IFN response and CD8+T cells, but do not rely on tumor cell-intrinsic STING. Our data illustrate the importance of targeting innate immune suppression to facilitate PARPi-mediated engagement of anti-tumor immunity in breast cancer.
Evidence for 4e charge of Cooper quartets in a biased multi-terminal graphene-based Josephson junction
Authors: Huang Ko-Fan , Ronen Yuval , Mélin Régis , Feinberg Denis , Watanabe Kenji , Taniguchi Takashi , Kim Philip 
Published: May 2022

AbstractIn a Josephson junction (JJ) at zero bias, Cooper pairs are transported between two superconducting contacts via the Andreev bound states (ABSs) formed in the Josephson channel. Extending JJs to multiple superconducting contacts, the ABSs in the Josephson channel can coherently hybridize Cooper pairs among different superconducting electrodes. Biasing three-terminal JJs with antisymmetric voltages, for example, results in a direct current (DC) of Cooper quartet (CQ), which involves a four-fermion entanglement. Here, we report half a flux periodicity in the interference of CQ formed in graphene based multi-terminal (MT) JJs with a magnetic flux loop. We observe that the quartet differential conductance associated with supercurrent exhibits magneto-oscillations associated with a charge of 4e, thereby presenting evidence for interference between different CQ processes. The CQ critical current shows non-monotonic bias dependent behavior, which can be modeled by transitions between Floquet-ABSs. Our experimental observation for voltage-tunable non-equilibrium CQ-ABS in flux-loop-JJs significantly extends our understanding of MT-JJs, enabling future design of topologically unique ABS spectrum.
History-dependent domain and skyrmion formation in 2D van der Waals magnet Fe3GeTe2
Authors: Birch M. T. , Powalla L. , Wintz S. , Hovorka O. , Litzius K. , Loudon J. C. , Turnbull L. A. , Nehruji V. , Son K. , Bubeck C. , Rauch T. G. , Weigand M. , Goering E. , Burghard M. , Schütz G. 
Published: May 2022

AbstractThe discovery of two-dimensional magnets has initiated a new field of research, exploring both fundamental low-dimensional magnetism, and prospective spintronic applications. Recently, observations of magnetic skyrmions in the 2D ferromagnet Fe3GeTe2 (FGT) have been reported, introducing further application possibilities. However, controlling the exhibited magnetic state requires systematic knowledge of the history-dependence of the spin textures, which remains largely unexplored in 2D magnets. In this work, we utilise real-space imaging, and complementary simulations, to determine and explain the thickness-dependent magnetic phase diagrams of an exfoliated FGT flake, revealing a complex, history-dependent emergence of the uniformly magnetised, stripe domain and skyrmion states. The results show that the interplay of the dominant dipolar interaction and strongly temperature dependent out-of-plane anisotropy energy terms enables the selective stabilisation of all three states at zero field, and at a single temperature, while the Dzyaloshinksii-Moriya interaction must be present to realise the observed Néel-type domain walls. The findings open perspectives for 2D devices incorporating topological spin textures.
The long-tail effect of the COVID-19 lockdown on Italians’ quality of life, sleep and physical activity
Authors: Natilli Michela , Rossi Alessio , Trecroci Athos , Cavaggioni Luca , Merati Giampiero , Formenti Damiano 
Published: May 2022

AbstractFrom March 2020 to May 2021, several lockdown periods caused by the COVID-19 pandemic have limited people’s usual activities and mobility in Italy, as well as around the world. These unprecedented confinement measures dramatically modified citizens’ daily lifestyles and behaviours. However, with the advent of summer 2021 and thanks to the vaccination campaign that significantly prevents serious illness and death, and reduces the risk of contagion, all the Italian regions finally returned to regular behaviours and routines. Anyhow, it is unclear if there is a long-tail effect on people’s quality of life, sleep- and physical activity-related behaviours. Thanks to the dataset described in this paper, it will be possible to obtain accurate insights of the changes induced by the lockdown period in the Italians’ health that will permit to provide practical suggestions at local, regional, and state institutions and companies to improve infrastructures and services that could be beneficial to Italians’ well being.
The effects of post-activation performance enhancement and different warm-up protocols on swim start performance
Authors: Đurović Marko , Stojanović Nikola , Stojiljković Nenad , Karaula Dajana , Okičić Tomislav 
Published: May 2022

AbstractThis study aimed to examine the effects of post-activation performance enhancement (PAPE) on swim start performance and lower body power performance after different warm-up protocols. Ten male national-level swimmers performed three different warm-ups: (i) a swim-specific warm-up (SW, control protocol); (ii) PAPE (an experimental protocol); and (iii) SW followed by PAPE (SW + PAPE, an experimental protocol). PAPE consisted of performing three series of 5 drop jumps. A repeated-measures ANOVA showed significant differences between the protocols in the swim start performance (F = 8.89; P < 0.001) and countermovement jump (F = 2.22; P = 0.047). SW + PAPE induced greater improvements in swim start time to 15 m (ES = − 0.47, P = 0.017) and entry time (ES = − 1.83, P < 0.001), the countermovement jump reactive strength index modified (ES = − 1.83, P < 0.001), eccentric rate of force development (ES = 0.69, P = 0.047), and index of explosive strength (ES = 0.94, P = 0.005) compared to SW. The current findings of this study indicate that the drop jump PAPE protocol, in addition to SW, is an effective tool because it could improve athletes' capacity for a more efficient swim start and their countermovement jump performance. Furthermore, the results of this study indicate that PAPE induced by drop jumps could be time-efficient and practically applicable in facilities with limited resources.
Online symptoms self-assessment during COVID-19 pandemic: an analysis of a COVID-19 portal responses from Canada
Authors: Egbujie Bonaventure A. , Francisco Krizia , Alarakhia Mohamed , Hirdes John P. 
Published: May 2022

AbstractCOVID-19 case was first identified in Canada on January 25, 2020, on a Toronto resident who had travelled to Wuhan China, and not long after, the WHO declared the viral infection a pandemic. Ontario health West created an online self-assessment portal that allowed individuals in the health region and adjourning areas to report any COVID related symptoms. The purpose of this study was to evaluate the utility and usefulness of the Ontario Heath West online COVID-19 self-assessment portal. Record level data obtained from the Ontario Health West self-assessment portal was analyzed. Descriptive statistics using charts and graphs were used to characterize the distribution of responses to the portal. In-depth analysis using correlation, lead-lag analysis, and trend comparison with actual Government of Ontario COVID-19 cases for the region were also conducted. A total of 34,144 distinct responses were recorded on the portal between April 10 and July 29, 2020, with 1,250 (3.7%) responding positively to one of the emergency symptoms questions. Trend analysis showed a peak portal response in May 2020 with a smaller rise subsequently in July 2020, coinciding with the actual COVID-19 peak in the region. The five most reported symptoms on the portal were sore throat (17.2%), headache (12.9%), fatigue (12.3%), digestive problems (12.2%) and cough (9.1%). For four sub-regions, the trend of self-report on the portal positively lagged actual Public Health Ontario reported COVID-19 cases, while for one sub-region, the trend positively led the actual Public Health Ontario reported COVID-19 cases for the area. We found correlation between online COVID-19 self- assessment data and the confirmed COVID-19 cases in the Southwestern region of Ontario. Trends in the COVID-19 associated emergency symptoms reported on the portal also tracked confirmed COVID-19 cases in the community. Peak response to the portal coincided with the peak volume of confirmed cases in Ontario during the first wave of COVID-19 pandemic in Canada, suggesting some consistency between the experiences of portal users and patterns of COVID-19 illness in the community. The portal was a useful tool at the person-level because it provided guidance to individuals about how to access appropriate health services according to the symptoms that they reported and connected them with primary care, reducing unnecessary visit to health facilities for COVID-19 related care.
Emerging concepts in designing next-generation multifunctional nanomedicine for cancer treatment
Authors: Chakraborty Kasturee , Tripathi Archana , Mishra Sukumar , Mallick Argha Mario , Roy Rituparna Sinha 
Published: May 2022

Abstract
Nanotherapy has emerged as an improved anticancer therapeutic strategy to circumvent the harmful side effects of chemotherapy. It has been proven to be beneficial to offer multiple advantages, including their capacity to carry different therapeutic agents, longer circulation time and increased therapeutic index with reduced toxicity. Over time, nanotherapy evolved in terms of their designing strategies like geometry, size, composition or chemistry to circumvent the biological barriers. Multifunctional nanoscale materials are widely used as molecular transporter for delivering therapeutics and imaging agents. Nanomedicine involving multi-component chemotherapeutic drug-based combination therapy has been found to be an improved promising approach to increase the efficacy of cancer treatment. Next-generation nanomedicine has also utilized and combined immunotherapy to increase its therapeutic efficacy. It helps in targeting tumor immune response sparing the healthy systemic immune function. In this review, we have summarized the progress of nanotechnology in terms of nanoparticle designing and targeting cancer. We have also discussed its further applications in combination therapy and cancer immunotherapy. Integrating patient-specific proteomics and biomarker based information and harnessing clinically safe nanotechnology, the development of precision nanomedicine could revolutionize the effective cancer therapy.
Gaps in Framing and Naming: Commentary to “A Viewpoint on Accent Services”
Authors: Yu Betty , Nair Vishnu KK , Brea Maria Rosa , Soto-Boykin Xigrid , Privette Chelsea , Sun Lei , Khamis Reem , Chiou Hsinhuei Sheen , Fabiano-Smith Leah , Epstein Laura , Hyter Yvette D. 
Published: May 2022

Purpose:
In this commentary, we offer a critique of “A Viewpoint on Accent Services: Framing and Terminology Matter” (Grover et al., 2022). We argue that the authors' proposal to rename and reframe accent modification lacks criticality, which actually hinders—rather than advances—the movement toward equitable, culturally sustaining, and emancipatory practices.

Method:
We offer an analysis of the shortfall between the authors' calls for linguistic justice in “A Viewpoint on Accent Services” and the actual changes they proposed. We break down major gaps in criticality, reflexivity, practice, and vision and discuss their potential for undercutting meaningful progress as it relates to linguistic justice.

Results:
We found that the frameworks for the pursuit of equity, cultural sustenance, and emancipatory practices were misrepresented in the article in such a way that suggests that these goals could be achieved through superficial changes in terminology and attitudes. “A Viewpoint on Accent Services” upholds a power-neutral frame of operation that does not address the deeper systemic forces that make accent modification problematic. The lack of criticality toward accent intervention fosters complacency toward real transformation.

Conclusion:
We advocate for a serious and critical interrogation of accent practices and commitment to an emancipatory practice that addresses linguistic discrimination above all else. We emphasize the need to decenter standardized languages and to co-envision linguistic liberation using critical methods in scholarship, pedagogy, clinical practice, and policy.
Speech Sound Disorder Treatment Approaches Used by School-Based Clinicians: An Application of the Experience Sampling Method
Authors: Cabbage Kathryn , Farquharson Kelly , DeVeney Shari 
Published: May 2022

Purpose:Children with speech sound disorders (SSDs) comprise a large portion of caseloads for school-based speech-language pathologists (SLPs). Despite the existence of several evidence-based SSD intervention approaches, the translation from research to practice is often limited by ecological validity because of various factors unique to school settings (e.g., scheduling constraints, caseload size, child availability). The purpose of this study was to use the experience sampling method (ESM) to examine the current practices of school-based SLPs when treating children with SSDs on their caseloads.Method:SLPs (N= 106) from 42 different states working full-time in school-based K–12 settings participated in this study. At the beginning of the study, each SLP completed a one-time demographic survey about treatment practices for children with SSDs. The SLPs then participated in a series of brief surveys every day for one workweek using a specialized ESM phone application that randomly alerted participants to report on their treatment practices for children with SSDs.Results:Findings revealed that although most SLPs reported using a variety of SSD intervention approaches in a one-time survey, the majority of SLPs reported using one of three approaches in situ: the traditional articulation therapy approach, cycles, and minimal pairs. We also report a significant negative relationship between the years of experience of an SLP and the number of different approaches used.Conclusions:This study is the first to use the ESM to determine which approaches school-based SLPs use to treat children with SSDs. Findings demonstrate that SLPs have knowledge of many different SSD approaches but tend to utilize only a few in school-based settings.