bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic Thermal Corridor May Connect Endangered Loggerhead Sea Turtles Across the Pacific Ocean
Authors: Briscoe Dana K. , Turner Tomaszewicz Calandra N. , Seminoff Jeffrey A. , Parker Denise M. , Balazs George H. , Polovina Jeffrey J. , Kurita Masanori , Okamoto Hitoshi , Saito Tomomi , Rice Marc R. , Crowder Larry B.
Published: April 2021

The North Pacific Loggerhead sea turtle (Caretta caretta) undergoes one of the greatest of all animal migrations, nesting exclusively in Japan and re-emerging several years later along important foraging grounds in the eastern North Pacific. Yet the mechanisms that connect these disparate habitats during what is known as the “lost years” have remained poorly understood. Here, we develop a new hypothesis regarding a possible physical mechanism for habitat connectivity – an intermittent “thermal corridor” – using remotely sensed oceanography and 6 juvenile loggerhead sea turtles that formed part of a 15 year tracking dataset of 231 individuals (1997–2013). While 97% of individuals remained in the Central North Pacific, these 6 turtles (about 3%), continued an eastward trajectory during periods associated with anomalously warm ocean conditions. These few individuals provided a unique opportunity to examine previously unknown recruitment pathways. To support this hypothesis, we employed an independently derived data set using novel stable isotope analyses of bone growth layers and assessed annual recruitment over the same time period (n = 33, 1997–2012). We suggest evidence of a thermal corridor that may allow for pulsed recruitment of loggerheads to the North American coast as a function of ocean conditions. Our findings offer, for the first time, the opportunity to explore the development of a dynamic ocean corridor for this protected species, illuminating a longstanding mystery in sea turtle ecology.
Transcriptomic Responses of Deep-Sea Corals Experimentally Exposed to Crude Oil and Dispersant
Authors: DeLeo Danielle M. , Glazier Amanda , Herrera Santiago , Barkman Alexandria , Cordes Erik E.
Published: April 2021

Resource extraction from the ocean comes with ecosystem-wide risks, including threats to its biota such as the habitat forming corals that support elevated biomass and biodiversity. Despite catastrophic incidents like theDeepwater Horizonoil spill (DWHOS) disaster that occurred in 2010, offshore oil and gas drilling continues to occur around the world. Previous work investigating the toxicity of oil and the chemical dispersant used in an attempt to mitigate the effects of the DWHOS revealed that the dispersant elicits a stronger, negative physiological response than oil alone. However, little is known regarding the specific ways in which these anthropogenic pollutants impact organisms at the cellular level. To investigate the impacts of each pollutant and their synergistic effects on corals, we analyzed the transcriptional responses of the deep-sea octocoralsCallogorgia deltaandParamuriceatype B3 following 12 h of exposure to oil, dispersant, and mixtures of oil and dispersant. Analyses revealed that the highest levels of significant differential gene expression were found among the treatments containing dispersant, which corresponds to the significant effects observed in physiological experiments. Functional analyses of annotated transcripts further suggest both species- and colony-specific responses to the exposures, likely due to underlying cellular and physiological differences. However, some commonalities were observed among the responses to chemical stress across treatments and species, including immune and cellular stress responses, altered energy metabolism, and oxidative stress, elucidating how corals respond to chemical pollutants. As resource extraction is an ongoing threat, this study demonstrates the importance of considering the varied and diverse responses of biota to anthropogenic disturbances and the implications of introducing chemicals into vulnerable ecosystems like those associated with deep-sea corals.
Mortality Benefit of Convalescent Plasma in COVID-19: A Systematic Review and Meta-Analysis
Authors: Bansal Vikas , Mahapure Kiran S. , Mehra Ishita , Bhurwal Abhishek , Tekin Aysun , Singh Romil , Gupta Ishita , Rathore Sawai Singh , Khan Hira , Deshpande Sohiel , Gulati Shivam , Armaly Paige , Sheraton Mack , Kashyap Rahul
Published: April 2021

Importance/Background: With a scarcity of high-grade evidence for COVID-19 treatment, researchers and health care providers across the world have resorted to classical and historical interventions. Immunotherapy with convalescent plasma (CPT) is one such therapeutic option.

Methods: A systematized search was conducted for articles published between December 2019 and 18th January 2021 focusing on convalescent plasma efficacy and safety in COVID-19. The primary outcomes were defined as mortality benefit in patients treated with convalescent plasma compared to standard therapy/placebo. The secondary outcome was pooled mortality rate and the adverse event rate in convalescent plasma-treated patients.

Results: A total of 27,706 patients were included in the qualitative analysis, and a total of 3,262 (2,127 in convalescent plasma-treated patients and 1,135 in the non-convalescent plasma/control group) patients died. The quantitative synthesis in 23 studies showed that the odds of mortality in patients who received plasma therapy were significantly lower than those in patients who did not receive plasma therapy [odds ratio (OR) 0.65, 95% confidence interval (CI) 0.53–0.80, p < 0.0001, I2 = 15%). The mortality benefit remains the same even for 14 trials/prospective studies (OR 0.59, 95% CI 0.43–0.81, p = 0.001, I2 = 22%) as well as for nine case series/retrospective observational studies (OR 0.78, 95% CI 0.65–0.94, p = 0.01, I2 = 0%). However, in a subgroup analysis for 10 randomized controlled trials (RCTs), there was no statistically significant reduction in mortality between the CPT group compared to the non-CPT group (OR 0.76, 95% CI 0.53–1.08, p = 0.13, I2 = 7%). Furthermore, the sensitivity analysis of 10 RCTs, excluding the study with the highest statistical weight, displayed a lower mortality rate compared to that of non-CPT COVID-19 patients (OR 0.64, 95% CI 0.42–0.97, p = 0.04, I2 = 0%). The observed pooled mortality rate was 12.9% (95% CI 9.7–16.9%), and the pooled adverse event rate was 6.1% (95% CI 3.2–11.6), with significant heterogeneity.

Conclusions and Relevance: Our systemic review and meta-analysis suggests that CPT could be an effective therapeutic option with promising evidence on the safety and reduced mortality in concomitant treatment for COVID-19 along with antiviral/antimicrobial drugs, steroids, and other supportive care. Future exploratory studies could benefit from more standardized reporting, especially in terms of the timing of interventions and clinically relevant outcomes, like days until discharge from the hospital and improvement of clinical symptoms.
Thrombotic Microangiopathy After Kidney Transplantation: An Underdiagnosed and Potentially Reversible Entity
Authors: Ávila Ana , Gavela Eva , Sancho Asunción
Published: April 2021

Thrombotic microangiopathy is a rare but serious complication that affects kidney transplant recipients. It appears in 0.8–14% of transplanted patients and negatively affects graft and patient survival. It can appear in a systemic form, with hemolytic microangiopathic anemia, thrombocytopenia, and renal failure, or in a localized form, with progressive renal failure, proteinuria, or arterial hypertension. Post-transplant thrombotic microangiopathy is classified as recurrent atypical hemolytic uremic syndrome orde novothrombotic microangiopathy.De novothrombotic microangiopathy accounts for the majority of cases. Distinguishing between the 2 conditions can be difficult, given there is an overlap between them. Complement overactivation is the cornerstone of all post-transplant thrombotic microangiopathies, and has been demonstrated in the context of organ procurement, ischemia-reperfusion phenomena, immunosuppressive drugs, antibody-mediated rejection, viral infections, and post-transplant relapse of antiphospholipid antibody syndrome. Although treatment of the causative agents is usually the first line of treatment, this approach might not be sufficient. Plasma exchange typically resolves hematologic abnormalities but does not improve renal function. Complement blockade with eculizumab has been shown to be an effective therapy in post-transplant thrombotic microangiopathy, but it is necessary to define which patients can benefit from this therapy and when and how eculizumab should be used.
Influence of the ABC Transporter YtrBCDEF of Bacillus subtilis on Competence, Biofilm Formation and Cell Wall Thickness
Authors: Benda Martin , Schulz Lisa Maria , Stülke Jörg , Rismondo Jeanine
Published: April 2021

Bacillus subtilis develops genetic competence for the uptake of foreign DNA when cells enter stationary phase and a high cell density is reached. These signals are integrated by the competence transcription factor ComK, which is subject to transcriptional, post-transcriptional and post-translational regulation. Many proteins are involved in the development of competence, both to control ComK activity and to mediate DNA uptake. However, for many proteins, the precise function they play in competence development is unknown. In this study, we assessed whether proteins required for genetic transformation play a role in the activation of ComK or rather act downstream of competence gene expression. While these possibilities could be distinguished for most of the tested factors, we assume that two proteins, PNPase and the transcription factor YtrA, are required both for full ComK activity and for the downstream processes of DNA uptake and integration. Further analyses of the role of the transcription factor YtrA for the competence development revealed that the overexpression of the YtrBCDEF ABC transporter in the ytrA mutant causes the loss of genetic competence. Moreover, overexpression of this ABC transporter also affects biofilm formation. Since the ytrGABCDEF operon is naturally induced by cell wall-targeting antibiotics, we tested the cell wall properties upon overexpression of the ABC transporter and observed an increased thickness of the cell wall. The composition and properties of the cell wall are important for competence development and biofilm formation, suggesting that the observed phenotypes are the result of the increased cell wall thickness as an outcome of YtrBCDEF overexpression.
Cloning, Expression, Characterization, and Antioxidant Protection of Glutaredoxin3 From Psychrophilic Bacterium Psychrobacter sp. ANT206
Authors: Wang Yatong , Hou Yanhua , Wang Quanfu
Published: April 2021

Glutaredoxins (Grxs) are proteins that catalyze the glutathione (GSH)-dependent reduction of protein disulfides. In this study, a Grx-related gene (264 bp), encoding a Ps-Grx3, was cloned from Psychrobacter sp. ANT206. Sequence analysis indicated the presence of the active site motif CPYC in this protein. Homology modeling showed that Ps-Grx3 had fewer hydrogen bonds and salt bridges, as well as a lower Arg/(Arg + Lys) ratio than its mesophilic homologs, indicative of an improved catalytic ability at low temperatures. Site-directed mutagenesis demonstrated that the Cys13, Pro14, and Cys16 sites were essential for the catalytic activity of Ps-Grx3, while circular dichroism (CD) spectroscopy confirmed that point mutations in these amino acid residues led to the loss or reduction of enzyme activity. Furthermore, analysis of the biochemical properties of Ps-Grx3 showed that the optimum temperature of this enzyme was 25 °C. Importantly, Ps-Grx3 was more sensitive to tBHP and CHP than to H2O2, and retained approximately 40% activity even when the H2O2 concentration was increased to 1 mm Regarding substrate specificity, Ps-Grx3 had a higher affinity for HED, L-cystine, and DHA than for S-sulfocysteine and BSA. We also investigated the DNA-protective ability of Ps-Grx3 using the pUC19 plasmid, and found that Ps-Grx3 could protect supercoiled DNA from oxidation-induced damage at 15°C for 1.5 h. This study provides new insights into the structure and catalytic activity of a cold-adapted Grx3.
Rapidly Improving High Light and High Temperature Tolerances of Cyanobacterial Cell Factories Through the Convenient Introduction of an AtpA-C252F Mutation
Authors: Zhang Shanshan , Zheng Sini , Sun Jiahui , Zeng Xuexia , Duan Yangkai , Luan Guodong , Lu Xuefeng
Published: April 2021

Photosynthetic biomanufacturing is a promising route for green production of biofuels and biochemicals utilizing carbon dioxide and solar energy. Cyanobacteria are important microbial platforms for constructing photosynthetic cell factories. Toward scaled outdoor cultivations in the future, high light and high temperature tolerances of cyanobacterial chassis strains and cell factories would be determinant properties to be optimized. We proposed a convenient strategy for rapidly improving high light and high temperature tolerances of an important cyanobacterial chassis Synechococcus elongatus PCC 7942 and the derived cell factories. Through introduction and isolation of an AtpA-C252F mutation, PCC 7942 mutants with improved high light and high temperature tolerances could be obtained in only 4 days with an antibiotics-free mode. Adopting this strategy, cellular robustness and sucrose synthesizing capacities of a PCC 7942 cell factory were successfully improved.
Bioremediation of Crude Glycerol by a Sustainable Organic–Microbe Hybrid System
Authors: Chan Ho Shing , Xiao Kemeng , Tsang Tsz Ho , Zeng Cuiping , Wang Bo , Peng Xingxing , Wong Po Keung
Published: April 2021

Klebsiella pneumoniae with crude glycerol-utilizing and hydrogen (H2)-producing abilities was successfully isolated from return activated sludge from Shatin Sewage Treatment Works. The H2 production strategy used in this study was optimized with crude glycerol concentrations, and 1,020 μmol of H2 was generated in 3 h. An organic–microbe hybrid system was constructed with metal-free hydrothermal carbonation carbon (HTCC) microspheres to enhance the H2 production under visible light (VL) irradiation. Under optimized VL intensity and HTCC concentration, an elevation of 35.3% in H2 production can be obtained. Electron scavenger study revealed that the photogenerated electrons (e–) from HTCC contributed to the additional H2 production. The variation in intercellular intermediates, enzymatic activity, and reducing equivalents also suggested that the photogenerated e– interacted with K. pneumoniae cells to direct the metabolic flux toward H2 production. This study demonstrated the feasibility of using an organic–microbe hybrid system as a waste-to-energy technology.
A Conserved Phenylalanine Residue of Autographa Californica Multiple Nucleopolyhedrovirus AC75 Protein Is Required for Occlusion Body Formation
Authors: Chen Xingang , Yang Jian , Yang Xiaoqin , Lei Chengfeng , Sun Xiulian , Hu Jia
Published: April 2021

Autographa californica multiple nucleopolyhedrovirus (AcMNPV) orf75 (ac75) is a highly conserved gene that is essential for AcMNPV propagation. However, the key domains or residues of the AC75 protein that play a role in viral propagation have not been identified. In this study, sequence alignment revealed that residues Phe-54 and Gln-81 of AC75 were highly conserved among alphabaculoviruses and betabaculoviurses. Thus, Phe-54 and Gln-81 AC75 mutation bacmids were constructed. We found that Gln-81 was not required for viral propagation, whereas mutating Phe-54 reduced budded virus production by 10-fold and impaired occlusion body formation when compared with that of the wild-type AcMNPV. Electron microscopy observations showed that the Phe-54 mutation affected polyhedrin assembly and also occlusion-derived virus embedding, whereas western blot analysis revealed that mutating Phe-54 reduced the amount of AC75 but did not affect the localization of AC75 in infected cells. A protein stability assay showed that the Phe-54 mutation affected AC75 stability. Taken together, Phe-54 was identified as an important residue of AC75, and ac75 is a pivotal gene in budding virus production and occlusion body formation.
Sex Differences in the Relationship of Serum Vitamin B1 and B12 to Dementia Among Memory Clinic Outpatients in Japan
Authors: Miki Ayako , Kinno Ryuta , Ochiai Hirotaka , Kubota Satomi , Mori Yukiko , Futamura Akinori , Sugimoto Azusa , Kuroda Takeshi , Kasai Hideyo , Yano Satoshi , Hieda Sotaro , Kokaze Akatsuki , Ono Kenjiro
Published: April 2021

Dementia and cognitive impairment are considered to be one of the biggest social and medical problems. While there is a definite relationship between vitamin B and cognitive decline, this has yet to be fully assessed with regard to sex differences. Thus, the present study investigated the relationship of vitamin B1 or vitamin B12 with dementia in accordance with the sex in 188 patients who visited the Memory Clinic at Showa University Hospital in Japan from March 2016 to March 2019. Cognitive function was tested by the Japanese version of the Mini-Mental State Examination (MMSE) and Hasegawa Dementia Scale-Revised (HDS-R). Blood tests were performed to measure the vitamin levels. Logistic regression analysis was used to calculate the odds ratio (OR) for dementia and the 95% confidence interval (CI). Compared to the highest vitamin group (third tertile), the lowest vitamin group (first tertile) exhibited a significantly increased OR for dementia defined by MMSE for vitamin B1 (OR:3.73, 95% CI:1.52–9.16) and vitamin B12 (2.97, 1.22–7.28) among women. In contrast, vitamin levels were not significantly associated with dementia determined by MMSE in men. These findings were similar even when dementia was defined by HDS-R. The present study suggests that vitamin B1 plays a role in preventing development of dementia in women. Future longitudinal studies will need to be undertaken in order to examine whether decreasing vitamin levels occur before or after cognitive impairment, and whether maintaining a higher vitamin level can prevent a worsening of cognitive function and the development of dementia.
The Dystonia Coalition: A Multicenter Network for Clinical and Translational Studies
Authors: Kilic-Berkmen Gamze , Wright Laura J. , Perlmutter Joel S. , Comella Cynthia , Hallett Mark , Teller Jan , Pirio Richardson Sarah , Peterson David A. , Cruchaga Carlos , Lungu Codrin , Jinnah H. A.
Published: April 2021

Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal postures, repetitive movements, or both. Research in dystonia has been challenged by several factors. First, dystonia is uncommon. Dystonia is not a single disorder but a family of heterogenous disorders with varied clinical manifestations and different causes. The different subtypes may be seen by providers in different clinical specialties including neurology, ophthalmology, otolaryngology, and others. These issues have made it difficult for any single center to recruit large numbers of subjects with specific types of dystonia for research studies in a timely manner. The Dystonia Coalition is a consortium of investigators that was established to address these challenges. Since 2009, the Dystonia Coalition has encouraged collaboration by engaging 56 sites across North America, Europe, Asia, and Australia. Its emphasis on collaboration has facilitated establishment of international consensus for the definition and classification of all dystonias, diagnostic criteria for specific subtypes of dystonia, standardized evaluation strategies, development of clinimetrically sound measurement tools, and large multicenter studies that document the phenotypic heterogeneity and evolution of specific types of dystonia.
Early Rearing Conditions Affect Monoamine Metabolite Levels During Baseline and Periods of Social Separation Stress: A Non-human Primate Model (Macaca mulatta)
Authors: Wood Elizabeth K. , Gabrielle Natalia , Hunter Jacob , Skowbo Andrea N. , Schwandt Melanie L. , Lindell Stephen G. , Barr Christina S. , Suomi Stephen J. , Higley J. Dee
Published: April 2021

A variety of studies show that parental absence early in life leads to deleterious effects on the developing CNS. This is thought to be largely because evolutionary-dependent stimuli are necessary for the appropriate postnatal development of the young brain, an effect sometimes termed the “experience-expectant brain,” with parents providing the necessary input for normative synaptic connections to develop and appropriate neuronal survival to occur. Principal among CNS systems affected by parental input are the monoamine systems. In the present study,N= 434 rhesus monkeys (233 males, 201 females) were reared in one of two conditions: as mother-reared controls (MR;n= 269) or without adults with 24-h access to same-aged peers (PR;n= 165). When subjects were six-months-old, they underwent a separation paradigm involving 4, sequential, four-day social separations from their mothers or peers, with each separation followed by three-day reunions with their mothers or their peers. Prior to the separation paradigm, baseline cisternal CSF samples were obtained, as well as at the end of each the four social separations, and after final separation, during a recovery period. CSF was assayed for concentrations of monoamine metabolites and a blood sample was genotyped for the serotonin transporter (5-HTT) genotype. Replicating earlier landmark findings, PR subjects with thesallele exhibited lower baseline concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), when compared to PR subjects homozygous for theLallele. MR subjects were undifferentiated by genotype. PR subjects exhibited lower CSF 5-HIAA concentrations during baseline, but higher CSF 5-HIAA during social separations, when compared to MR subjects. There were rearing effects for the dopamine metabolite homovanillic acid (HVA) and for the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), with PR subjects showing higher HVA and lower MHPG when compared to MR subjects. These findings indicate that there are long-term deficits in the response of monoamines following early maternal absence. The results of this study confirm and extend earlier findings that early parental absence has deleterious consequences for the development of the monoamine systems, and that these consequences are modulated by the 5-HTT genotype.
Visual Perception and Visuomotor Reaction Speed Are Independent of the Individual Alpha Frequency
Authors: Hülsdünker Thorben , Mierau Andreas
Published: April 2021

While the resting-state individual alpha frequency (IAF) is related to the cognitive performance and temporal resolution of visual perception, it remains unclear how it affects the neural correlates of visual perception and reaction processes. This study aimed to unravel the relation between IAF, visual perception, and visuomotor reaction time. One hundred forty-eight (148) participants (28 non-athletes, 39 table tennis players, and 81 badminton players) investigated in three previous studies were considered. During a visuomotor reaction task, the visuomotor reaction time (VMRT) and EMG onset were determined. In addition, a 64-channel EEG system identified the N2, N2-r, and BA6 negativity potentials representing the visual and motor processes related to visuomotor reactions. Resting-state individual alpha frequency (IAF) in visual and motor regions was compared based on sport experience (athletes vs. non-athletes), discipline (badminton vs. table tennis), and reaction performance (fast vs. medium vs. slow reaction time). Further, the differences in the IAF were determined in relation to the speed of neural visual (high vs. medium vs. low N2/N2-r latency) and motor (high vs. medium vs. low BA6 negativity latency). Group comparisons did not reveal any difference in the IAF between athletes and non-athletes (p = 0.352, ηp2 = 0.02) or badminton and table tennis players (p = 0.221, ηp2 = 0.02). Similarly, classification based on the behavioral or neural performance indicators did not reveal any effects on the IAF (p ≥ 0.158, ηp2 ≤ 0.027). IAF was not correlated to any of the behavioral or neural parameters (r ≤ 0.10, p ≥ 0.221). In contrast to behavioral results on cognitive performance and visual temporal resolution, the resting state IAF seemed unrelated to the visual perception and visuomotor reaction speed in simple reaction tasks. Considering the previous results on the correlations between the IAF, cognitive abilities, and temporal sampling of visual information, the results suggest that a higher IAF may facilitate the amount and frequency but not the speed of information transfer.
Camptothecin Inhibits Neddylation to Activate the Protective Autophagy Through NF-κB/AMPK/mTOR/ULK1 Axis in Human Esophageal Cancer Cells
Authors: Heng Yongqing , Liang Yupei , Zhang Junqian , Li Lihui , Zhang Wenjuan , Jiang Yanyu , Wang Shiwen , Jia Lijun
Published: April 2021

The neddylation pathway is overactivated in esophageal cancer. Our previous studies indicated that inactivation of neddylation by the NAE inhibitor induced apoptosis and autophagy in cancer cells. Camptothecin (CPT), a well-known anticancer agent, could induce apoptosis and autophagy in cancer cells. However, whether CPT could affect the neddylation pathway and the molecular mechanisms of CPT-induced autophagy in esophageal cancer remains elusive. We found that CPT induced apoptosis and autophagy in esophageal cancer. Mechanistically, CPT inhibited the activity of neddylation and induced the accumulation of p-IkBa to block NF-κB pathway. Furthermore, CPT induced the generation of ROS to modulate the AMPK/mTOR/ULK1 axis to finally promote protective autophagy. In our study, we elucidate a novel mechanism of the NF-κB/AMPK/mTOR/ULK1 pathway in CPT-induced protective autophagy in esophageal cancer cells, which provides a sound rationale for combinational anti-ESCC therapy with CPT and inhibition AMPK/ULK1 pathway.
Safety and Efficacy of Degradable Starch Microspheres Transcatheter Arterial Chemoembolization (DSM-TACE) in the Downstaging of Intermediate-Stage Hepatocellular Carcinoma (HCC) in Patients With a Child-Pugh Score of 8-9
Authors: Minici Roberto , Ammendola Michele , Manti Francesco , Siciliano Maria Anna , Minici Marco , Komaei Iman , Currò Giuseppe , Laganà Domenico
Published: April 2021

According to the EASL Guidelines for the management of hepatocellular carcinoma, transcatheter arterial chemoembolization is the first-line treatment recommended for intermediate-stage HCC. Furthermore, it is widely accepted that patients beyond the Milan criteria can be considered for a liver transplant after successful downstaging to within the Milan criteria. Response to downstaging treatments significantly influences not just drop-outs, but also the rate of post-transplantation tumor recurrences. TACE with degradable starch microspheres represents an alternative to conventional TACE with lipiodol and TACE with drug-eluting beads, and it leads to transient arterial occlusion allowing lower activation of hypoxia-inducible factors and less release of vascular endothelial growth factor, a promoter of neoangiogenesis, tumor proliferation, and metastatic growth. In patients with intermediate-stage HCC and a Child-Pugh score of 8 or 9, life expectancy may be dominated by cirrhotic liver dysfunction, rather than by the tumor progression itself; hence, locoregional treatments might also be detrimental, precipitating liver dysfunction to an extent that survival is shortened rather than prolonged. Data on tolerability, toxicity, and effectiveness of DSM-TACE are limited but encouraging. Between January 2015 and October 2020, 50 consecutive patients with intermediate-stage hepatocellular carcinoma and a Child-Pugh score of 8/9, who had undergone DSM-TACE as the first-line treatment, were eligible for the study. A total of 142 DSM-TACEs were performed, with a mean number of 2.84 procedures per patient. The mean time-to-downstaging was 19.2 months, with six patients successfully downstaged. OS was about 100% at six months, 81.8% at 12 months, and 50% at 24 months. Twenty-two patients experienced adverse events after chemoembolization. The median OS and safety of DSM-TACE in this study are comparable with other published investigations in this field. Furthermore, 12% of patients were successfully downstaged. Hence, the results of the current investigation demonstrate that DSM-TACE is effective and safe in intermediate-stage HCC, achieving an interesting downstaging rate. Such data were observed in the population subset with a Child-Pugh score of 8 or 9, in which life expectancy may be determined by cirrhotic liver dysfunction, so the achievement of a balance between the safety and efficacy profile of the TACE treatment is crucial.
Influence of Intermittent Hypoxia/Hypercapnia on Atherosclerosis, Gut Microbiome, and Metabolome
Authors: Xue Jin , Allaband Celeste , Zhou Dan , Poulsen Orit , Martino Cameron , Jiang Lingjing , Tripathi Anupriya , Elijah Emmanuel , Dorrestein Pieter C. , Knight Rob , Zarrinpar Amir , Haddad Gabriel G.
Published: April 2021

Obstructive sleep apnea (OSA), a common sleep disorder characterized by intermittent hypoxia and hypercapnia (IHC), increases atherosclerosis risk. However, the contribution of intermittent hypoxia (IH) or intermittent hypercapnia (IC) in promoting atherosclerosis remains unclear. Since gut microbiota and metabolites have been implicated in atherosclerosis, we examined whether IH or IC alters the microbiome and metabolome to induce a pro-atherosclerotic state. Apolipoprotein E deficient mice (ApoE−/−), treated with IH or IC on a high-fat diet (HFD) for 10 weeks, were compared to Air controls. Atherosclerotic lesions were examined, gut microbiome was profiled using 16S rRNA gene amplicon sequencing and metabolome was assessed by untargeted mass spectrometry. In the aorta, IC-induced atherosclerosis was significantly greater than IH and Air controls (aorta, IC 11.1 ± 0.7% vs. IH 7.6 ± 0.4%, p < 0.05 vs. Air 8.1 ± 0.8%, p < 0.05). In the pulmonary artery (PA), however, IH, IC, and Air were significantly different from each other in atherosclerotic formation with the largest lesion observed under IH (PA, IH 40.9 ± 2.0% vs. IC 20.1 ± 2.6% vs. Air 12.2 ± 1.5%, p < 0.05). The most differentially abundant microbial families (p < 0.001) were Peptostreptococcaceae, Ruminococcaceae, and Erysipelotrichaceae. The most differentially abundant metabolites (p < 0.001) were tauro-β-muricholic acid, ursodeoxycholic acid, and lysophosphoethanolamine (18:0). We conclude that IH and IC (a) modulate atherosclerosis progression differently in distinct vascular beds with IC, unlike IH, facilitating atherosclerosis in both aorta and PA and (b) promote an atherosclerotic luminal gut environment that is more evident in IH than IC. We speculate that the resulting changes in the gut metabolome and microbiome interact differently with distinct vascular beds.
Neighbors, Drought, and Nitrogen Application Affect the Root Morphological Plasticity of Dalbergia odorifera
Authors: Xiang Li-Shan , Miao Ling-Feng , Yang Fan
Published: April 2021

In forest systems, neighbor-induced root morphological plasticity (RMP) is species specific and environment dependent. However, related studies on leguminous woody trees remain sparse. The objectives of this study were to evaluate the root morphological response of the leguminous woody Dalbergia odorifera T. Chen to different N-fixing niche neighbors under models of root system contact and isolation and to evaluate whether such response can be modified by drought or the application of nitrogen (N). The relationship between root morphology and the relative competitiveness of the whole D. odorifera plantlet was also assessed. D. odorifera plantlets from the woody Leguminosae family were used as target species and were grown with either identical N-fixing niche D. odorifera, the heterogeneous but con-leguminous Delonix regia, or the non-leguminous Swietenia mahagoni. All plants were grown under two water conditions (100% and 30% field capacity) and two N treatments (no N application and N application). Two planting models (root system contact in Experiment 1, root system isolation in Experiment 2) were applied to neighboring plantlets. The RMP of D. odorifera was assessed based on root morphology, root system classification, root nodules, and RMP-related indices. The growth of D. odorifera was estimated based on the relative growth ratio, net assimilation rate, and leaf N content. The relative competitiveness of the whole D. odorifera plantlet was evaluated through relative yield. The results of Experiment 1 showed that D. odorifera had different RMP responses to a different N-fixing niche neighbor with root system contact. The RMP of D. odorifera was promoted by a different N-fixing niche neighbor under conditions of drought or N deficiency. Drought improved the RMP of D. odorifera exposed to a different N-fixing niche neighbor. N application converted the promoting effect of D. regia on RMP to an inhibitory effect under well-watered conditions. Experiment 2 showed that belowground interaction with a different N-fixing niche neighbor may be the only way to influence RMP, as effects of aboveground interaction were negligible. Finally, correlation analysis showed that neighbor-induced RMP might predict the relative competitiveness of the whole D. odorifera plantlet under conditions of drought or N deficiency. These findings highlight the influences of neighbors, drought, and N application on the RMP of D. odorifera and contribute to understanding neighbor-induced dynamic changes in the root traits of leguminous woody species in forest systems in the context of climate change.
Auxin Response Factor 2 (ARF2), ARF3, and ARF4 Mediate Both Lateral Root and Nitrogen Fixing Nodule Development in Medicago truncatula
Authors: Kirolinko Cristina , Hobecker Karen , Wen Jiangqi , Mysore Kirankumar S. , Niebel Andreas , Blanco Flavio Antonio , Zanetti María Eugenia
Published: April 2021

Auxin Response Factors (ARFs) constitute a large family of transcription factors that mediate auxin-regulated developmental programs in plants.ARF2,ARF3, andARF4are post-transcriptionally regulated by the microRNA390 (miR390)/trans-acting small interference RNA 3 (TAS3) module through the action ofTAS3-derivedtrans-acting small interfering RNAs (ta-siRNA). We have previously reported that constitutive activation of the miR390/TAS3pathway promotes elongation of lateral roots but impairs nodule organogenesis and infection by rhizobia during the nitrogen-fixing symbiosis established betweenMedicago truncatulaand its partnerSinorhizobium meliloti. However, the involvement of the targets of the miR390/TAS3pathway, i.e.,MtARF2, MtARF3, MtARF4a, andMtARF4b, in root development and establishment of the nitrogen-fixing symbiosis remained unexplored. Here, promoter:reporter fusions showed that expression of bothMtARF3andMtARF4awas associated with lateral root development; however, only theMtARF4apromoter was active in developing nodules. In addition, up-regulation ofMtARF2,MtARF3, andMtARF4a/bin response to rhizobia depends on Nod Factor perception. We provide evidence that simultaneous knockdown ofMtARF2, MtARF3, MtARF4a, andMtARF4bor mutation inMtARF4aimpaired nodule formation, and reduced initiation and progression of infection events. Silencing ofMtARF2, MtARF3, MtARF4a, andMtARF4baltered mRNA levels of the early nodulation gene nodulation signaling pathway 2 (MtNSP2). In addition, roots with reduced levels ofMtARF2, MtARF3, MtARF4a, andMtARF4b, as well asarf4amutant plants exhibited altered root architecture, causing a reduction in primary and lateral root length, but increasing lateral root density. Taken together, our results suggest that these ARF members are common key players of the morphogenetic programs that control root development and the formation of nitrogen-fixing nodules.
Patterns of Contagious Yawning and Itching Differ Amongst Adults With Autistic Traits vs. Psychopathic Traits
Authors: Helt Molly S. , Sorensen Taylor M. , Scheub Rachel J. , Nakhle Mira B. , Luddy Anna C.
Published: April 2021

Both individuals with diagnosed with Autism Spectrum Disorder (ASD) and individuals high in psychopathic traits show reduced susceptibility to contagious yawning; that is, yawning after seeing or hearing another person yawn. Yet it is unclear whether the same underlying processes (e.g., reduced eye gaze) are responsible for the relationship between reduced contagion and these very different types of clinical traits. College Students (n = 97) watched videos of individuals yawning or scratching (a form of contagion not reliant on eye gaze for transmission) while their eye movements were tracked. They completed the Interpersonal Reactivity Index (IRI), the Autism-Spectrum Quotient (AQ), the Psychopathy Personality Inventory-Revised (PPI-R), and the Adolescent and Adult Sensory Processing Disorder Checklist. Both psychopathic traits and autistic traits showed an inverse relationship to contagious yawning, consistent with previous research. However, the relationship between autistic (but not psychopathic) traits and contagious yawning was moderated by eye gaze. Furthermore, participants high in autistic traits showed typical levels of contagious itching whereas adults high in psychopathic traits showed diminished itch contagion. Finally, only psychopathic traits were associated with lower overall levels of empathy. The findings imply that the underlying processes contributing to the disruptions in contagious yawning amongst individuals high in autistic vs. psychopathic traits are distinct. In contrast to adults high in psychopathic traits, diminished contagion may appear amongst people with high levels of autistic traits secondary to diminished attention to the faces of others, and in the absence of a background deficit in emotional empathy.
Are Self-Efficacy Gains of University Students in Adapted Physical Activity Influenced by Online Teaching Derived From the COVID-19 Pandemic?
Authors: Roldan Alba , Reina Raul
Published: April 2021

Due to the lockdown caused by the COVID-19 pandemic, e-learning suddenly spread to different levels of education, including university. In Spain, students of sports sciences are prepared during a 4-year study program to work in different areas (including physical education) and with different populations (including people with disabilities). The aims of this study were (1) to assess the effect of pandemic-driven online teaching on self-efficacy (SE) for the inclusion of people with disabilities in a group of university students enrolled in a compulsory course on adapted physical activity (APA); (2) compare the gains from SE before and after the APA course with a sample of students who followed the same course before the pandemic; and (3) explore the influence on SE scores according to three demographic variables: gender, previous SE training, and previous experience with people with disabilities. The study involved a sample of 124 university students (22.1 ± 2.6 years), distributed into two groups: prepandemic (n = 86) and pandemic (n = 38). They voluntarily completed the Spanish version of the Scale of Self-Efficacy of Physical Education Teachers of Physical Education toward Children with Disabilities, obtaining pre- and postcourse measurements. Due to the sudden lockdown, two-thirds of the pandemic course was taught online, and changes in the teaching strategies and tasks had to be made. Similar gains were obtained in both groups for the three subscales of the SE scale (p < 0.001, large effect sizes): intellectual, physical, and visual disability. No significant differences were found for comparisons between groups and the interaction effect of the course taught, nor for the three demographic co-variables. This study shows that teaching strategies that encourage student participation and reflections on learning increase student SE, regardless of the teaching format (i.e., face-to-face vs. online teaching). Moreover, the gains in SE are invariable to demographic co-variables.
Looking Back to Move Forward: Reflections on the Strengths and Challenges of the COVID-19 UK Mental Health Research Response
Authors: Demkowicz Ola , Panayiotou Margarita , Parsons Sam , Feltham Amy , Arseneault Louise , Ingram Beth , Patalay Praveetha , Edge Dawn , Pierce Matthias , Creswell Cathy , Victor Christina , O'Connor Rory C. , Qualter Pamela
Published: April 2021

In the face of the COVID-19 pandemic, the swift response of mental health research funders and institutions, service providers, and academics enabled progress toward understanding the mental health consequences. Nevertheless, there remains an urgent need to understand the true extent of the short- and long-term effects of the COVID-19 pandemic on mental health, necessitating ongoing research. Although the speed with which mental health researchers have mobilized to respond to the pandemic so far is to be commended, there are valid concerns as to whether speed may have compromised the quality of our work. As the pandemic continues to evolve, we must take time to reflect on our initial research response and collectively consider how we can use this to strengthen ensuing COVID-19 mental health research and our response to future crises. Here, we offer our reflections as members of the UK mental health research community to discuss the continuing progress and persisting challenges of our COVID-19 response, which we hope can encourage reflection and discussion among the wider research community. We conclude that (1) Fragmentation in our infrastructure has challenged the efficient, effective and equitable deployment of resources, (2) In responding quickly, we may have overlooked the role of experts by experience, (3) Robust and open methods may have been compromised by speedy responses, and (4) This pandemic may exacerbate existing issues of inequality in our workforce.
Parents Are Stressed! Patterns of Parent Stress Across COVID-19
Authors: Adams Elizabeth L. , Smith Danyel , Caccavale Laura J. , Bean Melanie K.
Published: April 2021

Background: The Coronavirus Disease 2019 (COVID-19) pandemic has caused numerous unexpected challenges for many families, and these long-lasting demands likely contribute to higher stress for parents. The aim of this study was to describe changes in parent stress longitudinally from before (retrospective) to two timepoints during COVID-19. Stressors that influenced parenting and strategies to manage parenting difficulties at each timepoint during COVID-19 are also described.

Methods: Parents (N = 433; 95% female) in the US with >1 child aged 5–18 years completed an online survey in May 2020 (T1; at the peak of stay-at-home mandates) and in September 2020 (T2; children's return to school). Surveys included the 10-item Perceived Stress Scale (PSS) and questions on parenting-specific stress, stressors that influenced parenting, and strategies to manage parenting difficulties during COVID-19. Retrospective report of pre-COVID-19 stress was assessed at T1; current stress was assessed at T1 and T2. Repeated measures analysis of variance examined changes in stress over time.

Results: Parent's stress increased from before COVID-19 to T1 (PSS score: 16.3 ± 5.7 to 22.0 ± 6.4, respectively; p < 0.01), and decreased by T2 (19.2 ± 6.0), but remained elevated above pre-COVID-19 values (p < 0.01). Most parents (71.1%) reported an increase parenting-specific stress from before COVID-19 to T1, which continued to increase for 55% of parents at T2. Common stressors that impacted parenting during COVID-19 were changes in children's routines, worry about COVID-19, and online schooling demands. Common strategies parents used to manage parenting difficulties included doing family activities together, keeping in touch with family/friends virtually, and keeping children on daily routines.

Conclusions: Parent stress increased substantially during COVID-19 and has not returned to pre-COVID-19 levels, suggesting the need for enhanced mental health resources and supports. Public health interventions should address parenting-specific stressors and effective strategies for managing parenting difficulties to mitigate their deleterious impact.
The Influencing Factors of Participation in Online Timebank Nursing for Community Elderly in Beijing, China
Authors: Wu Yan , Ding Yanran , Hu Cong , Wang Lei
Published: April 2021

This study uses the logit model through questionnaire data of Beijing in 2019 to investigate the participation willingness of online timebank elderly care, especially to discover different influencing factors on the participation willingness between the youth group and the elderly group. We find that: First, the health status of elderly people and the number of elder families of young people have significant positive impacts on their willingness to participate in online timebank. Second, the experience of participating in voluntary activities has a significant positive effect and it has a far greater impact in the young group than that in the elderly group. Third, the more the free time, the higher the participation willingness in the young group, but it is the opposite in the elderly group. Fourth, the years of education and party member have significant promoting effects on the participation willingness in both groups. Such heterogeneous influencing factors can help develop online timebank nursing for dealing with the increasingly serious population aging problem in China and also other developing countries.
Computed Tomography Radiomics Kinetics as Early Imaging Correlates of Osteoradionecrosis in Oropharyngeal Cancer Patients
Authors: Barua Souptik , Elhalawani Hesham , Volpe Stefania , Al Feghali Karine A. , Yang Pei , Ng Sweet Ping , Elgohari Baher , Granberry Robin C. , Mackin Dennis S. , Gunn G. Brandon , Hutcheson Katherine A. , Chambers Mark S. , Court Laurence E. , Mohamed Abdallah S. R. , Fuller Clifton D. , Lai Stephen Y. , Rao Arvind
Published: April 2021

Osteoradionecrosis (ORN) is a major side-effect of radiation therapy in oropharyngeal cancer (OPC) patients. In this study, we demonstrate that early prediction of ORN is possible by analyzing the temporal evolution of mandibular subvolumes receiving radiation. For our analysis, we use computed tomography (CT) scans from 21 OPC patients treated with Intensity Modulated Radiation Therapy (IMRT) with subsequent radiographically-proven ≥ grade II ORN, at three different time points: pre-IMRT, 2-months, and 6-months post-IMRT. For each patient, radiomic features were extracted from a mandibular subvolume that developed ORN and a control subvolume that received the same dose but did not develop ORN. We used a Multivariate Functional Principal Component Analysis (MFPCA) approach to characterize the temporal trajectories of these features. The proposed MFPCA model performs the best at classifying ORN vs. Control subvolumes with an area under curve (AUC) = 0.74 [95% confidence interval (C.I.): 0.61–0.90], significantly outperforming existing approaches such as a pre-IMRT features model or a delta model based on changes at intermediate time points, i.e., at 2- and 6-month follow-up. This suggests that temporal trajectories of radiomics features derived from sequential pre- and post-RT CT scans can provide markers that are correlates of RT-induced mandibular injury, and consequently aid in earlier management of ORN.