bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of Multimodal Brain Connectomics in Patients With Schizophrenia and the Unaffected First-Degree Relatives
Authors: Lin Xiao , Li WeiKai , Dong Guangheng , Wang Qiandong , Sun Hongqiang , Shi Jie , Fan Yong , Li Peng , Lu Lin
Published: February 2021

Objective

Increasing pieces of evidence suggest that abnormal brain connectivity plays an important role in the pathophysiology of schizophrenia. As an essential strategy in psychiatric neuroscience, the research of brain connectivity-based neuroimaging biomarkers has gained increasing attention. Most of previous studies focused on a single modality of the brain connectomics. Multimodal evidence will not only depict the full profile of the brain abnormalities of patients but also contribute to our understanding of the neurobiological mechanisms of this disease.

Methods

In the current study, 99 schizophrenia patients, 69 sex- and education-matched healthy controls, and 42 unaffected first-degree relatives of patients were recruited and scanned. The brain was parcellated into 246 regions and multimodal network analyses were used to construct brain connectivity networks for each participant.

Results

Using the brain connectomics from three modalities as the features, the multi-kernel support vector machine method yielded high discrimination accuracies for schizophrenia patients (94.86%) and for the first-degree relatives (95.33%) from healthy controls. Using an independent sample (49 patients and 122 healthy controls), we tested the model and achieved a classification accuracy of 64.57%. The convergent pattern within the basal ganglia and thalamus–cortex circuit exhibited high discriminative power during classification. Furthermore, substantial overlaps of the brain connectivity abnormality between patients and the unaffected first-degree relatives were observed compared to healthy controls.

Conclusion

The current findings demonstrate that decreased functional communications between the basal ganglia, thalamus, and the prefrontal cortex could serve as biomarkers and endophenotypes for schizophrenia.
Withaferin A and Ovarian Cancer Antagonistically Regulate Skeletal Muscle Mass
Authors: Straughn Alex R. , Kelm Natia Q. , Kakar Sham S.
Published: February 2021

Cachexia is a complex wasting syndrome that overwhelmingly affects the majority of late-stage cancer patients. Additionally, there are currently no efficacious therapeutic agents to treat the muscle atrophy induced by the cancer. While several preclinical studies have investigated the molecular signals orchestrating cachexia, very little information exists pertaining to ovarian cancer and the associated cachexia. Work from our lab has recently demonstrated that the steroidal lactone Withaferin A (WFA) is capable of attenuating the atrophying effects of ovarian cancer in a preclinical mouse model. However, it remained to be determined whether WFA’s effect was in response to its anti-tumorigenic properties, or if it was capable of targeting skeletal muscle directly. The purpose of this study was to uncover whether WFA was capable of regulating muscle mass under tumor-free and tumor-bearing conditions. Treatment with WFA led to an improvement in functional muscle strength and mass under tumor-bearing and naïve conditions. WFA and ovarian cancer were observed to act antagonistically upon critical skeletal muscle regulatory systems, notably myogenic progenitors and proteolytic degradation pathways. Our results demonstrated for the first time that, while WFA has anti-tumorigenic properties, it also exerts hypertrophying effects on skeletal muscle mass, suggesting that it could be an anti-cachectic agent in the settings of ovarian cancer.
Activity-Based Probes to Utilize the Proteolytic Activity of Cathepsin G in Biological Samples
Authors: Burster Timo , Gärtner Fabian , Knippschild Uwe , Zhanapiya Anuar
Published: February 2021

Neutrophils, migrating to the site of infection, are able to release serine proteases after being activated. These serine proteases comprise cathepsin G (CatG), neutrophil elastase protease 3 (PR3), and neutrophil serine protease 4 (NSP4). A disadvantage of the uncontrolled proteolytic activity of proteases is the outcome of various human diseases, including cardiovascular diseases, thrombosis, and autoimmune diseases. Activity-based probes (ABPs) are used to determine the proteolytic activity of proteases, containing a set of three essential elements: Warhead, recognition sequence, and the reporter tag for detection of the covalent enzyme activity–based probe complex. Here, we summarize the latest findings of ABP-mediated detection of proteases in both locations intracellularly and on the cell surface of cells, thereby focusing on CatG. Particularly, application of ABPs in regular flow cytometry, imaging flow cytometry, and mass cytometry by time-of-flight (CyTOF) approaches is advantageous when distinguishing between immune cell subsets. ABPs can be included in a vast panel of markers to detect proteolytic activity and determine whether proteases are properly regulated during medication. The use of ABPs as a detection tool opens the possibility to interfere with uncontrolled proteolytic activity of proteases by employing protease inhibitors.
Gut Microbiota Signatures in Gestational Anemia
Authors: Long Yan , Liang Fang , Guo Ruochun , Zhu Chunyan , Zhao Xueqin , Wang Xifan , Liu Fei , Jiang Min , Liang Qihua , Zeng Shanshui , Han Mengru , Qin Junjie , Li Shenghui , Li Shaochuan , Yang Hongling
Published: February 2021

Gestational diseases are associated with altered intestinal microbiota in pregnant women. Characterizing the gut microbiota of gestational anemia (GA) may describe a novel role of gut microbial abnormality in GA. In this study, we investigated differences in gut microbiota between GA patients and healthy pregnant women from the first trimester (n = 24 vs. 54) and the third trimester (n = 30 vs. 56) based on the 16S rRNA gene sequencing method. No statistically significant differences in α-diversity were identified between GA patients and controls in the first trimester of pregnancy, whereas the Shannon index and observed OTUs were significantly lower in GA patients than in healthy controls in the third trimester. Distance-based redundancy analysis revealed striking differences in microbial communities in the third trimester between GA patients and controls. Four genera were significantly different in relative abundance between GA patients and healthy controls, while 12 genera differentiated significantly between GA patients and healthy controls in the third trimester. At the operational taxonomic unit (OTU) level, 17 OTUs and 30 OTUs were identified to be different between GA patients and healthy controls in the first and third trimesters, respectively. Changes in gut microbial composition of GA patients suggest a potential relation with GA, and provide insights into the prediction and intervention of gestational anemia.
Functional Mapping of AGO-Associated Zika Virus-Derived Small Interfering RNAs in Neural Stem Cells
Authors: Zeng Jianxiong , Luo Zhifei , Dong Shupeng , Xie Xiaochun , Liang Xinyan , Yan Youzhen , Liang Qiming , Zhao Zhen
Published: February 2021

Viral interfering RNA (viRNA) has been identified from several viral genomes via directly deep RNA sequencing of the virus-infected cells, including zika virus (ZIKV). Once produced by endoribonuclease Dicer, viRNAs are loaded onto the Argonaute (AGO) family proteins of the RNA-induced silencing complexes (RISCs) to pair with their RNA targets and initiate the cleavage of target genes. However, the identities of functional ZIKV viRNAs and their viral RNA targets remain largely unknown. Our recent study has shown that ZIKV capsid protein interacted with Dicer and antagonized its endoribonuclease activity, which requires its histidine residue at the 41st amino acid. Accordingly, the engineered ZIKV-H41R loss-of-function (LOF) mutant virus no longer suppresses Dicer enzymatic activity nor inhibits miRNA biogenesis in NSCs. By combining AGO-associated RNA sequencing, deep sequencing analysis in ZIKV-infected human neural stem cells (NSCs), and miRanda target scanning, we defined 29 ZIKV derived viRNA profiles in NSCs, and established a complex interaction network between the viRNAs and their viral targets. More importantly, we found that viRNA production from the ZIKV mRNA is dependent on Dicer function and is a limiting factor for ZIKV virulence in NSCs. As a result, much higher levels of viRNAs generated from the ZIKV-H41R virus-infected NSCs. Therefore, our mapping of viRNAs to their RNA targets paves a way to further investigate how viRNAs play the role in anti-viral mechanisms, and perhaps other unknown biological functions.
Influence of Gender in Advanced Heart Failure Therapies and Outcome Following Transplantation
Authors: García-Cosío María Dolores , González-Vilchez Francisco , López-Vilella Raquel , Barge-Caballero Eduardo , Gómez Bueno Manuel , Martínez-Selles Manuel , María Arizón Jose , Rangel Sousa Diego , González-Costello José , Mirabet Sonia , Pérez-Villa Félix , Molina Beatriz Díaz , Rábago Gregorio , Portolés Ocampo Ana , de la Fuente Galán Luis , Garrido Iris , Delgado Juan F.
Published: February 2021

Biological differences between males and females change the course of different diseases and affect therapeutic measures' responses. Heart failure is not an exception to these differences. Women account for a minority of patients on the waiting list for heart transplantation or other advanced heart failure therapies. The reason for this under-representation is unknown. Men have a worse cardiovascular risk profile and suffer more often from ischemic heart disease. Conversely, transplanted women are younger and more frequently have non-ischemic cardiac disorders. Women's poorer survival on the waiting list for heart transplantation has been previously described, but this trend has been corrected in recent years. The use of ventricular assist devices in women is progressively increasing, with comparable results than in men. The indication rate for a heart transplant in women (number of women on the waiting list for millions of habitants) has remained unchanged over the past 25 years. Long-term results of heart transplants are equal for both men and women. We have analyzed the data of a national registry of heart transplant patients to look for possible future directions for a more in-depth study of sex differences in this area. We have analyzed 1-year outcomes of heart transplant recipients. We found similar results in men and women and no sex-related interactions with any of the factors related to survival or differences in death causes between men and women. We should keep trying to approach sex differences in prospective studies to confirm if they deserve a different approach, which is not supported by current evidence.
The Succession of Upper Eocene- Upper Miocene Limestone Growth and Corresponding Tectonic Events in Luconia Shelf, Sarawak, Malaysia
Authors: Jamaludin Siti Nur Fathiyah , Sautter Benjamin , Pubellier Manuel , Beg Mirza Arshad
Published: February 2021

Using high quality regional seismic lines, we evidence major structures resulting from successive phases of tectonic events that affected the Luconia shelf from the Upper Cretaceous to Pliocene. Each tectonic event (Classified as Event 1–Event 3) is associated with different episodes of limestone growth in Luconia Province. The successive limestone growths are used as markers in constraining the timing and style of tectonic deformation. The poly-stage closure of the Proto South China Sea (PSCS) from the Upper Cretaceous to Lower Miocene led to the formation of compressional structures in its southern portion (South PSCS) providing elevated topography for the growth of the oldest limestone found in this area during the Upper Eocene to Lower Oligocene (Event 1). Based on contrasting seismic reflectors, morphology, and depositional patterns, the offshore Upper Eocene-Lower Oligocene limestone growth is correlated to the onshore Engkabang-Karap limestone. The southern part of Luconia was subjected to a continuous compression until the Lower Miocene at a time where the northern side of the Luconia Province was experiencing subsidence due to the rifting of the South China Sea (Event 2). The compression in the south generated elevated anticlines, triggering the growth of the Upper Oligocene to Lower Miocene limestone. By the end of the rifting event in the Lower Miocene, tectonic quiescence had enabled widespread carbonate growth in Luconia from the Middle to Upper Miocene. Regional compression due to the major uplift of Borneo hinterland (Event 3) triggered paramount clastic influx (gravity tectonics) to the offshore perturbating the limestone reef growth in Luconia. The impact of these interrelated shortening and stretching phases led to major crustal thickness variations and a prominent tilt of the Luconia platform that may highlight intricate feedbacks at the transition from compression to extension. While the southern side of the Luconia’s crustal fragment was anchored into Borneo hinterland, crustal extension in the northern region of Luconia led to a hyper-stretched crust characterized by low angle detachment faults and highly rotated blocks rising the mantle to its shallowest.
Tephrostratigraphy and Magma Evolution Based on Combined Zircon Trace Element and U-Pb Age Data: Fingerprinting Miocene Silicic Pyroclastic Rocks in the Pannonian Basin
Authors: Lukács Réka , Guillong Marcel , Bachmann Olivier , Fodor László , Harangi Szabolcs
Published: February 2021

We present a novel approach to use zircon as a correlation tool as well as a monitor for magma reservoir processes in silicic volcanic systems. Fingerprinting eruption products based on trace element content and U-Pb dates of zircon offers a promising, previously underestimated tephra correlation perspective, particularly in cases where the main minerals and glass are altered. Using LA-ICP-MS analyses, a rapid and cost-effective method, this study presents U-Pb dates and trace element concentration data of more than 950 zircon crystals from scattered occurrences of early to mid-Miocene silicic ignimbrites in the northern Pannonian Basin, eastern-central Europe. This magmatic phase produced >4000 km3of erupted material, which provide unique stratigraphic marker horizons in central and southern Europe. The newly determined zircon U-Pb eruption ages for the distal pyroclastic deposits are between 17.5 and 14.3 Ma, comparable with the previously published ages of the main eruptive events. Multivariate discriminant analysis of selected trace element concentrations in zircon proved to be useful to distinguish the main volcanic units and to correlate the previously ambiguously categorized pyroclastic deposits with them. Using the zircon trace element content together with published glass data from crystal-poor ignimbrites, we determined the zircon/melt partition coefficients. The obtained values of the distinct eruption units are very similar and comparable to published data for silicic volcanic systems. This suggests that zircon/melt partition coefficients in calc-alkaline dacitic to rhyolitic systems are not significantly influenced by the melt composition at >70 wt% SiO2at near solidus temperature. The partition coefficients and zircon trace element data were used to calculate the equilibrium melt composition, which characterizes the eruption products even where glass is thoroughly altered or missing. Hence, our results provide important proxies for tephrostratigraphy in addition to yielding insights into the complex processes of silicic magma reservoirs.
The North American Spring Coldness Response to the Persistent Weak Stratospheric Vortex Induced by Extreme El Niño Events
Authors: Zhou Xin , Chen Quanliang , Li Yang , Yang Yawei , Zhang Shaobo , Zhao Yong , Qi Yulei , Zhou Jingtao
Published: February 2021

The stratospheric pathway is a major driver of El Niño–Southern Oscillation (ENSO) impacts on mid-latitude tropospheric circulation and winter weather. The weak vortex induced by El Niño conditions has been shown to increase the risk of cold spells, especially over Eurasia, but its role for North American winters is less clear. This study involved idealized experiments with the Whole Atmosphere Community Climate Model to examine how the weak winter vortex induced by extreme El Niño events is linked to North American coldness in spring. Contrary to the expected mid-latitude cooling associated with a weak vortex, extreme El Niño events do not lead to North American cooling overall, with daily cold extremes actually decreasing, especially in Canada. The expected cooling is absent in most of North America because of the advection of warmer air masses guided by an enhanced ridge over Canada and a trough over the Aleutian Peninsula. This pattern persists in spring as a result of the trapping of stationary waves from the polar stratosphere and troposphere, implying that the stratospheric influence on North America is sensitive to regional downward wave activities.
An Automatic System for Continuous Monitoring and Sampling of Groundwater Geochemistry in Earthquake-Prone Regions of SW Taiwan
Authors: Fu Ching-Chou , Lai Chun-Wei , Yang Tsanyao Frank , Hilton David R. , Chen Cheng-Hong , Walia Vivek , Kumar Arvind , Lee Lou-Chuang
Published: February 2021

Previous studies have revealed that gas compositions of fluid samples collected from southwestern Taiwan, where many hot springs and mud volcanoes are distributed along with tectonic structures, show significant variation before and after some disaster seismic events. Such variations, including radon activity, CH4/CO2, and 3He/4He ratios of gas compositions, are considered precursors of earthquakes in this area. An automatic system for continuous on-line gas monitoring and groundwater sampling was established at Yun-Shui (YS), where an artesian well located at an active fault zone in SW Taiwan, to validate the relationship between fluid compositions and seismicity. It is equipped with a quadrupole mass spectrometer (QMS) and a radon detector for in-situ measurement of the dissolved gas composition. Variations of dissolved gas compositions are transmitted to the laboratory through the internet. Furthermore, a syringe pump apparatus for the retrieval and temporal analysis of helium (SPARTAH) is also installed for off-line laboratory analysis for obtaining the detailed time-series records of helium, hydrogen, oxygen, and dissolved inorganic carbon (DIC) isotopic compositions as well as dissolved inorganic carbon and chloride concentration of water samples at this station. After continuous monitoring for several months, two substantial anomalies of multiparameter were observed prior to the significant earthquakes. This automated system has been demonstrated to be feasible for long-term continuous seismo-geochemical research in this area.
Comparison of Social Validity Ratings With the Effects of a Video-Feedback Intervention for Communication Partners of Individuals With Deafblindness
Authors: Damen Saskia , Schuengel Carlo , Ruijssenaars Wied , Janssen Marleen J.
Published: February 2021

The parents, teachers, and professional caregivers of individuals with disabilities may benefit from interventions to enhance their educational skills. In previous studies, positive effects were observed of a video-feedback intervention for caregivers (i.e. parents, teachers, and professional caregivers) on their communication with an individual with congenital deafblindness. The intervention they received, was the High-Quality Communication (HQC) intervention. The aim of the current study was to gain insight into the perceived relevance, feasibility, and effectiveness (i.e., social validity) of the HQC-intervention according to these caregivers, and the correspondence between the social validity ratings and the observational effects of the HQC-intervention. Responses on the Social Validity Scale from 25 caregivers who participated in the High-Quality Communication (HQC) intervention revealed that they considered the HQC intervention to be a relevant, feasible, and effective intervention. Comparing the caregiver ratings with observational effects of the HQC intervention at the individual case level, we found no association between the observed effectiveness of this intervention and caregivers’ opinions about its relevance, feasibility and effectiveness. There was however, an association between the rated feasibility and effectiveness, which suggests that the perceived success of the intervention was influenced by caregivers’ experienced competency in supporting the communication of individuals with CDB. The combination of observational and social validity data enabled a critical analysis of the clinical value of the HQC intervention. We recommend that future studies use multiple data source for social validity assessment.
Impact of COVID-19 on Educational Services in Canadian Children With Attention-Deficit/Hyperactivity Disorder
Authors: Hai Tasmia , Swansburg Rose , MacMaster Frank P. , Lemay Jean-François
Published: February 2021

The COVID-19 pandemic led to school closures and a rapid transition to online classes. However, little is known about the impact of online learning in Canadian children with Attention-Deficit/Hyperactivity Disorder (ADHD). An online survey created on Qualtrics was distributed to families across Canada. Data collection was conducted over a total of five weeks in May and June 2020. We reviewed 587 surveys (4% margin of error using a 95% confidence interval) completed by caregivers/parents of children with ADHD (mean child age 10.14 years, SD = 3.06). Survey questions focused on hours of schoolwork completed and whether the learning needs of children with ADHD were met during school closures. Results indicated 90% of children with ADHD received web-based learning during the pandemic. Parents (41%) reported < 5 h of schoolwork per week, and 35% indicated between 5 to 10 h. Of the parents who said their child with ADHD had a modified curriculum (68%), 40% reported receiving educational materials that met their learning expectations during online classes. Parents (59%) reported that their child found it “very challenging” adjusting to online classes. The results indicated that children with ADHD faced significant challenges in adapting to online learning during the pandemic. Binary logistic regression indicated significant associations between depression severity, difficulties with starting and managing tasks and challenges adjusting to online learning. Long-term consequences of these challenges will need to be determined to ensure children with ADHD are able to meet their academic expectations.
Long-Term Outcomes and Prognoses of Elderly Patients (≥65-Years-Old) With Distant Metastases From Well-Differentiated Thyroid Cancer During Radioiodine Therapy and Follow-Up
Authors: Qiu Zhong-Ling , Shen Chen-Tian , Sun Zhen-Kui , Song Hong-Jun , Xi Chuang , Zhang Guo-Qiang , Wang Yang , Luo Quan-Yong
Published: February 2021

Objective

The objective of this study was to investigate the clinicopathological characteristics, long-term outcomes, and prognostic factors of elderly patients with distant metastases at initial diagnosis from well-differentiated thyroid cancer (WDTC) during radioactive iodine (131I) treatment and follow-up.

Methods

A retrospective review of medical records identified 183 elderly patients with DTC who underwent 131I treatment at our institution between 2006 and 2019.

Results

In total, 57 elderly WDTC patients with distant metastases were enrolled in this study. After 131I treatment, 32 (56.14%) patients had 131I avidity and 25 (43.86%) had non-131I avidity; 35 (61.40%) cases were classified as radioiodine refractory (RR)-WDTC and 22 (38.60%) as non-RR-WDTC. At the end of follow-up, 25 (43.86%) patients had died and 32 (56.14%) were alive. The 5- and 10-year overall survival (OS) rates were 71.50% and 30.49%, respectively, while the 5- and 10-year disease-specific survival (DSS) rates were 76.89% and 48.71%, respectively. Multivariate analyses showed that gross extrathyroidal extension and RR-DTC were independent prognostic factors for poor OS (P=0.04 and P=0.03, respectively), while gross extrathyroidal extension, extrapulmonary distant metastases, and RR-WDTC were independent prognostic factors for poor DSS at the end of follow-up (P=0.02, P=0.03, and P=0.02, respectively).

Conclusions

WDTC with distant metastases at initial diagnosis accounted for 31.15% of all elderly patients with DTC. Gross extrathyroidal extension and RR-DTC were the major factors associated with poor OS; gross extrathyroidal extension, extrapulmonary distant metastases, and RR-DTC were independent prognostic factors for poor DSS in elderly DTC patients with distant metastases.
Iron Deficiency, a Risk Factor of Thyroid Disorders in Reproductive-Age and Pregnant Women: A Systematic Review and Meta-Analysis
Authors: Luo Jingyi , Wang Xiaoxia , Yuan Li , Guo Lixin
Published: February 2021

Background

Iron deficiency (ID) is concerned as the most common nutritional deficiency worldwide. The effects of ID on thyroid function and autoimmunity in pregnant women and reproductive-age women are controversial. The aim of the current study was to summarize the evidences and evaluate the relationship between ID and thyroid disorders.

Methods

In this systematic review and meta-analysis, studies published on the Cochrane, Embase, Medline, and PubMed databases by October 2020 were searched. A total of 636 studies which discussed the correlation between ID and thyroid disorders were eligible in the initial search. Pooled mean differences (MD) and 95% confidence intervals (CI) were calculated for the assessment of thyrotropin (TSH) and free thyroxine (FT4) levels. Combined odd ratios (OR) and 95% CI were calculated for the assessment of the prevalence of overt and subclinical hypothyroidism, positive thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb).

Results

For women of reproductive age, ID could significantly increase the risk of positive TPOAb (OR: 1.89; 95% CI: 1.17, 3.06:P= 0.01) and both positive TPOAb and TgAb (OR: 1.48; 95% CI: 1.03, 2.11:P= 0.03). The meta-analysis of pregnant women showed that pregnant women with ID had increased serum TSH levels (MD: 0.12; 95% CI: 0.07, 0.17; P < 0.00001) and decreased FT4 levels (MD: −0.73; 95% CI: −1.04, −0.41; P < 0.00001). Meanwhile, the prevalence of overt (OR: 1.60; 95% CI: 1.17, 2.19; P = 0.004) and subclinical (OR: 1.37; 95% CI: 1.13, 1.66; P = 0.001) hypothyroidism in pregnant women with ID was significantly increased.

Conclusions

ID may adversely affect thyroid function and autoimmunity of pregnant and reproductive-age women and it is very necessary for monitoring iron nutritional status and early treatment of ID for them.
Study of Flow and Heat Transfer Characteristics of Lead-Based Liquid Metals in a Turbulent Tube Flow and the Impacts of Roughness
Authors: Shen Yaou , Peng Shinian , Yan Mingyu , Zhang Yu , Deng Jian , Yu Hongxing , Huang Daishun , Li Zhongchun
Published: February 2021

Lead-based liquid metals (LLMs) such as lead–bismuth eutectic (LBE) and lead, are currently the most interesting candidate coolants for fast reactors because of their excellent physical properties, which can improve safety and reduce costs. However, in comparison to other liquid metals, previous research on the flow and heat-transfer characteristics of LLMs has been limited. Therefore, this work carried out flow and heat-transfer experiments in LBE flowing through a circular tube in the Natural Circulation Capability Loop (NCCL) facility. The results show a significantly higher friction factor than that of water flowing in a smooth pipe. Furthermore, the Nusselt numbers were found to be lower than those found in data in the literature for experiments carried out in a smooth tube at low Péclet numbers, while they were higher at high Péclet numbers. Therefore, theoretical analyses were performed for LLMs flowing in both smooth and rough pipes, and the impacts of roughness on the heat transfer of an LLM were examined. The theoretical relations for a smooth pipe and a rough pipe were validated using experimental data from the literature and the results of the NCCL experiments, respectively. The results of the theoretical relation for a smooth pipe fitted the literature data well. The derived theoretical relation for a rough pipe with a relative roughness of 0.004 fitted the NCCL data best. Moreover, it was established from the theoretical analysis that roughness has two competitive impacts on the heat transfer of an LLM: it reduces conductive heat transfer while enhancing convective heat transfer. Because conductive heat transfer is important for liquid metals, even with turbulent flow, a small roughness will lead to heat-transfer deterioration at low Péclet numbers, and it may even deteriorate across the whole typical Péclet-number range. This discovery has important implications for the thermal–hydraulic design of LLM reactors, because corrosion and erosion by an LLM will lead to a rough surface after long operating times.
Prevention, Protection and Participation: Children Affected by Armed Conflict
Authors: Baillie Abidi Catherine
Published: February 2021

Children are disproportionately impacted in fragile and conflict environments. Through a critical analysis of the ways in which violence is normalized and inherently gendered, this article explores the typology of violence embedded in fragile and conflict environments, the disproportionate impact of forced migration on children affected by conflict, how these interconnected forms of violence are gendered, and the importance of participatory and collective child protection and violence prevention action. Concluding with a discussion of the gaps in peace and security frameworks, the author identifies opportunities to strengthen child protection and recruitment prevention from a gender transformative perspective.
Galectin-Levels Are Elevated in Infants Born Preterm Due to Amniotic Infection and Rapidly Decline in the Neonatal Period
Authors: Faust Kirstin , Freitag Nancy , Barrientos Gabriela , Hartel Christoph , Blois Sandra M.
Published: February 2021

Galectin (gal)-1, -3, and -9 are members of a family of glycan binding proteins that mediate complex interactions between decidual, inflammatory and trophoblast cells modulating several processes during gestation, control of the maternal immune system, and parturition. Their immunomodulatory role in preterm birth and postnatal expression in preterm infants is unknown. We performed a single center prospective study of 170 preterm infants with a gestational age below 35 weeks. Peripheral venous blood samples were collected during the neonatal period and galectin-1, -3, and -9 were determined by ELISA. We noted a strong decline of circulating gal-1 and -3 levels but not gal-9 from birth to day 7 of life. There was an inverse correlation of gal-1 and -3 levels at birth with gestational age. Gal-1 levels were remarkably increased in infants born to amniotic infection syndrome (AIS), which was also observed for gal-9 levels. Infants who developed early-onset sepsis had higher levels of gal-3 at day 1 as compared to unaffected infants. Our observational data imply that galectin-1, -3, and -9 levels are elevated in preterm infants born in an inflammatory milieu such as AIS or EOS. Future studies need to address whether galectins mediate inflammation-induced preterm birth and could therefore be a target for clinical trials.
Cross With Caution: Antibiotic Cross-Reactivity and Co-Reactivity Patterns in Severe Cutaneous Adverse Reactions
Authors: Thompson Grace , McLean-Tooke Andrew , Lucas Michaela
Published: February 2021

Current understanding of cross-reactivity in severe cutaneous adverse reactions to beta-lactam antibiotics is limited, thereby making recommendations for future prescribing difficult. The underlying immunopathogenesis of these reactions is not completely understood but involves interactions between small molecule drugs, T cells and HLA molecules. Historically, these reactions were considered to be specific to the inciting antibiotic and therefore likely to have minimal cross-reactivity. We assessed patients presenting with non-SJS/TEN severe cutaneous adverse reactions to a tertiary hospital drug allergy clinic. In our case series cross-reactivity or co-reactivity commonly occurred among the beta-lactam antibiotic class, however further research is required to investigate and understand patterns of cross-reactivity. Based on our experience we provide clinicians with a practical algorithm for testing for cross-reactivity in non-SJS/TEN severe cutaneous adverse reactions.
Human β-Defensin 2 Mutations Are Associated With Asthma and Atopy in Children and Its Application Prevents Atopic Asthma in a Mouse Model
Authors: Borchers Natascha S. , Santos-Valente Elisangela , Toncheva Antoaneta A. , Wehkamp Jan , Franke Andre , Gaertner Vincent D. , Nordkild Peter , Genuneit Jon , Jensen Benjamin A. H. , Kabesch Michael
Published: February 2021

Asthma and allergies are complex, chronic inflammatory diseases in which genetic and environmental factors are crucial. Protection against asthma and allergy development in the context of farming environment is established by early animal contact, unpasteurized milk consumption and gut microbiota maturation. The human β-defensin 2 (hBD-2) is a host defense peptide present almost exclusively in epithelial tissues, with pronounced immunomodulatory properties, which has recently been shown to ameliorate asthma and IBD in animal models. We hypothesized that adequate hBD-2 secretion plays a role in the protection against asthma and allergy development and that genetic variations in the complex gene locus coding for hBD-2 may be a risk factor for developing these diseases, if as a consequence, hBD-2 is insufficiently produced. We used MALDI-TOF MS genotyping, sequencing and a RFLP assay to study the genetic variation including mutations, polymorphisms and copy number variations in the locus harboring both genes coding for hBD-2 (DEFB4A and DEFB4B). We administered hBD-2 orally in a mouse model of house dust mite (HDM)-asthma before allergy challenge to explore its prophylactic potential, thereby mimicking a protective farm effect. Despite the high complexity of the region harboring DEFB4A and DEFB4B we identified numerous genetic variants to be associated with asthma and allergy in the GABRIELA Ulm population of 1,238 children living in rural areas, including rare mutations, polymorphisms and a lack of the DEFB4A. Furthermore, we found that prophylactic oral administration of hBD-2 significantly curbed lung resistance and pulmonary inflammation in our HDM mouse model. These data indicate that inadequate genetic capacity for hBD-2 is associated with increased asthma and allergy risk while adequate and early hBD-2 administration (in a mouse model) prevents atopic asthma. This suggests that hBD-2 could be involved in the protective farm effect and may be an excellent candidate to confer protection against asthma development.
Single-Cell Profiling to Explore Immunological Heterogeneity of Tumor Microenvironment in Breast Cancer
Authors: Yuan Xiao , Wang Jinxi , Huang Yixuan , Shangguan Dangang , Zhang Peng
Published: February 2021

Immune infiltrates in the tumor microenvironment (TME) of breast cancer (BRCA) have been shown to play a critical role in tumorigenesis, progression, invasion, and therapy resistance, and thereby will affect the clinical outcomes of BRCA patients. However, a wide range of intratumoral heterogeneity shaped by the tumor cells and immune cells in the surrounding microenvironment is a major obstacle in understanding and treating BRCA. Recent progress in single-cell technologies such as single-cell RNA sequencing (scRNA-seq), mass cytometry, and digital spatial profiling has enabled the detailed characterization of intratumoral immune cells and vastly improved our understanding of less-defined cell subsets in the tumor immune environment. By measuring transcriptomes or proteomics at the single-cell level, it provides an unprecedented view of the cellular architecture consist of phenotypical and functional diversities of tumor-infiltrating immune cells. In this review, we focus on landmark studies of single-cell profiling of immunological heterogeneity in the TME, and discuss its clinical applications, translational outlook, and limitations in breast cancer studies.
Invariant Gametogenic Response of Dominant Infaunal Bivalves From the Arctic Under Ambient and Near-Future Climate Change Conditions
Authors: Reed Adam J. , Godbold Jasmin A. , Solan Martin , Grange Laura J.
Published: February 2021

Arctic marine ecosystems are undergoing a series of major rapid adjustments to the regional amplification of climate change, but there is a paucity of knowledge about how changing environmental conditions might affect reproductive cycles of seafloor organisms. Shifts in species reproductive ecology may influence their entire life-cycle, and, ultimately, determine the persistence and distribution of taxa. Here, we investigate whether the combined effects of warming and ocean acidification based on near-future climate change projections affects the reproductive processes in benthic bivalves (Astarte crenata and Bathyarca glacialis) from the Barents Sea. Both species present large oocytes indicative of lecithotrophic or direct larval development after ∼4 months exposure to ambient [<2°C, ∼400 ppm (CO2)] and near-future [3–5°C, ∼550 ppm (CO2)] conditions, but we find no evidence that the combined effects of acidification and warming affect the size frequency distribution of oocytes. Whilst our observations are indicative of resilience of this reproductive stage to global changes, we also highlight that the successful progression of gametogenesis under standard laboratory conditions does not necessarily mean that successful development and recruitment will occur in the natural environment. This is because the metabolic costs of changing environmental conditions are likely to be offset by, as is common practice in laboratory experiments, feeding ad libitum. We discuss our findings in the context of changing food availability in the Arctic and conclude that, if we are to establish the vulnerability of species and ecosystems, there is a need for holistic approaches that incorporate multiple system responses to change.
State of Satiation Partially Regulates the Dynamics of Vertical Migration
Authors: Bos Ryan P. , Sutton Tracey T. , Frank Tamara M.
Published: February 2021

Vertical migrations into shallower waters at night are beneficial for migrators as they reduce predation risk and allow migrators to encounter a higher density of prey. Nevertheless, ocean acoustics data and trawl data have shown that a portion of some vertically migrating populations remain at depth and do not migrate. One hypothesis for this phenomenon is the Hunger-Satiation hypothesis, which in part states that the non-migrating portion of the migrating species-assemblage refrains from migrating if they have full or partially full stomachs from daytime or nocturnal feeding. However, stomach fullness of the non-migrating subpopulation compared to the migrating portion has rarely been studied, due to the difficulty in obtaining sufficient samples. The stomach fullness levels of numerically abundant crustacean and fish species with well-known depth distributions were quantified in the present study. Animals were captured during night trawls from discrete-depth intervals between 0 and 1,500 m. Stomach fullness indices were assigned from 0 to 5 and compared between migratory taxa caught in shallow and deep waters. Data from the crustaceansAcanthephyra purpurea, Gardinerosergia splendens, Plesionika richardi, andSystellaspsis debilis, as well as the fishesLampanyctus alatus, Lepidophanes guentheri, andNotolychnus valdiviae, provided support for the Hunger-Satiation hypothesis, while data from the crustaceansGennadas capensisandGennadas valensand the fishBenthosema suborbitaledid not. These findings suggest that stomach vacancy may be just one of several factors regulating the dynamics of vertical migration in those species whose behavioral plasticity suggests daily “choices” in whether or not to vertically migrate.
Comparative Genomics Analysis Demonstrated a Link Between Staphylococci Isolated From Different Sources: A Possible Public Health Risk
Authors: Cave Rory , Misra Raju , Chen Jiazhen , Wang Shiyong , Mkrtchyan Hermine V.
Published: February 2021

Coagulase-negative staphylococci (CoNS) have been recovered from different ecological niches, however, little is known about the genetic relatedness of these isolates. In this study, we used whole genome sequencing to compare mecA positive (mecA+) Staphylococcus epidermidis, Staphylococcus haemolyticus and Staphylococcus hominis isolates recovered from hand-touched surfaces from general public settings in East and West London with data of isolates deposited to European Nucleotide Archive (ENA) by other research groups. These included isolates associated with hospital settings (including those recovered from patients), healthy humans, livestock, pets, plants and natural, and other public environments. Using core and accessory phylogenetic analyses we were able to identify that the mecA+ S. epidermidis and S. haemolyticus isolates recovered from general public settings were genetically related to isolates recovered from the bloodstream, urinary tract and eye infections. S. epidermidis isolates recovered in our study were also shown to be genetically related to isolates previously recovered from livestock/livestock housing, whereas S. haemolyticus isolates were genetically related to isolates recovered from a dog and kefir (fermented cow milk drink). MecA+S. hominis isolates were not genetically related to any isolates recovered from clinical samples but were genetically related to isolates recovered from mosquitoes, air samples (residential areas) and kefir. All three species showed to have genetic relatedness to isolates recovered from healthy humans. These results show that CoNS isolates in this study share genetic similarities with those of different lineages and that mecA+ S. epidermidis and S. haemolyticus isolates found in general public settings in this study may pose a risk to public health.
Nitrogen Fixing Azotobacter Species as Potential Soil Biological Enhancers for Crop Nutrition and Yield Stability
Authors: Aasfar Abderrahim , Bargaz Adnane , Yaakoubi Kaoutar , Hilali Abderraouf , Bennis Iman , Zeroual Youssef , Meftah Kadmiri Issam
Published: February 2021

Biological nitrogen fixation (BNF) refers to a microbial mediated process based upon an enzymatic “Nitrogenase” conversion of atmospheric nitrogen (N2) into ammonium readily absorbable by roots. N2-fixing microorganisms collectively termed as “diazotrophs” are able to fix biologically N2in association with plant roots. Specifically, the symbiotic rhizobacteria induce structural and physiological modifications of bacterial cells and plant roots into specialized structures called nodules. Other N2-fixing bacteria are free-living fixers that are highly diverse and globally widespread in cropland. They represent key natural source of nitrogen (N) in natural and agricultural ecosystems lacking symbiotic N fixation (SNF). In this review, the importance ofAzotobacterspecies was highlighted as both important free-living N2-fixing bacteria and potential bacterial biofertilizer with proven efficacy for plant nutrition and biological soil fertility. In addition, we describedAzotobacterbeneficial plant promoting traits (e.g., nutrient use efficiency, protection against phytopathogens, phytohormone biosynthesis, etc.). We shed light also on the agronomic features ofAzotobacterthat are likely an effective component of integrated plant nutrition strategy, which contributes positively to sustainable agricultural production. We pointed outAzotobacterbased-biofertilizers, which possess unique characteristics such as cyst formation conferring resistance to environmental stresses. Such beneficial traits can be explored profoundly for the utmost aim to research and develop specific formulations based on inoculantAzotobactercysts. Furthermore,Azotobacterspecies still need to be wisely exploited in order to address specific agricultural challenges (e.g., nutrient deficiencies, biotic and abiotic constraints) taking into consideration several variables including their biological functions, synergies and multi-trophic interactions, and biogeography and abundance distribution.
Dependence on Mincle and Dectin-2 Varies With Multiple Candida Species During Systemic Infection
Authors: Thompson Aiysha , da Fonseca Diogo M. , Walker Louise , Griffiths James S. , Taylor Philip R. , Gow Neil A. R. , Orr Selinda J.
Published: February 2021

More than 95% of invasiveCandidainfections are caused by fourCandidaspp. (C. albicans, C. glabrata, C. tropicalis, C. parapsilosis). C-type lectin-like receptors (CLRs), such as Dectin-1, Dectin-2, and Mincle mediate immune responses toC. albicans. Dectin-1 promotes clearance ofC. albicans, C. glabrata, C. tropicalis, andC. parapsilosis, however, dependence on Dectin-1 for specific immune responses varies with the differentCandidaspp. Dectin-2 is important for host immunity toC. albicansandC. glabrata, and Mincle is important for the immune response toC. albicans.However, whether Dectin-2 drives host immunity toC. tropicalisorC. parapsilosis, and whether Mincle mediates host immunity toC. glabrata, C. tropicalisorC. parapsilosisis unknown. Therefore, we compared the roles of Dectin-2 and Mincle in response to these fourCandidaspp. We demonstrate that these fourCandidaspp. cell walls have differential mannan contents. Mincle and Dectin-2 play a key role in regulating cytokine production in response to these fourCandidaspp. and Dectin-2 is also important for clearance of all fourCandidaspp. during systemic infection. However, Mincle was only important for clearance ofC. tropicalisduring systemic infection. Our data indicate that multipleCandidaspp. have different mannan contents, and dependence on the mannan-detecting CLRs, Mincle, and Dectin-2 varies between differentCandidaspp. during systemic infection.
Six Metabolism Related mRNAs Predict the Prognosis of Patients With Hepatocellular Carcinoma
Authors: Wu Xiwen , Lan Tian , Li Muqi , Liu Junfeng , Wu Xukun , Shen Shunli , Chen Wei , Peng Baogang
Published: February 2021

Background: Hepatocellular carcinoma (HCC) is one of the most common aggressive solid malignant tumors and current research regards HCC as a type of metabolic disease. This study aims to establish a metabolism-related mRNA signature model for risk assessment and prognosis prediction in HCC patients.

Methods: HCC data were obtained from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Enrichment Analysis (GSEA) website. Least absolute shrinkage and selection operator (LASSO) was used to screen out the candidate mRNAs and calculate the risk coefficient to establish the prognosis model. A high-risk group and low-risk group were separated for further study depending on their median risk score. The reliability of the prediction was evaluated in the validation cohort and the whole cohort.

Results: A total of 548 differential mRNAs were identified from HCC samples (n = 374) and normal controls (n = 50), 45 of which were correlated with prognosis. A total of 373 samples met the screening criteria and there were randomly divided into the training cohort (n = 186) and the validation cohort (n = 187). In the training cohort, six metabolism-related mRNAs were used to construct a prognostic model with a LASSO regression model. Based on the risk model, the overall survival rate of the high-risk cohort was significantly lower than that of the low-risk cohort. The results of a time-ROC curve proved that the risk score (AUC = 0.849) had a higher prognostic value than the pathological grade, clinical stage, age or gender.

Conclusion: The model constructed by the six metabolism-related mRNAs has a significant value for survival prediction and can be applied to guide the evaluation of HCC and the designation of clinical therapy.