bluuebunny/crossref_metadata_2025 huggingface dataset:
Food insecurity and mental health: a systematic review and meta-analysis
Authors: Pourmotabbed Ali , Moradi Sajjad , Babaei Atefeh , Ghavami Abed , Mohammadi Hamed , Jalili Cyrus , Symonds Michael E , Miraghajani Maryam
Published: March 2020

Objective:

Food security has been suggested to be a risk factor for depression, stress and anxiety. We therefore undertook a systematic review and meta-analysis of available publications to examine these associations further.

Design:

Relevant studies were identified by searching Web of Science, Embase, Scopus and PubMed databases up to January 2019.

Setting:

OR was pooled using a random-effects model. Standard methods were used for assessment of heterogeneity and publication bias.

Participants:

Data were available from nineteen studies with 372 143 individual participants from ten different countries that were pooled for the meta-analysis.

Results:

The results showed there was a positive relationship between food insecurity (FI) and risk of depression (OR = 1·40; 95 % CI: 1·30, 1·58) and stress (OR = 1·34; 95 % CI: 1·24, 1·44) but not anxiety. Subgroup analysis by age showed that subjects older than ≥65 years exhibited a higher risk of depression (OR = 1·75; 95 % CI: 1·20, 2·56) than younger participants (OR = 1·34; 95 % CI: 1·20, 1·50), as well as a greater risk of depression in men (OR = 1·42; 95 % CI: 1·17, 1·72) than women (OR = 1·30; 95 % CI: 1·16, 1·46). Finally, subgroup analysis according to geographical location illustrated that food insecure households living in North America had the highest risk of stress and anxiety.

Conclusions:

The evidence from this meta-analysis suggests that FI has a significant effect on the likelihood of being stressed or depressed. This indicates that health care services, which alleviate FI, would also promote holistic well-being in adults.
Review on the feasibility of using PRESAGE® dosimeter in various radiotherapy techniques
Authors: Shamsi Qurat-ul-ain , Buzdar Saeed Ahmad , Jabeen Shagufta , Iqbal Khalid
Published: March 2020

The emergence of advanced radiotherapy techniques, such as intensity-modulated radiotherapy (IMRT), brachytherapy, conformal radiotherapy, magnetic resonance-guided radiotherapy (MRgRT), stereotactic synchrotron radiotherapy (SSRT) and microbeam radiotherapy (MRT), has increased the importance of the verification of volumetric dose distribution. The verification of dose distribution is usually done by 2D films and 3D gel dosimeters, but PRESAGE® due to its affordability, reproducibility, precision, accuracy, unique dosimetric and physical properties is considered as an effective candidate in providing 3D dose data. PRESAGE® is insensitive to oxygen contamination, machinable and can be molded to a variety of shapes and sizes. It is absorbing rather than scattering light which facilitates high-accuracy readout by optical computed tomography (OP-CT). This review focuses on the feasibility of using PRESAGE® in various complicated radiotherapy techniques by comparing its measured doses with 2D films and treatment planning system (TPS) calculated doses.
“I want to go home”: How location at death influences caregiver well-being in bereavement
Authors: Waldrop Deborah P. , McGinley Jacqueline M.
Published: March 2020

Objectives

Goal concordant or congruent care involves having expressed wishes upheld. Yet, the preferred location for end-of-life care may be unaddressed. Caregiver–patient congruence between preferred and actual locations of care may influence the quality of life in bereavement. The study aimed to explore how the congruence between caregiver–patient preferred and actual locations of death influenced well-being in bereavement.

Methods

Mixed methods were employed. In-depth in-person interviews were conducted with 108 bereaved caregivers of a hospice patient about 4 months after the death. An interview guide was used to collect quantitative and qualitative data: demographics, decision-making, Core Bereavement Items (CBI), Health Related Quality of Life, and perspectives on the end-of-life experiences. Data were analyzed with a convergent mixed methods one-phase process.

Results

Patient preference–actual location congruence occurred for 53%; caregiver preference–actual location congruence occurred for 74%; caregiver–patient preference and location of death occurred for 48%. Participants who reported some type of incongruence demonstrated higher levels of distress, including more days of being physically and emotionally unwell and more intense bereavement symptoms. The Acute Separation subscale and CBI total scores demonstrated significant differences for participants who experienced incongruence compared with those who did not. Preference location congruence themes emerged: (1) caregiver–patient location congruence, (2) caregiver–patient location incongruence, and (3) location informed bereavement.

Conclusions

Congruence between a dying person's preferred and actual locations at death has been considered good care. There has been little focus on the reciprocity between caregiver–patient wishes. Discussing preferences about the place of end-stage care may not make location congruence possible, but it can foster shared understanding and support for caregivers’ sense of coherence and well-being in bereavement.
No Age Trends in Oak Stable Isotopes
Authors: Büntgen Ulf , Kolář Tomáš , Rybníček Michal , Koňasová Eva , Trnka Mirek , Ač Alexander , Krusic Paul J. , Esper Jan , Treydte Kerstin , Reinig Fredrick , Kirdyanov Alexander , Herzig Franz , Urban Otmar
Published: March 2020

Although the importance of stable isotope ratios in tree rings is increasing for high‐resolution climate reconstructions, it is still unclear if such values exhibit age trends that require some form of standardization. Here we present 13,496 and 13,584 annually resolved and absolutely dated δ18O and δ13C measurements from 147 living and relict oaks (Quercus spp.) that grew over the past 2,000 years in the Czech Republic. In contrast to their heteroscedastic ring widths, the stable isotopes reveal constant spread versus level relationships over the trees' life span. Together with high signal strength, the absence of age‐related constraints makes δ18O and δ13C from oak latewood alpha cellulose a superior climate proxy in regions where traditional tree‐ring parameters are limited.
Comment on “The Mesozoic Margin of the Maghrebian Tethys in the Rif Belt (Morocco): Evidence for Polyphase Rifting and Related Magmatic Activity” by Gimeno‐Vives et al.
Authors: Michard A. , Saddiqi O. , Chalouan A. , Chabou M.C. , Lach P. , Rossi P. , Bertrand H. , Youbi N.
Published: March 2020

Key Points

The main Mesorif gabbros emplaced in a Liassic oceanic domain and do not belong to the Central Atlantic Magmatic Province (CAMP)

CAMP dolerites may occur separately next to the oceanic gabbros in the structurally complex Mesorif zone

The prerift/synrift cover of the distal margin could have emplaced by gravity sliding onto the Mesorif oceanic crust
Profile of Suspended Sediment Concentration in Submerged Vegetated Shallow Water Flow
Authors: Li Y. , Xie L. , Su T. C.
Published: March 2020

The vertical distribution pattern of the fine suspended sediment concentration (SSC) plays an important role in the aquatic ecosystem of shallow water. To investigate the SSC profile in submerged vegetated river flow, a series of indoor flume experiments was conducted. Glass spherical balls of three different diameters (40, 77, and 90 μm) with a uniform specific gravity of 2.5 were used for the model sediments. A set of sampling devices was designed for the simultaneous measurements of SSCs at multipoints along a vertical line. Experimental results show that the SSC profile was re‐distributed in the vegetated region, gradually forming a new equilibrium pattern in the overcanopy flow layer with its maximum occurring near the canopy top. From this maximum point near the canopy top, the suspended sediment formed a dynamic balance between upward turbulent diffusion and downward gravitational settling. Meanwhile, the momentum diffusivity was observed to linearly decrease upward from the maximum‐SSC elevation toward the water surface, thereby allowing us to deduce an empirical negative linear formula. Based on the convection‐diffusion equilibrium mechanism and with assistance of the empirical formula of flow momentum diffusivity, a new form of the Rouse formula was derived for the overcanopy flow layer. In general, this equation agrees well with the measured data. Some undercalculated deviations appear in the well‐above canopy zone due to the upskewed turbulence and the weak upward secondary flow. This deviation decreases with increasing sediment diameter. The bed deposition mainly comes from the deep part of canopy‐occupied flow layer.
Hydrologically Informed Machine Learning for Rainfall‐Runoff Modeling: A Genetic Programming‐Based Toolkit for Automatic Model Induction
Authors: Chadalawada Jayashree , Herath H. M. V. V. , Babovic Vladan
Published: March 2020

Models of water resources systems are conceived to capture the underlying environmental dynamics occurring within watersheds. All such models can be regarded as working hypotheses, differing in the aspects of process representation and conceptualization. Most of the associated efforts in the water resources research community is dedicated to development of new models that perform well under specific atmospheric conditions and catchment properties. In this context, flexible modeling frameworks are gaining importance as they facilitate the model building process by providing the model building blocks, whereby the hydrologist is free to assemble the model for task at hand. Such flexible models have high degree of transferability, which in turn aid in progressing toward a unified hydrological theory at catchment scale. However, in cases without sufficient insights regarding a catchment characteristics and/or lack of expert's knowledge, one may have to try a large number of model configurations based on available model building blocks to construct an appropriate model for the catchment of interest. Undoubtedly, this may be time consuming and computationally intensive. This paper proposes a novel model building algorithm, which uses the full potential of flexible modeling frameworks by searching the model space and inferring suitable model configurations relying on machine learning. Proposed machine learning algorithm is based on evolutionary computation approach using genetic programming (GP). State‐of‐art GP applications in rainfall‐runoff modeling so far used the algorithm as a short‐term forecasting tool that generates an expected future time series very similar to neural networks application. In this case, the proposed algorithm develops a physically meaningful rainfall‐runoff model. Although at the moment we learn models using two flexible modeling frameworks (SUPERFLEX and FUSE), the model induction toolkit can be armed with any internal coherence building blocks. The model induction capabilities of the proposed framework have been evaluated on the Blackwater River basin, Alabama, United States. The model configurations evolved through the model induction toolkit are consistent with the fieldwork investigations and previously reported research findings.
O-FIB: far-field-induced near-field breakdown for direct nanowriting in an atmospheric environment
Authors: Li Zhen-Ze , Wang Lei , Fan Hua , Yu Yan-Hao , Chen Qi-Dai , Juodkazis Saulius , Sun Hong-Bo
Published: March 2020

Nanoscale surface texturing, drilling, cutting, and spatial sculpturing, which are essential for applications, including thin-film solar cells, photonic chips, antireflection, wettability, and friction drag reduction, require not only high accuracy in material processing, but also the capability of manufacturing in an atmospheric environment. Widely used focused ion beam (FIB) technology offers nanoscale precision, but is limited by the vacuum-working conditions; therefore, it is not applicable to industrial-scale samples such as ship hulls or biomaterials, e.g., cells and tissues. Here, we report an optical far-field-induced near-field breakdown (O-FIB) approach as an optical version of the conventional FIB technique, which allows direct nanowriting in air. The writing is initiated from nanoholes created by femtosecond-laser-induced multiphoton absorption, and its cutting “knife edge” is sharpened by the far-field-regulated enhancement of the optical near field. A spatial resolution of less than 20 nm (λ/40, with λ being the light wavelength) is readily achieved. O-FIB is empowered by the utilization of simple polarization control of the incident light to steer the nanogroove writing along the designed pattern. The universality of near-field enhancement and localization makes O-FIB applicable to various materials, and enables a large-area printing mode that is superior to conventional FIB processing.
Programmed cell death 4 as an endogenous suppressor of BDNF translation is involved in stress-induced depression
Authors: Li Yuan , Jia Yufeng , Wang Dongdong , Zhuang Xiao , Li Yan , Guo Chun , Chu Hongxia , Zhu Faliang , Wang Jianing , Wang Xiaoyan , Wang Qun , Zhao Wei , Shi Yongyu , Chen Wanjun , Zhang Lining
Published: March 2020

Brain-derived neurotrophic factor (BDNF) is a growth factor that plays vital roles in the neuron survival, growth, and neuroplasticity. Alteration to BDNF expression is associated with major depressive disorder. However, the BDNF translational machinery in depression remains unknown. Herein, we pointed that Pdcd4, a suppressor oncogene, acted as an endogenous inhibitor for the translation of BDNF, and selectively repressed the translation of BDNF splice variant IIc mRNA in an eIF4A-dependent manner. Chronic restraint stress (CRS) up-regulated Pdcd4 expression in hippocampus via decreasing mTORC1-mediated proteasomes degradation pathway, which resulted in the reduction of BDNF protein expression. Moreover, over-expression of Pdcd4 in the hippocampus triggered spontaneous depression-like behaviors under the non-stressed conditions in mice, while systemic or neuron-specific knockout of Pdcd4 reverses CRS-induced depression-like behaviors. Importantly, administration of Pdcd4 siRNA or an interfering peptide that interrupts the Pdcd4-eIF4A complex substantially promoted BDNF expression and rescued the behavioral disorders which were caused by CRS. Overall, we have discovered a previously unrecognized role of Pdcd4 in controlling BDNF mRNA translation, and provided a new method that boosting BDNF expression through blocking the function of Pdcd4 in depression, indicating that Pdcd4 might be a new potential target for depressive disorder therapy.
Elevated serum chemokine CCL22 levels in first-episode psychosis: associations with symptoms, peripheral immune state and in vivo brain glial cell function
Authors: Laurikainen Heikki , Vuorela Arja , Toivonen Anna , Reinert-Hartwall Linnea , Trontti Kalevi , Lindgren Maija , Keinänen Jaakko , Mäntylä Teemu , Paju Janina , Ilonen Tuula , Armio Reetta-Liina , Walta Maija , Tuisku Jouni , Helin Semi , Marjamäki Päivi , Hovatta Iiris , Therman Sebastian , Vaarala Outi , Linnaranta Outi , Kieseppä Tuula , Salokangas Raimo K. R. , Honkanen Jarno , Hietala Jarmo , Suvisaari Jaana
Published: March 2020

Several lines of research support immune system dysregulation in psychotic disorders. However, it remains unclear whether the immunological marker alterations are stable and how they associate with brain glial cell function. This longitudinal study aimed at investigating whether peripheral immune functions are altered in the early phases of psychotic disorders, whether the changes are associated with core symptoms, remission, brain glial cell function, and whether they persist in a one-year follow-up. Two independent cohorts comprising in total of 129 first-episode psychosis (FEP) patients and 130 controls were assessed at baseline and at the one-year follow-up. Serum cyto-/chemokines were measured using a 38-plex Luminex assay. The FEP patients showed a marked increase in chemokine CCL22 levels both at baseline (p < 0.0001; Cohen’s d = 0.70) and at the 12-month follow-up (p = 0.0007) compared to controls. The group difference remained significant (p = 0.0019) after accounting for relevant covariates including BMI, smoking, and antipsychotic medication. Elevated serum CCL22 levels were significantly associated with hallucinations (ρ = 0.20) and disorganization (ρ = 0.23), and with worse verbal performance (ρ = −0.23). Brain glial cell activity was indexed with positron emission tomography and the translocator protein radiotracer [11C]PBR28 in subgroups of 15 healthy controls and 14 FEP patients with serum CCL22/CCL17 measurements. The distribution volume (VT) of [11C]PBR28 was lower in patients compared to controls (p = 0.026; Cohen’s d = 0.94) without regionally specific effects, and was inversely associated with serum CCL22 and CCL17 levels (p = 0.036). Our results do not support the over-active microglia hypothesis of psychosis, but indicate altered CCR4 immune signaling in early psychosis with behavioral correlates possibly mediated through cross-talk between chemokine networks and dysfunctional or a decreased number of glial cells.
Targeting CD133 reverses drug-resistance via the AKT/NF-κB/MDR1 pathway in colorectal cancer
Authors: Yuan Zeting , Liang Xin , Zhan Yueping , Wang Ziyuan , Xu Jian , Qiu Yanyan , Wang Jie , Cao Yijun , Le Van-Minh , Ly Hai-Trieu , Xu Jianhua , Li Wei , Yin Peihao , Xu Ke
Published: March 2020

Background

Recent studies have shown that multidrug resistance may be induced by the high stemness of cancer cells. Following prolonged chemotherapy, MDR protein 1 (MDR1) and CD133 increase in CRC, but the relationship between them is unclear.

Methods

The relationship between MDR and CSC properties in CRC was determined via CCK-8 assay, apoptosis assay, DOX uptake and retention, immunohistochemistry, immunofluorescence and flow cytometry. The correlations between their expression levels were evaluated using Spearman’s rank statistical test and the Mann-Whitney test. Furthermore, the effect of CD133 on the repression of the AKT/NF-κB/MDR1 signalling pathway was investigated in vitro and in vivo.

Results

We found that CD133 increased with the emergence of drug-resistance phenotypes, and the high expression of MDR1/P-gp was consistently accompanied by positive expression of CD133 as demonstrated by the analysis of patient samples. Up- or downregulation of CD133 could regulate MDR via AKT/NF-κB/MDR1 signalling in CRC. A rescue experiment showed that the AKT/NF-κB signalling pathway is the main mechanism by which CD133 regulates MDR1/P-gp expression in CRC.

Conclusions

Taken together, our results suggest that targeting CD133 reverses drug resistance via the AKT/NF-κB/MDR1 pathway and that this pathway might serve as a potential therapeutic target to reverse MDR in CRC.
PRDM3 attenuates pancreatitis and pancreatic tumorigenesis by regulating inflammatory response
Authors: Ye Jie , Huang Anpei , Wang Haitao , Zhang Anni M. Y. , Huang Xiaojun , Lan Qingping , Sato Tomohiko , Goyama Susumu , Kurokawa Mineo , Deng Chuxia , Sander Maike , Schaeffer David F. , Li Wen , Kopp Janel L. , Xie Ruiyu
Published: March 2020

Pancreatic ductal adenocarcinoma (PDAC) is associated with metaplastic changes in the pancreas but the transcriptional program underlying these changes is incompletely understood. The zinc finger transcription factor, PRDM3, is lowly expressed in normal pancreatic acini and its expression increases during tumorigenesis. Although PRDM3 promotes proliferation and migration of PDAC cell lines, the role of PRDM3 during tumor initiation from pancreatic acinar cells in vivo is unclear. In this study, we showed that high levels of PRDM3 expression in human pancreas was associated with pancreatitis, and well-differentiated but not poorly differentiated carcinoma. We examined PRDM3 function in pancreatic acinar cells during tumor formation and pancreatitis by inactivating Prdm3 using a conditional allele (Ptf1aCreER;Prdm3flox/flox mice) in the context of oncogenic Kras expression and supraphysiological cerulein injections, respectively. In Prdm3-deficient mice, KrasG12D-driven preneoplastic lesions were more abundant and progressed to high-grade precancerous lesions more rapidly. This is consistent with our observations that low levels of PRDM3 in human PDAC was correlated significantly with poorer survival in patient. Moreover, loss of Prdm3 in acinar cells elevated exocrine injury, enhanced immune cell activation and infiltration, and greatly increased acinar-to-ductal cell reprogramming upon cerulein-induced pancreatitis. Whole transcriptome analyses of Prdm3 knockout acini revealed that pathways involved in inflammatory response and Hif-1 signaling were significantly upregulated in Prdm3-depleted acinar cells. Taken together, our results suggest that Prdm3 favors the maintenance of acinar cell homeostasis through modulation of their response to inflammation and oncogenic Kras activation, and thus plays a previously unexpected suppressive role during PDAC initiation.
The Chaotic Terrains of Mercury Reveal a History of Planetary Volatile Retention and Loss in the Innermost Solar System
Authors: Rodriguez J. Alexis P. , Leonard Gregory J. , Kargel Jeffrey S. , Domingue Deborah , Berman Daniel C. , Banks Maria , Zarroca Mario , Linares Rogelio , Marchi Simone , Baker Victor R. , Webster Kevin D. , Sykes Mark
Published: March 2020

Mercury’s images obtained by the 1974 Mariner 10 flybys show extensive cratered landscapes degraded into vast knob fields, known as chaotic terrain (AKA hilly and lineated terrain). For nearly half a century, it was considered that these terrains formed due to catastrophic quakes and ejecta fallout produced by the antipodal Caloris basin impact. Here, we present the terrains’ first geologic examination based on higher spatial resolution MESSENGER (MErcury Surface Space ENvironment GEochemistry and Ranging) imagery and laser altimeter topography. Our surface age determinations indicate that their development persisted until ~1.8 Ga, or ~2 Gyrs after the Caloris basin formed. Furthermore, we identified multiple chaotic terrains with no antipodal impact basins; hence a new geological explanation is needed. Our examination of the Caloris basin’s antipodal chaotic terrain reveals multi-kilometer surface elevation losses and widespread landform retention, indicating an origin due to major, gradual collapse of a volatile-rich layer. Crater interior plains, possibly lavas, share the chaotic terrains’ age, suggesting a development associated with a geothermal disturbance above intrusive magma bodies, which best explains their regionality and the enormity of the apparent volume losses involved in their development. Furthermore, evidence of localized, surficial collapse, might reflect a complementary, and perhaps longer lasting, devolatilization history by solar heating.
Author Correction: Air pollution-derived particulate matter dysregulates hepatic Krebs cycle, glucose and lipid metabolism in mice
Authors: Reyes-caballero Hermes , Rao Xiaoquan , Sun Qiushi , Warmoes Marc O. , Lin Penghui , Sussan Tom E. , Park Bongsoo , Fan Teresa W.-M. , Maiseyeu Andrei , Rajagopalan Sanjay , Girnun Geoffrey D. , Biswal Shyam
Published: March 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Common variants of fetal and maternal complement genes in preeclampsia: pregnancy specific complotype
Authors: Banadakoppa Manu , Balakrishnan Meena , Yallampalli Chandra
Published: March 2020

Preeclampsia (PE) is a pregnancy specific hypertensive disorder. If untreated PE leads to life threatening condition, eclampsia. Systemic complement activation levels are increased during pregnancy compared to non-pregnant women of childbearing age. In PE, systemic complement levels are further increased, and higher complement deposition has been observed on placentas. We hypothesize that combinations of common SNPs in maternal and fetal complement genes constitute pregnancy specific complotypes and predispose women to PE. In this study, we sequenced two maternal (factor H and C3) and one fetal (CD46) complement genes and identified a total of 9 common SNPs. Minor allele frequencies of two fetal CD46 SNPs were significantly higher in PE. Further, complotypes consisting of fetal CD46 variants and maternal CFH/C3 variants were highly prevalent in PE patients compared to normotensive pregnancies. Placental complement deposition and maternal alternative pathway 50 (AP50) values were higher in PE pregnancies. Irrespective of disease status, two CD46 variants were associated with reduced placental CD46 expression and one CFH variant was associated with increased maternal AP50 values.
A new risk score to assess atrial fibrillation risk in hypertensive patients (ESCARVAL-RISK Project
Authors: Orozco-Beltran Domingo , Quesada Jose A. , Bertomeu-Gonzalez Vicente , Lobos-Bejarano Jose M. , Navarro-Perez Jorge , Gil-Guillen Vicente F. , Garcia Ortiz Luis , Lopez-Pineda Adriana , Castellanos-Rodriguez Angel , Lopez-Domenech Angela , Cardona-Llorens Antonio Francisco J. , Carratala-Munuera Concepcion
Published: March 2020

This study aimed to assess atrial fibrillation (AF) incidence and predictive factors in hypertensive patients and to formulate an AF risk assessment score that can be used to identify the patients most likely to develop AF. This was a cohort study of patients recruited in primary healthcare centers. Patients aged 40 years or older with hypertension, free of AF and with no previous cardiovascular events were included. Patients attended annual visits according to clinical practice until the end of study or onset of AF. The association between AF incidence and explanatory variables (age, sex, body mass index, medical history and other) was analyzed. Finally, 12,206 patients were included (52.6% men, and mean age was 64.9 years); the mean follow-up was 36.7 months, and 394 (3.2%) patients were diagnosed with AF. The incidence of AF was 10.5/1000 person-years. Age (hazard ratio [HR] 1.06 per year; 95% confidence interval [CI] 1.05–1.08), male sex (HR 1.88; 95% CI 1.53–2.31), obesity (HR 2.57; 95% CI 1.70–3.90), and heart failure (HR 2.44; 95% CI 1.45–4.11) were independent predictors (p < 0.001). We propose a risk score based on significant predictors, which enables the identification of people with hypertension who are at the greatest risk of AF.
Internal crack characteristics in very-high-cycle fatigue of a gradient structured titanium alloy
Authors: Pan Xiangnan , Qian Guian , Wu Shengchuan , Fu Yanan , Hong Youshi
Published: March 2020

Gradient structure (GS) is commonly designed and processed in engineering materials to improve mechanical properties especially fatigue performance by taking advantage of the strengthened surface. However, whether the very-high-cycle fatigue (VHCF) property can be improved by GS is questioning due to the different crack initiation mechanisms between low-, high-cycle and VHCF. In this paper, GS of a Ti-6Al-4V alloy is generated by pre-torsion and characterized by electron backscatter diffraction. Then the VHCF behavior of the GS specimen is studied. The fractography and synchrotron radiation X-ray microtomography presented detailed characteristics of the internal crack initiation region in VHCF of the titanium alloy with GS. The results indicated that, in contrast to the low- and high-cycle regimes, the VHCF strength is reduced for the specimens with GS. Thus, the GS induced by pre-torsion cannot enhance the VHCF strength of the titanium alloy. This implies that VHCF test (property) is an important consideration for the microstructural designed materials. The graphical abstract is available in Supplementary information.
Photonic Crystal Circular Nanobeam Cavity Laser with Type-II GaSb/GaAs Quantum Rings as Gain Material
Authors: Lin Hsiang-Ting , Hsu Kung-Shu , Chang Chih-Chi , Lin Wei-Hsun , Lin Shih-Yen , Chang Shu-Wei , Chang Yia-Chung , Shih Min-Hsiung
Published: March 2020

The optical emission from type-II semiconductor nanostructures is influenced by the long carrier lifetime and can exhibit remarkable thermal stability. In this study, utilizing a high quality photonic crystal circular nanobeam cavity with a high quality factor and a sub-micrometer mode volume, we demonstrated an ultra-compact semiconductor laser with type-II gallium antimonide/gallium arsenide quantum rings (GaSb/GaAs QRs) as the gain medium. The lasing mode localized around the defect region of the nanobeam had a small modal volume and significant coupling with the photons emitted by QRs. It leads the remarkable shortening of carrier lifetime observed from the time-resolved photoluminescence (TRPL) and a high Purcell factor. Furthermore, a high characteristic temperature of 114 K was observed from the device. The lasing performances indicated the type-II QRs laser is suitable for applications of photonic integrated circuit and bio-detection applications.
Microbial community structure and functional properties in permanently and seasonally flooded areas in Poyang Lake
Authors: Liu Yang , Ren Ze , Qu Xiaodong , Zhang Min , Yu Yang , Zhang Yuhang , Peng Wenqi
Published: March 2020

Water level fluctuations are an inherent feature regulating the ecological structures and functions of lakes. It is vital to understand the effects of water level fluctuations on bacterial communities and metabolic characteristics in freshwater lakes in a changing world. However, information on the microbial community structure and functional properties in permanently and seasonally flooded areas are lacking. Poyang Lake is a typical seasonal lake linked to the Yangtze River and is significantly affected by water level fluctuations. Bottom water was collected from 12 sampling sites: seven inundated for the whole year (inundated areas) and five drained during the dry season (emerged areas). High-throughput 16S rRNA gene sequencing was used to identify the bacterial communities. The results showed that the taxonomic structure and potential functions of the bacterial communities were significantly different between the inundated and emerged areas. Cyanobacteria was dominant in both areas, but the relative abundance of Cyanobacteria was much higher in the emerged areas than in the inundated areas. Bacterial communities were taxonomically sensitive in the inundated areas and functionally sensitive in the emerged areas. Nitrogen, phosphorus, and dissolved organic carbon concentrations and their ratios, as well as dissolved oxygen, played important roles in promoting the bacterial taxonomic and functional compositional patterns in both areas. According to the metabolic predictions based on 16S rRNA gene sequences, the relative abundance of functional genes related to assimilatory nitrate reduction in the emerged areas was higher than in the inundated areas, and the relative abundance of functional genes related to dissimilatory nitrate reduction in the inundated areas was higher. These differences might have been caused by the nitrogen differences between the permanently and seasonally flooded areas caused by intra-annual water level fluctuations. The relative abundance of functional genes associated with denitrification was not significantly different in the inundated and emerged areas. This study improved our knowledge of bacterial community structure and nitrogen metabolic processes in permanently and seasonally flooded areas caused by water level fluctuations in a seasonal lake.
Safety Profile of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: A Disproportionality Analysis of FDA Adverse Event Reporting System
Authors: Huang Jing , Meng Long , Yang Bing , Sun Shusen , Luo Zhigang , Chen Hong
Published: March 2020

Adverse event reports submitted to the US Food and Drug Administration (FDA) were analyzed to map the safety profile of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). We conducted a disproportionality analysis of the adverse events (AEs) of EGFR-TKIs (gefitinib, erlotinib, afatinib, osimertinib) by data mining using the FDA adverse event reporting system (AERS) database, and by calculating the reporting odds ratios (ROR) with 95% confidence intervals. The FDA AERS database contained 27,123 EGFR-TKI-associated AERs within the reporting period from January 1, 2004 to March 31, 2018. Thirty-three preferred terms (PTs) were selected for analysis, and significant RORs were most commonly observed in the skin, nail, gastrointestinal tract, hepatic, eyes, and lungs. Unexpected adverse drug reactions were found in the “intestinal obstruction” and “hypokalaemia” in gefitinib and erlotinib, “hyponatraemia” in gefitinib, erlotinib and afatinib, “alopecia”in erlotinib, “hair growth abnormal” in afatinib, but not in “nausea” and “vomiting” listed on drug labels. The results of this study are consistent with clinical observation, suggesting the usefulness of pharmacovigilance research should be corroborated with the real-world FAERS data.
Myocardial Minimal Damage After Rapid Ventricular Pacing – the prospective randomized multicentre MyDate-Trial
Authors: Semmler Verena , Deutschmann Clara , Haller Bernhard , Lennerz Carsten , Brkic Amir , Grebmer Christian , Blazek Patrick , Weigand Severin , Karch Martin , Busch Sonia , Kolb Christof
Published: March 2020

Therapy of choice for the primary and secondary prevention of sudden cardiac death is the implantation of an implantable cardioverter defibrillator (ICD). Whereas appropriate and inappropriate ICD shocks lead to myocardial microdamage, this is not known for antitachycardia pacing (ATP). In total, 150 ICD recipients (66 ± 12 years, 81.3% male, 93.3% primary prevention, 30.0% resynchronization therapy) were randomly assigned to an ICD implantation with or without intraoperative ATP. In the group with ATP, the pacing maneuver was performed twice, each time applying 8 impulses à 6 Volt x 1.0 milliseconds to the myocardium. High sensitive Troponin T (hsTnT) levels were determined prior to the implantation and thereafter. There was no significant difference in the release of hsTnT between the two randomization groups (delta TnT without ATP in median 0.010 ng/ml [min. −0.016 ng/ml–max. 0.075 ng/ml] vs. with ATP in median 0.013 ng/ml [min. −0.005–0.287 ng/ml], p = 0.323). Setting a hsTnT cutoff of 0.059 ng/dl as a regularly augmented postoperative hsTnT level, no relevant difference between the two groups regarding the postoperative hsTnT levels above this cutoff could be identified (without ATP n = 10 [14.7%] vs. with ATP n = 16 [21.9%], p = 0.287). There was no significant difference in the release of high sensitive Troponin between patients without intraoperative ATP compared to those with intraoperative ATP. Hence, antitachycardia pacing does not seem to cause significant myocardial microdamage. This may further support its use as a painless and efficient method to terminate ventricular tachycardia in high-risk patients.
Generation and Manipulation of Superoscillatory Hotspots Using Virtual Fourier Filtering and CTF Shaping
Authors: Sanjeev Abhijit , Shabairou Nadav , Attar Arrad , Scherbaum Daniel , Kapellner Yuval , Sinvani Moshe , Zalevsky Zeev
Published: March 2020

Superoscillation is a technique that is used to produce a spot of light (known as ‘hotspot’) which is smaller than the conventional diffraction limit of a lens and even smaller than the optical wavelength. Over the past few years, several techniques have been realized for the generation of the superoscillatory hotspot. In this article, for the first time to the best of our knowledge, we propose a novel and a more efficient technique for producing superoscillation in microscopic imaging by shaping the Coherent Transfer Function (CTF) of a lens via virtual Fourier filtering followed by a phase retrieval algorithm. We design and realize a phase mask which when placed at the pupil plane of a diffraction-limited lens produces a superoscillatory hotspot with sidelobes properly matched to the field of view (FOV) required in microscopic imaging applications, i.e. hotspot always coexists with huge intense rings known as ‘sidebands’ close to it and hence limiting the FOV. Our technique is also capable of extending the FOV with minimal loss in resolution of the hotspot generated and considerable ratio between the intensity of the hotspot to that of the side lobes while optimizing the obtainable FOV to the requirement of microscopy.
Modulation of glycine receptor single-channel conductance by intracellular phosphorylation
Authors: Moraga-Cid Gustavo , San Martín Victoria P. , Lara Cesar O. , Muñoz Braulio , Marileo Ana M. , Sazo Anggelo , Muñoz-Montesino Carola , Fuentealba Jorge , Castro Patricio A. , Guzmán Leonardo , Burgos Carlos F. , Zeilhofer Hanns U. , Aguayo Luis G. , Corringer Pierre-Jean , Yévenes Gonzalo E.
Published: March 2020

Glycine receptors (GlyRs) are anion-permeable pentameric ligand-gated ion channels (pLGICs). The GlyR activation is critical for the control of key neurophysiological functions, such as motor coordination, respiratory control, muscle tone and pain processing. The relevance of the GlyR function is further highlighted by the presence of abnormal glycinergic inhibition in many pathophysiological states, such as hyperekplexia, epilepsy, autism and chronic pain. In this context, previous studies have shown that the functional inhibition of  GlyRs containing the α3 subunit is a pivotal mechanism of pain hypersensitivity. This pathway involves the activation of EP2 receptors and the subsequent PKA-dependent phosphorylation of α3GlyRs within the intracellular domain (ICD), which decrease the GlyR-associated currents and enhance neuronal excitability. Despite the importance of this mechanism of glycinergic dis-inhibition associated with dysfunctional α3GlyRs, our current understanding of the molecular events involved is limited. Here, we report that the activation of PKA signaling pathway decreases the unitary conductance of α3GlyRs. We show in addition that the substitution of the PKA-targeted serine with a negatively charged residue within the ICD of α3GlyRs and of chimeric receptors combining bacterial GLIC and α3GlyR was sufficient to generate receptors with reduced conductance. Thus, our findings reveal a potential biophysical mechanism of glycinergic dis-inhibition and suggest that post-translational modifications of the ICD, such as phosphorylation, may shape the conductance of other pLGICs.
Identifying mutation hotspots reveals pathogenetic mechanisms of KCNQ2 epileptic encephalopathy
Authors: Zhang Jiaren , Kim Eung Chang , Chen Congcong , Procko Erik , Pant Shashank , Lam Kin , Patel Jaimin , Choi Rebecca , Hong Mary , Joshi Dhruv , Bolton Eric , Tajkhorshid Emad , Chung Hee Jung
Published: March 2020

Kv7 channels are enriched at the axonal plasma membrane where their voltage-dependent potassium currents suppress neuronal excitability. Mutations in Kv7.2 and Kv7.3 subunits cause epileptic encephalopathy (EE), yet the underlying pathogenetic mechanism is unclear. Here, we used novel statistical algorithms and structural modeling to identify EE mutation hotspots in key functional domains of Kv7.2 including voltage sensing S4, the pore loop and S6 in the pore domain, and intracellular calmodulin-binding helix B and helix B-C linker. Characterization of selected EE mutations from these hotspots revealed that L203P at S4 induces a large depolarizing shift in voltage dependence of Kv7.2 channels and L268F at the pore decreases their current densities. While L268F severely reduces expression of heteromeric channels in hippocampal neurons without affecting internalization, K552T and R553L mutations at distal helix B decrease calmodulin-binding and axonal enrichment. Importantly, L268F, K552T, and R553L mutations disrupt current potentiation by increasing phosphatidylinositol 4,5-bisphosphate (PIP2), and our molecular dynamics simulation suggests PIP2 interaction with these residues. Together, these findings demonstrate that each EE variant causes a unique combination of defects in Kv7 channel function and neuronal expression, and suggest a critical need for both prediction algorithms and experimental interrogations to understand pathophysiology of Kv7-associated EE.
Congruency and reactivation aid memory integration through reinstatement of prior knowledge
Authors: van Kesteren Marlieke T. R. , Rignanese Paul , Gianferrara Pierre G. , Krabbendam Lydia , Meeter Martijn
Published: March 2020

Building knowledge schemas that organize information and guide future learning is of great importance in everyday life. Such knowledge building is suggested to occur through reinstatement of prior knowledge during new learning, yielding integration of new with old memories supported by the medial prefrontal cortex (mPFC) and medial temporal lobe (MTL). Congruency with prior knowledge is also known to enhance subsequent memory. Yet, how reactivation and congruency interact to optimize memory integration is unknown. To investigate this question, we used an adapted AB-AC inference paradigm in combination with functional Magnetic Resonance Imaging (fMRI). Participants first studied an AB-association followed by an AC-association, so B (a scene) and C (an object) were indirectly linked through A (a pseudoword). BC-associations were either congruent or incongruent with prior knowledge (e.g. bathduck or hammer in a bathroom), and participants reported subjective B-reactivation strength while learning AC. Behaviorally, both congruency and reactivation enhanced memory integration. In the brain, these behavioral effects related to univariate and multivariate parametric effects in the MTL, mPFC, and Parahippocampal Place Area (PPA). Moreover, mPFC exhibited larger PPA-connectivity for more congruent associations. These outcomes provide insights into the neural mechanisms underlying memory enhancement, which has value for educational learning.
Dynamic FoxP2 levels in male zebra finches are linked to morphology of adult-born Area X medium spiny neurons
Authors: Kosubek-Langer Jennifer , Scharff Constance
Published: March 2020

The transcription factor FOXP2 is crucial for the formation and function of cortico-striatal circuits. FOXP2 mutations are associated with specific speech and language impairments. In songbirds, experimentally altered FoxP2 expression levels in the striatal song nucleus Area X impair vocal learning and song production. Overall FoxP2 protein levels in Area X are low in adult zebra finches and decrease further with singing. However, some Area X medium spiny neurons (MSNs) express FoxP2 at high levels (FoxP2high MSNs) and singing does not change this. Because Area X receives many new neurons throughout adulthood, we hypothesized that the FoxP2high MSNs are newly recruited neurons, not yet integrated into the local Area X circuitry and thus not active during singing. Contrary to our expectation, FoxP2 protein levels did not predict whether new MSNs were active during singing, assayed via immediate early gene expression. However, new FoxP2high MSNs had more complex dendrites, higher spine density and more mushroom spines than new FoxP2low MSNs. In addition, FoxP2 expression levels correlated positively with nucleus size of new MSNs. Together, our data suggest that dynamic FoxP2 levels in new MSNs shape their morphology during maturation and their incorporation into a neural circuit that enables the maintenance and social modulation of adult birdsong.
A Switchable High-Performance RF-MEMS Resonator with Flexible Frequency Generations
Authors: Chen Zeji , Kan Xiao , Yuan Quan , Wang Tianyun , Yang Jinling , Yang Fuhua
Published: March 2020

Resonators with multi-frequency generations at the device-level are highly desired in the future multi-band, reconfigurable, and compact wireless communications. In this work, a switchable radio frequency micro-electro-mechanical system (RF-MEMS) resonator with multiple electrodes is presented. The resonator is designed to operate at the whispering gallery modes (WGMs). Simultaneous excitations of the second to seventh modes with high Q values are implemented within a single device using a pair of electrodes for driving and sensing. For effective multi-frequency excitations, the electrode span angle is optimized. The frequencies of the 37 μm and 18 μm-radius resonators range from 53 MHz to 176 MHz and 112 MHz to 366 MHz, respectively. The Q values in each mode are over 104. Moreover, with the multi-electrode configurations, the specific mode can be enhanced with other modes suppressed. A more than 6 dB improvement of the spectrum peak is realized and the high Q values are maintained. A comprehensive theory is built up to clarify the driving/sensing principles under different electrode configurations. Furthermore, the air damping is found to have a significant effect on Q values for resonator with high stiffness vibrating in all the WGMs. The Q values in vacuum have at least two times improvement. The high-performance switchable resonator could dramatically reduce the power consumption, simplify the processing circuits, and occupy less footprint, which has great potential applications in future advanced RF front end systems.
Metabolomics-based study reveals the effect of lead (Pb) in the culture environment on Whitmania pigra
Authors: Luo Xuemei , Meng Jieqin , Chen Xiufen , Cheng Liangke , Yan Shaopeng , Gao Luying , Xue Miao , Yang Yaojun
Published: March 2020

Whitmania pigra, called Mahuang (MH) in Chinese, has been used as a traditional Chinese medicine for many years and is susceptible to Pb exposure in aquaculture environments. To understand the impact of Pb in the culture environment on MHs, we carried out a 50-day culture of MHs in environments with different levels of Pb pollution. Then, tissue samples of MHs reared in the different Pb-polluted environments were collected and analysed by UPLC-Q/TOF-MS. The results showed that the Pb residue in MHs increased with increasing Pb in the culture environment. There was no significant difference in MH Pb content (P < 0.05) between the low-Pb residue group (PbL) and the blank control group (BC), and those of the middle-Pb residue group (PbM) and the high-Pb residue group (PbH) were significantly different from that of the BC group. Metabolomics results showed significant changes in 24 metabolites in the PbL, PbM and PbH groups, some of which were dose-dependent. These metabolites were mainly lipids, nucleotides, and dipeptides, which are involved in metabolic pathways such as glycerophospholipid metabolism, sphingolipid metabolism, and nucleotide metabolism. Overall, the results proved that metabolomics can be an effective tool to understand the effects of Pb on the metabolic responses of MHs.
Introspective and Neurophysiological Measures of Mind Wandering in Schizophrenia
Authors: Iglesias-Parro S. , Soriano M. F. , Prieto M. , Rodríguez I. , Aznarte J. I. , Ibáñez-Molina A. J.
Published: March 2020

Patients with schizophrenia have often been considered to be “in their own world”. However, this casual observation has not been proven by scientific evidence so far. This can be explained because scientific research has usually addressed cognition related to the processing of external stimuli, but only recently have efforts been made to explain thoughts, images and feelings not directly related to the external environment. This internally directed cognition has been called mind wandering. In this paper, we have explored mind wandering in schizophrenia under the hypothesis that a predominance of mind wandering would be a core dysfunction in this disorder. To this end, we collected verbal reports and measured electrophysiological signals from patients with schizophrenia spectrum disorders and matched healthy controls while they were presented with segments of films. The results showed that mind wandering was more frequent in patients than in controls. This higher frequency of mind wandering did not correlate with deficits in attentional, memory or executive functioning. In addition, mind wandering in patients was characterized by a different pattern of Electroencephalography (EEG) complexity in patients than in controls, leading to the suggestion that mind wandering in schizophrenia could be of a different nature. These findings could have relevant implications for the conceptualization of this severe mental disorder.