bluuebunny/crossref_metadata_2025 huggingface dataset:
Constraining organic matter composition and dynamics as a dominant driver of hypoxic blackwater risk during river Murray floodplain inundation
Authors: Gibbs Matthew S. , Wallace Todd , Mosley Luke M.
Published: February 2022

The ecology of floodplain ecosystems evolved according to the historical frequency and extent of inundation. In many dryland rivers, inundation frequency has reduced due to regulation, competition for water resources and climate change. In some rivers infrastructure has been constructed to enable temporary rises in water level and more frequent floodplain inundation, delivering environmental water to ecosystems that are dependent on surface water. During such events, the release of dissolved organic carbon (DOC) from inundated plant material may result in depletion of dissolved oxygen (DO). If the rate of DO depletion exceeds re‐aeration, hypoxic conditions can occur. Models have been developed to represent these processes, however, there is a wide range of chemical and biological interactions, and hence model parameters, involved. The aim of this research was: (1) identify the dominant parameters through sensitivity analysis, (2) design and implement a field monitoring program to quantify the inherent variability in those parameters, and (3) translate that input variability into the modelled DO, ultimately to support risk management decisions when planning delivery of environmental water. The results indicated that the mass of organic matter on a floodplain had the greatest impact on the modelled DO concentrations. Based on the field monitoring results, the steady state load of organic matter, that is, when the accumulation and decay rates are equal, was estimated, and vegetation mapping used to apply the field monitoring results across the floodplain for a 206 km reach of river of the River Murray, Australia. The model results from multiple, cumulative, operations identified one particular high‐risk operational site. The results are useful to prioritize monitoring effort to focus on the most sensitive model parameters and indicate that the likelihood of hypoxic conditions can be reduced through slower rates of inundation and timing events to coincide with periods with lower water temperature. The methodology developed can be transferred to other sites where hypoxic conditions are a potential outcome associated with delivery of environmental water.
Dose and exposure route analyses inform relationships between liver steatosis and 2‐amino‐2‐methyl‐1‐propanol: Implications for hazard characterization
Authors: Garnick Lindsey , Bates Christopher , Massarsky Andrey , Spencer Pamela , Sura Priyanka , Monnot Andrew D. , Maier Andrew
Published: February 2022

2‐Amino‐2‐methyl‐1‐propanol (AMP™) is widely used as a neutralizer/pH stabilizer in personal care products (PCPs); however, the potential health implications of dermal AMP exposure remain to be fully elucidated. Consequently, an in‐depth analysis was performed to determine if PCPs containing AMP pose an elevated risk in humans under the intended use conditions. Animal studies have shown that at high doses, oral AMP exposure could lead to liver steatosis; thus, this study focused on hepatotoxicity. Our assessment revealed that the derived margin of exposure (MoE) values for AMP‐containing PCPs were above 100, indicating that dermal exposure to AMP is unlikely to present an elevated risk of hepatotoxicity. Further, mode of action (MOA) analysis was conducted to elucidate the potential mechanisms underlying the observed hepatotoxicity in animal studies. Our analysis proposed that AMP interferes with the CDP‐choline pathway in hepatocytes via the inhibition of one or more enzymes integral to the pathway and/or the replacement of choline in the assembly of the phospholipid unit. Ultimately, these events halt the lipid export via very low‐density lipoproteins, which can subsequently develop into fatty liver accompanied by hepatotoxicity and other pathological changes if AMP exposure persists at sufficiently high doses. MOA analysis corroborated that dermal exposure to AMP expected from use of PCPs is highly unlikely to result in toxicologically significant systemic concentrations of AMP and thus hepatotoxicity. We concluded that dermal exposure to AMP in PCPs is not anticipated to result in an increased risk of hepatotoxicity.
Complex machine learning model needs complex testing: Examining predictability of molecular binding affinity by a graph neural network
Authors: Nikolaienko Tymofii , Gurbych Oleksandr , Druchok Maksym
Published: February 2022

Drug discovery pipelines typically involve high‐throughput screening of large amounts of compounds in a search of potential drugs candidates. As a chemical space of small organic molecules is huge, a “navigation” over it urges for fast and lightweight computational methods, thus promoting machine‐learning approaches for processing huge pools of candidates. In this contribution, we present a graph‐based deep neural network for prediction of protein‐drug binding affinity and assess its predictive power under thorough testing conditions. Within the suggested approach, both protein and drug molecules are represented as graphs and passed to separate graph sub‐networks, then concatenated and regressed towards a binding affinity. The neural network is trained on two binding affinity datasets—PDBbind and data imported from RCSB Protein Data Bank. In order to explore the generalization capabilities of the model we go beyond traditional random or leave‐cluster‐out techniques and demonstrate the need for more elaborate model performance assessment – six different strategies for test/train data partitioning (random, time‐ and property‐arranged, protein‐ and ligand‐clustered) with a k‐fold cross‐validation are engaged. Finally, we discuss the model performance in terms of a set of metrics for different split strategies and fold arrangement. Our code is available at https://github.com/SoftServeInc/affinity-by-GNN.
Does “who I am” influence “how I feel”? Cultural identity and mental health among Hong Kong Chinese adolescents
Authors: Wu Qiaobing , Ou Ying
Published: February 2022

Securing a clear sense of identity is a critical issue in adolescence, yet the role that cultural identity plays in the well‐being of youths remains unclear. This study aims to examine the relationship between cultural identity and mental health among three groups of adolescents in Hong Kong with different residential backgrounds. Data came from a cross‐sectional survey with 2180 4th–9th grade students in Hong Kong. Cultural identity was assessed by whether the youths identify themselves as local Hong Kong people, mainland Chinese, both Hong Kong and mainland Chinese, or confused about which group to belong to. Mental health was assessed by self‐esteem, mental well‐being, happiness, social anxiety, and depression. Multiple linear regression was performed to examine the relationship between cultural identity and mental health, adjusting for sociodemographic variables. The regression results suggested adolescents with confused cultural identity scored lower in all positive indicators of mental health compared with those with a clear cultural identification. No significant association was found between cultural identity and social anxiety/depression. Uncertainty in cultural identification may be detrimental for the mental health of adolescents living in a multicultural society. Interventions may consider cultivating clear cultural identities among adolescents to promote their mental health.
Sex‐specific vulnerability to depressive symptoms across adolescence and during the COVID‐19 pandemic: The role of the cingulum bundle
Authors: Chahal Rajpreet , Ho Tiffany C. , Miller Jonas G. , Borchers Lauren R. , Gotlib Ian H.
Published: February 2022

Background

Females are at higher risk for developing depression during adolescence than are males, particularly during exposure to stressors like the COVID‐19 pandemic. Examining structural connections between brain regions involved in executive functioning may advance our understanding of sex biases in stress and depression. Here, we examined the role of the cingulum bundle in differentiating trajectories of depressive symptoms in males and females across adolescence and during the pandemic.

Methods

In a longitudinal study of 214 youth (121 females; ages 9–13 years at baseline), we examined whether fixel‐based properties of the cingulum bundle at baseline predict changes in females' and males' severity of depressive symptoms across four timepoints (4–7 years) in adolescence, including during the COVID‐19 pandemic. We also tested whether cingulum properties predict self‐reported resilience and stress during the pandemic.

Results

Females had lower fiber density and cross‐section (FDC) of the cingulum than did males, a neural pattern that predicted greater increases in depressive symptoms, lower resilience, and higher stress during the COVID‐19 pandemic. Cingulum morphometry predicted changes in depressive trajectories in females, but not in males; specifically, females with lower FDC had significant increases in symptoms throughout adolescence, whereas females with higher cingulum FDC did not. Conversely, males had low, stable depressive symptoms throughout adolescence and higher resilience and lower stress during the pandemic compared to females. Higher cingulum FDC predicted higher resilience and lower stress in both sexes.

Conclusions

In adults, the cingulum has been implicated in sex differences in stress reactivity. We show that in adolescents, the cingulum reflects sex differences in reports of stress and resilience that might contribute to the increased risk of stress‐related mood disorders in females. Adolescent females might benefit from cognitive interventions that strengthen the structural properties of the cingulum and increase their perceived resilience during periods of adversity and disruption.
Dynamic changes of serum metabolites associated with infection and severity of patients with acute hepatitis E infection
Authors: Wu Jian , Xu Yanping , Cui Yubao , Bortolanza Mariza , Wang Minjie , Jiang Bin , Yan Meina , Liang Wei , Yao Yiwen , Pan Qiaoling , Yang Jinfeng , Yu Jiong , Wang Dawei , Cao Hongcui , Li Lanjuan
Published: February 2022

Dynamic changes in metabolites may affect liver disease progression, and provide new methods for predicting liver damage. We used ultra‐performance liquid chromatography–mass spectroscopy to assess serum metabolites in healthy controls (HC), and patients with acute hepatitis E (AHE) or hepatitis E virus acute liver failure (HEV‐ALF). The principal component analysis, partial least squares discriminant analysis, and discriminant analysis of orthogonal projections to latent structures models illustrated significant differences in the metabolite components between AHE patients and HCs, or between HEV‐ALF and AHE patients. In pathway enrichment analysis, we further identified two altered pathways, including linoleic acid metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis, when comparing AHE patients with HCs. Linoleic acid metabolism and porphyrin and chlorophyll metabolism pathways were significantly different in HEV‐ALF when compared with AHE patients. The discriminative performances of differential metabolites showed that taurocholic acid, glycocholic acid, glycochenodeoxycholate‐3‐sulfate, and docosahexaenoic acid could be used to distinguish HEV‐ALF from AHE patients. The serum levels of glycocholic acid, taurocholic acid, deoxycholic acid glycine conjugate, and docosahexaenoic acid were associated with the prognosis of HEV‐ALF patients. Dynamic changes in serum metabolites were associated with AHE infection and severity. The identified metabolites can be used to diagnose and predict the prognosis of HEV‐ALF.
Record summers in Europe: Variations in drought and heavy precipitation during 1901–2018
Authors: Hänsel Stephanie , Hoy Andreas , Brendel Christoph , Maugeri Maurizio
Published: February 2022

During the last 20 years some very hot and dry summers affected Europe, resulting in regionally record‐breaking high temperature or low precipitation values. Long‐term changes of such extremely hot and dry summers are of great relevance for our society, as they are connected with manifold negative impacts on human society, natural ecosystems, and diverse economic sectors. Long‐term variations in drought and five record drought summer half years are studied based on 63 stations across Europe with high‐quality precipitation and temperature time series spanning the period 1901–2018. Eight drought indices are deployed to analyse drought intensity, frequency, and duration; four of them purely precipitation‐based and four integrating potential evapotranspiration in the computation. Additionally, three heavy precipitation indices and simultaneous increases in drought and heavy precipitation are studied. The five driest summer half years over Europe are identified (1947, 2018, 2003, 1921, and 1911). They are analysed by aggregating eight drought indices into the aggregated drought evaluation index (ADE) for five subregions. The ADE shows increasing summer drought conditions over most of Europe, except for some stations in northern Europe. The increase in drought conditions during the warm part of the year is particularly pronounced for indices integrating evapotranspiration in their definition. At the same time, the intensity of heavy precipitation events shows a positive trend, as well as an increased contribution to total precipitation. Several stations in central Europe show simultaneously increasing drought conditions and increasing heavy precipitation events. This increases the risks connected with precipitation extremes.
Dexmedetomidine inhibits the growth and metastasis of esophageal cancer cells by down‐regulation of lncRNA MALAT1
Authors: Zhang Wei , Zhang Li , Cai Xiao‐Jun , Li Dong , Cao Feng‐Jun , Zuo Zhi‐Gang , Song Ying , Yu Xiong‐Jie , Liu Shan
Published: February 2022

This study aims to evaluate the effect of dexmedetomidine (DEX)—on esophageal cancer (EC) via regulating long noncoding RNA (lncRNA) metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1). The effect of DEX on MALAT1 expression and EC cell viability was detected. EC cells were divided into Blank, DEX, scrambled/MALAT1 siRNA, and DEX + control/MALAT1 groups, followed by a series of experiments including quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR), western blotting, 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide (MTT), Annexin V‐FITC/PI staining, wound healing, and Transwell assays. Additionally, mice were subjected to the subcutaneous injection of Eca109 cells transfected by control/MALAT1 activation lentiviral vector to construct EC models with the DEX treatment, and then the tumor volume and the expression of Ki‐67 and active caspase‐3 were determined. DEX reduced the expression of MALAT1 in EC cells in a dose‐dependent manner. DEX inhibited the viability of EC cells, but increased the cell apoptosis, which, however, was reversed by MALAT1 overexpression. Moreover, MALAT1 overexpression abolished the inhibitory effect of DEX on the epithelial–mesenchymal transition (EMT) of EC cells, with enhanced migration and invasion. Furthermore, DEX succeeded in decreasing the tumor volume with the down‐regulation of MALAT1. In comparison with the DEX group, mice in the DEX + MALAT1 group had larger tumors, with the up‐regulation of Ki‐67 and the down‐regulation of active caspase‐3. DEX can reduce the expression of MALAT1 in EC cells, thereby inhibiting the proliferation, invasion and migration, as well as EMT, and promoting the apoptosis of EC cells.
CERS6‐AS1 promotes cell proliferation and represses cell apoptosis in pancreatic cancer via miR‐195‐5p/WIPI2 axis
Authors: Gao Kan‐Fei , Zhao Yu‐Fang , Liao Wu‐Jun , Xu Guo‐Li , Zhang Jian‐Dong
Published: February 2022

Pancreatic cancer (PC) is a lethal malignancy that threatens human health. Long noncoding RNAs (lncRNAs) act as important mediators in PC development. Our study aimed to investigate the function and mechanism of lncRNA ceramide synthase 6 antisense RNA 1 (CERS6‐AS1) in PC. As shown by RT‐qPCR, CERS6‐AS1 was significantly upregulated in PC cells and tissues. Silencing CERS6‐AS1 suppressed PC cell viability and proliferation while enhancing cell apoptosis according to colony formation assays, EdU assays, and flow cytometry analyses. Mechanistically, CERS6‐AS1 interacted with miR‐195‐5p to elevate the expression level of the WD repeat domain phosphoinositide interacting 2 (WIPI2), which is a downstream target gene of miR‐195‐5p in PC. Moreover, miR‐195‐5p expression was negatively associated with CERS6‐AS1 expression (or WIPI2 expression) in PC tissues. Rescue assays revealed that WIPI2 overexpression rescued the effects of CERS6‐AS1 deficiency on cell viability, proliferation, and apoptosis. In summary, CERS6‐AS1 facilitates PC cell proliferation while inhibiting PC cell apoptosis by upregulating WIPI2 via miR‐195‐5p. This study might provide promising insight into the role of CERS6‐AS1 in PC development.
Sentinel Lymph Node Identification in Cutaneous Head & Neck Cancer ‐ Lymphoscintigraphy Late Phase
Authors: Hirshoren Nir , abd el Qadir Narmeen , Weinberger Jeffrey M. , Eliashar Ron , Ben‐Haim Simona
Published: February 2022

Objective

Sentinel node (SN) biopsy following lymphoscintography is recommended for high‐risk cutaneous malignancies. Herein, we investigate different lymphoscintography phases, focusing on the importance of the late static phase and the resultant discovery of distal echelon solitary positive sentinel nodes that would otherwise have been overlooked.

Methods

In this retrospective cohort study, conducted in a tertiary referral medical center, we assessed SN localization and time from tracer injection to SN identification on lymphoscintigraphy. Findings on scan were compared with SN found in the surgical field, and with the final pathological investigation.

Results

Seventy‐three patients, undergoing SN biopsy for head and neck skin malignancies, were investigated. Most patients were male (n = 50). The average age was 65.7 (±15.7) years and the average follow‐up time was 29.1 (±22.4) months. Overall, 101 SNs were histologically investigated, demonstrating 7 positive SN. Eleven patients (15%) benefited from the late lymphoscintigraphy phase. In four studies, an SN was identified only in the late static phase, one of which was positive for the disease. In seven patients, SN was identified in the early phase with additional, different, SN on the late phase, one of which was positive for the disease. Comparing the yield (positive SNs) of early versus late phases, demonstrated the same importance (p = 0.275).

Conclusions

The late lymphoscintigraphy phase has a crucial role in high‐risk HN cutaneous cancer.

Level of Evidence

3 Laryngoscope, 132:2164–2168, 2022
Finite‐time and fixed‐time stabilization by dual closed‐loop controllers
Authors: Michalak Anna , Nowakowski Andrzej
Published: February 2022

The problem we consider is to find a dual closed‐loop controller which will steer the trajectory starting at point to zero in a finite time (and in a fixed time in the second part of the article). We assume that our system is asymptotic stable at the origin, and we give the sufficient conditions for the finite and fixed‐time stability. In the second part, we present a new tool for effective finding the dual closed‐loop control.
Influence of carbon structures on the properties and photodegradation of LDPE/LLDPE films
Authors: López‐Martínez Erick Daniel , Martínez‐Colunga Juan Guillermo , Ramírez‐Vargas Eduardo , Sanchez‐Valdes Saul , Ramos ‐de Valle Luis Francisco , Benavides‐Cantu Roberto , Rodríguez‐Gonzalez Jose Alberto , Mata‐Padilla Jose Manuel , Cruz‐Delgado Victor Javier , Borjas‐Ramos Jose Javier , Da Silva Luciano
Published: February 2022

The effect of different carbon structures on the properties of low density polyethylene film and linear low density polyethylene blends (LDPE/LLDPE) subjected to artificial weathering, was studied. The carbon structures used were carbon black (CB), multi wall carbon nanotubes (MWCNT) and Graphene nanoparticles (GNP), at various loadings: 0.05, 0.1, 0.3, 0.5, 1.0, and 2 wt%. The PE‐Carbon structure composite films were characterized by optical microscopy (MOP), Haze, visible light transmission, UV–visible, thermogravimetric analysis (TGA), melt flow determinations (MFI) and tensile properties. Weathering measurements were evaluated in a QUV panel chamber with UV fluorescent lamps. The films degradation was analyzed following the change in carbonyl index of FTIR spectra, mechanical properties, and molecular weight. A noticeable better dispersion of CB and CNT particles in polyethylene matrix was observed compared with GNP. MWCNTs and CB produced high Haze and low visible light transmission. Thermal stability measured by TGA increased with the presence of GNP and CB. The crystallinity, melting, and crystallinity temperature (Tm and Tc) of the polymers increased with MWCNT and GNP. All the films with carbon structures presented an increase in the modulus of elasticity, with CB giving the highest elastic modulus. Artificial weathering of films with carbon structures showed that CB particles and CNT provided the highest UV protection to polyethylene, with a noticeable increase in low molecular weights and a retention in tensile strength and elongation at break which was reflected in maintaining their flexibility. Films with CNT showed the least significant changes in their properties, being more resistant to photo‐degradation.
Monodispersed polymer particles with tunable surface structures: Droplet microfluidic‐assisted fabrication and biomedical applications
Authors: Mao Xi , Wang Mian , Jin Shaohong , Rao Jingyi , Deng Renhua , Zhu Jintao
Published: February 2022

Polymer particles are key materials in various biomedical applications, including drug delivery, cellular immunity, cell capture, biochip, etc. Droplets produced by microfluidics have been widely applied as templates for the fabrication of polymer particles with controllable sizes and narrow size distributions. Compared to smooth polymer particles, those with surface microstructures (e.g., tentacles, bubbles, wrinkles and pits) are more attractive due to their increased surface area and biomimetic structural characteristics. In this review, we summarized representative methods for the preparation of monodispersed polymer particles with various surface microstructures based on droplet microfluidics, as well as their typical bioapplications in drug delivery, cellular immunity and cell capture. Finally, the current challenges and further development in this research area are discussed.
Intersectionality in cancer care: A systematic review of current research and future directions
Authors: Kelly‐Brown Joseph , Palmer Kelly Elizabeth , Obeng‐Gyasi Samilia , Chen JC , Pawlik Timothy M.
Published: February 2022

Objectives

The objective of the current review was to synthesize the literature on intersectionality relative to disparities across the cancer care continuum. A model to support future intersectional cancer research was proposed.

Methods

Web‐based discovery services and discipline‐specific databases were queried for both peer‐reviewed and gray literature. Study screening and data extraction were facilitated through the Covidence software platform.

Results

Among 497 screened studies, 28 met study inclusion criteria. Most articles were peer‐reviewed empirical studies (n = 22) that focused on pre‐diagnosis/screening (n = 19) and included marginalized racial/ethnic (n = 22) identities. Pre‐cancer diagnosis, sexual orientation and race influenced women's screening and vaccine behaviors. Sexual minority women, particularly individuals of color, were less likely to engage in cancer prevention behaviors prior to diagnosis. Race and socioeconomic status (SES) were important factors in patient care/survivorship with worse outcomes among non‐white women of low SES. Emergent themes in qualitative results emphasized the importance of patient intersectional identities, as well as feelings of marginalization, fears of discrimination, and general discomfort with providers as barriers to seeking cancer care.

Conclusions

Patients with intersectional identities often experience barriers to cancer care that adversely impact screening, diagnosis, treatment, as well as survivorship. The use of an “intersectional lens” as a future clinical and research framework will facilitate a more multidimensional and holistic approach to the care of cancer patients.
Evaluating the Capacitive Response in Metal Halide Perovskite Solar Cells
Authors: Taukeer Khan Mohd , Khan Firoz , Al‐Ahmed Amir , Ahmad Shahzada , Al‐Sulaiman Fahad
Published: February 2022

The perovskites solar cells (PSCs) is composed of multifaceted device architecture and involve complex charge extraction (both electronic and ionic), this makes the task demanding to unlock the origin of the different physical process that occurs in a PSC. The capacitance in PSCs depends on several external perturbations including frequency, illumination, temperature, applied bias, and importantly on the interface modification of perovskites/charge selective contact. Arguably, different features including interfacial and bulk; ionic, and electronic charge transport in PSCs occur at different time scales. Capacitance spectroscopy is a prevailing technique to unravel the various physical phenomenon that occurs in a PSC at different time scales. A deeper knowledge of the capacitive response of a PSCs is essential to understand the charge carrier kinetics and unlock the device physics. This work highlights the capacitive response of PSCs and its application to unlock the device physics which is essential for the further optimization and improvement of the device performance.
Hybrid DC Circuit Breaker Using a SiC‐Semiconductor Module at 1 kA Interruption
Authors: Kubo Shoya , Sato Shunsuke , Yasuoka Koichi , Zen Shungo
Published: February 2022

Hybrid direct current circuit breakers (DCCBs) have become prominent because of their low on‐state power dissipation and small arc erosion compared with conventional semiconductor and mechanical circuit breakers (CBs). After a fault occurs in a DC circuit, the current commutates from the mechanical contacts to the semiconductor devices of the hybrid DCCB, and finally, the current is interrupted by the semiconductor devices. Thus, a low turn‐on voltage or a low on‐state resistance of the devices is needed to reduce the commutation time and power dissipation of the current interruption. This paper presents a comparison of DCCB performances metrics, such as the maximum interruption current, power dissipation, and junction temperature, using a silicon carbide metal‐oxide‐field‐effect transistor (SiC‐MOSFET) and silicon insulated‐gate‐bipolar transistor (Si‐IGBT) module. An interruption of 1.1 kA was achieved in 4.3 ms using the SiC‐MOSFET module of which rated current was 444 A. The junction temperature after the interruption was determined to be 275°C, which exceeded the maximum junction temperature of 175°C. In the case of the Si‐IGBT module of which rated current was 1110 A, the maximum interrupting current was limited to 900 A; however, the maximum junction temperature was 41°C. © 2022 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC.
Realist International Theory and the Military
Authors: Schmidt Brian C
Published: February 2022

Realism is generally seen as one of the most influential theories of international politics. Military and foreign policy officials adhere to the apparent timeless insights of realism. They stress the importance of power, especially military power, and the need to ensure the survival and security of the state. Ontologically, realism depicts a hostile world of power-seeking states. Some realists explain this in terms of human nature while others emphasize the anarchical structure of international politics. The chapter begins with a brief overview of the development of realist theory from Thucydides, who was an Athenian military official, to the present day. The next section explains the various epistemological, methodological, and ontological positions that realists hold. Next, the common elements that comprise the essence of realism will be identified: rationality, statism, survival, and self-help (the three S’s). In the third section, the differences between two variants of realist theory, classical and structural realism, are explained. In the conclusion the timeless wisdom of realism is revisited by considering the rise of China and the implications this has for international order.
Defective IGF-1 prohormone N-glycosylation and reduced IGF-1 receptor signaling activation in congenital disorders of glycosylation
Authors: Di Patria Laura , Annibalini Giosuè , Morrone Amelia , Ferri Lorenzo , Saltarelli Roberta , Galluzzi Luca , Diotallevi Aurora , Bocconcelli Matteo , Donati Maria Alice , Barone Rita , Guerrini Renzo , Jaeken Jaak , Stocchi Vilberto , Barbieri Elena
Published: February 2022

The insulin-like growth factor-1 (IGF-1) signaling pathway is crucial for the regulation of growth and development. The correct processing of the IGF-1Ea prohormone (proIGF-1Ea) and the IGF-1 receptor (IGF-1R) peptide precursor requires proper N-glycosylation. Deficiencies of N-linked glycosylation lead to a clinically heterogeneous group of inherited diseases called Congenital Disorders of Glycosylation (CDG). The impact of N-glycosylation defects on IGF-1/IGF-1R signaling components is largely unknown. In this study, using dermal fibroblasts from patients with different CDG [PMM2-CDG (n = 7); ALG3-CDG (n = 2); ALG8-CDG (n = 1); GMPPB-CDG (n = 1)], we analyzed the glycosylation pattern of the proIGF-1Ea, IGF-1 secretion efficiency and IGF-1R signaling activity. ALG3-CDG, ALG8-CDG, GMPPB-CDG and some PMM2-CDG fibroblasts showed hypoglycosylation of the proIGF-1Ea and lower IGF-1 secretion when compared with control (CTR). Lower IGF-1 serum concentration was observed in ALG3-CDG, ALG8-CDG and in some patients with PMM2-CDG, supporting our in vitro data. Furthermore, reduced IGF-1R expression level was observed in ALG3-CDG, ALG8-CDG and in some PMM2-CDG fibroblasts. IGF-1-induced IGF-1R activation was lower in most PMM2-CDG fibroblasts and was associated with decreased ERK1/2 phosphorylation as compared to CTR. In general, CDG fibroblasts showed a slight upregulation of Endoplasmic Reticulum (ER) stress genes compared with CTR, uncovering mild ER stress in CDG cells. ER-stress-related gene expression negatively correlated with fibroblasts IGF-1 secretion. This study provides new evidence of a direct link between N-glycosylation defects found in CDG and the impairment of IGF-1/IGF-1R signaling components. Further studies are warranted to determine the clinical consequences of reduced systemic IGF-1 availability and local activity in patients with CDG.
Genome sequences of Arthrobacter spp. that use a modified sulfoglycolytic Embden–Meyerhof–Parnas pathway
Authors: Kaur Arashdeep , van der Peet Phillip L. , Mui Janice W.-Y. , Herisse Marion , Pidot Sacha , Williams Spencer J.
Published: February 2022

Sulfoglycolysis pathways enable the breakdown of the sulfosugar sulfoquinovose and environmental recycling of its carbon and sulfur content. The prototypical sulfoglycolytic pathway is a variant of the classical Embden–Meyerhof–Parnas (EMP) pathway that results in formation of 2,3-dihydroxypropanesulfonate and was first described in gram-negative Escherichia coli. We used enrichment cultures to discover new sulfoglycolytic bacteria from Australian soil samples. Two gram-positive Arthrobacter spp. were isolated that produced sulfolactate as the metabolic end-product. Genome sequences identified a modified sulfoglycolytic EMP gene cluster, conserved across a range of other Actinobacteria, that retained the core sulfoglycolysis genes encoding metabolic enzymes but featured the replacement of the gene encoding sulfolactaldehyde (SLA) reductase with SLA dehydrogenase, and the absence of sulfoquinovosidase and sulfoquinovose mutarotase genes. Excretion of sulfolactate by these Arthrobacter spp. is consistent with an aerobic saprophytic lifestyle. This work broadens our knowledge of the sulfo-EMP pathway to include soil bacteria.
Utility of indocyanine green angiography in delaying breast reconstruction postmastectomy
Authors: Nguyen Chu Luan , Liu Yi Hui Angella , Lata Tahmina , Easwaralingam Neshanth , Seah Jue Li , Chan Carina , Cao Felicia , Azimi Farhad , Mak Cindy , Pulitano Carlo , Warrier Sanjay Kumar
Published: February 2022

Background

Perfusion mapping with indocyanine green angiography (ICGA) in breast reconstruction can change intraoperative plans and reduce the risk of flap necrosis. We evaluated the utility of ICGA in the decision to delay reconstruction postmastectomy and its predictive power for necrosis.

Methods

Single-institution retrospective study of implant-based breast reconstructions following mastectomy using ICGA from 2015 to 2021. A decision was made to proceed with immediate reconstruction or delay reconstruction based on clinical assessment and perfusion analysis. Incidence of complications in the immediate and delayed cohorts were assessed. Intraoperative ICGA perfusion values were correlated with postoperative outcomes to calculate diagnostic accuracy.

Results

Three hundred twenty breast reconstructions were performed. Two hundred fifty-nine of these underwent immediate reconstruction, while 61 underwent delayed reconstruction due to poor perfusion. Median time between mastectomy and delayed reconstruction was 7.3 days (range, 4–21 days). All 8 cases (3.1%) of necrosis were in the immediate cohort. Cases of necrosis had significantly lower intraoperative ICGA perfusion values compared to cases without necrosis (absolute values 13.1 versus 27.1 units, p = 0.017). Increasing our ICGA cut-off score for necrosis from 14 to 22 units would have increased sensitivity from 63 to 100% but reduced specificity from 70 to 48%.

Conclusions

Delayed breast reconstruction due to poor perfusion on ICGA resulted in no cases of necrosis. A higher ICGA cut-off score for predicting necrosis is more sensitive but less specific. ICGA is useful as a supplement rather than a substitute for clinical assessment in flap perfusion evaluation.

Level of Evidence Level III, Risk / Diagnostic Study.
Reef complexity influences distribution and habitat choice of the corallivorous seastar Culcita schmideliana in the Maldives
Authors: Montalbetti Enrico , Fallati Luca , Casartelli Marco , Maggioni Davide , Montano Simone , Galli Paolo , Seveso Davide
Published: February 2022

The cushion seastar Culcita schmideliana has gained major attention in the last few years because of its selective predation on juvenile corals, as well as its ability to generate large demographic assemblages, causing delays in coral recovery after large mortality events in the Republic of Maldives. However, a lack of data regarding the factors affecting its distribution and habitat selection still persists in this area. Here, we adopted a novel approach in the study of corallivorous seastar habitat selection that combined ecological and digital photogrammetry data. In this regard, we tested 3 different parameters as factors influencing seastar habitat choice in the South-East region of Faafu Atoll, Republic of Maldives, namely prey abundance, Linear Rugosity Index (LRI), and Average Slope (AS). The analysis of selectivity coefficient (Ei) of seastars for different habitat types showed a preference for reefs characterized by medium AS values (Ei = 0.268), a LRI included between 2 and 2.5 (Ei = 0.180), and a juvenile coral density ranging between 10 and 20 colonies m−2 (Ei = 0.154). A multiple linear regression analysis showed that different AS and LRI values explained the 43.1% (R2 = 0.431, P = 0.007) and the 48.1% (R2 = 0.481, P = 0.024) of variance in seastars abundance, respectively, while juvenile coral densities did not significantly affect this (R2 = 0.132, P = 0.202). These results provide new information on the distribution and behaviour of an important corallivore of Maldivian reefs, such as C. schmideliana.
Correlation between olfactory function, age, sex, and cognitive reserve index in the Italian population
Authors: Masala Carla , Cavazzana Annachiara , Sanna Fabrizio , Cecchini Maria Paola , Zanini Alice , Gasperi Flavia , Menghi Leonardo , Endrizzi Isabella , Borgogno Monica , Drago Serena , Cantone Elena , Ciofalo Andrea , Macchi Alberto , Monti Giulia , Parma Valentina , Piochi Maria , Pinna Ilenia , Torri Luisa , Cabrino Giorgia , Ottaviano Giancarlo , Pendolino Alfonso Luca , Pignatelli Angela , Pighin Faride , Bochicchio Vincenzo , Motta Gaetano , Fontana Giorgia , Pasquariello Benedetta , Cavaliere Carlo , Iacono Valentina , Hummel Thomas
Published: February 2022

Purpose

Loss of smell decreases the quality of life and contributes to the failure in recognizing hazardous substances. Given the relevance of olfaction in daily life, it is important to recognize an undiagnosed olfactory dysfunction to prevent these possible complications. Up to now, the prevalence of smell disorders in Italy is unknown due to a lack of epidemiological studies. Hence, the primary aim of this study was to evaluate the prevalence of olfactory dysfunction in a sample of Italian adults.

Methods

Six hundred and thirty-three participants (347 woman and 286 men; mean age 44.9 years, SD 17.3, age range 18–86) were recruited from 10 distinct Italian regions. Participants were recruited using a convenience sapling and were divided into six different age groups: 18–29 years (N = 157), 30–39 years (N = 129), 40–49 years (N = 99), 50–59 years (N = 106), > 60 years (N = 142). Olfactory function, cognitive abilities, cognitive reserve, and depression were assessed, respectively, with: Sniffin’ Sticks 16-item Odor Identification Test, Montreal Cognitive Assessment, Cognitive Reserve Index, and the Beck Depression Inventory. Additionally, socio-demographic data, medical history, and health-related lifestyle information were collected.

Results

About 27% of participants showed an odor identification score < 12 indicating hyposmia. Multiple regression analysis revealed that OI was significantly correlated with age, sex, and cognitive reserve index, and young women with high cognitive reserve index showing the highest olfactory scores.

Conclusion

This study provides data on the prevalence of olfactory dysfunction in different Italian regions.
Ventrolateral periaqueductal gray matter integrative system of defense and antinociception
Authors: de Mello Rosa Gustavo Henrique , Ullah Farhad , de Paiva Yara Bezerra , da Silva Juliana Almeida , Branco Luiz Guilherme S. , Corrado Alexandre Pinto , Medeiros Priscila , Coimbra Norberto Cysne , Franceschi Biagioni Audrey
Published: February 2022

Defensive responses are neurophysiological processes crucial for survival during threatening situations. Defensive immobility is a common adaptive response, in rodents, elaborated by ventrolateral periaqueductal gray matter (vlPAG) when threat is unavoidable. It is associated with somatosensory and autonomic reactions such as alteration in the sensation of pain and rate of respiration. In this study, defensive immobility was assessed by chemical stimulation of vlPAG with different doses of NMDA (0.1, 0.3, and 0.6 nmol). After elicitation of defensive immobility, antinociceptive and respiratory response tests were also performed. Results revealed that defensive immobility was followed by a decrease in the nociceptive perception. Furthermore, the lowest dose of NMDA induced antinociceptive response without eliciting defensive immobility. During defensive immobility, respiratory responses were also disturbed. Interestingly, respiratory rate was increased and interspersed with prolonged expiratory phase of breathing. These findings suggest that vlPAG integrates three different defensive behavioral responses, contributing to the most effective defensive strategies during threatening situations.
WT1 complete gonadal dysgenesis with membranoproliferative glomerulonephritis: case series and literature review
Authors: Anderson Erin , Aldridge Melanie , Turner Ross , Harraway James , McManus Sam , Stewart Anna , Borzi Peter , Trnka Peter , Burke John , Coman David
Published: February 2022

Background

Intronic WT1 mutations are usually causative of Frasier syndrome with focal segmental glomerulosclerosis as the characteristic nephropathy. Membranoproliferative glomerulonephritis is not commonly associated with disorders of sex development but has been recently identified as a WT1-associated nephropathy, but usually in cases of exonic mutations in either isolated Wilms tumor or Denys-Drash syndrome.

Methods

The clinical and genetic data from 3 individuals are reported.

Results

This report describes the kidney manifestations in 3 individuals from 2 unrelated families with Frasier syndrome intronic WT1 mutations, noting that 2 of the 3 individuals have histologically confirmed membranoproliferative glomerulonephritis.

Conclusions

These case reports support expansion of the clinical spectrum of the kidney phenotypes associated with Frasier syndrome providing evidence of an association between WT1 mutation and an immune complex-related membranoproliferative glomerulonephritis.

Graphical abstract

A higher resolution version of the Graphical abstract is available as Supplementary information
Exploring the relevance of NUP93 variants in steroid-resistant nephrotic syndrome using next generation sequencing and a fly kidney model
Authors: Bierzynska Agnieszka , Bull Katherine , Miellet Sara , Dean Philip , Neal Chris , Colby Elizabeth , McCarthy Hugh J. , Hegde Shivaram , Sinha Manish D. , Bugarin Diz Carmen , Stirrups Kathleen , Megy Karyn , Mapeta Rutendo , Penkett Chris , Marsh Sarah , Forrester Natalie , Afzal Maryam , Stark Hannah , BioResource NIHR , Williams Maggie , Welsh Gavin I. , Koziell Ania B. , Hartley Paul S. , Saleem Moin A.
Published: February 2022

Background

Variants in genes encoding nuclear pore complex (NPC) proteins are a newly identified cause of paediatric steroid-resistant nephrotic syndrome (SRNS). Recent reports describing NUP93 variants suggest these could be a significant cause of paediatric onset SRNS. We report NUP93 cases in the UK and demonstrate in vivo functional effects of Nup93 depletion in a fly (Drosophila melanogaster) nephrocyte model.

Methods

Three hundred thirty-seven paediatric SRNS patients from the National cohort of patients with Nephrotic Syndrome (NephroS) were whole exome and/or whole genome sequenced. Patients were screened for over 70 genes known to be associated with Nephrotic Syndrome (NS). D. melanogaster Nup93 knockdown was achieved by RNA interference using nephrocyte-restricted drivers.

Results

Six novel homozygous and compound heterozygous NUP93 variants were detected in 3 sporadic and 2 familial paediatric onset SRNS characterised histologically by focal segmental glomerulosclerosis (FSGS) and progressing to kidney failure by 12 months from clinical diagnosis.

Silencing of the two orthologs of human NUP93 expressed in D. melanogaster, Nup93-1, and Nup93-2 resulted in significant signal reduction of up to 82% in adult pericardial nephrocytes with concomitant disruption of NPC protein expression. Additionally, nephrocyte morphology was highly abnormal in Nup93-1 and Nup93-2 silenced flies surviving to adulthood.

Conclusion

We expand the spectrum of NUP93 variants detected in paediatric onset SRNS and demonstrate its incidence within a national cohort. Silencing of either D. melanogaster Nup93 ortholog caused a severe nephrocyte phenotype, signaling an important role for the nucleoporin complex in podocyte biology.

Graphical Abstract

A higher resolution version of the Graphical abstract is available as Supplementary information
Detection of DZIP1L mutations by whole-exome sequencing in consanguineous families with polycystic kidney disease
Authors: Hertz Jens Michael , Svenningsen Per , Dimke Henrik , Engelund Morten Buch , Nørgaard Hanne , Hansen Anita , Marcussen Niels , Thiesson Helle Charlotte , Bergmann Carsten , Larsen Martin J.
Published: February 2022

Background

Autosomal recessive polycystic kidney disease is a cystic kidney disease with early onset and clinically characterized by enlarged echogenic kidneys, hypertension, varying degrees of kidney dysfunction, and liver fibrosis. It is most frequently caused by sequence variants in the PKHD1 gene, encoding fibrocystin. In more rare cases, sequence variants in DZIP1L are seen, encoding the basal body protein DAZ interacting protein 1-like protein (DZIP1L). So far, only four different DZIP1L variants have been reported.

Methods

Four children from three consanguineous families presenting with polycystic kidney disease were selected for targeted or untargeted exome sequencing.

Results

We identified two different, previously not reported homozygous DZIP1L sequence variants: c.193 T > C; p.(Cys65Arg), and c.216C > G; p.(Cys72Trp). Functional analyses of the c.216C > G; p.(Cys72Trp) variant indicated mislocalization of mutant DZIP1L.

Conclusions

In line with published data, our results suggest a critical role of the N-terminal domain for proper protein function. Although patients with PKHD1-associated autosomal recessive polycystic kidney disease often have liver abnormalities, none of the present four patients showed any clinically relevant liver involvement. Our data demonstrate the power and efficiency of next-generation sequencing-based approaches. While DZIP1L-related polycystic kidney disease certainly represents a rare form of the disease, our results emphasize the importance of including DZIP1L in multigene panels and in the data analysis of whole-exome sequencing for cystic kidney diseases.

Graphical abstract

A higher resolution version of the Graphical abstract is available as Supplementary information
Evaluation of the VITEK2 AST-XN17 card for the detection of carbapenemase-producing Enterobacterales in isolates primarily producing metallo β-lactamase
Authors: Kuchibiro Tomokazu , Komatsu Masaru , Yamasaki Katsutoshi , Nakamura Tatsuya , Niki Makoto , Nishio Hisaaki , Kida Kaneyuki , Ohama Masanobu , Nakamura Akihiro , Nishi Isao
Published: February 2022

Carbapenemase-producing Enterobacterales (CPE) are not always resistant to carbapenem antimicrobial susceptibility testing (AST) and can be difficult to detect. With the newly created VITEK2 AST-XN17 card, the types of antibiotics measured in AST can be increased. In this study, we evaluated the detectability of CPE using the results of AST with multiple antimicrobial agents with additional measurements of the AST-XN17 card. In addition, we evaluated the CPE detectability of comments on CPE using the VITEK2 Advance Expert System (AES). In total, 169 Enterobacterales samples, including 76 non-CPE and 93 CPE, collected from multiple medical institutions in the Kinki region of Japan, were used in this investigation. AST with VITEK2 was performed by adding the AST-XN17 card in addition to the AST-N268 or AST-N404 card. Measurement results were identified using cutoff values, primarily Clinical and Laboratory Standards Institute breakpoints, and the CPE detection capability of each antibiotic was evaluated in several terms, including sensitivity and specificity. The drugs highly sensitive to CPE detection were faropenem (FRPM) > 2 µg/mL at 100% and meropenem > 0.25 µg/mL at 98.9%; the highest specificity to CPE detection was for avibactam/ceftazidime (AVI/CAZ) > 8 µg/mL at 100%. The sensitivity and specificity of each card in the AES output were 86.2% and 94.7% for AST-N404 and AST-XN17 and 91.5% and 90.8% for AST-N268 and AST-XN17, respectively. AST using the VITEK2 AST-XN17 card is a useful test method of screening for CPE.