bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Pediatric Traumatic Brain Injury on Verbal IQ: A Systematic Review and Meta-Analysis
Authors: Cermak Carly A. , Scratch Shannon E. , Reed Nick P. , Kakonge Lisa , Beal Deryk S.
Published: November 2021

Objectives:

To examine the effects of pediatric traumatic brain injury (TBI) on verbal IQ by severity and over time.

Methods:

A systematic review and subsequent meta-analysis of verbal IQ by TBI severity were conducted using a random effects model. Subgroup analysis included two epochs of time (e.g., <12 months postinjury and ≥12 months postinjury).

Results:

Nineteen articles met inclusion criteria after an extensive literature search in MEDLINE, PsycInfo, Embase, and CINAHL. Meta-analysis revealed negative effects of injury across severities for verbal IQ and at both time epochs except for mild TBI < 12 months postinjury. Statistical heterogeneity (i.e., between-study variability) stemmed from studies with inconsistent classification of mild TBI, small sample sizes, and in studies of mixed TBI severities, although not significant. Risk of bias on estimated effects was generally low (k = 15) except for studies with confounding bias (e.g., lack of group matching by socio-demographics; k = 2) and measurement bias (e.g., outdated measure at time of original study, translated measure; k = 2).

Conclusions:

Children with TBI demonstrate long-term impairment in verbal IQ, regardless of severity. Future studies are encouraged to include scores from subtests within verbal IQ (e.g., vocabulary, similarities, comprehension) in addition to functional language measures (e.g., narrative discourse, reading comprehension, verbal reasoning) to elucidate higher-level language difficulties experienced in this population.
An Anglican Odyssey: The Ecumenical Vision of Canon David John Garland (1864–1939) OBE and his Hidden Christian Agenda for Anzac Day
Authors: Moses John A.
Published: November 2021

There is still much unclear about the nature of the origins of Australia’s most respected and hallowed national day, namely Anzac Day, 25 April, and about who was primarily responsible for instituting a day of solemn commemoration for the fallen in the Great War of 1914–18. Much has been written by mostly unqualified would-be ‘authorities’ that is either patently false, uninformed or hostile to the commemoration. This is either because of resentment in some quarters of the distinctly Anglican contribution to the nature of the commemoration or pacifist misunderstanding that the celebration of Anzac Day is somehow a glorification of war. This paper based on original research into the files of the Queensland Anzac Day Commemoration Committee establishes the key role of Canon David John Garland (1864–1939) in shaping a liturgy of civic religion for the day which he hoped would become a means of reminding the population of their calling as part of the British Empire to emphasize the reign of Almighty God over all nations of the earth. That was the hidden Christian agenda in the mind of Canon Garland. Naturally he had his opponents to this objective.
Adapting group schema therapy for older adults with personality disorders: lessons learnt
Authors: Videler A. C. , van Beest K. A. , Ouwens M. A. , Rossi G. , van Royen R. J. J. , van Alphen S. P. J.
Published: November 2021

A first empirical study into group schema therapy in older adults with mood disorders and personality disorder (PD) features has shown that brief group schema therapy has potential to decrease psychological distress and to change early maladaptive schemas (EMS). Effect sizes however were smaller than those found in similar studies in younger adults. Therefore, we set out to adapt the treatment protocol for older adults in order to enhance its feasibility and outcome in this age group. We examined this adapted protocol in 29 older adults (mean age 66 years) with PDs from four Dutch mental health institutes. The primary outcome was symptomatic distress, measured by the Brief Symptom Inventory. Secondary outcomes were measured by the Young Schema Questionnaire, the Schema Mode Inventory, and the short version of the Severity Indices of Personality Problems. Contrary to our expectations, the adapted treatment protocol yielded only a small effect size in our primary outcome, and no significant improvement in EMS, modes and personality functioning. Patients pointed out that they were more aware of their dysfunctional patterns, but maybe they had not been able yet to work on behavioural change due to this schema therapy treatment being too brief. We recommend more intensive treatment for older patients with PDs, as they might benefit from more schema therapy sessions, similar to the treatment dosage in younger PD patients. They might also benefit from a combination of group therapy and individual treatment sessions.

Key learning aims

(1)

How to adapt group schema therapy for older adults.

(2)

How to explore feasibility and outcome.

(3)

Treat older personality disorder patients as intensively as younger adults.
Coupling Mineralogy and Oxygen Isotopes to Seasonal Environmental Shifts Recorded in Modern Freshwater Pearl Nacre From Kentucky Lake
Authors: Farfan G. A. , Zhou C. , Valley J. W. , Orland I. J.
Published: November 2021

Biominerals that accrete shell or skeleton are commonly used as windows to past geochemical environments. Using biominerals as paleoproxies depends on the assumption that biominerals faithfully and predictably record environmental parameters, yet little has been done from a mineralogical perspective to understand how various environmental shifts impact shell and skeleton mineralogy and how mineralogy influences proxy calibrations. In this study, we correlate a suite of environmental data from the Kentucky Lake Long‐Term Monitoring Program with mineralogical and chemical signatures of modern cultured pearl nacre. Six transects were measured across three pearls from nucleus to edge for oxygen isotope ratio (δ18O) using SIMS (10‐μm spots) and for mineralogy via nacre tablet thickness using SEM and via carbonate bonding environments using Raman spectroscopy. After confirming a strong seasonal correlation between δ18O and temperature, we extend δ18O correlations to relative nacre OH/O ratios, lake dissolved oxygen, and lake light levels at 1 m depth. Although nacre tablet thicknesses are not clearly correlated with temperature, we observe correlative trends with lake conductivity and relative nacre OH/O ratios. For the Raman spectroscopy measurements, there was a modest inverse correlation between increasing carbonate ν1 and ν4 vibrational mode peak heights with δ18O and lake dissolved oxygen levels. Standard deviations in Raman T:L peak area ratios, as an estimation of angle spread of tablet crystallographic orientation, correlate with lake reduction potential. This approach of combining geochemical, isotopic, mineralogical, and environmental data lends a more holistic view to biomineralization in natural systems and to the decoding of environmental mineral signatures.
Turbulent Thermal Image Velocimetry at the Immediate Fire and Atmospheric Interface
Authors: Katurji Marwan , Zhang Jiawei , Satinsky Ashley , McNair Hamish , Schumacher Benjamin , Strand Tara , Valencia Andres , Finney Mark , Pearce Grant , Kerr Jessica , Seto Daisuke , Wallace Hugh , Zawar‐Reza Peyman , Dunker Christina , Clifford Veronica , Melnik Katharine , Grumstrup Torben , Forthofer Jason , Clements Craig
Published: November 2021

We present novel in‐field vegetation fire observations and the analyses using brightness temperatures recorded by longwave infrared camera and thermal image velocimetry. The brightness temperatures from a wind‐driven stubble wheat fire were obtained with a 60 frames per second (fps) video acquisition. Multi‐level sonic anemometers on a 10m in‐fire tower were used for measurements of turbulent velocity and air temperatures, while fuel level air and flame temperatures were collected by an array of thermocouples (TCs). The camera's image pixel resolution was adequate to discern thermal structures in accordance with the in‐fire TC measurements and its spacing distances. The in‐situ and remotely measured flaming zone dynamics were derived using two different methodologies, Thermal Image Velocimetry (TIV) and Image Segmentation (IS). The results highlight spatial and spectral information of coherent turbulent and mean velocity structures. The power spectra decomposition of the TIV showed similar spectral characteristics to the sonic speed measurements during the fire passage under the tower with a similar inertial subrange slope. This result reveals plausible evidence of interaction between the flaming zone and wind turbulence for a prescribed rapidly moving stubble wheat fire. This research presents a new field measurement methodology for understanding fire‐atmospheric interactions between the flaming zone and the immediate overlying atmospheric turbulent boundary layer.
Flexible thin-film acoustic wave devices with off-axis bending characteristics for multisensing applications
Authors: Ji Zhangbin , Zhou Jian , Lin Huamao , Wu Jianhui , Zhang Dinghong , Garner Sean , Gu Alex , Dong Shurong , Fu YongQing , Duan Huigao
Published: November 2021

Flexible surface acoustic wave (SAW) devices have recently attracted tremendous attention for their widespread application in sensing and microfluidics. However, for these applications, SAW devices often need to be bent into off-axis deformations between the acoustic wave propagation direction and bending direction. Currently, there are few studies on this topic, and the bending mechanisms during off-axis bending deformations have remained unexplored for multisensing applications. Herein, we fabricated aluminum nitride (AlN) flexible SAW devices by using high-quality AlN films deposited on flexible glass substrates and systematically investigated their complex deformation behaviors. A theoretical model was first developed using coupling wave equations and the boundary condition method to analyze the characteristics of the device with bending and off-axis deformation under elastic strains. The relationships between the frequency shifts of the SAW device and the bending strain and off-axis angle were obtained, and the results were identical to those from the theoretical calculations. Finally, we performed proof-of-concept demonstrations of its multisensing potential by monitoring human wrist movements at various off-axis angles and detecting UV light intensities on a curved surface, thus paving the way for the application of versatile flexible electronics.
Paradoxical effects of DNA tumor virus oncogenes on epithelium-derived tumor cell fate during tumor progression and chemotherapy response
Authors: He Jiang , Liu Liyu , Tang Feiyu , Zhou You , Liu Huan , Lu Can , Feng Deyun , Zhu Hong , Mao Yitao , Li Zhi , Zhang Lu , Duan Yuemei , Xiao Zhi , Zeng Musheng , Weng Liang , Sun Lun-Quan
Published: November 2021

Epstein-Barr virus (EBV) and human papillomavirus (HPV) infection is the risk factors for nasopharyngeal carcinoma and cervical carcinoma, respectively. However, clinical analyses demonstrate that EBV or HPV is associated with improved response of patients, although underlying mechanism remains unclear. Here, we reported that the oncoproteins of DNA viruses, such as LMP1 of EBV and E7 of HPV, inhibit PERK activity in cancer cells via the interaction of the viral oncoproteins with PERK through a conserved motif. Inhibition of PERK led to increased level of reactive oxygen species (ROS) that promoted tumor and enhanced the efficacy of chemotherapy in vivo. Consistently, disruption of viral oncoprotein-PERK interactions attenuated tumor growth and chemotherapy in both cancer cells and tumor-bearing mouse models. Our findings uncovered a paradoxical effect of DNA tumor virus oncoproteins on tumors and highlighted that targeting PERK might be an attractive strategy for the treatment of NPC and cervical carcinoma.
Regional variations in hepatocellular carcinoma incidence, routes to diagnosis, treatment and survival in England
Authors: Burton Anya , Balachandrakumar Vinay K. , Driver Robert J. , Tataru Daniela , Paley Lizz , Marshall Aileen , Alexander Graeme , Rowe Ian A. ,   HCC-UK/BASL/NCRAS Partnership, Palmer Daniel H. , Cross Tim J. S.
Published: November 2021

Background

Hepatocellular carcinoma (HCC) incidence, management and survival across England were examined to determine if geographical inequalities exist.

Method

15,468 HCC cases diagnosed 2010–2016 were included. Age-standardised incidence rates, net survival and proportions receiving potentially curative treatment and presenting through each route to diagnosis adjusted for age at diagnosis, sex and area-based deprivation quintile, were calculated overall and by Cancer Alliance.

Results

HCC incidence rates increased in men from 6.2 per 100,000 in 2010 to 8.8 in 2016, and in women from 1.5 to 2.2. The highest incidence rates, found in parts of the North of England and London, were nearly double the lowest. The adjusted proportion presenting as an emergency ranged 27–41% across Cancer Alliances. Odds increased with increasing deprivation quintile and age. Only one in five patients received potentially curative treatment (range 15–28%) and odds decreased with increasing deprivation and age. One-year survival in 2013–2016 ranged 38–53%.

Conclusion

This population-based, nationwide analysis demonstrates clear differences in HCC incidence, management and survival across England. It highlights socioeconomic-associated variation and the need for improvement in early diagnosis and curative treatment of HCC. This research should assist policymakers, service providers and clinicians to identify regions where additional training, services and resources would be best directed.
Artificial intelligence in oncology: current applications and future perspectives
Authors: Luchini Claudio , Pea Antonio , Scarpa Aldo
Published: November 2021

Artificial intelligence (AI) is concretely reshaping the landscape and horizons of oncology, opening new important opportunities for improving the management of cancer patients. Analysing the AI-based devices that have already obtained the official approval by the Federal Drug Administration (FDA), here we show that cancer diagnostics is the oncology-related area in which AI is already entered with the largest impact into clinical practice. Furthermore, breast, lung and prostate cancers represent the specific cancer types that now are experiencing more advantages from AI-based devices. The future perspectives of AI in oncology are discussed: the creation of multidisciplinary platforms, the comprehension of the importance of all neoplasms, including rare tumours and the continuous support for guaranteeing its growth represent in this time the most important challenges for finalising the ‘AI-revolution’ in oncology.
Misoprostol treatment prevents hypoxia-induced cardiac dysfunction through a 14-3-3 and PKA regulatory motif on Bnip3
Authors: Martens Matthew D. , Seshadri Nivedita , Nguyen Lucas , Chapman Donald , Henson Elizabeth S. , Xiang Bo , Falk Landon , Mendoza Arielys , Rattan Sunil , Field Jared T. , Kawalec Philip , Gibson Spencer B. , Keijzer Richard , Saleem Ayesha , Hatch Grant M. , Doucette Christine A. , Karch Jason M. , Dolinsky Vernon W. , Dixon Ian M. , West Adrian R. , Rampitsch Christof , Gordon Joseph W.
Published: November 2021

Systemic hypoxia is a common element in most perinatal emergencies and is a known driver of Bnip3 expression in the neonatal heart. Bnip3 plays a prominent role in the evolution of necrotic cell death, disrupting ER calcium homeostasis and initiating mitochondrial permeability transition (MPT). Emerging evidence suggests a cardioprotective role for the prostaglandin E1 analog misoprostol during periods of hypoxia, but the mechanisms for this protection are not completely understood. Using a combination of mouse and cell models, we tested if misoprostol is cardioprotective during neonatal hypoxic injury by altering Bnip3 function. Here we report that hypoxia elicits mitochondrial-fragmentation, MPT, reduced ejection fraction, and evidence of necroinflammation, which were abrogated with misoprostol treatment or Bnip3 knockout. Through molecular studies we show that misoprostol leads to PKA-dependent Bnip3 phosphorylation at threonine-181, and subsequent redistribution of Bnip3 from mitochondrial Opa1 and the ER through an interaction with 14-3-3 proteins. Taken together, our results demonstrate a role for Bnip3 phosphorylation in the regulation of cardiomyocyte contractile/metabolic dysfunction, and necroinflammation. Furthermore, we identify a potential pharmacological mechanism to prevent neonatal hypoxic injury.
Resident and migratory adipose immune cells control systemic metabolism and thermogenesis
Authors: Man Kevin , Kallies Axel , Vasanthakumar Ajithkumar
Published: November 2021

Glucose is a vital source of energy for all mammals. The balance between glucose uptake, metabolism and storage determines the energy status of an individual, and perturbations in this balance can lead to metabolic diseases. The maintenance of organismal glucose metabolism is a complex process that involves multiple tissues, including adipose tissue, which is an endocrine and energy storage organ that is critical for the regulation of systemic metabolism. Adipose tissue consists of an array of different cell types, including specialized adipocytes and stromal and endothelial cells. In addition, adipose tissue harbors a wide range of immune cells that play vital roles in adipose tissue homeostasis and function. These cells contribute to the regulation of systemic metabolism by modulating the inflammatory tone of adipose tissue, which is directly linked to insulin sensitivity and signaling. Furthermore, these cells affect the control of thermogenesis. While lean adipose tissue is rich in type 2 and anti-inflammatory cytokines such as IL-10, obesity tips the balance in favor of a proinflammatory milieu, leading to the development of insulin resistance and the dysregulation of systemic metabolism. Notably, anti-inflammatory immune cells, including regulatory T cells and innate lymphocytes, protect against insulin resistance and have the characteristics of tissue-resident cells, while proinflammatory immune cells are recruited from the circulation to obese adipose tissue. Here, we review the key findings that have shaped our understanding of how immune cells regulate adipose tissue homeostasis to control organismal metabolism.
Helicobacter pylori FabX contains a [4Fe-4S] cluster essential for unsaturated fatty acid synthesis
Authors: Zhou Jiashen , Zhang Lin , Zeng Liping , Yu Lu , Duan Yuanyuan , Shen Siqi , Hu Jingyan , Zhang Pan , Song Wenyan , Ruan Xiaoxue , Jiang Jing , Zhang Yinan , Zhou Lu , Jia Jia , Hang Xudong , Tian Changlin , Lin Houwen , Chen Hong-Zhuan , Cronan John E. , Bi Hongkai , Zhang Liang
Published: November 2021

Unsaturated fatty acids (UFAs) are essential for functional membrane phospholipids in most bacteria. The bifunctional dehydrogenase/isomerase FabX is an essential UFA biosynthesis enzyme in the widespread human pathogen Helicobacter pylori, a bacterium etiologically related to 95% of gastric cancers. Here, we present the crystal structures of FabX alone and in complexes with an octanoyl-acyl carrier protein (ACP) substrate or with holo-ACP. FabX belongs to the nitronate monooxygenase (NMO) flavoprotein family but contains an atypical [4Fe-4S] cluster absent in all other family members characterized to date. FabX binds ACP via its positively charged α7 helix that interacts with the negatively charged α2 and α3 helices of ACP. We demonstrate that the [4Fe-4S] cluster potentiates FMN oxidation during dehydrogenase catalysis, generating superoxide from an oxygen molecule that is locked in an oxyanion hole between the FMN and the active site residue His182. Both the [4Fe-4S] and FMN cofactors are essential for UFA synthesis, and the superoxide is subsequently excreted by H. pylori as a major resource of peroxide which may contribute to its pathogenic function in the corrosion of gastric mucosa.
Changes in notifiable infectious disease incidence in China during the COVID-19 pandemic
Authors: Geng Meng-Jie , Zhang Hai-Yang , Yu Lin-Jie , Lv Chen-Long , Wang Tao , Che Tian-Le , Xu Qiang , Jiang Bao-Gui , Chen Jin-Jin , Hay Simon I. , Li Zhong-Jie , Gao George F. , Wang Li-Ping , Yang Yang , Fang Li-Qun , Liu Wei
Published: November 2021

Nationwide nonpharmaceutical interventions (NPIs) have been effective at mitigating the spread of the novel coronavirus disease (COVID-19), but their broad impact on other diseases remains under-investigated. Here we report an ecological analysis comparing the incidence of 31 major notifiable infectious diseases in China in 2020 to the average level during 2014-2019, controlling for temporal phases defined by NPI intensity levels. Respiratory diseases and gastrointestinal or enteroviral diseases declined more than sexually transmitted or bloodborne diseases and vector-borne or zoonotic diseases. Early pandemic phases with more stringent NPIs were associated with greater reductions in disease incidence. Non-respiratory diseases, such as hand, foot and mouth disease, rebounded substantially towards the end of the year 2020 as the NPIs were relaxed. Statistical modeling analyses confirm that strong NPIs were associated with a broad mitigation effect on communicable diseases, but resurgence of non-respiratory diseases should be expected when the NPIs, especially restrictions of human movement and gathering, become less stringent.
The evolution of cheating in viruses
Authors: Leeks Asher , West Stuart A. , Ghoul Melanie
Published: November 2021

The success of many viruses depends upon cooperative interactions between viral genomes. However, whenever cooperation occurs, there is the potential for ‘cheats’ to exploit that cooperation. We suggest that: (1) the biology of viruses makes viral cooperation particularly susceptible to cheating; (2) cheats are common across a wide range of viruses, including viral entities that are already well studied, such as defective interfering genomes, and satellite viruses. Consequently, the evolutionary theory of cheating could help us understand and manipulate viral dynamics, while viruses also offer new opportunities to study the evolution of cheating.
Quinacrine-CASIN combination overcomes chemoresistance in human acute lymphoid leukemia
Authors: Wu Limei , Chatla Srinivas , Lin Qiqi , Chowdhury Fabliha Ahmed , Geldenhuys Werner , Du Wei
Published: November 2021

Chemoresistance posts a major hurdle for treatment of acute leukemia. There is increasing evidence that prolonged and intensive chemotherapy often fails to eradicate leukemic stem cells, which are protected by the bone marrow niche and can induce relapse. Thus, new therapeutic approaches to overcome chemoresistance are urgently needed. By conducting an ex vivo small molecule screen, here we have identified Quinacrine (QC) as a sensitizer for Cytarabine (AraC) in treating acute lymphoblastic leukemia (ALL). We show that QC enhances AraC-mediated killing of ALL cells, and subsequently abrogates AraC resistance both in vitro and in an ALL-xenograft model. However, while combo AraC+QC treatment prolongs the survival of primary transplanted recipients, the combination exhibits limited efficacy in secondary transplanted recipients, consistent with the survival of niche-protected leukemia stem cells. Introduction of Cdc42 Activity Specific Inhibitor, CASIN, enhances the eradication of ALL leukemia stem cells by AraC+QC and prolongs the survival of both primary and secondary transplanted recipients without affecting normal long-term human hematopoiesis. Together, our findings identify a small-molecule regimen that sensitizes AraC-mediated leukemia eradication and provide a potential therapeutic approach for better ALL treatment.
Genetic factors affecting dopaminergic deterioration during the premotor stage of Parkinson disease
Authors: Lee Myung Jun , Pak Kyoungjune , Kim Han-Kyeol , Nudelman Kelly N. , Kim Jong Hun , Kim Yun Hak , Kang Junho , Baek Min Seok , Lyoo Chul Hyoung
Published: November 2021

To estimate dopaminergic dysfunction in patients with Parkinson disease (PD) during the premotor stage and to investigate the effect of genetic factors on the trajectories. Using longitudinal dopamine transporter single-photon emission computed tomography data from 367 sporadic PD (sPD), 72 LRRK2 (G2019S), and 39 GBA (N370S) PD patients in the Parkinson’s Progression Markers Initiative (PPMI) study, we estimated the temporal trajectories of putaminal-specific binding ratios using an integrating function between baseline values and their annual change rates. In order to test reproducibility, we computed another trajectory for sPD using positron emission tomography data of 38 sPD patients at Gangnam Severance Hospital (GSH). Temporal trajectories of sPD were compared between the groups separated by age at onset (AAO) and polygenic load for common PD risk variants, and also compared with genetic PD. sPD patients in both the PPMI and GSH cohorts showed similar onset of dopaminergic degeneration around 10 years before motor onset. Early-onset PD patients exhibited later onset of degeneration and a faster decline in dopaminergic activity during the premotor period than late-onset patients. sPD patients with high polygenic load were associated with earlier onset and slower progression of dopaminergic dysfunction. Compared to the sPD and LRRK2 PD groups, GBA PD patients exhibited faster deterioration of dopaminergic function during the premotor stage. Dopaminergic dysfunction in PD appears to start about 10 years before motor onset. Genetic factors may be contributing to the heterogeneity of dopaminergic deterioration during the premotor stage.
CHIASM, the human brain albinism and achiasma MRI dataset
Authors: Puzniak Robert J. , McPherson Brent , Ahmadi Khazar , Herbik Anne , Kaufmann Jörn , Liebe Thomas , Gouws Andre , Morland Antony B. , Gottlob Irene , Hoffmann Michael B. , Pestilli Franco
Published: November 2021

We describe a collection of T1-, diffusion- and functional T2*-weighted magnetic resonance imaging data from human individuals with albinism and achiasma. This repository can be used as a test-bed to develop and validate tractography methods like diffusion-signal modeling and fiber tracking as well as to investigate the properties of the human visual system in individuals with congenital abnormalities. The MRI data is provided together with tools and files allowing for its preprocessing and analysis, along with the data derivatives such as manually curated masks and regions of interest for performing tractography.
Global daily 1 km land surface precipitation based on cloud cover-informed downscaling
Authors: Karger Dirk Nikolaus , Wilson Adam M. , Mahony Colin , Zimmermann Niklaus E. , Jetz Walter
Published: November 2021

High-resolution climatic data are essential to many questions and applications in environmental research and ecology. Here we develop and implement a new semi-mechanistic downscaling approach for daily precipitation estimate that incorporates high resolution (30 arcsec, ≈1 km) satellite-derived cloud frequency. The downscaling algorithm incorporates orographic predictors such as wind fields, valley exposition, and boundary layer height, with a subsequent bias correction. We apply the method to the ERA5 precipitation archive and MODIS monthly cloud cover frequency to develop a daily gridded precipitation time series in 1 km resolution for the years 2003 onward. Comparison of the predictions with existing gridded products and station data from the Global Historical Climate Network indicates an improvement in the spatio-temporal performance of the downscaled data in predicting precipitation. Regional scrutiny of the cloud cover correction from the continental United States further indicates that CHELSA-EarthEnv performs well in comparison to other precipitation products. The CHELSA-EarthEnv daily precipitation product improves the temporal accuracy compared with a large improvement in the spatial accuracy especially in complex terrain.
Wide-field mosaics of the corneal subbasal nerve plexus in Parkinson’s disease using in vivo confocal microscopy
Authors: Badian Reza A. , Allgeier Stephan , Scarpa Fabio , Andréasson Mattias , Bartschat Andreas , Mikut Ralf , Colonna Alessia , Bellisario Marco , Utheim Tor Paaske , Köhler Bernd , Svenningsson Per , Lagali Neil
Published: November 2021

In vivo confocal microscopy (IVCM) is a non-invasive imaging technique facilitating real-time acquisition of images from the live cornea and its layers with high resolution (1–2 µm) and high magnification (600 to 800-fold). IVCM is extensively used to examine the cornea at a cellular level, including the subbasal nerve plexus (SBNP). IVCM of the cornea has thus gained intense interest for probing ophthalmic and systemic diseases affecting peripheral nerves. One of the main drawbacks, however, is the small field of view of IVCM, preventing an overview of SBNP architecture and necessitating subjective image sampling of small areas of the SBNP for analysis. Here, we provide a high-quality dataset of the corneal SBNP reconstructed by automated mosaicking, with an average mosaic image size corresponding to 48 individual IVCM fields of view. The mosaic dataset represents a group of 42 individuals with Parkinson’s disease (PD) with and without concurrent restless leg syndrome. Additionally, mosaics from a control group (n = 13) without PD are also provided, along with clinical data for all included participants.
Change in Japanese children’s 24-hour movement guidelines and mental health during the COVID-19 pandemic
Authors: Hyunshik Kim , Jiameng Ma , Sunkyoung Lee , Ying Gu
Published: November 2021

Specialized guidelines are required for the health behaviors of vulnerable populations such as children. This is especially true during the COVID-19 pandemic, wherein major lifestyle changes have occurred, especially among young children. The present study aims to use longitudinal data to understand changes in the physical activity, screen time, sleep, and mental health of preschoolers in Japan during the COVID-19 pandemic, compared to pre-pandemic period. Subjective and objective measures were used to assess the variables of interest longitudinally. It was found that physical activity, adherence to WHO-recommended screen time, and prosocial behaviors decreased significantly. On the other hand, sedentary time and hyperactivity increased. Our results are consistent with findings from other countries. The implications with respect to outdoor playtime, screen-time in the context of online learning during the pandemic, and the effects of parents’ mental health on preschool-aged children are discussed.
Integration of neural architecture within a finite element framework for improved neuromusculoskeletal modeling
Authors: Volk Victoria L. , Hamilton Landon D. , Hume Donald R. , Shelburne Kevin B. , Fitzpatrick Clare K.
Published: November 2021

Neuromusculoskeletal (NMS) models can aid in studying the impacts of the nervous and musculoskeletal systems on one another. These computational models facilitate studies investigating mechanisms and treatment of musculoskeletal and neurodegenerative conditions. In this study, we present a predictive NMS model that uses an embedded neural architecture within a finite element (FE) framework to simulate muscle activation. A previously developed neuromuscular model of a motor neuron was embedded into a simple FE musculoskeletal model. Input stimulation profiles from literature were simulated in the FE NMS model to verify effective integration of the software platforms. Motor unit recruitment and rate coding capabilities of the model were evaluated. The integrated model reproduced previously published output muscle forces with an average error of 0.0435 N. The integrated model effectively demonstrated motor unit recruitment and rate coding in the physiological range based upon motor unit discharge rates and muscle force output. The combined capability of a predictive NMS model within a FE framework can aid in improving our understanding of how the nervous and musculoskeletal systems work together. While this study focused on a simple FE application, the framework presented here easily accommodates increased complexity in the neuromuscular model, the FE simulation, or both.
First tracking of the oceanic spawning migrations of Australasian short-finned eels (Anguilla australis)
Authors: Koster Wayne M. , Aarestrup Kim , Birnie-Gauvin Kim , Church Ben , Dawson David , Lyon Jarod , O’Connor Justin , Righton David , Rose Denis , Westerberg Håkan , Stuart Ivor
Published: November 2021

Anguillid eel populations have declined dramatically over the last 50 years in many regions of the world, and numerous species are now under threat. A critical life-history phase is migration from freshwater to distant oceans, culminating in a single life-time spawning event. For many anguillids, especially those in the southern hemisphere, mystery still shrouds their oceanic spawning migrations. We investigated the oceanic spawning migrations of the Australasian short-finned eel (Anguilla australis) using pop-up satellite archival tags. Eels were collected from river estuaries (38° S, 142° E) in south-eastern temperate Australia. In 2019, 16 eels were tracked for up to about 5 months, ~ 2620 km from release, and as far north as the tropical Coral Sea (22° S, 155° E) off the north-east coast of Australia. Eels from southern Australia appeared to access deep water off the Australian coast via two main routes: (i) directly east via Bass Strait, or (ii) south-east around Tasmania, which is the shortest route to deep water. Tagged eels exhibited strong diel vertical migrations, alternating between the warm euphotic zone (~ 100–300 m, 15–20 °C) at night and the mesopelagic zone (~ 700–900 m, 6–8 °C) during the day. Marine predators, probably lamnid sharks, tuna, or marine mammals, ended many eel migrations (at least ~ 30%), largely before the eels had left the Australian continental shelf. The long and risky marine migrations of Australasian eels highlight the need for better information on the processes contributing to eel mortality throughout the life cycle, including the impacts of future changes to oceanic currents, predator abundance and direct anthropogenic disturbances.
Cluster analysis and profiling of airway fluid metabolites in pediatric acute hypoxemic respiratory failure
Authors: Grunwell Jocelyn R. , Rad Milad G. , Stephenson Susan T. , Mohammad Ahmad F. , Opolka Cydney , Fitzpatrick Anne M. , Kamaleswaran Rishikesan
Published: November 2021

Hierarchal clustering of amino acid metabolites may identify a metabolic signature in children with pediatric acute hypoxemic respiratory failure. Seventy-four immunocompetent children, 41 (55.4%) with pediatric acute respiratory distress syndrome (PARDS), who were between 2 days to 18 years of age and within 72 h of intubation for acute hypoxemic respiratory failure, were enrolled. We used hierarchal clustering and partial least squares-discriminant analysis to profile the tracheal aspirate airway fluid using quantitative LC–MS/MS to explore clusters of metabolites that correlated with acute hypoxemia severity and ventilator-free days. Three clusters of children that differed by severity of hypoxemia and ventilator-free days were identified. Quantitative pathway enrichment analysis showed that cysteine and methionine metabolism, selenocompound metabolism, glycine, serine and threonine metabolism, arginine biosynthesis, and valine, leucine, and isoleucine biosynthesis were the top five enriched, impactful pathways. We identified three clusters of amino acid metabolites found in the airway fluid of intubated children important to acute hypoxemia severity that correlated with ventilator-free days < 21 days. Further studies are needed to validate our findings and to test our models.
Mapping the electrostatic potential of the nucleosome acidic patch
Authors: Zhang Heyi , Eerland Jelmer , Horn Velten , Schellevis Raymond , van Ingen Hugo
Published: November 2021

The nucleosome surface contains an area with negative electrostatic potential known as the acidic patch, which functions as a binding platform for various proteins to regulate chromatin biology. The dense clustering of acidic residues may impact their effective pKa and thus the electronegativity of the acidic patch, which in turn could influence nucleosome-protein interactions. We here set out to determine the pKa values of residues in and around the acidic patch in the free H2A-H2B dimer using NMR spectroscopy. We present a refined solution structure of the H2A-H2B dimer based on intermolecular distance restraints, displaying a well-defined histone-fold core. We show that the conserved histidines H2B H46 and H106 that line the acidic patch have pKa of 5.9 and 6.5, respectively, and that most acidic patch carboxyl groups have pKa values well below 5.0. For H2A D89 we find strong evidence for an elevated pKa of 5.3. Our data establish that the acidic patch is highly negatively charged at physiological pH, while protonation of H2B H106 and H2B H46 at slightly acidic pH will reduce electronegativity. These results will be valuable to understand the impact of pH changes on nucleosome-protein interactions in vitro, in silico or in vivo.
Curcumin derivative ST09 modulates the miR-199a-5p/DDR1 axis and regulates proliferation and migration in ovarian cancer cells
Authors: Ravindran Febina , Koroth Jinsha , Manjunath Meghana , Narayan Suchitra , Choudhary Bibha
Published: November 2021

Ovarian cancers are among the fatal malignancies affecting women globally, mainly due to their metastatic and chemoresistant nature. In this study, we report a potent curcumin derivative ST09 effective against ovarian cancers. Prior in-vitro studies with ST09 drug showed cytotoxicity in tumorigenic cells compared to normal cells and in-vivo, significant tumor reduction was observed with least systemic toxicity. ST09 induced cytotoxicity in the ovarian cancer cells triggering mitochondria-mediated intrinsic apoptotic pathway. Delving deeper to understand the underlying molecular mechanisms involved in ovarian cancer pathogenesis, we identified an inverse correlation of miR-199a-5p with DDR1, a collagen receptor with receptor tyrosine kinase activity. The ST09 treatment in ovarian cancer cell lines resulted in the deregulation of the miR-199a-5p/DDR1 axis, conferring tumor-suppressive functions. We established DDR1 to be a direct target of miR-199a-5p and that ST09-induced DDR1 loss in these ovarian cancer cells resulted in the inactivation of its downstream MMP activation, migration, EMT, and prosurvival NF-κB pathway. Overall this study demonstrates ST09, a potent drug candidate for ovarian cancer treatment which exhibits anti-invasive and migrastatic properties.
Long noncoding RNAs associated with nonalcoholic fatty liver disease in a high cholesterol diet adult zebrafish model
Authors: An Hyo Jung , Lee Yoon Jung , Choe Chong Pyo , Cho Hyun-Kyung , Song Dae Hyun
Published: November 2021

The mechanism of nonalcoholic fatty liver disease (NAFLD) has not been completely revealed. In this study, we investigated the association of liver histological changes and long noncoding RNAs (lncRNAs) in the NAFLD zebrafish model. Forty zebrafish were fed a high-cholesterol diet (1.5 g per day) for 8 weeks. We measured fatty liver changes in the zebrafish liver using oil red O staining and divided them into two groups based on high and low scores. We pooled each group of zebrafish livers and identified lncRNAs, miRNAs, and mRNAs using Next-generation sequencing. Human homologs of lncRNAs were identified using ZFLNC, Ensembl, and NONCODE. We found several significant genes, including 32 lncRNAs, 5 miRNA genes, and 8 protein-coding genes, that were associated with liver metabolism and NAFLD-related functions in zebrafish. In particular, eight conserved human homologs of lncRNAs were found. We discovered the human homologs of eight lncRNA candidates from fatty liver zebrafish for the first time. The spectrum of biological mechanisms by which lncRNAs mediate their functional roles in NAFLD in a high cholesterol diet adult zebrafish model remains to be uncovered.
A deep learning model for identifying diabetic retinopathy using optical coherence tomography angiography
Authors: Ryu Gahyung , Lee Kyungmin , Park Donggeun , Park Sang Hyun , Sagong Min
Published: November 2021

As the prevalence of diabetes increases, millions of people need to be screened for diabetic retinopathy (DR). Remarkable advances in technology have made it possible to use artificial intelligence to screen DR from retinal images with high accuracy and reliability, resulting in reducing human labor by processing large amounts of data in a shorter time. We developed a fully automated classification algorithm to diagnose DR and identify referable status using optical coherence tomography angiography (OCTA) images with convolutional neural network (CNN) model and verified its feasibility by comparing its performance with that of conventional machine learning model. Ground truths for classifications were made based on ultra-widefield fluorescein angiography to increase the accuracy of data annotation. The proposed CNN classifier achieved an accuracy of 91–98%, a sensitivity of 86–97%, a specificity of 94–99%, and an area under the curve of 0.919–0.976. In the external validation, overall similar performances were also achieved. The results were similar regardless of the size and depth of the OCTA images, indicating that DR could be satisfactorily classified even with images comprising narrow area of the macular region and a single image slab of retina. The CNN-based classification using OCTA is expected to create a novel diagnostic workflow for DR detection and referral.
Using explainable machine learning to characterise data drift and detect emergent health risks for emergency department admissions during COVID-19
Authors: Duckworth Christopher , Chmiel Francis P. , Burns Dan K. , Zlatev Zlatko D. , White Neil M. , Daniels Thomas W. V. , Kiuber Michael , Boniface Michael J.
Published: November 2021

A key task of emergency departments is to promptly identify patients who require hospital admission. Early identification ensures patient safety and aids organisational planning. Supervised machine learning algorithms can use data describing historical episodes to make ahead-of-time predictions of clinical outcomes. Despite this, clinical settings are dynamic environments and the underlying data distributions characterising episodes can change with time (data drift), and so can the relationship between episode characteristics and associated clinical outcomes (concept drift). Practically this means deployed algorithms must be monitored to ensure their safety. We demonstrate how explainable machine learning can be used to monitor data drift, using the COVID-19 pandemic as a severe example. We present a machine learning classifier trained using (pre-COVID-19) data, to identify patients at high risk of admission during an emergency department attendance. We then evaluate our model’s performance on attendances occurring pre-pandemic (AUROC of 0.856 with 95%CI [0.852, 0.859]) and during the COVID-19 pandemic (AUROC of 0.826 with 95%CI [0.814, 0.837]). We demonstrate two benefits of explainable machine learning (SHAP) for models deployed in healthcare settings: (1) By tracking the variation in a feature’s SHAP value relative to its global importance, a complimentary measure of data drift is found which highlights the need to retrain a predictive model. (2) By observing the relative changes in feature importance emergent health risks can be identified.
Quantification of contrast agent uptake in the hepatobiliary phase helps to differentiate hepatocellular carcinoma grade
Authors: Haimerl Michael , Utpatel Kirsten , Götz Andrea , Zeman Florian , Fellner Claudia , Nickel Dominik , Luerken Lukas , Brennfleck Frank , Stroszczynski Christian , Scheiter Alexander , Verloh Niklas
Published: November 2021

This study aimed to assess the degree of differentiation of hepatocellular carcinoma (HCC) using Gd-EOB-DTPA-assisted magnetic resonance imaging (MRI) with T1 relaxometry. Thirty-three solitary HCC lesions were included in this retrospective study. This study's inclusion criteria were preoperative Gd-EOB-DTPA-assisted MRI of the liver and a histopathological evaluation after hepatic tumor resection. T1 maps of the liver were evaluated to determine the T1 relaxation time and reduction rate between the native phase and hepatobiliary phase (HBP) in liver lesions. These findings were correlated with the histopathologically determined degree of HCC differentiation (G1, well-differentiated; G2, moderately differentiated; G3, poorly differentiated). There was no significant difference between well-differentiated (950.2 ± 140.2 ms) and moderately/poorly differentiated (1009.4 ± 202.0 ms) HCCs in the native T1 maps. After contrast medium administration, a significant difference (p ≤ 0.001) in the mean T1 relaxation time in the HBP was found between well-differentiated (555.4 ± 140.2 ms) and moderately/poorly differentiated (750.9 ± 146.4 ms) HCCs. For well-differentiated HCCs, the reduction rate in the T1 time was significantly higher at 0.40 ± 0.15 than for moderately/poorly differentiated HCCs (0.25 ± 0.07; p = 0.006). In conclusion this study suggests that the uptake of Gd-EOB-DTPA in HCCs is correlated with tumor grade. Thus, Gd-EOB-DTPA-assisted T1 relaxometry can help to further differentiation of HCC.
Simulation studies on the boot shape injection of a giant magnetostrictive injector
Authors: Xue Guangming , Ge Jitao , Ning Peng , Zhou Jun , Wang Ke , Cheng Ziyang , Pei Guoxu
Published: November 2021

Giant magnetostrictive injector using giant magnetostrictive material acting an electronic controlled injector may be one new promising injector to acquire adjustable injection rates while maintaining large injection quantity. An electronic controlled injector driven by a giant magnetostrictive actuator was designed through combining the driving requirement and output characteristics of the material. To promote responding speed of the coil current, the driving voltage with open-hold-fall type waveform was employed just like using in an electromagnetic injector. Simulation model for the injection characteristic of the injector was established using AMEsim software and verified using experimental results collected by the single injection meter. From simulation and experimental results, designed giant magnetostrictive injector showed good performances as maximum spray rate of 4.5 L/min and minimum spray pulse width of 0.21 ms, and realized the boot shape injection when generated by the designed voltage wave. Furthermore, duration time and amplitude of the pilot spray part in a boot shape injection were respectively adjusted through changing the dwell time and opening time. The boot shape injection reached by the giant magnetostrictive injector can reach quite accurate control of fuel injection and then promote fuel efficiency effectively.