bluuebunny/crossref_metadata_2025 huggingface dataset:
The magnitude of neurocognitive impairment is overestimated in depression: the role of motivation, debilitating momentary influences, and the overreliance on mean differences
Authors: Moritz Steffen , Xie Jingyuan , Penney Danielle , Bihl Lisa , Hlubek Niklas , Elmers Julia , Beblo Thomas , Hottenrott Birgit
Published: January 2022

Background

Meta-analyses agree that depression is characterized by neurocognitive dysfunctions relative to nonclinical controls. These deficits allegedly stem from impairments in functionally corresponding brain areas. Increasingly, studies suggest that some performance deficits are in part caused by negative task-taking attitudes such as poor motivation or the presence of distracting symptoms. A pilot study confirmed that these factors mediate neurocognitive deficits in depression. The validity of these results is however questionable given they were based solely on self-report measures. The present study addresses this caveat by having examiners assess influences during a neurocognitive examination, which were concurrently tested for their predictive value on performance.

Methods

Thirty-three patients with depression and 36 healthy controls were assessed on a battery of neurocognitive tests. The examiner completed the Impact on Performance Scale, a questionnaire evaluating mediating influences that may impact performance.

Results

On average, patients performed worse than controls at a large effect size. When the total score of the Impact on Performance Scale was accounted for by mediation analysis and analyses of covariance, group differences were reduced to a medium effect size. A total of 30% of patients showed impairments of at least one standard deviation below the mean.

Conclusions

This study confirms that neurocognitive impairment in depression is likely overestimated; future studies should consider fair test-taking conditions. We advise researchers to report percentages of patients showing performance deficits rather than relying solely on overall group differences. This prevents fostering the impression that the majority of patients exert deficits, when in fact deficits are only true for a subgroup.
Prevalence of antibodies against SARS-CoV-2 among pregnant women in Norway during the period December 2019 through December 2020
Authors: Eskild Anne , Mørkrid Lars , Mortensen Siri Beisland , Leegaard Truls Michael
Published: January 2022

We studied severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence among pregnant women in Norway by including all women who were first trimester pregnant (n = 6520), each month from December 2019 through December 2020, in the catchment region of Norway's second-largest hospital. We used sera that had been frozen stored after compulsory testing for syphilis antibodies in antenatal care. The sera were analysed with the Elecsys® Anti-SARS-CoV-2 immunoassay (Roche Diagnostics, Cobas e801). This immunoassay detects IgG/IgM against SARS-CoV-2 nucleocapsid antigen. Sera with equivocal or positive test results were retested with the Liaison® SARS-CoV-2 S1/S2 IgG (DiaSorin), which detects IgG against the spike (S)1 and S2 protein on the SARS-CoV-2 virus. In total, 98 women (adjusted prevalence 1.7%) had SARS CoV-2 antibodies. The adjusted seroprevalence increased from 0.3% (1/445) in December 2019 to 5.7% (21/418) in December 2020. Out of the 98 seropositive women, 36 (36.7%) had serological signs of current SARS-CoV-2 infection at the time of serum sampling, and the incidence remained low during the study period. This study suggests that SARS CoV-2 was present in the first half of December 2019, 6 weeks before the first case was recognised in Norway. The low occurrence of SARS-CoV-2 infection during 2020, may be explained by high compliance to extensive preventive measures implemented early in the epidemic.
Cardiovascular manifestations of Hutchinson–Gilford progeria syndrome
Authors: Palma Andreia , Silva Patrícia V. , Pires António
Published: January 2022

Cardiovascular complications are the most frequent cause of death in patients with the Hutchinson–Gilford progeria syndrome. However, due to its rarity, studying the course of cardiac abnormalities has been a challenge. The cardiovascular phenotype helps to provide greater insight into the natural history of these abnormalities.
Primary health care workers perspective towards cancer in Fiji: a qualitative study
Authors: Kumar Kaushal , Mohammadnezhad Masoud
Published: January 2022

Background:

By 2040, the predicted global cancer burden is expected to be more than 27 million new cancer cases per year. Understanding primary health care workers’ (HCWs) perception on cancer can highlight new ways in which cancer advocacy can be increased. This study aimed to explore the perceptions of primary HCWs in Lautoka, Fiji, towards common cancers with focus on knowledge, risk perceptions, barriers and preventive approaches.

Methods:

The study used a qualitative method approach. The study was conducted among primary HCWs at four purposively selected health centres in Lautoka Subdivision, Fiji, from 1 March 2021 to 1 April 2021. Focus group discussions (FGDs) were conducted with primary HCWs. A semi-structured open-ended questionnaire was used to collect data, and the FGDs were audio-recorded. These audio recordings were transcribed and analysed using thematic analysis.

Results:

The responses from the four FGDs with six primary HCWs in each group emerged four major themes. These themes were cancer knowledge, health professional training, barriers and challenges and awareness strategies. Primary HCWs were not fully aware about common cancers and were not confident to discuss about cancer with their patients which is an important role of primary HCWs in cancer management. This lack of knowledge was attributed to less training received in primary care setting. Barriers to accessing cancer screening included misconceptions about cancer, negative attitudes from patients, stigmatization, lack of resources at health facility and less informed health staff. Community outreach programmes, opportunistic screening, community HCWs and the concept of a cancer hub centre were awareness strategies highlighted by primary HCWs.

Conclusions:

Lack of knowledge about common cancers among primary HCWs is a concern that is depicted well in this study. This low knowledge was attributed to lack of training on cancers received by primary HCWs. Guidelines on cancer screening and diagnosis can be developed by the health ministry to assist primary HCWs in detecting patients at pre-cancerous stage.
Adaptive teaching for GCSE and A level classical literature
Authors: Coe Becky , Steven Hunt
Published: January 2022

The new ITT Common Core Framework (CCF) for teachers expects trainee and early-career teachers to adapt their teaching to support all students in class (Department for Education, 2021). What used to be called ‘differentiation’ is now referred to as ‘adaptive teaching’ and full details of what it consists of, as far as the Department for Education in England is concerned, can be found on pages 19–20 of the CCF document. Much of the advice of that document is about supporting students with special educational needs and disabilities, about teachers’ need to recognise that different students have different levels of prior attainment and may have barriers to learning, and how different types of student grouping may affect learning in different ways. It dismisses as a ‘common misconception’ that students have different learning styles and warns against teachers creating ‘distinct tasks for different groups of pupils’ or ‘setting lower expectations for particular pupils’.
Narben aus nichtsuizidalem selbstverletzendem Verhalten – therapeutische Möglichkeiten der plastischen Chirurgie
Authors: Köllensperger Eva , Walter Clara , Germann Günter , Engel Holger , Reichenberger Matthias
Published: January 2022

Zusammenfassung. Fragestellung: Nichtsuizidales selbstverletzendes Verhalten (NSSV) kann zu einem charakteristischen Narbenmuster führen, welches Rückschlüsse auf den Ursprung der Narben zulässt. Dies begünstigt eine Stigmatisierung der Betroffenen mit einem erheblichen Einfluss auf deren Alltag und Lebensqualität. Die chirurgischen Möglichkeiten zur Korrektur dieser Narben sind wenig bekannt, obwohl das Interesse daran seitens der Betroffenen oft groß ist und die chirurgische Therapie der stigmatisierenden Narben einen dauerhaften Abschluss mit der selbstverletzenden Vergangenheit und eine Entstigmatisierung der Betroffenen erleichtern kann. Methodik: Im Zeitraum von 5 Jahren stellten sich 600 Patient_innen mit dem Wunsch nach Korrektur ihrer NSSV-Narben erstmals in unserer plastisch-chirurgischen Narbensprechstunde vor. Dabei wurden standardisiert Daten zu den Gründen für die gewünschte Narbenkorrektur, dem Zustand der Narben und etwaigen Vorbehandlungen erhoben, außerdem die Anzahl, Lokalisation und Art der von uns durchgeführten Operationen analysiert. Ergebnisse: Stigmatisierung (57 %) und Einschränkungen bei der Kleidungswahl (18 %) wurden am häufigsten als Gründe für den Behandlungswunsch angegeben. Es wurden 358 Dermabrasionen, 55 Serienexzisionen, neun Kombinationsbehandlungen und 13 andere Eingriffe zur Korrektur der NSSV-Narben durchgeführt. Schlussfolgerungen: Plastisch-chirurgische Maßnahmen zur Korrektur von NSSV-Narben können ein wichtiger Bestandteil der Therapie von Patient_innen mit NSSV sein und sollten Betroffenen frühzeitig aufgezeigt werden.
Effects of CO2 and Ocean Mixing on Miocene and Pliocene Temperature Gradients
Authors: Lohmann Gerrit , Knorr Gregor , Hossain Akil , Stepanek Christian
Published: January 2022

Cenozoic climate changes have been linked to tectonic activity and variations in atmospheric CO2 concentrations. Here, we present Miocene and Pliocene sensitivity experiments performed with the climate model COSMOS. The experiments contain changes with respect to paleogeography, ocean gateway configuration, and atmospheric CO2 concentrations, as well as a range of vertical mixing coefficients in the ocean. For the mid‐Miocene, we show that the impact of ocean mixing on surface temperature is comparable to the effect of the possible range in reconstructed CO2 concentrations. In combination with stronger vertical mixing, relatively moderate CO2 concentrations of 450 ppmv enable global‐mean surface, deep‐water, and meridional temperature characteristics representative of mid‐Miocene Climatic Optimum (MMCO) reconstructions. The Miocene climate shows a reduced meridional temperature gradient and reduced seasonality. In the case of enhanced mixing, surface and deep ocean temperatures show significant warming of up to 5–10°C and an Arctic temperature anomaly of >12°C. In the Pliocene simulations, the impact of vertical mixing and CO2 is less important for the deep ocean, which we interpret as a different sensitivity dependence on the background state and mixed layer dynamics. We find a significant reduction in surface albedo and effective emissivity for either a high level of atmospheric CO2 or increased vertical mixing. Our mixing sensitivity experiments provide a warm deep ocean via ocean heat uptake. We propose that the mixing hypothesis can be tested by reconstructions of the thermocline and seasonal paleoclimate data indicating a lower seasonality relative to today.
Trophic State Assessment of a Freshwater Himalayan Lake Using Landsat 8 OLI Satellite Imagery: A Case Study of Wular Lake, Jammu and Kashmir (India)
Authors: Mushtaq Fayma , Nee Lala Mili Ghosh , Mantoo Afaan Gulzar
Published: January 2022

A new version of Trophic State Index for freshwater Himalayan Lake (TSIFHL) has been derived from Landsat 8 OLI to determine the aquatic health of the lake ecosystem. TSIFHL is based on chlorophyll‐a concentration (CChl‐a) which has been retrieved from Landsat 8 OLI data and laboratory measurements using an empirical approach. Further, in situ measurements have also been taken with Secchi disk depth (ZSD) in a freshwater Himalayan Lake (FHL). The derived CChl‐a exhibited lower and upper limit of 25.81 and 207.96 μg/L, respectively. The modeled ZSD values ranged between 0.18 and 0.66 m with an average depth of 0.50 m. The best‐fitted regression model, developed for CChl‐a with R2 = 0.89, exhibited model error of 0.77 μg/L for the standard error of estimate (SEE). The mean absolute percentage error (MAPE), and Nash‐Sutcliffe coefficient (E) values were 5.83% and 0.98 μg/L, respectively. For the ZSD, the best‐fitted model showed errors of 0.11 μg/L (SEE), 13.93% (MAPE), and 0.77 μg/L (E) with R2 = 0.84. The proposed model is useful for bio‐optical studies of Himalayan Lake ecosystems and could provide potential support for inland water management. Long term strategies like multisector monitoring and control of nutrient load entering the lake can be developed to alleviate problems of eutrophication.
Oscillatory Loading Can Alter the Velocity Dependence of Ice‐on‐Rock Friction
Authors: Skarbek Rob M. , McCarthy Christine , Savage Heather M.
Published: January 2022

Rate and state frictional parameters are typically determined using two types of experimental protocols: velocity steps and slide‐hold‐slide events. Here we take a new approach by examining the frictional response to controlled, harmonic oscillations in load point velocity. We present a Matlab graphical user interface software package, called RSFitOSC, that allows users to easily determine frictional parameters by fitting oscillation events using the rate and state friction equations. We apply our new methods to a set of ice‐rock friction experiments conducted over a temperature range of −16.4°C to −2°C, and described in a companion paper: McCarthy et al. (2021, https://doi.org/10.1002/essoar.10509831.110.1002/essoar.10509831.1). Values of the frictional stability parameter (a–b) determined from oscillations reveal dominantly velocity‐weakening behavior across the entire range of experimental conditions. However, values of (a–b) determined from velocity steps in the same experiments yield velocity‐strengthening behavior. We also show that the elastic stiffness of the ice‐rock system depends on the temperature, and is unlikely to be explained by changes in the elastic properties of ice. Load point velocity oscillations induce oscillations in applied shear stress. Many natural fault systems exhibit slip behaviors that depend on harmonic oscillations in applied tidal stresses. Our new method provides a way to study how frictional properties directly depend on parameters relevant to tidal forcing, and how oscillatory loading must be considered when extracting friction parameters.
Freshwater Transport in the Scotian Shelf and Its Impacts on the Gulf of Maine Salinity
Authors: Wang Zhengui , Li Denghui , Xue Huijie , Thomas Andrew C. , Zhang Yinglong J. , Chai Fei
Published: January 2022

A 3D unstructured‐grid ocean circulation model covering the continental shelf and coastal seas around New England is used to investigate freshwater transport (FWT) on the Scotian Shelf (SS) and its impact on the salinity in the Gulf of Maine (GoME). The model was first validated using observed elevation, velocity, temperature, and salinity at multiple locations, demonstrating generally high model skills. Intraseasonal variabilities of freshwater fluxes in 2017 and 2018 were then analyzed across different transects around SS and Browns Bank (BB). These indicated that the flow pattern in SS during 2017 was consistent with previous understanding: low salinity water flows southwestward along the shelf and turns into the GoME around BB. However, in 2018, most of the low salinity water did not enter the GoME, but was transported to the open ocean. The most striking difference occurred early in the year when the FWT, normally at its maximum, was practically stopped by an anticyclonic eddy impinging upon the shelf break near the western end of SS. Then in March, in contrast to the prevailing eastward wind, two southwestward wind events occurred that induced an excessive amount of FWT in SS. We further showed that when anticyclonic eddies impinge on the shelf break, the typical geostrophic balance associated with southwestward flow is interrupted, and a new geostrophic balance is established with the directions of pressure gradient force and flow reversed. The influence from anticyclonic eddies explains the abnormally low FWT in SS and higher GoME salinity in 2018.
A Moderate Mitigation Can Significantly Delay the Emergence of Compound Hot Extremes
Authors: Ma Feng , Yuan Xing , Wu Peili , Zeng Zhenzhong
Published: January 2022

Compound hot extremes (ChotEs) that refer to continuous heats throughout days and nights are projected to increase, causing more serious impacts on human health than daytime or nighttime heats alone. Previous studies have focused on daytime heats, but the timing of substantial increase in ChotEs relative to natural variability, which is defined as the time of emergence (ToE) for ChotEs, remains unknown. Here we examine ToE for duration of summertime ChotEs from coupled model intercomparison project phase 6 climate model projections under two shared socioeconomic pathway scenarios (i.e., SSP245 and SSP585). We further quantify the cumulative fraction of areal and population exposed to the emergence at global and continental scales. We find that, without implementation of climate mitigation policies (i.e., SSP585), global mean ToE is around 2062 (with 16%–84% uncertainty range of 2048–2072). On the basis of the ToE for each grid cell, 80.7% (with uncertainty range of 64.2%–96.7%) of global lands will expose to the emergence by 2080. Such substantial increases in ChotEs will lead to 75.2% (66.8%–93%) of global population exposed to the emergence by the end of 21st century. A moderate mitigation (i.e., SSP245) can delay the ToE by over 14 years and, more importantly, reduce the global land areal and population exposures by 50.3% and 39.7% respectively. Regionally, northern Europe, central America and western North America benefit the most. Therefore, early action towards moderate development socioeconomic pathways can remarkably cut back the possibility of large population exposure to ChotEs and relevant impacts.
Development and validation of a prediction index for recent mortality in advanced COPD patients
Authors: Tsai Sheng-Han , Shih Chia-Yin , Kuo Chin-Wei , Liao Xin-Min , Lin Peng-Chan , Chen Chian-Wei , Hsiue Tzuen-Ren , Chen Chiung-Zuei
Published: January 2022

The primary barrier to initiating palliative care for advanced COPD patients is the unpredictable course of the disease. We enroll 752 COPD patients into the study and validate the prediction tools for 1-year mortality using the current guidelines for palliative care. We also develop a composite prediction index for 1-year mortality and validate it in another cohort of 342 patients. Using the current prognostic models for recent mortality in palliative care, the best area under the curve (AUC) for predicting mortality is 0.68. Using the Modified Medical Research Council dyspnea score and oxygen saturation to define the combined dyspnea and oxygenation (DO) index, we find that the AUC of the DO index is 0.84 for predicting mortality in the validated cohort. Predictions of 1-year mortality based on the current palliative care guideline for COPD patients are poor. The DO index exhibits better predictive ability than other models in the study.
An exomoon survey of 70 cool giant exoplanets and the new candidate Kepler-1708 b-i
Authors: Kipping David , Bryson Steve , Burke Chris , Christiansen Jessie , Hardegree-Ullman Kevin , Quarles Billy , Hansen Brad , Szulágyi Judit , Teachey Alex
Published: January 2022

Exomoons represent a crucial missing puzzle piece in our efforts to understand extrasolar planetary systems. To address this deficiency, we here describe an exomoon survey of 70 cool, giant transiting exoplanet candidates found by Kepler. We identify only one exhibiting a moon-like signal that passes a battery of vetting tests: Kepler-1708 b. We show that Kepler-1708 b is a statistically validated Jupiter-sized planet orbiting a Sun-like quiescent star at 1.6 au. The signal of the exomoon candidate, Kepler-1708 b-i, is a 4.8σ effect and is persistent across different instrumental detrending methods, with a 1% false-positive probability via injection–recovery. Kepler-1708 b-i is ~2.6 Earth radii and is located in an approximately coplanar orbit at ~12 planetary radii from its ~1.6 au Jupiter-sized host. Future observations will be necessary to validate or reject the candidate.
Multi-ancestry fine mapping implicates OAS1 splicing in risk of severe COVID-19
Authors: Huffman Jennifer E. , Butler-Laporte Guillaume , Khan Atlas , Pairo-Castineira Erola , Drivas Theodore G. , Peloso Gina M. , Nakanishi Tomoko ,   COVID-19 Host Genetics Initiative, Ganna Andrea , Verma Anurag , Baillie J. Kenneth , Kiryluk Krzysztof , Richards J. Brent , Zeberg Hugo
Published: January 2022

The OAS1/2/3 cluster has been identified as a risk locus for severe COVID-19 among individuals of European ancestry, with a protective haplotype of approximately 75 kilobases (kb) derived from Neanderthals in the chromosomal region 12q24.13. This haplotype contains a splice variant of OAS1, which occurs in people of African ancestry independently of gene flow from Neanderthals. Using trans-ancestry fine-mapping approaches in 20,779 hospitalized cases, we demonstrate that this splice variant is likely to be the SNP responsible for the association at this locus, thus strongly implicating OAS1 as an effector gene influencing COVID-19 severity.
SARS-CoV-2 infection and COVID-19 vaccination rates in pregnant women in Scotland
Authors: Stock Sarah J. , Carruthers Jade , Calvert Clara , Denny Cheryl , Donaghy Jack , Goulding Anna , Hopcroft Lisa E. M. , Hopkins Leanne , McLaughlin Terry , Pan Jiafeng , Shi Ting , Taylor Bob , Agrawal Utkarsh , Auyeung Bonnie , Katikireddi Srinivasa Vittal , McCowan Colin , Murray Josie , Simpson Colin R. , Robertson Chris , Vasileiou Eleftheria , Sheikh Aziz , Wood Rachael
Published: January 2022

Population-level data on COVID-19 vaccine uptake in pregnancy and SARS-CoV-2 infection outcomes are lacking. We describe COVID-19 vaccine uptake and SARS-CoV-2 infection in pregnant women in Scotland, using whole-population data from a national, prospective cohort. Between the start of a COVID-19 vaccine program in Scotland, on 8 December 2020 and 31 October 2021, 25,917 COVID-19 vaccinations were given to 18,457 pregnant women. Vaccine coverage was substantially lower in pregnant women than in the general female population of 18−44 years; 32.3% of women giving birth in October 2021 had two doses of vaccine compared to 77.4% in all women. The extended perinatal mortality rate for women who gave birth within 28 d of a COVID-19 diagnosis was 22.6 per 1,000 births (95% CI 12.9−38.5; pandemic background rate 5.6 per 1,000 births; 452 out of 80,456; 95% CI 5.1−6.2). Overall, 77.4% (3,833 out of 4,950; 95% CI 76.2−78.6) of SARS-CoV-2 infections, 90.9% (748 out of 823; 95% CI 88.7−92.7) of SARS-CoV-2 associated with hospital admission and 98% (102 out of 104; 95% CI 92.5−99.7) of SARS-CoV-2 associated with critical care admission, as well as all baby deaths, occurred in pregnant women who were unvaccinated at the time of COVID-19 diagnosis. Addressing low vaccine uptake rates in pregnant women is imperative to protect the health of women and babies in the ongoing pandemic.
CellRank for directed single-cell fate mapping
Authors: Lange Marius , Bergen Volker , Klein Michal , Setty Manu , Reuter Bernhard , Bakhti Mostafa , Lickert Heiko , Ansari Meshal , Schniering Janine , Schiller Herbert B. , Pe’er Dana , Theis Fabian J.
Published: January 2022

Computational trajectory inference enables the reconstruction of cell state dynamics from single-cell RNA sequencing experiments. However, trajectory inference requires that the direction of a biological process is known, largely limiting its application to differentiating systems in normal development. Here, we present CellRank (https://cellrank.org) for single-cell fate mapping in diverse scenarios, including regeneration, reprogramming and disease, for which direction is unknown. Our approach combines the robustness of trajectory inference with directional information from RNA velocity, taking into account the gradual and stochastic nature of cellular fate decisions, as well as uncertainty in velocity vectors. On pancreas development data, CellRank automatically detects initial, intermediate and terminal populations, predicts fate potentials and visualizes continuous gene expression trends along individual lineages. Applied to lineage-traced cellular reprogramming data, predicted fate probabilities correctly recover reprogramming outcomes. CellRank also predicts a new dedifferentiation trajectory during postinjury lung regeneration, including previously unknown intermediate cell states, which we confirm experimentally.
Covalent coupling of Spike’s receptor binding domain to a multimeric carrier produces a high immune response against SARS-CoV-2
Authors:   Argentinian AntiCovid Consortium, Berguer Paula M. , Blaustein Matías , Bredeston Luis M. , Craig Patricio O. , D’Alessio Cecilia , Elias Fernanda , Farré Paola C. , Fernández Natalia B. , Gentili Hernán G. , Gándola Yamila B. , Gasulla Javier , Gudesblat Gustavo E. , Herrera María G. , Ibañez Lorena I. , Idrovo-Hidalgo Tommy , Nadra Alejandro D. , Noseda Diego G. , Paván Carlos H. , Pavan María F. , Pignataro María F. , Roman Ernesto A. , Ruberto Lucas A. M. , Rubinstein Natalia , Sanchez María V. , Santos Javier , Wetzler Diana E. , Zelada Alicia M.
Published: January 2022

The receptor binding domain (RBD) of the Spike protein from SARS-CoV-2 is a promising candidate to develop effective COVID-19 vaccines since it can induce potent neutralizing antibodies. We have previously reported the highly efficient production of RBD in Pichia pastoris, which is structurally similar to the same protein produced in mammalian HEK-293T cells. In this work we designed an RBD multimer with the purpose of increasing its immunogenicity. We produced multimeric particles by a transpeptidation reaction between RBD expressed in P. pastoris and Lumazine Synthase from Brucella abortus (BLS), which is a highly immunogenic and very stable decameric 170 kDa protein. Such particles were used to vaccinate mice with two doses 30 days apart. When the particles ratio of RBD to BLS units was high (6–7 RBD molecules per BLS decamer in average), the humoral immune response was significantly higher than that elicited by RBD alone or by RBD-BLS particles with a lower RBD to BLS ratio (1–2 RBD molecules per BLS decamer). Remarkably, multimeric particles with a high number of RBD copies elicited a high titer of neutralizing IgGs. These results indicate that multimeric particles composed of RBD covalent coupled to BLS possess an advantageous architecture for antigen presentation to the immune system, and therefore enhancing RBD immunogenicity. Thus, multimeric RBD-BLS particles are promising candidates for a protein-based vaccine.
Cryoprotectant treatment tests on three morphologically diverse marine dinoflagellates and the cryopreservation of Breviolum sp. (Symbiodiniaceae)
Authors: Kihika Joseph Kanyi , Wood Susanna A. , Rhodes Lesley , Smith Kirsty F. , Thompson Lucy , Challenger Sarah , Ryan Ken G.
Published: January 2022

Dinoflagellates are among the most diverse group of microalgae. Many dinoflagellate species have been isolated and cultured, and these are used for scientific, industrial, pharmaceutical, and agricultural applications. Maintaining cultures is time-consuming, expensive, and there is a risk of contamination or genetic drift. Cryopreservation offers an efficient means for their long-term preservation. Cryopreservation of larger dinoflagellate species is challenging and to date there has been only limited success. In this study, we explored the effect of cryoprotectant agents (CPAs) and freezing methods on three species: Vulcanodinium rugosum, Alexandrium pacificum and Breviolum sp. A total of 12 CPAs were assessed at concentrations between 5 and 15%, as well as in combination with dimethyl sulfoxide (DMSO) and other non-penetrating CPAs. Two freezing techniques were employed: rapid freezing and controlled-rate freezing. Breviolum sp. was successfully cryopreserved using 15% DMSO. Despite exploring different CPAs and optimizing the freezing techniques, we were unable to successfully cryopreserve V. rugosum and A. pacificum. For Breviolum sp. there was higher cell viability (45.4 ± 2.2%) when using the controlled-rate freezing compared to the rapid freezing technique (10.0 ± 2.8%). This optimized cryopreservation protocol will be of benefit for the cryopreservation of other species from the family Symbiodiniaceae.
Modulated anti-VEGF therapy under the influence of lipid metabolizing proteins in Age related macular degeneration: a pilot study
Authors: Sharma Kaushal , Battu Priya , Singh Ramandeep , Sharma Suresh Kumar , Anand Akshay
Published: January 2022

Age-related macular degeneration (AMD) is a devastating retinal disease that results in irreversible vision loss in the aged population. The complex genetic nature and degree of genetic penetrance require a redefinition of the current therapeutic strategy for AMD. We aimed to investigate the role of modifiers for current anti-VEGF therapy especially for non-responder AMD patients. We recruited 78 wet AMD cases (out of 278 AMD patients) with their socio-demographic and treatment regimen. Serum protein levels were estimated by ELISA in AMD patients. Data pertaining to the number of anti-VEGF injections given (in 1 year) along with clinical images (FFA and OCT) of AMD patients were also included. Visual acuity data (logMAR) for 46 wet AMD cases out of a total of 78 patients were also retrieved to examine the response of anti-VEGF injections in wet AMD cases. Lipid metabolizing genes (LIPC and APOE) have been identified as chief biomarkers for anti-VEGF response in AMD patients. Both genotypes ‘CC’ and ‘GC’ of LIPC have found to be associated with a number of anti-VEGF injections in AMD patients which could influence the expression of B3GALTL,HTRA1, IER3, LIPC and SLC16A8 proteins in patients bearing both genotypes as compared to reference genotype. Elevated levels of APOE were also observed in group 2 wet AMD patients as compared to group 1 suggesting the significance of APOE levels in anti-VEGF response. The genotype of B3GALTL has also been shown to have a significant association with the number of anti-VEGF injections. Moreover, visual acuity of group 1 (≤ 4 anti-VEGF injections/year) AMD patients was found significantly improved after 3 doses of anti-VEGF injections and maintained longitudinally as compared to groups 2 and 3. Lipid metabolising genes may impact the outcome of anti-VEGF AMD treatment.
Biochemical and structural characterization of quizalofop-resistant wheat acetyl-CoA carboxylase
Authors: Bough Raven , Dayan Franck E.
Published: January 2022

A novel nucleotide mutation in ACC1 resulting in an alanine to valine amino acid substitution in acetyl-CoA carboxylase (ACCase) at position 2004 of the Alopecurus myosuroides reference sequence (A2004V) imparts quizalofop resistance in wheat. Genotypes endowed with the homozygous mutation in one or two ACC1 homoeologs are seven- and 68-fold more resistant to quizalofop than a wildtype winter wheat in greenhouse experiments, respectively. In vitro ACCase activities in soluble protein extracts from these varieties are 3.8- and 39.4-fold more resistant to quizalofop with the homozygous mutation in either one or two genomes, relative to the wildtype. The A2004V mutation does not alter the specific activity of wheat ACCase, suggesting that this resistance trait does not affect the catalytic functions of ACCase. Modeling of wildtype and quizalofop-resistant wheat ACCase demonstrates that the A2004V amino acid substitution causes a reduction in the volume of the binding pocket that hinders quizalofop’s interaction with ACCase. Docking studies confirm that the mutation reduces the binding affinity of quizalofop. Interestingly, the models suggest that the A2004V mutation does not affect haloxyfop binding. Follow up in vivo and in vitro experiments reveal that the mutation, in fact, imparts negative cross-resistance to haloxyfop, with quizalofop-resistant varieties exhibiting higher sensitivity to haloxyfop than the wildtype winter wheat line.
Electrochemical performance of composite electrodes based on rGO, Mn/Cu metal–organic frameworks, and PANI
Authors: Le Quoc Bao , Nguyen Thanh-Huong , Fei Haojie , Bubulinca Constantin , Munster Lukas , Bugarova Nikola , Micusik Matej , Kiefer Rudolf , Dao Tran Trong , Omastova Maria , Kazantseva Natalia E. , Saha Petr
Published: January 2022

Benzendicarboxylic acid (BDC)-based metal–organic frameworks (MOFs) have been widely utilized in various applications, including supercapacitor electrode materials. Manganese and copper have solid diamond frames formed with BDC linkers among transition metals chosen for MOF formation. They have shown the possibility to enlarge capacitance at different combinations of MOFs and polyaniline (PANI). Herein, reduced graphene oxide (rGO) was used as the matrix to fabricate electrochemical double-layer SCs. PANI and Mn/Cu-MOF's effect on the properties of electrode materials was investigated through electrochemical analysis. As a result, the highest specific capacitance of about 276 F/g at a current density of 0.5 A/g was obtained for rGO/Cu-MOF@PANI composite.
Bivalent single domain antibody constructs for effective neutralization of Venezuelan equine encephalitis
Authors: Liu Jinny L. , Zabetakis Dan , Gardner Christina L. , Burke Crystal W. , Glass Pamela J. , Webb Emily M. , Shriver-Lake Lisa C. , Anderson George P. , Weger-Lucarelli James , Goldman Ellen R.
Published: January 2022

Venezuelan equine encephalitis virus (VEEV) is a mosquito borne alphavirus which leads to high viremia in equines followed by lethal encephalitis and lateral spread to humans. In addition to naturally occurring outbreaks, VEEV is a potential biothreat agent with no approved human vaccine or therapeutic currently available. Single domain antibodies (sdAb), also known as nanobodies, have the potential to be effective therapeutic agents. Using an immune phage display library derived from a llama immunized with an equine vaccine that included inactivated VEEV, five sdAb sequence families were identified that showed varying ability to neutralize VEEV. One of the sequence families had been identified previously in selections against chikungunya virus, a related alphavirus of public health concern. A key advantage of sdAb is the ability to optimize properties such as neutralization capacity through protein engineering. Neutralization of VEEV was improved by two orders of magnitude by genetically linking sdAb. One of the bivalent constructs showed effective neutralization of both VEEV and chikungunya virus. Several of the bivalent constructs neutralized VEEV in cell-based assays with reductions in the number of plaques by 50% at protein concentrations of 1 ng/mL or lower, making future evaluation of their therapeutic potential compelling.
eNAMPT neutralization reduces preclinical ARDS severity via rectified NFkB and Akt/mTORC2 signaling
Authors: Bermudez Tadeo , Sammani Saad , Song Jin H. , Hernon Vivian Reyes , Kempf Carrie L. , Garcia Alexander N. , Burt Jessica , Hufford Matthew , Camp Sara M. , Cress Anne E. , Desai Ankit A. , Natarajan Viswanathan , Jacobson Jeffrey R. , Dudek Steven M. , Cancio Leopoldo C. , Alvarez Julie , Rafikov Ruslan , Li Yansong , Zhang Donna D. , Casanova Nancy G. , Bime Christian , Garcia Joe G. N.
Published: January 2022

Despite encouraging preclinical data, therapies to reduce ARDS mortality remains a globally unmet need, including during the COVID-19 pandemic. We previously identified extracellular nicotinamide phosphoribosyltransferase (eNAMPT) as a novel damage-associated molecular pattern protein (DAMP) via TLR4 ligation which regulates inflammatory cascade activation. eNAMPT is tightly linked to human ARDS by biomarker and genotyping studies in ARDS subjects. We now hypothesize that an eNAMPT-neutralizing mAb will significantly reduce the severity of ARDS lung inflammatory lung injury in diverse preclinical rat and porcine models. Sprague Dawley rats received eNAMPT mAb intravenously following exposure to intratracheal lipopolysaccharide (LPS) or to a traumatic blast (125 kPa) but prior to initiation of ventilator-induced lung injury (VILI) (4 h). Yucatan minipigs received intravenous eNAMPT mAb 2 h after initiation of septic shock and VILI (12 h). Each rat/porcine ARDS/VILI model was strongly associated with evidence of severe inflammatory lung injury with NFkB pathway activation and marked dysregulation of the Akt/mTORC2 signaling pathway. eNAMPT neutralization dramatically reduced inflammatory indices and the severity of lung injury in each rat/porcine ARDS/VILI model (~ 50% reduction) including reduction in serum lactate, and plasma levels of eNAMPT, IL-6, TNFα and Ang-2. The eNAMPT mAb further rectified NFkB pathway activation and preserved the Akt/mTORC2 signaling pathway. These results strongly support targeting the eNAMPT/TLR4 inflammatory pathway as a potential ARDS strategy to reduce inflammatory lung injury and ARDS mortality.
Construction and validation of a risk prediction model for clinical axillary lymph node metastasis in T1–2 breast cancer
Authors: Luo Na , Wen Ying , Zou Qiongyan , Ouyang Dengjie , Chen Qitong , Zeng Liyun , He Hongye , Anwar Munawar , Qu Limeng , Ji Jingfen , Yi Wenjun
Published: January 2022

The current diagnostic technologies for assessing the axillary lymph node metastasis (ALNM) status accurately in breast cancer (BC) remain unsatisfactory. Here, we developed a diagnostic model for evaluating the ALNM status using a combination of mRNAs and the T stage of the primary tumor as a novel biomarker. We collected relevant information on T1–2 BC from public databases. An ALNM prediction model was developed by logistic regression based on the screened signatures and then internally and externally validated. Calibration curves and the area under the curve (AUC) were employed as performance metrics. The prognostic value and tumor immune infiltration of the model were also determined. An optimal diagnostic model was created using a combination of 11 mRNAs and T stage of the primary tumor and showed high discrimination, with AUCs of 0.828 and 0.746 in the training sets. AUCs of 0.671 and 0.783 were achieved in the internal validation cohorts. The mean external AUC value was 0.686 and ranged between 0.644 and 0.742. Moreover, the new model has good specificity in T1 and hormone receptor-negative/human epidermal growth factor receptor 2- negative (HR−/HER2−) BC and good sensitivity in T2 BC. In addition, the risk of ALNM and 11 mRNAs were correlated with the infiltration of M2 macrophages, as well as the prognosis of BC. This novel prediction model is a useful tool to identify the risk of ALNM in T1–2 BC patients, particularly given that it can be used to adjust surgical options in the future.
A digital twin auxiliary approach based on adaptive sparse attention network for diesel engine fault diagnosis
Authors: Jiang Jiajie , Li Hui , Mao Zhiwei , Liu Fengchun , Zhang Jinjie , Jiang Zhinong , Li He
Published: January 2022

Condition monitoring and fault diagnosis of diesel engines are of great significance for safety production and maintenance cost control. The digital twin method based on data-driven and physical model fusion has attracted more and more attention. However, the existing methods lack deeper integration and optimization facing complex physical systems. Most of the algorithms based on deep learning transform the data into the substitution of the physical model. The lack of interpretability of the deep learning diagnosis model limits its practical application. The attention mechanism is gradually developed to access interpretability. In this study, a digital twin auxiliary approach based on adaptive sparse attention network for diesel engine fault diagnosis is proposed with considering its signal characteristics of strong angle domain correlation and transient non-stationary, in which a new soft threshold filter is designed to draw more attention to multi decentralized local fault information dynamically in real time. Based on this attention mechanism, the distribution of fault information in the original signal can be better visualized to help explain the fault mechanism. The valve failure experiment on a diesel engine test rig is conducted, of which the results show that the proposed adaptive sparse attention mechanism model has better training efficiency and clearer interpretability on the premise of maintaining performance.
A high‐efficiency and stable perovskite solar cell fabricated in ambient air using a polyaniline passivation layer
Authors: Kim Dong In , Lee Ji Won , Jeong Rak Hyun , Boo Jin-Hyo
Published: January 2022

Over the past number of years, the power conversion efficiency of perovskite solar cells has remained at 25.5%, reflecting a respectable result for the general incorporation of organometallic trihalide perovskite solar cells. However, perovskite solar cells still suffer from long-term stability issues. Perovskite decomposes upon exposure to moisture, thermal, and UV-A light. Studies related to this context have remained ongoing. Recently, research was mainly conducted on the stability of perovskite against non-radiative recombination. This study improved a critical instability in perovskite solar cells arising from non-radiative recombination and UV-A light using a passivation layer. The passivation layer comprised a polyaniline (PANI) polymer as an interfacial modifier inserted between the active layer and the electron transport layer. Accordingly, the UV-A light did not reach the active layer and confined the Pb2+ ions at PANI passivation layer. This study optimized the perovskite solar cells by controlling the concentration, thickness and drying conditions of the PANI passivation layer. As a result, the efficiency of the perovskite solar cell was achieved 15.1% and showed over 84% maintain in efficiency in the ambient air for one month using the 65 nm PANI passivation layer.
Response of litter decomposition and the soil environment to one-year nitrogen addition in a Schrenk spruce forest in the Tianshan Mountains, China
Authors: Ding Zhaolong , Liu Xu , Gong Lu , Chen Xin , Zhao Jingjing , Chen Wenjing
Published: January 2022

Human activities have increased the input of nitrogen (N) to forest ecosystems and have greatly affected litter decomposition and the soil environment. But differences in forests with different nitrogen deposition backgrounds. To better understand the response of litter decomposition and soil environment of N-limited forest to nitrogen deposition. We established an in situ experiment to simulate the effects of N deposition on soil and litter ecosystem processes in a Picea schrenkiana forest in the Tianshan Mountains, China. This study included four N treatments: control (no N addition), low N addition (LN: 5 kg N ha−1 a−1), medium N addition (MN: 10 kg N ha−1 a−1) and high N addition (HN: 20 kg N ha−1 a−1). Our results showed that N addition had a significant effect on litter decomposition and the soil environment. Litter mass loss in the LN treatment and in the MN treatment was significantly higher than that in the control treatment. In contrast, the amount of litter lost in the HN treatment was significantly lower than the other treatments. N application inhibited the degradation of lignin but promoted the breakdown of cellulose. The carbon (C), N, and phosphorus (P) contents of litter did not differ significantly among the treatments, but LN promoted the release of C and P. Our results also showed that soil pH decreased with increasing nitrogen application rates, while soil enzyme activity showed the opposite trend. In addition, the results of redundancy analysis (RDA) and correlation analyses showed that the soil environment was closely related to litter decomposition. Soil enzymes had a positive effect on litter decomposition rates, and N addition amplified these correlations. Our study confirmed that N application had effects on litter decomposition and the soil environment in a N-limited P. schrenkiana forest. LN had a strong positive effect on litter decomposition and the soil environment, while HN was significantly negative. Therefore, increased N deposition may have a negative effect on material cycling of similar forest ecosystems in the near future.
Automated light-induced synthesis of 89Zr-radiolabeled antibodies for immuno-positron emission tomography
Authors: Klingler Simon , Holland Jason P.
Published: January 2022

Clinical production of 89Zr-radiolabeled antibodies (89Zr-mAbs) for positron emission tomography imaging relies on the pre-conjugation of desferrioxamine B (DFO) to the purified protein, followed by isolation and characterization of the functionalized intermediate, and then manual radiosynthesis. Although highly successful, this route exposes radiochemists to a potentially large radiation dose and entails several technological and economic hurdles that limit access of 89Zr-mAbs to just a specialist few Nuclear Medicine facilities worldwide. Here, we introduce a fully automated synthesis box that can produce individual doses of 89Zr-mAbs formulated in sterile solution in < 25 min starting from [89Zr(C2O4)4]4– (89Zr-oxalate), our good laboratory practice-compliant photoactivatable desferrioxamine-based chelate (DFO-PEG3-ArN3), and clinical-grade antibodies without the need for pre-purification of protein. The automated steps include neutralization of the 89Zr-oxalate stock, chelate radiolabeling, and light-induced protein conjugation, followed by 89Zr-mAb purification, formulation, and sterile filtration. As proof-of-principle, 89ZrDFO-PEG3-azepin-trastuzumab was synthesized directly from Herceptin in < 25 min with an overall decay-corrected radiochemical yield of 20.1 ± 2.4% (n = 3), a radiochemical purity > 99%, and chemical purity > 99%. The synthesis unit can also produce 89Zr-mAbs via the conventional radiolabeling routes from pre-functionalized DFO-mAbs that are currently used in the clinic. This automated method will improve access to state-of-the-art 89Zr-mAbs at the many Nuclear Medicine and research institutions that require automated devices for radiotracer production.
Recycling of clastics in coastal areas inferred from quantitative analysis of reworked radiocarbon samples
Authors: Tanabe Susumu , Nakanishi Toshimichi , Nakashima Rei
Published: January 2022

Studies of the evolution of coastal lowlands since the Last Glacial Maximum (LGM) typically ignore radiocarbon data from sediment samples that have undergone reworking. However, these samples contain information on their sediment sources and the timing of their redeposition. We analyzed 738 radiocarbon dates obtained from shell and plant material in samples of post-LGM coastal sediment from north of Tokyo Bay, Japan. Of these samples, 245 (33%) were reworked. Furthermore, the percentage of reworked samples and their average age offsets increased with the depth of the water environment (terrestrial, 15% and 360 ± 250 years, respectively; intertidal, 26% and 470 ± 620 years; subtidal, 39% and 550 ± 630 years). Taking these radiocarbon samples as a proxy for clastic material, our results imply that channel erosion accounted for relatively little clastic removal in the terrestrial and intertidal environments over short timescales, whereas ~ 40% of clastics were removed by storm winnowing and transported in stepwise fashion to deeper water over longer timescales and ~ 60% in the subtidal environment were transported by floods directly from river mouths. These findings imply that radiocarbon ages from reworked samples can be used to quantify clastic recycling processes and their history in coastal areas.