bluuebunny/crossref_metadata_2025 huggingface dataset:
Covid-19 and Families With Parental Mental Illness: Crisis and Opportunity
Authors: Furlong Mairead , McGilloway Sinead , Mulligan Christine , Killion Mary G. , McGarr Sharon , Grant Anne , Davidson Gavin , Donaghy Mary
Published: July 2021

The COVID-19 emergency has affected us all, but not equally. Families where parents have mental illness (PMI) are potentially at increased risk, but little is known about how they or their support services managed under lockdown/restrictions. We harnessed our existing partnerships with adult and child mental health services in the Republic of Ireland (RoI) and Northern Ireland (NI) to investigate the qualitative experiences of service users and families in coping during the first COVID-19 lockdown (March–May 2020), and how services were supporting them. Semi-structured phone/online interviews were conducted with 22 clinicians/managers (12 from RoI; 10 from NI) who provided information from their caseloads (~155 families with PMI). Sixteen family members (10 from RoI, 6 from NI) were also interviewed. Data were analysed using standard thematic analysis. Sixty percent of families reported improved mental health, primarily due to respite from daily stresses and the “normalisation” of mental distress in the general population. Approximately 30%, typically with more severe/enduring mental illness, reported additional challenges, and mental distress including: unmanageable child behaviours; fear of relapse/hospitalisation; financial difficulties; absence of child care; and a lack of routines. Service provision varied considerably across regions. The experiences within this case study highlight unique opportunities to address the multiple stresses of pre-emergency daily living. We also highlight how mental health services and governments might become more “pandemic ready” to more effectively support vulnerable families, including addressing service overload issues, optimising the use of digital technologies, and providing in-person contact and social supports where required.
Computational Mechanism for the Effect of Psychosis Community Treatment: A Conceptual Review From Neurobiology to Social Interaction
Authors: Benrimoh David , Sheldon Andrew , Sibarium Ely , Powers Albert R.
Published: July 2021

The computational underpinnings of positive psychotic symptoms have recently received significant attention. Candidate mechanisms include some combination of maladaptive priors and reduced updating of these priors during perception. A potential benefit of models with such mechanisms is their ability to link multiple levels of explanation, from the neurobiological to the social, allowing us to provide an information processing-based account of how specific alterations in self-self and self-environment interactions result in the experience of positive symptoms. This is key to improving how we understand the experience of psychosis. Moreover, it points us toward more comprehensive avenues for therapeutic research by providing a putative mechanism that could allow for the generation of new treatments from first principles. In order to demonstrate this, our conceptual paper will discuss the application of the insights from previous computational models to an important and complex set of evidence-based clinical interventions with strong social elements, such as coordinated specialty care clinics (CSC) in early psychosis and assertive community treatment (ACT). These interventions may include but also go beyond psychopharmacology, providing, we argue, structure and predictability for patients experiencing psychosis. We develop the argument that this structure and predictability directly counteract the relatively low precision afforded to sensory information in psychosis, while also providing the patient more access to external cognitive resources in the form of providers and the structure of the programs themselves. We discuss how computational models explain the resulting reduction in symptoms, as well as the predictions these models make about potential responses of patients to modifications or to different variations of these interventions. We also link, via the framework of computational models, the patient's experiences and response to interventions to putative neurobiology.
Rapid COVID-19 Antigen Testing in Croatia: Risk Perception Plays an Important Role in the Epidemic Control
Authors: Primorac Dragan , Perić Vitorio , Matišić Vid , Molnar Vilim , Zadro Renata , Vince Adriana , Lauc Gordan , Polašek Ozren
Published: July 2021

Aim: To explore the clinical presentation and epidemiological history of the subjects who underwent SARS-CoV-2 antigen testing.

Methods: We included 1,000 consecutive subjects who presented themselves at the diagnostic clinic in Croatia and analyzed their symptoms and epidemiological history. All subjects were classified into three groups, according to their reason of arrival; symptomatic, contacts of confirmed patients, and those who were tested due to administrative reasons.

Results: On average, there were 24% of positive antigen results; the positivity rate was 51% among symptomatic, 16% in contacts, and 5% of administrative patients. The commonest symptoms of the disease included febrility and anosmia. We developed a clinical score to predict SARS-CoV-2 positivity, which had an area under the curve of 79.3 [95% confidence intervals (CI) 75.8–82.8]. Contact with the isolated person [odds ratio 0.54 (95% CI 0.31–0.94)] and international travel had a protective effect [0.20 (0.09–0.43)], suggesting that risk perception and mandatory pretravel measures had a key role in the determination of the infection risk.

Conclusions: A combination of clinical symptoms can have reasonable predictive power for an antigen-positive test result. Risk perception seems to have a role in the epidemic spread, probably via stricter adherence to personal preventative measures.
Case Report: Sacral Nerve Root Pelvic Neural Retraining, With Long-Term Sustainability After the Device Explantation
Authors: Vassiliu Panteleimon , Patoulis Filippos , Naar Leon , Dendias Georgios , Arkadopoulos Nikolaos
Published: July 2021

Introduction: Sacral-Nerve-Neuromodulation (SNM) is an effective treatment increasingly used in patients with urinary (UI) and fecal incontinence (FI). The way it acts in the body at its full potential have not yet been elucidated. The authors review the literature on SNM and the way it possibly works, relating it to a case with an unusually favorable outcome.

Case Presentation: A female presented with UI and FI. Operated for meningocele as a neonate. It the age of 5 bilateral Cohen ureter reimplantation performed for persistent urinary infections due to vesicourethral reflux. At the age of 13, she started complaining about UI associated with a hyper functional detrusor muscle. After a diary incontinence evaluation with a standardized questionnaire, SNM was applied at the age of 18 and was retained for 4 years. She was re-evaluated with a yearly follow-up.

Results: The patient retained the positive effect of SNM even after its removal and in addition showed signs of improvement. The patient developed the sensation of fillingness of the bladder and the rectum, which she never had before the SNM implantation, sensation which she retained 29 months after (last follow-up) device removal, allowing her to control her voids.

Discussion: The modern literature hypothesis that SNM contributes to the plasticity of the nerves through the stimulated area is supported by the present case, in which the SNM effect remained and led to improvements even after its removal. Device settings are presented as they may correlate with the result. This reinforces and expands the frontiers of SNM application and research.
A Citizen Science Trial to Assess Perception of Wild Penguin Welfare
Authors: Freire Rafael , Massaro Melanie , McDonald Simon , Trathan Philip , Nicol Christine J.
Published: July 2021

Wild penguins are facing increased threats to their populations and their welfare as a consequence of human activities. Understanding the perception of animal welfare is essential to identify ethical concerns related to the negative impact of anthropogenic factors on wild species and to guide conservation efforts that reflect societal values. Since penguin conservation is of general interest, we examined the human dimension of welfare assessment across a range of interest groups concerned with penguins, seabird biology and wildlife conservation. We provided participants with a Penguin Welfare Assessment Tool (PWAT) based on the five domains model. The PWAT supports consideration of the impact of four physical aspects on welfare-relevant mental states. Bibliometric analysis of keywords from 347 scientific articles indicated that penguins around the world face five main types (themes) of anthropogenic factors and we then developed five hypothetical scenarios, each related to one theme. Seventy-five participants scored the overall impact of the events described in the scenarios on penguin welfare as negative using the PWAT. Participants rated short-duration, high-intensity events (i.e., being trapped in a ghost fishing net) as having a significantly more severe impact on penguin welfare than low-intensity, long-duration events (P< 0.0001). Scores provided by participants for each domain for each scenario were largely as expected and we found good correlation (allP< 0.0001) between the physical domains and “mental state” for all scenarios, indicating that the tool was facilitating the participants' assessment of welfare. No evidence was found that experience of working or studying penguins, or indeed any other demographic factor investigated, influenced the assessments of welfare. We found little agreement between participants in the scores provided (unalike scores mostly between 0.7 and 0.8), and agreement between participants with experience of working with penguins was no better than between participants without such experience. We discuss the possibility that low agreement within different interest groups may be improved by providing more scientific information to support the evaluation of penguin welfare. We conclude that scientific knowledge of penguin biological responses to anthropogenic factors is vital to support the evaluation of wild penguin welfare by the public and other stakeholders.
Relationships Linking the Colour and Elemental Concentrations of Blossom Honeys with Their Antioxidant Activity: A Chemometric Approach
Authors: Kędzierska-Matysek Monika , Teter Anna , Stryjecka Małgorzata , Skałecki Piotr , Domaradzki Piotr , Rudaś Michał , Florek Mariusz
Published: July 2021

The antioxidant activity of honey depends on the botanical origin, which also determines their physicochemical properties. In this study, a multivariate analysis was used to confirm potential relationships between the antioxidant properties and colour parameters, as well as the content of seven elements in five types of artisanal honey (rapeseed, buckwheat, linden, black locust, and multifloral). The type of honey was found to significantly influence most of its physicochemical properties, colour parameters, and the content of potassium, manganese and copper. Antioxidant parameters were shown to be significantly positively correlated with redness and concentrations of copper and manganese, but negatively correlated with the hue angle and lightness. The principal component analysis confirmed that the darkest buckwheat honey had the highest antioxidant activity in combination with its specific colour parameters and content of antioxidant minerals (manganese, copper and zinc). The level of these parameters can be potentially used for the identification of buckwheat honey.
Influence of Heat Stress, Variations in Soil Type, and Soil Amendment on the Growth of Three Drought–Tolerant Maize Varieties
Authors: Chukwudi Uchechukwu Paschal , Kutu Funso Raphael , Mavengahama Sydney
Published: July 2021

Food security in sub–Saharan Africa is threatened by the increasing incidence of heat stress. Therefore, ameliorating heat stress influence in plants is vital for sustainable crop production. A 2 × 3 × 3 × 2 factorial experiment fitted into a completely randomized design with four replications was performed. The factors were heat stress, maize variety, soil amendment, and soil type. The results showed that heat stress exerted a depressive effect on maize growth and yield attributes. It reduced the leaf chlorophyll content, leaf area, plant height, stem diameter, dry biomass yield, and harvest index by 35%, 36%, 41%, 59%, and 78%, respectively. Sandy clay loam soil provided a better maize growth condition than loamy sand soil. Organic manure soil amendment improved maize growth attributes over the mineral fertilizer in the non–heat–stress environment and ameliorated the negative impact of heat stress in the heat–stress environment. The ranking of the attributes identified leaf area, dry biomass yield, stem diameter, and plant height as the most discriminating and representative attributes. These attributes should be considered in maize development projects for heat–stress prone areas. Selection of appropriate maize variety and accompanying soil amendment should be integrated into food security strategy as they influenced maize growth and yield under (non–)heat–stress conditions.
Effects of Heated Drinking Water on the Growth Performance and Rumen Functionality of Fattening Charolaise Beef Cattle in Winter
Authors: Grossi Silvia , Rossi Luciana , Dell’Anno Matteo , Biffani Stefano , Sgoifo Rossi Carlo Angelo
Published: July 2021

The effects of heated drinking water on growth performance and rumen functionality in fattening beef cattle during winter were evaluated. Newly received Charolaise bulls (n = 224) were allocated to two experimental groups: (i) water at room temperature (RTW) (weight 408 ± 34 kg); (ii) constantly heated water (25 °C) (HW) (weight 405 ± 38 kg). Growth performances, feed intake, feed conversion rate, water intake and carcass characteristics were evaluated. Internal reticuloruminal wireless boluses were used to collect rumen pH and temperature values every 10 min. Bodyweight was not affected by the water temperature, but the overall average daily gain (ADG) was significantly higher in the HW group (1.486 vs. 1.438 kg/head/day in the RTW; p = 0.047). Dry matter intake was significantly higher in the HW group (p = 0.001), even though the final feed conversion rate (FCR) was not influenced. There was also a tendency for better cold carcass weight (CCW) and carcass yield (CY) in the HW group. Drinking heated water reduced the time (min/day) during which the ruminal pH was below pH 5.8 or 5.5, and the time during which the temperature was lower than 37 or 39 °C (p < 0.001). The use of heated drinking water is a plausible a strategy for enhancing ruminal stability and the overall production efficiency in fattening beef cattle, which will lead to both better growth performance and higher ruminal stability.
Late Gestation Maternal Feed Restriction Decreases Microbial Diversity of the Placenta While Mineral Supplementation Improves Richness of the Fetal Gut Microbiome in Cattle
Authors: Hummel Gwendolynn , Woodruff Kelly , Austin Kathleen , Knuth Ryan , Lake Scott , Cunningham-Hollinger Hannah
Published: July 2021

Feed intake restriction impacts both humans and ruminants in late gestation, although it is unknown whether this adverse maternal environment influences the microbiome of the reproductive tract, and through it, the colonization of the fetal gut. A 2 × 2 factorial design including a 70% feed intake restriction (feed restricted ‘FR’ or control diets ‘CON’) and mineral supplementation (unsupplemented ‘S−’ or supplemented ‘S+’) was used to analyze these effects in multiparous cows (n = 27). Vaginal swabs were obtained 60, 30, and 10 days prior to the estimated calving date, along with neonatal rumen fluid and meconium. Placental tissues and efficiency measurements were collected. Microbial DNA was extracted for 16S sequencing of the V4 region. Feed restriction decreased the diversity of the placental microbiome, but not the vagina, while mineral supplementation had little impact on these microbial communities. Mineral supplementation did improve the richness and diversity of the fetal gut microbiomes in relation to reproductive microbes. These differences within the placental microbiome may influence individual health and performance. Adequate maternal nutrition and supplementation yielded the greatest placental efficiency, which may aid in the establishment of a healthy placental microbiome and fetal microbial colonization.
An Optimization-Based Strategy for Solving Optimal Power Flow Problems in a Power System Integrated with Stochastic Solar and Wind Power Energy
Authors: Riaz Muhammad , Hanif Aamir , Hussain Shaik Javeed , Memon Muhammad Irfan , Ali Muhammad Umair , Zafar Amad
Published: July 2021

In an effort to reduce greenhouse gas emissions, experts are looking to substitute fossil fuel energy with renewable energy for environmentally sustainable and emission free societies. This paper presents the hybridization of particle swarm optimization (PSO) with grey wolf optimization (GWO), namely a hybrid PSO-GWO algorithm for the solution of optimal power flow (OPF) problems integrated with stochastic solar photovoltaics (SPV) and wind turbines (WT) to enhance global search capabilities towards an optimal solution. A solution approach is used in which SPV and WT output powers are estimated using lognormal and Weibull probability distribution functions respectively, after simulation of 8000 Monte Carlo scenarios. The control variables include the forecast real power generation of SPV and WT, real power of thermal generators except slack-bus, and voltages of all voltage generation buses. The total generation cost of the system is considered the main objective function to be optimized, including the penalty and reserve cost for underestimation and overestimation of SPV and WT, respectively. The proposed solution approach for OPF problems is verified on the modified IEEE 30 bus test system. The performance and robustness of the proposed hybrid PSO-GWO algorithm in solving the OPF problem is assessed by comparing the results with five other metaheuristic optimization algorithms for the same test system, under the same control variables and system constraints. Simulation results confirm that the hybrid PSO-GWO algorithm performs well compared to other algorithms and shows that it can be an efficient choice for the solution of OPF problems.
Carbon Nano-Onion Peroxidase Composite Biosensor for Electrochemical Detection of 2,4-D and 2,4,5-T
Authors: Sok Vibol , Fragoso Alex
Published: July 2021

Carbon nano-onions are emerging electrode materials in biosensing due to their high conductivity and biocompatibility. Phenoxy-based herbicides are a source of environmental contamination that can be detected using their property to inhibit the activity of some enzymes. Here we report a biosensor based on peroxidase immobilized on carbon nano-onions in a cyclodextrin polymer matrix for the amperometric detection of 2,4-D and 2,4,5-T. The inhibition mechanism of 2,4-D and 2,4,5-T on peroxidase activity was first elucidated by activity measurements and molecular docking. The biosensor was characterized by electrochemical and microscopy methods and applied to the amperometric detection of these herbicides. The incorporation of carbon nano-onions enhanced the sensitivity of the biosensor and improved its stability and repeatability. The application of the developed biosensor to the detection of 2,4-D in soil and 2,4,5-T in river water samples is also reported.
Accurate Prediction and Key Feature Recognition of Immunoglobulin
Authors: Gong Yuxin , Liao Bo , Peng Dejun , Zou Quan
Published: July 2021

Immunoglobulin, which is also called an antibody, is a type of serum protein produced by B cells that can specifically bind to the corresponding antigen. Immunoglobulin is closely related to many diseases and plays a key role in medical and biological circles. Therefore, the use of effective methods to improve the accuracy of immunoglobulin classification is of great significance for disease research. In this paper, the CC–PSSM and monoTriKGap methods were selected to extract the immunoglobulin features, MRMD1.0 and MRMD2.0 were used to reduce the feature dimension, and the effect of discriminating the two–dimensional key features identified by the single dimension reduction method from the mixed two–dimensional key features was used to distinguish the immunoglobulins. The data results indicated that monoTrikGap (k = 1) can accurately predict 99.5614% of immunoglobulins under 5-fold cross–validation. In addition, CC–PSSM is the best method for identifying mixed two–dimensional key features and can distinguish 92.1053% of immunoglobulins. The above proves that the method used in this paper is reliable for predicting immunoglobulin and identifying key features.
Creating Welsh Language Word Embeddings
Authors: Corcoran Padraig , Palmer Geraint , Arman Laura , Knight Dawn , Spasić Irena
Published: July 2021

Word embeddings are representations of words in a vector space that models semantic relationships between words by means of distance and direction. In this study, we adapted two existing methods, word2vec and fastText, to automatically learn Welsh word embeddings taking into account syntactic and morphological idiosyncrasies of this language. These methods exploit the principles of distributional semantics and, therefore, require a large corpus to be trained on. However, Welsh is a minoritised language, hence significantly less Welsh language data are publicly available in comparison to English. Consequently, assembling a sufficiently large text corpus is not a straightforward endeavour. Nonetheless, we compiled a corpus of 92,963,671 words from 11 sources, which represents the largest corpus of Welsh. The relative complexity of Welsh punctuation made the tokenisation of this corpus relatively challenging as punctuation could not be used for boundary detection. We considered several tokenisation methods including one designed specifically for Welsh. To account for rich inflection, we used a method for learning word embeddings that is based on subwords and, therefore, can more effectively relate different surface forms during the training phase. We conducted both qualitative and quantitative evaluation of the resulting word embeddings, which outperformed previously described word embeddings in Welsh as part of larger study including 157 languages. Our study was the first to focus specifically on Welsh word embeddings.
Microstructural Changes and Chemical Analysis of Fission Products in Irradiated Uranium-7 wt.% Molybdenum Metallic Fuel Using Atom Probe Tomography
Authors: Bachhav Mukesh , Miller Brandon , Gan Jian , Keiser Dennis , Leenaers Ann , Berghe S. Van den , Meyer Mitchell K.
Published: July 2021

Understanding the microstructural and phase changes occurring during irradiation and their impact on metallic fuel behavior is integral to research and development of nuclear fuel programs. This paper reports systematic analysis of as-fabricated and irradiated low-enriched U-Mo (uranium-molybdenum metal alloy) fuel using atom probe tomography (APT). This study is carried out on U-7 wt.% Mo fuel particles coated with a ZrN layer contained within an Al matrix during irradiation. The dispersion fuel plates from which the fuel samples were extracted are irradiated at Belgian Nuclear Research Centre (SCK CEN) with burn-up of 52% and 66% in the framework of the SELENIUM (Surface Engineering of Low ENrIched Uranium-Molybdenum) project. The APT studies on U-Mo particles from as-fabricated fuel plates enriched to 19.8% revealed predominantly γ-phase U-Mo, along with a network of the cell boundary decorated with α-U, γ’-U2Mo, and UC precipitates along the grain boundaries. The corresponding APT characterization of irradiated fuel samples showed formation of fission gas bubbles enriched with solid fission products. The intermediate burnup sample showed a uniform distribution of the typical bubble superlattice with a radius of 2 nm arranged in a regular lattice, while the high burnup sample showed a non-uniform distribution of bubbles in grain-refined regions. There was no evidence of remnant α-U, γ’-U2Mo, and UC phases in the irradiated U-7 wt.% Mo samples.
Reduced Dimensionality Multiphysics Model for Efficient VCSEL Optimization
Authors: Gullino Alberto , Tibaldi Alberto , Bertazzi Francesco , Goano Michele , Debernardi Pierluigi
Published: July 2021

The ICT scene is dominated by short-range intra-datacenter interconnects and networking, requiring high speed and stable operations at high temperatures. GaAs/AlGaAs vertical-cavity surface-emitting lasers (VCSELs) emitting at 850–980 nm have arisen as the main actors in this framework. Starting from our in-house 3D fully comprehensive VCSEL solver VENUS, in this work we present the possibility of downscaling the dimensionality of the simulation, ending up with a multiphysics 1D solver (D1ANA), which is shown to be capable of reproducing the experimental data very well. D1ANA is then extensively applied to optimize high-temperature operation, by modifying cavity detuning and distributed Bragg’s reflector lengths.
Spatial and Temporal Characteristics of Rainfall Anomalies in 1961–2010 in the Yangtze River Basin, China
Authors: Bai Shuying , Gao Jixi , Xue Yu , Mansour Romany
Published: July 2021

Understanding rainfall anomalies and their relationship with floods in the Yangtze River Basin (YRB) is essential for evaluating flood disasters, which have a great impact on the development of agriculture and the economy. On the basis of daily rainfall data from 1961 to 2010 from 178 meteorological stations, the temporal and spatial characteristics of rainfall anomalies in the YRB were studied on an annual scale, seasonal scale, and monthly scale. The annual rainfall of the YRB showed a generally increasing trend from 1961 to 2010 (14.22 mm/10 a). By means of the Bernaola–Galvan abrupt change test and Redfit spectrum analysis, it was found that the annual average rainfall increased abruptly after 1979 and had a cycle of 2–3 years. On the seasonal scale, the rainfall in spring and autumn showed a gradually decreasing trend, especially in September, while it showed a significant increasing trend in summer and winter in the YRB. As for the monthly scale, the rainfall in the rainy season from June to July presented a clear increasing trend during the study period, which greatly enhanced the probability of floods in the YRB. Additionally, through the analysis of the spatial distribution characteristics of rainfall in the entire YRB from 1961 to 2010, it was observed that the annual rainfall amount in the YRB presented an “increase–decrease–increase” tendency from east to west, accompanied by a rain belt that continuously moved from west to east. Moreover, the rainfall characteristics in flood years were summarized, and the results revealed that the years with rainfall anomalies were more likely to have flood disasters. However, anomalies alone would not result in big floods; the spatially and temporally inhomogeneous rainfall distribution might be the primary reason for flood disasters in the entire YRB.
The Existence of Nontrivial Solution for a Class of Kirchhoff-Type Equation of General Convolution Nonlinearity without Any Growth Conditions
Authors: Zhou Li , Zhu Chuanxi
Published: July 2021

In this paper, we consider the following Kirchhoff-type equation: {u∈H1(RN),−(a+b∫RN|∇u|2dx)Δu+V(x)u=(Iα∗F(u))f(u)+λg(u),inRN, where a>0, b≥0, λ>0, α∈(N−2,N), N≥3, V:RN→R is a potential function and Iα is a Riesz potential of order α∈(N−2,N). Under certain assumptions on V(x), f(u) and g(u), we prove that the equation has at least one nontrivial solution by variational methods.
Response Assessment and Prediction of Progression-Free Survival by 68Ga-PSMA-11 PET/CT Based on Tumor-to-Liver Ratio (TLR) in Patients with mCRPC Undergoing 177Lu-PSMA-617 Radioligand Therapy
Authors: Khreish Fadi , Wiessner Mona , Rosar Florian , Ghazal Zaidoon , Sabet Amir , Maus Stephan , Linxweiler Johannes , Bartholomä Mark , Ezziddin Samer
Published: July 2021

At present, little is known about the molecular imaging-based response assessment of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy with 177Lutetium (177Lu-PSMA-617 RLT) in metastatic castration-resistant prostate cancer (mCRPC). Our study evaluated the response to RLT using both molecular imaging and biochemical response assessments, and their potential prediction of progression-free survival (PFS). Fifty-one consecutive patients given two cycles of RLT at 6-week intervals were analyzed retrospectively. 68Ga-PSMA-11 PET/CT was obtained about 2 weeks prior to the first and 4–6 weeks after the second cycle. Molecular imaging-based response using SUVpeak and tumor-to-liver ratio (TLR) was determined by modified PERCIST criteria. ∆TLR and ∆SUV were significantly correlated with ∆PSA (p < 0.001, each). After a median follow-up of 49 months, the median PFS (95% CI) was 8.0 (5.9–10.1) months. In univariate analysis, responders showing partial remission (PRPSA and PRTLR) had significantly (p < 0.001, each) longer PFS (median: 10.5 and 9.3 months) than non-responders showing either stable or progressive disease (median: 4.0 and 3.5 months). Response assessment using SUVpeak failed to predict survival. In multivariable analysis, response assessment using TLR was independently associated with PFS (p < 0.001), as was good performance status (p = 0.002). Molecular imaging-based response assessment with 68Ga-PSMA-11 PET/CT using normalization of the total lesion PSMA over healthy liver tissue uptake (TLR) could be an appropriate biomarker to monitor RLT in mCRPC patients and to predict progression-free survival (PFS) of this treatment modality.
Anti-Phospholipid Antibodies and COVID-19 Thrombosis: A Co-Star, Not a Supporting Actor
Authors: Gil-Etayo Francisco Javier , Garcinuño Sara , Lalueza Antonio , Díaz-Simón Raquel , García-Reyne Ana , Pleguezuelo Daniel Enrique , Cabrera-Marante Oscar , Rodriguez-Frias Edgard Alfonso , Perez-Rivilla Alfredo , Serrano Manuel , Serrano Antonio
Published: July 2021

Background: COVID-19 clinical features include a hypercoagulable state that resembles the antiphospholipid syndrome (APS), a disease characterized by thrombosis and presence of antiphospholipid antibodies (aPL). The relationship between aPL-presence and the appearance of thrombi as well as the transience or permanence of aPL in COVID-19 patients is not sufficiently clear. Methods: A group of 360 COVID-19 patients were followed-up for 6 months. Classic aPL, anti-B2GPI IgA, anti-phosphatidylserine/prothrombin IgG/M and anti-SARS-CoV-2 antibodies were determined at acute phase and >12 weeks later. The reference group included 143 healthy volunteers of the same age-range distribution. Results: aPL prevalence was similar in COVID-19 patients and the reference population. aPL presence in both determinations was significantly associated with thrombosis (OR: 2.33 and 3.71), strong agreement being found for classic aPL and anti-B2GPI IgA (Weighted kappa: 0.85–0.91). Thrombosis-associated aPL occurred a median of 17 days after hospital admission (IQR: 6–28) vs. 4 days for the rest (IQR: 3–7). Although anti-SARS-CoV-2 antibodies levels increased during convalescence, aPL hardly changed. Conclusions: Most COVID-19 patients would carry these aPL before the infection. At least two mechanisms could be behind thrombosis, early immune-dysregulation-mediated thrombosis after infection and belated-aPL-mediated thrombosis, with SARS-CoV-2 behaving as a second hit.
Long-Term Impact of COVID-19: A Systematic Review of the Literature and Meta-Analysis
Authors: Sanchez-Ramirez Diana C. , Normand Kaylene , Zhaoyun Yang , Torres-Castro Rodrigo
Published: July 2021

Background: The long-term impact of COVID-19 is still unknown. This study aimed to explore post COVID-19 effects on patients chest computed tomography (CT), lung function, respiratory symptoms, fatigue, functional capacity, health-related quality of life (HRQoL), and the ability to return to work beyond 3 months post infection. Methods: A systematic search was performed on PubMed, Web of Science, and Ovid MEDLINE on 22 May 2021, to identify studies that reported persistent effects of COVID-19 beyond 3 months follow-up. Data on the proportion of patients who had the outcome were collected and analyzed using a one-group meta-analysis. Results: Data were extracted from 24 articles that presented information on a total of 5323 adults, post-infection, between 3 to 6 months after symptom onset or hospital discharge. The pooled prevalence of CT abnormalities was 59% (95% CI 44–73, I2 = 96%), abnormal lung function was 39% (95% CI 24–55, I2 = 94%), fatigue was 38% (95% CI 27–49, I2 = 98%), dyspnea was 32% (95% CI 24–40, I2 = 98%), chest paint/tightness was 16% (95% CI 12–21, I2 = 94%), and cough was 13%, (95% CI 9–17, I2 = 94%). Decreased functional capacity and HRQoL were found in 36% (95% CI 22–49, I2 = 97%) and 52% (95% CI 33–71, I2 = 94%), respectively. On average, 8 out of 10 of the patients had returned to work or reported no work impairment. Conclusion: Post-COVID-19 patients may experience persistent respiratory symptoms, fatigue, decreased functional capacity and decreased quality of life up to 6 months after infection. Further studies are needed to establish the extent to which post-COVID-19 effects continue beyond 6 months, how they interact with each other, and to clarify their causes and their effective management.
Oligonucleotide Therapies in the Treatment of Arthritis: A Narrative Review
Authors: Wijesinghe Susanne N. , Lindsay Mark A. , Jones Simon W.
Published: July 2021

Osteoarthritis (OA) and rheumatoid arthritis (RA) are two of the most common chronic inflammatory joint diseases, for which there remains a great clinical need to develop safer and more efficacious pharmacological treatments. The pathology of both OA and RA involves multiple tissues within the joint, including the synovial joint lining and the bone, as well as the articular cartilage in OA. In this review, we discuss the potential for the development of oligonucleotide therapies for these disorders by examining the evidence that oligonucleotides can modulate the key cellular pathways that drive the pathology of the inflammatory diseased joint pathology, as well as evidence in preclinical in vivo models that oligonucleotides can modify disease progression.
COVID-19 Pathogenesis: From Molecular Pathway to Vaccine Administration
Authors: Nappi Francesco , Iervolino Adelaide , Avtaar Singh Sanjeet Singh
Published: July 2021

The Coronavirus 2 (SARS-CoV-2) infection is a global pandemic that has affected millions of people worldwide. The advent of vaccines has permitted some restitution. Aside from the respiratory complications of the infection, there is also a thrombotic risk attributed to both the disease and the vaccine. There are no reliable data for the risk of thromboembolism in SARS-CoV-2 infection in patients managed out of the hospital setting. A literature review was performed to identify the pathophysiological mechanism of thrombosis from the SARS-CoV-2 infection including the role of Angiotensin-Converting Enzyme receptors. The impact of the vaccine and likely mechanisms of thrombosis following vaccination were also clarified. Finally, the utility of the vaccines available against the multiple variants is also highlighted. The systemic response to SARS-CoV-2 infection is still relatively poorly understood, but several risk factors have been identified. The roll-out of the vaccines worldwide has also allowed the lifting of lockdown measures and a reduction in the spread of the disease. The experience of the SARS-CoV-2 infection, however, has highlighted the crucial role of epidemiological research and the need for ongoing studies within this field.
Effective Cryopreservation of a Bioluminescent Auxotrophic Escherichia coli-Based Amino Acid Array to Enable Long-Term Ready-to-Use Applications
Authors: Ahn Hee Tae , Jang In Seung , Dang Thinh Viet , Kim Yi Hyang , Lee Dong Hoon , Choi Hyeun Seok , Yu Byung Jo , Kim Moon Il
Published: July 2021

Amino acid arrays comprising bioluminescent amino acid auxotrophic Escherichia coli are effective systems to quantitatively determine multiple amino acids. However, there is a need to develop a method for convenient long-term preservation of the array to enable its practical applications. Here, we reported a potential strategy to efficiently maintain cell viability within the portable array. The method involves immobilization of cells within agarose gel supplemented with an appropriate cryoprotectant in individual wells of a 96-well plate, followed by storage under freezing conditions. Six cryoprotectants, namely dimethyl sulfoxide, glycerol, ethylene glycol, polyethylene glycol, sucrose, and trehalose, were tested in the methionine (Met) auxotroph-based array. Carbohydrate-type cryoprotectants (glycerol, sucrose, and trehalose) efficiently preserved the linearity of determination of Met concentration. In particular, the array with 5% trehalose exhibited the best performance. The Met array with 5% trehalose could determine Met concentration with high linearity (R2 value = approximately 0.99) even after storage at −20 °C for up to 3 months. The clinical utilities of the Met and Leu array, preserved at −20 °C for 3 months, were also verified by successfully quantifying Met and Leu in spiked blood serum samples for the diagnosis of the corresponding metabolic diseases. This long-term preservation protocol enables the development of a ready-to-use bioluminescent E. coli-based amino acid array to quantify multiple amino acids and can replace the currently used laborious analytical methods.
Determination of Thermal Comfort Zones through Comparative Analysis between Different Characterization Methods of Thermally Dissatisfied People
Authors: Pereira Pedro Filipe da Conceição , Broday Evandro Eduardo
Published: July 2021

In order to maintain thermal comfort and preserve indoor environmental quality, people use heating, ventilation and air-conditioning (HVAC) systems inside buildings. However, buildings must be prepared not only to provide adequate thermal comfort to their occupants but also to align strategies that enable better energy performance. Thus, this work aimed to establish thermal comfort zones (TCZ) through different characterization methods of thermally dissatisfied people. Responses were collected from 481 students, through the application of questionnaires in classrooms, during the Brazilian winter of 2019. Three methods for determining the actual percentage of dissatisfied (APD) were adopted, which generated three different equations, namely: APD_1; APD_2 and APD_3, based on the original Predicted Percentage of Dissatisfied (PPD) equation. By using the probit model, three TCZ were calculated: 17.73–22.4 °C (APD_1); 20.71–20.93 °C (APD_2) and 17.89–24.83 °C (APD_3). In addition, a comfort zone based on the linear regression between the thermal sensation votes and the operative temperature was determined (18.77–22.69 °C). All thermal comfort zones resulting from this work have colder temperatures than that indicated by the American Society of Heating, Refrigerating and Air-Conditioning Engineers—ASHRAE (2017) of 23–26 °C for the winter, showing the potential for energy savings from the adoption of this type of strategy, while maintaining thermal comfort.
Utilization of Building Information Modeling for Arranging the Structural Kingposts
Authors: Peansupap Vachara , Nov Pisal , Tongthong Tanit
Published: July 2021

The kingpost was a vertical element that was used to support the structural strut in the deep excavation. The structural kingpost was commonly arranged by experienced engineers who used two-dimensional construction drawings. Thus, it was still time-consuming and error-prone. Currently, an available construction program has been developed to arrange the structural kingpost by identifying the clash problems in the 3D environment. However, they have a limitation for detecting the clash that was unable to visualize the concurrent clashes between kingpost and many underground structures. Then, the engineer cannot see all the clash incidents with each kingpost and move the kingpost to avoid the clashes successfully. Since the kingpost arrangement was still an inefficient practice that was limited in the visualization aspect, this research used engineering knowledge and advanced construction technology to detect and solve the clashes between kingposts and underground structures. The methodology used engineering knowledge of kingpost arrangement to develop the system modules by using a rule-based approach. Then, these modules were developed into the system by using visual programming of Building Information Modelling (BIM). To test the system, an underground structure from building construction was selected as a case study to apply the developed system. Finally, the finding of this study could overcome human judgment by providing less interaction in the kingpost arrangement and visualization improvement of clash occurrences in the 3D model.
Reactive Oxygen Species Downregulate Transient Receptor Potential Melastatin 6 Expression Mediated by the Elevation of miR-24-3p in Renal Tubular Epithelial Cells
Authors: Hirota Chieko , Takashina Yui , Yoshino Yuta , Hasegawa Hajime , Okamoto Ema , Matsunaga Toshiyuki , Ikari Akira
Published: July 2021

Background: A low level of serum magnesium ion (Mg2+) is associated with type 2 diabetes mellitus (T2D). However, the molecular mechanism of Mg2+ deficiency has not been fully clarified. The current study sought to assesses the effect of reactive oxygen species on the expression of Mg2+ channels and miRNA. Methods: The expression of Mg2+ channels and miRNA were examined by real-time polymerase chain reaction. Intracellular Mg2+ concentration was measured by Magnesium Green fluorescence measurement. Results: The mRNA level of transient receptor potential melastatin 6 (TRPM6), which functions as Mg2+ influx channel in the distal convoluted tubule (DCT) of the kidney, was decreased by glycated albumin (GA), but not by insulin in rat renal tubule-derived NRK-52E cells. The mRNA levels of TRPM7, a homologue of TRPM6, and CNNM2, a Mg2+ efflux transporter located at the basolateral membrane of DCT, were changed by neither GA nor insulin. The generation of reactive oxygen species (ROS) was increased by GA. Hydrogen peroxide (H2O2) dose-dependently decreased TRPM6 mRNA, but it inversely increased the reporter activity of TRPM6. H2O2 accelerated the degradation of TRPM6 mRNA in actinomycin D assay without affecting TRPM7 and CNNM2 mRNA expressions. Nine miRNAs were considered as candidates for the regulator of stability of TRPM6 mRNA. Among them, miR-24-3p expression was increased by H2O2. The H2O2-induced reduction of TRPM6 mRNA was rescued by miR-24-3p siRNA. Magnesium Green fluorescence measurement showed that Mg2+ influx is suppressed by H2O2, which was rescued by an antioxidant and miR-24-3p siRNA. Conclusions: We suggest that GA decreases TRPM6 expression mediated by the elevation of ROS and miR-24-3p in renal tubular epithelial cells of T2D.
Bone and Mineral Metabolism Phenotypes in MEN1-Related and Sporadic Primary Hyperparathyroidism, before and after Parathyroidectomy
Authors: Marini Francesca , Giusti Francesca , Cioppi Federica , Maraghelli Davide , Cavalli Tiziana , Tonelli Francesco , Brandi Maria Luisa
Published: July 2021

Primary hyperparathyroidism (PHPT) is the most common endocrinopathy in multiple endocrine neoplasia type 1 (MEN1). Persistent levels of increased parathyroid hormone (PTH) result in a higher incidence of osteopenia and osteoporosis compared to the general population. Surgical removal of hyper-functioning parathyroid tissue is the therapy of choice. This retrospective study evaluated the effect of parathyroidectomy (PTX) on bone metabolism and bone mass in two series of patients with MEN1 PHPT and sporadic PHPT (sPHPT) by comparing bone metabolism-related biochemical markers and bone mineral density (BMD) before and after surgery. Our data confirmed, in a higher number of cases than in previously published studies, the efficacy of PTX, not only to rapidly restore normal levels of PTH and calcium, but also to normalize biochemical parameters of bone resorption and bone formation, and to improve spine and femur bone mass, in both MEN1 PHPT and sPHPT. Evaluation of single-patient BMD changes after surgery indicates an individual variable bone mass improvement in a great majority of MEN1 PHPT patients. In MEN1 patients, PTX is strongly suggested in the presence of increased PTH and hypercalcemia to prevent/reduce the early-onset bone mass loss and grant, in young patients, the achievement of the bone mass peak; routine monitoring of bone metabolism and bone mass should start from adolescence. Therapy with anti-fracture drugs is indicated in MEN1 patients with BMD lower than the age-matched normal values.
Ultrastructural Profile Combined with Immunohistochemistry of a Hepatic Progenitor Cell Line in Pediatric Autoimmune Hepatitis: New Insights into the Morphological Pattern of the Disease
Authors: Lotowska Joanna Maria , Sobaniec-Lotowska Maria Elzbieta , Sobaniec Piotr
Published: July 2021

Considering that the heterogenic population of a hepatic progenitor cell line (HPCL) can play a vital role in autoimmune hepatitis (AIH), we decided to conduct pioneering retrospective evaluation of these cells in pediatric AIH by means of transmission electron microscopy (TEM). The aim of the study was to assess the ultrastructure of the HPCL in children with untreated AIH. Ultrastructural analysis of the HPCL population, preceded by immunohistochemical staining for cytokeratin 7 (CK7), was performed using pretreatment liver biopsies from 23 children with clinicopathologically diagnosed AIH. Immunohistochemical assessment for CK7 allowed detection of proliferating immature epithelial cells differentiating towards periportal and intralobular intermediate hepatocytes without marked formation of ductular reactions in AIH children. Using TEM, we distinguished three morphological types of HPCs: I—the most undifferentiated progenitor cells; III—intermediate hepatocyte-like cells; II—intermediate bile duct cells. Most frequent were the cells differentiating towards hepatocytes, most rare—those differentiating towards cholangiocytes. The results indicate that an HPCL may be an important source of hepatocyte regeneration. Ultrastructural analyses of the HPCL population, combined with immunohistochemistry for CK7, might be a useful tool to evaluate liver cell regeneration, including fibrogenesis, and may help better understand the morphological pattern of the disease, in pediatric AIH. Frequent appearance of an HPCL in the vicinity of fibrotic foci, often accompanied by hyperactive Kupffer cells and transitional hepatic stellate cells, may indicate their significant involvement in liver fibrogenesis.