bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurocognitive and Psychopathological Predictors of Weight Loss After Bariatric Surgery: A 4-Year Follow-Up Study
Authors: Bianciardi Emanuela , Raimondi Giulia , Samela Tonia , Innamorati Marco , Contini Lorenzo Maria , Procenesi Leonardo , Fabbricatore Mariantonietta , Imperatori Claudio , Gentileschi Paolo
Published: May 2021

Twenty to thirty percent of patients experience weight regain at mid and long-term follow-up. Impaired cognitive functions are prevalent in people suffering from obesity and in those with binge eating disorder, thereby, affecting the weight-loss outcomes. The aim of our study was to investigate neurocognitive and psychopathological predictors of surgical efficacy in terms of percentage of excess weight loss (%EWL) at follow-up intervals of one year and 4-year. Psychosocial evaluation was completed in a sample of 78 bariatric surgery candidates and included psychometric instruments and a cognitive battery of neuropsychological tests. A schedule of 1-year and 4-year follow-ups was implemented. Wisconsin Sorting Card Test total correct responses, scores on the Raven’s Progressive Matrices Test, and age predicted %EWL at, both, early and long-term periods after surgery while the severity of pre-operative binge eating (BED) symptoms were associated with lower %EWL only four years after the operation. Due to the role of pre-operative BED in weight loss maintenance, the affected patients are at risk of suboptimal response requiring ongoing clinical monitoring, and psychological and pharmacological interventions when needed. As a result of our findings and in keeping with the latest guidelines we encourage neuropsychological assessment of bariatric surgery candidates. This data substantiated the rationale of providing rehabilitative interventions tailored to cognitive domains and time specific to the goal of supporting patients in their post-surgical course.
Data Reduced Method for Cost Comparison of Wastewater Management Scenarios–Case Study for Two Settlements in Jordan and Oman
Authors: Khurelbaatar Ganbaatar , Al Marzuqi Bishara , Van Afferden Manfred , Müller Roland A. , Friesen Jan
Published: May 2021

Safe access to sanitation is at the core of the United Nations Sustainable Development Goal (SDG) #6. Currently, it is estimated that this goal cannot be met by 2030. Despite all kinds of administrational hurdles, meeting SDG#6 depends on considerable investment. In order to get a chance at fulfilling SGD#6, the most cost-effective wastewater management has to be identified. Wastewater can be managed in different ways ranging from central treatment plants connected to individual households through sewer networks down to tanker fleets servicing each household. Depending on the geographical setting, investment costs, operation and maintenance as well as social acceptance there is no single best solution. Instead, identifying the optimal wastewater management is highly localized and country-specific or even settlement-specific. Within this study we present a data-reduced scenario generation and assessment for wastewater management based on the ALLOWS method that can be applied to individual settlements. Results provide cost-ranked wastewater management scenarios that enable decision makers to select the most cost-effective and feasible scenario. Our study starts with a detailed step-by-step methodology of a data-reduced ALLOWS approach. The approach is applied to two small settlements in Jordan and Oman with comparable population size for which a set of five scenarios along a decentralization gradient is defined and generated: centralized, semi-centralized, decentralized, and on-site/tanker. Considering spatial specificities and country-specific cost data, the five scenarios are cost-ranked and discussed in view of the two settlement settings. For Jordan specific treatment costs range from 3.8 to 6.9 USD/m3of treated water and for Oman from 2.3 to 10.1 USD/m3. Although the scenario ranking differs, for both settlements the decentralized scenario is identified as the most cost effective, where wastewater is treated on-site for less-populated parts and by small cluster treatment plants for higher density parts. Further, potential extensions providing users with more functionality depending upon data availability for the data-reduced ALLOWS method are discussed. Using globally available data, the data-reduced can be applied worldwide. In view of SDG#6, we present a methodology that closes the gap between country-scale investment estimates and the most cost-effective wastewater management scenarios at settlement level.
Toward Efficient Bayesian Approaches to Inference in Hierarchical Hidden Markov Models for Inferring Animal Behavior
Authors: Sacchi Giada , Swallow Ben
Published: May 2021

The study of animal behavioral states inferred through hidden Markov models and similar state switching models has seen a significant increase in popularity in recent years. The ability to account for varying levels of behavioral scale has become possible through hierarchical hidden Markov models, but additional levels lead to higher complexity and increased correlation between model components. Maximum likelihood approaches to inference using the EM algorithm and direct optimization of likelihoods are more frequently used, with Bayesian approaches being less favored due to computational demands. Given these demands, it is vital that efficient estimation algorithms are developed when Bayesian methods are preferred. We study the use of various approaches to improve convergence times and mixing in Markov chain Monte Carlo methods applied to hierarchical hidden Markov models, including parallel tempering as an inference facilitation mechanism. The method shows promise for analysing complex stochastic models with high levels of correlation between components, but our results show that it requires careful tuning in order to maximize that potential.
Brief Report–Modeling Media Use: How Parents’ and Other Adults’ Posting Behaviors Relate to Young Adolescents’ Posting Behaviors
Authors: Reich Stephanie M. , Starks Allison , Santer Nicholas , Manago Adriana
Published: May 2021

Middle school is a period when young adolescents become more engaged with social media and adults become increasingly concerned about such use. Although research finds that parents often post about their children on social media, little is known about how adults’ social media behaviors relate to youths’ online behaviors. We surveyed 466 middle-school students about their social media habits, privacy-respecting behaviors, and their parents’, other adults’, and their own posting behaviors on social media. While 68% used social media, only 41% posted pictures. Of those, 33.5% also had parents and/or adults that posted about them. Using this subset, we found that adults’ privacy-respecting behaviors (e.g., asking permission to post, showing post first) were significantly related to youth using these same privacy-respecting behaviors when posting on social media. Like many areas of development, young adolescents may learn about social media use by modeling their parents’ and other adults’ behaviors.
Bispecific Antibodies: From Research to Clinical Application
Authors: Ma Jiabing , Mo Yicheng , Tang Menglin , Shen Junjie , Qi Yanan , Zhao Wenxu , Huang Yi , Xu Yanmin , Qian Cheng
Published: May 2021

Bispecific antibodies (BsAbs) are antibodies with two binding sites directed at two different antigens or two different epitopes on the same antigen. The clinical therapeutic effects of BsAbs are superior to those of monoclonal antibodies (MoAbs), with broad applications for tumor immunotherapy as well as for the treatment of other diseases. Recently, with progress in antibody or protein engineering and recombinant DNA technology, various platforms for generating different types of BsAbs based on novel strategies, for various uses, have been established. More than 30 mature commercial technology platforms have been used to create and develop BsAbs based on the heterologous recombination of heavy chains and matching of light chains. The detailed mechanisms of clinical/therapeutic action have been demonstrated with these different types of BsAbs. Three kinds of BsAbs have received market approval, and more than 110 types of BsAbs are at various stages of clinical trials. In this paper, we elaborate on the classic platforms, mechanisms, and applications of BsAbs. We hope that this review can stimulate new ideas for the development of BsAbs and improve current clinical strategies.
Natural Killer Cell Interactions With Myeloid Derived Suppressor Cells in the Tumor Microenvironment and Implications for Cancer Immunotherapy
Authors: Zalfa Cristina , Paust Silke
Published: May 2021

The tumor microenvironment (TME) is a complex and heterogeneous environment composed of cancer cells, tumor stroma, a mixture of tissue-resident and infiltrating immune cells, secreted factors, and extracellular matrix proteins. Natural killer (NK) cells play a vital role in fighting tumors, but chronic stimulation and immunosuppression in the TME lead to NK cell exhaustion and limited antitumor functions. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of myeloid cells with potent immunosuppressive activity that gradually accumulate in tumor tissues. MDSCs interact with innate and adaptive immune cells and play a crucial role in negatively regulating the immune response to tumors. This review discusses MDSC-mediated NK cell regulation within the TME, focusing on critical cellular and molecular interactions. We review current strategies that target MDSC-mediated immunosuppression to enhance NK cell cytotoxic antitumor activity. We also speculate on how NK cell-based antitumor immunotherapy could be improved.
Hyperforin Ameliorates Imiquimod-Induced Psoriasis-Like Murine Skin Inflammation by Modulating IL-17A–Producing γδ T Cells
Authors: Zhang Song , Zhang Jia , Yu Juanjuan , Chen Xiaolu , Zhang Fangyuan , Wei Wei , Zhang Lingyun , Chen Wenmao , Lin Nengxing , Wu Yan
Published: May 2021

Hyperforin is a major active constituent of Hypericum perforatum L. extract, which is widely used for the treatment of depressive disorders. Recent studies have reported that hyperforin reduced inflammation in stroke and suppressed proliferation and differentiation in keratinocytes. Psoriasis is a chronic immune-mediated inflammatory skin disease in which the IL-23/IL-17 axis plays an important role. To investigate the underlying inflammatory mechanisms and response of hyperforin in psoriasis, we use imiquimod (IMQ)-induced mice model, in vitro cultured murine splenic γδ T cells, and HaCaT cells in this study. Data showed that hyperforin reduced epidermal thickness and decreased IMQ-induced pathological scores of cutaneous skin lesions in mice. Meanwhile we proved that hyperforin suppressed infiltration of CD3+ T cells and downregulated expression of Il1, Il6, Il23, Il17a, Il22, antimicrobial peptides (AMPs) in the skin lesion. Hyperforin significantly inhibited imiquimod-induced splenomegaly, reduced serum levels of TNF-α and IL-6, and IL-17A in splenocytes and draining lymph nodes. Our study also suggested that hyperforin lessened the infiltration of γδ T cell and CCR6+ γδ T cells in spleen and lymph nodes. Hyperforin also suppressed the typical psoriasis-like inflammatory responses and the infiltration of IL-17A+ cells in dermal γδ T cells of IMQ treated Tcrd−/− mice transferred with γδ T cells. In vitro studies, hyperforin reduced the expression and secretion of IL-17A in γδ T cells, and suppressed the activation of MAPK/STAT3 pathways in human keratinocyte HaCaT cells and γδ T cells. In conclusion, hyperforin alleviates IMQ-induced inflammation in psoriasis through suppressing the immune responses exerted by IL-17 A-producing γδ T cells and related cytokines by modulating MAPK/STAT3 pathways. Our study provided a novel therapeutic tragedy for psoriasis by which hyperforin attenuates psoriasis-related inflammatory responses.
Ivacaftor Reduces Inflammatory Mediators in Upper Airway Lining Fluid From Cystic Fibrosis Patients With a G551D Mutation: Serial Non-Invasive Home-Based Collection of Upper Airway Lining Fluid
Authors: Mainz Jochen G. , Arnold Christin , Wittstock Kara , Hipler Uta-Christina , Lehmann Thomas , Zagoya Carlos , Duckstein Franziska , Ellemunter Helmut , Hentschel Julia
Published: May 2021

In cystic fibrosis (CF) therapy, the recent approval of CF-transmembrane conductance regulator (CFTR) channel modulators is considered to be the major breakthrough. However, the current first-line approach based mainly on pulmonary function to measure effects of the novel therapy, tested by forced expiratory volumes in one second (FEV1), provides restricted sensitivity to detect early structural damages. Accordingly, there is a need for new sensitive surrogate parameters. Most interestingly, these should quantify inflammation that precedes a decline of pulmonary function. We present a novel method assessing inflammatory markers in the upper airways’ epithelial lining fluid (ELF) obtained by nasal lavage (NL). In contrast to broncho-alveolar lavage, ELF sampling by NL is an attractive method due to its limited invasiveness which allows repeated analyses, even performed in a home-based setting. In a longitudinal cohort study (ClinicalTrials.gov, Identifier: NCT02311140), we assessed changes of inflammatory mediators in 259 serially obtained nasal lavages taken up to every second day before and during therapy with ivacaftor from ten CF patients carrying a G551D mutation. Patients were trained to sample NL-fluid at home, to immediately freeze and transfer chilled secretions to centers. Neutrophil Elastase, Interleukins IL-1β, IL-6 and IL-8 in NL were quantified. During 8-12 weeks of ivacaftor-treatment, median values of IL-1β and IL-6 significantly declined 2.29-fold (2.97→1.30 pg/mL), and 1.13-fold (6.48→5.72 pg/mL), respectively. In parallel, sweat tests and pulmonary function improved considerably. This is the first study assessing changes of airway inflammation on a day-to-day basis in CF patients receiving a newly administered CFTR-modulator therapy. It proves a decline of airway inflammation during ivacaftor-therapy.
Exploring the Gut-Brain Axis for the Control of CNS Inflammatory Demyelination: Immunomodulation by Bacteroides fragilis’ Polysaccharide A
Authors: Erturk-Hasdemir Deniz , Ochoa-Repáraz Javier , Kasper Dennis L. , Kasper Lloyd H.
Published: May 2021

The symbiotic relationship between animals and their resident microorganisms has profound effects on host immunity. The human microbiota comprises bacteria that reside in the gastrointestinal tract and are involved in a range of inflammatory and autoimmune diseases. The gut microbiota’s immunomodulatory effects extend to extraintestinal tissues, including the central nervous system (CNS). Specific symbiotic antigens responsible for inducing immunoregulation have been isolated from different bacterial species. Polysaccharide A (PSA) of Bacteroides fragilis is an archetypical molecule for host-microbiota interactions. Studies have shown that PSA has beneficial effects in experimental disease models, including experimental autoimmune encephalomyelitis (EAE), the most widely used animal model for multiple sclerosis (MS). Furthermore, in vitro stimulation with PSA promotes an immunomodulatory phenotype in human T cells isolated from healthy and MS donors. In this review, we discuss the current understanding of the interactions between gut microbiota and the host in the context of CNS inflammatory demyelination, the immunomodulatory roles of gut symbionts. More specifically, we also discuss the immunomodulatory effects of B. fragilis PSA in the gut-brain axis and its therapeutic potential in MS. Elucidation of the molecular mechanisms responsible for the microbiota’s impact on host physiology offers tremendous promise for discovering new therapies.
Epigenetic Regulation of BST-2 Expression Levels and the Effect on HIV-1 Pathogenesis
Authors: Singh Ravesh , Ramsuran Veron , Naranbhai Vivek , Yende-Zuma Nonhlanhla , Garrett Nigel , Mlisana Koleka , Dong Krista L. , Walker Bruce D. , Abdool Karim Salim S. , Carrington Mary , Ndung’u Thumbi
Published: May 2021

HIV-1 must overcome host antiviral restriction factors for efficient replication. We hypothesized that elevated levels of bone marrow stromal cell antigen 2 (BST-2), a potent host restriction factor that interferes with HIV-1 particle release in some human cells and is antagonized by the viral protein Vpu, may associate with viral control. Using cryopreserved samples, from HIV-1 seronegative and seropositive Black women, we measured in vitro expression levels of BST-2 mRNA using a real-time PCR assay and protein levels were validated by Western blotting. The expression level of BST-2 showed an association with viral control within two independent cohorts of Black HIV infected females (r=-0.53, p=0.015, [n =21]; and r=-0.62, p=0.0006, [n=28]). DNA methylation was identified as a mechanism regulating BST-2 levels, where increased BST-2 methylation results in lower expression levels and associates with worse HIV disease outcome. We further demonstrate the ability to regulate BST-2 levels using a DNA hypomethylation drug. Our results suggest BST-2 as a factor for potential therapeutic intervention against HIV and other diseases known to involve BST-2.
Origin and Persistence of Markings in a Long-Term Photo-Identification Dataset Reveal the Threat of Entanglement for Endangered Northern Bottlenose Whales (Hyperoodon ampullatus)
Authors: Feyrer Laura Joan , Stewart Madison , Yeung Jas , Soulier Colette , Whitehead Hal
Published: May 2021

Photo-identification methods depend on markings that are stable over time. Using a large dataset of photographs taken over a 31-year period, we evaluate the reliability, rate of change and demographic trends in different mark types on northern bottlenose whales (Hyperoodon ampullatus) in the Endangered Scotian Shelf population, and assess the prevalence and severity of anthropogenically caused markings. Only fin notches and back indentations were stable over long timescales, leading to 48% of the overall population being assessed as reliably marked. Males and mature males were found to have higher incidence of most mark types compared to females and juveniles. The proportion of reliably marked individuals increased over time, a trend that should be accounted for in any temporal analysis of population size using mark-recapture methods. An overall increase in marked individuals may reflect the accumulation of scars on an aging population post whaling. Anthropogenic markings, including probable entanglement and propeller-vessel strike scars, occurred at a steady rate over the study period and were observed on 6.6% of the population. The annual gain rate for all injuries associated with anthropogenic interactions was over 5 times the annual potential biological removal (PBR) calculated for the endangered population. As entanglement incidents and propeller-vessel strike injuries are typically undetected in offshore areas, we provide the first minimum estimate of harmful human interactions for northern bottlenose whales. With low observer effort for fisheries across the Canadian Atlantic, photo-identification offers an important line of evidence of the risks faced by this Endangered whale population.
Effect of COVID-19 Anthropause on Water Clarity in the Belize Coastal Lagoon
Authors: Callejas Ileana A. , Lee Christine M. , Mishra Deepak R. , Felgate Stacey L. , Evans Claire , Carrias Abel , Rosado Andria , Griffin Robert , Cherrington Emil A. , Ayad Mariam , Rudresh Megha , Page Benjamin P. , Jay Jennifer A.
Published: May 2021

The Coronavirus disease 2019 (COVID-19) pandemic halted human activities globally in multiple sectors including tourism. As a result, nations with heavy tourism, such as Belize, experienced improvements in water quality. Remote sensing technologies can detect impacts of “anthropauses” on coastal water quality. In this study, moderate resolution imaging spectroradiometer (MODIS) satellite data were employed along the Belizean coast to investigate impacts of the COVID-19 shutdown on water quality. The attenuation coefficient at 490 nm,Kd(490), was used as an indicator of water quality, with a lowerKd(490) indicating increased water clarity. Four Coastal Management Zones were characterized by marine traffic as high traffic areas (HTAs) and two as low traffic areas (LTAs). Monthly composites for two periods, 2002–2019 (baseline) and 2020 were examined forKd(490). For months prior to the COVID-19 shutdown in Belize, there was generally no significant difference inKd(490) (p> 0.05) between 2020 and baseline period in HTAs and LTAs. Through the shutdown,Kdwas lower in 2020 at HTAs, but not for LTAs. At the LTAs, theKd(490)s observed in 2020 were similar to previous years through October. In November, an unusually active hurricane season in 2020 was associated with decreased water clarity along the entire coast of Belize. This study provides proof of concept that satellite-based monitoring of water quality can complementin situdata and provide evidence of significant water quality improvements due to the COVID-19 shutdown, likely due to reduced marine traffic. However, these improvements were no longer observed following an active hurricane season.
The Next Frontier in Understanding the Evolution of Coral Reef Fish Societies
Authors: Rueger Theresa , Branconi Rebecca , Froehlich Catheline Y. M. , Heatwole Siobhan J. , Wong Marian Y. L. , Buston Peter M.
Published: May 2021

Research on sociality in marine fishes is a vibrant field that is providing new insights into social evolution more generally. Here, we review the past two decades of research, identifying knowledge gaps and new directions. Two coral reef fishes, with social systems similar to other cooperative breeders, have emerged as models: the clown anemonefish Amphiprion percula and the emerald goby Paragobiodon xanthosoma. In these systems, non-breeders do not forgo their own reproduction to gain indirect genetic benefits. Rather, they do so because they stand to inherit the territory in the future and there are strong ecological and social constraints. The reasons why breeders tolerate non-breeders remain obscure, though it is plausibly a combination of weak kin selection, bet-hedging, and benefits mediated via mutualistic interactions with cnidarian hosts. The latter is particularly interesting, given the parallels with other social animals with mutualistic partners, such as acacia ants. Looking beyond the two model species, our attention is turning to species with more complex social organization, such as the damselfish Dascyllus aruanus. Here, variable group stability, conflict intensity, and reproductive skew provide opportunities to test theories of social evolution that have only been tested in a few taxa. New methods like social network analysis are enabling us to uncover more subtle effects of ecology on social interactions. More recently, comparative methods have yielded insights into the correlates of interspecific variation in sociality in the genera to which our model species belong. Phylogenetically controlled contrasts within the genus Gobiodon, have revealed the role of ecology, life history traits, and their interaction in sociality: smaller bodied species are more social than larger bodied species, which are only social on large corals. As climate change affects coral reefs, there is a pressing need to understand the many ways in which environmental disturbance influences these unique social systems. In sum, coral reef fishes have enabled us to test the robustness of current theories of social evolution in new taxa and environments, and they have generated new insights into social evolution that are applicable to a wider variety of taxa.
Magnetic Hyperthermia in the 400–1,100 kHz Frequency Range Using MIONs of Condensed Colloidal Nanocrystal Clusters
Authors: Kouzoudis Dimitris , Samourgkanidis Georgios , Kolokithas-Ntoukas Argiris , Zoppellaro Giorgio , Spiliotopoulos Konstantinos
Published: May 2021

In the current study, we explored the magnetic hyperthermia performance of condensed–clustered magnetic iron oxide nanoparticles (MIONs) in the range of 400 kHz to 1.1 MHz at low field amplitudes. The strong interparticle interactions, present in such systems, can influence the hyperthermia power produced by MIONs. Herein, the heat dependence, as an increasing function of frequency, with a fixed magnetic field strength of 3 mT is recorded, revealing a direct relationship between the two physical quantities and a high heating efficiency for the condensed–clustered MIONs. In particular, the specific loss power (SLP) (or specific absorption rate [SAR]) parameter, which is the ratio of the heat power in watts produced per nanoparticle mass in grams, is linear to a good degree to the oscillating frequency with a step of roughly 30 W/g per 100 kHz increase. In addition, all the measurements were within the safety limits proposed by Hergt and Dutz criterion of H f ≤ 5 × 109A/ms for clinical application of magnetic fluid hyperthermia (MFH). Finally, the measured data of temperature vs. time at each frequency were interpreted in terms of simple thermodynamic arguments, thus extracting useful thermodynamic parameters for the heat power generated by the condensed–clustered MIONs.
Sarcopenia Is Associated With Increased Risks of Rotator Cuff Tendon Diseases Among Community-Dwelling Elders: A Cross-Sectional Quantitative Ultrasound Study
Authors: Han Der-Sheng , Wu Wei-Ting , Hsu Po-Cheng , Chang Hsiang-Chi , Huang Kuo-Chin , Chang Ke-Vin
Published: May 2021

Backgrounds: Recently, the association between sarcopenia and various musculoskeletal disorders, such as lumbar spine stenosis and fibromyalgia, has been highlighted. However, the relationship between sarcopenia and rotator cuff tendon diseases has rarely been investigated. This study aimed to evaluate whether sarcopenia was associated with shoulder pain and to determine whether rotator cuff tendons differed in echotexture between the sarcopenic and non-sarcopenic populations.

Methods: The thickness and echogenicity ratio of the tendon vs. the overlying muscle (ERTM) or subcutaneous tissue (ERTT) were measured using high-resolution ultrasonography in 56 sarcopenic patients and 56 sex- and age- matched controls. The association between ultrasound measurements of the rotator cuff tendon complex and sarcopenia was investigated using the generalized estimating equation (GEE).

Results: The sarcopenic group had an increased prevalence of shoulder pain. Based on the GEE analysis, sarcopenia was significantly associated with an increase in supraspinatus tendon thickness (β coefficient = 0.447, p < 0.001) and a decrease in the ERTM for the biceps long head and rotator cuff tendons. A negative trend of association was observed between sarcopenia and ERTT in the supraspinatus tendons (β coefficient = −0.097, p = 0.070). Nevertheless, sarcopenia was not associated with an increased risk of rotator cuff tendon tears.

Conclusions: Patients with sarcopenia have a higher risk of shoulder pain. A consistent tendinopathic change develops in the supraspinatus tendons in sarcopenic patients. However, sarcopenia is less likely to be associated with serious rotator cuff pathology, such as tendon tears. Prospective cohort studies are warranted to explore the causal relationship between sarcopenia and shoulder disorders.
Measuring Core Body Temperature Using a Non-invasive, Disposable Double-Sensor During Targeted Temperature Management in Post-cardiac Arrest Patients
Authors: Janke David , Kagelmann Niklas , Storm Christian , Maggioni Martina A. , Kienast Camilla , Gunga Hanns-Christian , Opatz Oliver
Published: May 2021

Background: Precisely measuring the core body temperature during targeted temperature management after return of spontaneous circulation is mandatory, as deviations from the recommended temperature might result in side effects such as electrolyte imbalances or infections. However, previous methods are invasive and lack easy handling. A disposable, non-invasive temperature sensor using the heat flux approach (Double Sensor), was tested against the standard method: an esophagus thermometer.

Methods: The sensor was placed on the forehead of adult patients (n = 25, M/F, median age 61 years) with return of spontaneous circulation after cardiac arrest undergoing targeted temperature management. The recorded temperatures were compared to the established measurement method of an esophageal thermometer. A paired t-test was performed to examine differences between methods. A Bland-Altman-Plot and the intraclass correlation coefficient were used to assess agreement and reliability. To rule out possible influence on measurements, the patients' medication was recorded as well.

Results: Over the span of 1 year and 3 months, data from 25 patients were recorded. The t-test showed no significant difference between the two measuring methods (t = 1.47, p = 0.14, n = 1,319). Bland-Altman results showed a mean bias of 0.02°C (95% confidence interval 0.00–0.04) and 95% limits of agreement of −1.023°C and 1.066°C. The intraclass correlation coefficient was 0.94. No skin irritation or allergic reaction was observed where the sensor was placed. In six patients the bias differed noticeably from the rest of the participants, but no sex-based or ethnicity-based differences could be identified. Influences on the measurements of the Double Sensor by drugs administered could also be ruled out.

Conclusions: This study could demonstrate that measuring the core body temperature with the non-invasive, disposable sensor shows excellent reliability during targeted temperature management after survived cardiac arrest. Nonetheless, clinical research concerning the implementation of the sensor in other fields of application should be supported, as well as verifying our results by a larger patient cohort to possibly improve the limits of agreement.
Progress in the Development of Anti-tissue Factor Pathway Inhibitors for Haemophilia Management
Authors: Mahlangu Johnny N.
Published: May 2021

The unprecedented progress in addressing unmet needs in haemophilia care to date includes developing several novel therapies that rebalance haemostasis by restoring thrombin generation in patients with haemophilia A or B with and without inhibitors. These novel therapies are FVIII mimetics, antithrombin interference RNA therapy and several monoclonal antibodies directed against the tissue factor pathway inhibitor (anti-TFPI). In this review, we provide an update on the progress made in developing anti-TFPI therapie. Phase 1 data from the three anti-TFPI studies showed acceptable safety profiles, and currently, available phase 2 data are encouraging. While these data support these molecules' further development progression, there is uncertainty on several aspects of their evolution. Two of the three anti-TFPIs have shown drug-related thrombosis, with one study consequently terminated. None of the thrombotic events is predictable with current monitoring tools, and none correlate with known coagulation parameters. All three anti-TFPIs undergo target mediated drug disposition, which impacts the formulation of dosing regimen fo these therapies. They would require more frequent dosing than some of the extended half-life clotting factor products and antithrombin RNAi therapy. There is no assay to measure the TFPI as the physiological levels are very low, which makes monitoring the impact of the anti-TFPI a challenge. The anti-TFPIs have several advantages, including their bioavailability when administered subcutaneously, their stable pharmacokinetics and their ability to prevent bleeds in haemophilia A or B patients with and without inhibitors. Whether these advantages can be realized will depend on the outcome of the currently ongoing studies.
DESP: Deep Enhanced Sampling of Proteins’ Conformation Spaces Using AI-Inspired Biasing Forces
Authors: Salawu Emmanuel Oluwatobi
Published: May 2021

The molecular structures (i.e., conformation spaces, CS) of bio-macromolecules and the dynamics that molecules exhibit are crucial to the understanding of the basis of many diseases and in the continuous attempts to retarget known drugs/medications, improve the efficacy of existing drugs, or develop novel drugs. These make a better understanding and the exploration of the CS of molecules a research hotspot. While it is generally easy to computationally explore the CS of small molecules (such as peptides and ligands), the exploration of the CS of a larger biomolecule beyond the local energy well and beyond the initial equilibrium structure of the molecule is generally nontrivial and can often be computationally prohibitive for molecules of considerable size. Therefore, research efforts in this area focus on the development of ways that systematically favor the sampling of new conformations while penalizing the resampling of previously sampled conformations. In this work, we present Deep Enhanced Sampling of Proteins’ Conformation Spaces Using AI-Inspired Biasing Forces (DESP), a technique for enhanced sampling that combines molecular dynamics (MD) simulations and deep neural networks (DNNs), in which biasing potentials for guiding the MD simulations are derived from the KL divergence between the DNN-learned latent space vectors of [a] the most recently sampled conformation and those of [b] the previously sampled conformations. Overall, DESP efficiently samples wide CS and outperforms conventional MD simulations as well as accelerated MD simulations. We acknowledge that this is an actively evolving research area, and we continue to further develop the techniques presented here and their derivatives tailored at achieving DNN-enhanced steered MD simulations and DNN-enhanced targeted MD simulations.
C9ORF72: What It Is, What It Does, and Why It Matters
Authors: Smeyers Julie , Banchi Elena-Gaia , Latouche Morwena
Published: May 2021

When the non-coding repeat expansion in theC9ORF72gene was discovered to be the most frequent cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) in 2011, this gene and its derived protein, C9ORF72, were completely unknown. The mutation appeared to produce both haploinsufficiency and gain-of-function effects in the form of aggregating expanded RNAs and dipeptide repeat proteins (DPRs). An unprecedented effort was then unleashed to decipher the pathogenic mechanisms and the functions of C9ORF72 in order to design therapies. A decade later, while the toxicity of accumulating gain-of-function products has been established and therapeutic strategies are being developed to target it, the contribution of the loss of function starts to appear more clearly. This article reviews the current knowledge about the C9ORF72 protein, how it is affected by the repeat expansion in models and patients, and what could be the contribution of its haploinsufficiency to the disease in light of the most recent findings. We suggest that these elements should be taken into consideration to refine future therapeutic strategies, compensating for the decrease of C9ORF72 or at least preventing a further reduction.
A Rodent Model of Mild Neonatal Hypoxic Ischemic Encephalopathy
Authors: Gotchac Julien , Cardoit Laura , Thoby-Brisson Muriel , Brissaud Olivier
Published: May 2021

In the brain of full-term newborns, Hypoxic Ischemic Encephalopathy (HIE), a consequence of severe hypoxia and ischemia due to low cardiac output, is frequently observed and results in cerebral injuries with dramatic consequences for life. To investigate the physiopathology of HIE, several animal models have been developed, but none closely replicate human cases, mostly because they are based on a single carotid ligation protocol. In the present study we aimed to develop a novel and more accurate HIE model in juvenile (post-natal days (PND) 14–16) rats. For this, we induced a 9 min hypoxic cardiac arrest (CA) by stopping mechanical ventilation of intubated, ventilated and curarized rats followed by a cardiopulmonary resuscitation. To evaluate the consequences of the CA we performed radiological (cerebral MRI), behavioral (Open Field, Elevated Plus Maze, Fear Conditioning), and histological (Cresyl Violet and Fluoro-Jade B) testing on treated animals. We found that rats in the CA group developed an anxiolytic-like behavioral profile in adulthood without any locomotor impairment, nor memory deficits. However, MRI investigation performed early after CA failed to reveal any change in apparent diffusion coefficient (ADC) in brain tissue (including the hippocampus, striatum, and thalamus), suggesting no massive anatomical lesion had occurred. In contrast, signs of neurodegeneration were found in the Dentate Gyrus and the CA1 region of the hippocampus at day 1 post-CA, suggesting that the anxiolytic-like phenotype observed in adulthood could be related to an abnormal degeneration of this brain region beginning immediately after CA. Thus, our model, despite not representing a severe condition of HIE, nonetheless constitutes a potential model for studying mild, yet persistent and region-specific cerebral injury resulting from an acute oxygen deprivation.
Mutation Screening of the GLE1 Gene in a Large Chinese Cohort of Amyotrophic Lateral Sclerosis Patients
Authors: Li Yanran , Sun Bo , Wang Zhanjun , He Zhengqing , Yang Fei , Wang Hongfen , Cui Fang , Chen Zhaohui , Ling Li , Wang Chaodong , Huang Xusheng
Published: May 2021

Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease involving the upper and lower motor neurons of the spinal cord, brainstem, and cerebral cortex. At least 30 genes have been implicated in familial ALS (fALS) and sporadic ALS (sALS). Kaneb et al. (2015) first carried out a large-scale sequencing study in ALS patients and identified two loss-of-function (LOF) variants in the GLE1 gene. The LOF mutation-induced disruption of RNA metabolism through the haploinsufficiency mechanism is implicated in ALS pathogenesis. A total of 628 ALS patients and 522 individuals without neurodegenerative disorders were enrolled in this study to explore the GLE1 gene contribution to ALS in the Chinese population. All 16 exons and the flanking intron of GLE1 were screened by Sanger sequencing. In total, we identified seven rare GLE1 coding variants, including one novel nonsense mutation and six rare missense mutations in 628 ALS patients. The frequency of GLE1 LOF mutations was 0.16% (1/628) among Chinese sALS patients, implying that it is an uncommon genetic determinant of ALS in Chinese patients. Additionally, the rare missense variants in the hCG1-binding domain of GLE1 impairing the distribution of the hGle1B isoform at the nuclear pore complex (NPC) region may be involved in the pathogenesis of ALS.
A Rare Cause of Pulmonary Nodules Diagnosed as Angiosarcoma Was Misdiagnosed as Vasculitis and Wegener’s Granuloma in an Elderly Man: A Case Report
Authors: Wang Peixia , Xu Liqian , Yang Yunmei
Published: May 2021

Background

Angiosarcoma is a rare, highly malignant tumor prone to recurrence and metastasis. Angiosarcoma is insidious in the initial stage, and its clinical manifestation lacks specificity. The diagnosis is based on histopathology and immunohistochemistry findings.

Case presentation

A 73-year-old man was hospitalized following complaints of persistent cough 6 months and hemoptysis for 2 months. Anti-infective treatment was ineffective. A CT-guided percutaneous core needle biopsy of pulmonary lesions revealed organized pneumonia, and the removed skin of purpuric rash area on the left calf revealed vasculitis. Chest CT was used during the patient follow-up. Hormonal therapy combined with immunoglobulins did not lead to improvement, and there was rapid progression of the lung lesions. Subsequently, the patient underwent a surgery, the diseased tissue was separated and removed completely beside the left submandibular gland under local anaesthesia. The immunohistochemical staining indicated CD31 (+) and CD34 (+) confirming a diagnosis of metastatic angiosarcoma. The expression of PD-L1 was 70%, therefore, anlotinib and pembrolizumab treatments were initiated. The patient eventually died.

Conclusion

Angiosarcoma is a malignant tumor in the clinic that lacks typical and specific signs and symptoms. The diagnosis depends on immunohistochemistry, which requires repeated biopsies of multiple sites in highly suspected cases.
Development and Prospective Validation of an Ultrasound Prediction Model for the Differential Diagnosis of Benign and Malignant Subpleural Pulmonary Lesions: A Large Ambispective Cohort Study
Authors: Bi Ke , Xia De-meng , Fan Lin , Ye Xiao-fei , Zhang Yi , Shen Meng-jun , Chen Hong-wei , Cong Yang , Zhu Hui-ming , Tang Chun-hong , Yuan Jing , Wang Yin
Published: May 2021

Objective

To develop and prospective validate an ultrasound (US) prediction model to differentiate between benign and malignant subpleural pulmonary lesions (SPLs).

Methods

This study was conducted retrospectively from July 2017 to December 2018 (development cohort [DC], n = 592) and prospectively from January to April 2019 (validation cohort [VC], n = 220). A total of 18 parameters of B-mode US and contrast-enhanced US (CEUS) were acquired. Based on the DC, a model was developed using binary logistic regression. Then its discrimination and calibration were verified internally in the DC and externally in the VC, and its diagnostic performance was compared with those of the existing US diagnostic criteria in the two cohorts. The reference criteria were from the comprehensive diagnosis of clinical-radiological-pathological made by two senior respiratory physicians.

Results

The model was eventually constructed with 6 parameters: the angle between lesion border and thoracic wall, basic intensity, lung-lesion arrival time difference, ratio of arrival time difference, vascular sign, and non-enhancing region type. In both internal and external validation, the model provided excellent discrimination of benign and malignant SPLs (C-statistic: 0.974 and 0.980 respectively), which is higher than that of “lesion-lung AT difference ≥ 2.5 s” (C-statistic: 0.842 and 0.777 respectively, P <0.001) and “AT ≥ 10 s” (C-statistic: 0.688 and 0.641 respectively, P <0.001) and the calibration curves of the model showed good agreement between actual and predictive malignancy probabilities. As for the diagnosis performance, the sensitivity and specificity of the model [sensitivity: 94.82% (DC) and 92.86% (VC); specificity: 92.42% (DC) and 92.59% (VC)] were higher than those of “lesion-lung AT difference ≥ 2.5 s” [sensitivity: 88.11% (DC) and 80.36% (VC); specificity: 80.30% (DC) and 75.00% (VC)] and “AT ≥ 10 s” [sensitivity: 64.94% (DC) and 61.61% (VC); specificity: 72.73% (DC) and 66.67% (VC)].

Conclusion

The prediction model integrating multiple parameters of B-mode US and CEUS can accurately predict the malignancy probability, so as to effectively differentiate between benign and malignant SPLs, and has better diagnostic performance than the existing US diagnostic criteria.

Clinical Trial Registration

www.chictr.org.cn, identifier ChiCTR1800019828.
Particle Therapy for Breast Cancer: Benefits and Challenges
Authors: Luo Wanrong , Ali Yasser F. , Liu Chong , Wang Yuchen , Liu Caorui , Jin Xiaoni , Zhou Guangming , Liu Ning-Ang
Published: May 2021

Hadron therapy with protons and carbon ions is widely attracting interest as a potential competitor of conventional photon radiotherapy. Exquisite dose distribution of charged particles allows for a higher local control of the tumor and lower probability of damage to nearby healthy tissues. Heavy ions have presumed biological advantages rising from their high-linear energy transfer (LET) characteristics, including greater cell-killing effectiveness and reduced heterogeneity dependence of radiation response. Although these advantages are clear and supported by data, only 18.0% of proton and carbon ion radiotherapy (CIRT) facilities in Europe are treating breast cancers. This review summarizes the physical and radiobiological properties of charged particles, clinical use of particle beam for breast cancer, and suggested approaches to overcome technical and financial challenges.
Intermittently Scanned and Continuous Glucose Monitor Systems: A Systematic Review on Psychological Outcomes in Pediatric Patients
Authors: Franceschi Roberto , Micheli Francesca , Mozzillo Enza , Cauvin Vittoria , Liguori Alice , Soffiati Massimo , Giani Elisa
Published: May 2021

Aim: To explore the impact of real-time continuous glucose monitoring (rtCGMs) or intermittently scanned/viewed CGM (isCGM) on psychological outcomes in children and caregivers, and to grade the level of evidence.

Method: Systematic review of the literature from PubMed, Embase, Cochrane Library, Web of Science, CINAHL, Nursing reference center, Up to date, Google Scholar, and PsycINFO databases. The studies selected used validated questionnaires for investigating the psychological outcomes. We applied GRADE (Grading of Recommendations Assessment, Development and Evaluation) to rank the quality of a body of evidence.

Results: A total of 192 studies were identified in the initial search and after the process of evaluation 25 studies were selected as appropriate to be included in this systematic review. We found in moderate quality studies that isCGM in adolescents can improve diabetes related distress, family conflicts, fear of hypoglycemia, and quality of life, while depression, anxiety, and quality of sleep have not yet been evaluated by validated questionnaires. In moderate—high quality studies, rtCGM technology does not impact on diabetes burden, diabetes specific family conflict, and depressive symptoms. The effect on fear of hypoglycemia, sleep quality, and anxiety is still debated and RCT studies powered to find significant results in psychological outcomes are lacking. RtCGM increases satisfaction and quality of life in parents and patients wearing rtCGM.

Conclusion: these data present an interesting point to consider when families are deciding whether or not to start CGM use, choosing between rtCGM to reach a tighter metabolic control, or isCGM which allows greater benefits on psychological outcomes.
The Shipibo Ceremonial Use of Ayahuasca to Promote Well-Being: An Observational Study
Authors: Gonzalez Debora , Cantillo Jordi , Perez Irene , Carvalho Maria , Aronovich Adam , Farre Magi , Feilding Amanda , Obiols Jordi E. , Bouso José Carlos
Published: May 2021

Promoting well-being is one of the main goals to improve health in the world. We examined the well-being and quality of life over the course of one year in a sample that participated in an Indigenous Shipibo healing program where traditional healers work in a series of ayahuasca ceremonies. We also explored the role of decentering as a mediator of psychological well-being. Participants who attended the program responded to an online survey that included a Psychological Well-Being Scale; Oxford Happiness Questionnaire; The World Health Organization Quality of Life Spirituality, Religiousness, and Personal Beliefs scale; the WHO Quality of Life-BREF scale; and Decentering scale. Baseline (T0) and postassessment (T1) were completed by 200 individuals. Of these, 101 completed the follow-up assessment at three months (T2), 91 at 6 months (T3), and 94 at 12 months follow-up (T4) after leaving the center. ANOVA test was performed in a representative subsample to control the passing of time two months before attending the program (T-1). Pearson’s test was performed to examine the relationship between psychological well-being and decentering during the period of T0 and T1. A significant increase was observed in all the scales at all time points (p≤ 0.01). The subgroup analysis performed in a representative subsample allowed us to infer that the significant differences in outcomes are due to the effect of their stay at the center and not the passing of time. We found a relationship between decentering and the improvement of psychological well-being (r= 0.57;p< 0.01). Our results suggest that the Indigenous Shipibo healing work with ayahuasca has value to improve long-term well-being and quality of life for Westerners.