bluuebunny/crossref_metadata_2025 huggingface dataset:
Protective Effects of Grape Seed Oligomeric Proanthocyanidins in IPEC-J2–Escherichia coli/Salmonella Typhimurium Co-Culture
Authors: Kovács Dóra , Palkovicsné Pézsa Nikolett , Jerzsele Ákos , Süth Miklós , Farkas Orsolya
Published: January 2022

Intestinal epithelium provides the largest barrier protecting mammalian species from harmful external factors; however, it can be severely compromised by the presence of bacteria in the gastrointestinal (GI) tract. Antibiotics have been widely used for the prevention and treatment of GI bacterial infections, leading to antimicrobial resistance in human and veterinary medicine alike. In order to decrease antibiotic usage, natural substances, such as flavonoids, are investigated to be used as antibiotic alternatives. Proanthocyanidins (PAs) are potential candidates for this purpose owing to their various beneficial effects in humans and animals. In this study, protective effects of grape seed oligomeric proanthocyanidins (GSOPs) were tested in IPEC-J2 porcine intestinal epithelial cells infected with Escherichia coli and Salmonella enterica ser. Typhimurium of swine origin. GSOPs were able to alleviate oxidative stress, inflammation and barrier integrity disruption inflicted by bacteria in the co-culture. Furthermore, GSOPs could decrease the adhesion of both bacteria to IPEC-J2 cells. Based on these observations, GSOPs seem to be promising candidates for the prevention and treatment of gastrointestinal bacterial infections.
Antimicrobial and Antibiotic Resistance from the Perspective of Polish Veterinary Students: An Inter-University Study
Authors: Sobierajski Tomasz , Mazińska Beata , Chajęcka-Wierzchowska Wioleta , Śmiałek Marcin , Hryniewicz Waleria
Published: January 2022

The phenomenon of antibiotic resistance is a global problem that affects the use of antibiotics by humans and animal husbandry. One of the primary reasons for the growing phenomenon of antibiotic resistance is the over-prescription of antibiotics by doctors in human medicine and the overuse of antibiotics in industrial animal farming. Adequate education of veterinary medical students on the use of antibiotics in animal husbandry may reduce antibiotic resistance. For this reason, a survey was conducted among students at four primary research and didactic centers teaching veterinary medicine in Poland. The survey aimed to find out the knowledge and attitude of students towards the use of antibiotics and antibiotic resistance. The survey was conducted in May/June 2021. Four hundred and sixty-seven students participated in the study. The study positively verified that antibiotics and antibiotic resistance knowledge increase with successive years of veterinary studies/education. For most students (82.2%), antibiotic resistance is a significant problem, but only 58.7% believe it is global, and one in three respondents heard about the One Health approach.
Reservoir of Antibiotic Residues and Resistant Coagulase Negative Staphylococci in a Healthy Population in the Greater Accra Region, Ghana
Authors: Bekoe Samuel Oppong , Hane-Weijman Sophie , Trads Sofie Louise , Orman Emmanuel , Opintan Japheth , Hansen Martin , Frimodt-Møller Niels , Styrishave Bjarne
Published: January 2022

Antimicrobial resistance threatens infectious disease management outcomes, especially in developing countries. In this study, the occurrence of resistant coagulase-negative staphylococci (rCoNS) and antibiotic residues in urine samples of 401 healthy individuals from Korle-Gonno (KG) and Dodowa (DDW) in Ghana was investigated. MALDI-ToF/MS with gram-staining techniques detected and identified the CoNS. SPE-LC-MS/MS detected and quantified nine commonly used antibiotics in the samples. The results showed 63 CoNS isolates detected in 47 (12%) samples, with S. haemolyticus (78%) and S. epidermidis (8%) being predominant. Most of the isolates (95%) were resistant to at least one antibiotic, with the highest resistance observed against sulphamethoxazole (87%). Resistance profiles in samples from DDW and KG were largely comparable, but with some differences. For instance, DDW isolates were more resistant to gentamicin (p = 0.0244), trimethoprim (p = 0.0045), and cefoxitin (p = 0.0078), whereas KG isolates were more resistant to erythromycin (p = 0.0356). Although the volunteers had not knowingly consumed antibiotics two weeks before sampling, antibiotic residues, ranging between 1.44–17000 ng mL−1 were identified in 22% of urine samples. Samples with antibiotic residues were likely to also contain rCoNS (89%). The most frequent antibiotics detected were tetracycline (63%) and ciprofloxacin (54%). Healthy individuals could thus be reservoirs of antibiotic residues and rCoNS at the community level.
Retrospective Cohort Analysis of the Effect of Antimicrobial Stewardship on Postoperative Antibiotic Therapy in Complicated Intra-Abdominal Infections: Short-Course Therapy Does Not Compromise Patients’ Safety
Authors: Surat Güzin , Meyer-Sautter Pascal , Rüsch Jan , Braun-Feldweg Johannes , Germer Christoph-Thomas , Lock Johan Friso
Published: January 2022

Background: Recent evidence suggests that short-course postoperative antibiotic therapy (PAT) of intra-abdominal infections is non-inferior considering clinical outcomes. The aim of this study was to compare the outcome of short vs. long PAT in complicated intra-abdominal infections (cIAIs) without sepsis. Methods: We performed a single center-quality improvement study at a 1500 bed sized university hospital in Bavaria, Germany, with evaluation of the length of antibiotic therapy after emergency surgery on cIAIs with adequate source control during 2016 to 2018. We reviewed a total of 260 cases (160 short duration vs. 100 long duration). The antibiotic prescribing quality was assessed by our in-house antimicrobial stewardship team (AMS). Results: No significant differences of patient characteristics were observed between short and long PAT. The frequency of long PAT declined during the observation period from 48.1% to 26.3%. Prolongation of PAT was not linked with any clinical benefits, on the contrary clinical outcome of patients receiving longer regimes were associated with higher postoperative morbidity. AMS identified additional educational targets to improve antibiotic prescribing quality on general wards like unnecessary postoperative switches of antibiotic regimes, e.g., unrequired switches to oral antibiotics as well as prolongation of PAT due to elevated CRP. Conclusion: Short-course antibiotic therapy after successful surgical source control in cIAIs is safe, and long-duration PAT has no beneficial effects.
Hydropersulfides (RSSH) and Nitric Oxide (NO) Signaling: Possible Effects on S-Nitrosothiols (RS-NO)
Authors: Fukuto Jon M. , Perez-Ternero Cristina , Zarenkiewicz Jessica , Lin Joseph , Hobbs Adrian J. , Toscano John P.
Published: January 2022

S-Nitrosothiol (RS-NO) formation in proteins and peptides have been implicated as factors in the etiology of many diseases and as possible regulators of thiol protein function. They have also been proposed as possible storage forms of nitric oxide (NO). However, despite their proposed functions/roles, there appears to be little consensus regarding the physiological mechanisms of RS-NO formation and degradation. Hydropersulfides (RSSH) have recently been discovered as endogenously generated species with unique reactivity. One important reaction of RSSH is with RS-NO, which leads to the degradation of RS-NO as well as the release of NO. Thus, it can be speculated that RSSH can be a factor in the regulation of steady-state RS-NO levels, and therefore may be important in RS-NO (patho)physiology. Moreover, RSSH-mediated NO release from RS-NO may be a possible mechanism allowing RS-NO to serve as a storage form of NO.
Acremonium terricola Culture’s Dose–Response Effects on Lactational Performance, Antioxidant Capacity, and Ruminal Characteristics in Holstein Dairy Cows
Authors: Kong Fanlin , Zhang Yijia , Wang Shuo , Cao Zan , Liu Yanfang , Zhang Zixiao , Wang Wei , Lu Na , Li Shengli
Published: January 2022

Acremonium terricola culture (ATC) has similar bioactive constituents to Cordyceps and is known for its nutrient and pharmacological value, indicating the potential of ATC as a new feed additive in dairy cow feeding. The primary aim of this experiment was to investigate the effects of increasing amounts of ATC in diets on milk performance, antioxidant capacity, and rumen fermentation, and the secondary aim was to evaluate the potential effects of high doses of ATC. A total of 60 multiparous Holstein cows (110 ± 21 days in milk; 2.53 ± 0.82 parity) were assigned into 15 blocks and randomly assigned to one of four groups: 0, 30, 60, or 300 g/d of ATC per cow for 97 days. Data were analyzed using repeated measures in the Mixed procedure. Dry-matter intake was not changed (p > 0.05), while energy-corrected milk and fat-corrected milk yields increased linearly and quadratically, and somatic cell count in milk decreased linearly and quadratically (p < 0.05). The lactation efficiency and the yields of milk fat and protein increased linearly (p < 0.05). On day 90, serum catalase level, total oxidative capacity, glutathione peroxidase, immunoglobulin A, and immunoglobulin M concentrations were significantly higher in the 60 and 300 g/d groups than in the 0 g/d group (p < 0.05). ATC addition showed linear effects on total volatile fatty acid (VFA), acetate, branched VFA concentrations, and rumen pH (p < 0.05). Supplementing 60 and 300 g/d ATC significantly affected the bacterial composition (p < 0.05). The relative abundance of Christensenellaceae_R–7_group and Lachnospiraceae_NK3A20_group were significantly increased by 60 g/d supplementation, and the relative abundance of Erysipelotrichaceae_UCG_002, Acetitomaculum, Olsenella, and Syntrophococcus were significantly increased by 300 g/d supplementation (p < 0.05). ATC was effective in enhancing rumen fermentation and reducing somatic cell count in milk, thereby improving milk yield. The optimized dose of ATC was 60 g/d for lactating cows, and there were no risks associated with high doses of ATC.
Combined Prediction Method for Thermal Conductivity of Asphalt Concrete Based on Meso-Structure and Renormalization Technology
Authors: Chen Jiaqi , Chen Xingzao , Dan Hancheng , Zhang Lanchun
Published: January 2022

Pavement temperature field affects pavement service life and the thermal environment the near road surface; thus, is important for sustainable pavement design. This paper developed a combined prediction method for the thermal conductivity of asphalt concrete based on meso-structure and renormalization technology, which is critical for determining the pavement temperature field. The accuracy of the combined prediction method was verified by laboratory experiments. Using the tested and proven model, the effect of coarse aggregate type, shape, content, spatial orientation, air void of asphalt concrete, and steel fiber on the effective thermal conductivity was analyzed. The analysis results show that the orientation angle and aspect ratio of the aggregate have a combined effect on thermal conductivity. In general, when the aggregate orientation is parallel with the heat conduction direction, the effective thermal conductivity of asphalt concrete in that direction tends to be greater. The effective thermal conductivity of asphalt concrete decreases with the decrease of coarse aggregate content or steel fiber content or with the increase of porosity, and it increases with the increase of the effective thermal conductivity of coarse aggregate.
Finite-Time Set Reachability of Probabilistic Boolean Multiplex Control Networks
Authors: Cui Yuxin , Li Shu , Shan Yunxiao , Liu Fengqiu
Published: January 2022

This study focuses on the finite-time set reachability of probabilistic Boolean multiplex control networks (PBMCNs). Firstly, based on the state transfer graph (STG) reconstruction technique, the PBMCNs are extended to random logic dynamical systems. Then, a necessary and sufficient condition for the finite-time set reachability of PBMCNs is obtained. Finally, the obtained results are effectively illustrated by an example.
The Efficacy of Selected Sodium Hypochlorite Heating Methods for Increasing and Maintaining Its Intracanal Temperature—An Ex Vivo Study
Authors: De Santis Roberto , Iaculli Flavia , Lodato Vincenzo , Gallicchio Vito , Simeone Michele , Spagnuolo Gianrico , Rengo Carlo
Published: January 2022

Background: Enhancement of the temperature of sodium hypochlorite (NaOCl) solution would increase its cleaning potential and decontamination of the root canal system. Therefore, the aim of the present in vitro investigation was to compare the efficacy of different methods of NaOCl heating by evaluating the temperature profiles developed at different levels of the root canal system. Methods: Five thermocouples were applied at different levels of the root canal system of extracted human premolars. NaOCl solution was heated according to two methods: extraoral heating (50 °C, 60 °C, and 70 °C) using a magnetic hotplate heater and intracanal heating by F-06, XF-30/04, and ML-12 pluggers at 100 °C, 150 °C, and 180 °C. Results: The extraoral heating method was ineffective to produce a significant temperature increase at the root apex. Comparable results were obtained using the intracanal heating method through the ML-12 plugger that showed slightly better results only when set at 180 °C. On the other hand, negligible differences were observed in terms of temperature maintenance at several levels of the root between the F-06 and XF-30/04 pluggers, even though the time intervals were higher in case of XF-30/04. Conclusions: The intracanal heating method provided a better temperature persistence in the middle third of the root canal system. Conversely, extraoral heating was ineffective to produce a significant temperature increase at the apex of the root. Comparable results were obtained even using the ML-12 plugger.
Hybrid Direction of Arrival Precoding for Multiple Unmanned Aerial Vehicles Aided Non-Orthogonal Multiple Access in 6G Networks
Authors: Pierucci Laura
Published: January 2022

Unmanned aerial vehicles (UAV) have attracted increasing attention in acting as a relay for effectively improving the coverage and data rate of wireless systems, and according to this vision, they will be integrated in the future sixth generation (6G) cellular network. Non-orthogonal multiple access (NOMA) and mmWave band are planned to support ubiquitous connectivity towards a massive number of users in the 6G and Internet of Things (IOT) contexts. Unfortunately, the wireless terrestrial link between the end-users and the base station (BS) can suffer severe blockage conditions. Instead, UAV relaying can establish a line-of-sight (LoS) connection with high probability due to its flying height. The present paper focuses on a multi-UAV network which supports an uplink (UL) NOMA cellular system. In particular, by operating in the mmWave band, hybrid beamforming architecture is adopted. The MUltiple SIgnal Classification (MUSIC) spectral estimation method is considered at the hybrid beamforming to detect the different direction of arrival (DoA) of each UAV. We newly design the sum-rate maximization problem of the UAV-aided NOMA 6G network specifically for the uplink mmWave transmission. Numerical results point out the better behavior obtained by the use of UAV relays and the MUSIC DoA estimation in the Hybrid mmWave beamforming in terms of achievable sum-rate in comparison to UL NOMA connections without the help of a UAV network.
Upper Airway Changes in Diverse Orthodontic Looms: A Systematic Review and Meta-Analysis
Authors: Alswairki Haytham Jamil , Alam Mohammad Khursheed , Rahman Shaifulizan Ab , Alsuwailem Rayan , Alanazi Sarah Hatab
Published: January 2022

Upper airway assessment is particularly important in the daily work of orthodontists, because of its close connection with the development of craniofacial structures and with other pathologies such as Obstructive Sleep Apnea Syndrome (OSAS). Three-dimensional cone-beam computed tomography images provide a more reliable and comprehensive tool for airway assessment and volumetric measurements. However, the association between upper airway dimensions and skeletal malocclusion is unclear. Therefore, the current systematic review evaluates the effects of different surgical movements on the upper airway. Materials and Methods: Medline (PubMed, OVID Medline, and EBSCO), Cochrane Library (Cochrane Review and Trails), Web of Knowledge (social science, and conference abstracts), Embase (European studies, pharmacological literature, and conference abstracts), CINAHL (nursing and allied health), PsycInfo (psychology and psychiatry), SCOPUS (conference abstracts, and scientific web pages), and ERIC (education) databases were searched. Two authors independently performed the literature search, selection, quality assessment, and data extraction. Inclusion criteria encompassed computed tomography evaluations of the upper airway spaces with retrospective, prospective, and randomised clinical trial study designs. To grade the methodological quality of the included studies a GRADE risk of bias tool was used. Results and conclusion: In total, 29 studies were included. Among these, 17 studies had a low risk of bias, whereas 10 studies had a moderate risk of bias. A meta-analysis was performed with the mean differences using a fixed-effects model. Heterogeneity was assessed with the Q-test and the I2 index. The meta-analysis revealed significant (p ≤ 0.001, 95% confidence interval) increases in upper airway volume after rapid maxillary expansion and surgical advancement for the correction of Class II.
Advances in Kombucha Tea Fermentation: A Review
Authors: Nyhan Laura M. , Lynch Kieran M. , Sahin Aylin W. , Arendt Elke K.
Published: January 2022

Kombucha is a carbonated, slightly acidic beverage traditionally produced by the fermentation of sweetened tea by a symbiotic culture of bacteria and yeast (SCOBY). The microbial community of kombucha is a complex one, whose dynamics are still not fully understood; however, the emergence of culture-independent techniques has allowed a more comprehensive insight into kombucha microbiota. In recent times, advancements have been made towards the optimisation of the fermentation process, including the use of alternative substrates, defined starter cultures and the modification of fermentation parameters, with the aim of producing an innovative beverage that is improved in terms of its physiochemical, sensory and bioactive properties. The global kombucha market is rapidly increasing, with the rising popularity of the tea attributed in part to its purported health benefits, despite the lack of research in human subjects to substantiate such claims. Accordingly, the incidence of kombucha home-brewing has increased, meaning there is a requirement for individuals to recognise the potential hazards associated with fermentation and the relevant preventative measures to be undertaken to ensure the safe preparation of kombucha. The aim of this review is to provide an update regarding the current knowledge of kombucha production, microbiology, safety and marketing.
Studies of the Dispersed Composition of Atmospheric Aerosol and Its Relationship with Small Gas Impurities in the Near-Water Layer of Lake Baikal Based on the Results of Ship Measurements in the Summer of 2020
Authors: Zhamsueva Galina , Zayakhanov Alexander , Khodzher Tamara , Tcydypov Vadim , Balzhanov Tumen , Dementeva Ayuna
Published: January 2022

The atmosphere over Lake Baikal covers a vast area (31,500 square meters) and has more significant differences in the composition and variability of gaseous and aerosol components in atmospheric air than in coastal continental areas and is still a poorly studied object. In recent years, the anthropogenic impact on the ecosystem of Lake Baikal has been increasing due to the development of industry in the region, the expansion of tourist infrastructure and recreational areas of the coastal zone of the lake. In addition, one of the significant sources of atmospheric pollution in the Baikal region is the emissions of smoke aerosol and trace gases from forest fires, the number of which is increasing in the region. This article presents the results of experimental studies of the dispersed composition of aerosols and gas impurities, such as ozone, sulfur dioxide, and nitrogen oxides during route ship measurements in the water area of Lake Baikal in the summer of 2020.
A New Proof for a Result on the Inclusion Chromatic Index of Subcubic Graphs
Authors: Chen Lily , Li Yanyi
Published: January 2022

Let G be a graph with a minimum degree δ of at least two. The inclusion chromatic index of G, denoted by χ⊂′(G), is the minimum number of colors needed to properly color the edges of G so that the set of colors incident with any vertex is not contained in the set of colors incident to any of its neighbors. We prove that every connected subcubic graph G with δ(G)≥2 either has an inclusion chromatic index of at most six, or G is isomorphic to K^2,3, where its inclusion chromatic index is seven.
Extracellular Vesicles Derived-LAT1 mRNA as a Powerful Inducer of Colorectal Cancer Aggressive Phenotype
Authors: Almeida Cristina , Teixeira Ana Luísa , Dias Francisca , Machado Vera , Morais Mariana , Martins Gabriela , Palmeira Carlos , Sousa Maria Emília , Godinho Inês , Batista Sílvia , Costa-Silva Bruno , Medeiros Rui
Published: January 2022

Colorectal cancer (CRC) is the third most common cancer in the world and represents the third most deadly tumor worldwide. About 15–25% of patients present metastasis in the moment of diagnosis, the liver being the most common site of metastization. Therefore, the development of new therapeutic agents is needed, to improve the patients’ prognosis. Amino acids transporters, LAT1 and ASCT2, are described as upregulated in CRC, being associated with a poor prognosis. Extracellular vesicles have emerged as key players in cell-to-cell communication due to their ability to transfer biomolecules between cells, with a phenotypic impact on the recipient cells. Thus, this study analyzes the presence of LAT1 and ASCT2 mRNAs in CRC-EVs and evaluates their role in phenotype modulation in a panel of four recipient cell lines (HCA-7, HEPG-2, SK-HEP-1, HKC-8). We found that HCT 116-EVs carry LAT1, ASCT2 and other oncogenic mRNAs being taken up by recipient cells. Moreover, the HCT 116-EVs’ internalization was associated with the increase of LAT1 mRNA in SK-HEP-1 cells. We also observed that HCT 116-EVs induce a higher cell migration capacity and proliferation of SK-HEP-1 and HKC-8 cells. The present study supports the LAT1-EVs’ mRNA involvement in cell phenotype modulation, conferring advantages in cell migration and proliferation.
Atrial Fibrillation in β-Thalassemia: Overview of Mechanism, Significance and Clinical Management
Authors: Malagù Michele , Marchini Federico , Fiorio Alessio , Sirugo Paolo , Clò Stefano , Mari Elisa , Gamberini Maria Rita , Rapezzi Claudio , Bertini Matteo
Published: January 2022

Thalassemia is an inherited blood disorder with worldwide distribution. Transfusion and chelation therapy have radically improved the prognosis of β-thalassemic patients in the developed world, but this has led to the development of new chronic cardiac complications like atrial fibrillation (AF). Prevalence of AF in patients with β-thalassemia is higher than in the general population, ranging from 2 to 33%. Studies are lacking, and the little evidence available comes from a small number of observational studies. The pathophysiology is not well understood but, while iron overload seems to be the principal mechanism, AF could develop even in the absence of iron deposition. Furthermore, the clinical presentation is mainly paroxysmal, and patients are highly symptomatic. The underlying disease, the pathophysiology, and the clinical presentation require a different management of AF in β-thalassemia than in the general population. Rhythm control should be preferred over rate control, and the most important antiarrhythmic therapy is represented by chelation drugs. Thromboembolic risk is high, but the available risk scores are not validated in β-thalassemia, and the choice of anticoagulation therapy should be considered early. The main purpose of this review is to summarize the actual knowledge about AF in β-thalassemia, with a specific focus on the clinical management of these complex patients.
Mass Spectrometry-Based Structural Proteomics for Metal Ion/Protein Binding Studies
Authors: Lin Yanchun , Gross Michael L.
Published: January 2022

Metal ions are critical for the biological and physiological functions of many proteins. Mass spectrometry (MS)-based structural proteomics is an ever-growing field that has been adopted to study protein and metal ion interactions. Native MS offers information on metal binding and its stoichiometry. Footprinting approaches coupled with MS, including hydrogen/deuterium exchange (HDX), “fast photochemical oxidation of proteins” (FPOP) and targeted amino-acid labeling, identify binding sites and regions undergoing conformational changes. MS-based titration methods, including “protein–ligand interactions by mass spectrometry, titration and HD exchange” (PLIMSTEX) and “ligand titration, fast photochemical oxidation of proteins and mass spectrometry” (LITPOMS), afford binding stoichiometry, binding affinity, and binding order. These MS-based structural proteomics approaches, their applications to answer questions regarding metal ion protein interactions, their limitations, and recent and potential improvements are discussed here. This review serves as a demonstration of the capabilities of these tools and as an introduction to wider applications to solve other questions.
Novel Insight into the Mechanisms of the Bidirectional Relationship between Diabetes and Periodontitis
Authors: Barutta Federica , Bellini Stefania , Durazzo Marilena , Gruden Gabriella
Published: January 2022

Periodontitis and diabetes are two major global health problems despite their prevalence being significantly underreported and underestimated. Both epidemiological and intervention studies show a bidirectional relationship between periodontitis and diabetes. The hypothesis of a potential causal link between the two diseases is corroborated by recent studies in experimental animals that identified mechanisms whereby periodontitis and diabetes can adversely affect each other. Herein, we will review clinical data on the existence of a two-way relationship between periodontitis and diabetes and discuss possible mechanistic interactions in both directions, focusing in particular on new data highlighting the importance of the host response. Moreover, we will address the hypothesis that trained immunity may represent the unifying mechanism explaining the intertwined association between diabetes and periodontitis. Achieving a better mechanistic insight on clustering of infectious, inflammatory, and metabolic diseases may provide new therapeutic options to reduce the risk of diabetes and diabetes-associated comorbidities.
Activation of STAT and SMAD Signaling Induces Hepcidin Re-Expression as a Therapeutic Target for β-Thalassemia Patients
Authors: Saad Hanan Kamel M. , Abd Rahman Alawiyah Awang , Ab Ghani Azly Sumanty , Taib Wan Rohani Wan , Ismail Imilia , Johan Muhammad Farid , Al-Wajeeh Abdullah Saleh , Al-Jamal Hamid Ali Nagi
Published: January 2022

Iron homeostasis is regulated by hepcidin, a hepatic hormone that controls dietary iron absorption and plasma iron concentration. Hepcidin binds to the only known iron export protein, ferroportin (FPN), which regulates its expression. The major factors that implicate hepcidin regulation include iron stores, hypoxia, inflammation, and erythropoiesis. When erythropoietic activity is suppressed, hepcidin expression is hampered, leading to deficiency, thus causing an iron overload in iron-loading anemia, such as β-thalassemia. Iron overload is the principal cause of mortality and morbidity in β-thalassemia patients with or without blood transfusion dependence. In the case of thalassemia major, the primary cause of iron overload is blood transfusion. In contrast, iron overload is attributed to hepcidin deficiency and hyperabsorption of dietary iron in non-transfusion thalassemia. Beta-thalassemia patients showed marked hepcidin suppression, anemia, iron overload, and ineffective erythropoiesis (IE). Recent molecular research has prompted the discovery of new diagnostic markers and therapeutic targets for several diseases, including β-thalassemia. In this review, signal transducers and activators of transcription (STAT) and SMAD (structurally similar to the small mothers against decapentaplegic in Drosophila) pathways and their effects on hepcidin expression have been discussed as a therapeutic target for β-thalassemia patients. Therefore, re-expression of hepcidin could be a therapeutic target in the management of thalassemia patients. Data from 65 relevant published experimental articles on hepcidin and β-thalassemia between January 2016 and May 2021 were retrieved by using PubMed and Google Scholar search engines. Published articles in any language other than English, review articles, books, or book chapters were excluded.
Pretherapeutic Serum Albumin as an Outcome Prognosticator in Head and Neck Adenoid-Cystic Carcinoma
Authors: Friedl Marlene , Stoiber Stefan , Brkic Faris F. , Kadletz-Wanke Lorenz
Published: January 2022

Background: A head and neck adenoid-cystic carcinoma is a rare malignant tumor arising from the salivary gland tissues. The long-term survival outcome is poor due to a high risk of recurrences and distant metastasis. The identification of prognostic markers could contribute to a better risk assessment of each patient. The aim of this study is to assess the potential prognostic value of serum albumin in patients with head and neck adenoid-cystic carcinomas. Patients and Methods: This retrospective cohort study included all patients treated for a head and neck adenoid-cystic carcinoma between 1993 and 1 June 2019 with available pretherapeutic albumin values and clinical follow-up data. The cohort was stratified into a high and low group according to the median albumin value. The log-rank test was used for comparing overall and disease-free survival. Results: A total of 37 patients with complete follow-up data and available pretreatment albumin values were available. The overall mortality and recurrence rates were 21.6% (n = 8) and 45.9% (n = 17), respectively. Survival was shorter in the low albumin group. In particular, the mean overall survival for the low and high albumin groups were 121.0 months and 142.8 months, respectively. However, the difference was not statistically significant (p = 0.155). A statistically significant difference was observed in context with disease-free survival (45.2 months, 95% confidence interval 31.7–58.8 months vs. 114.8 months, 95% confidence interval 79.3–150.4 months; p = 0.029). Conclusion: Our study suggests a potential prognostic value of serum albumin in patients with a head and neck ACC. A further, external validation of our results is warranted.
Quantified Explainability: Convolutional Neural Network Focus Assessment in Arrhythmia Detection
Authors: Varandas Rui , Gonçalves Bernardo , Gamboa Hugo , Vieira Pedro
Published: January 2022

In clinical practice, every decision should be reliable and explained to the stakeholders. The high accuracy of deep learning (DL) models pose a great advantage, but the fact that they function as black-boxes hinders their clinical applications. Hence, explainability methods became important as they provide explanation to DL models. In this study, two datasets with electrocardiogram (ECG) image representations of six heartbeats were built, one given the label of the last heartbeat and the other given the label of the first heartbeat. Each dataset was used to train one neural network. Finally, we applied well-known explainability methods to the resulting networks to explain their classifications. Explainability methods produced attribution maps where pixels intensities are proportional to their importance to the classification task. Then, we developed a metric to quantify the focus of the models in the heartbeat of interest. The classification models achieved testing accuracy scores of around 93.66% and 91.72%. The models focused around the heartbeat of interest, with values of the focus metric ranging between 8.8% and 32.4%. Future work will investigate the importance of regions outside the region of interest, besides the contribution of specific ECG waves to the classification.
Artificial Biomimetic Electrochemical Assemblies
Authors: Zidarič Tanja , Finšgar Matjaž , Maver Uroš , Maver Tina
Published: January 2022

Rapid, selective, and cost-effective detection and determination of clinically relevant biomolecule analytes for a better understanding of biological and physiological functions are becoming increasingly prominent. In this regard, biosensors represent a powerful tool to meet these requirements. Recent decades have seen biosensors gaining popularity due to their ability to design sensor platforms that are selective to determine target analytes. Naturally generated receptor units have a high affinity for their targets, which provides the selectivity of a device. However, such receptors are subject to instability under harsh environmental conditions and have consequently low durability. By applying principles of supramolecular chemistry, molecularly imprinted polymers (MIPs) can successfully replace natural receptors to circumvent these shortcomings. This review summarizes the recent achievements and analytical applications of electrosynthesized MIPs, in particular, for the detection of protein-based biomarkers. The scope of this review also includes the background behind electrochemical readouts and the origin of the gate effect in MIP-based biosensors.
Increased Pupil Size during Future Thinking in a Subject with Retrograde Amnesia
Authors: Boutoleau-Bretonnière Claire , Lamy Estelle , El Haj Mohamad
Published: January 2022

Recent research has assessed pupil size during past thinking in patients with retrograde amnesia. Building on this research, we assessed pupil size during future thinking in a retrograde amnesia patient. To this end, we measured pupil size during past and future thinking in L, a 19-year-old, right-handed man free of neurological/psychiatric disorders except for retrograde amnesia that occurred after an episode of fugue. During a past thinking condition, we invited L to retrieve retrograde events (i.e., events that occurred before amnesia) and anterograde events (i.e., events that occurred after amnesia). During a future thinking condition, we invited him to imagine events that might occur the following week, the following month, and in the new year. Past and future thinking occurred while L’s pupil size was monitored with eye-tracking glasses. L demonstrated higher specificity during future than during past thinking. Critically, the results demonstrated a larger pupil size during future than during past thinking. The larger pupil size during future thinking observed in L can be attributed to the high cognitive load involved in future thinking. Our study not only demonstrates preserved future thinking in a patient with dissociative retrograde amnesia, but also shows that pupillometry can be used for the physiological assessment of future thinking in retrograde amnesia patients.
Finding the Way to Improve Motor Recovery of Patients with Spinal Cord Lesions: A Case-Control Pilot Study on a Novel Neuromodulation Approach
Authors: Naro Antonino , Billeri Luana , Balletta Tina , Lauria Paola , Onesta Maria Pia , Calabrò Rocco Salvatore
Published: January 2022

Robot-assisted rehabilitation (RAR) and non-invasive brain stimulation (NIBS) are interventions that, both individually and combined, can significantly enhance motor performance after spinal cord injury (SCI). We sought to determine whether repetitive transcranial magnetic stimulation (rTMS) combined with active transvertebral direct current stimulation (tvDCS) (namely, NIBS) in association with RAR (RAR + NIBS) improves lower extremity motor function more than RAR alone in subjects with motor incomplete SCI (iSCI). Fifteen adults with iSCI received one daily session of RAR+NIBS in the early afternoon, six sessions weekly, for eight consecutive weeks. Outcome measures included the 6 min walk test (6MWT), the 10 m walk test (10MWT), the timed up and go (TUG) to test mobility and balance, the Walking Index for Spinal Cord Injury (WISCI II), the Functional Independence Measure-Locomotion (FIM-L), the manual muscle testing for lower extremity motor score (LEMS), the modified Ashworth scale for lower limbs (MAS), and the visual analog scale (VAS) for pain. The data of these subjects were compared with those of 20 individuals matched for clinical and demographic features who previously received the same amount or RAR without NIBS (RAR − NIBS). All patients completed the trial, and none reported any side effects either during or following the training. The 10MWT improved in both groups, but the increase was significantly greater following RAR + NIBS than RAR − NIBS. The same occurred for the FIM-L, LEMS, and WISCI II. No significant differences were appreciable concerning the 6MWT and TUG. Conversely, RAR − NIBS outperformed RAR + NIBS regarding the MAS and VAS. Pairing tvDCS with rTMS during RAR can improve lower extremity motor function more than RAR alone can do. Future research with a larger sample size is recommended to determine longer-term effects on motor function and activities of daily living.
Social Media Usage, Working Memory, and Depression: An Experimental Investigation among University Students
Authors: Almarzouki Abeer F. , Alghamdi Renad A. , Nassar Roaa , Aljohani Reem R. , Nasser Abdulrahman , Bawadood Manar , Almalki Rawan H.
Published: January 2022

Social media usage (SMU) and its relationship with working memory (WM) and academic performance remain unclear, and there is a lack of experimental evidence. We investigated whether WM mediates the association between SMU and academic performance, including the roles of depression, anxiety, and disordered social media use as possible contributors. A sample of 118 undergraduate students aged 19 to 28 from Saudi Arabia performed a WM test twice; for one assessment, participants were required to interact with social media before the test, and the other test was preceded by painting online. We also measured grade point average (GPA), habitual social media usage (SMU), depression (PHQ-9), anxiety (GAD-7), and disordered social media usage (SMDS). There was no significant difference between WM scores in the social media condition compared to the control condition, but when solely considering at least moderately depressed participants, social media use predicted significantly more errors in the social media condition compared to the control condition. Furthermore, higher SMDS scores were significantly predicted by higher PHQ-9 scores and more hours of habitual SMU. GPA scores were not predicted by WM performance or SMU. The present study is one of the first experimental attempts to compare the relationship between SMU and WM and highlights the priming effect of depression on the relationship between SMU and WM.
Python-LMDI: A Tool for Index Decomposition Analysis of Building Carbon Emissions
Authors: Xiang Xiwang , Ma Xin , Ma Zhili , Ma Minda , Cai Weiguang
Published: January 2022

A timely analysis for carbon emission reduction in buildings is an effective global response to the crisis of climate change. The logarithmic mean Divisia index (LMDI) decomposition analysis approach has been extensively used to assess the carbon emission reduction potential of the buildings sector. In order to simplify the calculation process and to expand its application scope, a new open-source Python tool (PyLMDI) developed in this article is used to compute the results of LMDI decomposition analysis, including multiplicative and additive decomposition. Users can quickly obtain the decomposition result by initializing the input data through a simple class data structure. In addition, the carbon emissions from commercial buildings are used as a numerical example to demonstrate the function of PyLMDI. In summary, PyLMDI is a potential calculation tool for index decomposition analysis that can provide calculation guidance for carbon emission reduction in the buildings sector. The data and codes for the numerical example are also included.
The Effect of the Bearing Width on the Buckling Capacity of Partially Loaded CLT Member
Authors: Wu Guofang , Huo Liangliang , Shen Yinlan , Ren Haiqing
Published: January 2022

The calculation method for buckling capacity of cross-laminated timber (CLT) under axial load with one-way members has been investigated and incorporated into design codes worldwide. However, the load may only be applied to a part of the CLT members. In this case, the available calculation method for buckling capacity is not applicable. To solve this problem, a 3D numerical model was developed to study the buckling behavior of axially loaded CLT members. After being validated by comparison with experimental results, the model was used to investigate the buckling capacity of axially loaded CLT members with different aspect ratios and bearing length ratios. The CLT members all consisted of three layers. The thickness of the CLT members was 105 mm, the width ranged from 300 mm to 2100 mm, and the height ranged from 1400 mm to 3500 mm. It was found that the unloaded part of CLT served as constraints to the loaded part. The longer the unloaded part, the stronger the constraint was. The buckling capacity increased with the increase in bearing length ratios. An equivalent width method (EWM) was proposed; i.e., the partially loaded CLT member was replaced by a fully loaded member with an equivalent width, which can be determined by the proposed formulas. It was found that the proposed calculation method is reliable and simple to apply. This study supplies the missing calculation method for the buckling behavior of partially loaded CLT members and helps to promote the engineering application of CLT members.
STAT3 Signaling in Breast Cancer: Multicellular Actions and Therapeutic Potential
Authors: To Sarah Q. , Dmello Rhynelle S. , Richards Anna K. , Ernst Matthias , Chand Ashwini L.
Published: January 2022

Interleukin (IL)-6 family cytokines, such as IL-6 and IL-11, are defined by the shared use of the gp130 receptor for the downstream activation of STAT3 signaling and the activation of genes which contribute to the “hallmarks of cancer”, including proliferation, survival, invasion and metastasis. Increased expression of these cytokines, or the ligand-specific receptors IL-6R and IL-11RA, in breast tumors positively correlate to disease progression and poorer patient outcome. In this review, we examine evidence from pre-clinical studies that correlate enhanced IL-6 and IL-11 mediated gp130/STAT3 signaling to the progression of breast cancer. Key processes by which the IL-6 family cytokines contribute to the heterogeneous nature of breast cancer, immune evasion and metastatic potential, are discussed. We examine the latest research into the therapeutic targeting of IL-6 family cytokines that inhibit STAT3 transcriptional activity as a potential breast cancer treatment, including current clinical trials. The importance of the IL-6 family of cytokines in cellular processes that promote the development and progression of breast cancer warrants further understanding of the molecular basis for its actions to help guide the development of future therapeutic targets.
Transforming Growth Factor-β Activated Kinase 1 (Tak1) Is Activated in Hepatocellular Carcinoma, Mediates Tumor Progression, and Predicts Unfavorable Outcome
Authors: Ridder Dirk Andreas , Urbansky Lana Louisa , Witzel Hagen Roland , Schindeldecker Mario , Weinmann Arndt , Berndt Kristina , Gerber Tiemo Sven , Köhler Bruno Christian , Nichetti Federico , Ludt Annekathrin , Gehrke Nadine , Schattenberg Jörn Markus , Heinrich Stefan , Roth Wilfried , Straub Beate Katharina
Published: January 2022

Although knowledge on inflammatory signaling pathways driving cancer initiation and progression has been increasing, molecular mechanisms in hepatocarcinogenesis are still far from being completely understood. Hepatocyte-specific deletion of the MAPKKK Tak1 in mice recapitulates important steps of hepatocellular carcinoma (HCC) development, including the occurrence of cell death, steatohepatitis, dysplastic nodules, and HCCs. However, overactivation of Tak1 in mice upon deletion of its deubiquitinase Cyld also results in steatohepatitis and HCC development. To investigate Tak1 and Cyld in human HCCs, we created a tissue microarray to analyze their expression by immunohistochemistry in a large and well-characterized cohort of 871 HCCs of 561 patients. In the human liver and HCC, Tak1 is predominantly present as its isoform Tak1A and predominantly localizes to cell nuclei. Tak1 is upregulated in diethylnitrosamine-induced mouse HCCs as well as in human HCCs independent of etiology and is further induced in distant metastases. A high nuclear Tak1 expression is associated with short survival and vascular invasion. When we overexpressed Tak1A in Huh7 cells, we observed increased tumor cell migration, whereas overexpression of full-length Tak1 had no significant effect. A combined score of low Cyld and high Tak1 expression was an independent prognostic marker in a multivariate Cox regression model.
Optimal Surgical Extent in Patients with Unilateral Multifocal Papillary Thyroid Carcinoma
Authors: Woo Joohyun , Kwon Hyungju
Published: January 2022

Multifocality increases the risk of recurrence in patients with papillary thyroid carcinoma (PTC); however, it is unclear whether multifocality justifies more extensive or aggressive surgical treatment. Here, we evaluated the effect of the operative extent on the recurrence-free survival (RFS) of patients with multifocal PTC. Between 2010 and 2019, 718 patients with unilateral multifocal PTC were enrolled; 115 patients (16.0%) underwent ipsilateral thyroid lobectomy, and 606 patients (84.0%) underwent total thyroidectomy. With a mean follow up of 5.2 years, RFS was comparable between the total thyroidectomy and lobectomy groups (p = 0.647) after adjusting for potential confounders. Multivariable Cox regression analysis also demonstrated that the operative extent was not an independent predictor of recurrence (HR 1.686, 95% CI: 0.321–8.852). Subgroup analyses further indicated that both total thyroidectomy and thyroid lobectomy resulted in comparable RFS for multifocal PTC patients with other high-risk factors, including tumor size > 1 cm (p = 0.711), lymph node metastasis (p = 0.536), and intermediate ATA risk of recurrence (p = 0.682). In conclusion, thyroid lobectomy was not associated with the risk of recurrence in patients with multifocal PTCs. Multifocality in PTC may not always require aggressive surgery.