bluuebunny/crossref_metadata_2025 huggingface dataset:
Health-related quality of life in persons post-COVID-19 infection in comparison to normative controls and chronic pain patients
Authors: Moens Maarten , Duarte Rui V. , De Smedt Ann , Putman Koen , Callens Jonas , Billot Maxime , Roulaud Manuel , Rigoard Philippe , Goudman Lisa
Published: October 2022

The Coronavirus disease 2019 (COVID-19) pandemic exerted a tremendous pressure on the healthcare system, people's social life, mental health and financial status with profound implications for the general population. The exact impact of the pandemic on the overall physical, mental and social wellbeing of COVID-19 infection survivors on the long term has not yet been explored in a thorough way. Based on the reporting of persistent pain, fatigue and dyspnea symptoms by these survivors, it is our hypothesis that their quality of life will be extremely impacted, as is observed in patients with chronic pain. Therefore, the first aim of this study was to perform an in-depth evaluation of the quality of life of post-COVID-19 infected persons. The second aim was to compare the quality of life of these persons with a normative population and with patients with chronic pain. Health-related quality of life, as a measure for a person's overall physical, mental, and social wellbeing, was measured with the 3-level EQ5D in 547 post-COVID-19 infected persons. These data were compared to reference data from normal population records for Belgium and to data from patients with chronic pain after spinal surgery with two-way analyses of variance. In total, 89.58% of the post-COVID-19 infected persons reported pain/discomfort and 82.45% indicated limitations when performing usual activities, when evaluated 287 days (SD: 150) after the infection. Self-care was preserved in most post-COVID-19 persons, whereby only 13.16% indicated problems. The mean EQ5D-3L index score was 0.57 (SD: 0.23) and EQ5D VAS mean score was 56.6 (SD: 18.2). The mean index score for the normative population was significantly higher than for COVID-19 infected persons [mean difference of 0.31 (95% from 0.29 to 0.33), p < 0.01] while the mean score of chronic pain patients was significantly lower than the score of COVID-19 infected persons [mean difference of −0.31 (95% from −0.29 to −0.33), p < 0.01]. Compared to age-and sex adjusted reference data, health-related quality of life of persons with long COVID is severely impacted. In relation to patients with chronic pain after spinal surgery, the quality of life of post-COVID-19 infected persons seemed to be better.

Clinical trial registration

https://www.clinicaltrials.gov/, identifier: NCT04912778.
Assessment of urban sanitation status and management gaps in a metropolitan city, Bangladesh: Potential challenges to achieve SDG 6
Authors: Ferdous Sazia , Chowdhury Farah Noshin , Ali Md. Liakath , Bodrud-Doza Md. , Rahman Md. Mostafizur
Published: October 2022

Concerns have been on the rise around the globe regarding better sanitation management, which is one of the basic human rights, owing especially to the present goal of sustainable development, more specifically Sustainable Development Goal (SDG) 6. Proper sanitation management is a challenging issue in Bangladesh. The purpose of this study was to investigate the current state of sanitation and hygiene facilities and management in Chattogram City, Bangladesh. This study was conducted via questionnaire survey, key informant information (KIIs), stakeholder meetings, and field visits. A survey was conducted on slum dwellers and non-slum dwellers (formal settlements) of the city. A total of 400(=n) randomly selected respondents were interviewed (200 from each group) from eight wards of the metropolitan city, six KIIs, and three stakeholder meetings. Field visits were made to observe the conditions along with a pilot survey to validate the questionnaires. A purposive sampling method was employed for this study, while both descriptive and quantitative statistical analyses were conducted. Statistical analysis of the survey results and field observation found inadequate sanitation and hygiene facilities, insufficient community toilets, improper waste disposal, and drainage facilities in the city. Sanitation was worse in slum areas than in the non-slum neighborhoods. 55.4% of slum dwellers had no/little awareness of the sanitary system. While 89% of families in slum areas use shared toilets, unhygienic toilets caused different diseases to 63.7% of respondents. Drainage conditions were almost equally insufficient in both groups. 65% of respondents did not have any community toilets in their locality. The sanitation management system is not well-equipped and it is a pressing need to make better plans and implement sufficient management strategy for the total sanitation of the city.
Stochastic multi-fidelity joint hydrogeophysical inversion of consistent geological models
Authors: Neven Alexis , Schorpp Ludovic , Renard Philippe
Published: October 2022

In Quaternary deposits, the characterization of subsurface heterogeneity and its associated uncertainty is critical when dealing with groundwater resource management. The combination of different data types through joint inversion has proven to be an effective way to reduce final model uncertainty. Moreover, it allows the final model to be in agreement with a wider spectrum of data available on site. However, integrating them stochastically through an inversion is very time-consuming and resource expensive, due to the important number of physical simulations needed. The use of multi-fidelity models, by combining low-fidelity inexpensive and less accurate models with high-fidelity expensive and accurate models, allows one to reduce the time needed for inversion to converge. This multiscale logic can be applied for the generation of Quaternary models. Most Quaternary sedimentological models can be considered as geological units (large scale), populated with facies (medium scale), and finally completed by physical parameters (small scale). In this paper, both approaches are combined. A simple and fast time-domain EM 1D geophysical direct problem is used to first constrain a simplified stochastic geologically consistent model, where each stratigraphic unit is considered homogeneous in terms of facies and parameters. The ensemble smoother with multiple data assimilation (ES-MDA) algorithm allows generating an ensemble of plausible subsurface realizations. Fast identification of the large-scale structures is the main point of this step. Once plausible unit models are generated, high-fidelity transient groundwater flow models are incorporated. The low-fidelity models are populated stochastically with heterogeneous facies and their associated parameter distribution. ES-MDA is also used for this task by directly inferring the property values (hydraulic conductivity and resistivity) from the generated model. To preserve consistency, geophysical and hydrogeological data are inverted jointly. This workflow ensures that the models are geologically consistent and are therefore less subject to artifacts due to localized poor-quality data. It is able to robustly estimate the associated uncertainty with the final model. Finally, due to the simplification of both the direct problem and the geology during the low-fidelity part of the inversion, it greatly reduces the time required to converge to an ensemble of complex models while preserving consistency.
A retrospective study of deltoid ligament repair versus syndesmotic fixation in lateral malleolus fracture combined with both deltoid ligament injury and inferior tibiofibular syndesmotic disruption
Authors: Liao Junyi , Zhang Jinsong , Ni Weidong , Luo Gang
Published: October 2022

Background

To compare clinical outcomes of deltoid ligament repair versus syndesmotic fixation in lateral malleolus fracture combined with both deltoid ligament injury and inferior tibiofibular syndesmotic disruption.

Methods

Patients diagnosed with lateral malleolus fracture combined with both deltoid ligament injury and inferior tibiofibular syndesmotic disruption who received open reduction and internal fixation (ORIF) were retrospectively reviewed. Seventy-eight patients were enrolled into the study, including 40 patients treated with lateral malleolus fracture ORIF and trans-syndesmotic fixation, and 38 patients treated with lateral malleolus fracture ORIF and deltoid ligament repair. Basic information and pre- and postoperative radiological materials were reviewed. Visual analog pain scale (VAS) score, Olerud–Molander score, and the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale were used for evaluating pain control and functional recovery postoperatively at different time points.

Results

No complication was reported in both groups. In the trans-syndesmotic fixation group, all patients received syndesmotic screw removal 6–8 weeks postoperatively. The Olerud–Molander score and AOFAS Ankle-Hindfoot Scale in the deltoid ligament repair group were higher than the trans-syndesmotic fixation group 3 months after operation. No statistical difference was found between the two groups in VAS score from 1 to 12 months postoperatively.

Conclusions

Lateral malleolus fracture ORIF and deltoid ligament repair is an effective method for lateral malleolus fracture combined with both deltoid ligament injury and inferior tibiofibular syndesmotic disruption. Compared with trans-syndesmotic fixation, deltoid ligament repair holds the advantage of not needing surgical removal of inferior tibiofibular screws postoperatively.
Experimentally controlled study indicates that the naturally occurring recombinant vaccine-like lumpy skin disease strain Udmurtiya/2019, detected during freezing winter in northern latitudes, is transmitted via indirect contact
Authors: Nesterov Alexander , Mazloum Ali , Byadovskaya Olga , Shumilova Irina , Van Schalkwyk Antoinette , Krotova Alena , Kirpichenko Vladimir , Donnik Irina , Chvala Ilya , Sprygin Alexander
Published: October 2022

Lumpy skin disease (LSD) caused by LSD virus (LSDV), is a member of the poxvirus genus Capripoxvirus. It is classified as a notifiable disease by the World Organization for Animal Health (WOAH) based on its potential for rapid spread and global economic impact. Due to these characteristics, the mode of LSDV transmission has prompted intensive research efforts. Previous experimental studies using the virulent vaccine-derived recombinant LSDV strain Saratov/2017, demonstrated that this strain has the capacity for transmission in a vector-proof environment. This study demonstrated that a second novel recombinant vaccine-derived LSDV strain Udmurtiya/2019, can infect bulls in contact with diseased animals, in the absence of insect vectors. Bulls were housed in an insect proof animal biosafety level 3 facility, where half the animals were inoculated intravenously with the recombinant LSDV (Udmurtiya/2019), whilst the remaining five animals were mock-inoculated but kept in contact with the inoculated group. Both the infected / inoculated group (IN) and uninfected / incontact group (IC), were monitored for 41 days with continuous registration of body temperature, observations for clinical signs and collection of blood samples and nasal swabs for testing of LSDV presence using real-time PCR. Results indicated that cohabitation of animals from both groups was sufficient to transmit the virus from the IN to the IC-group, with the onset of clinical signs including pyrexia (~41°C) and classical LSD nodular skin lesions starting at 10 dpi for the IN group and 16 dpi for the IC-group. Additionally, the presence of LSDV genomes as well as anti-LSDV antibodies were detected in swabs, blood and serum samples from animals belonging to both groups. These results provides additional evidence of LSDV transmission in a controlled environment without direct contact between diseased and healthy animals, yet in the absence of vectors. Based on these observations, the question concerning a hypothetical relation between mutations in the virus genome and its mode of transmission gains more importance and requires additional investigations with direct comparisons between classical and novel recombinant LSDV strains.
Natural product, bilobalide, improves joint health in rabbits with osteoarthritis by anti-matrix degradation and antioxidant activities
Authors: Ma Tianwen , Chen Hong , Ruan Hongri , Lv Liangyu , Yu Yue , Jia Lina , Zhao Jinghua , Li Xin , Zang Yuxin , Xu Xinyu , Zhang Jiantao , Gao Li
Published: October 2022

Osteoarthritis (OA) is a common chronic musculoskeletal disease reported in veterinary clinics that severely reduces the quality of life of animals. The natural product, bilobalide, has positive effects on chondroprotection but its exact mechanism of action is unclear. This study aimed to investigate the antioxidant and anti-matrix degradation activities of bilobalide in a rabbit model of OA and its protective effects on joints. We also investigated the possible mechanisms underlying these effects. The rabbit OA model was established by intra-articular injection of 4% papain. Thirty healthy male New Zealand rabbits were randomly divided into control, untreated OA, Cel (100 mg/kg celecoxib intervention as a positive control), BB-L and BB-H (40 mg /kg and 80 mg /kg bilobalide gavage treatment, respectively) groups. Two weeks after surgical induction, bilobalide or celecoxib was administered by gavage daily for 8 weeks. After 8 weeks of bilobalide intervention, cartilage macroscopic observation and histopathological images showed alleviation of cartilage damage after bilobalide treatment, and the Osteoarthritis Research Society International (OARSI) score was significantly lower than that in the OA group. Bilobalide reduced the expression of metalloproteinase 3 (MMP-3) and MMP-13 in cartilage tissue of OA rabbits and reversed the levels of serum C-telopeptides of type II collagen (CTX-II), cartilage oligomeric matrix protein (COMP), interleukin 1(IL-1), and tumor necrosis factor (TNF-α). Bilobalide (80 mg/kg) could improve the biomechanical properties and microstructural changes in subchondral bone in the early stage of OA in rabbits, thereby delaying subchondral bone damage. Mechanistically, bilobalide exerted antioxidant and anti-matrix degradation effects by upregulating the oxidative stress signaling Nrf2/HO-1 pathway and inhibiting cartilage degeneration in rabbit OA. We thus speculate that bilobalide supplements recovery from OA damage.
Effects of dietary Hyssop, Hyssopus officinalis, extract on physiological and antioxidant responses of rainbow trout, Oncorhynchus mykiss, juveniles to thermal stress
Authors: Yousefi Morteza , Hoseini Seyyed Morteza , Kulikov Evgeny Vladimirovich , Seleznev Sergey Borisovich , Petrov Aleksandr Konstantinovich , Babichev Nikolay Valerievich , Kochneva Margarita Vasilyevna , Davies Simon John
Published: October 2022

The present study aimed at assessing the effects of dietary Hyssop, Hyssopus officinalis, extract on rainbow trout, Oncorhynchus mykiss, responses to thermal stress. The juveniles (69.8 ± 0.38 g) were stocked in 12 through-flow tanks at a density of 12 fish per tank. Methanolic extract of Hyssop (HME) was added to diet at 0, 100, 250, and 500 mg/kg and the fish were fed (3% of biomass) over a 70-d period: 62 d at 13.3 ± 0.08°C and 7 d at 21–22°C. At the end of the trial, the plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), triiodothyronine (T3), thyroxin (T4), cortisol, glucose, lactate, total antioxidant capacity (TAC), ascorbate, and the gill glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), and malondialdehyde (MDA). The results showed that HME had no significant effects on fish growth performance, survival, and feed efficiency. Dietary 250 mg/kg HME significantly decreased plasma ALT activity (P < 0.001), but showed no significant effects on plasma AST) (P = 0.106) activity, T3 (P = 0.992), and T4 (P = 0.070) levels. Thermal stress significantly (P < 0.001) increased plasma ALT and AST activities, but lowered plasma T3 and T4 levels. Dietary HME and thermal stress had interaction effects on plasma cortisol (P < 0.001), glucose (P = 0.007), lactate (P = 0.010), LDH (P = 0.005), TAC (P = 0.038), ascorbate (P < 0.001), and the gill GPx (P = 0.001), GR (P < 0.001), GST (P < 0.001), and MDA (P = 0.001). Thermal stress significantly increased plasma cortisol, glucose, lactate, and LDH, the gill GPX, GR, and GST, but dietary HME supplementation significantly reduced such elevations, particularly at 250 mg/kg level. Dietary HME significantly increased plasma TAC before the thermal stress and mitigated the stress-induced decreased in TAC, particularly at 250 mg/kg level. Dietary HME significantly decreased the gill MDA before and after the thermal stress, and lowest MDA was observed in 250 mg/kg HME level. Based on the present results, 250 mg/kg HME is recommended as suitable dose to improve antioxidative responses and hepatoprotection in rainbow trout under heat stress.
Lyso-DGTS Lipid Derivatives Enhance PON1 Activities and Prevent Oxidation of LDL: A Structure–Activity Relationship Study
Authors: Khattib Ali , Musa Sanaa , Halabi Majdi , Hayek Tony , Khatib Soliman
Published: October 2022

Paraoxonase 1 (PON1) plays a role in regulating reverse cholesterol transport and has antioxidative, anti-inflammatory, antiapoptotic, vasodilative, and antithrombotic activities. Scientists are currently focused on the modulation of PON1 expression using different pharmacological, nutritional, and lifestyle approaches. We previously isolated a novel active compound from Nannochloropsis microalgae—lyso-diacylglyceryltrimethylhomoserine (lyso-DGTS)—which increased PON1 activity, HDL-cholesterol efflux, and endothelial nitric oxide release. Here, to explore this important lipid moiety’s effect on PON1 activities, we examined the effect of synthesized lipid derivatives and endogenous analogs of lyso-DGTS on PON1 lactonase and arylesterase activities and LDL oxidation using structure–activity relationship (SAR) methods. Six lipids significantly elevated recombinant PON1 (rePON1) lactonase activity in a dose-dependent manner, and four lipids significantly increased rePON1 arylesterase activity. Using tryptophan fluorescence-quenching assay and a molecular docking method, lipid–PON1 interactions were characterized. An inverse correlation was obtained between the lactonase activity of PON1 and the docking energy of the lipid–PON1 complex. Furthermore, five of the lipids increased the LDL oxidation lag time and inhibited its propagation. Our findings suggest a beneficial effect of lyso-DGTS or lyso-DGTS derivatives through increased PON1 activity and prevention of LDL oxidation.
Prevention of Testicular Damage by Indole Derivative MMINA via Upregulated StAR and CatSper Channels with Coincident Suppression of Oxidative Stress and Inflammation: In Silico and In Vivo Validation
Authors: Afsar Tayyaba , Razak Suhail , Trembley Janeen H. , Khan Khushbukhat , Shabbir Maria , Almajwal Ali , Alruwaili Nawaf W. , Ijaz Muhammad Umar
Published: October 2022

Cis-diamminedichloroplatinum (II) (CDDP) is a widely used antineoplastic agent with numerous associated side effects. We investigated the mechanisms of action of the indole derivative N’-(4-dimethylaminobenzylidene)-2-1-(4-(methylsulfinyl) benzylidene)-5-fluoro-2-methyl-1H-inden-3-yl) acetohydrazide (MMINA) to protect against CDDP-induced testicular damage. Five groups of rats (n = 7) were treated with saline, DMSO, CDDP, CDDP + MMINA, or MMINA. Reproductive hormones, antioxidant enzyme activity, histopathology, daily sperm production, and oxidative stress markers were examined. Western blot analysis was performed to access the expression of steroidogenic acute regulatory protein (StAR) and inflammatory biomarker expression in testis, while expression of calcium-dependent cation channel of sperm (CatSper) in epididymis was examined. The structural and dynamic molecular docking behavior of MMINA was analyzed using bioinformatics tools. The construction of molecular interactions was performed through KEGG, DAVID, and STRING databases. MMINA treatment reversed CDDP-induced nitric oxide (NO) and malondialdehyde (MDA) augmentation, while boosting the activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD) in the epididymis and testicular tissues. CDDP treatment significantly lowered sperm count, sperm motility, and epididymis sperm count. Furthermore, CDDP reduced epithelial height and tubular diameter and increased luminal diameter with impaired spermatogenesis. MMINA rescued testicular damage caused by CDDP. MMINA rescued CDDP-induced reproductive dysfunctions by upregulating the expression of the CatSper protein, which plays an essential role in sperm motility, MMINA increased testosterone secretion and StAR protein expression. MMINA downregulated the expression of NF-κB, STAT-3, COX-2, and TNF-α. Hydrogen bonding and hydrophobic interactions were predicted between MMINA and 3β-HSD, CatSper, NF-κβ, and TNFα. Molecular interactome outcomes depicted the formation of one hydrogen bond and one hydrophobic interaction between 3β-HSD that contributed to its strong binding with MMINA. CatSper also made one hydrophobic interaction and one hydrogen bond with MMINA but with a lower binding affinity of -7.7 relative to 3β-HSD, whereas MMINA made one hydrogen bond with NF-κβ residue Lys37 and TNF-α reside His91 and two hydrogen bonds with Lys244 and Thr456 of STAT3. Our experimental and in silico results revealed that MMINA boosted the antioxidant defense mechanism, restored the levels of fertility hormones, and suppressed histomorphological alterations.
Detection of Hepatitis E Virus (HEV) in Pigs and in the Wild Boar (Sus scrofa) Population of Chieti Province, Abruzzo Region, Italy
Authors: De Massis Fabrizio , Aprea Giuseppe , Scattolini Silvia , D’Angelantonio Daniela , Chiaverini Alexandra , Mangone Iolanda , Perilli Margherita , Colacicco Giulia , Olivieri Sabrina , Pomilio Francesco , Di Pasquale Adriano , Migliorati Giacomo , Di Paolo Giovanni , Morgani Chiara , Giammarino Angelo
Published: October 2022

Hepatitis E virus (HEV) is a zoonotic pathogen, causing infectious hepatitis in man. Pigs and wild boars are the natural asymptomatic reservoirs, while the disease in humans could be either asymptomatic or evolve in hepatitis. In Europe, an increasing number of human infections from HEV have been reported over the last few years. The main route of transmission is through contaminated food, by direct or indirect consumption of raw or undercooked pork and wild boar meat and meat products. Up to now, HEV prevalence in Italian northern regions has been extensively determined in wild boars and pigs, while less data have been collected from the southern ones. There is a need to report more data about HEV prevalence from wild boars and pigs in southern Italy in consideration of the potential risk posed by some specific traditional food products manufactured in these areas and produced from pig and wild boar livers (e.g., sausages and salami). The aim of this study was to demonstrate the circulation of the Hepatitis E virus (HEV) in pigs and in the wild boar population of the province of Chieti, Abruzzo Region, Central Italy. Moreover, potential HEV seroprevalence in hunters from that area was also assessed. The overall prevalence of HEV RNA in wild boars was 9.5% (CI 5.4–16.2%), but no HEV RNA was detected in samples from pigs.
Source Apportionment of Heavy Metals in Wet Deposition in a Typical Industry City Based on Multiple Models
Authors: Zhang Haixia , Zhao Zefei , Cai Angzu , Liu Bo , Wang Xia , Li Rui , Wang Qing , Zhao Hui
Published: October 2022

Handan city as a transportation hub in North China, air quality ranks at the bottom all year round, causing environmental pollution that has aroused widespread concern. In order to explore the pollution characteristics and main sources of heavy metals in atmospheric wet deposition in the city, and comparison of the applicability of multiple traceability models, a total of 76 wet deposition samples were collected in the three functional areas from December 2017 to November 2019 by a dry and wet deposition automatic sampler. Concentrations of Cu, Zn, Cr, Ni, Pb, and As were determined and enrichment factors were calculated. Sources of these heavy metals were apportioned by PMF, Unmix, and APCS-MLR models, and analyzed using a backward trajectory analysis model. The results showed that the concentrations of these heavy metals in the atmospheric wet deposition were in order of Zn, Cr, Pb, Cu, Ni, and As, and their mean concentrations were 29.53, 14.11, 9.18, 7.03, 6.41, and 1.21 μg·L−1, respectively. According to the results of EF, the studied heavy metals were mainly affected by anthropogenic activities. The source apportionment results showed that heavy metal pollution in the wet deposition was mainly affected by traffic sources, industrial sources, and coal combustion sources, and PMF identified an additional source factor: metal smelting source. By comparing the relevant parameters of the source apportionment results of the three models, the APCS-MLR model has better accuracy results than PMF and Unmix models. The analysis of the backward trajectory of the air mass showed that the wet deposition of Handan in the study time was mainly from the southwest direction, accounting for 54.35%. In the future, more evaluation methods and models will be used to compare and analyze the different application scenarios and parameter selection requirements in order to contribute to urban atmospheric environmental pollution prevention and control work.
Airborne Bacteria in Gliwice—The Industrialized City in Poland
Authors: Kowalski Michał , Pastuszka Jozef S. , Brąszewska Agnieszka , Cyrys Josef , Brągoszewska Ewa
Published: October 2022

The results of the study on the characteristics of the viable (culturable) and total bacterial particles in the ambient air in Gliwice, Poland, are presented. The concentration of viable bacteria in the air ranged from 57 CFU m−3 (Colony Forming Units per cubic meter) during winter to 305 CFU m−3 in spring, while the concentration of all bacteria (live and dead) in the air, measured in selected days, ranged from 298 cells m−3 in winter to over 25 thousand per m3 in autumn. A field study was also carried out to find out the level of the sterilization rate (k) for airborne bacteria. The obtained value of k for viable bacteria exposed to UV solar radiation in Gliwice was approximately 10 cm2 W−1s−1. The patterns of the size distributions of viable bacteria found in three seasons, spring, summer, and autumn, were similar, showing a peak in the range of 3.3–4.7 µm. In the winter season, the main peak was shifted into the smaller particles with an aerodynamic diameter ranging from 2.1 to 4.7 µm. The dominant group of culturable bacteria within the studied period was Gram-positive rods-forming endospores (34–55%), while the least frequent were Gram-negative rods (2%). This research can be used to assess the health effects of exposure to bacterial aerosols in people living in this area.
Cervical Net: A Novel Cervical Cancer Classification Using Feature Fusion
Authors: Alquran Hiam , Alsalatie Mohammed , Mustafa Wan Azani , Abdi Rabah Al , Ismail Ahmad Rasdan
Published: October 2022

Cervical cancer, a common chronic disease, is one of the most prevalent and curable cancers among women. Pap smear images are a popular technique for screening cervical cancer. This study proposes a computer-aided diagnosis for cervical cancer utilizing the novel Cervical Net deep learning (DL) structures and feature fusion with Shuffle Net structural features. Image acquisition and enhancement, feature extraction and selection, as well as classification are the main steps in our cervical cancer screening system. Automated features are extracted using pre-trained convolutional neural networks (CNN) fused with a novel Cervical Net structure in which 544 resultant features are obtained. To minimize dimensionality and select the most important features, principal component analysis (PCA) is used as well as canonical correlation analysis (CCA) to obtain the best discriminant features for five classes of Pap smear images. Here, five different machine learning (ML) algorithms are fed into these features. The proposed strategy achieved the best accuracy ever obtained using a support vector machine (SVM), in which fused features between Cervical Net and Shuffle Net is 99.1% for all classes.
Enhanced Effects of Iron on Mycelial Growth, Metabolism and In Vitro Antioxidant Activity of Polysaccharides from Lentinula edodes
Authors: Xiang Quanju , Zhang Huijuan , Chen Xiaoqian , Hou Shiyao , Gu Yunfu , Yu Xiumei , Zhao Ke , Zhang Xiaoping , Ma Menggen , Chen Qiang , Petri Penttinen , Chen Xiaoqiong
Published: October 2022

The polysaccharides found in Lentinula edodes have a variety of medicinal properties, such as anti-tumor and anti-viral effects, but their content in L. edodes sporophores is very low. In this study, Fe2+ was added to the liquid fermentation medium of L. edodes to analyze its effects on mycelial growth, polysaccharide and enzyme production, gene expression, and the activities of enzymes involved in polysaccharide biosynthesis, and in vitro antioxidation of polysaccharides. The results showed that when 200 mg/L of Fe2+ was added, with 7 days of shaking at 150 rpm and 3 days of static culture, the biomass reached its highest value (0.28 mg/50 mL) 50 days after the addition of Fe2+. Besides, Fe2+ addition also enhanced intracellular polysaccharide (IPS) and exopolysaccharide (EPS) productions, the levels of which were 2.98- and 1.79-fold higher than the control. The activities of the enzymes involved in polysaccharides biosynthesis, including phosphoglucomutase (PGM), phosphoglucose isomerase (PGI), and UDPG-pyrophosphorylase (UGP) were also increased under Fe2+ addition. Maximum PGI activity reached 1525.20 U/mg 30 days after Fe2+ addition, whereas PGM and UGP activities reached 3607.05 U/mg and 3823.27 U/mg 60 days after Fe2+ addition, respectively. The Pearson correlation coefficient showed a strong correlation (p < 0.01) between IPS production and PGM and UGP activities. The corresponding coding genes of the three enzymes were also upregulated. When evaluating the in vitro antioxidant activities of polysaccharides, EPS from all Fe2+-treated cultures exhibited significantly better capacity (p < 0.05) for scavenging -OH radicals. The results of the two-way ANOVA indicated that the abilities of polysaccharides to scavenge O2− radicals were significantly (p < 0.01) affected by Fe2+ concentration and incubation time. These results indicated that the addition of iron provided a good way to achieve desirable biomass, polysaccharide production, and the in vitro antioxidation of polysaccharides from L. edodes.
Flavor Profile Analysis of Instant and Traditional Lanzhou Beef Bouillons Using HS-SPME-GC/MS, Electronic Nose and Electronic Tongue
Authors: Zhang Zheqi , Jiang Jiaolong , Zang Mingwu , Zhang Kaihua , Li Dan , Li Xiaoman
Published: October 2022

The volatile profiles and taste properties of Lanzhou beef bouillons prepared with traditional (A1–A8) and modern (B1, B2) processing methods were evaluated. A total of 133 volatiles were identified: olefins, aldehydes and alcohols from spices in traditional bouillons were significantly higher (p < 0.05) than those in instant bouillons. The characteristic volatile substances in traditional beef bouillons were eucalyptol, linalool, 2-decanone, β-caryophyllene and geraniol; instant bouillons lacked 2-decanone and β-caryophyllene, and the contents of the other three substances were low. PCA (principal component analysis) and CA (clustering analysis) showed that the instant bouillons have a similar volatile profile to traditional bouillons, and the results of E-nose and sensory evaluation also supported this conclusion. The E-tongue showed that the taste profiles of instant bouillons were significantly different from those of traditional bouillons, mainly due to lack of umami; however, sensory evaluation revealed that taste differences were not perceptible.
Non-Insulin Novel Antidiabetic Drugs Mechanisms in the Pathogenesis of COVID-19
Authors: Salmen Teodor , Pietroșel Valeria-Anca , Mihai Bianca-Margareta , Bica Ioana Cristina , Teodorescu Claudiu , Păunescu Horia , Coman Oana Andreia , Mihai Doina-Andrada , Pantea Stoian Anca
Published: October 2022

The present study aimed to analyse the published data and to realize an update about the use and pathogenesis of the novel antidiabetic drugs, respectively, dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1 Ra), and sodium-glucose co-transporter-2 inhibitors (SGLT-2i), in patients with type 2 diabetes mellitus (T2DM) and coronavirus disease (COVID-19). Literature research in the PubMed and Web of Science database was performed in order to identify relevant published clinical trials and meta-analyses that include information about the treatment with novel antidiabetic agents in patients with T2DM and COVID-19. A total of seven articles were included, and their primary and secondary outcomes were reported and analysed. DPP-4i has mixed results on mortality in T2DM patients with COVID-19 but with an overall slightly favourable or neutral effect, whereas GLP-1 Ra seems to have a rather beneficial impact, while SGLT-2i may be useful in acute illness. Even if there are limited data, they seem to have favourable efficacy and safety profiles. The available evidence is heterogenous and insufficient to evaluate if the benefits of non-insulin novel antidiabetic drugs in COVID-19 treatment are due to the improvement of glycaemic control or to their intrinsic anti-inflammatory effects but highlights their beneficial effects in the pathogenesis and evolution of the disease.
Inhibition of TRIF-Dependent Inflammation Decelerates Afterload-Induced Myocardial Remodeling
Authors: Bettink Stephanie I. , Reil Jan-Christian , Kazakov Andrey , Körbel Christina , Millenaar Dominic , Laufs Ulrich , Scheller Bruno , Böhm Michael , Schirmer Stephan H.
Published: October 2022

Pressure-overload-induced cardiac hypertrophy represents one cause of the development of heart failure. The aim of this study is to characterize the influence of the TIR-domain-containing adapter-inducing interferon-β (TRIF) during afterload-induced myocardial remodeling. After trans-aortic constriction (TAC), cardiac pressure overload leads to an early increase in MyD88- (Myeloid differentiation primary response gene 88) and TRIF-dependent cytokines. The maximum cytokine expression appeared within the first week and decreased to its control level within five weeks. While cardiomyocyte hypertrophy was comparable, the myocardial accumulation of the inflammatory cells was lower in TRIF−/−mice. At d7, TRIF deficiency reduced transcription factors and TRIF-dependent cytokines. Through the modulation of the TGF-β-signaling pathway and anti-fibrotic microRNAs, TRIF was involved in the development of interstitial fibrosis. The absence of TRIF was associated with a decreased expression of proapoptotic proteins. In echocardiography and working heart analyses, TRIF deficiency slowed left-ventricular wall thickening, myocardial hypertrophy, and reduces the ejection fraction. In summary, TRIF is an important adapter protein for the release of inflammatory cytokines and the accumulation of inflammatory cells in the early stage of maladaptive cardiac remodeling. TRIF is involved in the development of cardiac fibrosis by modulating inflammatory and fibrotic signal transduction pathways.
Hepatocellular Carcinoma Recurrence and Mortality Rate Post Liver Transplantation: Meta-Analysis and Systematic Review of Real-World Evidence
Authors: Bzeizi Khalid I. , Abdullah Maheeba , Vidyasagar Kota , Alqahthani Saleh A. , Broering Dieter
Published: October 2022

Background: liver transplantation (LT) is the best curative option for eligible patients with hepatocellular carcinoma (HCC), however recurrence remains a major concern. This meta-analysis aimed to investigate the prevalence and risk factors of HCC recurrence. Methods: studies were selected using PubMed, Epistemonikas, and Google Scholar databases published from inception to 15 May 2022 and a meta-analysis of the proportions was conducted. Observational studies reporting the prevalence of recurrent HCC after an LT were included, with the analysis being stratified by an adherence to the Milan criteria (MC), geographical region, AFP levels, and donor type. Results: out of 4081 articles, 125 were included in the study. The prevalence of recurrent HCC was 17% (CI: 15–19). Patients beyond the MC were more likely to recur than patients within the MC. Asian populations had the greatest prevalence of HCC recurrence (21%; CI: 18–24), whereas North American populations had the lowest recurrence (10%; CI: 7–12). The mortality rate after HCC recurrence was 9%; CI: 8–11. North American populations had the greatest prevalence of mortality with 11% (CI: 5–17). Conclusions: the recurrence, overall survival, and mortality rates among patients with HCC post-LT remains high, with substantial differences between regions.
Resistance to Trastuzumab
Authors: Vivekanandhan Sneha , Knutson Keith L.
Published: October 2022

One of the most impactful biologics for the treatment of breast cancer is the humanized monoclonal antibody, trastuzumab, which specifically recognizes the HER2/neu (HER2) protein encoded by the ERBB2 gene. Useful for both advanced and early breast cancers, trastuzumab has multiple mechanisms of action. Classical mechanisms attributed to trastuzumab action include cell cycle arrest, induction of apoptosis, and antibody-dependent cell-mediated cytotoxicity (ADCC). Recent studies have identified the role of the adaptive immune system in the clinical actions of trastuzumab. Despite the multiple mechanisms of action, many patients demonstrate resistance, primary or adaptive. Newly identified molecular and cellular mechanisms of trastuzumab resistance include induction of immune suppression, vascular mimicry, generation of breast cancer stem cells, deregulation of long non-coding RNAs, and metabolic escape. These newly identified mechanisms of resistance are discussed in detail in this review, particularly considering how they may lead to the development of well-rationalized, patient-tailored combinations that improve patient survival.
Links between Breast and Thyroid Cancer: Hormones, Genetic Susceptibility and Medical Interventions
Authors: Lu Man , Liu Hanqing , Zheng Bilian , Sun Shengrong , Chen Chuang
Published: October 2022

Breast and thyroid glands are two common sites of female malignancies. Since the late 19th century, physicians have found that the cancers in either thyroid or mammary gland might increase the risk of second primary cancers in the other site. From then on, many observational clinical studies have confirmed the hypothesis and more than one theory has been developed to explain the phenomenon. Since the two glands both have secretory functions and are regulated by the hypothalamic–pituitary axis, they may share some common oncogenic molecular pathways. However, other risks factors, including medical interventions and hormones, are also observed to play a role. This article aims to provide a comprehensive review of the associations between the two cancers. The putative mechanisms, such as hormone alteration, autoimmune attack, genetic predisposition and other life-related factors are reviewed and discussed. Medical interventions, such as chemotherapy and radiotherapy, can also increase the risk of second primary cancers. This review will provide novel insights into the research designs, clinical managements and treatments of thyroid and breast cancer patients.
The Mechanistic Roles of Sirtuins in Breast and Prostate Cancer
Authors: Onyiba Cosmos Ifeanyi , Scarlett Christopher J. , Weidenhofer Judith
Published: October 2022

Mammalian sirtuins (SIRT1–7) are involved in a myriad of cellular processes, including apoptosis, proliferation, differentiation, epithelial-mesenchymal transition, aging, DNA repair, senescence, viability, survival, and stress response. In this review, we discuss the current information on the mechanistic roles of SIRT1–7 and their downstream effects (tumor promotion or suppression) in cancers of the breast and prostate. Specifically, we highlight the involvement of sirtuins in the regulation of various proteins implicated in proliferation, apoptosis, autophagy, chemoresistance, invasion, migration, and metastasis of breast and prostate cancer. Additionally, we highlight the available information regarding SIRT1–7 regulation by miRNAs, laying much emphasis on the consequences in the progression of breast and prostate cancer.
Enhanced Epithelial-to-Mesenchymal Transition and Chemoresistance in Advanced Retinoblastoma Tumors Is Driven by miR-181a
Authors: Suresh Babu Vishnu , Bisht Anadi , Mallipatna Ashwin , SA Deepak , Dudeja Gagan , Kannan Ramaraj , Shetty Rohit , Guha Nilanjan , Heymans Stephane , Ghosh Arkasubhra
Published: October 2022

Advanced retinoblastoma (Rb) tumors display high metastatic spread to distant tissues, causing a potent threat to vision and life. Through transcriptomic profiling, we discovered key upregulated genes that belonged to the epithelial–mesenchymal transition (EMT) and chemotherapy resistance pathways in advanced Rb tumors. Through in vitro models, we further showed that Rb null tumor cells under prolonged chemo drug exposure, acquires a metastasis-like phenotype through the EMT program mediated by ZEB1 and SNAI2 and these cells further acquires chemotherapeutic resistance through cathepsin-L- and MDR1-mediated drug efflux mechanisms. Using a miRNA microarray, we identified miR-181a-5p as being significantly reduced in advanced Rb tumors, which was associated with an altered EMT and drug-resistance genes. We showed that enhancing miR-181a-5p levels in Rb null chemo-resistant sublines reduced the ZEB1 and SNAI2 levels and halted the mesenchymal transition switch, further reducing the drug resistance. We thus identified miR-181a-5p as a therapeutically exploitable target for EMT-triggered drug-resistant cancers that halted their invasion and migration and sensitized them to low-dose chemotherapy drugs.
TRAIL in the Treatment of Cancer: From Soluble Cytokine to Nanosystems
Authors: Alizadeh Zeinabad Hojjat , Szegezdi Eva
Published: October 2022

The death ligand tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF cytokine superfamily, has long been recognized for its potential as a cancer therapeutic due to its low toxicity against normal cells. However, its translation into a therapeutic molecule has not been successful to date, due to its short in vivo half-life associated with insufficient tumor accumulation and resistance of tumor cells to TRAIL-induced killing. Nanotechnology has the capacity to offer solutions to these limitations. This review provides a perspective and a critical assessment of the most promising approaches to realize TRAIL’s potential as an anticancer therapeutic, including the development of fusion constructs, encapsulation, nanoparticle functionalization and tumor-targeting, and discusses the current challenges and future perspectives.
The Vitamin D Receptor–BIM Axis Overcomes Cisplatin Resistance in Head and Neck Cancer
Authors: Khamis Aya , Gül Désirée , Wandrey Madita , Lu Qiang , Knauer Shirley K. , Reinhardt Christoph , Strieth Sebastian , Hagemann Jan , Stauber Roland H.
Published: October 2022

Treatment success of head and neck squamous cell carcinoma (HNSCC) is often hindered by cisplatin resistance. As inherent and acquired therapy resistance counteracts improvement in long-term survival, novel multi-targeting strategies triggering cancer cell apoptosis are urgently required. Here, we identify the vitamin D receptor (VDR) as being significantly overexpressed in tumors of HNSCC patients (n = 604; p = 0.0059), correlating with tumor differentiation (p = 0.0002), HPV status (p = 0.00026), and perineural invasion (p = 0.0087). The VDR, a member of the nuclear receptor superfamily, is activated by its ligand vitamin D (VitD) and analogs, triggering multiple cellular responses. As we found that the VDR was also upregulated in our cisplatin-resistant HNSCC models, we investigated its effect on overcoming cisplatin resistance. We discovered that VitD/cisplatin combinations synergistically killed even cisplatin-resistant cells at clinically achievable levels. Similar results were obtained for the clinically used VitD analog Maxacalcitol. Moreover, VitD/cisplatin combinations inhibited tumor cell migration by E-cadherin upregulation. Signaling pathway analyses revealed that VitD co-treatments triggered cancer cell death by increasing the expression of the pro-apoptotic BCL-2 family protein BIM. BIM’s pro-apoptotic activity in HNSCC cells was confirmed by ectopic overexpression studies. Importantly, BIM expression is positively associated with HNSCC patients’ (n = 539) prognosis, as high expression correlated with improved survival (p = 0.0111), improved therapy response (p = 0.0026), and remission (p = 0.004). Collectively, by identifying, for the first time, the VDR/BIM axis, we here provide a molecular rationale for the reported anti-cancer activity of VitD/analogs in combination therapies. Our data also suggest its exploitation as a potential strategy to overcome cisplatin resistance in HNSCC and other malignancies by inducing additional pro-apoptotic pathways.
Anti-Hormonal Therapy in Breast Cancer and Its Effect on the Blood-Brain Barrier
Authors: Curtaz Carolin J. , Kiesel Ludwig , Meybohm Patrick , Wöckel Achim , Burek Malgorzata
Published: October 2022

The molecular receptor status of breast cancer has implications for prognosis and long-term metastasis. Although metastatic luminal B-like, hormone-receptor-positive, HER2−negative, breast cancer causes brain metastases less frequently than other subtypes, though tumor metastases in the brain are increasingly being detected of this patient group. Despite the many years of tried and tested use of a wide variety of anti-hormonal therapeutic agents, there is insufficient data on their intracerebral effectiveness and their ability to cross the blood-brain barrier. In this review, we therefore summarize the current state of knowledge on anti-hormonal therapy and its intracerebral impact and effects on the blood-brain barrier in breast cancer.
Utilization of Spent Sorbent in the Production of Ceramic Bricks
Authors: Daumova Gulzhan , Seraya Natalya , Azbanbayev Eldar , Assanov Daulet , Aubakirova Roza , Reutova Galina
Published: October 2022

The composition and technology for the production of semi-dry ceramic bricks using a nanostructured complex sorbent based on bentonite clay of the 11th horizon of the Tagan deposit of the Republic of Kazakhstan and basalt fiber (gabbro-diabase) of the Karauzek deposit of East Kazakhstan have been developed. The characteristics, chemical composition, and structure of the spent sorbent are given based on electron microscopic and X-ray phase analyses. A number of physical and mechanical parameters have been studied to evaluate the spent sorbent as a raw material for the production of ceramic products. The microstructures of fired ceramic samples with loam and spent sorbent have been studied, and the features of their structure have been revealed. The environmental safety of waste sorbents utilization by extraction in acidic, alkaline, and neutral media with the determination of the content of chromium, zinc, and iron ions has been studied. Experimentally obtained data indicate an insignificant concentration of chromium and zinc ions, not exceeding 3.5 µg/L. Relatively high concentrations of iron ions in ceramic bricks are associated with their high content in the feedstock and in the spent sorbent. It has been established that the introduction of the spent sorbent in the amount of 25% of the total mass increases the strength of the final product from 10.8 to 15.8 MPa, which corresponds to the M125 ceramic brick grade.