bluuebunny/crossref_metadata_2025 huggingface dataset:
Opracowanie anatomo-antropologiczne szczątków kostnych
Authors: Szostek Krzysztof , Lisowska-Gaczorek Aleksandra , Nowakowska Patrycja
Published: February 2021

Subjected to anthropological analysis were bone remains recovered from the archaeological site of Żelazna Nowa in 2007, 2008, 2015, and 2017. In addition, three burial urns complete with their contents were submitted to laboratory analysis (features 33, 37, and 39). The anthropological analysis sought to determine the number of individuals buried in a grave, the sex of the deceased and their age at death, to identify animal bones occurring in graves, pathological changes and traces of ornaments discernible on bones, and to determine the degree of burning of the skeletal material. The assessment of sex and age proved in most cases impossible due to poor preservation of the bones and their deformation stemming from exposure to high temperatures. The results obtained for those graves from Żelazna Nowa for which analysis was possible are presented in Table 7.2. Remains of 35 individuals were identified in 30 features. This is the total minimum number of determinable individuals. Among these 35 individuals are 25 adults (including 2 representing age class Adultus/Maturus and 1 Senilis), 1 individual from age class Iuvenis, and 3 children (including one Infans I and two Infans II). Animal bones were identified in 6 graves.
Zwierzęce szczątki kostne
Authors: Piątkowska-Małecka Joanna
Published: February 2021

Animal bone remains retrieved from six cremation graves and from layers in the immediate vicinity of damaged graves were subjected to archaeozoological analysis. There were 32 animal bone fragments in total, of which 23 could be identified with high probability in terms of species and anatomy. The remaining bones represent two types. The first, more common type is comprised of bone fragments showing no traces of processing, possibly consumption waste. The second type is that of fragments of damaged artefacts made from osseous material, bearing discernible traces of processing. Among the analysed materials, five fragments revealed traces of processing – two were fragments of combs, another two most likely belonged to one damaged gaming piece (dice), and the last was a small fragment of a polished plate. All these objects were made of deer antler. The remaining, unworked fragments identified in terms of species, which were consumption waste, belonged exclusively to domesticated mammals and birds: sheep, goat, pig, cattle, horse, and hen. They were found in six out of approximately 65 graves recorded in the explored part of the necropolis, which means in 9.2% of the graves. Animal bone remains are interpreted in many ways, could have been the traces of feasts held during the funeral ceremony. The remains could have provided food for the dead on their way to the afterlife or could have been related to some acts of sacrifice.
Metabolic profile and sex hormone binding globulin (SHBG) in different reproductive phases of Czech women and their relations to weight, body composition and fat distribution
Authors: Kosková I , Petrásek R , Vondra K , Dušková M , Stárka L
Published: February 2021

In our study, 213 healthy Czech women aged 20 to 65 years
were examined and divided into fully reproductive,
premenopausal, menopausal and postmenopausal groups. In all
subjects body composition was determined by classical
anthropometry and metabolic profile was assessed. A total of 146
subjects completed 3-year longitudinal study. Total and LDL
cholesterol increased and ratio HDL/total cholesterol decreased
with age (p<0.001), most significantly in menopause.
Triacylglycerols increased only up to menopause. HDL had a very
slight trend to decrease in menopause and postmenopause.
Fasting blood glucose level increased progressively (p<0.001), in
postmenopause frequently exceeded normal range. Higher BMI,
total fat mass and central fat indices were associated with higher
total and LDL cholesterol, triacylglycerols, C-peptide, insulin and
fasting blood glucose level (p<0.001; fasting blood glucose level
to waist-to-hip ratio: p<0.01) and lower HDL cholesterol
(p<0.001). Higher C-peptide and insulin were associated with
lower HDL cholesterol and higher triacylglycerols (p<0.001).
Fasting glucose correlated with LDL cholesterol (p<0.01). Higher
SHBG was associated with higher HDL and lower LDL cholesterol
(p<0.001). Hormone replacement treatment was related to lower
fasting blood glucose level in postmenopausal women (p<0.01).
Oral contraception is suggestive of a positive influence on lipid
spectrum by increasing the ratio HDL/total cholesterol. Markers
of lipid and carbohydrate metabolism are not only age-related,
but they are also related to BMI, total fat mass and central fat
indices. Therefore, preventive programs should be focused above
all on menopausal women.
The Covid19 Pandemic and the Emergent Need for Quarantine Medicine.
Authors: Tin Derrick , Hart Alexander , Ciottone Gregory
Published: February 2021

The scale of the Covid19 pandemic has changed the landscape of healthcare services around the world. Quarantine is one of many non- pharmaceutical interventions historically used in managing pandemics but there is currently no global medical consensus on the best format, with most countries employing a continuously reviewed system to determine needs.
NORMAL DOĞUMDA ÖĞRENCİ HEMŞİRE TARAFINDAN VERİLEN DESTEKLEYİCİ BAKIM İLE RUTIN BAKIMIN DOĞUM KONFORUNA ETKİSİNİN KARŞILAŞTIRILMASI
Authors: GÜN Çiğdem , GEZGİÇ Merve , DİNÇER Hilal
Published: February 2021

Araştırmanın amacı normal doğumda öğrenci hemşire tarafından verilen destekleyici bakım ile rutin bakımın doğum konforuna etkisini karşılaştırmaktır. Deneysel bir çalışmadır. Örneklemi Burdur ilinde vajinal doğum yapmış 108 kadın oluşturmuştur. Veriler tanıtıcı veri formu ve Doğum konfor Ölçeği kullanılarak yüz yüze görüşme yöntemi ile toplanmıştır. Toplamda 108 vaka çalışmaya alınmış olup; 54 deney (öğrenci hemşire tarafından destekleyici bakım verilen) ve 54 kontrol (rutin bakım verilen) grubu olarak ayrılmıştır. İstatistiksel anlamlılık p<0.05 kabul edilmiştir. Deney ve kontrol gruplarında yaş ortalaması sırasıyla 26.5±6.3, 26.2 ±5.3 iken; eşlerin yaş ortalaması 30.0±6.6 ve 30.2±6.4 olarak bulunmuştur (p>0.05). Eğitim durumu, meslek, ekonomik durum, eşin eğitim durumu, eşin mesleği açısından deney ve kontrol grupları benzerdir (p>0.05). Deney grubunda doğum konfor ölçeği puanı 36.0±3.7 iken; kontrol grubunda 34.7±4.2 olarak bulunmuştur (p<0.05). Doğum eyleminde öğrenci hemşirenin verdiği destekleyici yaklaşımla kadının kendisi ve bebeğiyle ilgili bakım ihtiyaçları ve beklentilerinin öğrenci hemşire tarafından birebir karşılanmasının kadınlarda doğum konforunu artırdığı saptanmıştır. Öğrenci hemşirelerin ulusal düzeyde hastane okul entegrasyonunun sağlandığı bir eğitim sistemiyle, uygulama alanlarına daha iyi ve hızlı oryante olması, kliniklerde çalışan ebe/hemşire sayısının artırılarak iş yükünün azaltılması gibi birebir bakımı destekleyen stratejiler konfor düzeyini yükselterek bakım kalitesini iyileştirebilir.
The required aerodynamic simulation fidelity to usefully support a gas turbine Digital Twin for manufacturing
Authors: Lee Wen Yao , Dawes William , Coull John
Published: February 2021

With the imminent digitalisation of the manufacturing processes of gas turbine components, a large volume of geometric data of as-manufactured parts is being generated. This geometric data can be used in aerodynamic simulations to predict component performance. Both the cost and accuracy of these simulations increase with their fidelity. To efficiently exploit Digital Twin technology, one must therefore understand how realistic the aerodynamic simulations need to be to give useful performance predictions.
This paper considers this issue for a sample of scrapped high-pressure turbine rotor blades from a civil aero engine. The measured geometric data was used to build aerodynamic models of varying degrees of realism, ranging from quasi-three-dimensional blade sections for an Euler solver to three-dimensional, multi-passage and multi-stage Reynolds-Averaged-Navier-Stokes models. The flow near the tip of these shrouded blades is sensitive to manufacturing variability and can switch between two quasi-stable horseshoe vortex modes. In general, capacity and exit flow angle can be adequately predicted by three-dimensional, single-passage calculations: averaging single-passage calculations gives a good prediction of the multi-passage behaviour. For efficiency and stage loading, the approach of averaging single-passage calculations is less accurate as the multi-passage behaviour requires an accurate prediction of the horseshoe vortex modes.
Body Shaming Through Social Media As a Digital Crime In The Era of Disruption
Authors: Puluhulawa Mohamad Rusdiyanto U. , Husain Riski
Published: February 2021

Digitalization has ushered in an era of disruption. The negative impact is body shaming. In the case of body shaming in Indonesia in 2018, “there were 966 cases of physical humiliation or body shaming handled by police from all over Indonesia throughout 2018. Most recently in 2019, public figures were also affected. No less surprising, this phenomenon does not only attack adults but also babies. The problem raised in this paper is what legal factors influence the rise of body shaming as a digital crime in the era of disruption. The approach method used is conceptual. In conclusion, the legal factors that influence the prevalence of body shaming are the substance of law and legal culture. In the aspect of legal substance, some areas have not been touched by current regulations, even though the legal realm is often used as a catalyst for digital body-shaming crimes. Meanwhile, in the aspect of legal culture, the problem of legal conflicts and low legal compliance are the main problems. To make matters worse, the attitude of the victim who prefers to ignore the treatment they receive without taking a fight justified by law makes the perpetrators of body shaming even wilder and more frontal,  because law enforcers, as part of the legal structure, are unable to take action because this act falls under the complaint offense. Suggestions, improved regulations and the role of the press and the public to change the way they view body-shaming behavior
The Tyranny of Openness: What Happened to Peer Production?
Authors: Schneider Nathan
Published: February 2021

This paper examines a “culture war” underway among software peer-production communities through relevant blog posts, legal documents, forum discussions, and other sources. Software licensing has been a defining strategy for peer producers, and much of the conflict at hand revolves around whether licensing should more fully incorporate ethics and economics, respectively. Feminist analysis can aid in tracing the contours of discontent through its emphasis on social processes that enable and infuse productive activity—processes that peer producers have trained themselves to ignore. The emerging critiques, and the experiments they have inspired, gesture toward fuller understandings of what “free” and “open” might mean.
Therapeutic Use of Mesenchymal Stromal Cells: The Need for Inclusive Characterization Guidelines to Accommodate All Tissue Sources and Species
Authors: Wright Adrienne , Arthaud-Day Marne L. , Weiss Mark L.
Published: February 2021

Following their discovery over 50 years ago, mesenchymal stromal cells (MSCs) have become one of the most studied cellular therapeutic products by both academia and industry due to their regenerative potential and immunomodulatory properties. The promise of MSCs as a therapeutic modality has been demonstrated by preclinical data yet has not translated to consistent, successful clinical trial results in humans. Despite the disparities across the field, MSC shareholders are unified under one common goal—to use MSCs as a therapeutic modality to improve the quality of life for those suffering from a malady in which the standard of care is suboptimal or no longer effective. Currently, there is no Food and Drug Administration (FDA)-approved MSC therapy on the market in the United States although several MSC products have been granted regulatory approval in other countries. In this review, we intend to identify hurdles that are impeding therapeutic progress and discuss strategies that may aid in accomplishing this universal goal of widespread therapeutic use.
Combined Administration of Metformin and Atorvastatin Attenuates Diabetic Cardiomyopathy by Inhibiting Inflammation, Apoptosis, and Oxidative Stress in Type 2 Diabetic Mice
Authors: Jia Weikun , Bai Tao , Zeng Jiang , Niu Zijing , Fan Daogui , Xu Xin , Luo Meiling , Wang Peijian , Zou Qingliang , Dai Xiaozhen
Published: February 2021

Diabetic cardiomyopathy (DCM), a common complication of diabetes mellitus, may eventually leads to irreversible heart failure. Metformin is the cornerstone of diabetes therapy, especially for type 2 diabetes. Statins are widely used to reduce the risk of cardiovascular diseases. In this study, we aimed to investigate whether the combined administration of metformin and atorvastatin could achieve superior protective effects on DCM and to elucidate its molecular mechanism. Here, db/db mice (9–10 weeks old) were randomly divided into four groups, including sterile water group (DM), metformin group (MET, 200 mg/kg/day), atorvastatin group (AVS, 10 mg/kg/day), and combination therapy group (MET + AVS). Mice were treated with different drugs via gavage once per day for 3 months. After 3 months of treatment, the pathological changes (inflammation, fibrosis, hypertrophy, and oxidative stress makers) were detected by histopathological techniques, as well as Western blotting. The H9C2 cardiomyocytes were treated with palmitate (PAL) to mimic diabetic condition. The cells were divided into control group, PAL treatment group, MET + PAL treatment group, AVS + PAL treatment group, and MET + AVS + PAL treatment group. The effects of MET and AVS on the cell viability and inflammation of H9C2 cells subjected to PAL condition were evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, immunofluorescence staining, and Western blotting. Both MET and AVS prevented diabetes-induced fibrosis, hypertrophy, and inflammation. The combination therapy showed superior effects in protecting myocardial tissue against diabetes-induced injury. Mechanistically, the combination therapy significantly inhibited oxidative stress and the expression levels of inflammation-related proteins, e.g., NLRP3, caspase-1, interleukin-1β (IL-1β), Toll-like receptor 4 (TLR4), and P-p65/p65, in both cardiac tissues and H9C2 cells. TUNEL assay showed that the combination therapy significantly attenuated the apoptosis of cardiomyocytes; decreased the expression level of pro-apoptotic-related proteins, such as cleaved caspase-3 and BAX; and enhanced the expression level of anti-apoptotic protein (Bcl-2). Furthermore, the combination therapy remarkably upregulated the expression levels of 5′-AMP-activated protein kinase (AMPK) and SIRT1. Our findings indicated that the anti-inflammation and anti-apoptosis effects of the combination therapy may be related to activation of AMPK/SIRT1 signaling pathway.
Ease and Difficulty in L2 Pronunciation Teaching: A Mini-Review
Authors: O’Brien Mary Grantham
Published: February 2021

Both L2 learners and their teachers are concerned about pronunciation. While an unspoken classroom goal is often native-accented speech (i.e., a spoken variety of the mother tongue that it not geographically confined to a place within a particular country), pronunciation researchers tend to agree that comprehensible speech (i.e., speech that can be easily understood by an interlocutor) is a more realistic goal. A host of studies have demonstrated that certain types of training can result in more comprehensible L2 speech. This contribution considers research on training the perception and production of both segmental (i.e., speech sounds) and suprasegmental features (i.e., stress, rhythm, tone, intonation). Before we can determine whether a given pronunciation feature is easy or difficult to teach and—more importantly—to learn, we must focus on: 1) setting classroom priorities that place comprehensibility of L2 speech at the forefront; and 2) relying upon insights gained through research into L2 pronunciation training. The goal of the mini-review is to help contextualize the papers presented in this collection.
A Novel Mechanism Regulating Dopamine Receptor Type 2 Signal Transduction in Pituitary Tumoral Cells: The Role of cAMP/PKA-Induced Filamin A Phosphorylation
Authors: Mangili Federica , Treppiedi Donatella , Catalano Rosa , Marra Giusy , Di Muro Genesio , Spada Anna , Arosio Maura , Peverelli Erika , Mantovani Giovanna
Published: February 2021

The actin binding protein filamin A (FLNA) is required for somatostatin receptor 2 (SSTR2) and dopamine receptor 2 (DRD2) expression and signaling in GH- and PRL-secreting PitNETs, respectively, playing a role in tumor responsiveness to somatostatin receptors ligands and dopaminergic drugs. FLNA functions are regulated by several mechanisms, including phosphorylation. It has been shown that in GH-secreting PitNETs FLNA phosphorylation on Ser2152 (P-FLNA) switches FLNA function from a scaffold that allows SSTR2 signal transduction, to a signal termination protein that hampers SSTR2 antitumoral effects. Aims of the present study were to evaluate in PRL- and ACTH-secreting PitNETs cell lines MMQ and AtT-20 the effects of cAMP pathway activation and DRD2 agonist on P-FLNA and the impact of P-FLNA on DRD2 signal transduction. We found that forskolin increased (+2.2 ± 0.8-fold, p < 0.01 in MMQ; +1.9 ± 0.58-fold, p < 0.05 in AtT-20), and DRD2 agonist BIM53097 reduced (-49.4 ± 25%, p < 0.001 in MMQ; -45.8 ± 28%, p < 0.05 in AtT-20), P-FLNA on Ser2152. The overexpression of a phosphomimetic (S2152D) FLNA mutant in both cell lines prevented DRD2 antiproliferative effects, that were comparable in cells transfected with empty vector, wild-type FLNA as well as phosphodeficient FLNA mutant (S2152A) (-20.6 ± 5% cell proliferation, p < 0.001 in MMQ; -36.6 ± 12%, p < 0.01 in AtT-20). Accordingly, S2152D FLNA expression abolished the expected ability of BIM53097 to increase or decrease, in MMQ and in AtT20 respectively, ERK phosphorylation, an effect that was maintained in S2152A FLNA expressing cells (+1.8 ± 0.65-fold, p < 0.05 in MMQ; -55 ± 13%, p < 0.01 in AtT-20). In addition, the inhibitory effects of DRD2 on hormone secretion (-34.3 ± 6% PRL, p < 0.05 in MMQ; -42.8 ± 22% ACTH, p < 0.05 in AtT-20, in cells expressing S2152A FLNA) were completely lost in S2152D FLNA transfected cells. In conclusion, our data demonstrated that cAMP pathway and DRD2 agonist regulated FLNA activity by increasing or decreasing, respectively, its phosphorylation. Moreover, we found that P-FLNA prevented DRD2 signaling in PRL- and ACTH-secreting tumoral pituitary cell lines, suggesting that this FLNA modification might represent a new regulatory mechanism shared by different GPCRs. In PitNETs expressing DRD2, modulation of P-FLNA might suggest new pharmacological strategies to overcome drug resistance, and P-FLNA might represent a new biomarker for tumor responsiveness to dopaminergic agents.
Imaging of Endoplasmic Reticulum Ca2+ in the Intact Pituitary Gland of Transgenic Mice Expressing a Low Affinity Ca2+ Indicator
Authors: Rojo-Ruiz Jonathan , Navas-Navarro Paloma , Nuñez Lucía , García-Sancho Javier , Alonso María Teresa
Published: February 2021

The adenohypophysis contains five secretory cell types (somatotrophs, lactotrophs, thyrotrophs, corticotrophs, and gonadotrophs), each secreting a different hormone, and controlled by different hypothalamic releasing hormones (HRHs). Exocytic secretion is regulated by cytosolic Ca2+ signals ([Ca2+]C), which can be generated either by Ca2+ entry through the plasma membrane and/or by Ca2+ release from the endoplasmic reticulum (ER). In addition, Ca2+ entry signals can eventually be amplified by ER release via calcium-induced calcium release (CICR). We have investigated the contribution of ER Ca2+ release to the action of physiological agonists in pituitary gland. Changes of [Ca2+] in the ER ([Ca2+]ER) were measured with the genetically encoded low-affinity Ca2+ sensor GAP3 targeted to the ER. We used a transgenic mouse strain that expressed erGAP3 driven by a ubiquitous promoter. Virtually all the pituitary cells were positive for the sensor. In order to mimick the physiological environment, intact pituitary glands or acute slices from the transgenic mouse were used to image [Ca2+]ER. [Ca2+]C was measured simultaneously with Rhod-2. Luteinizing hormone-releasing hormone (LHRH) or thyrotropin releasing hormone (TRH), two agonists known to elicit intracellular Ca2+ mobilization, provoked robust decreases of [Ca2+]ER and concomitant rises of [Ca2+]C. A smaller fraction of cells responded to thyrotropin releasing hormone (TRH). By contrast, depolarization with high K+ triggered a rise of [Ca2+]C without a decrease of [Ca2+]ER, indicating that the calcium-induced calcium-release (CICR) via ryanodine receptor amplification mechanism is not present in these cells. Our results show the potential of transgenic ER Ca2+ indicators as novel tools to explore intraorganellar Ca2+ dynamics in pituitary gland in situ.
Steam Turbine—Quo Vadis?
Authors: Gülen Seyfettin Can
Published: February 2021

In this article, a close look is taken at the state-of-the-art in steam turbine and steam (Rankine) cycle technology within the framework of conventional steam and gas turbine combined cycle power plants, specifically, the bottoming steam (Rankine) cycle of the latter. Using the second law of thermodynamics and the concept of exergy as a guide, cycle and technology factors are calculated to provide a simple but precise (and unassailable) yardstick to assess where the technology was, where it is at present, and how much farther it can go. In addition, the study takes a critical look at an emerging technology, supercritical CO2 cycle, that is being touted as a serious contender for steam turbine’s place in the fossil fuel-fired electric power generation portfolio—as a standalone system or as a waste heat recovery capacity (i.e., combined cycle).
Comprehensive circRNA Expression Profile and Construction of circRNAs-Related ceRNA Network in a Mouse Model of Autism
Authors: Wang Ji , Yang Zhongxiu , Chen Canming , Xu Yang , Wang Hongguang , Liu Bing , Zhang Wei , Jiang Yanan
Published: February 2021

Autism is a common disease that seriously affects the quality of life. The role of circular RNAs (circRNAs) in autism remains largely unexplored. We aimed to detect the circRNA expression profile and construct a circRNA-based competing endogenous RNA (ceRNA) network in autism. Valproate acid was used to establish an in vivo model of autism in mice. A total of 1,059 differentially expressed circRNAs (477 upregulated and 582 downregulated) in autism group was identified by RNA sequencing. The expression of novel_circ_015779 and novel_circ_035247 were detected by real-time PCR. A ceRNA network based on altered circRNAs was established, with 9,715 nodes and 150,408 edges. Module analysis was conducted followed by GO and KEGG pathway enrichment analysis. The top three modules were all correlated with autism-related pathways involving “TGF-beta signaling pathway,” “Notch signaling pathway,” “MAPK signaling pathway,” “long term depression,” “thyroid hormone signaling pathway,” etc. The present study reveals a novel circRNA involved mechanisms in the pathogenesis of autism.
Meiotic Heterogeneity of Trivalent Structure and Interchromosomal Effect in Blastocysts With Robertsonian Translocations
Authors: Zhang Shuo , Lei Caixia , Wu Junping , Zhou Jing , Xiao Min , Zhu Saijuan , Xi Yanping , Fu Jing , Sun Yijuan , Xu Congjian , Sun Xiaoxi
Published: February 2021

Background

Robertsonian translocations are common structural rearrangements and confer an increased genetic reproductive risk due to the formation of trivalent structure during meiosis. Studies on trivalent structure show meiotic heterogeneity between different translocation carriers, although the factors causing heterogeneity have not been well elaborated in blastocysts. It is also not yet known whether interchromosomal effect (ICE) phenomenon occurs in comparison with suitable non-translocation control patients. Herein, we aimed to evaluate the factors that cause meiotic heterogeneity of trivalent structure and the ICE phenomenon.

Methods

We designed a retrospective study, comprising 217 Robertsonian translocation carriers and 134 patients with the risk of transmitting monogenic inherited disorders (RTMIDs) that underwent preimplantation genetic testing (PGT). Data was collected between March 2014 and December 2019. The segregation products of trivalent structure were analyzed based on the carrier’s gender, age and translocation type. In addition, to analyze ICE phenomenon, aneuploidy abnormalities of non-translocation chromosomes from Robertsonian translocation carriers were compared with those from patients with RTMIDs.

Results

We found that the percentage of male carriers with alternate segregation pattern was significantly higher [P < 0.001, odds ratio (OR) = 2.95] than that in female carriers, while the percentage of adjacent segregation pattern was lower (P < 0.001, OR = 0.33). By contrast, no difference was observed between young and older carriers when performing stratified analysis by age. Furthermore, segregation pattern was associated with the D;G chromosomes involved in Robertsonian translocation: the rate of alternate segregation pattern in Rob(13;14) carriers was significantly higher (P = 0.010, OR = 1.74) than that in Rob(14;21) carriers, whereas the rate of adjacent segregation pattern was lower (P = 0.032, OR = 0.63). Moreover, the results revealed that the trivalent structure could significantly increase the frequencies of chromosome aneuploidies 1.30 times in Robertsonian translocation carriers compared with patients with RTMIDs (P = 0.026), especially for the male and young subgroups (P = 0.030, OR = 1.35 and P = 0.012, OR = 1.40), while the mosaic aneuploidy abnormalities presented no statistical difference.

Conclusions

Our study demonstrated that meiotic segregation heterogeneity of trivalent structure is associated with the carrier’s gender and translocation type, and it is independent of carrier’s age. ICE phenomenon exists during meiosis and then increases the frequencies of additional chromosome abnormalities.
The Dual Roles of Human γδ T Cells: Anti-Tumor or Tumor-Promoting
Authors: Li Yang , Li Gen , Zhang Jian , Wu Xiaoli , Chen Xi
Published: February 2021

γδ T cells are the unique T cell subgroup with their T cell receptors composed of γ chain and δ chain. Unlike αβ T cells, γδ T cells are non-MHC-restricted in recognizing tumor antigens, and therefore defined as innate immune cells. Activated γδ T cells can promote the anti-tumor function of adaptive immune cells. They are considered as a bridge between adaptive immunity and innate immunity. However, several other studies have shown that γδ T cells can also promote tumor progression by inhibiting anti-tumor response. Therefore, γδ T cells may have both anti-tumor and tumor-promoting effects. In order to clarify this contradiction, in this review, we summarized the functions of the main subsets of human γδ T cells in how they exhibit their respective anti-tumor or pro-tumor effects in cancer. Then, we reviewed recent γδ T cell-based anti-tumor immunotherapy. Finally, we summarized the existing problems and prospect of this immunotherapy.
CCR2 Is Dispensable for Disease Resolution but Required for the Restoration of Leukocyte Homeostasis Upon Experimental Malaria-Associated Acute Respiratory Distress Syndrome
Authors: Pollenus Emilie , Pham Thao-Thy , Vandermosten Leen , Robalo Queeny , Possemiers Hendrik , Knoops Sofie , Opdenakker Ghislain , Van den Steen Philippe E.
Published: February 2021

Malaria complications are often lethal, despite efficient killing of Plasmodium parasites with antimalarial drugs. This indicates the need to study the resolution and healing mechanisms involved in the recovery from these complications. Plasmodium berghei NK65-infected C57BL/6 mice develop malaria-associated acute respiratory distress syndrome (MA-ARDS) at 8 days post infection. Antimalarial treatment was started on this day and resulted in the recovery, as measured by the disappearance of the signs of pathology, in >80% of the mice. Therefore, this optimized model represents an asset in the study of mechanisms and leukocyte populations involved in the resolution of MA-ARDS. C-C chemokine receptor type 2 (CCR2) knock-out mice were used to investigate the role of monocytes and macrophages, since these cells are described to play an important role during the resolution of other inflammatory diseases. CCR2 deficiency was associated with significantly lower numbers of inflammatory monocytes in the lungs during infection and resolution and abolished the increase in non-classical monocytes during resolution. Surprisingly, CCR2 was dispensable for the development and the resolution of MA-ARDS, since no effect of the CCR2 knock-out was observed on any of the disease parameters. In contrast, the reappearance of eosinophils and interstitial macrophages during resolution was mitigated in the lungs of CCR2 knock-out mice. In conclusion, CCR2 is required for re-establishing the homeostasis of pulmonary leukocytes during recovery. Furthermore, the resolution of malaria-induced lung pathology is mediated by unknown CCR2-independent mechanisms.
Dietary Taxifolin Protects Against Dextran Sulfate Sodium-Induced Colitis via NF-κB Signaling, Enhancing Intestinal Barrier and Modulating Gut Microbiota
Authors: Hou Jinxiu , Hu Mingyang , Zhang Le , Gao Ya , Ma Libao , Xu Qingbiao
Published: February 2021

Taxifolin is a natural antioxidant polyphenol with various bioactivities and has many beneficial effects on human gut health. However, little is known of its function on colitis. In this study, the protective effects of taxifolin on colitis symptoms, inflammation, signaling pathways, and colon microbiota were investigated using dextran sulfate sodium (DSS)-induced colitis mice. Intriguingly, pre-administration of taxifolin alleviated the colitis symptoms and histological changes of the DSS-challenged mice. Supplementation of taxifolin significantly inhibited the secretions of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 and significantly increased the secretions of IL-10, secretory immunoglobulin A, superoxide dismutase, and immunoglobulins (IgA, IgG, and IgM) in DSS-induced colitis mice. In addition, the activation of nuclear factor kappa B (NF-κB; p65 and IκBα) signaling was significantly suppressed by taxifolin supplementation. The expression of tight junction proteins (claudin-1 and occludin) was significantly increased by taxifolin. Moreover, 16S rDNA sequencing revealed that the DSS-induced changes of colon microbiota composition and microbial functions (amino acid metabolism and MAPK signaling) were restored by taxifolin, including the decreases of the abundances of Bacteroides, Clostridium ramosum, Clostridium saccharogumia, Sphingobacterium multivorum, and the ratio of Bacteroidetes/Firmicutes, and the increases of the abundances of Desulfovibrio C21 c20 and Gemmiger formicilis at species level. In conclusion, these results revealed that dietary taxifolin has a great potential to prevent colitis by inhibiting the NF-κB signaling pathway, enhancing intestinal barrier, and modulating gut microbiota.
Alternative Pathway Involvement in Protoporphyria Patients Related to Sun Exposure
Authors: Granata Francesca , Duca Lorena , Brancaleoni Valentina , Fustinoni Silvia , De Luca Giacomo , Motta Irene , Graziadei Giovanna , Di Pierro Elena
Published: February 2021

The homeostasis of tissues in a chronic disease is an essential function of the alternative pathway (AP) of the complement system (CS). However, if not controlled, it may also be detrimental to healthy cells with a consequent aggravation of symptoms. The protoporphyria (PP) is a rare chronic disease that causes phototoxicity in visible light with local skin pain and general malaise. In order to establish if there is a systemic involvement of the CS during sun exposure, we designed a non-invasive method with a serum collection in winter and summer from 19 PP and 13 controls to detect the levels of CS protein: Properdin, Factor H (FH), and C5. Moreover, the global radiation data were collected from the regional agency of environmental protection (ARPA). The results show growing values for every protein in patients with PP, compared to control, in both seasons, in particular in summer compared to winter. To reinforce the evidence, we have estimated the personal exposure of patients based on the global radiation data. The main factors of the AP increased over the season, confirming the involvement of the AP in relation to light exposure. The systemic response could justify the general malaise of patients after long light exposure and can be exploited to elucidate new therapeutic approaches.
The Promise of Aggregation-Induced Emission Luminogens for Detecting COVID-19
Authors: Liu Zongwei , Meng Ting , Tang Xiaofang , Tian Ran , Guan Weijiang
Published: February 2021

The long-term pandemic of coronavirus disease 2019 (COVID-19) requires sensitive and accurate diagnostic assays to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and SARS-CoV-2 antibodies in infected individuals. Currently, RNA of SARS-CoV-2 virus is mainly detected by reverse transcription-polymerase chain reaction (RT-PCR)-based nucleic acid assays, while SARS-CoV-2 antigen and antibody are identified by immunological assays. Both nucleic acid assays and immunological assays rely on the luminescence signals of specific luminescence probes for qualitative and quantitative detection. The exploration of novel luminescence probes will play a crucial role in improving the detection sensitivity of the assays. As innate probes, aggregation-induced emission (AIE) luminogens (AIEgens) exhibit negligible luminescence in the free state but enhanced luminescence in the aggregated or restricted states. Moreover, AIEgen-based nanoparticles (AIE dots) offer efficient luminescence, good biocompatibility and water solubility, and superior photostability. Both AIEgens and AIE dots have been widely used for high-performance detection of biomolecules and small molecules, chemical/biological imaging, and medical therapeutics. In this review, the availability of AIEgens and AIE dots in nucleic acid assays and immunological assays are enumerated and discussed. By building a bridge between AIE materials and COVID-19, we hope to inspire researchers to use AIE materials as a powerful weapon against COVID-19.
Clinical Determinants Differentiating the Severity of SARS-CoV-2 Infection in Cancer Patients: Hospital Care or Home Recovery
Authors: Lin Dong D. , Wu Yunhong , Toom Sudhamshi , Sheth Niki , Becker Kevin , Burdette-Radoux Susan , D'Silva James , Huang Yiwu , Lipshitz Jay , Meghal Trishala , Mo Lan , Murthy Pooja , Rubin Philip , Natarajan Vijaya , Donahue Bernadine , Xu Yiqing
Published: February 2021

Background: Cancer patients may carry a worse prognosis with SARS-CoV-2 infection. Most of the previous studies described the outcomes of hospitalized cancer patients. We aimed to study the clinical factors differentiating patients requiring hospital care vs. home recovery, and the trajectory of their anti-cancer treatment.

Methods: This study was conducted in a community cancer center in New York City. Eligible patients were those who had cancer history and were diagnosed of SARS-CoV-2 infection between March 1 and May 30, 2020, with confirmatory SARs-CoV-2 virus test or antibody test. Four groups were constructed: (A) hospitalized and survived, (B) hospitalized requiring intubation and/or deceased, (C) non-hospitalized, asymptomatic, with suspicious CT image findings, close exposure, or positive antibody test, and (D) non-hospitalized and symptomatic.

Results: One hundred and six patients were included in the analysis. Thirty-five patients (33.0%) required hospitalization and 13 (12.3%) died. Thirty (28.3%) patients were asymptomatic and 41 (38.7%) were symptomatic and recovered at home. Comparing to patients who recovered at home, hospitalized patients were composed of older patients (median age 71 vs. 63 years old, p = 0.000299), more who received negative impact treatment (62.9 vs. 32.4%, p = 0.0036) that mostly represented myelosuppressive chemotherapy (45.7 vs. 23.9%, p = 0.0275), and more patients with poorer baseline performance status (PS ≥ 2 25.7 vs. 2.8%, p = 0.0007). Hypoxemia (35% in group A vs. 73.3% in group B, p = 0.0271) at presentation was significant to predict mortality in hospitalized patients. The median cumulative hospital stay for discharged patients was 16 days (range 5–60). The median duration of persistent positivity of SARS-CoV-2 RNA was 28 days (range 10–86). About 52.9% of patients who survived hospitalization and required anti-cancer treatment reinitiated therapy. Ninety-two percent of the asymptomatic patients and 51.7% of the symptomatic patients who recovered at home continued treatment on schedule and almost all reinitiated treatment after recovery.

Conclusions: Cancer patients may have a more severe status of SARS-CoV-2 infection after receiving myelosuppressive chemotherapy. Avoidance should be considered in older patients with poor performance status. More than two thirds of patients exhibit minimal to moderate symptoms, and many of them can continue or restart their anti-cancer treatment upon recovery.
A Simple-to-Use Web-Based Calculator for Survival Prediction in Acute Respiratory Distress Syndrome
Authors: Liu Yong , Liu Jian , Huang Liang
Published: February 2021

Background: The aim of this study was to construct and validate a simple-to-use model to predict the survival of patients with acute respiratory distress syndrome.

Methods: A total of 197 patients with acute respiratory distress syndrome were selected from the Dryad Digital Repository. All eligible individuals were randomly stratified into the training set (n=133) and the validation set (n=64) as 2: 1 ratio. LASSO regression analysis was used to select the optimal predictors, and receiver operating characteristic and calibration curves were used to evaluate accuracy and discrimination of the model. Clinical usefulness of the model was also assessed using decision curve analysis and Kaplan-Meier analysis.

Results: Age, albumin, platelet count, PaO2/FiO2, lactate dehydrogenase, high-resolution computed tomography score, and etiology were identified as independent prognostic factors based on LASSO regression analysis; these factors were integrated for the construction of the nomogram. Results of calibration plots, decision curve analysis, and receiver operating characteristic analysis showed that this model has good predictive ability of patient survival in acute respiratory distress syndrome. Moreover, a significant difference in the 28-day survival was shown between the patients stratified into different risk groups (P < 0.001). For convenient application, we also established a web-based calculator (https://huangl.shinyapps.io/ARDSprognosis/).

Conclusions: We satisfactorily constructed a simple-to-use model based on seven relevant factors to predict survival and prognosis of patients with acute respiratory distress syndrome. This model can aid personalized treatment and clinical decision-making.
Cellular and Genomic Properties of Haloferax gibbonsii LR2-5, the Host of Euryarchaeal Virus HFTV1
Authors: Tittes Colin , Schwarzer Sabine , Pfeiffer Friedhelm , Dyall-Smith Mike , Rodriguez-Franco Marta , Oksanen Hanna M. , Quax Tessa E. F.
Published: February 2021

Hypersaline environments are the source of many viruses infecting different species of halophilic euryarchaea. Information on infection mechanisms of archaeal viruses is scarce, due to the lack of genetically accessible virus–host models. Recently, a new archaeal siphovirus, Haloferax tailed virus 1 (HFTV1), was isolated together with its host belonging to the genus Haloferax, but it is not infectious on the widely used model euryarcheon Haloferax volcanii. To gain more insight into the biology of HFTV1 host strain LR2-5, we studied characteristics that might play a role in its virus susceptibility: growth-dependent motility, surface layer, filamentous surface structures, and cell shape. Its genome sequence showed that LR2-5 is a new strain of Haloferax gibbonsii. LR2-5 lacks obvious viral defense systems, such as CRISPR-Cas, and the composition of its cell surface is different from Hfx. volcanii, which might explain the different viral host range. This work provides first deep insights into the relationship between the host of halovirus HFTV1 and other members of the genus Haloferax. Given the close relationship to the genetically accessible Hfx. volcanii, LR2-5 has high potential as a new model for virus–host studies in euryarchaea.
Endogenous 2μ Plasmid Editing for Pathway Engineering in Saccharomyces cerevisiae
Authors: Zeng Bo-Xuan , Yao Ming-Dong , Xiao Wen-Hai , Luo Yun-Zi , Wang Ying , Yuan Ying-Jin
Published: February 2021

In Saccharomyces cerevisiae, conventional 2μ-plasmid based plasmid (pC2μ, such as pRS425) have been widely adopted in pathway engineering for multi-copy overexpression of key genes. However, the loss of partition and copy number control elements of yeast endogenous 2μ plasmid (pE2μ) brings the issues concerning plasmid stability and copy number of pC2μ, especially in long-term fermentation. In this study, we developed a method based on CRISPR/Cas9 to edit pE2μ and built the pE2μ multi-copy system by insertion of the target DNA element and elimination of the original pE2μ plasmid. The resulting plasmid pE2μRAF1 and pE2μREP2 demonstrated higher copy number and slower loss rate than a pC2μ control plasmid pRS425RK, when carrying the same target gene. Then, moving the essential gene TPI1 (encoding triose phosphate isomerase) from chromosome to pE2μRAF1 could increase the plasmid viability to nearly 100% and further increase the plasmid copy number by 73.95%. The expression using pE2μ multi-copy system demonstrated much smaller cell-to-cell variation comparing with pC2μ multi-copy system. With auxotrophic complementation of TPI1, the resulting plasmid pE2μRT could undergo cultivation of 90 generations under non-selective conditions without loss. Applying pE2μ multi-copy system for dihydroartemisinic acid (DHAA) biosynthesis, the production of DHAA was increased to 620.9 mg/L at shake-flask level in non-selective rich medium. This titer was 4.73-fold of the strain constructed based on pC2μ due to the more stable pE2μ plasmid system and with higher plasmid copy number. This study provides an improved expression system in yeast, and set a promising platform to construct biosynthesis pathway for valuable products.
Dual-Task Exercise to Improve Cognition and Functional Capacity of Healthy Older Adults
Authors: Jardim Naina Yuki Vieira , Bento-Torres Natáli Valim Oliver , Costa Victor Oliveira , Carvalho Josilayne Patricia Ramos , Pontes Helen Tatiane Santos , Tomás Alessandra Mendonça , Sosthenes Marcia Consentino Kronka , Erickson Kirk I. , Bento-Torres João , Diniz Cristovam Wanderley Picanço
Published: February 2021

Background

It has been suggested that physical inactivity and lack of stimulating cognitive activity are the two most significant modifiable risk factors to impair cognitive function. Although many studies that investigated the cognitive effects of physical exercise and cognitive stimuli in dual-task conditions showed improved cognitive performance, others have not confirmed these findings. The main aim of the present work is to analyze the effects of a dual-task multimodal physical exercise training, at moderate intensity, and cognitive stimulation on cognitive and physical function in healthy older adults.

Methods

This clinical trial was registered on the Brazilian Registry of Clinical Trials (RBR-9zrx3d). Here we tested the effects of a dual-task multimodal physical exercise training, at moderate intensity, on cognitive and physical function and quality of life in community dwelling older adults. The training protocol included 24 group sessions, 2/week, per 75 min. Cognition was assessed using CANTAB automated neuropsychological tests and Functional Capacity to Exercise tests. Performance was compared from baseline to post intervention and to a non-exercise control group using Mixed Linear Model for repeated measures.

Results

Control (CG) and dual-task (DTEx) groups progressed differentially over time on performance of episodic memory, sustained visual attention, functional mobility, cardiorespiratory fitness, lower limbs strength resistance, agility, quality of life and dual-task performance with significant improved DTEx performance. Control group did not show any significant changes on these tests except for showing a reduction in dual-task performance.

Conclusion

We suggest that the dual-task combination of multisensory cognitive stimulation and multimodal moderate physical exercise training, twice a week, may be adopted as an effective program to reduce progression of age-related cognitive decline and improve physical fitness and quality of life on healthy older adults.

Clinical Trial Registration

Brazilian Registry of Clinical Trials: https://ensaiosclinicos.gov.br/rg/RBR-9zrx3d -UTN code: U1111-1233-6349.
Dopaminergic and Metabolic Correlations With Cognitive Domains in Non-demented Parkinson’s Disease
Authors: Han Linlin , Lu Jiaying , Tang Yilin , Fan Yun , Chen Qisi , Li Ling , Liu Fengtao , Wang Jian , Zuo Chuantao , Zhao Jue
Published: February 2021

Background

Accruing positron emission tomography (PET) studies have suggested that dopaminergic functioning and metabolic changes are correlated with cognitive dysfunction in Parkinson’s disease (PD). Yet, the relationship between dopaminergic or cerebral metabolism and different cognitive domains in PD is poorly understood. To address this scarcity, we aimed to investigate the interactions among dopaminergic bindings, metabolic network changes, and the cognitive domains in PD patients.

Methods

We recruited 41 PD patients, including PD patients with no cognitive impairment (PD-NC; n = 21) and those with mild cognitive impairment (PD-MCI; n = 20). All patients underwent clinical evaluations and a schedule of neuropsychological tests and underwent both 11C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane (11C-CFT) and 18F-fluorodeoxyglucose (18F-FDG) PET imaging.

Results

11C-CFT imaging revealed a significant positive correlation between executive function and striatal dopamine transporter (DAT) binding at both the voxel and regional levels. Metabolic imaging revealed that executive function correlated with 18F-FDG uptake, mainly in inferior frontal gyrus, putamen, and insula. Further analysis indicated that striatal DAT binding correlated strictly with metabolic activity in the temporal gyrus, medial frontal gyrus, and cingulate gyrus.

Conclusion

Our findings might promote the understanding of the neurobiological mechanisms underlying cognitive impairment in PD.