bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined Extract of Leonurus japonicus Houtt, Eclipta prostrata L., and Pueraria lobata Ohwi Improved Hot Flashes and Depression in an Ovariectomized Rat Model of Menopause
Authors: Kang Eun Young , Kim Hyun Kyung , Jung Ji Yeon , Kim Ji Hyun , Woo Tan Kyung , Choi Jeong In , Kim Jong Hoon , Ahn Changwon , Lee Hyeon Gyu , Go Gwang-Woong
Published: January 2021

Menopause leads to ovarian hormone loss, which causes symptoms such as weight gain, hot flashes, and depression. Exploring nutraceuticals is important for treating menopausal symptoms that extensively impact women’s quality of life. We hypothesized that a combination of Leonurus japonicus Houtt, Eclipta prostrata L., and Pueraria lobata Ohwi (LEPE) would alleviate menopausal symptoms in an ovariectomized menopausal rat model. Bilateral ovariectomy was performed and animals were assigned to five groups: (1) Sham, (2) Vehicle, (-) Control, (3) LEPE (100 mg/kg bw), (4) LEPE (200 mg/kg bw), and (5) Estradiol (3 μg/kg bw). LEPE was orally administered daily for 12 weeks. LEPE supplementation did not affect growth performance (body weight and feed intake) or body composition (lean mass and fat in tissue). LEPE did not cause deviations in aspartate aminotransferase, alanine aminotransferase, estradiol, and follicle-stimulating hormone levels, indicating no hepatotoxicity or endocrine disturbance. LEPE decreased type I collagen (CTX-1) but did not affect bone mineral density or osteocalcin. LEPE decreased tail temperature and increased rectal temperature, improving menopause-related vasomotor symptoms. Furthermore, LEPE ameliorated depression-related behavior, including in forced swimming and tail suspension tests. Thus, LEPE may improve menopausal symptoms by enhancing vasomotor symptoms and depression in an ovariectomized rat menopause model.
Religious Coping, Depression and Anxiety among Healthcare Workers during the COVID-19 Pandemic: A Malaysian Perspective
Authors: Chow Soon Ken , Francis Benedict , Ng Yit Han , Naim Najmi , Beh Hooi Chin , Ariffin Mohammad Aizuddin Azizah , Yusuf Mohd Hafyzuddin Md , Lee Jia Wen , Sulaiman Ahmad Hatim
Published: January 2021

Anxiety and depression have been prevalent among Healthcare Workers (HCWs) amidst the COVID-19 pandemic. This study aims to evaluate the prevalence of anxiety and depression among HCWs amid the pandemic and their association with religious coping. A cross-sectional study design was applied. The scales utilized were Malay versions of the Brief Religious Coping Scale (Brief RCOPE M) and Hospital Anxiety and Depression Scale (HADS M). In total, 200 HCWs were recruited. HCWs scored higher in positive religious coping (mean: 21.33) than negative religious coping (mean: 10.52). The prevalence of anxiety and depression was 36.5% and 29.5%. Both positive and negative religious coping were significantly associated with anxiety (p < 0.01) and depression (p < 0.05, p < 0.01). Positive coping predicted reduction in anxiety (adjusted b = −0.15, p = 0.001) and log-transformed depression score (adjusted b = −0.019, p = 0.025). Negative coping predicted increment of anxiety (adjusted b = 0.289, p < 0.001) and log-transformed depression score (adjusted b = 0.052, p < 0.001). Positive religious coping is vital in reducing anxiety and depression among HCWs amid the pandemic. Strategies which increase positive religious coping and reduce negative religious coping must be emphasized to boost mental health among HCWs.
COVID-19 in China: Responses, Challenges and Implications for the Health System
Authors: Xing Cunhai , Zhang Ruilian
Published: January 2021

A public health crisis is a “touchstone” for testing the ability and capacity of a national health system. In the current era, public health crises are presenting new systematic and cross-border characteristics and uncertainty. The essence of a system for public health crisis governance is the rules administering the stimulus–response chain. The health system generally emphasizes joint participation and communication between different subjects, which may lead to overlap and redundancy as well as a lack of auxiliary support for major public health crisis events. In the context of coronavirus disease 2019 (COVID-19) in China, we track the responses, challenges, and implications of the temporary disruption of the health system and its response to this major public health crisis. We examine local governance capacity, performance in pandemic control, and the coordinated responses to COVID-19. Accordingly, we identify the challenges to the health system, including the imbalance in attention given to medical care versus health care, insufficient grassroots public health efforts and control capacity, and untimely information disclosure. It is strongly suggested that the government improve its cognitive ability and focus more attention on building and strengthening the emergency health system.
Age-Friendly Health Care: A Systematic Review
Authors: Tavares Jéssica , Santinha Gonçalo , Rocha Nelson P.
Published: January 2021

Background: Health care provided to older adults must take into account the characteristics of chronic diseases and the comorbidities resulting from ageing. However, health services are still too oriented towards acute situations. To overcome this problem, the World Health Organization (WHO) proposed a set of Age-Friendly Principles that seek to optimize the provision of health care for this population. This article aims to understand how such Principles are considered in the implementation of age-friendly health care worldwide. Methods: A systematic review was conducted to synthesize the literature on age-friendly health care in accordance with the PRISMA recommendations in the PubMed, Web of Science, and Scopus databases. Results: The research identified 34 articles, with only seven recognizing the WHO Principles and only four using the implementation toolkit. In addition, in the context of primary care, three studies recognize the WHO Principles, but only two use the toolkit. Conclusions: The WHO Principles are being implemented in health care, but in a smaller scale than desired, which reveals possible flaws in their dissemination and standardization. Thus, a greater scientific investment in age-friendly health care should be considered, which represents a greater operationalization of the Principles and an evaluation of their effectiveness and impacts.
Nurses’ Workplace Conditions Impacting Their Mental Health during COVID-19: A Cross-Sectional Survey Study
Authors: Havaei Farinaz , Ma Andy , Staempfli Sabina , MacPhee Maura
Published: January 2021

Among health workers, nurses are at the greatest risk of COVID-19 exposure and mortality due to their workplace conditions, including shortages of personal protective equipment (PPE), insufficient staffing, and inadequate safety precautions. The purpose of this study was to examine the impact of COVID-19 workplace conditions on nurses’ mental health outcomes. A cross-sectional correlational design was used. An electronic survey was emailed to nurses in one Canadian province between June and July of 2020. A total of 3676 responses were included in this study. We found concerning prevalence rates for post-traumatic stress disorder (47%), anxiety (38%), depression (41%), and high emotional exhaustion (60%). Negative ratings of workplace relations, organizational support, organizational preparedness, workplace safety, and access to supplies and resources were associated with higher scores on all of the adverse mental health outcomes included in this study. Better workplace policies and practices are urgently required to prevent and mitigate nurses’ suboptimal work conditions, given their concerning mental health self-reports during the COVID-19 pandemic.
A Case Series: Successfully Preventing COVID-19 Outbreak in a Residential Community Setting at a Drug and Alcohol Addiction Treatment Center
Authors: Hanton Kenneth , McHugh Douglas , Boris Gregory
Published: January 2021

Coronavirus disease 2019 (COVID-19) has reduced the capacity of many addiction treatment centers, limiting access to safe, continual treatment for people with substance use disorders (SUD) in the setting of a pandemic. Here, we describe the COVID-19 screening process of a residential addiction treatment center in rural Connecticut that has had no outbreaks, closures, or reductions in capacity since the pandemic began. Out of 420 patients screened for COVID-19 from 1 February to 1 July, five patients tested positive for COVID-19: four prior to entering its residential community setting, and one after entering the residential community, resulting in no COVID-19 spread to other patients. Patient 1 presented from home and tested positive during screening prior to entry into the community. The primary care provider for patient 2 notified staff of a recent pos-itive COVID-19 test prior to the patient’s arrival on-site. Patient 3 had a COVID-19 infection in the weeks prior to arrival and tested positive during initial screening. Patient 4 tested positive af-ter coming from another addiction treatment facility that was shut down due to a COVID-19 outbreak. Patient 5 tested negative for COVID-19 during initial screening, entered the residential community, and later tested positive. It is imperative that in-person support for SUD continues during the pandemic. This case report highlights the importance of implementing a variety of tools in an effective screening process, including polymerase chain reaction screening and daily symptomology and temperature screening, which may help prevent further closures or reductions in capacity of addiction treatment centers during the COVID-19 pandemic or future outbreaks.
Effectiveness of a Novel HIV Self-Testing Service with Online Real-Time Counseling Support (HIVST-Online) in Increasing HIV Testing Rate and Repeated HIV Testing among Men Who Have Sex with Men in Hong Kong: Results of a Pilot Implementation Project
Authors: Chan Paul Shing-fong , Chidgey Andrew , Lau Jason , Ip Mary , Lau Joseph T.F. , Wang Zixin
Published: January 2021

HIV self-testing (HIVST) with online real-time counseling (HIVST-online) is an evidence-based intervention to increase HIV testing coverage and to ensure linkage to care for men who have sex with men (MSM). A community-based organization (CBO) recruited 122 MSM who had ever used HIVST-online (ever-users) and another 228 new-users from multiple sources and promoted HIVST-online. A free oral fluid-based HIVST kit was sent to all the participants by mail. Experienced HIVST administrators implemented HIVST-online by providing real-time instruction, standard-of-care pre-test and post-test counseling via live-chat application. The number of HIVST-online sessions performed was documented by the administrators. The post-test evaluation was conducted 6 months after the pre-test survey. At month 6, 63.1% of ever-users and 40.4% of new-users received HIVST-online. Taking other types of HIV testing into account, 79.4% of ever-users and 58.6% of new-users being followed up at month 6 received any HIV testing during the project period. Ever-users were more likely to receive HIVST-online and any HIV testing as compared to new-users. Four HIVST-online users were screened to be HIV positive and linked to the treatment. The process evaluation of HIVST-online was positive. Implementation of HIVST-online was helpful to improve HIV testing coverage and repeated HIV testing among Chinese MSM. A larger scale implementation should be considered.
Diagnostic Agreement between Physicians and a Consultation–Liaison Psychiatry Team at a General Hospital: An Exploratory Study across 20 Years of Referrals
Authors: Marchi Mattia , Magarini Federica Maria , Mattei Giorgio , Pingani Luca , Moscara Maria , Galeazzi Gian Maria , Ferrari Silvia
Published: January 2021

Consultation–liaison psychiatry (CLP) manages psychiatric care for patients admitted to a general hospital (GH) for somatic reasons. We evaluated patterns in psychiatric morbidity, reasons for referral and diagnostic concordance between referring doctors and CL psychiatrists. Referrals over the course of 20 years (2000–2019) made by the CLP Service at Modena GH (Italy) were retrospectively analyzed. Cohen’s kappa statistics were used to estimate the agreement between the diagnoses made by CL psychiatrist and the diagnoses considered by the referring doctors. The analyses covered 18,888 referrals. The most common referral reason was suspicion of depression (n = 4937; 32.3%), followed by agitation (n = 1534; 10.0%). Psychiatric diagnoses were established for 13,883 (73.8%) referrals. Fair agreement was found for depressive disorders (kappa = 0.281) and for delirium (kappa = 0.342), which increased for anxiety comorbid depression (kappa = 0.305) and hyperkinetic delirium (kappa = 0.504). Moderate agreement was found for alcohol or substance abuse (kappa = 0.574). Referring doctors correctly recognized psychiatric conditions due to their exogenous etiology or clear clinical signs; in addition, the presence of positive symptoms (such as panic or agitation) increased diagnostic concordance. Close daily collaboration between CL psychiatrists and GH doctors lead to improvements in the ability to properly detect comorbid psychiatric conditions.
Surviving Burn Injury: Drivers of Length of Hospital Stay
Authors: Onah Chimdimma Noelyn , Allmendinger Richard , Handl Julia , Dunn Ken W.
Published: January 2021

With a reduction in the mortality rate of burn patients, length of stay (LOS) has been increasingly adopted as an outcome measure. Some studies have attempted to identify factors that explain a burn patient’s LOS. However, few have investigated the association between LOS and a patient’s mental and socioeconomic status. There is anecdotal evidence for links between these factors; uncovering these will aid in better addressing the specific physical and emotional needs of burn patients and facilitate the planning of scarce hospital resources. Here, we employ machine learning (clustering) and statistical models (regression) to investigate whether segmentation by socioeconomic/mental status can improve the performance and interpretability of an upstream predictive model, relative to a unitary model. Although we found no significant difference in the unitary model’s performance and the segment-specific models, the interpretation of the segment-specific models reveals a reduced impact of burn severity in LOS prediction with increasing adverse socioeconomic and mental status. Furthermore, the socioeconomic segments’ models highlight an increased influence of living circumstances and source of injury on LOS. These findings suggest that in addition to ensuring that patients’ physical needs are met, management of their mental status is crucial for delivering an effective care plan.
Spatially Characterizing Major Airline Alliances: A Network Analysis
Authors: Chan Chun-Hsiang , Chu Tzu-How , Wu Jiun-Huei Proty , Wen Tzai-Hung
Published: January 2021

An airline alliance is a group of member airlines that seek to achieve the same goals through routes and airports. Hence, airports’ connectivity plays an essential role in understanding the linkage between different markets, especially the impact of neighboring airports on focal airports. An airline alliance airport network (AAAN) comprises airports as nodes and routes as edges. It could reflect a clear collaborative proportion within AAAN and competitive routes between AAANs. Recent studies adopted an airport- or route-centric perspective to evaluate the relationship between airline alliances and their member airlines; meanwhile, they mentioned that an airport community could provide valuable air transportation information because it considers the entire network structure, including the impacts of the direct and indirect routes. The objectives are to identify spatial patterns of market region in an airline alliance and characterize the differences among airline alliances (Oneworld, Star Alliance, and SkyTeam), including regions of collaboration, competition, and dominance. Our results show that Star Alliance has the highest collaboration and international market dominance among three airline alliances. The most competitive regions are Asia-Pacific, West Asia, Europe, and North and Central America. The network approach we proposed identifies market characteristics, highlights the region of market advantages in the airline alliance, and also provides more insights for airline and airline alliances to extend their market share or service areas.
The Interaction of the Senescent and Adjacent Breast Cancer Cells Promotes the Metastasis of Heterogeneous Breast Cancer Cells through Notch Signaling
Authors: Zhang Na , Ji Jiafei , Zhou Dandan , Liu Xuan , Zhang Xinglin , Liu Yingqi , Xiang Weifang , Wang Meida , Zhang Lian , Wang Guannan , Huang Baiqu , Lu Jun , Zhang Yu
Published: January 2021

Chemotherapy is one of the most common strategies for tumor treatment but often associated with post-therapy tumor recurrence. While chemotherapeutic drugs are known to induce tumor cell senescence, the roles and mechanisms of senescence in tumor recurrence remain unclear. In this study, we used doxorubicin to induce senescence in breast cancer cells, followed by culture of breast cancer cells with conditional media of senescent breast cancer cells (indirect co-culture) or directly with senescent breast cancer cells (direct co-culture). We showed that breast cancer cells underwent the epithelial–mesenchymal transition (EMT) to a greater extent and had stronger migration and invasion ability in the direct co-culture compared with that in the indirect co-culture model. Moreover, in the direct co-culture model, non-senescent breast cancer cells facilitated senescent breast cancer cells to escape and re-enter into the cell cycle. Meanwhile, senescent breast cancer cells regained tumor cell characteristics and underwent EMT after direct co-culture. We found that the Notch signaling was activated in both senescent and non-senescent breast cancer cells in the direct co-culture group. Notably, the EMT process of senescent and adjacent breast cancer cells was blocked upon inhibition of Notch signaling with N-[(3,5-difluorophenyl)acetyl]-l-alanyl-2-phenyl]glycine-1,1-dimethylethyl ester (DAPT) in the direct co-cultures. In addition, DAPT inhibited the lung metastasis of the co-cultured breast cancer cells in vivo. Collectively, data arising from this study suggest that both senescent and adjacent non-senescent breast cancer cells developed EMT through activating Notch signaling under conditions of intratumoral heterogeneity caused by chemotherapy, which infer the possibility that Notch inhibitors used in combination with chemotherapeutic agents may become an effective treatment strategy.
X-Linked Retinitis Pigmentosa Caused by Non-Canonical Splice Site Variants in RPGR
Authors: Kortüm Friederike , Kieninger Sinja , Mazzola Pascale , Kohl Susanne , Wissinger Bernd , Prokisch Holger , Stingl Katarina , Weisschuh Nicole
Published: January 2021

We aimed to validate the effect of non-canonical splice site variants in the RPGR gene in five patients from four families diagnosed with retinitis pigmentosa. Four variants located in intron 2 (c.154 + 3_154 + 6del), intron 3 (c.247 + 5G>A), intron 7 (c.779-5T>G), and intron 13 (c.1573-12A>G), respectively, were analyzed by means of in vitro splice assays. Splicing analysis revealed different aberrant splicing events, including exon skipping and intronic nucleotide addition, which are predicted to lead either to an in-frame deletion affecting relevant protein domains or to a frameshift of the open reading frame. Our data expand the landscape of pathogenic variants in RPGR, thereby increasing the genetic diagnostic rate in retinitis pigmentosa and allowing patients harboring the analyzed variants to be enrolled in clinical trials.
Rational Design of CYP3A4 Inhibitors: A One-Atom Linker Elongation in Ritonavir-Like Compounds Leads to a Marked Improvement in the Binding Strength
Authors: Samuels Eric R. , Sevrioukova Irina F.
Published: January 2021

Inhibition of the major human drug-metabolizing cytochrome P450 3A4 (CYP3A4) by pharmaceuticals and other xenobiotics could lead to toxicity, drug–drug interactions and other adverse effects, as well as pharmacoenhancement. Despite serious clinical implications, the structural basis and attributes required for the potent inhibition of CYP3A4 remain to be established. We utilized a rational inhibitor design to investigate the structure–activity relationships in the analogues of ritonavir, the most potent CYP3A4 inhibitor in clinical use. This study elucidated the optimal length of the head-group spacer using eleven (series V) analogues with the R1/R2 side-groups as phenyls or R1–phenyl/R2–indole/naphthalene in various stereo configurations. Spectral, functional and structural characterization of the inhibitory complexes showed that a one-atom head-group linker elongation, from pyridyl–ethyl to pyridyl–propyl, was beneficial and markedly improved Ks, IC50 and thermostability of CYP3A4. In contrast, a two-atom linker extension led to a multi-fold decrease in the binding and inhibitory strength, possibly due to spatial and/or conformational constraints. The lead compound, 3h, was among the best inhibitors designed so far and overall, the strongest binder (Ks and IC50 of 0.007 and 0.090 µM, respectively). 3h was the fourth structurally simpler inhibitor superior to ritonavir, which further demonstrates the power of our approach.
Immunological Dysfunction in Tourette Syndrome and Related Disorders
Authors: Hsu Chia-Jui , Wong Lee-Chin , Lee Wang-Tso
Published: January 2021

Chronic tic disorder and Tourette syndrome are common childhood-onset neurological diseases. However, the pathophysiology underlying these disorders is unclear, and most studies have focused on the disinhibition of the corticostriatal–thalamocortical circuit. An autoimmune dysfunction has been proposed in the pathogenetic mechanism of Tourette syndrome and related neuropsychiatric disorders such as obsessive–compulsive disorder, autism, and attention-deficit/hyperactivity disorder. This is based on evidence from animal model studies and clinical findings. Herein, we review and give an update on the clinical characteristics, clinical evidence, and genetic studies in vitro as well as animal studies regarding immune dysfunction in Tourette syndrome.
P2Y11 Agonism Prevents Hypoxia/Reoxygenation- and Angiotensin II-Induced Vascular Dysfunction and Intimal Hyperplasia Development
Authors: Piollet Marie , Sturza Adrian , Chadet Stéphanie , Gabillard-Lefort Claudie , Benoist Lauriane , Muntean Danina-Mirela , Aburel Oana-Maria , Angoulvant Denis , Ivanes Fabrice
Published: January 2021

Vascular dysfunction in cardiovascular diseases includes vasomotor response impairments, endothelial cells (ECs) activation, and smooth muscle cells (SMCs) proliferation and migration to the intima. This results in intimal hyperplasia and vessel failure. We previously reported that activation of the P2Y11 receptor (P2Y11R) in human dendritic cells, cardiofibroblasts and cardiomyocytes was protective against hypoxia/reoxygenation (HR) lesions. In this study, we investigated the role of P2Y11R signaling in vascular dysfunction. P2Y11R activity was modulated using its pharmacological agonist NF546 and antagonist NF340. Rat aortic rings were exposed to angiotensin II (AngII) and evaluated for their vasomotor response. The P2Y11R agonist NF546 reduced AngII-induced vascular dysfunction by promoting EC-dependent vasorelaxation, through an increased nitric oxide (NO) bioavailability and reduced AngII-induced H2O2 release; these effects were prevented by the use of the P2Y11R antagonist NF340. Human vascular SMCs and ECs were subjected to AngII or H/R simulation in vitro. P2Y11R agonist modulated vasoactive factors in human ECs, that is, endothelial nitric oxide synthase (eNOS) and endothelin-1, reduced SMC proliferation and prevented the switch towards a synthetic phenotype. H/R and AngII increased ECs secretome-induced SMC proliferation, an effect prevented by P2Y11R activation. Thus, our data suggest that P2Y11R activation may protect blood vessels from HR-/AngII-induced injury and reduce vascular dysfunctions. These results open the way for new vasculoprotective interventions.
Liraglutide Has Anti-Inflammatory and Anti-Amyloid Properties in Streptozotocin-Induced and 5xFAD Mouse Models of Alzheimer’s Disease
Authors: Paladugu Leela , Gharaibeh Abeer , Kolli Nivya , Learman Cameron , Hall Tia C. , Li Lixin , Rossignol Julien , Maiti Panchanan , Dunbar Gary L.
Published: January 2021

Recent clinical and epidemiological studies support the contention that diabetes mellitus (DM) is a strong risk factor for the development of Alzheimer’s disease (AD). The use of insulin cell toxin, streptozotocin (STZ), when injected into the lateral ventricles, develops an insulin resistant brain state (IRBS) and represents a non-transgenic, or sporadic AD model (SAD), with several AD-like neuropathological features. The present study explored the effects of an anti-diabetic drug, liraglutide (LIR), in reversing major pathological hallmarks in the prodromal disease stage of both the 5xFAD transgenic and SAD mouse models of AD. Three-month-old 5xFAD and age-matched wild type mice were given a single intracerebroventricular (i.c.v) injection of STZ or vehicle (saline) and were subsequently treated with LIR, intraperitoneally (IP), once a day for 30 days. The extent of neurodegeneration, Aβ plaque load, and key proteins associated with the insulin signaling pathways were measured using Western blot and neuroinflammation (via immunohistological assays) in the cortical and hippocampal regions of the brain were assessed following a series of behavioral tests used to measure cognitive function after LIR or vehicle treatments. Our results indicated that STZ significantly increased neuroinflammation, Aβ plaque deposition and disrupted insulin signaling pathway, while 25 nmol/kg LIR, when injected IP, significantly decreased neuroinflammatory responses in both SAD and 5xFAD mice before significant cognitive changes were observed, suggesting LIR can reduce early neuropathology markers prior to the emergence of overt memory deficits. Our results indicate that LIR has neuroprotective effects and has the potential to serve as an anti-inflammatory and anti-amyloid prophylactic therapy in the prodromal stages of AD.
Mass Spectral Filtering by Mass-Remainder Analysis (MARA) at High Resolution and Its Application to Metabolite Profiling of Flavonoids
Authors: Nagy Tibor , Róth Gergő , Kuki Ákos , Zsuga Miklós , Kéki Sándor
Published: January 2021

Flavonoids represent an important class of secondary metabolites because of their potential health benefits and functions in plants. We propose a novel method for the comprehensive flavonoid filtering and screening based on direct infusion mass spectrometry (DIMS) analysis. The recently invented data mining procedure, the multi-step mass-remainder analysis (M-MARA) technique is applied for the effective mass spectral filtering of the peak rich spectra of natural herb extracts. In addition, our flavonoid-filtering algorithm facilitates the determination of the elemental composition. M-MARA flavonoid-filtering uses simple mathematical and logical operations and thus, it can easily be implemented in a regular spreadsheet software. A huge benefit of our method is the high speed and the low demand for computing power and memory that enables the real time application even for tandem mass spectrometric analysis. Our novel method was applied for the electrospray ionization (ESI) DIMS spectra of various herb extract, and the filtered mass spectral data were subjected to chemometrics analysis using principal component analysis (PCA).
Evaluation of Antimicrobial Effect of Air-Polishing Treatments and Their Influence on Human Dental Pulp Stem Cells Seeded on Titanium Disks
Authors: Di Tinco Rosanna , Bertani Giulia , Pisciotta Alessandra , Bertoni Laura , Bertacchini Jessika , Colombari Bruna , Conserva Enrico , Blasi Elisabetta , Consolo Ugo , Carnevale Gianluca
Published: January 2021

Dental implants are one of the most frequently used treatment options for tooth replacement, and titanium is the metal of choice due to its demonstrated superiority in resisting corrosion, lack of allergic reactions and mechanical strength. Surface roughness of titanium implants favors the osseointegration process; nevertheless, its topography may provide a suitable substrate for bacterial biofilm deposition, causing peri-implantitis and leading to implant failure. Subgingival prophylaxis treatments with cleansing powders aimed to remove the bacterial accumulation are under investigation. Two different air-polishing powders—glycine and tagatose—were assayed for their cleaning and antimicrobial potential against a Pseudomonas biofilm and for their effects on human dental pulp stem cells (hDPSCs), seeded on sandblasted titanium disks. Immunofluorescence analyses were carried out to evaluate cell adhesion, proliferation, stemness and osteogenic differentiation. The results demonstrate that both the powders have a great in vitro cleaning potential in the early period and do not show any negative effects during hDPSCs osteogenic differentiation process, suggesting their suitability for enhancing the biocompatibility of titanium implants. Our data suggest that the evaluated cleansing systems reduce microbial contamination and allow us to propose tagatose as an adequate alternative to the gold standard glycine for the air-polishing prophylaxis treatment.
Modulation of Intestinal Phosphate Transport in Young Goats Fed a Low Phosphorus Diet
Authors: Behrens Joie L. , Schnepel Nadine , Hansen Kathrin , Hustedt Karin , Burmester Marion , Klinger Stefanie , Breves Gerhard , Muscher-Banse Alexandra S.
Published: January 2021

The intestinal absorption of phosphate (Pi) takes place transcellularly through the active NaPi-cotransporters type IIb (NaPiIIb) and III (PiT1 and PiT2) and paracellularly by diffusion through tight junction (TJ) proteins. The localisation along the intestines and the regulation of Pi absorption differ between species and are not fully understood. It is known that 1,25-dihydroxy-vitamin D3 (1,25-(OH)2D3) and phosphorus (P) depletion modulate intestinal Pi absorption in vertebrates in different ways. In addition to the apical uptake into the enterocytes, there are uncertainties regarding the basolateral excretion of Pi. Functional ex vivo experiments in Ussing chambers and molecular studies of small intestinal epithelia were carried out on P-deficient goats in order to elucidate the transepithelial Pi route in the intestine as well as the underlying mechanisms of its regulation and the proteins, which may be involved. The dietary P reduction had no effect on the duodenal and ileal Pi transport rate in growing goats. The ileal PiT1 and PiT2 mRNA expressions increased significantly, while the ileal PiT1 protein expression, the mid jejunal claudin-2 mRNA expression and the serum 1,25-(OH)2D3 levels were significantly reduced. These results advance the state of knowledge concerning the complex mechanisms of the Pi homeostasis in vertebrates.
The Oral Ferroportin Inhibitor VIT-2763 Improves Erythropoiesis without Interfering with Iron Chelation Therapy in a Mouse Model of β-Thalassemia
Authors: Nyffenegger Naja , Flace Anna , Doucerain Cédric , Dürrenberger Franz , Manolova Vania
Published: January 2021

In β-thalassemia, ineffective erythropoiesis leads to anemia and systemic iron overload. The management of iron overload by chelation therapy is a standard of care. However, iron chelation does not improve the ineffective erythropoiesis. We recently showed that the oral ferroportin inhibitor VIT-2763 ameliorates anemia and erythropoiesis in the Hbbth3/+ mouse model of β-thalassemia. In this study, we investigated whether concurrent use of the iron chelator deferasirox (DFX) and the ferroportin inhibitor VIT-2763 causes any pharmacodynamic interactions in the Hbbth3/+ mouse model of β-thalassemia. Mice were treated with VIT-2763 or DFX alone or with the combination of both drugs once daily for three weeks. VIT-2763 alone or in combination with DFX improved anemia and erythropoiesis. VIT-2763 alone decreased serum iron and transferrin saturation (TSAT) but was not able to reduce the liver iron concentration. While DFX alone had no effect on TSAT and erythropoiesis, it significantly reduced the liver iron concentration alone and in the presence of VIT-2763. Our results clearly show that VIT-2763 does not interfere with the iron chelation efficacy of DFX. Furthermore, VIT-2763 retains its beneficial effects on improving ineffective erythropoiesis when combined with DFX in the Hbbth3/+ mouse model. In conclusion, co-administration of the oral ferroportin inhibitor VIT-2763 and the iron chelator DFX is feasible and might offer an opportunity to improve both ineffective erythropoiesis and iron overload in β-thalassemia.
Computational Functional Genomics-Based AmpliSeq™ Panel for Next-Generation Sequencing of Key Genes of Pain
Authors: Kringel Dario , Malkusch Sebastian , Kalso Eija , Lötsch Jörn
Published: January 2021

The genetic background of pain is becoming increasingly well understood, which opens up possibilities for predicting the individual risk of persistent pain and the use of tailored therapies adapted to the variant pattern of the patient’s pain-relevant genes. The individual variant pattern of pain-relevant genes is accessible via next-generation sequencing, although the analysis of all “pain genes” would be expensive. Here, we report on the development of a cost-effective next generation sequencing-based pain-genotyping assay comprising the development of a customized AmpliSeq™ panel and bioinformatics approaches that condensate the genetic information of pain by identifying the most representative genes. The panel includes 29 key genes that have been shown to cover 70% of the biological functions exerted by a list of 540 so-called “pain genes” derived from transgenic mice experiments. These were supplemented by 43 additional genes that had been independently proposed as relevant for persistent pain. The functional genomics covered by the resulting 72 genes is particularly represented by mitogen-activated protein kinase of extracellular signal-regulated kinase and cytokine production and secretion. The present genotyping assay was established in 61 subjects of Caucasian ethnicity and investigates the functional role of the selected genes in the context of the known genetic architecture of pain without seeking functional associations for pain. The assay identified a total of 691 genetic variants, of which many have reports for a clinical relevance for pain or in another context. The assay is applicable for small to large-scale experimental setups at contemporary genotyping costs.
Real-Time Fluorescence Image-Guided Oncolytic Virotherapy for Precise Cancer Treatment
Authors: Yano Shuya , Tazawa Hiroshi , Kishimoto Hiroyuki , Kagawa Shunsuke , Fujiwara Toshiyoshi , Hoffman Robert M.
Published: January 2021

Oncolytic virotherapy is one of the most promising, emerging cancer therapeutics. We generated three types of telomerase-specific replication-competent oncolytic adenovirus: OBP-301; a green fluorescent protein (GFP)-expressing adenovirus, OBP-401; and Killer-Red-armed OBP-301. These oncolytic adenoviruses are driven by the human telomerase reverse transcriptase (hTERT) promoter; therefore, they conditionally replicate preferentially in cancer cells. Fluorescence imaging enables visualization of invasion and metastasis in vivo at the subcellular level; including molecular dynamics of cancer cells, resulting in greater precision therapy. In the present review, we focused on fluorescence imaging applications to develop precision targeting for oncolytic virotherapy. Cell-cycle imaging with the fluorescence ubiquitination cell cycle indicator (FUCCI) demonstrated that combination therapy of an oncolytic adenovirus and a cytotoxic agent could precisely target quiescent, chemoresistant cancer stem cells (CSCs) based on decoying the cancer cells to cycle to S-phase by viral treatment, thereby rendering them chemosensitive. Non-invasive fluorescence imaging demonstrated that complete tumor resection with a precise margin, preservation of function, and prevention of distant metastasis, was achieved with fluorescence-guided surgery (FGS) with a GFP-reporter adenovirus. A combination of fluorescence imaging and laser ablation using a KillerRed-protein reporter adenovirus resulted in effective photodynamic cancer therapy (PDT). Thus, imaging technology and the designer oncolytic adenoviruses may have clinical potential for precise cancer targeting by indicating the optimal time for administering therapeutic agents; accurate surgical guidance for complete resection of tumors; and precise targeted cancer-specific photosensitization.
A Case Report of Germline Compound Heterozygous Mutations in the BRCA1 Gene of an Ovarian and Breast Cancer Patient
Authors: Kwong Ava , Ho Cecilia Y. S. , Shin Vivian Y. , Au Chun Hang , Chan Tsun Leung , Ma Edmond S. K.
Published: January 2021

The germline carrier of the BRCA1 pathogenic mutation has been well proven to confer an increased risk of breast and ovarian cancer. Despite BRCA1 biallelic pathogenic mutations being extremely rare, they have been reported to be embryonically lethal or to cause Fanconi anemia (FA). Here we describe a patient who was a 48-year-old female identified with biallelic pathogenic mutations of the BRCA1 gene, with no or very subtle FA-features. She was diagnosed with ovarian cancer and breast cancer at the ages of 43 and 44 and had a strong family history of breast and gynecological cancers.
Acute Cycling Exercise Induces Changes in Red Blood Cell Deformability and Membrane Lipid Remodeling
Authors: Nemkov Travis , Skinner Sarah C. , Nader Elie , Stefanoni Davide , Robert Mélanie , Cendali Francesca , Stauffer Emeric , Cibiel Agnes , Boisson Camille , Connes Philippe , D’Alessandro Angelo
Published: January 2021

Here we describe the effects of a controlled, 30 min, high-intensity cycling test on blood rheology and the metabolic profiles of red blood cells (RBCs) and plasma from well-trained males. RBCs demonstrated decreased deformability and trended toward increased generation of microparticles after the test. Meanwhile, metabolomics and lipidomics highlighted oxidative stress and activation of membrane lipid remodeling mechanisms in order to cope with altered properties of circulation resulting from physical exertion during the cycling test. Of note, intermediates from coenzyme A (CoA) synthesis for conjugation to fatty acyl chains, in parallel with reversible conversion of carnitine and acylcarnitines, emerged as metabolites that significantly correlate with RBC deformability and the generation of microparticles during exercise. Taken together, we propose that RBC membrane remodeling and repair plays an active role in the physiologic response to exercise by altering RBC properties.
An Advanced Abnormal Behavior Detection Engine Embedding Autoencoders for the Investigation of Financial Transactions
Authors: Demestichas Konstantinos , Peppes Nikolaos , Alexakis Theodoros , Adamopoulou Evgenia
Published: January 2021

Nowadays, (cyber)criminals demonstrate an ever-increasing resolve to exploit new technologies so as to achieve their unlawful purposes. Therefore, Law Enforcement Agencies (LEAs) should keep one step ahead by engaging tools and technology that address existing challenges and enhance policing and crime prevention practices. The framework presented in this paper combines algorithms and tools that are used to correlate different pieces of data leading to the discovery and recording of forensic evidence. The collected data are, then, combined to handle inconsistencies, whereas machine learning techniques are applied to detect trends and outliers. In this light, the authors of this paper present, in detail, an innovative Abnormal Behavior Detection Engine, which also encompasses a knowledge base visualization functionality focusing on financial transactions investigation.
Examining the Effects of Media-Generated Stereotypes on Receivers’ Trust and Attitude in Pakistan. Moderating Influence of Ethnicity and Gender
Authors: Raza Syed Hassan , Zaman Umer , Iftikhar Moneeba
Published: January 2021

There is a long-standing debate about the effects of media-generated stereotypes on receivers’ trust and attitude. However, there is insufficient consensus about their influence on the media receiver’s ecological perspective in determining their extent of trust and attitudes. Drawing an analogy from Differential Susceptibility to Media Effect Model (hereafter DSMM) notion that media effects are conditional and are contingent on differential-susceptibility, this study examines the influence of dispositional and social susceptibility to media. To do so, the study validates the influence of media user’s gender (dispositional susceptibility) and ethnicity (social susceptibility) in determining the outcomes of media-generated stereotypes, media trust (MT), and attitude towards media organization (AO). The survey method has been employed to collect data through a self-administered questionnaire from 1061 university students in public sector institutions in Pakistan. The results provide empirical evidence that media-generated stereotypes are a substantially negative predictor of media trust and attitudes towards the media organization. The results also validate that the influence of the stereotyping manifested by the receiver’s ecological perspective such as ethnicity and gender are crucial determinants of the receiver’s trust and attitudes. Managerially, the study urges that journalistic practices must be more ethnoculturally inclusive, to cope with the contemporary media landscape.
The Comparative Clinical Performance of Four SARS-CoV-2 Rapid Antigen Tests and Their Correlation to Infectivity In Vitro
Authors: Kohmer Niko , Toptan Tuna , Pallas Christiane , Karaca Onur , Pfeiffer Annika , Westhaus Sandra , Widera Marek , Berger Annemarie , Hoehl Sebastian , Kammel Martin , Ciesek Sandra , Rabenau Holger F.
Published: January 2021

Due to globally rising numbers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, resources for real-time reverse-transcription polymerase chain reaction (rRT-PCR)-based testing have been exhausted. In order to meet the demands of testing and reduce transmission, SARS-CoV-2 antigen-detecting rapid diagnostic tests (Ag-RDTs) are being considered. These tests are fast, inexpensive, and simple to use, but whether they detect potentially infectious cases has not been well studied. We evaluated three lateral flow assays (RIDA®QUICK SARS-CoV-2 Antigen (R-Biopharm), SARS-CoV-2 Rapid Antigen Test (Roche)), and NADAL® COVID-19 Ag Test (Nal von Minden GmbH, Regensburg, Germany) and one microfluidic immunofluorescence assay (SARS-CoV-2 Ag Test (LumiraDx GmbH, Cologne, Germany)) using 100 clinical samples. Diagnostic rRT-PCR and cell culture testing as a marker for infectivity were performed in parallel. The overall Ag-RDT sensitivity for rRT-PCR-positive samples ranged from 24.3% to 50%. However, for samples with a viral load of more than 6 log10 RNA copies/mL (22/100), typically seen in infectious individuals, Ag-RDT positivity was between 81.8% and 100%. Only 51.6% (33/64) of the rRT-PCR-positive samples were infectious in cell culture. In contrast, three Ag-RDTs demonstrated a more significant correlation with cell culture infectivity (61.8–82.4%). Our findings suggest that large-scale SARS-CoV-2 Ag-RDT-based testing can be considered for detecting potentially infective individuals and reducing the virus spread.
Translational Research in Retinopathy of Prematurity: From Bedside to Bench and Back Again
Authors: Arima Mitsuru , Fujii Yuya , Sonoda Koh-Hei
Published: January 2021

Retinopathy of prematurity (ROP), a vascular proliferative disease affecting preterm infants, is a leading cause of childhood blindness. Various studies have investigated the pathogenesis of ROP. Clinical experience indicates that oxygen levels are strongly correlated with ROP development, which led to the development of oxygen-induced retinopathy (OIR) as an animal model of ROP. OIR has been used extensively to investigate the molecular mechanisms underlying ROP and to evaluate the efficacy of new drug candidates. Large clinical trials have demonstrated the efficacy of anti-vascular endothelial growth factor (VEGF) agents to treat ROP, and anti-VEGF therapy is presently becoming the first-line treatment worldwide. Anti-VEGF therapy has advantages over conventional treatments, including being minimally invasive with a low risk of refractive error. However, long-term safety concerns and the risk of late recurrence limit this treatment. There is an unmet medical need for novel ROP therapies, which need to be addressed by safe and minimally invasive therapies. The recent progress in biotechnology has contributed greatly to translational research. In this review, we outline how basic ROP research has evolved with clinical experience and the subsequent emergence of new drugs. We discuss previous and ongoing trials and present the candidate molecules expected to become novel targets.
Fused Deposition Modelling of Fibre Reinforced Polymer Composites: A Parametric Review
Authors: Krajangsawasdi Narongkorn , Blok Lourens G. , Hamerton Ian , Longana Marco L. , Woods Benjamin K. S. , Ivanov Dmitry S.
Published: January 2021

Fused deposition modelling (FDM) is a widely used additive layer manufacturing process that deposits thermoplastic material layer-by-layer to produce complex geometries within a short time. Increasingly, fibres are being used to reinforce thermoplastic filaments to improve mechanical performance. This paper reviews the available literature on fibre reinforced FDM to investigate how the mechanical, physical, and thermal properties of 3D-printed fibre reinforced thermoplastic composite materials are affected by printing parameters (e.g., printing speed, temperature, building principle, etc.) and constitutive materials properties, i.e., polymeric matrices, reinforcements, and additional materials. In particular, the reinforcement fibres are categorized in this review considering the different available types (e.g., carbon, glass, aramid, and natural), and obtainable architectures divided accordingly to the fibre length (nano, short, and continuous). The review attempts to distil the optimum processing parameters that could be deduced from across different studies by presenting graphically the relationship between process parameters and properties. This publication benefits the material developer who is investigating the process parameters to optimize the printing parameters of novel materials or looking for a good constituent combination to produce composite FDM filaments, thus helping to reduce material wastage and experimental time.
Mechanical Characterization of Two Dental Restorative Materials after Acidic Challenge
Authors: Coelho Ana , Paula Anabela , Amaro Inês , Marto Carlos Miguel , Costa Nuno , Saraiva José , Ferreira Manuel Marques , Antunes Pedro , Carrilho Eunice
Published: January 2021

The aim of this study was to determine the effect of acidic beverages on the mechanical characteristics of a nanofilled composite resin and of a glass ionomer. Thirty specimens of each restorative material were produced and were evaluated at three different time points: before immersion (T0), after a 7 day immersion (T1) and after a 14 day immersion (T2) in water, beer and a soft drink. The studied parameters were microhardness and surface roughness. At T2, composite resin and glass ionomer specimens immersed in water, beer and the soft drink showed a statistically significant decrease in microhardness compared to T0 results. The surface roughness of composite resin specimens decreased between T0 and T1/T2 after immersion in beer and soft drink. A statistically significant increase was found between the roughness of glass ionomer specimens immersed in each one of the beverages at T0 and T1/T2. It is essential that clinicians are aware not only of available restorative materials, its characteristics and best handling techniques but also of the importance of performing an adequate assessment of patients’ dietary habits, thus making it possible to offer patients quality treatments with a predictable prognosis and longevity.