bluuebunny/crossref_metadata_2025 huggingface dataset:
TM9SF4 is a novel regulator in lineage commitment of bone marrow mesenchymal stem cells to either osteoblasts or adipocytes
Authors: Yu Libo , Xie Mingxu , Zhang Fengjie , Wan Chao , Yao Xiaoqiang
Published: November 2021

Background

Osteoporosis is a common bone disease in elderly population caused by imbalanced bone formation and bone resorption. Mesenchymal stem cells (MSCs) are responsible for maintaining this bone homeostasis. The phenotype of transmembrane 9 superfamily 4 (TM9SF4) knockout mice suggests a relationship between TM9SF4 proteins and bone homeostasis. But the effect of TM9SF4 in osteology has never been reported. In the present study, we investigated the function of TM9SF4 in MSC differentiation commitment, as well as its role in osteoporosis.

Methods

Primary bone marrow MSCs, isolated from TM9SF4 wildtype (TM9SF4+/+) and knockout (TM9SF4−/−) mice, were induced to differentiate into osteoblasts or adipocytes, respectively. The osteogenesis was examined by qRT-PCR detection of osteogenic markers, ALP staining and Alizarin Red S staining. The adipogenesis was tested by qRT-PCR quantification of adipogenic markers and Oil Red O staining. The cytoskeletal organization of MSCs was observed under confocal microscope. The osteoporotic model was induced by ovariectomy in TM9SF4+/+ and TM9SF4−/− mice, followed by Toluidine blue and H&E staining to assess lipid accumulation in trabecular bones, as well as micro-computed tomography scanning and immunohistochemistry staining for bone mass density assessment. The experiments on signaling pathways were conducted using qRT-PCR, Western blot and Alizarin Red S staining.

Results

We determined the role of TM9SF4 in MSC differentiation and found that TM9SF4−/− MSCs had higher potential to differentiate into osteoblasts and lower capability into adipocytes, without affecting osteoclastogenesis in vitro. In ovariectomy-induced osteoporotic model, TM9SF4−/− mice retained higher bone mass and less lipid accumulation in trabecular bones, indicating an important role of TM9SF4 in the regulation of osteoporosis. Mechanistically, TM9SF4-depleted cells showed elongated actin fibers, which may act through mTORC2/Akt/β-catenin pathway to promote their commitment into osteoblasts. Furthermore, TM9SF4-depleted cells showed higher activity of canonical Wnt pathway, suggesting the participation of Wnt/β-catenin during TM9SF4-regulated osteogenesis.

Conclusions

Our study demonstrates TM9SF4 as a novel regulator for MSC lineage commitment. Depletion of TM9SF4 preferentially drives MSCs into osteoblasts instead of adipocytes. Furthermore, TM9SF4−/− mice show delayed bone loss and reduced lipid accumulation during ovariectomy-induced osteoporosis. Our results indicate TM9SF4 as a promising target for the future clinical osteoporotic treatment.
Development of a human umbilical cord-derived mesenchymal stromal cell-based advanced therapy medicinal product to treat immune and/or inflammatory diseases
Authors: Mebarki Miryam , Iglicki Nathan , Marigny Céline , Abadie Camille , Nicolet Claire , Churlaud Guillaume , Maheux Camille , Boucher Hélène , Monsel Antoine , Menasché Philippe , Larghero Jérôme , Faivre Lionel , Cras Audrey
Published: November 2021

Background

Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) revealed their key role in immune regulation, offering promising therapeutic perspectives for immune and inflammatory diseases. We aimed to develop a production process of an UC-MSC-based product and then to characterize UC-MSC properties and immunomodulatory activities in vitro, related to their clinical use and finally, to transfer this technology to a good manufacturing practice (GMP) compliant facility, to manufacture an advanced therapy medicinal product (ATMP).

Methods

Fifteen human umbilical cords (UCs) were collected to develop the production process. Three batches of UC-MSCs from a single donor were characterized at basal state and after in vitro pro-inflammatory stimulation by interferon-γ (IFNγ) and tumor necrosis factor-α (TNFα). Proliferation, immunophenotype, activation markers’ expression and the inhibition of T cell proliferation were assessed. Finally, this technology was transferred to a GMP-compliant facility to manufacture an UC-MSC-based ATMP, from a single donor, using the explant method followed by the establishment of master and work cell stocks.

Results

Twelve UCs were processed successfully allowing to isolate UC-MSCs with doubling time and population doubling remaining stable until passage 4. CD90, CD105, CD73, CD44, CD29, CD166 expression was positive; CD14, CD45, CD31, HLA-DR, CD40, CD80 and CD86 expression was negative, while CD146 and HLA-ABC expression was heterogeneous. Cell morphology, proliferation and immunophenotype were not modified by inflammatory treatment. Indoleamine 2,3-dioxygenase (IDO) expression was significantly induced by IFNγ and IFNγ + TNFα versus non-treated cells. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expression was induced significantly after priming. T cell proliferation was significantly decreased in the presence of UC-MSCs in a dose-dependent manner. This inhibitory effect was improved by IFNγ or IFNγ + TNFα, at UC-MSCs:PBMC ratio 1:10 and 1:30, whereas only IFNγ allowed to decrease significantly T cell proliferation at ratio 1:100. The manufacturing process of the UC-MSC-based ATMP was qualified and authorized by the French regulatory agency for clinical use (NCT04333368).

Conclusion

This work allowed to develop an investigational UC-MSC-based ATMP authorized for clinical use. Our results showed that an inflammatory environment preserves the biological properties of UC-MSCs with an improvement of their immunomodulatory functions.
Hydrogel-hydroxyapatite-monomeric collagen type-I scaffold with low-frequency electromagnetic field treatment enhances osteochondral repair in rabbits
Authors: Yan Jiyuan , Liu Chaoxu , Tu Chang , Zhang Ruizhuo , Tang Xiangyu , Li Hao , Wang Huaixi , Ma Yongzhuang , Zhang Yingchi , Wu Hua , Sheng Gaohong
Published: November 2021

Background

Cartilage damage is a common medical issue in clinical practice. Complete cartilage repair remains a significant challenge owing to the inferior quality of regenerative tissue. Safe and non-invasive magnetic therapy combined with tissue engineering to repair cartilage may be a promising breakthrough.

Methods

In this study, a composite scaffold made of Hydroxyapatite-Collagen type-I (HAC) and PLGA-PEG-PLGA thermogel was produced to match the cartilage and subchondral layers in osteochondral defects, respectively. Bone marrow mesenchymal stem cells (BMSC) encapsulated in the thermogel were stimulated by an electromagnetic field (EMF). Effect of EMF on the proliferation and chondrogenic differentiation potential was evaluated in vitro. 4 mm femoral condyle defect was constructed in rabbits. The scaffolds loaded with BMSCs were implanted into the defects with or without EMF treatment. Effects of the combination treatment of the EMF and composite scaffold on rabbit osteochondral defect was detected in vivo.

Results

In vitro experiments showed that EMF could promote proliferation and chondrogenic differentiation of BMSCs partly by activating the PI3K/AKT/mTOR and Wnt1/LRP6/β-catenin signaling pathway. In vivo results further confirmed that the scaffold with EMF enhances the repair of osteochondral defects in rabbits, and, in particular, cartilage repair.

Conclusion

Hydrogel-Hydroxyapatite-Monomeric Collagen type-I scaffold with low-frequency EMF treatment has the potential to enhance osteochondral repair.
Biofunctionalised bacterial cellulose scaffold supports the patterning and expansion of human embryonic stem cell-derived dopaminergic progenitor cells
Authors: Robbins Miranda , Pisupati Venkat , Azzarelli Roberta , Nehme Samer I. , Barker Roger A. , Fruk Ljiljana , Schierle Gabriele S. Kaminski
Published: November 2021

Background

Stem cell-based therapies for neurodegenerative diseases like Parkinson’s disease are a promising approach in regenerative medicine and are now moving towards early stage clinical trials. However, a number of challenges remain including the ability to grow stem cells in vitro on a 3-dimensional scaffold, as well as their loss, by leakage or cell death, post-implantation. These issues could, however, be helped through the use of scaffolds that support the growth and differentiation of stem cells both in vitro and in vivo. The present study focuses on the use of bacterial cellulose as an in vitro scaffold to promote the growth of different stem cell-derived cell types. Bacterial cellulose was used because of its remarkable properties such as its wettability, ability to retain water and low stiffness, all of which is similar to that found in brain tissue.

Methods

We cultured human embryonic stem cell-derived progenitor cells on bacterial cellulose with growth factors that were covalently functionalised to the surface via silanisation. Epifluorescence microscopy and immunofluorescence were used to detect the differentiation of stem cells into dopaminergic ventral midbrain progenitor cells. We then quantified the proportion of cells that differentiated into progenitor cells and compared the effect of growing cells on biofunctionalised cellulose versus standard cellulose.

Results

We show that the covalent functionalisation of bacterial cellulose sheets with bioactive peptides improves the growth and differentiation of human pluripotent stem cells into dopaminergic neuronal progenitors.

Conclusions

This study suggests that the biocompatible material, bacterial cellulose, has potential applications in cell therapy approaches as a means to repair damage to the central nervous system, such as in Parkinson’s disease but also in tissue engineering.
Semi-automated workflow for molecular pair analysis and QSAR-assisted transformation space expansion
Authors: Yang Zi-Yi , Fu Li , Lu Ai-Ping , Liu Shao , Hou Ting-Jun , Cao Dong-Sheng
Published: November 2021

In the process of drug discovery, the optimization of lead compounds has always been a challenge faced by pharmaceutical chemists. Matched molecular pair analysis (MMPA), a promising tool to efficiently extract and summarize the relationship between structural transformation and property change, is suitable for local structural optimization tasks. Especially, the integration of MMPA with QSAR modeling can further strengthen the utility of MMPA in molecular optimization navigation. In this study, a new semi-automated procedure based on KNIME was developed to support MMPA on both large- and small-scale datasets, including molecular preparation, QSAR model construction, applicability domain evaluation, and MMP calculation and application. Two examples covering regression and classification tasks were provided to gain a better understanding of the importance of MMPA, which has also shown the reliability and utility of this MMPA-by-QSAR pipeline.
Deep scaffold hopping with multimodal transformer neural networks
Authors: Zheng Shuangjia , Lei Zengrong , Ai Haitao , Chen Hongming , Deng Daiguo , Yang Yuedong
Published: November 2021

Scaffold hopping is a central task of modern medicinal chemistry for rational drug design, which aims to design molecules of novel scaffolds sharing similar target biological activities toward known hit molecules. Traditionally, scaffolding hopping depends on searching databases of available compounds that can't exploit vast chemical space. In this study, we have re-formulated this task as asupervised molecule-to-molecule translationto generate hopped molecules novel in 2D structure but similar in 3D structure, as inspired by the fact that candidate compounds bind with their targets through 3D conformations. To efficiently train the model, we curated over 50 thousand pairs of molecules with increased bioactivity, similar 3D structure, but different 2D structure from public bioactivity database, which spanned 40 kinases commonly investigated by medicinal chemists. Moreover, we have designed a multimodal molecular transformer architecture by integrating molecular 3D conformer through a spatial graph neural network and protein sequence information through Transformer. The trained DeepHop model was shown able to generate around 70% molecules having improved bioactivity together with high 3D similarity but low 2D scaffold similarity to the template molecules. This ratio was 1.9 times higher than other state-of-the-art deep learning methods and rule- and virtual screening-based methods. Furthermore, we demonstrated that the model could generalize to new target proteins through fine-tuning with a small set of active compounds. Case studies have also shown the advantages and usefulness of DeepHop in practical scaffold hopping scenarios.
Radar signal recognition based on triplet convolutional neural network
Authors: Liu Lutao , Li Xinyu
Published: November 2021

Recently, due to the wide application of low probability of intercept (LPI) radar, lots of recognition approaches about LPI radar signal modulations have been proposed. However, facing the increasingly complex electromagnetic environment, most existing methods have poor performance to identify different modulation types in low signal-to-noise ratio (SNR). This paper proposes an automatic recognition method for different LPI radar signal modulations. Firstly, time-domain signals are converted to time-frequency images (TFIs) by smooth pseudo-Wigner–Ville distribution. Then, these TFIs are fed into a designed triplet convolutional neural network (TCNN) to obtain high-dimensional feature vectors. In essence, TCNN is a CNN network that triplet loss is adopted to optimize parameters of the network in the training process. The participation of triplet loss can ensure that the distance between samples in different classes is greater than that between samples with the same label, improving the discriminability of TCNN. Eventually, a fully connected neural network is employed as the classifier to recognize different modulation types. Simulation shows that the overall recognition success rate can achieve 94% at − 10 dB, which proves the proposed method has a strong discriminating capability for the recognition of different LPI radar signal modulations, even under low SNR.
Generalized proportional fractional integral Hermite–Hadamard’s inequalities
Authors: Aljaaidi Tariq A. , Pachpatte Deepak B. , Abdeljawad Thabet , Abdo Mohammed S. , Almalahi Mohammed A. , Redhwan Saleh S.
Published: November 2021

The theory of fractional integral inequalities plays an intrinsic role in approximation theory also it has been a key in establishing the uniqueness of solutions for some fractional differential equations. Fractional calculus has been found to be the best for modeling physical and engineering processes. More precisely, the proportional fractional operators are one of the recent important notions of fractional calculus. Our aim in this research paper is developing some novel ways of fractional integral Hermite–Hadamard inequalities in the frame of a proportional fractional integral with respect to another strictly increasing continuous function. The considered fractional integral is applied to establish some new fractional integral Hermite–Hadamard-type inequalities. Moreover, we present some special cases throughout discussing this work.
Early innovations in opioid use disorder treatment and harm reduction during the COVID-19 pandemic: a scoping review
Authors: Krawczyk Noa , Fawole Adetayo , Yang Jenny , Tofighi Babak
Published: November 2021

Background

The COVID-19 pandemic has exerted a significant toll on the lives of people who use opioids (PWUOs). At the same time, more flexible regulations around provision of opioid use disorder (OUD) services have led to new opportunities for facilitating access to services for PWUOs. In the current scoping review, we describe new services and service modifications implemented by treatment and harm reduction programs serving PWUO, and discuss implications for policy and practice.

Methods

Literature searches were conducted within PubMed, LitCovid, Embase, and PsycInfo for English-language studies published in 2020 that describe a particular program, service, or intervention aimed at facilitating access to OUD treatment and/or harm reduction services during the COVID-19 pandemic. Abstracts were independently screened by two reviewers. Relevant studies were reviewed in full and those that met inclusion criteria underwent final data extraction and synthesis (n = 25). We used a narrative synthesis approach to identify major themes around key service modifications and innovations implemented across programs serving PWUO.

Results

Reviewed OUD treatment and harm reduction services spanned five continents and a range of settings from substance use treatment to street outreach programs. Innovative service modifications to adapt to COVID-19 circumstances primarily involved expanded use of telehealth services (e.g., telemedicine visits for buprenorphine, virtual individual or group therapy sessions, provision of donated or publicly available phones), increased take-home medication allowances for methadone and buprenorphine, expanded uptake of long-acting opioid medications (e.g. extended-release buprenorphine and naltrexone), home delivery of services (e.g. MOUD, naloxone and urine drug screening), outreach and makeshift services for delivering MOUD and naloxone, and provision of a safe supply of opioids.

Conclusions

The COVID-19 pandemic has posed multiple challenges for PWUOs, while simultaneously accelerating innovations in policies, care models, and technologies to lower thresholds for life-saving treatment and harm reduction services. Such innovations highlight novel patient-centered and feasible approaches to mitigating OUD related harms. Further studies are needed to assess the long-term impact of these approaches and inform policies that improve access to care for PWUOs.
Comprehensive well-being scale: development and validation among Chinese in recovery of mental illness in Hong Kong
Authors: Sham Will W. L. , Yeung Gladys T. Y. , Mak Winnie W. S. , Powell Candice L. Y. M.
Published: November 2021

Background

Given the absence of a brief scale that reconciles and encompasses different conceptual definitions of well-being (physical, psychological, social and spiritual), the present research aimed at developing and validating a Comprehensive Well-Being Scale (CWBS) that encompasses these different conceptual definition and extend the definition of well-being to transcendental well-being among individuals in recovery of mental illness. The present research focuses on testing the scale among people in recovery of mental illness so that a brief and theoretically comprehensive scale would be available for mental health organization to evaluate the well-being of service users, and to develop and evaluate well-being related services.

Methods

A 56-item preliminary well-being scale was developed by a professional panel. In Study 1, 300 mental health service users in Hong Kong were recruited. Twenty items were selected through principal component analysis to form the CWBS. In Study 2, another sample of 300 service users was recruited. Confirmatory factor analysis was done to confirm a two-factor structure. Validity of the scale was also examined.

Results

The CWBS yielded good internal consistency (Cronbach’s alphas = .79–.91). The finding supported a two-factor structure, namely Intrapersonal Well-Being, and Transpersonal Well-Being, χ2 (169) = 335.61, p < .001, CFI = .90, RMSEA = .06, SRMR = .06.

Conclusions

The CWBS established concurrent and construct validity in assessing well-being among Chinese in recovery of mental illness in Hong Kong. It provided theoretical and practical implications for measuring well-being. Theoretically, it extended the concept of well-being to encompass transcendental well-being in model of recovery among individuals recovery from mental illness. Practically, it provided a tool for evaluation of well-being and service development in mental health organization.
A novel fragmented anode biofilm microbial fuel cell (FAB–MFC) integrated system for domestic wastewater treatment and bioelectricity generation
Authors: Atnafu Tesfalem , Leta Seyoum
Published: November 2021

Background

The critical MFC design challenge is to increase anode surface area. A novel FAB–MFC integrated system was developed and evaluated for domestic wastewater treatment. It was operated in fed-batch flow mode at 1–3 days of HRT with 755 mg/L CODIN and 0.76 kg-COD/m3/day. The study includes anaerobic-MFC and aerobic-MFC integrated systems. Microbial electrode jacket dish (MEJ-dish) with hybrid dimension (HD) was invented, first time to authors’ knowledge, to boost anode biofilm growth. The treatment system with MEJ+ (FAB) and MEJ− (MFC) anode are called FAB–MFC and MFC, respectively.

Results

Fragmented variable anode biofilm thickness was observed in FAB than MFC. The FAB–MFC (FAB+) simple technique increases the anode biofilm thickness by ~ 5 times MFC. Due to HD the anode biofilm was fragmented in FAB+ system than MFC. At the end of each treatment cycle, voltage drops. All FAB+ integrated systems reduced voltage drop relative to MFC. FAB reduces voltage drops better than MFC in anaerobic-MFC from 6 to 20 mV and aerobic-MFC from 35–47 mV at 1 kΩ external load. The highest power density was achieved by FAB in anaerobic-MFC (FAB = 104 mW/m2, MFC = 98 mW/m2) and aerobic-MFC integrated system (FAB = 59 mW/m2, MFC = 42 mW/m2).

Conclusions

The ∆COD and CE between FAB and MFC could not be concluded because both setups were inserted in the same reactor. The integrated system COD removal (78–97%) was higher than the solitary MFC treatment (68–78%). This study findings support the FAB+ integrated system could be applied for real applications and improve performance. However, it might depend on influent COD, the microbial nature, and ∆COD in FAB+ and MFC, which requires further study.

Graphic abstract
True grit: ingestion of small stone particles by hummingbirds in West Mexico
Authors: Maya-García Omar , Ortega-Flores Mauricio , Schondube Jorge E.
Published: November 2021

Background

Grit is used by birds mainly for grinding hard food items but can also serve a nutritional role as a source of minerals. Ingestion of grit by birds has been documented primarily in species that feed on seeds and invertebrates. Although feeding mainly on nectar and small arthropods, hummingbirds also ingest grit, but why they do so is unclear. We quantified the number of grit particles in the stomachs of six species of hummingbirds during an annual cycle in a seasonal ecosystem of West Mexico.

Methods

We compared the number of grit particles in the stomachs of different hummingbird species (Mexican VioletearColibri thalassinus, Amethyst-throated MountaingemLampornis amethystinus, White-eared HummingbirdBasilinna leucotis, Rivoli’s HummingbirdEugenes fulgens, Broad-tailed HummingbirdSelasphorus platycercus, and Rufous HummingbirdS. rufus), and between sex and age categories during the different seasons of a year. To determine if grit was used to grind ingested arthropods, we examined the relationships between the number of grit particles, the biomass of arthropods ingested, and their chitin content.

Results

Although species did not differ in the number of grit particles in their stomachs, we found that grit was mostly ingested by female individuals, with only one male of one species (Mexican Violetear) presenting grit in its stomach. We also found that female hummingbirds had grit in their stomachs during the rainy and the cold-dry season (June–February) but not during the warm-dry season (March–May). Our analyses revealed no relationship between the number of grit particles and the amount of ingested arthropods and arthropod chitin content. However, high grit consumption was related to wasp ingestion on Mexican Violetears.

Conclusions

Our results indicate that grit is used mainly by female hummingbirds. The seasonal variation in the ingestion of grit by female individuals suggests that it can be used to meet mineral requirements related to breeding; however, this topic needs further exploration. Additionally, the use of grit was proportionally higher in juvenile individuals, suggesting it is used for grinding arthropods during a period of fast development.
Treatment outcomes of implant-assisted removable partial denture with distal extension based on the Kennedy classification and attachment type: a systematic review
Authors: Putra Wigianto Adityakrisna Yoshi , Goto Takaharu , Iwawaki Yuki , Ishida Yuichi , Watanabe Megumi , Ichikawa Tetsuo
Published: November 2021

Background

Implant-assisted removable partial dentures (IARPDs) have recently become popular, but little information is available on the treatment outcomes based on the Kennedy classification and attachment types.

Objective

The objective of this review was to evaluate the treatment outcomes of IARPD delivered for distal extension edentulous areas based on the differences in the Kennedy classification and attachment type.

Materials and methods

English-language clinical studies on IARPD published between January 1980 and February 2020 were collected from MEDLINE (via PubMed), the Cochrane Library (via the Cochrane Central Register of Controlled Trials), Scopus online database, and manual searching. Two reviewers selected the articles based on pre-determined inclusion and exclusion criteria, followed by data extraction and analysis.

Results

Eighty-one studies were selected after evaluating the titles and abstracts of 2410 papers. Nineteen studies were finally included after the perusal of the full text. Fourteen studies focused on Class I, 4 studies investigated both Class I and II, and only 1 study was conducted on Kennedy’s class II. Eight types of attachments were reported. The ball attachment was the most frequently used attachment, which was employed in 8 of the included studies. The implant survival rate ranged from 91 to 100%. The reported marginal bone loss ranged from 0.3 mm to 2.30 mm. The patient satisfaction was higher with IARPD than with conventional RPDs or that before treatment. The results of prosthetic complications were heterogeneous and inconclusive.

Conclusion

IARPD exhibited favorable clinical outcomes when used as a replacement for distal extension edentulous areas. The comparison between the clinical outcomes of Kennedy’s class I and II was inconclusive owing to the lack of studies focusing on Kennedy Class II alone. The stud attachment was the most commonly used type in IARPDs. Overall, the different attachment systems did not influence the implant survival rate and patient satisfaction. Further high-quality studies are needed to investigate the attachment systems used in IARPD.
Enhancing banknote authentication by guiding attention to security features and manipulating prevalence expectancy
Authors: van der Horst Frank , Snell Joshua , Theeuwes Jan
Published: November 2021

All banknotes have security features which are intended to help determine whether they are false or genuine. Typically, however, the general public has limited knowledge of where on a banknote these security features can be found. Here, we tested whether counterfeit detection can be improved with the help of salient elements, designed to guide bottom-up visuospatial attention. We also tested the influence of the participant’s a priori level of trust in the authenticity of the banknote. In an online study (N = 422), a demographically diverse panel of Dutch participants distinguished genuine banknotes from banknotes with one (left- or right-sided) counterfeited security feature. Either normal banknotes (without novel design elements) or banknotes that contained a salient element (a pink rectangular frame) were presented for 1 s. To manipulate the participant’s level of trust, trials were administered in three blocks, whereby at the start of each block, participants were instructed that either one third, one half, or two thirds of the upcoming banknotes were counterfeit (though the true ratio was always 1:1). We hypothesized (i) that in the presence of a salient element, counterfeits would be better detected when the location of the salient element aligned with the location of the counterfeited security feature—i.e. that it would act as an attentional cue; and (ii) that this effect would be stronger with lower trust. Our hypotheses were partly confirmed: counterfeit detection improved with ‘valid cues’ and decreasing trust, but the level of trust did not modulate the cueing effect. As the overall detection performance was rather poor, we replicated the study with a sample of university students (N = 66), this time presenting stimuli until response. While indeed observing better overall performance, all other patterns were replicated. Our results provide evidence that attention can be guided to enhance banknote authentication.
Evaluation of insecticidal potential of organochemicals on SF9 cell line
Authors: Pandya Nishi , Thakkar Bhumi , Pandya Parth , Parikh Pragna
Published: November 2021

Background

Organophosphates and Pyrethroids are the most widely used pesticides worldwide and are known to have significant toxicity on the nervous system of the target pest. Assessment for combined toxicity of Organophosphate and Pyrethroid on Sf9 (Spodoptera frugiperda) cells is less explored. The present study demonstrates and compares the two organochemicals whose trade names are Ammo and Profex, for its cytotoxic potential on the insect Sf9 cells. Ammo and Profex were selected as the test chemicals as toxicity of these insecticides at molecular and cellular level is poorly understood.

Results

The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay demonstrated that Ammo and Profex exhibited significant cytotoxicity to Sf9 cells in a time- and dose-dependent manner. In our study, the IC50 value was obtained by MTT assay and the sub-lethal concentrations (IC50/20-17.5 µg/ml, IC50/10-35 µg/ml, and IC50/5–70 µg/ml for Ammo and IC50/20-20 µg/ml, IC50/10-40 µg/ml, and IC50/5-80 µg/ml for Profex) were selected for further tests. Acridine orange/ethidium bromide staining proved the apoptotic cell death on exposure of both the insecticides confirming its toxic potential. Furthermore, antioxidant status was assessed using DCF-DA staining and both the insecticides resulted into an increased reactive oxygen species (ROS) generation. A dose- and time-dependent significant (p < 0.05) alterations in lipid peroxidase (LPO), glutathione (GSH) and catalase (CAT) activity were observed.

Conclusion

The results showed that both Ammo and Profex triggered apoptosis in Sf9 cells through an intrinsic mitochondrial pathway via the generation of ROS. Of the two insecticides, Ammo was found to be more toxic compared to Profex. The present study is important to evaluate the environmental safety and risk factors of Organochemicals’ exposure to crops and livestock.
Regulated free banking in Switzerland (1881–1907)
Authors: Herger Nils
Published: November 2021

The free-banking history of Switzerland is subdivided into periods with unfettered competition (1826–1881), and strict banknote regulation (1881–1907). This paper suggests that the Federal Banknote Act of 1881 was introduced to remedy the fragmentation of the unfettered-competition period, during which private note-issuing banks were unable to issue standardised paper money. Although the corresponding minimum-reserve and mutual-acceptance rules led to a standardisation, they created new problems. For example, these regulatory interventions reduced the flexibility (or “elasticity”) of the paper-money supply. It turned out that a central note-issuing bank is needed to supply adequate amounts of standardised banknotes.
A comprehensive review on RAGE-facilitated pathological pathways connecting Alzheimer’s disease, diabetes mellitus, and cardiovascular diseases
Authors: Chakraborty Agnila , Sami Saad Ahmed , Marma Kay Kay Shain
Published: November 2021

Background

Alzheimer’s disease (AD), cardiovascular disease (CVD), and diabetes are some of the most common causes of morbidity and mortality among the aging populations and cause a heavy burden on the worldwide healthcare system. In this review, we briefly highlighted cellular inflammation-based pathways of diabetes mellitus and CVD through receptor for advanced glycation end products AGEs or RAGE leading to Alzheimer’s disease and interrelation between these vascular and metabolic disorders. The articles were retrieved from Google Scholar, Science Direct, and PubMed databases using the following terms: Alzheimer’s; AGEs; RAGE; RAGE in Alzheimer’s; AGEs in Alzheimer’s; RAGE in diabetes; RAGE related pathways of CVD; RAGE in hypertension; RAGE and RAS system; RAGE and oxidative stress.

Main body of the abstract

AD is a neurodegenerative disease characterized by cognitive dysfunction and neuronal cell death. Vascular complications like hypertension, coronary artery disease, and atherosclerosis as well as metabolic syndromes like obesity and diabetes are related to the pathophysiology of AD. RAGE plays significant role in the onset and progression of AD. Amyloid plaques and neurofibrillary tangles (NFT) are two main markers of AD that regulates via RAGE and other RAGE/ligands interactions which also induces oxidative stress and a cascade of other cellular inflammation pathways leading to AD. Though AD and diabetes are two different disorders but may be inter-linked by AGEs and RAGE. In long-term hyperglycemia, upregulated AGEs interacts with RAGE and produces reactive oxygen species which induces further inflammation and vascular complications. Aging, hypercholesterolemia, atherosclerosis, hypertension, obesity, and inflammation are some of the main risk factors for both diabetes and dementia. Chronic hypertension and coronary artery disease disrupt the functions of the blood-brain barrier and are responsible for the accumulation of senile plaques and NFTs.

Short conclusion

RAGE plays a role in the etiology of Aβ and tau hyperphosphorylation, both of which contribute to cognitive impairment. So far, targeting RAGE may provide a potential sight to develop therapies against some metabolic disorders.
Evaluation of tool performance and wear through vibration signature analysis in drilling of IS3048 steel
Authors: Sridhar Annavarapu Venkata , Prasad Balla Srinivasa , Mouli K. V. V. N. R. Chandra
Published: November 2021

In this paper, a connection between vibration amplitude and tool wear when drilling of IS3048 steel utilizing different dimensioned tools is dissected through tests. Discriminant features, which are sensitive to drill wear and breakage, were developed. These were discovered to be somewhat impervious toward sensor location and cutting conditions. In the process, the vibration amplitude features a checking highlight dependent on ascertaining both the tools and their performance over vibrations, which was discovered to be somewhat powerful for on-line identification of drill tool breakage in both frequency and time domains. These vibrational amplitude signal features are directly affected, related to the tool geometry, which give higher chances of tool selection criteria during the drilling process. The experiments were carried out using solid carbide tool with change in tool geometry under dry conditions where the vibration amplitude for both is evaluated. The results revealed that cutting tool vibrational amplitude and tool wear were relatively dependent showing the tool selection of suitable tool geometry.
Distinct Survival Outcomes in Subgroups of Stage III Pancreatic Cancer Patients: Taiwan Cancer Registry and Surveillance, Epidemiology and End Results registry
Authors: Lu Tzu-Pin , Wu Chien-Hui , Chang Chia-Chen , Chan Han-Ching , Chattopadhyay Amrita , Lee Wen-Chung , Chiang Chun-Ju , Lee Hsin-Ying , Tien Yu-Wen
Published: November 2021

Purpose

Pancreatic cancer is one of the most malignant cancers with poor survival. The latest edition of the American Joint Committee on Cancer (AJCC) staging system classifies the majority of operable pancreatic cancer patients as stage-III, while dramatic heterogeneity is observed among these patients. Therefore, subgrouping is required to accurately predict their prognosis and define a treatment plan. This study conducts a cohort study to provide a more precise classification system for stage-III pancreatic cancer patients by utilizing clinical variables.

Methods

We analyzed survival using log-rank tests, univariate Cox-regression models, and Kaplan-Meier survival curves for stage-III pancreatic ductal adenocarcinoma (PDAC) patients from the Taiwan Cancer Registry (TCR). Patients were further divided into subgroups using classification and regression tree (CART) algorithm. All results were validated using the SEER database.

Results

Among stage-III PDAC patients, lymph node and tumor grade showed significant association with survival. Patients with N2 stage had higher mortality risks (hazard ratio [HR] = 2.30, 95% confidence interval [CI] 1.71–3.08, p < 0.0001) than N0 patients. Patients with grade 3 also had higher risk of mortality (HR = 3.80, 95% CI 2.25–6.39, p < 0.0001) than grade 1 patients. The CART algorithm stratified stage-III patients into four subgroups with significantly different survival rates. The median survival of the four subgroups was 23.5, 18.4, 14.5, and 9.0 months, respectively (p < 0.0001). Similar results were observed with SEER data.

Conclusions

Lymph node involvement and tumor grade are predictive factors for survival in stage-III PDAC patients. This new precise classification system can be used to guide treatment planning in advanced-stage pancreatic cancer.
Low-Load Blood Flow Restriction and High-Load Resistance Training Induce Comparable Changes in Patellar Tendon Properties
Authors: Centner Christoph , Jerger Simon , Lauber Benedikt , Seynnes Olivier , Friedrich Till , Lolli David , Gollhofer Albert , König Daniel
Published: November 2021

Introduction

Low-load resistance training with blood flow restriction (LL-BFR) has emerged as a viable alternative to conventional high-load (HL) resistance training regimens. Despite increasing evidence confirming comparable muscle adaptations between LL-BFR and HL resistance exercise, only very little is known about tendinous mechanical and morphological adaptations after LL-BFR. Therefore, the aim of the present study was to examine the effects of 14 wk of LL-BFR and HL training on patellar tendon adaptations.

Methods

Twenty-nine recreationally active male participants were randomly allocated into the following two groups: LL-BFR resistance training (20%–35% one-repetition maximum (1RM)) or HL resistance training (70%–85% 1RM). Both groups trained three times per week for 14 wk. One week before and after the intervention, patellar tendon mechanical and morphological properties were assessed via ultrasound and magnetic resonance imaging. In addition, changes in muscle cross-sectional area were quantified by magnetic resonance imaging and muscle strength via dynamic 1RM measurements.

Results

The findings demonstrated that both LL-BFR and HL training resulted in comparable changes in patellar tendon stiffness (LL-BFR: +25.2%, P = 0.003; HL: +22.5%, P = 0.024) without significant differences between groups. Similar increases in tendon cross-sectional area were observed in HL and LL-BFR. Muscle mass and strength also significantly increased in both groups but were not statistically different between HL (+38%) and LL-BFR (+34%), except for knee extension 1RM where higher changes were seen in LL-BFR.

Conclusions

The present results support the notion that both HL and LL-BFR cause substantial changes in patellar tendon properties, and the magnitude of changes is not significantly different between conditions. Further studies that examine the physiological mechanisms underlying the altered tendon properties after LL-BFR training are needed.
Classification of Runners with High versus Low Hip Adduction Based on Measures of Pelvis and Femur Morphology
Authors: Liu Jia , Powers Christopher M.
Published: November 2021

Purpose

To determine the most relevant pelvis and femur morphological characteristics for differentiating runners with high versus low hip adduction during running.

Methods

Fifteen female and 14 male runners underwent instrumented kinematics analysis of overground running and computed tomography scanning of pelvis and femur. The peak hip adduction angle during the stance phase of running was identified for each participant. Using the cohort average of the peak hip adduction angle as the classifying threshold, participants were categorized into high or low hip adduction groups. To determine the most relevant morphologic features for discriminating high and low hip adduction runners, a feature selection-based support vector machine classification analysis was performed.

Results

Of the 15 morphology variables examined, femoral head anteversion and femur length were shown to be the best discriminant variables for group classification. Together, these variables achieved a prediction accuracy of 0.93, sensitivity of 1.0, and specificity of 0.88.

Conclusions

Our results highlight the importance of femur morphology in contributing to increased hip adduction during running.
Tart Cherry Supplement Enhances Skeletal Muscle Glutathione Peroxidase Expression and Functional Recovery after Muscle Damage
Authors: Wangdi Jimmy T. , O’Leary Mary F. , Kelly Vincent G. , Jackman Sarah R. , Tang Jonathan C. Y. , Dutton John , Bowtell Joanna L.
Published: November 2021

Introduction

Montmorency cherry concentrate (MCC) supplementation enhances functional recovery from exercise, potentially due to antioxidant and anti-inflammatory effects. However, to date, supporting empirical evidence for these mechanistic hypotheses is reliant on indirect blood biomarkers. This study is the first to investigate functional recovery from exercise alongside molecular changes within the exercised muscle after MCC supplementation.

Methods

Ten participants completed two maximal unilateral eccentric knee extension trials after MCC or placebo (PLA) supplementation for 7 d before and 48 h after exercise. Knee extension maximum voluntary contractions, maximal isokinetic contractions, single leg jumps, and soreness measures were assessed before, immediately, 24 h, and 48 h after exercise. Venous blood and vastus lateralis muscle samples were collected at each time point. Plasma concentrations of interleukin-6, tumor necrosis factor alpha, C-reactive protein, creatine kinase, and phenolic acids were quantified. Intramuscular mRNA expressions of superoxide dismutase 1 (SOD1), SOD3, glutathione peroxidase 1 (GPX1), GPX3, GPX4, GPX7, catalase, and nuclear factor erythroid 2–related factor 2 and relative intramuscular protein expressions of SOD1, catalase, and GPX3 were quantified.

Results

MCC supplementation enhanced the recovery of normalized maximum voluntary contraction 1-s average compared with PLA (postexercise PLA, 59.5% ± 18.0%, vs MCC, 76.5% ± 13.9%; 24 h PLA, 69.8% ± 15.9%, vs MCC, 80.5% ± 15.3%; supplementation effect P = 0.024). MCC supplementation increased plasma hydroxybenzoic, hippuric, and vanillic acid concentrations (supplementation effect P = 0.028, P = 0.002, P = 0.003); SOD3, GPX3, GPX4, GPX7 (supplement effect P < 0.05), and GPX1 (interaction effect P = 0.017) gene expression; and GPX3 protein expression (supplementation effect P = 0.004) versus PLA. There were no significant differences between conditions for other outcome measures.

Conclusions

MCC supplementation conserved isometric muscle strength and upregulated antioxidant gene and protein expression in parallel with increased phenolic acid concentrations.
Too Scared to Shop: the Role of Apatephobia, Trust, Risk, and Suspicion in Market Exchanges
Authors: Wardley Marcus
Published: November 2021

According to the U.S. Federal Trade Commission, in 2018 there were over 1.4 million reports of fraud resulting in an estimated loss to consumers of $1.48 billion (Federal Trade Commission, 2019). A natural reaction to the prevalence of fraudulent transactions is apatephobia,
or a fear of intentional deception leading to less desirable outcomes in a market exchange. The current paper relates apatephobia to the literature on trust, risk, suspicion, defensive processing, emotions, and counterfactual thinking and offers 15 propositions related to these constructs.
Further, a nomological network is proposed which relates these constructs together, identifies the conditions under which apatephobia will result in a consumer declining to engage in an exchange, and the feedback mechanism by which being deceived strengthens the motivation to avoid any future
reoccurrence. Little academic attention has been paid to a fear of being deceived, thus I expect the current work to be of interest to researchers in the area of trust, risk, and deception.
Antecedents of Satisfaction with Facebook in the Context of User Involvement, Privacy, and Trust
Authors: Sethna Beheruz N. , Hazari Sunil , Talpade Salil
Published: November 2021

Social media networks such as Facebook serve as effective channels for the distribution of marketing information and news. Constructs such as privacy, trust, and involvement may impact user satisfaction which impacts advertising revenue earned by Facebook. A survey was given to 400
Facebook users using scales developed from existing literature. Questions on Facebook use, elements related to privacy, trust, involvement, satisfaction, and demographic data were collected from survey questions. Using the theoretical lens of ExpectationConfirmation Theory, the constructs
of involvement, privacy, and trust were found to be significant determinants of satisfaction with Facebook. Gender, employment, and education tests showed interesting, though mixed, results, which are detailed in the study. Generational differences among Facebook users are also reported, which
shows the trust construct being lowest rated. Given the dominance of the Facebook platform, the major contributions of this study include implications of developing involvement, privacy, and trust among Facebook users with the objective of increasing satisfaction, as part of marketing strategy.
Understanding the Roles of Risk and Trust in the Context of Collaborative Consumption: A Test of Competing Models
Authors: Zhang Lixuan , Yang Hongwei , Pentina Iryna
Published: November 2021

Based on a survey of 266 ridesharing consumers in the United States, the study investigates relative impacts of trust and risk on intentions to continue using the service by comparing three alternative models via SEM analysis. We examine specific trust and risk sub-dimensions that are
salient in the online-tooffline environment and identify a mechanism of their joint effects on consumer decision-making. Our findings show that risk does not directly affect intentions in this collaborative consumption context but is mediated by consumer trust. The results highlight the importance
of trust-building efforts for ridesharing service providers.
ALZHEIMER’S ASSOCIATION: INITIATIVES & PUBLIC HEALTH PERSPECTIVE
Authors: Snyder H.M. , Carrillo M.C.
Published: November 2021

An estimated 47 million people worldwide are living with dementia in 2015 and this number is expected to triple by 2050. There is a clear urgency for therapies and / or interventions to slow, stop or prevent dementia. Amounting evidence suggests strategies to reduce risk of development dementia may be of growing import for reducing the number of individuals affected. The Alzheimer’s Association believes, from a population based perspective that: (1) Regular physical activity and management of cardiovascular risk factors (e.g. diabetes, obesity, smoking and hypertension) have been shown to reduce the risk of cognitive decline and may reduce the risk of dementia; (2) A healthy diet and lifelong learning/cognitive training may also reduce the risk of cognitive decline. The current evidence underscores the need to communicate to the broader population what the science indicates and to do so with diverse stakeholders and consistent messaging. There has never been a better time to define and distribute global messaging on public health for dementia.