bluuebunny/crossref_metadata_2025 huggingface dataset:
Worryingly high prevalence of resistance-associated mutations to macrolides and fluoroquinolones in Mycoplasma genitalium among men who have sex with men with recurrent sexually transmitted infections
Authors: De Baetselier Irith , Vuylsteke Bea , Reyniers Thijs , Smet Hilde , Van den Bossche Dorien , Kenyon Chris , Crucitti Tania
Published: January 2022

Background

Men who have sex with men (MSM) using pre-exposure prophylaxis (PrEP) recurrently infected with STIs are playing a pivotal role in contemporary Sexually transmitted infections (STI) epidemics. Our aim was to assess whether these individuals had more Mycoplasma genitalium ( M. genitalium) infections and more resistance to macrolides and fluoroquinolones of M. genitalium compared to those who were not recurrently infected with STIs.

Methods

The study was performed on 179 Belgian MSM PrEP users that were followed up for 18 months. STIs including M. genitalium were detected quarterly. Detection of resistance-associated mutations (RAMs) to macrolides and fluoroquinolones was performed via Sanger sequencing of the 23S rRNA gene and parC gene (conferring mutations at position 83/87 in ParC). Differences in M. genitalium positivity rate and presence of RAMs between both groups were assessed using mixed-effects logistic regression.

Results

A total of 91 new M. genitalium infections were detected among 70 participants. MSM experiencing recurrent STIs have significantly more M. genitalium infections compared to those without (11.7% vs. 4.7% OR: 2.69). Importantly, the prevalence of RAMs to macrolides (95.2% vs. 77.4%) and fluoroquinolones (35.7% vs. 12.9%) was much higher among individuals with recurrent STIs. The difference was only statistically significant for macrolides (OR 5.83, p = .036).

Conclusions

MSM recurrently infected with STIs play a central role in the emergence of antimicrobial resistance in M. genitalium. The use of macrolides and fluoroquinolones should preferably be minimized in this population in order to avoid further emergence of multi-resistant M. genitalium.
Effect of nano zinc oxide on proliferation and toxicity of human gingival cells
Authors: Chen Fang-Chuan , Huang Cong-Ming , Yu Xiao-Wan , Chen Ya-Yu
Published: January 2022

Background

Periodontal dressing is used to cover the gum surface and protect the wound after periodontal surgery. Nanomaterials have been widely applied in dentistry in recent years. Zinc oxide (ZnO) is one of the main components of periodontal dressing.

Aim

This study aims to explore the toxicity ZnO nanoparticles (ZnO NPs) causes to human gingival fibroblast cells (HGF-1) and its effect on cell proliferation.

Methods

First, we identified and analyzed HGF-1, including cell morphology, growth curve, and immunohistochemistry staining. Then, we treated HGF-1 with ZnO NP. Cell viability, the integrity of the cell membrane, oxidative damage, and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release assay, fluorescent probe, and flow cytometry. Furthermore, the expression of murine double minute 2 (MDM2) and p53 was determined by quantitative real-time polymerase chain reaction (qPCR) and Western blotting. We finally overexpressed MDM2 in HGF-1 to verify the relationship between MDM2 and cell proliferation.

Results

Our research indicated ZnO NPs did not affect cell proliferation at low concentrations. However, high-concentration ZnO NP inhibited cell proliferation, destroyed the integrity of cell membranes, and induced oxidative stress and apoptosis. In addition, high concentration of ZnO NPs inhibited the proliferation of HGF-1 by regulating the expression of MDM2 and p53.

Conclusion

High concentration of ZnO NP caused toxicity to HGF-1 cells and inhibited cell proliferation by regulating MDM2 and p53 expression.
The Localized Research and Development in the Industrialization Process of India
Authors: Mushtaq Saeed Owais , Majeed Mehak , Khan Javaid Iqbal
Published: January 2022

The survival of a firm in the modern day competitive globalized world is a knife-edge phenomenon. The scope for continuing to stay in a profitable business with obsolete and under-informed technical know-how is low as ever. Modern day firms need to evolve continually in light of up-to-date localized research and development in order to stay profitably in the competitive business environment. The current study is a novel attempt to contextualize the firm specific research and development process in India, using the latest available Annual Survey of Industries data. The study, using various descriptive statistics, confirms the low levels of localized research and development process at the firm level pan-India. Being the first empirical attempt in this direction of research, the current study proposes certain policy recommendations. It also raises some important research questions that are to be addressed by empirical analysis in order to place the industrialization process in India at a better place to compete in the global market.
Comparative Study on Selected Models of Entrepreneurship Education
Authors: Tatpuje Dipak U. , Jadhav Vaibhav , Ganbote Avinash
Published: January 2022

NEP 2020 is concentrating on the role of educational institutes in the various areas, such as traditional local arts, vocational crafts, entrepreneurship education, agriculture or any other subject where local expertise exists, to benefit students and help preserve and promote local knowledge and professions. However, the main goal of the entrepreneurial education has been intertwined in the NEP and it desires to make young generation more imaginative, innovative, ingenious, proactive, pioneering and prospect oriented ( NEP, 2020 ). Therefore, it needs to understand various models of entrepreneurship education and their application in the learning field. Some models have been tried out either in colleges, universities or entrepreneurship development programmes. These models have been developed based upon the pedagogical requirement or to get outcome of business start-ups after the entrepreneurial training. The Entrepreneur in Economic Modeling, Kakinada Model of Entrepreneurship Education with the experiment done by David McClelland, AIM pyramid of NITI Aayog, an emerging model of EE by Creative industries professionals of UK, Twenty-first Century Model of EE by H. Ramakrishna Hulugappa, TAILOR-C model of EE by Dipak Tatpuje, Model of Entrepreneurial Learning by David Rae, COBLAS model by the Japan ASEAN Integration fund with Takeru Ohe are the few of models of EE studied in this research. This comparative study is based upon the features, components, perspective and the environment in which it was developed. Each model contributed significantly in the area of entrepreneurship education and its pedagogical strength ‘in the higher education. Subsequently, this is urgent need to understand the models of entrepreneurship education. The entrepreneurship education is being carried out effectively in the higher education institutes across the European universities’ ( Liu, 2021 ). This is a literature survey-based study is done for understanding the various efforts and experiments done in the EE to promote self-employment.
Combining Visual Representations and a Powerful Retention Strategy With Peer-Mediated Strategies to Improve Mathematical Outcomes for Students With EBD
Authors: Riccomini Paul J. , Witzel Bradley S. , Deshpande Divya S.
Published: January 2022

Students with emotional and behavioral disorders struggle with learning and retaining many aspects of mathematics. Tasks requiring conceptual understanding and reasoning are especially challenging. Given these difficulties, it is essential that teachers use techniques designed to support mathematical learning. We explain how to infuse peer-mediated strategies with two promising instructional techniques to scaffold learning and remembering of mathematical concepts and skills. Examples are illustrated within the context of an inclusive middle school mathematics course.
Inplane vibration analysis of rotating beams with elastic restraints
Authors: Wang Lvsen , Su Zhu , Wang Lifeng
Published: January 2022

In this paper, the dynamic model of a rotating beam with elastic restraints is constructed by Euler–Bernoulli and Timoshenko beam theories. The study includes the Coriolis effect and the additional effect of dynamic centrifugal stiffness. A modified Fourier series method is used for expanding displacement field functions in the analysis. The standard eigenvalue equation is established and written in terms of the state space for dynamic analysis. Then, the natural frequencies of the rotating beam are calculated. The convergence analysis and the comparison of the results are carried out to verify the applicability of the method. The effects of the rotational velocity and boundary stiffness on the natural frequencies are analysed. The results show that the influence of the linear spring on the frequency is more evident than that of the torsional spring. The boundary can be considered to be elastic restraints when the boundary stiffness is within a certain interval. With the increase in the rotational velocity, the phenomenon of modal exchange appears. The elastic restraints cause the rotational velocity of the modal exchange to lag. Finally, the reason that the fundamental frequency goes to zero with increasing rotational velocity is explained. The Coriolis effect and elastic restraints reduce the critical velocity.
Non-symmetric indentation of an elastic half-plane
Authors: Saha Sandip , Das Apurba Narayan
Published: January 2022

In this work, the problems of wave propagation in a half-space due to the indentation by a rigid wedge at a constant speed and by a parabolic punch at a constant acceleration have been considered separately. The elastodynamics problems of non-symmetric indentation over a contact region expanding at a constant speed and constant acceleration have been solved using the method of homogeneous functions. Following Cherepanov and Cherepanov et al., the general solution of the problems has been derived in terms of an analytic function of complex variables. The expressions for the stress component under the contact region and the torque over the contact region have been derived. Numerical results of the particular cases of the Problems I and III and of the Problems II and IV have been presented in the form of graphs. This work and its applications are expected to be helpful in the study of indentation-related problems of solid mechanics.
Catheter-related superior vena cava obstruction: A rare cause of chylothorax in maintenance hemodialysis patients
Authors: Liu Ya-Min , Wei Yu-Juan , Lu Xiao-Qing , Wang Yu-Fei , Wang Pei , Liang Xian-Hui
Published: January 2022

With the extensive use of dialysis catheters in patients undergoing hemodialysis, superior vena cava (SVC) syndrome has gradually attracted attention in recent years. Chylothorax caused by SVC syndrome is rarely reported. In this paper, we report a case of chylothorax secondary to superior vena cava obstruction (SVCO) in a maintenance hemodialysis patient after multiple dialysis catheter placements. Relieving the SVCO through intravascular intervention could effectively treat chylothorax. In the past fourteen months, no recurrence of symptoms has been observed.
Chronotherapy of Early Colon Cancer: Advantage of Morning Dose Schedules
Authors: Axelrod David E
Published: January 2022

Colon adenomas with proliferating mutant cells may progress to invasive carcinomas. Proliferation of cells in human colorectal tissue is circadian, greater in the interval 4 to 12 hours after midnight than 16 to 24 hours after midnight. We have tested the hypothesis that chemotherapy administered during the time of greater cell proliferation will be more effective than chemotherapy administered during the time of lesser proliferation. An agent-based computer model of cell proliferation in colon crypts was calibrated with measurements of cell numbers in human biopsy specimens. It was used to simulate cytotoxic chemotherapy of an early stage of colon cancer, adenomas with about 20% of mutant cells. Chemotherapy doses were scheduled at different 4-hour intervals during the 24-hour day, and repeated at weekly intervals. Chemotherapy administered at 4 to 8 hours after midnight cured mutant cells in 100% of 50 trials with an average time to cure of 7.82 days (s.e.m. = 0.99). In contrast, chemotherapy administered at 20 to 24 hours after midnight cured only 18% of 50 trials, with the average time to cure of 23.51 days (s.e.m. = 2.42). These simulation results suggest that clinical chemotherapy of early colon cancer may be more effective when given in the morning than later in the day.
Democracy and public goods revisited: Local institutions, development, and access to water
Authors: Schiel Rebecca E , Wilson Bruce M , Langford Malcolm , Faulkner Christopher M
Published: January 2022

Democracies are commonly thought to provide greater levels of public goods than autocracies. Given that many public goods are provided locally, higher levels of local democracy are further thought to result in better rates of provision in both autocratic and democratic systems. However, several studies have cast doubt on democratic superiority in public goods provision both nationally and locally. We re-examine these contested relationships, investigating a locally provisioned public good: access to basic water. To determine what, if any, effects democracy has on public goods provision, we analyse the effects of both national and local democratic institutions, in conjunction with economic development. In cross-national regression analyses, we examine a global sample of 140 states from 2000 to 2015, arriving at three findings. First, access to basic water varies little by national regime type once accounting for development. Second, the existence of local elections and the degree to which they are free and competitive are positively correlated with basic water access rates in poor states. Finally, the positive effects of local democracy on water access in poor states increase with democratic institutional longevity. The findings of this study suggest two necessary additions to future research. First, more nuance is needed in the study of public goods provision beyond resources or a theoretical rationale for increased provision related to national regime characteristics. Second, considering the conditional influences of local institutional characteristics, development metrics could help illustrate the complicated circumstances determining access to basic public goods.
The coming of ‘age’: Educational and bureaucratic dimensions of the classification of children in elementary schools (Western Europe, 19th century)
Authors: Caruso Marcelo
Published: January 2022

Age-classes are a salient feature of modern schooling. Yet how did age-grouping come to prevail in entire school systems? And how was this form of grouping related to educational and pedagogic discussions at the time of its emergence? The article addresses these issues by looking at the historical context within which age classes came to a dominant position: the European nineteenth century. From the perspective of a governmental theorising of modern schooling, the article reconstructs the pace of their imposition and the main arguments in their favour through the analysis of a sample of 125 manuals of school management and organization of teaching. Against the usual description of age classification as a clear sign of the bureaucratic nature of modern schooling, the manuals show a concern about educational issues such as (de)motivation, encouragement and intelligence when discussing the role of age for the organization of elementary schools. The general idea of the modern school as an ‘assembling’ calls for more nuanced historical analyses of different combinations of the pastoral and the bureaucratic as techniques defining this institution.
Rediscovering a Jesuit Legacy of Natural History: Pierre-Martial Cibot and Sino-European Exchange of Fungus Knowledge in the Late 18th and 19th Centuries
Authors: Lu Di
Published: January 2022

The French Jesuit missionary Pierre-Martial Cibot stood conspicuous in Sino-European exchange of natural knowledge. However, his exploratory research on Chinese fungi, which is significant to the body of mycological knowledge, remains largely undiscussed and needs to be reappraised in the cross-cultural and historical context. Drawing on Cibot’s 1770s writings on Chinese fungi, this article provides a microhistorical treatment of their intricate interactions with late 18th- and 19th-century scientific scholarship. Cibot was arguably the author who wrote the first scientific treatise in China on local fungal species. His Christian faith and European epistemic base occasioned tensions with the acculturation of nature in China, which, together with his concerns with European natural history, agriculture and medicine, led to his critical appropriation of Chinese fungus lore. The writings were not published without change. Cibot's findings about Chinese fungi, mingled with confusion, also circulated unevenly in the European world. Nevertheless, they inspired new scientific studies, engaged with practical concerns, and even aided humanities research. Cibot's efforts highlight the agency of a multitude of border-crossing actors beyond European scientific centres, and invite a broader historical framework for understanding the making of modern mycology as a global enterprise.
An analysis of customer change, government support, and cash holdings
Authors: Wen Xuqian , Ye Yong
Published: January 2022

This paper uses a research sample listed manufacturing companies in China and systematically studies the impact of customer change and government support on corporate cash holdings and economic consequences. The empirical results show that there is a significant positive correlation between customer change and cash holdings, and the value of cash holdings is higher among enterprises with customer changes. This study enriches and expands the literature on customer relations and cash holdings, and we confirm the important practical significance of government support for the development of the manufacturing industry.
What Works and for Whom? Outcome Evaluation of an E-mail Walking Program Delivered Through Cooperative Extension
Authors: Richards Elizabeth A. , Woodcox Stephanie , Forster Anna
Published: January 2022

Introduction:

Get WalkIN’ is a 12-week, e-mail-based walking promotion program. The purpose of this study was to (1) compare sociodemographics of participants who enrolled versus completed the program; and (2) evaluate program feasibility/acceptability from perspectives of program participants and county-based Extension Educators who implemented the program.

Methods:

Participants (N = 875), recruited by county-based Extension Educators, were asked Likert-scale questions (eg, ease of reading the e-mails and frequency of e-mails) to assess program acceptability and open-ended questions regarding improvements. Educators (N = 55) were asked Likert-scale and open-ended questions regarding program training, recruitment, strengths, and areas for improvement. Descriptive statistics summarized participant characteristics, acceptability, and feasibility data. Open-ended responses were analyzed using thematic analysis.

Results:

There were no significant sociodemographic differences between participants (N = 875) who started the program and completed the program (n = 438). Participants reported intervention e-mails were easy to read (mean = 4.5 ± 0.7), understand (mean = 4.5 ± 0.7), and encouraged more walking (mean = 4.1 ± 0.9). Participants would like to connect/interact with other participants/Educators, have more monitoring tools for accountability, and more visuals/videos embedded within e-mails. Educators reported program training was adequate, e-mail messages were helpful and easy to use, and requested more visuals (eg, videos) to help with recruitment. Educators thought adding a social component (eg, kick-off walk or walking group) would be helpful.

Conclusions:

This Extension-delivered walking program is acceptable to participants and feasible to deliver. However, participants and Educators reported they would like more interaction, even if virtual. Future e-mail-based programs should consider ways to incorporate social interaction among users as well as provide a wide variety of recruitment resources.
Enhanced alumina extraction from kaolin by thermochemical activation using charcoal
Authors: ElDeeb Amr B. , Brichkin Vyacheslav N. , Bertau Martin , Awad Mahmoud E. , Savinova Yulia A.
Published: January 2022

The present work aims to increase the alumina percentage recovery (APR) extracted from kaolinviathe addition of 0.5–4.0 wt.% charcoal as a thermochemical fluxing agent in the lime-sintering process at 1260–1360°C. The transformation, microstructural and microtextural changes and self-disintegration performance were characterized using thermogravimetric analysis and differential scanning calorimetry, X-ray diffraction/X-ray fluorescence, scanning electron microscopy coupled with energy-dispersive spectroscopy and laser diffraction particle-size distribution analysis. The optimum enhancement of APR, from 77.7% to 87.40%, was obtained by sintering at 1360°C with the addition of 1.5% charcoal. With further increase of the charcoal content to 4%, the APR reduced to 75.6%. Combustion of ≤1.5% charcoal provided additional heat that amorphized the crystalline calcium aluminate into highly leachable amorphous phases with improved self-disintegration efficiency. Sintering at temperatures of >1360°C or with charcoal contents >4% led to mullite crystallization and decreased alumina leachability, thereby reducing the APR. Charcoal is a cost-effective and energy-efficient activator to increase the APR extracted from kaolin.
Improving eligibility criteria for first-line trials for patients with DLBCL using a US-based Delphi-method survey
Authors: Harkins R. Andrew , Patel Sharvil P. , Lee Michelle J. , Switchenko Jeffrey M. , Ansell Stephen M. , Bartlett Nancy L. , Blum Kristie A. , Cashen Amanda F. , Casulo Carla , Friedberg Jonathan W. , Johnston Patrick B. , Kahl Brad S. , Leonard John P. , Link Brian K. , Lossos Izidore S. , Martin Peter , Maurer Matt J. , Mehta-Shah Neha , Reagan Patrick M. , Westin Jason R. , Koff Jean L. , Flowers Christopher R.
Published: January 2022

Recent first-line randomized controlled trials (RCTs) for patients with diffuse large B-cell lymphoma (DLBCL) have shown negative results, which may be due in part to onerous eligibility criteria limiting enrollment of poor-risk patients who require immediate treatment. We conducted a Delphi-method survey with lymphoma experts in the United States to define recommendations for essential and potentially unnecessary enrollment criteria for modern first-line DLBCL RCTs aimed at increasing clinical diversity of ensuing study groups. We first tabulated enrollment criteria from 19 DLBCL RCTs spanning the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) era to identify common eligibility criteria from prior DLBCL RCTs for inclusion in the Delphi-method survey. We tabulated 451 total eligibility criteria comprising 51 criterion categories across 19 first-line DLBCL RCTs in the R-CHOP era. We then surveyed lymphoma clinical trial experts representing 8 academic medical centers in the United States regarding essential and unnecessary eligibility criteria for modern DLBCL RCTs. Seventeen of 29 invited clinical investigators completed the round-1 questionnaire (response rate, of 58.6%), 15 of 17 round-1 participants (88.2%) completed the round-2 survey, and all round-1 participants reviewed finalized recommendations for eligibility criteria for modern first-line DLBCL RCTs. We defined consensus recommendations for 31 modernized eligibility criteria including threshold values for 10 quantitative eligibility criteria aimed at facilitating enrollment of a clinically diverse study population in first-line DLBCL RCTs designed to improve standard-of-care therapy.
Gut microbiota in patients with obesity and metabolic disorders — a systematic review
Authors: XU Zhilu , JIANG Wei , HUANG Wenli , LIN Yu , CHAN Francis K.L. , NG Siew C.
Published: January 2022

Background

Previous observational studies have demonstrated inconsistent and inconclusive results of changes in the intestinal microbiota in patients with obesity and metabolic disorders. We performed a systematic review to explore evidence for this association across different geography and populations.

Methods

We performed a systematic search of MEDLINE (OvidSP) and Embase (OvidSP) of articles published from Sept 1, 2010, to July 10, 2021, for case–control studies comparing intestinal microbiome of individuals with obesity and metabolic disorders with the microbiome of non-obese, metabolically healthy individuals (controls). The primary outcome was bacterial taxonomic changes in patients with obesity and metabolic disorders as compared to controls. Taxa were defined as “lean-associated” if they were depleted in patients with obesity and metabolic disorders or negatively associated with abnormal metabolic parameters. Taxa were defined as “obesity-associated” if they were enriched in patients with obesity and metabolic disorders or positively associated with abnormal metabolic parameters.

Results

Among 2390 reports screened, we identified 110 full-text articles and 60 studies were included. Proteobacteria was the most consistently reported obesity-associated phylum. Thirteen, nine, and ten studies, respectively, reported Faecalibacterium, Akkermansia, and Alistipes as lean-associated genera. Prevotella and Ruminococcus were obesity-associated genera in studies from the West but lean-associated in the East. Roseburia and Bifidobacterium were lean-associated genera only in the East, whereas Lactobacillus was an obesity-associated genus in the West.

Conclusions

We identified specific bacteria associated with obesity and metabolic disorders in western and eastern populations. Mechanistic studies are required to determine whether these microbes are a cause or product of obesity and metabolic disorders.
Genome-wide run of homozygosity analysis reveals candidate genomic regions associated with environmental adaptations of Tibetan native chickens
Authors: Yuan Jingwei , Li Shijun , Sheng Zheya , Zhang Meikun , Liu Xuming , Yuan Zhengdong , Yang Ning , Chen Jilan
Published: January 2022

Background

In Tibet, the two most important breeds are Tibetan chicken and Lhasa white chicken, and the duo exhibit specific adaptations to the high altitude thereby supplying proteins for humans living in the plateau. These breeds are partly included in the conservation plans because they represent important chicken genetic resources. However, the genetic diversity of these chickens is rarely investigated. Based on whole-genome sequencing data of 113 chickens from 4 populations of Tibetan chicken including Shigatse (SH), Nyemo (NM), Dagze (DZ) and Nyingchi (LZ), as well as Lhasa white (LW) chicken breed, we investigated the genetic diversity of these chicken breeds by genetic differentiation, run of homozygosity (ROH), genomic inbreeding and selection signature analyses.

Results

Our results revealed high genetic diversity across the five chicken populations. The linkage disequilibrium decay was highest in LZ, while subtle genetic differentiation was found between LZ and other populations (Fst ranging from 0.05 to 0.10). Furthermore, the highest ROH-based inbreeding estimate (FROH) of 0.11 was observed in LZ. In other populations, the FROHranged from 0.04 to 0.06. In total, 74, 111, 62, 42 and 54 ROH islands containing SNPs ranked top 1% for concurrency were identified in SH, NM, DZ, LZ and LW, respectively. Genes common to the ROH islands in the five populations includedBDNF,CCDC34,LGR4,LIN7C,GLS,LOC101747789,MYO1B,STAT1andSTAT4. This suggested their essential roles in adaptation of the chickens. We also identified a common candidate genomic region harboringAMY2A,NTNG1andVAV3genes in all populations. These genes had been implicated in digestion, neurite growth and high-altitude adaptation.

Conclusions

High genetic diversity is observed in Tibetan native chickens. Inbreeding is more intense in the Nyingchi population which is also genetically distant from other chicken populations. Candidate genes in ROH islands are likely to be the drivers of adaptation to high altitude exhibited by the five Tibetan native chicken populations. Our findings contribute to the understanding of genetic diversity offer valuable insights for the genetic mechanism of adaptation, and provide veritable tools that can help in the design and implementation of breeding and conservation strategies for Tibetan native chickens.
Family caregiver quality of life and the care provided to older people living with dementia: qualitative analyses of caregiver interviews
Authors: Hazzan Afeez Abiola , Dauenhauer Jason , Follansbee Patti , Hazzan Joyce O , Allen Katy , Omobepade Ibukun
Published: January 2022

Background

While studies have examined the quality of life (QoL) of family caregivers for people living with dementia, it is not yet clear how these caregivers’ quality of life affects their ability to meet the care demands of their loved ones. The purpose of the study was to explore caregivers’ perceived quality of life in relation with the care provided to persons with dementia.

Methods

Twenty-three caregivers participated in this study. These caregivers participated in focus groups or one-on-one interviews after completing questionnaires regarding their own quality of life as well as the care provided to their loved ones with dementia. The interview and focus group transcripts were analyzed using qualitative description methodology.

Results

Regarding the relationship between caregiver QoL and the care provided to older people with dementia, the following themes were derived: (1) needs of the person with dementia; (2) caregivers’ ability to cope with progressing needs of the care recipient; (3) availability and accessibility of support for the caregiver; (4) unmet needs of the caregiver; and (5) ability of the caregiver to meet their own progressing needs as the condition of the care recipient deteriorates.

Conclusions

Findings from this study suggest that caregiver quality of life is important for the care they provide to their loved ones living with dementia. The study highlights the need for the provision of much needed support for caregivers and older people living with dementia. These issues are particularly important during and post-pandemic.
RNA-seq based transcriptome analysis of ethanol extract of saffron protective effect against corticosterone-induced PC12 cell injury
Authors: Chen Xi , Yang Ting , Zhang Congen , Ma Zhijie
Published: January 2022

Background

At present, oral antidepressants are commonly used in the clinical treatment of depression. However, the current drug treatment may lead to more serious adverse reactions. Therefore, we focus on Chinese traditional medicine, trying to find an effective and safe alternative or complementary medicine. Crocus sativus (saffron) is a traditional Chinese herbal medicine, which is typically used in the clinic to regulate anxiety, insomnia, amnesia, and other mental disorder. The study aimed to explore the neuroprotective effect of ethanol extract of saffron (EES) on corticosterone (CORT)- induced injury in PC12 cells and further explored its potential mechanism.

Methods

The authenticity of saffron and the active components of EES were identified by a water test and ultra-performance liquid chromatography-time of flight mass spectrometry system. The screening of cytotoxicity for PC12 cells was incubated with EES in different concentrations for 24 h, and the protective efficacy of EES on CORT (500 μM) -induced PC12 cell injury, cell viability was assessed by Cell Counting Kit-8 (CCK-8) assay. The differentially expressed genes (DEGs) of EES-protected PC12 cells were analyzed using the RNA-seq method, and the results were analyzed for GO and KEGG enrichment. The results of RNA-seq were verified by qPCR analysis.

Results

The saffron was initially identified as authentic in the water test and 10 compounds were identified by Ultra Performance Liquid Chromatography (UPLC)- Mass Spectrometry (MS). The results of CCK-8 demonstrated that EES at concentrations above 640 μg/mL exerted a certain cytotoxic effect, and PC12 cells pretreated with EES (20, 40, and 80 μg/mL) significantly reversed the 500 μM CORT-induced cell death. RNA-seq analysis showed that EES regulated 246 differential genes, which were mainly enriched in the MAPK signaling pathway. Dusp5, Dusp6, Gadd45b, Gadd45G, and Pdgfc were further validated by qPCR. Experimental data showed that the results of qPCR were consistent with RNA-seq.

Conclusions

These findings provide an innovative understanding of the molecular mechanism of the protective effect of EES on PC12 cells at the molecular transcription level, and Dusp5, Dusp6, Gadd45b, Gadd45g, and Pdgfc may be potential novel targets for antidepressant treatment.
In vitro and in vivo evaluations of antioxidative, anti-Alzheimer, antidiabetic and anticancer potentials of hydroponically and soil grown Lactuca sativa
Authors: Naseem Shahid , Ismail Hammad
Published: January 2022

Background

Lactuca sativa is an edible plant commonly used by local communities to manage diabetes and stomach problems.

Methods

This work aimed to investigate the anti-oxidant, anticancer, antidiabetic and Anti-Alzheimer effects of hydroponically (HyL) and soil-grown (SoL) Lactuca sativa. Streptozotocin-induced diabetes and AlCl3-induced Alzheimer’s disease model was used to evaluate the medicinal effects of Lactuca sativa.

Results

HyL showed significant activity in lipid peroxidation assay, DPPH and DNA protection assay, while SoL extract showed moderated activity, respectively. A similar activity response was quantified for α-glucosidase, α-amylase, acetylcholinesterase and butyrylcholinesterase inhibition assays. The cytotoxic potential of HyL and SoL extracts against MCF7, and HePG2 cancer cell lines exhibited significant activity. HyL and SoL showed a substantial decrease in blood glucose levels in streptozotocin-induced diabetic rats. Diabetes-related liver/kidney biomarkers and anti-oxidant enzyme trends moved toward normal after HyL and SoL treatment. In Anti-Alzheimer’s based Morris water and elevated plus maze tests, HyL and SoL displayed memory-enhancing response and anti-anxiety behaviour, respectively. HPLC quantification of dopamine and serotonin revealed a moderate but significant (p<0.05) increase in the level of these neurotransmitters in HyL and SoL groups.

Conclusion

Overall, the study revealed that hydroponic Lactuca sativa possesses the therapeutic potential to treat diseases like Alzheimer’s and diabetes.
Comparison of the performance of the CareStart Malaria Pf/Pan Combo test and field microscopy in the diagnosis of Plasmodium vivax malaria in North Sumatera, Indonesia
Authors: Pasaribu Ayodhia Pitaloka , Nasution Irma Sari , Sembiring Krisnarta , Fahmi Fahmi , Pasaribu Syahril
Published: January 2022

Background

In areas where malaria is endemic and where trained microscopists are not available, rapid diagnostic tests (RDTs) are needed not only to allow prompt treatment without delay but also to prevent overdiagnosis and overtreatment based on clinical judgements that may lead to drug resistance. This study aimed to compare the performances of the CareStart Pf/Pan Combo test to field microscopy, which is considered to be the gold standard for malaria diagnosis.

Methods

Any person with a fever or a history of fever within 48 h who came to the health centre was recruited for the study and tested both by the CareStart Pf/Pan test and by field microscopy. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were analysed with both methods.

Results

Two-hundred study participants were enrolled: 96 (48%) were found to be positive through microscopy, while 100 (50%) participants were found to be positive through RDT. The RDT produced four false-positive results. High sensitivity and specificity were observed for the CareStart Pf/Pan test (100 and 96.15%, respectively). The CareStart Pf/Pan test also showed excellent agreement with the field microscopy results.

Conclusion

The Carestart Pf/Pan could be used as an alternative diagnostic test in malaria-endemic areas where facility for performing microscopy is not available.
The COVID-19 patients' educational needs assessment questionnaire (COPENAQ): development and psychometrics
Authors: Hajialibeigloo Reza , Moradi Yaser , Habibzadeh Hossein , Baghaei Rahim , Alinejad Vahid , Namazi Nia Mohammad
Published: January 2022

Background

Despite the importance of assessing COVID-19 patients' educational needs, there is currently no standard tool for a comprehensive assessment of these needs. The present study was aimed at developing a questionnaire to assess the educational needs of COVID-19 patients and determining its psychometric properties.

Methods

This study was conducted using an exploratory sequential mixed methods design in 3 stages. At the first stage, patients' educational needs were explained and determined using conventional content analysis so that a total of 15 COVID-19 patients were first selected using purposive sampling and then interviewed. At the second stage, the questionnaire items were developed using the qualitative findings and a review of valid sources related to the study subject. At the third stage, the psychometric properties of the questionnaire were determined using internal consistency reliability and the face, content, and construct validities.

Results

The mean content validity ratio and the content validity index were obtained to be 0.94 and 0.92, respectively. The internal consistency was evaluated using Cronbach's alpha, which was measured to be 0.97. Based on the exploratory factor analysis, the questionnaire was developed with 36 items in four subscales of "disease recognition and treatment follow-up", "prevention of infection transmission", "medication regimen", and "psychological and physiological needs". The results of confirmatory factor analysis also showed appropriateness and approval of the structural model obtained from the questionnaire.

Conclusion

This questionnaire was found to have the necessary psychometric criteria (validity and reliability) so that it can be applied to assess the educational needs of COVID-19 patients and provide better and more effective patient education for them.
The efficacy and safety of intra-articular injection of triamcinolone acetonide versus triamcinolone hexacetonide for treatment of juvenile idiopathic arthritis
Authors: Rubin Shiri , Ohana Orly , Goldberg Ori , Peled Orit , Gendler Yulia , Habot-Wilner Zohar , Levinsky Yoel , Tal Rotem , Harel Liora , Amarilyo Gil
Published: January 2022

Objectives

Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease. Intra-articular corticosteroids joint injection (IAJI), with triamcinolone hexacetonide (TH) or triamcinolone acetonide (TA), is an effective additional treatment for oligo and polyarticular JIA. Previous studies have shown the benefits of TH over TA; however, TA is still used in many pediatric rheumatology centers. Our unit has experience with both regimens, and therefore we aimed to compare the efficacy and safety of TA versus TH for JIA patients.

Methods

Chart review of JIA patients who were randomly (based on drug availability) treated with TA or TH IAJI during 2010–2019. Primary outcomes for efficacy were defined as full recovery from arthritis one month after IAJI and a relapse rate of arthritis 3 months after IAJI. Primary outcome for safety was defined as the occurrence of adverse events (AEs) during the follow up period after IAJI.

Results

Overall, 292 joints of 102 JIA patients were treated (138 TA/154 TH joints). Complete recovery after one month was documented in 107 (69.6%) of TA treated joints and 96 (69.5%) of TH treated joints (P = 0.232). However, rate of relapse after 3 months was significantly higher for TA treated joints (27 (20.1%) vs. 13 (8.8%), respectively, P < 0.01). No AEs were documented except minor scars at four joint injection sites.

Conclusion

The recovery from arthritis was similar (~ 70%) with both regimens, however relapse rate was more than double in TA as compared to TH injected joints. These findings are important due to a contemporary shortage of TH in the US market.
Radiotherapy treatment modification for prostate cancer patients based on PSMA-PET/CT
Authors: Karagiannis Vasileios , Wichmann Viktor , Saarinen Juha , Eigeliene Natalja , Andersen Heidi , Jekunen Antti
Published: January 2022

Background

Prostate cancer is the most common cancer among men, and its diagnosis and treatment are improving. Our study evaluated how PSMA-PET/CT prior to treatment planning might improve the optimal management of prostate cancer radiotherapy.

Methods

This retrospective pilot study included 43 prostate cancer (PCa) patients referred to our radiation oncologist department, from the urology department, for radiation therapy. 18F-PSMA-PET/CT was ordered by the radiation oncologists mainly due to the lack of resent image staging. The patients were divided into three different groups according to their initially planned treatments: radical radiation therapy (RT) (newly diagnosed PCa patients), salvage RT (patients with biochemical recurrence after radical prostatectomy), or oligometastatic RT (oligometastatic PCa patients with good response after systemic treatment).

Results

Following PSMA-PET/CT, the initially planned RT was changed for 60.5% of the patients due to new findings (metastases and/or recurrent disease). The final treatment choice was effected by PSMA-PET/CT outcome in 60.5% (26/43) of the patients, and in 50% (16/32) of patients, the radiation treatment plan changed following PSMA-PET/CT. Only 39.5% (17/43) of the patients who underwent PSMA-PET/CT were treated according to their initial treatment plans.

Conclusions

Our results indicate that PSMA-PET/CT impacts treatment decisions and the selection of RT as well as adjuvant treatment protocols in the management of prostate cancer.
Gene expression predicts dormant metastatic breast cancer cell phenotype
Authors: Ren Qihao , Khoo Weng Hua , Corr Alexander P. , Phan Tri Giang , Croucher Peter I. , Stewart Sheila A.
Published: January 2022

Background

Breast cancer can recur months to decades after an initial diagnosis and treatment. The mechanisms that control tumor cell dormancy remain poorly understood, making it difficult to predict which patients will recur and thus benefit from more rigorous screening and treatments. Unfortunately, the extreme rarity of dormant DTCs has been a major obstacle to their study.

Methods

To overcome this challenge, we developed an efficient system to isolate and study rare dormant breast cancer cells from metastatic organs including bones, which represent a major site of metastasis. After isolation of cells from the long bones, we used single cell RNA-sequencing (scRNA-seq) to profile proliferative and dormant PyMT-Bo1 breast cancer cells. We also compared this signature to dormant versus proliferative tumor cells isolated from the lungs. Finally, we compared our dormant signature to human datasets.

Results

We identified a group of genes including Cfh, Gas6, Mme and Ogn that were highly expressed in dormant breast cancer cells present in the bone and lung. Expression of these genes had no impact on dormancy in murine models, but their expression correlated with disease-free survival in primary human breast cancer tumors, suggesting that these genes have predictive value in determining which patients are likely to recur.

Conclusions

Dormant breast cancer cells exhibit a distinct gene expression signature regardless of metastatic site. Genes enriched in dormant breast cancer cells correlate with recurrence-free survival in breast cancer patients.
25-hydroxyvitamin D levels are inversely related to metabolic syndrome risk profile in northern Chinese subjects without vitamin D supplementation
Authors: Xu Hanyuan , Han Guiyan , Wang Linjie , Ding Huihua , Wang Chunyan , Ping Xiaochuan , Dong Caixia , Zhang Dianxi , Dai Yufei , Li Naishi , Li Yufeng , Yang Hongbo , Zhu Huijuan , Pan Hui , Gong Fengying , Chen Jichun , Xing Xiaoping
Published: January 2022

Background

The comparatively low 25 hydroxyvitamin D [25(OH)D] levels have been reported in patients with metabolic syndrome (MetS). Herein we investigated the cross-sectional and longitudinal relationships between serum 25(OH)D levels and MetS risk profile in northern middle-aged Chinese subjects without vitamin D supplementation.

Methods

A cohort of 211 participants including 151 MetS patients and 60 controls at 20–69 years of age were enrolled from suburban Beijing, China. The recruited MetS patients were subjected to diet and exercise counselling for 1-year. All subjects at baseline and MetS patients after intervention underwent clinical evaluations.

Results

Serum 25(OH)D levels were significantly decreased in MetS patients. 25(OH)D levels were inversely related to MetS score, fasting blood glucose (FBG) and triglyceride-glucose index (TyG) after adjusting for cofounders (all P < 0.05). Participants in the lowest tertile of 25(OH)D levels had increased odds for MetS (P = 0.045), elevated FBG (P = 0.004) in all subjects, and one MetS score gain in MetS patients (P = 0.005). Longitudinally, the metabolic statuses as well as 25(OH)D levels of MetS patients were significantly improved (all P < 0.05), and the increase of 25(OH)D levels were inversely related to MetS scores, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), FBG, and TyG, while positively related to high-density lipoprotein cholesterol (HDL-C) after adjusting for confounders.

Conclusions

25(OH)D levels were significantly decreased in MetS patients, and it was negatively associated with metabolic dysfunctions at baseline and 1-year after. Metabolic aberrations of MetS patients were significantly ameliorated with 1-year follow-up counselling accompanying by notably elevated 25(OH)D levels.
A CYC–RAD–DIV–DRIF interaction likely pre-dates the origin of floral monosymmetry in Lamiales
Authors: Sengupta Aniket , Hileman Lena C.
Published: January 2022

Background

An outstanding question in evolutionary biology is how genetic interactions defining novel traits evolve. They may evolve either by de novo assembly of previously non-interacting genes or by en bloc co-option of interactions from other functions. We tested these hypotheses in the context of a novel phenotype—Lamiales flower monosymmetry—defined by a developmental program that relies on regulatory interaction among CYCLOIDEA, RADIALIS, DIVARICATA, and DRIF gene products. In Antirrhinum majus (snapdragon), representing Lamiales, we tested whether components of this program likely function beyond their previously known role in petal and stamen development. In Solanum lycopersicum (tomato), representing Solanales which diverged from Lamiales before the origin of Lamiales floral monosymmetry, we additionally tested for regulatory interactions in this program.

Results

We found that RADIALIS, DIVARICATA, and DRIF are expressed in snapdragon ovaries and developing fruit, similar to their homologs during tomato fruit development. In addition, we found that a tomato CYCLOIDEA ortholog positively regulates a tomato RADIALIS ortholog.

Conclusion

Our results provide preliminary support to the hypothesis that the developmental program defining floral monosymmetry in Lamiales was co-opted en bloc from a function in carpel development. This expands our understanding of novel trait evolution facilitated by co-option of existing regulatory interactions.