bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathogenic gain-of-function mutations in the prodomain and C-terminal domain of PCSK9 inhibit LDL binding
Authors: Sarkar Samantha K. , Matyas Angela , Asikhia Ikhuosho , Hu Zhenkun , Golder Mia , Beehler Kaitlyn , Kosenko Tanja , Lagace Thomas A.
Published: September 2022

Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a secreted protein that binds and mediates endo-lysosomal degradation of low-density lipoprotein receptor (LDLR), limiting plasma clearance of cholesterol-rich LDL particles in liver. Gain-of-function (GOF) point mutations in PCSK9 are associated with familial hypercholesterolemia (FH). Approximately 30%–40% of PCSK9 in normolipidemic human plasma is bound to LDL particles. We previously reported that an R496W GOF mutation in a region of PCSK9 known as cysteine-histidine–rich domain module 1 (CM1) prevents LDL binding in vitro [Sarkar et al., J. Biol. Chem. 295 (8), 2285–2298 (2020)]. Herein, we identify additional GOF mutations that inhibit LDL association, localized either within CM1 or a surface-exposed region in the PCSK9 prodomain. Notably, LDL binding was nearly abolished by a prodomain S127R GOF mutation, one of the first PCSK9 mutations identified in FH patients. PCSK9 containing alanine or proline substitutions at amino acid position 127 were also defective for LDL binding. LDL inhibited cell surface LDLR binding and degradation induced by exogenous PCSK9-D374Y but had no effect on an S127R-D374Y double mutant form of PCSK9. These studies reveal that multiple FH-associated GOF mutations in two distinct regions of PCSK9 inhibit LDL binding, and that the Ser-127 residue in PCSK9 plays a critical role.
Expression profiling and functional analysis of circular RNAs in vitro model of intermittent hypoxia-induced liver injury
Authors: Chen Li-Da , Huang Jie-Feng , Lin Xue-Jun , Huang Ya-Ping , Xu Qiao-Zhen , Chen Gong-Ping , Lin Qi-Chang
Published: September 2022

Intermittent hypoxia (IH) is a prominent feature of obstructive sleep apnea (OSA) which is increasingly recognized as a key risk factor for liver injury. Circular RNAs (circRNAs) has been suggested to act as a regulator of multiple biological processes. However, there is no study evaluating circRNAs alterations and potential role of circRNAs in OSA-related liver injury. The present study aimed to investigate circRNA expression profiles in vitro model of IH-induced liver injury, as well as potential functional characterization of the differentially expressed circRNAs (DE circRNAs). BRL-3A cells were exposed to IH or normoxia. Cell apoptosis and cell viability were evaluated using flow cytometry and cell counting kit-8, respectively. The expression profile of circRNAs was depicted by circRNA sequencing. The selected circRNAs were verified by quantitative real-time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analyses were employed to predict DE circRNAs functions. The circRNA-miRNA-mRNA regulatory network was constructed. IH treatment caused cell injury in BRL-3A cells. 98 circRNAs were identified as being dysregulated in IH-treated BRL-3A cells. Among them, 58 were up-regulated and 40 were down-regulated. Go and KEGG analyses suggested that the DE circRNAs were predominantly enriched in the biological process such as positive regulation of NF−kappaB transcription factor activity and pathways such as circadian entrainment, Wnt signaling pathway, MAPK signaling pathway, and protein export. 3 up-regulated circRNAs and 3 down-regulated circRNAs with high number of back-splicing sites were chosen for qRT-PCR validation and were consistent with the sequencing data. CircRNA1056 and circRNA805 were predicted to interact with microRNAs that might thereby regulate downstream genes. The study characterized a profile of dysregulated circRNAs in IH-induced BRL-3A cell injury. DE circRNAs may play vital roles in the pathophysiology of IH-induced liver injury. Our findings provide preliminary support for further research in mechanisms and a new theory for the pathogenesis of OSA-related liver injury.
A variable gene family encoding nodule-specific cysteine-rich peptides in pea (Pisum sativum L.)
Authors: Zorin Evgeny A. , Kliukova Marina S. , Afonin Alexey M. , Gribchenko Emma S. , Gordon Mikhail L. , Sulima Anton S. , Zhernakov Aleksandr I. , Kulaeva Olga A. , Romanyuk Daria A. , Kusakin Pyotr G. , Tsyganova Anna V. , Tsyganov Viktor E. , Tikhonovich Igor A. , Zhukov Vladimir A.
Published: September 2022

Various legume plants form root nodules in which symbiotic bacteria (rhizobia) fix atmospheric nitrogen after differentiation into a symbiotic form named bacteroids. In some legume species, bacteroid differentiation is promoted by defensin-like nodule-specific cysteine-rich (NCR) peptides. NCR peptides have best been studied in the model legume Medicago truncatula Gaertn., while in many other legumes relevant information is still fragmentary. Here, we characterize the NCR gene family in pea (Pisum sativum L.) using genomic and transcriptomic data. We found 360 genes encoding NCR peptides that are expressed in nodules. The sequences of pea NCR genes and putative peptides are highly variable and differ significantly from NCR sequences of M. truncatula. Indeed, only one pair of orthologs (PsNCR47–MtNCR312) has been identified. The NCR genes in the pea genome are located in clusters, and the expression patterns of NCR genes from one cluster tend to be similar. These data support the idea of independent evolution of NCR genes by duplication and diversification in related legume species. We also described spatiotemporal expression profiles of NCRs and identified specific transcription factor (TF) binding sites in promoters of “early” and “late” NCR genes. Further, we studied the expression of NCR genes in nodules of Fix– mutants and predicted potential regulators of NCR gene expression, one among them being the TF ERN1 involved in the early steps of nodule organogenesis. In general, this study contributes to understanding the functions of NCRs in legume nodules and contributes to understanding the diversity and potential antibiotic properties of pea nodule-specific antimicrobial molecules.
Studying tree response to biotic stress using a multi-disciplinary approach: The pine pitch canker case study
Authors: Amaral Joana , Valledor Luis , Alves Artur , Martín-García Jorge , Pinto Glória
Published: September 2022

In an era of climate change and global trade, forests sustainability is endangered by several biotic threats. Pine pitch canker (PPC), caused byFusarium circinatum, is one of the most important disease affecting conifers worldwide. To date, no effective control measures have been found for this disease. Earlier studies on PPC were mainly focused on the pathogen itself or on determining the levels of susceptibility of different hosts toF. circinatuminfection. However, over the last years, plenty of information on the mechanisms that may explain the susceptibility or resistance to PPC has been published. This data are useful to better understand tree response to biotic stress and, most importantly, to aid the development of innovative and scientific-based disease control measures. This review gathers and discusses the main advances on PPC knowledge, especially focusing on multi-disciplinary studies investigating the response of pines with different levels of susceptibility to PPC upon infection. After an overview of the general knowledge of the disease, the importance of integrating information from physiological and Omics studies to unveil the mechanisms behind PPC susceptibility/resistance and to develop control strategies is explored. An extensive review of the main host responses to PPC was performed, including changes in water relations, signalling (ROS and hormones), primary metabolism, and defence (resin, phenolics, and PR proteins). A general picture of pine response to PPC is suggested according to the host susceptibility level and the next steps and gaps on PPC research are pointed out.
Integrated analysis of transcriptome and metabolome reveals molecular mechanisms of salt tolerance in seedlings of upland rice landrace 17SM-19
Authors: Zhou Longhua , Zong Yingjie , Li Luli , Wu Shujun , Duan Mingming , Lu Ruiju , Liu Chenghong , Chen Zhiwei
Published: September 2022

Salt stress is a major abiotic stress that threatens global rice production. It is particularly important to improve salt tolerance in upland rice because of its growth environment. Upland rice landrace 17SM-19 with high salt tolerance was obtained from a previous study. In this study, an integrated analysis of transcriptome and metabolome was performed to determine the responses of the rice seedling to salt stress. When treated with 100 mm NaCl, the rice seedling growth was significantly inhibited at 5 d, with inhibition first observed in shoot dry weight (SDW). Changes in potassium (K+) content were associated with changes in SDW. In omics analyses, 1,900 differentially expressed genes (DEGs) and 659 differentially abundant metabolites (DAMs) were identified at 3 d after salt stress (DAS), and 1,738 DEGs and 657 DAMs were identified at 5 DAS. Correlation analyses between DEGs and DAMs were also conducted. The results collectively indicate that salt tolerance of upland rice landrace 17SM-19 seedlings involves many molecular mechanisms, such as those involved with osmotic regulation, ion balance, and scavenging of reactive oxygen species.
Soil and foliar selenium application: Impact on accumulation, speciation, and bioaccessibility of selenium in wheat (Triticum aestivum L.)
Authors: Wang Min , Zhou Fei , Cheng Nan , Chen Ping , Ma Yuanzhe , Zhai Hui , Qi Mingxing , Liu Nana , Liu Yang , Meng Li , Bañuelos Gary S. , Liang Dongli
Published: September 2022

A comprehensive study in selenium (Se) biofortification of staple food is vital for the prevention of Se-deficiency-related diseases in human beings. Thus, the roles of exogenous Se species, application methods and rates, and wheat growth stages were investigated on Se accumulation in different parts of wheat plant, and on Se speciation and bioaccessibility in whole wheat and white all-purpose flours. Soil Se application at 2 mg kg–1 increased grains yield by 6% compared to control (no Se), while no significant effects on yield were observed with foliar Se treatments. Foliar and soil Se application of either selenate or selenite significantly increased the Se content in different parts of wheat, while selenate had higher bioavailability than selenite in the soil. Regardless of Se application methods, the Se content of the first node was always higher than the first internode. Selenomethionine (SeMet; 87–96%) and selenocystine (SeCys2; 4–13%) were the main Se species identified in grains of wheat. The percentage of SeMet increased by 6% in soil with applied selenite and selenate treatments at 0.5 mg kg–1 and decreased by 12% compared with soil applied selenite and selenate at 2 mg kg–1, respectively. In addition, flour processing resulted in losses of Se; the losses were 12–68% in white all-purpose flour compared with whole wheat flour. The Se bioaccessibility in whole wheat and white all-purpose flours for all Se treatments ranged from 6 to 38%. In summary, foliar application of 5 mg L–1 Se(IV) produced wheat grains that when grounds into whole wheat flour, was the most efficient strategy in producing Se-biofortified wheat. This study provides an important reference for the future development of high-quality and efficient Se-enriched wheat and wheat flour processing.
Relationships between depression, anxiety, type D personality, and worry and rumination in patients with coronary heart disease
Authors: Tunheim Kristoffer , Dammen Toril , Baardstu Silje , Moum Torbjørn , Munkhaugen John , Papageorgiou Costas
Published: September 2022

Psychological distress, including depression and anxiety, and Type-D personality are prevalent in patients with coronary heart disease (CHD) and associated with poor cardiovascular outcomes. Worry and rumination may be among the core features responsible for driving psychological distress in these patients. However, the nature of associations between these constructs remains to be delineated, yet they may have implications for the assessment and treatment of CHD patients. This study aimed to (1) explore the factorial structure and potential overlap between measures of depression, anxiety and the Type-D personality factors known as negative affectivity and social inhibition, and (2) examine how these constructs relate to worry and rumination in a sample of 1,042 CHD outpatients who participated in the in the cross-sectional NORwegian CORonary Prevention study. We conducted confirmatory factor analyses (n = 1,042) and regression analyses (n = 904) within a structural equation modeling framework. Results showed all constructs to have acceptable factor structure and indicated an overlap between the constructs of depression and negative affectivity. Worry was most strongly associated with anxiety, whereas rumination was most strongly associated with depression and negative affectivity. The results suggest conceptual similarities across the measures of depression and negative affectivity. They further suggest that intervention efforts could benefit from targeting worry and/or rumination in the treatment of CHD outpatients presenting with symptoms of psychological distress.
Teachers’ dissatisfaction during the COVID-19 pandemic: Factors contributing to a desire to leave the profession
Authors: Gillani Amreen , Dierst-Davies Rhodri , Lee Sarah , Robin Leah , Li Jingjing , Glover-Kudon Rebecca , Baker Kayilan , Whitton Alaina
Published: September 2022

Introduction

The COVID-19 pandemic required more responsibilities from teachers, including implementing prevention strategies, changes in school policies, and managing their own mental health, which yielded higher dissatisfaction in the field.

Methods

A cross-sectional web survey was conducted among educators to collect information on their experiences teaching during the COVID-19 pandemic throughout the 2020–2021 academic year. Qualtrics, an online survey platform, fielded the survey from May 6 to June 8, 2021 to a national, convenience sample of 1,807 respondents.

Results

Findings revealed that overall, 43% of K-12 teachers reported a greater intention to leave the profession than previously recalled prior to the COVID-19 pandemic. Intention to leave was multi-level, and associated with socio-demographic factors (e.g., age: AOR = 1.87, p < 0.05), individual factors (e.g., perceived COVID risks: AOR = 1.44, p < 0.05), and teachers’ agency (e.g., dissatisfaction with school/district communications and decisions: AOR = 1.34, p < 0.05). We also found demographic disparities with respect to race and gender (e.g., female teachers: AOR: 1.78, p < 0.05) around teachers’ ability to provide feedback to schools on opening/closing and overall dissatisfaction with school/district COVID-19 prevention strategies implementation and policies.

Conclusion

These findings are consistent with the Job-Demand and Resources Model (JD-R), which posits that lack of organizational support can exacerbate job stressors, leading to burnout. Specifically, dissatisfaction with the way school policies were implemented took a toll on teachers’ mental health, leading to a desire to leave the profession. These findings are also consistent with research conducted once in-person teaching resumed in 2020–2021, specifically that the COVID-19 pandemic exacerbated preexisting teacher shortages that led to self-reported issues of stress, burnout, and retention.

Implications

Further research is necessary to understand the resources that may be most useful to reduce the demands of teaching in the context of the COVID-19 pandemic. Some teachers are more likely to leave the field, and educational agencies may wish to target their teacher-retention efforts with emphasis on strong employee wellness programs that help educators to manage and reduce their stress. Education agency staff may wish to review policies and practices to provide meaningful opportunities to give input to school/district decisions and enable proactive communication channels.
Familiarization with meaningless sound patterns facilitates learning to detect those patterns among distracters
Authors: Wisniewski Matthew G.
Published: September 2022

Initially “meaningless” and randomly generated sounds can be learned over exposure. This is demonstrated by studies where repetitions of randomly determined sound patterns are detected better if they are the same sounds presented on previous trials than if they are novel. This experiment posed two novel questions about this learning. First, does familiarization with a sound outside of the repetition detection context facilitate later performance? Second, does familiarization enhance performance when repeats are interleaved with distracters? Listeners were first trained to categorize a unique pattern of synchronous complex tone trains (210 ms in duration) from other tone trains with similar qualities (familiarization phase). They were then tasked to detect repeated pattern presentations interleaved with similar distracters in 4.2 s long excerpts (repetition detection phase). The familiarized pattern (Familiar Fixed – FF), an unfamiliar pattern that remained fixed throughout (Unfamiliar Fixed – UF), or patterns that were uniquely determined on each trial (Unfamiliar Unfixed – UU) could be presented as repeats. FF patterns were learned at a faster rate and achieved higher repetition detection sensitivity than UF and UU patterns. Similarly, FF patterns also showed steeper learning slopes in their response times (RTs) than UF patterns. The data show that familiarity with a “meaningless” sound pattern on its own (i.e., without repetition) can facilitate repetition detection even in the presence of distracters. Familiarity effects become most apparent in the potential for learning.
Work-life balance practices and organizational cynicism: The mediating role of person-job fit
Authors: Kakar Abdul Samad , Kruger Niel , Durrani Dilawar Khan , Khan Muhammad Asif , Meyer Natanya
Published: September 2022

This study aims to elaborate on how work-life balance (WLB) practices influence organizational cynicism (OC) through the mediation effects of person-job fit (PJF). We collected data from 331 nurses through a self-administered survey, and we tested our hypothesized model through partial least square structural equation modeling techniques using SmartPLS software. The findings revealed that WLB practices influenced OC negatively and PJF positively. We further found that PJF negatively influenced OC and mediated WLB practices’ effect on OC. These findings imply that nurses should be provided WLB practices to meet their job and home responsibilities and thus have a less cynical attitude toward the organization.
Support staff liaising effectively with family caregivers: Findings from a co-design event and recommendation for a staff training resource
Authors: Deb Shoumitro , Limbu Bharati
Published: September 2022

A high proportion of people with intellectual disabilities (ID) and autism spectrum disorder (ASD) are prescribed psychotropic medications such as antipsychotics, antidepressants etc., outside their licensed indications, primarily for the management of behaviors that challenge (BtC) in the absence of a psychiatric disorder. Examples of BtC are aggression to people and property or self-injury. BtC could be challenging to manage and may cause the person with ID/ASD and their caregivers distress, breakdown of community placement leading to hospitalization, and restrictive practices such as restraint or inappropriate medication use. Caregivers play a pivotal role in the prescribing process. However, many family caregivers feel that they have not been fully involved in the shared decision-making process about the care planning of their relatives with ID/ASD. To address the public health concern regarding the overuse of off-license prescribing in people with ID/ASD, we have recently developed a training programme called SPECTROM (Short-term Psycho-Education for Carers To Reduce OverMedication of people with intellectual disabilities) for direct care staff who support people with ID/ASD within community settings. We used co-production and a modified Experience-Based Co-Design (EBCD) method to develop SPECTROM, which involved a literature review, four focus groups and a co-design event day involving 26 stakeholders. Recommendations from the co-design event day were analyzed by a Programme Development Group (PDG) consisting of 21 stakeholders who made the final recommendations to the project team regarding the contents and the format of SPECTROM, which was finalized after receiving feedback from further 59 stakeholders. SPECTROM has web-based resources introduced through two core modules in face-to-face workshops/training. A small field test found SPECTROM was effective in improving staff's knowledge of psychotropic medications and attitude toward BtC and people with ID (p < 0.05). One of the 14 STOMP modules is “Effective liaison with family carers and advocates”. In this paper, we have presented data from the co-design event day recommendations for this particular module. The group recommended ways to improve collaborative working and effective shared decision-making with family caregivers and people with ID/ASD.
Marital duration in China: Trends and gender differences, 1982–2015
Authors: Zhu Yingrun , Yu Xiao , Jiang Quanbao
Published: September 2022

Objectives

With the postponement in age at marriage, increase in life expectancy, and acceptance of divorce in China, the marital duration in each state has changed gradually. This study seeks to depict the trends and gender differences of marital duration in China from 1982 to 2015.

Design

We calculated and depicted the trends of and gender differences in marital duration, including single, marriage, divorce, widowhood duration and the proportion of each duration to the remaining life expectancy at 15.

Results

The single duration of Chinese men and women was slightly reduced and then extended, with that of men longer than women, showing a narrowing trend in gender difference. The marriage duration of Chinese men and women is lengthening, with that of women longer than men, demonstrating a widening gap in gender difference. However, the proportion of marriage duration in life expectancy at age 15 increased and then declined, with that of men higher than women. The divorce duration of Chinese men and women slightly reduced and then lengthened, but men tend to stay divorced for longer periods than women, and the gender difference is narrowing. The widowhood duration of Chinese men and women is shortening, with women having longer widowhood than men, and the gender difference has been shrinking.

Conclusions

With the socio-economic and demographic transition, the marital duration in each state has changed gradually, and will have an important impact on fertility level and pension burden.
Preterm, early term, and post-term infants from Riyadh mother and baby multicenter cohort study: The cohort profile
Authors: Fayed Amel , Wahabi Hayfaa A. , Esmaeil Samia , Elmorshedy Hala , AlAniezy Hilala
Published: September 2022

Background

Birth before 37 or beyond 42 gestational weeks is associated with adverse neonatal and maternal outcomes. Studies investigating determinants and outcomes of these deliveries are scarce. The objective of this study was to determine the neonatal birth profile in relation to the gestational age at delivery and to evaluate its influence on the immediate maternal and neonatal outcomes.

Methods

This is a multicenter cohort study of 13,403 women conducted in three hospitals in Riyadh. Collected data included sociodemographic characteristics, obstetric history, and physical and laboratory measurements. Regression models were developed to estimate the adjusted odds ratio (OR) and confidence intervals (CI) to determine factors associated with preterm, early term, and post-term births and to evaluate common maternal and neonatal risks imposed by deliveries outside the full term.

Results

The incidence of preterm, early term, and post-term delivery was 8.4%, 29.8%, and 1.4%, respectively. Hypertensive events during pregnancy consistently increased the risk of all grades of preterm births, from more than 3-fold for late preterm (OR = 3.40, 95% CI = 2.21–5.23) to nearly 7-fold for extremely early preterm (OR = 7.11, 95% CI = 2.24–22.60). Early term was more likely to occur in older mothers (OR = 1.30, 95% CI = 1.13–1.49), grand multiparous (OR = 1.21, 95% CI = 1.06–1.38), pregestational diabetes (OR = 1.91, 95% CI = 1.49–2.44), and gestational diabetes women (OR = 1.18, 95% CI = 1.05–1.33). The risk of post-term birth was higher in primiparous. In preterm births, the adverse outcome of neonates having an APGAR score of <7 at 5 min and admission to neonatal intensive care units increased progressively as the gestational age decreased. Post-term births are 2-fold more likely to need induction of labor; meanwhile, preterm births were more likely to deliver by cesarean section.

Conclusion

This large cohort study was the first in Saudi Arabia to assess the delivery profile across a continuum of gestational age and the associated maternal and neonatal adverse outcomes of deliveries outside the full-term period. The study showed that the prevalence of preterm and post-term birth in Saudi Arabia is similar to the prevalence in other high-income countries. The immediate adverse pregnancy outcomes inversely increased with the decrease in gestational age at delivery. In addition, maternal age, hypertension, diabetes, and parity influenced the gestational age at delivery.
Who initiates price competition when generic entrants are introduced into the South Korean pharmaceutical market?
Authors: Son Kyung-Bok
Published: September 2022

Background

Price competition has the potential to reduce health expenditures without hindering pharmaceutical innovation. However, empirical evidence on price competition after generic drugs are introduced is scarce. This study investigates product- and substance-level determinants of price competition following the entry of generics into the South Korean market.

Methods

We selected substances that were approved by the Ministry of Food and Drug Safety from 2000 to 2019, linked their corresponding pharmaceutical products, measured the degree of price competition under various scenarios, and utilized multilevel analysis to investigate the determinants of price competition.

Results

A total of 986 substances and 12,109 corresponding pharmaceutical products were identified. Only 11% of products were affected by price competition in the 10% scenario. However, the number increased to 43% when we measured price competition at the substance level. Major domestic manufacturers mainly initiated price competition at the product level, while foreign manufacturers were reluctant to initiate price competition. At the substance level, the maximum reimbursement price was a significant determinant of price competition.

Conclusion

Price competition at the product level is rare in South Korea. In contrast, the market is quite price competitive at the substance level. Policy options could be introduced to encourage “discounted generic” substitution in an effort to maximize the effects of price competition at the substance level. Major domestic manufacturers are essential in the introduction of discounted generics into the South Korean health system.
The way forward to achieve high COVID-19 vaccination and revaccination coverage in a city amid a period of tranquility
Authors: Kwok Kin On , Li Kin Kit , Leung Cyrus Lap Kwan , Tang Arthur , Chan Emily Ying Yang , Tsoi Margaret Ting Fong , Wei Wan In , McNeil Edward B. , Wong Samuel Yeung Shan
Published: September 2022

Background

Amid the current COVID-19 pandemic, there is an urgent need for both vaccination and revaccination (“boosting”). This study aims to identify factors associated with the intention to receive a booster dose of the coronavirus (COVID-19) vaccine among individuals vaccinated with two doses and characterize their profiles in Hong Kong, a city with a low COVID-19 incidence in the initial epidemic waves. Among the unvaccinated, vaccination intention is also explored and their profiles are investigated.

Methods

From December 2021 - January 2022, an online survey was employed to recruit 856 Hong Kong residents aged 18 years or over from an established population-based cohort. Latent class analysis and multivariate logistic regression modeling approaches were used to characterize boosting intentions.

Results

Of 638 (74.5%) vaccinated among 856 eligible subjects, 42.2% intended to receive the booster dose. Four distinct profiles emerged with believers having the highest intention, followed by apathetics, fence-sitters and skeptics. Believers were older and more likely to have been vaccinated against influenza. Older age, smoking, experiencing no adverse effects from a previous COVID-19 vaccination, greater confidence in vaccines and collective responsibility, and fewer barriers in accessing vaccination services were associated with higher intentions to receive the booster dose. Of 218 unvaccinated, most were fence-sitters followed by apathetics, skeptics, and believers.

Conclusion

This study foretells the booster intended uptake lagging initial vaccination across different age groups and can help refine the current or future booster vaccination campaign. Given the fourth COVID-19 vaccine dose may be offered to all adults, strategies for improving boosting uptake include policies targeting young adults, individuals who experienced adverse effects from previous doses, fence-sitters, apathetics, and the general public with low trust in the health authorities.
Using 5 consecutive years of NICE guidance to describe the characteristics and influencing factors on the economic evaluation of orphan oncology drugs
Authors: Shengnan Duan , Zixuan Lv , Na Zhou , Weikai Zhu , Yuanyuan Yi , Jiasu Liu , Ni Yuan
Published: September 2022

Objective

Orphan oncology drugs used in this article were defined by the type of disease treated by drugs, as drugs used to treat rare diseases with a prevalence of ≤ 500 per million people per year. In this article, our concern was to explore focus on the economic evaluation of the National Institute for Health and Care Excellence (NICE), when orphan oncology drugs were appraised for reimbursement, and provide advice and suggestions to decision-makers.

Methods

A retrospective study was used in this study. Thirty guidance were gathered as our subject by NICE from 2016 to 2020, excluded drugs were not identified as orphan by European Medicines Agency (EMA) and orphan drugs were not used for cancer, and orphan oncology drugs were terminated at the time of data collection at NICE. Qualitative analysis, descriptive statistics, and Fisher's exact test were conducted.

Results

Of all guidance, the partitioned survival model was used most to appraise orphan oncology drugs, and every drug had a kind of commercial arrangement such as patient access scheme (PAS), managed access arrangements (MAAs), and commercial access agreement (CAAs). End of life is an important indicator that had been defined by NICE in the methods of technology appraisal in 2013, and drugs that met the criterion would be given a higher threshold of ICER. In addition, we found that potential health benefits were increasingly concerned such as drug delivery.

Conclusion

In the setting of uncertain clinical and cost efficacy, orphan oncology drugs are comprehensively evaluated in multiple additional dimensions, which include life-extending benefits, and innovation. NICE uses a combination of special considerations for incomplete data, appropriate economic models, and appropriate health technology assessment (HTA) methods during the assessment process, besides, orphan oncology drugs with insufficiency evidence were recommended Cancer Drugs fund (CDF) to afford for patients, which would obtain more availability and accessibility, based on which, high-quality drugs for treating rare cancers can fall within the scope of affordable healthcare provided by the English medical insurance fund.
Circulating (1 → 3)-β-D-Glucan as an immune activation marker decreased after ART in people living with HIV
Authors: Xun Jingna , Guo Shuyan , Xu Yumin , Chen Rong , Tang Qi , Zhang Xinyu , Liu Danping , Zhang Renfang , Shen Yinzhong , Liu Li , Wan Jiangrong , Chen Jun , Lu Hongzhou
Published: September 2022

Background

Plasma level of polysaccharide (1 → 3)-β-D-Glucan (βDG), as a diagnostic marker of invasive fungal infection has been reported to be elevated in people living with HIV (PLWH). We assessed the association of circulating βDG to inflammation and systemic immune activation and the effect of antiretroviral therapy (ART) on βDG in PLWH.

Method

Plasma and peripheral blood monocular cell samples from 120 PLWH naive to ART and after 1 year's ART were collected. Plasma levels of βDG, markers of bacterial translocation, gut damage, and cellular immune activation were quantified.

Result

The plasma βDG levels were negatively correlated with CD4+ T cells count (r = −0.25, p = 0.005) and positively with HIV viral load (r = 0.28, p = 0.002) before ART. It was also positively correlated with immune activation markers, including PD-1 expression on CD4+ T cell (r = 0.40, p = 0.01) and CD8+ T cell (r = 0.47, p = 0.002), as well as HLADR+CD38+ co-expression on CD8+ T cell (r = 0.56, p = 0.0002), but not with the plasma levels of LPS (r = 0.02, p = 0.84), LPS binding protein (LBP, r = 0.11, p = 0.36), soluble LPS receptor sCD14 (r = 0.04, p = 0.68), intestinal fatty acid binding protein (IFABP, r = −0.12, p = 0.18), and regenerating islet-derived protein 3α (REG3α, r = 0.18, p = 0.06). After 1 year's ART, the levels of βDG were significantly decreased compared to that in pre-ART (1.31 ± 0.24 Log10 pg/ml vs. 1.39 ± 0.18 Log10 pg/ml, p < 0.001).

Conclusion

The level of plasma βDG was associated with cellular immune activation and decreased after ART in PLWH, suggesting it could serve as a biomarker of immune activation and efficacy monitoring.
The positive aspects of caregiving in dementia: A scoping review and bibliometric analysis
Authors: Wang Jun , Li Xuelian , Liu Weichu , Yang Bing , Zhao Qinghua , Lü Yang , Xiao Mingzhao
Published: September 2022

Purpose

The increasing incidence of dementia and home-based care exposes family caregivers to a variety of challenges as they endure strong stressors underlying the caregiver role. Despite growing publications on positive aspects of caregiving in dementia, few studies have identified the extent, nature, and gaps in the existing literature based on a holistic view. The aim was to identify key issues and a holistic view of literature regarding positive aspects of caregiving in dementia.

Methods

A scoping review was conducted underlying a five-stage framework by Arksey and O'Malley. Five databases, including PubMed, CINAHL, PsycINFO, Embase, and Web of Science, were searched, and references were listed accordingly. Data were extracted by two researchers, comprising article characteristics, forms of positive aspects of caregiving and measurements, theories, forms of dementia and family caregiver, and keywords. Descriptive statistics and narrative synthesis were performed to analyze data. Network analysis of keywords and authors was conducted using VOSviewer software. Word cloud analysis of titles was examined by NVivo.

Results

The review included 230 articles, most of which have been published in the last decade (62.61%). Most articles (40.00%) were contributed by the United States. Cross-sectional studies (41.30%) ranked first, followed by qualitative studies (13.48%). Over a quarter of the literature (28.26%) focused on Alzheimer's care, and nearly 90% included all forms of family caregivers. The Positive Aspects of Caregiving Scale and stress coping theory were most frequently cited. Four clusters dominated by Casey D, Quinn C, Joling KJ, and Teahan A were identified in the network of co-authorship. Six themes were identified: current situations of caregiver experiences, antecedents, consequences, measurement development, effects of interventions, and the concept of positive aspects of caregiving. These were in line with network analysis of keywords and word cloud analysis of titles.

Conclusions

Positive aspects of caregiving in dementia have been widely concerned, but most of them are based on the theory of the negative stress process and are limited to current situations and influencing factors. Building theories focus on the positive aspects of caregiving, subsequently developing a comprehensive measurement and effective interventions, should be further studied.
Deaf and non-deaf basketball and volleyball players' multi-faceted difference on repeated counter movement jump performances: Height, force and acceleration
Authors: Soslu Recep , Özer Ömer , Uysal Abdullah , Pamuk Ömer
Published: September 2022

The aim of this study was to compare the performances of Repetitive Counter Movement Jumping (basketball/volleyball) of deaf/non-deaf athletes. Athletes playing in the Turkish Deaf Basketball and Volleyball national teams and in Basketball and Volleyball First Leagues participated in the study. The study group consisted of 51 male athletes, including deaf basketball (n = 11; age: 26.18 ± 4.79 years), deaf volleyball (n = 12, age: 26.33 ± 4.27 years), non-deaf basketball (n = 14, age: 26.93 ± 4.87 years), and non-deaf volleyball (n = 14, age: 24.93 ± 5.10 years) players. As a result of the test, Jump Height from Take Off Velocity, Jump Height from Take Off Velocity, Jump Height from Flight Time, Counter Movement Acceleration, Push Off Acceleration, Average Velocity, Average Power, and Average Force were analyzed. Differences in the jump performances among the groups (deaf basketball and volleyball, non-deaf basketball, and volleyball) were tested by one-way analyses of variance (ANOVA) with Tukey's post-hoc follow-up testing when necessary for jump test. As a result, this is the first study to investigate the number of jumps and jump height, the force produced, acceleration at the time of jump, and jump velocity during 30 s in deaf and non-deaf basketball and volleyball players within the scope of individual Repeated Counter Movement Jump test. Based on the biomechanical changes according to our results, our findings show a greater decrease in the number of jumps and jump heights, the force produced, the acceleration at the moment of the jump and the jump velocity in all athletes, especially those that affect the deaf.
The Impact of Foreign Trade on Health Inequality in China: Evidence From China Family Panel Studies (CFPS)
Authors: Xu Pei , Ye Penghao
Published: September 2022

Objectives: To assess the health inequality caused by foreign trade in China using individual self-rated health data from China Family Panel Studies (CFPS).

Methods: The GMM model was used to explore the direct and indirect effects of foreign trade on health level, and the concentration index method was then used to decompose the contribution of foreign trade to health inequality.

Results: The direct effect of foreign trade does not contribute to the current health inequality, although the indirect effects of trade contribute to health inequality through inequalities in income and healthcare utilization. The indirect pollution effect of trade does not cause health inequality. Subsequently, the direct effect of trade aggravates the dynamic expansion trend of health inequality, whereas the indirect effects of trade alleviate the increasing trend of health inequality.

Conclusion: Although foreign trade improves the overall health level in China, it contributes to health inequality. Optimizing product structure of trade, adjusting income distribution, and enhancing medical securities for low-income groups are necessary to alleviate the health inequality caused by foreign trade.
Classification of Program Texts Represented as Markov Chains with Biology-Inspired Algorithms-Enhanced Extreme Learning Machines
Authors: Demidova Liliya A. , Gorchakov Artyom V.
Published: September 2022

The massive nature of modern university programming courses increases the burden on academic workers. The Digital Teaching Assistant (DTA) system addresses this issue by automating unique programming exercise generation and checking, and provides means for analyzing programs received from students by the end of semester. In this paper, we propose a machine learning-based approach to the classification of student programs represented as Markov chains. The proposed approach enables real-time student submissions analysis in the DTA system. We compare the performance of different multi-class classification algorithms, such as support vector machine (SVM), the k nearest neighbors (KNN) algorithm, random forest (RF), and extreme learning machine (ELM). ELM is a single-hidden layer feedforward network (SLFN) learning scheme that drastically speeds up the SLFN training process. This is achieved by randomly initializing weights of connections among input and hidden neurons, and explicitly computing weights of connections among hidden and output neurons. The experimental results show that ELM is the most computationally efficient algorithm among the considered ones. In addition, we apply biology-inspired algorithms to ELM input weights fine-tuning in order to further improve the generalization capabilities of this algorithm. The obtained results show that ELMs fine-tuned with biology-inspired algorithms achieve the best accuracy on test data in most of the considered problems.
Double Redundancy Electro-Hydrostatic Actuator Fault Diagnosis Method Based on Progressive Fault Diagnosis Method
Authors: Qi Hai-Tao , Zhao Dong-Ao , Liu Duo , Liu Xu
Published: September 2022

The electro-hydrostatic actuator (EHA) is the key component of most electric aircraft, and research on its fault diagnosis technology is of great significance to improve the safety and reliability of aircraft flight. However, traditional fault diagnosis methods only focus on partial failures and cannot completely diagnose the whole EHA system. In this paper, the progressive fault diagnosis method (PFDM) is proposed for overall diagnosis of whole EHA system, which can be divided into four levels for health detection and fault diagnosis of the overall EHA system. PFDM combines fault diagnosis methods based on Kalman filter, threshold, logic, and EHA system analysis model to diagnose the whole EHA system layer by layer. At the same time, in order to ensure the normal operation of the EHA system after fault diagnosis, double redundancy design is creatively carried out for the EHA system to facilitate system reconstruction after fault detection. It can be continuously modified according to different EHA system parameters and measured signals to improve the accuracy of fault diagnosis. The experimental results show that PFDM can accurately locate and identify 22 faults of the double redundancy EHA system by using the accurate EHA system mathematical model. PFDM improves the fault diagnosis response time to 4 ms, greatly improving the safety and reliability of the double redundancy EHA system.
Aerodynamic Optimization of Transonic Rotor Using Radial Basis Function Based Deformation and Data-Driven Differential Evolution Optimizer
Authors: Liu Yi , Chen Jiang , Cheng Jinxin , Xiang Hang
Published: September 2022

The complicated flow conditions and massive design parameters bring two main difficulties to the aerodynamic optimization of axial compressors: expensive evaluations and numerous optimization variables. To address these challenges, this paper establishes a novel fast aerodynamic optimization platform for axial compressors, consisting of a radial basic function (RBF)-based blade parameterization method, a data-driven differential evolution optimizer, and a computational fluid dynamic (CFD) solver. As a versatile interpolation method, RBF is used as the shape parameterization and deformation technique to reduce optimization variables. Aiming to acquire competitive solutions in limited steps, a data-driven evolution optimizer is developed, named the pre-screen surrogate model assistant differential evolution (pre-SADE) optimizer. Different from most surrogate model-assisted evolutionary algorithms, surrogate models in pre-SADE are used to screen the samples, rather than directly estimate them, in each generation to reduce expensive evaluations. The polynomial regression model, Kriging model, and RBF model are integrated in the surrogate model to improve the accuracy. To further save optimization time, the optimizer also integrates parallel task management programs. The aerodynamic optimization of a transonic rotor (NASA Rotor 37) is performed as the validation of the platform. A differential evolution (DE) optimizer and another surrogate model-assisted algorithm, committee-based active learning for surrogate model assisted particle swarm optimization (CAL-SAPSO), are introduced for the comparison runs. After optimization, the adiabatic efficiency, total pressure ratio, and surge margin are, respectively, increased by 1.47%, 1.0%, and 0.79% compared to the initial rotor. In the same limited steps, pre-SADE gets a 0.57% and 0.51% higher rotor adiabatic efficiency than DE and CAL-SAPSO, respectively. With the help of parallel techniques, pre-SADE and DE save half the optimization time compared to CAL-SAPSO. The results verify the effectiveness and the rapidity of the fast aerodynamic optimization platform.
Effects of Conservation Tillage on Soil Properties and Maize Yield in Karst Regions, Southwest China
Authors: Bai Lizhen , Kong Xiangying , Li Hui , Zhu Huibin , Wang Chengwu , Ma Shiao
Published: September 2022

Karst rocky desertification associated with human disturbance is one of the most serious eco-environmental problems, threatening the sustainable development of agriculture in southwestern China. In the current study, the practice of conservation tillage as one of the best ways of reducing the constraints is addressed. During a two-year trial (2014–2015), the effects of no tillage with straw cover (NT) and traditional tillage (TT) on soil properties and maize yields were investigated in karst regions, Southwest China. The results showed that the trial with NT increased soil moisture content by 3%, while decreasing soil bulk density by 7% in the top 30 cm compared with TT. In 2014, within 0–30 cm of soil depth, total nitrogen under NT treatment was 5% higher than that under TT treatment. In 2015, the mean soil organic matter (SOM) and available P were enhanced to 12% and 13% in 0–30 cm soil depth more than that under TT, respectively. The trial with NT significantly (p < 0.05) increased available N in the top 20 cm by 9% as compared to TT. This improvement in soil physical and chemical properties might have increased the crop yield. After the two-year trial with NT, the mean maize yields increased by 11% compared with the TT trial. Therefore, conservation tillage is the better option considering long-term environmental sustainability in karst regions.