bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of direct challenges to student endorsement of teleological reasoning on understanding and acceptance of natural selection: an exploratory study
Authors: Wingert Jason R. , Bassett Gennie M. , Terry Caitlin E. , Lee Jimin
Published: April 2022

Background

Teleological reasoning is a cognitive bias purported to disrupt student ability to understand natural selection. Few studies have described pedagogical efforts to decrease student endorsement of teleological reasoning and measure the effects of this attenuation on the understanding and acceptance of evolution. This exploratory study examined the influence of explicit instructional activities directly challenging student endorsement of teleological explanations for evolutionary adaptations on their learning of natural selection over a semester-long undergraduate course in evolutionary medicine. In a convergent mixed methods design this study combined pre- and post-semester survey data (N = 83) on understanding natural selection, student endorsement of teleological reasoning, and acceptance of evolution, with thematic analysis of student reflective writing on their understanding and acceptance of natural selection and teleological reasoning.

Results

Student endorsement of teleological reasoning decreased and understanding and acceptance of natural selection increased during a course on human evolution with teleological intervention (p ≤ 0.0001), compared to a control course. Endorsement of teleological reasoning was predictive of understanding of natural selection prior to the semester. Thematic analysis revealed that prior to the course students were largely unaware of the concept of teleological reasoning and their own tendency to think about evolution in a purpose-directed way, but perceived attenuation of their own teleological reasoning by the end of the semester.

Conclusions

This exploratory study provides initial evidence that class activities to directly challenge student endorsement of unwarranted design teleological reasoning reduces the level and effects of teleological reasoning in an evolution course. Students were unaware of their high levels of endorsement of teleological reasoning upon entrance into the undergraduate human evolution course, which is consequential because teleological reasoning is a predicter of natural selection understanding. As a result of developed anti-teleological pedagogy, students had decreased unwarranted teleological reasoning and increased acceptance and understanding of natural selection over the course of the semester. The data presented show that students are receptive to explicit instructional challenges to their teleological reasoning and that attenuation of this bias is associated with gains in natural selection understanding and acceptance.
Configuring user information by considering trust threatening factors associated with automated vehicles
Authors: Yun Hanna , Yang Ji Hyun
Published: March 2022

Background

The accelerated development of automated driving technology has raised the expectation that commercially available automated vehicles will be increasingly become ubiquitous. It has been claimed that automated vehicles are safer than conventional manual vehicles, leading to the expectation of fewer accidents. However, people expect not only better but also near-perfect machines. Given that accidents involving automated vehicle do occur and are highlighted by the media, negative reactions toward automated vehicles have increased. For this reason, it is critical to research human–machine interaction to develop suitable levels of trust between human users and newly introduced automated vehicle systems.

Method

We start this study by defining user distrust toward automated vehicles in terms of four types of trustthreatening factors (TTFs) along with trust-threatening situations. Next, with 30 volunteer participants, we conduct a survey and a humanin-the-loop experiment involving riding in a simulated automated vehicle and experiencing 21 distrust scenarios.

Result

In terms of the information configuration type suitable for alleviating the TTFs, the participants preferred to receive information on external object recognition for all TTFs in general with an average necessity level score of 24.2, which was 8.0 points higher on average than the scores of the other information configuration types. The haptic modality-based method was the least preferred compared to the other information configuration methods, namely visual and auditory.

Conclusion

In this study, we focused on participants’ subjective responses and complementary quantitative studies, and the results of these studies put together are expected to serve as a foundation for designing a user interface that can induce trust toward automated vehicle among users.
Olfactory function and discrimination ability in the elderly: a pilot study
Authors: Uchida Sae , Shimada Chiho , Sakuma Naoko , Kagitani Fusako , Kan Akiko , Awata Shuichi
Published: April 2022

We recently reported that subjects with a higher olfactory identification threshold for rose odor declined more in attentional ability in the elderly. This study focuses on discrimination ability and olfactory identification threshold in twelve elderly subjects living in a community (age: 80.9 ± 1.6). Olfactory function was assessed by the rose odor identification threshold. We assessed the discrimination ability by distinguishing 5 similar odor pairs. Our results showed that the subjects with a higher olfactory identification threshold (≥ 5) declined more in discrimination ability (14% ± 14%, p = 0.03) compared to those with a lower threshold (≤ 4) (averaged value set at 100%). As discrimination ability is related to the basal forebrain cholinergic system, our results suggest that olfactory impairment links to the decline in cognitive function relating the cholinergic system.
Chromatin-remodeling factor CHR721 with non-canonical PIP-box interacts with OsPCNA in Rice
Authors: Zhang Yushun , Chen Qiong , Zhu Guanlin , Zhang Dechun , Liang Weihong
Published: April 2022

Background

Proliferating cell nuclear antigen (PCNA) is one of the key factors for the DNA replication process and DNA damage repair. Most proteins interacting with PCNA have a common binding motif: PCNA interacting protein box (PIP box). However, some proteins with non-canonical PIP-box have also been reported to be the key factors that interacted with PCNA.

Results

Here we discovered the C terminal of a chromatin-remodeling factor CHR721 with non-canonical PIP-box was essential for interacting with OsPCNA in rice. Both OsPCNA and CHR721 were localized in the nuclei and function in response to DNA damages.

Conclusions

Based on the results and previous work, we proposed a working model that CHR721 with non-canonical PIP-box interacted with OsPCNA and both of them probably participate in the DNA damage repair process.
Low irrigation water minimizes the nitrate nitrogen losses without compromising the soil fertility, enzymatic activities and maize growth
Authors: Muhammad Ihsan , Lv Ju Zhi , Yang Li , Ahmad Shakeel , Farooq Saqib , Zeeshan Muhammad , Zhou Xun Bo
Published: April 2022

Nitrate nitrogen (NO3−_N) leaching increased with nitrogen (N) fertilization under high water supply to the field negatively affected the maize growth and performance. This study aimed to understand the mechanisms of NO3−_N leaching on a biochemical basis and its relationship with plant performance with 5 different doses (0, 200, 250, 300, 350 kg N ha− 1) of N fertilizers under low (60%; LW) and high (80%; HW) water holding capacity. Soil and plant enzymes were observed at different growth stages (V9, R1, R3, and R6) of the maize, whereas the leachates were collected at 10-days intervals from the sowing date. The LW had 10.15% lower NO3−_N leachate than HW, with correspondence increases in grain yield (25.57%), shoot (17.57%) and root (28.67%) dry matter. Irrespective of the irrigation water, RubisCo, glutamine synthase (GS), nitrate reductase (NR), nitrite reductase (NiR), and glutamate synthase (GOGAT) activities increased with increasing N fertilizer up to the V9 growth stage and decreased with approaching the maturity stage (R6) in maize. In HW irrigation, soil total N, GOGAT, soil nitrate (NO3−_N), leached nitrate (LNO3−_N), root N (RN), leaf N (LN) were positively correlated with N factors suggesting the higher losses of N through leaching (11.3%) compared to LW irrigation. However, the malondialdehyde (MDA), hydrogen peroxide (H2O2), superoxide (O2−), and proline were negatively correlated with the other enzymatic activities both under LW and HW irrigation. Thus, minimizing the NO3−_N leaching is possibly correlated with the LW and N300 combination without compromising the yield benefit and improving enzyme activities.
Impact of a dementia-friendly program on detection and management of patients with cognitive impairment and delirium in acute-care hospital units: a controlled clinical trial design
Authors: Weldingh NM , Mellingsæter MR , Hegna BW , Benth J Saltyte , Einvik G , Juliebø V , Thommessen B , Kirkevold M
Published: March 2022

Background

Frail older persons with cognitive impairment (CI) are at special risk of experiencing delirium during acute hospitalisation. The purpose of this study was to investigate whether a dementia-friendly hospital program contributes to improved detection and management of patients with CI and risk of delirium at an acute-care hospital in Norway. Furthermore, we aimed to explore whether the program affected the detection of delirium, pharmacological treatment, 30-day re-hospitalisation, 30-day mortality and institutionalisation afterwards.

Methods

This study was part of a larger quality improvement project aiming at developing and implementing a new program for early screening and management of patients with CI. This study, evaluating the program are designed as a controlled clinical trial with a historical control group. It was conducted at two different medical wards at a large acute-care hospital in Norway from September 2018 to December 2019. A total of 423 acute hospitalised patients 75 years of age or older were included in the study. Delirium screening and cognitive tests were recorded by research staff with the 4 ‘A’s Test (4AT) and the Confusion Assessment Measure (CAM), while demographic and medical information was recorded from the electronic medical records (EMR).

Results

Implementation of the dementia-friendly hospital program did not show any significant changes in the identification of patients with CI. However, the share of patients screened with 4AT within 24 h increased from 0% to 35.5% (P < .001). The proportion of the patients with CI identified by the clinical staff, who received measures to promote “dementia-friendly” care and reduce the risk for delirium increased by 32.2% (P < .001), compared to the control group. Furthermore, the number of patients with CI who were prescribed antipsychotic, hypnotic or sedative medications was reduced by 24.5% (P < .001). There were no differences in delirium detection, 30-day readmission or 30-day mortality.

Conclusions

A model for early screening and multifactorial non-pharmacological interventions for patients with CI and delirium may improve management of this patient group, and reduce prescriptions of antipsychotic, hypnotic and sedative medications. The implementation in clinical practice of early screening using quality improvement methodology deserves attention.

Trial registration

The protocol of this study was retrospectively registered in the ClinicalTrials.gov Protocol Registration and Results System with the registration number: NCT04737733 and date of registration: 03/02/2021.
Reliability and validity of the fall risk self-assessment scale for community-dwelling older people in China: a pilot study
Authors: Wang Zhizhuo , Rong Yuetong , Gu Li , Yang Yanyan , Du Xinmin , Zhou Mouwang
Published: April 2022

Background

Falls are a common and serious public health issue among older adults, contributing to the loss of independence, psychological distress, and incapability to engage in meaningful occupations, etc. However, there is a lack of abundant information about the fall risk self-evaluation scale for community-dwelling older people. Therefore, this study aimed to evaluate the preliminary reliability and validity of the fall risk self-assessment scale (FRSAS) among community-dwelling older adults.

Methods

A cross-sectional study was conducted. A total of 230 individuals aged 65 years and over were recruited by a convenience sampling between October and December 2020 from three communities in Haidian district, Beijing. Eligible participants were required to fill in the general condition questionnaire and the fall risk self-assessment scale. The reliability and validity were analyzed by using SPSS 20.0.

Results

Two hundred twenty-two participants completed the assessment as required (the completion rate was 96.52%). The most items of FRSAS were understood by older adults, which was completed in 10 min. Cronbach’s α and intraclass correlation coefficient ICC (2,1) of the scale were 0.757 and 0.967 respectively, suggesting good internal consistency and test-retest reliability. Exploratory factor analysis yielded 14 factors that explained 61.744% of the variance. Five items failed to be categorized into any factors because the factor loading of these items was less than 0.4. A future large-sample study needs to be conducted to explore its construct validity. The total scores and dimensional scores except for C-dimension showed significant differences between participants who had experienced a fall in the previous 6 months and those who had not (P < 0.05), indicating good discriminant validity.

Conclusions

The fall risk self-assessment scale including 41 items demonstrated relatively high feasibility as well as satisfactory results in the internal consistency, test-retest reliability, and discriminant validity.

Trial registration

Registration number: ChiCTR2000038856; Date of registration: 7 Oct 2020.
Distribution of FFRCT in single obstructive coronary stenosis and predictors for major adverse cardiac events: a propensity score matching study
Authors: Jin Xianglan , Jin Xiangyu , Wu Xiaoyun , Chen Luguang , Wang Tiegong , Zang Wangfu
Published: March 2022

Background

Fractional flow reserve derived from computed tomography (FFRCT) has been demonstrated to improve identification of lesion-specific ischemia significantly compared with coronary computed tomography angiography (CCTA). It remains unclear whether the distribution of FFRCT values in obstructive stenosis between patients who received percutaneous coronary intervention (PCI) or not in routine clinical practice, as well as its association with clinical outcome. This study aims to reveal the distribution of FFRCT value in patients with single obstructive coronary artery stenosis and explored the independent factors for predicting major adverse cardiac events (MACE).

Methods

This was a retrospective study of adults with non-ST-segment elevation acute coronary syndrome undergoing FFRCT assessment by using CCTA data from January 1, 2016 to December 31, 2020. Propensity score matching (PSM) method was used to account for patient selection bias. The risk factors for predicting MACE were evaluated by a Cox proportional hazards regression analysis.

Results

Overall, 655 patients with single obstructive (≥ 50%) stenosis shown on CCTA were enrolled and divided into PCI group (279 cases) and conservative group (376 cases) according to treatment strategy. The PSM cohort analysis demonstrated that the difference in history of unstable angina, Canadian Cardiovascular Society Class (CCSC) and FFRCT between PCI group (188 cases) and conservative group (315 cases) was statistically significant, with all P values < 0.05, while the median follow-up time between them was not statistically significant (24 months vs. 22.5 months, P = 0.912). The incidence of MACE in PCI group and conservative group were 14.9% (28/188) and 23.5% (74/315) respectively, P = 0.020. Multivariate analysis of Cox proportional hazards regression revealed that history of unstable angina (adjusted odds ratio (adjOR), 3.165; 95% confidence interval (CI), 2.087–4.800; P < 0.001), FFRCT ≤ 0.8 (OR, 1.632;95% CI 1.095–2.431; P = 0.016), and PCI therapy (OR 0.481; 95% CI 0.305–0.758) were the independent factors for MACE.

Conclusions

History of unstable angina and FFRCT value of ≤ 0.8 were the independent risk factors for MACE, while PCI therapy was the independent protective factor for MACE.
Coping with Covid-19: stress, control and coping among pregnant women in Ireland during the Covid-19 pandemic
Authors: Crowe Sarah , Sarma Kiran
Published: April 2022

Background

The aim of the current study is to investigate the relationship between perceived control, coping and psychological distress among pregnant women in Ireland during the Covid-19 pandemic. It is hypothesised that lower levels of perceived control, greater use of avoidant coping and greater Covid-19 related pregnancy concern will be associated with psychological distress. In addition, it is hypothesised that the relationship between Covid-19 related pregnancy concern and psychological distress will be moderated by perceived control and avoidant coping.

Method

The study is cross-sectional, utilizing an online questionnaire, which was completed by 761 women in January 2021. The questionnaire includes measures of perceived control, coping style, perceived stress, anxiety and depression.

Results

Correlation analyses found that lower levels of perceived control were associated with higher levels of avoidant coping and psychological distress. There was also a significant positive relationship between avoidant coping and psychological distress. Using multiple regression, perceived control, avoidant coping and Covid-19 related pregnancy concern were found to predict 51% of the variance in psychological distress. However, in the moderation analysis, perceived control and avoidant coping were not found to moderate the relationship between Covid-19 related pregnancy concern and psychological distress.

Conclusion

The results from this study suggest that pregnant women in Ireland are experiencing increased levels of psychological distress during the Covid-19 pandemic. The findings also suggest that perceptions of control and avoidant coping are associated with psychological distress in this group and could be used as intervention targets.
Ninjinyoeito ameliorated cigarette smoke extract-induced apoptosis and inflammation through JNK signaling inhibition in human lung fibroblasts
Authors: Murata Kenta , Fujita Nina , Takahashi Ryuji
Published: March 2022

Background

Cigarette smoke is a major risk factor for various lung diseases, such as chronic obstructive pulmonary disease (COPD). Ninjinyoeito (NYT), a traditional Chinese medicine, has been prescribed for patients with post-illness or post-operative weakness, fatigue, loss of appetite, rash, cold limbs, and anemia. In addition to its traditional use, NYT has been prescribed for treating frailty in gastrointestinal, respiratory, and urinary functions. Further, NYT treatment can ameliorate cigarette smoke-induced lung injury, which is a destructive index in mice; however, the detailed underlying mechanism remains unknown. The purpose of this study was to investigate whether NYT ameliorates cigarette smoke-induced cell injury and inflammation in human lung fibroblasts and determine its mechanism of action.

Methods

We prepared a cigarette smoke extract (CSE) from commercially available cigarettes to induce cell injury and inflammation in the human lung fibroblast cell line HFL1. The cells were pretreated with NYT for 24 h prior to CSE exposure. Cytotoxicity and cell viability were measured by lactate dehydrogenase (LDH) cytotoxicity assay and cell counting kit (CCK)-8. IL-8 level in the cell culture medium was measured by performing Enzyme-Linked Immuno Sorbent Assay (ELISA). To clarify the mechanisms of NYT, we used CellROX Green Reagent for reactive oxygen species (ROS) production and western blotting analysis for cell signaling.

Results

Exposure of HFL1 cells to CSE for 24 h induced apoptosis and interleukin (IL)-8 release. Pretreatment with NYT inhibited apoptosis and IL-8 release. Furthermore, CSE exposure for 24 h increased the production of ROS and phosphorylation levels of p38 and JNK. Pretreatment with NYT only inhibited CSE-induced JNK phosphorylation, and not ROS production and p38 phosphorylation. These results suggest that NYT acts as a JNK-specific inhibitor.

Conclusion

NYT treatment ameliorated CSE-induced apoptosis and inflammation by inhibiting the JNK signaling pathway. Finally, these results suggest that NYT may be a promising therapeutic agent for patients with COPD.
How do internal medicine subspecialty societies support clinician-educator careers? A qualitative exploratory study
Authors: Santhosh Lekshmi , Abdoler Emily , O’Brien Bridget C. , Schwartz Brian
Published: March 2022

Background

Internal Medicine (IM) subspecialty professional societies can provide valuable community, recognition, resources, and leadership opportunities that promote career success. Historically, this support focused on clinical and research dimensions of academic careers, but educational dimensions have gained more attention recently. This study explores how IM subspecialty professional societies support their clinician-educator members.

Methods

Using a qualitative study with two phases, the authors collected information from each IM subspecialty society’s website about support for medical education. Using information from the first phase, we developed an interview guide for subspecialty society leaders. We used inductive thematic analysis to analyze interview transcripts.

Results

Website analysis identified various mechanisms used by several IM subspecialty societies to promote medical education. These included websites focused on medical education, dedicated medical education poster/abstract sessions at annual meetings, and strategies to promote networking among clinician-educators. Interviews with eight subspecialty society leaders about the professional societies’ roles with respect to medical education yielded four main themes: [1] varying conceptions of “medical education” in relation to the society [2] strategies to advance medical education at the society level [3] barriers to recognizing medical education [4] benefits of clinician-educators to the societies. Integrating these themes, we describe recommended strategies for professional societies to better serve clinician-educators.

Conclusions

We explore how IM subspecialty societies attend to a growing constituency of clinician-educators, with increasing recognition and support of the career path but persistent barriers to its formalization. These conversations shed light on opportunities for professional subspecialty societies to better serve the needs of their clinician-educator members while also enabling these members to make positive contributions in return.
Release of moth pheromone compounds from Nicotiana benthamiana upon transient expression of heterologous biosynthetic genes
Authors: Xia Yi-Han , Ding Bao-Jian , Dong Shuang-Lin , Wang Hong-Lei , Hofvander Per , Löfstedt Christer
Published: March 2022

Background

Using genetically modified plants as natural dispensers of insect pheromones may eventually become part of a novel strategy for integrated pest management.

Results

In the present study, we first characterized essential functional genes for sex pheromone biosynthesis in the rice stem borer Chilo suppressalis (Walker) by heterologous expression in Saccharomyces cerevisiae and Nicotiana benthamiana, including two desaturase genes CsupYPAQ and CsupKPSE and a reductase gene CsupFAR2. Subsequently, we co-expressed CsupYPAQ and CsupFAR2 together with the previously characterized moth desaturase Atr∆11 in N. benthamiana. This resulted in the production of (Z)-11-hexadecenol together with (Z)-11-hexadecenal, the major pheromone component of C. suppressalis. Both compounds were collected from the transformed N. benthamiana headspace volatiles using solid-phase microextraction. We finally added the expression of a yeast acetyltransferase gene ATF1 and could then confirm also (Z)-11-hexadecenyl acetate release from the plant.

Conclusions

Our results pave the way for stable transformation of plants to be used as biological pheromone sources in different pest control strategies.
Assignment of unimodal probability distribution models for quantitative morphological phenotyping
Authors: Ghanegolmohammadi Farzan , Ohnuki Shinsuke , Ohya Yoshikazu
Published: March 2022

Background

Cell morphology is a complex and integrative readout, and therefore, an attractive measurement for assessing the effects of genetic and chemical perturbations to cells. Microscopic images provide rich information on cell morphology; therefore, subjective morphological features are frequently extracted from digital images. However, measured datasets are fundamentally noisy; thus, estimation of the true values is an ultimate goal in quantitative morphological phenotyping. Ideal image analyses require precision, such as proper probability distribution analyses to detect subtle morphological changes, recall to minimize artifacts due to experimental error, and reproducibility to confirm the results.

Results

Here, we present UNIMO (UNImodal MOrphological data), a reliable pipeline for precise detection of subtle morphological changes by assigning unimodal probability distributions to morphological features of the budding yeast cells. By defining the data type, followed by validation using the model selection method, examination of 33 probability distributions revealed nine best-fitting probability distributions. The modality of the distribution was then clarified for each morphological feature using a probabilistic mixture model. Using a reliable and detailed set of experimental log data of wild-type morphological replicates, we considered the effects of confounding factors. As a result, most of the yeast morphological parameters exhibited unimodal distributions that can be used as basic tools for powerful downstream parametric analyses. The power of the proposed pipeline was confirmed by reanalyzing morphological changes in non-essential yeast mutants and detecting 1284 more mutants with morphological defects compared with a conventional approach (Box–Cox transformation). Furthermore, the combined use of canonical correlation analysis permitted global views on the cellular network as well as new insights into possible gene functions.

Conclusions

Based on statistical principles, we showed that UNIMO offers better predictions of the true values of morphological measurements. We also demonstrated how these concepts can provide biologically important information. This study draws attention to the necessity of employing a proper approach to do more with less.
Molecular phylogeny of coronaviruses and host receptors among domestic and close-contact animals reveals subgenome-level conservation, crossover, and divergence
Authors: Bentum Kingsley , Shaddox Sage , Ware Crystal , Reddy Gopal , Abebe Woubit , Folitse Raphael , Martin Pamela , Samuel Temesgen
Published: April 2022

Background

Coronaviruses have the potential to cross species barriers. To learn the molecular intersections among the most common coronaviruses of domestic and close-contact animals, we analyzed representative coronavirus genera infecting mouse, rat, rabbit, dog, cat, cattle, white-tailed deer, swine, ferret, mink, alpaca, Rhinolophus bat, dolphin, whale, chicken, duck and turkey hosts; reference or complete genome sequences were available for most of these coronavirus genera. Protein sequence alignments and phylogenetic trees were built for the spike (S), envelope (E), membrane (M) and nucleocapsid (N) proteins. The host receptors and enzymes aminopeptidase N (APN), angiotensin converting enzyme 2 (ACE2), sialic acid synthase (SAS), transmembrane serine protease 2 (TMPRSS2), dipeptidyl peptidase 4 (DPP4), cathepsin L (and its analogs) and furin were also compared.

Results

Overall, the S, E, M, and N proteins segregated according to their viral genera (α, β, or γ), but the S proteins of alphacoronaviruses lacked conservation of phylogeny. Interestingly, the unique polybasic furin cleavage motif found in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) but not in severe acute respiratory syndrome coronavirus (SARS-CoV) or Middle East respiratory syndrome coronavirus (MERS-CoV) exists in several β-coronaviruses and a few α- or γ-coronaviruses. Receptors and enzymes retained host species-dependent relationships with one another. Among the hosts, critical ACE2 residues essential for SARS-CoV-2 spike protein binding were most conserved in white-tailed deer and cattle.

Conclusion

The polybasic furin cleavage motif found in several β- and other coronaviruses of animals points to the existence of an intermediate host for SARS-CoV-2, and it also offers a counternarrative to the theory of a laboratory-engineered virus. Generally, the S proteins of coronaviruses show crossovers of phylogenies indicative of recombination events. Additionally, the consistency in the segregation of viral proteins of the MERS-like coronavirus (NC_034440.1) from pipistrelle bat supports its classification as a β-coronavirus. Finally, similarities in host enzymes and receptors did not always explain natural cross-infections. More studies are therefore needed to identify factors that determine the cross-species infectivity of coronaviruses.
The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases
Authors: Alsheikh Ammar J. , Wollenhaupt Sabrina , King Emily A. , Reeb Jonas , Ghosh Sujana , Stolzenburg Lindsay R. , Tamim Saleh , Lazar Jozef , Davis J. Wade , Jacob Howard J.
Published: April 2022

Background

The remarkable growth of genome-wide association studies (GWAS) has created a critical need to experimentally validate the disease-associated variants, 90% of which involve non-coding variants.

Methods

To determine how the field is addressing this urgent need, we performed a comprehensive literature review identifying 36,676 articles. These were reduced to 1454 articles through a set of filters using natural language processing and ontology-based text-mining. This was followed by manual curation and cross-referencing against the GWAS catalog, yielding a final set of 286 articles.

Results

We identified 309 experimentally validated non-coding GWAS variants, regulating 252 genes across 130 human disease traits. These variants covered a variety of regulatory mechanisms. Interestingly, 70% (215/309) acted through cis-regulatory elements, with the remaining through promoters (22%, 70/309) or non-coding RNAs (8%, 24/309). Several validation approaches were utilized in these studies, including gene expression (n = 272), transcription factor binding (n = 175), reporter assays (n = 171), in vivo models (n = 104), genome editing (n = 96) and chromatin interaction (n = 33).

Conclusions

This review of the literature is the first to systematically evaluate the status and the landscape of experimentation being used to validate non-coding GWAS-identified variants. Our results clearly underscore the multifaceted approach needed for experimental validation, have practical implications on variant prioritization and considerations of target gene nomination. While the field has a long way to go to validate the thousands of GWAS associations, we show that progress is being made and provide exemplars of validation studies covering a wide variety of mechanisms, target genes, and disease areas.
Association of air pollution exposure with exercise-induced oxygen desaturation in COPD
Authors: Lee Kang-Yun , Wu Sheng-Ming , Kou Hsiao-Yun , Chen Kuan-Yuan , Chuang Hsiao-Chi , Feng Po-Hao , Chung Kian Fan , Ito Kazuhiro , Chen Tzu-Tao , Sun Wei-Lun , Liu Wen-Te , Tseng Chien-Hua , Ho Shu-Chuan
Published: March 2022

Background

There is a link between exposure to air pollution and the increased prevalence of chronic obstructive pulmonary disease (COPD) and declining pulmonary function, but the association with O2 desaturation during exercise in COPD patients with emphysema is unclear. Our aims were to estimate the prevalence of O2 desaturation during exercise in patients with COPD, and determine the association of exposure to air pollution with exercise-induced desaturation (EID), the degree of emphysema, and dynamic hyperinflation (DH).

Methods

We assessed the effects of 10-year prior to the HRCT assessment and 7 days prior to the six-minute walking test exposure to particulate matter with an aerodynamic diameter of < 10 µm (PM10) or of < 2.5 µM (PM2.5), nitrogen dioxide (NO2), and ozone (O3) in patients with emphysema in this retrospective cohort study. EID was defined as a nadir standard pulse oximetry (SpO2) level of < 90% or a delta (△)SpO2 level of ≥ 4%. Ambient air pollutant (PM2.5, PM10, O3, and NO2) data were obtained from Taiwan Environmental Protection Administration (EPA) air-monitoring stations, usually within 10 km to each participant’s home address.

Results

We recruited 141 subjects with emphysema. 41.1% of patients with emphysema exhibited EID, and patients with EID had more dyspnea, worse lung function, more severe emphysema, more frequent acute exacerbations, managed a shorter walking distance, had DH, and greater long-term exposure to air pollution than those without EID. We observed that levels of 10-year concentrations of PM10, PM2.5, and NO2 were significantly associated with EID, PM10 and PM2.5 were associated with the severity of emphysema, and associated with DH in patients with emphysema. In contrast, short-term exposure did not have any effect on patients.

Conclusion

Long-term exposure to ambient PM10, PM2.5 and NO2, but not O3, was associated with EID.
The function and regulation network mechanism of circRNA in liver diseases
Authors: Wang Panpan , Zhang Yunhuan , Deng Lugang , Qu Zhi , Guo Peisen , Liu Limin , Yu Zengli , Wang Peixi , Liu Nan
Published: March 2022

Circular RNA (circRNA), a new type of endogenous non-coding RNA, is abundantly present in eukaryotic cells, and characterized as stable high conservation and tissue specific expression. It has been generated increasing attention because of their close association with the progress of diseases. The liver is the vital organ of humans, while it is prone to acute and chronic diseases due to the influence of multiple pathogenic factors. Moreover, hepatocellular carcinoma (HCC) is the one of most common cancer and the leading cause of cancer death worldwide. Overwhelming evidences indicate that some circRNAs are differentially expressed in liver diseases, such as, HCC, chronic hepatitis B, hepatic steatosis and hepatoblastoma tissues, etc. Additionally, these circRNAs are related to proliferation, invasion, migration, angiogenesis, apoptosis, and metastasis of cell in liver diseases and act as oncogenic agents or suppressors, and linked to clinical manifestations. In this review, we briefly summarize the biogenesis, characterization and biological functions, recent detection and identification technologies of circRNA, and regulation network mechanism of circRNA in liver diseases, and discuss their potential values as biomarkers or therapeutic targets for liver diseases, especially on HCC.
Low density neutrophils are increased in patients with Behçet’s disease but do not explain differences in neutrophil function
Authors: Murad Mariam , Low Liying , Davidson Matthew , Murray Philip I. , Rauz Saaeha , Wallace Graham R.
Published: March 2022

Background

Behçet’s disease (BD) is a multisystem autoinflammatory disease characterised by mucosal ulceration, ocular, neural, joint and skin inflammation. The cause of BD is not known but there is a strong genetic association with HLA-B*51, IL10 and IL23R. Neutrophils are a first line of defence against invading pathogens and have been described as activated in patients with BD. Neutrophils can now be separated into different subsets, such as low density (LDN) and normal density (NDN) that have diverse functional roles. We wished to address neutrophil heterogeneity in patients with BD.

Methods

Peripheral blood neutrophils were obtained from 32 BD patients and 37 healthy aged-matched controls. Percoll isolation was used to isolate all neutrophils, while Ficol-Hypaque was used to obtain LDN and NDN. Phagocytic capacity and production of reactive oxygen species (ROS), and neutrophil extracellular traps (NET) stimulated with phorbol 12-myristate 13-acetate (PMA) and Escherichia coli (E.coli) were assessed in both groups.

Results

We have demonstrated reduced phagocytic capacity and ROS production but greater NET production by total neutrophils stimulated with PMA or E.coli from BD patients in comparison with healthy controls. Patients with BD had elevated numbers of LDN and lower number of NDN compared with healthy controls. However, both neutrophil subsets showed the same reduced ROS production and phagocytic function as total neutrophils in both groups.

Conclusion

Our novel findings indicate that the neutrophil population in BD is heterogeneous and the increased number of LDN in combination with greater NET production may contribute to the inflammatory response and pathogenesis.
High relaxivity Gd3+-based organic nanoparticles for efficient magnetic resonance angiography
Authors: Liu Zhuang , Zhao Menglong , Wang Han , Fu Zi , Gao Hongbo , Peng Weijun , Ni Dalong , Tang Wei , Gu Yajia
Published: March 2022

Contrast-enhanced MR angiography (MRA) is a critical technique for vascular imaging. Nevertheless, the efficacy of MRA is often limited by the low rate of relaxation, short blood-circulation time, and metal ion-released potential long-term toxicity of clinical available Gd-based contrast agents. In this work, we report a facile and efficient strategy to achieve Gd-chelated organic nanoparticles with high relaxivity for T1-weighted MRA imaging. The Gd-chelated PEG-TCPP nanoparticles (GPT NPs) have been engineered composite structured consisting of Gd-chelated TCPP and PEG. The spherical structure of TCPP offers more chemical sites for Gd3+ coordination to improve the relaxivity and avoid leakage of the Gd3+ ions. The synthesized GPT NPs exhibit a high relaxation rate of 35.76 mM− 1 s− 1 at 3.0 T, which is higher than the rates for most reported MR contrast agents. Therefore, GPT NPs can be used for MRA with much stronger vascular signals, longer circulation time, and high-resolution arterial vascular visualization than those using clinical MR contrast agents at the same dose. This work may make the T1 MRI contrast agents for high-resolution angiography possible and offer a new candidate for preclinical and clinical applications of MR vascular imaging and vascular disease diagnosis.

Graphical Abstract
An objective metric of individual health and aging for population surveys
Authors: Li Qing , Legault Véronique , Girard Vincent-Daniel , Ferrucci Luigi , Fried Linda P. , Cohen Alan A.
Published: March 2022

Background

We have previously developed and validated a biomarker-based metric of overall health status using Mahalanobis distance (DM) to measure how far from the norm of a reference population (RP) an individual’s biomarker profile is. DM is not particularly sensitive to the choice of biomarkers; however, this makes comparison across studies difficult. Here we aimed to identify and validate a standard, optimized version of DM that would be highly stable across populations, while using fewer and more commonly measured biomarkers.

Methods

Using three datasets (the Baltimore Longitudinal Study of Aging, Invecchiare in Chianti and the National Health and Nutrition Examination Survey), we selected the most stable sets of biomarkers in all three populations, notably when interchanging RPs across populations. We performed regression models, using a fourth dataset (the Women’s Health and Aging Study), to compare the new DM sets to other well-known metrics [allostatic load (AL) and self-assessed health (SAH)] in their association with diverse health outcomes: mortality, frailty, cardiovascular disease (CVD), diabetes, and comorbidity number.

Results

A nine- (DM9) and a seventeen-biomarker set (DM17) were identified as highly stable regardless of the chosen RP (e.g.: mean correlation among versions generated by interchanging RPs across dataset of r = 0.94 for both DM9 and DM17). In general, DM17 and DM9 were both competitive compared with AL and SAH in predicting aging correlates, with some exceptions for DM9. For example, DM9, DM17, AL, and SAH all predicted mortality to a similar extent (ranges of hazard ratios of 1.15–1.30, 1.21–1.36, 1.17–1.38, and 1.17–1.49, respectively). On the other hand, DM9 predicted CVD less well than DM17 (ranges of odds ratios of 0.97–1.08, 1.07–1.85, respectively).

Conclusions

The metrics we propose here are easy to measure with data that are already available in a wide array of panel, cohort, and clinical studies. The standardized versions here lose a small amount of predictive power compared to more complete versions, but are nonetheless competitive with existing metrics of overall health. DM17 performs slightly better than DM9 and should be preferred in most cases, but DM9 may still be used when a more limited number of biomarkers is available.
China’s fertility change: an analysis with multiple measures
Authors: Yang Shucai , Jiang Quanbao , Sánchez-Barricarte Jesús J.
Published: March 2022

Background

The period fertility in China has declined to very low levels, and the completed cohort fertility rate (CFR) has also decreased significantly. However, the exact fertility rate remains controversial. While the tempo effect has played a significant role in China’s period fertility decline, child underreporting has to be taken into consideration in China’s fertility research.

Methods

By using the census data from 1982 to 2010, and the 1% population sample survey data from 1995 to 2015, we systematically analyzed China’s fertility and its trends since the 1980s using period fertility measures, adjusted period fertility measures, cohort fertility measures, and indirect estimation methods.

Results

The results show that marriage postponement significantly affects the TFR decline. Even after eliminating the tempo and parity structure effect, the adjusted TFR has fallen below 1.5, and the first-order fertility rate dropped to 0.9 in 2015. The CFR for women aged 45–49 declined from 5.37 in 1982 to 1.62 in 2015 mainly because of a decrease in fourth and higher-order births from 1982 to 1990, a decrease in second and third births from 1990 to 2000, and a decrease in second births from 2000 to 2015. Indirect estimation methods yielded a TFR in the range of 1.5–1.6 for the period 2000–2010 and an average TFR of 1.49 for the period 2011–2020.

Conclusions

The traditional norm of universal marriage and childbearing for Chinese women is changing. China’s fertility has been steadily declining, as measured by both period and cohort indicators. Following the historical change, fertility may continue to decline even after introducing the universal three-child policy in China in 2021.
Alternative autophagy: mechanisms and roles in different diseases
Authors: Feng Hong , Wang Nian , Zhang Nan , Liao Hai-han
Published: March 2022

As an important mechanism to maintain cellular homeostasis, autophagy exerts critical functions via degrading misfolded proteins and damaged organelles. Recent years, alternative autophagy, a new type of autophagy has been revealed, which shares similar morphology with canonical autophagy but is independent of Atg5/Atg7. Investigations on different diseases showed the pivotal role of alternative autophagy during their physio-pathological processes, including heart diseases, neurodegenerative diseases, oncogenesis, inflammatory bowel disease (IBD), and bacterial infection. However, the studies are limited and the precise roles and mechanisms of alternative autophagy are far from clear. It is necessary to review current research on alternative autophagy and get some hint in order to provide new insight for further study.
Secular trends and customer characteristics of sweetened beverage and water purchasing at US convenience and other small food stores, 2014–2017
Authors: Winkler Megan R. , Lenk Kathleen , Erickson Darin , Laska Melissa N.
Published: March 2022

Background

Cardiovascular health is linked to sugar- and artificially-sweetened beverages (SSBs and ASBs). Prior studies document declines in SSB purchases. However, it is unclear if similar trends exist at convenience and other small food outlets, which often serve lower-income communities and where objective point-of-sales data are difficult to obtain. We examined trends (2014–2017) in observed SSB, ASB, and water purchases at convenience and other small stores as well as differences in purchasing by customer characteristics.

Methods

We used observational purchase data collected annually (2014–2017) from 3010 adult customers at 147 randomly-sampled stores in Minneapolis/St. Paul, USA. SSB sub-types included any ready-to-drink sweetened soda, fruit, sport, energy, tea, or other drink, and ASBs included artificially-sweetened versions. Unsweetened water included ready-to-drink water. Mixed regression models examined trends over time and associations with customer characteristics, accounting for customers nested within stores and stores repeatedly measured over time.

Results

Nearly 50% of purchases included an SSB. Approximately 10% included an ASB. There was no evidence of change over time in SSB or ASB purchasing. Customer purchasing of unsweetened water significantly increased over time (5.7 to 8.4%; P for trend = 0.05). SSB purchasing was highest among men, young adults, customers with lower education/ income, and customers that shopped frequently. ASB purchasing was highest among women, those 40–59 years, non-Hispanic White, Hispanic, and customers with higher education/ income.

Conclusions

Despite research suggesting previous declines in SSB consumption and purchasing in the US, we identified a persistent, high trend of SSB purchasing overtime at convenience and other small food stores. Consumption of SSBs and water are growing targets for public policy and health campaigns. Results demonstrate additional work is needed curb sweetened beverage purchasing and promote water purchasing at convenience and other small food stores, which are often prevalent in low-income and marginalized communities.