bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

AbstractBackgroundCell 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.ResultsHere, 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.ConclusionsBased 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

Abstract
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

AbstractBackgroundThe 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.MethodsTo 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.ResultsWe 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).ConclusionsThis 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

Abstract
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

AbstractCircular 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

Abstract
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

AbstractContrast-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

Abstract
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

AbstractBackgroundThe 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.MethodsBy 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.ResultsThe 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.ConclusionsThe 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

AbstractAs 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.