bluuebunny/crossref_metadata_2025 huggingface dataset:
A Problem for the Ideal Worlds Account of Desire
Authors: Blumberg Kyle
Published: June 2021

The Ideal Worlds Account of Desire says that S wants p just in case all of S’s most highly preferred doxastic possibilities make p true. The account predicts that a desire report ⌜S wants p⌝ should be true so long as there is some doxastic p-possibility that is most preferred (by S). But we present a novel argument showing that this prediction is incorrect. More positively, we take our examples to support alternative analyses of desire, and close by briefly considering what our cases suggest about the logic of desire.
EcTracker: Tracking and elucidating ectopic expression leveraging large-scale scRNA-seq studies
Authors: Gautam Vishakha , Mittal Aayushi , Kalra Siddhant , Mohanty Sanjay Kumar , Gupta Krishan , Rani Komal , Naidu Srivatsava , Mishra Tripti , Sengupta Debarka , Ahuja Gaurav
Published: June 2021

Dramatic genomic alterations, either inducible or in a pathological state, dismantle the core regulatory networks, leading to the activation of normally silent genes. Despite possessing immense therapeutic potential, accurate detection of these transcripts is an ever-challenging task, as it requires prior knowledge of the physiological gene expression levels. Here, we introduce EcTracker, an R-/Shiny-based single-cell data analysis web server that bestows a plethora of functionalities that collectively enable the quantitative and qualitative assessments of bona fide cell types or tissue-specific transcripts and, conversely, the ectopically expressed genes in the single-cell ribonucleic acid sequencing datasets. Moreover, it also allows regulon analysis to identify the key transcriptional factors regulating the user-selected gene signatures. To demonstrate the EcTracker functionality, we reanalyzed the CRISPR interference (CRISPRi) dataset of the human embryonic stem cells differentiated into endoderm lineage and identified the prominent enrichment of a specific gene signature in the SMAD2 knockout cells whose identity was ambiguous in the original study. The key distinguishing features of EcTracker lie within its processing speed, availability of multiple add-on modules, interactive graphical user interface and comprehensiveness. In summary, EcTracker provides an easy-to-perform, integrative and end-to-end single-cell data analysis platform that allows decoding of cellular identities, identification of ectopically expressed genes and their regulatory networks, and therefore, collectively imparts a novel dimension for analyzing single-cell datasets.
Evaluation of in silico tools for the prediction of protein and peptide aggregation on diverse datasets
Authors: Prabakaran R , Rawat Puneet , Kumar Sandeep , Gromiha M Michael
Published: June 2021

Several prediction algorithms and tools have been developed in the last two decades to predict protein and peptide aggregation. These in silico tools aid to predict the aggregation propensity and amyloidogenicity as well as the identification of aggregation-prone regions. Despite the immense interest in the field, it is of prime importance to systematically compare these algorithms for their performance. In this review, we have provided a rigorous performance analysis of nine prediction tools using a variety of assessments. The assessments were carried out on several non-redundant datasets ranging from hexapeptides to protein sequences as well as amyloidogenic antibody light chains to soluble protein sequences. Our analysis reveals the robustness of the current prediction tools and the scope for improvement in their predictive performances. Insights gained from this work provide critical guidance to the scientific community on advantages and limitations of different aggregation prediction methods and make informed decisions about their research needs.
Structural discrimination analysis for constraint selection in protein modeling
Authors: Bottino Guilherme F , Ferrari Allan J R , Gozzo Fabio C , Martínez Leandro
Published: June 2021

Motivation

Protein structure modeling can be improved by the use of distance constraints between amino acid residues, provided such data reflects—at least partially—the native tertiary structure of the target system. In fact, only a small subset of the native contact map is necessary to successfully drive the model conformational search, so one important goal is to obtain the set of constraints with the highest true-positive rate, lowest redundancy and greatest amount of information. In this work, we introduce a constraint evaluation and selection method based on the point-biserial correlation coefficient, which utilizes structural information from an ensemble of models to indirectly measure the power of each constraint in biasing the conformational search toward consensus structures.

Results

Residue contact maps obtained by direct coupling analysis are systematically improved by means of discriminant analysis, reaching in some cases accuracies often seen only in modern deep-learning-based approaches. When combined with an iterative modeling workflow, the proposed constraint classification optimizes the selection of the constraint set and maximizes the probability of obtaining successful models. The use of discriminant analysis for the valorization of the information of constraint datasets is a general concept with possible applications to other constraint types and modeling problems.

Availability and implementation

MSA for the targets in this work is available on https://github.com/m3g/2021_Bottino_Biserial. Modeling data supporting the findings of this study was generated at the Center for Computing in Engineering and Sciences, and is available from the corresponding author LM on request.

Supplementary information

Supplementary data are available at Bioinformatics online.
Muslim Social Workers and Imams’ Recommendations in Marital and Child Custody Cases of Persons with Intellectual or Mental Disability
Authors: Leena Badran , Arie Rimmerman
Published: June 2021

Arab society in Israel is undergoing modernisation and secularisation. However, its approach to disability and mental illness is still dominated by religious and traditional stereotypes, as well as folk remedies and community practices. The present study examines differences in Muslim social workers and Imams’ recommendations in marriage/divorce and child custody cases of persons with intellectual disabilities (IDs) or mental illness. The study has two goals: (1) To examine differences in recommendations between Imams and Muslim social workers and (2) to explore variables related to their differential recommendations as observed in their responses to vignettes. Quantitative study using vignettes resembling existing Muslim religious (Sharia) court cases. Muslim social workers (138) and Imams (forty-eight) completed a background questionnaire, a religiosity questionnaire and a questionnaire that included twenty-five vignettes constructed by the researcher based on court rulings, adapted for the study. Muslim social workers tended to consider the religious recommendation when the family of person with ID or mental illness was portrayed in the vignette as religious. The same applied to Imams, albeit to a greater extent. The findings call for raising awareness amongst social workers and academics regarding the importance of religion and tradition in formulating professional recommendations.
Building a theoretical foundation for cognitive rehabilitation
Authors: Whyte John , Turkstra Lyn S
Published: June 2021

This scientific commentary refers to ‘A randomized clinical trial of plasticity-based cognitive training in mild traumatic brain injury’ by Mahncke et al. (doi:10.1093/brain/awab202).
Dual inhibition of cMET and EGFR by microRNA-338-5p suppresses metastasis of esophageal squamous cell carcinoma
Authors: Cui Di , Zhu Yun , Yan Dongdong , Lee Nikki P Y , Han Liang , Law Simon , Tsao George S W , Cheung Annie L M
Published: June 2021

MicroRNAs, as a group of post-transcriptional regulators, regulate multiple pathological processes including metastasis during tumor development. Here, we demonstrated the metastasis-suppressive function of microRNA (miR)-338-5p in esophageal squamous cell carcinoma (ESCC). Overexpression of miR-338-5p had inhibitory effect on invasive ability of ESCC cells and extracellular matrix degradation, whereas silencing miR-338-5p had opposite effects. Mechanistically, miR-338-5p directly targeted the 3′ untranslated regions of hepatocellular growth factor receptor cMet (cMET) and epidermal growth factor receptor (EGFR). As a result, miR-338-5p inhibited the downstream signaling cascades of cMET and EGFR and repressed cMET- and EGFR-mediated ESCC cell invasion. Re-expression of cMET or EGFR in miR-338-5p overexpressing ESCC cells was sufficient to derepress ESCC cell invasion both in vitro and in vivo. We further showed that such manipulation downregulated the expression and secretion of matrix metalloproteinases 2 and 9, which resulted in impaired extracellular matrix degradation and cell invasion. Most importantly, systemic delivery of miR-338-5p mimic significantly inhibited metastasis of ESCC cells in nude mice. Taken together, our results uncovered a previously unknown mechanism through which miR-338-5p suppresses ESCC invasion and metastasis by regulating cMET/EGFR-matrix metalloproteinase 2/9 axis and highlighted the potential significance of miR-338-5p-based therapy in treating patients with metastatic ESCC.
Assessment of Olfactory Function in Children and Adolescents: An Overview
Authors: Gellrich Janine , Zickmüller Claudia , Schriever Valentin A
Published: June 2021

Valid and reliable tools for assessing olfactory function are necessary for the diagnosis of olfactory dysfunction. Olfactory testing can be challenging in a pediatric population due to shorter attention span, linguistic development, and lower olfactory experience in this age group. The aim of this article is to present an overview about olfactory tests that are suitable for a pediatric population. Publications were included when reporting new developed methods of psychophysical olfactory testing in children or adaptation and applications of existing olfactory tests for a pediatric population. Olfactory tests for all 3 major aspects of olfactory function—olfactory threshold, odor discrimination, and odor identification—were included. Olfactory tests were evaluated regarding test validity, test reliability, normative data, and test availability. The current literature shows that several tests are available to assess olfactory function in children. Especially odor identification abilities in a pediatric population are well examined and understood. Tests for olfactory threshold and odor discrimination are less frequently used. In terms of the abovementioned evaluation criteria, only a few tests met all or 3 of these 4 criteria. Based on the current literature the following tests can be recommended for valid and reliable olfactory testing in children: “U-Sniff” odor identification test, the “Sniffin’ Sticks” olfactory threshold test, pBOT-6 olfactory threshold and odor identification test, NIH-Toolbox, and Smell Wheel. Age has to be considered when evaluating olfactory function in children.
Identification and Virulence of Cordyceps javanica Strain wf GA17 Isolated From a Natural Fungal Population in Sweetpotato Whiteflies (Hemiptera: Aleyrodidae)
Authors: Wu Shaohui , Toews Michael D , Castrillo Louela A , Barman Apurba K , Cottrell Ted E , Shapiro-Ilan David I
Published: June 2021

A new strain of the entomopathogenic fungus, identified as Cordyceps javanica (Frieder. & Bally) Kepler, B. Shrestha & Spatafora (Hypocreales: Cordycipitaceae) wf GA17, was found naturally infecting the sweetpotato whitefly, Bemisia tabaci (Gennadius) MEAM1 in southern Georgia, US, in September 2017. The fungus was tested for pathogenicity and virulence in comparison with commercially available entomopathogenic fungal strains against several insect species in the laboratory. In specific, it was compared with Cordyceps fumosorosea (Wize) Kepler, B. Shrestha & Spatafora (Hypocreales: Cordycipitaceae) Apopka 97, Beauveria bassiana (Bals.-Criv.) Vuill. (Hypocreales: Cordycipitaceae) strain GHA, and Metarhizium brunneum Petch (Hypocreales: Clavicipitaceae) strain F52 for virulence against B. tabaci (4th instars) and cotton aphid, Aphis gossypii Glover (Hemiptera: Aphididae) (4th instars with or without wingbuds), on leaf-discs, and against last instars of pecan weevil Curculio caryae (Horn) (Coleoptera: Curculionidae) and citrus root weevil Diaprepes abbreviatus (L.) (Coleoptera: Curculionidae) in soil cups. Against B. tabaci, C. javanica exhibited higher mortality and mycosis development at 5 d post inoculation than other fungi. In assays against A. gossypii with and without wingbuds, C. javanica and C. fumosorosea had the highest mortality and mycosis levels and B. bassiana had the lowest; nymphs with wingbuds were more susceptible to some fungal infection than those without. Against C. caryae, B. bassiana was more effective than other fungi. For D. abbreviatus, B. bassiana also caused the highest mortality while M. brunneum had the lowest, with Cordyceps spp. being intermediate. Overall, the findings suggest high potential of the new strain, C. javanica wf GA17, for managing whiteflies and aphids, while it was not as effective as B. bassiana against the curculionids.
The presence and characteristics of ‘spin’ among randomized controlled trial abstracts in orthodontics
Authors: Guo Feiyang , Fang Xiaolin , Li Chang , Qin Danchen , Hua Fang , He Hong
Published: June 2021

Objectives

To identify the presence and characteristics of spin (using reporting strategies to distort study results and mislead readers) within randomized controlled trial (RCT) abstracts published in orthodontic journals, and to explore the association between spin and potentially related factors.

Methods

A manual search was conducted to identify abstracts of RCTs with statistically non-significant primary outcomes published in five leading orthodontic journals between 2015 and 2020. Spin in the Results and Conclusions sections of each included abstract was evaluated and categorized according to pre-determined spin strategies. Logistic regression analyses were employed to explore the association between spin and relevant factors.

Results

A total of 111 RCT abstracts were included, of which 69 (62.2 per cent) were identified with spin. In the Results section, 47 (42.3 per cent) abstracts had spin, and ‘focusing on significant within-group comparison for primary outcomes’ was the most frequent spin strategy. In the Conclusions section, 57 (51.4 per cent) abstracts presented spin, with the most common strategy being ‘claiming equivalence or non-inferiority for statistically nonsignificant results’. According to multivariable logistic regression analysis, a significantly lower presence of spin was found in studies with international collaboration (odds ratio [OR]: 0.331, 95 per cent confidence interval [CI]: 0.120–0.912, P = 0.033) and trial registration (OR: 0.336, 95 per cent CI: 0.117–0.962, P = 0.042).

Conclusion

The prevalence of spin is high among RCT abstracts in orthodontics. Clinicians need to be aware of the definition and presence of spin. Concerted efforts are needed from researchers and other stakeholders to address this issue.
Phonetic symbols vs keywords in perceptual training: the learners’ views
Authors: Fouz-González Jonás , Mompean Jose A
Published: June 2021

The potential of high-variability phonetic training (HVPT) to help FL learners improve their pronunciation is well documented. However, research exploring learners’ perceptions of the approach adopted after having experienced training is scarce. Likewise, the choice of labels adopted for training is not self-evident and has not been studied empirically. This study investigates EFL learners’ perceptions towards HVPT and the use of phonetic symbols vs keywords as labels for perceptual training. Seventy-one EFL learners followed four HVPT sessions using two types of labels (symbols and keywords). The results of Likert-type items and open questions in a questionnaire completed after training suggest that learners considered HVPT useful and that they would be willing to adopt it as part of their routine. The participants’ perceptions were positive towards both labels, although the group trained with symbols generally showed more positive attitudes towards training and were willing to continue using it more often.
Acute mental stress drives vascular inflammation and promotes plaque destabilization in mouse atherosclerosis
Authors: Hinterdobler Julia , Schott , Simin , Jin Hong , Meesmann Almut , Steinsiek Anna-Lena , Zimmermann Anna-Sophia , Wobst Jana , Müller Philipp , Mauersberger Carina , Vilne Baiba , Baecklund Alexandra , Chen Chien-Sin , Moggio Aldo , Braster Quinte , Molitor Michael , Krane Markus , Kempf Wolfgang E , Ladwig Karl-Heinz , Hristov Michael , Hulsmans Maarten , Hilgendorf Ingo , Weber Christian , Wenzel Philip , Scheiermann Christoph , Maegdefessel Lars , Soehnlein Oliver , Libby Peter , Nahrendorf Matthias , Schunkert Heribert , Kessler Thorsten , Sager Hendrik B
Published: June 2021

Aims 

Mental stress substantially contributes to the initiation and progression of human disease, including cardiovascular conditions. We aim to investigate the underlying mechanisms of these contributions since they remain largely unclear.

Methods and results 

Here, we show in humans and mice that leucocytes deplete rapidly from the blood after a single episode of acute mental stress. Using cell-tracking experiments in animal models of acute mental stress, we found that stress exposure leads to prompt uptake of inflammatory leucocytes from the blood to distinct tissues including heart, lung, skin, and, if present, atherosclerotic plaques. Mechanistically, we found that acute stress enhances leucocyte influx into mouse atherosclerotic plaques by modulating endothelial cells. Specifically, acute stress increases adhesion molecule expression and chemokine release through locally derived norepinephrine. Either chemical or surgical disruption of norepinephrine signalling diminished stress-induced leucocyte migration into mouse atherosclerotic plaques.

Conclusion 

Our data show that acute mental stress rapidly amplifies inflammatory leucocyte expansion inside mouse atherosclerotic lesions and promotes plaque vulnerability.
Knee osteonecrosis after COVID-19
Authors: Angulo-Ardoy María , Ureña-Aguilera Álvaro
Published: June 2021

Background

COVID-19 is an emergent infection, the long-term complications of which are still under study. While hypercoagulability is a common feature in severe cases, the incidence of ischemic complications such as osteonecrosis remains unknown. Previous studies on SARS-CoV1 found an increase in osteonecrosis 3–36 months after infection, and it is still unclear if this was related to the use of corticosteroids or to the virus itself.

Methods

We introduce a 78-year-old woman who complained of right knee pain and swelling a month after COVID-19 infection onset. Her knee radiography showed no significant changes compared to previous ones. MRI, on the other hand, found osteonecrosis in the internal femoral condyle. No coagulation abnormalities were found in blood tests.

Results

While knee replacement should be her main treatment, it will be long delayed due to the pandemic. In the meantime, we increased her tapentadol and salicylic acid doses and gave her home exercises to improve functionality.

Conclusion

In the follow-up after COVID-19, any muscular or joint pain with unusual characteristics should be carefully examined.
International comparison of guidelines for management of impetigo: a systematic review
Authors: Hall Leanne M , Gorges Hilary J , van Driel Mieke , Magin Parker , Francis Nick , Heal Clare F
Published: June 2021

Background

Impetigo is a common superficial skin infection that affects people worldwide and is usually treated with antibiotics; therefore, its management has implications for global antibiotic stewardship.

Objective

This systematic review and narrative synthesis compares and contrasts international impetigo management guidelines.

Methods

Guidelines for treatment of impetigo that were produced by a national authority; available to primary care physicians; and published since 2008 were included. Following a comprehensive search strategy, data extraction from eligible studies was performed independently in duplicate. Details of antiseptic and antibiotic treatment; methicillin-resistant Staphylococcus aureus treatment; and conservative management and preventative measures were tabulated and analysed descriptively.

Results

Fifty-one guidelines were included from 42 different countries. All guidelines recommended systemic antibiotics, 78% of these only for widespread lesions or failure of topical antibiotic treatment. The first-line systemic antibiotic treatment was restricted to narrow-spectrum options in 21 (41%) whilst 7 (14%) recommended only broad-spectrum antibiotics first-line. Thirty-four (67%) guidelines included recommendations for topical antibiotic use. Twenty guidelines (39%) did not mention antiseptic treatment for impetigo. Guidelines did not always provide clear indications for different treatment options.

Conclusions

Despite potentially equal efficacy to systemic antibiotics, only two-thirds of guidelines include topical antibiotic options. Many fail to include recommendations for non-antibiotic treatments such as antiseptics, preventative measures and conservative management, despite potential for antibiotic-sparing. Provision of clear definitions of disease severity and indications for treatment would enhance the ability of clinicians to adhere to recommendations.

Systematic review registration

PROSPERO CRD42018117770
Adaptive evolution of sulfite tolerance inBrettanomyces bruxellensis
Authors: Bartel Caroline , Roach Michael , Onetto Cristobal , Curtin Chris , Varela Cristian , Borneman Anthony
Published: June 2021

Brettanomyces bruxellensis is considered one of the most problematic microbes associated with wine production. Sulfur dioxide is commonly used to inhibit the growth of B. bruxellensis and limit the potential wine spoilage. Brettanomyces bruxellensis wine isolates can grow at higher concentrations of this preservative than isolates from other sources. Thus, it has been suggested that the use of sulfite may have selected for B. bruxellensis strains better adapted to survive in the winemaking environment. We utilized laboratory adaptive evolution to determine the potential for this to occur. Three B. bruxellensis strains, representative of known genetic variation within the species, were subjected to increasing sublethal sulfur dioxide concentrations. Individual clones isolated from evolved populations displayed enhanced sulfite tolerance, ranging from 1.6 to 2.5 times higher than the corresponding parental strains. Whole-genome sequencing of sulfite-tolerant clones derived from two of the parental strains revealed structural variations affecting 270 genes. The region containing the sulfite efflux pump encoding gene, SSU1, showed clear copy number variants in all sequenced clones. Regardless of parental strain genetic background, SSU1 copy number changes were reproducibly associated with one SSU1 haplotype. This work clearly demonstrates adaptive evolution of B. bruxellensis when exposed to sublethal sulfites and suggests that, similar to Saccharomyces cerevisiae wine yeast, the mechanism responsible involves the gene SSU1.
Numerical simulation of seismic waves in 3-D orthorhombic poroelastic medium with microseismic source implementation
Authors: Tohti Munirdin , Wang Yibo , Xiao Wenjiao , Di Qingyun , Zhou Kefa , Wang Jinlin , An Shaole , Liao Shibin
Published: June 2021

We have carried out microseismic forward modelling in orthorhombic poroelastic medium. The seismic response to isotropic (ISO) source, double couple (DC) source and compensated linear vector dipole (CLVD) source was solved by finite-difference algorithm in time domain, respectively. We used analytical solution to test our numerical algorithm and find that the match between the analytical solutions and numerical solutions is sufficiently close. We then designed several different models to calculate the seismic response and analyse the effect of medium parameters and source mechanism on the propagation of seismic waves. We observed from the modelling results that ISO source excites two kinds of waves in isotropic medium, which are fast longitudinal wave and slow longitudinal wave, while the DC and CLVD sources excite three kinds of waves in isotropic medium, including a transverse wave in addition to the fast and slow longitudinal waves. All of these three kinds of sources generate four kinds of seismic waves in orthorhombic poroelastic medium. These are two separable transverse waves in addition to the fast and slow longitudinal waves. The fluid viscosity and medium tortuosity has an effect on the propagation of the slow longitudinal wave. The slow longitudinal wave appears in propagating mode under the effect of low fluid viscosity and appears at the source location in a static mode under the effect of high fluid viscosity. The wavefield snapshot of the slow longitudinal wave has a circular shape when the tortuosity is isotropic, whereas it has an oval shape when the tortuosity is anisotropic. As far as the anisotropic parameters are concerned, the anisotropy of the fast longitudinal wave is more sensitive to the value of $\varepsilon ( {{\varepsilon _1},{\varepsilon _2}} )$, while the value of ${\rm{\delta }}( {{{\rm{\delta }}_1},{{\rm{\delta }}_2},{{\rm{\delta }}_3}} )$ has more effect on the anisotropic behaviour of the two separable transverse waves.
The policy implications of ‘thinking problematically’: problematizing Big Food’s role in obesity policymaking
Authors: Loughnane Cliona
Published: June 2021

Practitioners need to engage with the contested nature of public health policymaking. This study, stemming from a concern that the involvement of Big Food is not widely problematized in health promotion practice, used ‘What’s the Problem Represented to Be?’ discourse analysis to examine how Big Food, as a discursive actor, reacted to and shaped a problem representation of childhood obesity. Analysis of Big Food documents, including Coca-Cola and Burger King, developed during the regulation of broadcast advertising to children in Ireland found that Big Food constructs the problem of childhood obesity in a way which privileges its role as policy actor; it draws on and undermines public health discourses of obesity; and it negates the impact of corporate practices on obesity and on related policymaking. An in-depth analysis of Big Food’s own documents provides access to the processes of knowledge production and governing undertaken by Big Food. The study offers two tools of resistance for health promotion practitioners to interrogate and challenge Big Food—problematization as a policy tool and ‘corporate influence’ as a critical public health discourse.
Transcript isoforms of Reep6 have distinct functions in the retina
Authors: Liang Qingnan , Wu Nathaniel , Zaneveld Smriti , Liu Hehe , Fu Shangyi , Wang Keqing , Bertrand Renae , Wang Jun , Li Yumei , Chen Rui
Published: June 2021

Much of the complexity of the eukaryotic cell transcriptome is due to the alternative splicing of mRNA. However, knowledge on how transcriptome complexity is translated into functional complexity remains limited. For example, although different isoforms of a gene may show distinct temporal and spatial expression patterns, it is largely unknown whether these isoforms encode proteins with distinct functions matching their expression pattern. In this report, we investigated the function and relationship of the two isoforms of Reep6, namely Reep6.1 and Reep6.2, in rod photoreceptor cells. These two isoforms result from the alternative splicing of exon 5 and show mutually exclusive expression patterns. Reep6.2 is the canonical isoform that is expressed in non-retinal tissues, whereas Reep6.1 is the only expressed isoform in the adult retina. The Reep6.1 isoform-specific knockout mouse, Reep6E5/E5, is generated by deleting exon 5 and a homozygous deletion phenotypically displayed a rod degeneration phenotype comparable to a Reep6 full knockout mouse, indicating that the Reep6.1 isoform is essential for the rod photoreceptor cell survival. Consistent with the results obtained from a loss-of-function experiment, overexpression of Reep6.2 failed to rescue the rod degeneration phenotype of Reep6 knockout mice whereas overexpression of Reep6.1 does lead to rescue. These results demonstrate that, consistent with the expression pattern of the isoform, Reep6.1 has rod-specific functions that cannot be substituted by its canonical isoform. Our findings suggested that a strict regulation of splicing is required for the maintenance of photoreceptor cells.
Maternal stress and sex ratio at birth in Sweden over two and a half centuries: a retest of the Trivers–Willard hypothesis
Authors: Wu Hanbo
Published: June 2021

STUDY QUESTION

Is there a negative relationship, as predicted in the Trivers–Willard hypothesis (TWH), between the intensity of maternal stress and sex ratio at birth (SRB)?

SUMMARY ANSWER

Using a comprehensive data set with multiple indicators of maternal stress, most measures of stress show no statistically significant association with SRB over a period spanning 243 years, indicating no support for the TWH.

WHAT IS KNOWN ALREADY

Evolutionary biologists have proposed a widely discussed hypothesis that women in poor and stressful conditions during pregnancy are more likely to give birth to girls, and exposure to stressful events may therefore lead to a reduction in sex (male-to-female) ratio at birth. The empirical evidence so far is mixed.

STUDY DESIGN, SIZE, DURATION

Annual time series data, spanning 243 years between 1749 and 1991 for Sweden at the national level, were drawn from multiple sources. The outcome is defined as the percentage of male births relative to all births in Sweden in a given year. The covariates include a set of economic and climatic variables as proxies for maternal stress.

PARTICIPANTS/MATERIALS, SETTING, METHODS

We conduct a series of ARIMA (autoregressive integrated moving average) models to examine the relationship between maternal stress and SRB during three periods: 1749–1991, 1749–1861 and 1862–1991.

MAIN RESULTS AND THE ROLE OF CHANCE

In 1749–1991, economic proxies for maternal stress showed no statistically significant association with SRB. In 1749–1861, two indicators were significantly associated with SRB, but the coefficients were opposite in direction to the TWH. In 1862–1991, five out of six covariates showed no significant association with SRB. An additional analysis found no significant correlation between sex ratio of stillbirths and all covariates in 1862–1991. Our results are incompatible with the TWH and suggest that previous findings in support of the TWH are not robust.

LIMITATIONS, REASONS FOR CAUTION

This study provides population-level evidence that may not necessarily reflect the nature of all individuals due to the ecological fallacy. The time series analysed in this study are annual data, and we cannot examine the potential seasonality due to the lack of disaggregated monthly data. Our findings may not be generalised to the contexts of extreme maternal stress conditions such as famine and war.

WIDER IMPLICATIONS OF THE FINDINGS

The results from existing studies in this topic may be speculative, and additional research with more comprehensive design, data and covariates is needed to reconsider the robustness of previous findings.

STUDY FUNDING/COMPETING INTEREST(S)

The author receives no external funding and has no conflict of interest to declare.

TRIAL REGISTRATION NUMBER

N/A.
Toxic oil syndrome: health-related quality-of-life assessment using the SF-36 Health Survey
Authors: Posada de la Paz Manuel , Díaz-Guerra Enrique , Alonso-Ferreira Verónica , Villaverde-Hueso Ana , Arias-Merino Greta , Garrido-Estepa Macarena
Published: June 2021

Background

Toxic oil syndrome (TOS) is a multisystemic disease due to a massive intoxication that occurred in Spain in 1981 affecting >20 000 persons. This study aims to evaluate the quality of life of the survivors’ cohort after 38 years of follow-up using the Short Form 36 (SF-36) Health Survey.

Methods

One thousand patients were selected among the 14 084 alive TOS cohort members in 2018 using a stratified random sampling method. Stratification was performed by the 2017 self-rated health status reported by patients. SF-36 results were compared directly and as standardized (T scores) with the Spanish-population reference values. Relationship between self-rated health status and SF-36 results was assessed.

Results

Overall, 900 cohort members participated and 895 valid responses were included in the study. Participants’ average age was 65.2 (standard deviation: 13.8) years and 563 (62.9%) participants were women. Participants’ distribution by self-rated health status was: 219 (24.5%) good/very good, 415 (46.4%) fair and 261 (29.1%) poor/very poor. Quality of life was below the Spanish-population reference in 84% of the TOS patients (87.2% for women and 78.6% for men) for the Physical Component Summary (PCS) and in 75.4% (81.7% for women and 64.8% for men) for the Mental Component Summary (MCS). PCS and MCS scores decreased similarly for both sexes with worse self-rated health.

Conclusions

Very low quality of life and self-rated health, especially for women, were found in the total TOS participants that can be extrapolated to the TOS survivors’ cohort. The TOS cohort still requires standardization of care with integral plans around the country.
Exploring the Effects of Pharmacological, Psychosocial, and Alternative/Complementary Interventions in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder: Meta-Regression Approach
Authors: Yang Kung-Han , Lane Hsien-Yuan , Chang Yue-Cune , Tzang Ruu-Fen
Published: June 2021

Background

There have been various therapies for attention-deficit/hyperactivity disorder (ADHD), but the previous meta-analysis of ADHD efficacy remains unclear. This study aims to systemically meta-regress the effect sizes (ES) of psychostimulant pharmacotherapy (methylphenidate and lisdexamfetamine), non-stimulant pharmacotherapy (atomoxetine and alpha-2 agonists), psychosocial therapy (parental behavioral therapy [PBT]), combination therapy (psychostimulant plus PBT), and alternative/complementary interventions to determine the right treatment for ADHD.

Methods

We searched various ADHD interventions from the MEDLINE and PubMed databases (National Center for Biotechnology Information) between January 1, 1980, and July 30, 2018. Following the meta-analysis of random effects, the meta-regression analyses were used to explore factors potentially influencing treatment efficacy. The confounding variables included type of treatment, type of study, age, type of symptom scale used, and year of publication.

Results

A total of 107 trials (n = 9883 participants) were included. After adjustment, compared with the psychostimulant therapy (28 trial, 2134 participants), non-stimulant pharmacotherapy (28 trials, 4991 participants) and alternative/complement intervention (25 trials, 1195 participants) were less effective by the ES of −0.384 (P = .004) and −0.419 (P = .028), respectively. However, compared with psychostimulant, PBT (19 trials, 1122 participants; ES = −0.308, P = .095) and the combination of psychostimulant and PBT (7 trials, 441participants; ES = −0.196, P = .209) did not differ significantly.

Conclusions

Psychostimulant therapy surpassed non-stimulant pharmacotherapy and alternative/complement intervention. Psychostimulant therapy, PBT, and the combination of psychostimulant therapy and PBT appear to be similar in efficacy according to this meta-regression.
Mobility-related inequality in healthcare utilization between floating and native populations and its influencing factors: evidence from China
Authors: Tang Daisheng , Bu Tao , Liu Yahong
Published: June 2021

Our goal was to examine inequality in healthcare utilization and the factors that contribute to inequality between China's floating and native populations. Based on the China Labor-force Dynamics Surveys from 2014 to 2018, which used three rounds of data, we utilized a panel probit model that included fixed effects for time and province to estimate the probability of healthcare utilization for floating and native populations. In addition, we calculated the degree of inequality in healthcare utilization by using the method of mobility-related inequality and a decomposition approach was used to explain the contribution of each factor to the inequality. The floating population utilized healthcare at a lower rate, with a 10.5% probability of visiting a hospital and a 20.9% probability of receiving hospitalized treatment. The concentration index of mobility-related inequality in healthcare utilization shows a negative coefficient of −0.137 for hospital visits and −0.356 for hospitalized treatment. Contribution decomposition shows that self-assessed health, job category and household registration account for the largest contribution to the inequality in hospital visits, contributing −0.038, 0.021 and −0.017, respectively. Age, household registration and insurance account for the largest contribution to the inequality in hospitalized treatment, contributing −0.053, 0.024 and −0.023, respectively. The floating population was less likely to use health services and faced an inequality in treatment compared with the native population.
Tracking immunization coverage, dropout and equity gaps among children ages 12–23 months in Malawi – bottleneck analysis of the Malawi Demographic and Health Survey
Authors: Mmanga Kondwani , Mwenyenkulu Tisungane E , Nkoka Owen , Ntenda Peter A M
Published: June 2021

Background

Between 2010 and 2016, the proportion of children 12–23 months of age who received full immunization in Malawi decreased from 81% to 76%. Most studies on immunization have mainly focused on the risk factors of vaccination coverage while data on dropouts and equity gaps is very scanty. Thus the aim of the present study was to describe the trend in immunization coverage, dropout rates and effective immunization coverage (EIC) among children ages 12–23 months in Malawi.

Methods

Secondary analyses of the cross-sectional data obtained from the three waves of the Demographic and Health Surveys (2004, 2010 and 2015–16) were conducted. Using bottleneck analysis, outputs were generated based on service coverage, demand/equity (service utilization) and quality (full immunization). The World Health Organization benchmarks were used to assess gaps in the immunization coverage indicators.

Results

The coverage was >90.0% in most of the antigens while full immunization status was estimated at 65%, 84% and 73% in 2004, 2010 and 2015, respectively. The highest coverage was observed in Bacillus Calmette–Guérin (BCG) and lowest in oral polio vaccine 1 (OPV1). OPV1 coverage was <90% in the 2004 cohort year, while pentavalent 3 (Penta3) and measles-containing vaccine 1 (MCV1) coverages were <90% in 2004. Dropout rates of Penta3 and MCV1 were significantly >10% in 2004. The logistic regression analyses showed that children were significantly less likely to be immunized with Penta3 and MCV1 in all cohort years compared with Penta1.

Conclusions

Although immunization coverage was in line with the national and district targets for various antigens, full vaccination coverage (FVC) is still lagging behind. Furthermore, the dropout rates for Penta3 and MCV1 showed upside U-shaped patterns. Thus health education, supervision and orientation of service providers are urgently needed to address disparities that are existing in FVC.
Blockade of checkpoint ILT3/LILRB4/gp49B binding to fibronectin ameliorates autoimmune disease in BXSB/Yaa mice
Authors: Su Mei-Tzu , Inui Masanori , Wong Yi Li , Takahashi Maika , Sugahara-Tobinai Akiko , Ono Karin , Miyamoto Shotaro , Murakami Keiichi , Itoh-Nakadai Ari , Kezuka Dai , Itoi So , Endo Shota , Hirayasu Kouyuki , Arase Hisashi , Takai Toshiyuki
Published: June 2021

The extracellular matrix (ECM) is the basis for virtually all cellular processes and is also related to tumor metastasis. Fibronectin (FN), a major ECM macromolecule expressed by different cell types and also present in plasma, consists of multiple functional modules that bind to ECM-associated, plasma, and cell-surface proteins such as integrins and FN itself, thus ensuring its cell-adhesive and modulatory role. Here we show that FN constitutes an immune checkpoint. Thus, FN was identified as a physiological ligand for a tumor/leukemia/lymphoma- as well as autoimmune-associated checkpoint, ILT3/LILRB4 (B4, CD85k). Human B4 and the murine ortholog, gp49B, bound FN with sub-micromolar affinities as assessed by bio-layer interferometry. The major B4-binding site in FN was located at the N-terminal 30-kDa module (FN30), which is apart from the major integrin-binding site present at the middle of the molecule. Blockade of B4–FN binding such as with B4 antibodies or a recombinant FN30-Fc fusion protein paradoxically ameliorated autoimmune disease in lupus-prone BXSB/Yaa mice. The unexpected nature of the B4–FN checkpoint in autoimmunity is discussed, referring to its potential role in tumor immunity.
Efficacy assessment of lysin CF-296 in addition to daptomycin or vancomycin against Staphylococcus aureus in the murine thigh infection model
Authors: Asempa Tomefa E , DeRosa Nicole A , Cassino Cara , Lehoux Dario , Schuch Raymond , Nicolau David P
Published: June 2021

Objectives

CF-296 is a lysin in pre-clinical development for the treatment of MSSA and MRSA infections, used in addition to standard-of-care (SOC) antibiotics. We evaluated the efficacy of CF-296 alone and in addition to daptomycin or vancomycin against Staphylococcus aureus in the neutropenic mouse thigh infection model.

Methods

Eight isolates (one MSSA and seven MRSA) were studied. Mice were administered five CF-296 monotherapy doses ranging from 0.5 to 50 mg/kg intravenously. To assess adjunctive therapy, mice received sub-therapeutic daptomycin alone, sub-therapeutic vancomycin alone, or the five CF-296 doses in addition to either daptomycin or vancomycin.

Results

Relative to starting inoculum (5.80 ± 0.31 log10 cfu/thigh), bacterial density in vehicle controls increased by +2.49 ± 0.98 across all eight strains. Relative to 24 h controls, a dose–response in bacterial killing (range −0.22 ± 0.87 to −2.01 ± 1.71 log10 cfu/thigh) was observed with increasing CF-296 monotherapy against the eight isolates. Daptomycin and vancomycin resulted in −1.36 ± 0.77 and −1.37 ± 1.01 log10 cfu/thigh bacteria reduction, respectively, relative to 24 h controls. Escalating CF-296 exposures (0.5–50 mg/kg) in addition to daptomycin resulted in an enhanced dose–response, ranging from bacterial killing of −0.69 to −2.13 log10 cfu/thigh, relative to daptomycin alone. Similarly, in addition to vancomycin, escalating CF-296 exposures resulted in bacterial reduction ranging from −1.37 to −2.29 log10 cfu/thigh, relative to vancomycin alone.

Conclusions

Relative to SOC antibiotics (daptomycin or vancomycin), addition of CF-296 resulted in robust and enhanced antibacterial dose–response, achieving ≥1 log10 cfu/thigh decrease across most doses, highlighting a potential role for CF-296 adjunctive therapy against MSSA and MRSA isolates.
Impact of implementing electronic prior authorization on medication filling in an electronic health record system in a large healthcare system
Authors: Lauffenburger Julie C , Stults Cheryl D , Mudiganti Satish , Yan Xiaowei , Dean-Gilley Lisa M , He Mengdong , Tong Angela , Fischer Michael A
Published: June 2021

Objective

Medications frequently require prior authorization from payers before filling is authorized. Obtaining prior authorization can create delays in filling prescriptions and ultimately reduce patient adherence to medication. Electronic prior authorization (ePA), embedded in the electronic health record (EHR), could remove some barriers but has not been rigorously evaluated. We sought to evaluate the impact of implementing an ePA system on prescription filling.

Materials and Methods

ePA was implemented in 2 phases in September and November 2018 in a large US healthcare system. This staggered implementation enabled the later-implementing sites to be controls. Using EHR data from all prescriptions written and linked information on whether prescriptions were filled at pharmacies, we 1:1 matched ePA prescriptions with non-ePA prescriptions for the same insurance plan, medication, and site, before and after ePA implementation, to evaluate primary adherence, or the proportion of prescriptions filled within 30 days, using generalized estimating equations. We also conducted concurrent analyses across sites during the peri-implementation period (Sept–Oct 2018).

Results

Of 74 546 eligible ePA prescriptions, 38 851 were matched with preimplementation controls. In total, 24 930 (64.2%) ePA prescriptions were filled compared with 26 731 (68.8%) control prescriptions (Adjusted Relative Risk [aRR]: 0.92, 95%CI: 0.91–0.93). Concurrent analyses revealed similar findings (64.7% for ePA vs 62.3% control prescriptions, aRR: 1.03, 95%CI: 0.98–1.09).

Discussion

Challenges with implementation, such as misfiring and insurance fragmentation, could have undermined its effectiveness, providing implications for other health informatics interventions deployed in outpatient care.

Conclusion

Despite increasing interest in implementing ePA to improve prescription filling, adoption did not change medication adherence.
Programming of postnatal phenotype caused by exposure of cultured embryos from Brahman cattle to colony-stimulating factor 2 and serum
Authors: Estrada-Cortés Eliab , Jannaman Elizabeth A , Block Jeremy , Amaral Thiago F , Hansen Peter J
Published: June 2021

Alterations in the environment of the preimplantation embryo can affect competence to establish pregnancy and phenotype of resultant calves. In this study, the bovine embryo produced in vitro was used to evaluate postnatal programming actions of the embryokine colony-stimulating factor 2 (CSF2) and serum, which is a common additive of culture media. Oocytes were collected by ovum pick up from Brahman donors and fertilized with semen from Brahman bulls. Embryos were randomly assigned to one of the three treatments: vehicle, CSF2 10 ng/mL, or 1% (v/v) serum. Treatments were added to the culture medium from day 5 to 7 after fertilization. Blastocysts were harvested on day 7 and transferred into crossbred recipients. Postnatal body growth and Longissimus dorsi muscle characteristics of the resultant calves were measured. The percent of cleaved embryos becoming blastocysts was increased by serum and, to a lesser extent, CSF2. Treatment did not affect survival after embryo transfer but gestation length was shortest for pregnancies established with serum-treated embryos. Treatment did not significantly affect postnatal body weight or growth. At 3 mo of age, CSF2 calves had lower fat content in the Longissimus dorsi muscle and less subcutaneous fat over the muscle than vehicle calves. There was a tendency for cross-sectional area of the muscle to be smaller for serum calves than vehicle calves. Results confirm the importance of the preimplantation period as a window to modulate postnatal phenotype of resultant calves. In particular, CSF2 exerted actions during the preimplantation period to program characteristics of accumulation of intramuscular and subcutaneous fat of resultant calves. The use of a low serum concentration in culture medium from day 5 to 7 of development can increase the yield of transferrable embryos without causing serious negative consequences for the offspring.