bluuebunny/crossref_metadata_2025 huggingface dataset:
How Data Security Concerns Can Hinder Natural Experiment Research: Background and Potential Solutions
Authors: Pesko Michael F
Published: March 2022

Health economists conducting cancer-related research often use geocoded data to analyze natural experiments generated by policy changes. These natural experiments can provide causal interpretation under certain conditions. Despite public health benefit of this rigorous natural experiment methodology, data providers are often reluctant to provide geocoded data because of confidentiality concerns. This paper provides an example of the value of natural experiments from e-cigarette research and shows how this research was hindered by security concerns. Although the tension between data access and security will not be resolved overnight, this paper offers 3 recommendations: 1) provide public access to aggregated data at area levels (eg, state) where possible; 2) approve projects with enough time to allow for publication in journals with lengthy peer-review times; and 3) improve communication and transparency between data providers and the research community. The Foundations for Evidence Based Policymaking Act of 2018 also presents a unique opportunity for improving the ability of researchers to use geocoded data for natural experiment research without compromising data security.
Transcatheter aortic valve replacement failure: a case report of the bicuspid aortic valve type 0 with a single coronary artery
Authors: Suzuki Ryo , Suzuki Masato , Takayanagi Ryo , Ohori Shunsuke , Ito Toshiro
Published: March 2022

Transcatheter aortic valve replacement (TAVR) is the treatment of choice for aortic stenosis. However, its safety and efficacy in patients with the bicuspid aortic valve (BAV) remain controversial. Especially, whether the BAV phenotype affects outcomes following TAVR remains debated. Despite the higher ellipticity index and more calcifications of the aortic annulus in type 1 BAV, a high residual gradient was observed in type 0 anatomy. Moreover, severe calcification of the cusps rather than aortic annulus in type 0 is predisposed to asymmetrical under-expansion of the prosthesis at the edge of the native aortic cusp. We report the rare case of a patient with BAV stenosis type 0 and single coronary artery receiving TAVR, subsequently requiring surgical aortic valve replacement. The extensive non-coronary cusp calcification caused under-expansion of the prosthesis and was protruded into the left ventricular outflow tract, leading to an obstruction.
Adaptation of travel medicine practitioners to the COVID-19 pandemic: a cross-sectional survey of ISTM members
Authors: Acosta Rebecca W , Visser Jenny T , Chen Lin H , Leggat Peter A , Flaherty Gerard T
Published: March 2022

This cross-sectional study evaluated the adaptations of current International Society of Travel Medicine (ISTM) members in relation to the disruption caused by the coronavirus disease 2019 (COVID-19) pandemic. It demonstrates that the majority of members remain engaged with travel medicine and ISTM educational activities, while adapting to COVID-related clinical demands.
Systematic upper limits on the size of missing pulsar glitches in the first UTMOST open data release
Authors: Dunn L , Melatos A , Suvorova S , Moran W , Evans R J , Osłowski S , Lower M E , Bailes M , Flynn C , Gupta V
Published: February 2022

A systematic, semi-automated search for pulsar glitches in the first UTMOST public data release is presented. The search is carried out using a hidden Markov model which incorporates both glitches and timing noise into the model of the assumed phase evolution of the pulsar. Glitches are detected through Bayesian model selection between models with and without glitches present with minimal human intervention. Nine glitches are detected among seven objects, all of which have been previously reported. No new glitches were detected. Injection studies are used to place 90 per cent frequentist upper limits on the size of undetected glitches in each of the 282 objects searched. The mean upper limit obtained is $\Delta f^{90{{\%}}}/f = 1.9 \times 10^{-8}$, with a range of $4.1 \times 10^{-11} \le \Delta f^{90{{\%}}}/f \le 2.7 \times 10^{-7}$, assuming step events with no post-glitch recoveries. It is demonstrated that including glitch recovery has a mild effect, in most cases increasing the upper limit by a factor of ≲5 conservatively assuming complete recovery on a time-scale of $100\ \mathrm{d}$.
The cosmological simulation code CONCEPT 1.0
Authors: Dakin Jeppe , Hannestad Steen , Tram Thomas
Published: March 2022

We present version 1.0 of the cosmological simulation code $\rm{{\small CO}{{\small N}}{\small CEPT}}$, designed for simulations of large-scale structure formation. $\rm{{\small CO}{\rm{\small N}}{\small CEPT}}$ 1.0 contains a P3M gravity solver, with the short-range part implemented using a novel (sub)tiling strategy, coupled with individual and adaptive particle time-stepping. A primary objective of $\rm{{\small CO}{\rm{\small N}}{\small CEPT}}$ is ease of use. To this end, it has built-in initial condition generation and can produce output in the form of snapshots, power spectra, and direct visualizations. $\rm{{\small CO}{\rm{\small N}}{\small CEPT}}$ is the first massively parallel cosmological simulation code written in Python. Despite of this, excellent performance is obtained, even comparing favourably to other codes such as gadget at similar precision, in the case of low to moderate clustering. By means of power-spectrum comparisons we find extraordinary good agreement between $\rm{{\small CO}{\rm{\small N}}{\small CEPT}}$ 1.0 and gadget. At large and intermediate scales the codes agree to well below the per mille level, while the agreement at the smallest scales probed ($k \sim 13\ h\, {\rm Mpc}^{-1}$) is of the order of 1 per cent. The $\rm{{\small CO}{\rm{\small N}}{\small CEPT}}$ code is openly released and comes with a robust installation script as well as thorough documentation.
3-methylhistidine and clinical outcomes in maintenance haemodialysis patients
Authors: Bres Emilie , Pagan Cécile , Bouchara Anaïs , Pastural Myriam , Granjon Samuel , Laville Maurice , Fouque Denis , Soulage Christophe O , Koppe Laetitia
Published: February 2022

Background

Chronic kidney disease is an important contributor to morbidity and mortality. 3-methylhistidine (3-MH) is the by-product of actin and myosin degradation reflecting skeletal muscle turnover. Markedly elevated 3-MH levels have been documented in uraemic patients, but the interpretation of high 3-MH concentration in maintenance haemodialysis (MHD) patients remains unclear. Indeed, it is not known whether elevated serum 3-MH levels are a marker of excessive muscle catabolism or a better lean tissue mass. Here, we evaluated the association between serum 3-MH levels and clinical outcomes in these patients.

Methods

Serum 3-MH concentration was measured by reverse-phase liquid chromatography/tandem mass spectrometry in a cohort of MHD patients. We analysed the relationships between various clinical/laboratory indices, lean tissue mass measured by bioimpedance spectroscopy, mortality and cardiovascular (CV) events.

Results

Serum 3-MH concentration was positively correlated with serum albumin, normalized protein catabolic rate (nPCR), simplified creatinine index (SCI) and lean tissue mass. Of 291 MHD patients, during a mean follow-up of 847 days, 91 patients died and 101 patients experienced a CV event. Survival was significantly better in patients with high 3-MH concentrations (P = .002). A higher level of 3-MH was also associated with a lower CV mortality and lower incidence of CV events (P = .015 and P < .001, respectively). Low serum 3-MH levels remained significantly associated with CV events but not with mortality after adjustment for demographic, metabolic and CV risk factors.

Conclusion

Elevated serum 3-MH concentration appears to be a marker of better lean tissue mass and nutritional status. Low serum 3-MH is a robust and independent predictor of CV events in the MHD population.
Proposal for individualized dosing of eculizumab in atypical haemolytic uraemic syndrome: patient friendly and cost-effective
Authors: ter Avest Mendy , Bouwmeester Romy N , Duineveld Caroline , Wijnsma Kioa L , Volokhina Elena B , van den Heuvel Lambertus P W J , Burger David M , Wetzels Jack F M , van de Kar Nicole C A J , ter Heine Rob ,   CUREiHUS study group, van Kempen E , Altena W , Adang E , Moes D J A R , van Zuijlen A D , Berger S P , Bemelman F J , van der Heijden J W , van de Wetering J , de Vries A P J , van Paasen P , Wetzels J F M , van Wijk J A E , Bouts A H M , Dorresteijn E M , Gracchi V , Engels F A P T Horuz , Keijzer-Veen M G , van Rooij R W G , van de Kar N C A J
Published: March 2022

Background

Eculizumab is a lifesaving yet expensive drug for atypical haemolytic uraemic syndrome (aHUS). Current guidelines advise a fixed-dosing schedule, which can be suboptimal and inflexible in the individual patient.

Methods

We evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) [classical pathway (CP) activity levels] of eculizumab in 48 patients, consisting of 849 time-concentration data and 569 CP activity levels. PK–PD modelling was performed with non-linear mixed-effects modelling. The final model was used to develop improved dosing strategies.

Results

A PK model with parallel linear and non-linear elimination rates best described the data with the parameter estimates clearance 0.163 L/day, volume of distribution 6.42 L, maximal rate 29.6 mg/day and concentration for 50% of maximum rate 37.9 mg/L. The PK–PD relation between eculizumab concentration and CP activity was described using an inhibitory Emax model with the parameter estimates baseline 101%, maximal inhibitory effect 95.9%, concentration for 50% inhibition 22.0 mg/L and  Hill coefficient 5.42. A weight-based loading dose, followed by PK-guided dosing was found to improve treatment. On day 7, we predict 99.95% of the patients to reach the efficacy target (CP activity <10%), compared with 94.75% with standard dosing. Comparable efficacy was predicted during the maintenance phase, while the dosing interval could be prolonged in ∼33% of the population by means of individualized dosing. With a fixed-dose 4-week dosing interval to allow for holidays, treatment costs will increase by 7.1% and we predict 91% of the patients will reach the efficacy target.

Conclusions

A patient-friendly individualized dosing strategy of eculizumab has the potential to improve treatment response at reduced costs.
Do neurocognitive impairments explain the differences between brain tumor patients and their proxies when assessing the patient’s IADL?
Authors: Oort Quirien , Dirven Linda , Sikkes Sietske A M , Aaronson Neil , Boele Florien , Brannan Christine , Egeter Jonas , Grant Robin , Klein Martin , Lips Irene M , Narita Yoshitaka , Sato Hitomi , Sztankay Monika , Stockhammer Günther , Talacchi Andrea , Uitdehaag Bernard M J , Reijneveld Jaap C , Taphoorn Martin J B
Published: February 2022

Background

Neurocognitive impairments are common among brain tumor patients, and may impact patients’ awareness of performance in instrumental activities in daily life (IADL). We examined differences between patient- and proxy-reported assessments of the patient’s IADL, and whether the level of (dis)agreement is associated with neurocognitive impairments.

Methods

Brain tumor patients and their proxies completed the phase 3 version of the EORTC IADL-BN32 questionnaire measuring IADL, and patients completed six neurocognitive measures. Patient-proxy difference scores in IADL were compared between patients who were defined as neurocognitively impaired (≥2 neurocognitive measures ≥2.0 standard deviations below healthy controls) and non-neurocognitively impaired. With multinomial logistic regression analyses we examined if neurocognitive variables were independently associated with patient-proxy disagreement in IADL ratings.

Results

Patients (n = 81) did not systematically (P < .01) rate IADL outcomes different than their proxies. Proxies did report more problems on 19/32 individual items and all five scales. This effect was more apparent in dyads with a neurocognitively impaired patient (n = 37), compared to dyads with non-neurocognitively impaired patients (n = 44). Multinomial logistic regression analyses showed that several neurocognitive variables (e.g., cognitive flexibility and verbal fluency) were independently associated with disagreement between patients and proxies on different scales.

Conclusion

Neurocognitive deficits seem to play a role in the discrepancies between brain tumor patients and their proxies assessment of patient’s level of IADL. Although replication of our results is needed, our findings suggests that caution is warranted in interpreting self-reported IADL by patients with neurocognitive impairment, and that such self-reports should be supplemented with proxy ratings.
High-entropy-alloy nanoparticles with 21 ultra-mixed elements for efficient photothermal conversion
Authors: Liao Yijun , Li Yixing , Zhao Rongzhi , Zhang Jian , Zhao Lizhong , Ji Lianze , Zhang Zhengyu , Liu Xiaolian , Qin Gaowu , Zhang Xuefeng
Published: March 2022

Multi-metallic nanoparticles have been proven to be an efficient photothermal conversion material, for which the optical absorption can be broadened through the interband transitions (IBTs), but it remains a challenge due to the strong immiscibility among the repelling combinations. Here, assisted by an extremely high evaporation temperature, ultra-fast cooling and vapor-pressure strategy, the arc-discharged plasma method was employed to synthesize ultra-mixed multi-metallic nanoparticles composed of 21 elements (FeCoNiCrYTiVCuAlNbMoTaWZnCdPbBiAgInMnSn), in which the strongly repelling combinations were uniformly distributed. Due to the reinforced lattice distortion effect and excellent IBTs, the nanoparticles can realize an average absorption of >92% in the entire solar spectrum (250 to 2500 nm). In particular, the 21-element nanoparticles achieve a considerably high solar steam efficiency of nearly 99% under one solar irradiation, with a water evaporation rate of 2.42 kg m–2 h–1, demonstrating a highly efficient photothermal conversion performance. The present approach creates a new strategy for uniformly mixing multi-metallic elements for exploring their unknown properties and various applications.
Dental care in children with medical complexity: A retrospective study
Authors: Parmar Arpita , Shannon Kelsey , Casas Michael , Orkin Julia
Published: March 2022

Background and Objectives

Children with medical complexity (CMC) are defined by complex, chronic multi-system disease with significant medical fragility. Limited research exists on dental care in CMC, which is an important part of oral health and overall health. Objectives of this study were to (1) determine the frequency and type of dental visits at a tertiary paediatric hospital of all CMC between 2015 and 2020 and (2) identify the factors associated with dental visits.

Methods

A retrospective chart review of the electronic records of CMC who were seen at a paediatric hospital from 2015 to 2020 was completed. The number and type of dental visits, demographic and clinical information were reviewed. Poisson regression models were used to test the association between the outcome (number of dental visits) and potential factors associated with receiving dental care.

Results

Four hundred and eighty-seven CMC (mean age=7.3 ± 4.6 years, 43.7% female) were included in this study. CMC were seen by dentists at the hospital 4.4 ± 3.8 times since 2015, which is approximately once per year over a 5-year period. Dental visits were mostly preventative (66.4% of all visits). CMC had more dental visits if they had dental care funding compared to no funding if they were living in a community with a population >100,000 people and if they were being followed by a greater number of sub-specialists.

Conclusions

This study highlights the importance of funding, access to paediatric dental specialists, and care coordination support to improve access to dental care for CMC to optimize oral health.
Hysteresis in PHYTOCHROME-INTERACTING FACTOR 4 and EARLY-FLOWERING 3 dynamics dominates warm daytime memory in Arabidopsis
Authors: Murcia Germán , Nieto Cristina , Sellaro Romina , Prat Salomé , Casal Jorge J
Published: March 2022

Despite the identification of temperature sensors and downstream components involved in promoting stem growth by warm temperatures, when and how previous temperatures affect current plant growth remain unclear. Here we show that hypocotyl growth in Arabidopsis thaliana during the night responds not only to the current temperature but also to preceding daytime temperatures, revealing a short-term memory of previous conditions. Daytime temperature affected the levels of PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) and LONG HYPOCOTYL 5 (HY5) in the nucleus during the next night. These factors jointly accounted for the observed growth kinetics, whereas nighttime memory of prior daytime temperature was impaired in pif4 and hy5 mutants. PIF4 promoter activity largely accounted for the temperature-dependent changes in PIF4 protein levels. Notably, the decrease in PIF4 promoter activity triggered by cooling required a stronger temperature shift than the increase caused by warming, representing a typical hysteretic effect; this hysteretic pattern required EARLY-FLOWERING 3 (ELF3). Warm temperatures promoted the formation of nuclear condensates of ELF3 in hypocotyl cells during the afternoon but not in the morning. These nuclear speckles showed poor sensitivity to subsequent cooling. We conclude that ELF3 achieves hysteresis and drives the PIF4 promoter into the same behavior, enabling a short-term memory of daytime temperature conditions.
GmMDE genes bridge the maturity gene E1 and florigens in photoperiodic regulation of flowering in soybean
Authors: Zhai Hong , Wan Zhao , Jiao Shuang , Zhou Jingwen , Xu Kun , Nan Haiyang , Liu Yingxiang , Xiong Shangshang , Fan Rong , Zhu Jinlong , Jiang Wenting , Pang Tian , Luo Xiao , Wu Hongyan , Yang Guang , Bai Xi , Kong Fanjiang , Xia Zhengjun
Published: March 2022

Soybean (Glycine max) is highly sensitive to photoperiod, which affects flowering time and plant architecture and thus limits the distribution range of elite soybean cultivars. The major maturity gene E1 confers the most prominent effect on photoperiod sensitivity, but its downstream signaling pathway remains largely unknown. Here, we confirm that the encoded E1 protein is a transcriptional repressor. The expression of seven GmMDE genes (Glycine max MADS-box genes downregulated by E1) was suppressed when E1 was overexpressed and promoted when E1 was knocked out through clustered regularly-interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9)-mediated mutagenesis. These GmMDEs exhibited similar tissue specificity and expression patterns, including in response to photoperiod, E1 expression, and E1 genotype. E1 repressed GmMDE promoter activity. Results for two GmMDEs showed that E1 epigenetically silences their expression by directly binding to their promoters to increase H3K27me3 levels. The overexpression of GmMDE06 promoted flowering and post-flowering termination of stem growth. The late flowering phenotype of E1-overexpressing soybean lines was reversed by the overexpression of GmMDE06, placing GmMDE06 downstream of E1. The overexpression of GmMDE06 increased the expression of the soybean FLOWERING LOCUS T orthologs GmFT2a and GmFT5a, leading to feedback upregulation of GmMDE, indicating that GmMDE and GmFT2a/GmFT5a form a positive regulatory feedback loop promoting flowering. GmMDE06 also promoted post-flowering termination of stem growth by repressing the expression of the shoot identity gene Dt1. The E1-GmMDEs-GmFT2a/5a-Dt1 signaling pathway illustrates how soybean responds to photoperiod by modulating flowering time and post-flowering stem termination.
Polarization in Black and White
Authors: Enders Adam M , Thornton Judd R
Published: February 2022

While the alignment of partisan and ideological identities—sorting—serves as a primary explanation for the rise in affective polarization, we theorize that this connection does not hold for all Americans, especially racial subgroups with unique political experiences. Using both cross-sectional and panel data, we find that even though Whites have sorted, and differences between the South and elsewhere have diminished over time, Black Americans have not sorted since 1972. However, affective polarization is just as high among Blacks as it is Whites. Thus, sorting does not appear to explain Black affective polarization. Multivariate models provide additional evidence that sorting does not adequately explain affective polarization among Blacks. Instead, we find that group norms and group consciousness (e.g., linked fate) better account for affective polarization among Black Americans. These findings provide important nuance to the sorting thesis and shed light on the relationship between sorting and affective polarization.
Prevalence of hypertension and determinants of treatment-seeking behaviour among adolescents and young adults in India: an analysis of NFHS-4
Authors: Krishnamoorthy Yuvaraj , Rajaa Sathish , Sulgante Sudheera , Chinnakali Palanivel , Jaswal Nidhi , Goel Sonu
Published: February 2022

Background

Previous evidences have reported that almost three-fourth of young hypertensives are not seeking care for their condition leading to severe complications. This study was conducted to assess the determinants of treatment-seeking behaviour among the young hypertensives in India.

Methods

The National Family Health Survey-4 data were analysed. Sampling weights and clustering was accounted using svyset command. Screening, awareness, prevalence and control status were reported with 95% confidence interval (CI). Poisson regression was done to identify the determinants of treatment-seeking behaviour.

Results

In total, 13.8% of younger adults had hypertension, 51.1% were aware of their status and 19.5% sought treatment. Participants in 15–19 years (adjusted Prevalence Ratio (aPR) = 0.70) and 20–29 years (aPR = 0.63), male gender (aPR = 0.84), Muslim religion (aPR = 1.14), urban region (aPR = 0.87), secondary (aPR = 0.88) and higher education (aPR = 0.86), residing in Northern (aPR = 0.79), Central (aPR = 0.76), Southern region (aPR = 0.65), preferring home treatment, medical shop or any other care (aPR = 0.63) were significant determinants of treatment-seeking behaviour.

Conclusion

More than 1 in 10 younger adults in India have hypertension and only half of them were aware of their status and one-fifth sought treatment. Adolescents, males, Hindus, urban population, higher education and residing in Northern, Central and Southern region had poor treatment-seeking behaviour.
The benefits of data sharing and ensuring open sources of systematic review data
Authors: Yoong Sze Lin , Turon Heidi , Grady Alice , Hodder Rebecca , Wolfenden Luke
Published: February 2022

Aims

The benefits of increasing public access to data from clinical trials are widely accepted. Such benefits extend to the sharing of data from high-quality systematic reviews, given the time and cost involved with undertaking reviews. We describe the application of open sources of review data, outline potential challenges and highlight efforts made to address these challenges, with the intent of encouraging publishers, funders and authors to consider sharing review data more broadly.

Results

We describe the application of systematic review data in: (i) advancing understanding of clinical trials and systematic review methods, (ii) repurposing of data to answer public health policy and practice relevant questions, (iii) identification of research gaps and (iv) accelerating the conduct of rapid reviews to inform decision making. While access, logistical, motivational and legal challenges exist, there has been progress made by systematic review, academic and funding agencies to incentivise data sharing and create infrastructure to support greater access to systematic review data.

Conclusion

There is opportunity to maximize the benefits of research investment in undertaking systematic reviews by ensuring open sources of systematic review data. Efforts to create such systems should draw on learnings and principles outlined for sharing clinical trial data.
Mechanisms underlying DMARD inefficacy in difficult-to-treat rheumatoid arthritis: a narrative review with systematic literature search
Authors: Roodenrijs Nadia M T , Welsing Paco M J , van Roon Joël , Schoneveld Jan L M , van der Goes Marlies C , Nagy György , Townsend Michael J , van Laar Jacob M
Published: March 2022

Management of RA patients has significantly improved over the past decades. However, a substantial proportion of patients is difficult-to-treat (D2T), remaining symptomatic after failing biological and/or targeted synthetic DMARDs. Multiple factors can contribute to D2T RA, including treatment non-adherence, comorbidities and co-existing mimicking diseases (e.g. fibromyalgia). Additionally, currently available biological and/or targeted synthetic DMARDs may be truly ineffective (‘true’ refractory RA) and/or lead to unacceptable side effects. In this narrative review based on a systematic literature search, an overview of underlying (immune) mechanisms is presented. Potential scenarios are discussed including the influence of different levels of gene expression and clinical characteristics. Although the exact underlying mechanisms remain largely unknown, the heterogeneity between individual patients supports the assumption that D2T RA is a syndrome involving different pathogenic mechanisms.
Neuropsychological Performance Among Individuals at Clinical High-Risk for Psychosis vs Putatively Low-Risk Peers With Other Psychopathology: A Systematic Review and Meta-Analysis
Authors: Millman Zachary B , Roemer Caroline , Vargas Teresa , Schiffman Jason , Mittal Vijay A , Gold James M
Published: February 2022

Background and Hypothesis

Youth at clinical high-risk (CHR) for psychosis present with neuropsychological impairments relative to healthy controls (HC), but whether these impairments are distinguishable from those seen among putatively lower risk peers with other psychopathology remains unknown. We hypothesized that any excess impairment among CHR cohorts beyond that seen in other clinical groups is minimal and accounted for by the proportion who transition to psychosis (CHR-T).

Study Design

We performed a systematic review and meta-analysis of studies comparing cognitive performance among CHR youth to clinical comparators (CC) who either sought mental health services but did not meet CHR criteria or presented with verified nonpsychotic psychopathology.

Study Results

Twenty-one studies were included representing nearly 4000 participants. Individuals at CHR showed substantial cognitive impairments relative to HC (eg, global cognition: g = −0.48 [−0.60, −0.34]), but minimal impairments relative to CC (eg, global cognition: g = −0.13 [−0.20, −0.06]). Any excess impairment among CHR was almost entirely attributable to CHR-T; impairment among youth at CHR without transition (CHR-NT) was typically indistinguishable from CC (eg, global cognition, CHR-T: g = −0.42 [−0.64, −0.19], CHR-NT: g = −0.09 [−0.18, 0.00]; processing speed, CHR-T: g = −0.59 [−0.82, −0.37], CHR-NT: g = −0.12 [−0.25, 0.07]; working memory, CHR-T: g = −0.42 [−0.62, −0.22], CHR-NT: g = −0.03 [−0.14, 0.08]).

Conclusions

Neurocognitive impairment in CHR cohorts should be interpreted cautiously when psychosis or even CHR status is the specific clinical syndrome of interest as these impairments most likely represent a transdiagnostic vs psychosis-specific vulnerability.
Production performance, nutrient use efficiency, and predicted enteric methane emissions in dairy cows under confinement or grazing management system
Authors: Brito Andre F , Almeida Kleves V , Oliveira Andre S
Published: February 2022

There has been an intense debate regarding the economic, social, and environmental sustainability of confinement versus grazing dairy systems. Our goal was to conduct a meta-analysis to compare dry matter intake, milk yield and composition, nutrient use efficiency (i.e., feed efficiency, milk N efficiency), and predicted enteric CH4 emissions using studies that simultaneously evaluated confinement and grazing. We were able to include in the meta-analysis 8 peer-reviewed articles that met the following selection criteria: (1) publication between 1991 and 2021 in English language, (2) report either SEM or SD, (3) inclusion of at least 1 confinement [total mixed ration or fresh cut herbage fed indoors (i.e., zero-grazing)] and 1 grazing treatment in the same study, and (4) use of markers (internal or external) to estimate herbage dry matter intake. Two unpublished experiments were added to the data set resulting in a total of 10 studies for comparing confinement and grazing. The magnitude of the effect (i.e., effect size) was evaluated using weighted raw mean differences between grazing and confinement systems for a random effect model. Enteric CH4 production was predicted as follows: CH4 (g/d) = 33.2 (13.54) + 13.6 (0.33) × dry matter intake + 2.43 (0.245) × neutral detergent fiber. Dry matter intake (–9.5%), milk yield (–9.3%), milk fat yield (–5.8%), milk protein yield (–10%), and energy-corrected milk (–12%) all decreased in grazing versus confined dairy cows. In contrast, concentration of milk fat and feed efficiency (energy-corrected milk/dry matter intake) were not affected by management system. Whereas milk protein concentration increased, milk nitrogen (N) efficiency (milk N/N intake) tended to decrease in grazing compared with confinement. Predicted enteric CH4 production was 6.1% lower in grazing than confined dairy cows. However, CH4 yield (g/kg of dry matter intake) and CH4 intensity (g/kg of energy-corrected milk) did not change between confinement and grazing. In conclusion, while production performance decreased in grazing dairy cows, nutrient use efficiency and predicted enteric CH4 emissions were relatively similar in both management systems. Results of our meta-analysis should be interpreted with caution due to the small number of studies that met our inclusion criteria leading to a limited number of treatment mean comparisons.
Mitigating an Epidemic of Resistance with Integrated Disease Management Tactics: Conflicting Management Recommendations from Insecticide Resistance and Epidemiological Models
Authors: Sisterson Mark S.
Published: March 2022

Insect-transmitted plant pathogens threaten crop production worldwide. Because a single feeding bout may be sufficient for a vector to transmit a pathogen that kills the plant, treatment thresholds for vectors of plant pathogens are low. For many vector species, overreliance on chemical controls has resulted in evolution of insecticide resistance. Analysis of complementary insecticide resistance and epidemiological models indicated that tactics for delaying resistance evolution conflict with tactics for limiting pathogen spread. Insecticide resistance models support maintaining untreated refuges that serve as a source of susceptible insects that reduce the likelihood of mating among rare resistant insects. In contrast, epidemiological models indicate that movement of vectors from untreated areas to insecticide-treated areas contributes to pathogen spread. Accordingly, epidemiological models support area-wide insecticide spray programs, although resistance models indicate that such an approach is likely to lead to rapid resistance. To mitigate risk of insecticide resistance, additional management approaches must be integrated into plant disease management strategies. The resistance and epidemiological models were used to evaluate effects of integrating application of insecticides with two additional management strategies: deployment of partially resistant plants (plants that are not immune to infection but have lower acquisition and inoculation rates than susceptible plants) and mating disruption (reduced vector birth rate in mating disruption-treated areas). Deployment of partially resistant plants reduced the risk that untreated areas served as a source of inoculative vectors. Mating disruption reduced the risk of resistance by suppressing growth of insecticide-resistant populations and benefited disease management by reducing vector abundance. Simulation results indicated that by targeting multiple aspects of the plant–pathogen–vector system, pathogen spread could be suppressed and resistance delayed. Implementation of such an approach will require innovations in vector control and sustained efforts in plant breeding.
High Diversity of emm Types and Marked Tetracycline Resistance of Group A Streptococci and Other ß-Hemolytic Streptococci in Gabon, Central Africa
Authors: Arnold Benjamin , Bélard Sabine , Alabi Abraham , Hufnagel Markus , Berner Reinhard , Toepfner Nicole
Published: February 2022

Background:

Group A ß-hemolytic streptococcus (GABHS) is a leading pathogen worldwide and post-streptococcal sequelae is a major cause of morbidity and mortality in resource-limited countries. The M protein (coded by the emm gene) is a key virulence factor and a component of GABHS vaccine candidates. As data on BHS in Central Africa are scarce, antibiotic resistance, emm diversity and potential vaccine coverage were investigated.

Methods:

In a prospective cross-sectional study, 1014 Gabonese were screened for streptococcal throat carriage, tonsillopharyngitis and pyoderma by throat and skin smear tests. All BHS were isolated, species were identified and analysis of antibiotic resistance, emm types and emm clusters was performed.

Results:

One hundred sixty-five BHS were detected, comprising 76 GABHS, 36 group C ß-hemolytic streptococcus (GCBHS) and 53 group G ß-hemolytic streptococcus (GGBHS) in 140 carrier, 9 tonsillopharyngitis and 16 pyoderma isolates. Eighty percentage of GABHS, 78% of GCBHS and 79% of GGBHS were tetracycline resistant. Forty-six emm types were identified. GABHS emm58, emm65 and emm81 were most prevalent (26%). Emm diversity of GABHS was the highest, GCBHS and GGBHS were less divers. Every second GABHS, every third GCBHS and every tenth GGBHS carrier was colonized with emm types detected in tonsillopharyngitis or pyoderma isolates.

Conclusions:

Tetracycline resistance and emm type diversity was high among BHS carriers in Gabon with a potential coverage of 58% by the 30-valent GABHS vaccine. A relevant overlap of carrier emm types with emm types found in tonsillopharyngitis and pyoderma characterizes a shared pool of circulating BHS strains.
Suicide Deaths Before and During the Coronavirus Disease 2019 Pandemic
Authors: Rossom Rebecca C. , Penfold Robert B. , Owen-Smith Ashli A. , Simon Greg E. , Ahmedani Brian K.
Published: March 2022

Introduction:

With stressors that are often associated with suicide increasing during the coronavirus disease 2019 (COVID-19) pandemic, there has been concern that suicide mortality rates may also be increasing. Our objective was to determine whether suicide mortality rates increased during the COVID-19 pandemic.

Methods:

We conducted an interrupted time-series study using data from January 2019 through December 2020 from 2 large integrated health care systems. The population at risk included all patients or individuals enrolled in a health plan at HealthPartners in Minnesota or Henry Ford Health System in Michigan. The primary outcome was change in suicide mortality rates, expressed as annualized crude rates of suicide death per 100,000 people in 10 months following the start of the pandemic in March 2020 compared with the 14 months prior.

Results:

There were 6,434,675 people at risk in the sample, with 55% women and a diverse sample across ages, race/ethnicity, and insurance type. From January 2019 through February 2020, there was a slow increase in the suicide mortality rate, with rates then decreasing by 0.45 per 100,000 people per month from March 2020 through December 2020 (SE=0.19, P=0.03).

Conclusions:

Overall suicide mortality rates did not increase with the pandemic, and in fact slightly declined from March to December 2020. Our findings should be confirmed across other settings and, when available, using final adjudicated state mortality data.
Sero-reactivity to three distinct regions within the hepatitis C virus alternative reading frame protein (ARFP/core+1) in patients with chronic HCV genotype-3 infection
Authors: Elsheikh Mosaab E. A. , McClure C. Patrick , Tarr Alexander W. , Irving William L.
Published: March 2022

Hepatitis C virus (HCV) infection affects more than 71 million people worldwide. The disease slowly progresses to chronic, long-term liver injury which leads to hepatocellular carcinoma (HCC) in 5 % of infections. The alternative reading frame protein (ARFP/core+1) is encoded by a sequence overlapping the HCV core gene in the +1 reading frame. Its role in hepatitis C pathogenesis and the viral life cycle is unclear, although some observers have related its production to disease progression and the development of HCC. The aim of this study was to determine whether ARFP is immunogenic in patients with chronic HCV genotype 3 infection and to assess whether sero-reactivity is associated with disease progression, particularly to HCC. Immunogenic epitopes within the protein were predicted by a bioinformatics tool, and three −20 aa length-peptides (ARFP-P1, ARFP-P2 and ARFP-P3) were synthesized and used in an avidin-biotin ARFP/core+1 peptide ELISA. Serum samples from 50 patients with chronic HCV genotype 3 infection, 50 genotype-1 patients, 50 HBV patients and 110 healthy controls were tested. Sero-reactivity to the ARFP peptides was also tested and compared in 114 chronic HCV genotype-3 patients subdivided on the basis of disease severity into non-cirrhotic, cirrhotic and HCC groups. Chronic HCV genotype-3 patients showed noticeable rates of reactivity to ARFP and core peptides. Seropositivity rates were 58% for ARFP-P1, 47 % for ARFP-P2, 5.9 % for ARFP-P3 and 100 % for C22 peptides. There was no significant difference between these seroreactivities between HCV genotype-3 patients with HCC, and HCV genotype-3 patients with and without liver cirrhosis. Patients with chronic HCV genotype-3 infection frequently produce antibodies against ARFP/core+1 protein. ARFP peptide reactivity was not associated with disease severity in patients with HCV genotype-3. These results support the conclusion that ARFP/core+1 is produced during HCV infection, but they do not confirm that antibodies to ARFP can indicate HCV disease progression.
Health Provider and Sexual and Gender Minority Service User Perspectives on Provision of Mental Health Services During the Early Phase of the COVID-19 Pandemic in British Columbia, Canada
Authors: Kennedy A. M. , Black S. , Watt S. , Vitkin N. , Young J. , Reeves R. , Salway T.
Published: February 2022

While the COVID-19 pandemic impacted everyone, social determinants of health and structural inequities have had compounding effects that shaped the experiences of some sub-populations during the pandemic. Stigmatization, discrimination, and exclusion contribute to a disproportionately high burden of mental health concerns among sexual minority (i.e., lesbian, gay, bisexual, queer, and other sexually-diverse) and gender minority people. Pre-pandemic, these health inequities are exacerbated by barriers to adequate mental health services including cost, waitlists, and experiences of sexual and gender minority stigma when accessing providers. During the COVID-19 pandemic, these barriers were further complicated by drastic changes in service delivery and access during the pandemic—i.e., a shift to online/virtual provision of care to reduce risk of COVID-19 transmission. To better understand the experiences of sexual and gender minority people accessing mental health services during the first three to nine months of the COVID-19 pandemic, we conducted semi-structured interviews with a purposive sample of 15 health care providers and administrators (summer 2020) and 14 sexual and gender minority individuals interested in accessing mental health services (fall 2020) in British Columbia, Canada. We used interpretive description to inductively analyze interview data. Triangulating between the provider and service user datasets, we examined changes in mental health and coping during the COVID-19 pandemic. We recorded increases in isolation and lack of identity affirmation; inequities in accessing mental health services during the pandemic, perceived opportunities for mental health support, and avenues for reducing mental health inequities through system-level changes that deserve particular attention during the pandemic.
Multivariate Genomic Architecture of Cortical Thickness and Surface Area at Multiple Levels of Analysis
Authors: Grotzinger Andrew D. , Mallard Travis T. , Liu Zhaowen , Seidlitz Jakob , Ge Tian , Smoller Jordan W.
Published: February 2022

Recent work in imaging genetics suggests high levels of genetic overlap within cortical regions for cortical thickness (CT) and surface area (SA). We model this multivariate system of genetic relationships by applying Genomic Structural Equation Modeling (Genomic SEM) to parsimoniously define five genomic brain factors for both CT and SA. We reify these factors by demonstrating the generalizability of the model in a semi-independent sample and show that the factors align with biologically and functionally relevant parcellations of the cortex. We apply Stratified Genomic SEM to identify specific categories of genes (e.g., neuronal cell types) that are disproportionately associated with pleiotropy across specific subclusters of brain regions, as indexed by the genomic factors. Finally, we examine genetic associations with psychiatric and cognitive correlates, finding that SA is associated with both broad aspects of cognitive function and specific risk pathways for psychiatric disorders. These analyses provide key insights into the multivariate genomic architecture of two critical features of the cerebral cortex.
Astrocytic Ca2+ signals partake in inhibitory neurovascular coupling in a brain state-dependent manner
Authors: Krogsgaard Aske , Sperling Leonora , Dahlqvist Matilda , Thomsen Kirsten , Vydmantaite Gabriele , Lauritzen Martin , Lind Barbara Lykke
Published: February 2022

Neurovascular coupling (NVC) modulates cerebral blood flow to match increased metabolic demand during neuronal excitation. Activation of inhibitory interneurons also increase blood flow, but the basis for this inhibitory NVC is unclear. We performed two-photon microscopy in awake mice to examine the correlation between astrocytic Ca2+ and NVC, evoked by activity in either all (VGATIN) or parvalbumin-positive GABAergic interneurons (PVIN). Optogenetic stimulation of VGATIN and PVIN in the somatosensory cortex triggered astrocytic Ca2+ increases that were abolished by anaesthesia. PVIN evoked astrocytic Ca2+ responses with a short latency that preceded NVC, whereas VGATIN evoked Ca2+ increases that were delayed relative to the NVC response. The early onset in PVIN evoked Ca2+ increases dependent on noradrenaline release from locus coeruleus, which also affected inhibitory NVC. Therefore, NVC mechanisms should be studied in awake mice and, though the relationship between interneuron activity and astrocytic Ca2+ is complex, we found a correlation between astrocyte activity and NVC in PVIN.
Direct and delayed synergistic effects of marine heatwaves, metals and food limitation on tropical reef-associated fish larvae
Authors: Le Minh-Hoang , Dinh Khuong V. , Vo Xuan Thi , Pham Hung Quoc
Published: February 2022

Tropical fish are fast-growing and high energetic-demand organisms, which can be highly vulnerable to long-lasting effects of heat stress and pollution, particularly under food shortages. We tested this by assessing highly complex direct and delayed interactive effects of an extreme temperature (32°C) from a simulated marine heatwave (MHW), copper (Cu, 0, 100, 150 and 175 µg L-1) and food availability (limited and saturated food) on larvae of a tropical, reef-associated seaperch (Psammoperca waigiensis). Cu, MHW, and food limitation independently reduced survival and growth, partly explained by reduced feeding. The negative effect of Cu on fish survival was more substantial under MHW, particularly under limited food. Delayed interactive effects of Cu, MHW, and food limitation were still lethal to fish larvae during the post-exposure period. These results indicate that reef-associated fish larvae are highly vulnerable to these dominant stressors, impairing their ecological function as predators in the coral reefs.

Graphical abstract
Multisensory interactions on auditory and somatosensory information in expert pianists
Authors: Hirano Masato , Furuya Shinichi
Published: February 2022

Fine-tuned sensory functions are bases of efficient motor control and learning and typically characterize skilled individuals. Although numerous studies demonstrated enhanced unimodal sensory functions at both neural and behavioral levels in skilled individuals, little is known about their multisensory interaction, especially multisensory integration and selective attention that involve volitional control of information derived from multiple sensory organs. Here, we show unique multisensory interaction functions of expert pianists. Expert pianists and musically untrained individuals performed five sets of intensity discrimination tasks at the auditory and somatosensory modalities with different conditions: (1) auditory stimulus, (2) somatosensory stimulus, (3) congruent auditory and somatosensory stimuli (i.e., multisensory integration), (4) auditory and task-irrelevant somatosensory stimuli, and (5) somatosensory and task-irrelevant auditory stimuli. In the fourth and fifth conditions, participants were instructed to ignore a task-irrelevant stimulus and to pay attention to a task-relevant stimulus (i.e., selective attention). The unimodal intensity discrimination of the pianists was superior to that of the nonmusicians at the auditory modality but not at the somatosensory modality. While the discrimination perception was superior in the condition (3) compared to the better one of the individual unimodal conditions (i.e., conditions 1 and 2) only in the pianists, the task-irrelevant somatosensory stimulus worsened the auditory discrimination more in the pianists than the nonmusicians. These findings indicate efficient processing of multisensory information in expert pianists, which enables to benefit from multisensory integration of the auditory and somatosensory information, but exacerbates top-down selective inhibition of somatosensory information during auditory processing.