bluuebunny/crossref_metadata_2025 huggingface dataset:
Sarcopenia definition, diagnosis and treatment: consensus is growing
Authors: Sayer Avan Aihie , Cruz-Jentoft Alfonso
Published: October 2022

Sarcopenia is a skeletal muscle disorder that commonly occurs with advancing age as well as with a number of long-term conditions. Recognition in clinical practice is relatively recent but important because of the association between sarcopenia and a range of adverse effects on health including impaired mobility, increased morbidity and mortality. Originally characterised as loss of muscle mass, the definition has evolved to focus on loss of skeletal muscle function, particularly strength, through a number of international definitions such as that of the European Working Group on Sarcopenia in Older People most recently revised in 2019. Progress in the decades ahead is likely to be seen with regard to use of routine health data, prescription of resistance exercise, translation of biology and epidemiology into first in man studies for new treatments, and focus on sarcopenia in low and middle-income countries. Immediate next steps include the newly formed Global Leadership Initiative on Sarcopenia to develop international consensus on definition and diagnosis.
The Impact of COVID-19 on the All of Us Research Program
Authors: Hedden Sarra L , McClain James , Mandich Allison , Baskir Rubin , Caulder Mark S , Denny Joshua C , Hamlet Michelle R J , Prabhu Das Irene , McNeil Ford Nicole , Lopez-Class Maria , Elmi Ahmed , Wallace Roshedah , Linkie Amantha , Garriock Holly A
Published: October 2022

The All of Us Research Program, a health and genetics epidemiologic data collection program, has been substantially affected by the coronavirus disease 2019 (COVID-19) pandemic. Although the program is highly digital in nature, certain aspects of the data collection require in-person interaction between staff and participants. Before the pandemic, the program was enrolling approximately 12,500 participants per month at more than 400 clinical sites. In March 2020, because of the pandemic, all in-person activity at program sites and by engagement partners was paused to develop processes and procedures for in-person activities that incorporated strict safety protocols. In addition, the program adopted new data collection methodologies to reduce the need for in-person activities. Through February 2022, a total of 224 clinical sites had reactivated in-person activity, and all enrollment and engagement partners have adopted new data collection methods that can be used remotely. As the COVID-19 pandemic persists, the program continues to require safety procedures for in-person activity and continues to generate and pilot methodologies that reduce risk and make it easier for participants to provide information.
Provider beliefs about the ideal design of an opioid deprescribing and substitution intervention for older adults
Authors: Margraf Alissa M , Davoodi Natalie M , Chen Kevin , Shield Renee R , McAuliffe Laura M , Collins Christine M , Zullo Andrew R
Published: October 2022

Purpose

Opportunities exist to meaningfully reduce suboptimal prescription opioid use among older adults. Deprescribing is one possible approach to reducing suboptimal use. Appropriate interventions should outline how to carefully taper opioids, closely monitor adverse events, substitute viable alternative and affordable nonopioid pain treatments, and initiate medications for opioid use disorder to properly manage use disorders, as needed. We sought to document and understand provider perceptions to begin developing effective and safe opioid deprescribing interventions.

Methods

We conducted 3 semistructured focus groups that covered topics such as participant perspectives on opioid deprescribing in older adults, how to design an ideal intervention, and how to identify potential barriers or facilitators in implementing an intervention. Focus group transcripts were double coded and qualitatively analyzed to identify overarching themes.

Results

Healthcare providers (n = 17), including physicians, pharmacists, nurses, social workers, and administrative staff, participated in 3 focus groups. We identified 4 key themes: (1) involve pharmacists in deprescribing and empower them as leaders of an opioid deprescribing service; (2) ensure tight integration and close collaboration throughout the deprescribing process from the inpatient to outpatient settings; (3) more expansive inclusion criteria than age alone; and (4) provision of access to alternative pharmacological and nonpharmacological pain management modalities to patients.

Conclusion

Our findings, which highlight various healthcare provider beliefs about opioid deprescribing interventions, are expected to serve as a framework for other organizations to develop and implement interventions. Future studies should incorporate patients’ and family caregivers’ perspectives.
Black and orange coloration predict success during male–male competition in the guppy
Authors: Guerrera Alexa G , Daniel M J , Hughes K A
Published: October 2022

Investigating how intrasexual competition and intersexual mate choice act within a system is crucial to understanding the maintenance and diversity of sexually-dimorphic traits. These two processes can act in concert by selecting for the same trait, or in opposition by selecting for different extremes of the same trait; they can also act on different traits, potentially increasing trait complexity. We asked whether male–male competition and female mate choice act on the same male traits using Trinidadian guppies, which exhibit sexual size dimorphism and male-limited color patterns consisting of different colors arranged along the body and fins. We used behavioral assays to assess the relationship between color and competitive success and then compared our results to the plethora of data on female choice and color in our study population. Males initiated more contests if they were larger than their competitor. Males won contests more often if they had more black coloration than their competitor, and the effect of black was stronger when males had less orange than their competitor. Additionally, males won more often if they had either more structural color (iridescence) and more orange, or less structural color and less orange than their competitor, suggesting multiple combinations of color traits predict success. Females from our study population exhibit a strong preference for more orange coloration. Thus, traits favored in male contests differ from those favored by intersexual selection in this population. These results suggest that inter- and intrasexual selection, when acting concurrently, can promote increased complexity of sexually selected traits.
Leveraging a pharmacogenomics knowledgebase to formulate a drug response phenotype terminology for genomic medicine
Authors: Zhao Yiqing , Brush Matthew , Wang Chen , Wagner Alex H , Liu Hongfang , Freimuth Robert R
Published: October 2022

Motivation

Despite the increasing evidence of utility of genomic medicine in clinical practice, systematically integrating genomic medicine information and knowledge into clinical systems with a high-level of consistency, scalability and computability remains challenging. A comprehensive terminology is required for relevant concepts and the associated knowledge model for representing relationships. In this study, we leveraged PharmGKB, a comprehensive pharmacogenomics (PGx) knowledgebase, to formulate a terminology for drug response phenotypes that can represent relationships between genetic variants and treatments. We evaluated coverage of the terminology through manual review of a randomly selected subset of 200 sentences extracted from genetic reports that contained concepts for ‘Genes and Gene Products’ and ‘Treatments’.

Results

Results showed that our proposed drug response phenotype terminology could cover 96% of the drug response phenotypes in genetic reports. Among 18 653 sentences that contained both ‘Genes and Gene Products’ and ‘Treatments’, 3011 sentences were able to be mapped to a drug response phenotype in our proposed terminology, among which the most discussed drug response phenotypes were response (994), sensitivity (829) and survival (332). In addition, we were able to re-analyze genetic report context incorporating the proposed terminology and enrich our previously proposed PGx knowledge model to reveal relationships between genetic variants and treatments. In conclusion, we proposed a drug response phenotype terminology that enhanced structured knowledge representation of genomic medicine.

Supplementary information

Supplementary data are available at Bioinformatics online.
How does foetal exposure to valproate produce adverse neurodevelopmental outcomes?
Authors: Meador Kimford J , Li Yi
Published: October 2022

This scientific commentary refers to ‘Integrative genomics reveals pathogenic mediator of valproate-induced neurodevelopmental disability’ by Feleke et al. (https://doi.org/10.1093/brain/awac296).
Improved pre-test likelihood estimation of coronary artery disease using phonocardiography
Authors: Larsen Bjarke Skogstad , Winther Simon , Nissen Louise , Diederichsen Axel , Bøttcher Morten , Renker Matthias , Struijk Johannes Jan , Christensen Mads Græsbøll , Schmidt Samuel Emil
Published: October 2022

Aims

Current early risk stratification of coronary artery disease (CAD) consists of pre-test probability scoring such as the 2019 ESC guidelines on chronic coronary syndromes (ESC2019), which has low specificity and thus rule-out capacity. A newer clinical risk factor model (risk factor-weighted clinical likelihood, RF-CL) showed significantly improved rule-out capacity over the ESC2019 model. The aim of the current study was to investigate if the addition of acoustic features to the RF-CL model could improve the rule-out potential of the best performing clinical risk factor models.

Methods and results

Four studies with heart sound recordings from 2222 patients were pooled and distributed into two data sets: training and test. From a feature bank of 40 acoustic features, a forward-selection technique was used to select three features that were added to the RF-CL model. Using a cutoff of 5% predicted risk of CAD, the developed acoustic-weighted clinical likelihood (A-CL) model showed significantly (P < 0.05) higher specificity of 48.6% than the RF-CL model (specificity of 41.5%) and ESC 2019 model (specificity of 6.9%) while having the same sensitivity of 84.9% as the RF-CL model. Area under the curve of the receiver operating characteristic for the three models was 72.5% for ESC2019, 76.7% for RF-CL, and 79.5% for A-CL.

Conclusion

The proposed A-CL model offers significantly improved rule-out capacity over the ESC2019 model and showed better overall performance than the RF-CL model. The addition of acoustic features to the RF-CL model was shown to significantly improve early risk stratification of symptomatic patients suspected of having stable CAD.
Effect of an enzyme-containing mouthwash on the dental biofilm and salivary microbiome in patients with fixed orthodontic appliances: a randomized placebo-controlled pilot trial
Authors: Hoffstedt Tove , Skov Hansen Lea Benedicte , Twetman Svante , Sonesson Mikael
Published: October 2022

Background

Mouthwashes containing oral antiseptics or enzymes are suggested suitable for controlling biofilm accumulation in patients with fixed appliances and thereby limiting unwanted side effects during the orthodontic treatment.

Objectives

To evaluate the effect of an enzyme-based mouthwash on the amount of dental biofilm and the composition of the salivary microbiome in patients undergoing treatment with fixed orthodontic appliances.

Trial design

Randomized double-blind placebo-controlled trial.

Material and methods

In total, 35 young adolescents (14–18 years) under treatment with fixed appliances were consecutively enrolled and randomly allocated to an experimental or a placebo group by opening a computer-generated numbered envelope. The subjects were instructed to rinse twice daily during an intervention period of 8 days with experimental mouthwash or placebo without active enzymes. Unstimulated whole saliva samples were collected at baseline and after 8 days. The participants and examiner were blinded for the allocation. The primary outcome was the Orthodontic Plaque Index (OPI) and the secondary was the composition of the salivary microbiome.

Results

In total, 28 adolescents (21 females and 7 males) completed the trial and there were no differences in age, clinical, or microbial findings between the test (n = 14) and the placebo group (n = 14) at baseline. We found a decreased OPI in the test group after 8 days and the difference was statistically significant compared with the placebo group (P < 0.05). There were no significant treatment effects on the richness and global composition of the salivary microbiome.

Harms

In total, one participant in the test group claimed nausea and abandoned the project. In total, two participants did not like the taste of the mouthwash but used it as instructed. No other adverse events or side effects were reported.

Limitations

Short-term pilot trials may by nature be sensitive for selection and performance biases and are not designed to unveil persisting effects.

Conclusion

Daily use of enzyme-containing mouthwash reduced the amount of dental biofilm in adolescents under treatment with the fixed orthodontic appliances, without affecting the composition of the salivary microbiota.

Ethical approval

Approved by the Regional Ethical Board, Lund, Sweden (Dnr 2020-05221).

Clinical Trial Registration

NCT05033015.
Price minimizing behaviours by smokers in Europe (2006–20): evidence from the International Tobacco Control Project
Authors: Geboers Cloé , Nagelhout Gera E , de Vries Hein , Candel Math J J M , Driezen Pete , Mons Ute , Andler Raphaël , Fong Geoffrey T , Willemsen Marc C
Published: October 2022

Background

Effectiveness of tobacco taxation can be undermined through smokers applying price-minimizing behaviours rather than quitting or reducing consumption. Common price-minimizing strategies are buying cheaper tobacco [discount brands or roll-your-own (RYO) tobacco], bulk buying and cross-border purchasing. This study analyses trends in and factors associated with such behaviours in four European countries from 2006 to 2020.

Methods

Data came from adult smokers participating in the International Tobacco Control (ITC) Surveys conducted between 2006 and 2020 in England (9 waves, n = 768–4149), France (4 waves, n = 1415–1735), Germany (5 waves, n = 513–1515) and the Netherlands (10 waves, n = 1191–2177). Country-specific generalized estimating equation regression models were fit to assess trends in smoking RYO tobacco, discount brands, bulk buying and cross-border purchasing within the European Union.

Results

Buying discount brands or RYO tobacco was the most common strategy in all countries, except France. Except for buying discount brands, estimates of price-minimizing behaviours were highest in France (2019: RYO = 27.2%, discount brands = 17.3%, bulk buying = 34.1%, cross-border purchasing = 34.2%), and lowest in Germany (2018: RYO = 18.6%, discount brands = 43.7%, bulk buying = 8.0%, cross-border purchasing = 9.8%). Direction and magnitude of trends differed by country, and behaviour. Young smokers were less likely to buy in bulk. Low-income and low-education smokers were more likely to purchase RYO tobacco or discount brands. The association with discount brands was not found for French low-income smokers.

Conclusions

Smoking cheaper tobacco is the most prevalent price-minimizing strategy in three countries (England, Germany and Netherlands), and more prevalent among low-income individuals. Harmonizing prices across products and countries would reduce switching to cheaper tobacco.
Psychiatric and neurodevelopmental diagnoses in adolescence and adulthood over-indebtedness among Finns born in 1987
Authors: Hiilamo Aapo , Keski-Säntti Markus , Pirkola Sami , Lallukka Tea , Kääriälä Antti
Published: October 2022

Background

Adolescence psychiatric and neurodevelopmental diagnoses are common but their link to adulthood over-indebtedness is unknown. This study aims to determine this relationship and explores the possible mediating role of upper secondary education completion.

Methods

We analyzed the 1987 Finnish Birth Cohort, which consisted of a complete census of children born in Finland in 1987 and registered in the Medical Birth Register (n = 53 743). Records of debt payment defaults, at the age of 33, were used as a measure of over-indebtedness. Adolescent psychiatric and neurodevelopmental diagnoses at ages 13–17 were derived from the national hospital discharge register. Inverse probability treatment weighting was used to investigate the role of pre-exposure variables in this relationship, and the mediating role of upper secondary education completion.

Results

Compared to unexposed individuals, those affected by an adolescent psychiatric or neurodevelopmental diagnosis had a 15 percentage points higher prevalence of over-indebtedness in adulthood. This association was more common for males and was additionally notably strong for suicidality and conduct and oppositional disorders. Controlling for measured potential confounding factors, the diagnoses were linked to a 11-percentage point (95% confidence interval 9–12) higher risk of over-indebtedness. Completing at least upper secondary education reduced this effect by some 39%.

Conclusion

People with psychiatric and neurodevelopmental disorders diagnosed in adolescence are at elevated risk of over-indebtedness in adulthood. Recognizing this high risk may help in efforts to prevent further debt problems. Better education may serve as a protective factor against over-indebtedness and perhaps similar other behavioural consequences.
Adjuvants to increase immunogenicity of SARS-CoV-2 RBD and support maternal–fetal transference of antibodies in mice
Authors: Lima Gabrielle Gimenes , Portilho Amanda Izeli , De Gaspari Elizabeth
Published: October 2022

Adjuvants are important components of vaccines, increasing immunogenicity and modulating the immune response. SARS-CoV-2 vaccines are still being developed in order to improve worldwide access to immunization. Specific populations should be addressed in these investigations, such as pregnant women—to protect both mothers and neonates. In this study, female adult mice were immunized with Receptor-binding domain (RBD) from SARS-CoV-2 adjuvanted by a mixture of DDA and Saponin and put to mating to verify the maternal transference of IgG. For comparison, other group received RBD adjuvanted by OMVs from Neisseria meningitidis and Alum. The adjuvants enhanced IgG production and neutralization. DDA/Sap contributed to increase IgG1, IgG2a, IgG2b, and IgG3 isotypes. Total IgG avidity was considered high, as well as IgG1, IgG2a, and IgG2b avidity. IgG antibodies were effectively transferred to the offspring, predominantly IgG2a, IgG2b, and IgG3. The passive transferred immunoglobulin maintained the neutralizing ability, although it lost avidity. ELISA data was confirmed in Dot-ELISA and immunoblotting assays. DDA and Saponin seem a promising adjuvant mixture to enhance the humoral response of SARS-CoV-2 antigens. Further studies considering the effects of maternal immunization in the protection of offspring are needed, regardless the platform used in COVID-19 vaccines.
Suppression of classical nuclear import pathway by importazole and ivermectin inhibits rotavirus replication
Authors: Sarkar Rakesh , Banerjee Shreya , Halder Prolay , Koley Hemanta , Komoto Satoshi , Chawla-Sarkar Mamta
Published: October 2022

Background

Rotavirus is the foremost cause of acute gastroenteritis among infants in resource-poor countries, causing severe morbidity and mortality. The currently available rotavirus vaccines are effective in reducing severity of the disease but not the infection rates, thus antivirals as an adjunct therapy are needed to reduce the morbidity in children. Viruses rely on host cellular machinery for nearly every step of the replication cycle. Therefore, targeting host factors that are indispensable for virus replication could be a promising strategy.

Objectives

To assess the therapeutic potential of ivermectin and importazole against rotaviruses.

Methods

Antirotaviral activity of importazole and ivermectin was measured against various rotavirus strains (RV-SA11, RV-Wa, RV-A5-13, RV-EW) in vitro and in vivo by quantifying viral protein expression by western blot, analysing viroplasm formation by confocal microscopy, and measuring virus yield by plaque assay.

Results

Importin-β1 and Ran were found to be induced during rotavirus infection. Knocking down importin-β1 severely impaired rotavirus replication, suggesting a critical role for importin-β1 in the rotavirus life cycle. In vitro studies revealed that treatment of ivermectin and importazole resulted in reduced synthesis of viral proteins, diminished production of infectious virus particles, and decrease in viroplasm-positive cells. Mechanistic study proved that both drugs perform antirotavirus activity by inhibiting the function of importin-β1. In vivo investigations in mice also confirmed the antirotavirus potential of importazole and ivermectin at non-toxic doses. Treatments of rotavirus-infected mice with either drug resulted in diminished shedding of viral particles in the stool sample, reduced expression of viral protein in the small intestine and restoration of damaged intestinal villi comapared to untreated infected mice.

Conclusions

The study highlights the potential of importazole and ivermectin as antirotavirus therapeutics.
Evaluation of federated learning variations for COVID-19 diagnosis using chest radiographs from 42 US and European hospitals
Authors: Peng Le , Luo Gaoxiang , Walker Andrew , Zaiman Zachary , Jones Emma K , Gupta Hemant , Kersten Kristopher , Burns John L , Harle Christopher A , Magoc Tanja , Shickel Benjamin , Steenburg Scott D , Loftus Tyler , Melton Genevieve B , Gichoya Judy Wawira , Sun Ju , Tignanelli Christopher J
Published: October 2022

Objective

Federated learning (FL) allows multiple distributed data holders to collaboratively learn a shared model without data sharing. However, individual health system data are heterogeneous. “Personalized” FL variations have been developed to counter data heterogeneity, but few have been evaluated using real-world healthcare data. The purpose of this study is to investigate the performance of a single-site versus a 3-client federated model using a previously described Coronavirus Disease 19 (COVID-19) diagnostic model. Additionally, to investigate the effect of system heterogeneity, we evaluate the performance of 4 FL variations.

Materials and methods

We leverage a FL healthcare collaborative including data from 5 international healthcare systems (US and Europe) encompassing 42 hospitals. We implemented a COVID-19 computer vision diagnosis system using the Federated Averaging (FedAvg) algorithm implemented on Clara Train SDK 4.0. To study the effect of data heterogeneity, training data was pooled from 3 systems locally and federation was simulated. We compared a centralized/pooled model, versus FedAvg, and 3 personalized FL variations (FedProx, FedBN, and FedAMP).

Results

We observed comparable model performance with respect to internal validation (local model: AUROC 0.94 vs FedAvg: 0.95, P = .5) and improved model generalizability with the FedAvg model (P < .05). When investigating the effects of model heterogeneity, we observed poor performance with FedAvg on internal validation as compared to personalized FL algorithms. FedAvg did have improved generalizability compared to personalized FL algorithms. On average, FedBN had the best rank performance on internal and external validation.

Conclusion

FedAvg can significantly improve the generalization of the model compared to other personalization FL algorithms; however, at the cost of poor internal validity. Personalized FL may offer an opportunity to develop both internal and externally validated algorithms.
Dietary benzoic acid and supplemental enzymes alter fiber-fermenting taxa and metabolites in the cecum of weaned pigs
Authors: Diether Natalie E , Nam Seo Lin , Fouhse Janelle , Le Thanh Bich V , Stothard Paul , Zijlstra Ruurd T , Harynuk James , de la Mata Paulina , Willing Benjamin P
Published: October 2022

Inclusion of enzymes and organic acids in pig diets is an important strategy supporting decreased antibiotic usage in pork production. However, limited knowledge exists about how these additives impact intestinal microbes and their metabolites. To examine the effects of benzoic acid and enzymes on gut microbiota and metabolome, 160 pigs were assigned to one of four diets 7 days after weaning: a control diet or the addition of 0.5% benzoic acid, 0.045% dietary enzymes (phytase, β-glucanase, xylanase, and α-amylase), or both and fed ad libitum for 21 to 22 d. Individual growth performance and group diarrhea incidence data were collected throughout the experimental period. A decrease of 20% in pen-level diarrhea incidence from days 8 to 14 in pigs-fed both benzoic acid and enzymes compared to the control diet (P = 0.047). Cecal digesta samples were collected at the end of the experimental period from 40 piglets (n = 10 per group) and evaluated for differences using 16S rRNA sequencing and two-dimensional gas chromatography and time-of-flight mass spectrometry (GCxGC-TOFMS). Analysis of cecal microbiota diversity revealed that benzoic acid altered microbiota composition (Unweighted Unifrac, P = 0.047, r2 = 0.07) and decreased α-diversity (Shannon, P = 0.041; Faith’s Phylogenetic Diversity, P = 0.041). Dietary enzymes increased fiber-fermenting bacterial taxa such as Prevotellaceae. Two-step feature selection identified 17 cecal metabolites that differed among diets, including increased microbial cross-feeding product 1,2-propanediol in pigs-fed benzoic acid-containing diets. In conclusion, dietary benzoic acid and enzymes affected the gut microbiota and metabolome of weaned pigs and may support the health and resolution of postweaning diarrhea.
Investigation on Pathological Aspects, Mode of Transmission, and Tissue Tropism of Antheraea proylei Nucleopolyhedrovirus Infecting Oak Tasar Silkworm
Authors: Khajje Diksha , Devi Sinam Subharani , Subrahmanyam Gangavarapu , Kobayashi Jun , Sivaprasad Vankadara , Terenius Olle , Ponnuvel Kangayam M
Published: October 2022

The temperate oak tasar silkworm, Antheraea proylei, is frequently infested with Antheraea proylei nucleopolyhedrovirus (AnprNPV) causing tiger band disease. This disease is one of the key factors that obstructs production and productivity of oak tasar sericulture. The current study aimed to investigate the pathogenicity of AnprNPV, its mode of transmission, and detection of AnprNPV in different tissues. Transmission electron micrographs of AnprNPV showed single rod-shaped bodies and occlusion derived virus (ODV) enclosed within multiple envelopes. The infecting AnprNPV displayed tissue tropism with higher copy numbers detected in the insect fat body and ovary. The virus was observed to multiply in all developmental stages of the silkworm such as egg, larva, pupa, and moth, confirming its ability to spread throughout the silkworm lifecycle. Baculovirus isolated from infected A. proylei showed cross-infectivity in other Saturniidae wild silkworm species such as Antheraea pernyi, A. frithi, and Samia ricini, widening their probable host range for infection. Baculoviruses generally display a horizontal mode of transmission, mainly through ingestion of occlusion bodies (OBs); however, the present study revealed a trans-ovum vertical mode of transmission in addition to a horizontal mode. The observations made in this study aid a detailed understanding of the tiger band disease and its causative pathogen AnprNPV, which will support future studies and disease management in oak tasar sericulture.
Pharmacists’ involvement with and pharmacy clients’ awareness of adverse drug reaction reporting in Nigeria – a mixed-methods approach
Authors: Showande Segun Johnson , Ikuomola Iretomiwa Faith
Published: October 2022

Objectives

Adverse drug reactions are one of the leading causes of death, yet they are under-reported. This study assessed the involvement of community pharmacists in the identification, documentation, and reporting of adverse drug reactions and pharmacy clients’ awareness of the adverse drug reaction reporting system.

Methods

A cross-sectional questionnaire-guided survey was conducted among 780 pharmacy clients in six selected community pharmacies, and seven mystery clients visited 125 community pharmacies in Ibadan, Nigeria. Information on pharmacy clients’ experience of adverse drug reactions, to whom and how they were reported, was obtained. Female and male mystery clients’ performed two scripted scenarios, complaining of black patches on their thighs and blood in their faeces, respectively. The proportion of pharmacists who identified the complaints as adverse drug reactions, documented and reported them, was described.

Key findings

The response rate for the pharmacy clients’ survey was 98.5%. Some pharmacy clients, 385 (50.1%), had experienced adverse drug reactions; 49 (12.7%) of these pharmacy clients were hospitalised and 73 (19.0%) of them reported the adverse drug reactions to physicians or pharmacists. Most of the pharmacy clients, 706 (91.9%), did not use the available reporting system. A total of 218 mystery client visits were made. The proportion of pharmacists who recognised the mystery client complaints as adverse drug reactions was 4.9–60.3% depending on the scenario presented and up to two pharmacists documented and supposedly reported the adverse drug reactions.

Conclusions

Some of the pharmacy clients reported experiencing adverse drug reactions to healthcare professionals, but most did not report through the existing reporting scheme. Community pharmacists could identify adverse drug reactions but most failed to document or report them.
WTAP regulates postnatal development of brown adipose tissue by stabilizing METTL3 in mice
Authors: Wang Yuqin , Li Xinzhi , Liu Cenxi , Zhou Liying , Shi Lei , Zhang Zhiguo , Chen Long , Gao Ming , Gao Lanyue , Xu Yuanyuan , Huang He , Li Jin , Chen Zheng
Published: October 2022

Brown adipocyte maturation during postnatal development is essential for brown adipose tissue (BAT) to protect animals against cold. Impaired maturation of brown adipocytes leads to cold intolerance. However, the molecular mechanisms that determine the maturation of brown adipocytes during postnatal development are not fully understood. Here, we identify Wilms’ tumor 1-associating protein (WTAP) as an essential regulator in the postnatal development and maturation of BAT. BAT-specific knockout of Wtap (Wtap-BKO) severely impairs maturation of BAT in vivo by decreasing the expression of BAT-selective genes, leading to the whitening of interscapular BAT (iBAT). Single nucleus RNA-sequencing analysis shows the dynamic changes of cell heterogeneity in iBAT of Wtap-BKO mice. Adult mice with WTAP deficiency in BAT display hypothermic and succumb to acute cold challenge. Mechanistically, WTAP deficiency decreases m6A mRNA modification by reducing the protein stability of METTL3. BAT-specific overexpression of Mettl3 partially rescues the phenotypes observed in Wtap-BKO mice. These data demonstrate that WTAP/METTL3 plays an essential role in iBAT postnatal development and thermogenesis.
Optical polarimetry of the May 2022 lunar eclipse
Authors: Steele Iain A , Wiersema Klaas , McCall Callum , Newsam Andrew , Shrestha Manisha
Published: October 2022

The sunlight reflected from the Moon during a total lunar eclipse has been transmitted through the Earth’s atmosphere on the way to the Moon. The combination of multiple scattering and inhomogeneous atmospheric characteristics during that transmission can potentially polarize that light. A similar (although much smaller) effect should also be observable from the atmosphere of a transiting exoplanet. We present the results of polarization observations during the first 15 min of totality of the lunar eclipse of 2022 May 16. We find degrees of polarization of 2.1 ± 0.4 per cent in B, 1.2 ± 0.3 per cent in V, 0.5 ± 0.2 per cent in R, and 0.2 ± 0.2 per cent in I. Our polarization values lie in the middle of the range of those reported for previous eclipses, providing further evidence that the induced polarization can change from event to event. We found no significant polarization difference (<0.02 per cent) between a region of dark Mare and nearby bright uplands or between the lunar limb and regions closer to the disc centre due to the different angle of incidence. This further strengthens the interpretation of the polarization’s origin being due to scattering in the Earth’s atmosphere rather than by the lunar regolith.
Measurements of one-point statistics in 21-cm intensity maps via foreground avoidance strategy
Authors: Kittiwisit Piyanat , Bowman Judd D , Murray Steven G , Gehlot Bharat K , Jacobs Daniel C , Beardsley Adam P
Published: October 2022

Measurements of the one-point probability distribution function and higher-order moments (variance, skewness, and kurtosis) of the high-redshift 21-cm fluctuations are among the most direct statistical probes of the non-Gaussian nature of structure formation and evolution during re-ionization. However, contamination from astrophysical foregrounds and instrument systematics pose significant challenges in measuring these statistics in real observations. In this work, we use forward modelling to investigate the feasibility of measuring 21-cm one-point statistics through a foreground avoidance strategy. Leveraging the characteristic wedge-shape of the foregrounds in k-space, we apply a wedge-cut filtre that removes the foreground contaminated modes from a mock data set based on the Hydrogen Epoch of Re-ionization Array (HERA) instrument, and measure the one-point statistics from the image-space representation of the remaining non-contaminated modes. We experiment with varying degrees of wedge-cutting over different frequency bandwidths and find that the centre of the band is the least susceptible to bias from wedge-cutting. Based on this finding, we introduce a rolling filtre method that allows reconstruction of an optimal wedge-cut 21-cm intensity map over the full bandwidth using outputs from wedge-cutting over multiple sub-bands. We perform Monte Carlo simulations to show that HERA should be able to measure the rise in skewness and kurtosis near the end of re-ionization with the rolling wedge-cut method if foreground leakage from the Fourier transform window function can be controlled.
Collapsing molecular clouds with tracer particles – I. What collapses?
Authors: Collins David C , Le Dan , Jimenez Vela Luz L
Published: October 2022

To understand the formation of stars from clouds of molecular gas, one essentially needs to know two things: what gas collapses, and how long it takes to do so. We address these questions by embedding pseudo-Lagrangian tracer particles in three simulations of self-gravitating turbulence. We identify prestellar cores at the end of the collapse, and use the tracer particles to rewind the simulations to identify the preimage gas for each core at the beginning of each simulation. This is the first of a series of papers, wherein we present the technique and examine the first question: What gas collapses? For the preimage gas at t = 0, we examine a number of quantities – the probability distribution function (PDF) for several quantities, the structure function for velocity, several length scales, the volume filling fraction, the overlap between different preimages, and fractal dimension of the preimage gas. Analytical descriptions are found for the PDFs of density and velocity for the preimage gas. We find that the preimage of a core is large and sparse, and we show that gas for one core comes from many turbulent density fluctuations and a few velocity fluctuations. We find that binary systems have preimages that overlap in a fractal manner. Finally, we use the density distribution to derive a novel prediction of the star formation rate.
Comprehensive catalogue of the overall best distances and properties of 402 galactic novae
Authors: Schaefer Bradley E
Published: October 2022

I derive the overall best distances for all 402 known Galactic novae, and I collect their many properties. The centrepiece is the 74 novae with accurate parallaxes from the new Gaia data release. For the needed priors, I have collected 171 distances based on old methods (including expansion parallaxes and extinction distances). Further, I have collected the V-magnitudes at peak and the extinction measures, so as to produce absolute magnitudes at peak and then derive a crude distance as a prior. Further, I have recognized that 41 per cent of the known novae are concentrated in the bulge, with 68 per cent of these <5.4° from the Galactic Centre, so the 165 bulge novae must have distances of 8000 ± 750 parsecs. Putting this all together, I have derived distances to all 402 novae, of which 220 have distances to an accuracy of better than 30 per cent. I find that the disc novae have an exponential scale height of 140 ± 10 pc. The average peak absolute V-magnitude is −7.45, with an RMS scatter of 1.33 mag. These peak luminosities are significantly correlated with the decline rate (t3 in days) as MV, peak = −7.6 + 1.5log (t3/30). The huge scatter about this relation masks the correlation in many smaller data sets, and makes this relation useless for physical models. The bulge novae are indistinguishable from the disc novae in all properties, except that the novae with red giant companion stars have a strong preference for residing in the bulge population.
Predicted COVID-19 molecular effects on endometrium reveal key dysregulated genes and functions
Authors: Henarejos-Castillo I , Devesa-Peiro A , de Miguel-Gomez L , Sebastian-Leon P , Romeu M , Aleman A , Molina-Gil C , Pellicer A , Cervello I , Diaz-Gimeno P
Published: October 2022

COVID-19 exerts systemic effects that can compromise various organs and systems. Although retrospective and in silico studies and prospective preliminary analysis have assessed the possibility of direct infection of the endometrium, there is a lack of in-depth and prospective studies on the impact of systemic disease on key endometrial genes and functions across the menstrual cycle and window of implantation. Gene expression data have been obtained from (i) healthy secretory endometrium collected from 42 women without endometrial pathologies and (ii) nasopharyngeal swabs from 231 women with COVID-19 and 30 negative controls. To predict how COVID-19-related gene expression changes impact key endometrial genes and functions, an in silico model was developed by integrating the endometrial and COVID-19 datasets in an affected mid-secretory endometrium gene co-expression network. An endometrial validation set comprising 16 women (8 confirmed to have COVID-19 and 8 negative test controls) was prospectively collected to validate the expression of key genes. We predicted that five genes important for embryo implantation were affected by COVID-19 (downregulation of COBL, GPX3 and SOCS3, and upregulation of DOCK2 and SLC2A3). We experimentally validated these genes in COVID-19 patients using endometrial biopsies during the secretory phase of the menstrual cycle. The results generally support the in silico model predictions, suggesting that the transcriptomic landscape changes mediated by COVID-19 affect endometrial receptivity genes and key processes necessary for fertility, such as immune system function, protection against oxidative damage and development vital for embryo implantation and early development.
Combining iron affinity-based fractionation with non-targeted LC-ESI-TOFMS for the study of iron-binding molecules in dissolved organic matter
Authors: Rathgeb Anna , Causon Tim , Krachler Regina , Hann Stephan
Published: October 2022

The low solubility of inorganic iron(III) in seawater leads to very limited availability of this important micronutrient for marine organisms. Estuarine or oceanic iron is almost entirely bound to organic ligands of mainly unknown chemical structure. In this context, riverine input of iron rich, land-derived dissolved organic matter (DOM) can play an important role in coastal areas and investigation of potential Fe-ligands in DOM is of high interest. Previous studies have suggested that iron is predominantly bound to the high molecular weight fraction of DOM, but distributed over the entire size range. Logically, structural elucidation needs to start from the smallest building blocks. A model study targeting low molecular weight iron-binding constituents in Suwannee River natural organic matter (NOM) using Fe-loaded Chelex or silica for immobilized-metal affinity (IMAC)-based fractionation was undertaken. The binding strengths of different compounds could be qualitatively assessed using a differential analysis workflow. IMAC-fractionated samples were acidified and analyzed via liquid chromatography high resolution mass spectrometry (LC-HRMS) and molecular formulas were assigned using state of the art software. A total of 144 Fe-binding constituents in Suwannee River NOM were found to be of interest with the largest number observed to interact with Chelex at pH 4 (55%), and the smallest with silica at neutral pH (24%). Most binding constituents were found in the lignin- and tannin-type region of the van Krevelen plot. Results from this study support the hypothesis that very low molecular weight constituents (below 300 Da) can play a role in the iron binding mechanism of DOM and demonstrate that the employed analytical workflow is suitable for their detection.
Zinc trafficking to apo-Zn-proteins 2. Cellular interplay of proteome, metallothionein, and glutathione
Authors: Mahim Afsana , Petering David H
Published: October 2022

A recent study investigated the impact of glutathione (GSH) on the transfer of zinc (Zn) from proteome to apo-carbonic anhydrase. Here, we probed the requirement of glutathione for zinc trafficking in LLC-PK1 pig kidney epithelial cells. Depletion of GSH by at least 95% left cells viable and able to divide and synthesize Zn-proteins at the control rate over a 48-h period. Loss of GSH stimulated the accumulation of 2.5x the normal concentration of cellular Zn. According to gel filtration chromatography, differential centrifugal filtration, and spectrofluorimetry with TSQ, the extra Zn was distributed between the proteome and metallothionein (MT). To test the functionality of proteome and/or MT as sources of Zn for the constitution of Zn-proteins, GSH-deficient cells were incubated with CaEDTA to isolate them from their normal source of nutrient Zn. Control cells plus CaEDTA stopped dividing; GSH-depleted cells plus CaEDTA continued to divide at ∼40% the rate of GSH deficient cells. Evidently, proteome and/or MT served as a functional source of Zn for generating Zn-proteins. In vitro insertion of Zn bound to proteome into apo-carbonic anhydrase occurred faster at larger concentrations of Zn bound to proteome. These results support the hypothesis that enhanced transport of Zn into cells drives the conversion of apo-Zn-proteins to Zn-proteins by mass action. Similar results were also obtained with human Jurkat T lymphocyte epithelial cells. This study reveals a powerful new model for studying the chemistry of Zn trafficking, including transport processes, involvement of intermediate binding sites, and constitution of Zn-proteins.
Deep brain–machine interfaces: sensing and modulating the human deep brain
Authors: Sui Yanan , Yu Huiling , Zhang Chen , Chen Yue , Jiang Changqing , Li Luming
Published: October 2022

Different from conventional brain–machine interfaces that focus more on decoding the cerebral cortex, deep brain–machine interfaces enable interactions between external machines and deep brain structures. They sense and modulate deep brain neural activities, aiming at function restoration, device control and therapeutic improvements. In this article, we provide an overview of multiple deep brain recording and stimulation techniques that can serve as deep brain–machine interfaces. We highlight two widely used interface technologies, namely deep brain stimulation and stereotactic electroencephalography, for technical trends, clinical applications and brain connectivity research. We discuss the potential to develop closed-loop deep brain–machine interfaces and achieve more effective and applicable systems for the treatment of neurological and psychiatric disorders.
Cue Reactivity Effects of Heated Tobacco Product Use in Current, Former, and Never Smokers in the United States
Authors: Brett Emma I , Lee Zoe , Leavens Eleanor L S , Fridberg Daniel J , King Andrea C
Published: October 2022

Introduction

Heated tobacco products (HTPs) share similar characteristics as combustible cigarettes and electronic nicotine delivery systems (ENDS) and thus may serve as cues for smoking and vaping. While HTP familiarity is low in the United States, HTPs may be perceived as a less harmful alternative to cigarettes.

Aims and Methods

The present study examined if visual exposure to HTP use influenced cigarette and e-cigarette craving in a large national sample of adults with varied smoking patterns. Current, former, and never cigarette smokers (N = 515; Mage = 40) were recruited from online crowd-sourcing panels throughout the United States from January to April 2020. Participants completed surveys before and after watching a video depicting the use of an HTP, cigarette, or bottled water. Main outcomes were changes in cigarette craving after exposure to the video cue. Secondary outcomes included changes in e-cigarette craving.

Results

Relative to the water cue, the HTP and cigarette cues increased cigarette craving in current smokers. The HTP cue also increased e-cigarette craving (desire for a mod or vape pen and JUUL) across all subgroups.

Conclusions

Current smokers demonstrated cue reactivity to the use of an HTP as they reported increases in both cigarette and e-cigarette craving after exposure. All smoking groups reported e-cigarette reactivity to the HTP cue. As HTPs gain traction globally, it is crucial to consider how their use may influence active users and passive viewers to inform future health policies.

Implications

Noncombustible nicotine delivery systems are known cues for cigarette smoking and e-cigarette vaping, and this study examined whether relatively novel heated tobacco products (HTPs) may also act as a smoking or vaping cue in adults across varied smoking backgrounds. Results showed that passive exposure to HTP use increased desire for both a cigarette and an e-cigarette in current smokers and also increased desire for an e-cigarette in former and nonsmokers. Thus given its similarity to smoking and vaping, HTP use may affect passive observers and could play a role in perpetuating the dual use of cigarettes and vape products.