bluuebunny/crossref_metadata_2025 huggingface dataset:
The Concise Guide to PHARMACOLOGY 2023/24: Introduction and Other Protein Targets
Authors: Alexander Stephen P. H. , Kelly Eamonn , Mathie Alistair A. , Peters John A. , Veale Emma L. , Armstrong Jane F. , Buneman O. Peter , Faccenda Elena , Harding Simon D. , Spedding Michael , Cidlowski John A. , Fabbro Doriano , Davenport Anthony P. , Striessnig Jörg , Davies Jamie A. , Ahlers‐Dannen Katelin E. , Alqinyah Mohammed , Arumugam Thiruma V. , Bodle Christopher , Dagner Josephine Buo , Chakravarti Bandana , Choudhuri Shreoshi P. , Druey Kirk M. , Fisher Rory A. , Gerber Kyle J. , Hepler John R. , Hooks Shelley B. , Kantheti Havish S. , Karaj Behirda , Layeghi‐Ghalehsoukhteh Somayeh , Lee Jae‐Kyung , Luo Zili , Martemyanov Kirill , Mascarenhas Luke D. , McNabb Harrison , Montañez‐Miranda Carolina , Ogujiofor Osita , Phan Hoa , Roman David L. , Shaw Vincent , Sjogren Benita , Sobey Christopher , Spicer Mackenzie M. , Squires Katherine E. , Sutton Laurie , Wendimu Menbere , Wilkie Thomas , Xie Keqiang , Zhang Qian , Zolghadri Yalda
Published: December 2023

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16176. In addition to this overview, in which are identified ‘Other protein targets’ which fall outside of the subsequent categorisation, there are six areas of focus: G protein‐coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
Rare forms of congenital adrenal hyperplasia
Authors: Gurpinar Tosun Busra , Guran Tulay
Published: December 2023

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders due to pathogenic variants in genes encoding enzymes and cofactors involved in adrenal steroidogenesis. Although 21‐hydroxylase, 11β‐hydroxylase, 3β‐hydroxysteroid dehydrogenase type 2, 17α‐hydroxylase/17,20‐lyase, P450 oxidoreductase, steroidogenic acute regulatory protein, cholesterol side‐chain cleavage enzyme deficiencies are considered within the definition of CAH, the term ‘CAH’ is often used to refer to ‘21‐hydroxylase deficiency (21OHD)’ since 21OHD accounts for approximately 95% of CAH in most populations. The prevalence of the rare forms of CAH varies according to ethnicity and geographical location. In most cases, the biochemical fingerprint of impaired steroidogenesis points to the specific subtypes of CAH, and genetic testing is usually required to confirm the diagnosis. Despite there are significant variations in clinical characteristics and management, most data about the rare CAH forms are extrapolated from 21OHD. This review article aims to collate the currently available data about the diagnosis and the management of rare forms of CAH.
Screening for multidrug‐resistant organisms in high‐risk hospitalized patients with hematologic diseases
Authors: Delanote Valentine , Callens Rutger , Vogelaers Dirk , Deeren Dries
Published: December 2023

Objectives

Patients treated for hematologic malignancies are at higher risk for blood stream infections (BSI) and multidrug‐resistant organisms (MDRO) are increasingly involved. Studies showed a significant association between rectal colonization status and a higher risk of subsequent MDRO BSI. The objective of our study was to probe the practice of surveillance cultures in Belgian hematology centers.

Methods

A questionnaire was sent to the 13 hematology centers participating in the acute leukemia board of the Belgian Hematology Society. 21 questions probed for the method of surveillance cultures, MDRO screened, antimicrobial prophylaxis, and empirical therapy and their relationship with colonization status.

Results

All centers completed the questionnaire in full. Routine gastrointestinal surveillance cultures in hematologic patients are taken in 10 hospitals. Organisms tested for included mostly ESBL (n = 9) and carbapenem‐resistant (n = 8) Enterobacterales. All centers with a screening strategy adapt empiric antibiotic therapy based on MDRO colonization. Prophylaxis strategies are variable, only two centers adapt prophylaxis upon documentation of fluoroquinolone resistance.

Conclusions

The majority of the Belgian centers perform routine surveillance cultures and adapt empiric therapy for neutropenic fever accordingly. Other reasons for testing include to gain insight into local epidemiology and to prevent in‐hospital transmission. In general, there was significant variability in surveillance dimensions.
Fracture behavior of S355J2W steel and weld at low temperature
Authors: Li Yuanxing , Liu Yi , He Yongpan , Zhu Zongtao , Chen Hui
Published: December 2023

The weather‐resistant steel S355J2W shows potential for use in the bogies of high‐speed trains operating in extremely cold regions. In this study, the mechanical properties and fracture behavior of S355J2W steel and its MAG welding joints were investigated using low‐temperature uniaxial tensile tests, Charpy impact tests, and three‐point bending tests (TPB), which play an important role in the safety and reliability of train operation. The ductility and toughness indices decreased as the temperature decreased from room temperature to −114°C, and the weld is more dangerous and prone to fracture than the base material area. The бs/бb values of WM and HAZ samples slightly increased by 3.7% and 3.8% from 20 to −114°C, respectively. And the ductile–brittle transition temperature (DBTT) of BM, WM, and HAZ were −75.6, −46.1, and −56.6°C, respectively. The fracture micro‐mechanisms were evaluated by analyzing the grain misorientation along the residual cracks using electron backscatter diffraction (EBSD) and transmission electron microscopy (TEM). The high‐angle grain boundaries (GBs) in the base metal were observed to greatly contribute to stopping or deflecting the crack propagation, thereby improving the low‐temperature toughness. In contrast, the cracks easily penetrate the low‐angle GBs of the weld (which made up 38% of the grain boundaries of the welds), thereby decreasing the lower temperature fracture toughness of the weld. The dislocations of S355J2W steel and the weld metal were investigated by TEM analysis.
Controls and significance of priming effects in lake sediments
Authors: Bartosiewicz Maciej , Przytulska Anna , Birkholz Axel , Zopfi Jakob , Lehmann Moritz F.
Published: December 2023

Warming and eutrophication influence carbon (C) processing in sediments, with implications for the global greenhouse‐gas budget. Temperature effects on sedimentary C loss are well understood, but the mechanism of change in turnover through priming with labile organic matter (OM) is not. Evaluating changes in the magnitude of priming as a function of warming, eutrophication, and OM stoichiometry, we incubated sediments with 13C‐labeled fresh organic matter (FOM, algal/cyanobacterial) and simulated future climate scenarios (+4°C and +8°C). We investigated FOM‐induced production of CH4 and microbial community changes. C loss was primed by up to 17% in dominantly allochthonous sediments (ranging from 5% to 17%), compared to up to 6% in autochthonous sediments (−9% to 6%), suggesting that refractory OM is more susceptible to priming. The magnitude of priming was dependent on sediment OM stoichiometry (C/N ratio), the ratio of fresh labile OM to microbial biomass (FOM/MB), and temperature. Priming was strongest at 4°C when FOM/MB was below 50%. Addition of FOM was associated with activation and growth of bacterial decomposers, including for example, Firmicutes, Bacteroidetes, or Fibrobacteres, known for their potential to degrade insoluble and complex structural biopolymers. Using sedimentary C/N > 15 as a threshold, we show that in up to 35% of global lakes, sedimentation is dominated by allochthonous rather than autochthonous material. We then provide first‐order estimates showing that, upon increase in phytoplankton biomass in these lakes, priming‐enabled degradation of recalcitrant OM will release up to 2.1 Tg C annually, which would otherwise be buried for geological times.
Impact of the anti‐inflammatory diet on serum high‐sensitivity C‐Reactive protein and new‐onset frailty in community‐dwelling older adults: A 7‐year follow‐up of the Kashiwa cohort study
Authors: Son Bo‐Kyung , Lyu Weida , Tanaka Tomoki , Yoshizawa Yasuyo , Akishita Masahiro , Iijima Katsuya
Published: December 2023

Aim

Chronic inflammation is a pathophysiological cause of age‐related diseases, including frailty. Although diet is a determinant of inflammation, few prospective studies have investigated its role in frailty onset. This study used the dietary inflammatory index to investigate whether a proinflammatory diet affects the incidence of frailty in a 7‐year follow‐up of older Japanese adults.

Methods

We enrolled community‐dwelling older adults without frailty from the 2014 Kashiwa cohort study. Energy‐adjusted dietary inflammatory index (E‐DII) scores were calculated using a brief self‐administered diet history questionnaire. Serum high‐sensitivity C‐reactive protein (hsCRP) levels were measured by immunoassays. Frailty was defined as meeting three of Fried's five phenotypic criteria. Cox regression was used to analyze associations between E‐DII scores and new‐onset frailty after adjusting for relevant confounders.

Results

Overall, 95 (11.7%) of 811 participants (73.7 ± 4.8 years, women 47.3%) developed new‐onset frailty during the 7‐year follow‐up. The baseline E‐DII scores significantly correlated with log‐hsCRP levels, even after adjustment (β = 0.075, P = 0.035). The highest tertile of E‐DII scores (proinflammatory diet) showed a 2.03 times (95% confidence interval, 1.22–3.36) higher risk of new‐onset frailty than that associated with the lowest tertile (P = 0.006). When E‐DII was calculated on the basis of anti‐inflammatory food parameters only, the highest tertile showed a 2.32 times (95% confidence interval, 1.36–3.95) higher risk than that associated with the lowest tertile (P = 0.002).

Conclusions

E‐DII scores significantly correlated with serum hsCRP levels. High E‐DII scores caused by low intake of anti‐inflammatory foods are associated with frailty incidence. For community‐dwelling older adults, dietary interventions that lower E‐DII scores (e.g., encouraging dietary fiber intake) may help prevent frailty. Geriatr Gerontol Int 2024; 24: 189–195.
Biology of cognitive aging across species
Authors: Kakizawa Sho , Park Joong‐Jean , Tonoki Ayako
Published: December 2023

Aging is associated with cognitive decline, which can critically affect quality of life. Examining the biology of cognitive aging across species will lead to a better understanding of the fundamental mechanisms involved in this process, and identify potential interventions that could help to improve cognitive function in aging individuals. This minireview aimed to explore the mechanisms and processes involved in cognitive aging across a range of species, from flies to rodents, and covers topics, such as the role of reactive oxygen species and autophagy/mitophagy in cognitive aging. Overall, this literature provides a comprehensive overview of the biology of cognitive aging across species, highlighting the latest research findings and identifying potential avenues for future research. Geriatr Gerontol Int 2024; 24: 15–24.
A modified protocol for studying filaggrin degradation using a reconstructed human epidermis model under low and high humidity
Authors: Chen Qilong , Wei Ning , Lu Yina
Published: December 2023

Background

Filaggrin (FLG) is an essential protein that plays a vital role in maintaining skin barrier function and moisture levels, allowing the skin to adapt to dry environments. However, the precise temporal dynamics of FLG metabolism in the human epidermis remain poorly understood, and suitable tools to study these time‐dependent effects are currently lacking.

Objective

To investigate the molecular mechanisms and time course of FLG metabolism and skin barrier function under high‐ and low‐humidity conditions, utilizing a reconstructed epidermis model.

Methods

EpiSkin specimens cultured under humid or dry conditions for varying durations (2–48 h) were compared by assessing FLG degradation and skin barrier formation using immunofluorescence staining and western blotting.

Results

Under conditions of low humidity, the proteolysis of FLG in EpiSkin increased between 4 and 12 h and was accompanied by elevated levels of cysteine–aspartic protease (caspase)‐14. The expression of peptidyl arginine deiminase 1 and calpain 1 also increased at 4 h. However, after 24 h, the expression of these three FLG‐degrading proteins significantly decreased. Conversely, the levels of pyrrolidone‐5‐carboxylic acid and urocanic acid initially decreased at 2 h and then increased between 12 and 24 h. Additionally, the expression of skin barrier proteins, such as FLG, transglutaminase 5, loricrin and zonula occludens‐1, decreased starting from 12 h. Notably, epidermal cell viability and activity were also inhibited.

Conclusion

We propose a reliable and ethical model to study the temporal dynamics of FLG metabolism and its role in skin barrier function. Using a commercially reconstructed epidermis to mimic dry skin formation obviates the need for animal and human testing.
Excess cash and equity option liquidity
Authors: Deng Min , Nguyen Minh
Published: December 2023

We examine the relation between excess corporate cash holdings and equity option market liquidity from January 3, 2005 to December 31, 2019. We show that the level of cash reserve in excess of what can be captured by firm characteristics significantly explains stock option liquidity. Trading volume and option open interest increase in companies with a higher magnitude of excess cash, whereas the bid–ask spreads of stock options decline in excess cash. Our findings confirm the theoretical prediction that excess cash improves option market liquidity as it reduces adverse selection problems caused by uncertainty in firm valuations. This relation remains more pronounced with put options, out‐of‐the‐money contracts, and short‐maturity contracts. In addition, excess cash has a stronger impact on option liquidity within firms that have a greater degree of informed trading and during high‐volatility periods in financial markets. Our results show that when uncertainty about firm prospects rises, excess cash becomes more valuable and affects option market liquidity.
Mapping potentially inappropriate medications in older adults using the Anatomical Therapeutic Chemical (ATC) classification system
Authors: Ndai Asinamai , Al Bahou Julie , Morris Earl , Wang Hsin‐Min , Marcum Zach , Hung Anna , Brandt Nicole , Steinman Michael A. , Vouri Scott Martin
Published: December 2023

Background

Potentially inappropriate medications (PIMs) in older adults are medications in which risks often outweigh benefits and are suggested to be avoided. Worldwide, many distinct guidelines and tools classify PIMs in older adults. Collating these guidelines and tools, mapping them to a medication classification system, and creating a crosswalk will enhance the utility of PIM guidance for research and clinical practice.

Methods

We used the Anatomical Therapeutic Chemical (ATC) Classification System, a hierarchical classification system, to map PIMs from eight distinct guidelines and tools (2019 Beers Criteria, Screening Tool for Older Person's Appropriate Prescriptions [STOPP], STOPP‐Japan, German PRISCUS, European Union‐7 Potentially Inappropriate Medication [PIM] list, Centers for Medicare & Medicaid Services [CMS] High‐Risk Medication, Anticholinergic Burden Scale, and Drug Burden Index). Each PIM was mapped to ATC Level 5 (drug) and to ATC Level 4 (drug class). We then used the crosswalk (1) to compare PIMs and PIM drug classes across guidelines and tools to determine the number of PIMs that were index (drug‐induced adverse event) or marker (treatment of drug‐induced adverse event) drug of prescribing cascades, and (2) estimate the prevalence of PIM use in older adults continuously enrolled with fee‐for‐service Medicare in 2018 as use cases. Data visualization and descriptive statistics were used to assess guidelines and tools for both use cases.

Results

Out of 480 unique PIMs identified, only three medications—amitriptyline, clomipramine, and imipramine and two drug classes—N06AA (tricyclic antidepressants) and N06AB (selective serotonin reuptake inhibitors), were noted in all eight guidelines and tools. Using the crosswalk, 50% of classes of index drugs and 47% of classes of marker drugs of known prescribing cascades were PIMs. Additionally, 88% of Medicare beneficiaries were dispensed ≥1 PIM across the eight guidelines and tools.

Conclusion

We created a crosswalk of eight PIM guidelines and tools to the ATC classification system and created two use cases. Our findings could be used to expand the ease of PIM identification and harmonization for research and clinical practice purposes.
The evaluation of salivary leucine‐rich alpha‐2 glycoprotein (LRG) and C‐reactive protein (CRP) in humans with periodontal health or periodontal disease
Authors: Özer Ece , Yilmaz Huriye Erbak , Narin Figen , Sağlam Mehmet
Published: December 2023

Objective

The purpose of the present research is to evaluate the salivary levels of leucine‐rich alpha‐2 glycoprotein (LRG) and C‐reactive protein (CRP) in periodontal health and disease (gingivitis and stage III periodontitis) and also to compare the discriminative efficiencies of both biomarkers in periodontal disease.

Background

LRG is a new acute‐phase protein whose functions are still being investigated. LRG and CRP are both biomarkers that are increased by inflammation. No clinical study has yet investigated the comparison of the level of LRG and CRP in periodontal health, gingivitis and periodontitis in saliva samples.

Methods

A total of 60 individuals, including 20 periodontally healthy (control group/group C), 20 with gingivitis (group G), and 20 with Stage III periodontitis (group P), who were systemically healthy and non‐smokers, participated in this study. Periodontal charts were used for recording clinical periodontal parameters and saliva LRG and CRP levels were measured by ELISA. Analyzing the area under the curve (AUC) was performed by the receiver‐operating characteristics curve.

Results

Salivary levels of LRG and CRP were significantly higher in disease groups than in group C (p < .05). Positive statistically significant correlations were observed between both biomarkers and clinical parameters (p < .05). There was also a strong positive correlation between two biomarkers (p < .05). In distinguishing periodontal disease from periodontal health, LRG (AUC = 0.833) and CRP (AUC = 0.826) were found to have similar accuracy (p = .923).

Conclusion

LRG and CRP may be useful and similarly effective biomarkers in the diagnosis of periodontal diseases based on the findings of this study.
Rebel with a cause: The effects of leadership encouragement and psychological safety on professionals' prosocial rulebreaking behavior
Authors: Bernards Bernard , Schmidt Eduard , Groeneveld Sandra
Published: December 2023

A core idea of bureaucratic organizations is that rule‐following is a necessary precondition to pursue the public interest. However, rules may sometimes become dysfunctional, burdensome, and even interfere with public value delivery. In those situations, professionals sometimes engage in prosocial rule‐breaking (PSRB), rather than rule‐following, with the aim to deliver meaningful public services. This article examines leadership encouragement and psychological safety as antecedents of PSRB behavior. Data from two waves of a multi‐source dataset consisting of professionals' self‐reported PSRB behavior and psychological safety (n = 837 and 965 respondents) and their supervisor‐reported encouragement for PSRB behavior (n = 58 and 64 respondents) is used. Findings point to a positive relationship between psychological safety and PSRB. Moreover, the study partly supports the hypothesis that leadership encouragement is associated with higher levels of PSRB, but only under conditions of high psychological safety.
The power of framing: The role of information provision in promoting whistleblowing
Authors: Novaro Riccardo , Nasi Greta , Cucciniello Maria , Grimmelikhuijsen Stephan
Published: December 2023

Whistleblowing policies are seldom effective in inducing civil servants to report misconduct. While current literature focusses more upon the identification of the chief factors that prevent witnesses from reporting, it overlooks potentially effective strategies to stimulate active behavior. In particular, it neglects the framing and impact of information provision. According to the prospect theory, information that frames the consequences of non‐reporting as negative is more effective in enhancing the intention to report misconduct, as opposed to information that frames the consequences of reporting as positive. This study tested these propositions through an online survey experiment targeted at the civil servants of a major European city. We exposed participants to four different frames of economic and psychological consequences of reporting wrongdoing, in order to analyze the impact of various frames upon participants' reporting intentions. The results of this study confirm the relevance of the prospect theory and clearly indicate how the presentation of information affects active behavior.
Transcriptional convergence after repeated duplication of an amino acid transporter gene leads to the independent emergence of the black husk/pericarp trait in barley and rice
Authors: Li Bo , Jia Yong , Xu Le , Zhang Shuo , Long Zhoukai , Wang Rong , Guo Ying , Zhang Wenying , Jiao Chunhai , Li Chengdao , Xu Yanhao
Published: December 2023

The repeated emergence of the same trait (convergent evolution) in distinct species is an interesting phenomenon and manifests visibly the power of natural selection. The underlying genetic mechanisms have important implications to understand how the genome evolves under environmental challenges. In cereal crops, both rice and barley can develop black‐coloured husk/pericarp due to melanin accumulation. However, it is unclear if this trait shares a common origin. Here, we fine‐mapped the barley HvBlp gene controlling the black husk/pericarp trait and confirmed its function by gene silencing. The result was further supported by a yellow husk/pericarp mutant with deletion of the HvBlp gene, derived from gamma ray radiation of the wild‐type W1. HvBlp encodes a putative tyrosine transporter homologous to the black husk gene OsBh4 in rice. Surprisingly, synteny and phylogenetic analyses showed that HvBlp and OsBh4 belonged to different lineages resulted from dispersed and tandem duplications, respectively, suggesting that the black husk/pericarp trait has emerged independently. The dispersed duplication (dated at 21.23 MYA) yielding HvBlp occurred exclusively in the common ancestor of Triticeae. HvBlp and OsBh4 displayed converged transcription in husk/pericarp tissues, contributing to the black husk/pericarp trait. Further transcriptome and metabolome data identified critical candidate genes and metabolites related to melanin production in barley. Taken together, our study described a compelling case of convergent evolution resulted from transcriptional convergence after repeated gene duplication, providing valuable genetic insights into phenotypic evolution. The identification of the black husk/pericarp genes in barley also has great potential in breeding for stress‐resilient varieties with higher nutritional values.
The effect of emotion recognition and mindfulness on depression symptoms: A case–control study
Authors: Aydın Orkun , Tvrtkovic Selma , Çakıroğlu Elif , Ünal‐Aydın Pınar , Esen‐Danacı Ayşen
Published: December 2023

Abnormalities in emotion recognition (ER) are frequently reported in depression, with lower recognition accuracy in patients with major depressive disorder (MDD) when compared to healthy individuals. Mindfulness was found to directly impact the severity of depressive symptoms, by recognizing negative cognitions and dysfunctional reactions. The aims of this study were to compare ER and mindfulness levels between MDD patients and healthy controls (HCs), as well as to examine whether ER and mindfulness are related to symptom severity in MDD patients. Sixty‐eight patients with MDD and 93 HCs participated in the study. A sociodemographic form, reading the mind in the eyes test (RMET), five facet mindfulness questionnaire‐short form (FFMQ‐S) and the Montgomery–Asberg depression scale (MADRS) were administered. Group comparison in ER and mindfulness was performed using the multivariate analysis of covariance (MANCOVA). Bivariate correlations and hierarchical linear regression analyses were performed to assess the associations between depression severity, ER and mindfulness in the patient group. Higher level of mindfulness was found in HCs relative to MDD group, however, no ER difference was present between the groups. A positive association between depression severity and the non‐reactivity facet of mindfulness was found. On the other hand, ER was not significantly associated with symptom severity among individuals with MDD. Non‐reactivity, unlike other dimensions of mindfulness, seems to increase with the severity of depressive symptoms among MDD patients. A particular focus on this subdimension in mindfulness techniques may yield better outcomes in alleviation of depressive symptoms.
Examining predictors of suicide by firearm in young, middle, and late adulthood
Authors: Docherty Meagan , Kubik Joanna , Drawve Grant
Published: December 2023

Introduction

Suicide remains a leading cause of death in the U.S., and firearms are one of the most lethal methods of suicide. This study examines personal and contextual factors that predict suicide with a firearm compared to other methods across stages of adulthood.

Methods

Data on adult suicide decedents from 2009 to 2019 were obtained from Colorado's National Violent Death Reporting System (NVDRS) data (N = 11,512). The dataset includes incident and person characteristics collected by law enforcement and coroners. Zip code level data were integrated from the American Community Survey.

Results

Age, sex, race, marital status, military service, substance use, suicide attempt history, mental health, and location characteristics (population density, as well as age, education, veteran status, and household status of population) predicted suicide by firearm. Risk was particularly high for males in older adulthood. We further explored age‐specific models (young, middle‐aged, and older adults) to determine salient risk factors for each group.

Conclusion

This study highlights the need for comprehensive suicide prevention approaches that consider both individual and contextual risk factors, as well as unique risks in each stage of adulthood.
Completion of isoniazid preventive therapy for latent tuberculosis infection among children and adolescents compared to adults living with HIV in Kinshasa, Democratic Republic of the Congo
Authors: Bidashimwa Dieudonné , Ditekemena John D. , Sigwadhi Lovemore Nyasha , Nkuta Lievain Maluentesa , Engetele Elodie , Kilundu Apolinaire , Chabikuli Otto N. , Nachega Jean B.
Published: December 2023

Background

Little is known about isoniazid preventive therapy (IPT) completion rates among children or adolescents compared to adults living with HIV in Kinshasa, Democratic Republic of the Congo (DRC).

Methods

We conducted a retrospective cohort analysis including children, adolescents, and adults living with HIV who were treated at FHI360 and partners‐implemented HIV care programs at six health zones in Kinshasa, DRC, from 2004 to 2020. The primary outcome was the proportion of children, adolescents versus adults who did complete 6 months of daily self‐administered IPT. Log‐binomial regression assessed independent predictors of IPT non‐completion and Kaplan–Meier technique for survival analysis.

Results

Of 11,691 eligible patients on ART who initiated IPT, 429 were children (<11 years), 804 adolescents (11–19 years), and 10,458 adults (≥20 years). The median age was 7 (IQR: 3–9) years for children, 15 (IQR: 13–17) years for adolescents, and 43 (35–51) years for adults. Among those who were initiated on IPT, 5625 out of 11,691 people living with HIV (PLHIV) had IPT completion outcome results, and an overall 3457/5625 (61.5%) completion rate was documented. Compared to adults, children and adolescents were less likely to complete IPT [104/199 (52.3%) and 268/525 (51.0%), respectively, vs. 3085/4901 (62.9%)]. After adjustment, the only independent predictors for IPT non‐completion were health zone of residence and type of ART regimen. Kaplan–Meier analysis showed comparable poor survival among patients who completed IPT versus those who did not (p‐value for log‐rank test, 0.15).

Conclusions

The overall sub‐optimal IPT completion rate in adults as well as children/adolescents in this setting is of great concern. Prospective studies are needed to elucidate the specific barriers to IPT completion among children, adolescents, and adults in DRC as well as the scale‐up of evidence‐informed interventions to improve IPT completion, such as adoption of shorter TB preventive regimens.
Arabidopsis thaliana GLYCINE RICH RNA‐BINDING PROTEIN 7 interaction with its iCLIP target LHCB1.1 correlates with changes in RNA stability and circadian oscillation
Authors: Lewinski Martin , Steffen Alexander , Kachariya Nitin , Elgner Mareike , Schmal Christoph , Messini Niki , Köster Tino , Reichel Marlene , Sattler Michael , Zarnack Kathi , Staiger Dorothee
Published: December 2023

The importance of RNA‐binding proteins (RBPs) for plant responses to environmental stimuli and development is well documented. Insights into the portfolio of RNAs they recognize, however, clearly lack behind the understanding gathered in non‐plant model organisms. Here, we characterize binding of the circadian clock‐regulated Arabidopsis thaliana GLYCINE‐RICH RNA‐BINDING PROTEIN 7 (AtGRP7) to its target transcripts. We identified novel RNA targets from individual‐nucleotide resolution UV crosslinking and immunoprecipitation (iCLIP) data using an improved bioinformatics pipeline that will be broadly applicable to plant RBP iCLIP data. 2705 transcripts with binding sites were identified in plants expressing AtGRP7‐GFP that were not recovered in plants expressing an RNA‐binding dead variant or GFP alone. A conserved RNA motif enriched in uridine residues was identified at the AtGRP7 binding sites. NMR titrations confirmed the preference of AtGRP7 for RNAs with a central U‐rich motif. Among the bound RNAs, circadian clock‐regulated transcripts were overrepresented. Peak abundance of the LHCB1.1 transcript encoding a chlorophyll‐binding protein was reduced in plants overexpressing AtGRP7 whereas it was elevated in atgrp7 mutants, indicating that LHCB1.1 was regulated by AtGRP7 in a dose‐dependent manner. In plants overexpressing AtGRP7, the LHCB1.1 half‐life was shorter compared to wild‐type plants whereas in atgrp7 mutant plants, the half‐life was significantly longer. Thus, AtGRP7 modulates circadian oscillations of its in vivo binding target LHCB1.1 by affecting RNA stability.
Effectiveness of intrathecal dexmedetomidine vs fentanyl as additives to hyperbaric bupivacaine for postoperative analgesia in women undergoing cesarean section: a systematic review protocol
Authors: Boshoff Jorica , Fourtounas Maria , Pegu Kylesh , McInerney Patricia
Published: December 2023

Objective:

The aim of this review is to compare the effectiveness of intrathecal dexmedetomidine vs fentanyl as additives to hyperbaric bupivacaine in providing postoperative analgesia in patients undergoing cesarean section.

Introduction:

Pain following cesarean section remains a challenge, with limited treatment options due to potential undesirable parturient and neonatal side effects. Intrathecal dexmedetomidine has emerged as a favorable alternative to opioid additives to hyperbaric bupivacaine in prolonging postoperative analgesia, but its effectiveness requires further investigation.

Inclusion criteria:

The review will evaluate studies of patients who underwent cesarean section under spinal anesthesia where dexmedetomidine and fentanyl were compared as intrathecal additives to hyperbaric bupivacaine for postoperative analgesia. This review will consider randomized controlled trials, non-randomized controlled trials, and prospective cohort studies for inclusion. No limits regarding publication date or language will be applied.

Methods:

A preliminary search of PubMed and Cochrane Central Register of Controlled Trials has been conducted to identify relevant index terms and keywords, which will be applied in a second search across PubMed, Cochrane CENTRAL, Scopus, and Embase. Google Scholar, National Library of Medicine (Clinicaltrials.gov), and the World Health Organization International Clinical Trial Registry Platform will be searched to identify unpublished literature. Full-text studies will be subjected to an assessment of methodological quality, and data extraction will be performed independently by 2 reviewers. The results will be presented in both tabular and narrative format and, where possible, pooled into a meta-analysis. A Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Summary of Findings will be created to grade the certainty of evidence of the reported outcomes.

Review registration:

PROSPERO CRD42022364815
Sliding Mode Wheel Slip Control for Regenerative Braking of an All-Wheel-Drive Electric Vehicle
Authors: Majumdar Abhigyan , Nazari Shima
Published: December 2023

Regenerative braking is one of the main advantages of electric propulsion systems. In such systems, the vehicle brake controller has to prioritize safety while maximizing the recovered energy at all times. This paper proposes a two-step hierarchical brake controller for a dual-motor all-wheel-drive electric vehicle. In the first step, a novel sliding mode controller (SMC) generates the total braking torque on each axle to independently control the slip on the front and rear wheels. In the second step, the torque split controller assigns motor and friction brake torques to maximize the recovered energy. By incorporating the effects of changing vehicle speed, the proposed SMC controller accounts for the nonlinearities in vehicle dynamics and tire model and considers the weight transfer due to vehicle deceleration while being robust to disturbances. Using simulations, we show that while the traditional SMC formulation is not effective during emergency braking scenarios, the proposed formulation successfully generates control commands to bring the vehicle to a stop position at a minimum distance. Furthermore, our controller can maintain both wheels in the stable slip region, even when starting from a locked position. The performance of the proposed controller is evaluated for an emergency braking scenario and on an aggressive segment of the US06 cycle.
Supercapacitor Voltage Doubling Equalization Method Based on Adaptive Grouping
Authors: Wang Chao , Liu Xiaohu , Han Li , Wu Tiezhou , Wang Xiangyu
Published: December 2023

In order to improve the inconsistency of lithium-ion battery packs, an adaptive grouping supercapacitor voltage-doubling equalization circuit is proposed on the basis of capacitor equalization circuits, which combines switching arrays with clustering algorithms for grouping, and multiple batteries can be equalized at the same moment according to the energy state. The supercapacitor energy storage module can realize parallel energy storage and series energy release, which greatly improves the equalization speed and solves the problem of slowing down the equalization speed at the later stage of equalization. Building six series-connected battery simulation platforms for experiments, the experimental data results show that the scheme proposed in this paper compared with the control group program equalization time is shortened by about 50%, has a faster equalization speed, and can effectively improve the inconsistency of the battery pack, effectively verifying the feasibility of the equalization program and superiority.
Quantification of Mixing Quality Effects on Flashback Limits for H2-Rich Fuel Gases in Lean Premixed Combustion Using Laser-Induced Fluorescence of Acetone
Authors: Kim Taesung , Doll Ulrich , Faldella Filippo , Jansohn Peter
Published: December 2023

One of the main challenges arising from hydrogen-rich fuel mixtures is to prevent flame flashback. In typical gas turbines, the fuel is commonly injected through holes in the axial swirler vanes to achieve a high mixing quality. However, this injection method is not perfect and can cause nonhomogeneous mixing regions, so that locally rich fuel clusters can significantly increase flashback propensity. This work aims to establish a link between the local mixing quality of fuel and air and flashback limits obtained experimentally under elevated pressure conditions. The nonreacting experiments have been conducted at an atmospheric mockup test rig and acetone-planar laser-induced fluorescence (PLIF) has quantified the local fuel concentration. Zones of high equivalence ratio are evident close to the center body wall. The near-wall equivalence ratio fields reveal that the critical probability of the local equivalence ratio being greater than the one for perfect premixing is between 20% and 35% for all hydrogen concentrations at the flashback limits observed. A probability of 35% is selected as a critical threshold to derive a correlation between the local and the global equivalence ratio in technical premixing. Even though the correlation is specific to the investigated burner configuration, the presented methodology offers valuable insights into the impact of the local mixing quality on flashback propensity, which can improve flashback prediction models formulated for perfect premixing conditions.
A new species of genus Molothrognathus Summers & Schlinger and a newly discovered male of Neognathus ozkani Akyol & Koç (Acariformes: Caligonellidae) from Türkiye
Authors: Akyol Mustafa
Published: December 2023

A new species viz. Molothrognathus manisaensis sp. nov., collected from litter and soil under Verbascum sp. (Scrophulariaceae), Inula viscosa (Asteraceae), Quercus coccifera and Q. infectoria (Fagaceae), and the unknown male of Neognathus ozkani Akyol & Koç, 2012, collected from litter and soil under Olea europaea (Oleaceae) in Manisa province, Türkiye, are described and illustrated. A key to the species of Molothrognathus from Türkiye is updated.
An Invar-based dual Fabry–Perot cavity refractometer for assessment of pressure with a pressure independent uncertainty in the sub-mPa region
Authors: Silander I. , Zakrisson J. , Zelan M. , Axner O.
Published: December 2023

An updated version of an Invar-based dual Fabry–Perot cavity refractometer utilizing the gas modulation methodology has been characterized with regard to its ability to assess gas pressure in the low pressure regime, defined as the regime in which the instrumentation is mainly limited by the constant term a in the [(a)2+(b×P)2]1/2 expression for the uncertainty. It is first concluded that this ability is predominantly limited by three entities, viz., the empty cavity repeatability, the residual gas pressures in the evacuated (measurement) cavity, and the contamination of the gas residing in the measurement cavity that originates from leaks and outgassing. We then present and utilize methods to separately estimate the uncertainty of the updated refractometer from these entities. It was found that, when utilizing gas modulation cycles of 100 s and when addressing nitrogen, the system can assess pressure in the low pressure regime with an expanded uncertainty (k=2) of 0.75 mPa, mainly limited by the empty cavity repeatability and outgassing of hydrogen. This is more than 1 order of magnitude below the previously assessed low pressure performance of the instrumentation.
How the air slows a closing book
Authors: Pantaleone J.
Published: December 2023

When two flat surfaces approach each other, the fluid in between is accelerated and ejected from the sides at large speeds. This situation occurs often in everyday life, such as when you step in a puddle and create splashes of water, or when you clap your hands or close a book and create jets of air. For these systems, the inertia of the fluid resists the acceleration, creating large nonlinear forces on the flat surfaces. In this work, we study the case of a closing book. The fluid motion in this case is relatively easy to model, using the conservation of mechanical energy, and to measure using a MEMS gyroscopic sensor. This study reveals the unusual forces that occur when two plates collide in an experiment that can be performed by students at home.
Acoustic trapping in the undergraduate laboratory
Authors: Boskovic Andrea , Jones Kate M. , Velasquez Alejandra , Hardy Isabel P. , Bulos Maya L. , Carter Ashley R. , Wiklund Martin
Published: December 2023

Acoustic trapping is used in modern biophysics laboratories to study cell adhesion or aggregation, to sort particles, or to build model tissues. Here, we create an acoustic trapping setup in liquid for an undergraduate instructional laboratory that is low-cost, easy to build, and produces results in a 1-hour laboratory period. In this setup, we use a glass slide, cover slip, and double-sided tape to make the sample chamber. A piezo-electric transducer connected to a function generator serves as the acoustic source. We use this setup to measure the node spacing (millimeters) and the acoustic trap force (picoNewtons). We anticipate that the simplicity of the experimental setup, the tractability of the theoretical equations, and the richness of the research topics on the subject will lead to an undergraduate laboratory with many interesting student projects.
Concepts in Monte Carlo sampling
Authors: Tartero Gabriele , Krauth Werner
Published: December 2023

We discuss contemporary ideas in Monte Carlo algorithms in the simplified setting of the one-dimensional anharmonic oscillator. After reviewing the connection between molecular dynamics and Monte Carlo, we introduce the Metropolis and the factorized Metropolis algorithms and lifted non-reversible Markov chains. We, furthermore, illustrate the concept of thinning, where moves are accepted by simple bounding potentials rather than the harmonic and quartic contributions to the anharmonic oscillator. We point out the multiple connections of our example algorithms with real-world sampling problems. This paper is self-contained, and Python implementations are provided.
Glia transmit negative valence information during aversive learning in
Drosophila
Authors: Miyashita Tomoyuki , Murakami Kanako , Kikuchi Emi , Ofusa Kyouko , Mikami Kyohei , Endo Kentaro , Miyaji Takaaki , Moriyama Sawako , Konno Kotaro , Muratani Hinako , Moriyama Yoshinori , Watanabe Masahiko , Horiuchi Junjiro , Saitoe Minoru
Published: December 2023

During
Drosophila
aversive olfactory conditioning, aversive shock information needs to be transmitted to the mushroom bodies (MBs) to associate with odor information. We report that aversive information is transmitted by ensheathing glia (EG) that surround the MBs. Shock induces vesicular exocytosis of glutamate from EG. Blocking exocytosis impairs aversive learning, whereas activation of EG can replace aversive stimuli during conditioning. Glutamate released from EG binds to
N
-methyl-
d
-aspartate receptors in the MBs, but because of Mg
2+
block, Ca
2+
influx occurs only when flies are simultaneously exposed to an odor. Vesicular exocytosis from EG also induces shock-associated dopamine release, which plays a role in preventing formation of inappropriate associations. These results demonstrate that vesicular glutamate released from EG transmits negative valence information required for associative learning.
Autonomous, multiproperty-driven molecular discovery: From predictions to measurements and back
Authors: Koscher Brent A. , Canty Richard B. , McDonald Matthew A. , Greenman Kevin P. , McGill Charles J. , Bilodeau Camille L. , Jin Wengong , Wu Haoyang , Vermeire Florence H. , Jin Brooke , Hart Travis , Kulesza Timothy , Li Shih-Cheng , Jaakkola Tommi S. , Barzilay Regina , Gómez-Bombarelli Rafael , Green William H. , Jensen Klavs F.
Published: December 2023

A closed-loop, autonomous molecular discovery platform driven by integrated machine learning tools was developed to accelerate the design of molecules with desired properties. We demonstrated two case studies on dye-like molecules, targeting absorption wavelength, lipophilicity, and photooxidative stability. In the first study, the platform experimentally realized 294 unreported molecules across three automatic iterations of molecular design-make-test-analyze cycles while exploring the structure-function space of four rarely reported scaffolds. In each iteration, the property prediction models that guided exploration learned the structure-property space of diverse scaffold derivatives, which were realized with multistep syntheses and a variety of reactions. The second study exploited property models trained on the explored chemical space and previously reported molecules to discover nine top-performing molecules within a lightly explored structure-property space.
A landmark environmental law looks ahead
Authors: Fischman Robert L. , Ruhl J. B. , Forester Brenna R. , Lama Tanya M. , Kardos Marty , Rojas Grethel Aguilar , Robinson Nicholas A. , Shirey Patrick D. , Lamberti Gary A. , Ando Amy W. , Palumbi Stephen , Wara Michael , Schwartz Mark W. , Williamson Matthew A. , Berger-Wolf Tanya , Beery Sara , Rolnick David , Kitzes Justin , Thau David , Tuia Devis , Rubenstein Daniel , Hickman Caleb R. , Thorstenson Julie , Kaebnick Gregory E. , Collins James P. , Jayaram Athmeya , Deleuil Thomas , Zhao Ying
Published: December 2023

In late December 1973, the United States enacted what some would come to call “the pitbull of environmental laws.” In the 50 years since, the formidable regulatory teeth of the Endangered Species Act (ESA) have been credited with considerable successes, obliging agencies to draw upon the best available science to protect species and habitats. Yet human pressures continue to push the planet toward extinctions on a massive scale. With that prospect looming, and with scientific understanding ever changing,
Science
invited experts to discuss how the ESA has evolved and what its future might hold.
—Brad Wible