bluuebunny/crossref_metadata_2025 huggingface dataset:
C. elegansDicer acts with the RIG-I-like helicase DRH-1 and RDE-4 to cleave dsRNA
Authors: Consalvo Claudia D. , Aderounmu Adedeji M. , Donelick Helen M. , Aruscavage P. Joe , Eckert Debra M. , Shen Peter S. , Bass Brenda L.
Published: September 2023

Abstract/Summary

Invertebrates use the endoribonuclease Dicer to cleave viral dsRNA during antiviral defense, while vertebrates use RIG-I-like Receptors (RLRs), which bind viral dsRNA to trigger an interferon response. While some invertebrate Dicers act alone during antiviral defense,C. elegansDicer acts in a complex with a dsRNA binding protein called RDE-4, and an RLR ortholog called DRH-1. We used biochemical and structural techniques to provide mechanistic insight into how these proteins function together. We found RDE-4 is important for ATP-independent and ATP-dependent cleavage reactions, while helicase domains of both DCR-1 and DRH-1 contribute to ATP-dependent cleavage. DRH-1 plays the dominant role in ATP hydrolysis, and like mammalian RLRs, has an N-terminal domain that functions in autoinhibition. A cryo-EM structure indicates DRH-1 interacts with DCR-1’s helicase domain, suggesting this interaction relieves autoinhibition. Our study unravels the mechanistic basis of the collaboration between two helicases from typically distinct innate immune defense pathways.
Comparative dynamics of gene expression during in vitro and in vivoCandida albicansfilamentation
Authors: Wakade Rohan S. , Krysan Damian J.
Published: September 2023

Candida albicansis one of them most common causes of fungal disease in humans and is a commensal member of the human microbiome. The ability ofC. albicansto cause disease is tightly correlated with its ability to undergo a morphological transition from budding yeast to a filamentous form (hyphae and pseudohyphae). This morphological transition is accompanied by the induction of a set of well characterized hyphae-associated genes and transcriptional regulators. To date, the vast majority of data regarding this process has been based on in vitro studies of filamentation using a range of inducing conditions. Recently, we developed an in vivo imaging approach that allows the direct characterization of morphological transition during mammalian infection. Here, we couple this imaging assay with in vivo expression profiling to characterize the time course of in vivo filamentation and the accompanying changes in gene expression. We also compare in vivo observations to in vitro filamentation using a medium (RPMI 1640 tissue culture medium with 10% bovine calf serum) widely used to mimic host conditions. From these data, we make the following conclusions regarding in vivo and in vitro filamentation. First, the transcriptional programs regulating filamentation are rapidly induced in vitro and in vivo. Second, the tempo of filamentation in vivo is prolonged relative to in vitro filamentation and the period of high expression of genes associated with that process is also prolonged. Third, hyphae are adapting to changing infection environments after filamentation has reached steady-state.

Importance

Candida albicansfilamentation is correlated with virulence and is an intensively studied aspect ofC. albicansbiology. The vast majority of studies onC. albicansfilamentation are based on in vitro induction of hyphae and pseudohyphae. Here we used an in vivo filamentation assay and in vivo expression profiling to compare the tempo of morphogenesis and gene expression between in vitro and in vivo filamentation. Although the hyphal gene expression profile is induced rapidly in both conditions, it remains stably expressed over the 24hr time course in vivo while the expression of other environmentally responsive genes is dynamic. As such, it is important to regard the filamentation process as a separate growth phase ofC. albicansthat is as adaptable to changing growth conditions as the more familiar yeast phase.
Bacteroides thetaiotaomicronmetabolic activity decreases with polysaccharide molecular weight
Authors: Wong Jeremy P. H. , Chillier Noémie , Fischer-Stettler Michaela , Zeeman Samuel C. , Battin Tom J. , Persat Alexandre
Published: September 2023

The human colon hosts hundreds of commensal bacterial species, many of which ferment complex dietary carbohydrates. To transform these fibers into metabolically-accessible compounds, microbes often express series of dedicated enzymes homologous to the starch utilization system (sus) encoded in polysaccharide utilization loci (PULs). The genome ofBacteroides thetaiotaomicron (Bt),a common member of the human gut microbiota, encodes nearly 100 PULs, conferring a strong metabolic versatility. While the structures and functions of individual enzymes within the PULs have been investigated, little is known about how polysaccharide complexity impacts the function of sus-like systems. We here show that the activity of sus-like systems depends on polysaccharide size, ultimately impacting bacterial growth. We demonstrate the effect of size-dependent metabolism in the context of dextran metabolism driven by the specific utilization system PUL48. We find that as molecular weight of dextran increases,Btgrowth rate decreases and lag time increases. At the enzymatic level, the dextranase BT3087 is the main glycosylhydrolase for dextran utilization and that BT3087 and BT3088 contribute toBtdextran metabolism in a size-dependent manner. Finally, we show that the polysaccharide size-dependent metabolism ofBtimpacts its metabolic output in a way that modulates the composition of a producer-consumer community it forms withBacteroides fragilis. Altogether, our results expose an overlooked aspect ofBtmetabolism which can impact the composition and diversity of microbiota.
GENOMES UNCOUPLED1: an RNA-binding protein required for early PSII biogenesis
Authors: Cui Chaojun , Sun Shuyi , Zhang Siyuan , Zhang Yu , Kim Chanhong
Published: September 2023

Genomes Uncoupled1 (GUN1), a nuclear-encoded chloroplast pentatricopeptide repeat (PPR) protein, serves as a master integrator of diverse retrograde signals, mediating chloroplast-to-nucleus retrograde signaling. Although PPR proteins primarily function in organelle RNA metabolism, a target RNA of GUN1 remained unknown. This study reveals that GUN1 recognizespsbDtranscripts derived from a blue light-responsive promoter (BLRP), transcripts referred to aspsbDBLRP. Overexpression of GUN1 significantly reduces the levels ofpsbDBLRP, whereas the loss of GUN1 leads to the accumulation of the putative target RNA. Thein vitroRNA andin vivogenetic studies further demonstrate the critical role of the C-terminal small MutS-related (SMR) domain in stimulatingpsbDBLRP processing and PsbD (D2, a PSII core protein) synthesis. The GUN1-dependentpsbDBLRP processing promotes PSII biogenesis during the early seedling development and de-etiolation phase. This finding underscores the role of GUN1 as an RNA-binding protein, highlighting the essential function of the SMR domain in processing the target RNA.

Significance

Biogenic retrograde signaling is essential in regulating chloroplast biogenesis, and it entails a nuclear-encoded chloroplast protein, Genomes Uncoupled1 (GUN1). Since its initial discovery in 1993, thegun1mutant has been widely used to reveal the precise function of GUN1 in plastids as well as its downstream signaling components. Although GUN1 contains pentatricopeptide repeat motifs, it has been considered a non-canonical PPR protein because no one could demonstrate GUN1-RNA interaction in planta. However, through our computational analysis of PPR codes and subsequent biochemical studies, we were able to unravel its putative target RNA, namelypsbDBLRP. Therefore, our finding may lead to a reevaluation of GUN1 research in the context of RNA metabolism and a revision of our current understanding of GUN1.
Paternal starvation affects metabolic gene expression during zebrafish offspring development and life-long fitness
Authors: Jimenez-Gonzalez Ada , Ansaloni Federico , Nebendahl Constance , Alavioon Ghazal , Murray David , Robak Weronika , Sanges Remo , Müller Ferenc , Immler Simone
Published: September 2023

Dietary restriction is a putative key to a healthier and longer life, but these benefits may come at a trade-off with reproductive fitness and may affect the following generation(s). The potential inter- and transgenerational effects of starvation are particularly poorly understood in vertebrates when they originate from the paternal line. We utilised the externally fertilising zebrafish amenable to a split-egg clutch design to explore the male-specific effects of starvation on fertility and fitness of offspring independently of maternal contribution. Eighteen days of fasting resulted in reduced fertility in exposed males. While average offspring survival was not affected, we detected higher larval growth in offspring from starved males and increased malformation rates at 24 hours post fertilisation in the F2 embryos produced by the offspring of the starved males. The transcriptome analysis of embryos from starved and fed fathers revealed robust and reproducible induction of muscle composition genes and a contrasting repressive effect on lipid metabolism and lysosome genes. A large proportion of these genes showed enrichment in the yolk syncytial layer suggesting gene regulatory responses associated with metabolism of nutrients through paternal impact on extra embryonic tissues which are loaded with maternally deposited factors. We compared the embryo transcriptome to adult transcriptome datasets and demonstrated comparable repressive effects on metabolism-associated genes. These similarities suggest a physiologically relevant, directed and potentially adaptive response transmitted by the father, independently from the offspring’s nutritional state, which was defined by the mother.
The evolution of the duckweed ionome mirrors losses in structural complexity
Authors: Smith Kellie E , Zhou Min , Flis Paulina , Jones Dylan , Bishopp Anthony , Yant Levi
Published: September 2023

Background and Aims

The duckweeds consist of 36 species exhibiting impressive phenotypic variation, including the progressive evolutionary loss of a fundamental plant organ, the root. Loss of roots and reduction of vascular tissues in recently derived taxa occur in concert with genome expansions of up to 14-fold. Given the paired loss of roots and reduction in structural complexity in derived taxa, we focus on the evolution of the ionome (whole-plant elemental contents) in the context of these fundamental body plan changes. We expect that progressive vestigiality and eventual loss of roots may have both adaptive and maladaptive consequences which are hitherto unknown.

Methods

We quantify the ionomes of 34 accessions in 21 species across all duckweed genera, spanning 70 million years in this rapid cycling plant (doubling times are as low as 24 hours). We relate both micro– and macroevolutionary ionome contrasts to body plan remodelling and show nimble microevolutionary shifts in elemental accumulation and exclusion in novel accessions.

Key Results

We observe a robust directional trend in calcium and magnesium levels decreasing from the ancestral representativeSpirodelagenus towards the derived rootlessWolffia, with the latter also accumulating cadmium. We also identify abundant within-species variation and hyperaccumulators of specific elements, with this extensive variation at the fine– as opposed to broad-scale.

Conclusions

These data underscore the impact of root loss, and reveal the very fine scale of microevolutionary variation in hyperaccumulation and exclusion of a wide range of elements. Broadly, they may point to trade-offs not well recognized in ionomes.
In situ synchrotron X-ray total scattering measurements and analysis of colloidal CsPbX
3 nanocrystals during flow synthesis
Authors: Greenberg Matthew W. , Lin Cheng-Hung , Chodankar Shirish , Ghose Sanjit K.
Published: September 2023

In situ X-ray scattering measurements of CsPbX
3 (X = Cl, Br, I) nanocrystal formation and halide exchange at NSLS-II beamlines were performed in an automated flow reactor. Total scattering measurements were performed at the 28-ID-2 (XPD) beamline and small-angle X-ray scattering at the 16-ID (LiX) beamline. Nanocrystal structural parameters of interest, including size, size distribution and atomic structure, were extracted from modeling the total scattering data. The results highlight the potential of these beamlines and the measurement protocols described in this study for studying dynamic processes of colloidal nanocrystal synthesis in solution with timescales on the order of seconds.
Redeveloping the compact city: the challenges of strata collective sales
Authors: Easthope Hazel , Crommelin Laura , Gillon Charles , Pinnegar Simon , Ruming Kristian , Liu Sha
Published: September 2023

Purpose

High-density development requires large land parcels, but fragmented land ownership can impede redevelopment. While earlier compact city development in Sydney occurred on large-scale brownfield sites, redeveloping and re-amalgamating older strata-titled properties is now integral to further densification. The purpose of this study is to examine collective sales activity in one Sydney suburb where multiple strata-titled redevelopments and re-amalgamations have been attempted. The authors explore how owners navigate the process of selling collectively, focusing on their experience of legislation introduced to facilitate this process, the Strata Schemes Development Act 2015 [New South Wales (NSW)].

Design/methodology/approach

By reviewing sales listings, development applications and media coverage, and interviewing owners, lawyers and estate agents, the authors map out collective sale activity in a case study area in Sydney’s northwest.

Findings

Strata collective sales are slow and difficult to complete, even when planning and market drivers align. Owners find the Strata Scheme Development Act 2015 (NSW) difficult to navigate and it has not prevented strategic blocking attempts by competing developers. The long timelines required to organise collective sales can result in failure if the market shifts in the interim. Nonetheless, owners remain interested in selling collectively.

Originality/value

This case study is important for understanding the barriers to redevelopment to achieve a more compact city. It highlights lessons for other jurisdictions considering similar legislative changes. It also suggests that legislative change alone is insufficient to resolve the planning challenges created by hyper-fragmentation of land through strata-title development.
Designing policy based on entrepreneurial venture type: the effects of innovation, hiring practices and patent ownership on enterprise development
Authors: Matricano Diego
Published: September 2023

Purpose

The Italian government enacted two laws: ruling innovative startups (Law 221/2012) and innovative SMEs (Law Decree 3/2015), respectively. Despite renowned differences between them, the parameters selected and included in these laws are the same: investments in research and development (R&D) activities, hiring specialized researchers and holding patents/property rights. Taking a cue from the Italian case, the following research question emerges: whether small business policies, concerning innovative startups and SMEs, should be differentiated to be effective and support enterprise development. The Italian case is invoked to offer suggestions and recommendations to policymakers around the world.

Design/methodology/approach

Stochastic frontier analyses (SFA) were conducted by using data provided by the Italian Ministry of Economic Development (MISE) about 14,595 innovative startups and 2,338 innovative SMEs.

Findings

Statistical results reveal that enterprise development processes are different between innovative startups and SMEs. Innovative startups may start a virtuous model, while innovative SMEs may not. This corroborates the idea that small business policies need to be differentiated in order to be effective.

Originality/value

Unlike other papers, small businesses are not considered as a whole. Innovative startups and SMEs are two different types of firms, so specific investigations are conducted to remark on the already-known differences and disclose new ones.
Do prosumers behave differently from other consumers on collaborative consumption platforms?
Authors: Giglio Carlo , Popescu Irina Alina , Verteramo Saverino
Published: September 2023

Purpose

This paper aims at understanding the differences between user profiles in collaborative consumption (CC) platforms in order to improve their management approaches and set up customized strategies. Particularly, the authors investigate the emerging role of prosumers and their influence on the active participation and growth of CC platforms. Moreover, the authors study user experience to help promoting users' recommendation and offering intention.

Design/methodology/approach

The sample includes responses from 6,388 users of CC platforms across the EU. The data were collected through the European Commission's Flash Eurobarometer survey 467 and analyzed through a partial least squares structural equation modeling (PLS-SEM) and a fuzzy set qualitative comparative analysis (fsQCA).

Findings

The PLS-SEM findings suggest that prosumers are more likely than consumers to recommend and offer services through CC platforms. Furthermore, previous experience using platforms positively affects the switch from consumers to prosumers. The fsQCA suggests that only economic advantages affect the switchover decision.

Research limitations/implications

This study deepens the hitherto unexplored prosumer role in CC platforms and its antecedents and drivers.

Practical implications

The main limitations concern the generalizability outside of the EU, the unbalanced coverage of sectors and the number of moderator variables.

Social implications

Prosumers act as golden actors because they contribute to enlarge both the customer base (through recommendations) and the provider base (through offering intention). Hence, managers should focus on prosumers' experiences to increase the critical mass and positive externalities of CC platforms.

Originality/value

This study helps understand the importance of the role of prosumers in the growth of CC platforms. The study provides more robust results through a cross-country and mixed-method research.
How leader humility influences team reflexivity: a team level analysis
Authors: Son SuJin , Yang Tae Seok
Published: September 2023

Purpose

The purpose of this study is to examine the effect of leader humility on team reflexivity. This study also investigates the mediating role of relation-oriented shared leadership and the moderating role of leader trust.

Design/methodology/approach

This study collected data from the information technology (IT) service provider of a large telecommunications company in South Korea. A total of 311 employees (individual response rate of 31.2%) in 59 teams (team response rate of 83.01%) were included in the final analysis. Several hierarchical regression analyses and PROCESS macro were used.

Findings

The results indicate that leaders’ humble behaviour is positively associated with team reflexivity and facilitates relation-oriented shared leadership among team members, particularly when they have a higher level of affect-based trust in leaders.

Practical implications

This study may help researchers and practitioners better understand the conditions influencing the impact of leader humility on team members’ behaviour.

Originality/value

The main value of this study is to add to the knowledge on team reflexivity by identifying leader humility as a critical factor affecting team reflexivity. Furthermore, this study provides a deeper understanding of why leader humility influences team reflexivity.
A survey of preferences for respiratory support in the intensive care unit for patients with acute hypoxaemic respiratory failure
Authors: Aslam Tayyba N. , Klitgaard Thomas L. , Ahlstedt Christian A. O. , Andersen Finn H. , Chew Michelle S. , Collet Marie O. , Cronhjort Maria , Estrup Stine , Fossum Ole K. , Frisvold Shirin K. , Gillmann Hans‐Joerg , Granholm Anders , Gundem Trine M. , Hauss Kristin , Hollenberg Jacob , Huanca Condori Maria E. , Hästbacka Johanna , Johnstad Bror A. , Keus Eric , Kjær Maj‐Brit N. , Klepstad Pål , Krag Mette , Kvåle Reidar , Malbrain Manu L. N. G. , Meyhoff Christian S. , Morgan Matt , Møller Anders , Pfortmueller Carmen A. , Poulsen Lone M. , Robertson Andrew C. , Schefold Joerg C. , Schjørring Olav L. , Siegemund Martin , Sigurdsson Martin I. , Sjövall Fredrik , Strand Kristian , Stueber Thomas , Szczeklik Wojciech , Wahlin Rebecka R. , Wangberg Helge L. , Wian Karl‐Andre , Wichmann Sine , Hofsø Kristin , Møller Morten H. , Perner Anders , Rasmussen Bodil S. , Laake Jon H. ,   the SVALBARD investigators
Published: September 2023

Background

When caring for mechanically ventilated adults with acute hypoxaemic respiratory failure (AHRF), clinicians are faced with an uncertain choice between ventilator modes allowing for spontaneous breaths or ventilation fully controlled by the ventilator. The preferences of clinicians managing such patients, and what motivates their choice of ventilator mode, are largely unknown. To better understand how clinicians' preferences may impact the choice of ventilatory support for patients with AHRF, we issued a survey to an international network of intensive care unit (ICU) researchers.

Methods

We distributed an online survey with 32 broadly similar and interlinked questions on how clinicians prioritise spontaneous or controlled ventilation in invasively ventilated patients with AHRF of different severity, and which factors determine their choice.

Results

The survey was distributed to 1337 recipients in 12 countries. Of these, 415 (31%) completed the survey either fully (52%) or partially (48%). Most respondents were identified as medical specialists (87%) or physicians in training (11%). Modes allowing for spontaneous ventilation were considered preferable in mild AHRF, with controlled ventilation considered as progressively more important in moderate and severe AHRF. Among respondents there was strong support (90%) for a randomised clinical trial comparing spontaneous with controlled ventilation in patients with moderate AHRF.

Conclusions

The responses from this international survey suggest that there is clinical equipoise for the preferred ventilator mode in patients with AHRF of moderate severity. We found strong support for a randomised trial comparing modes of ventilation in patients with moderate AHRF.
Labor elasticities, market failures, and misallocation: Evidence from Indian agriculture
Authors: Merfeld Joshua D.
Published: September 2023

This article presents evidence of misallocation across households in rural Indian agriculture. I show that household demographics predict own farm labor demand for smallholder farmers but not non‐smallholder farmers. A simple model of labor allocation predicts a clear consequence of this duality: smallholder farmers will reallocate labor across plots less in response to price changes than non‐smallholders. Detailed household panel data confirms this theoretical prediction. Three additional facts suggest that a lack of off‐farm labor opportunities may be partly responsible for the behavior of smallholders, leading smallholders to over allocate labor to agricultural production. First, smallholders report fewer hours of involuntary unemployment when their own crop prices increase. Second, yield is substantially higher for smallholders on plots of the same size. Finally, estimated marginal revenue products of labor are consistently lower for smallholders.
Managing mothers' and fathers' uncertainty during their journey through early neurodevelopmental follow‐up for their high‐risk infants—A qualitative account
Authors: Fortune Alice , Perkins Elizabeth , Paize Fauzia , Palanisami Balamurugan , Gladstone Melissa
Published: September 2023

Background

Early diagnosis of cerebral palsy is possible by 5 months corrected age for ‘at‐risk’ infants, using diagnostic tools such as the Hammersmith Infant Neurological Examination (HINE), Prechtl's General Movements Assessment (GMA) and magnetic resonance imaging (MRI). This is an uncertain and stressful time for parents where provision of appropriate information and support is essential.

Aim

To explore parents' views and experiences in relation to the new early neurodevelopmental follow‐up of ‘at‐risk’ infants.

Methods

Thirteen in‐depth one‐to‐one qualitative interviews were conducted by the primary researcher, with eight parents (six mothers and two fathers) of ‘at‐risk’ infants eligible for a follow‐up clinic where the GMA and HINE were performed at 12‐week corrected age. Interviews used a pre‐piloted topic guide and took place before and after the clinic. Interviews were audio‐recorded, transcribed verbatim and analysed using inductive coding and thematic analysis using the framework approach.

Findings

Seven themes were identified: (1) attempting to manage uncertainty, (2) taking priority, (3) trusting professionals, (4) independence in the parent role, (5) feeling understood, (6) patterns of care and (7) individuality. Parents reported experiencing uncertainty about their current situation and future. Adequate preparation for and timing of information are vital. When uncertainty is poorly managed, parents' wellbeing suffers. Individual parents' perspectives and infants' developmental trajectories differ, and information should be tailored specifically for this.

Conclusion

A parent's understanding of the journey through neurodevelopmental care for their high risk infants is initially very limited. Implementing a counselling service for parents to access psychological support and digital reminder system for clinic appointments, as well as providing more tailored information through trusted professionals, could all improve future parents' experiences.
Continuous glucose monitoring metrics and pregnancy outcomes in insulin‐treated diabetes: A post‐hoc analysis of the GlucoMOMS trial
Authors: Rademaker Doortje , van der Wel Anne W. T. , van Eekelen Rik , Voormolen Daphne N. , de Valk Harold W. , Evers Inge M. , Mol Ben Willem , Franx Arie , Siegelaar Sarah E. , van Rijn Bas B. , DeVries J. Hans , Painter Rebecca C. ,   GlucoMOMS studygroup
Published: September 2023

Aim

To investigate the association between continuous glucose monitoring (CGM) metrics and perinatal outcomes in insulin‐treated diabetes mellitus in pregnancy.

Materials and Methods

In a post‐hoc analysis of the GlucoMOMS randomized controlled trial, we investigated the association between the metrics of an offline, intermittent CGM, glycated haemoglobin (HbA1c) and perinatal outcomes per trimester in different types of diabetes (type 1, 2 or insulin‐treated gestational diabetes mellitus [GDM]). Data were analysed using multivariable binary logistic regression. Outcomes of interest were neonatal hypoglycaemia, pre‐eclampsia, preterm birth, large for gestational age (LGA) and Neonatal Intensive Care Unit (NICU) admission. The glucose target range was defined as 3.5–7.8 mmol/L (63–140 mg/dL).

Results

Of the 147 participants (N = 50 type 1 diabetes, N = 94 type 2 diabetes/insulin‐treated GDM) randomized to the CGM group of the GlucoMOMS trial, 115 participants had CGM metrics available and were included in the current study. We found that, in pregnancies with type 1 diabetes, a higher second trimester mean glucose was associated with LGA (odds ratio 2.6 [95% confidence interval 1.1–6.2]). In type 2 and insulin‐treated gestational diabetes, an increased area under the curve above limit was associated with LGA (odds ratio 10.0 [95% confidence interval 1.4–72.8]). None of the CGM metrics were associated with neonatal hypoglycaemia, pre‐eclampsia, shoulder dystocia, preterm birth and NICU admission rates for pregnancies complicated by any type of diabetes.

Conclusion

In this study, in type 2 diabetes or insulin‐treated GDM, the glucose increased area under the curve above limit was associated with increased LGA. In type 1 diabetes, the mean glucose was the major determinant of LGA. Our study found no evidence that other CGM metrics determined adverse pregnancy outcomes.
Treatment patterns in essential tremor: Real‐world evidence from a United Kingdom and France primary care database
Authors: Antonazzo Ippazio Cosimo , Rozza Davide , Conti Sara , Fornari Carla , Cortesi Paolo Angelo , Eteve‐Pitsaer Caroline , Paris Claire , Gantzer Laurène , Valentine Dennis , Mantovani Lorenzo Giovanni , Mazzaglia Giampiero
Published: September 2023

Background and purpose

Essential tremor (ET) is one of the most common neurological disorders, but information on treatment pattern is still scant. The aim of this study was to describe the demographic and clinical characteristics, treatment patterns, and determinants of drug use in patients with newly diagnosed ET in France and the United Kingdom.

Methods

Incident cases of ET diagnosed between January 1, 2015 and December 31, 2018 with 2 years of follow‐up were identified by using The Health Improvement Network (THIN®) general practice database. During the follow‐up, we assessed the daily prevalence of use and potential switches from first‐line to second‐line treatment or other lines of treatment. Logistic regression models were conducted to assess the effect of demographic and clinical characteristics on the likelihood of receiving ET treatment.

Results

A total of 2957 and 3249 patients were selected in the United Kingdom and France, respectively. Among ET patients, drug use increased from 12 months to 1 month prior the date of index diagnosis (ID). After ID, nearly 40% of patients received at least one ET treatment, but during follow‐up drug use decreased and at the end of the follow‐up approximately 20% of patients were still on treatment. Among treated patients, ≤10% maintained the same treatment throughout the entire follow‐up, nearly 20% switched, and 40%–75% interrupted any treatment. Results from the multivariate analysis revealed that, both in France and the United Kingdom, patients receiving multiple concomitant therapies and affected by psychiatric conditions were more likely to receive an ET medication.

Conclusion

This study shows that ET is an undertreated disease with a lower‐than‐expected number of patients receiving and maintaining pharmacological treatment. Misclassification of ET diagnosis should be acknowledged; thus, results require cautious interpretation.
Rapidly progressive dementia due to intravascular lymphoma: A prion disease reference center experience
Authors: Bentivenga Giuseppe Mario , Baiardi Simone , Righini Lorenzo , Ladogana Anna , Capellari Sabina , Sabattini Elena , Parchi Piero
Published: September 2023

Background

Intravascular large B‐cell lymphoma (IVLBCL) is a rare extranodal lymphoma that is characterized by the selective growth of neoplastic cells in blood vessels, representing a potentially treatable cause of rapidly progressive dementia (RPD). Given its diverse clinical and instrumental presentation, it is often misdiagnosed with more common RPD causes, for example, Creutzfeldt‐Jakob disease (CJD) or vascular dementia.

Methods

This study presents the clinical and histopathological characteristics of four IVLBCL cases that we diagnosed post‐mortem over 20 years among over 600 brain samples received as suspected CJD cases at our prion disease reference center.

Results

Our patients exhibited various presenting symptoms, including behavioral disturbances, disorientation, and alertness fluctuations. The diagnostic tests performed at the time, including blood work, cerebrospinal fluid (CSF) analyses, electroencephalography, and neuroimaging, yielded nonspecific and occasionally misleading results. Consequently, the patients were repeatedly diagnosed as variably having CJD, epilepsy, vascular dementia, and encephalitis. The stored CSF samples of two patients tested negative at prion real‐time quaking‐induced conversion (RT‐QuIC), which we performed afterwards for research purposes. Neuropathological analysis revealed a differential involvement of various brain areas, with frontotemporal neocortices being the most affected.

Conclusions

Our results confirm the significant clinical and instrumental heterogeneity of IVLBCL. Neuropathological evidence of the preferential involvement of frontotemporal neocortices, potentially conditioning the clinical phenotype, could be relevant to reach an early diagnosis. Finally, given the therapeutic implications of its misdiagnosis with CJD, we emphasize the utility of prion RT‐QuIC as a test for ruling out CJD in these patients.
The Collaborative Study on the Genetics of Alcoholism: Overview
Authors: Agrawal Arpana , Brislin Sarah J. , Bucholz Kathleen K. , Dick Danielle , Hart Ronald P. , Johnson Emma C. , Meyers Jacquelyn , Salvatore Jessica , Slesinger Paul ,   COGA Collaborators, Almasy Laura , Foroud Tatiana , Goate Alison , Hesselbrock Victor , Kramer John , Kuperman Samuel , Merikangas Alison K. , Nurnberger John I. , Tischfield Jay , Edenberg Howard J. , Porjesz Bernice
Published: September 2023

Alcohol use disorders (AUD) are commonly occurring, heritable and polygenic disorders with etiological origins in the brain and the environment. To outline the causes and consequences of alcohol‐related milestones, including AUD, and their related psychiatric comorbidities, the Collaborative Study on the Genetics of Alcoholism (COGA) was launched in 1989 with a gene‐brain‐behavior framework. COGA is a family based, diverse (~25% self‐identified African American, ~52% female) sample, including data on 17,878 individuals, ages 7–97 years, in 2246 families of which a proportion are densely affected for AUD. All participants responded to questionnaires (e.g., personality) and the Semi‐Structured Assessment for the Genetics of Alcoholism (SSAGA) which gathers information on psychiatric diagnoses, conditions and related behaviors (e.g., parental monitoring). In addition, 9871 individuals have brain function data from electroencephalogram (EEG) recordings while 12,009 individuals have been genotyped on genome‐wide association study (GWAS) arrays. A series of functional genomics studies examine the specific cellular and molecular mechanisms underlying AUD. This overview provides the framework for the development of COGA as a scientific resource in the past three decades, with individual reviews providing in‐depth descriptions of data on and discoveries from behavioral and clinical, brain function, genetic and functional genomics data. The value of COGA also resides in its data sharing policies, its efforts to communicate scientific findings to the broader community via a project website and its potential to nurture early career investigators and to generate independent research that has broadened the impact of gene‐brain‐behavior research into AUD.
Late Cretaceous–Paleogene terrestrial sequence in the northern Kitakami Mountains, Northeast Japan: Depositional ages, clay mineral contents, and vitrinite reflectance
Authors: Noda Atsushi , Morimoto Kazuya , Takahashi Koji U. , Danhara Tohru , Iwano Hideki , Hirata Takafumi
Published: September 2023

Forearc basin deposits on continental margins contain important information that can be used to reconstruct the tectonic setting, volcanism, and climate at the time of their deposition. Coal‐bearing terrestrial to shallow marine strata in Northeast Japan were deposited in a forearc basin along the Eurasian continental margin during the Cretaceous–Paleogene. The rocks exposed in the Kado district, Iwate Prefecture, in the northern Kitakami Mountains include the Upper Cretaceous Yokomichi Formation and the Paleogene Kogawa Group; the latter is known for high‐quality refractory clay (kaolin clay). However, their stratigraphy and sedimentological characteristics are not yet fully understood. To reconstruct the formation and filling of the basin, we investigated field observations, U–Pb dating of tuff samples, XRD analysis of tuff and mudstone samples, and vitrinite reflectance of coal samples in this sequence. The U–Pb ages of the Yokomichi Formation and the Kogawa Group are ∼86 Ma and 58–52 Ma, respectively. The U–Pb age of the kaolin‐dominated tuffaceous rock (“red rocks”) is 56.1 ± 0.2 Ma. The mean random vitrinite reflectance (VRr) ranges from 0.37% to 0.53% through the sequence. We propose the following sequence for the formation and filling of the basin. (1) The basin initially formed during the Coniacian–Santonian (Late Cretaceous) and was filled by fluvial–lacustrine sediment. (2) These sediments kept the shallow burial depths during a ∼28 Myr and made a hiatus (86–58 Ma). (3) The basin was reactivated and covered by tuffs during the Thanetian, and the tuffs were altered to kaolin clay during the Paleocene–Eocene Thermal Maximum. (4) The basin was filled rapidly by alluvial fan deposits and subsided <2300 m (assuming a geothermal gradient of >30 K/km). (5) The basin was uplifted and exhumed at a rate of >50 m/Myr faster than the mean exhumation rate of the Kitakami Mountains since the Paleogene.
Trophic level and specialization moderate effects of habitat loss and landscape diversity on cavity‐nesting bees, wasps and their parasitoids
Authors: Klaus Felix , Tscharntke Teja , Grass Ingo
Published: September 2023

Habitat loss is a primary driver of biodiversity decline, but differences in species responses to habitat loss from local to landscape scales are poorly understood.

Trophic level, food and habitat specialization have been suggested to be important predictors of species responses to habitat loss, landscape diversity and landscape scale.

Using cavity‐nesting communities of bees, wasps and their parasitoids on calcareous grasslands as a model system allowed us to compare responses of species differing regarding their trophic level, and degree of specialization on habitat and food.

We found that species from higher trophic levels experienced semi‐natural habitat at larger spatial scales than those of lower trophic levels, but only, when they were generalists (abundance of bees, 150 m radius, vs. wasps feeding on herbivores, 450 m radius), not specialists (bees, 150 m, vs. bee parasitoids, 150 m).

Parasitoids, which are typically more specialized regarding their food resources (hosts), compared to predators such as predatory wasps, responded to habitat loss at the same spatial scales as their hosts, suggesting strong bottom‐up effects of resource availability, that is, host availability driving parasitoid abundance.

Bees were mostly habitat specialists of calcareous grasslands and mainly driven by local habitat loss, whereas wasps as habitat generalists were mostly affected by landscape diversity.

Our study highlights the need to consider the different spatial scales contingent on trophic level and specialization of target species groups, maintaining or restoring both local habitat and landscape diversity, as this is needed for their successful conservation.
Transparent silicone‐free shampoo containing proteins with strong hair conditioning properties
Authors: Li Ping , Zhang Tongtong , Zhao Shizhi
Published: September 2023

Objective

With the constant upgrading of healthcare concepts, silicone‐free hair products have attracted more attention among consumers. In the present study, transparent silicone‐free shampoo containing proteins was successfully fabricated by mixing mild non‐sulphate surfactants, compound cationic conditioners, natural silicone oil substitutes, protein conditioners, thickeners, and other auxiliary ingredients. The effects of the type of surfactants, hair conditioners and thickeners, the type and content of proteins, and the mass ratio of compound proteins on the hair foaming performance, hair grooming performance, and penetration performance were investigated.

Methods

The basic formulation framework for transparent silicone‐free shampoo was established at first. Then, various hydrolyzed proteins were further added to the basic formulation in the form of single use or compound use to prepare transparent silicone‐free shampoo containing different proteins. The morphology of hair samples and penetration of protein in hair were evaluated with a scanning electron microscope and laser confocal fluorescence microscopy, respectively. And the hair grooming performance was also determined by a dynamic combing tester.

Results

The compound proteins of Croquat WKP PE‐LQ‐WD and Gluadin® Kera‐PLM with mass ratios of 1:9 and 1:1 at 2 wt% total protein content added to the silicone‐free shampoo brought a higher contact angle and a lower frictional coefficient than commercial silicone‐free shampoo without proteins. In addition, the compound proteins also have the dual effect of adsorbing the hair surface and penetrating deep into the interior of the hair.

Conclusion

The combination of cationic modified hydrolyzed protein (e.g., Croquat WKP PE‐LQ‐WD) and hydrolyzed protein with low molecular weight (e.g., Gluadin® Kera‐P LM) at an appropriate mass ratio exhibited a strong synergistic effect on hair conditioning properties. It could provide a significant reference for developing silicone‐free hair products with more benefits.
Correlation analysis of IL‐37 gene polymorphisms and susceptibility to chronic HBV infection among Han people in Central China
Authors: Cheng Hai , Sun Fenglan , Ouyang Yaoling , Li Chengbin
Published: September 2023

Hepatitis B virus (HBV) is responsible for various liver diseases, such as chronic hepatitis B (CHB), liver fibrosis, liver cirrhosis (LC) and hepatocellular carcinoma (HCC), which pose a significant threat to human health. An ineffective immune response to HBV can result in viral chronicity. Interleukin‐37 (IL‐37), an immunomodulator, is capable of inhibiting both innate and adaptive immune responses. It is believed that single nucleotide polymorphisms (SNPs) within the IL‐37 gene could contribute to the regulation of HBV clearance. Our aim to conduct this study was to investigate whether SNPs in the IL‐37 gene were associated with the risk of chronic HBV infection in adults. A total of 342 participants, consisting of 171 cases and 171 controls, were recruited for this study. Sanger sequencing was employed for genotyping six SNPs (rs3811042 G/A, rs3811043 G/C, rs2466449 A/G, rs3811045 C/T, rs3811046 T/G and rs3811047G/A). There was no significant difference in allele and genotype distribution between the two groups, and the constructed haplotypes were not found to be associated with the risk of chronic HBV infection. Our results revealed that there was no relationship between these six SNPs (rs3811042G/A, rs3811043G/C, rs2466449A/G, rs3811045C/T, rs3811046T/G and rs3811047G/A) in the IL‐37 gene and susceptibility to chronic HBV infection among Han people in Central China.
Boardroom backscratching and stock price crash risk
Authors: Hanlon Dean , Khedmati Mehdi , Lim Edwin KiaYang , Truong Cameron
Published: September 2023

We empirically capture boardroom backscratching, or cronyism, as when a firm's Chief Executive Officer (CEO) and directors concurrently receive excessive remuneration. We argue that boardroom backscratching can inhibit a board's constructive criticism and monitoring, resulting in a greater likelihood of bad news hoarding. Using 14,104 US firm‐year observations spanning 1999–2020, we document a significant positive relationship between boardroom backscratching and stock price crash risk. In additional analyses, we show that boardroom backscratching firms produce less readable annual reports and engage in greater upward real earnings management as channels for concealing bad news. We also find that external monitoring mechanisms weaken the positive association between boardroom backscratching and stock price crash risk. Our main findings withstand several endogeneity tests including propensity score matching, entropy balancing, difference‐in‐differences analysis using firms’ commencement of boardroom backscratching and CEO turnover event analysis. Our study offers insights to securities regulators and policymakers to revisit the notion of board independence, develop relevant market oversight and revise director and executive remuneration disclosure requirements so as to mitigate adverse stock market performance associated with boardroom backscratching.
Current and novel percutaneous epicardial access techniques for electrophysiological interventions: A comparison of procedural success and safety
Authors: Tonko Johanna B. , Lambiase Pier D.
Published: September 2023

Accessing the pericardial space safely and efficiently is an important skill for interventional cardiac electrophysiologist. With the increased recognition of the complexity of the 3‐dimensional arrhythmogenic substrate due to advances in imaging and mapping technologies there has been an expansion of epicardial procedures in recent years. Equally, minimally invasive implantation of epicardial pacing, cardiac resynchronization, or defibrillation leads is expanding in specific patients where transvenous systems are contraindicated or their long term sequelae should be ideally avoided. Selective delivery of intrapericardial pharmacological antiarrhythmic therapy is yet another potential indication, albeit still investigational. The expanding indications for percutaneous epicardial procedures is contrasted by the still substantial risk and challenges associated with accessing the pericardial space. Myocardial perforation, coronary artery laceration, and damage to the surrounding organs are all recognized and feared complications. A number of innovative epicardial access techniques have been proposed to overcome the difficulties and risks of traditional dry subxiphoid punctures and may allow for more widespread use of epicardial access in the future. We review 10 different established and novel subxiphoidal epicardial access techniques describing procedural success rates, safety profile and overall experience. The technical aspects as well as access times and costs for extra equipment will be reviewed. Finally, an outlook of reported preclinical techniques awaiting in‐human feasibility studies is provided.
Effects of the Informed Health Choices secondary school intervention on the ability of students in Rwanda to think critically about health choices: A cluster‐randomized trial
Authors: Mugisha Michael , Nyirazinyoye Laetitia , Simbi Clarisse Marie Claudine , Chesire Faith , Senyonga Ronald , Oxman Matt , Nsangi Allen , Semakula Daniel , Rose Christopher James , Moberg Jenny , Dahlgren Astrid , Kaseje Margaret , Lewin Simon , Sewankambo Nelson K. , Rosenbaum Sarah , Oxman Andrew D
Published: September 2023

Aim

The aim of this trial was to evaluate the effects of the Informed Health Choices intervention on the ability of students in Rwandan to think critically and make Informed Health Choices.

Methods

We conducted a two‐arm cluster‐randomized trial in 84 lower secondary schools from 10 districts representing five provinces of Rwanda. We used stratified randomization to allocate schools to the intervention or control. One class in each intervention school had ten 40‐min lessons taught by a trained teacher in addition to the usual curriculum. Control schools followed the usual curriculum. The primary outcome was a passing score (≥ 9 out of 18 questions answered correctly) for students on the Critical Thinking about Health Test completed within 2 weeks after the intervention. We conducted an intention‐to‐treat analysis using generalized linear mixed models, accounting for the cluster design using random intercepts.

Results

Between February 25 and March 29, 2022, we recruited 3,212 participants. We assigned 1,572 students and 42 teachers to the intervention arm and 1,556 students and 42 teachers to the control arm. The proportion of students who passed the test in the intervention arm was 915/1,572 (58.2%) compared to 302/1,556 (19.4%) in the control arm, adjusted odds ratio 10.6 (95% CI: 6.3–17.8),p < 0.0001, adjusted difference 37.2% (95% CI: 29.5%–45.0%).

Conclusions

The intervention is effective in helping students think critically about health choices. It was possible to improve students’ ability to think critically about health in the context of a competence‐based curriculum in Rwanda, despite challenging postpandemic conditions.