bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychotropic medication deprescribing in residential aged care facilities: An exploratory study of the knowledge and attitudes of family members of residents with dementia
Authors: Lai Rhoda , Withiel Toni Dianne , Angelone Melissa , Redpath Cameron , O’Connor Daniel W. , Plakiotis Christos
Published: February 2022

Objectives

General practitioners face many barriers to deprescribing psychotropic medications in people with dementia in nursing homes, including a lack of knowledge about their medication histories. This study explored the knowledge of family members about residents’ medications and their willingness to support deprescribing.

Methods

Sixty‐six family members of residents from seven residential aged care facilities participated in this cross‐sectional study. Participation involved nomination of recognised medications, rating their effectiveness and rating level of support for deprescribing.

Results

Fifty‐five per cent of medications were recognised by family members; significantly fewer psychotropics were recognised than non‐psychotropic medications. Though rated as just as effective, support for deprescribing psychotropics was significantly higher. Most family members were agreeable to deprescribing with general practitioner support.

Conclusions

Although there is a gap in family members’ knowledge about psychotropic medications, overall they are supportive of deprescribing. Findings emphasise the need for psychoeducation among family members. Providing family members with a list of prescribed medications, specifying the type of and reason for prescription and side effects of each, is recommended to facilitate their advocacy for deprescribing on behalf of nursing home residents.
What influences student situational engagement in smart classrooms: Perception of the learning environment and students' motivation
Authors: Lu Guoqing , Xie Kui , Liu Qingtang
Published: February 2022

Situational engagement plays a critical role in promoting students' academic performance. In a smart classroom environment, this study collected longitudinal real‐time data for 105 college students at a university in central China to investigate the relationship among situational engagement, personal characteristics and learning environment perceptions. Hierarchical linear modelling showed that environmental perception and students' personal factors have different effects on situational engagement. Specifically, (1) social support perceptions, autonomous motivation and controlled motivation have a significant impact on behavioural engagement; (2) perceptions of social and media support, autonomous motivation and controlled motivation have a significant impact on shallow cognitive engagement; and (3) perceptions of teacher and social support, self‐efficacy and autonomous motivation significantly predict deep cognitive and emotional engagement. This study suggests that the effect of the perception regarding advanced technology‐supported learning environments on students' situational engagement is limited, and instructors should pay more attention to improving students' perceptions of teacher and social support, self‐efficacy and autonomous motivation to promote students' situational deep cognitive engagement in smart classrooms.

Practitioner notes

What is already known about this topic

Compared with overall engagement, situational engagement fluctuates and changes with time and context.

Situational engagement is a product of environmental and personal factors.

Few studies have focused on the nature of situational engagement and how environmental and personal factors influence situational engagement in smart classrooms.

What the paper adds

This study contributes to the existing literature by investigating the critical factors that predict situational engagement, using the experience sampling method in a smart classroom at a Chinese university.

Environmental perception, self‐efficacy and students' motivation factors have different effects on situational engagement in a smart classroom.

Perceptions of teacher and social support, self‐efficacy and autonomous motivation significantly predict deep cognitive and emotional engagement, while perceptions of media support only have a significant impact on shallow cognitive engagement.

Personal factors (controlled and autonomous motivation) moderate the relationship between environmental perception factors and situational engagement.

Implications for practice and/or policy

Rather than only providing external technology‐rich conditions, instructors should focus more on improving students' perceptions of teacher and social support, self‐efficacy and autonomous motivation in the smart classroom environment.

Instructors should promote students' perception of teacher support and their autonomous motivation to enhance their deep cognitive engagement.
Trends in autologous stem cell transplantation for newly diagnosed multiple myeloma: Changing demographics and outcomes in European Society for Blood and Marrow Transplantation centres from 1995 to 2019
Authors: Swan Dawn , Hayden Patrick J. , Eikema Dirk‐Jan , Koster Linda , Sauer Sandra , Blaise Didier , Nicholson Emma , Rabin Neil , Touzeau Cyrille , Byrne Jennifer , Huynh Anne , Cornelissen Jan J. , Potter Victoria , Forcade Edouard , Parrish Christopher , Gribben John , Chretien Marie‐Lorraine , Mielke Stephan , Gedde‐Dahl Tobias , Reményi Péter , Tsirigotis Panagiotis , Garcia Guiñón Antoni , Beksac Meral , Schönland Stefan , Yakoub‐Agha Ibrahim
Published: February 2022

Multiple myeloma (MM) accounts for 10% of haematological malignancies. Overall survival (OS) has improved in recent years due to increased use of autologous stem cell transplantation (ASCT) in the treatment of newly diagnosed MM and the advent of novel agents, including proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies. To assess trends in ASCT including patient selection, choice of induction regimen, depth of response and survival, we performed a retrospective analysis of all patients undergoing first ASCT for MM in European Society for Blood and Marrow Transplantation centres between 1995 and 2019. A total of 117 711 patients across 575 centres were included. The number of transplants performed increased sevenfold across the study period. The median age increased from 55 to 61 years, and the percentage of patients aged >65 years rose from 7% to 30%. Use of chemotherapy‐based induction fell significantly, being largely replaced by bortezomib‐based regimens. The two‐year complete response rate increased from 22% to 42%. The five‐year progression‐free survival and OS rates increased from 28% to 31% and from 52% to 69%, respectively. Transplant mortality fell from 5.9% to 1.5%. Ongoing advances in MM treatment may challenge the future role of ASCT. However, at the current time, ASCT remains central to the MM treatment paradigm.
Astrocytes expressing Vitamin D‐activating enzyme identify Parkinson’s disease
Authors: Mazzetti Samanta , Barichella Michela , Giampietro Federica , Giana Angelica , Calogero Alessandra M , Amadeo Alida , Palazzi Nicola , Comincini Alessandro , Giaccone Giorgio , Bramerio Manuela , Caronni Serena , Cereda Viviana , Cereda Emanuele , Cappelletti Graziella , Rolando Chiara , Pezzoli Gianni
Published: February 2022

Introduction

Astrocytes are involved in Parkinson's disease (PD) where they could contribute to α‐Synuclein pathology but also to neuroprotection via α‐Synuclein clearance. The molecular signature underlying their dual role is still elusive. Given that vitamin D has been recently suggested to be protective in neurodegeneration, the aim of our study was to investigate astrocyte and neuron vitamin D pathway alterations and their correlation with α‐Synuclein aggregates (ie, oligomers and fibrils) in human brain obtained from PD patients.

Methods

The expression of vitamin D pathway components CYP27B1, CYP24A1, and VDR was examined in brains obtained from PD patients (Braak stage 6; n = 9) and control subjects (n = 4). We also exploited proximity ligation assay to identified toxic α‐Synuclein oligomers in human astrocytes.

Results

We found that vitamin D‐activating enzyme CYP27B1 identified a subpopulation of astrocytes exclusively in PD patients. CYP27B1 positive astrocytes could display neuroprotective features as they sequester α‐Synuclein oligomers and are associated with Lewy body negative neurons.

Conclusion

The presence of CYP27B1 astrocytes distinguishes PD patients and suggests their contribution to protect neurons and to ameliorate neuropathological traits.
Translating stem cell research into development of cellular drugs—a perspective from manufacture of stem cell products and CMC considerations
Authors: Zhang Yu Alex , Stacey Glyn N.
Published: February 2022

The development of human pluripotent stem cell (PSC)‐derived medicinal products has been gathering steam in recent years, but the translation of research protocols into GMP production remains a daunting task. The challenges not only reside with the nature of cellular therapeutics but are also rooted in the general inexperience in industry‐scale production of stem cell products. Manufacturers of PSC‐derived products should be aware of the technical nuances and take a holistic approach toward early planning and engagement with their academic partners. While not all issues will be readily resolved soon, the collective knowledge and consensus by the manufacturers and key stakeholders will help to guide rapid progression of the field.
Simultaneous effect of habitat remnancy, exotic species, and anthropogenic disturbance on orchid diversity in South Australia
Authors: Martín‐Forés Irene , Bywaters Samantha L. , Sparrow Ben , Guerin Greg R.
Published: February 2022

Orchids are potentially useful as ecological indicators because of their sensitivity to habitat fragmentation and anthropogenic disturbance. While many studies explore the effect of single factors on orchid diversity, few investigate how the extent, configuration, and condition of surrounding habitat affect whole orchid communities. Here, we unravel the effect of biological invasions, anthropogenic disturbance (i.e., grazing pressure, ecological condition), and habitat fragmentation on an Australian orchid community. We sampled 39 plots across nine sites in the Mount Lofty Ranges, Australia. We recorded the number of orchid species and number of individuals per species in mid‐winter, early‐spring, and late‐spring to account for the effect of season on species visibility, with 115 surveys in total. We ranked grazing intensity and ecological condition, and estimated cover of exotic species. We analyzed the response of richness and diversity through generalized linear mixed models, and differences in species composition through non‐metric multidimensional scaling. Habitat configuration in the surrounding landscape had different effects at increasing radii, explaining 29%–87% of variance. Patch‐level orchid diversity was positively correlated with habitat edges in the immediate area, and with habitat cohesion at medium scales, whereas diversity was negatively correlated with increasing mean patch habitat area across larger surrounding areas. Orchids co‐existed with exotic species but were negatively affected once exotic cover exceeded 20%. Species composition was correlated with exotic cover. Our findings reveal a complex relationship between orchid communities and their surrounding environments suggesting orchids benefit from a somewhat disturbed environment at patch and landscape scales. These idiosyncratic responses suggest orchid diversity may be unreliable as early‐warning indicators of habitat disturbance.
Effects of empagliflozin on markers of liver steatosis and fibrosis and their relationship to cardiorenal outcomes
Authors: Kahl Sabine , Ofstad Anne Pernille , Zinman Bernard , Wanner Christoph , Schüler Elke , Sattar Naveed , Inzucchi Silvio E. , Roden Michael
Published: February 2022

Aims

Empagliflozin treatment reduced liver fat in small type 2 diabetes cohorts. This post‐hoc study evaluated effects of empagliflozin on risk for non‐alcoholic fatty liver disease‐related steatosis and fibrosis, as well as the relationship between risk categories and cardiorenal outcomes in the randomized, placebo‐controlled EMPA‐REG OUTCOME trial.

Materials and methods

EMPA‐REG OUTCOME treated 7020 people with type 2 diabetes and cardiovascular disease with 10/25 mg/day empagliflozin or placebo. For this analysis, the Dallas steatosis index, hepatic steatosis index, non‐alcoholic fatty liver disease fibrosis score and Fibrosis‐4 score were calculated to assess steatosis and fibrosis risk. Changes from baseline in scores were examined by mixed model repeated measures and their associations with cardiorenal outcomes and mortality by Cox regression.

Results

At baseline, 73% and 84% of participants had high steatosis risk by Dallas steatosis index and hepatic steatosis index, whereas 23% and 4% had a high risk of advanced fibrosis by non‐alcoholic fatty liver disease fibrosis score and Fibrosis‐4 score. Percentages of people at high steatosis risk slightly decreased with empagliflozin only, whereas empagliflozin did not improve percentages of individuals at high fibrosis risk over time compared with placebo. The high risk of advanced fibrosis at baseline related to higher risk for cardiovascular events. Effects of empagliflozin on cardiorenal and all‐cause mortality outcomes were consistent across all risk groups.

Conclusions

Empagliflozin may reduce steatosis but not fibrosis risk in individuals with type 2 diabetes and cardiovascular disease. The improvements in cardiorenal outcomes and mortality associated with empagliflozin therapy appear to be independent of steatosis and fibrosis risk.
Neurodevelopmental trajectories in children with cleft lip and palate: A longitudinal study based on the Japan Environment and Children's Study
Authors: Tsuchiya Shinobu , Tsuchiya Masahiro , Momma Haruki , Aida Jun , Nagatomi Ryoichi , Yaegashi Nobuo , Arima Takahiro , Igarashi Kaoru ,   the Japan Environment and Children's Study Group
Published: February 2022

Cleft lip and/or palate (CL/P), the most prevalent congenital anomaly, is understood to negatively affect a wide range of child development. Since the concept remains controversial, because most published work is from cross‐sectional studies, we examined the neurodevelopmental trajectories in participants with CL/P through a longitudinal comparison with the general population during early childhood using data from a nationwide birth cohort study in Japan. The linear mixed models for each domain of the Ages and Stages Questionnaire, third edition (ASQ‐3), were used to detect differences in standardised mean scores between groups. The ASQ‐3 is a general neurodevelopmental screening tool comprising communication, gross motor, fine motor, problem‐solving, and personal‐social domains. Participants’ neurodevelopment was determined semi‐annually from 6 to 36 months of age. The trajectories of standardised mean scores in each domain showed several significant differences between the control and CL/P groups, with the maximum difference at 24 months of age in the communication domain. Indeed, CL/P was associated with significantly lower scores in the communication (coefficient: –3.31, 95% CI: –5.09 to –1.14), problem‐solving (coefficient: –3.13, 95% CI: –5.07 to –1.18), and personal‐social domains (coefficient: –1.99, 95% CI: –3.87 to –0.11). Trajectories of ASQ‐3 scores suggest neurodevelopmental delays in children with CL/P.
Epidemiology of exertional heat illness in Thoroughbred racehorses in temperate eastern Australia: The role of extrinsic (environmental) factors in disease causation
Authors: Brownlow M. , Mizzi J. X.
Published: February 2022

A simple epidemiological model of disease causation is proposed for exertional heat illness (EHI) in Thoroughbred racehorses. The agent of disease causation that must be present for the condition to occur is strenuous exercise, producing substantial quantities of metabolic heat. This is stored during racing but must be dissipated rapidly in the post‐race period to prevent core body temperature rising to a critical level and causing the clinical manifestations of EHI. Environmental factors are next in the epidemiological triad, and it is a common misconception that these are the direct cause of EHI. In fact, environmental conditions enable EHI by either diminishing the evaporative capacity of the environment or promoting internal heat gain. This article deals with the specific effects of the four thermal elements, separately and in combination, on individual thermo‐effector mechanisms. The final component in the epidemiological triad is individual host factors. A critical premise of epidemiology is that conditions such as EHI may not occur randomly in a population but may be more likely to occur in some individuals due to the presence of certain factors that predispose them to the condition. For the purpose of assessing risk, it is not feasible to examine the balance between metabolic heat production and the intrinsic and extrinsic factors, which collectively determine each individual's heat stress response. Therefore, the measurement of environmental factors remains the only practical way of obtaining a credible risk assessment for EHI, so that effective countermeasures can be instigated and the welfare of our racehorses ensured.
Using the “MyPlate Musical” to Increase Nutrition and Exercise Knowledge in Children
Authors: Besnilian Annette , Plunkett Scott W. , Butleroff‐Leahy Helen
Published: February 2022

We evaluated the effectiveness of a school‐based, educational theater program (i.e., MyPlate Musical) on nutrition/exercise knowledge of elementary student performers and viewers. Data were collected in four elementary schools with high percentages of Latinos and students eligible for free/reduced price meals. In Schools 1–3, pretest and posttest data were used from a total of 425 viewers and 220 performers. At School 4, 267 viewers and 75 performers served as their own control. Results indicated that student performers and student viewers of the theatrical performances had increased general nutrition/exercise knowledge and MyPlate knowledge from pretest to posttest and the effects were stronger in the treatment group than the control group. Educational theater appears to be a viable method to increase nutrition/exercise knowledge.
A critical analysis of research methods and experimental models to study tooth discolouration from endodontic materials
Authors: Athanassiadis Basil , Abbott Paul V. , Walsh Laurence J.
Published: February 2022

As a range of materials used in endodontics may cause tooth discolouration, exploration of factors responsible for the darkening of the tooth crown or root is warranted. This narrative review paper discusses the range of technical factors that apply in laboratory studies that assess endodontic discolouration. As an example of how these factors operate, particular examples relating to discolouration caused by endodontic medicaments containing tetracycline antibiotics are used. Following the PRILE 2021 guideline approach, a summary of key variables to be addressed in the methodology for laboratory studies is presented, to inform future work.
The effect of sodium polymethacrylate on the rheology of the positive paste and performance of the lead‐acid battery
Authors: Kosacki Julian , Feys Dimitri , Dogan Fatih
Published: February 2022

Due to its rheological properties, positive lead‐acid battery paste can be difficult to spread on lead current collectors accurately and efficiently under industry machinery and setting. Sodium polymethacrylate dispersant was studied as an effective positive paste additive that could lower the yield stress of the paste without affecting paste density and battery performance. Under a four‐blade vane rheometer setup, stress growth and oscillatory amplitude strain sweep experiments evaluated the rheological properties of positive paste with the addition of varying amounts of sodium polymethacrylate. Further, the electrochemical effects of sodium polymethacrylate were also evaluated in 2V batteries by testing positive active material utilization and cycle life.
Fresh beef tumbling at different post‐mortem times to improve tenderness and proteolytic features of M. longissimus lumborum
Authors: Nondorf Mariah J. , Kim Yuan H. Brad
Published: February 2022

The aim of this study was to determine the effects of tumbling at different post‐mortem times on the proteolytic features and quality attributes of beef loins (M. longissimus lumborum). Loins (n = 12) were cut into 4 sections and assigned to tumbling at 1, 6 or 11 days post‐mortem or non‐tumbled control. Upon tumbling, additional ageing was applied to a common post‐mortem time of 16 days. In general, tumbling had no considerable impacts on water‐holding ability of samples. Tumbling resulted in an immediate decrease in shear force values (WBSF) of beef samples. Tumbling at 1 day post‐mortem with no ageing had similar WBSF compared to the non‐tumbled controls at 16 days (P > 0.05). With ageing, tumbling increased amounts of protein degradation, myofibrillar fragmentation and calpain‐1 autolysis of samples. These results suggest that early post‐mortem tumbling coupled with ageing can synergistically impact the tenderness development of beef loins and shorten the necessary ageing period.
High and temperature‐stable dielectric constants in PNb9O25 ceramic
Authors: Fu Jie
Published: February 2022

PNb9O25 ceramic was prepared using a sparking plasma sintering (SPS) method. Microstructure, dielectric and electrical properties of the ceramic were investigated. Dense ceramic was obtained, and the ceramic exhibited a high dielectric constant (>1000) and a low dielectric loss (∼2%) in the investigated frequency range of 100 Hz‐100 kHz at room temperature. Dielectric relaxations with strong frequency dispersion occurred at temperatures higher than 250°C, which were due to oxygen vacancies. A highly stable capacitance (< 10% deviation) over a wide temperature range of –30°C to –200°C was obtained. The ceramic also showed a relatively high electrical conductivity (>4 × 10−8 S/cm) with an activation energy of approximately 0.9 eV in the temperature range of >200°C.
Can the Caribbean localize its food system?: Evidence from biomass flow accounting
Authors: Rahman Shupa , Singh Simron , McCordic Cameron
Published: February 2022

Small island economies are highly dependent on food imports. Self‐sufficiency through food localization is therefore often advocated. Can a small Caribbean island nation localize its food system? To answer this question, we conducted socio‐metabolic research on four Caribbean nations: Barbados, Dominica, Grenada, and Jamaica. Derived indicators from a diachronic biomass flow accounting from 1961 to 2019 suggest a declining trend in local food production for all cases. While in Barbados and Jamaica this decline already began in the 1960s, for Dominica and Grenada, this did not start until the late 1970s–1980s. The physical trade balance of biomass is similar across all cases: from net exporters at the start of the study period to net importers as countries developed, albeit at different time periods. By disaggregating biomass flow data to crop level, Barbados and Jamaica indicate a trend that is moving away from food localization, while Dominica and Grenada appear to be modestly moving toward localization in recent years. Given the many resource security challenges small island economies face, this study provides a biophysical perspective to the Caribbean's food security debate and questions the extent to which food localization is possible in a small island context, and whether other strategies are urgently needed.
The MIEL1‐ABI5/MYB30 regulatory module fine tunes abscisic acid signaling during seed germination
Authors: Nie Kaili , Zhao Hongyun , Wang Xiaopei , Niu Yanli , Zhou Huapeng , Zheng Yuan
Published: February 2022

The transcription factor ABSCISIC ACID INSENSITIVE5 (ABI5) plays a crucial role in abscisic acid (ABA) signaling during seed germination. However, how ABI5 is regulated during this process is poorly understood. Here, we report that the ubiquitin E3 ligase MIEL1 and its target transcription factor MYB30 modulate ABA responses in Arabidopsis thaliana during seed germination and seedling establishment via the precise regulation of ABI5. MIEL1 interacts with and ubiquitinates ABI5 to facilitate its degradation during germination. The transcription factor MYB30, whose turnover is mediated by MIEL1 during seed germination, also interacts with ABI5 to interfere with its transcriptional activity. MYB30 functions downstream of MIEL1 in the ABA response, and both are epistatic to ABI5 in ABA‐mediated inhibition of seed germination and postgerminative growth. ABA treatment induces the degradation of MIEL1 and represses the interaction between MIEL1 and ABI5/MYB30, thus releasing both ABI5 and MYB30. Our results demonstrate that MIEL1 directly mediates the proteasomal degradation of ABI5 and inhibits its activity via the release of its target protein MYB30, thus ensuring precise ABA signaling during seed germination and seedling establishment.
No effect of thyroid hormones on 5‐year mortality in patients with subjective cognitive decline, mild cognitive disorder, and Alzheimer’s disease
Authors: Đapić Blaž , Schernhammer Eva , Haslacher Helmuth , Stögmann Elisabeth , Lehrner Johann
Published: February 2022

The present study aimed to investigate differences in circulating thyroid hormone levels, gender, education, depressive symptoms, and cognitive performance among patients with cognitive impairment, and also to examine their associations, as well as that of cognitive decline, with 5‐year mortality. Between 1998 and 2017, a hospital‐based, single‐centre (Neurology Department of the General Hospital in Vienna, Austria), retrospective follow‐up study enrolled 2102 patients with mild to severe cognitive impairment (grouped into subjective cognitive decline, mild cognitive impairment, and Alzheimer's disease). Cox proportional hazards models were used to calculate hazard ratios (HRs), with 95% confidence intervals (CIs), as well as to calculate stepwise adjustments for demographic variables (age, gender, and education), depressive symptoms (Geriatric Depression Scale, GDS‐15), and neuropsychological abilities (four domains of a neuropsychological test battery of Vienna, NTVB). In univariate analyses, total triiodothyronine (TT3) levels differed significantly between Alzheimer's disease and mild cognitive impairment patients (pdiff = .001). No other differences in cognitive impairment subgroups with any of the measured thyroid hormones were observed. Furthermore, in multivariate models, circulating TT3 was not associated with mortality (multivariable‐adjusted HR per unit increase in TT3 = 0.56; 95% CI = 0.29–1.07). In multivariate models, we observed significantly lower 5‐year mortality among women (HR = 0.56; 95% CI = 0.43–0.73) and those who scored higher on any of the four domains of the NBTV (e.g., attention and perceptual speed, HR = 0.63; 95% CI = 0.54–0.72); we also observed significantly higher 5‐year mortality among patients with depressive symptoms (HR per one point score increase in GDS‐15 = 1.06; 95% CI = 1.02–1.10), regardless of cognitive impairment subgroup. Among patients with various degrees of cognitive impairment, we found no associations of thyroid hormone levels with 5‐year mortality. Gender, neuropsychological abilities, and depressive symptoms were each significant predictors of 5‐year mortality. These results suggest that a neurocognitive test performance could serve as an important predictor of 5‐year mortality among patients with cognitive impairment, although further studies with a more complete adjustment for comorbidities are needed to confirm these findings.
Common myths of terrorism
Authors: Gaibulloev Khusrav , Sandler Todd
Published: February 2022

Drawing from statements by politicians, the media, policy analysts, and researchers, the current study identifies nine myths associated with terrorism and the practice of counterterrorism. We focus on those myths that have special policy relevance since the four al‐Qaida hijackings on September 11, 2001, and the ensuing heightened security concern. Many of those myths generated research articles that, at times, come to contradictory conclusions. Our goal is to provide recent statistics and a literature evaluation to sort out such contradictory results. In the case of the alleged macroeconomic consequences of terrorism to a typical country, we supply updated estimations. Throughout our presentation, we draw from the post‐2001 literature or statistical evidence. Often, empirical methods and procedures have evolved to a point where more clear‐cut and robust findings are now available through better identification and advanced estimation procedures.
No difference between slow oscillation up‐ and down‐state cueing for memory consolidation during sleep
Authors: Wang Jing‐Yi , Heck Katharina L. , Born Jan , Ngo Hong‐Viet V. , Diekelmann Susanne
Published: February 2022

The beneficial effects of sleep for memory consolidation are assumed to rely on the reactivation of memories in conjunction with the coordinated interplay of sleep rhythms like slow oscillations and spindles. Specifically, slow oscillations are assumed to provide the temporal frame for spindles to occur in the slow oscillations up‐states, enabling a redistribution of reactivated information within hippocampal–neocortical networks for long‐term storage. Memory reactivation can also be triggered externally by presenting learning‐associated cues (like odours or sounds) during sleep, but it is presently unclear whether there is an optimal time‐window for the presentation of such cues in relation to the phase of the slow oscillations. In the present within‐subject comparison, participants (n = 16) learnt word‐pairs visually presented with auditory cues of the first syllable. These syllables were subsequently used for real‐time cueing either in the up‐ or down‐state of endogenous slow oscillations. Contrary to our hypothesis, we found differences in memory performance neither between up‐ and down‐state cueing, nor between word‐pairs that were cued versus uncued. In the up‐state cueing condition, higher amounts of rapid eye movement sleep were associated with better memory for cued contents, whereas higher amounts of slow‐wave sleep were associated with better memory for uncued contents. Evoked response analyses revealed signs of cue processing in both conditions. Interestingly, both up‐ and down‐state cueing evoked a similar spindle response with the induced slow oscillations up‐state at ~1000 ms post‐cue. We speculate that our cueing procedure triggered generalised reactivation processes that facilitated the consolidation of both cued and uncued memories irrespective of the slow oscillation phase.
The association of co‐morbid insomnia and sleep apnea with prevalent cardiovascular disease and incident cardiovascular events
Authors: Lechat Bastien , Appleton Sarah , Melaku Yohannes Adama , Hansen Kristy , McEvoy R. Doug , Adams Robert , Catcheside Peter , Lack Leon , Eckert Danny J. , Sweetman Alexander
Published: February 2022

Insomnia and obstructive sleep apnea commonly co‐occur (co‐morbid insomnia and sleep apnea), and their co‐occurrence has been associated with worse cardiometabolic and mental health. However, it remains unknown if people with co‐morbid insomnia and sleep apnea are at a heightened risk of incident cardiovascular events. This study used longitudinal data from the Sleep Heart Health Study (N = 5803) to investigate potential associations between co‐morbid insomnia and sleep apnea and cardiovascular disease prevalence at baseline and cardiovascular event incidence over ~11 years follow‐up. Insomnia was defined as self‐reported difficulties initiating and/or maintaining sleep AND daytime impairment. Obstructive sleep apnea was defined as an apnea–hypopnea index ≥ 15 events per hr sleep. Co‐morbid insomnia and sleep apnea was defined if both conditions were present. Data from 4160 participants were used for this analysis. The prevalence of no insomnia/obstructive sleep apnea, insomnia only, obstructive sleep apnea only and co‐morbid insomnia and sleep apnea was 53.2%, 3.1%, 39.9% and 1.9%, respectively. Co‐morbid insomnia and sleep apnea was associated with a 75% (odd ratios [95% confidence interval]; 1.75 [1.14, 2.67]) increase in likelihood of having cardiovascular disease at baseline after adjusting for pre‐specified confounders. In the unadjusted model, co‐morbid insomnia and sleep apnea was associated with a twofold increase (hazard ratio, 95% confidence interval: 2.00 [1.33, 2.99]) in risk of cardiovascular event incidence. However, after adjusting for pre‐specified covariates, co‐morbid insomnia and sleep apnea was not significantly associated with incident cardiovascular events (hazard ratio 1.38 [0.92, 2.07]). Comparable findings were obtained when an alternative definition of insomnia (difficulties initiating and/or maintaining sleep without daytime impairment) was used.
Local adaptation and spatiotemporal patterns of genetic diversity revealed by repeated sampling of Caenorhabditis elegans across the Hawaiian Islands
Authors: Crombie Timothy A. , Battlay Paul , Tanny Robyn E. , Evans Kathryn S. , Buchanan Claire M. , Cook Daniel E. , Dilks Clayton M. , Stinson Loraina A. , Zdraljevic Stefan , Zhang Gaotian , Roberto Nicole M. , Lee Daehan , Ailion Michael , Hodgins Kathryn A. , Andersen Erik C.
Published: February 2022

The nematode Caenorhabditis elegans is among the most widely studied organisms, but relatively little is known about its natural ecology. Genetic diversity is low across much of the globe but high in the Hawaiian Islands and across the Pacific Rim. To characterize the niche and genetic diversity of C. elegans on the Hawaiian Islands and to explore how genetic diversity might be influenced by local adaptation, we repeatedly sampled nematodes over a three‐year period, measured various environmental parameters at each sampling site, and whole‐genome sequenced the C. elegans isolates that we identified. We found that the typical Hawaiian C. elegans niche comprises moderately moist native forests at high elevations (500–1,500 m) where ambient air temperatures are cool (15–20°C). Compared to other Caenorhabditis species found on the Hawaiian Islands (e.g., Caenorhabditis briggsae and Caenorhabditis tropicalis), we found that C. elegans were enriched in native habitats. We measured levels of genetic diversity and differentiation among Hawaiian C. elegans and found evidence of seven genetically distinct groups distributed across the islands. Then, we scanned these genomes for signatures of local adaptation and identified 18 distinct regions that overlap with hyper‐divergent regions, which may be maintained by balancing selection and are enriched for genes related to environmental sensing, xenobiotic detoxification, and pathogen resistance. These results provide strong evidence of local adaptation among Hawaiian C. elegans and contribute to our understanding of the forces that shape genetic diversity on the most remote volcanic archipelago in the world.
Greener One‐step Synthesis of Novel In Situ Selenium‐doped Framework Photocatalyst by Melem and Perylene Dianhydride for Enhanced Solar Fuel Production from CO2
Authors: Singh Chandani , Yadav Rajesh K. , Kim Tae Wu , Baeg Jin‐Ook , Singh Atul P.
Published: February 2022

To minimize the ever‐increasing global warming and environmental problems, the conversion of atmospheric CO2 into value‐added solar chemicals/fuels is one of the most challenging tasks. As a means to accomplish this, herein we have synthesized first time novel in situ selenium‐doped polyimide frameworks (Se‐PIFs) photocatalyst via thermal co‐polymerization approach between melem (M) and perylene 3, 4, 9, 10‐tetracarboxylic dianhydride (PTDA) along with selenium (Se) as a dopant. The Se‐PIFs photocatalyst shows outstanding photocatalytic stability and activity for high solar fuel production (HCOOH ~ formic acid) from CO2. The solar light active Se‐PIFs photocatalyst was demonstrating the ~ 10‐fold higher photo‐conversion of CO2 to formic acid with yields of 250. 6 μmol. The current work is providing a facile and scalable avenue as well as sheds light on creating a new route for in situ judicious design highly efficient Se‐PIFs photocatalyst. The outcome is a benchmark instance for the use of selenium‐doped polyimide frameworks as a highly practical and efficient solar light active photocatalyst for carrying out the selective production of formic acid from environmental CO2.
Task choice shields against incidental affective influences on effort‐related cardiovascular response
Authors: Falk Johanna R. , Gollwitzer Peter M. , Oettingen Gabriele , Gendolla Guido H. E.
Published: February 2022

In an attempt to integrate theorizing on action shielding with affective influences on effort‐related cardiovascular response, an experiment with N = 115 university students (90% women) tested whether working on a task by personal choice versus external assignment moderates the effect of happy versus sad background music on effort‐related cardiovascular response during task performance. We predicted strong action shielding and low receptivity for incidental affective influences when participants could ostensibly choose the task to be performed. Given the difficult nature of the task, we thus expected strong effort‐related cardiovascular responses due to high commitment when the task was chosen. By contrast, for assigned‐task participants, we expected high receptivity for incidental affective influences and thus predicted strong cardiovascular reactivity when they were exposed to happy music but low responses due to disengagement when they were exposed to sad music. Effects on responses of cardiac pre‐ejection period, systolic blood pressure, and heart rate confirmed our effort‐related predictions. Apparently, personal choice of a task can immunize individuals against incidental affective influences on resource mobilization.
Retrospective evaluation of the use of quick Sepsis‐related Organ Failure Assessment (qSOFA) as predictor of mortality and length of hospitalization in dogs with pyometra (2013‐2019): 52 cases
Authors: Donati Pablo , Londoño Leonel A. , Tunes Marcela , Villalta Cesar , Guillemi Eliana C.
Published: February 2022

Objective

To evaluate the prognostic utility of quick Sepsis‐related Organ Failure Assessment (qSOFA) for prediction of in‐hospital mortality and length of hospitalization in dogs with pyometra.

Design

Retrospective cohort study from February 2013 to April 2019

Setting

Tertiary referral hospital

Animals

Fifty‐two dogs referred with confirmed diagnosis of pyometra

Interventions

None

Measurements and principal outcomes

Sixty‐five percent of dogs survived to discharge. A cut‐off score of ≥2 for qSOFA was associated with in‐hospital mortality (odds ratio 6.51 [95% CI: 1.35 ‐ 31.3]) P = 0.019. The area under the receiver operator characteristic curve for a qSOFA score ≥ 2 for mortality was 0.72 (95% CI: 0.59‐0.85), with a sensitivity of 77.8% and a specificity of 66.7%. The mean ± SD number of organs with dysfunction was significantly higher in dogs with a qSOFA score ≥2 1.76 ± 0.83 compared to dogs with a qSOFA score < 2 1.08 ± 1.09, P = 0.015. The presence of a qSOFA score ≥ 2 was associated with a longer time of hospitalization in survivors with a median (interquartile range) length of stay in qSOFA < 2 (48 [33]) hours versus qSOFA score ≥ 2 (78 [52]) hours, P = 0.027.

Conclusions

In dogs with pyometra, the qSOFA score was associated with mortality and length of hospitalization. This score might be useful to improve the risk stratification in dogs with pyometra. Further studies are necessary to evaluate the predictive capacity of qSOFA in other septic patient populations.
Generation and transplantation of hepatocytes‐like cells using human origin hepatogenic serum for acute liver injury treatment
Authors: Gupta Santosh , Sharma Akriti , Paneerselvan Sugan , Kandoi Sangeetha , Patra Bamadeb , Bishi Dillip Kumar , Verma Rama Shanker
Published: February 2022

Liver failure is a critical disease for which regenerative therapies are still being explored. The major limitation in the use of a clinical grade, viable cell‐based therapy approach is the scarce availability of sufficient number of in‐vitro differentiated hepatocyte‐like cells (HLC) that can induce regeneration and ameliorate liver injury. Here, we report for the first time an approach to engineer HLCs using sera of hyperbilirubin patients that act as a reservoir of differentiation factor. Utilizing our humanized approach, mesenchymal stem cells (hMSC) derived from umbilical cord tissue were transdifferentiated into HLC using patient‐derived serum along with dimethyl sulfoxide (DMSO). We studied the effects of serum on the proliferation, cell cycle analysis, and apoptosis of hMSC by various differentiation combinations. We optimized the hepatic transdifferentiation ability of hMSC with hyperbilirubin serum treatment for a period of 7 days. Assessment of HLC functionalities was shown by quantifying the HLC spent medium for albumin and urea secretions. Transplantation of HLC in an acute liver injury (ALI) rat model showed an effective improvement in the liver function and histological changes in the liver. The results of this study suggest that hMSC‐derived HLC using humanized hepatogenic serum holds a promising potential for cell transplantation, as an efficient therapy modality for liver failure in humans.
hEPCR.hTBM.hCD47.hHO‐1 with donor clodronate and DDAVP treatment improves perfusion and function of GalTKO.hCD46 porcine livers perfused with human blood
Authors: Cimeno Arielle , Kuravi Kasinath , Sorrells Lori , Dandro Amy , Sendil Selin , Burdorf Lars , Parsell Dawn M. , Eyestone Will , Phelps Carol , Ayares David , Azimzadeh Agnes M. , Pierson Richard N. , Barth Rolf N. , LaMattina John C.
Published: February 2022

Introduction

Platelet sequestration, inflammation, and inappropriate coagulation cascade activation are prominent in liver xenotransplant models and are associated with poor outcomes. Here, we evaluate a cassette of six additional genetic modifications to reduce anti‐pig antibody binding (α‐1,3‐galactosyl transferase knockout [GalTKO]) and target coagulation dysregulation (human endothelial protein C receptor [hEPRC] and thrombomodulin [hTBM]), complement pathway regulation (human membrane cofactor protein, hCD46), inflammation heme oxygenase 1 [hHO‐1]), and a self‐recognition receptor (integrin‐associated protein [hCD47]), as well as donor pharmacologic treatments designed to blunt these phenomena.

Methods

Livers from GaltKO.hCD46 pigs (“2‐gene,” n = 3) and GalTKO.hCD46 pigs also transgenic for hEPRC, hTBM, hCD47, and hHO‐1 (“6‐gene,” n = 4) were perfused ex vivo with whole human blood. Six‐gene pigs were additionally pretreated with desmopressin (DDAVP) and clodronate liposomes to deplete vWF and kupffer cells, respectively.

Results

The average perfusion times increased from 304 (±148) min in the 2‐gene group to 856 (±61) min in the 6‐gene group (p = .010). The average heparin administration was decreased from 8837 U/h in the 2‐gene to 1354 U/h in the 6‐gene group (p = .047). Platelet sequestration tended to be delayed in the 6‐gene group (p = .070), while thromboxane B2 (TXB2, a platelet activation marker) levels were lower over the first hour (p = .044) (401 ± 124 vs. 2048 ± 712 at 60 min). Thrombin production as measured by F1+2 levels tended to be lower in the 6‐gene group (p = .058).

Conclusions

The combination of the hEPCR.hTBM.hCD47.hHO‐1 cassette along with donor pig DDAVP and clodronate liposome pretreatment was associated with prolonged function of xenoperfused livers, reduced coagulation pathway perturbations, and decreased TXB2 elaboration, and reflects significant progress to modulate liver xenograft injury in a pig to human model.
Frequency‐dependent characteristics of nerve‐mediated ATP and acetylcholine release from detrusor smooth muscle
Authors: Chakrabarty Basu , Aitchison Katie , White Paul , McCarthy Carly J. , Kanai Anthony J. , Fry Christopher H.
Published: February 2022

New Findings

What is the central question of this study?

Is the frequency dependence of co‐transmitter release from postganglionic nerve fibres different for each transmitter?

What is the main finding and its importance?

Release of co‐transmitters from the parasympathetic supply to detrusor smooth muscle can be independently regulated. This offers a targeted drug model to reduce selectively the release of transmitter associated with human pathologies (ATP) and may also be applicable to other smooth muscle‐based disorders of visceral tissues.

Nerve‐mediated contractions of detrusor smooth muscle are mediated by acetylcholine (ACh) and ATP release in most animals. However, with the normal human bladder, only ACh is a functional transmitter, but in benign pathologies such as overactive bladder (OAB), ATP re‐emerges as a secondary transmitter. The selective regulation of ATP release offers a therapeutic approach to manage OAB, in contrast to current primary strategies that target ACh actions. However, the release characteristics of nerve‐mediated ACh and ATP are poorly defined and this study aimed to measure the frequency dependence of ACh and ATP release and determine if selective regulation of ATP or ACh was possible. Experiments were carried out in vitro with mouse detrusor with nerve‐mediated ATP and ACh release measured simultaneously with tension recording. ATP was released in two frequency‐dependent components, both at lower frequencies (mid‐range 0.4 and 5.5 Hz stimulation) compared to a single compartment release of ACh at 14 Hz. Intervention with the phosphodiesterase type‐5 inhibitor sildenafil attenuated ATP release, equally from both components, but had no effect on ACh release. These data demonstrate that nerve‐mediated ACh and ATP release characteristics are distinct and may be separately manipulated. This offers a potential targeted drug model to manage benign lower urinary tract conditions such as OAB.
Los diseños de índices de divulgación de información financiera en Internet. Una revisión sistemática de la literatura
Authors: Rincón Soto Carlos Augusto , Gómez Villegas Mauricio , Rivera Arrubla Yaismir Adriana
Published: February 2022

El propósito de este artículo es sintetizar y describir los diseños de los índices utilizados en la investigación sobre la divulgación de Información Financiera en Internet (IFI). Se hizo una revisión sistemática de la literatura y se analizaron 46 artículos de investigación con enfoque cuantitativo-explicativo, dedicados a estudiar la divulgación de IFI y que publican el diseño del índice usado. Los resultados permiten sistematizar los diseños más comunes en los índices, dimensiones, cantidad de ítems, así como las teorías, metodologías, variables determinantes y los hallazgos más significativos en la investigación académica. Se concluye que la heterogeneidad en la construcción y en las características de estos índices, es producto de la evolución en la que se encuentra dicho campo de investigación.