bluuebunny/crossref_metadata_2025 huggingface dataset:
Beef quality, biochemical attributes, and descriptive sensory scores of gluteus medius, biceps femoris, and tensor fasciae latae muscles subjected to combined tumbling and postmortem aging
Authors: Tuell Jacob R. , Nondorf Mariah J. , Abdelhaseib Maha , Setyabrata Derico , Barker Samantha , Legako Jerrad F. , Kim Yuan H. Brad
Published: August 2022

This study assessed how fresh beef tumbling without brine inclusion combined with aging would affect quality, biochemical attributes, and descriptive sensory scores of sirloin muscles. Paired gluteus medius (GM), biceps femoris (BF), and tensor fasciae latae (TFL) muscles from beef carcasses (n = 16) at 5 days postmortem were assigned to 0 or 120 min of tumbling, after which sections were aged 0 or 10 days. Tumbled GM (p < 0.001) and TFL (p < 0.01) muscles had increased objective tenderness compared to respective controls. Greater cook and initial purge losses were induced in all muscles with tumbling (p < 0.05), while thawing loss and purge loss with aging were similar (p > 0.05). Fragmentation of myofibrils was increased with tumbling and aging main effects (p < 0.001), although degradation of troponin T and desmin were primarily affected by aging only. In general, neither tumbling nor aging affected properties of collagen. Trained panelists assessed muscles aged 10 days for descriptive sensory scores including tenderness (myofibrillar, connective tissue, and overall), flavor (beef flavor identity, bloody/serumy, fat‐like, liver‐like, oxidized, umami, metallic, and sour), and juiciness (overall). Tumbled GM had greater myofibrillar tenderness than the control group (p < 0.05). Most sensory scores were unaffected by tumbling; however, tumbling increased oxidized and liver‐like flavors of GM and TFL, respectively, as well as decreased overall juiciness of BF (p < 0.05). These findings indicate tumbling combined with postmortem aging can improve tenderness of certain sirloin muscles like GM, although some impairments to flavor and juiciness could also occur.

Practical Application

The findings of this study are applicable to the beef industry to develop postharvest strategies to ensure sufficient tenderization of fresh beef sirloin muscles is achieved. However, the effectiveness of this process would differ between individual cuts, and minimizing possible impairments to flavor and juiciness would be critical.
Improvement of fitness and biocontrol properties of Pseudomonas putida via an extracellular heme peroxidase
Authors: Santamaría‐Hernando Saray , De Bruyne Lieselotte , Höfte Monica , Ramos‐González María‐Isabel
Published: August 2022

The extracellular 373‐kDa PehA heme peroxidase of Pseudomonas putida KT2440 has two enzymatic domains which depend on heme cofactor for their peroxidase activity. A null pehA mutant was generated to examine the impact of PehA in rhizosphere colonization competence and the induction of plant systemic resistance (ISR). This mutant was not markedly hampered in colonization efficiency. However, increase in pehA dosage enhanced colonization fitness about 30 fold in the root and 900 fold in the root apex. In vitro assays with purified His‐tagged enzymatic domains of PehA indicated that heme‐dependent peroxidase activity was required for the enhancement of root tip colonization. Evaluation of live/dead cells confirmed that overexpression of pehA had a positive effect on bacterial cell viability. Following root colonization of rice plants by KT2440 strain, the incidence of rice blast caused by Magnaporthe oryzae was reduced by 65% and the severity of this disease was also diminished in comparison to non‐treated plants. An increase in the pehA dosage was also beneficial for the control of rice blast as compared with gene inactivation. The results suggest that PehA helps P. putida to cope with the plant‐imposed oxidative stress leading to enhanced colonization ability and concomitant ISR‐elicitation.
Extracting abundance information from DNA‐based data
Authors: Luo Mingjie , Ji Yinqiu , Warton David , Yu Douglas W.
Published: August 2022

The accurate extraction of species‐abundance information from DNA‐based data (metabarcoding, metagenomics) could contribute usefully to diet analysis and food‐web reconstruction, the inference of species interactions, the modelling of population dynamics and species distributions, the biomonitoring of environmental state and change, and the inference of false positives and negatives. However, multiple sources of bias and noise in sampling and processing combine to inject error into DNA‐based data sets. To understand how to extract abundance information, it is useful to distinguish two concepts. (i) Within‐sample across‐species quantification describes relative species abundances in one sample. (ii) Across‐sample within‐species quantification describes how the abundance of each individual species varies from sample to sample, such as over a time series, an environmental gradient or different experimental treatments. First, we review the literature on methods to recover across‐species abundance information (by removing what we call “species pipeline biases”) and within‐species abundance information (by removing what we call “pipeline noise”). We argue that many ecological questions can be answered with just within‐species quantification, and we therefore demonstrate how to use a “DNA spike‐in” to correct for pipeline noise and recover within‐species abundance information. We also introduce a model‐based estimator that can be used on data sets without a physical spike‐in to approximate and correct for pipeline noise.
Positional errors in species distribution modelling are not overcome by the coarser grains of analysis
Authors: Gábor Lukáš , Jetz Walter , Lu Muyang , Rocchini Duccio , Cord Anna , Malavasi Marco , Zarzo‐Arias Alejandra , Barták Vojtěch , Moudrý Vítězslav
Published: August 2022

The performance of species distribution models (SDMs) is known to be affected by analysis grain and positional error of species occurrences. Coarsening of the analysis grain has been suggested to compensate for positional errors. Nevertheless, this way of dealing with positional errors has never been thoroughly tested. With increasing use of fine‐scale environmental data in SDMs, it is important to test this assumption. Models using fine‐scale environmental data are more likely to be negatively affected by positional error as the inaccurate occurrences might easier end up in unsuitable environment. This can result in inappropriate conservation actions.

Here, we examined the trade‐offs between positional error and analysis grain and provide recommendations for best practice. We generated narrow niche virtual species using environmental variables derived from LiDAR point clouds at 5 × 5 m fine‐scale. We simulated the positional error in the range of 5 m to 99 m and evaluated the effects of several spatial grains in the range of 5 m to 500 m. In total, we assessed 49 combinations of positional accuracy and analysis grain. We used three modelling techniques (MaxEnt, BRT and GLM) and evaluated their discrimination ability, niche overlap with virtual species and change in realized niche.

We found that model performance decreased with increasing positional error in species occurrences and coarsening of the analysis grain. Most importantly, we showed that coarsening the analysis grain to compensate for positional error did not improve model performance. Our results reject coarsening of the analysis grain as a solution to address the negative effects of positional error on model performance.

We recommend fitting models with the finest possible analysis grain and as close to the response grain as possible even when available species occurrences suffer from positional errors. If there are significant positional errors in species occurrences, users are unlikely to benefit from making additional efforts to obtain higher resolution environmental data unless they also minimize the positional errors of species occurrences. Our findings are also applicable to coarse analysis grain, especially for fragmented habitats, and for species with narrow niche breadth.
Optimizing an existing prediction model for quality of life one‐year post‐intensive care unit: An exploratory analysis
Authors: de Jonge Manon , Wubben Nina , van Kaam Christiaan R. , Frenzel Tim , Hoedemaekers Cornelia W. E. , Ambrogioni Luca , van der Hoeven Johannes G. , van den Boogaard Mark , Zegers Marieke
Published: August 2022

Background

This study aimed to improve the PREPARE model, an existing linear regression prediction model for long‐term quality of life (QoL) of intensive care unit (ICU) survivors by incorporating additional ICU data from patients' electronic health record (EHR) and bedside monitors.

Methods

The 1308 adult ICU patients, aged ≥16, admitted between July 2016 and January 2019 were included. Several regression‐based machine learning models were fitted on a combination of patient‐reported data and expert‐selected EHR variables and bedside monitor data to predict change in QoL 1 year after ICU admission. Predictive performance was compared to a five‐feature linear regression prediction model using only 24‐hour data (R2 = 0.54, mean square error (MSE) = 0.031, mean absolute error (MAE) = 0.128).

Results

The 67.9% of the included ICU survivors was male and the median age was 65.0 [IQR: 57.0–71.0]. Median length of stay (LOS) was 1 day [IQR 1.0–2.0]. The incorporation of the additional data pertaining to the entire ICU stay did not improve the predictive performance of the original linear regression model. The best performing machine learning model used seven features (R2 = 0.52, MSE = 0.032, MAE = 0.125). Pre‐ICU QoL, the presence of a cerebro vascular accident (CVA) upon admission and the highest temperature measured during the ICU stay were the most important contributors to predictive performance. Pre‐ICU QoL's contribution to predictive performance far exceeded that of the other predictors.

Conclusion

Pre‐ICU QoL was by far the most important predictor for change in QoL 1 year after ICU admission. The incorporation of the numerous additional features pertaining to the entire ICU stay did not improve predictive performance although the patients' LOS was relatively short.
Postoperative pain in a prospectively assessed surgical short‐stay cohort: A subgroup analysis
Authors: Lappalainen Emma , Ruohoaho Ulla‐Maija , Kokki Hannu , Aaltomaa Sirpa , Anttila Maarit , Gissler Mika , Kokki Merja
Published: August 2022

Background

There is sparse information about postoperative pain after short stay surgery. We explored the incidence of immediate postoperative pain and its relationship with persistent pain or opioid use 2 weeks after surgery.

Methods

This was a subgroup analysis of prospective and controlled data from adult patients (n = 931) who underwent short‐stay surgery in a tertiary care hospital. Data comprised patient demographics, surgical category, pain scores and analgesic management during the recovery unit stay, before discharge on the postoperative morning after surgery and again 2 weeks after surgery.

Results

Half of the patients had severe dynamic pain in the recovery unit. It was commonest after orthopaedic (70% of patients), followed by gynaecological (54%), gastrointestinal (51%) and spine surgery (49%). Multimodal pain management was used for most patients (n = 811, 87%) with opioid use predominant. The median oxycodone dose during short‐stay was the highest after orthopaedic surgery (39 mg). The first individual dynamic pain score after surgery was associated with follow‐up pain score at rest (OR = 1.37), dynamic pain (OR = 1.35) and pain interference (OR = 1.34) at 2 weeks after surgery. Maximum dynamic pain reported in the recovery unit was associated with pain at rest (OR = 1.56), dynamic pain (OR = 1.65) and pain interference (OR = 1.45) at 2 weeks after surgery. Pain scores at 2 weeks were highest and analgesic use greatest in those patients who underwent spinal surgery.

Conclusions

Intense postoperative pain remains common after short‐stay surgery in some surgical categories including orthopaedic surgery and is associated with a greater likelihood of pain at 2 weeks.
Risk of serious adverse events associated with non‐steroidal anti‐inflammatory drugs in orthopaedic surgery. A protocol for a systematic review
Authors: Leth Morten Fiil , Bukhari Shaheer , Laursen Christina Cleveland Westerdahl , Larsen Mia Esta , Tornøe Anders Schou , Jakobsen Janus Christian , Maagaard Mathias , Mathiesen Ole
Published: August 2022

Background

Postoperative pain is a common condition following orthopaedic surgeries and causes prolonged hospitalisation, delayed rehabilitation and hamper the quality of life. Non‐steroidal anti‐inflammatory drugs (NSAIDs) are effective analgesics and anti‐inflammatory mediators in the treatment of postoperative pain. The association of NSAIDs with serious adverse events may however keep some clinicians and clinical decision makers from using NSAIDs perioperatively. The evidence regarding the risks of serious adverse events following perioperative use of NSAIDs in orthopaedic surgery is sparse and needs to be assessed in a systematic review. This is a protocol for a systematic review that aims to identify the risks of serious adverse events from perioperative use of NSAIDs in orthopaedic patients.

Methods

Our methodology is based on the Preferred Reporting Items for Systematic Review and Meta‐Analysis Protocols and the eight‐step assessment procedure suggested by Jakobsen and colleagues. We wish to assess if NSAIDs versus placebo, usual care or no intervention, will influence the risks of serious adverse events in patients undergoing orthopaedic surgery. We will include all randomised trials assessing the use of NSAIDs perioperatively. To identify trials we will search the Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Cochrane Central Register, Science Citation Index Expanded on Web of Science and BIOSIS. Two authors will screen the literature and extract data. We will use the ‘Risk of Bias 2 tool’ to assess trials. Extracted data will be analysed using RStudio and Trial Sequential Analysis. We will create a ‘Summary of Findings’ table in which we will present our primary and secondary outcomes. We will assess the quality of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE).

Discussion

This systematic review can potentially aid clinicians and clinical decision makers in the use of NSAIDs for treatment of postoperative pain following orthopaedic surgeries.
Fluid management of emergency department patients with sepsis—A survey of fluid resuscitation practices
Authors: Jessen Marie Kristine , Simonsen Birgitte Y. , Thomsen Marie‐Louise H. , Andersen Lars W. , Kolsen‐Petersen Jens Aage , Kirkegaard Hans
Published: August 2022

Background

Fluid administration and resuscitation of patients with sepsis admitted through emergency departments (ED) remains a challenge, and evidence is sparse especially in sepsis patients without shock. We aimed to investigate emergency medicine physicians' and nurses' perceptions, self‐reported decision‐making and daily behavior, and challenges in fluid administration of ED sepsis patients.

Methods

We developed and conducted a multicenter, web‐based, cross‐sectional survey focusing on fluid administration to ED patients with sepsis sent to all nurses and physicians from the five EDs in the Central Denmark Region. The survey consisted of three sections: (1) baseline information; (2) perceptions of fluid administration and daily practice; and (3) clinical scenarios about fluid administration. The survey was performed from February to June, 2021.

Results

In total, 138 of 246 physicians (56%) and 382 of 595 nurses (64%) responded to the survey. Of total, 94% of physicians and 97% of nurses regarded fluid as an important part of sepsis treatment. Of total, 80% of physicians and 61% of nurses faced challenges regarding fluid administration in the ED, and decisions were usually based on clinical judgment. The most common challenge was the lack of guidelines for fluid administration. Of total, 96% agreed that they would like to learn more about fluid administration, and 53% requested research in fluid administration of patients with sepsis. For a normotensive patient with sepsis, 46% of physicians and 44% of nurses administered 1000 ml fluid in the first hour. Of total, 95% of physicians and 89% of nurses preferred to administer ≥1000 ml within an hour if the patients' blood pressure was 95/60 at admission. There was marked variability in responses. Blood pressure was the most commonly used trigger for fluid administration. Respondents preferred to administer less fluid if the patient in the scenario had known renal impairment or heart failure. Normal saline was the preferred fluid.

Conclusion

Fluid administration is regarded as an important but challenging aspect of sepsis management. Responses to scenarios revealed variability in fluid volumes. Blood pressure was the most used trigger. ED nurses and physicians request evidence‐based guidelines to improve fluid administration.
Quantification of noradrenergic‐, dopaminergic‐, and tectal‐neurons during aging in the short‐lived killifish Nothobranchius furzeri
Authors: Bagnoli Sara , Fronte Baldassare , Bibbiani Carlo , Terzibasi Tozzini Eva , Cellerino Alessandro
Published: August 2022

Parkinson's disease (PD) is characterized by phosphorylation and aggregation of the protein α‐Synuclein and ensuing neuronal death progressing from the noradrenergic locus coeruleus to midbrain dopaminergic neurons. In 2019, Matsui and colleagues reported a spontaneous age‐dependent degeneration of dopaminergic neurons and an even greater neurodegeneration of the noradrenergic neurons in the short‐lived killifish Nothobranchius furzeri. Given the great possible relevance of a spontaneous model for PD, we assessed neurodegeneration of noradrenergic and dopaminergic neurons in two further laboratory strains of N. furzeri. We implemented, for the first time in N. furzeri, a whole‐brain clarification technique and proceeded to entire 3D nuclei reconstruction to quantify total cell numbers in two different stains of N. furzeri. In both strains, we observed that age‐dependent neurodegeneration is limited to the locus coeruleus and does not involve the posterior tuberculum. We also applied 3D counting to the optic tectum, an area of active adult neurogenesis, and detected an increase of neurons with age. Our results confirm age‐dependent neurodegeneration of noradrenergic neurons, a condition reminiscent of the presymptomatic stage of PD indicating that N. furzeri could be used in the future to identify modifying factors for age‐dependent neurodegeneration and open the intriguing possibility that natural genetic variation may influence the susceptibility of dopaminergic neurons.
Economic impacts of food safety incidents in a modern supply chain: E. coli in the romaine lettuce industry
Authors: Spalding Ashley , Goodhue Rachael E. , Kiesel Kristin , Sexton Richard J.
Published: August 2022

Food‐safety incidents disrupt impacted markets, cause destruction of edible product, shake consumer confidence, and impose economic losses upon participants across the implicated supply chain. Despite the prevalence of such incidents, we know surprisingly little about their supply chain impacts, especially in modern produce markets where contracts may impede the diffusion of price impacts through the supply chain. The November 2018 E. coli incident for romaine lettuce in Central California roiled North American produce markets throughout the fall of 2018 and well into 2019. Our study of the economic impacts of this incident benefited from access to disaggregate information on prices and sales for romaine and substitute leafy greens at all stages of the supply chain, enabling us to overcome data limitations that have impeded prior studies. We decompose impacts from the incident into price and quantity components. Romaine growers were largely protected from damage due to fixed‐price provisions in grower‐processor contracts. Economic losses were incurred mostly by romaine shippers and processors, and grocery retailers who pulled saleable product from the supply chain and lost sales during and well after the incident due to reduced consumer demand. We estimate that the total societal loss from the incident was in the range of $276–$343 million. Widespread and long‐lasting impacts from a food‐safety incident demonstrate the economic benefit of industries adopting mandatory food‐safety standards and improved traceability to minimize the occurrence and impacts of such incidents.
Phantom Counterfactuals
Authors: Slough Tara
Published: August 2022

Researchers often seek to identify the effects of a treatment on a sequence of behaviors, such as whether citizens register to vote and whether they then cast ballots. I show that average treatment effects (ATEs) are only identified until the first behavior (registering to vote) that affects the set of possible subsequent actions (voting). When one action changes the set of possible subsequent actions, it creates ‘phantom counterfactuals,’ or undefined potential outcomes, which render ATEs unidentified. I show that applied theory allows researchers to diagnose phantom counterfactuals, which helps to recognize unidentified ATEs and focus instead on other estimands that are identified. I illustrate this approach using a stylized model of crime reporting, showing how different theories generate different sets of identified estimands while holding constant an experimental design. I thereby establish the necessity of applied theory for causal identification in empirical research with sequential behavioral outcomes.
Steep repolarization time gradients in pig hearts cause distinct changes in composite electrocardiographic T‐wave parameters
Authors: van der Waal Jeanne , Bear Laura , Meijborg Veronique , Dubois Rémi , Cluitmans Matthijs , Coronel Ruben
Published: August 2022

Background

The T wave of the electrocardiogram (ECG) reflects ventricular repolarization. Repolarization heterogeneity is associated with reentrant arrhythmias. Several T‐wave markers (including QT interval) have been associated with ventricular arrhythmias, but studies linking such markers to underlying local repolarization time (RT) inhomogeneities are lacking. We aimed to investigate the relation of several T‐wave markers to controlled drug‐induced regional RT gradients in intact pig hearts.

Methods

Repolarization time gradients were created by regional infusion of dofetilide and pinacidil in four atrially paced porcine Langendorff‐perfused hearts placed inside a torso tank. From the 12‐lead ECG on the torso tank, the mean, maximum, and dispersion (max–min) of QTtime, JTtime, Tpeak–end, Twidth, TQratio, dV/dtmax, Tarea, Tamp, and T‐upslope duration were determined, as well as upslope end difference between leads V1 and V6.

Results

Temporal T‐wave parameters Tpeak–end, Twidth, and TQratio show a significant and high correlation with RT gradient, best reflected by mean value. Tarea (mean, max and dispersion) and dV/dtmax dispersion show only a moderate significant correlation. T‐upslope duration shows a significant correlation in particular for mean values. Mean, maximum, or dispersion of QTtime and V1–V6 upslope end difference were not significantly correlated with RT gradient.

Conclusion

Composite 12‐lead ECG T‐wave parameters Tpeak–end, Twidth, TQratio, upslope duration, and Tarea show a good correlation with underlying RT heterogeneity, whereas standard clinical metrics such as QTtime do not reflect local RT heterogeneity. The composite T‐wave metrics may thus provide better insights in arrhythmia susceptibility than traditional QTtime metrics.
The role of extracorporeal membrane oxygenation in adult kidney transplant patients: A qualitative systematic review of literature
Authors: Reid Trista D. , Kratzke Ian , Dayal Diana , Raff Lauren , Serrano Pablo , Kumar Aman , Boddie Olivia , Zendel Alex , Gallaher Jared , Carlson Rebecca , Boone Joshua , Charles Anthony G. , Desai Chirag S.
Published: August 2022

Background

A paucity of evidence exists regarding the risks and benefits of Extracorporeal Membrane Oxygenation (ECMO) in adult kidney transplantation.

Methods

This was a systematic review conducted from Jan 1, 2000 to April 24, 2020 of adult kidney transplant recipients (pre‐ or post‐ transplant) and donors who underwent veno‐arterial or veno‐venous ECMO cannulation. Death and graft function were the primary outcomes, with complications as secondary outcomes.

Results

Twenty‐three articles were identified that fit inclusion criteria. 461 donors were placed on ECMO, with an overall recipient 12‐month mortality rate of 1.3% and a complication rate of 61.5%, the majority of which was delayed graft function. Fourteen recipients were placed on ECMO intraoperatively or postoperatively, with infection as the most common indication for ECMO. The 90‐day mortality rate for recipients on ECMO was 42.9%, with multisystem organ failure and infection as the ubiquitous causes of death. 35.7% of patients experienced rejection within 6 months of decannulation, yet all were successfully treated.

Conclusions

ECMO use in adult kidney transplantation is a useful adjunct. Recipient morbidity and mortality from donors placed on ECMO mirrors that of recipients from standard criteria donors. The morbidity and mortality of recipients placed on ECMO are also similar to other patient populations requiring ECMO.
Social connectedness, emotional regulation, and health behaviors as correlates of distress during lockdown for COVID‐19: A diary study
Authors: Muñoz‐Martínez Amanda M. , Naismith Iona
Published: August 2022

Mass lockdowns are a powerful infection‐reduction strategy but are a significant stressor. This study aimed to explore whether various factors known to predict distress in normal contexts (e.g. social connectedness, emotional‐regulation strategies, and health‐related behaviors) are associated with daily distress under lockdown conditions. A time‐based diary study evaluated how perceived social connectedness, health‐promoting, and risk behaviors predicted within‐person and between‐person psychological distress. One hundred and nine adults completed surveys on these variables daily for 15 days while under stringent COVID‐19 lockdown in Colombia. Emotional suppression and reappraisal were measured at the start of the study to explore whether they predicted distress. Distress was lower on the days that people experienced greater social connectedness (within‐person analyses) but was not significantly predicted by between‐participant differences in emotional regulation. Health‐promoting behaviors such as exercising and meaningful activity were associated with lower distress, while watching COVID‐19 news and eating high‐calorie food were associated with higher distress. Looking at individual dynamics provides meaningful insights on daily behaviors associated with distress that might improve people's wellbeing during lockdown, such as social connectedness, meaningful activity, nutrition, exercise, and minimizing news exposure. Future research with alternative designs will enable causal conclusions to be drawn.
Integrated morphometric and molecular analyses indicate three male morphotypes in the freshwater prawn Macrobrachium olfersii (Decapoda, Palaemonidae) along the Brazilian neotropical region
Authors: Rossi Natália , Pantaleão João Alberto Farinelli , Mantelatto Fernando L.
Published: August 2022

Males of Macrobrachium olfersii have a large cheliped (second pereiopod) with individual variations in shape and ornamentation, and they vary in size within and between populations. Some misidentification or doubts about taxonomic validity occur due to this morphological variability throughout their geographic distribution. We carried out a morphometric analysis to detect specific patterns and the potential occurrence of morphotypes in M. olfersii from different populations. Our data set included 52 females and 109 males collected in the Neotropical region, between the north and south limits of Brazilian territory, in coastal rivers from the states of Rio Grande do Norte, Bahia, Espírito Santo, Rio de Janeiro, São Paulo, Paraná and Santa Catarina. Body measurements were size standardized by allometric methods and explored by the principal component analysis (PCA) and non‐hierarchical analysis of K‐means clustering and canonical variate analysis (CVA). Our results suggested three distinct morphological groups (morphotypes) only for males in M. olfersii. Furthermore, the confirmation of monophyly of the different populations of M. olfersii was accomplished by sequences of 16S rDNA. Additional studies about relative growth in other populations and the analysis of the entire ontogenetic development of males in the laboratory will be important to complement the knowledge about morphotypes in this species.
Hospital pharmacists' opinions on a risk prediction tool for medication‐related harm in older people
Authors: Hussain Ahmed , Ali Khalid , Davies J. Graham , Stevenson Jennifer M. , Lippett Samantha , O'Malley Mairead , Parekh Nikesh , Rajkumar Chakravarthi
Published: August 2022

Aim

Older adults are particularly affected by medication‐related harm (MRH) during transitions of care. There are no clinical tools predicting those at highest risk of MRH post hospital discharge. The PRIME study (prospective study to develop a model to stratify the risk of MRH in hospitalized patients) developed and internally validated a risk‐prediction tool (RPT) that provides a percentage score of MRH in adults over 65 in the 8 weeks following hospital discharge. This qualitative study aimed to explore the views of hospital pharmacists around enablers and barriers to clinical implementation of the PRIME‐RPT.

Methods

Ten hospital pharmacists: (band 6, n = 3; band 7, n = 2; band 8, n = 5) participated in semistructured interviews at the Royal Sussex County Hospital (Brighton, UK). The pharmacists were presented with five case‐vignettes each with a calculated PRIME‐RPT score to help guide discussion. Case‐vignettes were designed to be representative of common clinical encounters. Data were thematically analysed using a “framework” approach.

Results

Seven themes emerged in relation to the PRIME‐RPT: (1) providing a medicine‐prioritisation aide; (2) acting as a deprescribing alert; (3) facilitating a holistic review of patient medication management; (4) simplifying communication of MRH to patients and the multidisciplinary team; (5) streamlining community follow‐up and integration of risk discussion into clinical practice; (6) identifying barriers for the RPTs integration in clinical practice; and (7) acknowledging its limitations.

Conclusion

Hospital pharmacists found the PRIME‐RPT beneficial in identifying older patients at high risk of MRH following hospital discharge, facilitating prioritising interventions to those at highest risk while still acknowledging its limitations.
Preclinical efficacy in investigator's brochures: Stakeholders' views on measures to improve completeness and robustness
Authors: Haslberger Martin , Schorr Susanne Gabriele , Strech Daniel , Haven Tamarinde
Published: August 2022

Aims

Research ethics committees and regulatory agencies assess whether the benefits of a proposed early‐stage clinical trial outweigh the risks based on preclinical studies reported in investigator's brochures (IBs). Recent studies have indicated that the reporting of preclinical evidence presented in IBs does not enable proper risk‐benefit assessment. We interviewed different stakeholders (regulators, research ethics committee members, preclinical and clinical researchers, ethicists, and metaresearchers) about their views on measures to increase the completeness and robustness of preclinical evidence reporting in IBs.

Methods

This study was preregistered (https://osf.io/nvzwy/). We used purposive sampling and invited stakeholders to participate in an online semistructured interview between March and June 2021. Themes were derived using inductive content analysis. We used a strengths, weaknesses, opportunities and threats matrix to categorize our findings.

Results

Twenty‐seven international stakeholders participated. The interviewees pointed to several strengths and opportunities to improve completeness and robustness, mainly more transparent and systematic justifications for the included studies. However, weaknesses and threats were mentioned that could undermine efforts to enable a more thorough assessment: The interviewees stressed that current review practices are sufficient to ensure the safe conduct of first‐in‐human trials. They feared that changes to the IB structure or review process could overburden stakeholders and slow drug development.

Conclusion

In principle, more robust decision‐making processes align with the interests of all stakeholders and with many current initiatives to increase the translatability of preclinical research and limit uninformative or ill‐justified trials early in the development process. Further research should investigate measures that could be implemented to benefit all stakeholders.
Preventing atopic eczema: vitamin D supplementation another piece of the puzzle?
Authors: Orchard David
Published: August 2022

Linked Article:  El-Heis et al. Br J Dermatol 2022; 187:659–666.
Efficacy and safety of topical brepocitinib for the treatment of mild-to-moderate atopic dermatitis: a phase IIb, randomized, double-blind, vehicle-controlled, dose-ranging and parallel-group study
Authors: Landis Megan N. , Arya Mark , Smith Stacy , Draelos Zoe , Usdan Lisa , Tarabar Sanela , Pradhan Vivek , Aggarwal Sudeepta , Banfield Christopher , Peeva Elena , Vincent Michael S. , Sikirica Vanja , Xenakis Jason , Beebe Jean S.
Published: August 2022

Background

Atopic dermatitis (AD) is a prevalent inflammatory, pruritic skin disease. The Janus kinase (JAK) pathway is a treatment target.

Objectives

To assess the efficacy, safety and pharmacokinetics of topical cream brepocitinib, a small-molecule tyrosine kinase 2 (TYK2)/JAK1 inhibitor, in participants with mild-to-moderate AD.

Methods

In this phase IIb, double-blind, dose-ranging study, participants were randomized to receive one of eight treatments for 6 weeks: brepocitinib 0·1% once daily (QD), 0·3% QD or twice daily (BID), 1·0% QD or BID, 3·0% QD, or vehicle QD or BID. The primary endpoint was the percentage change from baseline in the Eczema Area and Severity Index (EASI) total score at week 6. Adverse events (AEs) were monitored.

Results

Overall, 292 participants were enrolled and randomized. The brepocitinib 1% QD and 1% BID groups achieved statistically significantly greater (with multiplicity-adjusted P < 0·05 due to Hochberg’s step-up method) percentage reductions from baseline in EASI total score at week 6 [least squares mean (90% confidence interval, CI): QD: –70·1 (–82·1 to –58·0); BID: –75·0 (–83·8 to –66·2)] compared with respective vehicle [QD: –44·4 (–57·3 to –31·6); BID: –47·6 (–57·5 to –37·7)]. There was not a dose-dependent trend in AE frequency, and there were no serious AEs or deaths.

Conclusions

Topical brepocitinib is effective and well tolerated in participants with mild-to-moderate AD.

What is already known about this topic?  Janus kinase (JAK) inhibitors are in development for treatment of atopic dermatitis (AD).The tyrosine kinase 2 and JAK 1 inhibition by brepocitinib may bring a new profile for topical JAK inhibitors for treatment of mild-to-moderate AD.

What does this study add?  Topical brepocitinib can provide rapid, effective symptom reduction, and could offer a novel alternative to current topical treatments for mild-to-moderate AD.
Exploring the promotion of youth voice in community‐based youth development programmes
Authors: Bloomer Rebecka , Harris Lesley M. , Brown Aishia A. , Crosby Shantel
Published: August 2022

This constructivist grounded theory study used semi‐structured interviews with 19 youth service providers in community‐based youth development programmes to develop a context‐specific framework of how and why youth voice promotion occurred. Factors external to the youth programmes, such as funder expectations, influenced the conceptualization of role for youth workers. The social process of meaning making in relation to role identity impacted how youth workers perceived self‐efficacy when working with youth, especially when engaged with behaviours falling outside programmatic expectations or norms. Workers prioritized fostering physical and psychological safe spaces for youth participants. When conflict occurred, perceptions of efficacy guided workers in taking positions that either promoted or restricted youth voice based on their perceptions of efficacy in resolving conflict safely. Youth programmes have the capacity to resist or replicate oppression present within the educational system. The adoption and adaptation of educational models of resistance offer a strategy for community‐based youth organizations to promote equity and thriving youth.
Predicting the Structure of a Lexical Environment from Properties of Verbal Working Memory
Authors: Tanida Yuki , Saito Satoru
Published: August 2022

We analyzed a Japanese lexical database to investigate the structure of the lexical environment based on the hypothesis that the lexical environment is optimized for the functioning of verbal working memory. Our prediction was that, as a consequence of the cultural transmission of language, low‐imageable meanings tend to be represented by frequent phonological patterns in the current vocabulary rather than infrequent phonological patterns. This prediction was based on two findings of previous laboratory studies on verbal working memory. (1) The quality of phonological (phonemic and accent) representations in verbal working memory depends on phonological regularity knowledge; therefore, short‐term phonological representations are less robust for words with infrequent phonological patterns. (2) Phonological representations are underpinned by contributions from semantic knowledge; therefore, phonological representations of highly imageable words are more robust than those for low‐imageable words. Our database analyses show that nouns with less imageable meanings tend to be associated with more frequent phonological patterns in Japanese vocabulary. This lexical structure can maintain the quality of phonological representations in verbal working memory through contributions of semantic and phonological regularity knowledge. Larger semantic contributions compensate for the less robust phonological representations of infrequent phonological forms. The quality of phonological representations is preserved by phonological regularity knowledge when larger semantic contributions are not expected.
Cystathionine β‐synthase is required for oocyte quality by ensuring proper meiotic spindle assembly
Authors: Cao Yan , Zhu Xinyu , Zhen Panpan , Tian Ying , Ji Dengyu , Xue Ke , Yan Wenjing , Chai Jiayin , Liu Huirong , Wang Wen
Published: August 2022

Objectives

Poor oocyte quality is detrimental to fertilization and embryo development, which causes infertility. Cystathionine β‐synthase (CBS) is one of the key enzymes modulating the metabolism of homocysteine (Hcy). Studies have shown that CBS plays an important role in female reproduction. However, the role of CBS in regulating oocyte quality during meiotic maturation still needs further investigation.

Materials and Methods

Immunohistochemistry, immunofluorescence, drug treatment, western blot, cRNA construct and in vitro transcription, microinjection of morpholino oligo and cRNA were performed for this study.

Results

We found that CBS was expressed both in human and mouse oocytes of follicles. In mouse oocytes, CBS was distributed in the nucleus at germinal vesicle (GV) stage and localized to spindle from germinal vesicle breakdown (GVBD) to metaphase II (MII). The expression of CBS was reduced in ovaries and oocytes of aged mice. CBS depletion resulted in meiotic arrest, spindle abnormality and chromosome misalignment, disrupted kinetochore‐microtubule attachments and provoked spindle assembly checkpoint (SAC). CBS was disassembled when microtubules were disrupted with nocodazole, and co‐localized with the stabilized microtubules after taxol treatment. Furthermore, CBS depletion decreased the acetylation of α‐tubulin.

Conclusions

These results reveal that CBS is required for the acetylation of α‐tubulin to ensure proper spindle assembly in regulating oocyte quality during meiotic maturation.
Senescent cells: A therapeutic target for osteoporosis
Authors: Wang Tiantian , Huang Shishu , He Chengqi
Published: August 2022

Background

Osteoporosis (OP) is a prevalent disorder characterized by the loss of bone mass and the deterioration of bone microarchitecture. OP is attributed to various factors, including menopause (primary), ageing (primary) and the adverse effects of medications (secondary). Recently, cellular senescence has been shown to have a crucial role in the maintenance of cellular homeostasis and organ function. The purpose of this review is to summarize recent findings regarding the roles of bone cellular senescence and senescence‐associated secretory phenotype (SASP) in OP.

Methods

A comprehensive search of the PubMed database from inception to July 2022 was performed regarding the molecular mechanism of bone cell senescence in OP progression.

Results

We describe the pathophysiology of senescent bone cells and SASP, and how each contributes to OP. We also provide new options for treating OP by targeting cellular senescence pathways.

Conclusion

Cellular senescence plays an important role in bone homeostasis, with variations based on the different types of OP. These variations are associated with pathogenic factors, bone turnover rate and systemic metabolism. Understanding the molecular relationship between bone cells and senescence provides for the possible targeting of senescence as a means by which to treat OP.
Genetic patterns in three South African specialist antelope species: Threats, conservation management and their implications
Authors: Phukuntsi Metlholo Andries , Dalton Desire Lee , Mwale Monica , Selier Jeanetta , Cebekhulu Thando , Sethusa Mamadi Theresa
Published: August 2022

Genetic diversity is a fundamental measure of a populations ability to adapt to future environmental change. Subpopulations may carry unique genetic lineages that contribute to fitness and genetic diversity of species across their distribution range. Therefore, considerations, or lack thereof, of genetic diversity in wildlife management practices may result in either population persistence or extinction over time. Some management tools may pose a greater risk to a species' survival than others when populations are impacted. In South Africa, there has been great interest to translocate animals, sometimes with little consideration to the potential impacts on the species and/or populations survival. Thus, there is a need to collate scientific information to better inform decision‐making and review these management practices and their effects on populations. Here, we focus on three antelope species, the blue duiker (Philantomba monticola), oribi (Ourebia ourebi), and tsessebe (Damaliscus lunatus). We review the genetic status of each species across South Africa, with regards to taxonomy, genetic diversity and population structure, threats that may compromise the genetic diversity within species and across populations, conservation management actions and how they may compromise or benefit the genetic status and lastly make recommendations on possible alternative management actions and future research to inform conservation policy and sustainable management practice.
Alternative splicing for germ cell‐specific Mga transcript can be eliminated without compromising mouse viability or fertility
Authors: Kitamura Yuka , Suzuki Ayumu , Uranishi Kousuke , Nishimoto Masazumi , Mizuno Seiya , Takahashi Satoru , Okuda Akihiko
Published: August 2022

The stimulated by retinoic acid gene 8 (STRA8)/MEIOSIN complex and polycomb repressive complex (PRC) 1.6, a PRC1 subtype, are believed to be positive and negative regulators of meiotic onset, respectively. During meiotic initiation, the transcription repressive activity of PRC1.6 must be attenuated so that meiosis‐related genes can be effectively activated by the STRA8/MEIOSIN complex. However, the molecular mechanisms that control the impairment of PRC1.6 function remain unclear. We recently demonstrated that the Mga gene, which encodes a scaffolding component of PRC1.6, produces variant mRNA by alternative splicing specifically during meiosis. Furthermore, the anomalous MGA protein encoded by the variant mRNA bears an intrinsic ability to function as a dominant negative regulator against the construction of PRC1.6 and is therefore assumed to be, at least in part, involved in impairment of the complex. Therefore, to unequivocally evaluate the physiological significance of Mga variant mRNA production in gametogenesis, we examined the consequences of a genetic manipulation that renders mice unable to produce Mga variant mRNA. Our data revealed that mutant mice were equivalent to wild‐type mice in terms of viability and fertility. Our detailed examination of spermatogenesis also revealed that this genetic alteration is not associated with any apparent abnormalities in testis size, spermatogenic cycle, timing of meiotic onset, or marker gene expression of spermatogonia and spermatocytes. Taken together, these data indicate that the production of germ cell‐specific Mga variant mRNA is dispensable not only for viability but also for gametogenesis.
Brain‐derived neurotrophic factor overexpression in taste buds diminishes chemotherapy induced taste loss
Authors: Vukmanovic Nosrat Irina , Palacios Jerry L. , Kezian Steven , Luong Gloria , Tran Andrew , Vu Kim , Henson Bradley S. , Nosrat Philip , Lutfy Kabirullah , Nosrat Christopher A.
Published: August 2022

Vismodegib is used in patients suffering from advanced basal cell carcinoma (BCC), but 100% of the patients taking it report dysgeusia and 50% discontinue the treatment. Treatment with neurotrophic factors can stimulate neuronal survival and functional improvement in injured organs. Here, we analysed novel transgenic mouse lines in which brain‐derived neurotrophic factor (BDNF) is overexpressed in taste buds, to examine whether higher levels of BDNF would reduce or prevent negative side effects of vismodegib in the taste system. BDNF plays crucial roles for development, target innervation, and survival of gustatory neurons and taste buds. The behavioural test in this study showed that vehicle‐treated wild‐type mice prefered 10 mM sucrose over water, whereas vismodegib treatment in wild‐type mice caused total taste loss. Gustducin‐BDNF mice had a significantly increased preference for low concentration of sucrose solution over water compared to wild‐type mice, and most importantly the transgenic mice were able to detect low concentrations of sucrose following vismodegib treatment. We evaluated taste cell morphology, identity, innervation and proliferation using immunohistochemistry. All drug‐treated mice exhibited deficits, but because of a possible functional upcycled priming of the peripheral gustatory system, GB mice demonstrated better morphological preservation of the peripheral gustatory system. Our study indicates that overexpression of BDNF in taste buds plays a role in preventing degeneration of taste buds. Counteracting the negative side effects of vismodegib treatment might improve compliance and achieve better outcome in patients suffering from advanced BCC.