bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Host Cell’s Endoplasmic Reticulum Proteostasis Network Profoundly Shapes the Protein Sequence Space Accessible to HIV Envelope
Authors: Yoon Jimin , Nekongo Emmanuel E. , Patrick Jessica E. , Phillips Angela M. , Ponomarenko Anna I. , Hendel Samuel J. , Butty Vincent L. , Brandon Ogbunugafor C. , Lin Yu-Shan , Shoulders Matthew D. 
Published: April 2021

AbstractThe sequence space accessible to evolving proteins can be enhanced by cellular chaperones that assist biophysically defective clients in navigating complex folding landscapes. It is also possible, however, for proteostasis mechanisms that promote strict quality control to greatly constrain accessible protein sequence space. Unfortunately, most efforts to understand how proteostasis mechanisms influence evolution rely on artificial inhibition or genetic knockdown of specific chaperones. The few experiments that perturb quality control pathways also generally modulate the levels of only individual quality control factors. Here, we use chemical genetic strategies to tune proteostasis networks via natural stress response pathways that regulate levels of entire suites of chaperones and quality control mechanisms. Specifically, we upregulate the unfolded protein response (UPR) to test the hypothesis that the host endoplasmic reticulum (ER) proteostasis network shapes the sequence space accessible to human immunodeficiency virus-1 (HIV) envelope (Env) protein. Elucidating factors that enhance or constrain Env sequence space is critical because Env evolves extremely rapidly, yielding HIV strains with antibody and drug escape mutations. We find that UPR-mediated upregulation of ER proteostasis factors, particularly those controlled by the IRE1-XBP1s UPR arm, globally reduces Env mutational tolerance. Conserved, functionally important Env regions exhibit the largest decreases in mutational tolerance upon XBP1s activation. This phenomenon likely reflects strict quality control endowed by XBP1s-mediated remodeling of the ER proteostasis environment. Intriguingly and in contrast, specific regions of Env, including regions targeted by broadly neutralizing antibodies, display enhanced mutational tolerance when XBP1s is activated, hinting at a role for host proteostasis network hijacking in potentiating antibody escape. These observations reveal a key function for proteostasis networks in decreasing instead of expanding the sequence space accessible to client proteins, while also demonstrating that the host ER proteostasis network profoundly shapes the mutational tolerance of Env in ways that could have important consequences for HIV adaptation.
An RNA-based feed-forward mechanism ensures motor switching in oskar mRNA transport
Authors: Gáspár Imre , Phea Ly Jane , McClintock Mark A. , Heber Simone , Bullock Simon L. , Ephrussi Anne 
Published: April 2021

ABSTRACTRegulated recruitment and activity of motor proteins is essential for intracellular transport of cargoes, including messenger ribonucleoprotein complexes (RNPs). Here we show that orchestration ofoskarRNP transport in theDrosophilagermline relies on the interplay of two double-stranded RNA binding proteins, Staufen and the dynein adaptor Egalitarian (Egl). We find that Staufen antagonizes Egl-mediated transport ofoskarmRNA by dynein bothin vitroandin vivo. Following delivery of nurse cell-synthesizedoskarmRNA into the oocyte by dynein, recruitment of Staufen to the RNPs results in dissociation of Egl and a switch to kinesin-1-mediated translocation of the mRNA to its final destination at the posterior pole of the oocyte. We additionally show that Egl associates withstaufen(stau)mRNA in the nurse cells, mediating its enrichment and translation in the ooplasm. Our observations identify a novel feed-forward mechanism, whereby dynein-dependent accumulation ofstaumRNA, and thus protein, in the oocyte enables motor switching onoskarRNPs by downregulating dynein activity.
Basal forebrain cholinergic neurons selectively drive coordinated motor learning in mice
Authors: Li Yue , Hollis Edmund 
Published: April 2021

AbstractMotor control requires precise temporal and spatial encoding across distinct motor centers that is refined through the repetition of learning. The coordination of circuit refinement across motor regions requires modulatory input to shape circuit activity. Here we identify a role for the basocortical cholinergic pathway in the acquisition of a coordinated motor skill in mice. Targeted depletion of basal forebrain cholinergic neurons results in significant impairments in training on the rotarod task of coordinated movement. Cholinergic neuromodulation is required during training sessions as chemogenetic inactivation of cholinergic neurons also impairs task acquisition. Rotarod learning drives coordinated refinement of corticostriatal neurons arising in both medial prefrontal cortex (mPFC) and motor cortex, and we have found that cholinergic input to both motor regions is required for task acquisition. Critically, the effects of cholinergic neuromodulation are restricted to the acquisition stage, as depletion of basal forebrain cholinergic neurons after learning does not affect task execution. Our results indicate a critical role for cholinergic neuromodulation of distant cortical motor centers during coordinated motor learning.
Brewers’ spent grain in food systems: Processing and final products quality as a function of fiber modification treatment
Authors: Naibaho Joncer , Korzeniowska Małgorzata 
Published: April 2021

AbstractThe nutritional properties of brewers’ spent grain (BSG) have been widely studied, considering its potential as a healthy food ingredient. Because of its fiber composition (amount and ratio), however, adding BSG into the food matrix to bring about changes in physical properties has been believed to impact negatively on the acceptability of the final products’ properties, particularly color and texture. Fiber modification can enhance the quality of fiber and can be applied to BSG. Although it appears challenging, modifying fiber composition requires further study, particularly if the acceptability of the final products is to be improved. Furthermore, the level of fiber degradation during the modification treatment needs to be examined to meet the increased demand for BSG in final food products. This concise synthesis provides a new perspective for increasing the use of BSG as a food ingredient that is characterized by high nutrition and acceptability.
Deployment of response surface methodology to optimize microencapsulation of peroxidases from turnip roots (Brassica rapa L.) by double emulsion in PLA polymer
Authors: Dahdouh Amel , Kati Djamel Edine , Bachir‐bey Mostapha , Aksas Ali , Rezgui Farouk 
Published: April 2021

AbstractIn order to improve the preservation conditions and stability of peroxidase catalytic properties, a number of immobilization techniques have been widely developed. In this context, we set as objective, the optimization of synthesis and stability of microcapsules of peroxidases (POD) from turnip using polylactic acid (PLA) polymer with the double emulsion technique. The surfactant, polymer, and peroxidase concentrations were the optimized parameters. According to the results obtained using the Box–Behnken design, the optimal parameters found were 1.55% of PVA, 55 mg/mL of peroxidases, and 30 mg/mL of PLA polymer with an encapsulation efficiency of 57.29%. The scanning electron microscopy morphological characterization of the optimized microcapsules showed a regular spherical structure. Fourier transform infrared spectroscopy identified the specific functional groups and chemical bonds before and after microencapsulation. The elaborated microcapsules were characterized by an average size of 200 µm (mainly from 150 to 500 µm) with a low residual moisture content (2.26%) and the encapsulated peroxidases showed better thermal stability. The in vitro release of peroxidases confirmed that the microcapsules have an excellent sustained release in simulated gastric digestion. Encapsulated peroxidases’ storage under 25 and 4 °C displays a good residual POD activity with about 60% of initial activities during 80 days of storage, whereas free POD losses its initial activity within 15 and 30 days, respectively. The obtained results are promising for the development of effective therapeutic treatment of some intestinal troubles due to oxidative stress.Practical ApplicationBrassica rapa L. root is well known for its richness on peroxidases and thus presents an interesting potential for developing high added value products. In order to preserve the activity of extracted peroxidases (POD) from turnip roots, microencapsulation was optimized using a polylactic acid polymer. The encapsulated POD showed the maintenance of its activity under the effect of different storage conditions (time and temperature) and demonstrated resistance to gastric acidity. According to the obtained results, the encapsulation of peroxidases opens up medicine and pharmaceutical applications such as intestinal and colic protection against inflammations.
Frailty and survival in elderly intensive care patients in Norway
Authors: Andersen Finn H. , Ariansen Haaland Øystein , Klepstad Pål , Flaatten Hans 
Published: April 2021

BackgroundToday, 10%‐15% of Norwegian intensive care patients are ≥80 years. This proportion will increase significantly over the next 20 years, but it is unlikely that resources for intensive care increase correspondingly. Thus, it is important to establish which patients among elderly people will benefit from intensive care. The main objective of the study was to investigate the relationships between geriatric scoring tools and 30‐day mortality.MethodsThe study included 451 Norwegian patients ≥80 years who were included in two prospective European observation studies (VIP (very old intensive care patient)1 of VIP2). Both studies included clinical frailty scale (CFS) while VIP2 also obtained the geriatric scores, comorbidity and polypharmacy score (CPS), Short Form of Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), and Katz Activity of Daily Living score (Katz ADL).ResultsSurvival after 30 days was 59.9%. Risk factors for 30‐day mortality were increasing Sequential Organ Failure Assessment (SOFA) score (odds ratio (OR) 1.30; confidence interval (CI) 95% 1.22‐1.39) and (CFS) > 3 (CFS 4: OR 1.96 (CI 95% 1.01‐3.81); CFS 5‐9: OR 1.81 (CI) 95% 1.12‐2.93)). Data from VIP2 showed that CFS was the only independent predictor of 30‐day mortality when these scores were tested in multivariate analyses separately together with age, SOFA, and gender (OR 1.21 (95% CI 1.03‐1.41)).ConclusionsElderly intensive care patients had a 30‐day survival rate of 59.9%. Factors strongly associated with 30‐day mortality were increasing SOFA score and increasing frailty (CFS). Other geriatric scores had no significant association with survival in multivariate analyses.
Lack of experience is a main cause of maternal death in placenta accreta spectrum patients
Authors: Nieto‐Calvache Albaro J. , Palacios‐Jaraquemada Jose M. , Osanan Gabriel , Cortes‐Charry Rafael , Aryananda Rozi A. , Bangal Vidyadhar B. , Slaoui Aziz , Abbas Ahmed M. , Akaba Godwin O. , Joshua Zaman N. , Vergara Galliadi Lina M. , Nieto‐Calvache Alejandro S. , Sanín‐Blair José E. , Burgos‐Luna Juan M ,   the Latin American group for the study of placenta accreta spectrum
Published: April 2021

AbstractIntroductionPlacenta accreta spectrum (PAS) is a serious condition with a mortality as high as 7%. However, the factors associated with this type of death have not been adequately described, with an almost complete lack of publications analyzing the determining factors of death in this disease. The aim of our work is to describe the causes of death related to PAS and to analyze the associated diagnosis and treatment problems.Material and methodsThis is an inter‐continental, multicenter, descriptive, retrospective study in low‐ and middle‐income countries. Maternal deaths related to PAS between January 2015 and December 2020 were included. Crucial points in the management of PAS, including prenatal diagnosis and details of the surgical treatment and postoperative management, were evaluated.ResultsEighty‐two maternal deaths in 16 low‐ and middle‐income countries, on three continents, were included. Almost all maternal deaths (81 cases, 98.8%) were preventable, with inexperience among surgeons being identified as the most relevant problem in the process that led to death among 87% (67 women) of the cases who had contact with health services. The main cause of death associated with PAS was hemorrhage (69 cases, 84.1%), and failures in the process leading to the diagnosis were detected among 64.6% of cases. Although the majority of cases received medical attention and 50 (60.9%) were treated at referral centers for severe obstetric disease, problems were identified during treatment in all cases.ConclusionsLack of experience and inadequate surgical technique are the most frequent problems associated with maternal deaths in PAS. Continuous training of interdisciplinary teams is critical to modify this tendency.
Assessment of surgeon and hospital volume for robot‐assisted and laparoscopic benign hysterectomy in Sweden
Authors: Brunes Malin , Forsgren Catharina , Warnqvist Anna , Ek Marion , Johannesson Ulrika 
Published: April 2021

AbstractIntroductionThe study aims to analyze differences between robot‐assisted total laparoscopic hysterectomy (RATLH) and total laparoscopic hysterectomy (TLH) in benign indications, emphasizing surgeon and hospital volume.Material and methodsAll women in Sweden undergoing a total hysterectomy for benign indications with or without a bilateral salpingo‐oophorectomy from January 1, 2015 to December 31, 2017 (n = 12 386) were identified from three national Swedish registers. Operative time, blood loss, conversion rate, complications, readmission, reoperation, length of hospital stays, and time to daily life activity were evaluated by univariable and multivariable regression models in RATLH and TLH. Surgeon and hospital volume were obtained from the Swedish National Quality Register of Gynecological Surgery and divided into subclasses.ResultsTLH was associated with a higher rate of intraoperative complications (adjusted odds ratios [aOR] 2.8, 95% CI 1.3–5.8) and postoperative bleeding complications (aOR 1.8, 95% CI 1.2–2.9) compared with RATLH. Intraoperative data showed a higher conversion rate (aOR 13.5, 95% CI 7.2–25.4), a higher blood loss (200–500 mL aOR 3.5, 95% CI 2.7–4.7; > 500 mL aOR 7.6, 95% CI 4.0–14.6) and a longer operative time (1–2 h aOR 16.7 95% CI 10.2–27.5; >2 h aOR 47.6, 95% CI 27.9–81.1) in TLH compared with RATLH. The TLH group had a lower caseload per year than the RATLH group. Higher surgical volume was associated with lower median blood loss, shorter operative time, a lower conversion rate, and a lower perioperative complication rate. Differences in conversion rate or operative time in RATLH were not affected by surgeon volume when compared with TLH. One year after surgery, patient satisfaction was higher in RATLH than in TLH (aOR 0.6, 95% CI 0.4–0.9).ConclusionsRATLH led to better perioperative outcome and higher patient satisfaction 1 year after surgery. These outcome differences were slightly more pronounced in very low‐volume surgeons but persisted across all surgeon volume groups.
Defining a minimal clinically meaningful difference in 12‐month estimated glomerular filtration rate for clinical trials in deceased donor kidney transplantation
Authors: Mayne Tracy J. , Nordyke Robert J. , Schold Jesse D. , Weir Matthew R. , Mohan Sumit 
Published: April 2021

AbstractBackgroundA Minimal Clinically Meaningful Difference (MCMD) has not been defined for Estimated glomerular filtration rate (eGFR). Our goal was to define the MCMD for eGFR anchored to kidney graft failure.MethodsA systematic review of studies with 12‐month eGFR and subsequent renal graft failure was conducted. For observational studies, we calculated hazard ratio (HR) differences between adjacent eGFR intervals weighted by population distribution. Interventional trials yielded therapeutically induced changes in eGFR and failure risk. OPTN data analysis divided 12‐month eGFR into bands for Cox regressions comparing adjacent eGFR bands with a death‐censored graft survival outcome.ResultsObservational studies indicated that lower eGFR was associated with increased death‐censored graft failure risk; each 5 ml/min/1.73 m2 12‐month eGFR band associated with a weighted incremental HR = 1.12 to 1.23. Clinical trial data found a 5 ml/min/1.73 m2 difference was associated with incremental HR = 1.16 to 1.35. OPTN analyses showed weighted mean HRs across 10, 7, and 5 ml/min/1.73 m2 bands of 1.47, 1.30, and 1.19.ConclusionsA 5 ml/min/1.73 m2 difference in 12‐month eGFR was consistently associated with ~20% increase in death‐censored graft failure risk. The magnitude of effect has been interpreted as clinically meaningful in other disease states and should be considered the MCMD in renal transplantation clinical trials.
Prevalence and correlates of alcohol dependence in an Australian Aboriginal and Torres Strait Islander representative sample: Using the Grog Survey App
Authors: Weatherall Teagan J. , Conigrave James H. , Conigrave Katherine M. , Perry Jimmy , Wilson Scott , Room Robin , Fitts Michelle S. , Hayman Noel , Lee K. S. Kylie 
Published: April 2021

AbstractIntroductionLittle is known about the prevalence of current alcohol dependence in Indigenous Australian communities. Here we identify the frequency of reported symptoms, estimate the prevalence and describe the correlates of current alcohol dependence.MethodsA representative sample of Indigenous Australians (16+ years) was recruited from an urban and remote community in South Australia. Data were collected between July and October 2019 via a tablet computer‐based application. Participants were likely dependent if they reported two or more dependence symptoms (ICD‐11; in the last 12 ‐months), weekly or more frequently. Chi‐square tests described the relationship between demographics, remoteness and alcohol dependence. Spearman correlations estimated the relationship between symptoms of dependence, consumption characteristics and demographics.ResultsA total of 775 Indigenous Australians participated. The most frequently reported symptoms were prioritising alcohol over other things and loss of control. Overall, 2.2% were likely dependent on alcohol (n = 17/775). Prevalence did not vary by remoteness. Participants who drank more and more frequently tended to report more frequent symptoms of dependence. In the urban site, men tended to report more frequent symptoms of dependence than women. Age, income and schooling were not linked to dependence.Discussion and ConclusionsThe prevalence of current alcohol dependence in this representative sample was similar to that of the general Australian and international estimates. Understanding risk factors for current alcohol dependence will be useful to inform the allocation of funding and support. Accurate estimates of the prevalence of current alcohol dependence are important to better identify specialist treatment needs.
Association between abnormal body weight and stroke outcome: A meta‐analysis and systematic review
Authors: Zhang Peng , Yan Xiu‐Li , Qu Yang , Guo Zhen‐Ni , Yang Yi 
Published: April 2021

AbstractBackground and purposeTo test the hypothesis that “obesity paradox” exists in stroke patients, we conducted a meta‐analysis and systematic review on the association between abnormal body weight (obesity, overweight, or underweight) and the outcome of different types of stroke.MethodsThis meta‐analysis and systematic review was performed in conformity to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analysis) guidelines in Appendix S2. Studies investigating the association between abnormal body weight and the outcome of different types of stroke were searched for in the PubMed and Embase databases from their inception to 20 March 2021.ResultsThirty‐three articles including 84,660 patients were included in this study. Obesity and overweight were associated with longer survival in mixed‐stroke patients (acute ischemic stroke [AIS] combined with one or more other stroke subtypes) than was normal weight, whereas underweight was related to shorter survival; the pooled hazard ratios (HRs) of mortality were 0.77 (95% confidence interval [CI] = 0.71–0.83) for obesity, 0.76 (95% CI = 0.72–0.80) for overweight, and 1.71 (95% CI = 1.56–1.87) for underweight. However, only obesity was associated with longer survival in AIS patients compared with normal weight, and underweight was related to shorter survival; the pooled HR of mortality was 0.75 (95% CI = 0.64–0.88) for obesity and 1.53 (95% CI = 1.27–1.85) for underweight. After merging mixed‐stroke and AIS patients, we obtained similar results as in mixed‐stroke patients.ConclusionsOur results suggested that in patients with mixed stroke or AIS, obesity was associated with a longer survival time than normal weight, whereas underweight was associated with a shorter survival time.
When workload predicts exposure to bullying behaviours in nurses: The protective role of social support and job recognition
Authors: Trépanier Sarah‐Geneviève , Peterson Clayton , Fernet Claude , Austin Stéphanie , Desrumaux Pascale 
Published: April 2021

AbstractAimsThis study examined the moderating role of two resources (social support and recognition) in the longitudinal relationship between workload and bullying behaviours in nurses.DesignA two‐wave (12‐month) longitudinal study was conducted.MethodFrench‐Canadian nurses (n = 279) completed an online survey (October 2014 and October 2015) assessing their perceptions of job characteristics within the work environment (workload, social support, job recognition) as well as exposure to negative behaviours at work.ResultsWorkload positively predicted exposure to bullying behaviours over time, but only when job recognition and social support were low. Workload was unrelated to bullying when social support was high and was negatively related to bullying when job recognition was high.ConclusionThis study aligns with the work environment hypothesis, showing that poorly designed and stressful job environments provide fertile ground for bullying behaviours.ImpactBullying is a growing concern in the nursing profession that not only undermines nurses’ well‐being but also compromises patient safety and care. It is thus important to identify work‐related factors that can contribute to the presence of bullying behaviours in nurses in the hopes of reducing their occurrence and repercussions. This study contributes to this endeavour and identifies two key social coping resources that can help manage the stress associated with workload, resulting in less perceived bullying behaviour among nurses.