bluuebunny/crossref_metadata_2025 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

The 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

Regulated 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

Motor 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

The 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

In 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 Application

Brassica 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

Background

Today, 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.

Methods

The 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).

Results

Survival 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)).

Conclusions

Elderly 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

Introduction

Placenta 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 methods

This 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.

Results

Eighty‐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.

Conclusions

Lack 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

Introduction

The 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 methods

All 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.

Results

TLH 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).

Conclusions

RATLH 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

Background

A 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.

Methods

A 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.

Results

Observational 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.

Conclusions

A 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

Introduction

Little 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.

Methods

A 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.

Results

A 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 Conclusions

The 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

Background and purpose

To 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.

Methods

This 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.

Results

Thirty‐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.

Conclusions

Our 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

Aims

This study examined the moderating role of two resources (social support and recognition) in the longitudinal relationship between workload and bullying behaviours in nurses.

Design

A two‐wave (12‐month) longitudinal study was conducted.

Method

French‐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.

Results

Workload 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.

Conclusion

This study aligns with the work environment hypothesis, showing that poorly designed and stressful job environments provide fertile ground for bullying behaviours.

Impact

Bullying 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.
Lymphogranuloma venereum: a retrospective analysis of an emerging sexually transmitted disease in a Lisbon Tertiary Center
Authors: Neves J.M. , Ramos Pinheiro R. , Côrte‐Real R. , Borrego M.J. , Rodrigues A. , Fernandes C.
Published: April 2021

Background

Lymphogranuloma venereum (LGV) is a sexual transmitted infection (STI), currently endemic within the population of men who have sex with men (MSM) of Western Countries. L2B variant has been reported as the predominant strain in the current LGV epidemics, although a shift towards L2‐434 has been observed in some European countries.

Objectives

To evaluate and characterize the population with LGV infection diagnosed in Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal.

Methods

A retrospective analysis of all LGV diagnoses between 2016 and 2019 was performed. The diagnosis was established through ompA‐genotyping of samples yielding a positive result to Chlamydia trachomatis (CT). All considered samples were retrieved from the clinician activity, through swabbing and urine analysis and CT infection diagnosis was obtained using real‐time PCR.

Results

During the period studied 16 279 CT diagnostics tests were employed, with a striking increase from 2016 (n = 467) to 2019 (n = 9362). A total of 1602 diagnoses of CT were established, from which 168 (10.5%) corresponded to LGV, with both infections showing a rising evolution, between 2016 and 2019, of 2.9 and 2.7 times, respectively. The majority of the LGV strains were genotyped as L2/434 (67.3%; n = 113). LGV predominantly affected MSM and men who have sex with men and women (97.0%; n = 163). Anorectal infection was the most prevalent one (90.5%; n = 152), being proctitis the main clinical presentation (76.2%; n = 128). Absence of symptoms was reported in almost 15% of the cases (n = 24). The presence of concomitant infection with human immunodeficiency virus was dominant (73.2%; n = 123) and the prevalence of one or more STI co‐infections was about 60.1% (n = 99).

Conclusions

An increasing evolution of CT and LGV testing and diagnosing was observable throughout the studied period. Characteristics of the population are similar with those described within LGV epidemics. In accordance with recent European studies, predominance towards L2 genotype was identified.
Coexistence of bullous pemphigoid with neuropsychiatric comorbidities is associated with anti‐BP230 seropositivity
Authors: Ständer S. , Hammers C.M. , Vorobyev A. , Schmidt E. , Hundt J.E. , Sadik C.D. , Lange T. , Zillikens D. , Ludwig R.J. , Kridin K.
Published: April 2021

Background

While clustering of bullous pemphigoid (BP) with neuropsychiatric diseases is well‐established, the clinical and immunological profile of BP patients with this comorbidity remains to be decisively determined.

Objectives

To evaluate the burden of neurological and psychiatric comorbidities among patients with BP and to elucidate the clinical, immunological and immunopathological features of patients with BP and comorbid neuropsychiatric conditions.

Methods

We performed a retrospective study encompassing patients diagnosed with BP throughout the years 2009–2020 in a specialized tertiary referral centre. Multivariate logistic regression model was used to identify predictors of neuropsychiatric conditions among patients with BP.

Results

The study included 273 patients with BP, of whom 123 (45.1%) presented with comorbid neuropsychiatric disease. Compared to the remaining patients with BP (n = 150), those with pre‐existing neuropsychiatric diseases demonstrated older mean [standard deviation (SD)] age [81.7 (9.1) vs. 76.9 (10.1); P < 0.001], female preponderance (65.0% vs. 49.3%; P = 0.009), higher seropositivity rate of anti‐BP230 (67.7% vs. 36.5%; P = 0.006) and higher levels of anti‐BP180 NC16A IgG [651.3 (1279.6) vs. 370.4 (818.6) U/mL; P = 0.039]. In multivariate analysis, anti‐BP230 seropositivity was independently associated with coexistence of BP with neuropsychiatric conditions [adjusted odds ratio (OR), 3.43; 95% CI, 1.24–9.52; P = 0.018]. In a sensitivity analysis confined to patients with neurological diseases (n = 103), older age [82.1 (8.4) vs. 77.2 (10.3); P < 0.001] and increased anti‐BP230 seropositivity (68.0% vs. 39.7%; P = 0.018) were identified.

Conclusions

The coexistence of BP with neuropsychiatric diseases is independently associated with the generation of anti‐BP230 antibodies.
Comparative analysis of the superoxide dismutase gene family in Cetartiodactyla
Authors: Tian Ran , Geng Yuepan , Guo Han , Yang Chen , Seim Inge , Yang Guang
Published: April 2021

Cetacea, whales, dolphins and porpoises form an order of mammals adapted to aquatic life. Their transition to an aquatic habitat resulted in exceptional protection against cellular insults, including oxidative and osmotic stress. Here, we considered the structure and molecular evolution of the superoxide dismutase (SOD) gene family, which encodes essential enzymes in the mammalian antioxidant system, in the superorder Cetartiodactyla. To this end, we juxtaposed cetaceans and their closest extant relatives (order Artiodactyla). We identified 94 genes in 23 species, of which 70 are bona fide intact genes. Although the SOD gene family is conserved in Cetartiodactyla, lineage‐specific gene duplications and deletions were observed. Phylogenetic analyses show that the SOD2 subfamily diverged from a clade containing SOD1 and SOD3, suggesting that cytoplasmic, extracellular and mitochondrial SODs have started down independent evolutionary paths. Specific‐amino acid changes (e.g. K130N in SOD2) that may enhance ROS elimination were identified in cetaceans. In silico analysis suggests that the core transcription factor repertoire of cetartiodactyl SOD genes may include Sp1, NF‐κB, Nrf2 and AHR. Putative transcription factors binding sites responding to hypoxia were (e.g. Suppressor of Hairless; Su(H)) found in the cetacean SOD1 gene. We found significant evidence for positive selection in cetaceans using codon models. Cetaceans with different diving abilities also show divergent evolution of SOD1 and SOD2. Our genome‐wide analysis of SOD genes helps clarify their relationship and evolutionary trajectory and identify putative functional changes in cetaceans.
Efficacy and safety of peginterferon alpha monotherapy in Chinese inactive chronic hepatitis B virus carriers
Authors: Wu Fengping , Lu Rui , Liu Yixin , Wang Yikai , Tian Yan , Li Yaping , Li Mei , Wang Wenjun , Zhang Xin , Jia Xiaoli , Dang Shuangsuo
Published: April 2021

Background & Aims

The effectiveness and safety of peginterferon alpha (peg‐IFN‐α) monotherapy in inactive hepatitis B virus (HBV) carriers (IHCs) have not been fully evaluated.

Methods

This observational study prospectively enrolled 298 IHCs in China from 2015 to 2019. Participants were given the right to choose to either receive peg‐IFN‐α monotherapy (treatment group, n = 142) or be monitored without treatment (control group, n = 156) according to their wishes. The scheduled treatment duration was 48 weeks. All participants were followed up to 72 weeks. The main efficacy endpoint was hepatitis B surface antigen (HBsAg) clearance at 72 weeks.

Results

Baseline characteristics were similar between both groups. At 72 weeks, intention‐to‐treat analysis showed that the rates of HBsAg clearance and seroconversion of the treatment group were 47.9% (68/142) and 36.6% (52/142), respectively, which were significantly higher than the HBsAg clearance rate of 1.9% (3/156) and the seroconversion rate of 0.6% (1/156) in the control group (both P < .001). Baseline HBV DNA < 20 IU/mL, lower HBsAg levels at baseline, 12 and 24 weeks, alanine aminotransferase elevation at 12 weeks, and greater HBsAg reduction from baseline to 12 and 24 weeks were independent predictors of HBsAg clearance. Generally, the therapy was well tolerated. Only five participants discontinued therapy as a result of peg‐IFNα‐related adverse events.

Conclusions

Peg‐IFN‐α monotherapy results in high rates of HBsAg clearance and seroconversion and the treatment is safe for IHCs.
Definite and indeterminate nonalcoholic steatohepatitis share similar clinical features and prognosis: A longitudinal study of 1893 biopsy‐proven nonalcoholic fatty liver disease subjects
Authors: Ampuero Javier , Aller Rocío , Gallego‐Durán Rocío , Crespo Javier , Abad Javier , González‐Rodríguez Águeda , Gómez‐Camarero Judith , Caballería Joan , Lo Iacono Oreste , Ibañez Luis , García‐Samaniego Javier , Martín‐Mateos Rosa , Francés Rubén , Fernández‐Rodríguez Conrado , Diago Moisés , Soriano Germán , Andrade Raúl J. , Latorre Raquel , Jorquera Francisco , Morillas Rosa M. , Escudero Desam , Estévez Pamela , Hernández‐Guerra Manuel , Augustín Salvador , Pareja‐Megia María Jesús , Banales Jesús M. , Aspichueta Patricia , Benlloch Salvador , Rosales José Miguel , Salmerón Javier , Turnes Juan , Romero‐Gómez Manuel ,   HEPAmet Registry
Published: April 2021

Background and Aim

Histological score systems may not fully capture the essential nonalcoholic steatohepatitis (NASH) features, which is one of the leading causes of screening failure in clinical trials. We assessed the NASH distribution and its components across the fibrosis stages and their impact on the prognosis and their relationship with the concept of metabolic‐associated fatty liver disease (MAFLD).

Methods

Spanish multicenter study including 1893 biopsy‐proven nonalcoholic fatty liver disease (NAFLD) patients from HEPAmet registry. NASH was diagnosed by NAS score ≥4 (including steatosis, ballooning and lobular inflammation) and fibrosis by Kleiner score. The presence of MAFLD was determined. Progression to cirrhosis, first episode of decompensated cirrhosis and death were collected during the follow‐up (4.7 ± 3.8 years).

Results

Fibrosis was F0 34.3% (649/1893), F1 27% (511/1893), F2 16.5% (312/1893), F3 15% (284/1893) and F4 7.2% (137/1893). NASH diagnosis 51.9% (982/1893), and its individual components (severe steatosis, ballooning and lobular inflammation), increased from F0 (33.6%) to F2 (68.6%), and decreased significantly in F4 patients (51.8%) (P = .0001). More than 70% of non‐NASH patients showed some inflammatory activity (ballooning or lobular inflammation), showing a similar MAFLD rate than NASH (96.2% [945/982] vs. 95.2% [535/562]) and significantly higher than nonalcoholic fatty liver (NAFL) subjects (89.1% [311/349]) (P < .0001). Progression to cirrhosis was similar between NASH (9.5% [51/539]) and indeterminate NASH (7.9% [25/316]), and higher than steatosis (5% [14/263]) (logRank 8.417; P = .015). Death and decompensated cirrhosis were similar between these.

Conclusions

The prevalence of steatohepatitis decreased in advanced liver disease. However, most of these patients showed some inflammatory activity histologically and had metabolic disturbances. These findings should be considered in clinical trials whose main aim is to prevent cirrhosis progression and complications, liver transplant and death.
Incidence and mortality of COVID‐19‐associated pulmonary aspergillosis: A systematic review and meta‐analysis
Authors: Mitaka Hayato , Kuno Toshiki , Takagi Hisato , Patrawalla Paru
Published: April 2021

COVID‐19‐associated pulmonary aspergillosis (CAPA) has been reported worldwide. However, basic epidemiological characteristics have not been well established. In this systematic review and meta‐analysis, we aimed to determine the incidence and mortality of CAPA in critically ill patients with COVID‐19 to improve guidance on surveillance and prognostication. Observational studies reporting COVID‐19‐associated pulmonary aspergillosis were searched with PubMed and Embase databases, followed by an additional manual search in April 2021. We performed a one‐group meta‐analysis on the incidence and mortality of CAPA using a random‐effect model. We identified 28 observational studies with a total of 3148 patients to be included in the meta‐analysis. Among the 28 studies, 23 were conducted in Europe, two in Mexico and one each in China, Pakistan and the United States. Routine screening for secondary fungal infection was employed in 13 studies. The modified AspICU algorithm was utilised in 15 studies and was the most commonly used case definition and diagnostic algorithm for pulmonary aspergillosis. The incidence and mortality of CAPA in the ICU were estimated to be 10.2% (95% CI, 8.0–12.5; I2 = 82.0%) and 54.9% (95% CI, 45.6–64.2; I2 = 62.7%), respectively. In conclusion, our estimates may be utilised as a basis for surveillance of CAPA and prognostication in the ICU. Large, prospective cohort studies based on the new case definitions of CAPA are warranted to validate our estimates.
Respiratory syncytial virus and airway microbiota – A complex interplay and its reflection on morbidity
Authors: Rossi Giovanni A. , Ballarini Stefania , Silvestri Michela , Sacco Oliviero , Colin Andrew A.
Published: April 2021

The immunopathology of respiratory syncytial virus (RSV) infection varies considerably, severe disease occurring only in a minority of the affected children. The variability of the clinical presentation is in part explained by viral and environmental factors but, in infants and young children, disease severity is certainly linked to the physiologic immaturity of the innate and adaptive immune system. There is evidence that the maturation of the host immune response is positively influenced by the composition of the nasopharyngeal microbiome that, promoting an efficient reaction, can counteract the predisposition to develop viral respiratory infections and lower the risk of disease severity. However, interaction between the nasopharyngeal microbiota and respiratory viruses can be bidirectional since microbial dysbiosis may also represent a reflection of the disease‐induced alterations of the local milieu. Moreover, viruses like RSV can also increase the virulence of potential pathogens in nasopharynx, a main reservoir of bacteria, and therefore promote their spread to the lower airways causing superinfection. Moreover, if negative changes in microbial community composition in early life may constitute a heightened risk toward severe RSV respiratory infection, on the contrary specific groups of microorganisms seem to be associated with protection. A better understanding into the potential negative and positive role of the different nasopharyngeal bacterial species on RSV infection may improve primary prevention and possibly care of this highly contagious disorder.
Metal‐Catalyzed Hydride Transfer from Alcohols to Photoexcited Dipyridophenazine†
Authors: Aslan Joseph M. , Reardon Melissa M. , Alatrash Nagham , Nastasi Francesco , MacDonnell Frederick M.
Published: April 2021

Dipyridophenazine (dppz) is known to react with alcohols upon photoexcitation into an n‐π* transition at 378 nm to yield dihydrodipyridophenazine (dppzH2). This process occurs via H‐atom abstraction from alcohols and subsequent disproportionation of the dppzH• radical species, to the final product. This reaction shows a primary kinetic isotope effect (KIE = 4.9) in methanol/perdeuteromethanol solvents, consistent with H‐atom transfer processes. Addition of excess Zn(II) ions to the dppz solution not only accelerates the rate of photoreduction, but also lowers the KIE to 1.7, indicating a change in reaction mechanism. We postulate that the coordination of the alcoholic solvent to Zn(II) activates the alcohol α C‐H bonds toward hydride transfer processes which would be consistent with the lowered KIE and faster overall reduction of the aromatic ligand. Interestingly, this appears to be an intramolecular process in which the Zn(II) is coordinated to both the dppz ligand and the reactive alcohol, as a sharp inflection in the overall rate increase is observed at a Zn:dppz ratio of 2:1. At this ratio, the dominant dppz species involves a Zn(II) bound to one dppz and several solvent molecules (methanol and water).
Severe leg swelling following removal of a temporary femoral venous hemodialysis catheter
Authors: Gunawardena Thilina , Subramaniyam Prasath , Cassim Rezni , Wijeyaratne Mandika
Published: April 2021

Temporary central venous catheters are commonly used for patients who require emergency hemodialysis (HD). An arteriovenous fistula (AVF) is a rare complication of this procedure. In this case report, we present a patient who was diagnosed with an iatrogenic femoral AVF after cannulation of the right femoral vein with a temporary HD catheter.
The Morphosyntax of Magahi Addressee Agreement
Authors: Alok Deepak
Published: April 2021

This article analyzes addressee agreement (allocutive agreement) in Magahi, an Eastern Indo‐Aryan language. Magahi finite verbs encode the honorificity (social status) of the addressee, in addition to encoding the person and honorificity of the subject. Magahi addressee agreement is special in two respects. First, it is associated with finiteness: it is available in all finite clauses, main and embedded. Second, addressee agreement and subject honorification combine features for spellout, indicating that heads involved in both phenomena are syntactically adjacent. I claim that the covert syntactically expressed representation of the addressee, which undergoes addressee agreement, is relatively low in the clause structure: it is a coordinate of FinP, the layer just above TP. I further propose that the functional head associated with Magahi addressee agreement is the Fin head. The proposal diverges from previous analyses, in which the locus of addressee agreement is the highest projection of a clause (Speech Act Phrase or Context Phrase), found primarily in root clauses. This study implies that the addressee is syntactically present in every finite clause. Crosslinguistic differences (e.g., root–embedded asymmetries) depend on what syntactic category acts as a probe in a language.
Bovine major histocompatibility complex (BoLA) heterozygote advantage against the outcome of bovine leukemia virus infection
Authors: Lo Chieh‐Wen , Takeshima Shin‐nosuke , Wada Satoshi , Matsumoto Yasunobu , Aida Yoko
Published: April 2021

Bovine leukemia virus (BLV) causes enzootic bovine leucosis. Host genetic heterozygosity at the major histocompatibility complex can enhance the ability to combat infectious diseases. However, heterozygote advantage is loci specific and depends on disease type. Bovine leukocyte antigen (BoLA)‐DRB3 polymorphisms are related with BLV‐infection outcome; however, whether BoLA‐DRB3 heterozygotes have an advantage against BLV‐induced lymphoma and proviral load (PVL) remains unclear. By analyzing 1567 BLV‐infected individuals, we found that BoLA‐DRB3 heterozygous status was significantly associated with lymphoma resistance irrespective of cattle breeds (p < 0.0001). Similarly, decreased PVL was observed in BoLA‐DRB3 heterozygotes (p = 0.0407 for Holstein cows; p = 0.0889 for Japanese Black cattle). Our report provides first evidence of BoLA‐DRB3 heterozygote advantage against BLV infection outcome.
Clinical presentation and outcomes of COVID‐19 following hematopoietic cell transplantation and cellular therapy
Authors: Camargo Jose F. , Mendoza Maria A. , Lin Rick , Moroz Ilona V. , Anderson Anthony D. , Morris Michelle I. , Natori Yoichiro , Natori Akina , Raja Mohammed , Lekakis Lazaros , Beitinjaneh Amer , Jimenez Antonio , Goodman Mark , Wang Trent , Komanduri Krishna V. , Pereira Denise
Published: April 2021

Background

One year into the pandemic, published data on hematopoietic cell transplantation (HCT) recipients with coronavirus disease 2019 (COVID‐19) remain limited.

Methods

Single‐center retrospective cohort study of adult HCT recipients with polymerase chain reaction (PCR)‐confirmed severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection.

Results

Twenty‐eight consecutive transplantation and cellular therapy patients (autologous, n = 12; allogeneic, n = 15; chimeric antigen receptor T‐cell therapy [CAR‐T], n = 1) with COVID‐19 were identified. The median age was 57 years. The median time from HCT to COVID‐19 diagnosis was 656 days (interquartile range [IQR], 33‐1274). Patients were followed for a median of 59 days (IQR, 40‐88). Among assessable patients (n = 19), 10 (53%) had documented virological clearance; median time to clearance was 34 days (range, 21‐56). Out of 28, 12 (43%), 6 (21%), and 10 (36%) patients had mild, moderate, and severe/critical disease, respectively. Overall mortality was 25%, nearly identical for autologous and allogeneic HCT, and exclusively seen in hospitalized patients, older than 50 years of age with severe COVID‐19. None of the patients with mild (n = 12) or moderate (n = 6) COVID‐19 died whereas 7/10 patients (70%) with severe/critical COVID‐19 died (P = .0001). Patients diagnosed with COVID‐19 within 12 months of HCT exhibited higher mortality (57% vs 14%; P = .04). All‐cause 30‐day mortality (n = 4) was 14%. A higher proportion of patients who died within 30 days of COVID‐19 diagnosis (3/4) were receiving ≥2 immunosuppressants, compared with patients who survived beyond 30 days after COVID‐19 diagnosis (2/24; 75% vs. 8%; P = .01).

Conclusions

Mortality in COVID‐19 HCT patients is higher than that of the age‐comparable general population and largely dependent on age, disease severity, timing from HCT, and intensity of immunosuppression.
ANTI-QUORUM SENSING AND ANTIBIOTIC ENHANCEMENT OF ALLYLPYROCATECHOL AND METHYL GALLATE
Authors: Lim Carine S. S. , W. C. Chan Eric , Wong C.  W. , Tan Joash B. L. , Anggraeni V. S. , Loong Z.  J. , Teo Y. K.
Published: April 2021

In this study, the antibiotic enhancement and quorum sensing (QS) inhibition of allylpyrocatechol (APC) and methyl gallate (MG) isolated from leaves of Piper betle (betel) and leaf shoots of Anacardium occidentale (cashew), respectively, were compared. When applied with streptomycin and tested against Staphylococcus aureus and Pseudomonas aeruginosa, the effect of APC was additive while that of MG was synergistic. In terms of QS inhibition against Chromobacterium violaceum, both compounds were equally effective with violacein inhibition observed at concentrations of 60 μg/mL. We successfully increased the purity of APC in the methanol betel leaf extract from 13.2% to 31.5% w/w through solvent partitioning. This study is the first to document the anti-QS activity of APC, which is comparable to that of MG.
EVOLUTIONS IN VIRGIN COCONUT OIL: LIQUID TO POWDER
Authors: Aman Nor Nor Farahiyah , Ya’akob Harisun , Ngadiran Sulaiman , Idris Ani , Shamsul Anuar Nurarbainah , Sarmidi Mohamad Roji
Published: April 2021

Awareness of virgin coconut oil (VCO) as a functional food supplement has grown enormously. The treatment of raw material and processing parameters is crucial as they affect the overall yield and quality of the oil. Meanwhile, the microencapsulation technology offers better handling, good oxidative stability, and longer shelf life of the VCO powder. Although good quality liquid and powdered oils can be obtained through sophisticated methods, the process involved is expensive and required high maintenance. By utilising dry kernel and coconut milk-based extractions methods, high-grade quality of VCO can be achieved. During microencapsulation, the spray drying method can preserve the phenolic and antioxidant compounds and maintain the low rancidity of the VCO. This paper evaluates the recent findings of the oil extraction methods and the development of VCO microencapsulation. These methods offer good quality, reproducible and economic viability.
EVALUATING SURFACE WATER QUALITY AND WATER MONITORING PARAMETERS IN THE TIEN RIVER, VIETNAMESE MEKONG DELTA
Authors: Nguyen Thanh Giao , Minh Vo Quang
Published: April 2021

The study aimed to evaluate the surface water quality of the Tien River and identify water quality parameters to be monitored using the water quality monitoring data in the period of 2011 - 2019. The water samples were collected at five locations from Tan Chau to Cho Moi districts, An Giang province for three times per year (i.e., in March, June, and September). Water quality parameters included temperature (oC), pH, dissolved oxygen (DO), total suspended solids (TSS), nitrate (NO3--N), orthophosphate (PO43--P), biological oxygen demand (BOD), and coliforms. These parameter results were compared with the national technical regulation on surface water quality QCVN 08-MT: 2015/BTNMT, column A1. Principal component analysis (PCA) was used to identify the sources of pollution and the main factors affecting water quality. The results of this study showed that DO concentration was lower and TSS, BOD, PO43--P, coliforms concentrations in the Tien river exceeded QCVN 08-MT: 2015/BTNMT, column A1. pH, temperature, and NO3--N values were in accordance with the permitted regulation. The water monitoring parameters were seasonally fluctuated. DO, BOD, TSS, and coliforms concentrations were higher in the rainy season whereas NO3--N and PO43--P were higher in the dry season. The PCA results illustrated that pH, TSS, DO, BOD, PO43--P and coliforms should be included in the monitoring program. Other indicators such as temperature and NO3--N could be considered excluded from the program to save costs.