bluuebunny/crossref_metadata_2025 huggingface dataset:
Stillbirth in Khayelitsha Hospital, South Africa: Women's Experiences of Care
Authors: Lappeman Maura , Swartz Leslie
Published: March 2022

In this study we explore the hospital care experience of women following stillbirths in an impoverished urban setting in the Western Cape Province of South Africa. A qualitative research methodology was used with the collection of primary data using the Free Association Narrative Interview Method with 10 women who experienced stillbirths at a government hospital. The study found that the women generally felt well looked after medically, but also felt an emotional disconnect from, and a need to be seen by, the medical staff. A stillbirth can confront both the woman and the clinician with their own helplessness. Without attention to the emotional needs of the staff, who seemed to be offering optimal care within their capacity, it is unlikely that the staff will be able to provide fully accessible emotional care for the women. The stories told to us by our participants suggest that more expenditure on the emotional needs of caregivers in the health system may contribute to a more emotionally accessible, sustainable workforce.
Factors in workers’ dehumanization: Multiple stigmatization, social status, and workers’ sex
Authors: Agadullina Elena R. , Terskova Maria A. , Erokhina Daria A. , Ankushev Vladislav V.
Published: February 2022

The aim of this study is to examine how different factors (multiple stigmatization, perceived social status, and workers’ sex) as well as their interactions are associated with the dehumanization of workers. In the preliminary study (N = 991), we selected 16 occupations with different types of stigmatization and perceived status relevant to the Russian socio‐cultural context. In two experimental studies (N1 = 1060, N2 = 1081), we demonstrated that multiple stigmatization increases metaphor‐based and attribute‐based animalistic but not mechanistic dehumanization: low‐status workers were more animalistically dehumanized than high‐status workers; the high status decreased the metaphor‐based animalistic dehumanization of occupations with multiple stigmatization, and the attribute‐based animalistic and mechanistic dehumanization of workers regardless of their stigmatization; and male workers were more mechanistically dehumanized than female ones but there were no differences in animalistic dehumanization. The results obtained are discussed in the context of understanding the specificity of workers’ dehumanization and the possible consequences of this dehumanization.
Bioprosthetic mitral valve stenosis secondary to hypereosinophilic syndrome
Authors: Quan Xin , Song Yunhu , Wang Hongyue , Yang Sun , Zhu Zhenhui
Published: February 2022

Herein we present a case of hypereosinophilic syndrome (HES) with recurrent involvement of mitral valve. The patient developed mitral regurgitation secondary to HES. Surgical mitral valve replacement was performed successfully. The prosthetic valve dysfunction occurred 3 years later and echocardiography showed severe mitral valve stenosis. Extensive mural thrombi were discovered on both sides of the stenotic valve with eosinophilic infiltration. The patient underwent a repeated mechanical prosthesis replacement and recovered uneventfully.
Understanding HAIs: Ally proteins in the fight against cancer
Authors: Nonboe Annika W. , Bald Zuzanna H. , Vogel Lotte K.
Published: February 2022

Understanding how HAI‐1 and HAI‐2 regulate the epithelial serine protease matriptase may hold the key to curing epithelial‐derived cancer. HAIs are serine protease inhibitors that inhibit matriptase and have a poorly understood effect on the presence of matriptase protein in cells. In this issue of The FEBS Journal, Yamashita et al. provide much‐needed new insights into this effect, describing it as a ‘chaperone‐like function’ of HAI‐1. However, several observations suggest that matriptase folds correctly without HAIs and that HAIs are not chaperones. We introduce the concept of ‘ally proteins’ to categorize the poorly understood function of HAIs, distinguishing them from chaperones.

Comment on: https://doi.org/10.1111/febs.16348
Pfprex from Plasmodium falciparum can bypass oxidative stress‐induced DNA lesions
Authors: Sharma Minakshi , Nair Deepak T.
Published: February 2022

Apicomplexans such as the malaria parasite Plasmodium falciparum possess a unique organelle known as the apicoplast that has its own circular genome. The apicoplast genome is AT rich and is subjected to oxidative stress from the byproducts of the normal biochemical pathways that operate in the apicoplast. It is expected that oxidative stress will lead to the appearance of DNA lesions such as 2‐hydroxydeoxyadenine, thymine glycol, and 8‐oxodeoxyguanine in the apicoplast genome. The apicoplast genome is replicated by the DNA polymerase activity present in the Pfprex enzyme. We have named the polymerase module of Pfprex as PfpPol and the enzyme belongs to the A family of DNA polymerases. Similar to other members of this family, PfpPol also exhibits high fidelity of DNA synthesis. We show that this enzyme is also capable of carrying out translesion DNA synthesis past common DNA lesions that arise due to oxidative stress. The residues N505 and Y509 from the fingers sub‐domain, which are unique to PfpPol, play an important role in the ability of PfpPol to bypass the three lesions. The observed lesion‐bypass ability of the Pfprex enzyme will minimize the adverse effects of oxidative stress on the apicoplast genome of the malaria parasite. These findings also have implications regarding the evolution of the machinery responsible for replication of organellar genomes.
Quantifying past, current, and future forest carbon stocks within agroforestry systems in central Alberta, Canada
Authors: An Zhengfeng , Bork Edward W. , Duan Xinyi , Gross Cole D. , Carlyle Cameron N. , Chang Scott X.
Published: February 2022

Information about regional‐level carbon (C) stocks in agroforestry systems (AFS), as well as the annual loss of agroforests and associated C stocks, is scarce, limiting our capacity for increasing C sequestration through establishing, retaining, and enhancing these systems. This study quantified regional‐level C stocks and the associated incremental economic value in the forest land‐use component of three common AFS (hedgerows, shelterbelts, and silvopastures), estimated the annual loss of hedgerow and silvopasture forests and the associated C, and assessed the potential to enhance C storage through the expansion of shelterbelts in central Alberta, Canada, using publicly available satellite imagery, previously collected field data and the Google Earth Engine platform. Results showed that forests in the three AFS stored 699.9 million tons (Mt) C across 9.5 million hectares (Mha) of land in central Alberta and were valued at $102.7 billion based on the 2021 Canadian C tax rate of $40 t−1 CO2‐equivalent. Silvopasture forests in the studied region had the highest C stocks, which were 14.2 and 67.2 times that found in hedgerow and shelterbelt forests, respectively. Between 2001 and 2020, forests in hedgerows and silvopastures declined at rates of 468.1 and 1957.1 ha year−1, respectively, leading to an 8.4 Mt decline in total C storage over the 20 years. However, there is potential to establish new shelterbelts at many road/field margins, which could increase C stocks by 2.3 times the current C stocks in shelterbelt forests. These results highlight the importance of retaining existing and establishing new AFS for increasing C sequestration, emphasizing the impact of agroforest loss on reducing C storage within agroecosystems. The development of policies that assist or reward landowners for providing the ecosystem service of C storage by retaining, establishing, and enhancing agroforests as part of existing agroecosystem management should be encouraged for mitigating climate change.
Environmental hazards as risk factors for trips and slips at home among Japanese older people: A pilot study toward the development of a self‐assessment tool for the home environment
Authors: Sawa Ryuichi , Tanaka Buichi , Yamamoto Junshiro , Yamada Minoru
Published: March 2022

Aim

Housing structures differ according to the local culture, climate, and lifestyle, and these unique characteristics usually act as potential hazards for falls, trips, and slips. The purpose of this study was to identify environmental hazards in a Japanese house and their association with falls, trips, and slips among older people.

Methods

A total of 97 older people aged ≥75 years were included in this cross‐sectional study. The number of environmental hazards was measured using a 46‐item tool designed specifically for this study, and the associations of environmental hazards with falls, trips, and slips were analyzed using univariate and multivariate logistic regressions.

Results

All houses had at least one environmental hazard, and 3–30 environmental hazards were identified. Although the number of environmental hazards was not associated with falls experienced during the past 6 months, a greater number of environmental hazards at home was correlated with the daily experience of trips and slips (odds ratio [OR]: 1.10; 95% confidence interval [CI]: 1.02–1.18). The association remained significant even after adjusting for demographic characteristics and other fall risk factors (OR: 1.11; 95% CI: 1.02–1.21).

Conclusion

We found that Japanese housing structures had unique environmental hazards that might cause trips and slips in older people. Appropriate housing assessments and modifications may help to promote aging‐in‐place among older people. Geriatr Gerontol Int 2022; 22: 305–310.
GO FIGURE: FREDRIC JAMESON ON WALTER BENJAMIN
Authors: Jay Martin
Published: March 2022

Fredric Jameson's new book, The Benjamin Files, gives him an opportunity to revisit a figure he initially discussed more than fifty years ago. At that time, he lamented what he saw as Walter Benjamin's melancholic resignation at the failure of his redemptive hopes; now, he wants to affirm the future‐oriented implications of Benjamin's work as coming from a “time‐traveler from some messianic future.” Focusing on theological strains in Benjamin's thinking, Jameson takes seriously Benjamin's Adamic view of a lost “language as such,” his nostalgia for a world of cosmic correspondences, and his adoption of the idea of apocatastasis—the redemption of all souls in the Final Judgment—and tries to integrate them with his historical materialist reading of history. That reading, Jameson avers, depends on a unified notion of history as a meaningful narrative, which, to be sure, is not equivalent to complacent notions of progress. But how one can reconcile Benjamin's advocacy of disrupting narratives of any kind and his spatialization of our relation to the past through synchronic “dialectical images” with a faith in a totalizing narrative of redemption is not clear. Jameson tacitly admits the difficulty when he falls back on Alain Badiou's notion of “fidelity to the event” and Erich Auerbach's ideas about figural iteration, which depend on a faith that past interruptions in conventional historical narratives, even failed attempts at revolution, foretell their completion in the future. As a result, it is hard not to be skeptical that the wind of world history is, despite all indications to the contrary, blowing us toward the restoration of cosmic harmonies, an Adamic “language as such,” and the universal salvation called apocatastasis.
Predictors of low‐level HIV viraemia and virological failure in the era of integrase inhibitors: A Spanish nationwide cohort
Authors: Álvarez Hortensia , Rava Marta , Martínez Cristina , Portilla Joaquín , Peraire Joaquim , Rivero Antonio , Cervero Miguel , Mariño Ana , Poveda Eva , Llibre Josep M. ,   CoRIS Study Group
Published: March 2022

Objectives

To pinpoint factors associated with low‐level viraemia (LLV) and virological failure (VF) in people living with HIV in the era of high‐efficacy antiretroviral treatment (ART) and widespread use of integrase strand transfer inhibitor (INSTIs)‐based ART.

Methods

We included adults aged > 18 years starting their first ART between 2015 and 2018 in the Spanish HIV/AIDS Research Network National Cohort (CoRIS). Low‐level viraemia was defined as plasma viral load (pVL) of 50–199 copies/mL at weeks 48 and 72 and VF was defined as pVL ≥ 50 copies/mL at week 48 and pVL ≥ 200 copies/mL at week 72. Multivariable logistic regression models assessed the impact on LLV and VF of baseline CD4 T‐cell count, CD4/CD8 T‐cell ratio and pVL, initial ART classes, age at ART initiation, time between HIV diagnosis and ART initiation, gender and transmission route.

Results

Out of 4186 participants, 3120 (76.0%) started INSTIs, 455 (11.1%) started boosted protease inhibitors (bPIs) and 443 (10.8%) started nonnucleoside reverse transcriptase inhibitors (NNRTIs), either of them with two nucleos(t)ide reverse transcriptase inhibitors (NRTIs). Low‐level viraemia was met in 2.5% of participants and VF in 4.3%. There were no significant differences throughout the years for both virological outcomes. Baseline HIV‐1 RNA > 5 log10 copies/mL was the only consistent predictor of higher risk of LLV [adjusted odds ratio (aOR) = 9.8, 95% confidence interval (CI): 2.0–48.3] and VF (aOR = 5.4, 95% CI: 1.9–15.1), even in participants treated with INSTIs.

Conclusions

The rates of LLV and VF were low but remained steady throughout the years. Baseline HIV‐1 RNA > 5 log10 copies/mL showed a persistent association with LLV and VF even in participants receiving INSTIs.
Effect of Asian sea bass bio‐calcium on textural, rheological, sensorial properties and nutritive value of Indian mackerel fish spread at different levels of potato starch
Authors: Wijayanti Ima , Benjakul Soottawat , Chantakun Kasidate , Prodpran Thummanoon , Sookchoo Pornsatit
Published: February 2022

Effect of potato starch (2%–4%) and Asian sea bass bone bio‐calcium (BC) (0%–10%) on characteristics of Indian mackerel fish spread was investigated. Starch levels had higher impact than bio‐calcium concentration on characteristics of fish spread (P < 0.05). Firmness, consistency and cohesiveness of fish spread were raised with increasing starch and BC levels (P < 0.05). Highest lightness (L*) was found in fish spread added with 2% starch and 10% BC (P < 0.05). Highest a*, b*, C*‐values but lowest hue angle were obtained in fish spread added with 4% starch and 10% BC (P < 0.05). Higher G' and viscosity were observed in sample added with 4% starch when BC was incorporated at higher level. All fish spreads generally showed shear thinning flow behaviour. Higher acceptability was attained for fish spread containing 4% starch and 10% BC without grittiness. This fish spread showed higher ash with lower moisture, protein and lipid contents than those without BC. Calcium solubility of fish spread was augmented after in vitro gastrointestinal tract system when fortified with 10% BC, and higher solubility of calcium was also noticeable, compared to BC itself. Overall high PUFA, acceptable PV and TBARS value were attained for fish spread fortified with 4% starch and 10% BC.
Efficacy of intravenous hydration during extracorporeal shock wave lithotripsy in improving ureteral stone treatment success rate
Authors: Cheng Weiming , Chiu Yi‐Chun , Fan Yu‐Hua , Chang Chang‐Chi , Kao Kuo‐Wei
Published: February 2022

Objective

The treatment efficacy of extracorporeal shock wave lithotripsy for urolithiasis depends on several factors. We aimed to evaluate the impact of intravenous hydration during shock wave lithotripsy on stone treatment success rate in patients with ureteral stones.

Methods

We retrospectively evaluated patients with ureteral stones <2 cm in diameter treated with extracorporeal shock wave lithotripsy at two sites. Patients from one of the sites received intravenous hydration with 500 mL of 0.9% NaCl. Stone treatment success status was defined as stone‐free or residual ureteral stones <0.4 cm in diameter 1 month after the procedure. Predictive factors associated with treatment success were evaluated using univariate and multivariate logistic regression.

Results

Overall, 146 consecutive patients with ureteral stones were included. Eighty (54.8%) patients received intravenous hydration. The overall stone treatment success rate was 66.4%. Those with intravenous hydration during the shock wave lithotripsy had significantly smaller stone size, lower serum creatinine levels, lower rate of alpha‐blockers use, and higher rate of nonsteroidal anti‐inflammatory drug use. Upon multivariate analysis, stone treatment success status postprocedure was significantly associated with stone size (odds ratio 4.118, 95% confidence interval 1.920–8.832, P < 0.0001) and intravenous hydration during the procedure (odds ratio 2.475, 95% confidence interval 1.176–5.208, P = 0.017).

Conclusion

Besides small ureteral stone size, concomitant intravenous hydration with 500 mL of normal saline during extracorporeal shock wave lithotripsy was significantly associated with subsequent stone passage. Administering 0.9% NaCl may be a simple and effective measure to improve the treatment efficacy of extracorporeal shock wave lithotripsy.
Multiethnic intergenerational perspectives on interethnic marriages in Peninsular Malaysia: The challenge of ethno‐religionist identity
Authors: Foong Andrew L.S. , Teoh Eliza J.Y.
Published: February 2022

Against the background of a long history of acceptance of transmigration from various parts of the world and interethnic marriages being embraced, political agendas that prevailed following the independence of Malaysia culminated in a society with increasing ethnic polarisation impacting on social cohesion and reports of aversion to interethnic marriages. This study is aimed at exploring the perspectives of people who have lived through the different socio‐political changes impacting on the social fabric. Using an exploratory cross‐sectional qualitative design, 36 participants from the three main ethnic groups, across three generations (Baby Boomers, Generation Xers, and Millennials) were interviewed to explore their views on interethnic marriages in Peninsular Malaysia. Iterative questioning was adopted to enhance reliability of data, which were processed by thematic analysis. Although each of the generational groups had different lived experiences, the findings indicate commonalities identified in terms of two main themes, i.e., challenges and facilitators. The predominant perception is the challenge of religion conversion required by non‐Muslims in relationships with Muslims. The issue of ethnicity did not arise as of concern amongst the different ethnic groups from this urban sample. Of significance is the heightened ethno‐religionist consciousness with implications on social cohesion for community relations and nation building.
Mechanisms of cooperation between airlines and online travel agencies for flight crowdfunding
Authors: Ling Liuyi , Bao Xuefeng , Zhang Zihao , Yang Feng
Published: February 2022

With the development of crowdfunding and e‐commerce, a novel selling strategy for airlines called flight crowdfunding has been recently applied to the airline industry. In this paper, we propose a micro‐foundation to analyze consumers' purchase behavior, the interaction between airlines and OTAs for launching crowdfunding flights and design contracts to coordinate the supply chain. We find that airlines tend to reduce the participation threshold below the break‐even point to attract more consumers, even if doing so will incur losses when the demand is insufficient. We also examine the conditions under which crowdfunding dominates the traditional selling and find that airlines will adopt crowdfunding as the selling strategy if the competition is sufficiently intense in the market or flights' fixed cost is sufficiently high. Moreover, all consumers always strictly benefit from the crowdfunding offer. Crowdfunding can create a win–win–win situation for airlines, the OTA and consumers if the number of airlines in the market is in an intermediate range. We also investigate the supply chain coordination contracts and demonstrate that cost‐sharing contracts can coordinate the supply chain and achieve its optimal performance, whereas some other contracts, such as wholesale‐price, revenue‐sharing, and profit‐sharing contracts cannot do that. This paper highlights the importance of crowdfunding in the cooperation between airlines and OTAs.
Pyroptosis‐related molecular classification and immune microenvironment infiltration in breast cancer: A novel therapeutic target
Authors: Luo Jiayue , Lai Jianguo
Published: March 2022

The underlying role of pyroptosis in breast cancer (BC) remains unknown. Herein, we investigated the correlations of 33 pyroptosis‐related genes (PRGs) with immune checkpoints and immune cell infiltrations in BC patients based on The Cancer Genome Atlas cohort (n = 996) and Gene Expression Omnibus cohort (n = 3,262). Enrichment analysis revealed that these PRGs mainly functioned in pyroptosis, inflammasomes and regulation of autophagy pathway. Four prognostic independent PRGs (CASP9, TIRAP, GSDMC and IL18) were identified. Then, cluster 1/2 was recognized using consensus clustering for these four PRGs. Patients from cluster 1 had a favourable prognosis and diverse immune cell infiltrations. A nomogram was developed based on age, TNM stage, tumour subtype and pyroptosis score. Patients with the high‐risk group exhibited worse 5‐year OS, and the result was consistent in the external cohort. Additionally, high‐risk group patients were associated with downregulated immune checkpoint expression. Further analysis suggested that the high‐risk group patients were associated with a higher IC50 of paclitaxel, doxorubicin, cisplatin, methotrexate and vinorelbine. In summarizing, the pyroptosis score‐based nomogram might serve as an independent prognostic predictor and could guide medication for chemotherapy. Additionally, it may bring novel insight into the regulation of tumour immune microenvironment in BC and help to achieve precision immunotherapy.
Conducting a good ward round: How do leaders do it?
Authors: Merriman Clair , Freeth Della
Published: February 2022

Rationale, Aims and Objectives

Ward rounds (WRs) are complex social processes. Done well, WR discussions and decisions contribute to timely, safe, effective progression of care. However, literature highlights medical dominance; marginalisation or absence of other perspectives, safety risks and suboptimal resource use. This study examined leadership behaviours and what supported good interprofessional WRs, defined as enabling interprofessional collaboration and decision making which progresses patient care in a safe and timely manner. Deepening appreciation of this art should support learning and improvements.

Method

Mixed‐method appreciative inquiry (AI) into how WRs go well and could go well more often. Context: daily interprofessional consultant‐led WRs in a large adult critical care unit. Data: ethnographic and structured observations (73 h, 348 patient reviews); AI conversations and interviews (71 participants). Inductive iterative analysis shaped by Activity Theory. Participants: 256 qualified healthcare professionals working in the unit.

Results

Leadership of good WRs supported (and minimized contradictions to): making good use of expertise and time, and effective communication. These three key activities required careful and skilled orchestration of contributions to each patient review, which was achieved through four distinct phases (a broadly predictable script), ensuring opportunity to contribute while maintaining focus and a productive pace. This expertise is largely tacit knowledge, learnt informally, which is difficult to analyse and articulate oneself, or explain to others. To make this easier, and thus support learning, we developed the metaphor of a conductor leading musicians.

Conclusions

Whilst everyone contributes to the joint effort of delivering a good WR, WR leadership is key. It ensures effective use of time and diverse expertise, and coordinates contributions rather like a conductor working with musicians. Although WR needs and approaches vary across contexts, the key leadership activities we identified are likely to transfer to other settings.
Mucosal interleukin‐8 expression as a predictor of subsequent relapse in ulcerative colitis patients with Mayo endoscopic subscore 0
Authors: Uchiyama Kazuhiko , Takagi Tomohisa , Mizushima Katsura , Asaeda Kohei , Kajiwara Mariko , Kashiwagi Saori , Toyokawa Yuki , Hotta Yuma , Tanaka Makoto , Inoue Ken , Dohi Osamu , Okayama Tetsuya , Yoshida Naohisa , Katada Kazuhiro , Kamada Kazuhiro , Ishikawa Takeshi , Yasuda Hiroaki , Konishi Hideyuki , Kishimoto Mitsuo , Naito Yuji , Itoh Yoshito
Published: March 2022

Background and Aim

Complete endoscopic mucosal healing is defined as a Mayo endoscopic subscore of 0. Some patients diagnosed with a Mayo endoscopic subscore 0 may present with subsequent clinical relapse. Here, we aimed to demonstrate mucosal cytokine profile as a predictor of clinical relapse in ulcerative colitis patients with a Mayo endoscopic subscore of 0 as a marker of mucosal healing.

Methods

We conducted prospective observational pilot study to examine the relationship between mucosal cytokine expression and subsequent relapse of UC patients diagnosed with a Mayo endoscopic subscore of 0. We enrolled 55 patients, and expression of cytokines tumor necrosis factor‐α, interferon γ, interleukin‐1β, interleukin‐2, interleukin‐4, interleukin‐5, interleukin‐6, interleukin‐7, interleukin‐8, interleukin‐9, interleukin‐10, interleukin‐12, interleukin‐13, interleukin‐15, interleukin‐17A, interleukin‐17F, interleukin‐18, interleukin‐21, interleukin‐22, interleukin‐23, interleukin‐27, and interleukin‐33 was measured by quantitative real‐time PCR using rectal mucosa biopsy materials. Cytokine expression levels were compared between patients who relapsed between March 1, 2016, and March 30, 2020, of the study period and those who remained in remission.

Results

Ten cytokines, including interleukin‐2, interleukin‐4, interleukin‐8, interleukin‐10, interleukin‐12, interleukin‐15, interleukin‐17A, interleukin‐21, interleukin‐23, and interleukin‐33, were significantly elevated in patients with subsequent relapse compared with those who remained in remission. Interleukin‐8 expression was the most useful predictor.

Conclusions

In the rectal mucosa of ulcerative colitis patients with Mayo endoscopic subscore 0, levels of several cytokines were elevated in cases of subsequent relapse. Among these, interleukin‐8 expression was the most useful for predicting relapse.
Modulation of autophagy by an innovative phytocosmetic preparation (Myrothamnus flabelifolia and Coffea arabica) in human fibroblasts and its effects in a clinical randomized placebo‐controlled trial
Authors: Biscaro Rafael C. , Mussi Lilian , Sufi Bianca , Padovani Giovana , Camargo Junior Flavio B. , Magalhães Wagner V. , Di Stasi Luiz C.
Published: February 2022

Background

Autophagy is a natural and evolutionary mechanism that reduces cell toxic components and reutilizes metabolites to provide energy and renew cell function, which is linked to a wide range of age‐related diseases, including those that affect the skin. Positive modulation of autophagy is useful to treat skin disorders and new active herbal products are potential candidates as autophagy modulators.

Aims

The present study aimed to evaluate the effects of a phytocosmetic formulation containing Myrothamnus flabellifolia leaf and Coffea arabica seed plant extracts (MflCas) on the ubiquitin‐proteasome and autophagy markers in human dermal fibroblasts, and investigate its topical skin effects in a randomized, simple‐blind, and placebo‐controlled trial.

Methods

Human dermal fibroblasts were used to determine proteasome activity, protein carbonylation, LC3B protein, and lipofuscin production by luminescence and immune‐enzymatic assays, and to determinate gene expression of autophagy biomarkers (Atg5, Atg7, EI24, EIF2A, Park2, foxo1, and mTOR) by RT‐PCR. A clinical trial was conducted to evaluate the effects of MflCas on the hand, face, and forearms skin features after treatment by 56 days.

Results

Topical treatment with MflCas improved several skin features of volunteers, mainly skin aging and pigmentation signals. On the hand skin, MflCas 2% after 56 days of treatment, reduced the spots length (30.8%), skin contrast (42.2%), and increased skin homogeneity (63.2%) and skin lightening effect (1.4%). On the face skin, topical treatment after 56 days reduced the spots length (21.5%), wrinkles area (8.1%), and wrinkles volume (5.6%) with an increment in face skin homogeneity (59.5%). These effects were related to the ability of MflCas to reduce proteasome activity protein carbonylation, and lipofuscin level, increase LC3B production, downregulate Atg7 and mTOR genes, and upregulate Park2 gene expressions.

Conclusions

The phytocosmetic preparation containing Myrothamnus flabellifolia leaf and Coffea arabica seed modulated ubiquitin‐proteasome and autophagy process, representing an innovative and safe herbal preparation to improve skin features, mainly acting as skin anti‐aging and lightening agent.
Effect of rifaximin on infections, acute‐on‐chronic liver failure and mortality in alcoholic hepatitis: A pilot study (RIFA‐AH)
Authors: Jiménez César , Ventura‐Cots Meritxell , Sala Margarita , Calafat Margalida , Garcia‐Retortillo Montserrat , Cirera Isabel , Cañete Nuria , Soriano Germán , Poca María , Simón‐Talero Macarena , Altamirano José , Lucey Michael , Garcia‐Tsao Guadalupe , Brown Robert S. , Schwabe Robert F. , Verna Elizabeth C. , Schnabl Bernd , Bosques‐Padilla Francisco , Mathurin Philippe , Caballería Juan , Louvet Alexandre , Shawcross Debbie L. , Abraldes Juan G. , Genescà Joan , Bataller Ramon , Vargas Víctor
Published: February 2022

Background & Aims

Alcoholic hepatitis (AH) is associated with a high incidence of infection and mortality. Rifaximin reduces bacterial overgrowth and translocation. We aimed to study whether the administration of rifaximin as an adjuvant treatment to corticosteroids decreases the number of bacterial infections at 90 days in patients with severe AH compared to a control cohort.

Methods

This was a multicentre, open, comparative pilot study of the addition of rifaximin (1200 mg/day/90 days) to the standard treatment for severe AH. The results were compared with a carefully matched historical cohort of patients treated with standard therapy and matching by age and model of end‐stage liver disease (MELD). We evaluated bacterial infections, liver‐related complications, mortality and liver function tests after 90 days.

Results

Twenty‐one and 42 patients were included in the rifaximin and control groups respectively. No significant baseline differences were found between groups. The mean number of infections per patient was 0.29 and 0.62 in the rifaximin and control groups, respectively (p = .049), with a lower incidence of acute‐on‐chronic liver failure (ACLF) linked to infections within the treatment group. Liver‐related complications were lower within the rifaximin group (0.43 vs. 1.26 complications/patient respectively) (p = .01). Mortality was lower in the treated versus the control groups (14.2% vs. 30.9, p = .15) without significant differences. No serious adverse events were associated with rifaximin treatment.

Conclusions

Rifaximin is safe in severe AH with a significant reduction in clinical complications. A lower number of infections and a trend towards a lower ACLF and mortality favours its use in these patients.
Knowledge of liver fibrosis stage among adults with NAFLD/NASH improves adherence to lifestyle changes
Authors: Carrieri Patrizia , Mourad Abbas , Marcellin Fabienne , Trylesinski Aldo , Calleja José Luis , Protopopescu Camelia , Lazarus Jeffrey V.
Published: February 2022

Background & Aims

Though lifestyle interventions can reverse disease progression in people with non‐alcoholic fatty liver disease/non‐alcoholic steatohepatitis (NAFLD/NASH), unawareness about disease severity might compromise behavioural changes. Data from this first international cross‐sectional survey of individuals with NAFLD/NASH were used to identify correlates of both unawareness about fibrosis stage and its association with adherence to lifestyle adjustments.

Methods

Adults with NAFLD/NASH registered on the platform Carenity were invited to participate in an online 20‐min, six‐section survey in Canada, France, Germany, Italy, Spain and the United Kingdom to describe their experience with NAFLD/NASH and its care (N = 1411). Weighted binary and multinomial logistic regressions were performed to estimate the effect of explanatory variables on unawareness of fibrosis stage and poor adherence to lifestyle changes respectively.

Results

In the study group, 15.5% had obesity and 59.2% did not know their fibrosis stage. After multiple adjustments, individuals with a body mass index (BMI) ≥35 were over twice as likely to not know their fibrosis stage. People with a BMI >30 had a threefold higher risk of having poor adherence to lifestyle changes. Unawareness about fibrosis stage was also significantly associated with poor adherence to lifestyle adjustments.

Conclusions

As fibrosis stage is becoming the main predictor of NAFLD progression, improving patient–provider communication—especially for people with obesity—about liver fibrosis stage, its associated risks and how to mitigate them, is needed. Training for healthcare professionals and promoting patient educational programmes to support behaviour changes should also be included in the liver health agenda.
Screening and surveillance of oesophageal varices in patients with HCV‐positive liver cirrhosis successfully treated by direct‐acting antiviral agents
Authors: Ciancio Alessia , Ribaldone Davide Giuseppe , Salamone Rossella , Bruno Mauro , Caronna Stefania , Debernardi Venon Wilma , Giordanino Chiara , Mondardini Alessandra , Musso Alessandro , Pennazio Marco , Rolle Emanuela , Sacco Marco , Sprujevnik Tatiana , De Angelis Claudio , Saracco Giorgio Maria
Published: February 2022

Background & Aims

limited evidence is available to guide hepatologists regarding endoscopic surveillance of oesophageal varices (EV) in Hepatitis C Virus (HCV)‐positive cirrhotic patients achieving a sustained virologic response. To address these issues, we conducted a long‐term prospective study on 427 HCV‐positive cirrhotic patients successfully treated by Direct Antiviral Agents (DAAs).

Methods

Patients were divided into two groups according to their baseline Baveno VI status: Group 1 (92, 21.5%, favourable Baveno VI status) and Group 2 (335, 78.5%, unfavourable Baveno VI status). Each patient underwent baseline endoscopy and was endoscopically monitored for a median follow‐up of 65.2 months according to Baveno VI recommendations.

Results

About 4.3% of Group 1 patients showed baseline EV compared with 30.1% of Group 2 patients (p < .0001). No patients belonging to Group 1 without baseline EV developed EV at follow‐up endoscopy compared with 6.5% in Group 2 patients (p = .02); 69/107 (64.5%) patients with baseline EV showed small varices. During the endoscopic follow‐up, EV disappeared/improved in 36 (33.6%), were stable in 39 (36.4%) and worsened in 32 (29.9%) patients, all belonging to Group 2 (p = .001). Improvement in Baveno VI status was observed in 118/335 (35.2%, p < .0001) of Group 2 patients and among those without pre‐therapy EV, none developed EV throughout the follow‐up.

Conclusions

HCV‐positive cirrhotic patients cured by DAAs showing baseline favourable Baveno VI status and no worsening during follow‐up can safely avoid endoscopic screening and surveillance. Patients having unfavourable Baveno VI status without baseline EV who improve their status may suspend further endoscopic surveillance.
Durability of sustained virological response to glecaprevir/pibrentasvir and resistance development: A long‐term follow‐up study
Authors: Poordad Fred , Felizarta Franco , Yao Betty B. , Overcash J. Scott , Hassanein Tarek , Agarwal Kosh , Gane Edward , Shaw David , Waters Michael , Krishnan Preethi , Topp Andrew , Burroughs Margaret , Nevens Frederik
Published: February 2022

Background and Aims

This study aimed to determine durability of sustained virologic response (SVR) in hepatitis C virus‐infected participants treated with glecaprevir‐ and/or pibrentasvir‐containing regimens.

Methods

M13‐576, a rollover study, evaluated the durability of SVR in a follow‐up period of approximately 3 years after hepatitis C virus genotype 1–6‐infected participants received a glecaprevir‐ and/or pibrentasvir‐containing regimen in previous phase 2/3 clinical trials. The primary efficacy endpoint was the percentage of participants maintaining SVR and the percentage of participants experiencing relapse or reinfections. Resistance‐associated substitutions and safety outcomes related to liver progression were also assessed.

Results

Of 384 participants enroled, 377 participants were included in the as‐observed population and 287 participants completed the study. In prior studies, 99.7% (376/377) of participants achieved SVR12; of those, an observed 99.5% (374/376) and 100% (286/286) completing the study, maintained SVR. After non‐responder imputation of missing data, 286/376 participants (76%) maintained SVR. The participant previously not achieving SVR was a treatment‐experienced male with compensated cirrhosis who had NS3 and NS5A substitutions at enrolment, which remained detectable for 12 months. Of the two participants not maintaining SVR, one was re‐infected and one experienced late relapse at post‐treatment week 60. Five participants (all with a fibrosis stage ≥F3) had hepatocellular carcinoma. No events were deemed related to glecaprevir/pibrentasvir.

Conclusions

Glecaprevir/pibrentasvir demonstrated long‐term durability of efficacy after SVR12 was achieved. Hepatic‐related decompensation events were not seen. Owing to low incidence of virologic failure, conclusions were not drawn on persistence of resistance‐associated substitutions.
Seroprevalence of hepatitis C virus infection in children: A systematic review and meta‐analysis
Authors: Abdel‐Gawad Muhammad , Abd‐elsalam Sherief , Abdel‐Gawad Ibrahim , Tag‐Adeen Mohammed , El‐Sayed Marwa , Abdel‐Malek Dalia
Published: February 2022

Background and Aims

Estimates of paediatric hepatitis C virus (HCV) seroprevalence are needed to aid treatment scaling‐up, screening and detection approach in this age range, with the ultimate goal of global HCV eradication. The aim of this study was to gather all of the available information on HCV seroprevalence in children all around the world.

Methods

We searched PubMed, Scopus, Web of Science (WOS), Wiley and EBSCO databases for all studies evaluating HCV seroprevalence in children; however, studies examining seroprevalence in high‐risk children or specific groups were excluded.

Results

Only 20 articles with 48 963 people met our inclusion criteria, with an overall prevalence of 0.904% and a 95% confidence interval (CI) of 0.543 to 1.355. Seroprevalence was higher in research published prior to 2010 than in those published after 2010 (0.77% vs. 0.53%).

Conclusion

Few studies were conducted to assess the seroprevalence of HCV in children worldwide. However, the worldwide pooled seroprevalence of HCV in children in these studies is low (less than 1%).
Liver pathology and biochemistry in patients with mutations in TRIM37 gene (Mulibrey nanism)
Authors: Sivunen Johanna , Karlberg Susann , Kivisaari Reetta , Lohi Jouko , Karlberg Niklas , Jokinen Eero , Sarkola Taisto , Jahnukainen Timo , Lipsanen‐Nyman Marita , Jalanko Hannu
Published: February 2022

Background and Aims

Mulibrey nanism (MUL) is a multiorgan disease caused by recessive mutations in the TRIM37 gene. Chronic heart failure and hepatopathy are major determinants of prognosis in MUL patients, which prompted us to study liver biochemistry and pathology in a national cohort of MUL patients.

Methods

Clinical, laboratory and imaging data were collected in a cross‐sectional survey and retrospectively from hospital records. Liver histology and immunohistochemistry for 10 biomarkers were assessed.

Results

Twenty‐one MUL patients (age 1–51 years) with tumour suspicion showed moderate congestion, steatosis and fibrosis in liver biopsies and marginally elevated levels of serum GGT, AST, ALT and AST to platelet ratio index (APRI) in 20%–66%. Similarly, GGT, AST, ALT and APRI levels were moderately elevated in 12%–69% of 17 MUL patients prior to pericardiectomy. In a cross‐sectional evaluation of 36 MUL outpatients, GGT, total bilirubin and galactose half‐life (Gal½) correlated with age (r = 0.45, p = .017; r = 0.512, p = .007; r = 0.44, p = .03 respectively). The frequency of clearly abnormal serum values of 15 parameters analysed, however, was low even in patients with signs of restrictive cardiomyopathy. Transient elastography (TE) of the liver revealed elevated levels in 50% of patients with signs of heart failure and TE levels correlated with several biochemistry parameters. Biomarkers of fibrosis, sinusoidal capillarization and hepatocyte metaplasia showed increased expression in autopsy liver samples from 15 MUL patients.

Conclusion

Liver disease in MUL patients was characterized by sinusoidal dilatation, steatosis and fibrosis with individual progression to cirrhosis and moderate association of histology with cardiac function, liver biochemistry and elastography.
Serum keratin 19 (CYFRA21‐1) is a prognostic biomarker in severe alcoholic hepatitis
Authors: Atkinson Stephen Rahul , Aly Mahmoud , Remih Katharina , Tyson Luke David , Guldiken Nurdan , Goldin Robert , Quaglia Alberto , Thursz Mark , Strnad Pavel
Published: February 2022

Background and Aims

Up to 30% of patients with severe alcoholic hepatitis (sAH) die within 3 months of presentation. The degree of ductular reaction, characterized by accumulation of biliary and liver progenitor cells, confers a poor prognosis. Keratin fragments are established serological surrogates of liver injury and keratin 19 (K19) is a histological marker of the ductular reaction. We assessed the relationship between serum K19 levels (viz. CYFRA21‐1), histology and outcome in patients with sAH.

Methods

Serum CYFRA21‐1 was quantified in pre‐treatment serum samples from 824 patients enrolled in the STOPAH trial. The cohort was randomly divided into two groups to test mortality associations; histological analyses were performed using the 87 cases with suitable samples.

Results

CYFRA21‐1 levels were elevated in sAH and strongly predicted alcoholic steatohepatitis (ASH) on biopsy (area under the receiver operated characteristic [AUROC] 0.785 [95% Confidence Interval 0.602–0.967]) and 90‐day survival (AUROC 0.684/0.693). The predictive ability of CYFRA21‐1 was comparable with the model of end‐stage liver disease (MELD) score and was independently associated with survival in multivariable analysis. CYFRA21‐1 moderately correlated with hepatocellular injury markers M30/M65 but displayed a more robust predictive ability. A combination of MELD and CYFRA21‐1 conferred a modest improvement in the AUROC value (0.731/0.743).

Conclusions

In sAH serum, CYFRA21‐1 levels associate with the presence of ASH on biopsy and independently predict 90‐day survival. As a single marker performance is comparable to established scoring systems. Therefore, CYFRA21‐1, which is available in many clinical laboratories, may become a useful component of prognostic models.
Sr distribution as proxy for Ca distribution at depth in SXRF analysis of mm‐sized carbonaceous chondrites: Implications for asteroid sample return missions
Authors: Tkalcec B. J. , Tack P. , De Pauw E. , Vekemans B. , Nakamura T. , Garrevoet J. , Falkenberg G. , Vincze L. , Brenker F. E.
Published: March 2022

Reliable identification of chondrules, calcium‐aluminum‐rich inclusions (CAIs), carbonate grains, and Ca‐phosphate grains at depth within untouched, unprepared chondritic samples by a nondestructive analytical method, such as synchrotron X‐ray fluorescence (SXRF) computed tomography (CT), is an essential first step before intrusive analytical and sample preparation methods are performed. The detection of a local Ca‐enrichment could indicate the presence of such a component, all of which contain Ca as major element and/or Ca‐bearing minerals, allowing it to be precisely located at depth within a sample. However, the depth limitation from which Ca‐K fluorescence can travel through a chondrite sample (e.g., ∼115 µm through material of 1.5 g cm−3) to XRF detectors leaves many Ca‐bearing components undetected at deeper depths. In comparison, Sr‐K lines travel much greater distances (∼1700 µm) through the same sample density and are, thus, detected from much greater depths. Here, we demonstrate a clear, positive, and preferential correlation between Ca and Sr and conclude that Sr‐detection can be used as proxy for the presence of Ca (and, thus, Ca‐bearing components) throughout mm‐sized samples of carbonaceous chondritic material. This has valuable implications, especially for sample return missions from carbonaceous C‐type asteroids, such as Ryugu or Bennu. Reliable localization, identification, and targeted analysis by SXRF of Ca‐bearing chondrules, CAIs, and carbonates at depth within untouched, unprepared samples in the initial stages of a multianalysis investigation insures the valuable information they hold of pre‐ and post‐accretion processes in the early solar system is neither corrupted nor destroyed in subsequent processing and analyses.
AnfO controls fidelity of nitrogenase FeFe protein maturation by preventing misincorporation of FeV‐cofactor
Authors: Pérez‐González Ana , Jimenez‐Vicente Emilio , Salinero‐Lanzarote Alvaro , Harris Derek F. , Seefeldt Lance C. , Dean Dennis R.
Published: February 2022

Azotobacter vinelandii produces three genetically distinct, but structurally and mechanistically similar nitrogenase isozymes designated as Mo‐dependent, V‐dependent, or Fe‐only based on the heterometal contained within their associated active site cofactors. These catalytic cofactors, which provide the site for N2 binding and reduction, are, respectively, designated as FeMo‐cofactor, FeV‐cofactor, and FeFe‐cofactor. Fe‐only nitrogenase is a poor catalyst for N2 fixation, when compared to the Mo‐dependent and V‐dependent nitrogenases and is only produced when neither Mo nor V is available. Under conditions favoring the production of Fe‐only nitrogenase a gene product designated AnfO preserves the fidelity of Fe‐only nitrogenase by preventing the misincorporation of FeV‐cofactor, which results in the accumulation of a hybrid enzyme that cannot reduce N2. These results are interpreted to indicate that AnfO controls the fidelity of Fe‐only nitrogenase maturation during the physiological transition from conditions that favor V‐dependent nitrogenase utilization to Fe‐only nitrogenase utilization to support diazotrophic growth.