bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between germline pathogenic variants in cancer‐predisposing genes and lymphoma risk
Authors: Usui Yoshiaki , Iwasaki Yusuke , Matsuo Keitaro , Endo Mikiko , Kamatani Yoichiro , Hirata Makoto , Sugano Kokichi , Yoshida Teruhiko , Matsuda Koichi , Murakami Yoshinori , Maeda Yoshinobu , Nakagawa Hidewaki , Momozawa Yukihide
Published: September 2022

The application of advanced molecular technology has significantly expanded lymphoma classification, allowing risk stratification and treatment optimization. Limited evidence suggests the presence of a genetic predisposition in lymphoma, indicating the potential for better individualized clinical management based on a novel lymphoma classification. Herein, we examined the impact of germline pathogenic variants in 27 cancer‐predisposing genes with lymphoma risk and explored the clinical characteristics of pathogenic variant carriers. This study included 2,066 lymphoma patients and 38,153 cancer‐free controls from the Japanese population. Following quality control of sequencing data, samples from 1,982 lymphoma patients and 37,592 controls were further analyzed. We identified 309 pathogenic variants among 4,850 variants in the 27 cancer‐predisposing genes. Pathogenic variants in the following four cancer‐predisposing genes were associated with a high risk of lymphoma: ATM (odds ratio [OR], 2.63; 95% confidence interval [CI], 1.25–5.51; p = 1.06 × 10−2), BRCA1 (OR, 5.88; 95% CI, 2.65–13.02; p = 1.27 × 10−5), BRCA2 (OR, 2.94; 95% CI, 1.60–5.42; p = 5.25 × 10−4), and TP53 (OR, 5.22; 95% CI, 1.43–19.02; p = 1.23 × 10−2). The proportion of carriers of these genes was 1.6% of lymphoma patients. Furthermore, pathogenic variants in these genes were especially associated with a higher risk of mantle cell lymphoma (OR, 21.57; 95% CI, 7.59–61.26; p = 8.07 × 10−9). These results provide novel insights concerning monogenic form into lymphoma classification. Some lymphoma patients may benefit from surveillance and targeted treatment, such as other neoplasms.
Predictors of renal recovery in recipients of liver transplant alone who met 2017 simultaneous liver‐kidney transplant criteria
Authors: Cui Jiawei , Spann Ashley , Shingina Alexandra , Schaefer Heidi , Slaughter James C. , Matsuoka Lea , Alexopoulos Sophoclis , Izzy Manhal
Published: September 2022

Background

Severe renal dysfunction is common among liver transplant (LT) candidates and often prompts simultaneous liver‐kidney transplantation (SLKT) consideration. In view of 2017 United Network of Organ Sharing (UNOS) criteria for SLKT, we investigated the likelihood and predictors of renal recovery among patients who met the aforementioned criteria yet received liver transplant alone (LTA).

Methods

We retrospectively analyzed relative renal recovery (RRR; increase in eGFR to >30 ml/min) in adult LTA recipients between 1/2009 and 1/2019.

Results

Of 1165 LT recipients, 54 met 2017 UNOS criteria, with 37 receiving LTA. RRR occurred in 84% of LTA recipients, none of whom had pre‐LT eGFR <20 ml/min. Sustained RRR (>180 days) occurred in 43% of patients. While prolonged pre‐LT severe renal impairment (eGFR <30 ml/min) predicted failure to have sustained RRR (HR .19 per 90‐day, CI .04–.87, p < .005), having an eGFR measurement of >30 ml/min within 90 days pre‐LT (HR 5.52, CI 1.23–24.79, p .01) associated with achieving sustained RRR. Sustained RRR was protective against the composite outcome of renal replacement therapy, kidney transplant, and death (HR .21, p .01).

Conclusion

LT candidates who meet 2017 UNOS criteria for SLKT yet undergo LTA can still have relative renal recovery post‐LT, exceeding 80% on short‐term follow‐up and 40% on long‐term follow‐up. eGFR trends within 90 days pre‐LT can predict sustained renal recovery, which appears protective of adverse outcomes. These recovery rates advocate for applying the more restrictive criteria for SLKT outlined in this article and increasing utilization of the safety net (SN) policy for those who do not meet the proposed criteria.
Client and staff perceptions of the integration of trauma informed care and specialist posttraumatic stress disorder treatment in residential treatment facilities for substance use: A qualitative study
Authors: Mefodeva Valeriya , Carlyle Molly , Walter Zoe , Hides Leanne
Published: September 2022

Introduction

Comorbid posttraumatic stress disorder (PTSD) is prevalent among people seeking residential treatment for substance use disorders (SUD). We examined client and staff perceptions of the relationship between trauma and SUDs, and the integration of trauma‐informed care (TIC) and specialist‐delivered treatment for PTSD in residential alcohol and other drug (AOD) treatment facilities.

Methods

Individual semi‐structured interviews were conducted with frontline staff (n = 20) and clients (n = 18) in two residential AOD treatment facilities in Queensland, Australia. Interviews were audio recorded, transcribed and shared client and staff data was analysed using thematic analysis.

Results

Major staff and client themes emerged: PTSD was perceived as an underlying cause of SUD, where AOD is used to cope with and avoid PTSD and related symptoms (Theme 1). Residential facilities were perceived to provide a safe and supportive environment for clients (Theme 2). Psychoeducation on SUD and PTSD was also highlighted to normalise experiences associated with comorbid SUD/PTSD and promote help‐seeking pathways for specialist PTSD treatment. Concurrent treatment of SUD and PTSD in the residential setting was sought after and was perceived to enhance treatment outcomes (Theme 3). Staff saw the need for implementing TIC into the organisation and perceived TIC as a multi‐faceted and consistent approach of service delivery.

Discussion and Conclusions

Both clients and staff perceive comorbid SUD/PTSD as a challenge in residential treatment, that may be overcome through integrating TIC and PTSD treatment in residential treatment facilitates for substance use. Organisational and practical implications are discussed.
Role of the SEC62 gene in dermato‐oncology – impact on tumor cell biology, prognostication, and personalized therapy management
Authors: Linxweiler Maximilian , Müller Cornelia S. L.
Published: September 2022

The SEC62 gene encodes for a transmembrane protein of the endoplasmic reticulum (ER). Sec62 protein is involved in the post‐translational transport of secretory and membrane‐bound proteins in eukaryotic cells, regulates intracellular calcium homeostasis through direct interaction with the Sec61 channel and makes a decisive contribution to the cellular compensation of ER stress in the context of recovER‐phagy. A significantly increased expression of the SEC62 gene has already been demonstrated in various tumor entities. First approaches of a targeted therapy have been tested for various tumor entities in vitro and in vivo with promising results that motivate further preclinical and clinical studies. Nevertheless, many questions remain unanswered, in particular with regard to the molecular mechanisms underlying the observed clinical effects, and require further investigation in future studies. The protein also plays a relevant role in dermato‐oncology. The overexpression of SEC62 in atypical fibroxanthomas and malignant melanomas has already been demonstrated and a correlation of SEC62 expression with various clinical and pathological features has been observed. Future studies, especially in vivo and clinical, will show whether Sec62 can be established as a prognostic marker in dermato‐oncology and whether it can serve as a starting point for targeted therapy.
Conditioning with melphalan 200 mg/m2 and subsequent ASCT improves progression‐free and overall survival in elderly myeloma patients compared to standard of care
Authors: Afram Gabriel , Chaireti Roza , Uttervall Katarina , Luong Vincent , Lund Johan , Kashif Muhammad , Gahrton Gösta , Alici Evren , Nahi Hareth
Published: September 2022

Objectives

Despite the effectiveness of newer drugs for the treatment of multiple myeloma (MM), the outcomes are further improved by subsequent autologous stem cell transplantation (ASCT). Data on effectiveness in older patients are limited. We compared outcomes in patients aged 65–75 years depending on whether they were treated with ASCT or not and compared those to outcomes in patients <65 years.

Methods

This was a retrospective, single‐center study. We compared progression‐free survival (PFS) and overall survival (OS) for all MM patients below and above the age of 65 years treated ± ASCT at the Karolinska University Hospital between 2010 and 2020. PFS and OS were calculated by the Kaplan–Meier method. Variables affecting PFS and OS were evaluated using Cox regression model.

Results

Both PFS and OS were improved in the group 65–75 years treated +ASCT compared to those treated pharmacologically (p = 0.008 and p < 0.001, respectively). There were no significant differences between patients <65 years and those 65–75 years treated with ASCT.

Conclusion

The findings indicate that even patients >65 years should be evaluated as candidates for ASCT. An individualized approach supported by a frailty/geriatric assessment score could assist clinicians to select the appropriate treatment for each patient.
Credit variance risk premiums
Authors: Ammann Manuel , Moerke Mathis
Published: September 2022

This paper studies variance risk premiums in the credit market using a novel data set of swaptions quotes on the CDX North America Investment Grade and High‐Yield indices. The returns of credit variance swaps are negative and economically large, irrespective of the credit rating class. They are robust to transaction costs and cannot be explained by established risk factors and structural model variables. We also dissect the overall variance risk premium into receiver and payer variance risk premiums. We show that credit variance risk premiums are mainly driven by the payer corridor, which is associated with worsening macroeconomic conditions.
Tracking dietary fatty acids in triacylglycerols and phospholipids of zooplankton
Authors: Mathieu Francine , Guo Fen , Kainz Martin J.
Published: September 2022

Fatty acids (FA) in lake zooplankton are largely provided by dietary FA and affected by taxonomic composition of zooplankton, temperature, and other environmental conditions. However, the extent to which dietary FA are retained and/or bioconverted in zooplankton remains unclear. In this lake study, we examined how dietary FA (seston), temperature and physico‐chemical variables (i.e., concentrations of chlorophyll a, dissolved organic carbon, nitrate, ammonium, phosphate) explained the FA variation in membrane (phospholipids; PL) and storage (triacylglycerols; TAG) lipids of zooplankton.

We tested the hypotheses that: (1) increasing dietary FA increases the FA content stored as TAG by zooplankton, whereas the FA content in PL remains unaffected by naturally occurring changes in dietary FA supply; and (2) FA in seston better predict the FA variations stored by zooplankton as TAG, whereas lake temperature better predicts the FA variations in zooplankton PL.

Results show that an increase in dietary polyunsaturated FA increased polyunsaturated FA in TAG and PL of zooplankton, but not eicosapentaenoic acid or docosahexaenoic acid in PL. Moreover, the FA content of seston was more similar to that of zooplankton TAG than it was to the content of PL, indicating major taxon‐specific differences in membrane FA.

Dietary FA are a major predictor of FA in TAG of zooplankton, while the taxonomic composition of zooplankton is a major predictor of FA in PL. Temperature and physico‐chemical variables explained little of the variations in zooplankton FA. This field study improves our understanding of how FA in PL and TAG of different zooplankton taxa respond to changes of dietary FA, temperature, concentrations of chlorophyll‐a, dissolved organic carbon, nitrate, ammonium, and phosphate to fulfil their physiological requirements.
Efficacy of adding chemical and microbial additives to silage on beef cattle performance: Systematic review and meta‐analysis
Authors: Menezes Guilherme Lobato , de Oliveira Alan Figueiredo , de Assis Pires Frederico Patrus Ananias , Gonçalves Lúcio Carlos , de Menezes Rafael Araújo , de Sousa Pamella Grossi , de Medeiros Paulo Henrique Arruda , de Pinho Matheus Morais , Lana Ângela Maria Quintão , de Araújo Vânia Eloisa , Jayme Diogo Gonzaga
Published: September 2022

The effects of different additives on farm‐scale silage quality and beef cattle performance are inconsistent. This study aimed to carry out a systematic review and meta‐analysis to evaluate the efficacy of chemical and microbial additives to silage on beef cattle performance. Systematic searches were performed using databases and scientific journals, and 42 articles were selected. Data for all variables were grouped into subgroups according to the additive type. For dry matter intake and average daily gain, the data were also grouped by forage type due to greater comparison numbers. The treatment mean differences and 95% confidence intervals (p < 0.05) were analysed using a random‐effects model. The use of homo‐ and heterofermentative microbial inoculant mixtures and chemical additives (Ch) increased the average daily gain of beef cattle fed maize/sorghum silage. Homofermentative microbial inoculant (Ho), Ch, and a mixture of microbial inoculant and chemical additives also increased the average daily gain of beef cattle fed temperate grasses. Only Ch increased dry matter intake. Ch increased feed efficiency, and Ch and Ho increased carcass weight. The evaluated additives improved the silage fermentation process mainly via pH and ammonia nitrogen reduction. Overall, this meta‐analysis demonstrated that silage additives improved the ensiling process and beef cattle performance, with better results with Ch use. Due to the aerobic stability and microbiological profile analyses being carried out more in laboratory‐scale silos, more studies are needed to determine these silage parameters after opening the silo at the farm scale.
Analysis of pulmonary nodules detected by annual low‐dose computed tomography in the elderly during a 10‐year follow‐up
Authors: Liu Zhonghui , Liu Xinmin , Ni Lianfang
Published: September 2022

Aim

To describe pulmonary nodules detected by annual low‐dose computed tomography (LDCT) in the elderly during a 10‐year follow‐up, and to provide a basis for clinical decision‐making in the elderly.

Methods

In this retrospective study, patients who completed at least a 3‐year follow‐up visit with annual LDCT imaging data were eligible for inclusion. The evolution of pulmonary nodules was evaluated, including malignant, suspicious malignant, benign and undetermined nodules. Additionally, the nature and outcome of new nodules during the follow‐up were analyzed.

Results

For the 365 subjects included, 899 positive pulmonary nodules were detected in 286 patients. Among these there were 788 solid nodules, 20 part‐solid nodules and 91 nonsolid nodules. The detection rate of positive nodules and of lung cancer was 78.4% and 5.5%, respectively. 99.7% (786/788) of solid nodules were benign, and 75% (15/20) of part‐solid nodules and 28.6% (26/91) of nonsolid nodules were malignant or suspected malignant. 124 new positive nodules appeared during the annual follow‐up, but 58.9% of them subsequently disappeared. Significant higher detection rates of 10–20‐mm nodules (P = 0.0485) and suspicious malignant nodules (P = 0.017) were observed in subjects over 75 years old as compared with those under 75 years old.

Conclusions

Solid nodules accounted for the highest proportion of lung nodules screened at baseline, and most of them were benign. The malignant probability of part‐solid nodules was the highest. Most newly appeared nodules disappeared during subsequent follow‐up. The proportions of suspicious malignant nodules and 10–20‐mm nodules in subjects over 75 years old were higher than in those under 75 years old. Geriatr Gerontol Int 2022; 22: 865–869.
Reference intervals for erythrocyte parameters and hemoglobin electrophoresis parameters for young children in Guangxi
Authors: Zhou Chaofan , He Sheng , Liu Dun , Zuo Yangjin , Chen Qiuli , Wang Liang , Chen Biyan , Chen Faqin , Luo Jingsi , Xu Xiangmin , Lin Li
Published: September 2022

Background

Erythrocyte parameter analysis is the important means for diagnosis and treatment of hematological diseases, which are essential for screening of thalassemia in southern China combined with hemoglobin electrophoresis analysis. But little is known regarding the reference intervals (RIs) in healthy pediatrics in these two areas.

Methods

95% RIs of erythrocyte parameters were calculated from 853 healthy preschoolers, aged from 1 days to <6 years, according to the C28‐A3C guidelines of the Institute of Clinical and Laboratory Standards. To express the magnitude of sex and age variation, standard deviation ratio (SDR) was calculated using ANOVA. Concurrently, we selected 3814 thalassemia carriers as carriers group and drew receiver operating characteristic (ROC) curves to establish the optimal cut‐off values of hemoglobin electrophoresis parameters, which were used as the upper/lower limits of RIs to efficiently screen thalassemia.

Results

All parameters except red blood cell (RBC) required age partitioning, confirmed by SDRage above .4. There was no need for sex partitioning on all parameters, confirmed by SDRsex below .4. The optimal cut‐off value of Hemoglobin A2 (Hb A2) in the four subgroups was <7.8% (Hb A), 2.3%–3.2%, 2.5%–3.6% and 2.6%–3.6%, respectively.

Conclusion

In this study, the establishment of RIs improved the diagnostic efficiency of hematological disease (especially thalassaemia) for children in Guangxi. It provides reliable hematological references for the identification and diagnosis, treatment monitoring, and health screening of children's clinical diseases.
Computing efficiently the nondominated subset of a set sum
Authors: Kerbérénès Antoine , Vanderpooten Daniel , Vanpeperstraete Jean‐Michel
Published: September 2022

We study the computation of the nondominated subset of the Minkowski sum (or set sum) of a finite family of finite sets of multidimensional, real‐valued points. When points are the images of solutions to multiobjective optimization problems, this computation is a key algorithmic component for solving coupled systems problems. At first sight, this computation may be thought of as computing all combinations of points and applying dominance filtering to the resulting set of points. However, structural properties can be exploited algorithmically to perform this task more efficiently, avoiding some comparisons. We propose two main approaches of doing so. First, we show that using lexicographic ordering over each set to be added to the sum, we can speed up the sorting phase required to efficiently apply dominance filtering to elements of the set sum. Second, we introduce box‐based methods, defining dominance relations between sets of combinations of points.
Implementing a bivariate ordering and replacement policy for deteriorating systems with two failure types
Authors: Dong Wenjie , Du Junliang , Yang Mengyue , Liu Sifeng
Published: September 2022

For plenty of existing maintenance policies in literature, it is always assumed that the spare unit for replacement is available at any time if needed, while this perquisite may be unrealistic or even impossible. In this paper, we investigate an ordering and replacement modeling framework for a deteriorating repairable system with two failure types, involving a repairable failure (Type I failure) and a nonrepairable failure (Type II failure). A regular order and an expedited order are both incorporated into the spare unit ordering policy while a preventive replacement and a corrective replacement are both considered into the replacement policy, of which the ordering and replacement policy is scheduled in regard to the number of repairable failures. The expected profit per unit of time over an infinite time span is maximized to seek the optimal solutions in terms of the renewal reward theorem with a recursive algorithm procedure. An illustrative example is designed to validate the applicability and effectiveness of the developed ordering and replacement policy. In addition, the sensitivity of the optimal ordering‐replacement policy is studied and the effect of some key characteristics on the optimal decisions is discussed.
The comparison between experimental nursing and routine nursing interventions on the quality of life of stoma patients: A systematic review and meta‐analysis
Authors: Guo Yanyan , Zhang Yuanyuan , Guo Xianzhen , Zhao Wenting , Wang Qiuyan , Liu Xinxin , Li Shuang , Che Jinze , Zhou Ti
Published: September 2022

The advance in nursing care for stoma patients is a challenging issue, which will influence the life quality. The quality of life is a major issue in the recovery of stoma patients. The evidence of experimental nursing has not been explored enough. A systematic search and a meta‐analysis were performed for the studies of experimental nursing interventions versus routine warming interventions on patients with a stoma. The comparisons between nursing interventions were performed to find which kind of intervention will be superior in improving life quality. After a restricted selection, 10 studies, 460 subjects with experimental nursing intervention, and 478 controls with the routine nursing intervention were enrolled in a variety of causes of the stoma. The focused outcome was the quality of life. The meta‐analysis was performed by Review Manager 5.4. Among the stoma patients, the meta‐analysis favours the experimental nursing intervention group with higher scores of life quality when compared to the routine nursing intervention group. The meta‐analysis results were with positive mean differences, significant tests for overall effect, and significant heterogeneities in the random‐effects model. The experimental nursing intervention showed higher positive effects on the quality of life when compared to routine nursing intervention for stoma patients. Experimental nursing intervention might be an option for stoma nursing practitioners to improve stoma care.
Rapid pruritus reduction with ruxolitinib cream treatment in patients with atopic dermatitis
Authors: Blauvelt Andrew , Kircik Leon , Papp Kim A. , Simpson Eric L. , Silverberg Jonathan I. , Kim Brian S. , Kwatra Shawn G. , Kuligowski Michael E. , Venturanza May E. , Wei Shaoceng , Szepietowski Jacek C.
Published: September 2022

Background

Ruxolitinib cream is a topical formulation of ruxolitinib, a Janus kinase (JAK) 1/JAK2 inhibitor.

Objectives

To report timing and magnitude of effect of ruxolitinib cream on itch in patients with atopic dermatitis (AD), a highly pruritic inflammatory skin disease.

Methods

Two phase 3 trials (TRuE‐AD1 [NCT03745638]/TRuE‐AD2 [NCT03745651]) enrolled patients aged ≥12 years with AD for ≥2 years, Investigator's Global Assessment score of 2 or 3, and 3%–20% affected body surface area. Patients (total N = 1249; median age, 32 years) were randomised (2:2:1) to twice daily 0.75% ruxolitinib cream, 1.5% ruxolitinib cream or vehicle cream for 8 weeks of double‐blinded treatment. Worst itch was measured using the numerical rating scale (NRS).

Results

Significantly more patients who applied ruxolitinib cream (either strength) achieved a ≥2‐point itch reduction (NRS2) within approximately 12 h versus vehicle (0.75%/1.5% ruxolitinib cream, 16.3%/13.1%; vehicle, 6.9%; both P < 0.05), with further improvements through Week 8 (58.3%/65.1% vs 29.4%; both P < 0.0001). A ≥4‐point itch reduction (NRS4) was achieved by significantly more patients who applied 0.75%/1.5% ruxolitinib cream versus vehicle by Day 2 (8.9%/11.2% vs 2.1%; P < 0.005); higher rates were observed at Week 8 (41.5%/51.5% vs 15.8%; P < 0.0001). Median time for the 0.75%/1.5% ruxolitinib cream groups to achieve NRS4 from baseline was 15.0/13.0 days; this endpoint was not reached by the vehicle group.

Conclusions

Ruxolitinib cream demonstrated rapid improvement in itch in patients with mild to moderate AD that was sustained for 8 weeks. Significantly more patients applying ruxolitinib cream achieved itch NRS2 within approximately 12 h and itch NRS4 by Day 2 versus vehicle.
Sicyopterus garra Hora, 1925, a valid species of sicydiine goby from the Andaman Islands, India
Authors: Praveenraj Jayasimhan , Kiruba‐Sankar Rajendran , Saravanan Kandasamy , Thackeray Tejas , Singh Pratima , Knight John Daniel Marcus , Keith Philippe
Published: September 2022

Sicyopterus garra Hora, 1925 from the insular streams of South Andaman Islands was synonymized with Sicyopterus microcephalus described from Java, South East Asia and has retained this taxonomic status since then. Recent collections of Sicyopterus from the type locality of S. garra and the examination of syntypes of this species revealed significant morphological and genetic differences from S. microcephalus and the other Sicyopterus species with papillae on upper lip. S. garra is thus a valid species and not a synonym of S. microcephalus. S. garra differs from S. microcephalus in having fewer lateral scales 53–59 vs. 57–68, fewer zigzag series (12–14 vs. 13–16), a longer caudal peduncle length (16–21 vs. 13–17), and by having a high percentage of divergence in COI gene (5.5%–5.8%).
METTL3 contributes to slow transit constipation by regulating miR‐30b‐5p/PIK3R2/Akt/mTOR signaling cascade through DGCR8
Authors: Gong Wen‐jing , Li Rong , Dai Qiao‐qiong , Yu Peng
Published: September 2022

Background

N6‐methyladenosine (m6A) is the most prevalent methylation modification of eukaryotic RNA, and methyltransferase‐like 3 (METTL3) plays a vital role in multiple cell functions. This study aimed to investigate the role of m6A methylase METTL3 in slow transit constipation (STC).

Material and Method

The expression of METTL3 and DGCR8 was measured in STC tissues and glutamic acid‐induced interstitial cells of Cajal (ICCs). The effects of METTL3, miR‐30b‐5p, and DGCR8 on the biological characteristics of ICCs were investigated on the basis of loss‐of‐function analyses. Luciferase reporter assay was used to identify the direct binding sites of miR‐30b‐5p with PIK3R2.

Results

The results showed that the METTL3, DGCR8, miR‐30b‐5p, and the methylation level of m6A were significantly increased in STC tissues and glutamic acid‐induced ICCs. Silencing of METTL3 and miR‐30b‐5p inhibited apoptosis, autophagy, and pyroptosis of glutamic acid‐induced ICCs. Moreover, overexpression of miR‐30b‐5p reversed the cytoprotection of METTL3 knockdown in glutamic acid‐induced ICCs. Besides, DGCR8 knockdown could facilitate cell growth and decrease apoptotic glutamic acid‐induced ICCs. Mechanically, we illustrated that METTL3 in glutamic acid‐induced ICCs significantly accelerated the maturation of pri‐miR‐30b‐5p by m6A methylation modification, resulting in the reduction of PIK3R2, which results in the inhibition of PI3K/Akt/mTOR pathway and ultimately leads to the cell death of STC.

Conclusions

Collectively, these data demonstrated that METTL3 promoted the apoptosis, autophagy, and pyroptosis of glutamic acid‐induced ICCs by interacting with the DGCR8 and successively modulating the miR‐30b‐5p/PIK3R2 axis in an m6A‐dependent manner, and METTL3 may be a potential therapeutic target for STC.
Role of m6A RNA methylation in the development of hepatitis B virus‐associated hepatocellular carcinoma
Authors: Zhang Cheng , Dai Dongjun , Zhang Wangjian , Yang Wenjun , Guo Yinglu , Wei Qichun
Published: September 2022

Hepatocellular carcinoma (HCC) is the most common liver malignancy that can be developed from hepatitis B and cirrhosis. Many pathophysiological alterations, including hepatitis B virus (HBV) DNA integration, oxidative stress, cytokine release, telomerase homeostasis, mitochondrial damage, epigenetic modification, and tumor microenvironment, are involved in the biological process from hepatitis B to cirrhosis and HCC. N6‐methyladenosine (m6A), as an epitranscriptomic modification of RNAs, can regulate the stability, splicing, degradation, transcription, and translation of downstream target RNAs in HBV and liver cancer cells. m6A regulators (writers, erasers, and readers) play an important role in the pathogenesis of HBV‐associated HCC by regulating cell proliferation, apoptosis, migration, autophagy, differentiation, inflammation, angiogenesis, and tumor microenvironment. This review summarizes the current progress of m6A methylation in the molecular mechanisms, biological functions, and potential clinical implications of HBV‐associated HCC.
The Phytophthora effector Avh94 manipulates host jasmonic acid signaling to promote infection
Authors: Zhao Yao , Yang Bo , Xu Huawei , Wu Jinbin , Xu Zhiyang , Wang Yuanchao
Published: September 2022

The oomycete pathogen Phytophthora sojae is a causal agent of soybean root rot. Upon colonization of soybeans, P. sojae secretes various RXLR effectors to suppress host immune responses, supporting successful infection. Previous research has demonstrated that the RXLR effector Avh94 functions as a virulence effector, but the molecular mechanism underlying its role in virulence remains unknown. Here, we demonstrate that Avh94 overexpression in plants and pathogens promotes Phytophthora infection. Avh94 interacts with soybean JAZ1/2, which is a repressor of jasmonic acid (JA) signaling. Avh94 stabilizes JAZ1/2 to inhibit JA signaling and silencing of JAZ1/2 enhances soybean resistance against P. sojae. Moreover, P. sojae lines overexpressing Avh94 inhibit JA signaling. Furthermore, exogenous application of methyl jasmonate improves plant resistance to Phytophthora. Taken together, these findings suggest that P. sojae employs an RXLR effector to hijack JA signaling and thereby promote infection.
Job satisfaction among small rural hospital nurses: A cross‐sectional study
Authors: Smith Sarah , Lapkin Samuel , Halcomb Elizabeth , Sim Jenny
Published: September 2022

Purpose

To explore the relationships between job satisfaction, community satisfaction, practice environment, burnout, and intention to leave of nurses working in Australian small rural hospitals.

Design

A national cross‐sectional survey of 383 nurses from Australian rural public hospitals of less than 99 beds during 2018.

Methods

Job satisfaction was measured on a four‐point Likert scale. Factors associated with community satisfaction, practice environment, burnout and intention to leave were analyzed using multiple linear regression to explore the predictors of job satisfaction.

Findings

Overall job satisfaction was positive, with most nurses moderately (n = 146, 38.1%) or very satisfied (n = 107, 27.9%) with their current job. Emotional exhaustion, nurse manager ability, leadership and support of nurses were the most significant predictors of job satisfaction.

Conclusion

This study provides new insight into the factors impacting the job satisfaction of nurses working in rural hospitals. The knowledge gained is important to inform strategies to retain nurses in rural areas and, in turn, ensure rural communities have access to quality health care.

Clinical relevance

The impact of nurses' job satisfaction on burnout, patient safety, and intention to leave is well recognized; however, there is limited understanding of job satisfaction in a rural hospital context. This study provides an understanding of the factors that impact job satisfaction of nurses working in small rural hospitals and highlights the importance of improving the practice environment to reduce the high attrition rates of this workforce.
Diphyodont tooth replacement of Brasilodon—A Late Triassic eucynodont that challenges the time of origin of mammals
Authors: Cabreira Sergio F. , Schultz Cesar L. , da Silva Lúcio R. , Lora Luiz Henrique Puricelli , Pakulski Cristiane , do Rêgo Rodrigo C. B. , Soares Marina B. , Smith Moya Meredith , Richter Martha
Published: September 2022

Two sets of teeth (diphyodonty) characterise extant mammals but not reptiles, as they generate many replacement sets (polyphyodonty). The transition in long‐extinct species from many sets to only two has to date only been reported in Jurassic eucynodonts. Specimens of the Late Triassic brasilodontid eucynodont Brasilodon have provided anatomical and histological data from three lower jaws of different growth stages. These reveal ordered and timed replacement of deciduous by adult teeth. Therefore, this diphyodont dentition, as contemporary of the oldest known dinosaurs, shows that Brasilodon falls within a range of wide variations of typically mammalian, diphyodont dental patterns. Importantly, these three lower jaws represent distinct ontogenetic stages that reveal classic features for timed control of replacement, by the generation of only one replacement set of teeth. This data shows that the primary premolars reveal a temporal replacement pattern, importantly from directly below each tooth, by controlled regulation of tooth resorption and regeneration. The complexity of the adult prismatic enamel structure with a conspicuous intra‐structural Schmelzmuster array suggests that, as in the case of extant mammals, this extinct species would have probably sustained higher metabolic rates than reptiles. Furthermore, in modern mammals, diphyodonty and prismatic enamel are inextricably linked, anatomically and physiologically, to a set of other traits including placentation, endothermy, fur, lactation and even parental care. Our analysis of the osteodental anatomy of Brasilodon pushes back the origin of diphyodonty and consequently, its related biological traits to the Norian (225.42 ± 0.37 myr), and around 25 myr after the End‐Permian mass extinction event.
Body weight and body fat are negatively associated with severe dyspareunia in postmenopausal women
Authors: Terauchi Masakazu , Odai Tamami , Kato Kiyoko , Miyasaka Naoyuki
Published: September 2022

Aim

This cross‐sectional study aimed to investigate the factors associated with dyspareunia in pre‐, peri‐, and postmenopausal Japanese women participating in the health and nutrition education program at a menopause clinic.

Methods

First‐visit records of 1702 pre‐, peri‐, and postmenopausal Japanese women (aged 40–79 years) were analyzed. The relationship between severe dyspareunia and background characteristics was examined by multivariate logistic regression analysis.

Results

The average age of the participants was 53.0 ± 6.3 years. The percentage of women who suffered from severe dyspareunia in the pre‐, peri‐, postmenopausal, and the hormone therapy receiving groups were 7.1%, 10.5%, 14.6%, and 7.8%, respectively. In the postmenopausal group, the percentage of women affected by severe dyspareunia was the highest between 2 and 5 years after menopause (18.8%), presumably owing to the gradual postmenopausal decline in the number of sexually active women. In sexually active postmenopausal women, body weight, body mass index (BMI), and body fat percentage (BF%) differed significantly among those who had severe dyspareunia (N = 119) and those who did not (N = 334). BMI and BF% were negatively associated with severe dyspareunia, even after adjustment for age and years since menopause (adjusted odds ratio [95% confidence interval]: BMI, 0.894 [0.825–0.964],p = 0.003; BF%, 0.947 [0.909–0.985],p = 0.006).

Conclusions

BMI and BF% were negatively associated with dyspareunia in sexually active postmenopausal women. In addition to aging, the loss of body weight and fat could negatively impact intercourse in sexually active postmenopausal women.
Prevalence of high flow nasal cannula therapy use for management of infants with bronchiolitis in Australia and New Zealand
Authors: O'Brien Sharon , Haskell Libby , Schembri Rachel , Gill Fenella J , Wilson Sally , Borland Meredith L , Oakley Ed , Dalziel Stuart R ,   the Paediatric Research in Emergency Departments International Collaborative (PREDICT) network, Australasia
Published: September 2022

Aim

To determine the prevalence of high flow nasal cannula (HFNC) therapy in infants presenting to hospital in Australia and New Zealand with bronchiolitis over four bronchiolitis seasons. Secondary aims were to determine temporal trends in HFNC use, and associations between HFNC, hospital length of stay (LOS) and intensive care unit (ICU) admission.

Methods

A planned sub‐study of a multi‐centre international cluster randomised controlled trial investigating knowledge translation strategies for a bi‐national bronchiolitis guideline. Demographics, management and outcomes data were collected retrospectively for infants presenting with bronchiolitis to 26 hospitals between 1 May 2014 and 30 November 2017. Prevalence data are presented as absolute frequencies (95% confidence interval (CI)) with differences between groups for continuous and categorical variables analysed using linear and logistic regression, respectively.

Results

11 715 infants were included with 3392 (29.0%, 95% CI (28.1–29.8%)) receiving oxygen therapy; of whom 1817 (53.6%, 95% CI (51.9–55.3%)) received HFNC. Use of oxygen therapy did not change over the four bronchiolitis seasons (P = 0.12), while the proportion receiving HFNC increased (2014, 336/2587 (43.2%); 2017, 609/3720 (57.8%); P ≤ 0.001). Infants who received HFNC therapy were not substantially different to infants who received oxygen therapy without HFNC. HFNC use was associated with increases in both hospital LOS (P < 0.001) and ICU admissions (P < 0.001).

Conclusion

Use of HFNC therapy for infants with bronchiolitis increased over 4 years. Of those who received oxygen therapy, the majority received HFNC therapy without improvement in hospital LOS or ICU admissions. Strategies to guide appropriate HFNC use in infants with bronchiolitis are required.
Predictors of delayed retirement intention in older Chinese workers
Authors: Kong Wenwen , Ren Minmin , Li Yuqin , Feng Danjun
Published: September 2022

The aim of the current study was to explore delayed retirement intention and its influencing factors in a large sample of older Chinese workers. A cross‐sectional questionnaire survey was conducted among a convenience sample of 2776 older Chinese workers. Multinomial logistic regression analyses were performed separately for male and female workers to examine the association between work characteristics, family factors, personal health and the neuroticism trait and delayed retirement intention. Results showed that workers had low delayed retirement intention, while female workers were more reluctant to delay retirement than male workers. Job demand‐control, job satisfaction, family economic status, family caregiving responsibilities, chronic diseases, physical health, mental health and neuroticism were predictors of male workers' delayed retirement intention, while job effort‐reward imbalance, job satisfaction, family caregiving responsibilities and neuroticism were predictors of female workers' delayed retirement intention after controlling for demographic factors.
Pollen DNA metabarcoding reveals cryptic diversity and high spatial turnover in alpine plant–pollinator networks
Authors: Encinas‐Viso Francisco , Bovill Jessica , Albrecht David E. , Florez‐Fernandez Jaime , Lessard Bryan , Lumbers James , Rodriguez Juanita , Schmidt‐Lebuhn Alexander , Zwick Andreas , Milla Liz
Published: September 2022

Alpine plant–pollinator communities play an important role in the functioning of alpine ecosystems, which are highly threatened by climate change. However, we still have a poor understanding of how environmental factors and spatiotemporal variability shape these communities. Here, we investigate what drives structure and beta diversity in a plant–pollinator metacommunity from the Australian alpine region using two approaches: pollen DNA metabarcoding (MB) and observations. Individual pollinators often carry pollen from multiple plant species, and therefore we expected MB to reveal a more diverse and complex network structure. We used two gene regions (ITS2 and trnL) to identify plant species present in the pollen loads of 154 insect pollinator specimens from three alpine habitats and construct MB networks, and compared them to networks based on observations alone. We compared species and interaction turnover across space for both types of networks, and evaluated their differences for plant phylogenetic diversity and beta diversity. We found significant structural differences between the two types of networks; notably, MB networks were much less specialized but more diverse than observation networks, with MB detecting many cryptic plant species. Both approaches revealed that alpine pollination networks are very generalized, but we estimated a high spatial turnover of plant species (0.79) and interaction rewiring (0.6) as well as high plant phylogenetic diversity (0.68) driven by habitat differences based on the larger diversity of plant species and species interactions detected with MB. Overall, our findings show that habitat and microclimatic heterogeneity drives diversity and fine‐scale spatial turnover of alpine plant–pollinator networks.
Examining the concordance of retinal ganglion cell counts generated using measures of structure and function
Authors: Stapley Victoria , Anderson Roger S. , Saunders Kathryn , Mulholland Pádraig J.
Published: September 2022

Purpose

There are several indirect methods used to estimate retinal ganglion cell (RGC) count in an individual eye, but there is limited information as to the agreement between these methods. In this work, RGC receptive field (RGC‐RF) count underlying a spot stimulus (0.43°, Goldmann III) was calculated and compared using three different methods.

Methods

RGC‐RF count was calculated at a retinal eccentricity of 2.32 mm for 44 healthy adult participants (aged 18–58 years, refractive error −9.75 DS to +1.75 DS) using: (i) functional measures of achromatic peripheral grating resolution acuity (PGRA), (ii) structural measures of RGC‐layer thickness (OCT‐model, based on the method outlined by Raza and Hood) and (iii) scaling published histology density data to simulate a global expansion in myopia (Histology‐Balloon).

Results

Whilst average RGC‐RF counts from the OCT‐model (median 105.3, IQR 99.6–111.0) and the Histology‐Balloon model (median 107.5, IQR 97.7–114.6) were similar, PGRA estimates were approximately 65% lower (median 37.7, IQR 33.8–46.0). However, there was poor agreement between all three methods (Bland–Altman 95% limits of agreement; PGRA/OCT: 55.4; PGRA/Histology‐Balloon 59.3; OCT/Histology‐Balloon: 52.4). High intersubject variability in RGC‐RF count was evident using all three methods.

Conclusions

The lower PGRA RGC‐RF counts may be the result of targeting only a specific subset of functional RGCs, as opposed to the coarser approach of the OCT‐model and Histology‐Balloon, which include all RGCs, and also likely displaced amacrine cells. In the absence of a ‘ground truth’, direct measure of RGC‐RF count, it is not possible to determine which method is most accurate, and each has limitations. However, what is clear is the poor agreement found between the methods prevents direct comparison of RGC‐RF counts between studies utilising different methodologies and highlights the need to utilise the same method in longitudinal work.
Class IV semaphorins in disease pathogenesis
Authors: Nojima Satoshi
Published: September 2022

Semaphorins are a large family of secreted and/or transmembrane proteins, originally identified as proteins that function in axon guidance during neuronal development. However, semaphorins play crucial roles in other physiological and pathological processes, including immune responses, angiogenesis, maintenance of tissue homeostasis, and cancer progression. Class IV semaphorins may be present as transmembrane and soluble forms and are implicated in the pathogenesis of various diseases. This review discusses recent progress on the roles of class IV semaphorins determined by clinical and experimental pathology studies.
Nonparametric asymptotic confidence intervals for extreme quantiles
Authors: Gardes Laurent , Maistre Samuel
Published: September 2022

In this paper, we propose new asymptotic confidence intervals for extreme quantiles, that is, for quantiles located outside the range of the available data. We restrict ourselves to the situation where the underlying distribution is heavy‐tailed. While asymptotic confidence intervals are mostly constructed around a pivotal quantity, we consider here an alternative approach based on the distribution of order statistics sampled from a uniform distribution. The convergence of the coverage probability to the nominal one is established under a classical second‐order condition. The finite sample behavior is also examined and our methodology is applied to a real dataset.
On the robustness to outliers of the Student‐t process
Authors: Andrade J. Ailton A.
Published: September 2022

The theory of Bayesian robustness modeling uses heavy‐tailed distributions to resolve conflicts of information by rejecting automatically the outlying information in favor of the other sources of information. In particular, the Student's‐t process is a natural alternative to the Gaussian process when the data might carry atypical information. Several works attest to the robustness of the Student process, however, the studies are mostly guided by intuition and focused mostly on the computational aspects rather than the mathematical properties of the involved distributions. This work uses the theory of regular variation to address the robustness of the Student process in the context of nonlinear regression, that is, the behavior of the posterior distribution in the presence of outliers in the inputs, in the outputs, or in both sources of information. In all these cases, under certain conditions, it is shown that the posterior distribution tends to a quantity that does not depend on the atypical information, then, for every case, the limiting posterior distribution as the outliers tend to infinity is provided. The impact of outliers on the predictive posterior distribution is also addressed. The theory is illustrated with a few simulated examples.
Dealing with drift: Comparing social care reform in the four nations of the UK
Authors: Needham Catherine , Hall Patrick
Published: September 2022

Reform of social care for older and disabled people has become a pressing political issue, given demographic change and shifting public expectations. In the UK, social insurance for long‐term care wasn't included in the post‐war welfare state and remains unfinished business. Drawing on semi‐structured interviews with policy stakeholders and analysis of policy documents, the concept of policy drift is used here to explain the incomplete and variable progress on social care funding reform in England, Scotland, Wales and Northern Ireland. Each nation has jurisdiction over its own care system and each has taken a different path towards introducing a form of risk pooling for social care. Of the factors which are known to create policy drift (e.g., veto players, complexity, agenda overload), Scotland has the least of these and England the most. This is consistent with the reform trajectories in which Scotland has gone furthest on care funding reform, introducing free personal care in 2002, whereas England has lagged behind the others and is only now introducing reform. The article contributes to the drift literature by exposing its comparative element: polities define their progress or justify their delays in reference to their neighbours.