bluuebunny/crossref_metadata_2025 huggingface dataset:
APE2: catalytic function and synthetic lethality draw attention as a cancer therapy target
Authors: McMahon Anne , Zhao Jianjun , Yan Shan
Published: February 2023

AP endonuclease 2 (APE2, APEX2 or APN2) is an emerging critical protein involved in genome and epigenome integrity. Whereas its catalytic function as a nuclease in DNA repair is widely accepted, recent studies have elucidated the function and mechanism of APE2 in the immune response and DNA damage response. Several genome-wide screens have identified APE2 as a synthetic lethal target for deficiencies of BRCA1, BRCA2 or TDP1 in cancer cells. Due to its overexpression in several cancer types, APE2 is proposed as an oncogene and could serve as prognostic marker of overall survival of cancer treatment. However, it remains to be discovered whether and how APE2 catalytic function and synthetic lethality can be modulated and manipulated as a cancer therapy target. In this review, we provide a current understanding of alterations and expression of APE2 in cancer, the function of APE2 in the immune response, and mechanisms of APE2 in ATR/Chk1 DNA damage response. We also summarize the role of APE2 in DNA repair pathways in the removal of heterogenous and complexed 3’-termini and MMEJ. Finally, we provide an updated perspective on how APE2 may be targeted for cancer therapy and future directions of APE2 studies in cancer biology.
Hand–arm vibration: Swedish carpenters’ perceptions of health and safety management
Authors: Fisk K , Nordander C , Ek Å
Published: February 2023

Background

Workers in the construction industry are highly exposed to vibration from handheld equipment, which can have negative effects on the nerves and blood vessels in the hands. Employers in this industry often fail to comply with legislation regarding vibration exposure.

Aims

To assess carpenters’ perceptions of proactive health and safety (H&S) management regarding hand–arm vibration exposure at construction sites in Sweden.

Methods

The carpenters answered a questionnaire on their perception of the implementation of H&S management, on symptoms indicating injury and on the use of vibrating equipment.

Results

One hundred and ninety-four carpenters from 4 construction companies and 18 construction sites completed the questionnaire. Attitudes to H&S management were generally positive. However, 36% of the carpenters reported that the H&S regulations and routines did not function in practice, and 40% claimed they did not receive necessary information on the exposure and effects of vibration. Most respondents (74%) perceived a high risk of injury in general in their work. Younger carpenters, carpenters employed at smaller companies and carpenters with symptoms indicating injury or with higher vibration exposure reported more negative perceptions.

Conclusions

In general, the carpenters were positive about management’s commitment to H&S management. However, the results indicate deficiencies in the way in which this commitment is applied in practice at the workplace. This highlights the importance of raising awareness concerning vibration exposure and possible injuries, and strengthening proactive H&S programmes, especially in smaller companies.
Cognitive mechanisms and resilience in UK-based general practitioners: cross-sectional findings
Authors: Kaleta F O , Kristensen C B , Duncan M , Crutchley P , Kerr P , Hirsch C R
Published: February 2023

Background

Being a general practitioner (GP) is a stressful occupation, and the strain GPs are under can have negative effects on their psychological well-being, as well as on the patients’ experience of healthcare. Resilience can help buffer against this and is a dynamic process by which one can cope with adversity and stress.

Aims

This study aimed to identify modifiable cognitive mechanisms related to resilience in GPs, specifically interpretation bias and cognitive reappraisal.

Methods

One hundred and fourteen GPs completed an online cross-sectional correlational study. This comprised questionnaires assessing resilience, emotional distress, work environment and cognitive mechanisms (emotion regulation), as well as a task assessing interpretation bias.

Results

Resilience of GPs was negatively correlated with measures of emotional distress. Furthermore, resilience was positively correlated with positive interpretation bias (r = 0.60, ρ = 0.60, P < 0.01) and cognitive reappraisal (r = 0.39, ρ = 0.40, P < 0.01). In a hierarchical regression, positive interpretation bias (B = 0.25, SE B = 0.06, β = 0.39, P < 0.01) was a significant independent predictor of resilience when controlling for depression, anxiety and stress.

Conclusions

This is the first study to establish an association between resilience and positive interpretation bias and cognitive reappraisal in GPs. Future research should use longitudinal designs to determine if they have a causal role in promoting resilience, and importantly whether interventions focusing on these processes may foster resilience in less resilient GPs.
The potential role of descriptive and dynamic norms in promoting climate change advocacy
Authors: Campbell Eryn , Kotcher John E , Myers Teresa , Munson Sammi , Borth Amanda C , Rosenthal Seth A , Leiserowitz Anthony , Maibach Edward
Published: February 2023

Political advocacy is arguably the most powerful form of action that citizens concerned about climate change can take. One motivator for political advocacy is the perception that there is a social norm (i.e. inherently understood social rules and standards that serve to guide social behaviors) for doing so. Using nationally representative survey data (N = 1303), we examined the association of three types of social norms—descriptive norms (i.e. perceptions about how many other people perform a behavior), retrospective and prospective dynamic norms (i.e. perceptions that a behavior has become more or less common in the past or will in the future)—with intentions to engage in political advocacy in the upcoming year and past advocacy. We found that descriptive norms and prospective dynamic norms were positively related to advocacy intentions, while only prospective dynamic norms were positively related to past advocacy (retrospective dynamic norms were negatively related to both outcomes, contrary to our theorized direction). Furthermore, we examined whether the relationship between norms and intentions/behaviors differed based on political party identification and four potential mediators of this relationship: identification with climate activists; collective efficacy (i.e. the belief that people can engage in climate advocacy and that it will make a difference); collective response efficacy (i.e. beliefs about the results of advocacy); and injunctive norms (i.e. perceptions of others’ approval of advocacy). In the moderated mediation models, we found that party identification moderated the relationships between descriptive norms and prospective dynamic norms and advocacy intention, while retrospective dynamic norms were not related as theorized. These relationships were mediated by identification with climate activists and collective efficacy as well as by injunctive norms in the case of descriptive norms. Party identification also moderated the relationship between descriptive norms and past advocacy; this relationship was mediated by identification with climate activists and injunctive norms. Taken together, these findings underscore the potential importance of perceived descriptive norms and prospective dynamic norms on political advocacy to address climate change, extending both well-established and emerging research and providing insights useful for academics and practitioners alike.
PET vascular activity score for predicting new angiographic lesions in patients with Takayasu arteritis: a Chinese cohort study
Authors: Ma Lingying , Wu Bing , Sun Ying , Ding Zhenqi , Dai Xiaomin , Wang Li , Dai Xiaojuan , Zhang Lijuan , Chen Huiyong , Ma Lili , Lv Peng , Shi Hongcheng , Jiang Lindi
Published: February 2023

Objective

To investigate the ability of 18F-fluorodeoxyglucose PET/CT to predict new lesions in Takayasu arteritis.

Methods

Eighty-two Chinese patients with newly diagnosed Takayasu arteritis were recruited. Their clinical characteristics, serum biomarkers and imaging results were recorded at baseline and every visit. They were followed up for at least 2 years. New angiographic lesions were evaluated by magnetic resonance angiography. Baseline PET vascular activity scores (PETVAS) for predicting new lesions were evaluated.

Results

At baseline, a moderate correlation was observed between PETVAS and ESR (r = 0.74, P < 0.01) and CRP level (r = 0.69, P < 0.01). Overall, 18 (22%) patients showed new lesions on imaging during a median follow-up time of 36 months. The median time to the first occurrence of new lesions was 18 months. Compared with patients without new lesions, the patients with new lesions included more female patients (67.2% vs 94.4%, P = 0.03), patients with higher ESR values (20 vs 49, P = 0.02) and patients with active disease (62.5% vs 94.4%, P < 0.01). Multivariate Cox regression analysis revealed PETVAS was an independent risk factor for new angiographic lesions (PETVAS ≥8, hazard ratio = 7.56; 95% CI 2.20, 26.01, P < 0.01) with adjustment of age, sex, chest pain, ESR and Physician Global Assessment. Furthermore, patients with PETVAS ≥8 at baseline were more likely to experience adverse events including arterial ischaemic events during the follow-up.

Conclusion

PETVAS showed good performance in predicting new lesions in Takayasu arteritis.
Sexual dysfunction in male childhood cancer survivors and adolescent and young adult survivors of hematologic malignancies
Authors: Crist Nikos , Egert Melissa C , Bernie Helen L
Published: February 2023

Sexual Health is an important aspect of overall health and quality of life (QoL) among adolescent and young adult (AYA) as well as childhood cancer survivors (CCS). Sexual health encompasses psychosocial, physical, developmental, emotional and relationship factors that impact sexual function. Cancer and its associated treatments are associated with negative effects on sexual health, body image, relationships, as well as overall physical and mental health. Data shows that CCS are known to experience diminished QoL compared to their peers. However, limited information is available to guide the assessment and treatment of sexual dysfunction in AYA and CCS. Further, exploration into specific cancer types, treatment methods and their resultant effects on sexual function within these populations is far more limited. We conducted an extensive review of the literature that focused on sexual dysfunction in male survivors of hematologic malignancies (HM). Our review identified an increased incidence of sexual dysfunction within male AYA and CCS of HM, and the negative impact this has on overall QoL. Our results show the degree to which survivors of HM experience increased sexual dysfunction, and the therapies and pathophysiologic mechanisms that may contribute to the development of sexual dysfunction within this population. These findings highlight the lack of research on this topic and need for further exploration into AYA and CCS sexual health to improve patient care and close the knowledge gaps to better assess and treat sexual dysfunction in this patient population.
Sequences and Genome-Wide Analysis of mRNA and microRNA Expression in Tea (Camellia sinensis) Leaves in Response to Epicoccum sorghinum Infection
Authors: Huang Hongke , Jiang Xinyue , Huang Chen , Xia Zhongqiu , Yang Yuqin , Yin Jiayu , Zhao Hong , Mo Bin , Zhao Yongtian , Wang Delu , Chen Zhuo
Published: February 2023

Due to our lack of understanding of the host-pathogen epidemiology and the absence of effective control measures, tea leaf spot, caused by the fungus Epicoccum sorghinum, continues to reduce the productivity and quality of tea leaves in plantations in Guizhou Province, southwestern China. Here, samples of tea ( Camellia sinensis [L.] O Kuntze) leaves either infected or uninfected by E. sorghinum were used as the study model. The mRNA and microRNA (miRNA) sequences in tea leaves from the two treatments were determined using the Illumina NovaSeq 6000 and the Illumina HiSeq 2500 platforms, respectively. In total, 33,932 genes or transcripts from tea leaves were annotated. In response to infection by E. sorghinum, 1,068 or 467 of the differentially expressed mRNAs (DEmRNAs) were up- or downregulated, respectively, and the DEmRNAs containing peroxidase 21 and LRR receptor-like serine/threonine-protein kinase ERECTA were enriched in terms of defense response. Meanwhile, 1,889 miRNAs were identified from infected or uninfected leaves. Nine or seven of the differentially expressed miRNAs (DEmiRNAs) were up- or downregulated, respectively. The DEmiRNAs MIR5303j-p5, MIR6173-p5, miR858-3p, and novel-miR0377-3p were predicted to bind to DEmRNAs. Fifteen DEmRNAs annotated into transcription factor proteins enriched with respect to the plant-pathogen interaction pathway were predicted to be bound by the DEmiRNA miR858-3p. The sequences and abundances of the mRNAs and miRNAs from tea leaves infected by E. nigrum, and the prediction of the interaction between DEmiRNAs and DEmRNAs could contribute to our understanding of this plant-pathogen interaction.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
The Effect of Tomato Cultivar on Pythium Root Rot and Efficacy of Biopesticides
Authors: DeGenring Liza , Poleatewich Anissa
Published: February 2023

Barriers to broad commercial use of biopesticides include inconsistent efficacy, which can be influenced by plant species, soil type, and production system. Few studies have evaluated the effect of plant cultivar on the efficacy of commercial biopesticides to suppress disease under greenhouse production conditions. The objective of this study was to evaluate the effect of tomato cultivar on Pythium root rot and the efficacy of commercially available microbial biopesticides (Rootshield WP and Cease). Under low to moderate disease, plants treated with Rootshield had lower Pythium root rot severity compared with the control, and this efficacy was influenced by cultivar. The tomato cultivars ‘Ailsa Craig’, ‘Glamour’, and ‘Maxifort’ had up to 75% less disease when treated with Rootshield compared with the water control. This effect was not observed on cultivar ‘Trust’, a scion cultivar used in greenhouse vegetable production. Cease had no effect on Pythium root rot severity. The aboveground dried biomass of plants treated with Rootshield was lower for tomato cultivars Trust and Glamour. This research suggests that cultivar can explain some of the variability of biopesticide efficacy in reducing root rot disease.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Pediatric trauma center vs. adult trauma center: which is better?
Authors: Russell Katie , Biswas Subarna
Published: February 2023

Purpose of Review

Pediatric trauma centers (PTCs) have been championed as multidisciplinary facilities specializing in the care of pediatric trauma, the leading cause of childhood mortality in the United States.1 However, the vast majority of pediatric trauma is still seen in trauma centers focused on treating adults. This article reviews the latest evidence comparing the relative strengths of PTCs and adult trauma centers (ATCs) in treating childhood injury.

Recent findings

Recent multicenter studies comparing outcomes of pediatric injury in PTCs and ATCs have found no differences in mortality or hospital length of stay, contradicting earlier findings. However, fewer invasive procedures and CT scans were performed at PTCs, and more children were discharged back to their homes.

It is difficult to demonstrate a difference in outcomes for children treated at PTCs vs. ATCs. However, PTCs do offer a multidisciplinary, nuanced approach to pediatric trauma care, which may result in long term benefits and offer opportunities for regional collaboration.
The X-Mas Box Osteosuture: A New Technique for Coracoid Process Fracture
Authors: Lollino Nicola , Coltella Leonardo
Published: February 2023

A fracture of the tip of the coracoid is a rare but challenging fracture. A surgical indication is required in case of a displaced fracture. Screws and suture anchors often do not offer a reliable fixation in the case of very small fragments. We describe our hardwareless technique that consists of an osteosuture with a 90-degree suture threads configuration that we called the x-mas box technique. This procedure is cost-effective and it provides stable fixation and low complications rate.
Entering a new era of molecular classification of brain tumors: An update of 2021 World Health Organization classification in adult gliomas
Authors: Wang Ching-Ying , Lin Shih-Chieh , Chen Ming-Teh , Lee Yi-Yen
Published: February 2023

Glioma is the most common primary central nervous system tumor. The World Health Organization (WHO) 2021 classification of gliomas extended from WHO 2016 in the integration of molecular and histological classifications. WHO 2021 aims to establish a specific diagnosis that could reflect the biological and clinical features of the tumors, and further transform into more specific clinical studies or trials and therapeutics. Major updates of WHO 2021 classification focusing on glioma were reviewed in this article.
EGF receptor modulates HEV entry in human hepatocytes
Authors: Schrader Jil A. , Burkard Thomas L. , Brüggemann Yannick , Gömer André , Meister Toni L. , Fu Rebecca M. , Mehnert Ann-Kathrin , Dao Thi Viet L. , Behrendt Patrick , Durantel David , Broering Ruth , Vondran Florian W. R. , Todt Daniel , Kinast Volker , Steinmann Eike
Published: February 2023

Background and Aims:

Being the most common cause of acute viral hepatitis with >20 million cases per year and 70,000 deaths annually, HEV presents a long-neglected and underinvestigated health burden. Although the entry process of viral particles is an attractive target for pharmacological intervention, druggable host factors to restrict HEV entry have not been identified so far.

Approach and Results:

Here we identify the EGF receptor (EGFR) as a novel host factor for HEV and reveal the significance of EGFR for the HEV entry process. By utilizing RNAi, chemical modulation with Food and Drug Administration–approved drugs, and ectopic expression of EGFR, we revealed that EGFR is critical for HEV infection without affecting HEV RNA replication or assembly of progeny virus. We further unveiled that EGFR itself and its ligand-binding domain, rather than its signaling function, is responsible for the proviral effect. Modulation of EGF expression in HepaRG cells and primary human hepatocytes affected HEV infection.

Conclusions:

Taken together, our study provides novel insights into the life cycle of HEV and identified EGFR as a possible target for future antiviral strategies against HEV.
Intraocular lens tilt and decentration after cataract surgery with and without primary posterior continuous curvilinear capsulorhexis
Authors: Liu Xiaobao , Yu Mengting , Huang Yue , Li Qiong , Wu Wenjie
Published: February 2023

Purpose:

To evaluate intraocular lens (IOL) tilt and decentration and their effects on higher-order aberrations (HOAs) after cataract surgery with and without primary posterior continuous curvilinear capsulorhexis (PPCCC).

Setting:

Fujian Provincial Hospital, Fujian, China.

Design:

Prospective, intraindividual, randomized, comparative clinical trial.

Methods:

64 eyes of 32 patients with age-related cataract who underwent bilateral cataract surgery and IOL implantation were enrolled in this study. In randomized order, all patients had phacoemulsification cataract surgery with PPCCC in 1 eye (PPCCC group) and routine cataract surgery in the contralateral eye (NPCCC group). IOL decentration, tilt, HOAs, modulation transfer function, and point spread function were measured at 1 day, 1 week, 1 month, and 3 months after surgery using OPD-Scan III.

Results:

52 eyes of 26 patients were available for analysis. The mean overall decentration in the NPCCC group was significantly higher than in the PPCCC group at 3 months (0.302 ± 0.157 mm vs 0.187 ± 0.099 mm, P < .001). Under 3 mm pupil, internal spherical aberration (SA) 1 day after surgery and coma 1 week after surgery were lower in the PPCCC group compared with the NPCCC group (0.15 ± 0.10 μm vs 0.30 ± 0.21 μm, P < .001, and 0.34 ± 0.18 μm vs 0.47 ± 0.31 μm, P = .03, respectively). IOL decentration was significantly correlated with ocular and internal coma, ocular and internal SA, and internal HOAs at 5 mm pupil (R = 0.083 and R = 0.099, R = 0.650 and R = 0.613, and R = 0.418, respectively, all P < .01).

Conclusions:

Less IOL decentration was observed in the PPCCC group at 3 months after surgery, indicating that PPCCC may result in better IOL centrality.
The Influence of Informal Caregivers' Preparedness on Psychological Symptoms and Quality of Life Among Patients With Heart Failure And Insufficient Self-care
Authors: Su Yue , Cheng Ming , Zhu Chenya , Ge Yingying , Ke Yufei , Shi Yixing , Luo Meiling , Gu Xi , Ge Yutong , Ma Tianyu , Chi Meixuan , Wang Naijuan , Hou Yunying
Published: February 2023

Background

Most patients with heart failure find self-care difficult to perform and rely on family caregivers for support. Informal caregivers, however, often face insufficient psychological preparation and challenges in providing long-term care. Insufficient caregiver preparedness not only results in psychological burden for the informal caregivers but may also lead to a decline in caregiver contributions to patient self-care that affects patient outcomes.

Objective

Our objective was to test (1) the association of baseline informal caregivers' preparedness with psychological symptoms (anxiety and depression) and quality of life 3 months after baseline among patients with insufficient self-care and (2) the mediating effects of caregivers' contributions to self-care of heart failure (CC-SCHF) on the relationship of caregivers' preparedness with patients' outcomes at 3 months.

Methods

A longitudinal design was used to collect data between September 2020 and January 2022 in China. Data analyses were conducted using descriptive statistics, correlations, and linear mixed models. We used model 4 of the PROCESS program in SPSS with bootstrap testing to evaluate the mediating effect of CC-SCHF of informal caregivers' preparedness at baseline with psychological symptoms or quality of life among patients with HF 3 months later.

Results

Caregiver preparedness was positively associated with CC-SCHF maintenance (r = 0.685, P < .01), CC-SCHF management (r = 0.403, P < .01), and CC-SCHF confidence (r = 0.600, P < .01). Good caregiver preparedness directly predicted lower psychological symptoms (anxiety and depression) and higher quality of life for patients with insufficient self-care. The associations of caregiver preparedness with short-term quality of life and depression of patients with HF with insufficient self-care were mediated by CC-SCHF management.

Conclusions

Enhancing the preparedness of informal caregivers may improve psychological symptoms and quality of life of heart failure patients with insufficient self-care.
Aggressive Incidents by Incarcerated People With Psychiatric Illness and Their Relationship With Psychiatric Symptoms
Authors: van Beek Janneke , Meijers Jesse , Scherder Erik J. A. , Harte Joke M.
Published: February 2023

Aim

A prospective design was used to investigate the relationship of current psychiatric symptoms of incarcerated people with serious mental illness (SMI) and aggressive behavior on a penitentiary ward for crisis intervention.

Methods

One hundred sixty detainees with SMI, detained in a high-security penitentiary psychiatric facility, were screened every 2 weeks with the Brief Psychiatric Rating Scale-Extended (BPRS-E) by trained clinicians, to ensure that the data on psychiatric symptoms were up-to-date. Aggressive behavior was registered with the Staff Observation Aggression Scale–Revised. A binary logistic regression analysis was performed to examine the relationships between factor scores of the BPRS-E and aggressive behavior.

Results

Significant relationships between the BPRS-E factor hostility, antisocial traits, and aggressive incidents were found, but not between the positive symptoms or manic factor scores and aggressive incidents.

Discussion

Symptoms of SMI measured with the BPRS-E did not help to explain the occurrence of aggressive behavior. This is not in line with what is commonly found. The implication is that it can be expected that this population will display aggressive behavior but that symptoms do not help in predicting when this will occur. In addition, hostility and antisocial traits were related to aggressive behavior. For this specific population, an interactional approach might be more effective in the management of aggression than treatment of symptoms of SMI.
Helping patients with substance use disorder: The nurse practitioner role in access to treatment
Authors: Bressan John , Kenig Kathryn Chenin
Published: February 2023

Over 21 million people in the United States require substance use disorder (SUD) treatment. However, less than 4 million people receive treatment. The surge of deaths due to opioid overdose requires aggressive public health interventions. This article will describe the role of the hospital emergency department (ED), not simply in emergency treatment of overdose but as a provider of care for underlying addiction and as a catalyst for change in our approach to drug use as a society. It has been found that EDs and hospitals serve as an important point for initiating treatment for SUDs. It is important to provide equitable access to care because the ED serves as an important access point for those with socioeconomic disadvantages. This article presents case studies and the nurse practitioner role in providing medication for addiction and treatment in the ED while also addressing misconceptions about treatment.
A Pilot Study of a Screening Program for Human Papillomavirus–Related Squamous Intraepithelial Lesion and Malignancy in Gynecologic Oncology Patients
Authors: Watson Catherine H. , Spinosa Daniel , Hayes Taylor , Scott Amelia , Jackson Louise , Thacker Julie K. , Sherman Karen L. , Moss Haley A. , Havrilesky Laura J. , McNally J. Leah
Published: February 2023

Objective

Human papillomavirus (HPV)–related squamous intraepithelial lesion (SIL) or malignancy is associated with a significantly increased risk of second-site SIL or malignancy. The primary objective of this study was to determine the feasibility and acceptability of concurrent anal, cervical, and vulvovaginal screening in patients with a history of HPV-related gynecologic high-grade SIL or malignancy. The secondary objective was to assess subjects' knowledge regarding HPV screening and risks.

Methods

Women with high-grade cervical, vulvar, or vaginal SIL or malignancy were enrolled during a 1-year pilot period. Subjects with cervical SIL or malignancy underwent vulvar examination and anoscopy. Subjects with vulvovaginal SIL or malignancy underwent Pap test if indicated and anoscopy. Appropriate referrals were made for abnormal findings. Feasibility was assessed by compliance using study acceptance rate, screening procedure adherence, and referral adherence. Acceptability was assessed using a Likert-scaled question after completion of screening procedures.

Results

One hundred three women with a diagnosis of high-grade vulvovaginal or cervical SIL or carcinoma were approached regarding study enrollment; of these, 74 (71.8%) enrolled. The median score on the HPV knowledge assessment was 8.1 ± 1.6 (max score 10). Seventy-three (98.6%) of 74 patients rated the screening procedures as acceptable (score of 5/5). On examination, 14 (18.9%) subjects had abnormalities noted; 7 (9.5%) were referred for colorectal surgical evaluation, and 6/7 (85.7%) were compliant with their referral appointments.

Conclusions

Screening examinations for other HPV-related SILs and malignancies, including Pap tests, vulvovaginal inspection, and anoscopy, are acceptable to patients, with abnormal findings in almost 1 in 5 women.
Cervicocerebral Computed Tomography Angiography for Older Patients Based on Time to Peak and Number of Time Points to Peak in the Test Bolus Technique
Authors: Zeng Yuli , He Rong , Ren Yong , Che Yilei , Wang Guiliang
Published: February 2023

Objective

This study sought to optimize image quality and reduce the contrast dose by adjusting contrast agent and normal saline doses used in cervicocerebral computed tomography angiography (CTA) of older patients.

Methods

Older patients who underwent cervicocerebral CTA were divided into group A (n = 110) and group B (n = 124). In the angiography scan, patients in group A were injected with 1.0 mL/kg contrast agent, followed by 40 mL saline chaser. In group B, contrast agent and normal saline doses were adjusted based on time to peak and number of time points to peak in the test bolus technique. The CT attenuation values, noise, signal-to-noise ratio, and contrast-to-noise ratio of target arteries and the right transverse sinus were objectively compared.

Results

Compared with group A, the contrast retention and artifacts in the right subclavian vein, right brachiocephalic veins, and superior vena cava were significantly decreased in group B. Furthermore, in group B, the noise at the bifurcation of the right common carotid artery increased by 1.7%, and the signal-to-noise ratio of the left middle cerebral artery M1 segment decreased by 6.6%. The contrast dose in group B decreased significantly (18.2%) as compared with group A.

Conclusion

Based on time to peak and number of time points to peak with the test bolus, adjusting contrast and normal saline doses in cervicocerebral CTA for older people reduces contrast retention and artifacts in the veins of the injection side. Further, it also decreases the contrast dose needed to obtain image quality that satisfies diagnostic requirements.
Conservation measures or hotspots of disease transmission? Agri-environment schemes can reduce disease prevalence in pollinator communities
Authors: Manley Robyn , Doublet Vincent , Wright Owen N. , Doyle Toby , Refoy Isobel , Hedges Sophie , Pascall David , Carvell Claire , Brown Mark J. F. , Wilfert Lena
Published: February 2023

Insects are under pressure from agricultural intensification. To protect pollinators, conservation measures such as the EU agri-environment schemes (AES) promote planting wildflowers along fields. However, this can potentially alter disease ecology by serving as transmission hubs or by diluting infections. We tested this by measuring plant–pollinator interactions and virus infections (DWV-A, DWV-B and ABPV) across pollinator communities in agricultural landscapes over a year. AES had a direct effect on DWV-B, reducing prevalence and load in honeybees, with a tentative general dilution effect on load in early summer. DWV-A prevalence was reduced both under AES and with increasing niche overlap between competent hosts, likely via a dilution effect. By contrast, AES had no impact on ABPV, its prevalence driven by the proportion of bumblebees in the community. Epidemiological differences were also reflected in the virus phylogenies, with DWV-B showing recent rapid expansion, while DWV-A and ABPV showed slower growth rates and geographical population structure. Phylogenies indicate that all three viruses freely circulate across their host populations. Our study illustrates how complex interactions between environmental, ecological and evolutionary factors may influence wildlife disease dynamics. Supporting pollinator nutrition can mitigate the transmission of important bee diseases, providing an unexpected boost to pollinator conservation.

This article is part of the theme issue ‘Infectious disease ecology and evolution in a changing world’.
Host developmental stages shape the evolution of a plant RNA virus
Authors: Melero Izan , González Rubén , Elena Santiago F.
Published: February 2023

Viruses are obligate pathogens that entirely rely on their hosts to complete their infectious cycle. The outcome of viral infections depends on the status of the host. Host developmental stage is an important but sometimes overlooked factor impacting host–virus interactions. This impact is especially relevant in a context where climate change and human activities are altering plant development. To better understand how different host developmental stages shape virus evolution, we experimentally evolved turnip mosaic virus (TuMV) on
Arabidopsis thaliana
at three different developmental stages: vegetative (juvenile), bolting (transition) and reproductive (mature). After infecting plants with an
Arabidopsis
-naive or an
Arabidopsis
-well-adapted TuMV isolate, we observed that hosts in later developmental stages were prone to faster and more severe infections. This observation was extended to viruses belonging to different genera. Thereafter, we experimentally evolved lineages of the naive and the well-adapted TuMV isolates in plants from each of the three developmental stages. All evolved viruses enhanced their infection traits, but this increase was more intense in viruses evolved in younger hosts. The genomic changes of the evolved viral lineages revealed mutation patterns that strongly depended on the founder viral isolate as well as on the developmental stage of the host wherein the lineages were evolved.

This article is part of the theme issue ‘Infectious disease ecology and evolution in a changing world’.
Out of the ‘host’ box: extreme off-host conditions alter the infectivity and virulence of a parasitic bacterium
Authors: Marcus Enav , Dagan Tal , Asli Weaam , Ben-Ami Frida
Published: February 2023

Disease agents play an important role in the ecology and life history of wild and cultivated populations and communities. While most studies focus on the adaptation of parasites to their hosts, the adaptation of free-living parasite stages to their external (off-host) environment may tell us a lot about the factors that shape the distribution of parasites.Pasteuria ramosais an endoparasitic bacterium of the water fleaDaphniawith a wide geographical distribution. Its transmission stages rest outside of the host and thus experience varying environmental regimes. We examined the life history ofP. ramosapopulations from four environmental conditions (i.e. groups of habitats): the factorial combinations of summer-dry water bodies or not, and winter-freeze water bodies or not. Our goal was to examine how the combination of winter temperature and summer dryness affects the parasite's ability to attach to its host and to infect it. We subjected samples of the four groups of habitats to temperatures of 20, 33, 46 and 60°C in dry and wet conditions, and exposed a susceptible clone ofDaphnia magnato the treated spores. We found that spores which had undergone desiccation endured higher temperatures better than spores kept wet, both regarding attachment and subsequent infection. Furthermore, spores treated with heightened temperatures were much less infective and virulent. Even under high temperatures (60°C), exposed spores from all populations were able to attach to the host cuticle, albeit they were unable to establish infection. Our work highlights the sensitivity of a host-free resting stage of a bacterial parasite to the external environment. Long heatwaves and harsh summers, which are becoming more frequent owing to recent climate changes, may therefore pose a problem for parasite survival.

This article is part of the theme issue ‘Infectious disease ecology and evolution in a changing world’.
B3GALT6 Promotes Dormant Breast Cancer Cell Survival and Recurrence by Enabling Heparan Sulfate-Mediated FGF Signaling
Authors: Sreekumar Amulya , Lu Michelle , Choudhury Biswa , Pan Tien-chi , Pant Dhruv K. , Sterner Christopher J. , Belka George K. , Toriumi Takashi , Benz Brian , Escobar-Aguirre Matias , Marino Francesco E. , Esko Jeffrey D. , Chodosh Lewis A.
Published: February 2023

Breast cancer mortality results primarily from incurable recurrent tumors seeded by dormant, therapy-refractory residual tumor cells (RTCs). Understanding the mechanisms enabling dormant RTC survival is therefore essential for improving patient outcomes. We derived a dormancy-associated RTC signature that mirrors the transcriptional response to neoadjuvant chemotherapy in patients and is enriched for extracellular matrix-related pathways. In vivo CRISPR-Cas9 screening of dormancy-associated candidate genes identified the galactosyltransferase B3GALT6 as a functional regulator of RTC fitness. B3GALT6 covalently attaches glycosaminoglycans (GAGs) to proteins to generate proteoglycans and its germline loss-of-function causes skeletal dysplasias. We determined that B3GALT6-mediated biosynthesis of the GAG heparan sulfate predicts poor patient outcomes, promotes tumor recurrence by enhancing dormant RTC survival in multiple contexts, and does so via a B3GALT6-heparan sulfate/HS6ST1-heparan 6-O-sulfation/FGF1-FGFR2 signaling axis. These findings identify a role for B3GALT6 in cancer and suggest targeting FGF signaling as a novel approach to preventing recurrence by eradicating dormant RTCs.
Detection and Phylogenetic Analysis of Highly Pathogenic A/H5N1 Avian Influenza Clade 2.3.4.4b Virus in Chile, 2022
Authors: Jimenez-Bluhm Pedro , Siegers Jurre Y. , Tan Shaoyuan , Sharp Bridgett , Freiden Pamela , Orozco Katherinne , Ruiz Soledad , Baumberger Cecilia , Galdames Pablo , Gonzalez Maria Antonieta , Rojas Camila , Karlsson Erik A. , Hamilton-West Christopher , Schultz-Cherry Stacey
Published: February 2023

Since the emergence of the Highly Pathogenic Avian Influenza H5N1 goose/Guangdong (Gs/GD) lineage in China in 1996, these viruses have spread globally. This includes the recent introduction of the Gs/GD lineage 2.3.4.4b in the Americas in 2021, which has affected both wild and domestic bird populations causing high mortality. Since November 2022, reports of mortality in wild birds in numerous South American countries along the Pacific Migratory Flyway have been attributed to this lineage. Through an ongoing longitudinal avian influenza virus (AIV) surveillance, we determined that AIV prevalence remained below 1% in the Lluta river wetland from August through October 2022. However, there was a significant increase in prevalence to 2.6% and 11.7% in November and December respectively, coinciding with the arrival of migratory birds from the Northern Hemisphere. Of the AIV RT-qPCR positive environmental feces samples 7 were identified as A/H5. Sequencing of the COI gene demonstrated that the H5 positive samples were obtained from Peruvian pelican (n=1), Franklin’s gull (n=1), Gray gull (n=1), Elegant tern (n=2) and Black skimmer (n=2). Full genomes were obtained from 3 samples and the putative cleavage site composition of the HA was polybasic REKRRKR/GLF for all. Phylogenetic analysis of the samples revealed them to belong to the H5 2.3.4.4b clade, closely related to isolates obtained in Peru in late November. The emergence of H5 clade 2.3.4.4b in South America has an immediate impact on public health, animal production and wildlife, hence increased active surveillance is warranted.
McrD binds asymmetrically to methyl-coenzyme M reductase improving active site accessibility during assembly
Authors: Chadwick Grayson L. , Joiner Aaron M.N. , Ramesh Sangeetha , Mitchell Douglas A. , Nayak Dipti D.
Published: February 2023

Methyl-coenzyme M reductase (MCR) catalyzes the formation of methane and its activity accounts for nearly all biologically produced methane released into the atmosphere. The assembly of MCR is an intricate process involving the installation of a complex set of post-translational modifications and the unique Ni porphyrin cofactor F430. Despite decades of research, details of MCR assembly remain largely unresolved. Here, we report the structural characterization of MCR in two intermediate states of assembly. These intermediate states lack one or both F430cofactors and form complexes with the previously uncharacterized McrD protein. McrD is found to bind asymmetrically to MCR, displacing large regions of the alpha subunit and increasing active site accessibility for the installation of F430—shedding light on the assembly of MCR and the role of McrD therein. This work offers crucial information for the expression of MCR in a heterologous host and provides new targets for the design of MCR inhibitors.

One-sentence summary

Structural characterization of methyl-coenzyme M reductase assembly intermediates.
The skin microbiome enhances disease through IL-1b and delays healing in cutaneous leishmaniasis patients
Authors: Farias Amorim Camila , Lovins Victoria M. , Singh Tej Pratap , Novais Fernanda O. , Harris Jordan C. , Lago Alexsandro S. , Carvalho Lucas P. , Carvalho Edgar M. , Beiting Daniel P. , Scott Phillip , Grice Elizabeth A.
Published: February 2023

Leishmania braziliensisinfection results in inflammation and skin injury, with highly variable and unpredictable clinical outcomes. Here, we investigated the potential impact of microbiota on infection-induced inflammatory responses and disease resolution by conducting an integrated analysis of the skin microbiome and host transcriptome on a cohort of 62L. braziliensis-infected patients. We found that overall bacterial burden and microbiome configurations dominated withStaphylococcusspp. were associated with delayed healing and enhanced inflammatory responses, especially by IL-1 family members. Dual RNA-seq of human lesions revealed that high lesionalS. aureustranscript abundance was associated with delayed healing and increased expression of IL-1β. This cytokine was critical for modulating disease outcome inL. braziliensis-infected mice colonized withS. aureus, as its neutralization reduced pathology and inflammation. These results implicate the microbiome in cutaneous leishmaniasis disease outcomes in humans and suggest host-directed therapies to mitigate the inflammatory consequences.
Aberrant perception of environmental volatility during social learning in emerging psychosis
Authors: Hauke Daniel J. , Wobmann Michelle , Andreou Christina , Mackintosh Amatya , de Bock Renate , Karvelis Povilas , Adams Rick A. , Sterzer Philipp , Borgwardt Stefan , Roth Volker , Diaconescu Andreea O.
Published: February 2023

Paranoid delusions or unfounded beliefs that others intend to deliberately cause harm are a frequent and burdensome symptom in early psychosis, but their emergence and consolidation still remains opaque. Recent theories suggest that aberrant prediction errors lead to a brittle model of the world providing a breeding ground for delusions. Here, we employ a Bayesian approach to test for a more unstable model of the world and investigate the computational mechanisms underlying emerging paranoia.

We modelled behaviour of 18 first-episode psychosis patients (FEP), 19 individuals at clinical high-risk for psychosis (CHR-P), and 19 healthy controls (HC) during an advice-taking task, designed to probe learning about others’ changing intentions. We formulated competing hypotheses comparing the standard Hierarchical Gaussian Filter (HGF), a Bayesian belief updating scheme, with a mean-reverting HGF to model an altered perception of volatility.

There was a significant group-by-volatility interaction on advice-taking suggesting that CHR-P and FEP displayed reduced adaptability to environmental volatility. Model comparison favored the standard HGF in HC, but the mean-reverting HGF in CHR-P and FEP in line with perceiving increased volatility, although model attributions in CHR-P were heterogeneous. We observed correlations between shifts in perceived volatility and positive symptoms generally as well as with frequency of paranoid delusions specifically.

Our results suggest that FEP are characterised by a different computational mechanism – perceiving the environment as increasingly volatile – in line with Bayesian accounts of psychosis. This approach may prove useful to investigate heterogeneity in CHR-P and identify vulnerability for transition to psychosis.
Disease severity of unvaccinated SARS-CoV-2 positive adults less than 65 years old without comorbidity, in the Omicron period and pre-Omicron periods
Authors: Wahlström Erik , Bruce Daniel , Bennet-Bark Anna M , Walther Sten , Hanberger Håkan , Strålin Kristoffer
Published: February 2023

Background

The reduced severity and burden of COVID-19 in 2022 can largely be attributable to vaccination and a shift to Omicron predominance. However, millions of individuals remain unvaccinated. In the present study, we aimed to study disease severity in unvaccinated individuals without risk factors during the Omicron period, compared to pre-Omicron periods.

Methods

This register-based study included all unvaccinated individuals in Sweden aged 18-64 years without comorbidity or care dependency who were SARS-CoV-2 positive between week 45 of 2020 and week 5 of 2022. Variant of concern (VOC) periods were periods with certain VOCs identified in ≥92% of sequenced cases nationwide. Outcomes were hospitalization with a main discharge code of COVID-19; severe illness, defined as high-flow nasal oxygen treatment or intensive care unit admission; and death with COVID-19 as the underlying cause of death on the death certificate.

Results

Among 788,895 individuals in the overall SARS-CoV-2 positive cohort, both hospitalization and death increased stepwise from the pre-VOC period to the Alpha and Delta periods, and decreased in the Omicron period. Among 15,179 patients hospitalized for COVID-19, the proportions with severe illness and death increased to the Delta period, but in the Omicron period, these outcomes returned to the level of the pre-VOC period.

Conclusion

In the Omicron period, compared to pre-Omicron periods, unvaccinated SARS-CoV-2 positive adults <65 years old without comorbidity had reduced proportions of hospitalization and death overall, but similar proportion of severe illness among patients hospitalized for COVID-19. These results support continuous efforts to prevent hospitalizations for COVID-19.
Antifungal activity of the novel compound M451 against phytopathogens
Authors: Tetz V , Kardava K , Krasnov K , Vecherkovskaya M , Tetz G
Published: February 2023

Phytopathogenic fungi are the dominant causal agents of plant diseases. Currently available fungicides have significant disadvantages, being insufficiently effective owing to both intrinsic tolerance and the spread of antibiotic resistance accumulating in plant tissues, posing a global threat to public health. Finding a new broad-spectrum fungicide is a challenge for plant protection. We studied the potency of a novel antimicrobial agent, M451, against different phytopathogenic fungi of the phylaAscomycota, Oomycota, andBasidiomycota. M451 exhibited significant antifungal activity with EC50 values ranging from 34 to 145 µg/mL. Analysis of the minimal fungicidal concentration and conidial destruction assay revealed that M451 possesses the highest activity compared with different polyene, azole, and phenylpyrrole antifungals againstFusarium oxysporum. Time-kill analysis revealed that M451 was the only antifungal agent tested that exhibited antifungal activity within 5 min of exposure. Spore production and germination were also significantly inhibited by M451 treatment. Based on the broad spectrum of antifungal effects across different plant pathogens, M451 could be a new chemical fungicide for plant disease management.