bluuebunny/crossref_metadata_2025 huggingface dataset:
The C-type Natriuretic Peptide: a new player in the development of the Marfan syndrome?
Authors: Clerc S , Bielmann C , Bouzourene K , Deglise T , Mazzolai L , Rosenblatt-Velin N
Published: June 2022

Funding Acknowledgements

Type of funding sources: Public hospital(s). Main funding source(s): CHUV

Background

Marfan Syndrome (MFS) is an autosomal dominant inherited connective tissue disorder affecting the cardio-vascular system. Aortic dissections and ruptures are the primary cause of morbidity and mortality in these patients. MFS is a genetic disorder due to mutations in the Fibrillin1 gene or in genes coding for the proteins of the TGF-beta signaling pathway. No treatment really cures Marfan patients.

Interestingly, in humans, mutations in the gene coding for the C-type natriuretic peptide (CNP) or its receptors lead to a "Marfan-like syndrome". CNP is a local regulator of skeletal growth and of vascular homeostasis, remodeling and angiogenesis. CNP binds to two receptors, NPR-B and NPR-C, expressed on endothelial and smooth muscle cells (SMCs). CNP is constitutively released by endothelial cells, whereas TGF-beta stimulates its secretion by SMCs.

The aim of this project is to determine whether altered CNP signaling pathway contributes to the development and progression of the vascular dysfunctions in MFS.

Methods

Plasma and vessel biopsies were taken from Marfan patients (RAVAD registery, CHUV Lausanne) and from Fbn1C1041G/+ mice, a mouse model which recapitulates several of the human phenotypes, including aortic wall degeneration and aneurysm development. CNP and TGF-beta concentrations were measured in the plasma. CNP, NPR-B and NPR-C protein levels were evaluated by Western blot analysis in aortic tissue during the development of MFS. In parallel, human and mouse SMCs were isolated and cultured in vitro with different CNP concentrations.

Results

CNP plasma concentration was decreased in Marfan patients compared to age and sex-matched non-Marfan patients (18 pmol/l versus 310; p=0.07). Two fold less CNP protein level was detected in the abdominal aorta of a Marfan patient.

In 6-7 week-old male Fbn1C1041G/+ mice, CNP protein levels were 1.5 and 2.5-fold increased in the ascending and descending aorta, respectively. NPR-B and NPR-C protein levels remained unchanged. In 24 week-old Marfan male mice, CNP protein level was normalized. In female mice, we detected no alterations of the CNP protein level but the NPR-B and NPR-C protein levels were decreased in the descending aorta 6 and 24 weeks after birth, respectively.  In vitro, CNP simulates both human and mouse SMC proliferation in a dose-dependent manner (+ 40% for human SMCs stimulated with 0.02 nM CNP).

Conclusion

Our results suggest that the early step of the syndrome is associated with high level of CNP (detected in 6 week-old male mice), whereas the late advanced stage of the disease is associated with decreased CNP protein level (detected in Marfan patients). These results could open the door to new therapies for Marfan patients.
Ivabradine rescues vascular abnormalities in a mouse model of duchenne muscular dystrophy
Authors: Acar E , Kuruppu Appuhamilage M , Szabo PL , Trojanek S , Abraham D , Hilber K , Podesser BK , Kiss A
Published: June 2022

Funding Acknowledgements

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Fonds zur Förderung der wissenschaftlichen Forschung

Ivabradine rescues vascular abnormalities in a mouse model of muscular dystrophy

Background

Duchenne muscular dystrophy (DMD) is a rare genetic disorder that primarily affects boys, initiated by the absence of dystrophin and is mainly differentiated by skeletal muscle degeneration and cardiac dysfunction. However, recent studies have underlined the importance of vascular abnormalities such as augmented arterial stiffness and endothelial dysfunction in the progression of cardiac complications in DMD. Several pleiotropic effects of ivabradine have been identified, including the reduction of vascular complications in coronary artery and ischemic heart disease patients. Nevertheless, whether chronic ivabradine treatment could improve the vascular complications in DMD is largely unknown.

Methods

In this study, vascular abnormalities in both dystrophin and utrophin deficient (mdx-utr KO) mice were examined, a severe and progressive animal model of DMD. Mice (4-6 weeks old) were subjected to ivabradine (10 mg/kg/day in drinking water) or vehicle treatments for 3 to 4 weeks. At the end of the treatment, aorta and lung tissue were collected to assess the vascular reactivity by wire myograph and the activity of angiotensin-converting enzyme (ACE) activity was measured in lung tissue respectively.

Results

Comparable with DMD patients, mdx-utr KO mice also exhibit vascular abnormalities and cardiac fibrosis. Ivabradine-treated mice showed a significantly improved endothelium-dependent vasodilation (p<0.05) and decreased vascular stiffness compared to vehicle-treated animals (p<0.01). In addition, lung ACE activity was significantly reduced in the treated mice in comparison to the control group (p<0.01) indicating less activation in the renin-angiotensin-aldosterone system, which causative plays role in the progression of vascular and cardiac dysfunction.

Conclusions

In conclusion, our study shows for the first time the beneficial effects of chronic ivabradine treatment on the progression of cardiac vascular complications in DMD and this may present a novel therapeutic approach. Further studies are needed to clarify the underling signalling mechanisms.
Dissecting the progression of cardiac dysfunction in tumor-bearing mice
Authors: Dostal C , Szabo LP , Aioanei C , Abraham D , Zins K , Bakiri L , Wagner E , Podesser BK , Kiss A
Published: June 2022

Funding Acknowledgements

Type of funding sources: None.

Background

Cancer patients undergoing heart-related complications result in high incidences of mortality. Nevertheless, it is still not fully understood whether localized tumors affect heart function prior to the onset of cachexia, hence, making the heart more vulnerable for functional abnormalities in later stages of the disease. In addition to analyse heart function, we focus on the expression BCL-2–associated athanogene 3 (BAG3), a co-chaperone protein and Hsp70, which are highly expressed in tumor but decrease in cardiomyocytes (CM) in heart failure (HF).

Methods

Colon-26 adenocarcinoma cells (C26; n=22) with/without shIL-6 (C26 shIL-6; n=22) were injected subcutaneously into the right flank of 10-11 weeks old BALB/c male mice. Control mice were injected with vehicle (PBS; n=8). Cardiac function was assessed by echocardiography and invasive hemodynamic measurements 10 (early) and 20 (late) days after the injection, respectively. In addition, the expression of BAG3 and Hsp70 were determined by Western blot as well as the extend of cardiac fibrosis was determined by Masson-Goldner's trichrome staining.

Results

The tumor size was comparable between the two injected groups. However, only C26 group showed a significant loss of subcutaneous fat and skeletal muscle (p<0.05, respectively), suggesting cachexia. Heart weight normalized to tibia length was not changed in the injected groups as compared to controls (day 20). However, left ventricular ejection fraction (LVEF) showed a tendency to decline in the early phase (p~0.08) in both injected group and it reached significance at late stage (p<0.05). Invasive hemodynamic assessment also confirmed the contractile dysfunction, resulting in a decrease in LV systolic pressure and increase of LV end-diastolic pressure (p<0.05, respectively). Importantly, these functional changes in the heart in tumor-bearing mice were associated with a marked reduction in both BAG3 and Hsp70 in the myocardium. Furthermore,  there was no sign of cardiac fibrosis in the injected groups.

Discussion

Our study shows for the first time that tumor rather than cancer cachexia plays a significant maladaptive role in the progression of cardiac dysfunction in a mouse model of C26 injection-induced cachexia. The progression of cardiac contractile dysfunction was associated with a decline in BAG3 and Hsp70 in tumor-bearing mice, suggesting changes of BAG3/Hsp 70 signalling may be a critical component as well as target.
Multivessel vs. culprit-vessel only percutaneous coronary interventions in acute myocardial infarction and cardiogenic shock: a systematic review and meta-analysis of prospective randomized and retrospective studies
Authors: Gill Gauravpal S , Sánchez Jorge Sanz , Thandra Abhishek , Kanmanthareddy Arun , Alla Venkata Mahesh , Garcia-Garcia Hector M
Published: June 2022

Aims

Studies comparing outcomes of multivessel (MV) vs. culprit-vessel (CV) only percutaneous coronary intervention (PCI) during index cardiac catheterization in patients presenting with acute myocardial infarction (MI) and cardiogenic shock (CS) have reported conflicting results. In this systematic review we aim to investigate outcomes with MV vs. CV-only revascularization strategies in patients with acute MI and CS.

Methods and results

PubMed, Google Scholar, CINAHL and Cochrane databases were queried for studies comparing MV vs. CV PCI in patients with acute MI and CS. Data were extracted and pooled by means of random effects model. Primary outcome was early all-cause mortality (up to 30 days), while the secondary outcomes included late all-cause mortality (mean, 11.4 months), stroke, new renal replacement therapy, reinfarction, repeat revascularization, and bleeding. Pooled odds ratio (OR), 95% confidence intervals (CIs), and number needed to harm (NNH) were calculated. A total of 16 studies enrolling 75  431 patients were included. The MV PCI was associated with higher risk of early mortality [OR 1.17, 95% CI (1.00–1.35); P = 0.04; NNH = 62], stroke [1.15 (1.03–1.29); P = 0.01; NNH = 351], and new renal replacement therapy [1.33 (1.06–1.67); P = 0.01; NNH = 61]; and with lower risk of repeat revascularization [0.61 (0.41–0.89); P = 0.01] when compared with CV PCI. No significant difference was observed in late-term mortality [1.02 (0.84–1.25); P = 0.84], risk of reinfarction [1.13 (0.94–1.35); P = 0.18], or bleeding [1.21 (0.94–1.55); P = 0.13] between groups.

Conclusion

Among patients with acute MI and CS, MV PCI during index cardiac catheterization was associated with higher risk of early mortality, stroke, and renal replacement therapy.
Impact of multicomponent integrated care on mortality and hospitalization after acute coronary syndrome: a systematic review and meta-analysis
Authors: Hoo Jia-Xin , Yang Ya-Feng , Tan Jia-Yin , Yang Jingli , Yang Aimin , Lim Lee-Ling
Published: June 2022

Aims

Multicomponent integrated care is associated with sustained control of multiple cardiometabolic risk factors among patients with type 2 diabetes. There is a lack of data in patients with acute coronary syndrome (ACS). We aimed to examine its efficacy on mortality and hospitalization outcomes among patients with ACS in outpatient settings.

Methods and results

A literature search was conducted on PubMed, EMBASE, Ovid, and Cochrane library databases for randomized controlled trials, published in English language between January 1980 and November 2020. Multicomponent integrated care defined as two or more quality improvement strategies targeting different domains (the healthcare system, healthcare providers, and patients) for one month or more. The study outcomes were all-cause and cardiovascular-related mortality, hospitalization, and emergency department visits. We pooled the risk ratio (RR) with 95% confidence interval (CI) for the association between multicomponent integrated care and study outcomes using the Mantel–Haenszel test. 74 trials (n = 93 278 patients with ACS) were eligible. The most common quality improvement strategies were team change (83.8%), patient education (62.2%), and facilitated patient-provider relay (54.1%). Compared with usual care, multicomponent integrated care was associated with reduced risks for all-cause mortality (RR 0.83, 95% CI 0.77–0.90; P < 0.001; I2 = 0%), cardiovascular mortality (RR 0.81, 95% CI 0.73–0.89; P < 0.001; I2 = 24%) and all-cause hospitalization (RR 0.88, 95 % CI, 0.78–0.99; P = 0.040; I2 = 58%). The associations of multicomponent integrated care with cardiovascular-related hospitalization, emergency department visits and unplanned outpatient visits were not statistically significant.

Conclusion

In outpatient settings, multicomponent integrated care can reduce risks for mortality and hospitalization in patients with ACS.
Widespread genomic signatures of reproductive isolation and sex-specific selection in the Eastern Yellow Robin, Eopsaltria australis
Authors: Kvistad Lynna , Falk Stephanie , Austin Lana
Published: June 2022

How new species evolve is one of the most fundamental questions in biology. Population divergence, which may lead to speciation, may be occurring in the Eastern Yellow Robin, a common passerine that lives along the eastern coast of Australia. This species is composed of 2 parapatric lineages that have highly divergent mitochondrial DNA; however, similar levels of divergence have not been observed in the nuclear genome. Here we re-examine the nuclear genomes of these mitolineages to test potential mechanisms underlying the discordance between nuclear and mitochondrial divergence. We find that nuclear admixture occurs in a narrow hybrid zone, although the majority of markers across the genome show evidence of reproductive isolation between populations of opposing mitolineages. There is an 8 MB section of a previously identified putative neo-sex chromosome that is highly diverged between allopatric but not parapatric populations, which may be the result of a chromosomal inversion. The neo-sex chromosomal nature of this region, as well as the geographic patterns in which it exhibits divergence, suggest it is unlikely to be contributing to reproductive isolation through mitonuclear incompatibilities as reported in earlier studies. In addition, there are sex differences in the number of markers that are differentiated between populations of opposite mitolineages, with greater differentiation occurring in females, which are heterozygous, than males. These results suggest that, despite the absence of previously observed assortative mating, mitolineages of Eastern Yellow Robin experience at least some postzygotic isolation from each other, in a pattern consistent with Haldane’s Rule.
‘The Black Sea Is Our Mallorca’: The Making of the Tourist Experience in the German Democratic Republic
Authors: López-Barajas José Luis Aguilar
Published: June 2022

This article analyses the construction of the East German holiday experience in the 1960s and 1970s, when tourism became a mass phenomenon on both sides of the Iron Curtain. First, it discusses the role played by the West in shaping the expectations of GDR tourists. Mallorca was the ultimate, but not sole, destination, that influenced how East Germans imagined tourism abroad. Secondly, the article tackles how expectations compared with actual experiences. State surveillance, scarcity and lack of means were common challenges that East Germans had to face and clashed with the glittering image of tourism with which they were inundated from West Germany. The Bulgarian Black Sea emerged as a substitute for that Western tourism as other possibilities, such as socialist Cuba or Yugoslavia, were limited. Touring in Bulgaria became a long-lasting experience. The article approaches the multiple meanings of this type of vacation abroad. Political, experiential and personal implications shaped East Germans’ holidays and entangled experiences and expectations, and the article provides a broad understanding of the meanings of vacation and tourism for citizens of East Germany.
Lower Leg Power and Grip Strength Are Associated With Increased Fall Injury Risk in Older Men: The Osteoporotic Fractures in Men Study
Authors: Winger Mary E , Caserotti Paolo , Cauley Jane A , Boudreau Robert M , Piva Sara R , Cawthon Peggy M , Orwoll Eric S , Ensrud Kristine E , Kado Deborah M , Strotmeyer Elsa S ,   Osteoporotic Fractures in Men (MrOS) Research Group, Orwoll E , Lapidus J , Nielson C , Marshall L , Pedersen C , Abrahamson M , Wang Y , Wiedrick J , Fino N , Hooker E , Nava J , Cummings S R , Bauer D C , Black D M , Cawthon P M , Stone K L , Collins R , Black B , Blackwell T , Burghardt A , Concepcion L , Ewing S , Harrison S L , Lui L Y , Majumdar S , Navy C , Parimi N , Patel S , Peters K , Schafer A , Schambach C , Schwartz A , Yu A , Shikany J , Lewis C , Kilgore M , Johnson P , Young M , Webb N , Felder S , Collier C , Hardy K , Ensrud K , Fink H , Diem S , Schousboe J , Taylor B , Langsetmo L , Potter S , Nelson N , Van Coevering P , Jacobson K , Kats A , Luthi S , Moen K , Penland-Miller E , Vo T , Stefanick M , Hoffman A , Ellsworth N , Kent K , Cauley J , Zmuda J , Strotmeyer E , Cusick D , Newman C , Flaugh A , Happe S , Kado D , Barrett-Connor E , Claravall L , Carrion-Petersen M L , Miller P , Stephens M , Smith J
Published: June 2022

Background

Past research has not investigated both lower-extremity power and upper-extremity strength in the same fall injury study, particularly nonfracture fall injuries.

Methods

In the Osteoporotic Fractures in Men Study (baseline: N = 5 994; age 73.7 ± 5.9 years; 10.2% non-White), fall injuries (yes/no) were assessed prospectively with questionnaires approximately every 3 years over 9 years. Maximum leg power (Watts) from Nottingham single leg press and maximum grip strength (kg) from handheld dynamometry were assessed at baseline and standardized to kg body weight. Physical performance included gait speed (6-m usual; narrow walk) and chair stands speed.

Results

Of men with ≥1/4 follow-ups (N = 5 178; age 73.4 ± 5.7 years), 40.4% (N = 2 090) had ≥1 fall injury. In fully adjusted repeated-measures logistic regressions, lower power/kg and grip strength/kg had higher fall injury risk (trend across quartiles: both p < .0001), with lower quartiles at significantly increased risk versus highest Q4 except for grip strength Q3 versus Q4. Fall injury risk was 19% higher per 1 standard deviation (SD) lower power/kg (95% confidence interval [CI]: 1.12–1.26) and 16% higher per SD lower grip strength/kg (95% CI: 1.10–1.23). In models including both leg power/kg and grip strength/kg, odds ratios (ORs) were similar and independent of each other and physical performance (leg power/kg OR per SD = 1.13, 95% CI: 1.06–1.20; grip strength/kg OR per SD = 1.11, 95% CI: 1.05–1.17).

Conclusions

Lower leg power/kg and grip strength/kg predicted future fall injury risk in older men independent of physical performance. Leg power potentially identifies fall injury risk better than grip strength at higher muscle function, though grip strength may be more suitable in clinical/practice settings.
Altered hydroxymethylome in the substantia nigra of Parkinson’s disease
Authors: Min Shishi , Xu Qian , Qin Lixia , Li Yujing , Li Ziyi , Chen Chao , Wu Hao , Han Junhai , Zhu Xiongwei , Jin Peng , Tang Beisha
Published: June 2022

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, and aging and genetic and environmental exposure can contribute to its pathogenesis. DNA methylation has been suggested to play a pivotal role in neurodevelopment and neurodegenerative diseases. 5-hydroxymethylcytosine (5hmC) is generated through 5-methylcytosine (5mC) oxidization by ten-eleven translocation proteins and is particularly enriched in the brain. Although 5hmC has been linked to multiple neurological disorders, little is known about 5hmC alterations in the substantia nigra of patients with PD. To determine the specific alterations in DNA methylation and hydroxymethylation in PD brain samples, we examined the genome-wide profiles of 5mC and 5hmC in the substantia nigra of patients with PD and Alzheimer’s disease (ad). We identified 4119 differentially hydroxymethylated regions (DhMRs) and no differentially methylated regions (DMRs) in the postmortem brains of patients with PD compared with those of controls. These DhMRs were PD-specific when compared with the results of AD. Gene ontology analysis revealed that several signaling pathways, such as neurogenesis and neuronal differentiation, were significantly enriched in PD DhMRs. KEGG enrichment analysis revealed substantial alterations in multiple signaling pathways, including phospholipase D (PLD), cAMP and Rap1. In addition, using a PD Drosophila model, we found that one of the 5hmC-modulated genes, PLD1, modulated α-synuclein toxicity. Our analysis suggested that 5hmC may act as an independent epigenetic marker and contribute to the pathogenesis of PD.
Introduction to “HaloDaSH: The Deep and Shallow History of Aquatic Life's Passages Between Marine and Freshwater Habitats”
Authors: Schultz Eric T , Park Boush Lisa
Published: June 2022

Synopsis

This series of papers highlights research into how biological exchanges between salty and freshwater habitats have transformed the biosphere. Life in the ocean and in freshwaters have long been intertwined; multiple major branches of the tree of life originated in the oceans and then adapted to and diversified in freshwaters. Similar exchanges continue to this day, including some species that continually migrate between marine and fresh waters. The series addresses key themes of transitions, transformations, and current threats with a series of questions: When did major colonizations of fresh waters happen? What physiographic changes facilitated transitions? What organismal characteristics facilitate colonization? Once a lineage has colonized freshwater, how frequently is there a return to the sea? Have transitions impelled diversification? How do organisms adapt physiologically to changes in halohabitat, and are such adaptive changes predictable? How do marine and freshwater taxa differ in morphology? How are present-day global changes in the environment influencing halohabitat and how are organisms contending with them? The purpose of the symposium and the papers in this volume is to integrate findings at multiple levels of biological organization and from disparate fields, across biological and geoscience disciplines.
Making Space for Creativity: Niche Construction and the Artist’s Studio
Authors: Saarinen Jussi A , Krueger Joel
Published: June 2022

It is increasingly acknowledged that creativity cannot be fully understood without considering the setting where it takes place. Building on this premise, we use the concepts of niche construction, scaffolding, coupling, and functional integration to expound on the environmentally situated nature of painters’ studio work. Our analysis shows studios to be multi-resource niches that are customized by artists to support various capacities, states, and actions crucial to painting. When at work in these personalized spaces, painters do not need to rely solely on their “inner” powers of imagination, memory, decision making, and technique to execute their paintings. Instead, with the help of carefully selected resources, they can offload elements of creative mentation and action onto the studio niche and enact different forms of a creative agency. To put more flesh on these ideas, we examine how painters use (1) existing artworks, (2) memory aids, and (3) music to scaffold the creative process. Overall, our analysis illuminates underexamined aspects of environmentally situated creativity and demonstrates the broader utility of the applied concepts for future creativity research.
Outbreak of Carbapenemase-Producing Enterobacteriaceae in a Regional Burn Center
Authors: Rehou Sarah , Rotman Sydney , Avaness Melisa , Salt Natasha , Jeschke Marc G , Shahrokhi Shahriar
Published: June 2022

Antimicrobial resistance is an increasing problem in hospitals worldwide; however, the prevalence of carbapenemase-producing Enterobacteriaceae (CPE) in our region is low. Burn patients are vulnerable to infection because of the loss of the protective skin barrier, thus burn centers prioritize infection prevention and control (IP&C). This report describes a CPE outbreak in a regional burn center. In a period of 2.5 months, four nosocomial cases of CPE were identified, three containing the Klebsiella pneumoniae carbapenemase (KPC) gene and one Verona integrin-encoded metallo-β-lactamase (VIM) gene. The first two cases were identified while there was no CPE patient source on the unit. CPE KPC gene was then isolated in sink drains of three rooms. In addition to rigorous IP&C practices already in place, we implemented additional outbreak measures including restricting admissions to patients with complex burns or burns ≥10% TBSA, admitting patients to other in-patient units, and not permitting elective admissions. We began cohorting patients using nursing team separation for CPE-positive and -negative patients and geographical separation on the unit. Despite aggressive IP&C measures already in place, hospital-acquired CPE colonization/infection occurred. Given that CPE contaminated sinks of the same enzyme were identified, we believe hospital sink drains may the source. This highlights the importance of sink design and engineering solutions to prevent the formation of biofilm and reduce splashing. CPE infections are associated with poor outcomes in patients and significant health system costs due to a longer length of stay and additional institutional resources.
Appraisal of clinicopathological prognosticators in advanced acral lentiginous melanoma with characterization of PD-L1 and CD8/CD4 immunoprofiles
Authors: Chuang I-Chieh , Jang Chiau-Sheng
Published: June 2022

Objective

Acral lentiginous melanoma is the most common subtype of cutaneous melanoma in Asian countries. This study aims to clarify the associations between certain histologic and immunohistochemical parameters, and identify their prognostic values.

Methods

We assessed several histologic features and conducted immunohistochemical study of programmed cell death ligand 1 (clone 22C3) and CD8/CD4 in 61 Taiwanese patients with Stage III/IV, non-BRAF acral lentiginous melanomas.

Results

A total of 41 males and 20 females were included, with a median age of 74 years. The majority of tumors occurred at nonungual locations (86.9%), with ‘foot’ being the most frequently affected site (85.2%). Positive programmed cell death ligand 1 staining (combined positive score ≥ 10) was significantly associated with the status of tumor-infiltrating lymphocytes (P = 0.036). Lack of skin ulceration was linked to the immunoexpression of CD8/CD4-high (P = 0.004). A superior clinical outcome was found in the tumor-infiltrating lymphocytes-present group (P = 0.011), and among which, CD8/CD4-high was significantly correlated with better survival (P < 0.001). Combined survival analysis revealed that the PD-L1(−) TIL(+) CD8/CD4-high subgroup was associated with favorable prognosis, and cases with PD-L1(+) TIL(−) showed the worst disease specific survival (P < 0.001). In the univariate analysis, lymphovascular invasion (P = 0.002), skin ulceration (P = 0.002), tumor-infiltrating lymphocytes (P = 0.015) and CD8/CD4 status (P < 0.001) were significant prognostic factors. At the multivariate level, the statuses of CD8/CD4-low (P < 0.001) and lymphovascular invasion (P = 0.014) represented the independent poor prognosticators.

Conclusion

For advanced, non-BRAF acral lentiginous melanomas, comprehensive assessments of these microscopic traits, along with CD8/CD4 and PD-L1 immunoprofiles, may help guide the clinicians and patients through treatment decisions.
Relevance of Spatial and Temporal Trends in Nymphal Tick Density and Infection Prevalence for Public Health and Surveillance Practice in Long-Term Endemic Areas: A Case Study in Monmouth County, NJ
Authors: Jordan Robert A , Gable Sydney , Egizi Andrea
Published: June 2022

Tick-borne diseases are a growing public health problem in the United States, and the US northeast has reported consistently high case rates for decades. Monmouth County, New Jersey, was one of the earliest jurisdictions to report Lyme disease cases in 1979 and reports several hundred cases per year nearly 40 yr later. In the time since, however, tick-borne health risks have expanded far beyond Lyme disease to include a variety of other bacterial pathogens and viruses, and additional vectors, necessitating a continually evolving approach to tick surveillance. In 2017, Monmouth County initiated an active surveillance program targeting sites across three ecological regions for collection of Ixodes scapularis Say (Acari: Ixodidae) and Amblyomma americanum L. (Acari: Ixodidae) as well as testing via qPCR for associated bacterial pathogens. During the first five years of this program (2017–2021), we report high levels of spatiotemporal variability in nymphal density and infection prevalence in both species, limiting the granularity with which human risk can be predicted from acarological data. Nonetheless, broader patterns emerged, including an ongoing trend of A. americanum dominance, risks posed by Borrelia miyamotoi, and the frequency of coinfected ticks. We present some of the first county-level, systematic surveillance of nymphal A. americanum density and infection prevalence in the northeastern US. We also documented a temporary decline in Borrelia burgdorferi that could relate to unmeasured trends in reservoir host populations. We discuss the implications of our findings for tick-borne disease ecology, public health communication, and tick surveillance strategies in endemic areas.
Israeli Parents’ Lived Experiences of Music Therapy With Their Preterm Infants Post-Hospitalization
Authors: Epstein Shulamit , Elefant Cochavit , Ghetti Claire
Published: June 2022

In the current study, we aimed to explore the lived experience of Israeli parents who engaged in musical dialogues with their preterm infants during music therapy (MT) after being discharged from the neonatal intensive care unit (NICU), as a part of the multinational LongSTEP RCT. Seven participants of the main trial were invited to engage in semi-structured in-depth interviews intertwining listening to audio recordings from their music therapy sessions in an adapted interpersonal process recall (IPR) procedure. The interviews were transcribed and analyzed using interpretative phenomenological analysis (IPA). We understood the participants’ experiences to reflect two main themes: 1) Music therapy as a potential means of transformation in communication skills, resourcefulness and sense of agency; and 2) emotional and musical preconditions for parental engagement in MT. The findings illustrate how a specific group of Israeli parents experienced MT as offering them a means of expanding their relationship with their preterm infants after discharge. Based on our findings, we recommend that music therapists consider parents’ musical and emotional resources during post-discharge MT to meet the individual needs of families.
Effect of medical treatments in disseminated peritoneal leiomyomatosis: a case report
Authors: Navarro Anne-Sophie , Angeles Martina Aida , Illac Claire , Boulet Bérénice , Ferron Gwenael , Martinez Alejandra
Published: June 2022

Disseminated peritoneal leiomyomatosis (DPL) is a rare gynecologic disease involving multifocal proliferation of myomas. The pathogenesis remains unclear. Although there is no standard treatment, medical therapies have attempted to suppress estrogen levels by using gonadotrophin-releasing hormone agonist and aromatase inhibitor (AI) therapy with differing degrees of success. Surgery is also an option in symptomatic patients, and in the event of partial or no response to medical treatments. We report a case of DPL in a young woman with a previous history of myomectomy. She was treated sequentially with ulipristal acetate and AI.
‘Medical Popes’ and ‘Vaccination Protestants’: Anti-Catholicism and the Campaign against Compulsory Vaccination in Victorian England
Authors: Cottrell-Boyce Aidan
Published: June 2022

The anti-vaccination campaign of the late nineteenth century has attracted the attention of historians in recent decades. The campaign against compulsory vaccination for smallpox gained the support of hundreds of thousands of people in Victorian Britain. Many objected to vaccination on scriptural grounds. Many others claimed that it was contradictory to their belief in mesmerism, Swedenborgianism or hydropathy. Still others argued that the Vaccination Acts of 1867 and 1871 represented a violation of individual liberties. One overlooked aspect of this movement relates to the use of anti-Catholic rhetoric in the speeches and literature which its leaders produced. A significant proportion of these leaders were drawn from the community of medical dissent. These individuals lived through a period when anti-Catholicism began to wane as a political force in England. Confronted with the new phenomenon of medical professionalization, they sought to style themselves as the inheritors of a Protestant tradition. In doing so, this article suggests that they attempted to repurpose the frailties of their movement – its reputation as crankish, plebeian or marginal – as strengths, and the avowed expertise of medical professionals as a weakness.
The transcription factor OsGATA6 regulates rice heading date and grain number per panicle
Authors: Zhang Yan-Jie , Zhang Yu , Zhang Liang-Li , He Jun-Xian , Xue Hong-Wei , Wang Jia-Wei , Lin Wen-Hui
Published: June 2022

Heading date, panicle architecture, and grain size are key traits that affect the yield of rice (Oryza sativa). Here, we identified a new gene, OsGATA6, whose product regulates heading date. Overexpression of OsGATA6 resulted in delayed heading, increased grain number, and decreased grain size. Knockdown lines generated by artificial microRNA (amiRNA) and CRISPR genome-edited lines of OsGATA6 both showed earlier heading, decreased grain number, and increased grain size. These results suggested that OsGATA6 negatively regulates heading date, positively regulates panicle development, and affects grain size. OsGATA6 was found to be constitutively expressed in rice, and strongly expressed in young leaves and panicles. In situ hybridization analyses showed that OsGATA6 was specifically localized in superficial cells of the panicle primordium. Overexpression lines show decreased expression of RFT1 and Hd3a, which promote heading. OsMFT1, which delays heading date and increases grain number, was down-regulated in amiRNA lines. Further analyses showed that OsGATA6 could bind to the promoter of OsMFT1 and induce its expression, thereby regulating heading date and panicle development. Overexpression of OsGATA6 in Arabidopsis resulted in repressed expression of AtFT and late flowering, suggesting that its function is similar. Taken together, we have identified a new GATA regulator that influences rice heading date and grain number, which potentially increases rice yield.
Altered collective mitochondrial dynamics in the Arabidopsismsh1mutant compromising organelle DNA maintenance
Authors: Chustecki Joanna M , Etherington Ross D , Gibbs Daniel J , Johnston Iain G
Published: June 2022

Mitochondria form highly dynamic populations in the cells of plants (and almost all eukaryotes). The characteristics and benefits of this collective behaviour, and how it is influenced by nuclear features, remain to be fully elucidated. Here, we use a recently developed quantitative approach to reveal and analyse the physical and collective ‘social’ dynamics of mitochondria in an Arabidopsis msh1 mutant where the organelle DNA maintenance machinery is compromised. We use a newly created line combining the msh1 mutant with mitochondrially targeted green fluorescent protein (GFP), and characterize mitochondrial dynamics with a combination of single-cell time-lapse microscopy, computational tracking, and network analysis. The collective physical behaviour of msh1 mitochondria is altered from that of the wild type in several ways: mitochondria become less evenly spread, and networks of inter-mitochondrial encounters become more connected, with greater potential efficiency for inter-organelle exchange—reflecting a potential compensatory mechanism for the genetic challenge to the mitochondrial DNA population, supporting more inter-organelle exchange. We find that these changes are similar to those observed in friendly, where mitochondrial dynamics are altered by a physical perturbation, suggesting that this shift to higher connectivity may reflect a general response to mitochondrial challenges, where physical dynamics of mitochondria may be altered to control the genetic structure of the mtDNA population.
Search for extended Lyman-α emission around 9k quasars at z = 2–3
Authors: Shimakawa Rhythm
Published: June 2022

Enormous Lyα nebulae (ELANe) around quasars have provided unique insights into the formation of massive galaxies and their associations with super-massive black holes since their discovery. However, their detection remains highly limited. This paper introduces a systematic search for extended Lyα emission around 8683 quasars at z = 2.34–3.00 using a simple but very effective broad-band gri selection based on the Third Public Data Release of the Hyper Suprime-Cam Subaru Strategic Program. Although the broad-band selection detects only bright Lyα emission (≳ 1 × 10−17 erg s−1cm−2 arcsec−2) compared with narrow-band imaging and integral field spectroscopy, we can apply this method to far more sources than such common approaches. We first generated continuum g-band images without contributions from Lyα emission for host and satellite galaxies using r- and i-bands. Then, we established Lyα maps by subtracting them from observed g-band images with Lyα emissions. Consequently, we discovered extended Lyα emission (with masked area >40 arcsec2) for 7 and 32 out of 366 and 8317 quasars in the Deep and Ultra-deep (35 deg2) and Wide (890 deg2) layers, parts of which may be potential candidates of ELANe. However, none of them seem to be equivalent to the largest ELANe ever found. We detected higher fractions of quasars with large nebulae around more luminous or radio-loud quasars, supporting previous results. Future applications to the forthcoming big data from the Vera C. Rubin Observatory will help us detect more promising candidates. The source catalogue and obtained Lyα properties for all the quasar targets are accessible as online material.
Spatiotemporal Regulation of a Single Adaptively EvolvingTrans-Regulatory Element Contributes to Spermatogenetic Expression Divergence inDrosophila
Authors: Huang Yumei , Shang Rui , Lu Guang-An , Zeng Weishun , Huang Chenglong , Zou Chuangchao , Tang Tian
Published: June 2022

Due to extensive pleiotropy, trans-acting elements are often thought to be evolutionarily constrained. While the impact of trans-acting elements on gene expression evolution has been extensively studied, relatively little is understood about the contribution of a single trans regulator to interspecific expression and phenotypic divergence. Here, we disentangle the effects of genomic context and miR-983, an adaptively evolving young microRNA, on expression divergence between Drosophila melanogaster and D. simulans. We show miR-983 effects promote interspecific expression divergence in testis despite its antagonism with the often-predominant context effects. Single-cyst RNA-seq reveals that distinct sets of genes gain and lose miR-983 influence under disruptive or diversifying selection at different stages of spermatogenesis, potentially helping minimize antagonistic pleiotropy. At the round spermatid stage, the effects of miR-983 are weak and distributed, coincident with the transcriptome undergoing drastic expression changes. Knocking out miR-983 causes reduced sperm length with increased within-individual variation in D. melanogaster but not in D. simulans, and the D. melanogaster knockout also exhibits compromised sperm defense ability. Our results provide empirical evidence for the resolution of antagonistic pleiotropy and also have broad implications for the function and evolution of new trans regulators.
Topoisomerase 1 inhibits MYC promoter activity by inducing G-quadruplex formation
Authors: Keller Josephine Geertsen , Hymøller Kirstine Mejlstrup , Thorsager Maria Eriksen , Hansen Noriko Y , Erlandsen Jens Uldum , Tesauro Cinzia , Simonsen Anne Katrine W , Andersen Anne Bech , Vandsø Petersen Kamilla , Holm Lise Lolle , Stougaard Magnus , Andresen Brage Storstein , Kristensen Peter , Frøhlich Rikke , Knudsen Birgitta R
Published: June 2022

We have investigated the function of human topoisomerase 1 (TOP1) in regulation of G-quadruplex (G4) formation in the Pu27 region of the MYC P1 promoter. Pu27 is among the best characterized G4 forming sequences in the human genome and it is well known that promoter activity is inhibited upon G4 formation in this region. We found that TOP1 downregulation stimulated transcription from a promoter with wildtype Pu27 but not if the G4 motif in Pu27 was interrupted by mutation(s). The effect was not specific to the MYC promoter and similar results were obtained for the G4 forming promoter element WT21. The other major DNA topoisomerases with relaxation activity, topoisomerases 2α and β, on the other hand, did not affect G4 dependent promoter activity. The cellular studies were supported by in vitro investigations demonstrating a high affinity of TOP1 for wildtype Pu27 but not for mutant sequences unable to form G4. Moreover, TOP1 was able to induce G4 formation in Pu27 inserted in double stranded plasmid DNA in vitro. This is the first time TOP1 has been demonstrated capable of inducing G4 formation in double stranded DNA and of influencing G4 formation in cells.
Work environment and labour market participation in early adulthood
Authors: Sandholm K , Winding T Nøhr
Published: June 2022

Background

Investigating whether a poor physical or psychosocial work environment is associated with low labour market participation in early adulthood is important to avoid negative health-related consequences and to improve job prospects.

Aims

To investigate associations between the physical or psychosocial work environment and labour market participation in early adulthood.

Methods

The study was based on data from the West Jutland Cohort, an ongoing study of individuals born in 1989 who lived in the western part of Jutland, Denmark, in 2004. Participants were employed individuals who had questionnaire data on their work environment at age 28 and register information on labour market participation at ages 28–29 (n = 1312). The outcome was categorized into low (>4 weeks) versus high (≤4 weeks) labour market participation based on the total number of weeks receiving any unemployment or health-related benefits during a 52-week period. Logistic regression analyses were performed to examine associations between work environment factors and labour market participation, taking confounders into account.

Results

Low influence, low quality of leadership, high job insecurity and temporary employment were associated with low labour market participation. High job insecurity (OR: 2.2; 95% CI 1.5–3.1) and temporary employment (OR: 3.1; 95% CI 2.1–4.5) were strongly associated with low labour market participation. An association was seen between hard physical work and low labour market participation.

Conclusions

Several physical and psychosocial work environment factors, especially high job insecurity and temporary employment, have a negative impact on labour market participation in early adulthood.
Antibodies to Human Herpesviruses and Rate of Incident Cardiovascular Events and All-Cause Mortality in the UK Biobank Infectious Disease Pilot Study
Authors: Chu Petrina , Cadogan Sharon Louise , Warren-Gash Charlotte
Published: June 2022

Background

Associations between human herpesviruses (HHVs) and cardiovascular disease/mortality have been reported, but evidence is inconsistent. We investigated associations between 3 common herpesviruses and (1) incident stroke or myocardial infarction (MI) and (2) all-cause mortality.

Methods

We included participants from the UK Biobank Infectious Disease pilot study with valid serum antibody (IgG) measurements taken at cohort entry (2006–2010) for herpes simplex virus type 1 (HSV1), varicella zoster virus (VZV), and cytomegalovirus (CMV). Linked hospital and mortality records up to December 30 2019 provided information on rates of (1) incident first stroke or MI and (2) all-cause mortality. Hazard ratios (HRs) from Cox proportional hazards regression models were used to assess relationships between (1) HHV seropositivity, (2) HHV titer and incident stroke/MI, and death outcomes. Fully adjusted models accounted for sociodemographic information (age, sex, ethnicity, education, deprivation quintile, birthplace, population density), baseline comorbidities (including diabetes and hypertension), smoking status, body mass index, and serum cholesterol.

Results

Of 9429 study participants (56% female, 95% White, median age 58 years), 41% were seropositive for all 3 HHVs. Human herpesvirus seropositivity was not associated with stroke/MI (fully adjusted HRs and 95% confidence intervals [CIs]: HSV1 = 0.93 [CI, 0.72–1.22], VZV = 0.78 [CI, 0.51–1.20], CMV = 0.91 [CI, 0.71–1.16]) or all-cause mortality (HSV1 = 1.21 [CI, 1.00–1.47], VZV = 0.79 [CI, 0.58–1.07], CMV = 0.90 [CI, 0.76–1.06]). Human herpesvirus titers were not associated with outcomes.

Conclusions

In this mostly White UK Biobank subset, neither HHV seropositivity nor titers were associated with stroke/MI or all-cause mortality.
SUPPRESSOR of MAX2 1 (SMAX1) and SMAX1-LIKE2 (SMXL2) Negatively Regulate Drought Resistance in Arabidopsis thaliana
Authors: Feng Zhonghui , Liang Xiaohan , Tian Hongtao , Watanabe Yasuko , Nguyen Kien Huu , Tran Cuong Duy , Abdelrahman Mostafa , Xu Kun , Mostofa Mohammad Golam , Ha Chien Van , Mochida Keiichi , Tian Chunjie , Tanaka Maho , Seki Motoaki , Liang Zhengwei , Miao Yuchen , Tran Lam-Son Phan , Li Weiqiang
Published: June 2022

Recent investigations in Arabidopsis thaliana suggest that SUPPRESSOR of MORE AXILLARY GROWTH 2 1 (SMAX1) and SMAX1-LIKE2 (SMXL2) are negative regulators of karrikin (KAR) and strigolactone (SL) signaling during plant growth and development, but their functions in drought resistance and related mechanisms of action remain unclear. To understand the roles and mechanisms of SMAX1 and SMXL2 in drought resistance, we investigated the drought-resistance phenotypes and transcriptome profiles of smax1 smxl2 (s1,2) double-mutant plants in response to drought stress. The s1,2 mutant plants showed enhanced drought-resistance and lower leaf water loss when compared with wild-type (WT) plants. Transcriptome comparison of rosette leaves from the s1,2 mutant and the WT under normal and dehydration conditions suggested that the mechanism related to cuticle formation was involved in drought resistance. This possibility was supported by enhanced cuticle formation in the rosette leaves of the s1,2 mutant. We also found that the s1,2 mutant plants were more sensitive to abscisic acid in assays of stomatal closure, cotyledon opening, chlorophyll degradation and growth inhibition, and they showed a higher reactive oxygen species detoxification capacity than WT plants. In addition, the s1,2 mutant plants had longer root hairs and a higher root-to-shoot ratio than the WT plants, suggesting that the mutant had a greater capacity for water absorption than the WT. Taken together, our results indicate that SMAX1 and SMXL2 negatively regulate drought resistance, and disruption of these KAR- and SL-signaling-related genes may therefore provide a novel means for improving crop drought resistance.