bluuebunny/crossref_metadata_2025 huggingface dataset:
A cetacean limb from the Middle Eocene of Ukraine sheds light on mammalian adaptations to life in water
Authors: Davydenko Svitozar , Solyanik Eugene , Tretiakov Roman , Kovalchuk Oleksandr , Gol’din Pavel
Published: November 2023

There are a few mammalian lineages secondarily adapted to life in water throughout their evolutionary history. Of them, only sirenians and cetaceans evolved as fully aquatic organisms. This transition was accompanied by changes in swimming mode, from foot paddling to tail-powered propulsion, with the forelimbs acting as efficient hydrofoils and the gradual loss of external hindlimbs. Here, we describe an isolated limb from the Middle Eocene of Ukraine, 43–42 Mya, identified as a hindlimb of a fully aquatic cetacean and being the earliest cetacean reported from Europe. It is represented by flattened, jointly articulated bones, identified as the tibia and fibula with a partly reduced knee joint and loose connection to the pes, and by flattened phalanges. This anatomy reveals a hitherto only presumed cetacean morphotype, showing that some of the early fully aquatic cetaceans were four-legged animals with functional hindlimbs that could be involved in advanced styles of swimming. They used either body undulation or lift-based propulsion powered by the tail or feet and could also use a transitional swimming style combining these modes.
Shear stress in the intervillous space promotes syncytial formation of iPS cells-derived trophoblasts
Authors: Inohaya Asako , Chigusa Yoshitsugu , Takakura Masahito , Io Shingo , Kim Min-A , Matsuzaka Yu , Yasuda Eriko , Ueda Yusuke , Kawamura Yosuke , Takamatsu Shiro , Mogami Haruta , Takashima Yasuhiro , Mandai Masaki , Kondoh Eiji
Published: November 2023

The intervillous space of human placenta is filled with maternal blood, and villous trophoblasts are constantly exposed to the shear stress generated by maternal blood pressure and flow throughout the entire gestation period. However, the effects of shear stress on villous trophoblasts and their biological significance remain unknown. Here, using our recently established naïve human pluripotent stem cells-derived cytotrophoblast stem cells (nCTs) and a device that can apply arbitrary shear stress to cells, we investigated the impact of shear stress on early-stage trophoblasts. After 72 h of exposure to 10 dyn/cm2 shear stress, nCTs became fused and multinuclear, and mRNA expression of the syncytiotrophoblast (ST) markers, such as glial cell missing 1, endogenous retrovirus group W member 1 envelope, chorionic gonadotropin subunit beta 3, syndecan 1, pregnancy specific beta-1-glycoprotein 3, placental growth factor, and solute carrier family 2 member 1 were significantly upregulated compared to static conditions. Immunohistochemistry showed that shear stress increased fusion index, human chorionic gonadotropin secretion, and human placental lactogen secretion. Increased microvilli formation on the surface of nCTs under flow conditions was detected using scanning electron microscopy. Intracellular cyclic adenosine monophosphate significantly increased under flow conditions. Moreover, transcriptome analysis of nCTs subjected to shear stress revealed that shear stress upregulated ST-specific genes and downregulated CT-specific genes. Collectively, these findings indicate that shear stress promotes the differentiation of nCTs into ST.
Protocol for transcriptome assembly by the TransBorrow algorithm
Authors: Zhao Dengyi , Liu Juntao , Yu Ting
Published: November 2023

High-throughput RNA-seq enables comprehensive analysis of the transcriptome for various purposes. However, this technology generally generates massive amounts of sequencing reads with a shorter read length. Consequently, fast, accurate, and flexible tools are needed for assembling raw RNA-seq data into full-length transcripts and quantifying their expression levels. In this protocol, we report TransBorrow, a novel transcriptome assembly software specifically designed for short RNA-seq reads. TransBorrow is employed in conjunction with a splice-aware alignment tool (e.g. Hisat2 and Star) and some other transcriptome assembly tools (e.g. StringTie, Cufflinks, and Scallop). The protocol encompasses all necessary steps, starting from downloading and processing raw sequencing data to assembling the full-length transcripts and quantifying their expressed abundances. The execution time of the protocol may vary depending on the sizes of processed datasets and computational platforms.
Future-proofing environmental DNA and trait-based predictions of food webs
Authors: Pereira Cátia Lúcio , Ersoy Zeynep , Gilbert M Thomas P , Gravel Dominique , Araújo Miguel B , Matias Miguel G
Published: November 2023

Food webs represent trophic interactions within ecosystems. Matching traits of consumers and resources helps infer trophic interactions and food-web properties. Environmental (e)DNA, commonly used for detecting species occurrences, is rarely used in trait-matching studies because abundance estimates and descriptions of relevant traits are generally missing. We synthesized recent literature on inferences of trophic interactions with eDNA and trait matching to identify challenges and opportunities for coupled eDNA–trait recording schemes. Our case study shows how coupling eDNA and trait data collection improves the ability to characterize greater numbers of food webs across multiple scales ranging from spatiotemporal to trait variation. Future-proofing eDNA data sets requires the collection of new traits or the compilation of existing trait data at spatiotemporal scales that are relevant to detect current and future changes in food webs and ecosystems.
Long noncoding RNA plasmacytoma variant translocation 1 is overexpressed in cutaneous squamous cell carcinoma and exon 2 is critical for its oncogenicity
Authors: Li Chen , Sun Chengxi , Mahapatra Kunal Das , Riihilä Pilvi , Knuutila Jaakko , Nissinen Liisa , Lapins Jan , Kähäri Veli-Matti , Homey Bernhard , Sonkoly Enikö , Pivarcsi Andor
Published: November 2023

Background

Cutaneous squamous cell carcinoma (cSCC) is one of the most common and fastest increasing forms of cancer worldwide with metastatic potential. Long noncoding RNAs (lncRNAs) are a group of RNA molecules with essential regulatory functions in both physiological and pathological processes.

Objectives

To investigate the function and mode of action of lncRNA plasmacytoma variant translocation 1 (PVT1) in cSCC.

Methods

Quantitative reverse transcriptase polymerase chain reaction and single-molecule in situ hybridization were used to quantify the expression level of PVT1 in normal skin, premalignant skin lesions, actinic keratosis (AK) and primary and metastatic cSCCs. The function of PVT1 in cSCC was investigated both in vivo (tumour xenografts) and in vitro (competitive cell growth assay, 5-ethynyl-2′-deoxyuridine incorporation assay, colony formation assay and tumour spheroid formation assay) upon CRISPR-Cas9-mediated knockout of the entire PVT1 locus, the knockout of exon 2 of PVT1, and locked nucleic acid (LNA) gapmer-mediated PVT1 knockdown. RNA sequencing analysis was conducted to identify genes and processes regulated by PVT1.

Results

We identified PVT1 as a lncRNA upregulated in cSCC in situ and cSCC, associated with the malignant phenotype of cSCC. We showed that the expression of PVT1 in cSCC was regulated by MYC. Both CRISPR-Cas9 deletion of the entire PVT1 locus and LNA gapmer-mediated knockdown of PVT1 transcript impaired the malignant behaviour of cSCC cells, suggesting that PVT1 is an oncogenic transcript in cSCC. Furthermore, knockout of PVT1 exon 2 inhibited cSCC tumour growth both in vivo and in vitro, demonstrating that exon 2 is a critical element for the oncogenic role of PVT1. Mechanistically, we showed that PVT1 was localized in the cell nucleus and its deletion resulted in cellular senescence, increased cyclin-dependent kinase inhibitor 1 (p21/CDKN1A) expression and cell cycle arrest.

Conclusions

Our study revealed a previously unrecognized role for exon 2 of PVT1 in its oncogenic role and that PVT1 suppresses cellular senescence in cSCC. PVT1 may be a potential biomarker and therapeutic target in cSCC.
S100 calcium-binding protein A9 promotes skin regeneration through toll-like receptor 4 during tissue expansion
Authors: Zhang Yu , Song Yajuan , Du Jing , Liu Wei , Dong Chen , Huang Zhaosong , Zhang Zhe , Yang Liu , Wang Tong , Xiong Shaoheng , Dong Liwei , Guo Yaotao , Dang Juanli , He Qiang , Yu Zhou , Ma Xianjie
Published: November 2023

Background

In plastic surgery, tissue expansion is widely used for repairing skin defects. However, low expansion efficiency and skin rupture caused by thin, expanded skin remain significant challenges in promoting skin regeneration during expansion. S100 calcium-binding protein A9 (S100A9) is essential in promoting wound healing; however, its effects on skin regeneration during tissue expansion remain unclear. The aim of the present study was to explore the role of S100A9 in skin regeneration, particularly collagen production to investigate its importance in skin regeneration during tissue expansion.

Methods

The expression and distribution of S100A9 and its receptors—toll-like receptor 4 (TLR-4) and receptor for advanced glycation end products were studied in expanded skin. These characteristics were investigated in skin samples of rats and patients. Moreover, the expression of S100A9 was investigated in stretched keratinocytes in vitro. The effects of S100A9 on the proliferation and migration of skin fibroblasts were also observed. TAK-242 was used to inhibit the binding of S100A9 to TLR-4; the levels of collagen I (COL I), transforming growth factor beta (TGF-β), TLR-4 and phospho-extracellular signal-related kinase 1/2 (p-ERK1/2) in fibroblasts were determined. Furthermore, fibroblasts were co-cultured with stretched S100A9-knockout keratinocytes by siRNA transfection and the levels of COL I, TGF-β, TLR-4 and p-ERK1/2 in fibroblasts were investigated. Additionally, the area of expanded skin, thickness of the dermis, and synthesis of COL I, TGF-β, TLR-4 and p-ERK1/2 were analysed to determine the effects of S100A9 on expanded skin.

Results

Increased expression of S100A9 and TLR-4 was associated with decreased extracellular matrix (ECM) in the expanded dermis. Furthermore, S100A9 facilitated the proliferation and migration of human skin fibroblasts as well as the expression of COL I and TGF-β in fibroblasts via the TLR-4/ERK1/2 pathway. We found that mechanical stretch-induced S100A9 expression and secretion of keratinocytes stimulated COL I, TGF-β, TLR-4 and p-ERK1/2 expression in skin fibroblasts. Recombined S100A9 protein aided expanded skin regeneration and rescued dermal thinning in rats in vivo as well as increasing ECM deposition during expansion.

Conclusions

These findings demonstrate that mechanical stretch promoted expanded skin regeneration by upregulating S100A9 expression. Our study laid the foundation for clinically improving tissue expansion using S100A9.
Tuning the potency and selectivity of ImmTAC molecules by affinity modulation
Authors: Robertson Ian B , Mulvaney Rachel , Dieckmann Nele , Vantellini Alessio , Canestraro Martina , Amicarella Francesca , O’Dwyer Ronan , Cole David K , Harper Stephen , Dushek Omer , Kirk Peter
Published: November 2023

T-cell-engaging bispecifics have great clinical potential for the treatment of cancer and infectious diseases. The binding affinity and kinetics of a bispecific molecule for both target and T-cell CD3 have substantial effects on potency and specificity, but the rules governing these relationships are not fully understood. Using immune mobilizing monoclonal TCRs against cancer (ImmTAC) molecules as a model, we explored the impact of altering affinity for target and CD3 on the potency and specificity of the redirected T-cell response. This class of bispecifics binds specific target peptides presented by human leukocyte antigen on the cell surface via an affinity-enhanced T-cell receptor and can redirect T-cell activation with an anti-CD3 effector moiety. The data reveal that combining a strong affinity TCR with an intermediate affinity anti-CD3 results in optimal T-cell activation, while strong affinity of both targeting and effector domains significantly reduces maximum cytokine release. Moreover, by optimizing the affinity of both parts of the molecule, it is possible to improve the selectivity. These results could be effectively modelled based on kinetic proofreading with limited signalling. This model explained the experimental observation that strong binding at both ends of the molecules leads to reduced activity, through very stable target-bispecific-effector complexes leading to CD3 entering a non-signalling dark state. These findings have important implications for the design of anti-CD3-based bispecifics with optimal biophysical parameters for both activity and specificity.
Serum sclerostin is associated with recurrent kidney stone formation independent of hypercalciuria
Authors: Rodríguez Daniel , Gurevich Ekaterina , Mohammadi Jouabadi Soroush , Pastor Arroyo Eva Maria , Ritter Alexander , Estoppey Younes Sandrine , Wagner Carsten A , Imenez Silva Pedro Henrique , Seeger Harald , Mohebbi Nilufar
Published: November 2023

Background

Kidney stones are frequent in industrialized countries with a lifetime risk of 10 to 15%. A high percentage of individuals experience recurrence. Calcium-containing stones account for more than 80% of kidney stones. Diet, environmental factors, behavior, and genetic variants contribute to the development of kidney stones. Osteocytes excrete the 21 kDa glycoprotein sclerostin, which inhibits bone formation by osteoblasts. Animal data suggests that sclerostin might directly or indirectly regulate calcium excretion via the kidney. As hypercalciuria is one of the most relevant risk factors for kidney stones, sclerostin might possess pathogenic relevance in nephrolithiasis.

Methods

We performed a prospective cross-sectional observational controlled study in 150 recurrent kidney stone formers (rKSF) to analyse the association of sclerostin with known stone risk factors and important modulators of calcium-phosphate metabolism. Serum sclerostin levels were determined at the first visit. As controls, we used 388 non-stone formers from a large Swiss epidemiological cohort.

Results

Sclerostin was mildly increased in rKSF in comparison to controls. This finding was more pronounced in women compared to men. Logistic regression indicated an association of serum sclerostin with rKSF status. In hypercalciuric individuals, sclerostin levels were not different from normocalciuric patients. In Spearman correlation analysis we found a positive correlation between sclerostin, age, and BMI and a negative correlation with eGFR. There was a weak correlation with iPTH and intact FGF 23. In contrast, serum sclerostin levels were not associated with 25-OH Vitamin D3, 1,25-dihydroxy-Vitamin D3, urinary calcium and phosphate or other urinary lithogenic risk factors.

Conclusion

This is the first prospective controlled study investigating serum sclerostin in rKSF. Sclerostin levels were increased in rKSF independent of hypercalciuria and significantly associated with the status as rKSF. It appears that mechanisms other than hypercalciuria may be involved and thus further studies are required to elucidate underlying pathways.
Preproject ‘Swiss Virtual Natural History Collection’
Authors: Petrus Ana , Wildi Tobias , Müller Stefanie
Published: November 2023

The initiative ‘Swiss Natural History Collection Network’ (SwissCollNet) aims to improve the accessibility of the Swiss natural history collections for research, education and the wider public. In the 2021–24 funding period, SwissCollNet is identifying, prioritizing and digitizing as many collections as possible and building an online portal called the ‘Swiss Virtual Natural History Collection’ (hereafter SVNHC) to provide open access to harmonized sample data from Swiss collections. The University of Applied Sciences of the Grisons developed scenarios for the technical implementation of the SVNHC portal in a preliminary study on behalf of SwissCollNet and based on the requirements of collections and data centres.
Sex-specific presentation, care, and clinical events in individuals admitted with NSTEMI: the ACVC-EAPCI EORP NSTEMI registry of the European Society of Cardiology
Authors: Nadarajah Ramesh , Ludman Peter , Laroche Cécile , Appelman Yolande , Brugaletta Salvatore , Budaj Andrzej , Bueno Hector , Huber Kurt , Kunadian Vijay , Leonardi Sergio , Lettino Maddalena , Milasinovic Dejan , Gale Chris P
Published: November 2023

Aims

Women have historically been disadvantaged in terms of care and outcomes for non-ST-segment elevation myocardial infarction (NSTEMI). We describe patterns of presentation, care, and outcomes for NSTEMI by sex in a contemporary and geographically diverse cohort.

Methods and results

Prospective cohort study including 2947 patients (907 women, 2040 men) with Type I NSTEMI from 287 centres in 59 countries, stratified by sex. Quality of care was evaluated based on 12 guideline-recommended care interventions. The all-or-none scoring composite performance measure was used to define receipt of optimal care. Outcomes included acute heart failure, cardiogenic shock, repeat myocardial infarction, stroke/transient ischaemic attack, BARC Type ≥3 bleeding, or death in-hospital, as well as 30-day mortality. Women admitted with NSTEMI were older, more comorbid, and more frequently categorized as at higher ischaemic (GRACE >140, 54.0% vs. 41.7%, P < 0.001) and bleeding (CRUSADE >40, 51.7% vs. 17.6%, P < 0.001) risk than men. Women less frequently received invasive coronary angiography (ICA; 83.0% vs. 89.5%, P < 0.001), smoking cessation advice (46.4% vs. 69.5%, P < 0.001), and P2Y12 inhibitor prescription at discharge (81.9% vs. 90.0%, P < 0.001). Non-receipt of ICA was more often due to frailty for women than men (16.7% vs. 7.8%, P = 0.010). At ICA, more women than men had non-obstructive coronary artery disease or angiographically normal arteries (15.8% vs. 6.3%, P < 0.001). Rates of in-hospital adverse outcomes and 30-day mortality were low and did not differ by sex.

Conclusion

In contemporary practice, women presenting with NSTEMI, compared with men, less frequently receive antiplatelet prescription, smoking cessation advice, or are considered eligible for ICA.
Association between myocardial work indices and cardiovascular events according to hypertension in the general population
Authors: Olsen Flemming Javier , Skaarup Kristoffer Grundtvig , Lassen Mats Christian Højbjerg , Johansen Niklas Dyrby , Jensen Gorm Boje , Schnohr Peter , Marott Jacob Louis , Søgaard Peter , Gislason Gunnar , Svendsen Jesper Hastrup , Møgelvang Rasmus , Aalen John Moene , Smiseth Otto Armin , Remme Espen Wattenberg , Biering-Sørensen Tor
Published: November 2023

Aims

Pressure-strain loop (PSL) analysis is a novel echocardiographic tool capable of assessing myocardial work non-invasively. In this study, we aim to evaluate the prognostic value of myocardial work indices in the general population.

Methods and results

This was a prospective community-based cohort study (n = 4466). PSL analyses were performed to acquire global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency (GWE). The endpoint was a composite of heart failure or cardiovascular death (HF/CVD). Survival analysis was applied. A total of 3932 participants were included in this analysis (median age: 58 years, 43% men). Of these, 124 (3%) experienced the outcome during a median follow-up period of 3.5 years [interquartile range (IQR): 2.6–4.4 years]. Hypertension significantly modified the association between all work indices and outcome (P for interaction < 0.05), such that work indices posed a higher risk of outcome in non-hypertensive than in hypertensive participants. After adjusting for Atherosclerosis Risk in Communities (ARIC)-HF risk variables, all work indices predicted outcome in non-hypertensive participants, but only GWI, GCW, and GWE predicted outcome in hypertensive participants [GWI: hazard ratio (HR) = 1.12 (1.07–1.16), per 100 mmHg% decrease; GCW: HR = 1.12 (1.08–1.17), per 100 mmHg% decrease; GWE: HR = 1.08 (1.04–1.12), per 1% decrease]. Only GWE significantly increased C-statistics when added to ARIC-HF risk variables in hypertensive participants (C-stat 0.865 vs. 0.877, P for increment = 0.003).

Conclusion

Hypertension modifies the association between myocardial work indices and HF/CVD in the general population. All work indices are associated with outcome in normotensive participants. GWI, GCW, and GWE are independently associated with outcome in hypertension, but only GWE improves risk prediction.
Distal His bundle pacing in a patient with surgically corrected complex Ebstein anomaly and symptomatic second-degree atrioventricular block: a case report
Authors: Koev Ivelin , Ng G Andre , Bolger Aidan P , Ibrahim Mokhtar
Published: November 2023

Background

Ebstein’s anomaly occurs when there is an apical displacement of the tricuspid valve with septal and posterior valve leaflets tethering. This condition often occurs in association with other congenital, structural, or conduction system diseases, including intracardiac shunts, valvular lesions, arrhythmias, accessory conduction pathways, and first-degree atrioventricular (AV) block. We present for the first time a case of a patient with Ebstein’s anomaly who presented with second-degree Mobitz II AV block and was successfully treated with conduction system pacing (CSP) due to her young age and the likelihood of a long-term high percentage of pacing.

Case summary

We present a case of a 42-year-old lady with a background of complex congenital heart disease, including severe pulmonary stenosis, Ebstein anomaly, and atrial septal defect (ASD). She required complex surgical intervention, including tricuspid valve (TV) repair and subsequently replacement, ASD closure, and pulmonary balloon valvuloplasty. She presented to our hospital with symptomatic second-degree Mobitz II AV block (dizziness, shortness of breath, and exercise intolerance) and right bundle branch block (RBBB) on her baseline ECG. Her echocardiogram showed dilated right ventricle (RV) and left ventricle (LV) with low normal LV systolic function. Due to her young age and the likelihood of a long-term high percentage of RV pacing, we opted for CSP after a detailed discussion and patient consent. The distal HIS position is the preferred pacing strategy at our centre. We could not cross the TV with the standard Medtronic C315 HIS catheter, so we had to use the deflectable C304 HIS catheter. Mapping and pacing of the distal HIS bundle were achieved by Medtronic Selectsecure 3830, 69 cm lead. HIS bundle pacing led to the correction of both second-degree Mobitz II AV block and pre-existing RBBB. The implantation was uneventful, and the patient was discharged home the next day without any acute complications.

Discussion

Distal HIS pacing is feasible in patients with surgically treated complex Ebstein anomaly and heart block. This approach can normalize the QRS complex with a high probability of preserving or improving LV function.
Diagnostic accuracy, clinical characteristics, and prognostic differences of patients with acute myocarditis according to inclusion criteria
Authors: Roy Roman , Cannata Antonio , Al-Agil Mohammad , Ferone Emma , Jordan Antonio , To-Dang Brian , Sadler Matthew , Shamsi Aamir , Albarjas Mohammad , Piper Susan , Giacca Mauro , Shah Ajay M , McDonagh Theresa , Bromage Daniel I , Scott Paul A
Published: November 2023

Introduction

The diagnosis of acute myocarditis (AM) is complex due to its heterogeneity and typically is defined by either Electronic Healthcare Records (EHRs) or advanced imaging and endomyocardial biopsy, but there is no consensus. We aimed to investigate the diagnostic accuracy of these approaches for AM.

Methods

Data on ICD 10th Revision(ICD-10) codes corresponding to AM were collected from two hospitals and compared to cardiac magnetic resonance (CMR)-confirmed or clinically suspected (CS)-AM cases with respect to diagnostic accuracy, clinical characteristics, and all-cause mortality. Next, we performed a review of published AM studies according to inclusion criteria.

Results

We identified 291 unique admissions with ICD-10 codes corresponding to AM in the first three diagnostic positions. The positive predictive value of ICD-10 codes for CMR-confirmed or CS-AM was 36%, and patients with CMR-confirmed or CS-AM had a lower all-cause mortality than those with a refuted diagnosis (P = 0.019). Using an unstructured approach, patients with CMR-confirmed and CS-AM had similar demographics, comorbidity profiles and survival over a median follow-up of 52 months (P = 0.72). Our review of the literature confirmed our findings. Outcomes for patients included in studies using CMR-confirmed criteria were favourable compared to studies with endomyocardial biopsy-confirmed AM cases.

Conclusion

ICD-10 codes have poor accuracy in identification of AM cases and should be used with caution in clinical research. There are important differences in management and outcomes of patients according to the selection criteria used to diagnose AM. Potential selection biases must be considered when interpreting AM cohorts and requires standardization of inclusion criteria for AM studies.
Characterization of unipolar electrogram morphology: a novel tool for quantifying conduction inhomogeneity
Authors: Ye Ziliang , van Schie Mathijs S , Pool Lisa , Heida Annejet , Knops Paul , Taverne Yannick J H J , Brundel Bianca J J M , de Groot Natasja M S
Published: November 2023

Aims

Areas of conduction inhomogeneity (CI) during sinus rhythm may facilitate the initiation and perpetuation of atrial fibrillation (AF). Currently, no tool is available to quantify the severity of CI. Our aim is to develop and validate a novel tool using unipolar electrograms (EGMs) only to quantify the severity of CI in the atria.

Methods and results

Epicardial mapping of the right atrium (RA) and left atrium, including Bachmann’s bundle, was performed in 235 patients undergoing coronary artery bypass grafting surgery. Conduction inhomogeneity was defined as the amount of conduction block. Electrograms were classified as single, short, long double (LDP), and fractionated potentials (FPs), and the fractionation duration of non-single potentials was measured. The proportion of low-voltage areas (LVAs, <1 mV) was calculated. Increased CI was associated with decreased potential voltages and increased LVAs, LDPs, and FPs. The Electrical Fingerprint Score consisting of RA EGM features, including LVAs and LDPs, was most accurate in predicting CI severity. The RA Electrical Fingerprint Score demonstrated the highest correlation with the amount of CI in both atria (r = 0.70, P < 0.001).

Conclusion

The Electrical Fingerprint Score is a novel tool to quantify the severity of CI using only unipolar EGM characteristics recorded. This tool can be used to stage the degree of conduction abnormalities without constructing spatial activation patterns, potentially enabling early identification of patients at high risk of post-operative AF or selection of the appropriate ablation approach in addition to pulmonary vein isolation at the electrophysiology laboratory.
Undermining support for COVID-19 public health policies: an analysis of the impact of subversive conspiracy narratives on Czech General Practitioners
Authors: Volek Jaromír , Moravec Václav
Published: November 2023

Background

Limited knowledge exists regarding the impact of COVID-19 conspiracy theories on the professional practice of general practitioners (GPs). This study aimed to identify the basic characteristics of GPs who endorse COVID-19 conspiracy beliefs and compare their level of support for COVID-19 health policies with GPs who do not believe in conspiracies.

Methods

Between January and February 2021, a representative online survey was conducted among 1163 GPs in the Czech Republic. The sample was designed to be representative of members of The Association of GPs of the Czech Republic.

Results

The survey revealed that nearly 14% of the GPs surveyed believed in one or more COVID-19 conspiracies. The average age of GPs who endorsed conspiracies was 58, which was higher than the rest of the sample (average age of 50). GPs who believed in conspiracies were less likely to support COVID-19 public health policies and therapy recommendations, including vaccination. Logistic and linear regression analyses indicated that doctors who believed in conspiracies were 2.62 times less likely to have received a COVID-19 vaccine. Mediation analysis showed that approximately one-quarter (23.21%) of the total effect of trust in government information on support for public health policies was indirectly mediated by the endorsement of COVID-19 conspiracy beliefs.

Conclusions

The study findings suggest a concerning association between belief in COVID-19 conspiracies and a reduced level of support for public health policies among GPs. These results underscore the importance of incorporating the ‘conspiracy agenda’ into medical authorities’ more effective public health communication strategies.
The eco-evolutionary origins of life
Authors: Kalambokidis Maria , Travisano Michael
Published: November 2023

The origin of life remains one of the greatest enigmas in science. The immense leap in complexity between prebiotic soup and cellular life challenges historically “chemistry-forward” and “biology-backwards” approaches. Evolution must have bridged this gap in complexity, so understanding factors that influence evolutionary outcomes is critical for exploring life’s emergence. Here, we review insights from ecology and evolution and their application throughout abiogenesis. In particular, we discuss how ecological and evolutionary constraints shape the evolution of biological innovation. We propose an “eco-evolutionary” approach, which is agnostic towards particular chemistries or environments and instead explores the several ways that an evolvable system may emerge and gain complexity.
Amor Mundi: The Ecology and Praise of Transience in Rilke’s Duino Elegies
Authors: Sorenson Alexander
Published: November 2023

Among the many puzzles in Rainer Maria Rilke's Duino Elegies is the ninth elegy’s declaration that the things of the world are disappearing, but that the only way to rescue them from this fate is to make them ‘invisible’. To make sense of this paradoxical scenario, the present article first examines in the light of several theoretical frameworks (for example, Walter Benjamin’s aura, Jean-Luc Maron’s apophasis and Hannah Arendt’s natality) how Rilke portrays the relationship between praise and mourning, proposing as an interpretive key hymnic language’s depicted capacity to illuminate transience. The article then demonstrates how this dimension of Rilke’s text articulates a vision of an authentically ecological relation to phenomena, one that involves an ecstatic exchange between subject and environment and that ultimately upends paradigmatic hierarchies of ‘human/non-human’ by introducing a modality of love grounded in loss rather than in possession.
Forest-Based Employment in the Southern United States amidst the COVID-19 Pandemic: A Causal Inference Analysis
Authors: Chizmar Stephanie , Parajuli Rajan , Bruck Sonia , Frey Gregory , Sills Erin
Published: November 2023

In response to the COVID-19 pandemic, some governments instituted mandatory stay-at-home policies. As these policies made exceptions for essential industries such as the forest sector, it is not clear a priori whether and how these policies would affect forest-based employment. This study examined the effect of mandatory stay-at-home orders on employment in the forest sector in forest dependent counties in eleven southern states in the United States. We estimated panel event study models in addition to difference-in-difference models to evaluate the policy effects with respect to initial treatment as well as average effects to the treated counties during treatment. We found that employment in wood product manufacturing was lower on average in counties under a lockdown order compared with employment in counties without an active order. We also found that employment in the aggregate forest sector in counties that implemented the policy was significantly lower than employment in counties without the policy up to 9 months following initial enactment compared with the underlying difference between treated and control counties one month prior to treatment. Overall, our findings suggest that lockdown policies had a limited effect on employment in essential industries such as wood-based manufacturing sectors in the southern states.

Study Implications: This study uses causal inference techniques to assess the effect of lockdown orders on forest-based employment in 11 southern states. Results suggest effects of lockdown orders were limited to the aggregate forest sector and wood product manufacturing, likely due to the rapid designation of the sector as essential and the reduced production of sawmills. The other industries within the sector were not significantly affected, implying that industries designated as essential may be more resilient to short-term shocks. These findings can be used to inform discussions on potential policy responses to future disasters, including how different interventions interact with one another.
Life Course Perspectives of Aging With Schizophrenia Spectrum Disorders in Psychiatric and Long-Term Care Facilities
Authors: Walker Verónica García , Harrison Tracie C
Published: November 2023

Background and Objectives

Individuals with schizophrenia spectrum disorders must manage residual symptoms as they age, and they may experience premature or accelerated aging in comparison with those without their diagnosis. To explore their life course perspectives, we interviewed institutionalized adults aging with schizophrenia spectrum disorders in middle and older age.

Research Design and Methods

We used an exploratory descriptive design and qualitative methods. Participants answered semistructured, open-ended questions about perceptions of their mental illness along the life course.

Results

Participants (N = 30, age 45–83 years) were from an acute care psychiatric facility and a long-term care facility: 16 (53%) men, 14 (47%) women; 6 (20%) Hispanic, 10 (33%) African American, 14 (47%) non-Hispanic White. Participants’ life course included traumas from violence, homelessness, and stigma; psychiatric symptoms such as worry and sadness; and age-related physiological symptoms including illness, loss of strength, falls, and incontinence, with falls and incontinence reported only in long-term care. Aging within institutionalization included lack of privacy and autonomy, and isolation (less socialization). Participants provided insights for potential improvements.

Discussion and Implications

Because these aging adults are experts on their own care, researchers should continue to seek their input to inform their healthcare.
Evaluating the impacts of environmental and fishery variability on the distribution of bigeye tuna in the Pacific Ocean
Authors: Lin H , Wang J , Zhu J , Chen X
Published: November 2023

Climate change-induced variabilities in the environment and fishing pressure affect the distribution and abundance of bigeye tuna in the Pacific Ocean. Understanding the causal relationships among these factors is complicated and challenging. We constructed a multi-output neural network model based on data from four types of bigeye tuna fisheries (longline and purse seine in the west-central and eastern Pacific Ocean, respectively) and marine environmental data, aiming to analyse the response of bigeye tuna to natural and anthropogenic factors from 1995 to 2019 in the Pacific Ocean. The input layer weights were used to explore the importance of environmental variable, while the output layer weights evaluated the contribution of fishing operations. These factors determined the final spatiotemporal distribution and abundance dynamics for bigeye tuna. The optimal model predicted a strong correlation between the locations of major habitats and El Niño southern Oscillation (ENSO) events, indicating that bigeye tuna abundance dynamics respond to the intensity of climate variability. During El Niño events, suitable conditions lead to an expansion of the main habitats east of 170°W, while during La Niña events, the strengthening of the westward advection leads to the contraction of major habitats west of 170°W. Furthermore, the resource abundance of bigeye tuna is predicted to be higher during moderate to weak El Niño events than during strong El Niño events. The abundances in purse seine and longline-dependent fisheries demonstrate significant different distribution patterns under different ENSO events, reflecting the unique environmental preferences at different life stages of bigeye tuna. Given the increasing frequency of climate variability and escalating fishing pressures, our findings provide beneficial insights for the sustainable development of bigeye tuna resource in the Pacific Ocean.
Development of novel waxy bone haemostatic agents composed of biodegradable polymers with osteogenic-enhancing peptides in rabbit models
Authors: Ohno Tsukasa , Suenaga Hiroto , Yamawaki-Ogata Aika , Kanie Kei , Kato Ryuji , Uto Koichiro , Ebara Mitsuhiro , Ito Hideki , Narita Yuji , Usui Akihiko , Mutsuga Masato
Published: November 2023

OBJECTIVES

The use of bone wax (BW) is controversial for sternal haemostasis because it increases the risk of wound infection and inhibits bone healing. We developed new waxy bone haemostatic agents made from biodegradable polymers containing peptides and evaluated them using rabbit models.

METHODS

We designed 2 types of waxy bone haemostatic agents: peptide wax (PW) and non-peptide wax (NPW), which used poly(ε-caprolactone)-based biodegradable polymers with or without an osteogenesis-enhancing peptide, respectively. Rabbits were randomly divided into 4 groups based on treatment with BW, NPW, PW or no treatment. In a tibial defect model, the bleeding amount was measured and bone healing was evaluated by micro-computed tomography over 16 weeks. Bone healing in a median sternotomy model was assessed for 2 weeks using X-ray, micro-computed tomography, histological examination and flexural strength testing.

RESULTS

The textures of PW and NPW (n = 12 each) were similar to that of BW and achieved a comparable degree of haemostasis. The crevice area of the sternal fracture line in the BW group was significantly larger than that in other groups (n = 10 each). The PW group demonstrated the strongest sternal flexural strength (n = 10), with complete tibial healing at 16 weeks. No groups exhibited wound infection, including osteomyelitis.

CONCLUSIONS

Waxy biodegradable haemostatic agents showed satisfactory results in haemostasis and bone healing in rabbit models and may be an effective alternative to BW.
MALDI–TOF bacterial subtyping for rapid detection of biomarkers in Staphylococcus aureus from subclinical bovine mastitis
Authors: Lopes Thainara , Fidelis Carlos E , Silva Amanda T F , Mota Rinaldo A , Rall Vera L M , dos Santos Marcos V , Gonçalves Juliano L
Published: November 2023

Aims

This study aimed to evaluate matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) bacterial subtyping for the rapid detection of biomarkers in Staphylococcus aureus from subclinical bovine mastitis.

Methods and results

A total of 229 S. aureus isolates were obtained from milk samples collected from cows with subclinical mastitis using microbiological culture. Staphylococcus aureus isolates were also submitted to PCR analysis targeting the mecA and mecC genes, which are indicative of methicillin resistance. Confirmation of the species was achieved through MALDI–TOF MS analysis. To analyze antimicrobial resistance patterns, the MALDI BioTyper Compass Explorer and ClinProTools Bruker software were employed, and dendrograms were generated using Bionumerics software.

Conclusions

MALDI–TOF MS successfully identified S. aureus at the species level, but no methicillin resistance was observed. Moreover, spectral typing displayed limited similarity when compared to pulsed-field gel electrophoresis (PFGE).
Flualprazolam and flubromazolam: Blood concentrations and prevalence of two novel psychoactive substances in forensic case work in Ontario, Canada
Authors: Vekic Nella , Armstrong-Price Delaney , Woodall Karen
Published: November 2023

Flualprazolam and flubromazolam are synthetic benzodiazepines that have not been approved for use in humans. They are categorized as novel psychoactive substances (NPS), and have been increasingly encountered in forensic case work. This report examines information from cases analyzed for flualprazolam and flubromazolam between July 1 and December 31, 2021 to identify the prevalence, trends and demographic data associated with these novel drugs in Ontario, Canada. Flualprazolam was identified in blood, serum or liver in 395 death investigations, 108 impaired driving and five sexual assault cases. Among all case types, blood concentrations were determined in 123 individuals aged 19–66 years. In impaired driving and sexual assault cases, flualprazolam blood concentrations ranged from <1.3 to 227 ng/mL (median 11.0 ng/mL), whereas a range of 3–59 ng/mL (median 6.8 ng/mL) was reported in death investigations. Flubromazolam was identified in blood, serum or liver in 137 death investigations, 55 impaired driving and one sexual assault case. Blood concentrations ranged from <1.3 to 323 ng/mL in 65 individuals, aged 14–61 years. In impaired driving and sexual assault cases, flubromazolam blood concentrations ranged from <1.3 to 323 ng/mL (median 7.7 ng/mL), which overlapped with the range of 2–220 ng/mL (median 8.0 ng/mL) reported in death investigations. Other drugs were frequently detected with flualprazolam and flubromazolam with opioids identified in more than 89% of positive flualprazolam and flubromazolam cases. These results demonstrated the prevalence of flualprazolam and flubromazolam in Ontario, Canada. Trends showed that over the 6-month period, as the number of flubromazolam cases decreased, the incidences of flualprazolam increased. An overlap in concentrations of these drugs was observed in both death investigations and cases involving living individuals. These data provide valuable information for the scientific community regarding the use of these drugs in antemortem and postmortem casework.
Does preoperative gabapentin or intraoperative ketorolac influence postoperative pain following hip arthroscopy?
Authors: Meyer Alex M , Petrachaianan Krit , Glass Natalie A , Westermann Robert W
Published: November 2023

Optimization of perioperative analgesia has important implications for patient satisfaction and short-term outcomes. This study’s purpose is to assess if preoperative gabapentin or intraoperative ketorolac influences postoperative pain or time to discharge following hip arthroscopy. In total, 409 patients who underwent hip arthroscopic femoroplasty and/or acetabuloplasty with a single surgeon for femoroacetabular impingement were retrospectively reviewed (September 2017 to February 2021). The effect of preoperative gabapentin or intraoperative ketorolac on postoperative visual analog scale (VAS) pain scores, perioperative opioids in morphine milligram equivalents (MMEs), time in post-anesthesia care unit (PACU), second-stage recovery and time to discharge was assessed using unadjusted and adjusted t-tests, and generalized linear models controlling for operative time, traction time, preoperative MME, intraoperative MME and postoperative MME were compared between the groups of gabapentin to no gabapentin and ketorolac to no ketorolac. There was no difference in first PACU VAS pain score, final PACU VAS score, VAS pain score prior to discharge, average VAS pain score or pain level on follow-up call in the unadjusted or adjusted analysis for the preoperative gabapentin or intraoperative ketorolac groups. Females had higher first PACU VAS pain score (6.05 versus 5.15 P = 0.0026), final PACU VAS pain score (4.43 versus 3.90, P = 0.0045), final VAS pain score prior to discharge (3.87 versus 3.03, P < 0.001) and average postoperative pain score (4.60 versus 4.03, P < 0.001), but no difference in VAS pain score on follow-up call following surgery. Gabapentin or ketorolac was not associated with decreased VAS pain scores or time to discharge after hip arthroscopy.
Unifying Estimation and Inference for Linear Regression with Stationary and Integrated or Near-Integrated Variables
Authors: Hong Shaoxin , Henderson Daniel J , Jiang Jiancheng , Ni Qingshan
Published: November 2023

There is a discrepancy in the limiting distributions of least-squares estimators for stationary and integrated variables. For statistical inference, it must be decided which distribution should be used in advance. This motivates us to develop a unifying inference procedure based on weighted estimation. The asymptotic distributions of the proposed estimators are developed and a random weighting bootstrap method is proposed for constructing confidence regions. The proposed method outperforms existing methods (with time constant or time-varying error variance) in simulations. We further study the predictability of asset returns in a setting where some of our state variables are endogenous.
Single-cell transcriptomics reveals tumor-infiltrating B cell function after neoadjuvant pembrolizumab and chemotherapy in non-small cell lung cancer
Authors: Hou Lingjie , Zhang Siyuan , Yu Wenwen , Yang Xuena , Shen Meng , Hao Xishan , Ren Xiubao , Sun Qian
Published: November 2023

Non-small cell lung cancer (NSCLC) is the most pervasive lung cancer subtype. Recent studies have shown that immune checkpoint inhibitors achieved favorable clinical benefits in resectable NSCLC; however, the associated mechanism remains unclear. The role of T cells in antitumor immunity has received considerable attention, while the antitumor effects of tumor-infiltrating B cells (TIBs) in NSCLC remain poorly understood. Here, we conducted a single-cell RNA sequencing analysis of immune cells isolated from 12 patients with stage IIIA NSCLC to investigate B cell subtypes and their functions following neoadjuvant chemoimmunotherapy. We confirmed the simultaneous existence of the 4 B cell subtypes. Among them, memory B cells were found to be associated with a positive therapeutic effect to neoadjuvant chemoimmunotherapy. Furthermore, we found that G protein–coupled receptor 183 was most prevalent in memory B cells and associated with a positive therapeutic response. Multiplex immunofluorescence and flow cytometry experiments in an additional cohort of 22 treatment-naïve and 30 stage IIIA/IIIB NSCLC patients treated with neoadjuvant chemoimmunotherapy verified these findings. Overall, our analysis revealed the functions of TIBs and their potential effect on clinical treatment in NSCLC.