bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient topical treatments of cutaneous lupus erythematosus: a systematic review and network ­meta-analysis
Authors: Fukasawa Takemichi , Yoshizaki-Ogawa Asako , Enomoto Atsushi , Miyagawa Kiyoshi , Sato Shinichi , Yoshizaki Ayumi
Published: August 2024

Although topical agents have been used to treat cutaneous lupus erythematosus (CLE), there was previously no high-quality evidence of which agents were most effective and which clinical scores were most suitable.

On 22 December 2023, a search was conducted across five databases to identify randomized controlled trials (RCTs) for CLE. Two authors independently screened the titles and abstracts of articles based on predetermined criteria. Selected articles were then assessed for inclusion in a blinded manner, with any disagreements resolved through consensus. Data were abstracted in duplicate, and a random-effects model was utilized for network meta-analysis. The certainty of the evidence was evaluated according to the PRISMA guidelines, using the GRADE approach. The analysis was finalized in January 2024, with the primary outcome focused on the change in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) from baseline.

Seven RCTs involving 231 participants were analysed. The network meta-analysis revealed that nicotinamide 4% demonstrated the highest probability of achieving the intended outcomes, with a mean difference (MD) of 3.10 and a 95% confidence interval (CI) of 1.99–4.21. Additionally, clobetasol 0.05%, nicotinamide 2% and tacrolimus 0.1% also exhibited statistically significant differences, with MDs of 2.30 (95% CI of 0.73–3.88), 2.30 (95% CI 0.97–3.63) and 1.30 (95% CI 0.03–2.57), respectively.

This NMA demonstrates with a high level of evidence that nicotinamide 4%, clobetasol 0.05%, nicotinamide 2% and tacrolimus 0.1% are statistically significant topical agents for CLE. CLASI may be an appropriate outcome to evaluate drug efficacy in CLE.
Assessment of clinician-reported outcome measures for alopecia areata: a systematic scoping review
Authors: Darchini-Maragheh Emadodin , Moussa Anthony , Rees Huw , Jones Leslie , Bokhari Laita , Sinclair Rodney
Published: August 2024

Background

Clinician-reported outcome measures (ClinROMs) are an important part of disease assessment in daily practice and clinical trials. There is a broad disagreement on the most appropriate ClinROM for a comprehensive assessment of alopecia areata (AA) severity.

Objectives

To identify the currently available ClinROMs for AA through a systematic literature search, address their practical strengths and weaknesses, and identify the road ahead for future research.

Methods

A search was conducted of the published, peer-reviewed literature via PubMed (MEDLINE) and Embase (via Ovid) databases. Articles published in English within the past 23 years (post-2000) that objectively measured AA severity were included. We did not select scoring systems that were solely based on patient-reported outcomes.

Results

The literature search identified 1376 articles, of which 27 were chosen for full-text review. Based on our eligibility criteria, 14 articles were identified, describing 16 different ClinROMs. Five ClinROMs solely measured scalp hair loss [Severity of Alopecia Tool (SALT), SALT II, Alopecia Density and Extent (ALODEX), pediatric SALT (pSALT) and Alopecia Areata Investigator Global Assessment Scale (AA-IGA)]. Three trichoscopy-based ClinROMs assessed disease activity [Alopecia Areata Progression Index (AAPI), Alopecia Areata Predictive Score (AAPS) and the coudability hair score]. Six ClinROMs exclusively assessed nonscalp areas [Brigham Eyebrow Tool for Alopecia Areata (BETA), Brigham Eyelash Tool for Alopecia Areata (BELA), Alopecia Barbae Severity (ALBAS), ClinRO Measure for Eyebrow Hair Loss™, ClinRO Measure for Eyelash Hair Loss™ and ClinRO Measure for Nail Appearance™]. Two ClinROMs assessed both scalp and nonscalp domains [Alopecia Areata Severity Index (AASI) and Alopecia Areata Scale (AASc)]. The practical strengths and weaknesses of each assessment tool are described.

Conclusions

Various practical limitations associated with their established tools have impeded the universal implementation in routine clinical practice. There is a significant need for a composite clinical severity scoring system to capture all the key severity identifiers beyond the involvement of the scalp.
Immune cell activity during anti-TNF treatment in patients with psoriasis and psoriatic arthritis
Authors: Petrovic Aleksandra , Samuelsen Victoria Marie , Davies Richard , Aarebrot Anders K , Holmes Timothy , Sarkar Irene , Bergum Brith , Jonsson Roland , Sandvik Lene F , Solberg Silje M , Appel Silke
Published: August 2024

Psoriasis is a chronic, inflammatory skin disease characterized by a dysregulated immune response and systemic inflammation. Up to one-third of patients with psoriasis have psoriatic arthritis (PsA). Targeted treatment with antibodies neutralizing tumor necrosis factor can ameliorate both diseases. We here explored the impact of long-term infliximab treatment on the composition and activity status of circulating immune cells involved in chronic skin and joint inflammation. Immune cells were analyzed by multicolor flow cytometry. We measured markers of immune activation in peripheral blood mononuclear cell populations in 24 infliximab-treated patients with psoriasis/PsA compared to 32 healthy controls. We observed a significant decrease in the frequency of both peripheral natural killer (NK) cells and their subset CD56dimCD16+ NK cells in PsA compared to healthy controls and patients with psoriasis. The latter had a strong-positive correlation with psoriasis area severity index (PASI) in these patients, while CD56brightCD16− NK cells were negatively correlated with PASI. In addition, we observed an upregulation of CD69+ intermediate CD14+CD16+ and CD69+ classical CD14+CD16− monocytes in PsA and increased activity of CD38+ intermediate CD14+CD16+ monocytes in patients with psoriasis. Compared to healthy controls, psoriasis patients demonstrated shifts of the three B-cell subsets with a decrease in transitional CD27-CD38high B cells. Our exploratory study indicates a preserved pathophysiological process including continuous systemic inflammation despite clinical stability of the patients treated with infliximab.
Circulating neutrophil extracellular trap-forming neutrophils in rheumatoid arthritis exacerbation are majority dual endothelin-1/signal peptide receptor+ subtype
Authors: Cross Andrew L , Wright Helen L , Choi Jacqueline , Edwards Steven W , Ruiz-Opazo Nelson , Herrera Victoria L M
Published: August 2024

Neutrophil extracellular traps (NETs) are associated with rheumatoid arthritis pathogenesis and severity. Since homeostatic NET-forming neutrophils [NET+Ns] have beneficial roles in defense against pathogens, their distinction from pro-injury [NET+N] subtypes is important, especially if they are to be therapeutically targeted. Having identified circulating, pro-injury DEspR+CD11b+[NET+Ns] in patients with neutrophilic secondary tissue injury, we determined whether DEspR+[NET+Ns] are present in rheumatoid arthritis (RA) flares. Whole blood samples of patients with RA flares on maintenance therapy (n = 6) were analyzed by flow cytometry (FCM) and immunofluorescence cytology followed by semi-automated quantitative confocal microscopy (qIFC). We assessed clinical parameters, levels of neutrophils and [NET+Ns], and plasma S100A8/A9. qIFC detected circulating DEspR+CD11b+neutrophils and [NET+Ns] in RA-flare patients but not healthy controls. DEspR+[NET+Ns] were positive for citrullinated histone H3 (citH3+), extruded DNA, decondensed but recognizable polymorphic nuclei, and [NET+N] doublet interactions in mostly non-ruptured NET-forming neutrophils. Circulating DNA+/DEspR+/CD11b+/citH3+microvesicles (netMVs) were observed. FCM detected increased %DEspR+CD11b+neutrophils and DEspR+ cell–cell doublets whose levels trended with DAS28 scores, as did plasma S100A8/A9 levels. This study identifies circulating DEspR+/CD11b+neutrophils and [NET+Ns] in RA-flare patients on maintenance therapy. Detection of circulating DEspR+citH3+[NET+Ns] and netMVs indicate a systemic neutrophilic source of citH3-antigen concordant with multi-joint RA pathogenesis. Increased S100A8/A9 alarmin levels are associated with cell injury and released upon NET-formation. As a ligand for TLR4, S100A8/A9 forms a positive feedback loop for TLR4-induced DEspR+neutrophils. These data identify DEspR+neutrophils and [NET+Ns] in RA pathogenesis as a potential biomarker and/or therapeutic target.
The proactive and reactive mechanisms of learned spatial suppression
Authors: Zhao Guang , Chen Jiahuan , Duan Yuhao , Li Shiyi , Wang Qiang , Li Dongwei
Published: August 2024

Selection history refers to the notion that previous allocations of attention or suppression have the potential to elicit lingering and enduring selection biases that are isolated from goal-driven or stimulus-driven attention. However, in the singleton detection mode task, manipulating the selection history of distractors cannot give rise to pure proactive inhibition. Therefore, we employed a combination of a working memory task and a feature search mode task, simultaneously recording cortical activity using EEG, to investigate the mechanisms of suppression guided by selection history. The results from event-related potential and reaction times showed an enhanced inhibitory performance when the distractor was presented at the high-probability location, along with instances where the target appeared at the high-probability location of distractors. These findings demonstrate that a generalized proactive inhibition bias is learned and processed independent of cognitive resources, which is supported by selection history. In contrast, reactive rejection toward the low-probability location was evident through the Pd component under varying cognitive resource conditions. Taken together, our findings indicated that participants learned proactive inhibition when the distractor was at the high-probability location, whereas reactive rejection was involved at low-probability location.
Development of diazirine–alkyne tag for protein–ligand interaction analysis with photoaffinity labeling
Authors: Nakatani Masatoshi , Ebihara Shohei , Kita Masaki
Published: August 2024

We have developed a diazirine–alkyne tag for target protein–ligand interaction analysis. A sulfonamide photoaffinity probe was readily prepared using copper-catalyzed azide–alkyne cycloaddition (CuAAC), which site-specifically formed a covalent bond with human carbonic anhydrase 1 (∼30% labeling yield). The photolabeled position (E58–H64 region) was determined based on the results of a tandem mass spectrometry (MS/MS) analysis of tryptic peptides and was supported by molecular modeling studies. Our method may be useful for determining unknown ligand-binding sites of various target biomolecules.
Sudden unexpected death in epilepsy: respiratory vs. cardiac contributions
Authors: Lin Susan , Schwartz Theodore H , Pitt Geoffrey S
Published: August 2024

Sudden unexpected death in epilepsy (SUDEP) poses a significant risk to life expectancy for individuals with epilepsy. Mechanistic insight, while incomplete, has advanced through clinical observational studies and animal models. Yet we lack preventative therapies, which will depend on understanding SUDEP mechanisms. Recurrent convulsive seizures are the major SUDEP risk factor. Cardiorespiratory dysfunction precedes SUDEP, but whether cardiac arrhythmias are major proximate culprits for SUDEP remains to be determined. Here, we highlight recent data from mouse models and clinical studies that provide increasing support for respiratory depression and decreasing evidence for tachyarrhythmia-induced SUDEP. Further, we review data from genetic and chemoconvulsant mouse models that have enabled a deeper understanding for how seizures initiated in the central nervous system propagate to the autonomic nervous system and drive seizure-induced respiratory depression and subsequent SUDEP, rather than supporting a proximate cardiac arrhythmia cause. Ongoing research will continue to identify predictive SUDEP biomarkers, improve animal models, and translate basic research into precision medicine approaches. Identifying and understanding the brainstem circuits vulnerable in seizure-induced apnoea will enable therapeutic interventions to enhance the quality of life and life expectancy for individuals with epilepsy.
Strength of parrot flight feathers is a function of position on the wing
Authors: Deeming Denis Charles , Hutchings Connor J , Seaward Fern G , Goodman Adrian M
Published: August 2024

Powered flight in birds is reliant on feathers forming an aerodynamic surface that resists air pressures. Many basic aspects of feather functionality are unknown, which hampers our understanding of wing function in birds. This study measured the dimensions of primary and secondary flight feathers of 19 species of parrots. The maximum force the feathers could withstand from below was also measured to mimic the pressures experienced during a downstroke. The analysis tested whether: (1) feather dimensions differed along the wing and among secondary and primary remiges; (2) the force that feathers could withstand varied among the remiges; and (3) there would be isometric relationships with body mass for feather characteristics. The results show that body mass significantly affected vane width, rachis thickness, maximum force, and ultimate bending moment, but the relationship for feather length only approached significance. Many of the proximal secondary feathers showed significantly lower values relative to the first primary, whereas for distal primaries the values were greater. There were isometric relationships for force measurements of primary and secondary feathers with body mass, but there was positive allometry for feather lengths and vane widths. The forces feathers can withstand vary along the wing may be a proxy for the aerodynamic properties of the feathers in situ. Broader taxonomic studies that explore these topics are required for other species representing a range of different orders. A better understanding of the functionality of feathers will improve our understanding of how avian flight works particularly considering the variety in flight style and wing shape in birds.
Esophagectomy after definitive chemoradiation in esophageal cancer: a safe therapeutic strategy
Authors: van Geffen Eline G M , Neelis Karen J , Putter Hein , Slingerland Marije , de Steur Wobbe O , van der Kraan Jolein , van der Molen Aart J , Crobach A Stijn L P , Hartgrink Henk H
Published: August 2024

The standard treatment regimen for esophageal cancer is chemoradiation followed by esophagectomy. However, the use of neoadjuvant chemoradiotherapy damages the surrounding tissue, which potentially increases the risk of postoperative complications, including anastomotic leakage. The impact of definitive chemoradiotherapy (dCRT, 50.4 Gy radiotherapy) compared to the standard neoadjuvant scheme (nCRT, 41.4 Gy radiotherapy) prior to surgery on the incidence of anastomotic leakage remains poorly understood. To study this, all patients who received dCRT between 2011 and 2021 followed by esophagectomy were included. For each patient, two patients who received nCRT were selected as matched controls. Outcomes included postoperative anastomotic leakage, pulmonary and other complications, anastomotic stenosis, pulmonary and other postoperative complications (Clavien Dindo Classification ≥1), and overall survival. One hundred and eight patients were included with a median follow-up of 28 months. The time between neoadjuvant treatment and surgery was longer in the dCRT group compared to the nCRT group (65 vs. 48 days, P < 0.001). Postoperatively, significantly more patients in the dCRT group suffered from anastomotic leakage (11% vs. 1%, P = 0.04) and anastomotic stenosis (42% vs. 17%, P < 0.01). No differences were found for other complications or overall survival between both groups. In conclusion, preoperative dCRT is associated with a higher risk of anastomotic leakage and stenosis. These complications, however, can be treated effectively. Therefore, esophagectomy after dCRT is considered to be an appropriate treatment strategy in a selected patient group.
The Costs of Home Monitoring by Telemedicine vs Standard Care for Inflammatory Bowel Diseases—A Danish Register-Based, 5-Year Follow-up Study
Authors: Al-Sheikh Marwah , Ankersen Dorit Vedel , Olsen Jens , Spanggaard Maria , Peters-Lehm Charlotte T , Naimi Rahim M , Bennedsen Mette , Burisch Johan , Munkholm Pia
Published: August 2024

Background and Aims

There are few studies on the cost-effectiveness of telemedicine for inflammatory bowel diseases. We assessed the long-term cost-effectiveness of a telemedicine solution compared to standard care (sCare), as well as its efficacy according to patient-reported outcomes (PROs).

Methods

Between 2015 and 2020, we conducted a retrospective, register-based study among patients with ulcerative colitis and Crohn’s disease. Direct and indirect healthcare costs over a 5-year period were obtained from Danish registers and compared to a control group. Costs were estimated on a yearly basis from 1 year before, until 5 years after, inclusion in the trial. Patients were divided into 2 groups: those not receiving biologics (Cohort 1) and those receiving biologics (Cohort 2).

Results

We recruited 574 patients with inflammatory bowel diseases. In Cohort 1 (61.5%), average total direct costs and total earnings per patient per year were €14 043 and €307 793, respectively, in telemedicine compared to €16 226 and €252 166, respectively, in sCare. In Cohort 2 (38.5%), average total direct costs and total earnings were €73 916 and €215 833, respectively, in telemedicine compared to €41 748 and €203 667, respectively, in sCare. PROs showed improved quality of life, which was higher in Cohort 1 than in Cohort 2. Disease activity among patients with Crohn’s disease increased after Years 3 and 4 in Cohorts 1 and 2, respectively.

Conclusion

Telemedicine is cost-effective for patients not receiving biologics. However, treatment with biologics is more expensive for patients enrolled in telemedicine. Careful attention to PROs in telemedicine improves quality of life and could prolong the time to relapse.
The left ventricular assist device ‘skeleton man’: case report—simple tools for skeletal muscle evaluation and very early aerobic/resistance/inspiratory training in cardiac cachexia
Authors: Laoutaris Ioannis D , Gkouziouta Aggeliki , Bonios Michael J , Katelouzos George , Kogerakis Nektarios , Chamogeorgakis Themistocles , Adamopoulos Stamatis
Published: August 2024

Background

Skeletal muscle wasting (SMW) is highly prevalent in patients with heart failure (HF) at left ventricular assist device (LVAD) implantation and is associated with morbidity and mortality. At the same time, SMW is clinically under-recognized, while exercise training (ET) studies in weak LVAD patients are lacking.

Case summary

A 60-year-old man with advanced HF, SMW, cardiac cachexia, and frailty was confined in bed for 6 months initially supported with intravenous inotropes and subsequently with an intra-aortic balloon pump. His frailty was recognized as an LVAD-responsive frailty, and patient was successfully implanted with a HeartWare (Medtronic). Post-surgery, patient was very weak, unable even to move in bed without assistance. We evaluated skeletal muscle using simple tools such as the Oxford scale, mid-thigh circumference, hand-held dynamometry, and maximum inspiratory pressure. Physical performance was assessed with the sit to stand test, gait speed test, pedal bike timing, and the 6 min walk test. On top of routine physiotherapy, patient underwent an 8-week modified aerobic/resistance/inspiratory (ARIS) ET programme at moderate intensity and showed significant improvements in skeletal muscle mass and strength and physical and functional capacity.

Discussion

We want to emphasize the importance of skeletal muscle evaluation at LVAD implantation and the feasibility and effectiveness of early ARIS training in very weak patients.
Eosinophilic myocarditis: a diagnostic challenge and treatment dilemma—a case report
Authors: Ammouri Zaid , Belkouchia Sami , Rezzouk Ibtissam , Moussaoui Salma , Habbal Rachida
Published: August 2024

Background

Eosinophilic myocarditis, a rare and potentially life-threatening condition, can resemble acute coronary syndrome (ACS) and presents diagnostic difficulties.

Case report

We describe the case of a 32-year-old man initially admitted with ACS-like symptoms, but ultimately diagnosed with eosinophilic myocarditis. The patient presented with intense retrosternal chest pain, significant eosinophilia, and elevated cardiac enzymes. Despite clinical indications suggesting myocardial involvement, an endomyocardial biopsy was not performed due to the patient’s reluctance. Non-invasive imaging and clinical findings led to the presumptive diagnosis of eosinophilic myocarditis. The patient was treated with high-dose corticosteroids and immunosuppressive therapy, resulting in clinical improvement.

Discussion

Our report highlights the importance of considering eosinophilic myocarditis and hypereosinophilic syndrome when evaluating patients with chest pain and hypereosinophilia. It emphasizes the subtleties of diagnosis and the critical need for early identification and appropriate treatment to improve prognosis in cases of eosinophilic myocarditis. This case underscores the diverse clinical manifestations of myocarditis and the essential need for a comprehensive diagnostic approach in the presence of chest pain and hypereosinophilia.
Metabolically healthy obesity in adults with X-linked hypophosphatemia
Authors: Lecoq Anne-Lise , Schilbach Katharina , Rocher Laurence , Trabado Séverine , Briot Karine , Herrou Julia , Forbes Aurélie , Garnier Anthony , Piketty Marie , Bidlingmaier Martin , Rothenbuhler Anya , Linglart Agnès , Carette Claire , Chaumet-Riffaud Philippe , Kamenický Peter
Published: August 2024

Objectives

X-linked hypophosphatemia (XLH) is characterized by increased concentrations of circulating fibroblast growth factor 23 (FGF-23) resulting in phosphate wasting, hypophosphatemia, atypical growth plate and bone matrix mineralization. Epidemiologic studies suggest a relationship between FGF-23, obesity, and metabolic dysfunction. The prevalence of overweight and obesity is high in children with XLH. We aimed to evaluate the prevalence of obesity and metabolic complications in adults with XLH.

Methods

We conducted a prospective cohort study in adult XLH patients from a single tertiary referral center. The proportion of patients with a BMI >25 kg/m2 was the main outcome measure. Body fat mass percentage (FM%) and adipose tissue surfaces were secondary outcome measures. Glucose homeostasis (plasma glucose and insulin concentrations after fasting and 2 hours after an oral glucose tolerance test) was explored in a subgroup of patients and compared with age-, sex-, and BMI-matched healthy controls.

Results

Among 113 evaluated patients, 85 (75%) were female and 110 (97%) carried a PHEX mutation. Sixty-three (56%) patients were overweight or obese, with a median BMI of 25.3 [IQR, 22.7; 29.2] kg/m2. BMI was correlated with FM%, abdominal and thigh subcutaneous and intra-abdominal adipose tissue surfaces. The prevalence of impaired fasting glucose, impaired glucose tolerance, and diabetes was not different between XLH patients and matched controls.

Conclusion

The prevalence of overweight and obesity is high among XLH patients and is associated with excess fat mass. However, the prevalence of glucose homeostasis abnormalities is not increased in patients compared to healthy controls, suggesting that metabolically healthy overweight or obesity predominates.
KCNQ1 suppression-replacement gene therapy in transgenic rabbits with type 1 long QT syndrome
Authors: Bains Sahej , Giammarino Lucilla , Nimani Saranda , Alerni Nicolo , Tester David J , Kim C S John , Christoforou Nicolas , Louradour Julien , Horváth András , Beslac Olgica , Barbieri Miriam , Matas Lluis , Hof Thomas S , Lopez Ruben , Perez-Feliz Stefanie , Parodi Chiara , Garcia Casalta Luisana G , Jurgensen Jacqulyn , Barry Michael A , Bego Mariana , Keyes Lisa , Owens Jane , Pinkstaff Jason , Koren Gideon , Zehender Manfred , Brunner Michael , Casoni Daniela , Praz Fabien , Haeberlin Andreas , Brooks Gabriel , Ackerman Michael J , Odening Katja E
Published: August 2024

Background and Aims

Type 1 long QT syndrome (LQT1) is caused by pathogenic variants in the KCNQ1-encoded Kv7.1 potassium channels, which pathologically prolong ventricular action potential duration (APD). Herein, the pathologic phenotype in transgenic LQT1 rabbits is rescued using a novel KCNQ1 suppression-replacement (SupRep) gene therapy.

Methods

KCNQ1-SupRep gene therapy was developed by combining into a single construct a KCNQ1 shRNA (suppression) and an shRNA-immune KCNQ1 cDNA (replacement), packaged into adeno-associated virus serotype 9, and delivered in vivo via an intra-aortic root injection (1E10 vg/kg). To ascertain the efficacy of SupRep, 12-lead electrocardiograms were assessed in adult LQT1 and wild-type (WT) rabbits and patch-clamp experiments were performed on isolated ventricular cardiomyocytes.

Results

KCNQ1-SupRep treatment of LQT1 rabbits resulted in significant shortening of the pathologically prolonged QT index (QTi) towards WT levels. Ventricular cardiomyocytes isolated from treated LQT1 rabbits demonstrated pronounced shortening of APD compared to LQT1 controls, leading to levels similar to WT (LQT1-UT vs. LQT1-SupRep, P < .0001, LQT1-SupRep vs. WT, P = ns). Under β-adrenergic stimulation with isoproterenol, SupRep-treated rabbits demonstrated a WT-like physiological QTi and APD90 behaviour.

Conclusions

This study provides the first animal-model, proof-of-concept gene therapy for correction of LQT1. In LQT1 rabbits, treatment with KCNQ1-SupRep gene therapy normalized the clinical QTi and cellular APD90 to near WT levels both at baseline and after isoproterenol. If similar QT/APD correction can be achieved with intravenous administration of KCNQ1-SupRep gene therapy in LQT1 rabbits, these encouraging data should compel continued development of this gene therapy for patients with LQT1.
Systematic review and meta-analysis on the impact on outcomes of device algorithms for minimizing right ventricular pacing
Authors: Mei Davide Antonio , Imberti Jacopo Francesco , Vitolo Marco , Bonini Niccolò , Serafini Kevin , Mantovani Marta , Tartaglia Enrico , Birtolo Chiara , Zuin Marco , Bertini Matteo , Boriani Giuseppe
Published: August 2024

Aims

Physiological activation of the heart using algorithms to minimize right ventricular pacing (RVPm) may be an effective strategy to reduce adverse events in patients requiring anti-bradycardia therapies. This systematic review and meta-analysis aimed to evaluate current evidence on clinical outcomes for patients treated with RVPm algorithms compared to dual-chamber pacing (DDD).

Methods and results

We conducted a systematic search of the PubMed database. The predefined endpoints were the occurrence of persistent/permanent atrial fibrillation (PerAF), cardiovascular (CV) hospitalization, all-cause death, and adverse symptoms. We also aimed to explore the differential effects of algorithms in studies enrolling a high percentage of atrioventricular block (AVB) patients. Eight studies (7229 patients) were included in the analysis. Compared to DDD pacing, patients using RVPm algorithms showed a lower risk of PerAF [odds ratio (OR) 0.74, 95% confidence interval (CI) 0.57–0.97] and CV hospitalization (OR 0.77, 95% CI 0.61–0.97). No significant difference was found for all-cause death (OR 1.01, 95% CI 0.78–1.30) or adverse symptoms (OR 1.03, 95% CI 0.81–1.29). No significant interaction was found between the use of the RVPm strategy and studies enrolling a high percentage of AVB patients. The pooled mean RVP percentage for RVPm algorithms was 7.96% (95% CI 3.13–20.25), as compared with 45.11% (95% CI 26.64–76.38) of DDD pacing.

Conclusion

Algorithms for RVPm may be effective in reducing the risk of PerAF and CV hospitalization in patients requiring anti-bradycardia therapies, without an increased risk of adverse symptoms. These results are also consistent for studies enrolling a high percentage of AVB patients.
Genetic mechanisms of axial patterning in Apeltes quadracus
Authors: Herbert Amy L , Lee David , McCoy Matthew J , Behrens Veronica C , Wucherpfennig Julia I , Kingsley David M
Published: August 2024

The genetic mechanisms underlying striking axial patterning changes in wild species are still largely unknown. Previous studies have shown that Apeltes quadracus fish, commonly known as fourspine sticklebacks, have evolved multiple different axial patterns in wild populations. Here, we revisit classic locations in Nova Scotia, Canada, where both high-spined and low-spined morphs are particularly common. Using genetic crosses and quantitative trait locus (QTL) mapping, we examine the genetic architecture of wild differences in several axial patterning traits, including the number and length of prominent dorsal spines, the number of underlying median support bones (pterygiophores), and the number and ratio of abdominal and caudal vertebrae along the anterior–posterior body axis. Our studies identify a highly significant QTL on chromosome 6 that controls a substantial fraction of phenotypic variation in multiple dorsal spine and pterygiophore traits (~15%–30% variance explained). An additional smaller-effect QTL on chromosome 14 contributes to the lengths of both the last dorsal spine and anal spine (~9% variance explained). 1 or no QTL were detected for differences in the numbers of abdominal and caudal vertebrae. The major-effect patterning QTL on chromosome 6 is centered on the HOXDB gene cluster, where sequence changes in a noncoding axial regulatory enhancer have previously been associated with prominent dorsal spine differences in Apeltes. The QTL that have the largest effects on dorsal spine number and length traits map to different chromosomes in Apeltes and Gasterosteus, 2 distantly related stickleback genera. However, in both genera, the major-effect QTL for prominent skeletal changes in wild populations maps to linked clusters of powerful developmental control genes. This study, therefore, bolsters the body of evidence that regulatory changes in developmental gene clusters provide a common genetic mechanism for evolving major morphological changes in natural species.
Single-cell measurement of microbial growth rate with Raman microspectroscopy
Authors: Caro Tristan A , Kashyap Srishti , Brown George , Chen Claudia , Kopf Sebastian H , Templeton Alexis S
Published: August 2024

Rates of microbial growth are fundamental to understanding environmental geochemistry and ecology. However, measuring the heterogeneity of microbial activity at the single-cell level, especially within complex populations and environmental matrices, remains a forefront challenge. Stable isotope probing (SIP) is a method for assessing microbial growth and involves measuring the incorporation of an isotopic label into microbial biomass. Here, we assess Raman microspectroscopy as a SIP technique, specifically focusing on the measurement of deuterium (2H), a tracer of microbial biomass production. We correlatively measured cells grown in varying concentrations of deuterated water with both Raman spectroscopy and nanoscale secondary ion mass spectrometry (nanoSIMS), generating isotopic calibrations of microbial 2H. Relative to Raman, we find that nanoSIMS measurements of 2H are subject to substantial dilution due to rapid exchange of H during sample washing. We apply our Raman-derived calibration to a numerical model of microbial growth, explicitly parameterizing the factors controlling growth rate quantification and demonstrating that Raman–SIP can sensitively measure the growth of microorganisms with doubling times ranging from hours to years. The measurement of single-cell growth with Raman spectroscopy, a rapid, nondestructive technique, represents an important step toward application of single-cell analysis into complex sample matrices or cellular assemblages.
The first high-altitude autotetraploid haplotype-resolved genome assembled (Rhododendron nivale subsp. boreale) provides new insights into mountaintop adaptation
Authors: Lyu Zhen-Yu , Zhou Xiong-Li , Wang Si-Qi , Yang Gao-Ming , Sun Wen-Guang , Zhang Jie-Yu , Zhang Rui , Shen Shi-Kang
Published: August 2024

Background

Rhododendron nivale subsp. boreale Philipson et M. N. Philipson is an alpine woody species with ornamental qualities that serve as the predominant species in mountainous scrub habitats found at an altitude of ∼4,200 m. As a high-altitude woody polyploid, this species may serve as a model to understand how plants adapt to alpine environments. Despite its ecological significance, the lack of genomic resources has hindered a comprehensive understanding of its evolutionary and adaptive characteristics in high-altitude mountainous environments.

Findings

We sequenced and assembled the genome of R. nivale subsp. boreale, an assembly of the first subgenus Rhododendron and the first high-altitude woody flowering tetraploid, contributing an important genomic resource for alpine woody flora. The assembly included 52 pseudochromosomes (scaffold N50 = 42.93 Mb; BUSCO = 98.8%; QV = 45.51; S-AQI = 98.69), which belonged to 4 haplotypes, harboring 127,810 predicted protein-coding genes. Conjoint k-mer analysis, collinearity assessment, and phylogenetic investigation corroborated autotetraploid identity. Comparative genomic analysis revealed that R. nivale subsp. boreale originated as a neopolyploid of R. nivale and underwent 2 rounds of ancient polyploidy events. Transcriptional expression analysis showed that differences in expression between alleles were common and randomly distributed in the genome. We identified extended gene families and signatures of positive selection that are involved not only in adaptation to the mountaintop ecosystem (response to stress and developmental regulation) but also in autotetraploid reproduction (meiotic stabilization). Additionally, the expression levels of the (group VII ethylene response factor transcription factors) ERF VIIs were significantly higher than the mean global gene expression. We suspect that these changes have enabled the success of this species at high altitudes.

Conclusions

We assembled the first high-altitude autopolyploid genome and achieved chromosome-level assembly within the subgenus Rhododendron. In addition, a high-altitude adaptation strategy of R. nivale subsp. boreale was reasonably speculated. This study provides valuable data for the exploration of alpine mountaintop adaptations and the correlation between extreme environments and species polyploidization.
Laboratory constraints on the anisotropic dynamic-to-static ratios for shale's elastic constants: an example from the Duvernay unconventional reservoir
Authors: Shen Luyi , Schmitt Douglas R , Jiao Yu-yong
Published: August 2024

Dynamic material constants obtained by wave-based methods are different from their static counterparts. Constraining rock's elastic constants’ dynamic-to-static ratios (Rij) are important for understanding the geomechanical properties of earth's materials, particularly in the context of hydraulic fracturing that requires the knowledge of shale's static elastic constants. Conducting experiments with dynamic and elastic constants’ anisotropy, on top of their pressure dependency, properly accounted for is challenging. Here, we measure suites of dynamic and static elastic constants, with anisotropy fully accounted for, on the shale samples extracted from the Duvernay unconventional reservoir; a comprehensive set of geochemical/petrophysical measurements are obtained too. We observe that the dynamic-to-static ratios are generally not sensitive to the increasing pressures at σ > 50 MPa; we do not find a correlation with the samples’ mineral contents either. However, we find that Rij strongly correlates to the dynamic elastic constants except for the R11. The correlation between Rij, particularly Ri3, and the dynamic elastic constants can be explained by the sedimentary rocks’ compactness and the horizontal void spaces parallel to the rock's laminated bedding planes.
European Commission’s Draft Regulation on SEPs: An IP Finance Assessment
Authors: Borgogno Oscar , Colangelo Giuseppe
Published: August 2024

The European Commission’s proposed Draft Regulation on Standard Essential Patents (SEPs) aims to overhaul the landscape of SEP licensing, addressing transparency deficits and fair, reasonable, and non-discriminatory (FRAND) terms amidst the burgeoning Internet of Things (IoT) market. Emphasizing concerns over hold-up risks, the Draft Regulation introduces mandatory essentiality checks and structured FRAND determinations to mitigate opportunistic behaviours among SEP holders. However, the practical implementation of these measures poses challenges, including the accuracy of essentiality assessments and the potential for increased transaction costs. Moreover, the Draft Regulation fails to consider the financial dimension of technological innovation, namely the potential of SEPs to function as valuable financial assets. By undermining the economic value of SEPs in terms of enforcement and monetisation, there is a risk of watering down their potential to serve as valuable financial collateral and therefore to help innovators access debt financing.
Unlocking the power of tobacco taxation to mitigate the social costs of smoking in Mexico: a microsimulation model
Authors: Saenz-de-Miera Belen , Reynales-Shigematsu Luz Myriam , Palacios Alfredo , Bardach Ariel , Casarini Agustin , Espinola Natalia , Cairoli Federico Rodriguez , Alcaraz Andrea , Augustovski Federico , Pichon-Riviere Andres
Published: August 2024

Despite being the most cost-effective tobacco control policy, tobacco taxation is the least implemented component of the World Health Organization MPOWER package to reduce smoking worldwide. In Mexico, both smoking prevalence and taxation have remained stable for more than a decade. This study aims to provide evidence about the potential effects of taxation to reduce the burden of tobacco-related diseases and the main attributable social costs in Mexico, including informal (unpaid) care costs, which are frequently ignored. We employ a first-order Monte Carlo microsimulation model that follows hypothetical population cohorts considering the risks of an adverse health event and death. First, we estimate tobacco-attributable morbidity and mortality, direct medical costs and indirect costs, such as labour productivity losses and informal care costs. Then, we assess the potential effects of a 50% cigarette price increase through taxation and two alternative scenarios of 25% and 75%. The inputs come from several sources, including national surveys and vital statistics. Each year, 63 000 premature deaths and 427 000 disease events are attributable to tobacco in Mexico, while social costs amount to MX$194.6 billion (US$8.5)—MX$116.2 (US$5.1) direct medical costs and MX$78.5 (US$3.4) indirect costs—representing 0.8% of gross domestic product. Current tobacco tax revenue barely covers 23.3% of these costs. Increasing cigarette prices through taxation by 50% could reduce premature deaths by 49 000 over the next decade, while direct and indirect costs averted would amount to MX$87.9 billion (US$3.8) and MX$67.6 billion (US$2.9), respectively. The benefits would far outweigh any potential loss even in a pessimistic scenario of increased illicit trade. Tobacco use imposes high social costs on the Mexican population, but tobacco taxation is a win-win policy for both gaining population health and reducing tobacco societal costs.
Health literacy and its determinants among school-going children: a school-based cross-sectional study in Nepal
Authors: Adhikari Prakash , Paudel Kiran , Bhusal Sandesh , Gautam Kamal , Khanal Pratik , Adhikari Tara Ballav , K. C. Prabhat , Shrestha Roman , Shrestha Sushan Man
Published: August 2024

Limited health literacy is linked to unhealthy behaviors, adverse health outcomes, poor quality of life and financial burdens on society. However, little is known about the level of health literacy, especially among school-going children. This cross-sectional study assesses health literacy levels and their determinants in 354 school children from Kathmandu Metropolitan City, utilizing a multi-stage cluster sampling method. The 10-item Health Literacy for School-Aged Children was used to measure the student’s literacy levels. Bivariate analysis and multivariable logistic regression at the significance level of 0.05 were performed to determine factors associated with limited health literacy. The majority of participants (76.6%) had moderate health literacy, while 13.8% had a high level and 9.6% had a low level of health literacy. Students from nuclear families had lower odds [adjusted odds ratio (aOR): 0.4; 95% CI: 0.2–0.8] of having limited health literacy. Students whose mother education was up to secondary school (aOR: 10.1; 95% CI: 1.3–78.9), students with pre-existing mental health conditions (aOR: 3.7; 95% CI: 1.4–9.6) and students with unsatisfactory health status (aOR: 3.9; 95% CI: 1.5–10.5) had higher odds to have limited health literacy. These results suggest the importance of prioritizing school health promotion and education activities for students with pre-existing mental health conditions and mothers with low educational attainment. Implementing peer support group programs for children with mental illnesses, mobilizing school health professionals and introducing interventions such as vocational training of mothers can collectively improve health literacy among school-going children.
Distribution of Serum Testosterone Concentrations in IBD Males and Associations With Inflammatory Bowel Disease Activity
Authors: Judge Ciaran , Lightowler Daniel , Singh Abhey , Yeap Bu B , Thin Lena
Published: August 2024

Background

An inverse relationship exists between inflammation and testosterone concentrations in non–inflammatory bowel disease (IBD) immune conditions but has not been objectively explored in the IBD male population. We aimed to characterize the distribution of testosterone concentrations in a cohort of males with IBD and identify any relationship between testosterone levels and disease activity.

Methods

We conducted a prospective cross-sectional study of male IBD patients. Demographics, disease characteristics, sex-hormone concentration, gonadotropins, C-reactive protein, fecal calprotectin, and patient-reported outcomes on quality of life and erectile function were collected. Relationships between disease activity, biomarkers, patient-reported outcome scores, and testosterone levels were analyzed using univariate and multivariate linear regression analyses.

Results

A total of 85 male IBD patients were included with a mean age 44 ± 14.1 years, of which 49.4% had Crohn’s disease. Mean testosterone concentration was 15.4 ± 5.2 nmol/L and 17.6% had a serum testosterone <10.4 nmol/L. Active disease was associated with lower testosterone concentrations in univariate analysis (β ± SE = −0.25 ± -1.99, P = .02) but not in multivariate analysis (β −0.18 ± 1.75, P = .06). Testosterone concentrations were independently associated with sex hormone–binding globulin levels (β ± SE = 0.45 ± 0.04, P < .0001) and a younger age (β ± SE = −0.32 ± 0.04, P <.0001). Erectile function scores (5-item International Index of Erectile Function) were lower in IBD patients with a longer duration of disease (β ± SE = −0.24 ± 0.006, P = .04).

Conclusions

Lower testosterone concentrations in men with IBD may reflect confounding from other factors and are not independently associated with disease activity. Greater awareness and screening for sexual dysfunction should occur in males with IBD, particularly in those with a longer disease duration.
Effect of environmental drivers on the spatiotemporal distribution of mackerel at age in the Nordic Seas during 2010−20
Authors: Ono K , Katara I , Eliasen S K , Broms C , Campbell A , dos Santos Schmidt T C , Egan A , Hølleland S N , Jacobsen J A , Jansen T , Mackinson S , Mousing E A , Nash R D M , Nikolioudakis N , Nnanatu C , Nøttestad L , Singh W , Slotte A , Wieland K , Olafsdottir A H
Published: August 2024

A joint spatio–temporal distribution model of mackerel (ages 3–10) was developed to investigate the age-based responses of mackerel to three environmental drivers: sea surface temperature (SST), mixed layer depth, and chlorophyll-a concentration during the summer months 2010–20 in the Nordic Seas. The study showed that SST was the most important variable amongst the ones tested and had the strongest impact on the distribution of the younger age classes (3–5), which had a narrower range of favourable SST and a stronger aversion to cold temperatures than older individuals. Consequently, the impact of SST differed regionally; in the polar front regions, SST explained up to 61% of the variability in the observed density of young individuals, where Arctic water masses likely acted as a barrier to these young individuals. That said, part of it could be confounded with the limited migration capability of young mackerels, which could not reach the furthest frontal regions. In warmer southern waters, the same environmental variables had less explanatory power for mackerel of all ages. Individuals in the south were likely not constrained by temperature and perhaps more influenced by other variables, such as food availability or ocean current (throughout their migration path), for which appropriate data are lacking. Moreover, the model showed that older mackerel were distributed more to the north and west, and their migration pattern changed when the 2013 year-class no longer migrated to the west compared to previous year-classes. Additionally, all-year classes started migrating more eastward from summer 2018.
Evaluation of university and training standards in clinical perfusion, a european-wide survey
Authors: Giesbrecht André , Klüß Christian , Debeuckelaere Gerdy , Bruño Maria Angeles , Wenzel Folker , Kohl Matthias , De Somer Filip , Bauer Adrian
Published: August 2024

OBJECTIVES

Adequate theoretical and practical training of prospective clinical perfusionists is essential for maintaining clinical standards and ensuring patient safety during cardiac surgery procedures. Perfusion schools play a crucial role in establishing and maintaining higher education and training standards in clinical perfusion. The aim of this study is to obtain a comprehensive overview of European training standards in clinical perfusion in 2023.

METHODS

For this study, 53 perfusion schools in Europe were found and contacted, of which 30 (56,6%) responded, giving a sample size of n = 30, which were then included in the data analysis. The quantitative data of the survey are analysed using descriptive methods.

RESULTS

The university and training standards in clinical perfusion in Europe vary in many respects. Starting with the entry criterion for studies (most frequently a required bachelor's degree 36.7% or second most common an university entrance qualification 30%), the duration (from less than 12 months (13.3%) up to 36 months (13.3%)) and regarding the content of the teaching in clinical perfusion (less than 30 ECTS (33.3%) and more than 180 ECTS (6.7%)). The mean value for teaching in clinical perfusion content is 62.63 ECTS credits.

CONCLUSIONS

The obtained results show important differences between countries and schools. As such they form a valuable database for future discussions establishing a common European curriculum and training standards for perfusionists. For the generalisability of the results, further evaluations and larger samples are needed.