bluuebunny/crossref_metadata_2025 huggingface dataset:
544 - Cost-per-responder analysis of tralokinumab versus dupilumab in patients with moderate-to-severe atopic dermatitis in the US and Canada
Authors: Wu Jashin J , Balu Sanjeev , Larsen Nikolaj Birk , Pulleyblank Ryan , Strømkjær Liv , Quah Aron , Wiseman Marni
Published: February 2024

Introduction/Background

Biologic treatments such as tralokinumab and dupilumab are therapeutic options for adult patients with moderate-to-­severe atopic dermatitis (AD) who do not achieve adequate control with topical treatments or phototherapy. To date, no trials have been conducted to directly evaluate the relative efficacy of these biologic treatments.

Objectives

Applying indirect comparison of efficacy, we examined the cost-per-responder of tralokinumab compared to dupilumab in combination with topical corticosteroids (TCS) for the treatment of moderate-to-serve AD in the United States (US) and Canada.

Methods

A cost-per-responder analysis was undertaken considering the Eczema Area and Severity Index 75 (EASI-75) and Investigator’s Global Assessment (IGA-0/1) response criteria over a 32-week period. For each treatment, the cost-per-­responder was computed by multiplying the treatment cost by the number needed to treat (NNT). Efficacy data were derived from an unanchored matching-adjusted indirect comparison (MAIC) utilizing patient-level data from ECZTRA-3 (tralokinumab) and aggregate data from LIBERTY AD CHRONOS (dupilumab). Treatment cost was defined as the drug cost of the biologic treatment with a duration corresponding to 32 weeks. TCS cost was not considered. Treatments were assumed to be administered every 2 weeks (Q2W). The costs were estimated based on Wholesale Acquisition Costs (WAC) from the US and ex-factory prices via the McKesson price list for Canada. All prices were converted to US dollars ($). Sensitivity analyses (SA) were conducted with every 4 week (Q4W) dosing beginning at week 16 for 10% and 20% of patients treated with tralokinumab.

Results

For the US, the average cost-per-responder was $62,714 (Q4W SA: 10%: $61,239; 20%: $59,763) for tralokinumab versus $63,993 for dupilumab considering the EASI-75 response criteria, while the average cost-per-responder was $82,419 (Q4W SA: 10%: $80,480; 20%: $78,450) for tralokinumab versus $118,835 for dupilumab considering the IGA 0/1 response criteria. For Canada, the average cost-per-responder was $22,846 (Q4W SA: 10%: $22,308; 20%: $21,771) for tralokinumab versus $26,475 for dupilumab considering the EASI-75 response criteria, while the average cost-per-responder was $30,024 (Q4W SA: 10%: $29,317; 20%: $28,611) for tralokinumab versus $49,165 for dupilumab considering the IGA 0/1 response criteria.

Conclusions

Assessing EASI-75 and IGA-0/1 response criteria at 32 weeks, this analysis indicates that tralokinumab in combination with TCS is associated with lower costs-per-responder compared with dupilumab in combination with TCS in the treatment of moderate-to-severe AD in the US and Canada.
Human papillomavirus infection and cardiovascular mortality: a cohort study
Authors: Cheong Hae Suk , Chang Yoosoo , Kim Yejin , Kwon Min-Jung , Cho Yoosun , Kim Bomi , Joo Eun-Jeong , Bae Young Ho , Kim Chanmin , Ryu Seungho
Published: February 2024

Background and Aims

High-risk human papillomavirus (HR-HPV) infection—a well-established risk factor for cervical cancer—has associations with cardiovascular disease (CVD). However, its relationship with CVD mortality remains uncertain. This study examined the associations between HR-HPV infection and CVD mortality.

Methods

As part of a health examination, 163 250 CVD-free Korean women (mean age: 40.2 years) underwent HR-HPV screening and were tracked for up to 17 years (median: 8.6 years). National death records identified the CVD mortality cases. Hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD mortality were estimated using Cox proportional hazard regression analyses.

Results

During 1 380 953 person-years of follow-up, 134 CVD deaths occurred, with a mortality rate of 9.1 per 105 person-years for HR-HPV(−) women and 14.9 per 105 person-years for HR-HPV(+) women. After adjustment for traditional CVD risk factors and confounders, the HRs (95% CI) for atherosclerotic CVD (ASCVD), ischaemic heart disease (IHD), and stroke mortality in women with HR-HPV infection compared with those without infection were 3.91 (1.85–8.26), 3.74 (1.53–9.14), and 5.86 (0.86–40.11), respectively. The association between HR-HPV infection and ASCVD mortality was stronger in women with obesity than in those without (P for interaction = .006), with corresponding HRs (95% CI) of 4.81 (1.55–14.93) for obese women and 2.86 (1.04–7.88) for non-obese women.

Conclusions

In this cohort study of young and middle-aged Korean women, at low risks for CVD mortality, those with HR-HPV infection had higher death rates from CVD, specifically ASCVD and IHD, with a more pronounced trend in obese individuals.
New Genomic Techniques applied to food cultures: a powerful contribution to innovative, safe, and sustainable food products
Authors: Dal Bello Fabio , Bocquet Laetitia , Bru Audrey , Laulund Svend , Machielsen Ronnie , Raneri Matteo , Sewalt Vincent , van Peij Noël , Ville Patrice , Volonté Federica , White Yolanda , Rusek Jakub
Published: February 2024

Nontransgenic New Genomic Techniques (NGTs) have emerged as a promising tool for food industries, allowing food cultures to contribute to an innovative, safe, and more sustainable food system. NGTs have the potential to be applied to microorganisms, delivering on challenging performance traits like texture, flavour, and an increase of nutritional value. This paper brings insights on how nontransgenic NGTs applied to food cultures could be beneficial to the sector, enabling food industries to generate innovative, safe, and sustainable products for European consumers. Microorganisms derived from NGTs have the potentials of becoming an important contribution to achieve the ambitious targets set by the European ‘Green Deal’ and ‘Farm to Fork’ policies. To encourage the development of NGT-derived microorganisms, the current EU regulatory framework should be adapted. These technologies allow the introduction of a precise, minimal DNA modification in microbial genomes resulting in optimized products carrying features that could also be achieved by spontaneous natural genetic evolution. The possibility to use NGTs as a tool to improve food safety, sustainability, and quality is the bottleneck in food culture developments, as it currently relies on lengthy natural evolution strategies or on untargeted random mutagenesis.
Peacekeeping armies: how the politics of peace operations shape military organizations
Authors: Wilén Nina , Williams Paul D
Published: February 2024

What is a ‘peacekeeping army’? Why do some states develop them? And what influence do they have on military organizations, their soldiers and the practices of peacekeeping more broadly? This article provides the first attempt to theorize this concept and illustrate its utility with reference to specific country examples. We develop the concept by drawing on a comparative analysis of troop contributions to peace operations over time, an examination of national security documents and institutional military reforms. Specifically, we define a ‘peacekeeping army’ as one which has undertaken institutional reforms to regularly perform the military functions of peacekeeping at a relatively large scale compared to the size of its active force and has prioritized international peacekeeping as one of its top-tier priorities. We find that political, economic and institutional motives for establishing a ‘peacekeeping army’ are more important than normative and security factors. Once established, a ‘peacekeeping army’ generates significant, and diverse effects on the soldiers, the military organization, the government and potentially the practices of peacekeeping more broadly. The conclusion summarizes our main findings and identifies implications for policy.
Consideration of within-patient diversity highlights transmission pathways and antimicrobial resistance gene variability in vancomycin-resistant Enterococcus faecium
Authors: McHugh Martin P , Pettigrew Kerry A , Taori Surabhi , Evans Thomas J , Leanord Alistair , Gillespie Stephen H , Templeton Kate E , Holden Matthew T G
Published: February 2024

Background

WGS is increasingly being applied to healthcare-associated vancomycin-resistant Enterococcus faecium (VREfm) outbreaks. Within-patient diversity could complicate transmission resolution if single colonies are sequenced from identified cases.

Objectives

Determine the impact of within-patient diversity on transmission resolution of VREfm.

Materials and methods

Fourteen colonies were collected from VREfm positive rectal screens, single colonies were collected from clinical samples and Illumina WGS was performed. Two isolates were selected for Oxford Nanopore sequencing and hybrid genome assembly to generate lineage-specific reference genomes. Mapping to closely related references was used to identify genetic variations and closely related genomes. A transmission network was inferred for the entire genome set using Phyloscanner.

Results and discussion

In total, 229 isolates from 11 patients were sequenced. Carriage of two or three sequence types was detected in 27% of patients. Presence of antimicrobial resistance genes and plasmids was variable within genomes from the same patient and sequence type. We identified two dominant sequence types (ST80 and ST1424), with two putative transmission clusters of two patients within ST80, and a single cluster of six patients within ST1424. We found transmission resolution was impaired using fewer than 14 colonies.

Conclusions

Patients can carry multiple sequence types of VREfm, and even within related lineages the presence of mobile genetic elements and antimicrobial resistance genes can vary. VREfm within-patient diversity could be considered in future to aid accurate resolution of transmission networks.
Non-empty open intervals of computably enumerable sQ1-degrees
Authors: Omanadze Roland , Chitaia Irakli
Published: February 2024

We prove that if $A$, $B$ are noncomputable c.e. sets, $A<_{sQ_{1}}B$ and [($B$ is not simple and $A\oplus B\leq _{sQ_{1}}B$) or $B\equiv _{sQ_{1}}B\times \omega $], then there exist infinitely many pairwise $sQ_{1}$-incomparable c.e. sets $\{C_{i}\}_{i\in \omega }$ such that $A<_{sQ_{1}}C_{i}<_{sQ_{1}}B$, for all $i\in \omega $. We also show that there exist infinite collections of $sQ_{1}$-degrees $\{\boldsymbol {a_{i}}\}_{i\in \omega }$ and $\{\boldsymbol {b_{i}}\}_{i\in \omega }$ such that for every $i, j,$ (1) $\boldsymbol {a_{i}}<_{sQ_{1}}\boldsymbol {a_{i+1}}$, $\boldsymbol {b_{j+1}}<_{sQ_{1}}\boldsymbol {b_{j}}$ and $\boldsymbol {a_{i}}<_{sQ_{1}}\boldsymbol {b_{j}}$; (2) every c.e set in $\boldsymbol {a_{i}}$ is a maximal set; and (3) every c.e. set in $\boldsymbol {b_{j}}$ is a non-maximal hyperhypersimple set.

We prove that a noncomputable c.e. $sQ$-degree contains either only one or infinitely many c.e. $sQ_{1}$-degrees. The $sQ_{1}$-degrees of c.e. cylinders are dense upper semilattice.
Microscopic thymoma with a thymic cyst that enlarged over a 2-year period
Authors: Komatsu Hiroaki , Furukawa Nao , Kinoshita Hirotaka , Okabe Kazunori
Published: February 2024

An 81-year-old woman was referred to our hospital because of right lung cancer. She underwent right upper lobectomy. Pathological examination revealed stage 1A adenocarcinoma. Four months postoperatively, chest computed tomography showed a small nodule with a diameter of 6 mm at the anterior mediastinum. After 2 years, the nodule had increased to 13 mm. To confirm the diagnosis and treat the mediastinal tumor, we resected the tumor and surrounding thymic tissue by a left robotic thoracic approach, considering the adhesion in the right thoracic cavity after right pulmonary resection. The operating time was 43 min. The patient had a favorable postoperative course and was discharged 3 days after surgery. Pathological examination revealed microscopic thymoma with a diameter of 400 μm very close to a thymic cyst. Microscopic thymoma can occur around a thymic cyst without myasthenia gravis, and the thymic tissue around the anterior mediastinal cyst should be resected.
How do SGLT2 inhibitors protect the kidney? A mediation analysis of the EMPA-REG OUTCOME trial
Authors: Wanner Christoph , Nangaku Masaomi , Kraus Bettina J , Zinman Bernard , Mattheus Michaela , Hantel Stefan , Schumacher Martin , Ohneberg Kristin , Schmoor Claudia , Inzucchi Silvio E
Published: February 2024

Introduction

Mechanisms underlying kidney benefits with sodium-glucose cotransporter-2 (SGLT2) inhibition in heart failure and/or type 2 diabetes (T2D) with established cardiovascular disease are currently unclear.

Methods

We evaluated post hoc the factors mediating the effect of empagliflozin on a composite kidney outcome (first sustained estimated glomerular filtration rate ≥40% reduction from baseline, initiation of renal replacement therapy or death due to kidney disease) in EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients). Variables, calculated as change from baseline or updated mean, were evaluated as time-dependent covariates and using a landmark approach (at Week 12) in Cox regression analyses. In multivariable analyses, variables with the greatest mediating effect were added using a step-up procedure.

Results

In univariable time-dependent updated mean covariate analyses, the strongest mediator was hematocrit (99.5% mediation). Hemoglobin, uric acid and urine albumin-to-creatinine ratio mediated 79.4%, 33.2% and 31.0%, respectively. Multivariable analyses were not performed due to the very strong mediation effect of hematocrit. In univariable Week 12 landmark change from baseline analyses, the strongest mediators included hematocrit (40.7%), glycated hemoglobin (28.3%), systolic blood pressure (16.8%) and free fatty acids (16.5%), which yielded a combined mediation of 78.9% in multivariable analysis.

Conclusions

Changes in hematocrit and hemoglobin were the strongest mediators of empagliflozin's kidney benefits in EMPA-REG OUTCOME participants with T2D and cardiovascular disease.
L’accès à des services d’interprétation appropriés, essentiel pour la santé des enfants
Authors: Hui Charles
Published: February 2024

Puisque 20 % des Canadiens déclarent avoir une autre langue maternelle que le français ou l’anglais, il n’est pas rare que les professionnels de la santé et les patients maîtrisent des langues différentes. Lorsqu’un médecin et son patient ne peuvent pas communiquer correctement, ils courent le risque de mal se comprendre, ce qui peut se solder par de mauvais résultats cliniques et une réadmission hospitalière. Les services d’interprétation professionnels sont associés à une amélioration de la communication, de l’utilisation des soins, des résultats cliniques et de la satisfaction envers les soins. Il est démontré que le recours à des interprètes non formés ou improvisés, y compris les membres de la famille, accroît les erreurs d’omission, les substitutions, les modifications volontaires et les ajouts. Les enfants et les adolescents n’ont pas acquis une maturité développementale suffisante pour agir en qualité d’interprètes dans le milieu de la santé. Dans un tel contexte, ils sont mis dans une situation inappropriée avec laquelle il peut être difficile de composer et qui peut compromettre durablement à la fois leur propre santé mentale et leur relation avec les autres membres de la famille.
New sights in ectopic varices in portal hypertension
Authors: He K , Pang K , Yan X , Wang Q , Wu D
Published: February 2024

Ectopic varices and associated bleeding, although rare, pose a significant risk to patients with portal hypertension, carrying a relatively high mortality rate. These varices can occur in various anatomical regions, excluding the gastroesophageal region, which is typically associated with portal vein drainage. The limited data available in the literature, derived mostly from case reports and series, make the diagnosis and treatment of ectopic variceal bleeding particularly challenging. Furthermore, it is crucial to recognize that ectopic varices in different sites can exhibit variations in key decision-making factors such as aetiology and vascular anatomy, severity and bleeding risk and hepatic reserve. These factors significantly influence treatment strategies and underscore the importance of adopting individualized management approaches. Therefore, the objective of this review is to provide a comprehensive overview of the fundamental knowledge surrounding ectopic varices and to propose site-oriented, stepwise diagnosis and treatment algorithms for this complex clinical issue. A multidisciplinary treatment approach is strongly recommended in managing ectopic varices. In addition, to enhance clinical reference, we have included typical case reports of ectopic varices in various sites in our review, while being mindful of potential publication bias.
Circulating Tfh cells are differentially modified by abatacept or TNF blockers and predict treatment response in rheumatoid arthritis
Authors: Monjo-Henry Irene , Uyaguari Mariela , Nuño Laura , Nieto-Carvalhal Beatriz , Fernández-Fernández Elisa , Peiteado Diana , Villalba Alejandro , García-Carazo Sara , Balsa Alejandro , Miranda-Carús María-Eugenia
Published: February 2024

Objective

CD4+CXCR5+PD-1hi follicular helper T (Tfh) cells dwell in the germinal centres (GCs) of lymphoid organs and participate in RA pathogenesis. The frequency of their circulating counterparts (cTfh frequency) is expanded in RA and correlates with the pool of GC Tfh cells. Our objective was to study the effect of abatacept (ABT) or TNF blockers (TNFbs) on the cTfh frequency in RA.

Methods

Peripheral blood was drawn from seropositive, long-standing RA patients chronically receiving conventional synthetic DMARDs (csDMARDs; n = 45), TNFb (n = 59) or ABT (n = 34) and healthy controls (HCs; n = 137). Also, patients with an incomplete response to csDMARDs (n = 41) who initiated TNFb (n = 19) or ABT (n = 22) were studied at 0 and 12 months. The cTfh frequency was examined by cytometry.

Results

As compared with HCs, an increased cTfh frequency was seen in seropositive, long-standing RA patients chronically receiving csDMARDs or TNFb but not ABT. After changing from csDMARDs, the cTfh frequency did not vary in patients who were given TNFb but decreased to HC levels in those given ABT. In the ABT group, the baseline cTfh frequency was higher for patients who attained 12-month remission (12mr) vs those who remained active (12ma): 0 month cut-off for remission >0.38% [sensitivity 92%, specificity 90%, odds ratio (OR) 25.3]. Conversely, in the TNFb group, the baseline cTfh frequency was lower for 12mr vs 12ma: 0 month cut-off for non-remission >0.44% (sensitivity 67%, specificity 90%, OR 8.5).

Conclusion

ABT but not TNFb was able to curtail the cTfh frequency in RA. A higher baseline cTfh frequency predicts a good response to ABT but a poor response to TNFb.
Glutathione safeguards TET‐dependent DNA demethylation and is critical for the acquisition of totipotency and pluripotency during preimplantation development
Authors: Liu Juan , Chu Meiqiang , Zhang Jingyu , He Jiale , Yang Qianying , Tao Li , Wang Zhaochen , Yao Fusheng , Zhao Wei , Ouyang Si , Chen Lei , Zhang Shuai , Gao Shuai , Tian Jianhui , Ren Likun , An Lei
Published: February 2024

During early development, both genome‐wide epigenetic reprogramming and metabolic remodeling are hallmark changes of normal embryogenesis. However, little is known about their relationship and developmental functions during the preimplantation window, which is essential for the acquisition of totipotency and pluripotency. Herein, we reported that glutathione (GSH), a ubiquitous intracellular protective antioxidant that maintains mitochondrial function and redox homeostasis, plays a critical role in safeguarding postfertilization DNA demethylation and is essential for establishing developmental potential in preimplantation embryos. By profiling mitochondria‐related transcriptome that coupled with different pluripotency, we found GSH is a potential marker that is tightly correlated with full pluripotency, and its beneficial effect on prompting developmental potential was functionally conformed using in vitro fertilized mouse and bovine embryos as the model. Mechanistic study based on preimplantation embryos and embryonic stem cells further revealed that GSH prompts the acquisition of totipotency and pluripotency by facilitating ten‐eleven‐translocation (TET)‐dependent DNA demethylation, and ascorbic acid (AsA)‐GSH cycle is implicated in the process. In addition, we also reported that GSH serves as an oviductal paracrine factor that supports development potential of preimplantation embryos. Thus, our results not only advance the current knowledge of functional links between epigenetic reprogramming and metabolic remodeling during preimplantation development but also provided a promising approach for improving current in vitro culture system for assisted reproductive technology.
Functional recovery following traumatic brain injury in rats is enhanced by oral supplementation with bovine thymus extract
Authors: Surzenko Natalia , Bastidas Johana , Reid Robert W. , Curaba Julien , Zhang Wei , Bostan Hamed , Wilson Mickey , Dominique Ashley , Roberson Julia , Ignacio Glicerio , Komarnytsky Slavko , Sanders Alexa , Lambirth Kevin , Brouwer Cory R. , El‐Khodor Bassem F.
Published: February 2024

Traumatic brain injury (TBI) is one of the leading causes of death worldwide. There are currently no effective treatments for TBI, and trauma survivors suffer from a variety of long‐lasting health consequences. With nutritional support recently emerging as a vital step in improving TBI patients' outcomes, we sought to evaluate the potential therapeutic benefits of nutritional supplements derived from bovine thymus gland, which can deliver a variety of nutrients and bioactive molecules. In a rat model of controlled cortical impact (CCI), we determined that animals supplemented with a nuclear fraction of bovine thymus (TNF) display greatly improved performance on beam balance and spatial memory tests following CCI. Using RNA‐Seq, we identified an array of signaling pathways that are modulated by TNF supplementation in rat hippocampus, including those involved in the process of autophagy. We further show that bovine thymus‐derived extracts contain antigens found in neural tissues and that supplementation of rats with thymus extracts induces production of serum IgG antibodies against neuronal and glial antigens, which may explain the enhanced animal recovery following CCI through possible oral tolerance mechanism. Collectively, our data demonstrate, for the first time, the potency of a nutritional supplement containing nuclear fraction of bovine thymus in enhancing the functional recovery from TBI.
Evaluating the Efficacy of Interatrial Shunt Devices in Heart Failure With Preserved Ejection Fraction: A Systematic Review and Meta-Analysis
Authors: Abouzid Mohamed Riad , Ali Karim
Published: February 2024

Heart failure with preserved ejection fraction (HFpEF) is a prevalent and challenging condition with limited therapeutic options. This meta-analysis aims to assess the feasibility and effectiveness of interatrial shunt devices (IASD) in the treatment of HFpEF, focusing on key hemodynamic parameters and clinical outcomes. Six clinical trials, encompassing 324 patients, were included in this analysis. The results showed a significant reduction in pulmonary capillary wedge pressure (PCWP) at rest after IASD implantation, with a mean difference of 1.55 mm Hg. PCWP during exercise also exhibited a decrease, indicating improved exercise tolerance. However, there was an increase in mean right atrial pressure following IASD implantation. These findings suggest that IASD implementation can effectively lower left atrial pressure, a critical target in HFpEF management. This results in substantial clinical improvements, including enhanced New York Heart Association class, quality of life, and 6-minute walk distance. Echocardiographic assessments revealed a reduction in left ventricular end-diastolic volume index and stable right ventricular changes. The meta-analysis underscores the potential benefits of IASD in ameliorating the symptoms and clinical outcomes of HFpEF patients. The increase in mean right atrial pressure warrants further investigation into its effects on right heart function. Additionally, this analysis emphasizes the need for larger, randomized clinical trials to validate these findings and determine optimal patient selection criteria. IASD implantation holds promise as a therapeutic option for HFpEF, offering the potential to improve the quality of life and functional status of affected patients. However, further research is imperative to confirm its efficacy relative to existing treatments and to address concerns regarding its impact on right heart function. This meta-analysis contributes to a deeper understanding of IASD’s role in HFpEF management.
Not all platelet-rich plasma are created equal
Authors: Cantero Manuel Muñoz
Published: February 2024

Purpose of review

This review aims to elucidate potential variations in clinical outcomes resulting from the use of different types of platelet-rich plasma (PRPs) in reproductive medicine. It seeks to explore the reasons behind the diverse results reported in various studies and assess the general features distinguishing different PRP formulations.

Recent findings

PRPs have found applications across diverse medical fields, generating controversy due to the variability in outcomes. The field of reproductive medicine, despite its limited published studies, is encountering a similar challenge as it integrates these treatments.

The multitude of PRP product brands in the market, coupled with ‘home-made’ PRPs, poses a significant barrier to establishing a common protocol for the preparation of standardized PRP products. This impediment hinders widespread adoption by clinicians, particularly in endometrial or ovarian treatments. Drawing from evidence in other medical disciplines, this review endeavors to compile essential characteristics that PRPs must possess, aiming to mitigate the impact of variables affecting results in forthcoming studies.
Single versus multiple arterial coronary artery bypass grafting in men and women: Results from Polish National Registry of Cardiac Surgery Procedures
Authors: Aboul-Hassan Sleiman Sebastian , Hirnle Grzegorz , Perek Bartlomiej , Jemielity Marek , Hirnle Tomasz , Brykczynski Miroslaw , Deja Marek , Rogowski Jan , Cisowski Marek , Krejca Michal , Anisimowicz Lech , Widenka Kazimierz , Gerber Witold , Pacholewicz Jerzy , Bugajski Pawel , Stepinski Piotr , Maruszewski Bohdan J , Cichon Romuald , Hrapkowicz Tomasz ,   KROK Investigators
Published: February 2024

Background:

The objective of this multicenter study aimed to investigate the impact of sex on long-term survival among patients with multivessel coronary artery disease undergoing coronary artery bypass grafting(CABG) using multiple arterial grafting (MAG) or a single artery with saphenous vein grafts (SAG).

Materials and methods:

Data were obtained from the Polish National Registry of Cardiac Surgery Procedures database. This study included 81,136 patients who underwent CABG for multivessel disease between January 2012 and December 2020 (22.9% were women and 77.1% were men). MAG was performed in 8.3% and 11.7% of female and male patients, respectively. A 1:1 propensity score (PS)-matching was performed. Long-term mortality was compared between matched groups of men and women. Subgroup analyses of patients aged <70 and ≥70 years, with an ejection fraction (EF) >40% and ≤40%, and with and without diabetes, obesity, peripheral artery disease (PAD), or chronic lung disease (CLD) were performed separately in women and men.

Results:

MAG was associated with lower long-term mortality than SAG in 1,528 PS-matched female pairs (hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.59–0.92; P = 0.007) and 7,283 PS-matched male pairs (HR: 0.80; 95% CI: 0.72–0.88; P <0.001). Subgroup analyses confirmed the results among female patients aged <70 years, with diabetes and EF >40%, and without PAD or CLD, and of male patients aged <70 and ≥70 years; with EF >40%; with or without diabetes, obesity, or PAD; and without CLD.

Conclusions:

In patients undergoing CABG, MAG was associated with significantly improved survival in both sexes. The long-term benefits of MAG observed across subgroups of men and women support the consideration of a multi-arterial revascularization strategy for a broader spectrum of patients.
Reliability of the Montreal Cognitive Assessment in people with stroke
Authors: Lau Hiu-ying , Lin Yi-hung , Lin Keh-chung , Li Yi-chun , Yao Grace , Lin Chih-yu , Wu Yi-hsuan
Published: February 2024

This study examined the relative and absolute reliability of the Taiwanese version of the MoCA (MoCA-T) in people with stroke. The study recruited 114 individuals who were at least 3 months after the onset of a first-ever unilateral stroke. The MoCA-T was administered twice, at a 6-week interval, to all participants. The relative reliability was assessed using the intraclass correlation coefficient (ICC), and the absolute reliability was assessed using standard error of measurement (SEM), the smallest real difference (SRD), the SRD percentage, and the Bland-Altman method. The ICC analysis showed the MoCA-T was highly reliable (ICC = 0.85). The absolute reliability was between an acceptable and excellent level, where the SEM and the SRD at the 95% confidence interval were 1.38 and 3.83, respectively. The Bland-Altman analyses showed no systematic bias between repeated measurements. The range of the 95% limits of agreement was narrow, indicating a high level of stability over time. These findings suggest that the MoCA-T has high agreement between repeated measurements without systematic bias. The threshold to detect real change stands between an acceptable and excellent level. The MoCA-T is a reliable tool for cognitive screening in stroke rehabilitation.
Hereditary spherocytosis in a young female in Eastern Nepal: a case report
Authors: Rayamajhi Anusha , Shrestha Manisha , K.C. Priyanka , Maskey Robin
Published: February 2024

Introduction and importance:

Hereditary spherocytosis (HS), a rare familial extravascular haemolytic disorder, typically follows an autosomal dominant inheritance pattern with variable expressivity. Despite its classical presentation of anaemia, jaundice, and splenomegaly, HS is infrequently reported among individuals of Asian descent, contributing to its under diagnosis or delayed diagnosis. The primary objective of this case report is to underscore the pivotal role of the osmotic fragility test in diagnosing HS, emphasizing the importance of accurate and timely identification for effective clinical management and improved patient outcomes.

Case presentation:

The patient, without known prior co-morbidities, presented with recurrent abdominal distension, early satiety, and easy fatigability persisting for 6 years. Physical examination revealed icterus, gnathopathy, left hypochondrium tenderness, and palpable splenomegaly. The osmotic fragility of red cells was significantly elevated. The patient underwent optimization before splenectomy, receiving immunization against encapsulated bacteria. Packed red blood cell transfusions were administered to achieve optimal haemoglobin levels. Follow-up showed symptom relief, significantly improving the patient’s quality of life.

Clinical discussion:

This case underscores the challenges of delayed HS diagnosis, with the patient enduring symptoms for years before seeking appropriate medical attention. Overlooking the simplicity and cost-effectiveness of an osmotic fragility test prolonged the diagnostic journey, emphasizing the impact on overall well-being.

Conclusion:

HS remains underdiagnosed, especially in our regions. The osmotic fragility test emerges as an economical diagnostic tool in resource-limited settings, particularly when spherocytosis is absent in the peripheral blood smears. Its inclusion in diagnostic protocols can expedite accurate HS identification and enhance patient outcomes.
Safety, pharmacokinetics, and potential neurological interactions of ivermectin, tafenoquine and chloroquine in Rhesus Macaques
Authors: Vanachayangkul Pattaraporn , Kodchakorn Chanikarn , Ta-aksorn Winita , Im-erbsin Rawiwan , Tungtaeng Anchalee , Tipthara Phornpimon , Tarning Joel , Lugo-Roman Luis A. , Wojnarski Mariusz , Vesely Brian A. , Kobylinski Kevin C.
Published: February 2024

Ivermectin could be used for malaria control as treated persons are lethal to blood feedingAnopheles, resulting in reduced transmission. Tafenoquine could be used in combination with ivermectin to clear persons of liver stagePlasmodium vivaxreservoir and as a prophylactic in high-risk populations. The safety of ivermectin and tafenoquine has not been evaluated. As earlier forms of 8-aminoquinolones were neurotoxic, and ivermectin is an inhibitor of the P-glycoprotein blood brain barrier transporter, there is concern that co-administration could be neurotoxic. The safety and pharmacokinetic interaction of tafenoquine, ivermectin, and chloroquine was evaluated in Rhesus macaques. No clinical, biochemistry, or hematological outcomes of concern were observed. The Cambridge Neuropsychological Test Automated Battery was employed to assess potential neurological deficits following drug administration. Some impairment was observed with tafenoquine alone and in the same monkeys with subsequent co-administrations. Co-administration of chloroquine and tafenoquine resulted in increased plasma exposure to tafenoquine. Urine concentrations of the 5,6 orthoquinone TQ metabolite were increased with co-administration of tafenoquine with ivermectin. There was an increase in ivermectin plasma exposure when co-administered with chloroquine. No interaction of tafenoquine on ivermectin was observedin vitro. Chloroquine and trace levels of ivermectin, but not tafenoquine, were observed in the cerebrospinal fluid. The 3”-O-demethyl ivermectin metabolite was observed in macaque plasma but not in urine or cerebrospinal fluid. Overall, the combination of ivermectin, tafenoquine, and chloroquine did not have clinical, neurological, or pharmacological interactions of concern in macaques, therefore this combination could be considered for evaluation in human trials.
Protocol for Cerebellar Stimulation for Aphasia Rehabilitation (CeSAR): A randomized, double-blind, sham-controlled trial
Authors: Lammers Becky , Sydnor Myra J. , Cust Sarah , Kim Ji Hyun , Yenokyan Gayane , Hillis Argye E. , Sebastian Rajani
Published: February 2024

In this randomized, double-blind, sham-controlled trial of Cerebellar Stimulation for Aphasia Rehabilitation (CeSAR), we will determine the effectiveness of cathodal tDCS (transcranial direct current stimulation) to the right cerebellum for the treatment of chronic aphasia (>6 months post stroke). We will test the hypothesis that cerebellar tDCS in combination with an evidenced-based anomia treatment (semantic feature analysis, SFA) will be associated with greater improvement in naming untrained pictures (as measured by the change in Philadelphia Picture Naming Test), 1-week post treatment, compared to sham plus SFA. We will also evaluate the effects of cerebellar tDCS on naming trained items as well as the effects on functional communication, content, efficiency, and word-retrieval of picture description, and quality of life. Finally, we will identify imaging and linguistic biomarkers to determine the characteristics of stroke patients that benefit from cerebellar tDCS and SFA treatment. We expect to enroll 60 participants over five years. Participants will receive 15, 25-minute sessions of cerebellar tDCS (3-5 sessions per week) or sham tDCS combined with 1 hour of SFA treatment. Participants will be evaluated prior to the start of treatment, one-week post-treatment, 1-, 3-, and 6-months post treatment on primary and secondary outcome variables. The long-term aim of this study is to provide the basis for a Phase III randomized controlled trial of cerebellar tDCS vs sham with concurrent language therapy for treatment of chronic aphasia.

Trial registration

The trial is registered withClinicalTrials.govNCT05093673.
Human Motor Cortex Encodes Complex Handwriting Through a Sequence of Primitive Neural States
Authors: Qi Yu , Zhu Xinyun , Xiong Xinzhu , Yang Xiaomeng , Ding Nai , Wu Hemmings , Xu Kedi , Zhu Junming , Zhang Jianmin , Wang Yueming
Published: February 2024

How the human motor cortex (MC) orchestrates sophisticated fine movements such as handwriting remains a puzzle1–3. Here, we investigate this question through Utah array recordings from human MC hand knob, during imagined handwriting of Chinese characters (306 characters tested, 6.3 ± 2.0 strokes per character). We find MC programs the writing of complicated characters by sequencing a small set of primitive states: The directional tuning of motor neurons remains stable within each primitive state but strongly varies across states. Furthermore, the occurrence of a primitive state is encoded by a separate set of neurons not directly involved in movement control. By automatically identifying the primitive states and corresponding neuronal tuning properties, we can reconstruct a recognizable writing trajectory for each character (84% improvement in reconstruction accuracy compared with baseline). Our findings unveil that skilled, sophisticated movements are decomposed into a sequence of primitive movements that are programmed through state-specific neural configurations, and this hierarchical control mechanism sheds new light on the design of high-performance brain-computer interfaces.
The Guinea Pig: A New Model for Human Preimplantation Development
Authors: Canizo Jesica Romina , Zhao Cheng , Petropoulos Sophie
Published: February 2024

Preimplantation development is an important window of human embryogenesis. During this time, the initial lineages are formed which largely govern embryo competence, implantation, and ultimately the developmental potential of the fetus. Ethical constraints and limitations surrounding human embryos research often necessitates the use of a model system. We now identify the guinea pig as a promising small animal model, which closely recapitulates early human embryogenesis in terms of the timing of compaction, early-, mid-, and late-blastocyst formation and implantation. We also observe conserved spatio-temporal expression of key lineage markers, roles of both Hippo and MEK-ERK signaling and an incomplete X-Chromosome inactivation. Further, our multi-species analysis highlights the spatio-temporal expression of conserved and divergent genes during preimplantation development. The guinea pig serves as an exciting new model which will enhance developmental and pluripotency research and can be leveraged to better understand the longer term impact of early exposures on offspring outcomes.
Neurometabolite differences in Autism as assessed with Magnetic Resonance Spectroscopy: a systematic review and meta-analysis
Authors: Thomson Alice R. , Pasanta Duanghathai , Arichi Tomoki , Puts Nicolaas A.
Published: February 2024

1H-Magnetic Resonance Spectroscopy (MRS)is a non-invasive technique that can be used to quantify the concentrations of metabolites in the brain in vivo. MRS findings in the context of autism are inconsistent and conflicting. We performed asystematic review and meta-analysisof MRS studies observing glutamate and gamma-aminobutyric acid (GABA), as well as brain metabolites involved in energy metabolism (glutamine, creatine), neural integrity (e.g. n-acetyl aspartate (NAA), choline, myo-inositol) and neuro-inflammation (glutathione) in autism cohorts. Data were extracted and grouped by metabolite, brain region and several other factors before calculation of standardised effect sizes. Overall, we find significantly lower concentrations of GABA and NAA in autism, indicative of disruptions to the balance between excitation/inhibition within brain circuits, as well as neural integrity. Further analysis found these alterations are most pronounced in autistic children and in limbic brain regions relevant to autism phenotypes. Additionally, we show how study outcome varies due to demographic and methodological factors (e.g. medication use), emphasising the importance of conforming with consensus study designs and transparent reporting.

Highlights

We performed a meta-analysis ofMagnetic Resonance Spectroscopyfindings in autism.

We find significantly lower concentrations of GABA and NAA in children with autism.

These alterations were most pronounced in limbic brain regions.

Demographic factors (including sex) contribute to MRS study outcome variation.
Impact of the noise knowledge uncertainty for the science exploitation of cosmological and astrophysical stochastic gravitational wave background with LISA
Authors: Muratore Martina , Gair Jonathan , Speri Lorenzo
Published: February 2024

This paper investigates the impact of a lack of knowledge of instrumental noise on the characterization of stochastic gravitational wave backgrounds with the Laser Interferometer Space Antenna (LISA). We focus on constraints on modeled backgrounds that represent the possible backgrounds from the mergers of binary black holes of stellar origin, from primordial black hole generation, from nonstandard inflation, and from sound wave production during cosmic fluid phase transitions. We use splines to model generic, slowly varying, uncertainties in the auto- and cross-spectral densities of the LISA time delay interferometry channels. We find that allowing for noise knowledge uncertainty in this way leads to 1–2 orders of magnitude degradation in our ability to constrain stochastic backgrounds and a corresponding increase in the background energy density required for a confident detection. We also find that, to avoid this degradation, the LISA noise would have to be known at the subpercent level, which is unlikely to be achievable in practice.

Published by the American Physical Society
2024
Crystal structure and Hirshfeld surface analysis of a salt of antineoplastic kinase inhibitor vandetanib
Authors: Yang Haiwu , Liang Minyi , Tian Fang
Published: February 2024

A salt of vandetanib, namely, 4-({4-[(4-bromo-2-fluorophenyl)amino]-6-methoxyquinazolin-7-yl}methoxy)-1-methylpiperazin-1-ium 2-(butylamino)-4-phenoxy-6-sulfamoylbenzoate acetonitrile monosolvate, C22H25BrFN4O2
+·C17H19N2O5S−·C2H3N, composed of kinase inhibitor vandetanib and sulfamyl diuretic bumetanide in a 1:1 molar ratio, is reported. There is proton transfer between the piperidine ring of vandetanib and the carboxyl group of bumetanide to form the salt. In the vandetanib cation, the arene and pyrimidine rings are not coplanar, their planes subtending a dihedral angle of 60.47 (14)°. The roles of the intermolecular interactions in the crystal packing were clarified using Hirshfeld surface analysis, and two-dimensional fingerprint plots indicate that the most important contributions to the crystal packing are from H...H (40.5%), O...H/H...C (20.7%), C...H/ H...C (18.8%) and N...C/C...N (9.0%) contacts.
Intraindividual variability and stability in rumination: examining the effect of rumination on negative affect across domains
Authors: Shi Xiaolin (Crystal) , Huang Xiaoting , Guo Zimeng , Gordon Susan Elizabeth
Published: February 2024

Purpose

The purpose of this paper is to investigate the influence of employees’ trait rumination on the variability of their state rumination and the continuing influence on their negative affect at home.

Design/methodology/approach

A time-lagged experience sampling method was used for the data collection from full-time employees in the hotel industry. The hypotheses were tested with multilevel modeling using a random coefficient modeling approach.

Findings

Hotel employees who are high in trait rumination generally show high levels of state rumination and greater within-person variability in state rumination over time. Additionally, the negative effects of workplace state rumination can last until employees come home and the next day before going to work. Furthermore, employees who are high in trait rumination are more likely to be influenced by state rumination, as they experience more negative affect after arriving home.

Practical implications

Rumination has been shown to decrease hotel employee overall well-being. The findings of this study provide suggestions for remedial measures that can be taken by hotel organizations to help employees address ruminative thinking.

Originality/value

Drawing on response styles and work/family border theories, this study contributes to the rumination literature by considering both trait rumination and state rumination in a broader context. For a comprehensive understanding of the dynamic temporal characteristics of state rumination, this study considers the net intraindividual variability of state rumination as the outcome of trait rumination.
Festivalization of business events: exploring a new strategy for designing more engaging conference experiences
Authors: Jung Shinyong , Fan Alei , Lehto Xinran , Shin Hhye Won
Published: February 2024

Purpose

This study aims to explore a potential conference experience design strategy, namely, festivalization. It investigates the potential festivalization effects on conference attendees in two formats of business conferences: virtual and in-person.

Design/methodology/approach

A series of two scenario-based experimental studies were conducted. A series of one-way analysis of covariance and PROCESS procedures (Model 6) were performed for data analysis.

Findings

The inclusion of festivalization elements significantly enhances positive responses of attendees, especially for in-person conferences. This effect is further explained by a serial mediation effect, where enhanced perceived values and conference engagement play key roles in improving attendees’ conference experience.

Practical implications

By incorporating festivalization elements, conference organizers can create a more engaging and satisfying event experience for attendees. This can lead to greater satisfaction, positive word-of-mouth and increased registrations.

Originality/value

This study represents a pioneering effort in revealing the underlining mechanisms that explain how festivalization affects attendee engagement and subsequent behaviors in business event management in both face-to-face and virtual settings.