bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolutionary allometry of the canid baculum (Carnivora: Mammalia)
Authors: de Latorre Daniel Varajão , Marshall Charles R 
Published: June 2024

Abstract
While the mammalian baculum shows enormous morphological variability, the baculum of canids is highly conserved, with most variation restricted to size. Here, we explore the allometric relationship between baculum length and body size in extant and extinct canids. Examination of 26 species in the extant subfamily Caninae using standard linear regression revealed isometry. Phylogenetic regression also revealed an allometric slope indistinguishable from isometry. This pattern differs from the substantially negative slopes seen in other mammalian clades. The strength of the canid allometric relationship (r2) is also greater than in other clades, suggesting functional constraints on their baculum size. The constraints may be related to the copulatory tie that is characteristic of canids, and/or their monogamous mating system. Complete bacula are known from just four extinct species. The two complete bacula from the extinct subfamily Borophaginae (Aelurodon ferox and Aelurodon stirtoni) fall on the same allometric relationship as the living canids. However, the baculum of the extinct dire wolf (Aenocyon dirus, from the extant subfamily Caninae) and from the extinct subfamily Herperocyoninae, Hesperocyon gregarius, are significantly longer than expected based on their body sizes, suggesting that they may have had a different reproductive biology from that of extant canines.
The role of OX40 ligand/OX40 axis signalling in atopic dermatitis
Authors: Guttman-Yassky Emma , Croft Michael , Geng Bob , Rynkiewicz Natalie , Lucchesi Davide , Peakman Mark , van Krinks Cassandra , Valdecantos Wendell , Xing Heming , Weidinger Stephan 
Published: June 2024

Lay Summary
Atopic dermatitis (AD) (also known as atopic eczema) is a common skin disease caused by inflammation, and affects 2–3 of every 10 people worldwide. AD affects people of all ages and can cause a range of symptoms, including dry thickened skin, itchiness, rashes and pain. Despite the recent addition of new targeted treatment options, there is still a need for new treatments for people with moderate-to-severe AD.
New drugs are being studied that target two important signalling molecules in the immune system, called OX40 ligand (OX40L) and OX40. OX40L and OX40 bind together to continue the cycle of immune system activation, leading to increasing symptoms of AD. Blocking the OX40L and OX40 interaction may ease or stop symptoms of AD.
This review outlines what is currently known about the causes of AD, including the role played by the immune system and specifically the role of OX40L and OX40. We also highlight the development of new treatments that target the OX40L and OX40 interaction to treat AD, and suggest what the future may hold for managing AD.
Nociceptors are functionally male or female: from mouse to monkey to man
Authors: Stratton Harrison , Lee Grace , Dolatyari Mahdi , Ghetti Andre , Cotta Tamara , Mitchell Stefanie , Yue Xu , Ibrahim Mohab , Dumaire Nicolas , Salih Lyuba , Moutal Aubin , François-Moutal Liberty , Martin Laurent , Navratilova Edita , Porreca Frank 
Published: June 2024

Abstract
The prevalence of many pain conditions often differs between sexes. In addition to such quantitative distinctions, sexual dimorphism may also be qualitative reflecting differences in mechanisms that promote pain in men and women. A major factor that influences the likelihood of pain perception is the threshold for activation of nociceptors. Peripheral nociceptor sensitization has been demonstrated to be clinically relevant in many pain conditions. Whether peripheral nociceptor sensitization can occur in a sexually dimorphic fashion, however, has not been extensively studied. To address this fundamental knowledge gap, we used patch clamp electrophysiology to evaluate the excitability of dorsal root ganglion neurons from male or female rodents, non-human primates, and humans following exposure to putative sensitizing agents.
Previous studies from our laboratory, and others, have shown that prolactin promotes female-selective pain responses in rodents. Consistent with these observations, dorsal root ganglion neurons from female, but not male, mice were selectively sensitized by exposure to prolactin. The sensitizing action of prolactin was also confirmed in dorsal root ganglion neurons from a female macaque monkey. Critically, neurons recovered from female, but not male, human donors were also selectively sensitized by prolactin. In the course of studies of sleep and pain, we unexpectedly observed that an orexin antagonist could normalize pain responses in male animals. We found that orexin B produced sensitization of male, but not female, mouse, macaque, and human dorsal root ganglion neurons. Consistent with functional responses, increased prolactin receptor and orexin receptor 2 expression was observed in female and male mouse dorsal root ganglia, respectively. Immunohistochemical interrogation of cultured human sensory neurons and whole dorsal root ganglia also suggested increased prolactin receptor expression in females and orexin receptor 2 expression in males.
These data reveal a functional double dissociation of nociceptor sensitization by sex, which is conserved across species and is likely directly relevant to human pain conditions. To our knowledge, this is the first demonstration of functional sexual dimorphism in human sensory neurons. Patient sex is currently not a common consideration for the choice of pain therapy. Precision medicine, based on patient sex could improve therapeutic outcomes by selectively targeting mechanisms promoting pain in women or men. Additional implications of these findings are that the design of clinical trials for pain therapies should consider the proportions of male or female patients enrolled. Lastly, re-examination of selected past failed clinical trials with subgroup analysis by sex may be warranted.
Colorectal cancer cells with high metastatic potential drive metastasis by transmitting exosomal miR-20a-3p through modulating NF1/MAPK pathway
Authors: Liang Yahang , Li Junyu , Li Tao , Li Mingming , Liao Hualin , Liu Yang , Yao Yao , Yang Lingling , Lei Xiong 
Published: June 2024

Abstract
Cancer cells exhibit heterogeneous metastatic potential, and high metastatic (HM) subclones can enhance the metastatic potential of low metastatic subclones by transmitting some factors. Exosomal miRNAs play a pivotal role in the crosstalk of heterogeneous metastatic subclones. This study discovered that miR-20a-3p was upregulated in colorectal adenocarcinoma (CRA), correlated with metastasis, and potentially served as a prognostic indicator for CRA. miR-20a-3p could promote the proliferation, migration, and invasion of CRA cells. Interestingly, HM CRA cells could promote malignant phenotypes of low metastatic CRA cells by transmitting exosomal miR-20a-3p. Mechanically, miR-20a-3p could inhibit neurofibromin 1(NF1), thereby activate the rat sarcoma viral oncogene (RAS)-mediated mitogen-activated protein kinases (MAPK) signaling pathway to drive the metastasis of CRA. In summary, our study provided evidence that colorectal cancer cells with HM potential drive metastasis by transmitting exosomal miR-20a-3p through modulating the NF1/MAPK pathway.
Visible-light-catalyzed synthesis of amino alcohols from N,N-dimethylaniline and aryl aldehyde
Authors: Jin Jia-Hui , Ma Yi-Jian , Yin Yu-Yun , Zhao Fu-Gang , Shen Cheng-Shuo , Xu Cheng-Miao , Shen Yong-Miao 
Published: June 2024

Abstract
Herein, we describe a direct radical addition reaction of aryl aldehyde and N, N-dimethylaniline using iridium complex as photocatalyst to form amino alcohols under mild conditions, offering a convenient and sustainable methodology. The reaction could be easily scaled up through continuous flow reaction with high yield. A series of amino alcohol compounds were synthesized with iridium complex as photocatalyst. The reaction could be scaled up with continuous flow reaction. The reaction mechanism has been investigated with the aid of density functional theory (DFT) calculations.
The impact of dialysate flow rate on haemodialysis adequacy: a systematic review and meta-analysis
Authors: Iman Yasmin , Bamforth Ryan , Ewhrudjakpor Ruth , Komenda Paul , Gorbe Kelley , Whitlock Reid , Bohm Clara , Tangri Navdeep , Collister David 
Published: June 2024

ABSTRACT

Background
Patients with kidney failure treated with maintenance haemodialysis (HD) require appropriate small molecule clearance. Historically, a component of measuring ‘dialysis adequacy’ has been quantified using urea kinetic modelling that is dependent on the HD prescription. However, the impact of dialysate flow rate on urea clearance remains poorly described in vivo and its influence on other patient-important outcomes of adequacy is uncertain.

Methods
We searched Embase, MEDLINE and the Cochrane Library from inception until April 2022 for randomized controlled trials and observational trials comparing a higher dialysate flow rate (800 ml/min) and lower dialysate flow rate (300 ml/min) with a standard dialysis flow rate (500 ml/min) in adults (age ≥18 years) treated with maintenance HD (&gt;90 consecutive days). We conducted a random effects meta-analysis to estimate the pooled mean difference in dialysis adequacy as measured by Kt/V or urea reduction ratio (URR).

Results
A total of 3118 studies were identified. Of those, nine met eligibility criteria and four were included in the meta-analysis. A higher dialysate flow rate (800 ml/min) increased single-pool Kt/V by 0.08 [95% confidence interval (CI) 0.05–0.10, P &lt; .00001] and URR by 3.38 (95% CI 1.97–4.78, P &lt; .00001) compared with a dialysate flow rate of 500 ml/min. Clinically relevant outcomes including symptoms, cognition, physical function and mortality were lacking and studies were generally at a moderate risk of bias due to issues with randomization sequence generation, allocation concealment and blinding.

Conclusion
A higher dialysate flow increased urea-based markers of dialysis adequacy. Additional high-quality research is needed to determine the clinical, economic and environmental impacts of higher dialysate flow rates.
Sex inequalities in cardiovascular risk prediction
Authors: Elliott Joshua , Bodinier Barbara , Whitaker Matthew , Wada Rin , Cooke Graham , Ward Helen , Tzoulaki Ioanna , Elliott Paul , Chadeau-Hyam Marc 
Published: June 2024

Abstract

Aims
Evaluate sex differences in cardiovascular disease (CVD) risk prediction, including use of (i) optimal sex-specific risk predictors and (ii) sex-specific risk thresholds.

Methods and results
Prospective cohort study using UK Biobank, including 121 724 and 182 632 healthy men and women, respectively, aged 38–73 years at baseline. There were 11 899 (men) and 9110 (women) incident CVD cases (hospitalization or mortality) with a median of 12.1 years of follow-up. We used recalibrated pooled cohort equations (PCEs; 7.5% 10-year risk threshold as per US guidelines), QRISK3 (10% 10-year risk threshold as per UK guidelines), and Cox survival models using sparse sex-specific variable sets (via LASSO stability selection) to predict CVD risk separately in men and women. LASSO stability selection included 12 variables in common between men and women, with 3 additional variables selected for men and 1 for women. C-statistics were slightly lower for PCE than QRISK3 and models using stably selected variables, but were similar between men and women: 0.67 (0.66–0.68), 0.70 (0.69–0.71), and 0.71 (0.70–0.72) in men and 0.69 (0.68–0.70), 0.72 (0.71–0.73), and 0.72 (0.71–0.73) in women for PCE, QRISK3, and models using stably selected variables, respectively. At current clinically implemented risk thresholds, test sensitivity was markedly lower in women than men for all models: at 7.5% 10-year risk, sensitivity was 65.1 and 68.2% in men and 24.0 and 33.4% in women for PCE and models using stably selected variables, respectively; at 10% 10-year risk, sensitivity was 53.7 and 52.3% in men and 16.8 and 20.2% in women for QRISK3 and models using stably selected variables, respectively. Specificity was correspondingly higher in women than men. However, the sensitivity in women at 5% 10-year risk threshold increased to 50.1, 58.5, and 55.7% for PCE, QRISK3, and models using stably selected variables, respectively.

Conclusion
Use of sparse sex-specific variables improved CVD risk prediction compared with PCE but not QRISK3. At current risk thresholds, PCE and QRISK3 work less well for women than men, but sensitivity was improved in women using a 5% 10-year risk threshold. Use of sex-specific risk thresholds should be considered in any re-evaluation of CVD risk calculators.
Host plant selection is linked to performance in Phthorimaea absoluta (Lepidoptera: Gelechiidae)
Authors: Aparna Shivanna , Kumar Amritha R V , Sotelo-Cardona Paola , Srinivasan Ramasamy 
Published: June 2024

Abstract
The evolution of oviposition preference in insects is considered a key evolutionary strategy in the context of host–plant interaction. It is hypothesized that insects maximize the survival and fitness of the subsequent generations by preferring specific host plant(s), known as the “preference-performance hypothesis.” In this study, we tested whether adult host preference reflects the immature performance in an oligophagous insect, Phthorimaea absoluta Meyrick, a rapidly emerging invasive pest in Asia, Africa, and Europe. Based on a preliminary survey of the potential host plants of P. absoluta, we selected 6 Solanaceae species, namely, tomato, potato, eggplant, black nightshade, sweet pepper, and tobacco, for the oviposition preference studies. The results indicated that the tomato was the most preferred host in no-, dual- and multiple-choice assays, followed by potato, eggplant, and black nightshade. Subsequently, the insect life-table parameters were found to be superior on tomato compared to other hosts. The order of oviposition preference on the host plants was strongly correlated with the life-table parameters of P. absoluta. Thus, we provide clear evidence for the preference–performance hypothesis in the host selection behavior of P. absoluta. We also emphasize the necessity of conducting oviposition behavior research at various geographic locations to develop tailor-made integrated pest management programs.
Ten-year prognosis of acute atrial fibrillation in ST-elevation myocardial infarction: recurrence and risk stroke
Authors: Martínez Membrive María José , Subirana Isaac , Fadeuilhe Edgar , Rueda Ferran , Carreras-Mora José , Oliveras Teresa , Giralt Teresa , Labata Carlos , Ferrer Marc , El Ouaddi Nabil , Montero Santiago , Elosúa Roberto , Ribas Núria , Bayés-Genís Antoni , García-García Cosme 
Published: June 2024

Abstract

Aims
Atrial fibrillation (AF) often complicates ST-elevation acute myocardial infarction (STEMI), with associated risks including stroke and mortality. Anticoagulation therapy for these patients and AF prognosis remain controversial. The aim was to evaluate long-term prognosis of STEMI patients complicated with AF in the acute phase.

Methods and results
We performed a retrospective analysis on a prospective register involving 4184 patients admitted for STEMI to the intensive cardiac care unit of two tertiary centres from 2007 to 2015. Patients with pre-existing permanent AF were excluded. Out of these, 269 (6.4%) patients developed AF within the first 48 h after STEMI and were matched with a control group based on age and left ventricular ejection fraction. After matching, a total of 470 patients were included (n = 235, AF-STEMI; n = 235, control group). Mean age was 69.0 years, and 31.7% were women. No differences were found in gender, cardiovascular risk factors, or ischaemic heart disease. AF-STEMI patients experienced more sustained ventricular tachycardia, advanced atrioventricular block, heart failure, and cardiogenic shock. In-hospital mortality was also higher in AF-STEMI patients (11.9% vs. 7.2%, P = 0.008). After a 10-year follow-up, the AF-STEMI group had remained with higher mortality (50.5% vs. 36.2%; P = 0.003) and a greater recurrence of AF (44.2% vs. 14.7%; P &lt; 0.001), without differences in stroke incidence (10.1% vs. 9.3%).

Conclusion
As a conclusion, patients with AF complicating STEMI have higher rates of heart failure, cardiogenic shock, and in-hospital mortality. After a 10-year follow-up, they exhibit a high risk of AF recurrence and mortality, with no significant differences in stroke incidence.
Association between overweight and obesity with coronary artery bypass graft failure: an individual patient data analysis of clinical trials
Authors: An Kevin R , Sandner Sigrid , Redfors Björn , Alexander John H , Alzghari Talal , Caldonazo Tulio , Cancelli Gianmarco , Dell’Aquila Michele , Dimagli Arnaldo , Gibson C Michael , Harik Lamia , Heise Rachel , Kulik Alexander , Lamy Andre , Leith Jordan , Peper Joyce , Perezgrovas-Olaria Roberto , Rossi Camilla S , Ruel Marc , Soletti Giovanni Jr , Ten Berg Jurrien M , Willemsen Laura M , Wojdyla Daniel M , Zhao Qiang , Zhu Yunpeng , Verma Subodh , Gaudino Mario F L 
Published: June 2024

Abstract

OBJECTIVES
The association between obesity and graft failure after coronary artery bypass grafting has not been previously investigated.

METHODS
We pooled individual patient data from randomized clinical trials with systematic postoperative coronary imaging to evaluate the association between obesity and graft failure at the individual graft and patient levels. Penalized cubic regression splines and mixed-effects multivariable logistic regression models were performed.

RESULTS
Six trials comprising 3928 patients and 12 048 grafts were included. The median time to imaging was 1.03 (interquartile range 1.00–1.09) years. By body mass index (BMI) category, 800 (20.4%) patients were normal weight (BMI 18.5–24.9), 1668 (42.5%) were overweight (BMI 25–29.9), 983 (25.0%) were obesity class 1 (BMI 30–34.9), 344 (8.8%) were obesity class 2 (BMI 35–39.9) and 116 (2.9%) were obesity class 3 (BMI 40+). As a continuous variable, BMI was associated with reduced graft failure [adjusted odds ratio (aOR) 0.98 (95% confidence interval (CI) 0.97–0.99)] at the individual graft level. Compared to normal weight patients, graft failure at the individual graft level was reduced in overweight [aOR 0.79 (95% CI 0.64–0.96)], obesity class 1 [aOR 0.81 (95% CI 0.64–1.01)] and obesity class 2 [aOR 0.61 (95% CI 0.45–0.83)] patients, but not different compared to obesity class 3 [aOR 0.94 (95% CI 0.62–1.42)] patients. Findings were similar, but did not reach significance, at the patient level.

CONCLUSIONS
In a pooled individual patient data analysis of randomized clinical trials, BMI and obesity appear to be associated with reduced graft failure at 1 year after coronary artery bypass grafting.
Impact of preoperative respiratory distress on outcomes of slide tracheoplasty
Authors: Nguyen Kien Trung , Van Nguyen Anh Thi , Tran Vinh Quang , Nguyen Yen Thi , Le Chuong Thanh , Van Dang Thuc , Jun Tae-Gook , Nguyen Truong Ly Thinh 
Published: June 2024

Abstract

OBJECTIVES
Children with congenital tracheal stenosis born in the developing world face a high risk of mortality due to limited access to proper treatment. Patients who required preoperative respiratory support were suspected to have poor survival after slide tracheoplasty; however, this was not clearly demonstrated in the previous studies. This study aims to investigate the impact of preoperative respiratory conditions on outcomes of slide tracheoplasty.

METHODS
From 2016 to 2022, children who underwent slide tracheoplasty were retrospectively reviewed. Patients with respiratory distress requiring emergency operations (group A) were compared with patients in stable condition who were scheduled for surgery (group B).

RESULTS
Perioperative results revealed that group A (n = 43) had a longer bypass time (P &lt; 0.001), operation time (P = 0.01), postoperative ventilation time (P &lt; 0.001) and length of intensive care unit stay (P = 0.00125) than group B (n = 60). The early mortality rate was 7.8%, and the actuarial 5-year survival rate was 85.3%. The cumulative incidence test revealed that group A was highly significant for overall mortality [sudistribution (SHR) 4.5; 95% confidence interval (CI) 1.23–16.4; P = 0.023]. Risk factors for overall mortality were prolonged postoperative ventilation time (hazard ratio 3.86; 95% CI 1.20–12.48; P = 0.024), bronchial stenosis (hazard ratio 5.77; 95% CI 1.72–19.31; P = 0.004), and preoperative tracheal mucositis (hazard ratio 5.67; 95% CI 1.51–21.31; P = 0.01). Four patients needed reintervention during a follow-up of 28.4 months (interquartile range 15.3–47.3).

CONCLUSIONS
Preoperative respiratory distress negatively affected the outcomes of patients who required slide tracheoplasty. Therefore, early detection of congenital tracheal stenosis and aggressive slide tracheoplasty are crucial and obligatory to enhance long-term survival in this lethal congenital airway disease.
Prognosis and treatment strategies for atrial fibrillation in heart failure with mildly reduced ejection fraction
Authors: Schupp Tobias , Schmitt Alexander , Reinhardt Marielen , Abel Noah , Lau Felix , Abumayyaleh Mohammad , Dudda Jonas , Weidner Kathrin , Ayoub Mohamed , Akin Muharrem , Müller Julian , Akin Ibrahim , Behnes Michael 
Published: June 2024

Abstract

Aims
The study investigates the prognosis of atrial fibrillation (AF) in patients with heart failure with mildly reduced ejection fraction (HFmrEF). Data concerning the prognostic impact of AF in patients with HFmrEF is scarce.

Methods and results
Consecutive patients with HFmrEF [i.e. left ventricular ejection fraction 41–49% and signs and/or symptoms of heart failure (HF)] were retrospectively included at one institution from 2016 to 2022. Patients with AF were compared with patients without with regard to the primary composite endpoint of all-cause mortality and HF-related rehospitalization at 30 months (median follow-up). Statistical analyses included Kaplan–Meier, multivariable Cox proportional regression analyses, and propensity score matching. A total of 2148 patients with HFmrEF were included with an overall prevalence of AF of 43%. The presence of AF was associated with a higher risk of the primary composite endpoint all-cause mortality and HF-related rehospitalization at 30 months [hazard ratio (HR) = 2.068; 95% confidence interval (CI) 1.802–2.375; P = 0.01], which was confirmed after propensity score matching (HR = 1.494; 95% CI 1.216–1.835; P = 0.01). AF was an independent predictor of both all-cause mortality (HR = 1.340; 95% CI 1.066–1.685; P = 0.01) and HF-related rehospitalization (HR = 2.061; 95% CI 1.538–2.696; P = 0.01). Finally, rhythm control may be associated with lower risk of all-cause mortality compared with rate control for AF (HR = 0.342; 95% CI 0.199–0.587; P = 0.01).

Conclusion
Atrial fibrillation affects 43% of patients with HFmrEF and represents an independent predictor of adverse long-term prognosis.