bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultra-high pressure balloon angioplasty for pulmonary artery stenosis in children with congenital heart defects: Short- to mid-term follow-up results from a retrospective cohort in a single tertiary center
Authors: Xia Shuliang , Li Jianbin , Ma Li , Cui Yanqin , Liu Techang , Wang Zhouping , Li Fengxiang , Liu Xumei , Li Shan , Sun Lu , Hu Lin , Liu Yubin , Ma Xun , Chen Xinxin , Zhang Xu
Published: January 2023

Objective

Balloon angioplasty (BA) has been the treatment of choice for pulmonary artery stenosis (PAS) in children. There remains, however, a significant proportion of resistant lesions. The ultra-high pressure (UHP) balloons might be effective in a subset of these lesions. In this study, we analyzed the safety and efficacy with short- to mid-term follow-up results of UHP BA for PAS in children with congenital heart defects (CHD) in our center.

Methods

This is a retrospective cohort study in a single tertiary heart center. Children diagnosed with PAS associated with CHD were referred for UHP BA. All data with these children were collected for analysis with updated follow-up.

Results

A total of 37 UHP BAs were performed consecutively in 28 children. The success rate was 78.4%. A significantly (P = 0.005) larger ratio of the balloon to the minimal luminal diameter at the stenotic waist (balloon/waist ratio) was present in the success group (median 3.00, 1.64–8.33) compared to that in the failure group (median 1.94, 1.41 ± 4.00). Stepwise logistic regression analysis further identified that the balloon/waist ratio and the presence of therapeutic tears were two independent predictors of procedural success. The receiver operating characteristic curve revealed a cut-off value of 2.57 for the balloon/waist ratio to best differentiate success from failure cases. Signs of therapeutic tears were present in eight cases, all of whom were in the success group. Perioperative acute adverse events were recorded in 16 patients, including 11 pulmonary artery injuries, three pulmonary hemorrhages, and two pulmonary artery aneurysms. During a median follow-up period of 10.4 (0.1–21.0) months, nine cases experienced restenosis at a median time of 40 (4–325) days after angioplasty.

Conclusions

The UHP BA is safe and effective for the primary treatment of PAS in infants and children with CHD. The success rate is high with a low incidence of severe complications. The predictors of success are a larger balloon/waist ratio and the presence of therapeutic tears. The occurrence of restenosis during follow-up, however, remains a problem. A larger number of cases and longer periods of follow-up are needed for further study.
Sex-Related Differences in Patients With Unexplained Syncope and Bundle Branch Block: Lower Risk of AV Block and Lesser Need for Cardiac Pacing in Women
Authors: Francisco-Pascual Jaume , Rivas-Gándara Nuria , Bach-Oller Montserrat , Badia-Molins Clara , Maymi-Ballesteros Manel , Benito Begoña , Pérez-Rodon Jordi , Santos-Ortega Alba , Sambola-Ayala Antonia , Roca-Luque Ivo , Cantalapiedra-Romero Javier , Rodríguez-Silva Jesús , Pascual-González Gabriel , Moya-Mitjans Àngel , Ferreira-González Ignacio
Published: January 2023

Graphical Abstract

Risk of AVB and need for cardiac pacing. Left: Percentage of patients diagnosed with aAVB/sCD in both sexes. Right-top: Multivariate logistic regression analyses for risk of aAVB/sCD. Odds ratio and 95% CI are plotted. Right-bottom: Kaplan-Meier pacemaker-free survival estimates curves in both sexes. aAVB/sCD, advanced atrio-ventricular block or severe conduction disturbances; HR, hazard ratio; CI, confidence interval; y.o, years old; IHD, ischemic heart disease; LVEF, left ventricular ejection fraction; BBB, bundle branch block; LBBB, left bundle branch block; RBBB, right bundle branch block; LAFB, left anterior fascicular block
Prognostic Power of Pulmonary Arterial Compliance Is Boosted by a Hemodynamic Unloading Test With Glyceryl Trinitrate in Heart Failure Patients With Post-capillary Pulmonary Hypertension
Authors: Rieth Andreas J. , Grün Dimitri , Zarogiannis Georgios , Kriechbaum Steffen D. , Wolter Sebastian , Richter Manuel J. , Tello Khodr , Krüger Ulrich , Mitrovic Veselin , Rosenkranz Stephan , Hamm Christian W. , Keller Till
Published: January 2023

Graphical Abstract
Molecular Changes in Prepubertal Left Ventricular Development Under Experimental Volume Overload
Authors: Hu Yuqing , Li Debao , Zhou Chunxia , Xiao Yingying , Sun Sijuan , Jiang Chuan , Chen Lijun , Liu Jinfen , Zhang Hao , Li Fen , Hong Haifa , Ye Lincai
Published: January 2023

Graphical Abstract

A prepubertal LV VO mouse model was first established. VO has an important influence on LV maturation and development, especially in cardiac conduction, suggesting the requirement of an early correction of AR in pediatric patients.
Effect of Sodium-Glucose Cotransporter 2 Inhibitors for Heart Failure With Preserved Ejection Fraction: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
Authors: Zhou Hufang , Peng Wenhua , Li Fuyao , Wang Yuelin , Wang Baofu , Ding Yukun , Lin Qian , Zhao Ying , Pan Guozhong , Wang Xian
Published: January 2023

Graphical Abstract

A systematic review and meta-analysis was performed to investigate the effect of sodium-glucose cotransporter 2 inhibitors for heart failure with preserved ejection fraction.
COVID-19 and atrial fibrillation: Intercepting lines
Authors: Donniacuo Maria , De Angelis Antonella , Rafaniello Concetta , Cianflone Eleonora , Paolisso Pasquale , Torella Daniele , Sibilio Gerolamo , Paolisso Giuseppe , Castaldo Giuseppe , Urbanek Konrad , Rossi Francesco , Berrino Liberato , Cappetta Donato
Published: January 2023

Almost 20% of COVID-19 patients have a history of atrial fibrillation (AF), but also a new-onset AF represents a frequent complication in COVID-19. Clinical evidence demonstrates that COVID-19, by promoting the evolution of a prothrombotic state, increases the susceptibility to arrhythmic events during the infective stages and presumably during post-recovery. AF itself is the most frequent form of arrhythmia and is associated with substantial morbidity and mortality. One of the molecular factors involved in COVID-19-related AF episodes is the angiotensin-converting enzyme (ACE) 2 availability. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses ACE2 to enter and infect multiple cells. Atrial ACE2 internalization after binding to SARS-CoV-2 results in a raise of angiotensin (Ang) II, and in a suppression of cardioprotective Ang(1–7) formation, and thereby promoting cardiac hypertrophy, fibrosis and oxidative stress. Furthermore, several pharmacological agents used in COVID-19 patients may have a higher risk of inducing electrophysiological changes and cardiac dysfunction. Azithromycin, lopinavir/ritonavir, ibrutinib, and remdesivir, used in the treatment of COVID-19, may predispose to an increased risk of cardiac arrhythmia. In this review, putative mechanisms involved in COVID-19-related AF episodes and the cardiovascular safety profile of drugs used for the treatment of COVID-19 are summarized.
Mechanical test relevance—A personal perspective on some methods and requirements
Authors: Darvell Brian W.
Published: January 2023

Mechanical tests of various kinds are widely used in dental research to study the behaviour of its materials. Unfortunately, despite its often long history, the relevance of a test or its outcome is hard to discern. But even for tests that have a more apparent appropriateness, many details that ensure good accuracy and reproducibility appear not to be appreciated or understood in that there is little evidence in the published literature that the necessary steps and precautions have been taken. The present purpose is to examine a number of these aspects in the context of a selection of tests to illustrate the care and attention that are essential for sound results.
Developmental programming of the neuroendocrine axis by steroid hormones: Insights from the sheep model of PCOS
Authors: Gurule Sara , Sustaita-Monroe Jessica , Padmanabhan Vasantha , Cardoso Rodolfo
Published: January 2023

The reproductive neuroendocrine system is a key target for the developmental programming effects of steroid hormones during early life. While gonadal steroids play an important role in controlling the physiological development of the neuroendocrine axis, human fetuses are susceptible to adverse programming due to exposure to endocrine disrupting chemicals with steroidal activity, inadvertent use of contraceptive pills during pregnancy, as well as from disease states that result in abnormal steroid production. Animal models provide an unparalleled resource to understand the effects of steroid hormones on the development of the neuroendocrine axis and their role on the developmental origins of health and disease. In female sheep, exposure to testosterone (T) excess during fetal development results in an array of reproductive disorders that recapitulate those seen in women with polycystic ovary syndrome (PCOS), including disrupted neuroendocrine feedback mechanisms, increased pituitary responsiveness to gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) hypersecretion, functional hyperandrogenism, multifollicular ovarian morphology, and premature reproductive failure. Similar to a large proportion of women with PCOS, these prenatally T-treated sheep also manifest insulin resistance and cardiovascular alterations, including hypertension. This review article focuses on the effects of prenatal androgens on the developmental programming of hypothalamic and pituitary alterations in the sheep model of PCOS phenotype, centering specifically on key neurons, neuropeptides, and regulatory pathways controlling GnRH and LH secretion. Insights obtained from the sheep model as well as other animal models of perinatal androgen excess can have important translational relevance to treat and prevent neuroendocrine dysfunction in women with PCOS and other fertility disorders.
Remodeling of the periodontal ligament and alveolar bone during axial tooth movement in mice with type 1 diabetes
Authors: Li Wenjin , Zheng Jing , Xu Yao , Niu Weiran , Guo Dong , Cui Jianing , Bian Wenjin , Wang Xiaohui , Niu Jinliang
Published: January 2023

Objectives

To observe the elongation of the axial tooth movement in the unopposed rodent molar model with type 1 diabetes mellitus and explore the pathological changes of periodontal ligament and alveolar bone, and their correlation with tooth axial movement.

Methods

The 80 C57BL/6J mice were randomly divided into the streptozotocin(STZ)-injected group (n = 50) and the control group (n = 30). Mice in the streptozotocin(STZ)-injected group were injected intraperitoneal with streptozotocin (STZ), and mice in the control group were given intraperitoneal injection of equal doses of sodium citrate buffer. Thirty mice were randomly selected from the successful models as the T1DM group. The right maxillary molar teeth of mice were extracted under anesthesia, and allowed mandibular molars to super-erupt. Mice were sacrificed at 0, 3, 6,9, and 12 days. Tooth elongation and bone mineral density (BMD) were evaluated by micro-CT analysis(0,and 12 days mice). Conventional HE staining, Masson staining and TRAP staining were used to observe the changes in periodontal tissue(0, 3, 6, 9, and 12 days mice). The expression differences of SPARC, FGF9, BMP4, NOGGIN, and type I collagen were analyzed by RT-qPCR.

Results

After 12 days of tooth extraction, our data showed significant super-eruption of mandibular mouse molars of the two groups. The amount of molar super-eruption in the T1DM group was 0.055mm( ± 0.014mm), and in the control group was 0.157( ± 0.017mm). The elongation of the T1DM mice was less than that of the control mice(P<0.001). It was observed that the osteoclasts and BMD increased gradually in both groups over time. Compared with the control group, the collagen arrangement was more disordered, the number of osteoclasts was higher (P<0.05), and the increase of bone mineral density was lower(2.180 ± 0.007g/cm3 vs. 2.204 ± 0.006g/cm3, P<0.001) in the T1DM group. The relative expression of SPARC, FGF9, BMP4, and type I collagen in the two groups increased with the extension of tooth extraction time while NOGGIN decreased. The relative expression of all of SPARC, FGF9, BMP4, and type I collagen in the T1DM group were significantly lower, and the expression of NOGGIN was higher than that in the control group (P<0.05).

Conclusion

The axial tooth movement was inhibited in type 1 diabetic mice. The result may be associated with the changes of periodontal ligament osteoclastogenic effects and alveolar bone remodeling regulated by the extracellular matrix and osteogenesis-related factors.
The mechanism and therapeutic strategies for neovascular glaucoma secondary to diabetic retinopathy
Authors: Tang Yizhen , Shi Yan , Fan Zhigang
Published: January 2023

Neovascular glaucoma (NVG) is a devastating secondary glaucoma characterized by the appearance of neovascular over the iris and the proliferation of fibrovascular tissue in the anterior chamber angle. Proliferative diabetic retinopathy (PDR) is one of the leading causes of NVG. Currently increasing diabetes population drive the prevalence rate of NVG into a fast-rising lane. The pathogenesis underlying NVG makes it refractory to routine management for other types of glaucoma in clinical practice. The combination of panretinal photocoagulation (PRP), anti-vascular endothelial growth factor (VEGF) injections, anti-glaucoma drugs, surgical intervention as well as blood glucose control is needed. Early diagnosis and aggressive treatment in time are crucial in halting the neovascularization process and preserving vision. This review provides an overview of NVG secondary to diabetic retinopathy (DR), including the epidemiology, pathogenesis and management, so as to provide a better understanding as well as potential therapeutic strategies for future treatment.
Continuous glucose monitoring for children with hypoglycaemia: Evidence in 2023
Authors: Worth Chris , Hoskyns Lucy , Salomon-Estebanez Maria , Nutter Paul W. , Harper Simon , Derks Terry G.J , Beardsall Kathy , Banerjee Indraneel
Published: January 2023

In 2023, childhood hypoglycaemia remains a major public health problem and significant risk factor for consequent adverse neurodevelopment. Irrespective of the underlying cause, key elements of clinical management include the detection, prediction and prevention of episodes of hypoglycaemia. These tasks are increasingly served by Continuous Glucose Monitoring (CGM) devices that measure subcutaneous glucose at near-continuous frequency. While the use of CGM in type 1 diabetes is well established, the evidence for widespread use in rare hypoglycaemia disorders is less than convincing. However, in the few years since our last review there have been multiple developments and increased user feedback, requiring a review of clinical application. Despite advances in device technology, point accuracy of CGM remains low for children with non-diabetes hypoglycaemia. Simple provision of CGM devices has not replicated the efficacy seen in those with diabetes and is yet to show benefit. Machine learning techniques for hypoglycaemia prevention have so far failed to demonstrate sufficient prediction accuracy for real world use even in those with diabetes. Furthermore, access to CGM globally is restricted by costs kept high by the commercially-driven speed of technical innovation. Nonetheless, the ability of CGM to digitally phenotype disease groups has led to a better understanding of natural history of disease, facilitated diagnoses and informed changes in clinical management. Large CGM datasets have prompted re-evaluation of hypoglycaemia incidence and facilitated improved trial design. Importantly, an individualised approach and focus on the behavioural determinants of hypoglycaemia has led to real world reduction in hypoglycaemia. In this state of the art review, we critically analyse the updated evidence for use of CGM in non-diabetic childhood hypoglycaemia disorders since 2020 and provide suggestions for qualified use.
The effects of three different low-volume aerobic training protocols on cardiometabolic parameters of type 2 diabetes patients: A randomized clinical trial
Authors: Gentil Paulo , Silva Lucas Raphael Bento e , Antunes Daniela Espíndola , Carneiro Luciana Barbosa , de Lira Claudio Andre Barbosa , Batista Gislene , Oliveira Jordana Campos Martins de , Cardoso John Sebastião , Souza Daniel CostaCosta , Rebelo Ana Cristina Silva
Published: January 2023

Objective

To compare the effects of different aerobic training protocols on cardiometabolic variables in patients with type 2 diabetes mellitus (T2DM).

Methods

This study was a parallel clinical trial. Fifty-two men and women with T2DM (>40 years) were randomly allocated into three groups, and 44 (22 males/22 females) were included in the final analysis. Exercise intensity was based on the speed corresponding to the maximum oxygen consumption (vV˙O2max). Moderate intensity continuous training (MICT) involved 14 minutes at 70% of vV˙O2max; short interval high-intensity interval training (S-HIIT) consisted of 20 bouts of 30 seconds at 100% of V˙O2max with 30 seconds passive recovery; long interval high-intensity training (L-HIIT) consisted of 5 bouts of 2 minutes at 100% of vV˙O2max with 2 minutes passive recovery. Training protocols were performed on a motorized treadmill two times per week for eight weeks. Glycated hemoglobin (Hb1Ac), total cholesterol, triglycerides, resting systolic blood pressure (SBP), resting diastolic blood pressure (DBP), resting heart rate (resting HR) and maximum oxygen consumption (V˙O2max) were measured before and after the exercise intervention. The study was registered on the Brazilian clinical trial records (ID: RBR45 4RJGC3).

Results

There was a significant difference between groups for changes on V˙O2max. Greater increases on V˙O2max were achieved for L-HIIT (p = 0.04) and S-HIIT (p = 0.01) in comparison to MICT group, with no significant difference between L-HIIT and S-HIIT (p = 0.9). Regarding comparison within groups, there were significant reductions on HbA1c and triglycerides levels only for L-HIIT (p< 0.05). V˙O2max significantly increased for both L-HIIT (MD = 3.2 ± 1.7 ml/kg/min, p< 0.001) and S-HIIT (MD = 3.4 ± 1.7, p< 0.001). There was a significant reduction on resting SBP for L-HIIT group (MD = -12.07 ± 15.3 mmHg, p< 0.01), but not for S-HIIT and MICT. There were no significant changes from pre- to post-training on fasting glycemia, total cholesterol, HDL, LDL, resting HR and resting DBP for any group (p > 0.05).

Conclusion

Low-volume HIIT promoted greater improvements in cardiorespiratory capacity in comparison with low-volume MICT, independent of the protocols used. There were no other differences between groups. All protocols improved at least one of the variables analyzed; however, the most evident benefits were after the high-intensity protocols, especially L-HIIT.
Spatial confinement of sliver nanoparticles in nitrogen-doped carbon framework with high catalytic activity and long-term cycling
Authors: Yang Meng , Zhang Jingwu , Wang Jinming , Gao Wei , Liu Di , Li Lanjie , Wang Yimin , Peng Qiuming
Published: January 2023

Graphical Abstract

We prepared a Ag NP@N-C-900 catalyst by a in-situ assisted spatial confinement method. This obtained Ag NP@N-C-900 possesses superior ORR performance with a half-wave potential of 0.83 V, excellent stability and methanol resistance ability. Attractively, the primary zinc–air battery based on the Ag NP@N-C-900 air-cathode offers a long cycle of 3600 minutes as well as excellent durability. The catalytic activity and stability exceed most of the Ag-based catalysts reported so far, and are completely comparable to commercially available Pt/C. Spatial confinement of sliver nanoparticles in nitrogen-doped carbon framework with high catalytic activity and long-term cycling.
Heat transfer enhancement and free convection assessment in a double-tube latent heat storage unit equipped with optimally spaced circular fins: Evaluation of the melting process
Authors: Shojaeinasab Chatroudi Ilia , Atashafrooz Meysam , Mohammed Hayder I. , Abed Azher M. , Talebizadehsardari Pouyan
Published: January 2023

To overcome the weak conduction heat transfer of phase change materials (PCM), this investigation aimed to assess the behavior of a double-tube latent heat storage unit with circular fins through the charging process. The influence of free convection in the presence of fins of various arrangements and sizes was comprehensively studied. The geometrical characteristics of the fins, i.e., their size and number, were assessed to optimize their performance. Moreover, a sensitivity assessment was performed on the characteristics of the heat transfer fluid passing through the inner tube, i.e., the Reynolds number and temperature. Charging time diminished by 179% when nine 15 mm fins were added compared with the finless scenario, assuming the same phase change materials volume. Moreover, the system’s thermal recovery rate improved from 20.5 to 32.9 W when nine fins with the heigth of 15 mm were added. The use of more fins improved the thermal behavior of the phase change materials because of the higher total fin area. The melting time and heat storage rate changed by 76% and 71%, respectively, for the system with 19 fins compared with those with four fins. Moreover, the outcomes indicated that a higher heat storage rate can be achieved when the working medium’s faster flow and inlet temperature were used.
Particle-size fractal dimensions and pore structure characteristics of soils of typical vegetation communities in the Kubuqi Desert
Authors: Sun Kai , Wang Han , Pei Zhiyong , Wang Haichao , Sun Xiaotian , Li Ying , Sun Guirong , Alatengsuhe  , Yang Jianjun , Su Xiaoming
Published: January 2023

The goal of this study was to investigate the soil particle-size distribution (PSD) and pore structure characteristics in the Kubuqi Desert in order to provide basic data for gaining insights into the soil-modifying properties of the local vegetation. Based on laser diffraction analysis, we measured the soil PSD and calculated the single and multi-fractal dimensions of the soils under typical artificial forest and natural grassland vegetation. The diameters, volumes and surface areas of the soil pores were determined via nitrogen adsorption experiments. The relationships between the fractal characteristics and pore structure parameters of the soil were investigated via redundancy analysis and stepwise regression. The clay content was less than 2.0%, and the sand content was greater than 75.0%. There was variability in the PSD and fractal dimension, which was mainly observed for the 0–20 cm, 20–80 cm, and 80–100 cm soil layers. In the 0–80 cm, the fine particle content, single fractal dimension (D), entropy dimension (D1), ratio of D1 to the capacity dimension (D1/D0), and correlation dimension (D2) were smaller for the forest soils than for the grassland soils. The fine particle (clay and silt) content of the 80–100 cm soil layer was approximately 37.8% higher for the Salix psammophila-8a than for the Salix psammophila-3a, and it was approximately 161.4% higher for the Populus popular-35a than for the Pinus sylvestris var. mongolica-8a. The silt content, D1, D1/D0, and D2 were significantly positively correlated with the specific surface area (SSA), total pore volume (TPV), and average pore diameter (APD) of the nanopores (p < 0.05, 0.01, or 0.001), and they were significantly negatively correlated with the percentage of the micropore volume (PMV) (p < 0.05 or 0.01). In the Kubuqi Desert, the fine particle content and fractal dimensions of the soil layer below the root zone of shrub and arbor vegetation increased with increasing stand age, but the trend was reversed in the shallower soil layers. The variability of the soil PSD characteristics was strongly correlated with the variability of the nanopore parameters on the microscopic scale, suggesting that the total pore volume, average pore diameter, and percentage of the micropore volume may be potential indicators of the soil structure and quality.
Exurban and suburban forests have superior healthcare benefits beyond downtown forests
Authors: Zhu Shuxin , He Shuangyu , Hu Feifei , Guo Yundan , Su Yan , Cui Guofa , Li Jiyue , Qiu Quan , He Qian
Published: January 2023

Forests in urban areas provide great healthcare benefits to citizens, but it is less well known whether this benefit is related to different geographical spaces. We selected exurban forest, suburban forest, downtown forest, and urban control in Guangzhou, China to analyze the change characteristics of negative air ion concentration (NAIC), air oxygen content (AOC), and human comfort index (HCI). Based on Criteria Importance Through Intercriteria Correlation (CRITIC) method, the urban forest comprehensive healthcare index (UFCHI) was established. Finally, the evaluation criteria for UFCHI were identified by cluster analysis. The results demonstrated that (1) The NAIC in exurban forest (2,713 ± 1,573 ions/cm3) and suburban forest (2,147 ± 923 ions/cm3) was evidently better than downtown forest (1,130 ± 255 ions/cm3) and urban control (531 ± 162 ions/cm3). (2) The AOC was in the order of exurban forest (21.17 ± 0.38%) > suburban forest (21.13 ± 0.30%) > downtown forest (21.10 ± 0.16%) > urban control (20.98 ± 0.12%). (3) The HCI in urban control (5.56 ± 2.32) and downtown forest (5.15 ± 1.80) is higher than suburban forest (4.02 ± 1.53) and exurban forest (3.71 ± 1.48). (4) The UFCHI in exurban forest (1.000), suburban forest (0.790), and downtown forest (0.378) were beneficial to human health to some extent, while urban control (0.000) was at Level IV, having no healthcare benefit. Except in winter, the UFCHI in exurban forest and suburban forest were all at Level II and above; while downtown forest and urban control were all at Level III and below at all seasons. Overall, urban forests in the exurbs and suburbs have better healthcare benefits than those in the downtowns. Furthermore, it is recommended that urban residents visit exurban and suburban forests for forest therapy in spring, summer, and autumn.
The LncRNA signature associated with cuproptosis as a novel biomarker of prognosis in immunotherapy and drug screening for clear cell renal cell carcinoma
Authors: Zhang Lishuo , Di Longjiang , Liu Jinhui , Lei Xianli , Gu Maoli , Zhang Wenjing , Wang Yufu
Published: January 2023

Cuproptosis is a new form of cell death, the second form of metal ion-induced cell death defined after ferroptosis. Recently, cuproptosis has been suggested to be associated with tumorigenesis. However, the relationship between cuproptosis and patient prognosis in clear cell renal cell carcinoma (ccRCC) in the context of immunotherapy remains unknown. The aim of this study was to investigate the correlation between cuproptosis-related long non-coding RNA (lncRNA) and ccRCC in terms of immunity as well as prognosis. Clinical information on lncRNAs associated with differences in cuproptosis genes in ccRCC and normal tissues was collected from The Cancer Genome Atlas (TCGA) dataset. Univariate Cox regression was used to screen lncRNAs. A total of 11 lncRNAs closely associated with cuproptosis were further screened and established using the least absolute shrinkage and selection operator (LASSO) algorithm and multivariate Cox regression, and the samples were randomly divided into training and test groups. A risk prognostic model was constructed using the training group, and the model was validated using the test group. We investigated the predictive ability of the prognostic risk model in terms of clinical prognosis, tumor mutation, immune escape, immunotherapy, tumor microenvironment, immune infiltration levels, and tumor drug treatment of ccRCC. Using the median risk score, patients were divided into low and high-risk groups. Kaplan-Meier curves showed that the overall survival (OS) of patients in the high-risk group was significantly worse than low-risk group (p < 0.001). Receiver operating characteristic (ROC) curves further validated the reliability of our model. The model consistently and accurately predicted prognosis at 1, 3, and 5 years, with an AUC above 0.7. Tumor cell genes generally precede morphological abnormalities; therefore, the model we constructed can effectively compensate for the traditional method of evaluating the prognosis of patients with renal cancer, and our model was also clinically meaningful in predicting ccRCC staging. In addition, lower model risk scores determined by mutational load indicated a good chance of survival. The high-risk group had greater recruitment of immune cells, while the anti-immune checkpoint immunotherapy was less efficacious overall than that of the low-risk group. Tumor and immune-related pathways were enriched, and anti-tumor agents were selected to improve the survival of ccRCC. This prognostic risk model is based on the levels of cuproptosis-associated lncRNAs and provides a new perspective in the clinical assessment and precise treatment of ccRCC.
Ancestry: How researchers use it and what they mean by it
Authors: Dauda Bege , Molina Santiago J. , Allen Danielle S. , Fuentes Agustin , Ghosh Nayanika , Mauro Madelyn , Neale Benjamin M. , Panofsky Aaron , Sohail Mashaal , Zhang Sarah R. , Lewis Anna C. F.
Published: January 2023

Background: Ancestry is often viewed as a more objective and less objectionable population descriptor than race or ethnicity. Perhaps reflecting this, usage of the term “ancestry” is rapidly growing in genetics research, with ancestry groups referenced in many situations. The appropriate usage of population descriptors in genetics research is an ongoing source of debate. Sound normative guidance should rest on an empirical understanding of current usage; in the case of ancestry, questions about how researchers use the concept, and what they mean by it, remain unanswered.

Methods: Systematic literature analysis of 205 articles at least tangentially related to human health from diverse disciplines that use the concept of ancestry, and semi-structured interviews with 44 lead authors of some of those articles.

Results: Ancestry is relied on to structure research questions and key methodological approaches. Yet researchers struggle to define it, and/or offer diverse definitions. For some ancestry is a genetic concept, but for many—including geneticists—ancestry is only tangentially related to genetics. For some interviewees, ancestry is explicitly equated to ethnicity; for others it is explicitly distanced from it. Ancestry is operationalized using multiple data types (including genetic variation and self-reported identities), though for a large fraction of articles (26%) it is impossible to tell which data types were used. Across the literature and interviews there is no consistent understanding of how ancestry relates to genetic concepts (including genetic ancestry and population structure), nor how these genetic concepts relate to each other. Beyond this conceptual confusion, practices related to summarizing patterns of genetic variation often rest on uninterrogated conventions. Continental labels are by far the most common type of label applied to ancestry groups. We observed many instances of slippage between reference to ancestry groups and racial groups.

Conclusion: Ancestry is in practice a highly ambiguous concept, and far from an objective counterpart to race or ethnicity. It is not uniquely a “biological” construct, and it does not represent a “safe haven” for researchers seeking to avoid evoking race or ethnicity in their work. Distinguishing genetic ancestry from ancestry more broadly will be a necessary part of providing conceptual clarity.
Cuproptosis-related gene FDX1 as a prognostic biomarker for kidney renal clear cell carcinoma correlates with immune checkpoints and immune cell infiltration
Authors: Yao Yimin , Chen Haixin , Lou Minjun , Chen Tingting
Published: January 2023

Background: Kidney renal clear cell carcinoma (KIRC) is not sensitive to radiotherapy and chemotherapy, and only some KIRC patients can benefit from immunotherapy and targeted therapy. Cuproptosis is a new mechanism of cell death, which is closely related to tumor progression, prognosis and immunity. The identification of prognostic markers related to cuproptosis in KIRC may provide targets for treatment and improve the prognosis of KIRC patients.

Methods: Ten cuproptosis-related genes were analyzed for differential expression in KIRC-TCGA and a prognostic model was constructed. Nomogram diagnostic model was used to screen independent prognostic molecules. The screened molecules were verified in multiple datasets (GSE36895 and GSE53757), and in KIRC tumor tissues by RT-PCR and immunohistochemistry (IHC). Clinical correlation of cuproptosis-related independent prognostic molecules was analyzed. According to the molecular expression, the two groups were divided into high and low expression groups, and the differences of immune checkpoint and tumor infiltrating lymphocytes (TILs) between the two groups were compared by EPIC algorithm. The potential Immune checkpoint blocking (ICB) response of high and low expression groups was predicted by the “TIDE” algorithm.

Results: FDX1 and DLAT were protective factors, while CDKN2A was a risk factor. FDX1 was an independent prognostic molecule by Nomogram, and low expressed in tumor tissues compared with adjacent tissues (p < 0.05). FDX1 was positively correlated with CD274, HAVCR2, PDCD1LG2, and negatively correlated with CTLA4, LAG3, and PDCD1. The TIDE score of low-FDX1 group was higher than that of high-FDX1 group. The abundance of CD4+ T cells, CD8+ T cells and Endothelial cells in FDX1-low group was lower than that in FDX1-high group (p < 0.05).

Conclusion: FDX1, as a key cuproptosis-related gene, was also an independent prognostic molecule of KIRC. FDX1 might become an interesting biomarker and potential therapeutic target for KIRC.
Pregnancy loss: Consequences for mental health
Authors: Cuenca Diana
Published: January 2023

Pregnancy loss, in all its forms (miscarriage, abortion, and fetal death), is one of the most common adverse pregnancy outcomes, but the psychological impact of such loss is often underestimated. The individual response to this outcome may vary between women—and could be influenced by age, race, culture, or religious beliefs—but most experience anxiety, stress, and symptoms of depression. Because pregnancy loss is not uncommon, health providers are used to dealing with this diagnosis, however the correct management of the process of diagnosis, information-gathering, and treatment can greatly ameliorate the adverse mental consequences for these women. The aim of this review is to examine the different types of pregnancy loss, and consider how each can influence the mental health of the women affected and their partners—in both the short- and long-term; to review the risk factors with the aim of identifying the women who may be at risk of consequential mental health problems; and to provide some advice for health providers to help these women better cope with pregnancy loss. Finally, we provide some points for health providers to follow in order to aid the management of a pregnancy loss, particularly for spontaneous, induced, or recurrent miscarriage, or stillbirth.
Bi-fluorescent Staphylococcus aureus infection enables single-cell analysis of intracellular killing in vivo
Authors: Hinman Kristina D. , Laforce-Nesbitt Sonia S. , Cohen Joshua T. , Mundy Miles , Bliss Joseph M. , Horswill Alexander R. , Lefort Craig T.
Published: January 2023

Techniques for studying the clearance of bacterial infections are critical for advances in understanding disease states, immune cell effector functions, and novel antimicrobial therapeutics. Intracellular killing of Staphylococcus aureus by neutrophils can be monitored using a S. aureus strain stably expressing GFP, a fluorophore that is quenched when exposed to the reactive oxygen species (ROS) present in the phagolysosome. Here, we expand upon this method by developing a bi-fluorescent S. aureus killing assay for use in vivo. Conjugating S. aureus with a stable secondary fluorescent marker enables the separation of infected cell samples into three populations: cells that have not engaged in phagocytosis, cells that have engulfed and killed S. aureus, and cells that have viable internalized S. aureus. We identified ATTO647N-NHS Ester as a favorable dye conjugate for generating bi-fluorescent S. aureus due to its stability over time and invariant signal within the neutrophil phagolysosome. To resolve the in vivo utility of ATTO647N/GFP bi-fluorescent S. aureus, we evaluated neutrophil function in a murine model of chronic granulomatous disease (CGD) known to have impaired clearance of S. aureus infection. Analysis of bronchoalveolar lavage (BAL) from animals subjected to pulmonary infection with bi-fluorescent S. aureus demonstrated differences in neutrophil antimicrobial function consistent with the established phenotype of CGD.
Identification of a forkhead box protein transcriptional network induced in human neutrophils in response to inflammatory stimuli
Authors: Ismailova Aiten , Salehi-Tabar Reyhaneh , Dimitrov Vassil , Memari Babak , Barbier Camille , White John H.
Published: January 2023

Introduction

Neutrophils represent the largest proportion of circulating leukocytes and, in response to inflammatory stimuli, are rapidly recruited to sites of infection where they neutralize pathogens.

Methods and results

We have identified a novel neutrophil transcription network induced in response to inflammatory stimuli. We performed the first RNAseq analysis of human neutrophils exposed to lipopolysaccharide (LPS), followed by a meta-analysis of our dataset and previously published studies of LPS-challenged neutrophils. This revealed a robustly enhanced transcriptional network driven by forkhead box (FOX) transcription factors. The network is enriched in genes encoding proinflammatory cytokines and transcription factors, including MAFF and ATF3, which are implicated in responses to stress, survival and inflammation. Expression of transcription factors FOXP1 and FOXP4 is induced in neutrophils exposed to inflammatory stimuli, and potential FOXP1/FOXP4 binding sites were identified in several genes in the network, all located in chromatin regions consistent with neutrophil enhancer function. Chromatin immunoprecipitation (ChIP) assays in neutrophils confirmed enhanced binding of FOXP4, but not FOXP1, to multiple sites in response to LPS. Binding to numerous motifs and transactivation of network genes were also observed when FOXP proteins were transiently expressed in HEK293 cells. In addition to LPS, the transcriptional network is induced by other inflammatory stimuli, indicating it represents a general neutrophil response to inflammation.

Discussion

Collectively, these findings reveal a role for the FOXP4 transcription network as a regulator of responses to inflammatory stimuli in neutrophils.
Year-round foraging across large spatial scales suggest that bowhead whales have the potential to adapt to climate change
Authors: Fortune Sarah M. E. , Trites Andrew W. , LeMay Valerie , Baumgartner Mark F. , Ferguson Steven H.
Published: January 2023

The ecological impact of environmental changes at high latitudes (e.g., increasing temperature, and decreased sea ice cover) on low-trophic species, such as bowhead whales, are poorly understood. Key to understanding the vulnerability of zooplanktivorous predators to climatic shifts in prey is knowing whether they can make behavioural or distributional adjustments to maintain sufficient prey acquisition rates. However, little is known about how foraging behaviour and associated environmental conditions fluctuate over space and time. We collected long-term movement (average satellite transmission days were 397 (± 204 SD) in 2012 and 484 (± 245 SD) in 2013) and dive behaviour data for 25 bowhead whales (Balaena mysticetus) equipped with time-depth telemetry tags, and used hierarchical switching-state-space models to quantify their movements and behaviours (resident and transit). We examined trends in inferred two-dimensional foraging behaviours based on dive shape of Eastern Canada-West Greenland bowhead whales in relation to season and sea ice, as well as animal sex and age via size. We found no differences with regards to whale sex and size, but we did find evidence that subsurface foraging occurs year-round, with peak foraging occurring in fall (7.3 hrs d-1 ± 5.70 SD; October) and reduced feeding during spring (2.7 hrs d-1 ± 2.55 SD; May). Although sea ice cover is lowest during summer foraging, whales selected areas with 65% (± 36.1 SD) sea ice cover. During winter, bowheads occurred in areas with 90% (± 15.5 SD) ice cover, providing some open water for breathing. The depth of probable foraging varied across seasons with animals conducting epipelagic foraging dives (< 200 m) during spring and summer, and deeper mesopelagic dives (> 400 m) during fall and winter that approached the sea bottom, following the seasonal vertical migration of lipid-rich zooplankton. Our findings suggest that, compared to related species (e.g., right whales), bowheads forage at relatively low rates and over a large geographic area throughout the year. This suggests that bowhead whales have the potential to adjust their behaviours (e.g., increased time allocated to feeding) and shift their distributions (e.g., occupy higher latitude foraging grounds) to adapt to climate-change induced environmental conditions. However, the extent to which energetic consumption may vary seasonally is yet to be determined.
Hypertension, type 2 diabetes, obesity, and p53 mutations negatively correlate with metastatic colorectal cancer patients’ survival
Authors: Ottaiano Alessandro , Santorsola Mariachiara , Circelli Luisa , Perri Francesco , Cascella Marco , Sabbatino Francesco , Capuozzo Maurizio , Granata Vincenza , Zappavigna Silvia , Lombardi Angela , Scrima Marianna , Petrillo Nadia , Ianniello Monica , Casillo Marika , Gualillo Oreste , Nasti Guglielmo , Caraglia Michele , Savarese Giovanni
Published: January 2023

Introduction

We studied the predictive and prognostic influences of hypertension (HT), type 2 diabetes (T2D), weight, and p53 mutations in metastatic colorectal cancer (CRC) patients.

Patients and methods

T2D was diagnosed according to the ADA criteria. HT was classified according to the ACC/AHA guidelines. BMI (body-mass index) was calculated and classified according to the WHO criteria. TruSigt™Oncology 500 kit was applied to construct the genomic libraries for Next Generation Sequencing (NGS) analysis. The Illumina NovaSeq 6000 technological platform and the Illumina TruSight Oncology 500 bioinformatics pipeline were applied to analyze results. Overall survival (OS) was calculated through Kaplan-Meier curves. Univariate and multivariate analyses were performed to assess the relationships between clinical and/or molecular covariates. Associations between HT, T2D, BMI, p53, and clinical variables were evaluated by the χ2 test. P < 0.05 were considered statistically significant.

Results

Two-hundred-forty-four patients were enrolled. One-hundred-twenty (49.2%), 110 (45.1%), and 50 (20.5%) patients were affected by overweight, HT, and T2D, respectively. DC (disease control) was achieved more frequently in patients without T2D (83.1%) compared to the diabetic ones (16.9%) (P = 0.0246). DC, KRAS mutational status, T2D, BMI, and concomitant presence of T2D, BMI, and HT associated with survival (P < 0.05). At multivariate analysis, age (≥65 vs. <65 years), response to first-line chemotherapy (DC vs. no DC), and concomitant presence of T2D, BMI, and HT (HR: 4.56; 95% CI: 2.40–8.67; P = 0.0217) emerged as independent prognostic variables. P53 was mutated in 31/53 analyzed cases (60.4%). The most frequent gene variants were p.Arg175His and p.Cys135Tyr. High BMI (>25 kg/m2) associated with occurrence of p53 mutations (P < 0.0001). P53 mutated patients presented a worse prognosis compared to the wild-type ones (HR: 3.21; 95% CI: 1.43–7.23; P = 0.0047).

Conclusion

Diabetic, hypertensive and overweight metastatic CRC patients are a negative prognostic subgroup deserving specific therapeutic strategies. P53 mutations associate with prognosis and BMI unrevealing complex and unexplored connections between metabolism and cancer occurrence.
Rapid disease progression on immune checkpoint inhibitors in young patients with stage IV melanoma
Authors: Machiraju Devayani , Schäfer Sarah , Beckhove Philip , Roth Jasmin , Schulz Carsten , Hassel Jessica C.
Published: January 2023

Background

Immune checkpoint inhibitors (ICIs) are the standard of care for metastatic cutaneous melanoma (mCM) patients, but their efficacy in young adults aged less than 40 years remains unclear.

Materials and methods

We retrospectively analyzed 303 stage IV melanoma patients of different ages treated with nivolumab, pembrolizumab, or ipilimumab plus nivolumab combination therapy. Clinical data and blood values such as LDH, CRP, and absolute immune cell counts were retrieved from the medical records. Pre-treatment serum concentrations of soluble immune checkpoint proteins were measured using ELISA. In addition, information on frequencies of various T cell subsets in the peripheral blood was collected from a previously reported study (ELEKTRA). Patient characteristics and clinical information was correlated with PFS and OS using univariate and multivariate cox regression analysis.

Results

Of 303 patients, 33 (11%) were ≤ 40 years old. The older patients had a median age of 64 (95% CI: 61–66). Concerning prognostic parameters, there was no difference between the age groups, e.g., in gender, LDH, or the existence of brain or liver metastases. Patients aged ≤ 40 years [p = 0.014; HR: 1.6 (95% CI: 1.1–2.4)], presence of liver metastases [p = 0.016; HR: 1.4 (95% CI: 1.0–1.9)], line of ICI treatment [p = 0.009; HR: 1.4 (1.0–1.9)], elevated LDH [p = 0.076; HR: 1.3 (95% CI: 0.97–1.8)], and brain metastasis [p = 0.080; HR: 1.3 (95% CI: 0.97–1.7)], were associated with shorter PFS in univariate analysis. Multivariate analysis revealed that the patient’s age (≤ 40 years) remains a high-risk factor upon adjusting for all potential confounders [p = 0.067; HR: 1.5 (95% CI: 0.97–2.3)]. Blood parameters revealed that patients ≤ 40 years have relatively higher frequencies of activated CD4 T cells (CD4 + Ki67 + CD4 + ICOS +) in the blood, and significantly lower number of basophils and CD45RA- memory T cells, compared to patients above 40 years (p < 0.05). In addition, patients ≤ 40 years experiencing disease progression within 6 months of ICI treatment had increased concentrations of sPDL1 (p = 0.05) and sTIM3 (p = 0.054) at baseline.

Conclusion

Young patients with stage IV melanoma may experience shorter progression-free survival upon ICI treatment compared to patients above 40 years and are characterized by fewer basophils and memory T cells in the blood.