bluuebunny/crossref_metadata_2025 huggingface dataset:
Zero fluoroscopy ablation for atrioventricular nodal reentrant tachycardia and typical atrial flutter is equally safe and effective with EnSite NavX, Carto3, and Rhythmia mapping systems
Authors: Piros Katalin , Perge Péter , Salló Zoltán , Herczeg Szilvia , Nagy Vivien Klaudia , Osztheimer István , Merkely Béla , Gellér László , Szegedi Nándor
Published: July 2023

Purpose

Our purpose was to compare the procedural characteristics, success rate, and complication rate of the conventional fluoroscopic (CF) and the zero-fluoroscopic (ZF) approach in patients undergoing catheter ablation of AVNRT or typical atrial flutter (Aflu).

Methods

186 consecutive patients with an indication for AVNRT or Aflu ablation were enrolled. Based on the operator's preference, the patients were assigned to either CF or ZF group. In the ZF group EnSite NavX, Carto3, or Rhythmia EAMS were used for catheter guidance.

Results

The median age was 56 (IQR = 42−68) years, 144 patients had AVNRT, and 42 had Aflu ablation. CF approach was chosen in 123 cases, while ZF in 63 cases. ZF approach was used more often in case of AVNRT patients [56 (39%) vs. 7 (17%), p = 0.006] and in the case of female patients [43 (68%) vs. 20 (32%), p = 0.008]. Acute procedural success was obtained in all cases. There was no difference in the complication rate (1 vs. 1, p > 0.99) between the two groups. No difference was found regarding the procedure time between the CF and ZF groups [CF: 55 (46–60) min, ZF 60 (47–65) min; p = 0.487] or in the procedure time for the different EAMS [EnSite NavX: 58 (50–63) min, Carto3: 60 (44.5–66.3) min, Rhythmia: 55 (35–69) min; p = 0.887]. A similar success rate was seen at the 3-month follow-up in the two groups [41 (100%) vs. 96 (97%); p = 0.55].

Discussion

The ZF approach demonstrated non-inferiority in safety and efficacy compared with CF for the AVNRT and Aflu ablations.
Changes in carotid artery texture by ultrasound and elastin features in a murine model
Authors: Mitchell Carol , Al Mukaddim Rashid , Liu Yuming , Graham Melissa , Eickhoff Jens C. , Weichmann Ashley M. , Tattersall Matthew C. , Korcarz Claudia E. , Stein James H. , Varghese Tomy , Eliceiri Kevin W.
Published: July 2023

Objective

In humans, arterial grayscale ultrasound texture features independently predict adverse cardiovascular disease (CVD) events and change with medical interventions. We performed this study to examine how grayscale ultrasound texture features and elastin fibers change in plaque-free segments of the arterial wall in a murine model prone to atherosclerosis.

Methods

A total of 10 Apoetm1Unc/J mice (n = 5 male, n = 5 female) were imaged at 6, 16, and 24 weeks of age. Two mice were euthanized at 6 and 16 weeks and the remaining mice at 24 weeks. Texture features were extracted from the ultrasound images of the distal 1.0 mm of the common carotid artery wall, and elastin measures were extracted from histology images. Two-way analysis of variance was used to evaluate associations between week, sex, and grayscale texture features. Texture feature and elastin number comparisons between weeks were conducted using the sex-by-week two-way interaction contrasts. Sex-specific correlations between the number of elastin fibers and grayscale texture features were analyzed by conducting non-parametric Spearman's rank correlation analyses.

Results

Arterial wall homogeneity changed significantly in male mice from 6 to 24 weeks, with a mean (SD) of 0.14 (0.03) units at 6 weeks and 0.18 (0.03) units at 24 weeks (p = 0.026). Spatial gray level dependence matrices-homogeneity (SGLD-HOM) also correlated with carotid artery plaque score (rs = 0.707, p = 0.033). Elastin fibers in the region of interest decreased from 6 to 24 weeks for both male and female mice, although only significantly in male mice. The mean (SD) number of elastin fibers for male mice was 5.32 (1.50) at 6 weeks and 3.59 (0.38) at 24 weeks (p = 0.023). For female mice, the mean (SD) number of elastin fibers was 3.98 (0.38) at 6 weeks and 3.46 (0.19) at 24 weeks (p = 0.051).

Conclusion

Grayscale ultrasound texture features that are associated with increased risk for CVD events in humans were used in a murine model, and the grayscale texture feature SGLD-HOM was shown to change in male mice from 6 weeks to 24 weeks. Structural alterations of the arterial wall (change in elastin fiber number) were observed during this time and may differ by sex.
Behaviourally modern humans in coastal southern Africa experienced an increasingly continental climate during the transition from Marine Isotope Stage 5 to 4
Authors: Göktürk Ozan Mert , Simon Margit H. , Sobolowski Stefan Pieter , Zhang Zhongshi , Van Der Bilt Willem , Mørkved Pål Tore , D’Andrea William J. , van Niekerk Karen L. , Henshilwood Christopher S. , Armitage Simon J. , Jansen Eystein
Published: July 2023

Linking human technological and behavioural advances to environmental changes is challenging, as it requires a robust understanding of past climate at local scales. Here, we present results from regional high-resolution numerical simulations along with climate data directly from the archaeological sequence of Blombos Cave (BBC), a well-studied site in coastal southern Africa. The model simulations cover two distinct periods centred at 82 and 70 thousand years (ka) ago (Marine Isotope Stage [MIS] 5 and the onset of MIS 4, respectively), when orbital parameters and global sea level were markedly different from one another. Climatic changes from 82 to 70 ka are determined through four simulations that use past and present-day coastline configurations. The hydrogen isotopic composition of leaf waxes (δ2Hwax) and n-alkane distributions and abundances are used to reconstruct hydroclimate around BBC. The leaf wax n-alkane record, one of the first produced in an archaeological setting in this region to date, can be interpreted as a drying signal from MIS 5c to 4. This agrees with our modelling results, which indicate a drier and more continental climate over coastal southern Africa at 70 ka, compared to 82 ka. The simulated aridification is most evident from the reduced precipitation amounts in both summer (∼20%) and winter (∼30%). The annual number of summer days (Tmax ≥ 25 °C) and cold nights (Tmin < 5 °C) in the vicinity of BBC increases more than 5 and 3-fold, respectively, under the more continental climate at 70 ka. Weaker westerly winds in winter, a cooler Agulhas Current, and a land surface expansion associated with the coastline shift due to lower sea levels at 70 ka all contribute to the simulated climate shift. Our approach highlights the importance of multiple lines of evidence for achieving robust results, while demonstrating how both large-scale forcing and local influences worked together in shaping the local climate that early humans lived in. Adaptation to a drier climate and increased continentality around BBC might have induced greater mobility, which led to increased population interactions, cultural transmission rates, skill exchange, and material complexity during the so-called Still Bay period.
Uniform thickness in the process of ore-mixed characteristics of particles passing through experimental research
Authors: Niu Xiangdong , Sun Huafen , Hou Kepeng
Published: July 2023

The nature of fine particulate matter is caused by the deterioration of the lean ore loss index and the important influence factors of a mine disaster accident. In this paper, fine moraine particles and coarse-grained ore from the Pulang Copper Mine are studied. The flow of fine particles in mixed particles under the condition of uniform ore drawing was studied by using the laboratory 3D physical model test method. This experiment explored the flow of hybrid particles in the system and characteristics of the particle size of fine particles passing through, and suggested a transit index to quantify the draining effect of fine particles. The experimental results show the following: ①Hybrid particles in the flow system of fine particulate matter under their own gravity use mixed ore particles flow in the process of formation of the pore to implement down through sports. ②The fine particles with the particle sizes of 2.5–1.25 mm, 1.25–0.63 mm, 0.63–0.315 mm, and 0.315–0.16 mm all have the flow-through characteristics, and the smaller the particle size, the more significant the flow-through degree. ③The cumulative ore drawing height of fine particles with different particle sizes increases, while the permeability index of the appropriate discharge decreases. ④The relative motion of coarse and fine particles is the internal control factor that leads to the flow of fine particles. The more significant the relative motion of coarse and finely mixed particles is, the more pores are randomly generated in the particle flow system and the larger the pores are, resulting in the more obvious fine particle flow effect. This study provides some theoretical reference value for revealing the flow-through characteristics of the fine particulate matter in the mixed particle flow system. At the same time, it has practical engineering significance for ore lean loss index control and mine disaster accident prevention and control in caving mining.
Turner syndrome: skin, liver, eyes, dental and ENT evaluation should be improved
Authors: Lam Jenny , Stoppa-Vaucher Sophie , Antoniou Maria Cristina , Bouthors Thérèse , Ruiz Inge , Sekarski Nicole , Rutz Tobias , Fries Sophie , Binz Pierre Alain , Bütschi Florence Niel , Vulliemoz Nicolas , Gawlik Aneta , Pitteloud Nelly , Hauschild Michael , Busiah Kanetee
Published: July 2023

Introduction

Turner syndrome association with multi-organ system comorbidities highlights the need for effective implementation of follow-up guidelines. We aimed to assess the adequacy of care with international guidelines published in 2007 and 2017 and to describe the phenotype of patients.

Methods

In this multicenter retrospective descriptive cohort study, we collected growth and pubertal parameters, associated comorbidities, treatment, and karyotype in patients diagnosed at age <18 years between 1993 and 2022. We assessed age-appropriate recommendation follow-up (children, adolescents and adults) according to the 2007 guidelines if the last visit was before 2017 (18 recommendations) and the 2017 guidelines if the last visit was after 2017 (19 recommendations).

Results

We included 68 patients followed at Lausanne University Hospital (n=64) and at Neuchatel Regional Hospital (RHNe) (n=4). 2.9% of patients underwent all recommended investigations.

Overall, 68.9 ± 22.5% and 78.5 ± 20.6% of the recommendations were followed, before and after 2017 respectively. High implementation rates were found for height, weight and BMI (100%), cardiac (80 to 100%) and renal (90 to 100%) imaging. Low implementation rates were found for Ear, Nose and Throat (ENT) (56.5%), skin (38.5%), dental (23.1%), ophthalmological (10%) and cholestasis (0 to 29%) assessments, depending on age and time of visit. In adults (n=33), the mean proportion of followed recommendations was lower before than after 2017: 63.5 ± 25.8% vs. 78.7 ± 23.4%, p=0.039.

Conclusion

Growth parameters, cardiac and renal imaging are well followed. However, efforts should be made for dental, ENT, ophthalmological, skin and cholestasis assessments. Adequacy of follow-up improved with the quality of transition to adult care.
Reactive oxygen species mediated apoptotic death of colon cancer cells: therapeutic potential of plant derived alkaloids
Authors: Nelson Vinod K. , Nuli Mohana Vamsi , Mastanaiah Juturu , Saleem T. S. Mohamed , Birudala Geetha , Jamous Yahya F. , Alshargi Omar , Kotha Kranthi Kumar , Sudhan Hari Hara , Mani Ravishankar Ram , Muthumanickam Alagusundaram , Niranjan Divya , Jain Nem Kumar , Agrawal Ankur , Jadon Arvind Singh , Mayasa Vinyas , Jha Niraj Kumar , Kolesarova Adriana , Slama Petr , Roychoudhury Shubhadeep
Published: July 2023

Colorectal cancer (CRC) is one of the most deaths causing diseases worldwide. Several risk factors including hormones like insulin and insulin like growth factors (e.g., IGF-1) have been considered responsible for growth and progression of colon cancer. Though there is a huge advancement in the available screening as well as treatment techniques for CRC. There is no significant decrease in the mortality of cancer patients. Moreover, the current treatment approaches for CRC are associated with serious challenges like drug resistance and cancer re-growth. Given the severity of the disease, there is an urgent need for novel therapeutic agents with ideal characteristics. Several pieces of evidence suggested that natural products, specifically medicinal plants, and derived phytochemicals may serve as potential sources for novel drug discovery for various diseases including cancer. On the other hand, cancer cells like colon cancer require a high basal level of reactive oxygen species (ROS) to maintain its own cellular functions. However, excess production of intracellular ROS leads to cancer cell death via disturbing cellular redox homeostasis. Therefore, medicinal plants and derived phytocompounds that can enhance the intracellular ROS and induce apoptotic cell death in cancer cells via modulating various molecular targets including IGF-1 could be potential therapeutic agents. Alkaloids form a major class of such phytoconstituents that can play a key role in cancer prevention. Moreover, several preclinical and clinical studies have also evidenced that these compounds show potent anti-colon cancer effects and exhibit negligible toxicity towards the normal cells. Hence, the present evidence-based study aimed to provide an update on various alkaloids that have been reported to induce ROS-mediated apoptosis in colon cancer cells via targeting various cellular components including hormones and growth factors, which play a role in metastasis, angiogenesis, proliferation, and invasion. This study also provides an individual account on each such alkaloid that underwent clinical trials either alone or in combination with other clinical drugs. In addition, various classes of phytochemicals that induce ROS-mediated cell death in different kinds of cancers including colon cancer are discussed.
Case Report: Aggressive neural crest tumors in a child with familial von Hippel Lindau syndrome associated with a germline VHL mutation (c.414A>G) and a novel KIF1B gene mutation
Authors: Landen Lucie , De Leener Anne , Le Roux Manon , Brichard Bénédicte , Aydin Selda , Maiter Dominique , Lysy Philippe A.
Published: July 2023

Introduction

Von Hippel Lindau (VHL) syndrome is caused by an autosomal dominant hereditary or sporadic germline mutation of the VHL gene with more than five hundred pathogenic mutations identified. Pheochromocytomas and rarely paragangliomas occur in 10-50% of patients with VHL syndrome usually around 30 years of age and exceptionally before the age of 10.

Case presentation

We diagnosed a 9-year-old girl of normal appearance and severe refractory hypertension, with a norepinephrine-secreting pheochromocytoma related to VHL syndrome due to a known familial germline heterozygous mutation of VHL gene (c.414A>G), also present in three members of her family. At age 13, a pelvic tumor and a left adrenal pheochromocytoma that showed to be multi-metastatic to both lungs were discovered in the patient leading to left adrenalectomy and pelvic tumor resection. In addition to the germline VHL gene mutation, blood analysis using Next Generation Sequencing identified a novel heterozygous germline mutation of the KIF1B gene (c.3331_3332del; p.Asn1111Glnfs*21), which is only present in the girl and not the other family members. The patient is currently under steroid substitution therapy and leads a normal life.

Discussion

This family is notable by the early age of onset of multiple neural crest tumors associated with a high propensity for malignancy and metastatic spread. Most reports in the literature associated the VHL mutation with a later onset in adulthood and a benign course, which contrast with our findings and question the role of this mutation in the phenotype expressed in this kindred. Also, the presence of concomitant mutations in two susceptibility genes for neural crest tumors poses the question of their respective roles in the development of tumors in this family. Our familial case description illustrates the potential for systematic use of targeted Next Generation Sequencing with multi-gene panels in patients with neural crest tumors to confirm the role of known susceptibility genes as well as identifying new ones, but also to contribute to comprehensive databases on gene variants and their phenotypic counterparts in this specific area of medicine.
Case Report: Severe McCune–Albright syndrome presenting with neonatal Cushing syndrome: navigating through clinical obstacles
Authors: Unsal Yagmur , Gozmen Onur , User İdil Rana , Hızarcıoglu Hayriye , Gulhan Bora , Ekinci Saniye , Karagoz Tevfik , Ozon Z. Alev , Gonc E. Nazlı
Published: July 2023

Background

Café-au-lait skin macules, Cushing syndrome (CS), hyperthyroidism, and liver and cardiac dysfunction are presenting features of neonatal McCune–Albright syndrome (MAS), CS being the rarest endocrine feature. Although spontaneous resolution of hypercortisolism has been reported, outcome is usually unfavorable. While a unified approach to diagnosis, treatment, and follow-up is lacking, herein successful treatment and long-term follow-up of a rare case is presented.

Clinical case

An 11-day-old girl born small for gestational age presented with deterioration of well-being and weight loss. Large hyperpigmented macules on the trunk, hypertension, hyponatremia, hyperglycemia, and elevated liver enzymes were noted. ACTH-independent CS due to MAS was diagnosed. Although metyrapone (300 mg/m2/day) was started on the 25th day, complete remission could not be achieved despite increasing the dose up to 1,850 mg/m2/day. At 9 months, right total and left three-quarters adrenalectomy was performed. Cortisol decreased substantially, ACTH remained suppressed, rapid tapering of hydrocortisone to physiological dose was not tolerated, and supraphysiological doses were required for 2 months. GNAS analysis from the adrenal tissue showed a pathogenic heterozygous mutation. During 34 months of follow-up, in addition to CS due to MAS, fibrous dysplasia, hypophosphatemic rickets, and peripheral precocious puberty were detected. She is still regularly screened for other endocrinopathies.

Conclusion

Neonatal CS due to MAS is extremely rare. Although there is no specific guideline for diagnosis, treatment, or follow-up, addressing side effects and identifying treatment outcomes will improve quality of life and survival.
Paternal developmental thyrotoxicosis disrupts neonatal leptin leading to increased adiposity and altered physiology of the melanocortin system
Authors: Martinez Maria Elena , Wu Zhaofei , Hernandez Arturo
Published: July 2023

Background

The genetic code does not fully explain individual variability and inheritance of susceptibility to endocrine conditions, suggesting the contribution of epigenetic factors acting across generations.

Methods

We used a mouse model of developmental thyrotoxicosis (Dio3-/- mouse) to analyze endocrine outcomes in the adult offspring of Dio3-/- males using standard methods for body composition, and baseline and fasting hormonal and gene expression determinations in serum and tissues of relevance to the control of energy balance.

Results

Compared to controls, adult females with an exposed father (EF females) exhibited higher body weight and fat mass, but not lean mass, a phenotype that was much milder in EF males. After fasting, both EF females and males exhibited a more pronounced decrease in body weight than controls. EF females also showed markedly elevated serum leptin, increased white adipose tissue mRNA expression of leptin and mesoderm-specific transcript but decreased expression of type 2 deiodinase. EF females exhibited decreased serum ghrelin, which showed more pronounced post-fasting changes in EF females than in control females. EF female hypothalami also revealed significant decreases in the expression of pro-opiomelanocortin, agouti-related peptide, neuropeptide Y and melanocortin receptor 4. These markers also showed larger changes in response to fasting in EF females than in control females. Adult EF females showed no abnormalities in serum thyroid hormones, but pituitary expression of thyrotropin-releasing hormone receptor 1 and thyroid gland expression of thyroid-stimulating hormone receptor, thyroid peroxidase and iodotyrosine deiodinase were increased at baseline and showed differential regulation after fasting, with no increase in Trhr1 expression and more pronounced reductions in Tshr, Tpo and Iyd. In EF males, these abnormalities were generally milder. In addition, postnatal day 14 (P14) serum leptin was markedly reduced in EF pups.

Discussion

A paternal excess of thyroid hormone during development modifies the endocrine programming and energy balance in the offspring in a sexually dimorphic manner, with baseline and dynamic range alterations in the leptin-melanocortin system and thyroid gland, and consequences for adiposity phenotypes. We conclude that thyroid hormone overexposure may have important implications for the non-genetic, inherited etiology of endocrine and metabolic pathologies.
Systematic analysis of the prognosis and immune infiltration of E2Fs in thyroid carcinoma
Authors: Fu Xinghao , Zhou Xing , Ji Feihong , He Qi , Qiu Xinguang
Published: July 2023

Purpose: To evaluate the diagnostic and prognostic utility of E2F transcription factors (E2Fs) in thyroid carcinoma (THCA) and their association with immune infiltration.

Methods: The transcription and protein levels of E2Fs in THCA tissues were examined using the R language and the Human Protein Atlas (HPA) database in this research. We utilized the UALCAN and GEPIA2 databases to analyze the association between the level of E2Fs and the clinicopathological features of THCA. The prognostic utility of E2F expression in THCA was studied using the R language and the Gene Set Cancer Analysis (GSCA) database. Over-representation analysis (ORA) and gene set enrichment analysis (GSEA) were employed to analyze the effect of E2F family members. The TISIDB database and Tumor Immune Estimation Resource (TIMER) database were utilized to investigate the relationship between E2F expression and the level of immune infiltration in thyroid cancer.

Results: E2Fs are highly conserved in thyroid carcinoma and rarely mutated. E2Fs are strongly expressed in THCA and are highly related with the clinicopathological stage of THCA. Patients with THCA have a poor prognosis when E2Fs are highly expressed. The function of E2Fs in THCA may be closely related to the renin–angiotensin system (Ras) signaling pathway, platelet-derived growth factor (PDGF) signaling pathway, apoptosis, and immune response. With regard to the immune infiltration, E2F expression and tumor-infiltrating lymphocytes exhibited a positive connection.

Conclusion: The level of E2Fs is connected with the prognosis and immune infiltration level in THCA, revealing that E2Fs may be a prognostic and immune infiltration cell marker in THCA patients.
Immunogenicity and reactogenicity of inactivated SARS-CoV-2 vaccines in healthy adults
Authors: Wu Yufei , Huang Ping , Xu Mingjie , Zhao Qianqian , Xu Yihui , Han Shuyi , Li Huanjie , Wang Yunshan
Published: July 2023

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly pathogenic to humans and has caused the ongoing coronavirus disease 2019 (COVID-19) pandemic. Vaccines are one of the efficient ways to prevent the viral infection. After COVID-19 vaccination, the monitoring of the dynamic change in neutralizing antibodies is necessary to determine booster requirements.

Methods

We estimated the effectiveness of the inactivated vaccines by monitoring dynamic SARS-CoV-2 neutralizing antibodies for over 2 years. Additionally, we also investigated the activation of T lymphocytes (CD3+ T cells) after three doses of the inactivated vaccine.

Result

The results showed that the rate of reduction of SARS-CoV-2 neutralizing antibody levels gradually showed after each booster dose. The IgG/IgM level at 9 months after the third vaccination were significantly higher than those at 6 months after the second dose (p<0.0001). The expression of CD25+T cell in 18–35 age group was significantly higher than that in the other groups. Nine months after the third dose (the time of last blood sample collection), the expression of CD25+T cell in the 18–35 age group was significantly higher than that at 6 months after the second dose. CD25+T cell in the 18-35 years old group was significantly higher than 6 months after the second vaccination.

Conclusion

CD25, a late activation marker of lymphocytes and high-activity memory T cell subgroup, exhibited higher levels at the later stages after vaccination. COVID-19 booster vaccination in older adults and regular testing of SARS-CoV-2 neutralizing antibodies are recommended. Booster doses should be administered if the antibody level falls below the 30% inhibition rate.
Cysticercus pisiformis-derived novel-miR1 targets TLR2 to inhibit the immune response in rabbits
Authors: Chen Guoliang , Pu Guiting , Wang Liqun , Li Yanping , Liu Tingli , Li Hong , Zhang Shaohua , Wang Xuelin , Liu Xiaolei , Luo Xuenong
Published: July 2023

Cysticercosis pisiformis, a highly prevalent parasitic disease worldwide, causes significant economic losses in the rabbit breeding industry. Previous investigations have identified a novel microRNA, designated as novel-miR1, within the serum of rabbit infected with Cysticercus pisiformis. In the present study, we found that C. pisiformis-derived novel-miR1 was released into the rabbit serum via exosomes. Through computational analysis using TargetScan, miRanda, and PITA, a total of 634 target genes of novel-miR1 were predicted. To elucidate the functional role of novel-miR1, a dual-luciferase reporter assay was utilized and demonstrated that novel-miR1 targets rabbit Toll-like receptor 2 (TLR2). Rabbit peripheral blood lymphocytes (PBLCs) were transfected with novel-miR1 mimic and mimic NC, and the in vitro experiments confirmed that novel-miR1 suppressed the expression of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 through the nuclear factor kappa B (NF-κB) pathway. In vivo experiments demonstrated that novel-miR1 was significantly upregulated during the 1–3 months following infection with C. pisiformis in rabbits. Notably, this upregulation coincided with a downregulation of TLR2, P65, pP65, TNF-α, IL-1β, and IL-6 in PBLCs. Collectively, these results indicate that the novel-miR1 derived from C. pisiformis inhibited the rabbits’ immune response by suppressing the NF-κB-mediated immune response. This immune modulation facilitates parasite invasion, survival, and establishment of a persistent infection.
Molecular signature associated with cladribine treatment in patients with multiple sclerosis
Authors: Fissolo Nicolas , Calvo-Barreiro Laura , Eixarch Herena , Boschert Ursula , Villar Luisa M. , Costa-Frossard Lucienne , Ferrer Mireia , Sanchez Alex , Borràs Eva , Sabidó Eduard , Espejo Carmen , Montalban Xavier , Comabella Manuel
Published: July 2023

Introduction

Little is known about the molecular profiling associated with the effect of cladribine in patients with multiple sclerosis (MS). Here, we aimed first to characterize the transcriptomic and proteomic profiles induced by cladribine in blood cells, and second to identify potential treatment response biomarkers to cladribine in patients with MS.

Methods

Gene, protein and microRNA (miRNA) expression profiles were determined by microarrays (genes, miRNAs) and mass spectrometry (proteins) in peripheral blood mononuclear cells (PBMCs) from MS patients after in vitro treatment with cladribine in its active and inactive forms. Two bioinformatics approaches to integrate the three obtained datasets were applied: (i) a multiomics discriminant analysis (DIABLO - Data Integration Analysis for Biomarker discovery using Latent variable approaches for Omics studies); and (ii) a multi-stage integration of features selected in differential expression analysis on each dataset and then merged. Selected molecules from the in vitro study were quantified by qPCR ex vivo in PBMCs from MS patients receiving cladribine.

Results

PBMCs treated in vitro with cladribine were characterized by a major downregulation of gene, protein, and miRNA expression compared with the untreated cells. An intermediate pattern between the cladribine-treated and untreated conditions was observed in PBMCs treated with cladribine in its inactive form. The differential expression analysis of each dataset led to the identification of four genes and their encoded proteins, and twenty-two miRNAs regulating their expression, that were associated with cladribine treatment. Two of these genes (PPIF and NHLRC2), and three miRNAs (miR-21-5p, miR-30b-5p, and miR-30e-5p) were validated ex vivo in MS patients treated with cladribine.

Discussion

By using a combination of omics data and bioinformatics approaches we were able to identify a multiomics molecular profile induced by cladribine in vitro in PBMCs. We also identified a number of biomarkers that were validated ex vivo in PBMCs from patients with MS treated with cladribine that have the potential to become treatment response biomarkers to this drug.
Nanocellulose from a colloidal material perspective
Authors: Sanchez-Salvador Jose Luis , Xu Hongyu , Balea Ana , Negro Carlos , Blanco Angeles
Published: July 2023

Cellulose nanomaterials present unique properties of interest for their many applications. Their behavior is mainly related to the colloidal properties that determine their self-assembly and stability mechanisms as well as their interaction with the particles present in different matrices. This review shows the state of the art of nanocellulose from a colloidal material perspective, from the approach of how to control these properties and their influence on the final products, such as drug delivery, coatings, nanocomposites, or tissue engineering, emphasizing the role of colloidal behavior in determining their performance.
Clinical efficacy and tendon integrity of patients with subscapularis tear by the technique of arthroscopic single external row repair
Authors: Zheng Weipeng , Weng Rui , Wu Xiaohang , Liu Zhijun , Liao Zhihao , Chen Sheng , Zheng Suming , Yi Zhiyong , Huang Xudong , Wei Hewei
Published: July 2023

Background

With the development of arthroscopic technology and equipment, arthroscopy can effectively repair the tear of the subscapular muscle. However, it is difficult to expose the subscapular muscle and operate it under a microscope. In this study, the SwiveLock® C external row anchor under arthroscopy was applied to repair the tear of the subscapular muscle in a single row, which is relatively easy to operate with reliable suture and fixation, and its efficacy was evaluated.

Purpose

This study aimed to assess the clinical efficacy and the tendon integrity of patients who had subscapularis tears by adopting the single-row repair technique with a SwiveLock® C external row anchor.

Methods

Patients who had the subscapular muscle tear either with or without retraction were included, and their follow-up time was at least 1 year. The degree of tendon injury was examined by magnetic resonance imaging (MRI) and confirmed by arthroscopy. The tendon was repaired in an arthroscopic manner by utilizing the single-row technique at the medial margin of the lesser tuberosity. One double-loaded suture SwiveLock® C anchor was applied to achieve a strong fixation between the footprint and tendon. The range of motion, pain visual simulation score, American Shoulder and Elbow Surgeons (ASES) score, and Constant score of shoulder joint were evaluated for each patient before the operation, 3 months after the operation, and at least 1 year after the operation.

Results

In total, 110 patients, including 31 males and 79 females, with an average age of 68.28 ± 8.73 years were included. Arthroscopic repair of the subscapular tendon with SwiveLock® C external anchor can effectively improve the range of motion of the shoulder joint. At the last follow-up, the forward flexion of the shoulder joint increased from 88.97 ± 26.33° to 138.38 ± 26.48° (P < 0.05), the abduction range increased from 88.86 ± 25.27° to 137.78 ± 25.64° (P < 0.05), the external rotation range increased from 46.37 ± 14.48° to 66.49 ± 14.15° (P < 0.05), and the internal rotation range increased from 40.03 ± 9.01° to 57.55 ± 7.43° (P < 0.05). The clinical effect is obvious. The constant shoulder joint score increased from 40.14 ± 15.07 to 81.75 ± 11.00 (P < 0.05), the ASES score increased from 37.88 ± 13.24 to 82.01 ± 9.65 (P < 0.05), and the visual analog scale score decreased from 5.05 ± 2.11 to 1.01 ± 0.85 (P < 0.05). In the 6th month after the operation, two cases (1.81%) were confirmed to have re-tears via MRI.

Conclusion

In this study, we repaired the subscapularis muscle with a single-row technique fixed by SwiveLock® C anchor and FiberWire® sutures and evaluated its efficacy. The results showed that the clinical effect of single-row arthroscopic repair was satisfactory and that reliable tendon healing could be achieved.
ATN profile classification across two independent prospective cohorts
Authors: Peretti Débora E. , Ribaldi Federica , Scheffler Max , Mu Linjing , Treyer Valerie , Gietl Anton F. , Hock Christoph , Frisoni Giovanni B. , Garibotto Valentina
Published: July 2023

Background

The ATN model represents a research framework used to describe in subjects the presence or absence of Alzheimer’s disease (AD) pathology through biomarkers. The aim of this study was to describe the prevalence of different ATN profiles using quantitative imaging biomarkers in two independent cohorts, and to evaluate the pertinence of ATN biomarkers to identify comparable populations across independent cohorts.

Methods

A total of 172 subjects from the Geneva Memory Clinic and 113 volunteers from a study on healthy aging at the University Hospital of Zurich underwent amyloid (A) and tau (T) PET, as well as T1-weigthed MRI scans using site-specific protocols. Subjects were classified by cognition (cognitively unimpaired, CU, or impaired, CI) based on clinical assessment by experts. Amyloid data converted into the standardized centiloid scale, tau PET data normalized to cerebellar uptake, and hippocampal volume expressed as a ratio over total intracranial volume ratio were considered as biomarkers for A, T, and neurodegeneration (N), respectively. Positivity for each biomarker was defined based on previously published thresholds. Subjects were then classified according to the ATN model. Differences among profiles were tested using Kruskal-Wallis ANOVA, and between cohorts using Wilcoxon tests.

Results

Twenty-nine percent of subjects from the Geneva cohorts were classified with a normal (A−T−N−) profile, while the Zurich cohort included 64% of subjects in the same category. Meanwhile, 63% of the Geneva and 16% of the Zurich cohort were classified within the AD continuum (being A+ regardless of other biomarkers’ statuses). Within cohorts, ATN profiles were significantly different for age and mini-mental state examination scores, but not for years of education. Age was not significantly different between cohorts. In general, imaging A and T biomarkers were significantly different between cohorts, but they were no longer significantly different when stratifying the cohorts by ATN profile. N was not significantly different between cohorts.

Conclusion

Stratifying subjects into ATN profiles provides comparable groups of subjects even when individual recruitment followed different criteria.
A cross-sectional study of the association between circulating sex hormone-binding globulin levels and selected adipokines in women with polycystic ovary syndrome
Authors: Ciura Dariusz , Owczarek Aleksander Jerzy , Franik Grzegorz , Kocełak Piotr , Markuszewski Leszek , Madej Paweł , Chudek Jerzy , Olszanecka-Glinianowicz Magdalena
Published: July 2023

Introduction

Changes in the proportion of pro-inflammatory and anti-inflammatory adipokines may reflect the accumulation of lipids in the liver and the development of insulin resistance. Both liver steatosis and insulin resistance result in decreased sex hormone-binding globulin (SHBG) synthesis. This study aimed to analyze associations between circulating SHBG and adipokines levels in women with polycystic ovary syndrome (PCOS).

Material and methods

A cross-sectional cohort study involved 87 women with phenotype A of PCOS (39 normal weight and 48 obese). Body mass, height, and waist circumference were measured, and BMI was calculated. In addition, body composition was assessed using the bioimpedance method. Serum SHBG levels and plasma apelin-36 and apelin-12, adiponectin, leptin, omentin-1, and RBP-4 were determined by using the ELISA method. The participants were divided into subgroups with SHBG concentrations above and below this lower limit [N = 35 (40.2%) and N = 52 (59.8%), respectively].

Results

The median adiponectin, apelin-12, and apelin-36 levels were significantly lower, and leptin levels were significantly higher in the subgroup with low SHBG levels than that in the subgroup above the lower limit of the reference range, while there were no differences in median omentin-1 and RBP-4 between the study subgroups. There were positive correlations between SHBG and omentin-1, adiponectin, apelin-36, and apelin-12 levels, as well as negative correlation with leptin levels. However, after adjustment by BMI, waist circumference, and body fat percentage, only the association between SHBG and omentin-1 remained significant.

Conclusion

Our results show associations between circulating SHBG and adipokine levels in women with PCOS and support the role of hormonal dysfunction of the adipose tissue in the pathogenesis of PCOS.
Antibodies against multiple post-translationally modified proteins aid in diagnosis of autoimmune hepatitis and associate with complete biochemical response to treatment
Authors: van den Beukel Michelle D. , Stoelinga Anna E. C. , van der Meer Adriaan J. , van der Meulen Stef , Zhang Lu , Tushuizen Maarten E. , van Hoek Bart , Trouw Leendert A.
Published: July 2023

Background

(Auto)immune mediated and cholestatic liver disease (AILD) includes autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Especially AIH is characterized by the presence of autoantibodies and elevated serum immunoglobulins. In rheumatoid arthritis, autoantibodies against post-translational modifications (PTMs) such as citrullination (Cit) and carbamylation (CarP) are used as diagnostic and prognostic markers, respectively. We studied the presence of six anti-PTM antibodies in patients with the three AILDs and non-AILD.

Methods

Antibodies against six PTMs (malondialdehyde–acetaldehyde adducts (MAA), advanced glycation end-products (AGE), CarP, acetylation (AL), Cit, and nitration (NT)) were tested in sera of patients with AILD (n = 106), non-AILD (n = 101) and compared with healthy controls (HC) (n = 100). Levels and positivity were correlated with clinical and biochemical features in a well-defined cohort of untreated AIH patients.

Results

Anti-PTM antibodies were more often detectable in sera from AILD patients compared with HCs (anti-MAA: 67.9% vs. 2.0%, anti-AGE: 36.8% vs. 4.0%, anti-CarP: 47.2% vs. 5.0% and anti-AL: 18.9% vs. 5.0%). In untreated AIH, time to complete biochemical response (CBR) was associated with anti-MAA, anti-AGE, anti-CarP and anti-AL antibodies. Significantly more patients with at least three anti-PTM antibodies attained CBR at 12  months of treatment (13 vs. 3 p = 0.01).

Conclusion

Anti-PTM antibodies are frequently present in AILD. The presence of anti-MAA, anti-AGE and anti-CarP antibodies correlates with the presence of AIH within this cohort. In AIH, harboring at least three anti-PTM antibody responses is positively associated with CBR. Determination of anti-PTM antibodies in liver disease may have diagnostic and prognostic value.
Subsequent maternal sleep deprivation aggravates neurobehavioral abnormalities, inflammation, and synaptic function in adult male mice exposed to prenatal inflammation
Authors: Zhang Yue-Ming , Zhang Meng-Ying , Wei Ru-Meng , Zhang Jing-Ya , Zhang Kai-Xuan , Luo Bao-Ling , Ge Yi-Jun , Kong Xiao-Yi , Li Xue-Yan , Chen Gui-Hai
Published: July 2023

Objective

Studies have suggested that prenatal exposure to inflammation increases the risk of neuropsychiatric disorders, including anxiety, depression, and cognitive dysfunction. Because of anatomical and hormonal alterations, pregnant women frequently experience sleep dysfunction, which can enhance the inflammatory response. The aim of this study was to explore the effects of maternal sleep deprivation on prenatal inflammation exposure-induced behavioral phenotypes in offspring and identify the associated mechanisms.

Methods

Pregnant mice received an intraperitoneal injection of lipopolysaccharide (LPS) on gestational day 15 and were subsequently subjected to sleep deprivation during gestational days 15–21. Anxiety-like behavior was evaluated by the open field test and the elevated plus maze test. Depression-like behavior was assessed by the tail suspension test and the forced swimming test. Cognitive function was determined using the Morris water maze test. The levels of markers of inflammation and synaptic function were examined employing general molecular biological techniques.

Results

The results showed that prenatal exposure to LPS resulted in anxiety- and depression-like symptoms and learning and memory deficits, and these effects were exacerbated by maternal sleep deprivation. Furthermore, maternal sleep deprivation aggravated the prenatal LPS exposure-induced increase in the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α and decrease in the levels of postsynaptic density-95 and synaptophysin in the hippocampus.

Discussion

Collectively, these results suggested that maternal sleep deprivation exacerbates anxiety, depression, and cognitive impairment induced by prenatal LPS exposure, effects that were associated with an inflammatory response and synaptic dysfunction.
Volume mismatch indicates tumors in paramedial bithalamic diseases: a retrospective study
Authors: Su Lu , Gao Peiyi
Published: July 2023

Objective

This study aimed to investigate the diagnostic performance of volume mismatch sign on discriminating paramedial bithalamic tumors from non-tumors.

Methods

In this study, we recruited patients with tumors or non-tumors of the paramedial bithalamus. We confirmed the diagnosis by pathology, laboratory tests documented in medical records, medical imaging at the baseline, or through at least 1 year of follow-up. Cases with paramedial thalamic lesions on only one side or purely midbrain illnesses were excluded. Additionally, any case without involvement of the medial thalami (i.e., those with one or both-sided anterior, lateral, or posterior thalamic lesions) was excluded. Two neuroradiologists were trained independently to evaluate volume mismatch sign on magnetic resonance T2-weighted images or T2 fluid-attenuated inversion recovery images. A positive volume mismatch sign means that the ratio of the larger-sided lesion volume to the smaller-sided lesion volume is >150%. The volume of each lesion was calculated by multiplying the anteroposterior diameter by the left-right diameter and by the height of the lesion and then dividing by 2. The kappa value was calculated to show the consistency between the two observers. The chi-square test was used to evaluate differences in volume mismatch sign between the bilthalamic midline tumor and non-tumor groups. The positive (PPV) and negative (NPV) predictive values, sensitivity, and specificity were calculated to evaluate the ability of volume mismatch sign to differentiate paramedial bilateral thalamus tumors from non-tumors. A two-tailed P ≤ 0.05 was considered to be statistically significant. The analyses were performed using the statistical software SPSS version 26.

Results

A total of 96 patients were enrolled in this study between March 2012 and October 2022. A high agreement between the two observers on the volume mismatch sign of bilateral paramedian thalamic diseases was found, and the Kappa value was 0.828. A statistically significant difference was observed for the volume mismatch sign between the paramedial bithalamic tumor and the non-tumorous groups (χ2 = 35.465, P < 0.001). The presence of volume mismatch sign in paramedial bithalamic illnesses predicted the presence of tumors with a sensitivity and specificity of 69.2% and 90.9%, respectively, and PPV and NPV were 90.0% and 71.4%.

Conclusion

Volume mismatch sign may indicate tumors in paramedian bithalamic diseases.
Management of metastatic colorectal cancer in patients ≥70 years - a single center experience
Authors: Huemer Florian , Dunkl Celine , Rinnerthaler Gabriel , Schlick Konstantin , Heregger Ronald , Emmanuel Klaus , Neureiter Daniel , Klieser Eckhard , Deutschmann Michael , Roeder Falk , Greil Richard , Weiss Lukas
Published: July 2023

Background

Age-standardized mortality rates for metastatic colorectal cancer (mCRC) are highest among elderly patients. In current clinical guidelines, treatment recommendations for this patient population are based on a limited number of clinical trials.

Patients and methods

In this monocentric, retrospective analysis we characterized patients aged ≥70 years undergoing systemic therapy for mCRC and overall survival (OS) was investigated.

Results

We included 117 unselected, consecutive mCRC patients aged ≥70 years undergoing systemic therapy for mCRC between February 2009 and July 2022. Median OS was 25.6 months (95% CI: 21.8-29.4). The median age was 78 years (range: 70-90) and 21%, 48%, 26% and 5% had an ECOG performance score of 0, 1, 2, and 3, respectively. The median number of systemic therapy lines was 2 (range: 1-5). The choice of first-line chemotherapy backbone (doublet/triplet versus mono) did not impact OS (HR: 0.83, p=0.50) or the probability of receiving subsequent therapy (p=0.697). Metastasectomy and/or local ablative treatment in the liver, lung, peritoneum and/or other organs were applied in 26 patients (22%) with curative intent. First-line anti-EGFR-based therapy showed a trend towards longer OS compared to anti-VEGF-based therapy or chemotherapy alone in left-sided mCRC (anti-EGFR: 39.3 months versus anti-VEGF: 27.3 months versus chemotherapy alone: 13.8 months, p=0.105). In multivariable analysis, metastasectomy and/or local ablative treatment with curative intent (yes versus no, HR: 0.22, p<0.001), the ECOG performance score (2 versus 0, HR: 3.07, p=0.007; 3 versus 0, HR: 3.66, p=0.053) and the presence of liver metastases (yes versus no, HR: 1.79, p=0.049) were independently associated with OS.

Conclusions

Our findings corroborate front-line monochemotherapy in combination with targeted therapy as the treatment of choice for elderly mCRC patients with palliative treatment intent. Metastasectomy and/or local ablative treatment with curative intent are feasible and may improve OS in selected elderly mCRC patients.