bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome and Physio-Biochemical Profiling Reveals Differential Responses of Rice Cultivars at Reproductive-Stage Drought Stress
Authors: Kaur Simardeep , Seem Karishma , Duhan Naveen , Kumar Suresh , Kaundal Rakesh , Mohapatra Trilochan
Published: January 2023

Drought stress severely affects the growth and development of rice, especially at the reproductive stage, which results in disturbed metabolic processes, reduced seed-set/grain filling, deteriorated grain quality, declined productivity, and lower yield. Despite the recent advances in understanding the responses of rice to drought stress, there is a need to comprehensively integrate the morpho-physio-biochemical studies with the molecular responses/differential expression of genes and decipher the underlying pathways that regulate the adaptability of rice at various drought-sensitive growth stages. Our comparative analysis of immature panicle from a drought-tolerant (Nagina 22) and a drought-sensitive (IR 64) rice cultivar grown under control (well-watered) and water-deficit/drought stress (treatment, imposed at the reproductive stage) conditions unraveled some novel stress-responsive genes/pathways responsible for reproductive-stage drought stress tolerance. The results revealed a more important role of upregulated (6706) genes in the panicle of N 22 at reproductive-stage drought stress compared to that (5590) in IR 64. Functional enrichment and MapMan analyses revealed that majority of the DEGs were associated with the phytohormone, redox signalling/homeostasis, secondary metabolite, and transcription factor-mediated mitigation of the adverse effects of drought stress in N 22. The upregulated expression of the genes associated with starch/sucrose metabolism, secondary metabolites synthesis, transcription factors, glutathione, linoleic acid, and phenylalanine metabolism in N 22 was significantly more than that in the panicle of IR 64. Compared to IR 64, 2743 genes were upregulated in N 22 under control conditions, which further increased (4666) under drought stress in panicle of the tolerant cultivar. Interestingly, we observed 6706 genes to be upregulated in the panicle of N 22 over IR 64 under drought and 5814 genes get downregulated in the panicle of N 22 over IR 64 under the stress. In addition, RT-qPCR analysis confirmed differential expression patterns of the DEGs. These genes/pathways associated with the reproductive-stage drought tolerance might provide an important source of molecular markers for genetic manipulation of rice for enhanced drought tolerance.
Obesity Modifies the Proteomic Profile of the Periodontal Ligament
Authors: Nogueira Andressa V. B. , Lopes Maria Eduarda S. , Marcantonio Camila C. , Salmon Cristiane R. , Mofatto Luciana S. , Deschner James , Nociti-Junior Francisco H. , Cirelli Joni A.
Published: January 2023

This study aimed to assess the obesity effects on the proteomic profile of the periodontal ligament of rats submitted to obesity induction by a high-fat diet. Eight Holtzman rats were divided into control (n = 3) and obese (n = 5) groups. The maxillae were histologically processed for laser capture microdissection of the periodontal ligament of the first maxillary molars. Peptide mixtures were analyzed by LC-MS/MS. A total of 1379 proteins were identified in all groups. Among them, 335 (24.30%) were exclusively detected in the obese group, while 129 (9.35%) proteins were uniquely found in the control group. Out of the 110 (7.98%) differentially abundant proteins, 10 were more abundant and 100 had decreased abundance in the obese group. A gene ontology analysis showed some proteins related to obesity in the “extracellular exosome” term among differentially identified proteins in the gene ontology cellular component terms Prelp, Sec13, and Sod2. These three proteins were upregulated in the obese group (p < 0.05), as shown by proteomic and immunohistochemistry analyses. In summary, our study presents novel evidence that the proteomic profile of the periodontal ligament is altered in experimental obesity induction, providing a list of differentially abundant proteins associated with obesity, which indicates that the periodontal ligament is responsive to obesity.
FABP4 Controls Fat Mass Expandability (Adipocyte Size and Number) through Inhibition of CD36/SR-B2 Signalling
Authors: Berger Emmanuelle , Géloën Alain
Published: January 2023

Adipose tissue hypertrophy during obesity plays pleiotropic effects on health. Adipose tissue expandability depends on adipocyte size and number. In mature adipocytes, lipid accumulation as triglycerides into droplets is imbalanced by lipid uptake and lipolysis. In previous studies, we showed that adipogenesis induced by oleic acid is signed by size increase and reduction of FAT/CD36 (SR-B2) activity. The present study aims to decipher the mechanisms involved in fat mass regulation by fatty acid/FAT-CD36 signalling. Human adipose stem cells, 3T3-L1, and its 3T3-MBX subclone cell lines were used in 2D cell cultures or co-cultures to monitor in real-time experiments proliferation, differentiation, lipolysis, and/or lipid uptake and activation of FAT/CD36 signalling pathways regulated by oleic acid, during adipogenesis and/or regulation of adipocyte size. Both FABP4 uptake and its induction by fatty acid-mediated FAT/CD36-PPARG gene transcription induce accumulation of intracellular FABP4, which in turn reduces FAT/CD36, and consequently exerts a negative feedback loop on FAT/CD36 signalling in both adipocytes and their progenitors. Both adipocyte size and recruitment of new adipocytes are under the control of FABP4 stores. This study suggests that FABP4 controls fat mass homeostasis.
Phosphatidylethanolamines Are Associated with Nonalcoholic Fatty Liver Disease (NAFLD) in Obese Adults and Induce Liver Cell Metabolic Perturbations and Hepatic Stellate Cell Activation
Authors: Shama Samaa , Jang Hyejeong , Wang Xiaokun , Zhang Yang , Shahin Nancy Nabil , Motawi Tarek Kamal , Kim Seongho , Gawrieh Samer , Liu Wanqing
Published: January 2023

Pathogenesis roles of phospholipids (PLs) in nonalcoholic fatty liver disease (NAFLD) remain incompletely understood. This study investigated the role of PLs in the progression of NAFLD among obese individuals via studying the alterations in serum PL composition throughout the spectrum of disease progression and evaluating the effects of specific phosphatidylethanolamines (PEs) on FLD development in vitro. A total of 203 obese subjects, who were undergoing bariatric surgery, were included in this study. They were histologically classified into 80 controls (C) with normal liver histology, 93 patients with simple hepatic steatosis (SS), 16 with borderline nonalcoholic steatohepatitis (B-NASH) and 14 with progressive NASH (NASH). Serum PLs were profiled by automated electrospray ionization tandem mass spectrometry (ESI-MS/MS). HepG2 (hepatoma cells) and LX2 (immortalized hepatic stellate cells or HSCs) were used to explore the roles of PL in NAFLD/NASH development. Several PLs and their relative ratios were significantly associated with NAFLD progression, especially those involving PE. Incubation of HepG2 cells with two phosphatidylethanolamines (PEs), PE (34:1) and PE (36:2), resulted in significant inhibition of cell proliferation, reduction of mitochondrial mass and membrane potential, induction of lipid accumulation and mitochondrial ROS production. Meanwhile, treatment of LX2 cells with both PEs markedly increased cell activation and migration. These effects were associated with a significant change in the expression levels of genes involved in lipogenesis, lipid oxidation, autophagy, apoptosis, inflammation, and fibrosis. Thus, our study demonstrated that elevated level of PEs increases susceptibility to the disease progression of obesity associated NAFLD, likely through a causal cascade of impacts on the function of different liver cells.
Proteome Mapping of Cervical Mucus and Its Potential as a Source of Biomarkers in Female Tract Disorders
Authors: Oždian Tomáš , Vodička Jan , Dostál Jiří , Holub Dušan , Václavková Jana , Ješeta Michal , Hamerníková Barbora , Kouřilová Pavla , Malchar Ondřej , Dvořák Vladimír , Hejtmánek Pavel , Sobková Kateřina , Ventruba Pavel , Pilka Radovan , Džubák Petr , Hajdúch Marián
Published: January 2023

Cervical mucus (CM) is a viscous fluid that is produced by the cervical glands and functions as a uterine cervix plug. Its viscosity decreases during ovulation, providing a window for non-invasive sampling. This study focuses on proteomic characterization of CM to evaluate its potential as a non-invasively acquired source of biomarkers and in understanding of molecular (patho)physiology of the female genital tract. The first objective of this work was to optimize experimental workflow for CM processing and the second was to assess differences in the proteomic composition of CM during natural ovulatory cycles obtained from intrauterine insemination (IUI) cycles and in vitro fertilization (IVF) cycles with controlled ovarian hyperstimulation. Proteomic analysis of CM samples revealed 4370 proteins involved in processes including neutrophil degranulation, cellular stress responses, and hemostasis. Differential expression analysis revealed 199 proteins enriched in IUI samples and 422 enriched in IVF. The proteins enriched in IUI were involved in phosphatidic acid synthesis, responses to external stimulus, and neutrophil degranulation, while those enriched in IVF samples were linked to neutrophil degranulation, formation of a cornified envelope and hemostasis. Subsequent analyses clarified the protein composition of the CM and how it is altered by hormonal stimulation of the uterus.
Profiling Microbial Communities in Idiopathic Granulomatous Mastitis
Authors: Ong Seeu Si , Xu Jia , Sim Choon Kiat , Khng Alexis Jiaying , Ho Peh Joo , Kwan Philip Kam Weng , Ravikrishnan Aarthi , Tan Kiat-Tee Benita , Tan Qing Ting , Tan Ern Yu , Tan Su-Ming , Putti Thomas Choudary , Lim Swee Ho , Tang Ee Ling Serene , Nagarajan Niranjan , Karnani Neerja , Li Jingmei , Hartman Mikael
Published: January 2023

Idiopathic granulomatous mastitis (IGM) is a rare and benign inflammatory breast disease with ambiguous aetiology. Contrastingly, lactational mastitis (LM) is commonly diagnosed in breastfeeding women. To investigate IGM aetiology, we profiled the microbial flora of pus and skin in patients with IGM and LM. A total of 26 patients with IGM and 6 patients with LM were included in the study. The 16S rRNA sequencing libraries were constructed from 16S rRNA gene amplified from total DNA extracted from pus and skin swabs in patients with IGM and LM controls. Constructed libraries were multiplexed and paired-end sequenced on HiSeq4000. Metagenomic analysis was conducted using modified microbiome abundance analysis suite customised R-resource for paired pus and skin samples. Microbiome multivariable association analyses were performed using linear models. A total of 21 IGM and 3 LM paired pus and skin samples underwent metagenomic analysis. Bray−Curtis ecological dissimilarity distance showed dissimilarity across four sample types (IGM pus, IGM skin, LM pus, and LM skin; PERMANOVA, p < 0.001). No characteristic dominant genus was observed across the IGM samples. The IGM pus samples were more diverse than corresponding IGM skin samples (Shannon and Simpson index; Wilcoxon paired signed-rank tests, p = 0.022 and p = 0.07). Corynebacterium kroppenstedtii, reportedly associated with IGM in the literature, was higher in IGM pus samples than paired skin samples (Wilcoxon, p = 0.022). Three other species and nineteen genera were statistically significant in paired IGM pus–skin comparison after antibiotic treatment adjustment and multiple comparisons correction. Microbial profiles are unique between patients with IGM and LM. Inter-patient variability and polymicrobial IGM pus samples cannot implicate specific genus or species as an infectious cause for IGM.
The Curcuminoid EF24 in Combination with TRAIL Reduces Human Renal Cancer Cell Migration by Decreasing MMP-2/MMP-9 Activity through a Reduction in H2O2
Authors: Ibáñez Gaspar Verónica , McMorrow Tara
Published: January 2023

Cancer cells present high levels of oxidative stress, and although an increase in reactive oxygen species (ROS), such as H2O2, can lead to apoptosis, it can also induce cell invasion and metastasis. As the increase in ROS can lead to an increase in the expression of MMP-2 and MMP-9, thus causing the degradation of the extracellular matrix, an increase in the ROS H2O2 might have an impact on MMP-2/MMP-9 activity. The natural compound curcumin has shown some anticancer effects, although its bioavailability hinders its therapeutic potential. However, curcumin and its analogues were shown to resensitize kidney cancer cells to TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. This study shows that the curcuminoid EF24 in combination with TRAIL increases peroxidase activity in the renal adenocarcinoma cell line ACHN, reducing the level of intracellular H2O2 and MMP-2/MMP-9 activity, a mechanism that is also observed after treatment with curcumin and TRAIL.
Amphiphilic Polypeptides Obtained by the Post-Polymerization Modification of Poly(Glutamic Acid) and Their Evaluation as Delivery Systems for Hydrophobic Drugs
Authors: Dzhuzha Apollinariia Yu. , Tarasenko Irina I. , Atanase Leonard Ionut , Lavrentieva Antonina , Korzhikova-Vlakh Evgenia G.
Published: January 2023

Synthetic poly(amino acids) are a unique class of macromolecules imitating natural polypeptides and are widely considered as carriers for drug and gene delivery. In this work, we synthesized, characterized and studied the properties of amphiphilic copolymers obtained by the post-polymerization modification of poly(α,L-glutamic acid) with various hydrophobic and basic L-amino acids and D-glucosamine. The resulting glycopolypeptides were capable of forming nanoparticles that exhibited reduced macrophage uptake and were non-toxic to human lung epithelial cells (BEAS-2B). Moreover, the developed nanoparticles were suitable for loading hydrophobic cargo. In particular, paclitaxel nanoformulations had a size of 170–330 nm and demonstrated a high cytostatic efficacy against human lung adenocarcinoma (A549). In general, the obtained nanoparticles were comparable in terms of their characteristics and properties to those based on amphiphilic (glyco)polypeptides obtained by copolymerization methods.
Transcripts of the Prostate Cancer-Associated Gene ANO7 Are Retained in the Nuclei of Prostatic Epithelial Cells
Authors: Metsälä Olli , Wahlström Gudrun , Taimen Pekka , Kellokumpu-Lehtinen Pirkko-Liisa , Schleutker Johanna
Published: January 2023

Prostate cancer affects millions of men globally. The prostate cancer-associated gene ANO7 is downregulated in advanced prostate cancer, whereas benign tissue and low-grade cancer display varying expression levels. In this study, we assess the spatial correlation between ANO7 mRNA and protein using fluorescent in situ hybridization and immunohistochemistry for the detection of mRNA and protein in parallel sections of tissue microarrays prepared from radical prostatectomy samples. We show that ANO7 mRNA and protein expression correlate in prostate tissue. Furthermore, we show that ANO7 mRNA is enriched in the nuclei of the luminal cells at 89% in benign ducts and low-grade cancer, and at 78% in high-grade cancer. The nuclear enrichment of ANO7 mRNA was validated in prostate cancer cell lines 22Rv1 and MDA PCa 2b using droplet digital polymerase chain reaction (ddPCR) on RNA isolated from nuclear and cytoplasmic fractions of the cells. The nuclear enrichment of ANO7 mRNA was compared to the nuclearly-enriched lncRNA MALAT1, confirming the surprisingly high nuclear retention of ANO7 mRNA. ANO7 has been suggested to be used as a diagnostic marker and a target for immunotherapy, but a full comprehension of its role in prostate cancer progression is currently lacking. Our results contribute to a better understanding of the dynamics of ANO7 expression in prostatic tissue.
Resequencing of 410 Sesame Accessions Identifies SINST1 as the Major Underlying Gene for Lignans Variation
Authors: Dossou Senouwa Segla Koffi , Song Shengnan , Liu Aili , Li Donghua , Zhou Rong , Berhe Muez , Zhang Yanxin , Sheng Chen , Wang Zhijian , You Jun , Wang Linhai
Published: January 2023

Sesame is a promising oilseed crop that produces specific lignans of clinical importance. Hence, a molecular description of the regulatory mechanisms of lignan biosynthesis is essential for crop improvement. Here, we resequence 410 sesame accessions and identify 5.38 and 1.16 million SNPs (single nucleotide polymorphisms) and InDels, respectively. Population genomic analyses reveal that sesame has evolved a geographic pattern categorized into northern (NC), middle (MC), and southern (SC) groups, with potential origin in the southern region and subsequent introduction to the other regions. Selective sweeps analysis uncovers 120 and 75 significant selected genomic regions in MC and NC groups, respectively. By screening these genomic regions, we unveiled 184 common genes positively selected in these subpopulations for exploitation in sesame improvement. Genome-wide association study identifies 17 and 72 SNP loci for sesamin and sesamolin variation, respectively, and 11 candidate causative genes. The major pleiotropic SNPC/A locus for lignans variation is located in the exon of the gene SiNST1. Further analyses revealed that this locus was positively selected in higher lignan content sesame accessions, and the “C” allele is favorable for a higher accumulation of lignans. Overexpression of SiNST1C in sesame hairy roots significantly up-regulated the expression of SiMYB58, SiMYB209, SiMYB134, SiMYB276, and most of the monolignol biosynthetic genes. Consequently, the lignans content was significantly increased, and the lignin content was slightly increased. Our findings provide insights into lignans and lignin regulation in sesame and will facilitate molecular breeding of elite varieties and marker-traits association studies.
Zero-Shot Blind Learning for Single-Image Super-Resolution
Authors: Yamawaki Kazuhiro , Han Xian-Hua
Published: January 2023

Deep convolutional neural networks (DCNNs) have manifested significant performance gains for single-image super-resolution (SISR) in the past few years. Most of the existing methods are generally implemented in a fully supervised way using large-scale training samples and only learn the SR models restricted to specific data. Thus, the adaptation of these models to real low-resolution (LR) images captured under uncontrolled imaging conditions usually leads to poor SR results. This study proposes a zero-shot blind SR framework via leveraging the power of deep learning, but without the requirement of the prior training using predefined imaged samples. It is well known that there are two unknown data: the underlying target high-resolution (HR) images and the degradation operations in the imaging procedure hidden in the observed LR images. Taking these in mind, we specifically employed two deep networks for respectively modeling the priors of both the target HR image and its corresponding degradation kernel and designed a degradation block to realize the observation procedure of the LR image. Via formulating the loss function as the approximation error of the observed LR image, we established a completely blind end-to-end zero-shot learning framework for simultaneously predicting the target HR image and the degradation kernel without any external data. In particular, we adopted a multi-scale encoder–decoder subnet to serve as the image prior learning network, a simple fully connected subnet to serve as the kernel prior learning network, and a specific depthwise convolutional block to implement the degradation procedure. We conducted extensive experiments on several benchmark datasets and manifested the great superiority and high generalization of our method over both SOTA supervised and unsupervised SR methods.
A Story of PA/BSA and Biomarkers to Diagnose Pulmonary Hypertension in Patients with Severe Aortic Valve Stenosis—The Rise of IGF-BP2 and GDF-15
Authors: Kletzer Joseph , Hecht Stefan , Ramsauer Susanne , Scharinger Bernhard , Kaufmann Reinhard , Kammler Jürgen , Kellermair Jörg , Akbari Kaveh , Blessberger Hermann , Steinwender Clemens , Hergan Klaus , Hoppe Uta C. , Lichtenauer Michael , Boxhammer Elke
Published: January 2023

(1) Background: Currently, echocardiography is the primary non-invasive diagnostic method used to screen patients with severe aortic valve stenosis (AS) for pulmonary hypertension (PH) by estimating systolic pulmonary artery pressure (sPAP). Other radiological methods have been a focus of research in the past couple of years, as it was shown that by determining the pulmonary artery (PA) diameter, prognostic statements concerning overall mortality could be made in these patients. This study compared established and novel cardiovascular biomarkers with the PA/BSA value to detect PH in patients with severe AS. (2) Methods: The study cohort comprised 188 patients with severe AS undergoing transcatheter aortic valve replacement (TAVR), who were then divided into two groups based on PA/BSA values obtained through CT-angiography. The presence of PH was defined as a PA/BSA ≥ 16.6 mm/m2 (n = 81), and absence as a PA/BSA < 16.6 mm/m2 (n = 107). Blood samples were taken before TAVR to assess cardiovascular biomarkers used in this study, namely brain natriuretic peptide (BNP), cardiac troponin I (cTnI), high-sensitive troponin (hsTN), soluble suppression of tumorigenesis-2 (sST2), growth/differentiation factor 15 (GDF-15), heart-type fatty acid-binding protein (H-FABP), insulin-like growth factor binding protein 2 (IGF-BP2), and soluble urokinase-type plasminogen activator receptor (suPAR). (3) Results: Patients with a PA/BSA ≥ 16.6 mm/m2 showed significantly higher levels of BNP (p = <0.001), GDF-15 (p = 0.040), and H-FABP (p = 0.007). The other investigated cardiovascular biomarkers did not significantly differ between the two groups. To predict a PA/BSA ≥ 16.6 mm/m2, cut-off values for the biomarkers were calculated. Here, GDF-15 (p = 0.029; cut-off 1172.0 pg/mL) and BNP (p < 0.001; cut-off 2194.0 pg/mL) showed significant results. Consequently, analyses of combined biomarkers were performed, which yielded IGF-BP2 + BNP (AUC = 0.721; 95%CI = 0.585–0.857; p = 0.004) as the best result of the two-way analyses and GDF-15 + IGF-BP2 + BNP (AUC = 0.727; 95%CI = 0.590–0.864; p = 0.004) as the best result of the three-way analyses. No significant difference regarding the 1-year survival between patients with PA/BSA < 16.6 mm/m2 and patients with PA/BSA ≥ 16.6 mm/m2 was found (log-rank test: p = 0.452). (4) Conclusions: Although PA/BSA aims to reduce the bias of the PA value caused by different body compositions and sizes, it is still a controversial parameter for diagnosing PH. Combining the parameter with different cardiovascular biomarkers did not lead to a significant increase in the diagnostic precision for detecting PH in patients with severe AS.
GRADE Use in Evidence Syntheses Published in High-Impact-Factor Gynecology and Obstetrics Journals: A Methodological Survey
Authors: Yang Hui-Juan , Zhang De-Yu , Hao Ying-Ying , Xu He-Li , Li Yi-Zi , Zhang Shuang , Li Xin-Yu , Gong Ting-Ting , Wu Qi-Jun
Published: January 2023

Objective: To identify and describe the certainty of evidence of gynecology and obstetrics systematic reviews (SRs) using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Method: Database searches of SRs using GRADE, published between 1 January 2016 to 31 December 2020, in the 10 “gynecology and obstetrics” journals with the highest impact factor, according to the Journal Citation Report 2019. Selected studies included those SRs using the GRADE approach, used to determine the certainty of evidence. Results: Out of 952 SRs, ninety-six SRs of randomized control trials (RCTs) and/or nonrandomized studies (NRSs) used GRADE. Sixty-seven SRs (7.04%) rated the certainty of evidence for specific outcomes. In total, we identified 946 certainty of evidence outcome ratings (n = 614 RCT ratings), ranging from very-low (42.28%) to low (28.44%), moderate (17.65%), and high (11.63%). High and very low certainty of evidence ratings accounted for 2.16% and 71.60% in the SRs of NRSs, respectively, compared with 16.78% and 26.55% in the SRs of RCTs. In the SRs of RCTs and NRSs, certainty of evidence was mainly downgraded due to imprecision and bias risks. Conclusions: More attention needs to be paid to strengthening GRADE acceptance and building knowledge of GRADE methods in gynecology and obstetrics evidence synthesis.
RANKL Is Independently Associated with Increased Risks of Non-Alcoholic Fatty Liver Disease in Chinese Women with PCOS: A Cross-Sectional Study
Authors: Lu Nan , Shan Chang , Fu Jia-Rong , Zhang Yi , Wang Yu-Ying , Zhu Yu-Chen , Yu Jie , Cai Jie , Li Sheng-Xian , Tao Tao , Liu Wei
Published: January 2023

Women with polycystic ovarian syndrome (PCOS) are more likely to have non-alcoholic fatty liver disease (NAFLD) than non-PCOS women; however, the exact mechanism underlying this trend is unknown. The receptor activator of NF-κB ligand (RANKL) is strongly involved in bone metabolism and has multiple functions. Recent studies suggest that RANKL is implicated in hepatic insulin resistance (IR), which is the highest risk factor for NAFLD. This study aimed to assess the role of RANKL in NAFLD in Chinese women with PCOS. A cross-sectional observational study was conducted on women newly diagnosed with PCOS, which included 146 patients with NAFLD and 142 patients without NAFLD. Sex hormones, glucose, insulin, and lipids were measured, and anthropometric data were collected. The concentration of serum total RANKL was measured using commercial ELISA kits. PCOS patients with NAFLD had a significantly higher mean age, body mass index (BMI), waist circumference (WC), and worsened metabolic profile than non-NAFLD subjects. The concentrations of high-sensitivity C-reactive protein, total cholesterol, and low-density lipoprotein cholesterol increased with the RANKL tertile (p for trend = 0.023, 0.026, and 0.035, respectively). A significantly positive association was found between RANKL (per SD change) and the risks of NAFLD (OR = 1.545, 95% CI = 1.086–2.199) after adjusting for confounders, including demographic factors, metabolic markers, and sex hormones. Subgroup multivariate logistic analyses stratified by age, BMI, and WC showed the same tendency. In addition, the positive association between RANKL and NAFLD seemed more prominent in lean patients with a BMI < 24 kg/m2 (OR = 1.70, 95% CI = 1.06–2.75) when compared to overweight/obesity subjects. Therefore, this study suggests that RANKL is positively associated with the increased risk of NAFLD in Chinese women with PCOS, independent of metabolic and reproductive factors.
Amniocentesis—When It Is Clear That It Is Not Clear
Authors: Ciortea Razvan , Malutan Andrei Mihai , Bucuri Carmen Elena , Berceanu Costin , Rada Maria Patricia , Ormindean Cristina Mihaela , Mihu Dan
Published: January 2023

A fetus identified to be at risk for chromosomal abnormalities may benefit from identification of genetic defects through amniocentesis. Although the risks associated with amniocentesis are considered to be minimal, being an invasive procedure it is not completely without complications. Background and Objectives: The current study aims to identify correlations between blood contamination of samples collected during amniocentesis and certain factors dependent on the instruments used (thickness of the needle used to aspirate the fluid), the location of the placenta, and uterine vascularity (more pronounced in multiparous patients). Materials and Methods: The study included 190 patients in the second trimester of pregnancy who met one of the criteria for invasive prenatal diagnosis (age over 35 years, high risk in first trimester screening, history of pregnancies with genetic abnormalities, etc.). The amniotic fluid samples collected from these patients were analyzed in terms of blood contamination of the amniotic fluid aspirated with maternal cells Results: Of the patients in whom the procedure was performed using 21 G size needles, 16 samples (13.33% of the total) were contaminated. None of the samples collected from patients where a 20 G needle was used were contaminated. There was a statistically significant association between the lack of contamination and the use of Doppler ultrasound in multiparous patients with anterior placenta in whom a 21-gauge needle was used for amniocentesis. Conclusions: There is an increased rate of sample contamination (statistically significant) when using 21 G needle sizes and a significant difference in contamination between primiparous and multiparous patients, with contamination being more frequent in multiparous patients. The use of Doppler ultrasonography may benefit the procedure, as the contamination rate was significantly reduced when used during amniocentesis.
Clinical Impact of Recipient-Derived Isoagglutinin Levels in ABO-Incompatible Hematopoietic Stem Cell Transplantation
Authors: Nam Minjeong , Hur Mina , Kim Hanah , Lee Tae-Hwan , Lee Gun-Hyuk , Yoon Sumi , Park Seungman , Kim Sung Yong , Lee Mark Hong
Published: January 2023

ABO incompatibility is not considered a contraindication for hematopoietic stem cell transplantation (HSCT). We hypothesized that recipient-derived isoagglutinin (RDI) levels could play a critical role in clinical outcomes. In this study, we compared clinical outcomes such as survival, GVHD, infection, relapse, transfusion, and engraftment, among ABO-compatible patients (ABOc), ABO-incompatible patients (ABOi) with low RDI, and ABOi patients with high RDI. The ABOi with high RDI group was defined as recipients with more than 1:16 RDI levels. We analyzed 103 recipients (ABOc, 53; ABOi with low RDI, 36; ABOi with high RDI, 14). The ABOi with high RDI group showed a decreased 1-year survival and increased acute GVHD grade IV and RBC transfusion (p = 0.017, 0.027, and 0.032, respectively). The ABOi with high RDI group was an independent risk factor for increased death, RBC transfusion, and poor platelet (PLT) engraftment (odds ratio (OR) = 3.20, p = 0.01; OR = 8.28, p = 0.02; OR = 0.18, p = 0.03, respectively). The ABOi with high RDI group showed significantly delayed PLT engraftment. In conclusion, this is the first study underscoring high RDI levels as a marker predicting unfavorable outcomes in ABOi HSCT.
Association between Remote Dielectric Sensing and Estimated Plasma Volume to Assess Body Fluid Distribution
Authors: Imamura Teruhiko , Izumida Toshihide , Narang Nikhil , Onoda Hiroshi , Nakagaito Masaki , Tanaka Shuhei , Nakamura Makiko , Ushijima Ryuichi , Fujioka Hayato , Kakeshita Kota , Kinugawa Koichiro
Published: January 2023

Background: Pulmonary congestion is quantified by a remote dielectric sensing (ReDSTM) system, while systemic congestion is estimated by calculated plasma volume. The type of clinical patient profile as defined by the ReDS system and calculated plasma volume remains uncertain. Methods: Hospitalized patients with or without heart failure were included in this prospective study. On admission, ReDS values were measured and plasma volume status (PVS) was estimated using their body weight at the same time. Cutoffs of ReDS value and PVS were defined at 34% and −2.7%, respectively. The association between the two parameters was assessed. Results: A total of 482 patients (median 76 years, 288 men) were included. The median ReDS value was 28% (25%, 32%) and median PVS was −16.4% (−26.3%, −5.9%). Of the patients, 64 had high ReDS value (and low PVS) and 80 had high PVS (and low ReDS value). The high ReDS group had a higher prevalence of clinical heart failure with a more elevated echocardiographic E/e’ ratio, whereas the high PVS group had a higher prevalence of chronic kidney disease (p < 0.05 for all). Four out of a total of six patients with high ReDS value and high PVS had both heart failure and chronic kidney disease profiles. Conclusion: The combination of ReDS value and PVS was able to clinically stratify the types of body fluid distribution and patient profiles. Utilizing these tools may assist the clinician in constructing a therapeutic strategy for the at-risk hospitalized patient.
Role of Surgery for Pancreatic Ductal Adenocarcinoma in the Era of Multidisciplinary Treatment
Authors: Takagi Kosei , Umeda Yuzo , Yoshida Ryuichi , Fuji Tomokazu , Yasui Kazuya , Yagi Takahito , Fujiwara Toshiyoshi
Published: January 2023

The incidence and mortality rates of pancreatic ductal adenocarcinoma (PDAC) have increased in recent years worldwide [...]
Crohn’s Disease-Associated and Cryptoglandular Fistulas: Differences and Similarities
Authors: Zhou Zhou , Ouboter Laura F. , Peeters Koen C. M. J. , Hawinkels Lukas J. A. C. , Holman Fabian , Pascutti Maria F. , Barnhoorn Marieke C. , van der Meulen-de Jong Andrea E.
Published: January 2023

Perianal fistulas are defined as pathological connections between the anorectal canal and the perianal skin. Most perianal fistulas are cryptoglandular fistulas, which are thought to originate from infected anal glands. The remainder of the fistulas mainly arises as complications of Crohn’s disease (CD), trauma, or as a result of malignancies. Fistulas in CD are considered as a consequence of a chronic and transmural inflammatory process in the distal bowel and can, in some cases, even precede the diagnosis of CD. Although both cryptoglandular and CD-associated fistulas might look similar macroscopically, they differ considerably in their complexity, treatment options, and healing rate. Therefore, it is of crucial importance to differentiate between these two types of fistulas. In this review, the differences between CD-associated and cryptoglandular perianal fistulas in epidemiology, pathogenesis, and clinical management are discussed. Finally, a flow chart is provided for physicians to guide them when dealing with patients displaying their first episode of perianal fistulas.
Patient Care Satisfaction and Emergency Room Utilization among Young Adult Colorectal Cancer Survivors during the SARS-CoV-2 Pandemic: Lessons Learned
Authors: Kagramanov Dalia , Miller Kimberly A. , Gallagher Phuong , Freyer David R. , Milam Joel E. , Lenz Heinz-Josef , Barzi Afsaneh
Published: January 2023

Introduction: Survivors of colorectal cancer (CRC) are at risk for late effects of therapy and recurrence of cancer. With recurrence rates ranging between 30–40%, follow-up care is needed for both early detection and management of late effects. Cancer care delivery for CRC patients was significantly disrupted by the SARS-CoV-2 pandemic, with decreases of 40% in such services in the United States between April 2020 and 2019. Survivors were left with fewer options for care, potentially causing increases in emergency room (ER) utilization. Methods: This cross-sectional study examined the patterns of ER utilization during the SARS-CoV-2 pandemic among young adult CRC survivors and assessed the relationship between self-reported care satisfaction and ER use. Eligible participants were colon or rectal cancer survivors diagnosed between 18–39 years of age, 6–36 months from diagnosis/relapse, English speaking and residing in the United States. Multivariable logistic regression assessed the association between patient care satisfaction and ER utilization, adjusting for pandemic factors. Covariates were chosen by significance of p < 0.1 at the univariate level and perceived clinical significance. Results: The overall sample (N = 196) had mean age (SD) 32.1 (4.5); 59% were male. Tumor location was colon or rectal in 42% and 57%, respectively, and the majority (56%) were diagnosed with stage 2 disease; 42.6% reported relapsed disease, and 20% had an ostomy. Most survivors (72.5%) had between 1–4 visits to an ER in the last 12 months and were categorized as normal utilizers. Approximately 24.7% of the sample had greater than 4 visits to the ER in the last 12 months and were categorized as super-utilizers. CRC survivors that reported a delay in their follow-up care as a result of the pandemic were two times (OR: 2.05, 95% CI 0.99, 4.24) more likely to be super-utilizers of the ER. Higher self-reported satisfaction with care was associated with a 13.7% lower likelihood of being a super-utilizer (OR: 0.86, 95%CI: −0.68, 1.09). Conclusions: This study found strong associations between delays in care, self-reported care satisfaction, and being a super-utilizer of the ER during the pandemic among young adult CRC survivors off treatment. Increasing patient satisfaction and minimizing care interruptions amongst this vulnerable population may aid in mitigating over-utilization in the ER during an ongoing pandemic.
A Novel Hair Restoration Technology Counteracts Androgenic Hair Loss and Promotes Hair Growth in A Blinded Clinical Trial
Authors: Thor Dominik , Pagani Andrea , Bukowiecki Julia , Houschyar Khosrow S. , Kølle Stig-Frederik T. , Wyles Saranya P. , Duscher Dominik
Published: January 2023

Androgenic alopecia (AGA) is a genetically predetermined condition that occurs as a result of stepwise miniaturization of the dermal papilla. During this process, the hair follicle suffers from increasing malnutrition and eventually dies, causing progressive hair loss. We recently highlighted that HIF-1α modulation may counteract hair loss. Here, we aim to demonstrate the positive influence of Tomorrowlabs HIF strengthening factor [HSF] hair restoration technology on hair biology in a monocentric blinded clinical trial over a total period of 9 months. A trial with 20 subjects (4 female and 16 male) and once-daily application of [HSF] hair restoration technology to the scalp was conducted. To assess the tolerability and efficacy of [HSF], testing included dermatological assessment, determination of hair loss by counting after combing, macro images of the head and TrichoScan evaluation of hair density as well as the proportion of anagen hair versus telogen hair. The clinical data show Tomorrowlabs [HSF] hair restoration to be safe and effective to counteract AGA. The use of Tomorrowlabs [HSF] hair restoration resulted in improvements in the clinical parameters of hair quality such as thickness (+7.2%), hair density (+14.3%) and shine and elasticity (+20.3%) during the test period. The effectiveness of the test product was further determined by a significant reduction in hair loss of an average of 66.8% in treatment-responsive subjects after 6 months and an increase in hair growth reaching up to 32.5%, with an average percentage change of 8.4% in all participants and 10.8% in the responsive patients (85% of the study cohort) after 9 months on TrichoScan evaluation. The hair growth cycle was harmonized with the result of an average anagen hair percentage increase of +8.0% and telogen hair percentage reduction of −14.0% shown in the test area. Applicable for both sexes in an alcohol-free formulation, beneficial to scalp health and free of complications or side effects, this novel product provides objectively measurable results counteracting hair loss paired with an improved look and feel of the hair.
Three-Dimensional-Enabled Surgical Planning for the Correction of Right Partial Anomalous Pulmonary Venous Return
Authors: Cattapan Claudia , Guariento Alvise , Bifulco Olimpia , Caraffa Raphael , Bertelli Francesco , Reffo Elena , Padalino Massimo , Di Salvo Giovanni , Vida Vladimiro
Published: January 2023

Objectives: The surgical technique for right partial anomalous pulmonary venous return (PAPVR) depends on the location of the anomalous pulmonary veins (PVs). With this in mind, we sought to evaluate the impact of 3D heart segmentation and reconstruction on preoperative surgical planning. Methods: A retrospective study was conducted on all patients who underwent PAPVR repair at our institution between January 2018 and October 2021; three-dimensional segmentations and reconstructions of all the heart anatomies were performed. A score (the PAPVR score) was established and calculated using two anatomical parameters (the distance between the most cranial anomalous PV and the superior rim of the sinus venosus defect/the sum of the latter and the distance between the PV and the azygos vein) to predict the type of correction. Results: A total of 30 patients were included in the study. The PAPVR score was found to be a good predictor of the type of surgery performed. A value > 0.68 was significantly associated with a Warden procedure (p < 0.001) versus single/double patch repair. Conclusions: Three-dimensional heart segmentations and reconstructions improve the quality of surgical planning in the case of PAPVR and allow for the introduction of a score that may facilitate surgical decisions on the type of repair required.
Identification of a Novel Non-Canonical Splice-Site Variant in ABCD1
Authors: Zheng Feixia , Lin Zhongdong , Hu Ying , Shi Xulai , Zhao Qianlei , Lin Zhenlang
Published: January 2023

Cerebral adrenoleukodystrophy (CALD) is a fatal genetic disease characterized by rapid, devastating neurological decline, with a narrow curative treatment window in the early stage. Non-canonical splice-site (NCSS) variants can easily be missed during genomic DNA analyses, and only a few of them in ABCD1 have been explored. Here, we studied a Chinese patient with clinical features similar to those of early-stage CALD but with a negative molecular diagnosis and a sibling who had presumably died of CALD. Trio-based whole-exome sequencing (trio-WES) and RNA sequencing (RNA-Seq) revealed a novel hemizygote NCSS variant c.901-25_901-9 del in ABCD1 intron 1, resulting in a complex splicing pattern. The in vitro minigene assay revealed that the c.901-25_901-9 del construct contained two aberrant transcripts that caused skipping of exon 2 and a small 48-bp deletion on left of the same exon. We identified a novel NCSS variant, that extends the spectrum of the known ABCD1 variants, and demonstrated the pathogenicity of this gene variant. Our findings highlight the importance of combining RNA-Seq and WES techniques for prompt diagnosis of leukodystrophy with NCSS variants.
High- vs. Low-Intensity Statin Therapy and Changes in Coronary Artery Calcification Density after One Year
Authors: Vogel Lukas Hermann , Dykun Iryna , Raggi Paolo , Schmermund Axel , Rassaf Tienush , Mahabadi Amir Abbas
Published: January 2023

Background: Statin therapy promotes the progression of coronary artery calcification (CAC). Comparing patients on high (HIST) vs. low-to-intermediate intensity statin therapy (LIST), randomized controlled trials with a one-year follow-up failed to document a relevant difference in the Agatston score and CAC volume. We evaluated whether statin intensity modifies CAC density at one year. Methods: We performed a pooled analysis of two randomized-controlled trials (BELLES, EBEAT), comparing the effects of HIST (Atorvastatin 80 mg) vs. LIST (Pravastatin 40 mg, Atorvastatin 10 mg) on CAC measures after one year. The differences in CAC density and its change were compared using the two-sided t-test. Results: Data from 852 patients (66.7% female) with available baseline and follow-up CT were evaluated from both trials. HIST vs. LIST more effectively reduced LDL-cholesterol (annualized change: −45.8 ± 38.5 vs. −72.9 ± 46.0 mg/dL, p < 0.001). Mean CAC density increased from 228.8 ± 35.4 HU to 232.6 ± 37.0 HU (p < 0.0001) at one-year follow-up. Comparing patients on HIST vs. LIST, CAC density at follow-up (HIST: 231.9 ± 36.1 HU vs. LIST: 233.3 ± 37.7 HU, p = 0.59) and its change from baseline (HIST: 4.0 ± 19.1 HU vs. LIST: 3.6 ± 19.6 HU, p = 0.73) did not differ. Subgroup analyses, stratifying by LDL reduction (<median: 2.0 ± 24.3 HU, ≥median: 3.6 ± 21.9 HU, p = 0.34), Agatston score at baseline (<100: 2.6 ± 22.5 HU vs. 3.2 ± 25.6 HU, p = 0.82; ≥100: 4.8 ± 17.0 HU vs. 3.8 ± 16.6 HU, p = 0.44, for HIST vs. LIST; respectively), and equal number of lesions in both CT scans (3.7 ± 20.3 HU vs. 7.0 ± 22.2 HU, p = 0.24) showed similar results. Conclusion: HIST vs. LIST leads to a higher reduction in cholesterol levels, which does not translate into relevant differences in the change of CAC density at one-year follow-up.
Fabrication Temperature-Related Porosity Effects on the Mechanical Properties of Additively Manufactured CFRP Composites
Authors: Adeniran Olusanmi , Osa-uwagboe Norman , Cong Weilong , Ramoni Monsuru
Published: January 2023

The use of additive manufacturing in fabricating composite components has been gaining traction in the past decade. However, some issues with mechanical performance still need to be resolved. The issue of material porosity remains a pertinent one which needs more understanding to be able to come up with more viable solutions. Different researchers have examined the subject; however, more research to quantitatively determine fabrication temperatures effects at the micro-scale are still needed. This study employed micro-CT scan analysis to quantitatively compare fabrication temperatures effect at 230 °C, 250 °C, 270 °C, and 290 °C on the mechanical properties of AM fabricated carbon-fiber-reinforces plastic (CFRP) composites, testing carbon fiber-reinforced polyamide (CF-PA) and carbon fiber-reinforced acrylonitrile butadiene styrene (CF-ABS) samples. This micro-CT examination followed an SEM evaluation, which was used to determine temperature effects on interlayer and intralayer porosity generation. The porosity volume was related to the mechanical properties, in which it was determined how temperatures influence porosity volumes. It was also determined that fabrication temperature generally affects semicrystalline composites more than amorphous composites. The overall porosity volumes from the interlayer and intralayer voids were determined, with the interlayer voids being more influential in influencing the mechanical properties.
Ion-Mediated Self-Assembly of Graphene Oxide and Functionalized Perylene Diimides into Hybrid Materials with Photocatalytic Properties
Authors: Sokolov Maksim , Nugmanova Alsu , Shkolin Andrey , Zvyagina Alexandra , Senchikhin Ivan , Kalinina Maria
Published: January 2023

A novel ion-mediated self-assembly method was applied for integration of graphene oxide (GO), propanoic- and glutaric-substituted perylenes (glu-PDI and PA-PDI), and Zn (OAc)2 into new hybrid materials with photocatalytic properties. The structuring of chromophores through coordination bonding on the GO surface is controlled by the chemistry of the PDI linkers. Four-substituted glu-PDI forms consolidated microporous particles, whereas di-substituted PA-PDI binds with GO into a macroporous gel-like structure. The GO/PDI controls without Zn2+ ions form only non-integrated dispersions. Both hybrids can initiate photodestruction of 1,5-dihydroxynaphtalene (DHN) due to the effective charge separation between the PDI components and GO by generating hydroxyl radicals determined by luminescent probing with terephthalic acid. The reduction mechanism of photodegradation was confirmed by MALDI-TOF spectroscopy. The structure of the hybrids controls the rate of photodegradation process. The glu-PDI-based photocatalyst shows a smaller rate of photoreduction of 3.3 × 10−2 min−1 than that with PA-PDA (4 × 10−2 min−1) due to diffusion limitations. Our results suggest that the ion-mediated synthesis is a useful and rational alternative for the conventional synthesis of GO-based functional hybrid materials through aromatic stacking between the graphene oxide and organic chromophores to produce new affordable and efficient photocatalysts.