Miracle-dz/UniFAR-FTUs huggingface dataset:
Comprehensive Analysis of Sex Differences at Disease Manifestation in ANCA-Associated Glomerulonephritis

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small vessel vasculitis affecting multiple organ systems, including the kidney. Besides investigations focusing on renal outcomes, sex differences associated with distinct clinical and histopathological findings in ANCA glomerulonephritis (GN) have not been systematically investigated. Therefore, we here aimed to systematically analyze sex differences in patients with AAV and biopsy-proven ANCA GN. We provide a comprehensive analysis of 53 kidney biopsies with ANCA GN retrospectively included between 2015 and 2020 and identified specific sex differences in ANCA GN concerning laboratory parameters and systematic scoring of renal histopathology glomerular and tubulointerstitial lesions, and extrarenal manifestations of AAV. We did not observe any correlation between sex and short-term clinical AAV course or disease severity by comparing general AAV parameters. AAV manifestations in females occurred at an older age with more joint involvement. Regarding histopathological findings, we, again, observed no sex difference among ANCA GN classification, but a significant correlation between females and distinct histopathological findings with less tubulointerstitial inflammation and vasculitis of peritubular capillaries. Finally, we here identified fewer associations between clusters of clinical, laboratory parameters, and histopathological findings in females as compared to males. These findings are of great relevance and further improve our understanding of sex differences in the pathogenesis of ANCA GN. While future studies about specific sex differences and conclusions in these clusters are crucial, our observations further support that sex differences are relevant, affect distinct parameters, and influence clinical, laboratory parameters, and histopathological findings in AAV, particularly ANCA GN.
Prediction Models for Complete Resection in Secondary Cytoreductive Surgery of Patients With Recurrent Ovarian Cancer

The most advanced epithelial ovarian cancer develops recurrent disease despite maximal surgical cytoreduction and adjuvant platinum-based chemotherapy. Treatment with secondary cytoreductive surgery (SCS) combined with chemotherapy or with chemotherapy alone for patients with platinum-sensitive recurrent ovarian cancer (ROC) is currently under heated discussion. Encouragingly, the results of the AGO DESKTOP III Study and the SOC1/SGOG-OV2 trial, which have been published recently, showed a striking advantage in terms of overall survival (OS) and progression-free survival (PFS) of ROC patients undergoing SCS compared to chemotherapy alone; moreover, a benefit of SCS exclusively for patients with complete gross resection (CGR) was particularly highlighted. CGR is considered the ultimate goal of SCS, on condition that the balance between maximal survival gain and minimal operative morbidity is maintained. Several models have been proposed to predict the rate of CGR, such as the MSK criteria, the AGO score, and the Tian model, over the last 15 years. This summary is mainly about the several previously published prediction models for CGR in SCS of ROC patients and discusses the effectiveness and limitations of these prediction models.
Impact of Storm-Enhanced Density (SED) on Ion Upflow Fluxes During Geomagnetic Storm

The impact of the dynamic evolution of the Storm-Enhanced Density (SED) on the upward ion fluxes during the March 06, 2016 geomagnetic storm is studied using comprehensive multi-scale datasets. This storm was powered by a Corotating Interaction Region (CIR), and the minimum Sym-H reached ∼−110 nT. During the ionospheric positive storm phase, the SED formed and the associated plume and polar cap patches occasionally drifted anti-sunward across the polar cap. When these high-density structures encountered positive vertical flows, large ion upward fluxes were produced, with the largest upward flux reaching 3 × 1014 m−2s−1. These upflows were either the type-1 ion upflow associated with fast flow channels, such as the subauroral polarization stream (SAPS) channel, or the type-2 ion upflow due to soft particle precipitations in the cusp region. The total SED-associated upflow flux in the dayside cusp can be comparable to the total upflow flux in the nightside auroral zone despite the much smaller cusp area compared with the auroral zone. During the ionospheric negative storm phase, the ionospheric densities within the SED and plume decreased significantly and thus led to largely reduced upward fluxes. This event analysis demonstrates the critical role of the ionospheric high-density structures in creating large ion upward fluxes. It also suggests that the dynamic processes in the coupled ionosphere-thermosphere system and the resulting state of the ionospheric storm are crucial for understanding the temporal and spatial variations of ion upflow fluxes and thus should be incorporated into coupled geospace models for improving our holistic understanding of the role of ionospheric plasma in the geospace system.
Snow Buntings Maintain Winter-Level Cold Endurance While Migrating to the High Arctic

Arctic breeding songbirds migrate early in the spring and can face winter environments requiring cold endurance throughout their journey. One such species, the snow bunting (Plectrophenax nivalis), is known for its significant thermogenic capacity. Empirical studies suggest that buntings can indeed maintain winter cold acclimatization into the migratory and breeding phenotypes when kept captive on their wintering grounds. This capacity could be advantageous not only for migrating in a cold environment, but also for facing unpredictable Arctic weather on arrival and during preparation for breeding. However, migration also typically leads to declines in the sizes of several body components linked to metabolic performance. As such, buntings could also experience some loss of cold endurance as they migrate. Here, we aimed to determine whether free-living snow buntings maintain a cold acclimatized phenotype during spring migration. Using a multi-year dataset, we compared body composition (body mass, fat stores, and pectoralis muscle thickness), oxygen carrying capacity (hematocrit) and metabolic performance (thermogenic capacity – Msum and maintenance energy expenditure – BMR) of birds captured on their wintering grounds (January–February, Rimouski, QC, 48°N) and during pre-breeding (April–May) in the Arctic (Alert, NU, 82°). Our results show that body mass, fat stores and Msum were similar between the two stages, while hematocrit and pectoralis muscle thickness were lower in pre-breeding birds than in wintering individuals. These results suggest that although tissue degradation during migration may affect flight muscle size, buntings are able to maintain cold endurance (i.e., Msum) up to their Arctic breeding grounds. However, BMR was higher during pre-breeding than during winter, suggesting higher maintenance costs in the Arctic.
Domain Organization of the UBX Domain Containing Protein 9 and Analysis of Its Interactions With the Homohexameric AAA + ATPase p97 (Valosin-Containing Protein)

The abundant homohexameric AAA + ATPase p97 (also known as valosin-containing protein, VCP) is highly conserved from Dictyostelium discoideum to human and a pivotal factor of cellular protein homeostasis as it catalyzes the unfolding of proteins. Owing to its fundamental function in protein quality control pathways, it is regulated by more than 30 cofactors, including the UBXD protein family, whose members all carry an Ubiquitin Regulatory X (UBX) domain that enables binding to p97. One member of this latter protein family is the largely uncharacterized UBX domain containing protein 9 (UBXD9). Here, we analyzed protein-protein interactions of D. discoideum UBXD9 with p97 using a series of N- and C-terminal truncation constructs and probed the UBXD9 interactome in D. discoideum. Pull-down assays revealed that the UBX domain (amino acids 384–466) is necessary and sufficient for p97 interactions and that the N-terminal extension of the UBX domain, which folds into a β0-α–1-α0 lariat structure, is required for the dissociation of p97 hexamers. Functionally, this finding is reflected by strongly reduced ATPase activity of p97 upon addition of full length UBXD9 or UBXD9261–573. Results from Blue Native PAGE as well as structural model prediction suggest that hexamers of UBXD9 or UBXD9261–573 interact with p97 hexamers and disrupt the p97 subunit interactions via insertion of a helical lariat structure, presumably by destabilizing the p97 D1:D1’ intermolecular interface. We thus propose that UBXD9 regulates p97 activity in vivo by shifting the quaternary structure equilibrium from hexamers to monomers. Using three independent approaches, we further identified novel interaction partners of UBXD9, including glutamine synthetase type III as well as several actin-binding proteins. These findings suggest a role of UBXD9 in the organization of the actin cytoskeleton, and are in line with the hypothesized oligomerization-dependent mechanism of p97 regulation.
Transcriptome Reprogramming of Tomato Orchestrate the Hormone Signaling Network of Systemic Resistance Induced by Chaetomium globosum

Chaetomium globosum is a potential biological control agent effective against various plant pathogens. Several reports are available on the mycoparastism and antibiosis mechanisms of C. globosum against plant pathogenic fungi, whereas a few states induced resistance. The potential induced defense component of C. globosum (Cg-2) was evaluated against early blight disease of tomato (Solanum lycopersicum) and further, global RNA sequencing was performed to gain deep insight into its mechanism. The expression of marker genes of hormone signaling pathways, such as PR1, PiII, PS, PAL, Le4, and GluB were analyzed using real-time quantitative reverse transcription PCR (qRT-PCR) to determine the best time point for RNA sequencing. The transcriptome data revealed that 22,473 differentially expressed genes (DEGs) were expressed in tomato at 12 h post Cg-2 inoculation as compared with control plants and among these 922 DEGs had a fold change of −2 to +2 with p < 0.05. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that most of the DEGs were belonging to metabolic pathways, biosynthesis of secondary metabolites, plant–pathogen interaction, chlorophyll metabolism, and plant hormone signal transduction. Gene Ontology (GO) analysis revealed that DEGs were enriched mainly related to binding activity (GO:0005488), catalytic activity (GO:0003824), metabolic process (GO:0008152), cellular process (GO:0009987), response to stimulus (GO:0050896), biological regulation (GO:0065007), and transcription regulator activity (GO:0140110). The gene modulations in hormone signaling transduction, phenylpropanoid biosynthesis, and mitogen-activated protein kinases (MPK) signaling indicated the upregulation of genes in these pathways. The results revealed active participation of jasmonic acid (JA) and salicylic acid (SA) signaling transduction pathways which further indicated the involvement of induced systemic resistance (ISR) and systemic acquired resistance (SAR) in the systemic resistance induced by Cg-2 in tomato.
Left Atrial Spontaneous Echo Contrast and Ischemic Stroke in Patients Undergoing Percutaneous Left Atrial Appendage Closure

Objectives: Spontaneous echo contrast (SEC) in the left atrium (LA) is frequently observed in atrial fibrillation (AF) patients and may lead to thromboembolic events. We aimed to investigate both periprocedural and long-term stroke risks associated with LA SEC in AF patients undergoing percutaneous left atrial appendage closure (LAAC). Methods: A total of 408 consecutive AF patients treated with LAAC between March 2015 and February 2019 were divided into two groups based on preprocedural transesophageal echocardiography: the study group (moderate/severe LA SEC; n = 41) and the control group (none, mild, or mild to moderate LA SEC; n = 367). To attenuate the observed imbalance in baseline covariates, a propensity score matching technique was used. Results: No periprocedural stroke/transient ischemic attack (TIA) was documented. The incidence of device-related thrombus was higher in the study group than in the control group (8.8 vs. 1.3%; P = 0.025). The mean follow-up period was 3.2 ± 1.1 years, during which 8 patients (2.2%) in the control group and 4 (9.8%) in the study group experienced stroke/TIA (P = 0.024). Moderate/severe LA SEC was identified as an independent predictor of stroke/TIA in both the original population (HR = 5.71, 95% CI 1.47–22.19, P = 0.012) and the matched population (HR = 9.79, 95% CI 1.44–66.86, P = 0.020). Conclusions: LA SEC did not show a relationship with periprocedural stroke events in patients undergoing percutaneous LAAC. However, moderate/severe LA SEC increased the incidence of device-related thrombus and the risk of late stroke/TIA.
PPAR-γ Modulators as Current and Potential Cancer Treatments

Worldwide, cancer has become one of the leading causes of mortality. Peroxisome Proliferator-Activated Receptors (PPARs) is a family of critical sensors of lipids as well as regulators of diverse metabolic pathways. They are also equipped with the capability to promote eNOS activation, regulate immunity and inflammation response. Aside from the established properties, emerging discoveries are also made in PPAR’s functions in the cancer field. All considerations are given, there exists great potential in PPAR modulators which may hold in the management of cancers. In particular, PPAR-γ, the most expressed subtype in adipose tissues with two isoforms of different tissue distribution, has been proven to be able to inhibit cell proliferation, induce cell cycle termination and apoptosis of multiple cancer cells, promote intercellular adhesion, and cripple the inflamed state of tumor microenvironment, both on transcriptional and protein level. However, despite the multi-functionalities, the safety of PPAR-γ modulators is still of clinical concern in terms of dosage, drug interactions, cancer types and stages, etc. This review aims to consolidate the functions of PPAR-γ, the current and potential applications of PPAR-γ modulators, and the challenges in applying PPAR-γ modulators to cancer treatment, in both laboratory and clinical settings. We sincerely hope to provide a comprehensive perspective on the prospect of PPAR-γ applicability in the field of cancer treatment.
Functional and Oncological Outcomes Following Robot-Assisted and Laparoscopic Radical Prostatectomy for Localized Prostate Cancer With a Large Prostate Volume: A Retrospective Analysis With Minimum 2-Year Follow-Ups

Objective We aimed to analyze the perioperative, functional, and oncologic outcomes following robot-assisted radical prostatectomy (RARP) and laparoscopic radical prostatectomy (LRP) for patients with localized prostate cancer (PCa) characterized by a large prostate volume (PV; ≥50 ml) over a minimum of 2 years follow-up. Materials and Methods Patients undergoing RARP and LRP for localized PCa with a large PV were included in the final analysis. The perioperative, functional, and oncologic outcomes were analyzed between the two groups. Results All operations were successfully completed without open conversion in both groups. The mean operative time and estimated blood loss in the RARP group were significantly decreased compared to those in the LRP group (139.4 vs. 159.0 min, p = 0.001, and 124.2 vs. 157.3 ml, p = 0.003, respectively). Patients in the RARP arm had significantly lower proportions of grade II or lower and of higher than grade II postoperative complications compared with those in the LRP group (7.9% vs. 17.1%, p = 0.033, and 1.6% vs. 6.7%, p = 0.047, respectively). No significant differences in terms of the rates of pT3 disease, positive surgical margin, and positive lymph node were noted between the two groups. Moreover, no significant difference in the median specimen Gleason score was observed between the RARP and LRP groups (6 vs. 7, p = 0.984). RARP vs. LRP resulted in higher proportions of urinary continence upon catheter removal (48.4% vs. 33.3%, p = 0.021) and at 3 (65.1% vs. 50.5%, p = 0.025) and 24 (90.5% vs. 81.0%, p = 0.037) months post-operation. The median erectile function scores at 6 and 24 months post-operation in the RARP arm were also significantly higher than those in the LRP arm (15 vs. 15, p = 0.042, and 15 vs. 13, p = 0.026, respectively). Kaplan–Meier analyses indicated that the biochemical recurrence-free survival and accumulative proportion of continence were statistically comparable between the two groups (p = 0.315 and p = 0.020, respectively). Conclusions For surgically managing localized PCa with a large prostate (≥50 ml), RARP had a tendency toward a lower risk of postoperative complications and better functional preservation without cancer control being compromised when compared to LRP.
Postural Balance Ability and the Effect of Visual Restriction on Older Dancers and Non-Dancers

Dance has been suggested to be an advantageous exercise modality for improving postural balance performance and reducing the risk of falls in the older population. The main purpose of this study was to investigate whether visual restriction impacts older dancers and non-dancers differently during a quiet stance balance performance test. We hypothesized higher balance performance and greater balance deterioration due to visual restriction in dancers compared with non-dancers, indicating the superior contribution of the visual channel in the expected higher balance performances of dancers. Sixty-nine (38 men, 31 women, 74 ± 6 years) healthy older adults participated and were grouped into a Greek traditional dance group (n = 31, two to three times/week for 1.5 h/session, minimum of 3 years) and a non-dancer control group (n = 38, no systematic exercise history). The participants completed an assessment of one-legged quiet stance trials using both left and right legs and with eyes open while standing barefoot on a force plate (Wii, A/D converter, 1,000 Hz; Biovision) and two-legged trials with both eyes open and closed. The possible differences in the anthropometric and one-legged balance parameters were examined by a univariate ANOVA with group and sex as fixed factors. This ANOVA was performed using the same fixed factors and vision as the repeated measures factor for the two-legged balance parameters. In the one-legged task, the dance group showed significantly lower values in anteroposterior and mediolateral sway amplitudes (p = 0.001 and p = 0.035) and path length measured in both directions (p = 0.001) compared with the non-dancers. In the two-legged stance, we found a significant vision effect on path length (p < 0.001) and anteroposterior amplitude (p < 0.001), whereas mediolateral amplitude did not differ significantly (p = 0.439) between closed and open eyes. The dance group had a significantly lower CoP path length (p = 0.006) and anteroposterior (p = 0.001) and mediolateral sway amplitudes (p = 0.003) both in the eyes-open and eyes-closed trials compared with the control group. The superior balance performance in the two postural tasks found in the dancers is possibly the result of the coordinated, aesthetically oriented intersegmental movements, including alternations between one- and two-legged stance phases, that comes with dance. Visual restriction resulted in a similar deterioration of balance performance in both groups, thus suggesting that the contribution of the visual channel alone cannot explain the superior balance performance of dancers.
Case Report: Eculizumab and ECMO Rescue Therapy of Severe ARDS in Goodpasture Syndrome

Introduction: Goodpasture's syndrome is a life-threatening autoimmune type IV collagen disease characterized by the presence anti–glomerular basement membrane antibodies, rapid progressive glomerulonephritis and/or pulmonary hemorrhage. Methods: Here, we describe new therapeutic options, which take recent advances in unraveling Goodpasture's pathogenesis into account. Results: In a 17-year old male, severe Goodpasture's syndrome resulted in acute respiratory distress syndrome (ARDS). Within 1 day after hospital admission, the patient required extracorporeal membrane oxygenation (ECMO). Despite steroid-pulse and plasmapheresis, ARDS further deteriorated. Eleven days after admission, the patient was in a pre-final stage. At last, we decided to block the complement-driven lung damage by Eculizumab. Three days after, lung-failure has stabilized in a way allowing us to initiate Cyclophosphamide-therapy. As mechanical ventilation further triggers Goodpasture-epitope exposure, the patient was taken from pressure support - breathing spontaneously by the help of maintaining ECMO therapy. After a total of 24 days, ECMO could be stopped and pulmonary function further recovered. Conclusions: In conclusion, our findings suggest that life-threatening organ-damage in Goodpasture's syndrome can be halted by Eculizumab as well as by lung-protective early withdrawal from pressure support by the help of ECMO. Both therapeutic options serve as new tools in otherwise hopeless situations to prevent further organ-damage and to gain time until the established immunosuppressive therapy works in otherwise lethal autoimmune-diseases.
Clinicopathological Characteristics and Response to Chemotherapy in Treatment-Naive Epstein–Barr Virus Associated Gastric Cancer: A Retrospective Study

Background Epstein–Barr virus associated gastric cancer (EBVaGC) is a special subtype of gastric cancer. However, the perioperative treatment plan and the response to chemotherapy are still uncertain. Methods We retrospectively enrolled patients diagnosed with EBVaGC from March 2013 to July 2020 in Beijing Cancer Hospital. Clinicopathological characteristics were recorded. Disease-free survival (DFS) were then calculated, and variants affecting DFS were tested in a Cox proportional regression model. Results One hundred sixty consecutive patients were finally included in our study. Of the patients, 96.9% had adenocarcinoma, while five had squamous cell carcinoma component. Most (70.9%) of them were poorly differentiated. Prevalent programmed death-ligand 1 (PD-L1) (69%) and minor HER-2 (3.8%) expression were noticed; all of the patients were MMR proficient (pMMR) or microsatellite stable (MSS). Among 33 patients who experienced neoadjuvant therapy, the number of tumor regression grade (TRG) 1, TRG 2, and TRG 3 was 5, 16, and 12, respectively. Patients with advanced tumor stage and T stage showed poorer response. Thirty-one patients experienced first-line chemotherapy; ORR was 33.3%, and DCR was 61.9%. One hundred forty-seven patients underwent surgery, and 27 of them showed disease recurrence; the 3-year DFS rate was 71.0%. Tumor stage, neoadjuvant chemotherapy, vascular invasion, and negative PD-L1 expression were associated with poorer DFS. Vascular invasion was the independent risk factor of DFS. Only seven patients reached OS with median follow-up time of 14 months. Conclusion EBVaGC exhibits unique clinicopathological characteristics. Neoadjuvant chemotherapy may not be suitable for EBVaGC, and EBVaGC exhibited relatively poor response to chemotherapy.